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MIDDLE EAST JOURNAL OF ANESTHESIOLOGY Department of Anesthesiology American University of Beirut Medical Center P.O. Box 11-0236. Beirut 1107-2020, Lebanon Editorial Executive Board Consultant Editors Editor-In-Chief: Ghassan Kanazi Assem Abdel-Razik (Egypt) Executive Editors Fouad Salim Haddad [email protected] Maurice A. Baroody Bassam Barzangi (Iraq) Izdiyad Bedran (Jordan) Chakib Ayoub Marie Aouad Sahar Siddik-Sayyid Dhafir Al-Khudhairi (Saudi Arabia) Mohammad Seraj (Saudi Arabia) Managing Editor Mohamad El-Khatib [email protected] Abdul-Hamid Samarkandi (Saudi Arabia) Founding Editor Bernard Brandstater Mohamad Takrouri (Saudi Arabia) Bourhan E. Abed (Syria) Mohamed Salah Ben Ammar (Tunis) Ramiz M. Salem (USA) Elizabeth A.M. Frost (USA) Halim Habr (USA) Editors Emeritus Editor-In-Chief Anis Baraka Honorary Editors Nicholas Greene Musa Muallem Webmaster Rabi Moukalled Secretary Alice Demirdjian [email protected] The Middle East Journal of Anesthesiology is a publication of the Department of Anesthesiology of the American University of Beirut, founded in 1966 by Dr. Bernard Brandstater who coined its famous motto: “For some must watch, while some must sleep” (Hamlet-Act. III, Sc. ii). and gave it the symbol of the poppy flower (Papaver somniferum), it being the first cultivated flower in the Middle East which has given unique service to the suffering humanity for thousands of years. The Journal’s cover design depicts The Lebanese Cedar Tree, with’s Lebanon unique geographical location between East and West. Graphic designer Rabi Moukalled The Journal is published three times a year (February, June and October) The volume consists of a two year indexed six issues. The Journal has also an electronic issue accessed at www.aub.edu.lb/meja The Journal is indexed in the Index Medicus and MEDLARS SYSTEM. E-mail: [email protected] Fax: +961 - (0)1-754249 All accepted articles will be subject to a US $ 100.00 (net) fee that should be paid prior to publishing the accepted manuscript Please send dues via: WESTERN UNION To Mrs. Alice Artin Demirjian Secretary, Middle East Journal of Anesthesiology OR TO Credit Libanaise SAL AG: Gefinor.Ras.Beyrouth Swift: CLIBLBBX Name of Beneficent Middle East Journal of Anesthesiology Acc. No. 017.001.190 0005320 00 2 (Please inform Mrs. Demirjian [email protected] - Name and Code of article - Transfer No. and date (WESTERN UNION) - Receipt of transfer to (Credit Libanaise SAL) Personal checks, credit cards and cash, are not acceptable “For some must watch, while some must sleep” (Hamlet-Act. III, Sc. ii) SYMPOSIUM ANNOUNCEMENT 29th Annual Symposium Clinical Update in Anesthesiology, Surgery and Perioperative Medicine January 16-21, 2011 St. Martin, French West Indies BROCHURE, ABSTRACT, POSTER AND PAPERS INFORMATION: (Deadline – October 25, 2010) Helen Philips Mount Sinai Medical Center 1 Gustave L. Levy Place Box 1010, Dept. of Anesthesiology New York, NY 10029-6574 Phone: 212 – 241 – 7467 Fax: 212 – 426 – 2009 Email: [email protected] 134 Kingdom of Saudi Arabiah National Guard Health Affairs DEPARTMENT OF INTENSIVE CARE The National Guard Health Affairs is considered a flagship facility in the Middle East, providing primary and tertiary healthcare services to the National Guard forces, their dependents and civilian employees. The National Guard group comprises of four major hospitals and sixty healthcare center, which operate to American JCI standards. As a Center Of Excellence, it performs all major surgeries-including cardiac surgery, liver transplants and conjoined twin separation. We are currently inciting applications for the following post: • Staff Physician – ICU Riyadh Our requirements in terms of academics and experience are as follows: MBBS/MD/Masters with Min 3 years experience in ICU/ Critical within a recognized healthcare facility. We in turn can offer a generous tax-free salary, generous holidays, annual flights and exceptional benefits. If you are interested send your CV with copies of your certificates to the recruitment office of the KAMC for the attention of John Quinn at Email: [email protected], or fax# +966-1-2520056. Yoyr application will be treated in strictest of confidence and all initial enquiries or requests for mor information are welcomed. For mor information please visit our website at www.ngha.med.sa Middle East Journal of Anesthesiology Vol. 20, No. 6, October 2010 CONTENTS EDITORIAL “ROUTINE” PREOXYGENATION BEFORE INDUCTION OF AND RECOVERY FROM ANESTHESIA (A SAFETY PRECAUTION) �� Anis Baraka 769 REVIEW ARTICLES ANESTHETIC MANAGEMENT Of PATIENTS WITH CORNELIA DE LANGE SYNDROME �� Veronica Washington and Alan D. Kaye PERIOPERATIVE MANAGEMENT OF THE PATIENT WITH GOODPASTURE’S SYNDROME 773 �� Keri Copponex and Alan D. Kaye 779 SCIENTIFIC ARTICLES TARGET-CONTROLLED INFUSION VERSUS MANUALLY CONTROLLED INFUSION ANESTHESIA WITH PROPOFOL AND REMIFENTANIL IN MASTOIDECTOMY ��Nasser Yeganeh, Bahman Roshani, Mitra Yari and Afshin Almasi Airway Management And Hemodynamic Response To Laryngoscopy And Intubation In Supine And Left Lateral Positions �� Muhammad Faisal Khan, Fawzia Anis Khan and Fawzia Nasim Minai Fentanyl Pretreatment For Alleviation Of Perineal Symptoms Following Preoperative Administration Of Intravenous Dexamethasone Sodium Phosphate – A Prospective, Randomized, Double Blind, Placebo Controlled Study �� Vimi Rewari, Rakesh Garg, Anjan Trikha and Chandralekha Transient Neurological Symptoms Following Spinal Anesthesia For Cesarean Section 785 795 803 ��Edomwonyi, N.P. and Isesele, T.O. Perioperative Cardiac Arrest – Analysis of Anesthetics over a 14–year Period 809 ��Farouk M. Messahel and Mary June Gregorio Efficacy Of Ultrasound-Guided Transversus Abdominis Plane (TAP) Block For PostCesarean Section Delivery Analgesia – A Double-Blind, Placebo- Controlled, Randomized Study �� Jumana M. Baaj, Raed A. AlSatli, Hayan A. Majaj, Zainab A. Babay and Ahmed K. Thallaj COMPLICATIONS AND INTERVENTIONS ASSOCIATED WITH EPIDURAL ANALGESIA FOR POSTOPERATIVE PAIN RELIEF IN A TERTIARY CARE HOSPITAL �� Faraz Shafiq, Mohammad Hamid and Khalid Samad CARDIOVASCULAR RESPONSES TO OROTRACHEAL INTUBATION IN PATIENTS UNDERGOING CORONARY ARTERY BYPASS GRAFT SURGERY �� Nahid Aghdaii, Rasoul Azarfarin, Forouzan Yazdanian and Seyede Zahra Faritus EFFECTS OF INTRAOPERATIVE INTRATHECAL SUFENTANIL INJECTION ON POSTOPERATIVE PAIN MANAGEMENT AFTER SINGLE LEVEL LUMBAR DISCECTOMY �� Saeid Abrishamkar, Mohammad Hossein Karimi Mohammad Reza Safavi, Azim Honarmand and Afshin Safavi 815 767 821 827 833 839 M.E.J. ANESTH 20 (6), 2010 The EFFECTS OF DURATION OF PROPOFOL INJECTION ON HEMODYNAMICS �� Abdul Zahoor and Nauman Ahmed CONTINUAL INFUSION OF INTRATHECAL BACLOFEN (ITB) LONG TERM EFFECT ON SPASTICITY 845 �� Dhafir Al-Khudhairi, Abdulrahman Shug’a Aldin, Yousef Hamdan, Abdullah Rababah, Mona Mathana, Jiri Pazdirek and Jalal Abdulsalam 851 CASE REPORTS THE VIDEO LARYNGOSCOPES BLIND SPOTS AND POSSIBLE LINGUAL NERVE INJURY BY THE GLIDERITE RIGID STYLET – Case Report and Review of Literature ��Magboul Magboul and Shaw Joel Subclavian Vein Injury And Massive Hemothorax Requiring Thoracotomy Following Insertion Of Tunneled Dialysis Catheter – A Case Report and Literature Review – ��Qutaiba Tawfic, Pradipta Bhakta, Ahmed Khamis, Jasvinder Sharma Cesarean Section Under Spinal Anesthesia In A Patient With Ankylosing Spondylitis – A Case Report – ��G. Ulufer Sivrikaya, Ayse Hansi, Hale Dobrucali and Aylin Yalcinkaya Levosimendan AS A Rescue Adjunct In Amlodipine Intoxication – A Case Report – �� M. Gokhan Teker, Haluk Ozdemir, Leyla Saidoglu, Kerem Erkalp and Gokcen Basaranoglu SUCCESSFUL MANAGEMENT OF HIGH DOSE METFORMIN INTOXICATION – ROLE OF VASOPRESSIN IN THE MANAGEMENT OF SEVERE LACTIC ACIDOSIS ��Yasin Al-Makadma and Tamer Riad AWAKE CRANIOTOMY USING INITIAL SLEEP WITH LARYNGEAL MASK AIRWAY IN A DEPRESSED AND AGITATED PATIENT �� Khalid Al-Suaibi CARDIAC ARRYTHMIA AFTER SUCCINYLCHOLINE ADMINISTRATION IN A PATIENT WITH GUILLAN-BARRE SYNDROME �� Jyh Yung Hor CONSCIOUS SEDATION FOR AWAKE CRANIOTOMY IN INTRA-OPERATIVE MAGNETIC RESONANCE IMAGING OPERATING THEATRE (IMRI-OT) ENVIRONMENT �� Mohamad Takrouri, Firas Shubbak, Aisha Al-Hajjaj, Ronaldo Delmaaestro, Lahbib Soualmi, Mashael Al-Khodair, Abrar Al-Duraibi and Najeeb Ghanem EFFECTIVE AWAKE THORACIC EPIDURAL ANESTHETIC FOR MAJOR ABDOMINAL SURGERY IN TWO HIGHRISK PATIENTS WITH SEVERE PULMONARY DISEASE – Case Report – ��E. Abd Elrazek, M. Thornton and A. Lannigan VARIANTS OF PHEOCHROMOCYTOMA AND THEIR ANESTHETIC IMPLICATIONS – A Case Report and Literature Review – �� Kathryn Dortzbach, Daniel Gainsburg, and Elizabeth Frost Anesthetic Management Of Achondroplastic Dwarf Undergoing Cesarean Section – A Case Report – �� Banu Cevic and Serhan Colakoglu 768 857 861 865 869 873 877 881 885 891 897 907 EDITORIAL “ROUTINE” PREOXYGENATION BEFORE INDUCTION OF AND RECOVERY FROM ANESTHESIA (A SAFETY PRECAUTION) Whenever you travel by air “fasten your seat belt” is the “minimum safety precaution” during take off and landing. Similar to air flying, the risk to patients undergoing general anesthesia is highest at induction (take off) and recovery (landing) and hence “routine” preoxygenation during these two critical periods, can be considered a “safety precaution”1-3. The potential for oxygen desaturation in otherwise smooth induction of anesthesia in healthy patients has led to previous calls for “routine” preoxygenation. Although it can be argued that such desaturation does not necessarily generate mortality or morbidity, there appears to be an overall weight of benefit favoring this practice1-3. Since the inception of the ASA Closed Claims project, adverse respiratory events have constituted the single largest source of injury4. Just three mechanisms of injury accounted for nearly three fourths of all claims for adverse respiratory events. These mechanisms are inadequate ventilation (38%), esophageal intubation (18%) and difficult tracheal intubation (17%). Most of these adverse respiratory events (72%) are readily diagnosed by pulse oximetry and end-tidal capnography. Also, the consequent hypoxemia can be ameliorated by the “routine” preoxygenation. Recent investigations have highlighted risk factors for the rapid development of hypoxemia during apneic episodes. These risk factors are additive. It included reduced functional residual capacity (FRC), increased oxygen consumption and/or airway obstruction. It also includes hypoventilation prior to apnea or inadequate preoxygenation. Patients with a combination of these factors are liable to develop rapid desaturation during apnea5. Preoxygenation will always be mandatory in the context of “rapid-sequence induction” of general anesthesia in patients with full stomach, and arguably so in an additional range of scenarios as the predictable “difficult airway”. Imperative preoxygenation exists for those patients who will not tolerate a fall in PO2 such as ischemic heart disease or atopic individuals. “Routine” preoxygenation would also be strongly advisable when FRC is low and oxygen consumption is high (the pregnant, the obese and children), as well as in patients with already low PO2 such as lung disease or right-to-left shunt2. In the absence of any of the above factors, “routine” preoxygenation offers identifiable “safety benefits” during induction of general anesthesia1-3, since many conditions may be unpredictable such as the “difficult intubation-difficult ventilation scenario”. Also, many adverse drug reactions can follow induction of anesthesia such as drug-induced anaphylaxis, hypotension and hypoventilation. Thus, the recommendation of “routine” preoxygenation will be in line with the promotion of patient safety. However, “routine” preoxygenation must be used as an adjunct rather than an alternative to a sequence of fundamental preoperative precautions than minimize adverse sequalae2. 769 M.E.J. ANESTH 20 (6), 2010 770 Anis BARAKA Recovery from anesthesia and tracheal extubation have received limited critical safety measures compared with attention to the identification and management of potentially difficult intubation, despite the observation that airway complications are more likely to be associated with tracheal extubation than intubation6,7. The American Society of Anesthesiologists (ASA) Task Force on Management of the Difficult Airway recommended that each anesthesiologist must have a pre-formulated strategy for extubation of the difficult airway, and an airway management plan for dealing with post extubation hypoventilation8. “High-risk” extubation is defined as a situation where in reestablishing a lost airway, be it due to failure of oxygenation, ventilation or loss of airway patency is likely to be difficult or incomplete without significant risk. Even routine discontinuation of anesthesia, reversal of neuromuscular block and tracheal extubation can be complicated with hypoxemia, hypoventilation and loss of airway patency. Hypoventilation and hypoxemia can result from the residual effects of anesthetics as well as the incomplete reversal of neuromuscular block9. Residual anesthesia and neuromuscular block can decrease the functional activity of the pharyngeal muscles resulting in upper airway obstruction and in fourfold to fivefold increase in the risk of aspiration10. The residual effects of anesthesia and relaxants can also decrease the contractions of the respiratory muscles resulting in hypoventilation, as well as inability of deep breathing and effective coughing which predispose to atelectasis. It can also obtund the hypoxic drive by the peripheral chemoreceptors11. In addition, Baraka has shown that adequate oxygenation must be ensured before reversal of neuromuscular block by neostigmine in order to achieve safe reversal and minimize neostigmineinduced cardiac arrhythmia12,13. Jacoby et al have shown that cardiac response to vagal stimulation is more frequent and serious in the presence of hypoxia14. There is evidence that “routine” preoxygenation with 100% oxygen prior to reversal of neuromuscular block and tracheal extubation is recommended not only to ensure safe reversal of neuromuscular block by neostigmine12,13 but also to improve the margin of safety, given the potential of unpredictable airway and ventilation problems. Preoxygenation of the awake patient before induction of general anesthesia increases the alveolar oxygen and decreases the alveolar nitrogen in a parallel fashion. “Denitrogenation” of the functional residual capacity (FRC) of the lungs is 95% complete within 3 minutes when the subject is breathing a normal tidal volume from a circle absorber system using a fresh gas flow equals to the alveolar ventilation volume about 5 L/min15. A higher oxygen flow up to 10 L/min is required whenever the alveolar ventilation volume is high as observed during pregnancy. Also, a high oxygen flow is required whenever “rapid” preoxygenation is achieved by the 8 deep breaths’ technique within 60 seconds16,17. In the anesthetized patient on intermittent positive pressure ventilation, preoxygenation during recovery from anesthesia can be also achieved by either the normal tidal volume ventilation for 3 minutes, or by the 8 deep breath technique for 60 seconds. The effectiveness of preoxygenation (denitrogenation) can be checked by an end-tidal oxygen >80%. The achievement of SpO2 100% is not a reason to stop denitrogenation and may occur before the lungs are adequately denitrogenated. Conversely, failure of SpO2 to increase substantially does not necessarily indicate failure of denitrogenation18. In conclusion, “routine” preoxygenation with 100% oxygen can be considered as a “safety” measure during induction of and recovery from general anesthesia. However, it must be used as an adjunct rather than an alternative to a sequence of fundamental precautions that minimized adverse sequalae. Baraka, MD,FRCA (Hon) Emeritus Editor-in-Chief Middle East Journal of Anesthesiology “ROUTINE” PREOXYGENATION BEFORE INDUCTION OF AND RECOVERY FROM ANESTHESIA (A SAFETY PRECAUTION) 771 References 1.Kung MC, Hung CT, Ng KP, et al. Arterial desaturation during induction in healthy adults; should preoxygenation be a routine? Anaesthesia and Intensive Care; 1991, 19:192-196. 2.Bell MDD: Routine preoxygenation-a new “minimum standard” of care. Anaesthesia; 2004, 59:943-945. 3.Baraka A: Routine preoxygenation. Anaesthesia; 2006, 61:612613. 4.Caplan RA: Adverse respiratory events in anesthesia: a closed claim analysis. Anesthesiology; 1990, 72:828-833. 5.Hardman JG, Wills JS, Aitkenhead AR: Factors determining the onset and course of hypoxemia during apnea. An investigation using physiological modeling. Anesth Analg; 2000, 38:96-102. 6.Miller KA, Harkin CO, Bailey PL: Postoperative tracheal extubation. Anesth Analg; 1995, 80:149-172. 7.Asai T, Koga K, Voughan RS: Respiratory complications associated with tracheal intubation and extubation. Br J Anaesth; 1998, 80:767775. 8. American Society of Anesthesiologists. Practice Guidelines for Management of the Difficult Airway. An update report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology; 2003, 98:1269-1277. 9.Baraka A: Irreversible tubocurarine neuromuscular block in the human. Br J Anaesth; 1967, 39:891-893. 10.Eriksson LI, Sundman E, Olsson R, et al: Functional assessment at rest and during swallowing in partially paralyzed humans. Simultaneous videomanometry and mechanography of awake human volunteers. Anesthesiology; 1997, 87:1035-1043. 11.Eriksson LI: The effects of residual neuromuscular blockade and volatile anesthetics on the control of ventilation. Anesth Analg; 1999, 89:243-251. 12.Baraka A: Safe reversal (1) atropine followed by neostigmine-an electrocardiographic study. Brit J Anaesth; 1968, 40:27-29. 13.Baraka A: Safe reversal (2) atropine-neostigmine mixture. An electrocardiographic study. Brit J Anaesth; 1968, 40:30-36. 14.Jacoby J, Ziegler C, Hamelberg W, et al: Cardiac arrhythmia: effect of vagal stimulation and hypoxia. Anesthesiology; 1955, 16:1004. 15.Hamilton WK, Eastwood DW: A study of denitrogenation with some inhalation anesthetic systems. Anesthesiology; 1955, 16:861867. 16.Baraka AS, Taha SK, Aouad MT, et al: Preoxygenation. Comparison of maximal breathing and tidal volume breathing techniques. Anesthesiology; 1999, 91:612-615. 17.Benumof JL: Preoxygenation. Best method for both efficacy and efficiency (Editorial). Anesthesiology; 1999, 91:603-605. 18.McCahon RA, Hardman JG: Fighting for breath: apnea vs the anaesthetized. Anaesthesia; 2007, 62:105-108. M.E.J. ANESTH 20 (6), 2010 review articles ANESTHETIC MANAGEMENT IN A PATIENT WITH CORNELIA DE LANGE SYNDROME Veronica Washington* And Alan David Kaye** Introduction Cornelia de Lange syndrome (CdLS), also known as Brachmann−de Lange syndrome, is a syndrome of multiple congenital anomalies of variable severity. This rare syndrome is genetically heterogeneous and sporadic, with an estimated prevalence of 1 in 10,000 to 30,000. First described by Cornelia de Lange as a diagnostic entity in 1933, Vrolik and Brachmann reported isolated cases in severely affected infants between 1849 and 1916. The syndrome is best characterized by distinctive facial appearance, prenatal and postnatal growth deficiency, psychomotor delay, and upper limb malformations. Although almost all organ systems can be affected, individuals with CdLS most notably display deficits in the development of neurosensory, craniofacial, musculoskeletal, cardiac and gastrointestinal systems. There is no known cure but the syndrome can be managed by treating associated clinical symptoms. Sixty six percent of CdLS individuals die before the first year of life1. Mortality occurs primarily from aspiration in infancy and from infection and bowel obstruction there after1. Pathogenesis Several genes have been discovered in CdLS (NIPBL, SMC1A, SMC3), all of which are involved in sister chromatid cohesion. Cohesion proteins are involved in chromosome segregation, regulation of gene expression, DNA repair and maintenance of genome stability. Mutations in NIPBL on chromosome 5 account for~ 60% of CdLS cases, while mutations in SMC1A on the inactivated X chromosome, and SMC3 on chromosome 10 account for ~5%2. NIPBL and SMC3 mutations are both believed to have an autosomal dominant inheritance. SMC1A mutations are believed to have an X-linked dominant pattern of inheritance, however males and females are affected similarly. The genotype-phenotype correlation reveals that mutations in NIPBL result in more severe phenotypes than mutations in SMCA1 and SMC3 genes2. Moreover, the associated phenotype in NIPBL mutations increases in severity as the severity of the mutation increases. More severe mutations occur in NIPBL deletions or truncations, while milder forms of CdLS occur in patients with NIPBL missense mutations. SMCA1 and SMC3 gene mutations are predominantly missense and small in-frame deletions. The phenotype in patients with SMCA1 and SMC3 mutations is milder, consisting mainly of mild to moderate mental retardation, without associated severe growth retardation, limb or systemic involvement3,4. Although mutations in these genes are implicated in 65% of patients, the pathogenesis of most cases of CdLS is sporadic and dominant2. * ** MD, MPH, Resident, LSU Dept. of Family Practice at Bogalusa Medical Center, Mississipi. MD PhD DABPM, Professor and Chairman, Department of Anesthesiology and Professor, Depart. of Pharmacology, LSU School of Medicine, Room 656, 1542 Tulane Ave. New Orleans, Louisiana, 70112. For additional information, contact Dr. Alan D. Kaye, MD PhD DABPM, Professor and Chairman, Department of Anesthesiology, LSU School of Medicine, 1542 Tulane Ave, New Orleans, Louisiana, U.S.A. Tel: 504-568-2319, E-mail: [email protected]. 773 M.E.J. ANESTH 20 (6), 2010 774 V. Washington & A. D. Kaye Clinical Manifestations CdLS is diagnosed based on clinical signs and symptoms (Table 1). Table 1 Diagnostic Criteria for Cornelia de Lange Syndrome Body category No. (1) Facial (2) Growth >2 of (3) Development >1 of (4) Behavior >2 of Main criteria With Secondary criteria Synophrys (arched, fine eyebrows) and >3 of Long eyelashes Short nose, anteverted nares Long, prominent philtrum Broad or depressed nasal bridge Small or square chin Thin lips, down-turned corners High palate Widely spaced or absent teeth (6) Neurosensory/ Skin >3 of Weight below 5th centile for age Height or length below 5th centile for age OFC below 2nd centile for age Developmental delays or mental retardation Learning disabilitites Attention deficit disorder ± hyperactivity Obsessive-compulsive characteristics Anxiety Constant roaming Aggression Self-injurious behavior Extreme shyness or withdrawal Autistic-like features Reduction defects with absent forearms alone Small hands and/or feet (below 3rd centile) or and >2 of Oligodactyly None of these and >3 of 5th finger clinodactyly Abnormal palmar crease Radial head dislocation/abnormal elbow extension Short 1st metacarpal/proximally placed thumb Bunion Partial 2,3 syndactyly toes Scoliosis Pectus excavatum Hip dislocation or dysplasia Ptosis (7) Other major systems >3 of Tear duct malformation or blepharitis Myopia -6.00 D Major eye malformation or peripapillary pigmentation Deafness or hearing loss Seizures Cutis marmarata Hirsutism, generalized Small nipples and/or umbilicus Gastrointestinal malformation/malrotation (5) Musculoskeletal OR OR Diaphragmatic hernia Gastroesophageal reflux disease Cleft palate or submucous cleft palate Congenital heart defect Micropenis Hypospadias Cryptorchidism Renal or urinary tract malformation OFC = head circumference. Diagnosis: (1) Positive mutation on CdLS gene testing; or (2) Facial findings and meet criteria from two of the growth, development or behavior categories; or (3) Facial findings and meet criteria for three other categories, including one from growth, development or behavior, and two from the other categories (see notes). Adapted from Kline AD et al. Cornelia de Lange syndrome: Clinical review, diagnostic and scoring systems, and Anticipatory guidance. American journal of medical genetics part A 2007; 143A: 1287-1296. ANESTHETIC MANAGEMENT IN A PATIENT WITH CORNELIA DE LANGE SYNDROME 775 Table 2 Anesthetic Considerations in CdLS Cardiac Anomalies Provide endocarditis prophylaxis. Pulmonary Anomalies Increase risk of respiratory infections, irritable airway, hypoxia, and hypercapnia. Renal dysfunction Renally dose drugs Airway Risk of aspiration, and occlusion of airway. Prepare for difficult intubation. Contraindicated drugs Halothane and nitrous oxide Recommended induction agents Sevoflurane, isoflurane, ketamine, etomidate, and narcotics Malignant Hyperthermia Associated with paralysis in the presence of strabismus. Cranio facial Facial features are the most distinctive clinical feature. The head is microcephalic, with a low hairline on the forehead and posterior neck. Eyebrows are confluent and well defined, extend down to the nasal ridge and are highly arched in 98%5. Eyelashes are thick and long with an exaggerated upward curve of upper eyelashes and an exaggerated downward curve of bottom eyelashes. Hypertelorism and antimongoloid slant of the eyes are also noted. The midface has a flattened appearance with a short nose and anteverted nares. The nasal bridge is usually broad or depressed. The philtrum is long, smooth, and prominent, while the lips are thin with downturned corners. These patients also have micrognathia or square chin with a high arched palate and cleft palate in 30%5. Dental anomalies include widely spaced small teeth, absent teeth, and crowded teeth. Ears are low set, posteriorly rotated, and often hirsute. Cardiovascular The incidence of congenital heart disease is as high as 20 – 30%, compared to 0.8% for all births5. The most common abnormalities include (in descending order): ventricular septal defects, atrial septal defects, pulmonic stenosis, tetralogy of Fallot, hypoplastic left heart syndrome, and tricuspid aortic valve. Some heart defects have obvious signs and symptoms at birth that will prompt an evaluation by a pediatric cardiologist. Other defects are subtle and are not always recognized at birth; therefore detection of congenital heart disease in CdLS patients may be delayed. It is recommended that every CdLS patient be evaluated by echocardiogram. Musculoskeletal Along with the distinctive craniofacial features, specific extremity findings help in establishing a diagnosis of CdLS. Although lower extremity findings are less common, over 80% of affected individuals have partial syndactyly of toes 2 and 35. Hands and feet are small in measurement in over 90%, and single palmar creases are observed in over 50%5. Fifth finger clinodactyly is observed in 74%, as well as bradydactyly5. The first metacarpal is usually disproportionately shortened with a proximally placed thumb6. Upper extremity malformations are observed in up to 30% of patients, and range from oligodactyly to ulnar deficiency to absent forearm, with digit(s) present distal to the elbow6. Other common extremity findings include radial head dislocation with abnormal elbow extension, clubbed feet and poikilothermia. Pectus excavatum, scoliosis and hip dislocation or dyplasia are other common musculoskeletal findings. Gastrointestinal Gastroesophageal reflux disease (GERD) is the most common GI complication in CdLS patients, with an incidence of over 90%6. Esophagitis, aspiration, chemical pneumonitis, and irritability are complications of GERD that can be avoided by diagnosis and treatment in the neonatal period. Pyloric stenosis has been reported, and may contribute to malnutrition and poor weight gain during the newborn period. Malrotation occurs in at least 10% and is associated with an increase risk of volvulus6. Congenital diaphragmatic hernia also occurs, however the reported incidence varies and may be underestimated secondary to infants who die in the perinatal period. Genitourinary Up to 40% of CdLS patients have structural kidney and/or urinary tract anomalies, the most M.E.J. ANESTH 20 (6), 2010 776 common are vesiculoureteral reflux, pelvic dilation and renal dysplasia, with the possibility of deficient renal function6. Genitalia malformations have also been reported in many CdLS cases. Crytorchidism has been reported in up to 73% of males, in addition to hypoplastic and micropenis in 57% and hypospadias6. Females may have small labia majora and abnormally formed uteri. Auditory and Vision Up to 60% of affected individuals have hearing loss, including both sensorineural and conductive6. Ear canals are narrow if not stenotic, which predisposes these patients to otits media and sinusitis6. The most common ophthalmologic findings are peripapillary pigmentations, high myopia, ptosis, microcornia, and blepharitis. Rare ophthalmologic findings include nasolacrimal duct obstruction, nystagmus, cataract and glaucoma. Neuropsychiatric Behavioral issues in CdLS patients are speculated to be secondary to frustration from an inability to communicate. Many individuals demonstrate behavior consistent with depression and attention deficit hyperactivity disorder, and display obsessivecompulsive behavior, autistic behavior, including selfdestructive tendencies, defiance, extreme shyness and avoidance of social interactions. Growth and Developmental Retardation Growth failure occurs in over 95% of patients with CdLS6. Proportionate small stature begins prenatally, although most significant by six months of age, and continues throughout life. Although growth in CdLS parallels standard growth curves, mean height and weight remain below the 5th percentile6. Developmental delay is observed in over 95%6. Patients with classic CdLS experience profound to severe developmental delays. The overall IQ ranges from below 30 to 102, with an average of 537,8. Patients with mild forms of CdLS have higher functioning with IQ ranging from normal to borderline IQ with learning disabilities9. However, most individuals experience disabilities in speech and language. V. Washington & A. D. Kaye Anesthetic Considerations Pharmacology General anesthesia is often necessary in CdLS patients due to non-cooperative and hyperactive behavior. However, perioperative sedation should be light due the possibility of upper airway obstruction and unpredictable responses to drugs secondary to endocrine disorders10. In cases in which rapid induction of anesthesia is necessary, ketamine or etomidate are often recommended due to limited cardiac depressant effects 10. In patients with suspected or confirmed pulmonary hypertension inhalational agents and narcotics are recommended10. Newer inhalation agents, including desflurane and sevoflurane, allow for faster recovery than older agents such as halothane. Nitrous oxide should be avoided since it can increase pulmonary vascular resistance10. Also, caution with induction of paralysis in patients with strabismus is warranted, as there is a reported association of malignant hyperthermia in these patients10. Cardiorespiratory Preanesthetic examination to access for cardiorespiratory system is extremely important and often difficult. Many have previously undiagnosed congenital cardiac anomalies including tetralogy of Fallot, pulmonary or aortic stenosis, atrial septal defect, ventricular septal defect, pulmonary ductus arteriosus, hypoplasia of the left ventricle and abnormal electrocardiographic findings (i.e. AV block, left ventricular hypertrophy, and right ventricular hypertrophy) that are unveiled during anesthetic management. Cases of right bundle branch block, with and without murmur, first observed during anesthetic management have been reported10. Confirmation of any of these cardiac anomalies necessitates administration of antibiotics for endocarditis prohylaxis10. Postoperative complications in such patients include unstable cardiac function and marked susceptibility to infections. In patients with both cardiac anomalies and repeated episodes of upper airway obstruction secondary to macroglossia and micrognathia, pulmonary hypertension may develop, which may complicate anesthesia with the development of hypoxia and hypercapnia10. Successful perioperative ANESTHETIC MANAGEMENT IN A PATIENT WITH CORNELIA DE LANGE SYNDROME management of such cases may include increasing FiO2 to achieve adequate O2 saturations, and if warranted, prostaglandins, and even nitric oxide10. Pulmonary hypoplasia and lobular anomalies predispose CdLS patients to respiratory infections. The most common causes of death in such patients are acute pneumonia and bronchitis11. The airway is considered to be irritable and the administration of intravenous hydrocortisone has been shown to relieve asthma-like symptoms that occurred during general anesthesia11. Renal/Endocrine Endocrine disorders and renal dysfunction, secondary to immaturity and malformation, necessitate preanesthetic evaluation to determine renal function and preparation for potential postoperative complications. Dosing of drugs excreted by the kidneys, should be carefully assessed. Airway Anesthetic management may pose a serious problem due to aspiration complications, and difficult intubation secondary to craniofacial anomalies characteristic of CdLS. The risk of aspiration secondary to GERD may be managed with premeditation including famotidine, metoclopramide and/or sodium bicitrate, and utilizing a rapid sequence induction with succinylcholine to offer some protection form stomach content aspiration. Intubation in patients with CdLS almost always requires a tube of smaller size than that which is age appropriate due to the immature development of airway structures, most notably the presence of a hypoplastic larynx11. The craniofacial features that pose a risk of difficult intubation include macroglossia, cleft lip/palate, midface hypoplasia, high arched palate, and mandibular hypoplasia. In the case of macroglossia, the enlarged tongue fills the oral cavity, which obstructs the airway and impedes visualization of the larynx. Obstruction by the tongue can also occur in individuals with cleft palates. In this case, the nasal airway is obstructed if the tongue falls into the cleft, and oropharynx will be completely occluded 777 if the tongue falls posteriorly with relaxation of the oropharyngeal musculature12. In midface hypoplasia, the palate is high and arched, and the nasal passages are small, therefore these individuals are primarily mouth breathers, which can potentially pose a problem during mask ventilation12. When the mouth is closed, the tongue occludes the small oral cavity and the small nasal passage creates resistance to nasal airflow, which can be overcome by holding the mouth open during induction12. Craniofacial dysostosis makes mask fit difficult; therefore maintaining a good mask seal is paramount12. In mandibular hypoplasia the anterior mandibular space is decreased, thereby decreasing the space into which the tongue is displaced during laryngoscopy, and making tracheal intubation more difficult12. Such patients should be managed with fiberoptic intubation, glide scope, or other advanced airway techniques. In general, difficult intubations encountered in CdLS are best managed by having an introducer, laryngeal mask or fiberoptic bronchoscope readily available. A laryngeal mask airway is recommended as an alternative to mask ventilation or tracheal intubation, and as a tool in fiberoptic scope assisted tracheal intubation13. Laryngeal mask airway is also beneficial in that it does not require paralysis, which may be relevant in individuals with strabismus, which can be associated with malignant hyperthermia13. Some literature advocates corticosteroid application prior to intubation to prevent airway trauma and edema from potential multiple intubation attempts14. Conclusion Although specific gene mutations can be found in some patients, genetic testing is usually reserved to confirm an already highly suspected CdLS diagnosis. At present there is no cure for CdLS. Treatment is symptomatic and therapy based. Early intervention by means of medical and surgical care are necessary for feeding difficulties, congenital heart disease, urinary, auditory and visual abnormalities, as well as psychomotor delay. In summary, the anesthetic care of the patient with CDLS is often challenging and a well thought out perioperative plan can potentially reduce morbidity and mortality. M.E.J. ANESTH 20 (6), 2010 778 V. Washington & A. D. Kaye References 1. Sargent, WW: Anesthetic management of a patient with Cornelia de Lange syndrome. Anesthesiology; 1991, 74:1162-1163. 2. Revekova E, Focarelli ML, Susani L, et al: Cornelia de Lange mutations in SMC1A or SMC3 affect binding to DNA. Human Molecular Genetics; 2009, 18: 418-427. 3. DeardoffM, Kaur M, Yaeger D, et al: Mutations in cohesion complex members SMC3 and SMC1A casue a mild variant of Cornelia de Lange syndrome with predominant mental retardation. American Journal of Human Genetics; 2007, 80:485-494. 16. 4. Musio A, Selicorni A, Focarelli ML, et al: X-linked Cornelia de Lange syndrome owing to SMC1L1 mutations. Nature Genetics; 2006, 38:528-530. 5. Jackson L, Kline AD, Barr MA, Koch S: De Lange syndrome: a clinical review of 310 individuals. American Journal of Medical Genetics; 1993, 47:940–946. 6. Kline AD, Krantz ID, Sommer A, Kliewer M., Jackson LG, Fitzpatrick DR, Levin AV, Selicorni A: Cornelia de Lange syndrome: Clinical review, diagnostic and scoring systems, and Anticipatory guidance. American journal of medical genetics part A; 2007, 143A:1287-1296. 6. 7. Kline AD, Stanley C, Belevich J, Brodsky K, Barr M, Jackson LG. Developmental data on individuals with the Brachmann-de Lange syndrome. American Journal of Medical Genetics; 1993, 47:1053–8. 8. Saal HM, Samango-Sprouse CA, Rodnan LA, Rosenbaum KN, Custer DA: Brachmann-de Lange syndrome with normal IQ. American Journal of Medical Genetics; 1993, 47:995–8. 9. Moeschler JB, Graham JM Jr: Mild Brachmann-de Lange syndrome. Phenotypic and developmental characteristics of mildly affected individuals. American Journal of Medical Genetics; 1993, 47:969–76. 10.Corsini LM, Stefano GD, Porras MC, Galindo S, Palencia J: Anaesthetic implications of Cornelia de Lange syndrome. Paediatric Anaesthesia; 1998, 8:159-162. 11.Takeshita T, Akita S, Kawahara M: Anesthetic management of a patient with Cornelia de Lange syndrome. Anesthesia Progress; 1987, 34: 63-65. 12.Nargozian C: The airway in patients with craniofacial abnormalities. Pediatric Anesthesia; 2004, 14:53-59. 13.Garcia RF, Mencia TP, Gutierrez-Jodra A, Garcia AL: Anesthetic management with laryngeal mask in a child with Brachmann de Lange syndrome. Pediatric Anesthesia; 2006, 16:698-700. 14.Küçükyavuz Z, Özkaynak Ö, Tüzüner AM, Kisnisçi R. Difficulties in anesthetic management of patients with micrognathia: report of a patient with Stickler Syndrome. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics; 2006, 102; e33-e36. PERIOPERATIVE MANAGEMENT OF THE PATIENT WITH GOODPASTURE’S SYNDROME Keri Copponex * and Alan David. Kaye ** Introduction Goodpasture’s Syndrome (GS) is characterized by the classic triad of diffuse pulmonary hemorrhage, glomerulonephritis, and circulating anti-basement membrane antibodies1. It is an uncommon disorder, with an incidence estimated to be 0.3 cases per 100,000 people per year2. There is a male predominance, with a male to female ratio between 2:1 and 9:13. The disease may present at any age, although it most commonly manifests between the ages of 20 and 30 years1. Goodpasture first described the pulmonary renal syndrome in 1919 during the influenza epidemic. However, it was not until 1958 that Stanton and Tange referenced Goodpasture’s original description in their report of young men with pulmonary hemorrhage and glomerulonephritis1. The role of anti-GBM antibodies in the pathogenesis of GS was discovered in 19671. Reported risk factors for the development of GS include exposure to hydrocarbons, cigarette smoking, and a preceding viral illness, especially influenza2. Clinical Manifestations While there is considerable variation in the clinical presentation of GS, the initial symptoms most cases include progressive dyspnea and hemoptysis (seen in 80% to 95%), which may range in severity from blood-tinged sputum to massive hemorrhage4. Additionally, some patients have alveolar hemorrhage, evident only on biopsy or bronchoalveolar lavage1. Between 20% and 40% of patients have only renal disease, and less than 10% have only pulmonary disease1. Patients may present initially with hemoptysis only, then develop glomerulonephritis months or years later. Alternatively, some patients may present with glomerulonephritis and either later develop pulmonary hemorrhage or never develop pulmonary hemorrhage2. Unlike systemic inflammatory disorders, GS typically does not cause clinical signs of inflammation, although some patients may have prodromal symptoms such as nausea, vomiting, fatigue, and weight loss. Continuous pulmonary hemorrhaging can result in hypoxemia and significant iron deficiency, with decreased levels of serum iron and ferritin1. If massive hemoptysis occurs, the alveolar spaces are rapidly flooded with blood, resulting in respiratory failure. Acute pulmonary hemorrhage is seen as bilateral patchy areas of dense alveolar infiltrates on chest radiographs, and air bronchograms are also often present2. The apices and costophrenic angles are generally not involved3. Some patients may have a normal chest radiograph; however, CT scan may reveal parenchymal abnormalities3. After a patient has an acute episode of pulmonary hemorrhage, serial chest radiographs demonstrate a predictable change in pattern. Within 2 to 3 days, the initial patchy areas of consolidation disappear and a reticulonodular pattern becomes evident3. The pattern becomes distinctly reticular within 1 week, and the chest radiograph usually returns to normal in 10 to 12 days3. * ** MD, Resident, Department of Anesthesiology, Louisiana State University School of Medicine in New Orleans. MD, PhD, Professor and Chairman, Department of Anesthesiology and Professor, Department of Pharmacology, Louisiana State University School of Medicine in New Orleans. Address Correspondence to: Alan D. Kaye, MD., Ph.D., DABPM, Professor and Chairman, Department of Anesthesiology, Louisiana State University School of Medicine, 1542 Tulane Ave, Room 656, New Orleans, LA 70112. Tele: (504) 5682319, Fax: (504) 568-2317, E-mail: [email protected] 779 M.E.J. ANESTH 20 (6), 2010 780 GS patients with renal disease usually have rapidly progressive glomerulonephritis (RPGN). Renal dysfunction causes azotemia, as well as proteinuria, hematuria, and red blood cell casts are seen on urinalysis. 1 Without treatment, end-stage renal failure may occur within days to weeks after the onset of symptoms2. Pathogenesis Genetics are likely involved in the pathogenesis of GS, given that there is a strong association between the disease and HLA-DR2. There is an increased incidence of HLA-DR2 in patients with GS when compared to the general population5. However, additional factors must also be involved, as most cases are sporadic. GS is defined by the presence of antibodies that target the carboxyl-terminal region of the alpha-3 chain of type IV collagen1. Only the lungs and kidneys, are involved despite the presence of type IV collagen throughout the body. This effect may be explained because the antigen is more accessible to the antibody in the alveoli and glomeruli or because of the predominance of the alpha-3 chain in the alveoli and glomeruli rather than in other tissues1. Structural differences between the alveoli and glomeruli may explain why some patients develop only alveolar hemorrhage or only glomerulonephritis, as opposed to the combination of the two pathologies. One such difference is the presence of fenestrae in the glomerular endothelium, which grant greater accessibility of the antibodies to the basement membrane1. These fenestrae are absent in the alveolar endothelium3. Diagnosis Microscopic abnormalities associated with GS include intra-alveolar blood, hemosiderin-laden macrophages in the alveoli and interstitium, interstitial fibrosis, and type II cell hyperplasia1. Occasionally, there may be a lymphocytic interstitial infiltrate. Results of electron microscopy have been inconsistent, with findings ranging from no abnormalities to thickening, splitting, discontinuity, or smudging of the basement membrane1. However, none of these findings is diagnostic of GS. Confirmation of the diagnosis is accomplished by performing a renal biopsy and proving the presence of tissue-bound anti-basement membrane K. Copponex & A. D. Kaye antibodies by enzyme-linked immunosorbent assay (ELISA)3. If a biopsy is contraindicated, the diagnosis can be made by serologic testing and demonstration of the presence of anti-basement membrane antibodies in the serum with either indirect immunofluorescence or ELISA. Focal or diffuse crescentic and necrotizing glomerulonephritis is seen on light microscopic examination of kidney tissue, and immunofluorescence shows linear staining of IgG along the glomerular basement membrane3. Immunofluorescence of lung tissue demonstrates diffuse linear staining along the alveolar wall, usually attributable to IgG. Pulmonary function testing is not useful in diagnosing GS, but may help in monitoring the course of the disease4. Patients generally demonstrate a restrictive pattern, along with a decreased diffusing capacity and a decrease in resting PaO2, which may exist even during remission of the disease3. The diffusing capacity of the lung for carbon monoxide (DLCO) may be increased due to intraalveolar blood binding to carbon monoxide4. When measured throughout the disease, the Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) may help to identify an acute pulmonary hemorrhage versus other causes of radiographic opacities4. Prognosis and Treatment Prior to the development of immunosuppressive therapy and plasmapheresis, GS was usually fatal, secondary to either lung hemorrhage or renal failure. However, corticosteroids, immunosuppressants, and plasmapheresis have greatly improved outcome, although some patients remain dependent on dialysis1. Three to six months of treatment are usually required, though symptoms begin to resolve within two months5. Plasmapheresis rapidly decreases the level of circulating anti-basement membrane antibody, while corticosteroids and immunosuppressants (namely, prednisone and cyclophosphamide) decrease the production of antibody6. If irreversible kidney damage has taken place at the time of diagnosis, the patient may receive a kidney transplant only after the antibasement membrane antibodies have been cleared from the serum3. Otherwise, if irreversible kidney damage has not occurred when the diagnosis is made, chronic immunosuppression can prevent progression PERIOPERATIVE MANAGEMENt OF THE PATIENT WITH GOODPASTURE’S SYNDROME of renal damage and a kidney transplant often is not necessary3. Anesthetic Considerations Preoperative Assessment Elective surgery should be delayed until the disease is in an inactive state5. Chest radiographs, pulmonary function studies, and arterial blood gases can be used to evaluate the patient’s pulmonary status, while renal function studies, urinalysis, and blood chemistries indicate renal function5. Causes of renal insufficiency, other than glomerulonephritis, should also be sought. Prerenal factors such as hypovolemia and decreased cardiac output can compound the GSinduced renal dysfunction, and should be corrected to avoid further kidney damage. Dialysis-dependent patients should be dialyzed shortly before surgery to correct volume overload, hyperkalemia, and acidosis5. Renal failure often demands that drug selection and dosing be modified. In general, the technique of choice when applicable would be the use of local anesthetics for local or regional blockade whenever possible with careful sedation. However, there are significant considerations in the delivery of anesthetics to GS patients. Pulmonary Due to the alveolar hemorrhage that occurs in GS, oxygenation of the patient during surgery is the principal challenge of the anesthesiologist5. Blood in the alveoli makes gas exchange difficult. Furthermore, continuous alveolar hemorrhaging results in anemia, which plays an additional role in diminished tissue oxygen delivery5. A larger than normal sized endotracheal tube should be used to intubate to allow for better pulmonary suction. Care should be taken to avoid high airway pressure, increased oxygen tension, and other stresses on the lungs, as this may worsen antibody-mediated lung injury5. Renal Renal failure in GS, as in all cases of renal failure, can affect the volume of distribution, metabolism, and excretion of certain anesthetic drugs. Watersoluble metabolites that are minimally active may 781 accumulate and prolong the effects of the parent drug7. The elimination half-life of drugs that are excreted unchanged by the kidneys can be prolonged in renal failure. The protein loss and uremia that occur in renal failure may potentiate the effects of drugs that are typically protein-bound7. Thiopental requires a decreased induction dose because its free fraction is nearly doubled in renal failure8. The dosing of ketamine, on the other hand, does not need to be altered because it is not highly protein-bound and its free fraction is minimally affected by renal failure9. Etomidate exhibits less protein binding in renal failure patients than it does in normal patients, but the larger free fraction does not appear to alter its clinical effects10. Propofol is quickly metabolized by the liver into inactive metabolites that are then excreted by the kidney; thus renal failure does not result in extension of its clinical effects11. The plasma free fraction of benzodiazepines is increased by renal failure because these drugs are normally highly protein-bound. Additionally, benzodiazepines have active metabolites that can accumulate after repeated doses in renal failure and lead to prolonged sedation7. Midazolam is metabolized to an active alpha-hydroxy compound, and 60-80% of the drug is excreted in this form12. The metabolite accumulates after long-term infusions in renal failure, therefore causing a longer time of sedation13. Renal failure patients are more sensitive to the sedative effects of alprazolam because it has less protein binding and an increased free fraction when compared to individuals with normal renal function14. Dexmedetomidine is hepatically metabolized. When given to patients with impaired renal function, sedation was longer when compared to patients with normal renal function, likely due to less protein binding in the presence of renal dysfunction15. While the pharmacokinetics of a single dose of morphine are unaffected in a chronic renal failure patient, long-term administration causes its active metabolite morphine-6-glucuronide to accumulate and exert potent analgesic and sedative effects16. Thus, the dose of morphine should be decreased in the presence of renal dysfunction. Meperidine is metabolized to the neurotoxic compound normeperidine, which must be excreted by the kidneys and therefore should not be administered to patients with renal failure7. M.E.J. ANESTH 20 (6), 2010 782 Hydromorphone’s active metabolite hydromorphone3-glucuronide also accumulates in renal failure patients and can cause cognitive dysfunction and myoclonus17. Renal failure patients have a longer elimination time for oxycodone, thus repeated doses cause prolonged effects18. Codeine is not recommended for long-term use in patients with renal dysfunction because it can also cause prolonged narcosis16. Because fentanyl does not have active metabolites, has an unchanged free fraction, and has a short redistribution phase, it is well-tolerated and is a good choice19. Alfentanil has decreased protein binding in the presence of renal disease, but because its elimination half-life and clearance are unaffected, the total dose should be similar to that for patients without renal disease20. With the exception of succinylcholine, atracurium, cis-atracurium, and mivacurium, muscle relaxants rely heavily on renal excretion and therefore result in prolonged effects in patients with chronic renal failure7. In renal failure, most nondepolarizing muscle relaxants must be either excreted by the liver or metabolized to inactive forms7. Some muscle relaxants, such as vecuronium, are metabolized to active compounds that must be excreted by the kidneys, resulting in prolonged effects in GS patients7. Because succinylcholine does not result in a major prolongation of clinical effects, it may be used for rapid-sequence intubation. Due to the shorter duration of action, the intermediate-acting atracurium, cis-atracurium, and K. Copponex & A. D. Kaye rocuronium are preferred over the long-acting muscle relaxants for patients with renal failure5. Atracurium and cis-atracurium are recommended because their metabolites do not depend on renal clearance and the elimination half-life, clearance, and duration of action are not affected by renal failure21. Vecuronium exhibits prolonged effects in patients with renal dysfunction due to decreased plasma clearance and increased elimination half-life22. An additional cause for lengthening of the clinical duration of vecuronium is that it is metabolized to 3-desmethylvecuronium, an active compound that accumulates in renal failure23. Mivacurium is a short-acting muscle relaxant that, like succinylcholine, is eliminated by pseudocholinesterase. In renal failure patients with a lower level of plasma pseudocholinesterase, recovery from a dose of mivacurium is slower24. Conclusion Although it is uncommon, Goodpasture’s Syndrome is a disease that anesthesiologists may encounter and which poses many challenges. The extensive renal involvement dictates which drugs should be administered and which avoided. Complex pulmonary manifestations require that special care be taken in management of the airway. Patients should be treated with corticosteroids, immunosuppressants, and plasmapheresis to render the disease dormant before elective surgery is performed. PERIOPERATIVE MANAGEMEnT OF THE PATIENT WITH GOODPASTURE’S SYNDROME 783 References 1.Ball JA, Young Jr KR: Pulmonary Manifestations of Goodpasture’s Syndrome. Clinics in Chest Medicine; 1998 Dec. (19)4:777-791. 2.Homer RJ: “Depositional Diseases of the Lungs”. Fishman’s Pulmonary Diseases and Disorders, vol. 1, 4th ed. Ed. Fishman AP, Elias JA, Fishman JA, Grippi MA, Senior RM, Pack AI. New York, NY: McGraw-Hill; 2008, 1239-1241, 1287-1288. 3.Fraser RS, Colman N, Muller NL, Paré PD: Fraser and Paré’s Diagnosis of Diseases of the Chest. vol. 3, 4th ed. Philadelphia, PA: W.B. Saunders Company; 1999, 1757-1765. 4.Morris DG, Botway MB, Homer RJ, Noble PW, Reynolds HY, Matthay RA: “Diffuse Parenchymal and Alveolar Lung Diseases”. Chest Medicine: Essentials of Pulmonary and Critical Care. 5th ed. Ed. George RB, Light RW, Matthay MA, Matthay RA. Philadelphia, PA: Lippincott, Williams & Wilkins; 2005, 265-266. 5.Cartagena R, Passannante A, Rock P: “Respiratory Diseases”. Anesthesia and Uncommon Diseases. 5th ed. Ed. Fleisher LA. Philadelphia, PA: W. B. Saunders Company; 2006, 136-137. 6.Levy JB, Turner AN, Rees AJ, Pusey CD: Long-term outcome of anti-glomerular basement membrane antibody disease treated with plasma exchange and immunosuppression. Annals of Internal Medicine; 2001, 134:1033. 7.Stafford-Smith M, Shaw A, George R, Muir H: “The Renal System and Anesthesia for Urologic Surgery”. Clinical Anesthesia, 6th ed. Ed. Barash PG, Cullen BF, Stoelting, RK. Philadelphia, PA: Lippincott, Williams & Wilkins; 2009, 1356-1358. 8.Burch PG, Stanski DR: Decreased Protein Binding and Thiopental Kinetics. Clinical Pharmacology & Therapeutics; 1982, 32:212. 9.Reich DL, Silvay G: Ketamine: An update on the first twenty-five years of clinical experience. Canadian Journal of Anaesthesia; 1989, 36:186. 10.Carlos R, Calvo R, Erill S: Plasma protein binding of etomidate in patients with renal failure or hepatic cirrhosis. Clinical Pharmacokinetics; 1979, 4:144. 11.Kirvela M, Olkkola KT, Rosenberg PH, et al: Pharmacokinetics of Propofol and Haemodynamic Changes during Induction of Anaesthesia in Uraemic Patients. British Journal of Anaesthesia; 1992, 68:178. 12.Vinik HR, Reves JG, Greenblatt DJ, et al: The pharmacokinetics of midazolam in chronic renal failure patients. Anesthesiology; 1983, 59:390. 13.Driessen JJ, Vree TB, Guelen PJ: The effects of acute changes in renal function on the pharmacokinetics of midazolam during longterm infusion in ICU patients. Acta Anaesthesiologica Belgica; 1991, 42:149. 14.Schmith VD, Piraino B, Smith RB, et al: Alprazolam in end-stage renal disease. II. Pharmacodynamics. Clinical Pharmacology & Therapeutics; 1992, 51:533. 15.De Wolf AM, Fragen RJ, Avram MJ, et al: The pharmacokinetics of dexmedetomidine in volunteers with severe renal impairment. Anesthesia and Analgesia; 2001, 93:1205. 16.Chan GL, Matzke GR: Effects of Renal Insufficiency on the Pharmacokinetics and Pharmacodynamics of Opioid Analgesics. Drug Intelligence & Clinical Pharmacy; 1987, 21:773. 17.Babul N, Darke AC, Hagen N: Hydromorphone Metabolite Accumulation in Renal Failure. Journal of Pain and Symptom Management; 1995, 10:184. 18.Kirvela M, Lindgren L, Seppala T, et al: The pharmacokinetics of oxycodone in uremic patients undergoing renal transplantation. Journal of Clinical Anesthesia; 1996, 8:13. 19.Sear JW: Kidney Transplants: Induction and Analgesic Agents. International Anesthesiology Clinics; 1995, 33:45. 20.Davis PJ, Stiller RL, Cook DR, et al: Effects of cholestatic hepatic disease and chronic renal failure on alfentanil pharmacokinetics in children. Anesthesia and Analgesia; 1989, 68:579. 21.Boyd AH, Eastwood NB, Parker CJ, et al: Pharmacodynamics of the 1R cis-1’R cis isomer of atracurium (51W89) in health and chronic renal failure. British Journal of Anaesthesia; 1995, 74:400. 22.Lynam DP, Cronnelly R, Castagnoli KP, et al: The pharmacodynamics and pharmacokinetics of vecuronium in patients anesthetized with isoflurane with normal renal function or with renal failure. Anesthesiology; 1988, 69:227. 23.Segredo V, Caldwell JE, Matthay MA, et al: Persistent paralysis in critically ill patients after long-term administration of vecuronium. New England Journal of Medicine; 1992, 20(327):524. 24.Cook DR, Freeman JA, Lai AA, et al: Pharmacokinetics of mivacurium in normal patients and in those with hepatic or renal failure. British Journal of Anaesthesia; 1992, 69:580. M.E.J. ANESTH 20 (6), 2010 TARGET-CONTROLLED INFUSION ANESTHESIA WITH PROPOFOL AND REMIFENTANIL COMPARED WITH MANUALLY CONTROLLED INFUSION ANESTHESIA IN MASTOIDECTOMY SURGERIES Naser Yeganeh*, Bahman Roshani*, Mitra Yari* and Afshin Almasi** Abstract Target-controlled infusion (TCI) system is increasingly used in anesthesia to control the concentration of selected drugs in the plasma or at the site of drug effect (effect-site). The performance of propofol TCI delivery when combined with remifentanil in patients undergoing elective surgeries has been investigated. Our aim in this study was to assess the anesthesia profile of the propofol and remifentanil target controlled infusion (TCI) anesthesia as compared to the manually controlled infusion (MCI), in mastoidectomy surgery, where a bloodless field is of utmost importance to the surgeon. Sixty patients, aged 18-60 years ASA I-II enrolled in the study, were divided into two equal groups. Group MCI received propofol and remifentanil by conventionaldose-weight infusion method, and Group TCI received propofol 4 µg/ml and remifentanil 4 ng/ml as effect-site target concentration. The hemodynamic variability, recovery profile, postoperative nausea and vomiting (PONV), surgeons satisfaction were assessed. Results were analyzed by SPSS version 11.5. The two groups were comparable with respect to age, ASA class, sex, weight, basal vital signs, operation time. The blood pressure and pulse were above desired levels in some data points in the MCI Group (P ≤ 0.05). The PACU stay time to reach Aldret score of 10 was longer in the MCI Group (42.54 ± 8 vs 59.01 ± 6 min) (P ≤ 0.05). The PONV was more common in the MCI Group (P ≤ 0.05). Surgeon’s satisfaction of the surgical field showed no significant differences except when described as “good”, more common in the TCI Group. TCI is capable to induce and maintain anesthesia as well as MCI. In some stages of anesthesia, the TCI control of vital signs are better than the MCI. In some stages of anesthesia, the TCI control of vital signs are beter than the MCI. Recovery profile and complication rate and surgeon’s satisfactions are more acceptable in the TCI than in the MCI. Group. Keywords: Target-controlled infusion anesthesia, manually controlled infusion anesthesia, remifentanil, propofol, mastoidectomy. * MD, Associate professor of anesthesia, Department of Anesthesiology and Intensive Care, Imam Khomeini Hospital, Kermanshah University of Medical Sciences, Iran. ** Assistant professor of anesthesia. ***MSc, Master of Science in Biostatistics, Kermanshah University of Medical Sciences, Kermanshah, Iran. Corresponding Author: Deputy of Education and Research in Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran. Tel: +98 9121459654, Fax: +98 831 427 6355, E-mail: [email protected]. 785 M.E.J. ANESTH 20 (6), 2010 786 Introduction Target controlled infusion (TCI) is increasingly used in anesthesia. This method of infusion of intravenous anesthetic drugs has been investigated for its ability to achieve targeted blood or effect site concentrations for selected drugs. Maintaining a constant plasma or effect compartment concentration of an IV anesthetic requires continuous adjustment of the infusion rate according to the pharmacokinetic properties of the drugs which can be achieved by commercially available target controlled infusion pumps. The main advantage of this infusion method among the other advantages is prompt response to signs of inappropriate anesthesia depth without any need to mathematical calculations for anesthesiologists1. Total intravenous anesthesia based on the administration of propofol combined with an opioid, has become a popular anesthesia technique. It allows independent modulation of the different components of anesthesia: unconsciousness, amnesia and loss of response, to noxious stimuli the first two components are controlled by hypnotics and the third by opioids. Remifentanil appears to be an ideal analgesic for total IV anesthesia (TIVA) in combination with propofol, because of its independent pathway from that of propofol as well as its rapid elimination and favorable controllability. The performance of propofol TCI delivery when combined with opioid in patients undergoing elective surgery has been investigated2-4. In the TCI system of delivery, the anesthesiologist, depending on the appearance of noxious stimuli, can adjust the target concentrations of propofol or remifentanil and change the infusion rate. Surgeons performing mastoidectomies as well as other otolaryngological procedures when working microscopically under high power visual field, request asanguinous surgical field. Decrease of bleeding could be accomplished by targeting higher plasma or effect site concentration of hypnotic and opioid by the TCI system. In contradistinction, the changes in infusion rates in the manually controlled infusion (MCI), could be difficult, inaccurate and time consuming. Our aim in this study was to assess the clinical effects of propofol and remifentanil target controlled N. Yeganeh et al infusion (TCI) and compare them to the manually controlled infusion (MCI), in mastoid or similar surgeries. Results There were no statistical difference between the two groups regarding ASA class, age, sex, weight, basal vital signs and surgery duration (Table 1). Two anesthesiologists performed 60 anesthesias and 6 surgeons performed the surgery. Table 1 Patient demographics and characteristics (Mean and SD in parenthesis) MCI TCI (n=30) (n=30) *P Value Sex (M/F) 18/12 17/13 0.55 Age (Y) 28.03 (9.79) 26.67 (8.73) 0.57 Weight (kg) 62.00 (9.70) 63.33 (12.90) 0.34 BMI (kg/m2) 23.65 (2.52) 23.50 (3.85) 0.66 BSA (m2) 1.58 (0.15) 1.65 (0.18) 0.054 ASA (I-II) 19 / 11 17 / 13 0.081 Surgery duration(min) 73.60 (17.66) 81.67 (19.63) 0.08 Baseline Systolic BP(mmHg) 125.13 (8.72) 121.27 (10.55) 0.67 Baseline Diastolic BP(mmHg) 79.37 (6.39) 79.67 (8.08) 0.69 Baseline Mean BP(mmHg) 86.60 (6.44) 84.50 (7.59) 0.98 Baseline Mean HR (Beats/min) 76.20 (8.32) 79.12 (7.61) 0.74 * P value < 0.05 is significant. The systolic and mean arterial pressure at T4 and systolic arterial pressure at T5 data points were higher in the MCI group (P value ≤ 0.05) and no statistical differences were remarkable in the other data points (Fig. 1). There were also no statistical difference in heart rates in data points (Fig. 2). The least BIS value recorded in data points were significantly lower in T4 and T5 data points in the MCI group (Fig. 3). TARGET-CONTROLLED INFUSION ANESTHESIA WITH PROPOFOL AND REMIFENTANIL COMPARED WITH MANUALLY CONTROLLED INFUSION ANESTHESIA IN MASTOIDECTOMY SURGERIES Fig. 1 Systolic, Mean and Diastolic arterial pressure in different data points in two groups (Mean±SD) 787 Fig. 2 Heart rate during different data points in two groups (Mean ± SD) 110 180 170 100 150 140 130 TCI MCI 120 110 100 Heart rate (per min) Systolic Blood Pressure(mmHg) 160 90 90 TCI MCI 80 70 60 80 70 50 60 T1 T2 T3 T4* T5* T6 T1 T7 T2 T3 T4* T5* T6 T7 Data points Data points *Significant difference between two groups Fig. 3 BIS changes during different data points in two groups (Mean±SD). 90 80 100 TCI MCI 70 60 50 40 T1 T2 T3 T4* T5* T6 90 80 Bispectral index(BIS) Diastolic Blood Pressure(mmHg) 100 T7 Data points 70 60 TCI MCI 50 40 30 Mean Blood Pressure (mmHg) 20 140 10 130 0 T1 120 T2 T3 T4* T5* T6 T7 Data points 110 *Significant difference between two groups 100 TCI MCI 90 80 70 60 50 Table 2 Duration of post anesthesia care unit (PACU) residence, incidence of postoperative side effects and recovery characteristics (Mean and standard deviation in parenthesis). 40 T1 T2 T3 T4* T5* T6 T7 Data points * Significant difference between two groups. In the PACU, though there were no statistical differences between the Aldrete score between the two groups, yet the staying time for acquiring score of 10 was longer in the MCI group. The nausea and vomiting incidences were higher in the MCI group and same symptoms continued higher in the surgical ward (Table 2). The total consumption and rate of consumption of Remifentanil and propofol were significantly higher in the MCI when compared to the TCI group (Table 3). There were no differences in the time from the end of administration of anesthetics to eye opening PACU Length of stay (min) Aldrete Scoring receiving PACU Nausea (n of patients) Vomiting (n of patients) Shivering (n of patients) Ward Nausea (n of Patients) Vomiting (n of patients) Shivering (n of patients) *P value < 0.05 is significant TCI (n=30) MCI (n=30) *P value 42.54 (8) 7.2 (1.0) 6 (18%) 3 (9%) 59.01 (6) 6.4 (0.4) 0.00 0.00 9 (27%) 14 (42%) 11 (33%) 10 (30%) 10 (30%) 2 (6%) 0 17 (51%) 6 (18%) 1 (3%) 0.01 0.06 0.00 0.40 0.00 0.50 M.E.J. ANESTH 20 (6), 2010 788 N. Yeganeh et al Table 3 Propofol and remifentanil consumed in two groups (Mean and standard deviations in parenthesis) *P MCI TCI Value Total Propofol administered 1178.83 872.73 0.000 (mg) (187.86) (274.05) Propofol used per weight and 138.81 107.84 0.007 (20.17) (25.09) time ( µg / kg / min ) Total remifentanil 1324.23 955.07 0.005 administered (mg) (189.18) (285.14) Remifentanil used per weight 0.33 0.19 0.001 (0.04) (0.04) and time ( µg / kg / min ) * P value < 0.05 is significant. Table 4 Prediction of awakening time by pump, eye opening time, obey to commands time (extubation time) , time to reach Aldrete score 10 and drug costs in two groups (Mean and standard deviation in parenthesis). *P MCI TCI Value Prediction of awakening 8.33 8.83 (2.53) 0.43 (min) (2.92) 8.76 Eye opening time (min) 9.00 (2.24) 0.72 (2.81) Obey to commands time 9.11 9.26 (2.19) 0.82 (min) (2.89) Time to reach Aldrete 59.01 42.54 0.00 score 10 (6.77) (8.32) 35.35 (6.53) Total cost of drugs ($) Cost per minute ($) 0.57 (0.10) * P value < 0.05 is significant. 29.09 (7.80) 0.45 (0.08) 0.00 0.00 (awakening time) and to extubation time (obey to commands time) in the two groups (Table 4). The costs of anesthetic drugs (propofol and remifentanil) and cost of one minute of anesthesia, was higher in the MCI than in the TCI group (0.57 ± 0.10 dollar vs 0.45 ± 0.08 dollar) (Table 4). Materials and Methods Following approval of the Ethics Committee of our institution and patient written informed consent, 60 patients 18-60 years. ASA I-II scheduled for mastoidectomy with a planned duration of what than 30 minutes, were included in the study. Exclusion criteria consisted of patients under 18 and above 60 years, ASA physical status more than II, hypertriglyceridemia, alcohol or opium dependence or drug abuse and use of beta adrenergic receptor blocking agents or α2 adrenergic receptor agonists. All patients were unpremedicated. Patients were randomly allocated into two groups (30 each) by sealed envelop technique; group target controlled infusion group (TCI) and group B or manually controlled infusion group (MCI). On arrival to the OR the weight of patients were measured by electronic weighing-machine and then, electrocardiogram leads, pulse oximetry and noninvasive blood pressure, were attached. A 20 gauge IV cannula was inserted in antecubital vein in all patients. Ringer solution 10 cc/kg of body weight was infused intravenously before induction of anesthesia. Bi-refferential electroencephalogram (EEG) leads (Aspect medical system BIS-XP version 3.23, USA) were attached after skin preparation and disinfection with alcohol and slight rubbing. When electrode impedance exceeded 10 KΩ, the electrode was replaced and skin preparation was repeated. In (TCI) group anesthesia was induced with propofol 1% (Braun Melsungen, Germany) and remifentanil 50 µg/ml (GSK, UK) simultaneously administered by two separate modules of a continuous computer assisted TCI system (Fresenius Kabi Company, Base Prima and DPS Module System, France). Before induction of anesthesia, patients' weight and height, age, sex and target of effect site concentration of propofol and remifentanil were entered into the TCI system. The initial effect site target of propofol was set at 4 µg/ml, titrated against clinical effect and BIS values, and the initial effect site target of remifentanil was 4 ng/ml, titrated against vital signs. We used Schnider and Minto three compartments pharmacokinetic models for propofol and remifentanil respectively (5-6). The goal of propofol administration was to maintain BIS level from 45 to 60. After hypnosis (lack of eyelid reflex), atracurium (0.5 mg/kg) was administered IV slowly to achieve muscle relaxation for endotracheal intubation. The atracurium dose was repeated to maintain post tetanic count zero. After intubation the effect site concentration of propofol and remifentanil were adjusted to maintain the BIS level from 45 to 60 and 55 < MAP > 85 mmHg. BIS values beyond the desired levels were managed with increasing or decreasing 1 µg/ml from propofol effect site target concentration, and MAP far from desired levels also managed with increasing or TARGET-CONTROLLED INFUSION ANESTHESIA WITH PROPOFOL AND REMIFENTANIL COMPARED WITH MANUALLY CONTROLLED INFUSION ANESTHESIA IN MASTOIDECTOMY SURGERIES Fig. 4 Satisfaction of surgeons about surgical field. * In good condition difference between two groups is significant. decreasing 0.5 ng/ml to effect site target concentration of remifentanil (Flowchart1). With decreasing of MAP < 55 mmHg, crystalloids (Ringer solution) were infused and until a clinically adequate volume load was achieved a vasopressor 789 (Ephedrine) 2.5 mg i.v was administered to restore MAP immediately. With increasing MAP > 85 mmHg increasing the effect site concentration of remifentanil was repeated step by step until reaching remifentanil target to 10 ng/ml and if this failed to reduce MAP < 85 mmHg, infusion of trinitroglycerine 5 µg/min was added. In the MCI group anesthesia was induced with bolus propofol infusion 1 mg/kg and after that 170 µg/ kg/min for 10 minutes, and then 130 µg/kg/min for 10 minutes and finally 100 µg/kg/min for maintenance of anesthesia. This method of propofol infusion produces and maintains propofol plasmatic concentration about 4 µg/ml7. Remifentanil infusion was started with Flowchart 1 Anesthetics administration algorithm in TCI group M.E.J. ANESTH 20 (6), 2010 790 N. Yeganeh et al Flowchart 2 Anesthetics administration algorithm in MCI group slow bolus dose of 1 µg/kg and then was continued 0.5 µg/kg/min. After loss of consciousness atracurium was administered, repeated and managed as the same manner as in TCI group. The goals of anesthesia were the same as in TCI group. BIS values and MAP out of the desired range was managed with increasing or decreasing of propofol and remifentanil infusion rate 10 µg/kg/min and 0.25 µg/kg/min respectively (Flowchart 2). In both groups patients were ventilated to maintain normocapnia (ETCO2 between 36-44 mmHg with mixture of oxygen in air (FIO2 40%). In all patients the continuous infusion of propofol and remifentanil were stopped at the beginning of skin closure when 2 mg morphine sulphate and 4 mg ondansetrone were administered intravenously for postoperative analgesia and prophylaxia of nausea and vomiting. The time from stopping the infusion until patients opened their eyes (eye opening time), obeyed to commands and underwent tracheal extubation (extubation time) and the time from stopping the infusion until Aldrete score of 10 were documented and compared in two the groups8. Six different surgeons blinded to anesthesia method conducted were asked TARGET-CONTROLLED INFUSION ANESTHESIA WITH PROPOFOL AND REMIFENTANIL COMPARED WITH MANUALLY CONTROLLED INFUSION ANESTHESIA IN MASTOIDECTOMY SURGERIES about their satisfaction about asanguineous surgical field which was described as good (without disturbing bleeding), moderate (minimal bleeding not disturbing surgery) and poor (bleeding disturbing surgery). Seven data points were defined for monitoring and documentation of vital signs and BIS: T1, before the induction of anesthesia; T2, before intubation; T3, three minutes after tracheal intubation; T4, three minutes after skin incision; T5, during mastoidectomy; T6, during tympanic membrane placement and T7, before skin closure. The costs of intravenous anesthetic drugs (disposables, nursing, staff, oxygen, air, vasopressors and antiemetics were not included) were taken from hospital pharmacy list. Data were presented as mean with standard deviation in parenthesis unless otherwise stated. For statistical analysis SPSS software (version 11.5) was used. Hemodynamic variables were analyzed with two factorial analysis of variance for repeated measurements. Student's t-test was applied at the end point of each measurement. In case of multiple comparisons, P values were corrected according to Bonferroni. Fisher's exact tests, X² tests, leven tests, Mann-Whitney U-tests, or nonpaired student's t-tests were used when appropriate. P values < 0.05 were considered significant. Discussion In this study we used propofol as hypnotic together with remifentanil as analgesic for induction and maintenance of anesthesia. Propofol is presently the most common intravenous anesthetic used for total intravenous anesthesia. Pharmacokinetic model-driven infusion of propofol has become widely available worldwide. In addition, remifentanil is the newest μ-agonist available for administration as an analgesic during surgery and it is best administered as an infusion because of its metabolism by general body esterases. Interaction of these two drugs in preventing responses to noxious stimulation is investigated. Increasing the duration of the infusion has minimal impact on recovery time if the optimal dose of remifentanil is not used9. Hence combination of these two drugs has become more popular for intravenous 791 anesthesia. Regardless of the kind of surgery, remifentanil improves intraoperative hemodynamic stability when compared to other opioids: Twersky reported better hemodynamic control when remifentanil used compared with fentanyl10 and Mackey confirmed better control of tachycardia and hypertension in very high risk outpatients laryngoscopies with remifentanil as compared to fentanyl11. In our study remifentanil was used as an analgesic in both TCI and MCI, however, the TCI group when surgical stimuli were profound showed more stable hemodynamic parameters in different data points at T4 (three minutes after skin incision) and T5 (during mastoidectomy). This is very important in mastoidectomy operations because bleeding in surgical field is directly related to blood pressure and even when minimal bleeding may disturb the ideal condition for surgery. Remifentanil is associated with faster recovery and extubation time because of its rapid hydrolysis and decreased hypnotic requirements. This can affect early and late recovery and discharge time of patients from operating table to the (PACU) and eventually to surgical wards and finally to home. Remifentanil as an anesthetic used as TCI method has showed superiority to the conventional manually controlled infusion (MCI). Various studies have shown that hemodynamic stability, recovery time, and discharge time have improved by the use of TCI for the administration of remifentanil and propofol in the induction and maintenance of anesthesia12-13. Despite these findings other authors could not show significant hemodynamic differences between TCI and MCI group during induction and maintenance of anesthesia14-15. We think the findings in our study are the result of administration both hypnotic and analgesic with TCI technique which allows fine titration of effectsite target concentration counter effecting the noxious stimuli. The TCI enables anesthesiologist to rapidly change the effect-site target concentration of desired drug for desired response without need to timeoccupying mathematical calculation to adjust infusion rate for body mass of the patient. Also our findings demonstrated the efficacy of TCI in controlling anesthesia depth during different stages of surgery as well as MCI. Although all patients were received M.E.J. ANESTH 20 (6), 2010 792 to PACU with comparable Aldrete score, the MCI patients, however, stayed more in this unit to reach Aldrete score 10. In other word, intermediate recovery time (discharge from PACU to surgical ward) was longer in the MCI group. This correlates with total propofol and remifentanil consumed during anesthesia observed more in the MCI group. Although we found less drug consummation and decreased drug cost in the TCI group, literature review is contradictory, Suttner found that TCI using propofol and remifentanil was the most expensive anesthesia regimen, with total intraoperative costs almost two fold compared with the standard IV propofol regimen and almost four times larger compared with a standard inhaled anesthetic with isoflurane in sixty patients undergoing elective laparoscopic cholecystectomies12. Fombeur and coworkers described a standard regimen of desflurane was more cost-effective than TCI propofol for anesthesia maintenance in achieving post operative nausea and vomiting free episodes in otlogical surgeries16 Russell and coworkers17 found significantly more propofol was administered during both induction and maintenance of anesthesia with the target controlled system while no clinically significant difference in heart rate and hemodynamic variables were observed. On the other hand De castro and coworkers reported significantly smaller requirements of remifentanil without a difference in propofol requirement and at the same time more common intraoperative hypotension episodes in MCI group patients than TCI group18. Limitation of our study lies in the fact that our data collection was not performed continuously in all times of the operation but in selected data points in which hemodynamic imbalance episodes were more probable. Despite this limitation data in the N. Yeganeh et al postoperative time were collected continuously in which the PONV and the shorter staying time in recovery room to reach Aldrete score of 10 the TCI group. The possible explanations can explain the contradictory results with the tel system, consiste that studies used only hypnotic or analgesic and in others both been administered by TCI. Fine titration of hypnotic and/or analgesic target concentration against clinical effects can rapidly produce desired clinical situation without time delay and uncontrolled hemodynamic changes. Changing effect-site target concentration of every drug and attention to drug pharmacodynamic instead of drug pharmacokinetic can result to more stable hemodynamic variables, less drug consumption and shorter recovery time19. On the other hand biovariabilty plays an important role in different responses to identical target concentration in various studies20. Several models have been proposed and validated for their ability to predict drug concentration in the plasma or effect site compartment for propofol and remifentanil. Biovariability and severeal pharmacokinetic models produces different results when TCI is used. In summary remifentanilpropofol TCI-based anesthesia achieved better hemodynamic stability through the stages, better recovery profile, decreases drug costs of anesthetics and more satisfaction of surgeons about surgical field condition, as compared to the manually controlled infusion (MCI) anesthesia, in mastoidectomy surgeries. Acknowledgement We would like to thank the research authorities of Kermanshah University of Medical Sciences and Health Services for funding this study. TARGET-CONTROLLED INFUSION ANESTHESIA WITH PROPOFOL AND REMIFENTANIL COMPARED WITH MANUALLY CONTROLLED INFUSION ANESTHESIA IN MASTOIDECTOMY SURGERIES 793 References 1. Holas A: total intravenous anesthesia: Target-controlled anesthesia. 2005/5/21. Available at http://www.anesthesia.at/anesthesiology/ tiva3.html. 2. Gale T, Leslie K, Kluger M: propofol anesthesia via targetcontrolled infusion or manually controlled infusion: Effects on the bispectral index as a measure of anesthetic depth. Anaesth Intensive Care; 2001, 29:579-584. 3. Schraags S, Mohl U, Hirsch M, Stolberg E, Geaorgieff M: Recovery from opioid anesthesia: The clinical implication of context-sensitive half-times. Anesthesiology; 1998, 86:184-190. 4. Vuyk J, Engbers FH: The pharmacodynamics interaction of propofol and alfentanil during lower abdominal surgery in women. Anesthesiology; 1995, 83: 8-22. 5. Schnider TW, Minto CF, Shafer SL, Gambus PL, Anderson C, Goodale DB, Youngs EJ: The influence of age on propofol pharmacodynamics. Anesthesiology; 1999, 90:1502-1516. 6. Minto CF, Schnider TW, Egan TD, Shafer SL: The influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil.I. Model development. Anesthesiology; 1997, 86:1023. 7. Glass PS, Shafer SL, Reves JG: Intravenous drug delivery system. In: Miller RD Anesthesia. New York: Churchill Livingstone; 2005, p. 461. 8. Aldrete JA: The post-anesthesia recovery score revisited. Clin Anesth; 1995, 7:89-91. 9. Vuyk J, Mertens MJ, Olofsen E: Propofol anesthesia and rational opioid selection: Determination of optimal EC50-EC95 concentrations that assure adequate anesthesia and a rapid return of consciousness. Anesthesiology; 1997, 87:1594-1562. 10.Twersky RS, Jamerson B, Warner DS: Hemodynamic and emergence profile of remifentanil versus fentanyl prospectly compared in a large population of surgical patients. J Clin Anesth; 2001, 13:407-16. 11.Mackey JJ, Parker SD, Nass CM: Effectiveness of remifentanil versus traditional fentanyl-based anesthesia in high-risk outpatient surgery. J Clin Anesth; 2000, 12:427-32. 12.Suttner S, Boldt J, Schmidt C: Cost analysis of target-controlled infusion based anesthesia compared with standard anesthesia regimen. Anesth Analg; 1999, 88:77-82. 13.Yeganeh N, Roshani B: A Bispectral index guided comparison of target-controlled versus manually-controlled infusion of propofol and remifentanil for attenuation of pressor response to laryngoscopy and tracheal intubation in non cardiac surgery. JRMS; 2006, 11(5):302-308. 14.Lehmann A, Boldt J, Thaler E, Piper S, Weisse U: Bispectral index in patients with target-controlled infusion of propofol. Anesth Analg; 2002, 95:639-44. 15.Breslin DS, Mirakhur RK, Reid JE, Kyle A: Manuall versus targetcontrolled infusion of propofol. Anesthesia; 2004, 59:1059-1063. 16.Fombeur PO, Patrick R, Beaussier TM, Lorente C, Yazid L, Lienhart AH: Cost-effectiveness of propofol anesthesia using target-controlled infusion compared with a standard regimen using desflurane. Am J Health-sys Pharm; 2002, 59(14):1344-1350. 17.Russell D, Wilkes M, Hunter SG, Glen JB, Hutton PK, Kenny GN: Manual compared with target-controlled infusion of propofol. Br J Anaesth; 1995, 75:562-6. 18.De Castro V, Godet G, Menica G, Raux M, Coriat P: Targetcontrolled infusion for remifentanil in vascular patients improves hemodynamics and decreases remifentanil requirements. Anesth Analg; 2003, 96:33-8. 19.Vuyk J: Pharmacokinetic and pharmacodynamic interaction between opioid and propofol. J Clin Anesth; 1997, 9(6 suppl):23s6s. 20.Pandin PC, Cantrain F, Ewalenko P, Deneu SC, Coussaert E, Hollander A: Predictive accuracy of target-controlled propofol and sufentanil co-infusion in long lasting surgery. Anesthesiology; 2000, 93:653-661. M.E.J. ANESTH 20 (6), 2010 AIRWAY MANAGEMENT AND HEMODYNAMIC RESPONSE TO LARYNGOSCOPY AND INTUBATION IN SUPINE AND LEFT LATERAL POSITIONS Muhamad Faisal Khan*, Fawzia Anis Khan** and Fawzia N asim M inai *** Abstract Introduction: Intubation in the lateral position is desirable in several conditions. We compared the technical ease and hemodynamic response to laryngoscopy and intubation in the lateral (group L) and supine (group S) positions in 120 patients with normal airway in a prospective randomized controlled study. Methods: This was a randomized, controlled observational study. All intubations were performed by a single investigator experienced in lateral intubation. Ventilation score with bag and mask ventilation, laryngoscopy duration and attempts, application of external pressure and Cormac & Lehane grade were measured. Blood pressure and heart rate were observed before and after induction of anesthesia, after laryngoscopy/intubation and then at one minute interval for 6 minutes. Results: 90% of patients in group S were ventilated by a single operator compared to 17% in group L. Duration of laryngoscopy was significantly longer in group L (32 seconds) compared to group S (12 seconds) [p<0.001]. 78% of the patients in group S had Cormack and Lehane grade 1 versus nil in group L. External pressure was required in 58% patients in group L and 5% in group S. In intra-group comparison at specified time lines no difference was observed in HR but the changes in BP were significantly higher in the lateral position (P-value <0.001). Conclusion: Ventilation and intubation in lateral position was more difficult technically than in the suprine position, and the BP response was exaggerated in the lateral position. Keywords: Laryngoscopy; intubation; supine; lateral; hemodynamic response. * FCPS (Pak), Senior Instructor, Department of Anaesthesia, Aga Khan University, P.O. Box 3500, Karachi 74800, Pakistan. ** FRCA (UK), Professor, Department of Anaesthesia, Aga Khan University, P.O. Box 3500, Karachi 74800, Pakistan. *** FCPS (Pak), Assistant Professor, Department of Anaesthesia, Aga Khan University, P.O. Box 3500, Karachi 74800, Pakistan. Author for Correspondence: Dr. Muhammad Faisal Khan, Senior Instructor, Department of Anaesthesia, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi-74800, Pakistan. Telephone: (92) 21 486-4639, Fax: (92) 21 493-4294, 493-2095, E-mail: [email protected] 795 M.E.J. ANESTH 20 (6), 2010 796 Introduction Anaesthesiologists should be able to performs tracheal intubations in the lateral position as this position may be encountered in trauma, accidental airway loss during surgery, in posteriorly located pathology, or in patients with oral bleed. The published literature on this topic is deficient. A recent randomized control trial has looked at the technical ease of tracheal intubation in the lateral position1, others have compared the use of different airway devices other than tracheal tube in supine versus lateral positions2,3. The aim of this study was to compare the technical ease and hemodynamic response of laryngoscopy and intubation in lateral and supine position in patients undergoing elective surgery under general anesthesia. All of these patients had a low predictive risk of difficult airway. Our rationale was that in the lateral position gravity will aid the laryngoscopist by displacing the tongue and this less force may be require thus altering the hemodynamic response. Methods After institutional ethical committee approval, written informed consent was obtained from 120 surgical patients scheduled to undergo general anesthesia for elective surgery for this prospective randomized controlled trial. The sealed opaque envelope technique was used to divide the patients into two groups of 60 patients each; a control group, where tracheal intubation was carried out in the supine position (S) and the study group in whom the tracheal intubation was performed in the lateral position (L). The inclusion criteria was American Society of Anesthesiology (ASA) class 1 and 2, adults of either sex 18 to 55 years of age with no predictors of difficult mask ventilation or difficult intubation. Detailed airway assessment was conducted on each enrolled patient by one of the primary investigators. The preoperative difficult airway predictors used were Langeron’s criteria of difficult mask ventilation4, Mallampati class, Wilson score5, and sub mandibular space assessment. Patients who had Langeron Difficult Mask Ventilation (DMV) score more than or equal to 2, Mallampatti class 2, 3 or 4, Wilsons score more than 4, thyromental distance less than 6 cm, mentohyoid Muhamad Faisal Khan et al distance less than 4 cm, or inadequate jaw protrusion, were excluded. Other patients who were excluded were those with facial trauma, emergency surgery, history of gastro-esophageal reflux, pregnancy, raised intracranial pressure, cervical spine disease, dental abnormalities, and obesity. Patients with hypertension, cardiovascular disease or atherosclerotic disease were also excluded. All patients were premedicated with 0.15 mgkg-1 of oral midazolam one hour before surgery. On arrival to the operating room patients were monitored with CM 5 lead for measuring the heart rate (HR) and ST segment changes. An 18 gauge iv catheter was inserted in an upper extremity vein. Blood pressure (BP) was measured at preset intervals by oscillotonometry using Datex Ohmeda monitor (AS 3; Datex, Helsinki Finland). Oxygen saturation using a finger pulse oximeter and EtCO2 were measured continuously. The BP and HR readings were taken preinduction (baseline), after a rest period of five minutes, one minute after induction and then every minute following laryngoscopy and intubation for six minutes by an anesthesiologist unconnected with the study. Prior to induction patients in group L were placed in the left lateral position with a pillow under the head and the head and neck in the sniffing position. Baseline readings were obtained. Those in group S stayed supine with a pillow under the occiput. The height of the table was adjusted so that the top of patients head was at the xiphisternum of the anesthesiologist in both groups. All patients were pre oxygenated with 4 liters of oxygen/min. Fentanyl 1.5 µgkg-1 was administered intravenously over a period of 5 sec. Anesthsia was induced with thiopentone 4mg kg-1 administered over a period of 30 seconds, and muscle relaxation was achieved with atracurium 0.6 mgkg-1 administered over a period of 10 secs. The lungs of all patients were ventilated with N2O/O2 60:40 mixture and 1% isoflurane. Hand ventilation was assessed by a ventilation score. This score looked at how the airway was maintained before tracheal tube insertion. A note was made whether a single operator could maintain the airway without insertion of oropharangeal airway, single operator along with insertion of oropharangeal airway, two operators without insertion of oral airway, or two operators with insertion of oral airway. All AIRWAY MANAGEMENT AND HEMODYNAMIC RESPONSE TO LARYNGOSCOPY AND INTUBATION IN SUPINE AND LEFT LATERAL POSITIONS induction and tracheal intubations were performed by a single investigator with anesthesia experience of seven years who underwent a learning curve for lateral intubation. Intubating conditions were assessed by ulnar nerve stimulation. Laryngoscopy was performed at train of four count zero with a size 3 Macintosh laryngoscope blade. Difficulty of intubation was graded I-IV according to Cormac and Lehane classification. A note was also made of the number of intubation attempts and application of any external pressure. Pressure was be applied at the level of cricoid cartilage. A size 7.5mm polyvinyl chloride tracheal tube was used in females and size 8.5mm in male patients. The time from insertion of laryngoscope to successful insertion of tracheal tube (appearance of capnograph on manual ventilation) was monitored by a stop watch by another anesthesiologist not connected to the study. Mucosal trauma and lip or dental injuries were also recorded. In case of failure of appearance of capnograph for three consecutive manual breaths, the tube was withdrawn and reinserted. Number of attempts of laryngoscopy for correct tracheal tube placement were noted. Any disturbance of cardiac rhythm, rate, inability to maintain the oxygen saturation of 95% or more, any ST segment depression of more than 1mm during the study period was also noted. In case of failure to intubate in the lateral position, with more than 3 attempts or more than five minutes, or desaturation to less than 92% the protocol required the patients to be turned supine and intubation performed in the supine position. For intubation in the left lateral position the laryngoscope was held in the left hand and inserted from the right side of the mouth, and the tracheal tube was held in the right hand. The duration of laryngoscopy was defined as the time from insertion of the laryngoscope to the time of appearance of capnograph trace with positive pressure ventilation. The end point of the study was six minutes after intubation. Results Demograhphic characteristics and baseline hemodynamic parameters There were 60 patients in each group. The demographic characteristics of the two groups are shown in Table 1. 797 Table 1 Demographic characteristics and baseline haemodynamic parameters of the two groups Mean (SD) Group S Group L P value Age: years 35.8 (12.8) 35.0 (11.3) 0.71 Weight: kg 69.0 (9.8) 66.7 (10.5) 0.22 Gender: m/f 38/22 38/22 1.0 SAP 126.6 (14.6) 119.8 (13.8) 0.009 DAP 78.9 (8.3) 72.5 (10.3) <0.001 MAP 64.4 (9.4) 86.6 (9.8) <0.001 HR 80.5 (16.4) 77.03 (12) 0.32 SD: Standard deviation; SAP: Systolic arterial pressure; DAP: Diastolic blood pressure; MAP: Mean arterial pressure; HR: Heart rate No significant difference was observed in age (p = 0.71), weight (p = 0.22) and gender (p = 1.0). Significant difference was observed between baseline systolic blood pressure (p = 0.009), diastolic (p <0.001), and mean arterial pressure (p <0.001) between the two groups. No difference was observed in heart rate (p = 0.32). Preoperative Airway Assessment The comparison is shown in Table 2. Table 2 Comparison of preoperative airway assessment between the two groups (SD deviation) Groups Airway assessment S L p value DMV Score 0 1 2 45 11 4 45 13 2 0.65 Wilson’s Score 0 1 58 2 55 5 0.41 Mean TM distance 9 . 8 6 (2.25) 10.13 (2.02) 0.49 Mean MH distance 7 . 5 0 (1.46) 7 . 2 7 (1.50) 0.39 DMV : Difficult mask ventilation TM distance : Temperomandibular distance MH distance : Mentohyoid distance No significant difference was observed between the two groups. Ease of mask ventilation 54 patients (90%) in group S were ventilated by a single operator, versus 10 (17%) in group L. M.E.J. ANESTH 20 (6), 2010 798 Muhamad Faisal Khan et al One patient in each group required two operators to ventilate. Five patients in group S needed one operator + oropharangeal airway versus 42 in group L. None of the patients in group S needed 2 operator + oropharangeal airway versus 7 in group L (p = <0.001). None of the patients required turning from lateral to supine position. Number of intubation attempts and applications of external pressure A significant difference in SAP, DAP and MAP was seen in the baseline parameters inspite of randomization. Average percentage change from baseline was therefore calculated in both groups for comparison. The trend was initial decrease from baseline blood pressures after induction, then increase after laryngoscopy and intubation, remaining high for three minutes and thereafter decreasing to baseline values. This difference was significant (p <0.001) when the percentage change from baseline was compared at different timelines in the same group. A significant difference was observed between the two groups with the values being higher in the lateral group (p <0.001). Similar changes were observed for SAP, DAP and MAP (Figures 1, 2 and 3). All patients in group S were intubated by a single attempt versus 41 in group L (68%). Nineteen patients in group L required two attempts. (CI 1.2, 1.44). In three (5%) patients in group S and, 35 (58%) in group L external laryngeal pressure was required to bring vocal cords in view. Duration of laryngoscopy Mean duration of laryngoscopy in group S was 12.9 seconds, SD 4.2 (95% CI 11.8 – 14.0), compared to 32 seconds, SD 12.7 (95% CI: 28.7-35.3) in group L. This difference was significant (p <0.001). Grade of intubation Forty seven patients (78%) in group S had Cormack and Lehane (C & L) grade 1 versus none in group L. Eleven patients in group S had C & L grade 2a and two were grade 2b. Eighteen patients in group L were C&L2a, and 39 were 2b. Three patients in group L were grade 3 C&L compared to none in group S. Fig. 1 Mean percentage change in systolic blood pressure associated with tracheal intubation at specified time points in the supine (●) and lateral (o) groups, with 95% confidence intervals. *P<0.05 between groups Hemodynamic Changes Blood pressure Heart rate There was no difference in baseline heart rate between the two groups. A significant difference was observed compared to baseline in both groups within intra group comparison (p <0.001). On inter group comparison the difference was significant at all time points with the readings being higher in the L group (Figure 4). AIRWAY MANAGEMENT AND HEMODYNAMIC RESPONSE TO LARYNGOSCOPY AND INTUBATION IN SUPINE AND LEFT LATERAL POSITIONS 799 Fig. 2 Mean percentage change in diastolic blood pressure associated with tracheal intubation at specified time points in the supine (●) and lateral (o) groups with 95% confidence intervals. *P<0.05 between groups Fig. 3 Mean percentage change in mean arterial blood pressure between groups associated with tracheal intubation at specified time points in the supine (●) and lateral (o) groups with 95% confidence intervals. *P<0.05 between groups Fig. 4 Mean percentage change in heart rate associated with tracheal intubation at specified time points in the supine (●) and lateral (o) groups with 95% confidence intervals. *P <0.05 between groups M.E.J. ANESTH 20 (6), 2010 800 Complications None of the patients in either group had a heart rate of less than 60 beats/minutes during the study period. No desaturation below 95%, as measured by pulse oximetry or ST segment changes were observed in either group. Esophageal intubation was not observed in either group. No mucosal or dental injury was reported. Discussion Supine position is the conventional position used for tracheal intubation, however intubation in left lateral position is recommended by some authorities in failed intubation drills6 and as a safer position for post tonsillectomy hemorrhage7. It may also be helpful in posteriorly located pathology like cervical meningomylocele, injuries, abscesses, and in large goiters. The left lateral position prevents the laryngeal structures from collapsing8; it also decreases upper airway obstruction in anesthetized adults and in children with sleep apnea9. McCaul recently looked at the airway management in the lateral position and subsequent use of tracheal tube or LMA1. The left lateral position resulted in deterioration of laryngoscopic view in 35% of patients. In eight out of 39 patients there was failure of tracheal tube insertion compared to one out of 30 in the LMA group. The paper did not mention whether the anesthetists were trained or felt comfortable in intubating in the lateral position. The exact duration of training to learn this technique is also not clear. In a study by Nathanson the reduction in intubation time from first to third attempt was 12% versus, 27% for supine and lateral positions10, but there are no universal recommendations. The intubation time in our study was 32 + 12.7 seconds in lateral position compared to 12.9 + 4.2 seconds in the supine position. We did not have any failed intubation. This difference in success of intubation in lateral position was probably due to the experience of the principle investigator who underwent a formal training period till he felt comfortable in airway management in the lateral position. Majority of our patients in supine position (90%) required a single operator for bag mask ventilation Muhamad Faisal Khan et al following muscle relaxation versus 17% in the lateral position. The laryngoscopic view also deteriorated in lateral position and 58% of the patients in this group required external pressure to bring vocal cords in view and tracheal intubation took significantly longer Time. Our results are similar to McCaul et al1, in this respect. Nathanson10 et al reported a higher rate of esophageal intubation in lateral position, whereas we did not encounter any esophageal intubation in our series. Other studies have compared alternate airway devices besides tracheal tubes in both supine and lateral positions e.g. intubating laryngeal mask airway (ILMA)11, LMA1 fiber optic laryngscope8, and light wand3. Both LMA and light wand provided reliable airway control in the lateral position. None of these studies looked at the hemodynamic responses. Laryngoscopy and intubation lead to hemodynamic instability due to sympathetic stimulation. The major stimulus is said to be the force exerted by the laryngoscope12. Our rationale to look at this response was that the force maybe different in the two positions as gravity aids the movement of the tongue and lesser laryngoscopic force maybe needed in the lateral position hence leading to a lesser hemodynamic response. There was a significant difference in the baseline systolic, diastolic and mean blood pressure in our groups inspite of random allocation. This has also been pointed out in a study by Whiteman et al13 who found cardiac output to be higher in the left lateral position compared to supine or right lateral position. Similar results were seen by Nakao et al14 in animals where cardiac output increased from supine to left lateral position. In order to overcome the difference in the baseline blood pressure we only compared the percentage rise in the values rather then the absolute rise. No change in the heart rate was observed. Our findings were similar with higher blood pressure recorded in left lateral position but the heart rate remained the same. The hemodynamic response to laryngoscopy and intubation was exaggerated in the lateral position compared to supine position. In supine position all readings post intubation were within 20% of baseline. In lateral position the parameters remained above 20% of baseline until three minutes post AIRWAY MANAGEMENT AND HEMODYNAMIC RESPONSE TO LARYNGOSCOPY AND INTUBATION IN SUPINE AND LEFT LATERAL POSITIONS intubation. A prolonged intubation time and a higher number of multiple attempts in lateral position could have exaggerated the response further. Duration of laryngoscopy is one of the factors that increase this response15. This could be a limitation in our study. Another limitation of our study is that an experienced user inserted the tracheal tube in the lateral position and our results may not be applicable to inexperienced users. Thirdly although patients were randomly assigned, double blinding was not practical in our study. We recommend that tracheal intubation in lateral position be formally taught in the training program but the exaggerated hemodynamic response should be kept in mind. This response still occurred inspite of giving fentanyl 1.5 micrograms kg-1 and though attenuated, but could be detrimental in patients with pre-existing ischemic heart diseases, hypertension or cerebrovascular pathology; and manipulating the airway in the lateral position in such patients may not be desirable. The hemodynamic response also needs to 801 be studied with other airway devices recommended for insertion in the lateral position. More work needs to be done on the teaching curve required to learn this skill. Conclusion Our study indicates that both mask ventilation and intubation are more difficult in the lateral position compared to supine, probably due to alteration in larangeal anatomy. The blood pressure response is also exaggerated in the lateral position but there is no change in the heart rate response. We recommend that lateral intubation should be formally taught as a skill in the residency programs and further work needs to be done in this area. Acknowledgement We would like to acknowledge the contribution of Mr. Iqbal Azam, Associate Professor for his support in designing the study and in statistical analysis of the results. M.E.J. ANESTH 20 (6), 2010 802 Muhamad Faisal Khan et al References 1. McCaul CL, Harney D, Ryan M, Moran C, Kavanagh BP, Boylan JF: Airway management in lateral position: A randomized controlled trial. Anesth Analg; 2005, 101:1221-25. 2. Biswas BK, Agarwal B, Bhattacharyya P, Badhani UK, Bhattarai B: Intubating laryngeal mask for airway management in lateral decubitus state: Comparative study of right and left lateral positions. Br J Anaesth; 2005, 95:715-18. 3. Dimitriou V, Voyagis GS, Iatrou C, Brimcombe J: Flexible lighwand-guided intubation using the intubating laryngeal mask airway in the supine, right and left lateral positions in healthy patients by experienced users. Anesth Analg; 2003, 96:896-98. 4. Langeron O, Masso E, Huraux C et al: Prediction of difficult mask ventilation. Anesthesiology; 2000, 92:1229-36. 5. Wilson ME, Spiegelhalter D, Robertson JA, Lesser P: Predicting difficult intubation. Br J Anaesth; 1988, 61:211-16. 6. Hawthorne L, Wilson R, Lyons G, Dresner M: Failed intubation revisited: 17-years experience in teaching maternity unit. Br J Anaesth; 1996; 76:680-84. 7. Nimmo AF, Spence AA: Postoperative recovery and oxygen therapy. In: Nimmo WS, Rowbotham D and Smith G (Ed.). Anaesthesia, Wiley Blackwell. 1995, 740-56. 8. Adachi YU, Satomoto M, Higuchi H: Fiberoptic orotracheal intubation in the left semilateral position (Correspondence). Anesth Analg; 2002, 94:477-78. 9. Litman RS, Wake N, Chan LM et al: Effect of lateral positioning on upper airway size and morphology in sedated children. Anesthesiology; 2005, 3:484-88. 10.Nathanson MH, Gajraj NM, Newson CD: Tracheal intubation in manikin: comparison of supine and left lateral positions. Br J Anaesth; 1994, 73:690-91. 11.Komatsu R, Nagata O, Sessler Dl, Ozaki M: The intubating laryngeal mask airway facilitates tracheal intubation in the lateral position. Anesth Analg; 2004, 98:858-61. 12.Shribman AJ, Smith G, Achola KJ: Cardiovascular and catecholamine response to laryngoscopy with and witout tracheal intubation. Br J Anaesth; 1987, 59:295-99. 13.Whitman GR, Howaniak DL, Verga TS: Comparison of cardiac output measurement in 20-degree supine and 20-degree right and left lateral recumbent position. Heart Lung; 1982, 11:256. 14.Nakao S, Come PC, Miller MJ et al: Effects of supine and lateral positions on cardiac output and intracardiac pressures: an experimental study. Circulation; 1986, 73:579-85. 15.Stoelting RK: Circulatory changes during direct laryngoscopy and tracheal intubation: Influence of duration of laryngoscopy with or without prior lidocaine. Anesthesiology; 1977, 47:381-83. FENTANYL PRETREATMENT FOR ALLEVIATION OF PERINEAL SYMPTOMS FOLLOWING PREOPERATIVE ADMINISTRATION OF INTRAVENOUS DEXAMETHASONE SODIUM PHOSPHATE A prospective, randomized, double blind, placebo controlled study Vimi Rewari*, Rakesh Garg**, Anjan Trikha*** and C handralekha **** Abstract Background: Corticosteroids have anti-inflammatory, analgesic and antiemetic effects but causes severe perineal symptoms when given intravenously. Simultaneous administration of dexamethasone and fentanyl have been known to decrease the duration of perineal pain but its role in alleviating perineal pain has not been studied. Therefore, we hypothesized that fentanyl pretreatment could prevent the perineal symptoms associated with the dexamethasone. Material and Methods: This prospective, randomized, double blind, placebo controlled study was done in 200 patients undergoing elective surgery requiring dexamethasone. The patients were randomized into two groups of 100 each. Group BD received 5 ml normal saline followed, 5 minutes later, by 8 mg dexamethasone bolus intravenously. Group FD received 1 µg/kg fentanyl diluted in saline to a volume of 5 ml followed by 8 mg dexamethasone bolus 5 minutes later. The time of onset, intensity, site, duration and nature of the pain after the drug administration were recorded. Results: The demographic profile was comparable in the two groups. The incidence and severity of pain was more in females as compared to males (p value = 0). The pain was located especially in the perineal region and was expressed as itching (62%), burning (13%) or both (25%). The incidence of pain, its duration and severity were significantly reduced after pretreatment with fentanyl (p value = 0). Discussion: Our study showed that the intravenous administration of dexamethasone sodium phosphate leads to significant perineal symptoms. These symptoms are alleviated by pretreatment with fentanyl (1 µg/kg) (incidence, severity and duration). The pharmacological mechanism explaining perineal pain with intravenous administration of dexamethasone remains poorly understood, but could be related to the phosphate ester. Department of Anaesthesiology and Intensive Care, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India. * Associate Professor. ** Senior Resident. ***Professor. ****Professor and Head. Corresponding Author: Dr Vimi Rewari, Department of Anaesthesiology and Intensive Care, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India. Phone: 91-11-9818304880, 91-11-9868397802, Email: [email protected] The paper was presented as poster in the 1st International Conference on Recent Advances in Anaesthesiology-INCRAA 2009, AIIMS, New Delhi, India on 1st Feb 2009 and was declared best clinical study. 803 M.E.J. ANESTH 20 (6), 2010 804 We conclude, that intravenous administration of dexamethasone sodium phosphate is associated with perineal pain and can be alleviated effectively by pretreatment with 1 µg/kg of fentanyl. Key Words: Corticosteroids, Dexamethasone; Pain, Perineal; Fentanyl Introduction Corticosteroids play an important role in the perioperative period because of their diverse antiinflammatory, analgesic and antiemetic effects1-3. Dexamethasone sodium phosphate is a water soluble inorganic ester of dexamethasone which is commonly used in the perioperative period because of its prolonged duration of action as well as lack of mineralocorticoid effect. In fact, it is now an established agent for the multimodal management of postoperative nausea and vomiting4,5. Timing of the treatment with dexamethasone is an integral part of the concept of preemptive analgesia and needs to be administered prior to anesthetic induction for its optimal effect6-9. This may be related to the presumed mechanism of action (on an intracellular receptor in the central nervous system), allowing sufficient time for dexamethasone to reach the effect site. Dexamethasone can be administered after induction of anesthesia, but this might limit the efficacy of dexamethasone to prevent postoperative nausea and vomiting as well as postoperative pain10. However, one of the disadvantages of administering dexamethasone in the preinduction period is that it leads to severe perineal symptoms like pruritis, burning and pain following a bolus intravenous injection that could be very distressing for an awake patient. Literature cites isolated case reports or case series related to perineal pain after intravenous administration of dexamethasone4,10-16. Till to date there is no randomized controlled trial evaluating the perineal symptoms caused by the administration of intravenous dexamethasone. It has been reported that simultaneous administration of dexamethasone and fentanyl may reduce the duration of pain but its role in alleviating perineal pain has not been studied11. Therefore, we hypothesize that the analgesic effect of Vimi Rewari et al fentanyl, a potent opioid could prevent the perineal symptoms associated with the dexamethasone. This study was planned to estimate the incidence of perineal symptoms (pruritis, burning, pain) after intravenous dexamethasone administered in the preoperative period and to evaluate the effect of fentanyl pretreatment for alleviation of these perineal symptoms. Material and Methods This prospective, double blind, placebo controlled, randomized study was done after obtaining the approval of the institutional ethics committee and a written informed consent from 200 ASA physical status I-III patients undergoing elective surgery at a tertiary care centre (All India Institute of Medical Sciences, New Delhi, India) requiring dexamethasone for multimodal management of postoperative nausea and vomiting (PONV) or postoperative analgesia. A thorough preanesthetic work up of all patients with clinical evaluation and relevant laboratory investigations was carried out. Patients were eligible for participation, if they were more than14 years of age and could cooperate and understand the Visual analogue score (VAS) scale. Only those patients, who were at increased risk for postoperative nausea and vomiting (laparoscopic procedures, gynaecologic procedures, middle ear surgery, and squint surgery) or in need for dexamethasone as multimodal analgesic requirement were included. Patients who were on regular medications with analgesic or analgesic use within 24 hours of anesthesia, drug or alcohol abuse, contraindications to steroid use [diabetes mellitus / impaired glucose tolerance, peptic ulcer disease, endocrine disorder, morbid obesity (BMI >30)] were excluded from the study. Patients were explained about the use of VAS for grading the severity of pain on a scale of 0 to 10. In the operating room, after attaching routine monitors (ECG, non invasive blood pressure, pulse oximeter), an 18 G intravenous cannula was secured on the dorsum of the left hand. The patients were randomized into two groups of 100 each based on computer generated random number list. FENTANYL PRETREATMENT FOR ALLEVIATION OF PERINEAL SYMPTOMS FOLLOWING PREOPERATIVE ADMINISTRATION OF INTRAVENOUS DEXAMETHASONE SODIUM PHOSPHATE (I) Group BD: Intravenous administration of 5 ml normal saline followed by 8 mg dexamethasone bolus 5 minutes later. (II) Group FD: Intravenous administration of 1 µg/kg fentanyl diluted in saline to a volume of 5 ml followed by 8 mg dexamethasone bolus 5 minutes later. The randomization was not disclosed to any of the personnel (those administering drugs, those observing study parameters, data analysts) or the patient throughout the study. An independent investigator not involved in the observation prepared the study drug. The effects of the drugs were observed by an investigator who was unaware of the drugs administered. The patient was observed for the next ten minutes and the rest of the anesthetic procedure was allowed to proceed. The following parameters were recorded continuously following the drug administration: =The time of onset and intensity (VAS) of the perineal symptoms after the end of the drug administration. 805 =The site of pain or other symptoms. =The duration of the symptoms. =The nature of the symptoms (pruritis, burning, pain). In the absence of any previous study, the sample size was calculated based on the case series by Perron et al4 with perineal symptoms as primary outcome and with an aim of 50% decrease in the symptoms with pretreatment with fentanyl, with a power of 90% and α-0.05. The comparison of sex and occurrence of pain was carried out using chi square test. The age, weight, onset and duration of pain and VAS was compared using independent t test. The p value <0.05 was taken as significant. Results A total of 227 patients were assessed for eligibility and 200 patients were enrolled in the study (Fig. 1). The demographic profile was comparable in the two groups (Table 1). Fig. 1 Flow chart showing patient enrollment for the study M.E.J. ANESTH 20 (6), 2010 806 Vimi Rewari et al Table 1 Demographic Profile Age (years) Sex (M:F) (%) Weight (kg) Group BD (n=100) Group FD (n=100) P value 35.6 ± 12.9 (14-75) 35.8 ± 11.4 (14-65) 0.906 40:60 (40:60) 38:62 (38:62) 0.085 58.3 ± 10.5 (37-93) 59.3 ± 9 (38-80) 0.487 Values as mean ± SD (Range) The incidence and severity of pain was more in females as compared to males (p value 0.001) (Table 2). The pain was located especially in the perineal region and was expressed as itching (62%), burning (13%) or both (25%). One patient mentioned generalized tingling sensation all over the body and another patient reported dizziness. The incidence, duration and severity of the perineal symptoms were significantly reduced following pretreatment with fentanyl (p value 0.001) (Table 3). Discussion Our study showed that the intravenous administration of dexamethasone sodium phosphate causes pain and itching in the perineal region. These symptoms were observed to be more severe and of a longer duration in females as compared to males. The pretreatment with fentanyl in a dose of 1 µg/kg reduced the pain and itching (incidence, severity and duration) caused by intravenous administration of dexamethasone. Table 2 Incidence of dexamethasone induced pain among males and females Male (n = 40) Female (n = 60) Pain (n) (%) P value 15/40 (37.5%) 56/60 (93.3%) 0.001 Pain Onset (sec) 25.7 ± 7.3 (20-40) 24.3 ± 7 (10-45) 0.505 Pain Duration (sec) 28.7 ± 19.2 (10-80) 77.8 ± 31 (21-120) 0.001 Pain VAS (median) 4 (3-6) 7 (4-9) 0.001 Values as mean ± SD (Range) or as otherwise stated Table 3 Effect of Fentanyl pretreatment on pain with intravenous dexamethasone n Group BD n Group FD P a i n perceived (n) (%) Pain Onset (sec) P a i n Duration (sec) Pain VAS (median) P value Total 100 71/100 (71%) 100 25/100 (25%) 0.001 Male 40 15/40 (37.5%) 38 0/38 (0%) 0.001 Female 60 56/60 (93.3%) 62 25/62 (40.3%) 0.001 Total 100 24.6 ± 7 (10-45) 100 17.6 ± 6 (10-35) 0.001 Male 40 25.7 ± 7.3 (20-40) 38 - - Female 60 24.3 ± 7 (10-45) 62 17.6 ± 6 (10-35) 0.001 Total 100 67.4 ± 35.2 (10-120) 100 11.6 ± 4 (5-20) 0.001 Male 40 28.7 ± 19.2 (10-80) 38 - - Female 60 77.8 ± 31 (20-120) 62 11.6 ± 4 (5-20) 0.001 Total 100 7 (3-9) 100 2 (1-3) 0.001 Male 40 4 (3-6) 38 0 0.001 7 (4-9) 62 2 (1-3) 0.001 Female 60 Values as mean ± SD or otherwise as stated FENTANYL PRETREATMENT FOR ALLEVIATION OF PERINEAL SYMPTOMS FOLLOWING PREOPERATIVE ADMINISTRATION OF INTRAVENOUS DEXAMETHASONE SODIUM PHOSPHATE The pharmacological mechanism explaining perineal pain with intravenous administration of dexamethasone remains poorly understood, but could be related to the phosphate ester of the corticosteroid (dexamethasone sodium phosphate) since perineal irritation has been described with hydrocortisone21-phosphate sodium and prednisolone phosphate as well4,11,12,15. The symptoms lasted only for a short period till the drug was hydrolysed into phosphate ions and dexamethasone. Opioids (fentanyl, remifentanil, alfentanil, tramadol) have been used to alleviate the pain of propofol intravenous administration17,21. Opioid receptors are found in the dorsal root ganglia, the central terminals of primary afferent nerves and peripheral sensory nerve fibres and their terminals. Opioids show their effects either centrally or peripherally. The reduction in pain due to propofol injection has been attributed to the interaction with peripheral m-opioid receptors17,22. It has also been suggested that prevention of propofol injection pain by opioids may be mediated via central opioid receptors21. In view of propofol pain being decreased by pretreatment with opioids, we thought of using it for alleviating pain with dexamethasone administration. Of interest in the perioperative setting is the decreased release of bradykinin, tumour necrosis factor, interleukin-1, interleukin-2 and interleukin-6 and decreased production of prostaglandins after administration of steroids. There is decreased transmission of impulses in C fibres23. So, we think that fentanyl probably acts via central action for alleviating dexamethasone pain. 807 sodium phosphate equivalent to 4 mg dexamethasone phosphate or 3.33 mg dexamethasone. The pH of both concentrations is 7.0-8.5. Other ingredients include methylparaben and propylparaben added as preservatives. The implication of methylparaben, propylparaben for causing perineal pain has not been reported25,26. The type of pain mentioned includes itching, burning and squeezing11. Perron reported perineal burning, itching and tingling after intravenous dexamethasone4. In our study, we observed the symptoms as burning and itching mainly and one patient complained of tingling and dizziness. Various measures to prevent perineal discomfort include administration of dexamethasone after induction of anesthesia, dilution of dexamethasone and giving it as a slow bolus11,12,14,27. Most of the effects of glucocorticoids are mediated through an altered protein synthesis3. So, onset of biological action is generally one to two hours. Wang et al designed a study to test the hypothesis that dexamethasone was more effective in preventing PONV when administered before the induction of anesthesia than at the end of anesthesia7. They observed that the administration of dexamethasone at the end of anesthesia did not provide an effective antiemetic effect during the immediate postoperative period of 0-2 hours. Based on this finding, they suggested that the onset time of dexamethasone antiemetic effect may be approximately two hours6. Though dexamethasone can cause side effects such as increased incidence and severity of infection, adrenal suppression and delayed healing in surgical patients, a single dose has not been reported to cause any such adverse effects3,29-31. Adverse effects reported in association with dexamethasone include perineal pain associated with intravenous injection. The incidence of this complication is unclear, with females at increased risk compared to men. The speed of injection and the dose may also influence the severity. Our study is limited by the fact that the use of fentanyl as pretreatment for alleviating dexamethasone pain can be used in the perioperative settings where fentanyl is a part of anesthetic management. Its use cannot be justified in other settings where dexamethasone is being used such as chemotherapy. Epidural administration of dexamethasone has not been associated with perineal pain24. We conclude, intravenous administration of dexamethasone sodium phosphate is associated with perineal pain which can be alleviated effectively by pretreatment with 1 µg/kg of fentanyl. Each milliliter of dexamethasone sodium phosphate injection, 4 mg/mL, contains dexamethasone M.E.J. ANESTH 20 (6), 2010 808 Vimi Rewari et al References 1.Filho JRL, Maurette PE, Allals M, Cotinho M, fernandes C: Clinical comparative study of the effectiveness of two dosages of dexamethasone to control postoperative swelling, trismus and pain after the surgical extraction of the mandibular impacted third molars. Med Oral Patol Oral Cir Bucal; 13:129-32, 2008. 2.Gupta P, Khanna J, Mitramustafi AK, Bhartia VK: Role of preoperative dexamethasone as prophylaxis for postoperative nausea and vomiting in laparoscopic surgery. J Min Access Surg; 2:12-16, 2006. 3.Bisgaard T, Klarskov B, Kehlet H, Rosenberg J: Preoperative dexamethasone improves surgical outcome after laparoscopic cholecystectomy-a randomized double blind placebo controlled trial. Ann Surg; 238:651-60, 2003. 4.Perron G, Dolbec P, Germain J, Bechard P: Perineal pruritis after iv dexamethasone administration. Can J Anesth; 50:749-750, 2003. 5.Jensen K, Kehlet H, Lund CM: Postoperative recovery profile after laparoscopic cholecystectomy: a prospective, observational studt of a multimodal anaesthestic regime. Acta Anaesthesiol scand; 51:46471, 2007. 6.Wang JJ, Ho ST, Tzeng JI, Tang CS: The effect of timing of dexamethasone administration on its efficacy as a prophylactic antiemetic for postoperative nausea and vomiting. Anesth Analg; 91:136-139, 2000. 7.Elhakim M, Nafie M, Mahmoud K, Atef A: Dexamethasone 8 mg in combination with ondansetron 4 mg appears to be the optimal dose for the prevention of nausea and vomiting after laparoscopic cholecystectomy. Can J Anaesth; 49:922-926, 2002. 8.Gan TJ, Meyer T, Apfel CC, Chung F, Davis PJ, Eubanks S, Kovac A, Philip BK, Sessler DI, Temo J, Tramer MR, Watcha M: Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg; 97:62-71, 2003. 9.Fujii Y, Nakayama M: dexamethasone for reduction of nausea, vomiting and analgesic use after gynecologic laparoscopic surgery. Internat J Gyn Obst; 100:27-30, 2007. 10.Crandell JT, Deer R: Perineal pruritis after the administration of iv dexamethasone. Can J Anesth; 51:398, 2004. 11.Neff SPW, Stapelberg E, Warmington A: Excruciating perineal pain after intravenous dexamethasone. Anaesth Intensive Care; 30:370-371, 2002. 12.Thomas VL: More on dexamethasone-induced perineal irritation. N Engl J Med; 314:1643–4, 1986. 13.Klygis LM: Dexamethasone-induced perineal irritation in head injury (Letter). Am J Emerg Med; 10:268, 1992. 14.Andrews D, Grunau VJ: An uncommon adverse effect following bolus administration of intravenous dexamethasone. J Can Dent Assoc; 52:309-11, 1986. 15.Taleb N, Geahchan N, Ghosn M, Brihi E, Sacre P: Vulvar pruritus after high-dose dexamethasone. Eur J Cancer Clin Oncol; 24:495, 1988. 16.Kuczkowski KM: Perineal pruritis and dexamethasone. Anaesthesia; 59:308, 2004. 17.Kwak K, Kim J, Park S, Lim D, Kim S, Baek W, Jeon Y: Reduction od pain on injection of propofol: combination of pretreatment of remifentanil and premixture of lidocaine with propofol. Eur J Anaesthesiol; 24:746-750, 2007. 18.Roehm KD, Piper SN, Maleck WH, Boldt J: Prevention of propofol induced injection pain by remifentanil: a placebo controlled comparison with lidocaine. Anaesthesia; 58:165-170, 2008. 19.Rahman AA, Al-Mujai H, Ivanova MP, Marzouk HM, Batra YK, Al-Qattan AR: Prevention of pain on injection of propofol: a comparison of remifentanil with alfentanil in children. Minerva Anestesiol; 73:219-223, 2007. 20.Aouad MT, Sayyid SMS, Al-Alami AA, Baraka AS: Multimodal analgesia to prevent propofol-induced pain: pretreatment with remifentanil and lidocaine versus remifentanil orlidocaine alone. Anesth Analg; 104:1540-4, 2007. 21.Lee JR, Jung CW, Lee YH: Reduction of pain during induction with target controlled propofol and remifentanil. Br J Anaesth; 99:876880, 2007. 22.Iyilikci L, Balkan BK, Gokel E, Gunerli A, Ellidokuz H: The effects of alfentanil or remifentanil pretreatment on propofol injection pain. J Clin Anesth; 16:499-502, 2004. 23.Werner MU, Lassen B, Kehlet H: Analgesic effects of dexamethasone in burn injury. Reg Anesth & Pain Med; 27(3):25460, 2002. 24.Thomas S, Beevi S: Epidural dexamethasone reduces postoperative pain and analgesic requirements. Can J Anesth; 53:899-905, 2006. 25.Soni MG, Taylor SL, Greenberg NA, Burdock GA: Evaluation of the health aspects of methyl paraben: a review of the published literature. Food and Chemical Toxicology; 40:1335-1373, 2002. 26.Soni MG, Taylor SL, Greenberg NA, Burdock GA: Safety aspects of propylparaben:: a review of the published literature. Food and Chemical Toxicology; 39:513-532, 2001. 27.Singh M, Mohta M, Sethi AK, Tyagi A: Efficacy of dexamethasone pretreatment for alleviation of propofol injection pain. Eur J Anaesthesiol; 22:887-894, 2005. 28.Czerwinski AW, Czerwinski AB, Whitsett TL, Clark ML: Effects of a single, large, intravenous injection ofdexamethasone. Clin Pharmacol Ther; 13:638-42, 1972. 29.Wattwil M, Thorn SE, Lovqvist A, Wattwil L, Gupta A, Liljeqren G: Dexamethasone is as effective as ondansetron for the prevention of postoperative nausea and vomiting following breast surgery. Acta Anaesthesiol Scand; 47:823-827, 2003. 30.Splinter W, Roberts J: Prophylaxis for vomiting by children after tonsillectomy: dexamethasone versus perphenazine. Anesth Analg; 85:534-537, 1997. 31.Wang JJ, Ho ST, Liu YH, Lee SC, Liu YC, Liao YC, Ho CM: Dexamethasone reduces nausea and vomiting after laparoscopic cholecystectomy. Br J Anaesth; 83:773-775, 1999. TRANSIENT NEUROLOGICAL SYMPTOMS FOLLOWING SPINAL ANESTHESIA FOR CESAREAN SECTION Edomwonyi NP* and Isesele TO * Abstract Background Transient neurological symptoms (TNS) are defined as symmetrical bilateral pain in the back or buttocks or pain radiating to the lower extremities after recovery from spinal anesthesia. About 80-85% of cesarean sections are performed under spinal anesthesia in our centre. Our aim was to determine the incidence of TNS, risk factors and outcome of management in pregnant women undergoing cesarean section. Patients and Methods Approval was obtained from the hospital ethic’s committee, and consent from the patients. ASA 1 and 2 pregnant women undergoing cesarean section under spinal anesthesia formed the subjects of this prospective study. They were evaluated and pre-medicated by the attending anesthetists. Spinal anesthesia was performed at the L2-3 or L3-4 interspaces, using a 25G Quincke or 25G pencil point spinal needle with 0.5% heavy bupivacaine. The investigators interviewed the patients in the ward for three consecutive days, in order to identify those that developed TNS. Results One hundred and twenty consecutive patients were studied. TNS were documented in 12 (10%) patients. Backache was recorded in 8 patients (6.6%), pain in the thighs in 2 (1.7%) and pain in the buttocks in 2 (1.7%). Onset time of symptoms was recorded as 6-12 hrs in 5 (4.2%) patients, 12-24 hrs in 5 (4.2%) and 24-48 hrs in 2 (1.6%). The patients that developed TNS were managed accordingly with satisfactory outcome. Conclusion A follow-up for all patients that receive spinal anesthesia for cesarean section should constitute a standard practice. Key words: Anesthetic technique: spinal anesthesia, anesthetics-local: bupivacaine, hyperbaric, surgery: cesarean section, complications: neurological. * MD, Obstetric Unit, Department of Anaesthesia, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria. Corresponding Author: Dr. NP Edomwonyi, Department of Anaesthesia, University of Benin Teaching Hospital, PMB 1111, Benin City, Nigeria. 809 M.E.J. ANESTH 20 (6), 2010 810 Introduction Transient neurological symptoms (TNS) are defined as symmetrical bilateral pain in the back or buttocks or pain radiating to the lower extremities after recovery from spinal anesthesia1. The first report of TNS with 5% lignocaine by Schneider and colleagues in 19931 was confirmed later by several other studies2-4. It is thought that a localized local anesthetic toxic effect may be an important contributing factor in the development of transient neurological symptoms after spinal anesthesia with concentrated solutions5,6. The occurrence of this complication is rare after the use of 0.5% bupivacaine for spinal anesthesia7,8. Hiller et al reported 3% incidence of TNS following the use of 0.5% bupivacaine against 30% after the use of mepivacaine9. The aim of our study was to determine the incidence of transient neurological symptoms after spinal anesthesia for cesarean section, the risk factors and outcome of management. Patients and Methods This was a prospective study carried out form February to October, 2007 after approval was obtained from the institutional Ethic’s committee, and consent from the patients. One hundred and twenty consecutive, ASA 1and 2 pregnant women who presented for cesarean section formed the subjects of study. Exclusion criteria were ASA 3 and above, patients with neurological diseases, presence of back ache and pain in the buttocks and legs (as a result of pressure from the fetal presentation). They were all seen, reviewed and pre-medicated by the anesthetists in attendance. Premedication consisted of 30 ml of mixture magnesium trisilicate, intravenous metoclopramide, 10 mg and 50 mg Ranitidine. In the theatre, multiparameter monitor was attached, after obtaining baseline vital signs (pulse rate, blood pressure and oxygen saturation), intravenous access was established with 18 gauge cannulae. Preloading of the circulation was achieved with 10-15 ml of 0.9% normal saline. Spinal anesthesia was performed at the L2-3 or L3-4 interspace with the patient in the sitting position, Edomwonyi NP & Isesele TO using a 25G Quincke spinal needle or 25G pencil point (SIMS Portex). 0.5% heavy bupivacaine, 2.2-2.5 ml was injected and patient repositioned supine with a 15o left lateral tilt and slight head up tilt. Vital signs were continuously monitored during the operation. After the delivery of the fetuses, the patients were repositioned supine. Intraoperative complications, such as hypotension, bradycardia, shivering were managed accordingly. Standard questionnaire was used to document patients’ characteristics, intraoperative clinical data, duration of anesthesia and surgery recovery room and complications in the ward, attempts at lumbar puncture. The type of spinal needle used was not by choice but was determined by what was available at the time of study. The investigators were anesthetists not primarily responsible for the conduct of the anesthesia. They interviewed the patients in the ward 24 hrs postoperatively, again at 48 hrs and 72 hrs postoperatively to identify those patients that developed transient neurological symptoms, the location of pain, and onset of pain after recovery of block, duration of pain after recovery of block, management and its outcome. Results One hundred and twenty patients were recruited in the study. Table 1 showed their demographic characteristics. Twelve (10%) patients complained of transient neurological symptoms. Variables of spinal anesthesia are shown in Table 2.Quincke spinal needle was used in 55 (45.8%) patients and pencil point in 65 (54.2%) patients. The mean dose of bupivacaine (ml) was 2.468 (0.29). The mean duration of surgery in minutes was 59.92 (21.86). Block height was T2-T10 with T6 as median range. Table 1 Demographic Characteristics Mean/Sd Age (yrs) 33.08 (3.94) Weight (kg) 76.5 (9.76) Height (cm) 160.172 (3.49) TRANSIENT NEUROLOGICAL SYMPTOMS FOLLOWING SPINAL ANESTHESIA FOR CESAREAN SECTION Table 2 Variables of Spinal Anaesthesia Needle type/size No of patients Quincke/2555 Pencil point/ 25 65 Mean duration of Surgery (minutes) -59.92 (21.86) Mean Volume of 0.5% Heavy bupivacaine (mls) -2.468 (0.29) Two attempts were made in 9 (75%) patients. Three attempts were made in two (16.7%) patients that reported severe pain. Ten (67%) out of the twelve patients complained of mild to moderate pain while 2 (33%) complained of severe pain. Table 3 shows onset of pain after recovery of block while Table 4 shows sites of symptoms. Table 3 Onset of pain after recovery of block (hr) 6-12 hrs5- (41.7%) patients 12-24 hrs-5 (41.7%) 24-48 hrs-2 (16.6%) Table 4 Location of pain Buttocks-2 (16.7%) Thighs-2 (16.7%) Back ache-8 (66.6%) Total-12 (100%) Quincke needle was used in ten (83%) of the patients that complained of symptoms against 2 (17%) in the pencil point group. The difference was considered statistically significant using Fisher’s exact test P = 0.0116, 95% CI: 1.462 to 33.513. With regard to the grade of the anesthetists who performed the block, 11 (91.7%) were done by residents (registrar1and senior registrars) while one (8.3%) was performed by a consultant. The difference was statistically significant, P = 0.0253, 95% CI: 0.01009 to 0.8192. The duration of pain in the thighs and back lasted for 24-72 hours and the pain in the buttocks lasted for 96 hrs. The risk factors for the development of TNS were the use of cutting spinal needle (Quincke), 811 number of attempts at lumbar puncture and the grade of anesthetist. Six (50%) patients were managed with non-steroidal anti-inflammatory drug, Ketorolac 30 mg 6 hourly while 3 (25%) were given opioid, tramadol hydrochloride 100mg, 8 hourly. Both drugs were administered intramuscularly. Three (25%) patients required no analgesics. The outcome of management was satisfactory. Discussion Although spinal anesthesia offers many advantages for cesarean section, it is not without complications, including transient neurological deficits. Previous control trials have reported a low incidence of 0-8% TNS in women undergoing cesarean section10 or postpartum tubal ligation (3%)11. Our study showed a slightly higher incidence of 10% TNS. In Great Britain, a number of high profile legal cases in the 1950s concerning complications of neuraxial techniques led to its decline for more than two decade12. Albert Woolley and Cecil Roe were healthy, middle aged men who became paraplegic after spinal anesthesia for minor surgery in 1947 in Britain. Phenol, in which the ampoules of local anesthetic had been immersed, had contaminated the local anesthetic through invisible cracks13. Transient neurological symptoms were also described as conditions characterized by back pain radiating to the lower extremities without sensory or motor deficits, which resolved spontaneously14,15. Injury may result from direct needle trauma to nervous tissues at the level of the spinal cord, nerve root or peripheral nerve, from spinal cord ischemia, from accidental injection of neurotoxic drugs or chemicals, from introduction of bacteria into the subarachnoid or epidural space or rarely from epidural hematoma16-18 and positioning (lithotomy). Avidan and colleagues, reported details of magnetic resonance imaging of a patient with TNS after spinal lidocaine. It indicated a local inflammatory process as the possible etiology for the symptoms, and concluded that TNS in some cases results in permanent neurological deficit19. In many cases, deficits are the results of administration of neurotoxic doses of local anesthetic or result from trauma after multiple attempts necessary to establish a technically difficult block10,20. M.E.J. ANESTH 20 (6), 2010 812 The risk factors for the development of TNS, identified in this study were the use of cutting spinal needle (Quincke), number of attempts at lumbar puncture and the grade of anesthetists who performed the block. A greater occurrence of neurological symptoms was associated with the use of cutting spinal needles. Three attempts were made in two patients that reported severe pain. Our findings showed that spinal anesthesia was performed by a registrar grade level in eight patients that complained of TNS. Although neurological complications may be secondary to the labour and delivery process, the neural block is usually considered causative until proven otherwise21. Auroy et al prospectively monitored neurologic complications in more than 103,000 regional anesthesia, all deficits were present within 48 hours after anesthesia. Most were transient with recovery occurring between two days and three months16. In a similar study involving 123,000 regional anesthetics in parturients, 46 cases of single nerve root neuropathies were reported (3.7/10,000) with complete recovery in all patients by three months22. Most of our patients reported an onset time of 12 to 24 hours after cesarean section and recovery lasted for two to four days. This is in agreement with previous study16. There is a suggestion that certain patients may have a predisposition to developing neurological deficit after spinal anesthesia23. It is best to avoid the technique in such cases as recommended nearly half a Edomwonyi NP & Isesele TO century ago24. Current therapeutic options include opioids, nonsteroidal anti-inflammatory drugs (NSAID), muscle relaxants and, symptomatic therapy25. One of the most successful classes of drugs for treating TNS has been the NSAID. Ibuprofen, naproxen and ketorolac have all been used successfully. Significant muscle spasm can be relieved with muscle relaxant, such as cyclobenzaprine. Symptomatic therapy, including leg elevation on pillows and heating pads, may provide an additional measure of patients’ comfort25. The patients that complained of transient neurological symptoms in our study were treated with NSAID and opioid with satisfactory outcome. Conclusion A follow-up for all patients that receive spinal anesthesia for cesarean section should constitute a standard practice in order to identify and manage associated complications. Aknowledgement We thank the resident doctors in the department of Anesthesia and the nurses in the maternity ward for their cooperation during the study. We are grateful to Abieyuwa Ima-Edomwonyi for her assistance in preparing the manuscript. TRANSIENT NEUROLOGICAL SYMPTOMS FOLLOWING SPINAL ANESTHESIA FOR CESAREAN SECTION 813 References 1.Schneider M, Ettlin T, Kaufmann M, Schumacher P, Urwyler A, Hampl K, Von Hochstetter A: Transient neurologic toxicity after hyperbaric subarachnoid anesthesia with 5% lidocaine. Anesthesia and Analgesia; 76:1154-1157, 1993. 2.Hampl KF, Schneider M, Drasner K, Stotz G, Drewe J: 5% hyperbaric lidocaine: A risk factor for transient radicular irritation? Anesthesiology; 79:3A, A875, 1993. 3.Tarkkila P, Huhtala J, Tuominen M: Transient radicular irritation after spinal anaesthesia with hyperbaric 5% lignocaine. Br J Anaes; 74:328-329, 1995. 4.Salmela L, Aromaa U, Cozanitis DA: Leg and back pain after spinal anaesthesia involving hyperbaric 5% lignocaine. Anaesthesia; 51:391-393, 1996. 5.Lambert LA, Lambert DH, Strichartz GR: Irreversible conduction block in isolated nerve by high concentrations of local anesthetics. Anesthesiology; 80:1082-1093, 1994. 6.Bainton C, Strichartz G: Concentration dependence of lidocaineinduced irreversible conduction loss in frog nerve. Anesthesiology; 81:657-667, 1994. 7.Hampl K, Schneider M, Ummenhofer W, Drewe: Transient neurologic symptoms after spinal anaesthesia. Anaes and Analg; 81:1148-1149, 1993. 8.Tarkkila P, Huhtala J, Tuominen M: Transient radicular irritation after bupivacaine spinal anesthesia. Reg Anaes; 21:26-29, 1996. 9. A Hiller and PH: Rosenberg, Transient neurological symptoms after spinal anaesthesia with 4% mepivacaine and 0.5% bupivacaine. Br J Anaes, 79:301-305, 1997. 10.Aouad M, Siddik S, Jalbout M, Baraka A: Does pregnancy protect against intrathecal lidocaine-induced transient neurologic symptoms. Anesth Analg; 92:401-404, 2001. 11.Philip J, Sharma S, Gottumukkla V, Perez B, Slay-Maker E, Wiley J: Transient neurologic symptoms after spinal anaesthesia with lidocaine in obstetric patients. Anesth Analg; 92:405-409, 2001. 12.Cope RW: The Wooley and Roe Case. Anesthesia; 50:162-173, 1995. 13.Maltby JR, Hutter CDD, Clayton KC: The Woolley and Roe Case. Anaesthesia; 84:121-126, 2000. 14.Hodgson PS, Liu SS: New developments in spinal anesthesia. Anesthesiol Clin North America; 18:235-249, 2000. 15.Horlocker TT: Complications of spinal and epidural anesthesia. Anesthesiol Clin North America; 18:235-249, 2000. 16.Auroy Y, Narchi P, Messiah A, Litt L, Rouvier B, Samii K: Serious complications related to regional anesthesia: results of a prospective survey in France. Anesthesiology; 87:479-486, 1997. 17.Wlody D: Complications of regional anesthesia in obstetrics. Clin Obstet Gynecol; 46:667-678, 2003. 18.Zaric D, Christiansen C, Pace NL, Punjasawadwon Y: Transient neurologic symptoms TNS following spinal anaesthesia with lidocaine versus other local anaesthetics. Cochrane Database Syst Rev; CD003006, 2003. 19.Avidan A; Gomori M, Davidson E: Nerve root inflammation demonstrated by magnetic resonance imaging in a patient with transient neurologic symptoms after intrathecal injection of lidocaine. Anesthesiology; 97:257-8, 2002. 20.Dahlgren N, Tornebrandt K: Neurological complications after anaesthesia. A follow-up of 18,000 spinal and epidural anaesthetics performed over three years. Acta Anaesthesiol Scand; 39:872-880, 1995. 21.Chestnut DH: Anesthesia and maternal mortality. Anesthesiology; 86:273-276, 1997. 22.Scott DB, Tunstall ME: Serious complications associated with epidural/spinal blockade in obstetrics:a two year prospective study. Int J. Obstet Anesth; 4:133-139, 1995. 23.Aldrete JA: Anaesthetic substances in the spine. In Arachnoiditis:the silent Epidemic J. Aldrete (ed). Futuremed: Denver, CO, 77-101, 2000. 24.Vandam LD, Dripps RD: Exacerbation of pre-existing neurological disease after spinal anaesthesia with lidocaine. N Engl J Med; 255:843 (Medline), 1956. 25Pullock JE: Transient Neurologic Symptoms: Etiology, Risk Factors, and Management. Regional Anesthesia and Pain Medicine, vol. 27, no. 6 (November-December), pp. 581-586, 2002. M.E.J. ANESTH 20 (6), 2010 INCIDENCE OF PERIOPERATIVE CARDIAC ARREST: Analysis of anesthetics over 18-year period. Farouk M Messahel* and Ali S Al-Qahtani** Abstract Objective: Several studies have surveyed perioperative cardiac arrests and their outcomes, regardless of whether patients were successfully resuscitated or died. No such studies have originated from the Kingdom of Saudi Arabia. This is a study of perioperative cardiac arrests and their outcome in a Saudi General Hospital, over an 18-year period. Methods: Armed Forces Hospital, Wadi Al-Dawasir, Kingdom of Saudi Arabia, serves military personnel and their families, in addition to eligible civilian members of the community. Operating theaters’ records were examined to collect details of patients who underwent some form of surgical procedure since the commission of the Hospital on 12.07.1992 up until 30.09.2010. Those surgical cases were traced in the Medical Records Department and the outcome of each case was reviewed. The numbers and causes of cardiac arrests and death occurring during the intraoperative and within the first postoperative 24 hours, were noted. Results: There were 15,832 patients received anesthesia during the 18-year period. Five patients died during this period (an incidence of 0.03%), all were emergency cases and were due to non-anesthetic causes; four of them died intraoperatively and the fifth died within the first 24 hour postoperatively. Conclusion: There were 5 non-anesthetic deaths in the perioperative period during the 18-year period. The absence of anesthesia-related cardiac arrests in such patient population has demonstrated that adopting quality improvement measures, teamwork approach and applying strict, but updated and evidence-based, guidelines are essential in the prevention of such catastrophes. A multicentre similar survey is needed to include all types of surgical operations. Key words: anesthesia; complications, cardiac arrest; outcomes. * DA, FRCA, Senior Consultant: Anesthesia & Intensive Care, Director: Continuous Quality Improvement & Patient Safety, Armed Forces Hospitals, Southern Region, Khamis Mushayt, Saudi Arabia. ** DLO, KSUF, Vice-Dean and Consultant ENT/Head & Neck Surgeon, College of Medicine, King Khalid University, Abha, Saudi Arabia. Corresponding author: Dr. Farouk M Messahel, Armed Forces Hospitals, Southern Region. P.O. Box 101, Khamis Mushayt, Saudi Arabia., Mobile: 0503434653, E-mail: [email protected] 815 M.E.J. ANESTH 20 (6), 2010 816 Introduction The incidence and causes of perioperative cardiac arrests related to anesthesia have been studied over the last two decades by many authors from Australia1, Brazil2, Canada3, France4,5, Japan6,7, Sweden8, Taiwan9, Thailand10, The Netherlands11, and the USA12,13,14,15. This period has seen the introduction of new anesthetic agents, improvements in anesthetic and monitoring techniques, optimization of patients' condition prior to surgery, the adoption of medical practice guidelines, and the implementation of quality standards in the healthcare service. This has led many researchers to believe that the frequency of anesthesia-related cardiac arrests have declined13,16,17,18. But although the risk of death attributable to anesthesia has fallen appreciably over the years, the number of perioperative deaths remains static19. However, a recent review questioned if there any change has happened over the last decades20. There are no data on the subject in the Saudi Medical Literature. This study is looking at the incidence and outcome of cardiac arrests in a surgical population as a result of anesthesia over an 18-year period in a Saudi general hospital. Methods Armed Forces Hospital at Wadi Al-Dawasir, Kingdom of Saudi Arabia, provides both primary and secondary medical care to military personnel and their dependants, and receives entitled patients from the civilian population. It acts as a referral centre for other hospitals in the region including major trauma cases. It is the first hospital in the Kingdom of Saudi Arabia to obtain the ISO 9000 (International Standard Organization) Certificate in 1997. It is also the first hospital in Saudi Arabia and among all military hospitals in the Kingdom to apply Total Quality Management standards in 2003. The hospital has facilities for all types of surgery except open heart operations and major neonatal and pediatric surgery. Following approval of the local Scientific and Ethics Committee, surgical records of the operating theater were examined since the commission of the hospital on 13.07.1992 until 30.09.2010. In addition to demographic data, the nature and type of surgery, whether elective or emergency, type of anesthetic administered (general, regional or local) was recorded F. M. Messahel & M. J. Gregorio in special forms. The medical records of all surgical cases during that period were traced in the Medical Records Department and the outcome of each case was observed. The causes of cardiac arrests and deaths were assigned to one of four groups2: (i) totally anesthesiarelated when anesthesia was only or the major contributory factor; (ii) partially related to anesthesia when patient condition or surgical procedure were contributory factors, but anesthesia represented an additional factor; (iii) totally surgery-related; or (iv) totally related to patient disease or condition. Results There were 15,832 surgical procedures performed during that period, of which 7561 were males (47.8%) and 8271 females (52.2%), a ratio of 0.9 M: 1.0 F. Age group ranged from one day to 104 years old (average 28.1-yr old). General anesthesia was administered to 10983 (69.4%) cases, 3769 (23.8%) received regional anesthesia (spinal, epidural or caudal), and 1080 (6.8%) plexus, nerve or regional intravenous IV (Bier’s) block. There were 4 intra- and one postoperative death during this period. All 4 cases were emergencies. The first case was a 29-yr old known case of placenta previa who was admitted in labour. Due to mis-communication the locum member of staff overlooked cross matching the necessary units of blood needed in these situations. When the patient bled profusely, attempts at circulatory resuscitation were not successful. The second intraoperative death occurred in a 67-yr old patient with massive hematemesis due to advanced liver cirrhosis. The third was a victim of road traffic accident who suffered irreversible circulatory shock as a result of pelvic fracture and extended deep rectal laceration. His heart came to standstill during surgical exploration. the fourth was 73-yr old patient who had a cardiac arrest 24 hrs following removal of chicken breast bone impacted in his hypopharynx. On admission, the patient was already showing signs of mediastinitis as a result of perforation of the pharynx. The fifth patient was a 54-yr old male run over by a motor vehicle and suffered crush injury to the right lower limb and penetrating perineal wound. Patient developed DIC (Dissiminated Intravascular Coagulopathy), was resuscitated by massive plasma expander, blood transfusion and fresh frozen plasma, PERIOPERATIVE CARDIAC ARREST and was on maximum inotropic circulatory support, but his heart stopped during surgical exploration of the wounds. Discussion There are considerable differences between previous studies regarding the definition of the perioperative period. While some defined it as, the intraoperative period only6,7,8,11,12,13, others defined it as the intraoperative and either the recovery from anesthesia period15, or the first 24 hr postoperatively14. In this study we adopted the last definition. Preoperative cardiac arrests may be due to patient disease/condition, surgical factors, or to adverse events related to anesthesia. The rate of anesthesia related mortality has been stable over the past decade at approximately 1 death per 13000 anesthetics20. Anesthesia-attributable cardiac arrests are mainly the result of airway management. But also they may be due to cardiovascular depression or medication-errors. The type of the anesthetic is at the discretion of the anesthetist with patient approval if there is a choice. The vast majority of cases in our study (69.4%) received general anesthesia, 23.8% received regional anesthesia (spinal, epidural or caudal), and 6.8% plexus, nerve or regional intravenous IV (Bier’s) block. Previous studies suggest that the incidence of cardiac arrest is 8.3-fold higher in general than in neuraxial (spinal and epidural) anesthesia15. Recent survey of cardiac arrest incidence during neuraxial anesthesia reported 2.7 cardiac arrests per 10000 anesthetics21. This is lower than an earlier study22. The improvement here is mainly due to the better knowledge of neuraxial block physiology and the use of new local anesthetic drugs with fewer side-effects, associated with more routinely used cardiac and oxygen monitoring. Increasing grades of surgical trauma and general anesthesia can initiate inflammatory and hypercoagulable states23. These factors may have a direct role in initiating plaque fissuring and acute coronary thrombosis24,25. The stress state associated with anesthesia and surgery involves increased levels of catecholamines and cortisol. Their levels increase with general anesthesia, anesthetic reversal, extubation, increasing 817 pain scores, increasing grades of surgical trauma, anemia, fasting and hypothermia26. Increased stress hormone levels result in increases in blood pressure, heart rate, coronary artery shear stress, relative insulin deficiency and free fatty acid levels27. Coronary artery shear stress may trigger plaque fissuring and acute coronary thrombosis26. The other factors increase oxygen demand and can result in perioperative myocardial ischemia, which is strongly associated with perioperative myocardial infarction28,29,30. Factors that can initiate a hypoxic state include anemia, hypothermia (through shivering), and anesthesia and analgesia (through suppression of breathing). Perioperative hypoxia can result in myocardial ischemia in the setting of a hemodynamically significant coronary artery stenosis. These factors were taken into consideration when the anesthetic service at our hospital. We believe that the low incidence of perioperative deaths in our series is due to many factors which we are following in our hospital. International specialty standards, approved guidelines, evidence-based practices, implementation of quality improvement standards, are all meticulously applied. Members of the anesthetic staff are experienced and have continuous practice in anesthesia. Trainees are well selected and closely supervised by senior members of staff. The use of modern anesthetic equipment and monitoring systems in the perioperative period which detect changes in ST segment of the electrocardiogram, and which are regularly checked and serviced, together with stringent measures of checking drugs and blood for transfusion before administration have all contributed to this favorable outcome. We would like also to emphasize that periodic morbidity and mortality meetings and the enforcement of the ISO and Total Quality Management roles which necessitate regular auditing of departmental activities are essential elements in persistently providing a quality patient service. We strongly believe in good teamworking. One of the 5 principles of the Institute of Medicine’s report “To Err is Human” concludes that healthcare organizations need to “promote effective team functioning”31. It has been shown that surgical teams who exhibited good team work had better outcomes than patients of teams M.E.J. ANESTH 20 (6), 2010 818 with poor teamwork32. Patients on the elective list are visited and assessed by the anesthetist at least 24 hours preoperatively. Patients with associated non-surgical findings are referred to the appropriate specialty for management and optimization of their condition before surgery. The case may be postponed until the maximum possible improvement has been reached. In emergency cases, at least 75% of patients should be seen and assessed prior to their surgery. Such cases are also assessed by the appropriate specialty teams. If there is any possibility of optimizing the co-morbid condition of the patient prior to surgery it will be initiated, otherwise the benefit/risk ratio is applied. F. M Messahel & M. J. Gregorio This study is the first of its kind in the Kingdom of Saudi Arabia and it looked at the incidence and outcome of perioperative cardiac arrests in a military general hospital. One factor which might have contributed to this favorable outcome is that military personnel tend to be younger and fitter than the general public. Similar studies need to be conducted in Saudi tertiary hospitals, but better still in multicenters to include all types of surgery and to compare results with those from other institutions4,6,7,9. Acknowledgment: The authors wish to thank staff nurse Mary June Gregorio of the operating theater for her help and assistance. PERIOPERATIVE CARDIAC ARREST 819 References 1. Morgan CA, Webb RK, Cockings J, Williamson JA: The Australan Incident Monitoring Study Cardiac Arrest: an analysis of 2000 incident report. Anaesth Intensive Care; 1993, 21:626-637. 2. Braz GL, Módolo NSP, do Nascimento P Jr, Bruscchi BAM, Castiglia YMM, de Carvalho LR, et al: Perioperative cardiac arrest: a study of 53718 anaesthetics over 9 yr from a Brazilian teaching hospital. Br J Anaesth; 2006, 96:569-575. 3. Cohen MM, Duncan PG, Pope WD, Wolkenstein C: A survey of 112,000 anaesthetics at one teaching hospital (1975-83). Can Anaesth Soc J; 1986, 33:22-31. 4. Tiret L, Desmonts JM, Hatton F, Vourc’h G: Complications associated with anaesthesia: a prospective survey in France. Can Aaesth Soc J; 1986, 3:336-344. 5. Biboulet P, Aubas P, Dubourdieu J, Rubenovitch J, Capdevila X, d'Athis F : Fatal and non-fatal cardiac arrests related to anaesthesia. Can J Anesth; 2001, 48:426-332. 6. Kubota Y, Toyoda Y, Kubota H, Ueda Y, Asada A, Okamoto T, et al: Frequency of anesthetic cardiac arrest and death in the operating room at a single general hospital over a 30-year period. J Clin Anesth; 1994, 6:227-238. 7. Kawashima Y, Takahashi S, Suzki M, Morita K, Irita K, Iwao Y, et al: Anaesthesia-related mortality and morbidity over a 5-year period in 2,363,038 patients in Japan. Acta Anaesthesiol Scand; 2003, 47:809-817. 8. Olsson GL, Hallen B: Cardiac arrest during anaesthesia. A computer-aided study in 250,543 anaesthetics. Acta Anaesthesiol Scand; 1988, 32:653-664. 9. Wu KH, Rau RH, Lin CF, Chan YL: Cardiac arrest during anesthesia in a teaching hospital. A 4 year survey. Int Surg; 1997, 82:254-256. 10.Aroonpruksakul N, Raksakiatisak M, Thapenthai Y, Wangtawesaup K, Chaiwat O, Vasharaksa K, et al: Perioperative cardiac arrest at Siriraj Hospital between 1999-2001. J Med Assoc Thai; 2002, 85 (Suppl 3): S993-999. 11.Chopra V, Bovill JG, Spierdijk J: Accidents, near accidents and complications during anaesthesia. A retrospective analysis of a 10year period in a teaching hospital. Anaesthesia; 1990, 45:3-6. 12.Keenan RL, Boyan CP: Cardiac arrest due to anesthesia. A study of incidence and causes. JAMA; 1985, 253:2372-2377. 13.Keenan RL, Boyan CP: Decreasing frequency of anesthetic cardiac arrests. J Clin Aneth; 1991, 3:354-457. 14.Newland MC, Ellis SJ, Lydiatt CA, Peters KR, Tinker JH, Romberger DJ, et al: Anesthetic-related cardiac arrest and its mortality: a report covering 72,959 anesthetics over 10 years from a US teaching hospital. Anesthesiology; 2002, 97:108-115. 15.Sprung J, Warner ME, Contreras MG, Schroeder DR, Beighly CM, Wilson GA, et al. Predictors of survival following cardiac arrest in patients undergoing noncardiac surgery: a study of 518,294 patients at a tertiary referral center. Anesthesiology; 2003, 99:259269. 16.Tikkanen J, Hovi-Viander M: Death associated with anaesthesia and surgery in Finland in 1986 compared to 1975. Acta Anaesthesiol Scand; 1995, 39:262-267. 17.Gaba DM: Anaesthesiology as a model for patient safety in health care. Br Med J; 2000, 320:785-788. 18.Cooper JB, Gaba D: No myth: anesthesia is a model for addressing patient safety. Anesthesiology; 2002, 97:1335-1337. 19.National confidential Enquiry into perioperative deaths (2000) Then and Now-1990-2000. General Data 1-16. London, www.ncepod.org. uk 20.Lagasse RS: Anesthesia safety: model or myth? A review of the published literature and analysis of current original data. Anesthesiology; 2002, 97:1609-1617. 21.Auroy Y, Benhamou D, Bargues L, Ecofffey C, Fallissard B, Mercier FJ, et al: Major complications of regional anesthesia in France: The SOS Regional Anesthesia Hotline Service. Anesthesiology; 2002, 97:1274-1280. 22.Auroy Y, Narchi P, Messiah A, Litt L, Rouvier B, Samii K: Serious complications related to regional anesthesia: results of a prospective survey in France. Anesthsiology; 1997, 87:479-486. 23.Rosenfeld BA, Beattie C, Christopherson R, Nortis EJ, Frank SM, Breslow MJ, et al: The effects of different anesthetic regimens on fibrinolysis and the development of postoperative arterial thrombosis. Perioperative Ischemia Randomized Anesthesia Trial Study Group. Anesthesiology; 1993, 79:435-43. 24.Blake GJ, Ridker PM: Inflammatory bio-markers and cardiovascular risk prediction. J Intern Med; 2002, 252:283-94. 25.Baxevanis CN, Papilas K, Dedoussis GV, Pavlis T, Papamichail M: Abnormal cytokine serum levels correlate with impaired cellular immune responses after surgery. Clin Immunol Immunopathol; 1994, 71:82-8. 26.Priebe HJ: Triggers of perioperative myocardial ischaemia and Infarction. Br J Anesth; 2004, 93:9-20. 27.Parker SD, Breslow MJ, Frank SM, Resenfeld BA, Norris EJ, Christopherson R, et al: Catecholamine and cortisol responses to lower extremity revascularization: correlation with outcome variables. Perioperative Ischemia Randomized Anesthesia Trial Study Group. Crit Care Med; 1995, 23:1954-61. 28.Fleisher LA, Nelson AH, Rosenbaum SH: Postoperative myocardial ischemia: etiology of cardiac morbility or manifestation of underlying disease? J Clin Anesth; 1995, 7:97-102. 29.Landesberg G, Mosseri M, Zahger D, Wolf Y, Perouansky M, Anner H, et al: Myocardial infarction after vascular surgery: the role of prolonged stress-induced, ST depression-type ischemia. J Am Coll Cardiol; 2001, 37:1839-45. 30.Mangano DT, Browner WS, Hollenberg M, London MJ, Tubau JF, Tateo IM: Association of perioperative myocardial ischemia with cardiac morbidity and mortality in men undergoing noncardiac surgery. The Study of Perioperative Ischemia Research Group. N Engl J Med; 1990, 323:1781-8. 31.Kohn LT, Corrigan JM, Donaldon MD. Eds. To Err Is Human. Washington DC: National Acaemy Press; 2000. 32.Mazzocco K, Petitti DB, Fong KT, et al: Surgical team behavior and patient outcomes. The American Journal of Surgery; 2009, 197:679-685. M.E.J. ANESTH 20 (6), 2010 EFFICACY OF ULTRASOUND-GUIDED TRANSVERSus ABDOMINIS PLANE (TAP) BLOCK FOR POSTCESAREAN SECTION DELIVERY ANALGESIA - A Double-Blind, Placebo-Controlled, Randomized Study - Jumana M Baaj*, Raed A Alsatli**, Hayan A Majaj***, Zainab A Babay**** and Ahmed K Thallaj***** Abstract Background: Ultrasound-guided transversus abdominis plane (TAP) block has been used for intra-operative and postoperative analgesia. Here we evaluate the efficacy of TAP block for postoperative cesarean delivery analgesia. Method: A randomized, double-blind, placebo-controlled trial was performed at King Khalid University Hospital on 40 patients undergoing cesarean delivery under spinal anesthesia with bupivacaine and fentanyl. At the end of surgery they received bilateral ultrasound-guided TAP block either with bupivacaine 0.25% (B group) 20 patients, or saline (S group, or placebo group) 20 patients, followed by patient controlled analgesia with IV morphine only. Each patient was assessed 24 hours after delivery for pain, morphine consumption, nausea, vomiting, sedation, patient’s satisfaction, and also pain relief during mobilization (24 hours post-cesarean section). Results: All 40 participants completed the study. Total morphine consumption was reduced more than 60% in the bupivacaine group; the bupivacaine group also reported improved satisfaction with their pain relief over 24 hours after surgery, reduced morphine consumption, less nausea, vomiting, and better patient’s satisfaction. Conclusion: Ultrasound-guided TAP block improved postoperative analgesia, reduced morphine consumption and improved patient’s satisfaction regarding analgesia after cesarean delivery. Key words: Ultrasound guided (USG), transversus abdominis plane (TAP), (U S) ultrasound. external oblique muscle (EOM), internal oblique muscle (IOM), transversus abdominis muscle (TAM), visual analogue scale (VAS), cesarean section C/S. From the Departments of Anaesthesia, Cardiac Science Obstetrics & Gynaecology, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia. * MD, Arab Board. Consultant Anesthesiologist, Department of Anaesthesia. ** MD, Facharzt, Assistant Professor and Consultant Cardiac Anaesthetist, Department of Cardiac Science, Cardiac Anaesthesia. *** MD, Arab Board, Senior Registrar, Department of Anaesthesia. ****MBBS, ABOG, Professor and Consultant, Obstetrician, Gynecologist and Perinatologist, Department of Obstetrics & Gynaecology. *****MD, Arab Board, Assistant Professor and Consultant Anaesthesiologist, Department of Anaesthesia. Address Correspondence to: Dr. Jumana BM Baaj, Consultant Anaesthetist, Department of Anaesthesia, College of Medicine, P.O Box: 2925, Riyadh 11461, Kingdom of Saudi Arabia. Tel: (+9661) 4692019/4692194, Fax: (+9661) 4692366, E-mail: [email protected] 821 M.E.J. ANESTH 20 (6), 2010 822 J. M. Baaj et al Introduction half way between costal margin and iliac crest. Post-cesarian section pain and discomfort may be anticipated due to skin incision, uterine incision and uterine contraction. The aim of this study is to evaluate the analgesic efficacy of ultrasound-guided TAP block for postoperative period. The satisfactory image was aimed to visualize the subcutaneous fat, external oblique muscle, internal oblique muscle, transversus abdominis muscle, peritoneum, and intraperitoneal cavity (Fig. 1). We hypothesized that the TAP block, as an analgesic regimen, would result in improved analgesia, decreased opioid consumption in the first 24 hours after cesarean delivery compared with placebo, facilitated early mobilization, and improved postoperative patient’s satisfaction. Fig. 1 Transversus abdominis plane, EOM (external oblique muscle), IOM (internal oblique muscle), TAM (transversus abdominis muscle) Method The study was performed in the period May 2009 to April 2010, in King Khalid University Hospital. It was approved by our institution’s Ethics Committee and a written informed consent was obtained from each patient. We studied 40 ASA I-II women having cesarean delivery at term in a randomized, doubleblind, placebo-controlled trial. A control group of 20 patients received saline for TAP block (S group), while other 20 patients received bupivacaine (B group). All participants were above 18 years old. Exclusion Criteria: Patients who were (ASA) classification III-IV, patients with contraindications to spinal anesthesia or history of allergy to bupivacaine, patients who received analgesics in the past 24 hours, and obese patients with a BMI >40 were not included in the study. A 100 mm long 20G short bevel needle (Stimuplex A B/BRAUN Melsungen AG, Germany) was inserted in plane to the probe of the ultrasound anteriorly to lie between internal oblique muscle and transversus abdominis muscle, a total of 20 ml study solution was injected in each side (left and right). Successful injection was obtained when an echoluescent lens-shape appeared between the two muscles (Fig. 2a and 2b). Fig. 2a Transverse ultrasound view of the EOM, IOM, and TAM at the beginning of local anesthetic injection, between the inner two muscles IOM and TAM All participants received spinal anesthesia using hyperbaric 0.5%, bupivacaine 10 mg, and fentanyl 20 µg. Antiemetics were not routinely administered but if required, metoclopromide 10 mg i.v. was given. An ultrasound-guided TAP block was performed at the end of surgery, skin was prepared with 2% chlorhexidine solution and a high-frequency (13-6 MHz) ultrasound probe (SonoSite M-Turbo Sonosite Inc., Bothel) was used. The injectate syringes were prepared under aseptic technique; syringes contained either normal saline 40 ml (placebo group) or bupivacaine 0.25% 40 ml. Investigators were blinded to the injected solution. Ultrasound probe was positioned in mid-axillary line Fig. 2b Transverse ultrasound view of the EOAM, IOAM, and TAM at the end of local anaesthetic injection EFFICACY OF ULTRASOUND-GUIDED TRANSVERSus ABDOMINIS PLANE (TAP) BLOCK FOR POST-CESAREAN SECTION DELIVERY ANALGESIA All patients received morphine patient-controlled analgesia with dose of 1mg bolus, and 10 minutes lock-out time for 24 hours postoperatively. The primary outcome was the total morphine consumption over 24 hours after surgery. Data were obtained from PCA pump. Accumulative morphine doses at 6, 10, 12, 18, 24 hours post-surgery were recorded, participants were asked about their pain experience on 10mm visual analogue scale (VAS) during the 24 hours postoperatively and during mobilization 24 hours after surgery. Satisfaction with pain relief was reported over 24 hours. Participants were asked for severity of nausea, vomiting, and sedation. The calculation assumed the use of Fisher’s exact test. Chi-square test was used to compare between patients in bupivacaine group and placebo group for nominal variables, i.e. sedation, satisfaction, postoperative nausea and vomiting, previous cesarean and previous surgical operations. 823 Table 2 Previous caesarean section (C/S) showing no significant difference between both groups of patients Parameter Bupivacaine group No. (%) Control group No. (%) P value No C/S 12 (63.2%) 9 (45%) Previous C/S 7 (36.8%) 11 (55%) 0.415 The TAP block with bupivacaine 0.25% compared with placebo reduced postoperative pain (Fig. 3). Fig. 3 The TAP block with bupivacaine reduced postoperative visual analog scale by 25% (± SD) compared with control group Student’s t-test was used for independent groups to compare between both groups for measurable variables, i.e. age, BMI, weight, height, morphine consumptions and visual analogue score. We assumed there was a statistically significant difference when P-value is less than 0.05 Results Forty patients were included in the study, all participants had elective cesarean deliveries, the baseline characteristics of the two groups were not significantly different (Table 1); ultrasound views were satisfactory in all participants, no blood aspiration occurred in all TAP block cases, no side effects were observed during and after 24 hours of surgery. Regarding previous cesarean sections there was no statistical difference between both groups (Table 2). Table 1 Baseline characteristic of the study participants; no statistically significant differences between the groups for all baseline characteristics Parameter Age (yrs) {mean range} Bupivacaine group Control group Total morphine requirements in the first postoperative 24 hours were also reduced in the bupivacaine group compared with the placebo group (25.89 ± 5.13 mg versus 62 ± 4.78, p <0.05) (Table 3, Fig. 4). Table 3 Postoperative morphine consumption in 24 hours period post surgery is reduced in Bupivacaine group compared to control group. Data are presented as mean ± (SD) Cumulative morphine dose at: Bupivacaine group Control group 6hr(mg) {mean(sd)} 3.89 ± 2.97 16.25 ± 2.99 10hr 8.3 ± 3.14 28.95 ± 4.5 12hr 13.11 ± 4.3 36.5 ±.28 29 30.75 Height (cm) {mean (SD)} 156.53 ± 4.12 155.25 ± 5.09 BWT(kg) {mean (SD)} 78.27 ± 9.33 75.7 ± 7.56 18hr 19.05 ± 3.97 50.4 ± 3.73 BM I {mean (SD)} 32.0 ± 2.91 31.35 ± 3.23 24hr 25. 79 ± 5.14 62.55 ± 4.72 M.E.J. ANESTH 20 (6), 2010 824 J. M. Baaj et al Fig. 4 Postoperative morphine consumption in 24 hours period postsurgery. Data are presented as mean (SD) There was less nausea and vomiting in bupivacaine group than placebo group; two patients from placebo group received antiemetic during 24 hours period, but only one patient from bupivacaine group received an antiemetic drug in the same period (Fig. 5). Fig. 5 Postoperative nausea and vomiting was less in the Bupivacaine group compared to control group. Fig. 6 Patient’s satisfaction with pain relief was significantly higher in Bupivacaine group. muscle and anteriorly by external oblique muscle. TAP block provides motoric and sensory block to anterior and lateral abdominal wall, it has been used for intra-operative and postoperative analgesia, either by anatomical landmarks or ultrasound-guided. It has been performed for the following procedures: caesarean delivery2, hysterectomy3, retropubic prostatectomy4, appendectomy5, laparoscopic cholecystectomy6, and laparoscopic hernia repair with mesh. The efficacy of TAP block was also studied by Belavy et al7 using Ropivacaine 0.5% as one tool of multimodal analgesia in addition to PCA morphine, paracetamol and NSAIDs regularly, but in this study, morphine is the single analgesic given to the patient if postoperative analgesia was required. Efficacy of block was evaluated by assessing pain level with VAS, and the postoperative morphine consumption. Patient’s satisfaction with pain relief was significantly higher in bupivacaine group (Fig. 6). Discussion TAP block is relatively a new regional anesthesiaanalgesia technique1; it was initiated by Raffi as a landmark-based technique within the iliolumbar triangle of Petit. The triangle of Petit was bounded inferiorly by iliac crest, posteriorly by latissimus dorsi Though ultrasonographic guidance enable exact placement of local anesthetics between internal oblique and transversus abdominis muscle, the safety of TAP block has been discussed by Zorica et al8. There are reports of visceral damage when the needle went too far like liver injury9, colon rupture10-11, and another reported complication is transient femoral nerve palsy12. Accidental intravascular injection of local anesthetic, infection, and catheter breakage should also be considered as potential complications of TAP block13. There are several suggestions to minimize such complications: (i) by using a fine-gauge, blunttipped, short-bevel needle to minimize risk of visceral EFFICACY OF ULTRASOUND-GUIDED TRANSVERSus ABDOMINIS PLANE (TAP) BLOCK FOR POST-CESAREAN SECTION DELIVERY ANALGESIA 825 damage, and (ii) directing the needle obliquely instead of perpendicularly to increase the resistance of each aponeurosis, and using smaller volume of local anesthetic to decrease the incidence of femoral nerve block. improved patient’s satisfaction and quality of pain relief. Conclusion Further research is essential to determine the ideal injected dose, volume of local anesthetics, duration of the block according to local anesthetic serum level, and the use of TAP block as intraoperative anesthetic technique for other procedures. This study demonstrates the analgesic efficacy of ultrasound-guided TAP block after cesarean delivery. The block reduced the postoperative pain, total morphine consumption, antiemetic drugs, and We recommend this block for all women undergoing cesarean delivery who are not given longacting neuroaxial opioids. M.E.J. ANESTH 20 (6), 2010 826 J. M. Baaj et al References 1. McDonnell JG, O'Donnell BD, Farrell T, Gough N, Tuite D, Power C, Laffey JG: Transversus abdominis plane block: a cadaveric and radiological evaluation. Reg Anesth Pain Med; 32(5):399-404, 2007. 2. McDonnell JG, Curley G, Carney J, Benton A, Costello J, Maharaj CH, Laffey JG: The analgesic efficacy of transversus abdominis plane block after cesarean delivery: a randomized controlled trial. Anesth Analg; 106(1):186-191, 2008. 3. McDonnell JG, O'Donnell B, Curley G, Heffernan A, Power C, Laffey JG: The analgesic efficacy of transversus abdominis plane block after abdominal surgery: a prospective randomized controlled trial. Anesth Analg; 104(5):193-197, 2007. 4. O'Donnell BD, McDonnell JG, McShane AJ: The transversus abdominis plane (TAP) block in open retropubic prostatectomy. Reg Anesth Pain Med; 31(1):91, 2006. 5. Niraj G, Searle A, Mathews M, Misra V, Baban M, Kiani S, Wong M: Analgesic efficacy of ultrasound-guided transversus abdominis plane block in patients undergoing open appendicectomy Br J Anaesth; 103(4):601-605, 2009. 6. El-Dawlatly AA, Turkistani A, Kettner SC, Machata AM, Delvi MB, Thallaj A, Kapral A, Marhofer P: Ultrasound-guided transversus abdominis plane block: description of a new technique and comparison with conventional systemic analgesia during laparoscopic cholecystectomy. Br J Anaesth; 102(6):763-767, 2009. 7. Belavy D, Cowlishaw PJ, Howes M, Phillips F: Ultrasound-guided transversus abdominis plane block for analgesia after Caesarean delivery. Br J Anaesth; 103(5):726-730, 2009. 8. Jankovic Z, Ahmad N, Ravishankar N, Archer F: Transversus abdominis plane block: how safe is it? Anesth Analg; 107(5):17581759, 2008. 9. Farooq M, Carey M: A case of liver trauma with a blunt regional anesthesia needle while performing transversus abdominis plane block. Reg Anesth Pain Med; 33(3):274-275, 2008. 10.Jöhr M, Sossair: Colonic puncture during ilioinguinal nerve block in a child. Anesth Analg; 88(5):1051-1052, 1999. 11.Frigon C, Mai R, Valois-Gomez T, Desparmet J: Bowel hematoma following an iliohypogastric-ilioinguinal nerve block. Paediatr Anaesth; 16(9):993-996, 2006. 12.Walter EJ, Smith P, Albertyn R, Uncles DR: Ultrasound imaging for transversus abdominis blocks. Anaesthesia; 63(2):211, 2008. 13.Weintraud M, Marhofer P, Bösenberg A, Kapral S, Willschke H, Felfernig M, Kettner S: Ilioinguinal/iliohypogastric blocks in children: where do we administer the local anesthetic without direct visualization? Anesth Analg; 106(1):89-93, 2008. COMPLICATIONS AND INTERVENTIONS ASSOCIATED WITH EPIDURAL ANALGESIA FOR POSTOPERATIVE PAIN RELIEF IN A TERTIARY CARE HOSPITAL Faraz Shafiq*, Mohammad Hamid** and K halid S amad *** Introduction Epidural analgesia is one of the commonly used methods of postoperative pain control despite its associated complications. Early recognition and intervention is required to minimize the effect of these complications. Present audit was conducted to find out the incidence of complications and type of interventions required to change the outcome. Methodology The record of all the patients who had epidural catheter placed for postoperative pain management reviewed from the departmental acute pain management register. Parameters included level of insertion, drugs used, number of days infusion continued and complications like nausea, vomiting, motor block, sedation, dural tap, catheter pull out, hypotension and itching. In addition, the intervention done to manage these complications was also recorded. Results Total 1706 entries of epidurals were recorded in study period 2001 to 2007. The overall incidence of the complication was 26.6%. The common complications were motor block (13.4%), dural tap (1.2%), ineffective pain control (2.4%), accidental catheter pull outs (3.8%) and problems associated with the delivery system of drug (1.7%). The 12% of patients required intervention for the particular complications. The regime was discontinued in 28%, drug concentration changed in 21.5% while the other modes of pain management were used in 19% of patients. 0.9% of patients required epidural blood patch while 2% of patients required catheterization for urinary retention. Conclusion This audit shows the importance of regular assessment and early intervention to manage epidural related complications in improving outcome. Key words: Pain management, epidural, complication. * MCPS, FCPS, Resident. ** MD, Associate Professor. *** MCPS, FCPS, Assistant Professor. Department of Anaesthesia, Aga Khan University Hospital, Karachi, Pakistan. Correspondence: Dr. Faraz Shafiq MCPS, FCPS, Resident, Department of Anaesthesia, Aga Khan University Hospital Karachi, Pakistan. Mobile: +92-03453179095, E-mail: [email protected], [email protected] 827 M.E.J. ANESTH 20 (6), 2010 828 Introduction Acute pain may be defined as pain that is present in patients because of preexisting diseases, the surgical procedure or the combination of disease or surgery related sources1. Acute pain in the postoperative period may be the worst experience in a life of patient, as most of them perceive it as one of the most ominous aspect of surgery. Inadequate postoperative pain relief is associated with increase in morbidity and mortality after surgery2. At our institution, we are using different modalities for acute pain management in the postoperative surgical patients. The epidural analgesia is the frequently used modality amongst them. Epidural analgesia is used for continuous administration of local anesthetic (LA) agent alone or in combination with narcotic agents in the epidural space. It has got the potential to reduce or eliminate the perioperative stress responses to the surgery. It also decreases the incidence of post operative surgical complications3 leading to the better outcome4. Pain management with the epidural analgesia is not free from side effects. The therapy can be made effective and safe by giving particular attention to the clinical assessment of the patient in terms of pain control and complications. Importance should be given to the educational and organizational aspects related to the delivery of pain relief modality. Regular audits and review of problematic areas are helpful in the identification and reduction of complications associated with the technique. The objective of the audit was to identify the complications associated with epidural analgesia in the postoperative period and interventions required for the associated complications by acute pain management service (APMS). Material and Methods The data of patients having epidural analgesia was reviewed retrospectively. It included all patients enrolled in the acute pain service from 2001 to 2006, requiring epidural catheter placement for postoperative pain management. Thoracic, labor and caudal epidurals were excluded. Similarly pediatric patients and data which was incomplete or missing was also excluded. F. Shafiq et al The record of all the patients who had epidural catheter for postoperative pain management was reviewed from the departmental APMS register by the primary investigator. The dedicated APMS organized the rounds, patients’ evaluation and other organizational aspects of the acute pain service in our hospital. The departmental APMS register is helpful in organizing patient’s record keeping in terms of medical record number, location and comorbids. The parameters which we recorded in the register also includes surgical procedure, level of catheter insertion, concentration of LA used. In our setup pharmacy prepared 100 ml piggy bags of three different concentrations of bupivicaine that is, M1-0.1%, M2-0.125%, M3-0.0625% with 2µg/ml of fentanyl respectively. Complications like nausea, vomiting, sedation, and unilateral/bilateral motor blocks which are common, have dedicated columns for their entries. Other complications which are rare or unusual as ineffective pain control, accidental catheter pull outs, hypotension, itching etc. are recorded in the miscellaneous column if they occurred. The assessment of pain, nausea, vomiting and sedation is based on the fixed proctols designed by the acute pain management service. Numerical pain rating scale of 0-3 is used to evaluate these parameters with 0 being no occurrence while the score of 3 indicates severity of the mentioned problem. Similarly numerical score of 0-3 is used for the evaluation of unilateral motor block (UMB) or bilateral motor block (BMB). The score of 0 indicates no motor block, while score of 3 is the motor block impairing the movement of limbs. Nurses record the patient’s status in dedicated monitoring forms. The APMS is 24hrs on call service, available to manage any particular complication associated with the pain relief modalities. Interventions and necessary action taken for the particular complications are also mentioned in the register. The team manages the particular complications on predesigned protocols as decreasing the concentration or rate of LA for BMB or pulling out of epidural catheter to a certain extent in the presence of UMB. Patient tilting to a lateral position that is the block side up is also followed for the UMB. Other complications are usually managed according to the cause and at the discretion of physician judgment. COMPLICATIONS AND INTERVENTIONS ASSOCIATED WITH EPIDURAL ANALGESIA FOR POSTOPERATIVE PAIN RELIEF IN A TERTIARY CARE HOSPITAL Results Total 1706 entries of epidurals were recorded. The lumbar intervertebral space was selected in 88% patients while the thoracic level was used in 11% of patients. Epidural was inserted for the perioperative pain management in different surgical procedures as shown in figure 1. The obstetric patients were the largest among group that receive epidural that is 32%. The different concentrations of LA were used as mentioned in table 1. Over all 63.54% of patients received M 2 regime in the infusion form. In 50% of patients the epidural was continued for 3 days, in 33% of patients it was continued for 2 days while in 17% the epidural was discontinued after 1 day, see figure 2. The regime was discontinued prematurely for different reasons in 3.8% of patients. The overall incidence of the complications as shown in table 2, in our audit was 26.5%. Common complications were UMB and BMB. Dural tap was occurred in 1.2% of patients while 0.17% of patients complained of moderate to severe post dural puncture head ache Fig. 1 Different Surgical Procedures 32% 24% 22% Table 1 Concentration of LA used Epidural Drug Percent% No. of Pts (n) M1 17.29 295 M2 63.54 1084 M3 19.1 327 Table 2 Complications of epidural Analgesia Complications Percentage Number % (n) 453 Unilateral motor Block (RT) 5.33 91 Unilateral motor Block (LT) 4.74 81 Bilateral motor Block 3.04 52 Dural Tap 1.23 21 Pull out 3.75 64 Filter Dislodgement 0.82 14 Hypotension 1.34 23 Nausea and Vomiting 0.29 5 Itching 0.35 6 Ineffective 2.4 41 Severe pain 0.4 7 Urinary retention 0.4 7 Head ache 0.17 3 System faults 1.69 29 Others 0.52 9 12% 8% Table 3 Interventions done by APMS team Intervention Percentage Number % (n) 2% 17% 33% Total 12.77 218 Discontinued 28.4 62 Change of regime 19.2 42 21.55 47 Pull out of catheter 6.42 14 Rate decrease 3.21 7 Holding of infusion 5.0 11 Change concentration Fig. 2 Number for days for which epidural used 50% 829 in 1 Day Positioning 5.96 13 2 Days Epidural Bolus 6.42 14 3 Days Blood patch 0.9 2 Catheterization 1.83 4 Others 0.9 2 M.E.J. ANESTH 20 (6), 2010 830 (PDPH). In 2.4% of patients epidural analgesia was ineffective. Systems fault leading to ineffective drug delivery were present in 1.7% of patients. The epidural catheter pull outs and filter dislodgement were the common causes of premature discontinuation of epidural infusions. Overall 12.1% of patients in the audit required intervention by the APMS team for the particular complications. Interventions done are shown in table 3 UMB and BMB were the common reasons for intervention. 21.5% of patients required change of LA regime to a lower concentration for this reason while 6.4% of patient required epidural catheter pulls out for unilateral motor blockade. 5.9% of patients require change of positioning for UMB. 19.2% of patients require change of regime due to ineffective pain relief. Discussion The epidural analgesia is the commonly used modality for the perioperative pain management and it has shown proven benefit particularly in dynamic pain control. The effective use of epidural analgesia in the postoperative period requires careful assessment of the patient physiological status, pain control and associated complications. It is also very important to monitor the functioning status of epidural drug delivery system and the location of catheter tip in the epidural space. The audit helped in the identification of common technical problems and complications in local population. Unilateral or bilateral motor block, hypotension, nausea, vomiting and itching were the frequent complications found. The problems associated with the epidural drug delivery system like catheter dislodgment and the filter disconnection were also identified. Use of LA agents in epidural space cause differential nerve blockage depending upon the concentration of LA agent and the fibers blocked. The more dilute the agent the chance of getting motor blockade will be low. The target is to achieve pain control in terms of minimal motor blockade. The motor block interfering with the lower limbs movement may be associated with higher incidence of pressure sores and deep vein thrombosis and if remain persist, despite of appropriate intervention may be the indicator of epidural hematoma or abscess. The overall incidence of BMB in our study was 3.0%. The incidence reported F. Shafiq et al by Scott DA et al in their prospective study was 3.0%5, with the combination of fentanyl and bupivicaine infusion. The incidence of UMB was higher in our patients as compared to bilateral (4.74-5.33 vs. 3.0%). The cause of which may be the increased length of catheter in epidural space. The usual practice in our hospital is to have a length of 3-5 cm of catheter in epidural space. The neuronal blockade at the level of T1-T4 involving cardiac sympathetic chain may be associated with the occurrence of hypotension and bradycardia. The concentration of LA agent and height of block which is planned to be achieved are additional factors associated with this hemodynamic instability. The reported incidence in literature is 0.7-3%6. In our patients the incidence was comparable that is 0.7%. The 63.5% of patients in our audit received bupiviacaine 0.125%, which may be reason of lower incidence of hypotension and bradycardia in this audit. Epidural administered opioids achieve analgesia via pre and post synaptic effects in dorsal horn of spinal cord. They also interfere with the nociceptive input but do not cause neuronal blockade. The use of opioids in epidural infusion is responsible for effects like respiratory depression, sedation, nausea, vomiting and itching. The reported incidence of respiratory depression is 0.24%7 depending upon the type of narcotic used. The incidence reduces with the use of more lipophilic agents like fentanyl. In our audit we didn’t find any report of respiratory depression due to the epidural infusion. We routinely monitor the sedation level and respiratory rate of the patients having epidural analgesia in progress. The narcotic we use in combination of LA is fentanyl 2µg\ml which may be the reason of undetectable incidence of respiratory depression in our patients. The nausea and vomiting associated with the opioids is the major cause of patient dissatisfaction. The opioid present in the epidural infusion stimulates the chemoreceptor trigger zone which in turn causes nausea and vomiting. The incidence was 024% in our patients which may be due to the low dose of fentanyl used. Itching is mu receptor mediated adverse effect of epidurally adminsitered opioids. It involves usually the face and upper chest. The incidence in our postoperative patients was 0.35%. COMPLICATIONS AND INTERVENTIONS ASSOCIATED WITH EPIDURAL ANALGESIA FOR POSTOPERATIVE PAIN RELIEF IN A TERTIARY CARE HOSPITAL The rare but most feared complications of epidural analgesia are epidural abscess, meningitis and epidural hematoma. No such cases were detected in this audit. The reported incidence in literature is 1-1000 to 1-500008. In a retrospective audit of 8100 epidural during six year period Christieet al9 identified six cases of epidural abscess, three of meningitis and three of epidural hematoma. Symptoms of epidural abscess or meningitis developed a median of 5 days after epidural catheter removal. Methicillin resistant Staphylococcus aureus was the predominant pathogen. In our hospital we usually discontinued epidural at the third postoperative day. Detection of motor power of leg is crucial in the presence of epidural analgesia10 which may be the sign of impending neurological deficit. The other area of concern was the premature catheter pull outs and filter disconnections due to negligence in catheter management. Alternate analgesia in the form of PCIA or intravenous narcotics was provided to these patients. The APMS service is actively involved in the teaching of paramedics and nursing staff to prevent such complications. But the compliance during different period varied. 2.4% of patients had ineffective pain relief for which regime was changed. The cause of which may be multi factorial including technical errors the findings of 831 which was not our objective. Different interventions were done for particular complications specially those for which APMS service was called. Over all 12.77% of patients required interventions. The motor block was the most common complication in our study for which the step wise approach has been followed as mentioned in the methodology like change of positioning or pulling out of epidural catheter to a certain length. For severe PDPH not responding to the conventional therapy only 0.9% of patients required epidural blood patch. The limitation of this study was the retrospective review, so the chance of getting missed data and incomplete information may be the source of error as the compliance of maintaining the pain management register is also noted to be varied at different times, but again the common problems were highlighted. Conclusion This audit helped us in identification of problems associated with epidural analgesia technique and emphasizes the effectiveness of early interventions done by APMS team. It also shows the importance of regular monitoring, multidisciplinary approach and early intervention to reduce disastrous complication and improve patient satisfaction. M.E.J. ANESTH 20 (6), 2010 832 F. Shafiq et al References 1. Practice guide line for acute pain management in perioperative setting. An updated report by the American society of Anesthesiology; 2004, 100:1573-8. 2.Sharrock NE, Cazan MG, Hargett MJ, Williams-Russo P, Wilson PD Jr: Changes in mortality after total hip and knee arthroplasty over a ten-year period. Anesth Analg; 1995, 80:242-248. 3.Grass JA: The role of epidural anesthesia and analgesia in postoperative outcome. Anesthesiol Clin North America; 2000, 18:407-428. 4.Park WY, Thompson JS, Lee KK: Effect of epidural anesthesia and analgesia on peri-operative outcome. Ann Surg; 2001, 234:560-571. 5.Scott DA, Beilby DS, Mc Clymont C: Postoperative analgesia using epidural infusions of fentanyl with bubivicaine. Aprospective analysis of 1,014 patients. Anesthesiology; 1995, 83:727-37. 6.Tsui SL, Irwin MG, Wong CM, et al: An audit of the safety of an acute pain service. Anesthesia; 1997, 52:1042-7. 7.Burstal R, Wegener F, Hayes C, Lantry G: Epidural analgesia: prospective audit of 1062 patients. Anaesth Intensive Care; 1998, 26(2):165-72. 8.Moen V, Dahlgren N, Irestedt L: Severe neurological complications after central neuraxial blockade in Sweden 1990-99. Anesthesiology; 2004, 101:950-9. 9.Christie I W, Mc Cabe S: Major complications of epidural analgesia after surgery: Results of a six-year survey. Anaesthesia; 2007, 62, pages 335-341. 10.Breivik H: Safe perioperative spinal and epidural analgesia. Acta Anaesthesiologica Scandinavica; 1995, 39:869-71. CARDIOVASCULAR RESPONSES TO OROTRACHEAL INTUBATION IN PATIENTS UNDERGOING CORONARY ARTERY BYPASS GRAFTING SURGERY Comparing Fiberoptic Bronchoscopy With Direct Laryngoscopy Nahid Aghdaii*, Rasoul Azarfarin**, Forouzan Yazdanian*** and S eyede Z ahra Faritus *** Abstract Background: The intubation by using fiberoptic brochoscop (FOB) can avoid the mechanical stimulus to oropharyngolaryngeal structures thereby it is likely to attenuate hemodynamic response during orotracheal intubation. Based on this hypothesis, we compared the hemodynamic responses to orotracheal intubation using an FOB and direct laryngoscope (DLS) in patients undergoing general anesthesia for coronary artery bypass grafting (CABG) surgery. Methods: Fifty patients with ASA physical status II and Mallampati score I and II were scheduled for elective CABG surgery under general anesthesia requiring orotracheal intubation were randomly allocated to either DLS group (n = 25) or FOB group (n = 25). The same protocol of anesthetic medications was used. Invasive systolic and diastolic blood pressure (SBP & DBP) and heart rate (HR) were recorded before and after anesthesia induction, during intubation and in the first and second minutes after intubation. The differences among the hemodynamic variables recorded over time and differences in the circulatory variables between the two study groups were compared. Results: Duration of intubation was shorter in DLS group (19.3 ± 4.7 sec) compared with FOB group (34.9 ± 9.8 sec; p = 0.0001). In both study groups basic SBP and DBP and HR were not significantly different (P >0.05). During the observation, there were no significant differences between the two groups in BP or HR at any time points or in their maximal values (all p values >0.05). Conclusion: We conclude that the FOB had no advantage in attenuating the hemodynamic responses to orotracheal intubation in patients undergoing CABG surgery. Keywords: Laryngoscopy-Hemodynamic responses-Fiberoptic bronchoscope-Orotracheal intubation. * MD, Associated Professor of Anesthesiology, Department of Anesthesiology, Shahid Rajaii cardiovascular Medical Center, Iran University of Medical Sciences, Tehran, Iran. ** MD, Associated Professor of Anesthesiology, Fellow in Cardiac Anesthesia, Cardiovascular Research Center, Madani Heart hospital, Tabriz University of Medical Sciences, Tabriz, Iran. *** MD, Assistant Professor of Anesthesiology. Correspondence and Reprints to: Rasoul Azarfarin MD, Cardiovascular Research Center, Madani Heart Hospital, Tabriz University of Medical Sciences, Tabriz, Iran. Tel: +98 411 3373950, Fax: +98 411 3373950, E-mail: [email protected], razarfarin@ yahoo.com 833 M.E.J. ANESTH 20 (6), 2010 834 Introduction The cardiovascular response to laryngoscopy and tracheal intubation has been extensively studied during the past three decades. Direct laryngoscopy and passage of a tracheal tube are noxious stimuli that can provoke adverse responses in the cardiovascular, respiratory, and other physiologic systems. Tracheal intubation causes a reflex increase in sympathetic activity that may result in hypertension, tachycardia, and arrhythmia1-3. The magnitude of the response is affected by many factors: the technique of laryngoscopy and tracheal intubation4-6, and the use of various airway instruments, like flexible fiberoptic bronchoscope and light wand intubating device1,3. Premedication and induction drugs may attenuate the circulatory response7-10, many drugs and techniques have been tried in an effort to attenuate adverse hemodynamic responses to laryngoscopy and endotracheal intubation1-3,6-11. A patient’s medical condition affects his physiologic response7-13. The cardiovascular response to tracheal intubation, include elevation in arterial pressure and typically starts within 5 seconds of laryngoscopy, peaks in 1 to 2 minutes, and returns to control levels within 5 minutes. Such hemodynamic changes can result in myocardial ischemia but seem to cause little harm to most patients. However they are undesirable in patients with cardiac disease. There are limited studies comparing differences in the circulatory responses to DLS and FOB in cardiac patients and we cannot find the previously published study on patients who undergoing coronary artery bypass graft (CABG) surgery. However, Tsubaki et al14 demonstrated that fiberoptic intubation should be used in patients with difficult airway, hypertension, ischemic heart disease, or cerebrovascular atherosclerosis. In this randomized clinical trial, we compared the circulatory responses to either direct laryngoscopy (DLS) or fiberoptic bronchoschopy (FOB) to determine whether there is a clinically relevant difference between the circulatory responses to FOB and DLS in patients undergoing CABG surgery. Methods After the study protocol was approved by the Division Ethics Committee of our institute, all of the N. Aghdaii et al 50 adult patients signed informed written consent to participate in this study. These patients were ASA physical status II, 35-65 years old and ejection fraction (EF) ≥40% and scheduled for elective coronary artery bypass graft surgery under general anesthesia and orotracheal intubation. No difficulties with their airway management or intubation were predicted during preoperative visits (Table1). Exclusion criteria were a history of reactive airway disease, gastroesophageal reflux, morbid obesity, co-existing cardiovascular diseases except coronary artery disease and opium addiction. The patients taking their medications before surgery had similar protocol. All of them were taking metoprolol, nitrocontin and aspirin. Patients were randomly allocated to either the FOB group (n = 25) or the DLS group (n = 25) using online randomization software (URL: http://www. graphpad.com). Patients in the first group underwent orotracheal intubation using fiberoptic bronchoscope. For intubation in FOB group, after placing the patient's head in the sniffing position, a jaw thrust was performed by an experienced assistant. He placed the fingers behind the posterior ramus of the mandible, at the same time the thrust directed upward and the thumbs opened the mouth. After exposure of the glottis, the FOB was passed between the vocal cords and downward into the trachea. To avoid stimulation of the carina, we advanced the tip of the FOB into the trachea no more than 3-4 cm below the glottis. A tracheal tube was then advanced over the FOB while rotated counterclockwise. After insertion of the tracheal tube into the trachea, the jaw thrust maneuver was stopped. The FOB was then removed after confirmation of the correct tracheal tube placement by auscultation of both lungs. All of patients in DLS group underwent conventional orotracheal intubation using a rigid Macintosh 3 (in women) or 4 (in men) laryngoscope blade. Fiberoptic and laryngoscopy intubations were performed by one anesthesiologist who was experienced in both methods. Before the induction of anesthesia, all patients were premedicated with intramuscular lorazepam 1 mg and morphine sulfate 0.1 mg/kg 1 hour before entering the operating room. Then, in the operating room, the electrocardiogram, invasive blood pressure, and arterial oxygen saturation by pulse oximetry were monitored. The electrodes of nerve stimulator were CARDIOVASCULAR RESPONSES TO OROTRACHEAL INTUBATION IN PATIENTS UNDERGOING CORONARY ARTERY BYPASS GRAFTING SURGERY applied at the volar side of the wrist for stimulation of the ulnar nerve. With placement of these electrodes, electrical stimulation normally elicits only finger flexion and thumb adduction. Induction of anesthesia with Etomidate 0.2 mg/kg, sufentanil 2.5 µg/kg and cisatracurium 0.2 mg/kg in both groups was done. After achieving hypnosis, determined as a loss of any response to verbal command and before muscle relaxant was injected, the mode of nerve stimulation was changed to TOF (train of four). Then, cisatracurium (0.2 mg/kg) was administered. Trachea was intubated when the response to TOF stimulation disappeared. Procedures were then started according to the study protocol. During the observation, a third person acted as the time keeper using a digital stopwatch, time zero was (zero seconds) when the response to TOF stimulation disappeared and facemask was removed from the patient. When the jaw thrust maneuver was stopped and ventilation was restarted through the tracheal tube and carbon dioxide was detected by capnography, this was recorded as total intubation time. Blood pressure and heart rate were measured and recorded before induction (T0), post induction (T1), at endotracheal intubation (T2), 1 and 2 minutes afterwards (T3, T4). The statistical analysis of data was performed with SPSS Version 15.0 statistical software (SPSS Inc, Chicago, IL). The intragroup differences among the circulatory variables recorded over time were analyzed using the repeated measures analysis of variance. Differences in mean values of circulatory variables were analyzed by using independent samples t test. The categorical variables in the two groups were analyzed by using Chi-square test or Fisher's exact test as appropriate. The differences in circulatory parameters in "the two consequent times" were analyzed by using paired t test. The hypothesis of this study was that there would be a clinically meaningful difference in the hemodynamic responses to two fiberoptic and laryngoscopy intubation methods. The quantitative data were expressed as mean ± SD. A P value of ≤0.05 was considered statistically significant for all tests. Results There were no significant differences between the two groups regarding the patients’ gender, age, 835 Mallampati score or ejection fraction. No significant differences were seen in the baseline values of BPs and HRs. The time required for intubation was significantly longer for the fiberoptic method compared with conventional intubation with laryngoscopy (34.9 ± 9.8 versus 19.3 ± 4.7 seconds, P = 0.0001; Table 1). Table 1 Clinical characteristics of the patients DLS N = 25 FOB* N = 25 P Age (yr) 53.0 ± 7.8 53.1 ± 6.9 0.970 Gender (male) 17 (68%) 16 (64%) 0.373 Ejection fraction 46.2 ± 3.9 47.4 ± 5.4 1.000 Mallampati score (I/II) 22/3 21/4 ? Intubation time(sec) 19.3 ± 4.7 34.9 ± 9.8 0.0001 = FOB: Fiberoptic bronchoscopy = DLS: Direct laryngoscopy After anesthesia induction, systolic and diastolic BP in the two groups decreased significantly compared with baseline values (p = 0.001). There was no statistically significant change in HR in FOB and DLS groups. Also, postinduction values of BP and HR were not significantly different between the two groups (p values >0.05). Compared with postinduction values, both FOB and DLS resulted in statistically significant increase in BP but not in HR (Fig. 1 and 2). There were no significant differences in the blood pressure or heart rate from before intubation to immediately after intubation between the FOB and DLS groups. At the second minute after intubation, no significant difference was observed between the two groups. BP and HR during intubation (T2) and after intubation were similar in both FOB and DLS group (p values> 0.05). The maximum values of SBP, DBP and HR during the observed periods were not statistically significantly different in the two study groups. During the observation, the times required to reach maximum values of SBP and HR were similar in the two groups, but the times required for recovery of SBP and HR to reach to the postinduction values were significantly slower in the FOB group than in the DLS group (Fig. 1 and 2). M.E.J. ANESTH 20 (6), 2010 836 Fig. 1 Variation in systolic (SBP) and diastolic blood pressure (DBP) in patients undergoing direct laryngoscopy or fiberoptic brnchoscopy (FOB) for orotracheal intubation Fig. 2 Variation in heart rate in direct laryngoscopy and fiberoptic brnchoscopy groups Discussion One advantage of the fiberoptic intubation is that it can avoid the mechanical stimulus to the base of tongue, epiglottis and the receptors in the pharyngeal muscles exerted by direct laryngoscope. Some studies have shown that the cardiovascular responses to tracheal intubation are greatly inhibited by attenuating or avoiding the oropharyngolaryngeal stimuli15-18. The primary goal of this investigation was to determine whether there is a clinically relevant difference between the circulatory responses to FOB and DLS in coronary artery disease patients anesthetized for CABG surgery. We examined whether fiberoptic intubation attenuated hemodynamic responses to orotracheal intubation, compared with those that occurred with N. Aghdaii et al laryngoscopy. The results of this investigation suggest that bronchoscopy do not suppress the hemodynamic response to endotracheal intubation more than the response to laryngoscopy. It is well known that the stimuli to airway structures are the main causes of circulatory responses to tracheal intubation19. Laryngoscopy itself is one of the most invasive stimuli during orotracheal intubation20-21. Many anesthesiologists agree that a skilled anesthesiologist applies only a small force to the patient’s larynx when using a laryngoscope and that reducing the force on the larynx might prevent excessive hyperdynamic responses to orotracheal intubation22-24. It is possible to separate the factors that contribute to the hemodynamic responses to orotracheal intubation21. The first is the response to laryngoscopy and the second is the response to endotracheal intubation. Hemodynamic changes start within seconds of direct laryngoscopy, and there is a further increase in heart rate and blood pressure with passage of the tracheal tube. It is not known which component is more responsible for the hyperdynamic response to orotracheal intubation. Although we attempted to reduce the hyperdynamic responses to intubation by using fiberoptic bronchoscopy without deep insertion in the trachea, there was no statistically significant difference in the cardiovascular variables between the fiberoptic bronchoscopy (FOB) and direct laryngoscopy (DLS) groups. The results of our study correspond with those of other previous studies25-29. whereas other investigators demonstrated the effectiveness of avoiding laryngoscopy using new devices4,13-17,22-25. This study shows that under the general anesthesia orotracheal intubation using the FOB and DLS caused similar increases in BPs and HRs. This suggests that the FOB can not attenuate the cardiovascular responses to orotracheal intubation compared to the DLS. This can be due to the longer intubation time in FOB group that cause hypercapnia, which can result in hypertention and tachycardia7,29, the airway clearance maneuver (jaw thrust maneuver) that is necessary for FOB intubation, or irritation of trachea by insertion and removal of FOB. In our study, the mean intubation time is significantly longer in the FOB group than in the DLS group. The lifting of the jaw upward to make a clear passage for the FOB and for the tracheal tube to enter the glottis can cause cardiovascular responses. Hirabayashi et al30. CARDIOVASCULAR RESPONSES TO OROTRACHEAL INTUBATION IN PATIENTS UNDERGOING CORONARY ARTERY BYPASS GRAFTING SURGERY demonstrated that, in anesthetized adults receiving lightwand-guided tracheal intubation, the magnitude of stimulus from the jaw thrust maneuver was sufficient to cause circulatory responses similar to those observed in laryngoscopic intubation. Thus, one might argue that the differences in nociceptive stimulation from the jaw thrust maneuver cause the differences in the circulatory responses between the fiberoptic and laryngoscopic intubation methods. In addition, the successful intubation (the advancement of the tracheal tube over the FOB) often requires some specific maneuvers e.g. rotating the tracheal tube, further lifting jaw upward and adjusting the patient's head-neck position. All these procedures are blind and invasive, and may further 837 stimulate pharyngolaryngeal structures and the trachea. In contrast, with the direct laryngoscopic intubation, only the tracheal tube is inserted into the trachea under direct vision. The laryngoscopy produces a balanced stimulation of vagal and cardiac accelerator fibers, whereas the intratracheal manipulation produces less vagal stimulation31. In conclusion, our study demonstrated that the orotracheal intubations using a FOB and a DLS produced similar hemodynamic responses. The FOB had no special advantage in attenuating hemodynamic responses to orotracheal intubation compared to the DLS. M.E.J. ANESTH 20 (6), 2010 838 N. Aghdaii et al References 1.McCoy EP, Mirakhur RK, McCloskey BV: A comparison of the stress response to laryngoscopy. The Macintosh versus the McCoy blade. Anaesthesia; 1995, 50:943-946. 2.Shinji T, Taro M, Masayuki M, Hidenori T: Hemodynamic responses to tracheal intubation with laryngoscope versus lightwand intubating device (Trachlight®) in adults with normal airway. Anesth Analg; 2002, 95:480-4. 3.Choyce A, Avidan MS, Harvey A, et al: The cardiovascular response to insertion of the intubating laryngeal mask airway. Anaesthesia; 2002, 57:330-333. 4.Yoshihiro H, Shuji D: Differences in cardiovascular response to airway stimulation at different sites and blockade of the responses by lidocaine. Anesthesiology; 2000, 93:95-103. 5.Latorre F, Hofmann M, Kleemann PP, Dick WF: Stress response to nasotracheal intubation: a comparative evaluation of fiberendoscopic vs. laryngoscopic intubation with and without topical anaesthesia of the larynx. Anaesthetist; 1993, 42:423-6. 6.Rose DK, Cohen MM: The airway: Problems and predictions in 18,500 patients. Can J Anaesth; 1994, 41:372-383. 7.Takita K, Morimoto Y, Kemmotsu O: Tracheal lidocaine attenuates the cardiovascular response to endotracheal intubation. Can J Anaesth; 2001, 48:732-736. 8.Schaefer HG, Marsch SC, Strebel SP, Drewe J: Cardiovascular effects of fibreoptic oral intubation. A comparison of a total intravenous and a balanced volatile technique. Anaesthesia; 1992, 47:1034-1036. 9.Mustola ST, Baer GA, Metsa-Ketela T, Laippala P: Haemodynamic and plasma catecholamine responses during total intravenous anaesthesia for laryngomicroscopy. Thiopentone compared with propofol. Anaesthesia; 1995, 50:108-113. 10.Maguire AM, Kumar N, Parker JL, Rowbotham DJ, Thompson JP: Comparison of effects of remifentanil and alfentanil on cardiovascular response to tracheal intubation in hypertensive patients. Br J Anaesth; 2001, 86:90-3. 11.Neidhart PP, Champion P, Vogel J, Zsigmond EK, Tassonyi E: A comparison of pipecuronium with pancuronium on haemodynamic variables and plasma catecholamines in coronary artery bypass patients. Can J Anaesth; 1994, 41:469-474. 12.Kirvela M, Scheinin M, Lindgren L: Haemodynamic and catecholamine responses to induction of anaesthesia and tracheal intubation in diabetic and non-diabetic uraemic patients. Br J Anaesth; 1995, 74:60-65. 13.Nishikawa K, Omote K, Kawana S, Namiki A: A comparison of hemodynamic changes after endotracheal intubation by using the lightwand device and the laryngoscope in normotensive and hypertensive patients. Anesth Analg; 2000, 90:1203-7. 14.Tsubaki T, Aono K, Nakajima T, Shigematsu A: A Blood pressure, heart rate and catecholamine response during fiberoptic nasotracheal intubation under general anesthesia. J Anesth; 1992, Oct. 6(4):4749. 15.Hawkyard SJ, Morrison A, Doyle LA, Croton RS, Wake PN: Attenuating the hypertensive response to laryngoscopy and endotracheal intubation using awake fiberoptic intubation. Acta Anaesthesiol Scand; 1992, 36:1-4. 16.Kitamura T, Yamada Y, Chinzei M, Du HL, Hamaoka K: Attenuation of haemodynamic responses to tracheal intubation by the StyletScope. Br J Anaesth; 2001, 86:275-7. 17.Nishikawa K, Kawana S, Namiki A: Comparison of the lightwand technique with direct laryngoscopy for awake endotracheal intubation in emergency cases. J Clin Anesth; 2001, 13:259-63. 18.Kimura A, Yamakage M, Chen X, Kamada Y, Namiki A: Use of the fibreoptic stylet scope (Styletscope) reduces the hemodynamic response to intubation in normotensive and hypertensive patients. Can J Anaesth; 2001, 48:919-23. 19.Xue FS, Li CW, Liu KP, Sun HT, Zhang GH, Xu YC, Liu Y: Circulatory Responses to Fiberoptic Intubation in Anesthetized Children: A Comparison of Oral and Nasal Routes. Anesth Analg; 2007, 104:283-288. 20.Kovak AL: Controlling the hemodynamic response to laryngoscopy and endotracheal intubation. J Clin Anesth; 1996, 8:63-79. 21.Adachi YU, Satomoto M, Higuchi H, Watanabe K: Fentanyl attenuates the hemodynamic response to endotracheal intubation more than the response to laryngoscopy. Anesth Analg; 2002, Jul. 95(1):233-7, table of contents. 22.Bishop MJ, Harrington RM, Tencer AF: Force applied during tracheal intubation. Anesth Analg; 1992, 74:411-4. 23.Bucx MJ, Snijders CJ, Van Geel RT, et al: Forces acting on the maxillary incisor teeth during laryngoscopy using the Macintosh laryngoscope. Anaesthesia; 1994, 49:1064-70. 24.Tong JL, Ashworth DR, Smith JE: Cardiovascular responses following laryngoscope assisted, fibreoptic orotracheal intubation. Anaesthesia; 2005, 60:754-8. 25.Adachi YU, Takamatsu I, Watanabe K, Uchihashi Y, Higuchi H, Satoh T: Evaluation of the cardiovascular responses to fiberoptic orotracheal intubation with television monitoring: comparison with conventional direct laryngoscopy. J Clin Anesth; 2000, 12:503-8. 26.Barak M, Ziser A, Greenberg A, Lischinsky S, Rosenberg B: Hemodynamic and catecholamine response to tracheal intubation:direct laryngoscopy compared with fiberoptic intubation. Journal of Clinical anesthesia; 2003, 15:132-6. 27.Xue FS, Zhang GH, Li XY, Sun HT, Li P, Li CW, Liu KP: Comparison of hemodynamic responses to orotracheal intubation with the GlideScope videolaryngoscope and the Macintosh direct laryngoscope. J Clin Anesth; 2007, Jun, 19(4):245-50. 28.Xue FS, Zhang GH, Sun HT, Li CW, Li P, Liu KP, Xu YC, Liu Y, Liu J: A comparative study of hemodynamic responses to orotracheal intubation with fiberoptic bronchoscope and laryngoscope in children. Paediatr Anaesth; 2006, Jul. 6(7):743-7. 29.Xue FS, Zhang GH, Li XY, Sun HT, Li P, Sun HY, et al: Comparison of haemodynamic responses to orotracheal intubation with glidescope (R) videolaryngoscope and fibreoptic bronchoscope. Eur J Anaesthesiol; 2006, 23:522-526. 30.Hirabayashi Y, Hiruta M, Kawakami T, Inoue S, Fukuda H, Saitoh K, Shimizu R: Effects of lightwand (Trachlight) compared with direct laryngoscopy on circulatory responses to tracheal intubation. Br J Anaesth; 1998, 81:253-5. 31.Shribman AJ, Smith G, Achola KJ: Cardiovascular and catecholamine responses to laryngoscopy with and without tracheal intubation. Br J Anaesth; 1987, 59:295-9. EFFECTS OF INTRAOPERATIVE-INTRATHECAL SUFENTANIL INJECTION ON POSTOPERATIVE PAIN MANAGEMENT AFTER SINGLE LEVEL LUMBAR DISCECTOMY Saeid Abrishamkar*, Mohammadhossein Karimi**, Mohammadreza Safavi***, Azim Honarmand*** and A fshin S afavi **** Abstract Background: For lumbar disc operation a chain of painful procedures including skin incision, muscle dissection and sometimes laminectomy should be performed. The combination of these manoeuvres results in significant post-operative pain. The standard way to reduce post-operative pain consist of intra-operative injection of local anaesthetic (Bupivicaine or Lidocaine) to the superficial tissues and intravenous, oral or rectal prescription of Opioid analgesics or other analgesics after operation, but inadequate analgesia, constipation and delayed mobilisation are frequent side effect of those treatments. The goal of this study was to reduce postoperative pain of patients which causes a reduction in analgesic consumption and eventually shortened hospital stay and acceleration in physical therapy programs and ambulation. Materials and Methods: After ethical comitte approval, patients allocated in two groups A and B. Each group consisted 30 patients which all of them underwent general anesthesia. All of operations performed by same surgeon... After discectomy and at the end of surgerybased on patients odd or even number of hospital admission, one group (group-A) received sufentanil (Iranian pharmaceutic company) 0.05/kg intrathecaly injected in surgical level and the placebo group (group-B) normal saline was injected. In recovery room when patients were sufficiently awake for pain assessment, patients were asked to score pain on the verbal pain assessment score In both groups we compaired pain scores pre and postoperativly. The total dose of opioid requirement for patients and its time after operation was recorded. From the Departments of Neurosurgery, Anesthesiology and Intensive Care units, Isfahan University of Medical Sciences, Isfahan, Iran. * MD, Associate Professor of Neurosurgery, and Intensive Care Unit. ** MD, Neurosurgery and Intensive Care Unit. *** MD, Assistant Professor of Anesthesia and Intensive Care Unit. **** MD, Anesthesiology and Intensive Care Unit. Corresponding Author: Mohammadreza Safavi, MD, Assistant Professor of Anesthesia and Intensive Care, Department of Anesthesiology and Intensive Care Unit, Isfahan University of Medical Sciences, Isfahan, Iran. Tel: 00989133152416, Fax: 0098 (311)2732659, E-mail: [email protected] 839 M.E.J. ANESTH 20 (6), 2010 840 S. Abrishamkar Et Al Results: Introduction Of the 60 patients (ASA classes I and II) entering the study, no one excluded during our study. 30 patients received intrathecal injection of sufentanil as group-A or case and 30 patients normal saline as group-B or control. Mean age between two groups showed no significant difference. 45.7 year (SD = 11.5) for group-A and 44.3 year (SD = 9.9) for group-B which did not differ between two groups (P = 0.617). Urinary retension happened in 3 patients of group-A and 3 patients of group-B (P = 1). Pruritis happened in 1 patient of group-A and no patient in group-B (P = 0.15). Patients in group-A had reduced analgesic requirments (P = 0.01). Preoperative low back pain based on NPS (numerical pain scores) criteria in group-A shows score 1, (n = 7) score 2, (n = 10) score 3, (n = 11) and score 4 (n = 2) (mean = 2.2667 and SD = 0.9072). These scores in group-B showed score 2 (n = 4) score 3 (n = 16) and score 4 (n = 10) (mean = 3.2 and SD = 0.6644) (P <0.001). After surgery low back pain assessment in two groups shows in group-A three patients had score 1, score 2, (n = 7) score 3, (n = 11) score 4, (n = 8) score 5 (n = 1) (mean = 2.9 and SD = 1.0289) and in group-B score 4 (n = 17) score 5 (n = 13) (mean = 4.4333 and SD = 0.5040) (P <0.001). Preoperative lower extremity radicular pain assessment in two groups shows a mean pain score of 8.3 with SD = 0.9523 in group-A and a mean of 8.3448 with SD = 1.1109 in group-B and after operation a mean pain score of 1.7333 with SD = 0.8277 in group-A and a mean of 4.1667 with SD = 0.7466 in group-B. In walking ability assessments pre and postoperatively based on Mann-Whitney test it is shown that in group-A walking ability is better than group-B (P <0.001). Lumbar disc herniation surgery is a common surgical procedure performed within neurosurgical and some orthopedics departments. It is usually carried out for lumbar degenerative condition mostly affecting those patients between 30 to 40 years old1. For lumbar disc operation a chain of painful procedures including skin incision, muscle dissection and sometimes laminectomy should be performed. The combination of these maneuvers results in significant post-operative pain. Conclusion: In this study we studied the efficacy of intraoperative-intrathecal sufentanil injection versus placebo on post operative pain management. Our study showed that intrathecal (IT) sufentanil provided more effective analgesia postoperatively after single level disccectomy. Urinary retention was equal in two groups. For more exact conclusions it is better to do a similar study on more patients. Key words: intrathecal sufentanil -postoperative pain-lumbar discectomy. The standard way to reduce post-operative pain consist of intra-operative injection of local anaesthetic (Bupivicaine or Lidocaine) to the superficial tissues and intravenous, oral or rectal prescription of Opioid analgesics or other analgesics after operation, but inadequate analgesia, constipation and delayed mobilization are frequent side effect of these treatments1,3. Lumbar intrathecal (IT) opioids have been used as an adjunct to post thoracotomy analgesia4,5,6,7 but the available literature6 has not clearly demonstrated the clinical usefulness of this technique for pain reduction in lumbar disc operaiton. Intrathecal analgesia has been used after “lumbar spine procedures”7, spinal fusion8, laminectomy, discectomy, hemilaminotomy, and foraminotomy9. Epidural analgesia was used after lumbar laminectomy10, posterior, anterior or combined fusion11, posterior fusion2,4 with or without decompression10, and after posterior or anterior-posterior lumbar fusion3. For continuous postoperative analgesia, epidural administration is an established and safe method used routinely for other operative procedures. Epidural opioids10, ropivacaine3,4, or a combination of opioids with bupivacaine2,11, have been reported to be useful after spine surgery. Patients’ postoperative functional rehabilitation is hampered by intense postoperative pain. Although fairly high doses of IV opioids are typically necessary, epidural analgesia may result in fewer side effects. The goal of this study was to reduce postoperative pain of patients which causes a reduction in analgesic consumption and eventually shortened hospital stay and acceleration in physical therapy programs and ambulation. EFFECTS OF INTRAOPERATIVE-INTRATHECAL SUFENTANIL INJECTION ON POSTOPERATIVE PAIN MANAGEMENT AFTER SINGLE LEVEL LUMBAR DISCECTOMY Materials and Methods The ethical committee of our university approved this interventional double blind &case series study. This study was performed on patients which needed a surgical intervention for lumbar disc herniation in ayatollah kashani hospital of Isfahan university of medical sciences. Number of patients allocated for this study was based on 1% of general population which experience low back pain during their life and 10% of them which may need surgical intervention (0.0001 of general population). Patients were excluded if they had more than one level disc herniation, previously underwent operation for disc herniation, age more than 60 years, spinal canal stenosis, patients refusal for intrathecal injection and patients who encountered a surgical complication (eg. nerve root injury, thecal or sac laceration…). Based on these statistical information and exclusive criteria 60 patients entered our study which were divided in to two 30 patients groups based on their hospital admission number. In all patients general anesthesia was induced with thiopental(5-7 mg/kg) and fentanyl (1-1.5 microgm/kg). Atracurium (0.6 mg/kg) was administrated to facilitate endotracheal intubation. Anesthesia was maintained with Nitrous Oxide (N20/O2 ratio50% /50%) and Isoflurane (up to1.3 MAC). Atracurium increments were used to facilitate mechanical ventilation of the lung. Also morphine (0.15 mg/kg administrated intravenously at the start of surgery. Whenever the blood pressure or heart rate increased by more than 30%, so that depth of anesthesia was judged inadequate, hemodynamic control was ensured with incremental doses of IV fentanyl (50-100 microgm). All operations were performed by the same surgeon. After discectomy and at the end of surgery based on patients number of hospital admission, one group (group-A) received sufentanil (Iranian pharmaceutic company) 0.05/kg intrathecaly injected in surgical level and the placebo group (group-B) normal saline was injected. Resident which should control post operative pain scores questionare don’t knows which substance is injected. Then it was blinded to type of injection. In recovery room when patients were sufficiently awake for pain assessment, patients were asked to score pain on the verbal pain assessment score (Table 1). 841 Table 1 Numerical pain score Score Quality of Pain 1 No pain 2 Mild pain 3 Pain that cause the patient discomfort 4 Pain that cause the patient searching medical care 5 Moderate pain that is still supportable 6 Pain that make the patient fill completely discomfort 7 Pain that cause the patient to stop all activities 8 Severe pain rarely have been experienced 9 Very severe pain 10 Pain as worst as possible The motor ability of patients was assessed based on 1-5 criteria. Pain assessment was performed every 12 hours for first two postoperative days and morphine was administrated if pain score was greater than 9 (0.05 mg/kg). Most of patients were discharged after two days of hospitalization. In both groups we compared pain scores pre and postoperativly. The total dose of opioid requirement for patients and its time after operation was recorded. Hemodynamic variables, vertigo, pruritis and urinary retention were recorded in two groups of study. All of these probable side effects were monitored in post operation period and if happened recorded. The primary outcome measure was a visual analogue pain score which recorded in recovery, on the first and second post-operative days. Secondary outcome measures were length of post-operative hospital stay, post-operative analgesia required-total dose and types per 24 hours for first two days. All opiod analgesics will be converted to morphine equivalents and side effects by day 2 including urinary retention, nausea, vomiting and pruritis and hemodynamic variables. Statistical Analysis Pain scores were ranked data that should be distributed in a normal distribution. Analysis was therefore by a Mann Whitney rank sum test. Length of hospital stay was continuous data so the t test was used for analyzing. M.E.J. ANESTH 20 (6), 2010 842 S. Abrishamkar Et Al The prevalence of side effects will be analysed using a Chi2 test. The total intra and post-operative analgesia requirement was converted to morphine equivalents and I\IIanalyzed using a t test. No subgroup analysis was undertaken. Trial termination The trial ended when the last patient was discharged from hospital Results Sixty patients were included, 30 in Group A and 30 in Group B. No patient was excluded from the study. The two groups were similar with respect to demographic variables, duration of surgery and anesthesia (Table 1). Table 1 Demographic and intra-operative data (ASA I\II) Group A (n = 30) Group B (n = 30) 45.7 ± 11.5 44.3 ± 9.9 21/9 19/11 Weight (kg) 82/3 ± 11.1 77.8 ± 12.3 Duration of anesthesia (min) 54.0 ± 7.1 52.7 ± 7.4 Duration of surgery (min) 39.0 ± 5.6 36.8 ± 5.8 Age (yr) Gender (M/F) Data are presented as mean± SD or number of patients. There was no significant difference between two groups. Three patients in each group had urinary retention (P = 1.0). One patient in group A and no patient in group B had pruritus (P = 0.15). The postoperative morphine requirements were significantly less in group A when compared with group B (5 mg vs 20. mg, P = 0.01). Preoperatively, there was no significant difference in mean (± SD) NPS score at rest in two groups (3.0 ± 0.5 in group A vs. 3.1 ± 0.6 in group B, P = 0.64). After surgery, mean (± SD) NPS score was significantly less in group A compared with group B (2.9 ± 1.03 in group A vs. 4.4 ± 0.5 in group B, P < 0.001). Incidence of different NPS scores in two groups was shown in figure 1. Preoperatively, there was no significant difference in mean (± SD) lower extremity radicular pain assessment score (NPS score) in two groups (8.3 ± 0.9 in group-A vs. 8.3 ± 1.1 in group-B, P = 0.803). After surgery, mean (± SD) lower extremity radicular pain assessment score (NPS score) was significantly Fig. 1 The incidence of different NPS scores in group A and group B Group A Group B 18 16 14 12 10 8 6 4 2 0 1 2 3 4 5 6 7 8 9 10 less in group-A compared with group-B (1.7 ± 0.8 in group-A vs. 4.2 ± 0.7 in group-B, P <0.000). Incidence of different lower extremity radicular pain assessment score (NPS score) in two groups was shown in figure 2. In walking ability assessments pre and postoperatively based on Mann-Whitney test it is shown that in group-A walking ability is better than group-B (P <0.001). Walking ability of patients was assessed based on scores listed in table 1. 1 Table 1 Walking ability scores after lumbar discectomy Patient is returned to near normal lifestyle and normal movements with no significant pain. 2 Significant improvement in patients’ movements with mild restriction due to low back pain and some degree of pain in extremities. 3 Partial improvement in patients movements with some intermediate pain and discomfort but the patient is able to walk. 4 Only mild improvement in movements and pain that make the patient fill completely discomfort. 5 There is no difference between preoperative and post operative pain and walking ability. Discussion The aim of postoperative pain relief is to provide subjective comfort in addition to inhibiting nociceptive impulses. Autonomic and somatic reflexes responses to pain can be blunted, allowing the patient to breathe, cough and move more easily. It is not only the humanitarian feature of pain that must be assessed but also its ability to restore normal function. It is therefore necessary to assess and treat pain not only at rest but also during activity. In this study we studied the efficacy of intraoperative-intrathecal sufentanil injection versus placebo on post operative pain EFFECTS OF INTRAOPERATIVE-INTRATHECAL SUFENTANIL INJECTION ON POSTOPERATIVE PAIN MANAGEMENT AFTER SINGLE LEVEL LUMBAR DISCECTOMY management. Our study showed that intrathecal (IT) sufentanil provided more effective analgesia postoperatively after single level disccectomy. Urinary retention was equal in two groups of sufentanil and distilled water IT injection. Urinary retention has not been studied in previous7 studies. Pruritis happened in one of patients in group-A which was mild and spontaneously releafed and would be an expected side effect of opioids. In the study of Schenk et al on Postoperative Analgesia After Major Spine Surgery after intrathecal morphin injection on 72 patients 5 experienced pruritis1. Patients in group-A had reduced pain scores and analgesic requirments in comparision with group-B which only received distilled water as placebo. Mean pain scores in group-A which received IT sufentanil was 2.2667 but in group-B our study showed a higher score of about2,3. In the study of Riad et al Patients in the morphine group had significantly lower median numerical rating score (NRS) for pain on movement at 4h [0 versus 3.5] (P = 0.0008) and 8h [0 versus 4] (P = 0.0083)12. In addition, median PCA morphine consumption was significantly reduced at 4h [0 versus 1] (P = 0.0005), 8h [0.5 versus 6] (P = 0.0063) and 12h [3 versus 8.5] (P = 0.0426) 843 in the morphine group12. After surgery low back pain assessment in two groups shows that in n group-A the mean pain score is 2.9 compared with 4.43 in group-B. Preoperative lower extremity radicular pain assessment in two groups shows a mean pain score of 8.3 with SD = 0.9523 in group-A and a mean of 8.3448 with SD = 1.1109 in group-B which shows an equlity. After operation a mean pain score of 1.7333 with SD = 0.8277 in group-A and a mean of 4.1667 with SD = 0.7466 in group-B that shows a very effective pain reduction with sufentanil. In walking ability assessments pre and postoperatively based on MannWhitney test it is shown that in group-A scores are better than group-B. (P <0.001) which means a better quality of walking ability between patients reaciving sufentanil inntraoperativly. As a final conclusion from this study it is obviated that intrathecal sufentanil causes better pain tolerance and eventually reduction of post operative analgesic needs and more satisfaction and better walking abilities after surgery compaired with patients who have reacived placebo. Side effects like pruritis or urinary retention were negligible for patients. For more exact conclusions it is better to do a similar study on more patients. M.E.J. ANESTH 20 (6), 2010 844 S. Abrishamkar Et Al References 1.Schenk MR, Putzier M, Kugler B, Tohtz S, Voigt K, Schink T, et al: Postoperative analgesia after major spine surgery: patientcontrolled epidural analgesia versus patient-controlled intravenous analgesia. Anesth Analg; 2006, 103(5):1311-1317. 2.Gottschalk A, Freitag M, Liehr K, Domke A, Schuster M, Standl T: [Does patient satisfaction correlate with pain level during patientmonitored epidural analgesia. Evaluation of data from postoperative pain service]. Schmerz; 2004, 18(2):145-150. 3.Bernards CM, Shen DD, Sterling ES, Adkins JE, Risler L, Phillips B, et al: Epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidural opioids (part 2): effect of epinephrine. Anesthesiology; 2003, 99(2):466-475. 4.Bernards CM, Shen DD, Sterling ES, Adkins JE, Risler L, Phillips B, et al: Epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidural opioids (part 1): differences among opioids. Anesthesiology; 2003, 99(2):455-465. 5.Bonhomme V, Doll A, Dewandre PY, Brichant JF, Ghassempour K, Hans P: Epidural administration of low-dose morphine combined with clonidine for postoperative analgesia after lumbar disc surgery. J Neurosurg Anesthesiol; 2002, 14(1):1-6. 6.Capogna G, Parpaglioni R, Lyons G, Columb M, Celleno D: Minimum analgesic dose of epidural sufentanil for first-stage labor analgesia: a comparison between spontaneous and prostaglandin- induced labors in nulliparous women. Anesthesiology; 2001, 94(5):740-744. 7.Liu N, Kuhlman G, Dalibon N, Moutafis M, Levron JC, Fischler M: A randomized, double-blinded comparison of intrathecal morphine, sufentanil and their combination versus IV morphine patient-controlled analgesia for postthoracotomy pain. Anesth Analg; 2001, 92(1):31-36. 8.Hormann C, Langmayr J, Schalow S, Benzer A: Low-dose sufentanil increases cerebrospinal fluid pressure in human volunteers. J Neurosurg Anesthesiol; 1995, 7(1):7-11. 9.Hansdottir V, Hedner T, Woestenborghs R, Nordberg G: The CSF and plasma pharmacokinetics of sufentanil after intrathecal administration. Anesthesiology; 1991, 74(2):264-269. 10.Bernards CM, Shen DD, Sterling ES, Adkins JE, Risler L, Phillips B, et al: Epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidural opioids (part 2): effect of epinephrine. Anesthesiology; 2003, 99(2):466-475. 11.Wiebalck A, Brodner G, Van AH: The effects of adding sufentanil to bupivacaine for postoperative patient controlled epidural analgesia. Anesth Analg; 1997, 85(1):124-129. 12.Riad T, Williams B, Musson J, Wheatley B: Intrathecal morphine compared with diamorphine for postoperative analgesia following unilateral knee arthroplasty. Acute Pain; volume 4, Issue1, page 5. THE EFFECTS OF DURATION OF PROPOFOL INJECTION ON HEMODYNAMICS Abdul Zahoor* and Nauman Ahmed** Abstract Objectives: The aim of study was to see whether increasing the time of injection of standard dose of Propofol during induction can prevent fall in blood pressure in female patients; as is commonly observed with this anesthetic agent. Design: Comparative, non-interventional, prospective, and randomized and single blind study. Place and duration: The study was carried out on female in-patients admitted and surgically operated at a specialized, tertiary care hospital and was completed with in 6-months. Patients and methods: The hemodynamic effects of Propofol were compared in three groups of patients undergoing minor surgical procedures. Each group comprised of 25 patients. A 2 mg/kg Propofol was administered for 30, 60 and 120 seconds in patients of group-A, group-B and group-C respectively. Baseline heart rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressures were recorded before induction of anesthesia. The same hemodynamic variables were recorded after induction at one-minute intervals for 10-minutes. Anesthesia was maintained with 1.5% enflurane and 60% nitrous oxide in oxygen. Complications such as pain on injection, dystonic movements, erythema, laryngeal spasm, episodes of desaturation, hypoventilation and the number of additional boluses required to induce hypnosis were also recorded. Results: The fall in blood pressure was statistically insignificant between the three groups of patients. The incidence of dystonic movements was the highest in group-A while pain on injection was highest in group-C. Additional boluses of Propofol to induce hypnosis were required for patients in group-B and group-C. Conclusion: Varying the speed of injection of Propofol during induction of anesthesia in adult female patients does not cause any major difference in the drop of their heart rate, systolic blood pressure, diastolic pressure and mean arterial pressure. Key words: Anesthetics, intravenous, Propofol, hemodynamics. * MD, FCPS. ** MBBS, FCPS. Department of Anesthesia, King Khaled Eye Specialist Hospital, PO Box 7191, Riyadh 11462, Kingdom of Saudi Arabia Corresponding Author: Abdul Zahoor, MD, FCPS, Consultant Anesthesiologist, King Khaled Eye Specialist Hospital. P.O Box: 7191, Riyadh 11462, Kingdom of Saudi Arabia. Phone; Mobile +966509003709, Phone: +966-1-4821234, ext. 3995, Fax: +9661-4821908, E-mail: [email protected] and [email protected]. 845 M.E.J. ANESTH 20 (6), 2010 846 Introduction Propofol is a well accepted intravenously administered anesthetic agent and, by virtue of its pharmacodynamic properties, is considered a popular choice both for the induction as well as in the maintenance of anesthesia1. Propofol was first introduced into clinical practice in about two decades back. Over the years, extensive clinical experiences with Propofol in a wide variety of patients during different surgical procedures have demonstrated its effectiveness2. Propofol has been claimed to be the best available drug because of its rapid and smooth induction, short duration of action and a swift and clear headed recovery3. The standard Propofol dose of 2 mg/kg given over the recommended time of 30-seconds to pre-medicated patients is associated with a few disadvantages. The patients may experience pain during injection of Propofol, some patients exhibit dystonic movements and in majority of patients, there is a significant drop in blood pressure on induction1,4,5. The pain on Propofol injection can be treated in different ways, including mixing Propofol with Lidocaine, injecting Lidocaine into the same vein before injecting Propofol, injecting cold saline before the injection or refrigerating the emulsion before injection. The pain on Propofol injection can also be reduced by selecting large size veins for administration of the drug6-9. Dystonic movements occur in a small percentage of patients, which are usually transient10. The fall in blood pressure in patients remains a major problem during induction with Propofol, especially in hypertensive patients, patients having ischemic heart disease and those with cerebro-vascular disease, where a fall in blood pressure can lead to myocardial or cerebral ischemia. The aim of this study was to see whether increasing the time of injection of a standard dose of Propofol prevents the fall in blood pressure. Methods The study was initiated after approval from the hospital’s project review board and ethics committee. Seventy five American society of anesthesiologists (ASA) grade I & II patients undergoing dilatation and A. Zahoor & N. Ahmed curettage (D & C) were randomly allocated to one of the three groups of patients. Patients with an ASA classIII or higher, patients with history of hypertension, peripheral vascular disease, diabetes and those with a history of sensitivity to egg proteins were excluded from the study. A written consent was obtained from all the patients who participated in the study. Patient demographics, including age, height and weight were recorded. All the patients were pre-medicated orally with 3 – 4 mg Lorazepam, 2 hours before administering anesthesia. Baseline measurement of heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure were recorded with a noninvasive automatic blood pressure measuring machine (Dinamap Pro 400 V2, GE healthcare, USA). One 18 gauge canula was inserted into a large peripheral vein in one of the patient’s forearm. Two-milliliters of 2% Lidocaine was injected through the same vein before starting the injection of Propofol. The patients in group-A, group-B and group-C were administered a 2 mg/kg dose of Propofol for 30, 60 and 120 seconds respectively, using an infusion pump (Imed Gemini PC-1, Alaris Medical systems, San Diego, CA, USA). The heart rate, systolic blood pressure, diastolic blood pressure and arterial pressures were recorded every minute after induction of anesthesia for 10 minutes. In all the groups, after the loss of verbal contact with patient, anesthesia was maintained with 1.5% enflurane and 60% nitrous oxide in oxygen via face mask. An additional 10 mg bolus of Propofol was given to patients with whom verbal contact was not lost after a full induction dose of Propofol. The number of boluses required in each group were noted. Pain on injection and any other side effect including erythema at the site of injection or dystonic movement were also documented. Endotracheal intubations, patient’s positioning and surgery were delayed for 10 – 12 minutes after induction in order to avoid any kind of stimulus which could affect the hemodynamics. The quality of anesthesia was ensured by monitoring laryngo-spasm, episodes of apnea, desaturation, hypoventilation and any abnormal movements. SPSS version 14 was used to analyze the data of the study. Numerical data was analyzed by one way analysis of variance (ANOVA) and expressed as mean THE EFFECTS OF DURATION OF PROPOFOL INJECTION ON HEMODYNAMICS and standard deviation. Non-parametric data were compared with chi-square test. The values of statistical significance were taken as p < 0.05. Results The data was successfully obtained in all cases. The demographic data was comparable between the three groups. No statistically significant differences were found between the groups with respect to age, weight and height (Table I). The baseline hemodynamic variables including the heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure were also comparable and statistically insignificant (Table II). Soon after induction of anesthesia, a 15 – 20% decrease in the heart rate from the base line was generally observed in all patients. The drop in the heart rate was comparable between the three groups and there was no statistically significant difference between them (p > 0.05) (Fig. 1A).The systolic blood pressure decreased generally by 20 – 25% from the base line in patients of all groups and no statistically significant difference was observed between the three groups (p > 0.05) (Fig. 1B). The diastolic blood pressure in patients of all groups also decreased after induction of anesthesia by 22 – 28% from the base line. The decrease in diastolic 847 blood pressure was gradual and a maximum decrease was observed at the last minute of recording. There was no statistically significant difference in the decrease of diastolic blood pressure among the three groups (p > 0.05). However, the percent decrease in mean diastolic pressure was slightly different (22 – 28 %) than the percent decrease in mean systolic blood pressure (20 – 25%) among the three groups of patients (Fig. 1C). A general decrease in the mean arterial pressure by 20 – 25% from the base line was also noted parallel to the decrease in systolic and diastolic blood pressures, but no statistically significant difference was noted between the three groups (p > 0.05) (Fig. 1D). Moderate to severe pain was observed on injection of Propofol in 8 (32%) patients in group-A, 9 (36%) in group-B and 11 (44%) in group-C. This was despite the fact that all these patients were injected with Lidocaine in the same vein before the injection of Propofol. Erythema at the site of injection was noted in only one patient in group-C. Dystonic movements were observed in 6 (24%) patients in group-A, 4 (16%) in group-B and 3 (12%) in group-C. Other complications including laryngeal spasm, apnea (longer than 30 seconds), desaturation (SpO2 < 90%) and hypoventilation (End tidal carbon dioxide > 45 mmHg) were not observed in any patient among the three groups. Verbal contact by the end of 2 mg/kg Propofol injection was lost with Table I Demographics of patients included in the study Group A Group B Group C P-Value Age (Years) 28.68 ±4.5 29.0 ± 6.1 28.91 ± 6.1 0.95 Weight (Kilograms) 62.1 ± 8.1 62.30 ± 9.34 59.4 ± 6.1 0.34 Height (Centimeters) 153.96 ± 6.5 154.28 ± 6.6 154.0 ± 6.2 0.98 The data is the mean ± standard deviation (SD) of 25 patients (n = 25) in each group. Table II Baseline hemodynamic variables included in the study Group A Group B Group C P-Value Heart Rate min-1 93 90 88 0.99 Systolic blood pressure (mmHg) 120 127 116 0.98 Diastolic blood pressure (mmHg) 77 79 73 0.92 Mean Arterial pressure (mmHg) 88 93 85 0.90 The data is the mean of at least three readings from each of the 25 patients. M.E.J. ANESTH 20 (6), 2010 848 A. Zahoor & N. Ahmed Fig. 1 Heart rate (Fig. 1-A), Systolic blood pressure (Fig. 1-B), Diastolic blood pressure (Fig. 1-C) and Mean Arterial pressure (Fig. 1-D) were recorded in female patients for 10 minutes after induction with Propofol in patients in group-1 (―■―), group- 2 (---∆---) and group-3 (―▼―). all patients in group-A. However, 3 patients in group-B and 5 patients in group-C required additional boluses of 10 mg and 20 mg of Propofol respectively before they lost verbal contact. Discussion Propofol induced hypotension has been thought to act by different mechanisms. Propofol may lead to a reduction in the systemic vascular resistance and cardiac output is decreased by less than 20%4. Propofol induced hypotension is mediated by inhibition of the sympathetic nervous system and impairment of the baroreflex regulatory mechanism11. Similarly Propofol is considered to have a direct relaxant effect on venous smooth muscles and in this way an increase in venous capacitance may contribute to the hypotension in patients12. Propofol also has a negative inotropic effect on the heart and moderately depresses cardiac function (more than thiopentone and ketamine). The mechanism is thought to be the attenuation of the autoregulation of the heart which also leads to coronary vasodilatation13. In our study, no significant difference between the three groups of patients was observed with respect to the established hemodynamic effects of propofol, while a fall in systolic blood pressure, diastolic blood pressure and mean arterial pressures were comparable to other reported studies14. Rapid administration of Propofol probably results in an early peak drug concentration in plasma, thus providing a larger gradient for Propofol uptake into the central nervous system and for drug redistribution to other body tissues. This observation was studied by Rolly et al, 1985 who failed to induce THE EFFECTS OF DURATION OF PROPOFOL INJECTION ON HEMODYNAMICS anesthesia in 10% of his non-premedicated patients who received 2 mg/kg Propofol injected over 60 seconds, whereas the same dose was effective in all patients when injected for over five seconds15. This explains the need for additional boluses in our study in some patients in group-B and group-C. On the other hand, the slow increase in plasma drug concentration associated with a slow infusion provides a lower but more sustained gradient for uniform drug delivery throughout the central nervous system. However, by slow infusion a larger total dose may be required to maintain a sustained gradient of drug delivery into central nervous system. Increasing the duration of induction delayed the loss of verbal contact in some patients in group-B and group-C in the present study, however, the hemodynamic response was similar in all the three groups of patients. Our results confirm the reported observations of Gillies and Lees, 1989 where they found that 2.5 mg/kg Propofol injected over 20, 40 or 80 seconds resulted in a significantly slower induction compared to Etomidate (0.3 mg/kg) injected at equivalent rates16. They also found that although increasing the length of injection resulted in a slower induction, the hemodynamic response was not different between the 20, 40 and 80 seconds groups of the Propofol administered patients. Some studies have observed an initial tachycardia in patients after Propofol administration. However, most of the studies reported no change or decrease in the heart rate of patients after a bolus or infusion of Propofol15. In our study, the heart rate generally decreased by 15 – 20% in all groups of patients, which may be due to the absence of baroreflex activity and direct vagotonic effects of Propofol17. The overall reported incidence of pain on injecting Propofol is 17.5 – 74%, however, the incidence varies with the technique of administration18. The size and site of the vein, temperature and concentration of the solution and the use of Lidocaine can help in pain reduction in patients injected with Propofol to 34%1819 . In our study, the incidence of pain in group-A and 849 Group-B was comparable with the generally accepted incidence, however the frequency was higher in group-C compared to other studies5. Theoretically, patients in group-A and B had a lower incidence of pain because the effect was transient due to shorter duration of induction. However, patients in group-C had a delayed loss of consciousness due to longer period of induction and therefore experience of pain was also probably longer. The reported incidence of excitatory effects, including spontaneous movements, twitching, tremor, hypertonus and hiccups in patients as a result of Propofol induction is 14%1. We noticed similar complications among 6 (24%) patients in group-A, 4 (16%) in group-B and 3 (12%) in group-C. The incidence of excitatory effects was comparable in group-B and C but was slightly higher in-group-A. These observations indicate towards the possibility of an indirect correlation between the speed of injection of Propofol and dystonic movements. Further studies with larger sample size may be required to firmly correlate the incidence of pain on injection and dystonic movements with the speed of injection of Propofol. Conclusions Propofol is a well accepted intravenously administered anesthetic agent but it causes a significant drop in blood pressure on induction. From the results obtained in this study we may conclude that varying the speed of injection of Propofol for induction of anesthesia in adult female patients does not prevent the decrease in heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure. Administration of induction dose of Propofol (2 mg/ kg) in 60 seconds and 120 seconds is associated with increased requirement for additional boluses to induce complete hypnosis. Incidence of pain at the site of injection is also higher in this group of patients, while injecting the same dose of Propofol in 30 seconds is associated with a relatively higher incidence of dystonic movements. M.E.J. ANESTH 20 (6), 2010 850 A. Zahoor & N. Ahmed References 1. Shafer SL: Advances in propofol pharmacokinetics and pharmacodynamics. J Clin Anesth; 1993, 5:14S–21S. 2. Overbaugh R, Jones P, Nguyen A, Swaney G: Effect of mixed versus unmixed lidocaine with propofol. Internet J Anesthesiol; 2003, Vol. 7(2). 3. Picard P, Tramèr MR: Prevention of pain on injection with propofol: a quantitative systematic review. Anesth Analg; 2000, 90:963-9. 4. Barker P, Langton JA, Murphy P, Rowbotham DJ: Effect of prior administration of cold saline on pain during propofol injection. A comparison with cold propofol and propofol with lignocaine. Anesthesia; 1991, 46:1069-70. 5. Tariq MA, Kamran M: Incidence of pain on Propofol injection and efficacy of addition of lignocaine or selecting big vein or both combined in reducing it: A randomized control trial. J Postgrad Med Inst; 2006, 20:8–11. 6. Claey MA, Gepts E, Camu F: Hemodynamic changes during anesthesia induced and maintained with propofol. Br J Anesth; 1988, 60:3-9. 7. Ebert TJ, Muzi.M, Berens R, Goff D, Kampine JP: Sympathetic responses to induction of anesthesia in humans with propofol or etomidate. Anesthesiology; 1992, 76:725-33. 8. Muzi M, Berens RA, Kampine JP, Ebert TJ: Venodilation contributes to propofol mediated hypotension in humans. Anesth Analg; 1992, 72:877-83. 9. Stowe DF, Bosnjak ZJ, Kampine JP: Comparison of etomidate, ketamine, midazolam, propofol and thiopentone on function and metabolism of isolated hearts. Anesth Analg; 1992, 74:547-48. 10.Kobayashi Y, Tsuchida A, Kamada Y, Seki S, Ichimiya T, Namiki A: Effects of speed of injection on anesthesia induction with propofol and fentanyl. Masui; 1999, 48:847-57. 11.Rolly G, Versichelen L, Huyghe L, Mungroop H: Effects of speed of injection on induction of anesthesia using propofol. Br J Anesth; 1985, 57:743-6. 12.Gillies GWA, Lees NW: The effects of speed of injection on induction with propofol. A comparison with etomidate. Anesthesia; 1989, 44:386-8. 13.Malyshev VD, Zhdanov AM, Andriukhin IM, Omarov Kh T, Kheĭmets GI, Sviridov SV, Vedenina IV, Orudzheva SA: The effects of diprivan on the indices of central hemodynamics and the heart conduction system. Anesteziol Reanimatol; 1993, 4:11-14. 14.Stokes DN, Robson N, Hutton P: Effects of diluting propofol on the incidence of pain on injection and venous sequelae. Br J Anesth; 1989, 62:202-3. 15.Tham CS, Khoo ST: Modulating effects of lignocaine on propofol. Anesth Intensive Care; 1995, 23:154-7. 16.McCulloch MJ, Lees NW: Assessment and modification of pain on induction with propofol (Diprivan). Anesthesia; 1985, 40:1117-20. 17.Stark RD, Binks SM, Dutka VN, O'Connor KM, Arnstein MJ, Glen JB: A review of the safety and tolerance of propofol. Postgrad Med J; 1985, 61:152-6. 18.Fulton B, Sorkin EM: Propofol: An overview of its pharmacology and a review of its clinical efficacy in intensive care sedation. Drugs; 1995, 50:636-57. 19.Ananthanarayan C: Dystonic reaction after anesthesia. Can J Anaesth; 2001, 48:101-3. CONTINUAL INFUSION OF INTRATHECAL BACLOFEN (ITB): LONG TERM EFFECT ON SPASTICITY Dhafir Al Khudhairi*, Abdulrahman Shug’a Aldin**, Yousef Hamdan***, Abdullah Rababah****, Mona Hafez Matthana*****, Jiri Pazdirek****** and J alal A bdulsalam ******* Abstract Background: Spasticity is a disorder of muscular function causing muscular tightness or spasm which occurs when there is damage to the central nervous system whether it is of spinal cord or brain origin. This insult could be either pathological or traumatic. Method: Thirty-three patients had intrathecal Baclofen pumps implanted for severe spasticity. These patients either did not respond to or tolerate oral medications. Results: All patients showed significant improvement in their spasms following the procedure. Improvement was noted not only in spasticity, but also in pain, management of sleep disturbance, activities of daily living, indoor and outdoor mobility and behavior. Conclusion: The number of complications was acceptable, and generally were not lifethreatening. Infection was the significant complication in two patients and this led to explantation of their pumps. Patient satisfaction was very high and was related to improvement in the quality of life for the patients. * Fellow of the Faculty of Anaesthesia of the Royal College of Surgeons of Ireland, Director of Anaesthesia and Critical Care, Prince Sultan Cardiac Centre Consultant Chronic Pain Management, Riyadh Military Hospital and Sultan Bin Abdulaziz Humanitarian City. ** MBBS, Doctor of Medicine. *** Ba GP, Consultant Physiatrist. **** MBBS, Consultant Physiatrist. ***** MBChB, Ms, PhD, Consultant Physiatrist. ****** MD, Board in Orthopedics, Board in Physical Medicine and Rehabilitation Consultant Physiatrist. *******MD, Ms in Physical Medicine and Rehabilitation. Corresponding Author: Dr. Dhafir Al Khudhairi, FFARSCI, Director of Anaesthesia Department, Prince Sultan Cardiac Centre, Consultant Chronic Pain Management, Riyadh Armed Forces Hospital, Consultant Chronic Pain Management, Sultan Bin Abdulaziz Humanitarian City. Tel: +9661-4791000, ext: 8554, Fax: +9661-4760543, P.O. Box: 7897, Riyadh 11159, Kingdom of Saudi Arabia, E-mail: [email protected] 851 M.E.J. ANESTH 20 (6), 2010 852 D. Al Khudhairi et al Introduction depressant properties. Spasticity is a disorder of muscle function causing muscle tightness or spasm which occurs when there is damage to the central nervous system. Spasticity is a major disorder characterized by a velocity-dependant increase in tonic stretch reflex (muscle tone) with exaggerated tendon jerks resulting from hyperexcitability of the stretch reflexes as one component of the upper motor neurone syndrome1. This damage may result from spinal cord injury, traumatic brain injury, stroke, tumour, cerebral palsy or multiple sclerosis2,3,4,5,6,7. When spasticity cannot be managed efficiently, some of the associated problems can be dealt with in a number of ways, in addition severe, late and long term spasticity could be managed with periodic injections of Botulinum toxin or Phenol into the spastic muscle, or implantation devices like intrathecal pumps. Surgery is also indicated and performed in very severe and late cases. In a clinical setting severe spasticity not only reduces rehabilitation goals but produces ailments such as joint contractures leading to bad posture, pressure sores, detrusor-sphinctre dyssynergia and impaired motor function. Some workers have reported 25-35% rates of such seriously effected patients8. Spasticity can be debilitating and causes suffering in many ways such as muscle spasms, limited functional movement, impaired functional capacity, scissoring (involuntary crossing of legs), altered personal hygiene and pain. The pain may be neuropathic, resulting from deafferentation, central collateral sprouting or neural disinhibition. The pain may also be nociceptive/ somatic directly due to muscle spasm. Uncontrolled spasticity causes multiple problems, for example orthopaedic deformities, such as hip dislocation, contractures or scoliosis. It impairs personal hygiene and effects many other activities of daily living. In addition to all of the above, spasm can interfere with sleep and can result in depression. Spasticity is usually managed by a combination of oral medication with antispastic agents such as Baclofen, Tizanidine or Diazepam and physiotherapy and rehabilitation. Most of the mild to moderate spasticity cases are effectively managed with the conservative measures and available oral therapy mentioned, but cases of severe spasticity are less responsive. Since unacceptable CNS effects often occur when high doses of Baclofen are taken orally the therapeutic effect usually cannot be improved by an increase in dose. Sedation, somnolence, ataxia and respiratory and cardiovascular depression are the drug’s CNS The most effective treatment, with the least side effects is intrathecal Baclofen (ITB) and this therapy can be used if oral medications fail and this consists of long term delivery of Baclofen to the intrathecal space. It was first carried out by Penn and Kroin in 19842. ITB therapy gained US FDA approval for managing severe spasticity of spinal origin in 1992, and for severe spasticity of cerebral origin in 1996. Since then, several studies supporting this have been published by various authors9,10. The abundance of GABA-B receptors in the superficial layers of spinal cord means that intrathecal administration of Baclofen results in a greater than four-fold increase in the cerebrospinal fluid level with 1% of the oral dose3. This treatment can be very effective. The benefits of ITB typically include reduced tone, spasm and pain and also increased mobility. The use of ITB therapy as a treatment for spasticity requires a four phase approach: (1) patient selection, (2) screening, (3) implantation, and (4) dose adjustment and maintenance. Materials and Methods Between April 2004 until June 2009, 33 patients with severe spasticity had intrathecal Baclofen pumps implanted. Thirty-three patients out of the 45 tested proved positive to the intrathecal Baclofen drug test, 9 female and 24 male, ages ranging from 12 to 57 years. There were 18 spinal injury patients, 6 with demyelination disease and 9 with brain insult. The pumps implanted were all Medtronic and we used 5 pumps of 20cc Synchromed II, 27 of 40cc Synchromed II and one of 20cc Synchromed L. When patients have persistent and uncontrollable spasticity despite oral antispasmodic medications, they CONTINUAL INFUSION OF INTRATHECAL BACLOFEN (ITB): LONG TERM EFFECT ON SPASTICITY will be offered implantation of intrathecal Baclofen pumps. As mentioned, selection of patients is the first step to plan screening and see if intrathecal diagnostic tests will be of benefit to the patient. If this is successful then the next step is implantation and later on dose adjustment. In our institute we give a bolus dose of 50-100µg of Baclofen injected intrathecally in the diagnostic phase and spasticity is assessed over the next 10 hours, although the significant effect of intrathecal Baclofen would occur four hours after injection. The spasticity is assessed according to the Ashworth Score and when the Score improved (reduced) by around two scales then the patient was considered eligible for implantation. There are two choices of pump size, 20ml and 40ml capacity, depending on the size of the patient and also on the anticipated daily dose of intrathecal Baclofen and the estimated refill intervals. When the decision is made to implant the Baclofen pump, the patient is usually put under general anaesthesia and with the patient on his side, a catheter is tunneled through a needle inserted through the L3-4 space, preferably in a paramedical approach and the catheter is guided upwards to the higher thoracic vertebrae and checked on fluoroscopy. The catheter which will be connected to the pump is then tunneled beneath the skin around the flank of the patient to the subcostal area. The pump is then implanted just beneath the skin in the subcutaneous fatty tissue which lies above the abdominal muscles of the lower abdomen. Usually the pump is prepared and filled with Baclofen before implantation and the surgical incision closed properly in layers and the patient given prophylactic antibiotic cover for 48 hours. Results All 33 patients who passed screening, showed significant improvement following pump implantation. The mean preoperative Ashworth Scale was reduced from 3.9 to 1.7. In addition to improvement of spasticity, there was significant clear improvement in patient behavior and activities of daily living. Also bladder and bowel functions were improved. It was noticed that after initiation of intraspinal treatment 853 most patients had an immediate reduction of muscle tone to normal levels and spontaneous spasms were eliminated. Many patients experienced less discomfort, significant pain relief, and daily activities were more easily accomplished. In our group of patients the intrathecal daily dose after adjustment was variable, between 50 and 850µg per day. We noticed small doses were needed for patients with demyelination disease, whereas larger doses were necessary to control spasticity in those with brain insult. One patient had Morphine and Baclofen mixed in the pump for both spasticity and pain. The pumps in two patients were explanted due to infection, one after three months and the other after four years. One patient had a damaged (broken) intrathecal catheter which was replaced. Other complications were minor, headache, swelling and pain at the site of the pump, but these were resolved within a few days. We found a definite improvement after the use of intrathecal Baclofen in patients with supraspinal spasticity and this has been reported by others11,12,13. Discussion The site of action of Baclofen in the spinal cord is not clear and Baclofen was first used in humans in 197414. It is a gamma-amino butyric acid (like GABA) analogue that binds to the GABA-B receptor resulting in inhibition of calcium influx at pre-synaptic terminals and thus suppressing release of excitary neuro transmitters. These GABA receptor sites occur widely throughout the central nervous system15,16,17. As complications are related to operator inexperience it is recommended that specific personnel or a specific centre should perform this procedure, where protocols can be standardised and long term results properly evaluated. Therefore the programme requires specific team designated leadership and identified co-ordination to ensure smooth transition between the different stages of therapy and effective long term follow up. Rehabilitation therapists, particularly Physical and Occupational Therapists are essential team members who can help monitor patients’ response to treatment and changing functional status over time. The team also involves a very experienced surgeon who should be actively involved with the M.E.J. ANESTH 20 (6), 2010 854 D. Al Khudhairi et al team for system-related problems which could arise at any time. ITB therapy could replace a number of orthopaedic and neurosurgical interventions for those cases suffering with irreversible, severe spasticity-with or without contractures. catheter breakage and the catheter was replaced after three years of implantation. We had four patients with headache and dizziness after the test dose and implantation, but these side effects were temporary and were resolved easily. There are several risks involved with placement of Baclofen pumps. A comprehensive study of ITB complications in a survey of 40 centres with a total of 1002 test doses and 936 pump placements was published17. Common test dose complications were nausea/vomiting (2.6%) and sedation (2.2%). Pump complications included CFS collection (3.3%), constipation (2.9%) and headache (2.4%). Common long-term complications were catheter kink or migration (4.5) and infection (1.2%). Intrathecal Baclofen is approximately 100 times more effective than oral alternatives and produces fewer side effects than large oral doses which can lead to drowsiness, sedation, ataxia, weakness and fatigue due to Baclofen crossing the blood-brain barrier. Other studies showed that complication rates ranged from 20-50%18,19. Even with safe surgical techniques, some common complications of Baclofen pump implantation still occur. Excessive swelling may be a sign of developing seroma, sometimes requiring percutaneous drainage. CSF leak may be detected by spongy swelling on the incision site on the back. Intrathecal use of Baclofen does not completely eradicate the central risks. The most frequent drugrelated side effects of ITB include drowsiness, dizziness, constipation and muscle hypertonia. Baclofen withdrawal is a serious risk if there is an abrupt decrease in drug infusion; causes include catheter failure (eg-obstruction, fracture or dislodging of the intrathecal catheter), pump malfunction or low pump reserves. Symptoms include pruritis without a rash, hyperthermia, hypertension, changes in mental status and aggravation of spasticity, immediate and active intensive treatment and care should be instituted with doses of Benzodiazepines and try to recommence intrathecal Baclofen infusion. In our study there were 2 out of 33 pumps explanted due to infection, and one patient needed significantly increasing doses; this was diagnosed as Although Intrathecal Baclofen is an alternative method requiring considerable initial outlay for the start up course, this can be reduced in the long term20. Nursing care and mobilization after Baclofen pump implantation become much easier with improvement in activities and daily living2,21. It also resulted in a decrease in the average length of subsequent hospitalisations21. As a whole, IBT can improve the quality of life in carefully selected patients and can be cost effective22,23. In our study we have demonstrated that ITB is an effective technique for relieving spasticity in patients who do not respond to conventional therapy. Conclusion Spasticity secondary to spinal cord injury and other central nervous system damage is common with clinical manifestations of hypertonicity, spastic paralysis and hyper-reflexia. Multimodal treatment should be aimed at preventing exacerbating factors, daily physical therapy with stretching, medications, contracture release and denervation of the motor neuron endplate. The most effective oral therapy for spasticity is Baclofen, Diazepam and Tizanidine, though all have limitations. Denervation of the motor neuron endplate with Phenol or Botulinum toxin can be effective, but the most effective treatment, with the least side effects, is intrathecal Baclofen, which should be considered when conservative methods fail. CONTINUAL INFUSION OF INTRATHECAL BACLOFEN (ITB): LONG TERM EFFECT ON SPASTICITY 855 References 1.Feldman RG, Young RR, Koella WP, Lace JW: Symposium synopsis: spasticity-disordered motor control. Chicago: Year Book Medical Publishers; 1980, p. 485. 2.Penn RD: Intrathecal baclofen for spasticity of spinal origin: 7 years of experience. J Neurosurg; 1992, 77:236-40. 3.Coffey JR, Cahill D, Steers W, et al: Intrathecal baclofen for intractable spasticity of spinal origin: results of a long term multicenter study. J Neurosurg; 1993, 78:226-32. 4.Albright AL, Barry MJ, Painter MJ, et al: Infusion of intrathecal baclofen for generalized dystonia in cerebral palsy. J Neurosurg; 1998, 88:73-6. 5.Albright AL, Kriel RL, Gilmartin RC, et al: Hip status in cerebral palsy after one year of continuous intrathecal baclofen infusion. Pediatr Neurol; 2004, Mar. 30(3):163-8. 6.Albright AL, Gilmartin R, Swift D, Krach LE, et al: Long term intrathecal baclofen therapy for sever spasticity of cerebral origin. J Neurosurg; 2003, Feb. 98(2):291-5. 7.Metz L: Multiple sclerosis: symptomatic therapies. Semin neurol; 1998, 18:389-95. 8.Corston RN, Johnson F, Goodwin-Austen RB: The assessment of drug treatment of spastic gait. J Neurol Neurosurg Psychiatry; 1981, 44:1035-9. 9.Penn RD, Kroin JS: Intrathecal baclofen alleviates spinal cord spasticity. Lancet; 1984, 1:1078. 10.Zierski J, Muller H, Dralle D, Wurdinger T: Implanted pump system for treatment of spasticity. Acta Neurochir Supp;l 1998, 43:94-9. 11.Milan R, Dimitrijevic: Spasticity. Scientific basis of clinical neurology. New York: Churchill Livingstone; 1985, pp. 108-15. 12.Saltuari K, Kronenberg M, Marosi MJ, Kofler M, Russegger L, Rifici C, et al: Long-term intrathecal baclofen treatment in supraspinal spasticity. Acta Neurol; 1992, 14:195-207. 13.Rifici C, Kofler M, Kronenberg M, Kofler A, Bramanti P, Saltuari L: Intrathecal baclofen application in patients with supraspinal spasticity secondary to severe traumatic brain injury. Funct Neurol; 1994, Jan-Feb. (1):29-34. 14.Pederson S, Arlien-Soberg P, Mai J: The mode of action of the FABA derivative baclofen in human spasticity. Acta Neurol Scand; 1994, 50:665-80. 15.Bowrey NG, Price GW, Hudson AL, Hill DR, Wilkin GP, Turnbull MJ: GABA receptor multiplicity: visualisation of different receptor types in the mammalian CNS. Neuropharmacology; 1984, 23:21931. 16.Davies J: Selective depression of synaptic excitation in cat spinal neurons by baclofen: an iontophoretic study. Br J Pharmacol; 1981, 72:373-84 17.Stempen, et al. Am J Med Rehab; 2000. 18.Follet K. Neuromodulation; 2003, 6(1):32-41. 19.Teddy P, Jamous A, Gardner B, et al. Br J Neurosurg, 1992, 6(2):115-18. 20.Ordia JI, Fischer E, Adamski E, Spatz E: Chronic intrathecal delivery of baclofen by programmable pump for the treatment of severe spasticity. J Neuro Surg; 1996, vol. 85:452-7. 21.Azouri P, Mane M, Thiebaut NB, Denys P, Remy-Neris O, Bussel B: Intrathecal baclofen administration for control of severe spinal spasticity: functional improvement and long term follow-up. Arch Phys Med Rehabil; 1996, 77:35-9. 22.Sampson FC, et al: Functional benefits and cost/benefit analysis of continuous intrathecal baclofen infusion for the management of severe spasticity. J Neurosurg; 2002, 96:1052-7. 23.Becker WJ, et al: Long-term intrathecal baclofen therapy in patients with intractable spasticity. Can J Neurol Sci; 1995, 22:208-17. M.E.J. ANESTH 20 (6), 2010 CASE REPORTS THE VIDEO LARYNGOSCOPES BLIND SPOTS AND POSSIBLE LINGUAL NERVE INJURY BY THE GLIDERITE® RIGID STYLET - Case Presentation and Review of literature - Magboul MA Magboul* and Shaw Joel** Summary We report the first case of near serious lingual nerve injury in an 80-y-old female caused by the Rigid GlideScope Stylet. This complication was discovered during oral surgery and may have been missed if the site of surgery was not oral cavity. Introduction The GlideScope Video Laryngoscope is a relatively new intubating device designed to provide better view of the glottis without alignment of the oral, pharyngeal and tracheal axes. The aim of this case presentation is to increase awareness for possible serious complications that may arise with increase popularity and usage of video laryngoscopes, and their Rigid Stylet. Key words: Glide Rite, Glide Scope, Complications, Lingual nerve injury. Case Presentation A morbidly obese 80-y-old female (Wt.102.1 kg, Ht. 157.5 cm, BMI of 41) presented with mouth pain and multiple carious teeth was scheduled for teeth extraction with an alveoplasty. Past Medical history of CVA, TIA, CHF, hypertension, and MI. ECG showed first degree heart block, prolonged QT with and anterolateral infarct. ECHO showed an ejection fraction of 45-50%, left atrial enlargement, mild pulmonary hypertension, and trace mitral regurgitation. Pre-operative airway assessment revealed a Mallampati score of IV, three finger breadth mouth opening, slight limitation of neck movement, and loose carious teeth. With this assessment the patient was predicted to be difficult to intubate. The anesthetic plan included management of the predicted difficult intubation with the GlideScope. Anesthesia was induced with fentanyl 150 micro grams, lidocaine 100 mg, propofol 150 mg and succinylcholine 100 mg. * ** MD, FFARCSI, Chief of Anesthesia VA Medical Center, Iowa City. Clinical Assistant Professor of Anesthesia, University of Iowa, College of Medicine, Iowa City, USA. BSN, SRNA, Student RN Anesthetist, University of Iowa, College of Medicine, Iowa City, USA. Correspondence: Magboul MA Magboul, MD, FFARCSI, Chief of anesthesia VA Medical Center Iowa City. Clinical Assistant Professor Anesthesia, University of Iowa, college of Medicine, Department of Anesthesia-6JCP, 200 Hawkins Drive, Iowa City, Iowa 52242-1009, USA. Tel: (319) 356 8497 (Office), Tel: (319) 356-2633 (Department), Tel: (319) 356 7471 (Sec. office), Fax: (319) 356 2940 (Department), E-mail: [email protected] 857 M.E.J. ANESTH 20 (6), 2010 858 The GlideScope blade tip was placed in the vallecula and the vocal cords and epiglottis were seen. A size 7 ETT was mounted in the GlideRite® Rigid stylet (Figure 2a, b) and then passed into the oral cavity for intubation. The ETT appeared to slide into the oropharynx with relative ease and the endotracheal tube was placed into the trachea. The stylet was removed, positive ETCO2 and equal bilateral breath sounds was confirmed. A successful GlideScope intubation was assumed. As the surgeon began the procedure he noticed that the endotracheal tube had pierced and entered the tissue of the Retromolar trigonum [the same space which holds the lingual nerve], and then proceeded to pass through the oropharyngeal space and re-enter the vocal cords (Figure 1a, b). Fig. 1a ETT had pierced into Retromolar Trigonum tissues, and then entered the vocal cords M. MA Magboul & S. Joel We decided to remove the endotracheal tube to avoid trauma to Lingual nerve, and re-insert another size 7 endotracheal tube with the aid of the GlideScope camera. Positive ETCO2 and equal bilateral breath sounds was confirmed. Surgery was completed uneventfully; however, the surgeon stated multiple times that the patient’s oral mucosa was very fragile and easily torn. The patient was easily extubated and transferred to PACU. The PACU staff was instructed to look for signs of lingual nerve injury (loss of tongue sensation, difficulty breathing, slurred speech, or bleeding from her oral cavity). The PACU stay was uneventful, the patient denied any of the above mentioned symptoms, and was discharged. Discussion The GlideScope and other video laryngoscope have improved tracheal intubation especially in patients with difficult Airway1. The GlideRite® Rigid stylet (Figure 2a, b) was introduced to over come difficulties found with intubation with GlideScope and other similar video laryngoscope and help reduce patient trauma2,5. Fig. 2a The GlideRite® Rigid Stylet is specifically designed to work with GlideScope® Video Laryngoscopes. Fig. 1b ETT had pierced into Retromolar Trigonum tissues, and then entered the vocal cords THE VIDEO LARYNGOSCOPES BLIND SPOTS, AND POSSIBLE LINGUAL NERVE INJURY BY THE GLIDERITE RIGID STYLET Figure 2b The GlideRite® Rigid Stylet is specifically designed to work with GlideScope® Video Laryngoscopes. 859 penetrating injury of the soft Palate during GlideScope® intubation17 Malik, and Frogel reported. The first Anterior tonsillar pillar perforation during Glidescope® Video laryngoscopy18. This is the first reported case of near serious lingual nerve injury by The Rigid GlideScope Stylet. Accidently discovered during oral surgery. Decision to reintubate, rather than cutting the oropharyngeal tissues to release the tube, has avoided a serious injury to the lingual nerve. Injuries to lingual nerve are now frequently reported with upper airway intubation and instrumentation. Lingual nerve injury was even reported with the use of LMA, Cuffed oropharyngeal airway, oropharyngeal airway, Proseal LMA, and conventional endotracheal intubation. Both unilateral and bilateral injuries have been reported. Potential predisposing factors included the use of nitrous oxide6,7,8,9,10,14,16 using an LMA that was too small6,9,11,12,13,16 and excessive pressure. Study by Tukstra et al showed that the dedicated GlideScope rigid stylet and the standard malleable ETT stylet are equally effective in facilitating endotracheal intubation4,5.The Flex-It® Stylet was no more effective in facilitating endotracheal intubation than the standard malleable endotracheal tube stylet3,5. In our case the Rigid stylet converted the endotracheal tube tip into a sharp knife like weapon that cut through the patient oral tissues. When Intubating with video laryngoscope the operator usually concentrate on the perfect image of the cords. The path of the tube from the mouth opening to the vocal cords is a “blind spot” to the intubating person. Hsu, Huang, and Chen reported the first We concluded that injuries from video laryngoscopes intubation aids could be avoided by careful attention to the following steps: The ETT must be passed close to the scope and away from the corners of the mouth. Close attention to the path of the tube from mouth entering to vocal cord intubation. The tube course must be re-inspected by the video scopes on the way out after intubation. When using rigid stylet, ETT with softer tips must be used. The parker ETT has a soft malleable tip and maybe helpful in these situations. The tip of the conventional ETT, if dipped into warm saline, will turn softer and less traumatic. We recommend the use of soft stylets and Soft tipped ETT to prevent such traumatic injuries. M.E.J. ANESTH 20 (6), 2010 860 M. MA Magboul & S. Joel References 1. RM Cooper, JA Pacey, MJ Bishop and SA McCluskey: Early clinical experience with a new videolaryngoscope (GlideScope) in 728 patients. Can J Anaesth; 2005, 52, pp. 191-198. Full Text via Cross Ref View Record in Scopus Cited By in Scopus (108). 2.Timothy Turkstra MDa, Christopher Jones MDa: Comparison of GlideScope-specific rigid stylet to standard malleable stylet. Journal of Clinical Anesthesia, Volume 20, Issue 1, February 2008, Page 75. 3. JV Cuchillo and MA: Rodriguez, Considerations aimed at facilitating the use of the new GlideScope videolaryngoscope [Letter], Can J Anaesth; 52 (2005), p. 661. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (18). 4. PM Jones, TP Turkstra and KP: Armstrong, Effect of stylet angulation and endotracheal tube camber, Can J Anaesth; 54 (2007), pp. 21–27. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (12). 5. Comparison of Flex-It Stylet to Malleable Stylet for GlideScope Intubation: A Randomized Controlled Trial Timothy Turkstra MDa, Christopher Jones MDa. 6. Ahmad NS, Yentis SM: Laryngeal mask airway and lingual nerve injury. Anaesthesia; 1996, 51:707. 7. Laxton CH, Kipling R: Lingual nerve paralysis following the use of the laryngeal mask airway. Anaesthesia; 1996, 51:869-70. 8. Majumder S, Hopkins PM: Bilateral lingual nerve injure following the use of the laryngeal mask airway. Anaesthesia; 1998, 53:184-6. 9. Gaylard D: Lingual nerve injury following the use of the laryngeal mask airway. Anaesth Intens Care; 1999, 27:668. 10.King C, Street MK: Twelfth cranial nerve paralysis following use of a laryngeal mask airway. Anaesthesia; 1994, 49:786-7. 11.Stewart A, Lindsay WA: Bilateral hypoglossal nerve injury following the use of the laryngeal mask airway. Anaesthesia; 2002, 57:264-5. 12.Sommer M, Schuldt M, Runge U, Gielen W, Marcus MA: Bilateral hypoglossal nerve injury following the use of the laryngeal mask without the use of nitrous oxide. Acta Anaesthesiol Scand; 2004, 48:377-8. 13.Morikawa M: [Vocal cord paralysis after use of the LM]. J Clin Anesth (Rinsho-Masui); 1992, 16:1194. 14.Inomata S, Nishikawa T, Suga A, Yamashita S: Transient bilateral vocal cord paralysis after insertion of a laryngeal mask airway. Anesthesiology; 1995; 82:787-8. 15.Daya H, Fawcett W, Weir N: Vocal cord palsy after use of the laryngeal mask airway. J Laryngol Otol; 1996, 110:383-4. 16.Laffon M, Ferrandiere M, Mercier C, Fusciardi J: Transient lingual and glossopharyngeal nerve injury: a complication of cuffed oropharyngeal airway. Anesthesiology; 2001, 94:719-20. 17. Hsu W-T, Hsu S-C, Lee Y-L, Huang J-S, Chen C-L: Penetrating injury of the soft palate during GlideScope® intubation. Anesth Analg; 2007, 104:1609-10. 18.Malik AM, Frogel JK: Anterior tonsillar pillar perforation during Glidescope® Video laryngoscopy. Anesth Analg; 2007, 104:1610-1. SUBCLAVIAN VEIN INJURY AND MASSIVE HEMOTHORAX REQUIRING THORACOTOMY FOLLOWING INSERTION OF TUNNELED DIALYSIS CATHETER - A Case Report and Review of Literature - Ahmed Qutaiba A. Tawfic*, Pradipta Bhakta**, Khamis Mohammed*** and Jasvinder Sharma**** Abstract Tunneled dialysis catheters are widely used for hemodialysis. Large caliber dilator is used for insertion of such catheter which can result in serious vascular injury leading to haemothorax. Here we report such an inadvertent central venous injury requiring thoracotomy following blind dilator advancement along with review of literature and recommendation to prevent such complication. Key words: Subclavian vein injury; Haemothorax; Tunneled dialysis catheter. Background Tunneled dialysis catheters (TDC) are widely used for hemodialysis1,2. Insertion of such catheters requires large caliber dilator which can cause devastating vascular injury leading to cardiac arrest or even death particularly if there are anatomical abnormalities, stenosis, history of previous multiple insertion attempts.1,3-5 Here we report such a case of vascular injury leading to hemo-pneumothorax requiring thoracotomy following TDC insertion. Case Report A 54 year old female patient with end-stage renal disease (ESRD), hypertension, diabetes mellitus, cardiomyopathy, and left ventricular failure was admitted to our hospital. Patient was on irregular hemodialysis. This time she was admitted with respiratory distress and features of fluid overload. Consultant nephrologist decided to resume hemodialysis using TDC (Quinton Permcath, Kendall, Tyco Healthcare, USA). Informed consent was taken after explaining the procedure. Pulse oximetry, electrocardiogram and blood pressure (BP) monitoring were started. Right internal jugular vein (RIJV) was punctured after lignocaine infiltration under aseptic precaution using From Sultan Qaboos University Hospital, Muscat, Oman. * FICMS, MBChB, Registrar. ** MD, DNB, MNAMS, FCARCSI-I, Senior Registrar. *** FICMS, MBChB, Registrar. ****MD, Senior Registrar. Correspondong author: Dr. Pradipta Bhakta (MD, DNB, MNAMS, FCARCSI-I), Senior Registrar, Department of Anaesthesia, Sultan Qaboos University Hospital, Al-Khoud, P.O. Box No: 38, Muscat, Oman. Zip Code: 123. Phone: (H) 00968-24414622, (M) 00968-95036291, (Fax) 00968-24144710, E-mail: [email protected] 861 M.E.J. ANESTH 20 (6), 2010 862 ultrasound (Site Rite 5, BARD, USA). After obtaining free flowing dark coloured blood, a guidewire was inserted under ultrasound guidance till arrhythmia was noted. Guidewire was then withdrawn a little bit. Skin was infiltrated once again with lignocaine for subcutaneous tunneling of TDC. Then a 12 French dilator with the sheath was introduced over the guidewire. While doing so guidewire came out a bit, but it was still inside the vein. The dilator was then pushed blindly to its full length. After that the dilator was pulled out and TDC was introduced through the sheath. At this time patient complained of shearing pain and shortness of breath. Further advancement of catheter was stopped. On aspiration back flow of blood was obtained only from the proximal lumen. Immediately intravenous portion of TDC along with sheath was removed and pressure was applied. At this time fluoroscopy was used which showed right sided pneumothorax. Patient became more tachypneic and hypoxic, so a chest tube was inserted. This resulted in some clinical improvement. Femoral catheter (FC) insertion was planned as she needed urgent dialysis. During FC insertion she became more dyspneic, irritable and hypotensive. Vascular injury was suspected and the radiologist performed an angiogram through FC which showed minor spillage of dye into pleural cavity indicating pleural tear (Fig. 1). She was shifted to ICU for further observation. She became more unstable with increasing breathlessness, desaturation, and hypotension. She was resuscitated with fluids and put on oxygen by mask. Routine blood investigations were sent and cardiothoracic opinion was sought. Repeat chest X-ray revealed complete whitening of the right hemi-thorax (Fig. 2). A new chest tube was inserted as previous one was not working well. Immediately about 400ml of blood came out. Her hemoglobin dropped from 11.4 to 5.2gm/dL. Dopamine (10µg/kg/min) was started for maintenance of BP. Cardiothoracic surgeon decided to do urgent thoracotomy because of suspicion of continued vascular leak. A large clot amounting to 1.5 liter of blood along with tear in right subclavian vein was found during thoracotomy. After surgery she was shifted back to ICU for observation and mechanical ventilation. She received seven packed red blood cells perioperatively and her hemoglobin improved to 10.7gm/dL. Her BP improved and she could be weaned off from inotrope and ventilator. Hemodyalysis was Q. A. Tawfic et al started through FC. Later she developed thrombosis of right femoral vein due to longer stay of FC. So the FC was removed and she was put on enoxaparin and warfarin. Afterwards arterio-venous fistula (AVF) was created for regular dialysis and she is doing fine with that. Fig. 1 An angiogram done via femoral catheter (which is clearely visible coming up from inferior vena cava) revealing leak of dye in pleural cavity. 1. Right tunneled catheter in situ (which was not fully removed from subcutaneous tunnel, but was removed from the vein). 2. Angiography catheter passed through femoral vein for doing venography. 3. Spillage of dye into pleural cavity. 4. Receeding of lung mergin due to pneumothorax. 5. Intial pigtail catheter inserted to drain pneumothorax. Fig. 2 Right sided haemothorax with whitening of right chest cavity (Chest drain tube in situ) 1. Spillage of dye into pleural cavity. 2. Whitening of right hemi thorax due to haemo-pneumothorax. 3. Standard chest drain tube in situ. SUBCLAVIAN VEIN INJURY AND MASSIVE HEMOTHORAX REQUIRING THORACOTOMY FOLLOWING INSERTION OF TUNNELED DIALYSIS CATHETER Discussion RIJV is often selected as ideal vein for hemodialysis access because of its straight course, reduced risk of malposition and thrombosis2,3,6. Central venous catheter (CVC) insertion and dilator manipulation can lead to complications like pneumothorax, subcutaneous emphysema, thoracic duct injury, arterial puncture, hemothorax, pericardial tamponade, and mediastinal hematoma2-5,7-10. In majority of reports hemothorax resulted from arterial injury, and rarely from venous injury due to faulty insertion of needle or catheter2-5,8,10. Venous injury is most commonly reported to occur during left sided CVC insertion and arterial injury during right sided CVC insertion2-5. Very rarely it has been reported to occur from dilator5. Too deep insertion of dilator can result in injury of vessel or heart5. Because of its stiff texture it can cause more serious vascular injury than needle or catheter5. Safer dilator design and insertion technique have also been recommended to prevent such complication5. In our case the dilator was blindly and mistakenly inserted to full length, even though the guidewire came out partially, which probably had resulted in venous injury. This is very dangerous maneuver and should never be attempted. Also undue force should never be applied while advancing the dilator. Direction of dilator advancement is also important as RIJV maintains a medial course while draining to superior vena cava. So the dilator should always be advanced along the course of the vein. Use of real-time sonography or fluoroscopy is recommended especially in difficult cases during insertion of the needle and dilator for prevention 863 of such complication1-4,6,7. Venography before or after CVC insertion may help to detect unexpected central venous anomalies, minimize the risk of complications and extravasal placement (as in our case)1,2,4,7. Postprocedure X-ray, CT Scan, ultrasound or echocardiography are recommended to detect such complication2-4,9,10. This is specifically indicated if patient complains of retrosternal pain and respiratory distress during insertion or aspiration of blood2,5. Management of vascular injury includes endovascular repair, stent placement, embolization and or balloon tamponade3,7,10. Even emergency thoracotomy like in our case may be needed to evacuate the hematoma and repair the vascular tear9,10. Rare occurrence of dilator induced venous injury leading to hemo-pneumothorax requiring emergency thoracotomy prompted us to report this case. Our purpose to report this case was to notify that this type of misadventure can lead to serious consequences. Inadvertent and blind insertion of large caliber dilator can result in serious vascular injury. Such dilator should never be inserted for a length more than necessary. We propose that graduated dilator with markings indicating the safe and dangerous lengths and should be used under real-time fluoroscopic and/ or ultrasound guidance. Acknowledgement We are thankful to Dr. Arvind Narayanan (MD), Mrs. Paromita Bose (MA, M. Phil) for editing our paper and to Dr. Amisha Bhakta (MSc, PhD) for editing the figures. M.E.J. ANESTH 20 (6), 2010 864 Q. A. Tawfic et al References 1. Taal MW, Chesterton LJ, McIntyre CW: Venography at insertion of tunnelled internal jugular vein dialysis catheters reveals significant occult stenosis. Nephrol Dial Transplant; 2004, 19:1542-5. 2. Tong MK, Siu YP, Ng YY, Kwan TH, Au TC: Misplacement of a right internal jugular vein haemodialysis catheter into the mediastinum. Hong Kong Med J; 2004, 10:135-8. 3. Kusminsky RE: Complication of central venous catheterization. J Am Coll Surg; 2007, 204:681-96. 4. Schummer W, Schummer C, Fritz H. [Perforation of the superior vena cava due to unrecognized stenosis. Case report of a lethal complication of central venous catheterization]. Anaesthesist; 2001, 50:772-7. 5. Oropello JM, Leibowitz AB, Manasia A, Del Guidice R, Benjamin E. Dilator-associated complications of central vein catheter insertion: possible mechanisms of injury and suggestions for prevention. J Cardiothorac Vasc Anesth; 1996, 10:634-7. 6. Schillinger F, Schillinger D, Montagnac R, Milcent T: Post catheterization vein stenosis in haemodialysis: comparative angiographic study of 50 subclavian and 50 internal jugular accesses. Nephrol Dial Transplant; 1991, 6:722-4. 7. Sandhu NS: Transpectoral ultrasound-guided catheterization of the axillary vein: an alternative to standard catheterization of the subclavian vein. Anesth Analg; 2004, 99:183-7. 8. Hama Y, Kaji T, Fujii M, Kosuda S: Internal mammary artery injury following subclavian catheterization. Emerg Radiol; 2005, 11:170-2. 9. Fangio P, Mourgeon E, Romelaer A, Goarin JP, Coriat P, Rouby JJ: Aortic injury and cardiac tamponade as a complication of subclavian venous catheterization. Anesthesiology; 2002, 96:1520-2. 10.Guilbert MC, Elkouri S, Bracco D, Corriveau MM, Beaudoin N, Dubois MJ, et al: Arterial trauma during central venous catheter insertion: case series, review and proposed algorithm. J Vasc Surg; 2008, 48:918-25. CESAREAN SECTION UNDER SPINAL ANESTHESIA IN A PATIENT WITH ANKYLOSING SPONDYLITIS - A Case Report - G. Ulufer Sivrikaya*, Ayse Hanci**, Hale Dobrucali* and Aylin Yalcinkaya * Abstract Introduction: It is generally accepted that neuraxial anesthesia is difficult to establish in patients with ankylosing spondylitis. General anesthesia also has some disadvantages, especially with respect to airway control in patients with ankylosing spondylitis. We present herein a gravida with ankylosing spondylitis who had a cesarean delivery performed under spinal anesthesia. Case: A 30-yr-old gravida at 38 weeks gestation with a 9 yr history of ankylosing spondylitis was admitted to our hospital in labor. She was scheduled for an elective repeat cesarean delivery. Spinal anesthesia was induced using a 22-gauge Quincke spinal needle with 1.8 mL of 0.5% heavy bupivacaine + 0.2 mL (10µg) of fentanyl at the L3-4 interspace in the left lateral position by the median approach. Adequate sensory and motor blockade were achieved. The postoperative period was uneventful and she was discharged home on postoperative day 3. Conclusion: We suggest that spinal anesthesia can be safely and effectively used as an alternative to general anesthesia in patients with ankylosing spondylitis. Neuraxial techniques should not be regarded as unachievable in such patients; however, all necessary precautions should be taken to avoid complications of spinal anesthesia, and facilities to secure the airway should be available. Introduction Ankylosing spondylitis (AS) is a seronegative spondyloarthropathy; it is a chronic and usually progressive inflammatory disease. The primary sites of involvement are the sacroiliac joints and the spine1,2. The disease prevalence varies ranging between 0.1 and 1.1% in different populations3,4. Patients with AS may require surgery of any type and these patients present specific challenges to the anesthesiologist. Both airway management and neuraxial access may prove to be difficult1,5. Pregnancy may also occur in patients with AS. Although most pregnant patients with AS have a normal spontaneous vaginal delivery, the manifestations of the disease may interfere with labor and delivery as well as the administration of general and regional anesthesia6. There are but a few reports on the use of anesthesia in gravidas with AS6-9. * ** MD, Staff Anesthesiologist. MD, Chief of the Anesthesiology and Reanimation Department. GUS, AH, HD: Sisli Etfal Training and Research Hospital, Department of 2nd Anesthesiology and Reanimation, Istanbul, TURKEY; AY: Dr. Munif Islamoğlu State Hospital, Department of Anesthesiology, Kastamonu, TURKEY. Corresponding author: G. Ulufer SIVRIKAYA, Kucukbahce Sk. No:28/34 Sisli. Istanbul-TURKEY. Telephone number: +90.532.2924173, Fax number: +90.212.2472576, E-mail: [email protected] 865 M.E.J. ANESTH 20 (6), 2010 866 Herein, we present a case of a gravida with AS who had a cesarean section under spinal anesthesia. Case Report A 30-yr-old gravida 3 para 2, at 38 weeks gestation with a weight of 66 kg and a height of 164 cm, was admitted to our hospital in labor. She had a 9 yr history of AS. The history and physical examination were consistent with moderate cervical AS involving the thoraco-lumbar vertebral column with kyphosis, but without lower limb neurologic involvement. She required two pillows to support her head and four pillows to support her back due to the disease process and curvature of the cervical and thoraco lumbar spines. An elective repeat cesarean section had been planned. She had undergone two cesarean deliveries 12 and 11 years previously under general anesthesia. Since AS had not been diagnosed at the time of her prior cesarean deliveries, the two general anesthesia experiences were uneventful. Her medical history was benign other than the AS. Her current medications were infliximab, indomethacin, and salicylazosulfapyridine. She could open her mouth 5 cm; physical examination revealed a Grade III Mallampati score. The problems of general anesthesia, with particular reference to difficult intubation, were explained to the patient and she opted for a regional anesthesia technique. Preoperative laboratory data were within normal limits. The patient was premedicated with ranitidine HCl (50 mg iv) and metoclopramide HCl (10 mg iv) 30 minutes before the planned surgery. In the operating room, an ECG, non-invasive blood pressure, and peripheral oxygen saturation were monitored and an intravenous infusion of Lactated Ringer’s solution was started. Spinal anesthesia was planned, but since the patient was a candidate for difficult endotracheal intubation, airway management devices for emergent use, including a percutaneous tracheostomy set, were kept ready. With the patient in the sitting position, two unsuccessful attempts were made to insert a 22-gauge Quincke spinal needle between the L3-4 intervertebral space using a median technique. The patient was then turned to the left lateral position. Free flow of G. U. SIVRIKAYA et. al cerebrospinal fluid was obtained using the midline technique at the same level on the first attempt in this position and 1.8 mL of 0.5% heavy bupivacaine and 0.2 mL (10 µg) of fentanyl were injected into this space. The patient was then returned to the supine position with pillow support and the operating table rotated toward the left in order to avoid supine hypotensive syndrome. Spinal anesthesia resulted in a complete sensory and motor block from T6 caudally. The APGAR scores were 9 and 10 for the 1. and 5. min respectively. Surgery was performed successfully within 45 minutes. The patient recovered without any complications and was discharged home following a good recovery on the 3rd postoperative day. Discussion AS is often a self-limiting disease with unknown etiology. It is a chronic and usually progressive inflammatory disease involving the articulations of the spine and adjacent soft tissues. It begins in the sacroiliac joints and moves cranially. The degree of the disease ranges from involvement of the sacroiliac joint alone to complete ankylosis of the spine1,2,10. The traditional anesthetic approach to patients with AS is to secure the airway using awake intubation because fusion of the vertebral column renders neuraxial anesthesia difficult or impossible2. In patients with a fixed cervical spine, it has been reported that it is usually not possible to see any part of the laryngeal inlet, emphasizing the difficulty with intubation3. Since the number of patients with AS are not adequate to perform a controlled study regarding the best method of anesthesia, case reports concerning the care of these patients have provided diverse anecdotal experiences. The largest series of patients with AS who underwent anesthetic procedures was reported by Schelew and Vaghadia2 as a retrospective analysis of 82 patients over 10 years. They reviewed the approach to patients with AS having surgical procedures at one institution to investigate the utilization of neuraxial anesthesia and to determine whether the success rate was acceptable, in an effort to make this a viable alternative to general anesthesia. Neuraxial anesthesia was planned in 19.5% (n=16) of the patients and CESAREAN SECTION UNDER SPINAL ANESTHESIA IN A PATIENT WITH ANKYLOSING SPONDYLITIS successful spinal anesthesia was achieved in 76.2% (n=10) of those in whom it was planned. Their results indicate that spinal anesthesia may be relatively underutilized in patients with AS presenting for surgery. In our review of the current literature, we found a few reports on epidural or combined spinal-epidural anesthesia11-13. In our patient, we preferred spinal anesthesia after consideration of the consequences and our anecdotal experience favored spinal anesthesia in patients with AS undergoing cesarean section. The presence of ossification in the interspinous ligament would suggest better success with a paramedian approach1. Kumar and Mehta14 reported three cases in which patients with AS were successfully administered spinal anesthesia using a paramedian approach after failed attempts with a median approach. Nevertheless, Schelew et al2. suggest that both midline and paramedian methods may be attempted with success. In our patient, spinal anesthesia was successfully administered by the median approach in the lateral position on the first attempt, but preceded by two failed attempts by the median approach in the sitting position. From the anesthetic point of view, preoperative assessment, including indirect laryngoscopy and preparation to overcome anticipated problems, should enable those patients with AS to be managed safely. But, as in the two cases described in detail by Wittmann et al3, the greatest danger occurs when patients present for surgery which is unrelated to their condition and 867 difficulties are not anticipated. On the other hand, even in the cases in which regional anesthesia is planned, emergent securing of the airway can be required, such as reported by Batra et al15. In the literature, total spinal anesthesia was achieved following an epidural test dose in a patient with AS undergoing total hip replacement and after an unsuccessful attempt to intubate the trachea with direct laryngoscopy, positive pressure ventilation was restored by placing a size 4 laryngeal mask airway. Intubation could hardly be achieved using a McCoy’s laryngoscope and a bougie in the patient. These are the important reasons for having intubating equipment ready for immediate use in patients with AS3. Therefore full consideration of airway control was included in our plan for anesthesia in this patient. In conclusion, patient anesthetic preference, potential airway maintanence problems, and specific requirements of the surgical intervention should all be considered for the anesthetic approach in patients with AS. If a central neuraxial blockade is chosen as the anesthetic technique, the likelihood of successful spinal anesthesia seems higher than other neuraxial interventions. Airway intervention and equipment and aids to secure the airway must be available. Acknowledgements Informed consent and approval were taken from the patient for this case report. M.E.J. ANESTH 20 (6), 2010 868 G. U. SIVRIKAYA et. al References 1. McCARREN JP: Respiratory diseases. In: Benumof JL, ed. Anesthesia & Uncommon Diseases, 4th edn. Philadelphia, Pennsylvania: W.B.Saunders Company, 1998, 51-69. 2.Schelew BL, Vaghadia H: Ankylosing spondylitis and neuroaxial anaesthesia-a 10 year review. Can J Anaesth; 1996, 43: 65-8. 3. Wittmann FW, Ring PA: Anaesthesia for hip replacement in ankylosing spondylitis. J R Soc Med; 1986, 79:457-9. 4. Braun J, Bollow M, Remlinger G, Eggens U, Rudwaleid M, Distler A, Sieper J: Prevalence of spondyloarthropathies in HLA B27-positive and –negative blood donors. Arthritis Rheum; 1998, 41: 58-67. 5. Ahmad N, Channa AB, Mansoor A, Hussain A: Management of difficult intubation in a patient with ankylosing spondylitis-a case report. Middle East J Anaesthesiol; 2005, 18:379-84. 6. Bourlier RA, Bırnbach DJ: Anesthetic management of the parturient with ankylosing spondylitis. Int J Obstet Anesth; 1995, 4: 244-7. 7. Mehrotra S, Gupta KL: Cesarean section in a patient with advanced ankylosing spondylitis. Int J Gynaecol Obstet; 2005, 89:272-3. 8. Hiruta A, Fukuda H, Hiruta M, Hirabayashi Y, Kasuda H, Seo N: Anesthetic management of caesarean section in a parturient with ankylosing spondylitis complicated with severe cervical myelitis. Masui; 2002, 51:759-61. 9. Broomhead CJ, Davies W, Higgins D: Awake oral fibreoptic intubation for caesarean section. Int J Obstet Anesth; 1995, 4:172-4. 10.Sharrock NE, Savarese JJ: Anesthesia for Orthopedic Surgery. In: Miller RD, ed. Anesthesia, 5th edn. USA: Churchill Livingstone Inc., 2000, 2118-39. 11.Deboard JW, Ghia JN, Guilford WB: Caudal anesthesia in a patient with ankylosing spondylitis for hip surgery. Anesthesiology; 1981, 54:164-6. 12.Hyderally HA: Epidural hematoma unrelated to combined spinalepidural anesthesia in a patient with ankylosing spondylitis receiving aspirin after total hip replacement. Anesth Analg; 2005, 100:882-3. 13.Wulf H: Epidural anaesthesia and spinal haematoma. Can J Anaesth; 1996, 43:1260-71. 14.Kumar CM, Mehta M: Ankylosing spondylitis: lateral approach to spinal anaesthesia for lower limb surgery. Can J Anaesth; 1995, 42:73-6. 15.Batra YK, Sharma A, Rajeev S: Total spinal anaesthesia following epidural test dose in an ankylosing spondylitic patient with anticipated difficult airway undergoing total hip replacement. Eur J Anaesthesiol; 2006, 23:897-8. LEVOSIMENDAN AS A RESCUE ADJUNCT IN AMLODIPINE INTOXICATION – A Case Report – M Gökhan Teker*, Haluk Özdemir*, Leyla Saidoglu* Kerem Erkalp*and Gökçen Başaranoğlu Introduction Calcium channel blockers (CCB) are the cardiovascular medicines most commonly associated with overdose death1. Amlodipine, a dihydropyridine CCB, can cause shock at overdose levels. The hemodynamic shock is likely caused by calcium channel blockade in myocardial smooth muscle and beta cells. This blockade leads to peripheral vasodilatation, hyperglycemia, hypoinsulinemia, metabolic acidosis and shock2. Here we describe the use of levosimendan, a calcium sensitizing agent, to treat a 16-year old woman who ingested 500 mg of amlodipine and failed to respond to conventional therapies including calcium salts, inotrope infusions and hyperinsulinemiaeuglycemia therapy. Case Report A 16-year old woman with no past medical history or psychiatric disorders was admitted to the intensive care unit of Private Hospital (Istanbul, Turkey) approximately 15 hours after attempting suicide by ingesting 50 tablets of amlodipine 10 mg (500 mg total). She was a student living with her family and denied tobacco and alcohol use. She had no known allergies and took no regular medications. She received gastric lavage and activated charcoal in the emergency department four hours after ingestion. She was admitted to the intensive care unit with a blood pressure of 75/34 mm Hg and a pulse of 125 bpm. She received intravenous crystalloid, intravenous dopamine 10 µg·kg1·min-1, and intravenous insulin 0.5 U·kg-1·h-1. Chest x-ray revealed pulmonary infiltration suggestive of pulmonary edema. During her seven-hour intensive care unit stay, she had received 2700 mL of crystalloids, but her urine output was only 50 mL. Her blood glucose was normal at each hourly check. For financial and logistics reasons, she was then transferred to the anesthesia intensive care unit of our hospital. Upon transfer, the patient was awake and conversant, with a Glascow Coma Scale (GCS) score of 15. Her blood pressure was 87/36 mm Hg, heart rate was 112 bpm, temperature was 36.0ºC, and oxygen saturation was 99% on oxygen 4 L/min by face mask. Her pupils were equal, round and reactive to light. Her neurological, cardiovascular and gastrointestinal systems were unremarkable. Laboratory tests disclosed the following values: sodium, 137 mmol/L (normal range 136-142); * MD, Department of Anesthesiology, Vakif Gureba Hospital, Istanbul, Turkey. Corresponding Author: Kerem Erkalp, MD, Şenlikköy Mah. Ekşinar Cad. İncir Sok. Sarı Konaklar Sitesi, No:3, B-Blok, Daire:6, Florya, Bakırköy, Istanbul, Turkey. Tel: 090 212 5346900, Fax: 090 212 6217580, E-mail: [email protected] 869 M.E.J. ANESTH 20 (6), 2010 870 potassium, 4.71 mmol/L (3.5-5.0); total calcium, 2.43 mmol/L (2.05-2.55) [9.7 mg/dL (8.2-10.2)]; ALT, 41 UL (10-14); AST, 40 (20-48). Her renal function values and other liver function values were normal. An electrocardiogram showed sinus tachycardia. Arterial blood gas analyses showed a mild metabolic alkalosis. Plasma amlodipine level was not measured. Hyperinsulinemia-euglycemia (HIE) therapy was provided with increasing rates of dopamine 10 µg·kg-1·min-1 and norepinephrine 0.2 µg·kg-1·min-1 delivery. Calcium chloride 10 g in serum saline over 3 hours was also given with the HIE therapy. On day three, the patient developed shortness of breath and subsequent respiratory arrest. Endotracheal intubation and mechanical ventilation were performed. A repeat chest x-ray showed uniform, diffuse pulmonary infiltrates with a normal-appearing heart. Continious ventilatory support and diuretic therapy for one day were successful in resolving the pulmonary infiltrates, metabolic alkalosis and fever. On the same day, the patient developed a leucocytosis of 28 cells/mL. Tracheal aspirates were pink and foamy, suggesting pulmonary edema. An echocardiogram revealed normal left ventricular function, minimal aortic insufficiency, and mild mitral insufficiency, making a cardiogenic cause for pulmonary edema unlikely. The ejection fraction was 50% and cardiac enzymes were within normal ranges. A subclavian catheter was inserted on the same day and her central venous pressure (CVP) was 21 mm Hg. Because the patient did not respond to initial treatment, she underwent plasma exchange to clear the amlodipine from her circulation. Dopamine 20 µg·kg1·min-1 and norepinephrine 15 µg·kg-1·min-1 were administered for hemodynamic support. On day four, she received levosimendan 12 µg·kg-1·min-1 for 10 min as a loading dose, then levosimendan 0.1 µg·kg-1·min-1 for 12 hours, then levosimendan 0.2 µg·kg-1·min-1 for 12 hours. The patient responded to levosimendan therapy (blood pressure and heart rate returned to normal levels) and inotropes were decreased. On day five, inotropes were stopped, and the patient was succesfully weaned from the ventilator on day six. She was transferred to the Internal Medicine ward after psychiatric consultation. M G. Teker et al Discussion In treating this patient, we searched the published literature and found that HIE therapy is the generally recommended treatment for CCB toxicity in the critical care setting6-12. Supportive care including the use of phosphodiesterase inhibitors, adrenergic agents, cardiac pacing, balloon pump or extracorporeal bypass is indicated if antidotal thearpy is ineffective17-19. Because our patient did not respond to HIE therapy and supportive treatment, we searched for alternative treatement strategies. A study by Buckley et al.20 discussed the use of calcium to overcome amlodipine’s competitive blockade of calcium channels in the cardiac conducting system. The degree of hypercalcemia required to overcome blockade depends on the degree of CCB intoxication and the body’s response20. Buckley et al.20 recommend administering one gram of calcium salts every two to three minutes until the cardiac block is reversed on electrocardiogram. In their experience, patients who were refractory to calcium therapy were refractory to other treatments as well20,21. Our patient received 14 g of calcium chloride, with a resultant serum calcium level of 15 mg/dL (3.75 mmol/L). However, we found no obvious response to this calcium therapy. Because CCBs are highly proteinbound, extensively distributed in tissues, and rapidly metabolized by the liver to inactive metabolites22, hemofiltration and dialysis are ineffective in the management of overdose. One case report by Ezidiegwu at al.23 described successful treatment of amlodipine overdose with plasma exchange after nonresponsiveness to conventional therapy. However, plasma exchange had no effect in our patient. After four days of treatment, our patient remained in shock with no evidence of improvement. We decided to use levosimendan, a calcium-sensitizing agent indicated for use in patients with acutely decompensated heart failure26. Levosimendan sensitizes contractile proteins to calcium by interacting with troponin in cardiac muscle, which prolongs troponin’s effect on contractile proteins26. Levosimendan also vasodilates via ATP-dependent potassium channels27. We used the intravenous levosimendan loading dose and infusion rates that are approved for the short-term treatment of acute severe decompensated heart failure26,28, and LEVOSIMENDAN AS A RESCUE ADJUNCT IN AMLODIPINE INTOXICATION observed blood pressure effects soon after initiating treatment. Conclusion To the best of our knowledge, this is the first report of using levosimendan to treat amlodipine intoxication. In our opinion, levosimendan can be used as a rescue adjunct in paitents with CCB overdoses 871 who fail to respond to conventional therapies such as calcium salts, inotropes, and hyperinsulinemiaeuglycemia therapy. Given the long half-life of CCB agents, levosimendan may be a useful alternative to invasive therapies like intra-aortic balloon pump in CCB overdoses17. Further clinical research is needed to support the current findings opinion and evaluate the role of levosimendan in calcium channel blocker intoxication. M.E.J. ANESTH 20 (6), 2010 872 M G. Teker et al References 1.Bruca DA, William TB: Amlodipine overdose causes prolonged calcium channel blocker toxicity: Am J Emerg Med; 16:527-8, 1998. 2.Vogt S, Mehlig A, Hunziker: Survival of severe amlodipine intoxicarion due to medical intensive care. Forensic Sci Int; 161:216-20, 2006. 3.Katz AM: Cardiac ion channels: N Eng J Med; 328:1244-51, 1993. 4.Hockerman GH, Peterson BZ, Johnson BD, Catterall WA: Molecular determinants of drug binding and action on L-type calcium channels. Annu Rev Pharmacol Toxicol; 37:361-96, 1997. 5.Brunton LL, Lazo JS, Parker KL, Buxton IL, Blumenthal D, editors. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 11th edition. New York, McGraw-Hill, 2005. 6.Ramoska EA, Spiller HA, Winter M, Borys D: A one-year evaluation of calcium channel blocker overdoses: toxicity and treatment. Ann Emerg Med; 22:196-200, 1993. 7.Shepherd G, Klein-Schwartz W: High-dose insulin therapy for calcium-channel blocker overdose. Ann Pharmacother; 39:923-30, 2005. 8.Megarbane B, Karyo S, Baud FJ: The role of insulin and glucose (hyperinsulinaemia/euglycaemia) therapy in acute calcium channel antagonist and beta-blocker poisoning. Toxicol Rev; 23:215-22, 2004. 9.Smith SW, Ferguson KL, Hoffman RS, Nelson LS, Greller HA: Prolonged severe hypotension following combined amlodipine and valsartan ingestion. Clin Toxicol (Phil); 46:470-4, 2008. 10.Greene SL, Gawarammana I, Wood DM, Jones AL, Dargan PI: Relative safety of hyperinsulinemia/euglycaemia therapy in the management of calcium channel blocker overdose:a prospective observational study. Intensive Care Med; 33:2019-24, 2007. 11.Lheureux PER, Zahir S, Gris M, Derrey AS, Penaloza A: Benchto-bedside review: hyperinsulinaemia/euglycaemia therapy in the management of overdose of calcium-channel blockers. Critical Care; 10:212, 2006. 12.Harris NS: Case records of MassachusettsGeneral Hospital. Case 24-2006. A 40 year-old woman with hypotension after an overdose of amlodipine. N Eng J Med; 355:602-11, 2006. 13.Yuan TH, Kerns WP II, Tomaszewski CA, Ford MD, Kline JA: Insulin-glucose as adjunctive therapy for severe calcium channel antagonist poisoning. J Toxicol Clin Toxicol; 36:463-74, 1999. 14.Kline JA, Raymond RM, Leonova ED, Williams TC, Watts JA: Insulin improves heart function and metabolism during nonischemic cardiogenic shock in awake canines. Cardiovasc Res; 34:289-98, 1997. 15.Whitlow PL, Rogers WJ, Smith LR, McDaniel HG, Papapietro SE, Mantle JA, et al: Enhancement of left ventricular function by glucose-insulin-potassium infusion in acute myocardial infarction. Am J Card; 49:811-20, 1982. 16.Rasmussen L, Husted SE, Johnsen SP: Severe intoxication after an intentional overdose of amlodipine Acta Anaesthesiol Scand; 47:1038-40, 2003. 17.Janion M, Stepien A, Sielski J, Gutkowski W: Is the Intra-aortic balloon pump a method of brain protection during cardiogenic shock after drug intoxication? J Emerg Med; Apr 8 (Epub ahead of print), 2008. 18.Ross FD: Calcium channel blockers. In: Goldfrank LR, Flomenbaum NE, Lewin NA, Hoffman RS, Nelson RS, editors. Goldfrank’s Toxicologic Emergencies,7th edtion, New York, McGraw-Hill, pp. 762-74, 2002. 19.Salhanick SD, Shannon MW: Management of calcium channel antagonist overdose. Drug Saf; 26:65-79, 2003. 20.Buckley NA, Dawson AH, Howarth DM, Whyte IM: Slow release verapamil poisoning. Use of polyethylene glycol wholebowel lavage and high-dose calcium. Med J Aust; 158:202-4, 1993. 21.Buckley NA, Whyte IM, Dawson AH: Overdose with calcium channel blockers. BMJ; 308:1639, 1994. 22.Kenny J: Treating overdose with calcium channel blockers. BMJ; 308:992-3, 1994. 23.Ezidiegwu C, Spektor Z, Nasr MR, Kelly KC, Rosales LG: A case report on the role of plasma exchange in the management of massive amlodipine besylate intoxication. Ther Apher Dial; 12:180-4, 2008. 24.Humbert VH JR, Munn NJ, Hawkins RF: Noncardiogenic pulmonary edema complicating massive diltiazem overdose. Chest; 99:258-9, 1991. 25.Stanek EJ, Nelson CE, DeNofrio D: Amlodipine overdose. Ann Pharmacother; 31:853-6, 1997. 26.Toller WG, Stranz C: Levosimendan, a new inotropic and vasodilator agent. Anesthesiology; 104:556-69, 2006. 27.Perrone SV, Kaplinsky EJ: Calcium sensitizer agents: a new class of inotropic agents in the treatment of decompensated heart failure. Int J Cardiol; 103:248-55, 2005. 28.Innes CA, Waqstaff AJ: Levosimendan: a review of its use in the management of acute decompansated heart failure. Drugs; 63:265171, 2003. SUCCESSFUL MANAGEMENT OF HIGH-DOSE METFORMIN INTOXICATION. ROLE OF VASOPRESSIN IN THE MANAGEMENT OF SEVERE LACTIC ACIDOSIS Yasin S Al-Makadma* and Tamer Riad** Case Report We report the case of a 49 year old, 100 kg male patient who, in a suicidal attempt, ingested an estimated dose of 40 to 45 grammes of Metformin. Three hours he presented to AE Department. Due to deterioration of consciousness and a marked irritability, he was sedated, intubated and ventilated at the receiving hospital. On induction of anesthesia (for intubation), the patient hemodynamics became very unstable prompting the initiation of both Epinephrine and Nor-Epinephrine Intra-venous (IV) infusions. Glucose 10% IV infusion and Insulin IV infusion were also started. The pre-transfer management also included Hydrocortisone IV justified by the marked hemodynamic instability and mediocre response to inotropic support. Arterial Blood Gas (ABG) analysis showed severe acidosis and Lactate level of 34 mmol/l, in addition to a Hyperkalemia of 7 mmol/l. He was then transferred to our Intensive Care Unit (ICU) to start Continuous Veno-Venous Hemofiltration (CVVH). On arrival to the ICU, patient was sedated, ventilated. His pupils were dilated and non-reactive. His hemodynamic was refractory, demanding significant inotropic support (at approximately 1mcg/kg/min of Nor-Epinephrine and Epinephrine). The systolic BP was at best 80 to 100 mmHg. His CVP was 19 mmHg. Arterial blood gas revealed a PaO2 of 50 kPa, and a PaCO2 of more than 10 Kpa despite hyperventilation. The arterial blood pH remained as low as 6.8. Lactate level was beyond the maximum titration limit of our ABG machine. ****Blood Sugar was at 11 g/l. The administration of 500 mls of Molar Sodium Bicarbonate failed to improve the metabolic acidosis and despite the initiation of CVVH, using Prisma System, the pH remained around 6.80 on repetitive analysis. As Catecholamines requirements were increasing with limited benefit on hemodynamic parameters, the decision to introduce Vasopressin IV infusion was taken. We used Pitressin*, diluted in Dextrose 5% solution for a final concentration of 1 IU/ml. The initial dose was 6 IU/hour. Rapid improvement of ABP parallel with rapid decrease of Epinephrine requirement allowed to be stopped by the next morning, less than 12 hours from the introduction of Vasopressin. We also noted a slow but consistent rise of the pH. * MD, FFA. **FRCA. Corresponding author: Dr. Yasin S. Al-Makadma, MD, CMU, FFA, FFPM, Security Forces Hospital, Riyadh, KSA, Co-author: Dr. Tamer Riad, FFA, Mid-Yorkshire Hospitals, Dewsbury, UK. 873 M.E.J. ANESTH 20 (6), 2010 874 Y. S Al-Makadma & T. Riad Table 1 pH and Base-Excess recorded first 48 hours of admission Time (hours) Base Deficit pH A&E “OUT OF RANGE” 6.8 ICU admission -28.3 6.79 4 -28.7 6.79 8 -26.7 6.86 16 -17.4 7.12 24 -16.8 7.13 28 -16.1 7.16 32 -15 7.17 40 -12.6 7.22 48 -9.8 7.28 The patient continued to rapidly improve from hemodynamic point of view and the Nor-Epinephrine was gradually weaned and stopped over few days. The Vasopressin infusion was gradually decreased and stopped as the stabilization of the hemodynamic state was confirmed. A Tracheostomy was performed followed by a successful weaning of Ventilator three days later. The patient was discharged to the HDU and then to a medical ward before leaving the hospital. Discussion Metformin is a Biguanide oral anti-diabetic agent. The pharmacological action of this molecule depends on decreasing Glucose transit through intestinal mucosal cells and decreasing gluconeogenesis as well as increasing peripheral glucose utilization. There are only few cases of Metformin overdose in the literature. To our knowledge, the highest dose reported as overdose was 25 g, at the time of our case. Dell'Anglio et al reported, more recently, a suspected much higher dose at 75 to 100 g1. Our patient's overdose remains however very significant at, 40 to 45 g of Metformin. Except in multiple drugs intoxication, combined with Metformin and considering the mode of action of Metformin, hypoglycemia is not a major issue1 in either normal therapeutic range or overdose. Lactic acidosis, however, is a well documented complication of Metformin overdose1-5, with risk of fatal outcome in over 50% of cases2. This risk is considerably increased if treatment is initiated after cardiovascular collapse occurs2. High plasmatic metformin level above 150 mcg/ml, high lactatemia and low pH would predict increased risk of mortality2,3,4. Lactic acidosis is not due to tissue hypoxemia and anaerobic metabolism but to reduction of cell redox function. The negative inotropism effect of Metformin could also contribute to the ability of hepatocytes to extract circulating lactate. This kind of Lactic acidosis, in the absence of anaerobic metabolism is known as type B Lactic acidosis. Prognosis of type B Lactic acidosis does not necessarily correlate with the level of lactatemia15. Aggressive therapy should be initiated as a soon as possible. The use of CVVH, when bicarbonate administration fails to correct the acidosis remains a corner stone in the management of its complication8,9,10. With this severe acidosis, Metformin overdose concomitantly presents with a refractory hemodynamic status6,7, of which the support can be very difficult. Death can be the unfortunate outcome in these overdoses if the intensive therapy fails to reverse the general trend of acidosis and circulatory failure. There is a vicious circle that starts with the acidosis and continues with the circulatory failure. A lot of emphasis is made for the treatment of acidosis8,9,10, but less clear advice is given for the modality of hemodynamic support. The use of high amounts of Nor-Epinephrine and Epinephrine is not always efficient in supporting the cardio-vascular system in the context of severe metabolic acidosis. We believe that our case supports that early use of Vasopressin can be very useful in the treatment of precarious haemodynamic states and circulatory failure in relation with Metformin overdose and probably in those circulatory failures linked to severe acidosis. This role could be due to the fact that below a pH of 6.9, the Catecholamines can be of limited effect6. In addition, Vasopressin seems to compromise regional perfusion less than does Noradrenaline. This would help in limiting the aggravation of metabolic acidosis as could be seen with Epinephrine and Norepinephrine. It is also well accepted that, in case of underutilization of lactate, like in Metformin overdose cases, the treatment of the underlying cause is of a major importance. The CVVH in such case is less efficient than in cases of Mineral metabolic acidosis. SUCCESSFUL MANAGEMENT OF HIGH-DOSE METFORMIN INTOXICATION. ROLE OF VASOPRESSIN IN THE MANAGEMENT OF SEVERE LACTIC ACIDOSIS The treatment of organic metabolic acidosis should be geared towards the correction of the cause rather than the symptoms8. This would mean that Renal dialysis techniques are not necessarily the unique answer to Lactic acidosis caused by Metformin overdose. Some authors found, however, that CVVH is successful in the treatment of such acidosis5. More recently, it is high flow CVVH that was recommended for Metformin overdose. In these circumstances, the CVVH would be efficient in the treatment of Lactic acidosis either by clearance of the Metformin or by the improvement of hemodynamic state of the patient. Why Vasopressin? It is admitted that the sympathetic effects of Catecholamines are less strong in acidotic conditions (()). Although a range of pH between 7.4 and 7 is considered, by some authors, to be compatible with the activity of Catecholamines, these drugs would 875 loose their effect however if the pH decreases below 6.96,7. In Metformin overdose complicated by a severe lactic acidosis, the hemodynamic instability is mainly due to the deep vasodilatation that occurs and not to the effect of acidosis on the myocardium10. Conclusion Intoxication by high dose of Metformin could lead to fatal outcome, mainly by the detrimental effects on the hemodynamic function. In this scenario, Catecholamines are not necessarily efficient. The management of severe lactic acidosis associated with Metformin overdose should include aggressive hemodynamic support and early introduction of Vasopressin. High flow, lactate-depleted CVVH could also be beneficial in reversing the trend towards fatality. References 1. Dell’aglio DM, Perino LJ, Todino JD, Algren DA, Morgan BW: Metformin overdose with a resultant serum pH of 6.59: Survival without sequalae; J Em Med, 2008, in press. 2. Perrone J, Phillips C, Gaieski D: Occult Metformin Toxicity in Three Patients with Profound Lactic Acidosis, J Emergency Medicine, 2008. 3. DM Dell’Aglio, LJ Perino, ZN Kazzi, BW Morgan, MD Schwartz and RJ Geller: Mortality in acute metformin overdose is predicted by serum pH, lactate, and metformin concentration, J Toxicol Clin Toxicol; 44 (2006), p. 712. 4. Nisse P, Mathieu-Nolf M, Deveaux M, Forceville X, Combes: A fatal case of metformin poisoning. AJ Toxicol Clin Toxicol; 2003, 41(7):1035-6. 5. Ben Harvey RSCN, Ceri Hickman RSCN, Gillian Hinson, MRPharmS, Tanya Ralph RSCN, Anton Mayer MRCPCH: Severe lactic acidosis complicating metformin overdose successfully treated with high-volume venovenous hemofiltration and aggressive alkalinization; Pediatr Crit Care Med; 2005, 6:598-601. 6. Smith NT, Corbascio AN: Myocardial resistance to metabolic acidosis. Arch Surg; 1966, 92:892-896. 7. Huang YG, Wong KC, Yip WH, et al: Cardiovascular responses to graded doses of three catecholamines during lactic and hydrochloric acidosis in dogs. Br J Anaesthesiol; 1995, 74:583-590. 8. Levraut J, Ciebiera JP, Jambou P, et al: Effect of continuous venovenous hemofiltration with dialysis on lactate clearance in critically ill patients. Crit Care Med; 1997, 25:58-62. 9. Hilton PJ, Taylor J, Forni LG, et al: Bicarbonate-based haemofiltration in the management of acute renal failure with lactic acidosis. Q J Med; 1998, 91:279-283. 10.Teale KFH, Devine A, Stewart H, Harper: The management of metformin overdose, Case Report, NJH, Anaesthesia; July 1998, 53(7), pp. 698-701. M.E.J. ANESTH 20 (6), 2010 AWAKE CRANIOTOMY USING INITIAL SLEEP WITH LARYNGEAL MASK AIRWAY IN DEPRESSED AGITATED PATIENT - A Case Report - Khalid M Al Shuaibi* Abstract Depressed patients with brain tumors are often not referred to awake craniotomy because of concern of uncooperation which may increase the risk of perioperative complications. This report describes an interesting case of Awake Craniotomy for frontal lobe glioma in 41 year old woman undergoing language and motor mapping intra-operatively. As she was fearful and apprehensive and was on antidepressant therapy to control depression the author adapted general anesthesia with laryngeal mask airway during initial stage of skull pinning and craniotomy procedures.Then patient reverted to awake state to continue the intended neurosurgical procedure. Patient tolerated the situation satisfactory and was cooperative till the finish without any event. Key words: craniotomy; awake. LMA. Parietal tumor. Introduction Intra-operative mapping, of targeted areas of brain resection, is an integral part of modern neurosurgery. Intraoperative stimulation of near speech and motor regions may prevent un-necessary nervous tissue damage. while using neuro navigation and intraoperative MRI (iMRI) allowing maximum resection of the tumor. This procedure requires an awake, cooperative patient to assess motor and verbal responses. Sometimes patient may be not cooperative during this procedure due to psychological profile or extreme fear from the notion of being awake during initial surgical intervention while the skull is fixed and then opened. This report describes the author’s experience with awake craniotomy in a middle aged woman having anxiety and treated for depression, using initial sleep and maintaining the airway by laryngeal mask airway initially then awake technique before testing and to the end of the surgery. * MD, Pain Medicine Fellow. Consultant of Anesthesiology, Pain Medicine &Chairman of Anesthesia, Department of Anesthesia, King Fahad Medical City, Riyadh, Kingdom Saudi Arabia. E-mail: [email protected] 877 M.E.J. ANESTH 20 (6), 2010 878 Case Report A 42 year old female (weight:59 kg. Hight:168 cm) presented to the Neuroscience Department at King Fahad Medical City (KFMC), complaining of progressively, increasing headaches of 18 months duration. She was placed on anticonvulsant therapy: valproic. Clinical history revealed reports of depression since a long time related to overwhelming psychosocial problems at home. Clinical examinations were unremarkable. Awake craniotomy was planned including intra-operative mapping for language and motor function. In the BrainSuite® Lab, intravenous line was started and sedation using both midazolam 1-2 mg iv. and fentanyl 25-50 µg iv. Standard anesthetic monitoring was initiated (ECG, NIBP and pulse oximetry). A right radial arterial line was inserted, under local anesthesia, for continuous blood pressure measurement and serial blood gases monitoring. A nasal cannula was placed in position. Scalp Block was established, with the use of 80 ml of 0.125% bupivacaine and 5 µg.ml-1 of adrenaline, by the surgeon. The patient was positioned in supine position and her head was rotated to the left side. A four-pin frame failed to fix after many trials due to irritable patient. We gave 20-30 mg propofol bolus with 25-50 µg fentanyl and still the patient was uncooperative during the pins application. Anesthesia was induced with propofol 2 mg.kg-1 and fentanyl 50 µg. iv. Laryngeal Mask Airway (LMA) size 3 was inserted easily and after demonstration of proper deep anesthesia. Airway and spontaneous breathing was maintained using 4 L.min-1 of 50% 02 in air. Anesthesia was maintained with combined continuous infusions of propofol 1% 20-30 ml.h-1 and fentanyl 25 ug.h-1. Patient then brought to the BrainSuite® Lab. for preoperative MRI and Neuronavigation. MRI- compatible monitoring was included i/ e. ECG, IBP, Capnography, Temperature and Pulse Oximetry. Patient; urinary bladder was catheterized and mannitol 0.5 mg.kg-1 was given in addition to Dexamethazone 8 mg iv. Surgery started and after the dura is opened the propofol and fentanyl was gradually decreased and later stopped. The patient became awake smoothly. LMA was removed without complications. Oxygenation was maintained with a nasal cannula. The patient Khalid M Al Shuaibi became completely awake, able to talk within 10 minutes following the removal of LMA. The surgery was commenced again while the patient was fully awake with proper intra-operative motor and language assessments. The course of the surgery went uneventful. Hemodynamic variables were thoroughly stable. There were no desaturation or airway obstruction. Another MRI study was done while patient was completely awake. After surgery patient was transferred to SICU with a good clinical condition. Discussion BrainSuite Lab is newly established at KFMC. Two years have passed and various difficult neurosurgical surgery operation with great success. Awake craniotomy was done to benefit from intraoperative MRi and navigation facilities1. Awake craniotomy for seizure foci resection is currently popular since a complete resolution of seizures foci without increasing neurological deficit2,-4. This requires “asleep, awake, asleep” anesthesia technique to keep an awake, comfortable patient who cooperates with intraoperative testing. Drugs are used to manage this state. They are selected according to their short half-lives and ease of titration. Using such drugs concurrently can cause powerful respiratory depression. Our selection of the prescribed regimen in accordance of reported success in literature2,5. Neuroanesthesia team should be vigilant for such events like: hypoventilation, apnea, and chest wall rigidity. Several options are available for airway management during awake craniotomy including endotracheal intubation, LMA, nasal airway and non intubation technique preserving natural airway. Adverse events during awake craniotomy can include nausea, intraoperative anxiety, seizures, and brain engorgement6,7. Nausea and/or vomiting may result in significant morbidity. We chose to reduce this risk, by administering ranitidine, ondansetron, metoclopramide, dexamethasone, and glycopyrrolate. Appropriate patient selection is critical to success. In this vase it was not an ideal patient for the technique but detailed pre-operative explanation of the anesthesia plan was important for operators AWAKE CRANIOTOMY USING INITIAL SLEEP WITH LARYNGEAL MASK AIRWAY, IN DEPRESSED AGITATED PATIENT to go ahead. Despite uncontrollable anxiety and the concurrent state of depression we expected that incorporation could still occur. Our efforts focus on reassure the patient followed by supplements of sedoanalgesics regimen and we explained, to the patient, that general anesthesia is possible for short period and there would be no pain when she will be waken up for testing. Intraoperative urgent intubation is technically difficult and slow to secure. The anesthesiologist in expectation of intraoperative seizers. Although, it did not happened in this case, the plan for its control swiftly should be in mind i.e. surgeon’s application of ice water irrigation and discontinuation of stimulation, anticonvulsants intravenously and if respiratory instability occur, intubation and controlled ventilation. Fig. 1 Briansuite ® settings: surgeon looking to mural screens showing integrated iMRI an imaging with microscopic operating field screen 879 In conclusion, a careful approach in handeling psychological patient may tolerate the current analgesia and anesthesia techniques during awake craniotomy, this case may open the field to operate on moderately disturbed patient and have more exposure rather keeping awake craniotomy for fully co-operative patient. Anesthesiologist should be malleable in his plan to the immediate needs of his patient. Acknowledgement The author would like to thank neurosurgical team lead by Dr Ahmad Larry for using information derived from their patient and iMRI brainsuite staff who performed the iMRI study. Fig. 2 MRI vault: the patient is drapped and protected by head coil before iMRI session M.E.J. ANESTH 20 (6), 2010 880 Khalid M Al Shuaibi References 1. M Said Maani Takrouri & OS Seif: Leap Into Future In Image Navigation Neurosurgery: Visit to the BrainSuite at King Fahad Medical City in Riyadh, KSA. The Internet Journal of Health; 2007, Volume 6 Number 1. 2. Sarang A, Dinsmore J: Anaesthesia for awake craniotomy evolution of a technique that facilitates awake neurological testing. Br J Anaesth; 2003, 90:161-5. 3. Ebeling U, Schmid UD, Ying H, et al: Safe surgery of lesions near the motor cortex using intra-operative mapping techniques: A report on 50 patients. Acta Neurochir; (Wien) 1992, 119:23-28. 4. Sahjpaul RL: Awake craniotomy: controversies, indications and techniques in the surgical treatment of temporal lobe epilepsy. Can J Neurol Sci; 2000, 27(S1):S55-63. 5. McDougall RJ, Rosenfeld JV, Wrennall JA, et al: Awake Craniotomy in an Adolescent. Anaesth Intensive Care; 2001, 29:423-425. 6. Archer DP, McKenna JM, Morin L, et al: Conscious-sedation analgesia during craniotomy for intractable epilepsy: a review of 354 consecutive cases. Can J Anaesth; 1988, 35(4):338-344. 7. Young DA: Awake craniotomy using a modified nasal airway, propofol, and remifentanil in an adolescent. http://www.pedsanesthesia.org/meetings/2004winter/pdfs/2004_ P23.pdf [last access: oct.23rd 2009]. CARDIAC ARRHYTHMIA AFTER SUCCINYLCHOLINE ADMINISTRATION IN A PATIENT WITH GUILLAIN-BARRÉ SYNDROME - A Case Report - Jyh Yung Hor* Abstract We report a case of cardiac arrhythmia occurring in a Guillain-Barré syndrome (GBS) patient after succinylcholine administration during third endotracheal intubation, on day 13 of illness. The probable cause of arrhythmia is succinylcholine-induced hyperkalemia. Of interest, this case demonstrated in the same patient that arrhythmia only occurred during third intubation, when duration of illness is prolonged, and not during previous two intubation episodes, despite succinylcholine was also being used. In GBS, muscle denervation resulted in up-regulation of acetylcholine receptors at neuromuscular junctions, causing the muscle cell membrane to become supersensitive to succinylcholine, leading to severe hyperkalemia and arrhythmia when succinylcholine was administered. Key words: Guillain-Barré syndrome, Succinylcholine, Cardiac arrhythmia, Endotracheal intubation, Acetylcholine receptor up-regulation, Denervation. Introduction Succinylcholine-induced hyperkalemia causing life-threatening cardiac arrhythmia has been reported in Guillain-Barré syndrome (GBS)1,2 and in chronic polyneuropathy3. Here, we present a case of cardiac arrhythmia in a patient with GBS after succinylcholine administration during the third endotracheal intubation, on day 13 of illness. Of interest, this case demonstrated in the same patient that arrhythmia only occurred during third intubation, when the duration of illness is prolonged, and not during previous two intubation episodes, despite succinylcholine was also being used. * MD, Department of Internal Medicine, Sultanah Bahiyah Hospital, Alor Star, Kedah, Malaysia. Corresponding Author: Jyh Yung Hor, MD, 5 Lebuh Batu Maung 6, 11960 Penang, Malaysia. Tel.: +60 12 4617842, Fax: +60 4 6563754, E-mail: [email protected] 881 M.E.J. ANESTH 20 (6), 2010 882 Case Report A 30-year-old woman presented with 4-day history of hands and feet numbness, followed by weakness of upper and lower limbs that started distally. One day prior to admission, she became unable to walk, breathless, and having dysphagia. On presentation, she was conscious, afebrile but tachypneic. Power of both upper and lower limbs was 2/5, and with generalized areflexia. A clinical diagnosis of GBS was made. She deteriorated fast and was intubated for respiratory failure. Midazolam 5mg intravenous (i.v.) and succinylcholine 100mg i.v. were given prior to intubation. She was admitted to intensive care unit (ICU) for mechanical ventilation, and was given i.v. immunoglobulin 0.4g/kg/day for 5 days. On day 6 of ICU stay (day 10 of illness), her muscle power improved to 4/5 for upper limbs and 3/5 for lower limbs. She was extubated and put on oxygen supplementation. However, 1 hour after extubation, she became breathless and was unable to speak. She was re-intubated, using i.v. midazolam and succinylcholine as before. The potassium level prior to re-intubation was 4.32 mmol/L. On day 9 of ICU stay (day 13 of illness), her condition has again improved clinically. She was extubated and given oxygen supplementation. However, 1.5 hour after extubation, she again became tachypneic. Nevertheless, she remained conscious and oxygen saturation by pulse oxymetry was maintained at 99%. Re-intubation was decided. To facilitate intubation, i.v. midazolam 5mg and i.v. succinylcholine 100mg were given. Just before attempt for intubation, ventricular tachycardia (VT) was noted on cardiac monitor. She was promptly intubated, and cardiopulmonary resuscitation (CPR) was immediately initiated, and was continued for about 15 minutes. During CPR, she was defibrillated 3 times for pulseless VT, before being reverted to sinus tachycardia. Her potassium level on that morning was 4.41mmol/L. The potassium level repeated after CPR was 4.63 mmol/L. On day 13 of ICU stay, there was a leak at the endotracheal tube. She was extubated and given non-invasive ventilation. She tolerated well and was weaned off ventilator the next day. Her muscle power Jyh Yung Hor eventually returned to normal. She could walk, talk and swallow well, and was discharged after 20 days of hospitalisation. Discussion The probable cause of cardiac arrhythmia in this patient is succinylcholine-induced hyperkalemia. Noxious stimuli such as laryngoscopy and endotracheal intubation may also trigger cardiac arrhythmia, but in this case arrhythmia has occurred prior to such manipulation. Normally, serum potassium increases by 0.5 to 1 mmol/L after succinylcholine administration4. In GBS, muscle denervation results in increased production of acetylcholine receptors5,6. With this up-regulation, the muscle cell membrane becomes supersensitive to succinylcholine, resulting in a great efflux of potassium upon succinylcholine administration, that may lead to severe hyperkalemia and cardiac arrhythmia. This supersensitivity increases dramatically by day 5, and can continue for weeks or even longer5-7. This explains why this patient did not develop arrhythmia on admission day and on day 6 when succinylcholine was used, but subsequently developed it on day 9 of ICU stay (day 13 of illness). It is important to note that prior to second intubation on day 6 and third intubation on day 9, the potassium levels were 4.32mmol/L and 4.41mmol/L, respectively. Despite the very similar potassium level, arrhythmia only happened on a later occasion. Succinylcholine-induced hyperkalemia is a transient phenomenon, where potassium level peaked at 3 - 5 minutes to around 8 or 9 mmol/L in denervated muscle, then started decreasing over time, and eventually back to normal range by 20 - 30 minutes3,7,8. This may explain why severe hyperkalemia was not seen in her post-CPR blood results, as blood was only withdrawn about 30 minutes after onset of VT. From the literature, succinylcholine-induced hyperkalemia has not been reported in patients with acquired pathologic states of < 4 days’ duration5. This case re-affirms the observation, where cardiac arrhythmia (most probably due to hyperkalemia) only occurred at day 13 of illness, and not earlier even though succinylcholine was used twice before CARDIAC ARRHYTHMIA AFTER SUCCINYLCHOLINE ADMINISTRATION IN A PATIENT WITH GUILLAIN-BARRÉ SYNDROME that. Of particular interest, this case demonstrated in the same patient that arrhythmia did not occur with succinylcholine administration on days 1 and 6 of admission, but happened on day 9 of admission during third intubation, despite the very similar pre-intubation potassium level of around 4.4mmol/L during each occasion. 883 In conclusion, succinylcholine should be avoided in GBS, as has been recommended by others1,2, especially when the duration of illness was > 4 days5. Instead, non-depolarizing muscle relaxant with relatively more rapid onset such as rocuronium should be considered. References 1. Reilly M, Hutchinson M: Suxamethonium is contraindicated in the Guillain-Barré syndrome. J Neurol Neurosurg Psychiatry; 1991, 54:1018-1019. 2. Dalman JE, Verhagen WIM: Cardiac arrest in Gullain-Barré syndrome and the use of suxamethonium. Acta Neurol Belg; 1994, 94:259-261. 3. Fergusson RJ, Wright DJ, Willey RF, Crompton GK, Grant IWB: Suxamethonium is dangerous in polyneuropathy. BMJ; 1981, 282:298-299. 4. Bevan DR, Donati F: Muscle relaxants. In: Barash PG, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2001, pp.419-447. 5. Martyn JAJ, Richtsfeld M: Succinylcholine-induced hyperkalemia in acquired pathologic states: etiologic factors and molecular mechanisms. Anesthesiology; 2006, 104:158-169. 6. Martyn JAJ, White DA, Gronert GA, Jaffe RS, Ward JM: Upand-down regulation of skeletal muscle acetylcholine receptors: effects on neuromuscular blockers. Anesthesiology; 1992, 76:822843. 7. Gronert GA, Theye RA: Pathophysiology of hyperkalemia induced by succinylcholine. Anesthesiology; 1975, 43:89-99. 8. Gronert GA, Lambert EH, Theye RA: The response of denervated skeletal muscle to succinylcholine. Anesthesiology; 1973, 39:13-22. M.E.J. ANESTH 20 (6), 2010 CONSCIOUS SEDATION FOR AWAKE CRANIOTOMY IN INTRA-OPERATIVE Magnetic RESONANCE IMAGING OPERATING THEATRE (IMRI OT) ENVIRONMENT Mohamad Said Maani Takrouri*, Firas A Shubbak**, Aisha Al Hajjaj***, Rolando F Del Maaestro****, Lahbib Soualmi*****, Mashael H Alkhodair******, Abrar M Alduraibi****** and Najeeb Ghanem******* Abstract This technical report disrobes the first case in Intra-operative Magnatic Resonance Imaging operating theatre (iMRI OT) (BrainSuite®), of Awake Craniotomy. The procedure was for frontal lobe glioma excision in 24 y. old man. He was scheduled to undergo eloquent cortex language mapping intra-operatively. He was motivated and was excited to see the operating theatre. He requested to take his photos while operated upon. The authors adapted conscious sedation technique with variable depth according to Ramsey’s scale , in order to revert to awake state to perform the intended neurosurgical procedure. Patient tolerated the situation satisfactory and was cooperative till the finish without any event. We elicit in this report the special environment of iMRI OT for lengthy operation in pinned fixed patient having craniotomy. The text shows the special environment, its demands and its possible difficulties. Key words: Awake craniotomy; scalp block ; language mapping motor testing. Intra-operative Magnatic Resonance Imaging operating theatre (iMRI OT); BrainSuite®: Coil head protection. Neuroanesthesia; Neurosurgery. Introduction Intra-operative mapping, of intended areas of brain resection, constitutes an essential part of modern neurosurgery1-4. It is well established that intra-operative stimulation of near speech and motor regions. Also using neuro-navigation and intra-operative MRI (iMRI) allows maximum resection of the tumor4,5. This procedure requires an awake, cooperative patient to assess motor and verbal responses. Sometimes patient may be not cooperative during this procedure due to psychological profile or extreme fear from the notion of being awake during surgical intervention while the skull is fixed and then opened. The anesthetic technique has to satisfy three parties; * MB. ChB. FRCA (I), Consultant. ** MD, CJBA, Assistant Consultant Anesthesiologist. *** MD, Consultant Neurosurgeon and Neurointervention. **** MD, PhD, FRCS(c), FRCE, DABNC, Profesor of Neurosurgery and Oncology. ***** PhD, Director of Neuronavigation Unit and Brain Suite. ****** BSc, SLP, Speech Language Pathologist II. *******MD, Consultant Interventional Radiologist. 885 M.E.J. ANESTH 20 (6), 2010 886 patient, surgeon and anesthesiologist4. Many anesthesia techniques may help to produce favorable operating condition based on Scalp block with local anesthesia and various sedation and anesthesia based on propofol titrated sedation and short acting narcotics (ramifentanil and fentanyl)5-20. This will allow stages of sleep-awake-sleep or sedation-awake-sedation. This report describes the authors experience with (nine hours duration) of awake craniotomy, interrupted by session of iMRI, on a man who was motivated to be subjected to awake technique before and during testing language mapping. It was carried out under conscious sedation which was interrupted during sessions of mapping then continued to the end of the surgery. Case Report A 24 year old male (weight: 69 kg. Hight:168 cm) presented to the Neurosciences Department at King Fahad Medical City (KFMC).He complained of one sudden episode of seizure, for which a brain CT scanwas done reveling a left frontal lobe tumor. Awake craniotomy was planned including intra-operative brain mapping, for resection of epileptogenic foci close to eloquent cortex, i.e. motor and speech areas of the brain, for language and motor function. In preoperative assessment he stated to be smoker of 20 cigarettes a day. Medically he was known to have mild intermittent bronchial asthma on treatment of β2 agonist (salbutamol nebulizer). On examination; the patient was conscious, oriented to place time and dates, alert, no signs of limbs weakness nore speech abnormalities. He was already seen by speech specialist and surgeon who informed him about all the expected operation and his role to reduce and prevent any side effects. Emphasis was put on that he is going to be awake during testing and he would have 2- 3 sessions of iMRI. Anesthesiologists answer all the questions regarding pain and sedation and being beside him all the operation. He was very excited about being operated upon in BrainSuite® theatre. He requested to have his pictures takrn during the procedures and he gave consent to use it for medical publications. M. S. Maani Takrouri et. al Vitals: HR:80 b.min-1, RR: 20 b.min-1, SPO2: 97% room air, BP: 130/80 mmHg, temp:36.9 Cº. Laboratory investigations were all within normal ranges. In iMRI OT, intravenous line was established and sedation using both propofol 1-2 mg iv. and fentanyl 25-50 µg iv. Standard, Monitoring was initiated (ECG, NIBP , skin temperature and pulse oximetry). The patient was placed in supine position. Oxygenation while breathing air was enriched through a nasal oxygen catheter, was delivering 2 l.min-1. Conscious sedation was maintained with continuous infusions of: - Propofol (20-40) ug.kg-1.min-1. - Fentanyl at the rate of 2 µg.kg-1.h-1 Infusion rates. Depth of sedation was adjusted by the attending anesthesiologists according to patient comfort, hemodynamic and respiratory parameters and was kept ar 2-4 Ramsay’s sedation scale. Scalp Block was established, with the use of 80 ml of 0.125% bupivacaine and 5 µg.ml-1 of adrenaline, by the surgeon. Concern in managing patient in iMRI theatre environment. MRI environment would dictate strict obedience to instruction and wornings for MRI compatibility. Fig. 1 The patient after scalp block and under conscious sedation pinned to the table and drapped ready for craniotomy CONSCIOUS SEDATION FOR AWAKE CRANIOTOMY IN INTRA-OPERATIVE MAGNETIC RESONANCE IMAGING OPERATING THEATRE (IMRI OT) ENVIRONMENT Fig. 2 Scalp incision under scalp block and conscious sedation 887 Fig. 5 Patient’s movement carried on surgical table top to and from MRI tube with extreme care for connected monitored and intravenous lines. One of the authors [FS]. is pictured in the far right caring for the patient. Fig. 3 Patient’s ears are plugged with earphones with recitation of quean as he requested to help him coping with iMRI noise Fig. 6a Pre operative: Left frontal lobe mass lesion, low signal in T1 WI, and High signal intensities in T2 WI , with homogeneous enhancement and necrotic area in Post Gad T1 WI Fig. 4 Patient’s head covered with head shield (coil) after ears are plugged with earphones with recitation of quean as he requested to help him coping with iMRI noise. The airway is protected by keeping the patient in conscious sedation (Natural airway). T1_WI_pre_op (A) Left frontal lobe mass lesion showed hypo intense signal intensity inT1 W Image T2_WI_pre_op (B) Left frontal lobe mass lesion showed high signal intensities in T2 W Image. Post_Gad_T1_WI_pre_op (C) Left frontal lobe mass showed inhomogeneous enhancement and necrotic area in Post Gad T1 W image M.E.J. ANESTH 20 (6), 2010 888 M. S. Maani Takrouri et. al Fig. 6b Post Operative: Left frontal surgical cavity ( Encephalomalacia) at previously removed frontal lobe mass in post GAD T1 WI with minimal linear enhancement representing reactiveenhancement with no residual mass. Pre-Operative language assessment: Within the same week of surgery, a full language and cognitive-linguistic assessments were done. Additionally, a trial of intra-operative assessment using pictures naming task (50 pictures or more) was done the same day .Patient presented with normal receptive and expressive language skills along with a normal cognitive-linguistics skills .Results were documented as patient's pre-operative baseline. After that patient was counseled regarding the intra-operative assessment that he will undergo. Intra-operative language assessment: T1_WI_post_op (D) Left frontal surgical cavity (Enchephalomalaxia) at previously removed frontal lobe mass showed low signal intensity (CSF intensity) in T1 W image T2_WI_post_op (E) Left frontal surgical cavity (Enchephalomalaxia) at previously removed frontal lobe mass showed high signal intensity (CSF intensity) in T2 W image Post_Gad_T1_WI__post_op (F) Left frontal surgical cavity (Enchephalomalaxia) at previously removed frontal lobe mass with minimal linear enhancement in post GAD T1 WI represent reactive enhancement without residual mass. Fig. 6 iMRI images with radiologist’s report Patient before entering the MRI tube should wear ear plugs to protect his ears from the noise. Also the head would be covered by head shield coil to protedt it from all possible contact inside the tube or incidental projectiles. The patient was planned for three iMRI sessions and he was prepared this way each time. Care was critically applied when the operating table top was moved to and from the MRI tube. Duration of the procedure: It took six hours operation and mapping, and three hours iMRI sessions Speech-Language pathologist ‘s role in Awake Brain Mapping of Dominant hemisphere protocol followed in this case Speech-language pathologists attended the surgery after the bone flap for the sensorimotor mapping. Speech-language pathologist arranged with the neurophysiologists and neurosurgeons regarding the timing and type of stimulation. The patient was asked to perform counting (regularly from 1 to 10 over and over) and provide naming (proceeded by the carrier phrase "this is a……").The two tasks were used to identify the essential language sites known to be inhibited by stimulation. (SLPs were observing for any disturbance in language functions during the stimulations and alerting the surgeon to it). During the tumor resection, patient continued to count and/or name pictures when the resection became closer to the subcortical language structures. Post-operative language assessment: The patient was assessed 2-days post surgery by the speech-language pathologist using the same language and cognitive-linguistics assessment tools that were used preoperatively. Assessment showed intact receptive and expressive language skills. Discussion The iMRI OT is newly established at KFMC21. Two years have passed and various difficult neurosurgical operations were performed with great success5. Awake craniotomy was done to benefit from intra-operative MRi and navigation facilities21. The surgeon would operate with advantage of dynamic imaging navigation allowing proper tumor tissue resection with elimination of brain tissue shift effect, which is experience in brian surgery. The updated pictures are projected on wall mounted huge screen CONSCIOUS SEDATION FOR AWAKE CRANIOTOMY IN INTRA-OPERATIVE MAGNETIC RESONANCE IMAGING OPERATING THEATRE (IMRI OT) ENVIRONMENT 889 and satellite screens in front of the eye of the surgeon and his assistants21. Table 2 The key components of the BrainSuite® iMRI Surgical team operate outside the effect of MRI influence put again they should observe MRI compatibility code. 1. Navigation System. Automatic Image Registration Operating inside this environment necessitate adaptation of MRI compatibility and other anesthesia technique adjustments [Table 1, 2]. 3. Data Billboard BrainSuite and Data Management System. Awake craniotomy for seizure foci resection is currently popular since it allows a complete resolution of seizures foci without increasing neurological deficit17-20. This requires “asleep, awake, asleep” anesthesia technique to keep an awake, comfortable patient who cooperates with intra-operative testing. Anesthetic drugs are selected according to their short half-lives and ease of titration. Propofol and fentanyl were selected in this case in accordance of reported success in literature17-20. Table 1 Issues of concern to anesthesia staff in iMRI OT Issues Anaesthetic Considerations Ferromagnetic Implant devices: Aneurismal clips. Objects Prosthetic heart valves. Tissue expanders with metallic ports. Cardiac pacemakers. Also antable defibrillators/cardioverters and implantable infusion pumps. Metallic based substancespens, key chains, scissors, Noise stethoscope, non lithium batteries etc. It comes from scanner due to torque of wire have gradient currents induced in them during RF pulses. This cause Occupational vibration and audible noise. There are no reports of harmful tissue Exposure Anaesthesia contact with the magnetic fields. Safety. Proper functioning in the magnetic Machines field. No effect on MRI image quality. Ventillators ECG Monitor can cause image degradation of MRI scans from the wire leads acting as antennas. Pulse Oximetry Burn to finger. Blood Pressure Adjustment and MRI compatible Monitoring measuring screens. Some irregular measurements transmission. Mohammad Bilal Delvi et al, MEJ ANESTH, 19 (1), 2007 [21]. Vector Vision software. 2. Microscope Zeiss OPMI Neuro NC4 MultiVision. 4. BrainSuite iMRI system: high-field MRI scanner (1.5 Tesla Siemens Magnetom Espree). 5. Rotating Operating Room (OR) table with integrated head clamp and coil. 6. Operating room (OR) lights with integrated video camera, ceiling supply unit, anesthesia equipment. 7. BrainSuite iMRI RF shielded OR cabin. MSM Takrouri, The Internet Journal of Health, 2007 Volume 6 [22]. Using such drugs concurrently can cause powerful respiratory depression. Neuroanesthesia team should be vigilant for such events like: hypoventilation, apnea, and chest wall rigidity. Several options are available for airway management during awake craniotomy including endotracheal intubation, LMA, nasal airway and non intubation technique preserving natural airway23,24. Adverse events during awake craniotomy can include nausea, intraoperative anxiety, seizures, and brain engorgement7,24. Nausea and/or vomiting may result in significant morbidity. We chose to reduce this risk, by administering ranitidine, ondansetron, metoclopramide, dexamethasone, and glycopyrrolate. Appropriate patient selection is critical to success. In this case it was an ideal patient for the technique. Nevertheless a detailed pre-operative explanation of the anesthesia plan was important for operators to go ahead. Our efforts focus on reassure the patient followed by supplements of sedo-analgesics regimen and we explained, to the patient, that there would be no pain when he will be subjected to testing. Intraoperative urgent intubation is technically difficult and slow to secure, in case of seizures, should be in the mind of anesthesia team. Although, it did not happen in this case, the plan for its control swiftly should be in mind i.e. surgeon’s application of ice water irrigation M.E.J. ANESTH 20 (6), 2010 890 and discontinuation of stimulation., anticonvulsants intravenously and if respiratory instability occur, intubation and controlled ventilation. In conclusion, a careful approach by supporting psychological aspect and motivation of the patient in order to tolerate the procedure the current analgesia and anesthesia techniques during awake craniotomy can be adjusted quickly to the benefit to a controlled operative time, this case may open the field to operate on co-operative patient. M. S. Maani Takrouri et. al Acknowledgement: This paper is based on Takrouri MM, Shubbak FA, Al Hajjaj A, Del Maestro RF, Soualmi L, Alkhodari MH, Alduraiby AM, Ghanem N. Conscious sedation for awake craniotomy in intraoperative magnetic resonance imaging operating theater. Anesth Essays Res [serial online] 2010 [cited 2011 Mar 5];4:33-7. Available from: http://www.aeronline.org/tex.asp?2010/4/1/33/69306 References 1. Black PM, Ronner SF: Cortical mapping for defining the limits of tumor resection. Neurosurgery; 1987, 20:914-9. 2. Ebeling U, Schmid UD, Ying H, Reulen HJ: Safe surgery of lesions near the motor cortex using intra-operative mapping techniques: a report on 50 patients. Acta Neurochir; (Wien), 1992, 119:23-8. 3. Haglund MM, Berger MS, Shamseldin M, Lettich E, Ojemann GA: Cortical localization of temporal lobe language sites in patients with gliomas. Neurosurgery; 1994, 34:567-76. 4. Khalifah N, Herrick I, Megyesi J, Parrent A, Steven D, Craen R: Patient satisfaction following awake craniotomy. Saudi J Anaesth [serial online] 2008 [cited 2010 Jan 1], 2:52-6. Available from: http://www.saudija.org/text.asp?2008/2/2/52/51856 5. Sabbagh AJ, Al-Yamany M, Bunyan RF, Takrouri MS, Radwan SM: Neuroanesthesia management of neurosurgery of brain stem tumor requiring neurophysiology monitoring in an iMRI OT setting. Saudi J Anaesth [serial online] 2009 [cited 2010 Jan 1], 3:91-3. Available from: http://www.saudija.org/text.asp?2009/3/2/91/57877 [serial online] 2008 [cited 2010 Jan 1];2:52-6. Available from: http:// www.saudija.org/text.asp?2008/2/2/52/51856 6. Archer DP, McKenna JM, Morin L, Ravussin P: Conscioussedation analgesia during craniotomy for intractable epilepsy: a review of 354 consecutive cases. Can J Anaesth; 1988; 35:338-44. 7. Sarang A, Dinsmore J: Anaesthesia for awake craniotomy evolution of a technique that facilitates awake neurological testing. Br J Anaesth; 2003, Feb, 90:161-5. 8. Danks RA, Rogers M, Aglio LS, Gugino LD, Black PM: Patient tolerance of craniotomy performed with the patient under local anesthesia and monitored conscious sedation. Neurosurgery; 1998, 42:28-34. 9. Herrick IA, Craen RA, Gelb AW, Miller LA, Kubu CS, Girvin JP, Parrent AG, Eliasziw M, Kirkby J: Propofol sedation during awake craniotomy for seizures: patient controlled administration versus neurolept analgesia. Anesth.Analg; 1997, Jun, 84:1285-91. 10.Johnson KB, Egan TD: Remifentanil and propofol combination for awake craniotomy: case report with pharmacokinetic simulations. J Neurosurg Anesthesiol; 1998, Jan, 10:25-9. 11.Berkenstadt H, Perel A, Hadani M, Unofrievich I, Ram Z: Monitored anesthesia care using remifentanil and propofol for awake craniotomy. J Neurosurg Anesthesiol; 2001, Jul, 13:246-9. 12.Taylor MD, Bernstein M: Awake craniotomy with brain mapping as the routine surgical approach to treating patients with supratentorial intraaxial tumors: a prospective trial of 200 cases. J Neurosurg; 1999, 90:35-41. 13.Blanshard HJ, Chung F, Manninen PH, Taylor MD, Bernstein M: Awake craniotomy for removal of intracranial tumor: considerations for early discharge. Anesth Analg; 2001, 92:89-94. 14.Hogue CW, Jr., Bowdle TA, O'Leary C, Duncalf D, Miguel R, Pitts M, Streisand J, Kirvassilis G, Jamerson B, McNeal S, et al: A multicenter evaluation of total intravenous anesthesia with remifentanil and propofol for elective inpatient surgery. Anesth Analg; 1996, Aug, 83:279-85. 15.Vuyk J, Mertens MJ, Olofsen E, Burm AG, Bovill JG: Propofol anesthesia and rational opioid selection: determination of optimal EC50-EC95 propofol-opioid concentrations that assure adequate anesthesia and a rapid return of consciousness. Anesthesiology; 1997, Dec, 87:1549-62. 16.Egan TD, Lemmens HJ, Fiset P, Hermann DJ, Muir KT, Stanski DR, Shafer SL: The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers. Anesthesiology; 1993, 79:881-92. 17.Egan TD: Remifentanil pharmacokinetics and pharmacodynamics. A preliminary appraisal. Clin Pharmacokinet; 1995, 29:80-94. 18.Borgeat A, Wilder-Smith OH, Saiah M, Rifat K: Subhypnotic doses of propofol possess direct antiemetic properties. Anesth Analg; 1992, 74:539-41. 19.Smith I, Monk TG, White PF, Ding Y: Propofol infusion during regional anesthesia: sedative, amnestic, and anxiolytic properties. Anesth Analg; 1994, 79:313-9. 20.Herrick IA, Gelb AW: Anesthesia for temporal lobe epilepsy surgery. Can J Neurol Sci; 2000, 27 Suppl, 1:S64 7, discussion S926.:S64-S67. 21.Delvi MB, Samarkandi A, Zahrani T, Faden A: Recovery profile for magnetic resonance imaging in pediatric daycase-sevoflurane vs. isoflurane. Middle East J Anesthesiol; 2007, Feb, 19(1):205-11. 22.Takrouri MSM & Seif OS: Leap Into Future In Image Navigation Neurosurgery: Visit to the BrainSuite at King Fahad Medical City in Riyadh, KSA. The Internet Journal of Health; 2007, Volume 6 Number 1. 23.Sahjpaul RL: Awake craniotomy: controversies, indications and techniques in the surgical treatment of temporal lobe epilepsy. Can J Neurol Sci; 2000, 27(S1):S55-63. 24.Young DA: Awake craniotomy using a modified nasal airway, propofol, and remifentanil in an adolescent. http://www. pedsanesthesia.org/meetings/2004winter/pdfs/2004_P23.pdf [last access: oct.23rd 2009]. EFFECTIVE AWAKE THORACIC EPIDURAL ANESTHETIC FOR MAJOR ABDOMINAL SURGERY IN TWO HIGH-RISK PATIENTS WITH SEVERE PULMONARY DISEASE - A Case Report - E Abd Elrazek*, M Thornton** and A Lannigan** Summary Awake thoracic epidural anaesthesia as the sole anaesthetic technique was successfully employed for two high risk surgical patients with chronic obstructive pulmonary disease undergoing abdominal surgery. The procedure was tolerated well and the anaesthetic technique which has been shown to reduce intra-operative and post-operative cardiac, respiratory and gastrointestinal complications, may have significantly contributed to the prompt, complication free recovery experienced by both patients. We report two cases of awake major abdominal surgery in two high-risk surgical patients with severe pulmonary disease, performed effectively under thoracic epidural anaesthesia as a sole technique. The first case was an elective open sigmoid colectomy in a sixty one year old cancerous patient with chronic obstructive pulmonary disease [COPD] and recent thoracotomy for a wedge resection of a bronchial adenocarcinoma [pT1NoMx]. The second case was an emergency open cholecystectomy in an adult patient with end-stage COPD. Reviewing the literature, no similar cases were reported recently. First Case A 61 year old male patient known to have end-stage COPD was diagnosed with a sigmoid adenocarcinoma in January 2008. Pre-operative staging identified a spiculated mass lesion in his right lung. A PET scan suggested that these were two independent primaries. In March 2008 he underwent a right thoracotomy under a combined anaesthetic technique of general anaesthesia in conjunction with a thoracic epidural. During surgery, it was difficult to ventilate him with secretions in his dependent lung and a decision was taken to limit the operative procedure to a wedge resection rather than a lobectomy. The first 10 post-operative days were complicated by atelectasis, reduced oxygen saturation and rapid atrial fibrillation, which converted to sinus rhythm with Amiodarone. At pre-anaesthetic assessment prior to colonic resection in July, the patient’s BMI was 32 and he was still smoking 4-5 per day, with a previous history of 50 packs per year. He had chronic productive cough and was on four different inhalers; Bricanyl, Spiriva and Symbicort regularly plus Salbutamol as required. Although his pre-operative chest xray was reported to be clear his * Consultant Anaesthetist, Wishaw General Hospital, Wishaw, UK. ** Consultant Surgeon, Wishaw General Hospital, Wishaw, UK. Correspondence to: Dr. Essam Abd Elrazek ([email protected]). 891 M.E.J. ANESTH 20 (6), 2010 892 chest sounded generally wheezy with reduced air entry bilaterally [Fig. 1]. The patient’s peak expiratory flow rate [PEFR] was very low [250 L/M]. Pulmonary function tests showed that his FEV1 was 1.5 liters [54% predicted] with an FEV1/FVC ratio of 45% pre and post bronchodilator. The six minutes walk test [6MWT] detected an overall low level at 223 meters [predicted distance in health elderly = 631 ± 93 meters]1, and he was diagnosed to have moderately irreversible COPD. Second Case A sixty six year old male ex-smoker was admitted to the emergency department of Wishaw General Hospital suffering from sudden onset epigastric and right upper quadrant pain. He had tenderness and guarding in the right upper quadrant with obviously palpable gall bladder consistent with acute cholecystitis. He had progressive shortness of breath, generalized expiratory wheeze with bilateral basal crepitations consistent with COPD for which he used three different inhalers regularly; Salbutamol, Seretide, and Spiriva. He could manage only 50 yards on the flat and one flight of stairs, with a PEFR of 250 L/M. His most recent pulmonary function tests showed that he had FEV1 of 1.14 L [45% predicted] and FEV1/FVC ratio of 41% giving him the diagnosis of moderate airflow obstruction with no significant irreversibility, air trapping and severe reduction in transfer factor. His chest x-ray showed COPD with bilateral basal consolidation [Fig. 2]. He was also on Amlodipine for a history of hypertension and Codydramol for osteoarthritis. On admission, his WCC was raised with slightly elevated LDH, but CRP was raised to over 300 which was settled to some extent on IV antibiotics. An ultrasound confirmed gallstones with acute inflammatory changes in the gallbladder. Imaging and clinical impression suggested he was developing a gallbladder empyema and concerns were raised about the viability of the gallbladder, suggesting surgery was necessary. Anesthetic Technique Pre-operatively, surgical and anaesthetic options were discussed and we decided to proceed to open E. Abd Elrazek et. al surgery under awake thoracic epidural anaesthesia to minimise potential chest complications. With each patient’s consent, they have had their laparotomies [case no. 1: lower abdominal for a sigmoid colectomy and case no. 2: sub-costal for a cholecystectomy] completed under thoracic epidural anaesthesia only. Both patients were received an awake thoracic epidural anaesthetic [case no. 1: T7-8 and case no.: 2: T6-7]. The technique was performed in a lateral position under complete aseptic technique and basic monitoring; heart rate (HR), arterial blood pressure (ABP), and pulse oximetry (SpO2%). Light sedation using 4-mg of Midazolam was given and Lignocaine 1% [5 ml] was used to infiltrate the chosen space. For the block induction, a recipe of Lignocaine 2% with Adrenaline 1:200.000 [total, 20 ml], Clonidine [150 ug] and Diamorphine [3 mg] were used. Up to T4 loss of sensation was obtained bilaterally 5 minutes post induction. This was confirmed using the ice test and we were confident that the surgery should proceed. Later, a bolus of 10 ml L-Bupivacaine 0.5% was given followed by an infusion of 0.1% L-Bupivacaine with Fentanyl, 2 ug/ml [10 – 15 ml / hour] to maintain the block through out the operation. The analgesic and the abdominal muscle relaxation conditions were optimum and the Surgeons were very satisfied. The two patients were conversing with the operative teams during surgeries, while they remained very comfortable, breathing spontaneously 4-6 L/M O2 via Hudson face mask. Because of potential complications, no further sedation was given. They were haemodynamically and respiratorily stable throughout the operations. The operation time was two hours in the first case and one hour in the second. No invasive monitoring was needed. Post-operatively, patients were transferred to the recovery room and, subsequently, to the high dependency unit [HDU] for post-operative observation, monitoring and continuous epidural analgesia which was very effective in both cases. No further analgesia was required. The upper level of the epidural block was consistent with the epidural scoring scale for arm movements of zero {ESSAM score = 0; able to perform a hand grip}2, and patients were breathing comfortably and no respiratory support was needed. Not having had a general anaesthetic, both EFFECTIVE AWAKE THORACIC EPIDURAL ANESTHETIC FOR MAJOR ABDOMINAL SURGERY IN TWO HIGH-RISK PATIENTS WITH SEVERE PULMONARY DISEASE made a remarkable recovery and later were able to be discharged home in good general condition. The first patient went home only 6 days post-operatively with a final diagnosis of a pT3 No adenocarcinoma, and was reviewed 4 and 8 weeks post-discharge and found to be well, having returned to all pre-operative activity levels. The cholecystectomy patient had to stay in hospital for 12 days post-operatively to optimise his chronic chest condition with nebulisers, antibiotics and physiotherapy. The postoperative histopathologic examination of his specimen has confirmed the diagnosis of acute diffuse suppurative cholecystitis with numerous suppurative foci within the necrotic gallbladder wall. Discussion General anesthesia in high risk surgical patients with significant pulmonary disease can trigger some adverse effects including; pneumonia, impaired cardiac performance, neuromuscular problems, biotrauma and barotrauma and subsequently intra and post-operative hypoxemia3. Avoiding endotracheal intubation decreases the risk of postoperative laryngospasm and bronchospasm, especially in elderly COPD patients with irritated upper and lower airway tracts. Awake thoracic epidural anaesthesia has been reported to be a safe technique in patients with end-stage COPD4. In order to reduce the adverse effects of general anaesthesia, thoracic epidural anaesthesia has been recently employed to perform awake cardiothoracic surgery procedures, including coronary artery bypass grafting, management of pueumothorax, resection of pulmonary nodules and solitary metastases, lung volume surgery, and trans-sternal thymectomy5,6. Thoracic epidural anaesthesia blunts the decrease of subcutaneous tissue oxygen tension caused by surgical stress and adrenergic vasoconstriction during major abdominal surgery providing sufficient tissue oxygenation, and improving cardiac, respiratory and gastrointestinal function and may decrease the incidence of surgical wound infection7. Splanchnic sympathetic nervous blockade results in reduced inhibitory gastrointestinal tone and increased intestinal blood flow, positive factors where a colonic anastomosis is to be performed8. Given that our two patients had end-stage COPD 893 and significant co-morbidity the advantages of epidural anaesthesia may have been vital contributor to the satisfactory recovery. Post-operative myocardial infarctions are reported to be significantly lower due to continuous thoracic epidural analgesia9. Two systemic reviews have found that epidural anaesthesia with or without post-operative epidural analgesia reduce postoperative pulmonary infections compared with general anaesthesia with or without post-operative systemic analgesia10,11. Ballantyne et al confirmed that postoperative epidural pain control can significantly decrease the incidence of pulmonary morbidity12. Furthermore, a comparative study of major abdominal surgery in the elderly reported that the epidural route of post-operative analgesia provides better pain relief, improved mental status and faster return of bowel activity13. In patients undergoing lower abdominal surgery, the neuroaxial blockade and surgical anaesthesia achieved by epidural local anaesthetics was associated with decreased post-operative analgesic demands as seen with our patients14. The pathophysiological response to surgical trauma, especially when it is major, could include pain, nausea, vomiting and ileus, stress-induced catabolism, impaired pulmonary function, increased cardiac demands, and risk of thromboembolism. Subsequently, further complications, need for treatment, and delayed recovery as well as discharge from hospital, could occur. Development of safe anaesthetic and analgesic techniques including regional anaesthesia have provided an important tool for excellent quality of surgery and enhanced recovery. We definitely agree with Kehlet and Dahl’s opinion regarding the pivotal role of the anasethetist facilitating early post-operative recovery providing a minimally invasive anaesthesia and analgesia and may be tailoring his anaesthetic strategy to meet the surgical demand in view of the patient’s general condition15. In 1994, awake epidural anaesthesia has been reported to be effective and safe technique in the highrisk colectomy patient16. Since then, there has been a paucity of data in the literature on the procedure performed under regional, especially awake epidural anaesthesia, in patients with co-existing pulmonary diseases. Also, awake laparoscopic cholecystectomy M.E.J. ANESTH 20 (6), 2010 894 has been reported to be safely done under thoracic epidural anaesthesia in COPD patients17. However, this anaesthetic technique is still unrecorded for open cholecystectomy, despite being known to adversely affect the post-operative pulmonary function more than the laparoscopic procedure18. In this article, the two reported patients had significant co-morbidity, presenting the need to consider all surgical and anaesthetic options. Thoracic epidural was preferred to combined spinal epidural (CSE) anaesthesia because it is simple, less invasive and more reliable. In a CSE technique, the clinician has no chance to test the effectiveness of his epidural until the effect of the spinal wears off, and it would be too late if it is found to be ineffective or not working at all and the only available option in this case scenario would be putting the patient off to sleep, the technique that the Anaesthetist initially tried to avoid. In our technique, we started with Lignocaine to speed up the block induction, but later, the longer acting L-Bupivacaine was used19. Diamorphine20 and Clonidine21 were added to improve the quality of the analgesic effect of the epidural. The risk of inadvertent high blockade post-operatively, may be reduced by monitoring the patien’s arm movements using the epidural scoring scale for arm movements [ESSAM], E. Abd Elrazek et. al which has been found to be very simple and reliable method for the early detection of the cephalad spread of thoracic epidural analgesia2. Finally, we believe that thoracic epidural anaesthesia and analgesia is very useful technique, especially when it is used for selected patients helping to avoid general anaesthesia when it is contraindicated. Encouraging this technique might help increase the safety margin of the surgery offered to the high-risk surgical co-morbid patients, especially those with severe pulmonary diseases. It could also help smooth the recovery period and enhance the discharge rate of those patients, increase the turnover of surgical cases, and subsequently, shorten the long waiting lists for surgery in the NHS. Needless to say that optimum anaesthetic and surgical experience as well as cooperation will be necessary in such circumstances. Acknowledgement The authors would like to thank Dr. Donald MacLean, Dr. Alison Simpson and Dr. Marisa Haetzman, Anaesthetic Consultants at Wishaw General Hospital for reviewing this article. Also, we would like to thank the theatre, HDU and physiotherapy staff for their efficiency and co-operation. EFFECTIVE AWAKE THORACIC EPIDURAL ANESTHETIC FOR MAJOR ABDOMINAL SURGERY IN TWO HIGH-RISK PATIENTS WITH SEVERE PULMONARY DISEASE 895 References 1. Troosters T, Gosselink R, Decramer M: Six minutes walk distance in healthy elderly subjects. European Respiratory Journal; 1999, 14: 270-274. 2. Abd Elrazek E, Scott NB, Vohra A: An epidural scoring scale for arm movements (ESSAM) in patients receiving high thoracic epidural analgesia for coronary artery bypass grafting. Anaesthesia; 1999, 54:1097-1109. 3. Jin F, Chung F: Minimising perioperative adverse events in the elderly. British Journal Anaesthesia; 2001, 87:608-624. 4.Gruber EM, Tshernko EM, Kritzinger M, Deviatko E, Wisser W, Zurakowski D, Haider W: The effects of thoracic Epidural Analgesia with Bupivacaine 0.25% on Ventilatory Mechanics in patients with Severe Chronic obstructive Pulmonary Disease. Anesthesia & Analgesia; 2001, 92:1015-1019. 5. Mineo TC: Epidural anaesthesia in awake thoracic surgery. European Journal Cardiothoracic Surgery; 2007, 32:13-19. 6. Noiseux N, Prieto I, Bracco D, Basile F, Hemmerling T: Coronary artery bypass grafting in the awake patient combining high thoracic epidural and femoral nerve block: first series of 15 patients. British Journal Anaesthesia; 2008, 100:184-189. 7. Kabon B, Fleischmann E, Treschan T, Tguchi A, Kapral S, Kurz A: Thoracic epidural anesthesia increases tissue oxygenation during major abdominal surgery. Anesthesia and Analgesia; 2003, 97:18121817. 8. Veering BT, Cousins MJ: Cardiovascular and pulmonary effects of epidural anaesthesia. Anaesthetic Intensive Care; 2000, 28:620-635. 9. Beattie SW: Epidural analgesia reduces postoperative myocardial infarction: A meta-analysis. Anesthesia and Analgesia; 2001, 93:853-858. 10.Jayr C, Thomas H, Rey A, Farhat F, Lasser P, Bourgain JL: Postoperative pulmonary complication: epidural analgesia using bupivacaine and opioids versus parentral opioids. Anaesthesiology; 1993, 78:666-676. 11.Rodgers A, Walker N, Schug S, et al: Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomized trials. British Medical Journal; 2000, 321:1493-1497. 12.Ballantyne JC, Carr DB, deFerranti A, et al: The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analysis of randomized controlled trials. Anesthesia and Analgesia; 1998, 86:598-612. 13.Mann C, Pouzeratte Y, Boccara G, et al: Comparison of Intravenous or epidural patient-controlled analgesia in the elderly after major abdominal surgery. Anesthsiology; 2000, 92:433-441. 14.Shir Y, Raja SN, Frank SM: The effect of epidural versus general anaesthesia on postoperative pain and analgesic requirements in patients undergoing radical prostatectomy. Anesthesiology; 1994, 80:49-56. 15.Kehlet H, Dahl JB: Anaesthesia, surgery, and challenges in postoperative recovery. Lancet; 2003, 362:1921-1928. 16.Koltun WA, McKenna K, Rung G: Awake epidural anaesthesia is effective and safe in the high-risk colectomy patient. Diseases of the Colon and Rectum; 1994, 37:1236-1241. 17.Pursnani KG, Bazza Y, Calleja M, Mughal MM: Laparoscopic cholecystectomy under epidural anaesthesia in patients with chronic respiratory disease. Surgical Endoscopy; 1998, 12:1082-1084. 18.Karayiannkis AJ, Makri GG, Mantzioka A, Karousos D, Karatzas G: Postoperative pulmonary function after laparoscopic and open cholecystectomy. British Journal Anaesthesia; 1996, 77:448-452. 19.McLeod IK: Local anaesthetics. http://www.emedicine.com/ent/ topic20.htm (accessed 17/11/2008). 20.Stoddart PA, Cooper A, Russel R, Reynolds F: A comparison of epidural diamorphine with intravenous patient-controlled analgesia using the Baxter infusor following Caesarean section. Anaesthesia; 1993, 48:1086-1090. 21.Dobrydnjov I, Axelsson K, Gupta A, Lundin A, Holström B, Granath B: Improved analgesia with clonidine when added to local anaesthetic during combined spinal-epidural anesthesia for hip arthroplasty: a double-blind, randomized and placebo-controlled study. Acta Anaesthesiolgica Scandinavica; 2005, 49:538-545. M.E.J. ANESTH 20 (6), 2010 VARIANTS OF PHEOCHROMOCYTOMA AND THEIR ANESTHETIC IMPLICATIONS – A Case Report And Literature Review – Kathryn Dortzbach, Daniel M Gainsburg* and E lizabeth AM F rost ** Anesthesiologists are trained to appreciate and respond appropriately to the considerable consequences of pheochromocytomas. It is however, less well appreciated that these tumors may be associated with other syndromes that can also carry significant anesthetic risk. We describe the case of a young man who had a rare disease in combination with multiple pheochromocytomas and suffered a fatal outcome after anesthesia. Possible causes for this disaster are suggested. Case History A 23 year-old male with a past medical history significant for Von Hippel-Lindau (VHL) syndrome presented for a laparoscopic right partial nephrectomy. The patient was diagnosed with renal cell carcinoma (RCC), which was found incidentally on CT scan, originally performed to assess for rib fractures after a motor vehicle accident. His past surgical history was significant for craniotomy with tumor resection secondary to hemangiomas related to VHL, and a right total adrenalectomy and left partial adrenalectomy both to remove pheochromocytomas. These surgeries were performed nine and eight years prior, respectively. The patient showed no other recurrences of lesions secondary to VHL other than the RCC. On preoperative assessment, the patient weighed 100 kg and stood 183cm tall. His blood pressure was 125/78 and his pulse was 80. Medications included only a muscle relaxant, which he took for back spasms following the accident He was otherwise asymptomatic. He reported a possible allergy to penicillin as a child. In the operating room, induction was performed and an arterial cannula was placed following intubation. Gentamycin 80mg and clindamycin 600mg were given as antibiotic prophylaxis. Tumor resection was difficult due to its deep location. The case lasted over six hours and was otherwise uneventful. Vital signs were stable throughout with a blood pressure ranging from 100-170/5080 and a pulse rate from 75-110. He received a total of fentanyl 925mcg, and was maintained with isoflurane, oxygen and nitrous oxide. Urine output was 500 ml and the estimated blood loss was 500 ml. Crystalloids, 4 liters were infused. At the end of the case, the patient was awakened and extubated without difficulty. He was transported to the recovery room in stable condition. Vital signs were blood pressure of 140/70, pulse rate 90, respiratory rate 20, temperature 37.4. Chemistry panel was within normal limits and the hematocrit was 40. Vital signs upon discharge from the recovery room five hours later were blood pressure of 120/50, pulse rate 85, respiratory rate 14. The patient indicated at that time that he was not experiencing pain. Around 4:45 am, several hours after he was transferred to the ward, the patient was found asystolic, pulseless and apneic and with evidence of emesis. Immediate resuscitation was performed but the patient could not be revived. Attending Anesthesiologist, New York Eye & Ear Infirmary, New York, NY. * MD, Assistant Professor. ** MD, Professor. Dept of Anesthesiology, Mount Sinai Medical Center, New York NY. 897 M.E.J. ANESTH 20 (6), 2010 898 K. Dortzbach et. al Introduction Incidence and Epidemiology Pheochromocytoma is one of the more challenging medical conditions faced by the anesthesiologist. Its hallmark paroxysmal hypertensive crises and cardiac manifestations including sinus tachycardia and bradycardia as well as arrhythmias, require the anesthesiologist to exercise the highest degree of vigilance. Significant improvements have been made in the management of pheochromocytomas since the first reports of their resection in the mid to late 1920s. Today, the mortality rate is less than 5%1. With greater awareness in diagnosing and treating pheochromocytomas, anesthesiologists can work perioperatively to reduce the mortality rate even further. The greatest incidence of pheochromocytomas occurs in the fourth and fifth decades. Among patients diagnosed with hypertension, roughly 0.1 percent are attributable to 2 pheochromocytomas , a small but not insignificant statistic given the incidence of hypertension. Also, these patients have a medical condition, which in most instances can be cured if diagnosed and treated correctly. Patients who remain undiagnosed are at great risk for further morbidity and high mortality, particularly if they must undergo surgical procedures. Of those patients with undiagnosed pheochromocytomas, as many as 25-50% die from complications occurring during induction of anesthesia or during anesthesia for procedures for other medical conditions3. Pheochromocytomas are very vascular tumors comprised of chromaffin tissue, which secretes varying quantities of epinephrine and norepinephrine which account for the clinical presentation. These tumors are most commonly found in the adrenal medulla but can be found anywhere chromaffin cells reside within or close to sympathetic ganglia, including the spleen, broad ligament, bladder, right atrium and at the bifurcation of the aorta3. While isolated pheochromocytomas of a nonfamilial etiology comprise most cases, it is important to understand the threat of a pheochromocytoma in more complex clinical settings. Approximately 5% of pheochromocytomas are associated with other syndromes such as VHL3. Our case serves as an example of one of many atypical contexts in which pheochromocytomas arise. Pheochromocytomas in the setting of VHL, and other familial syndromes, as well as in the setting of recurrence and clinically silent cases and the general management are presented. In the adult population, roughly 80% of tumors are solitary and unilateral, occurring in one of the adrenal glands. The remaining 20% are divided between bilateral lesions or extraadrenal masses. “The rule of 10s” refers to the statistic that 10% of tumors are extraadrenal, 10% are bilateral and 10% are malignant. Malignant spread is most typically to the liver via lymphatics and venous routes3. Recurrence is estimated at 8%1. Five percent of pheochromocytomas are inherited, either as an isolated phenomenon or as part of a familial syndrome. Symptoms Catecholamine release from pheochromocytomas accounts for most symptoms, usually headaches, palpitations and sweating. Both epinephrine and norepinephrine are synthesized, stored and secreted in pheochromocytomas. However, every tumor releases a different ratio of the two catecholamines and some tumors contain only one catecholamine. Epinephrine secreting tumors produce palpitations, sweating, heat intolerance, tremulousness, pallor and flushing, headache and weight loss. With the potential for very strong beta-stimulation, these tumors can infrequently cause severe hypotension or shock. Characteristically, norepinephrine secreting tumors are associated with more benign symptoms and can be misdiagnosed as essential hypertension3. Tumors that secrete both catecholamines exert a wide spectrum of symptoms. Few patients are asymptomatic. Around 50% of patients experience nonparoxysmal hypertension, either sustained or labile. The rest experience paroxysmal elevated blood pressure with the worst symptoms associated with the greatest fluctuations in plasma catecholamine levels. The frequency of symptoms is also variable, as patients may live for years without a recurrent attack while others suffer over 20 attacks of sudden onset daily. Most attacks last for a few minutes to a few hours but some may be as short as several seconds and others may persist for days1-3. In addition to hypertension, pheochromocytomas VARIANTS OF PHEOCHROMOCYTOMA AND THEIR ANESTHETIC IMPLICATIONS can cause deleterious but less common cardiac manifestations. Sinus tachycardia, sinus bradycardia, supraventricular dysrhythmias and premature ventricular contractions have all been reported. Patients without a history of coronary artery disease may suffer anginal pain and myocardial infarctions, believed to be a result of catecholamine induced coronary artery spasm. Electrocardiographic changes include right and left bundle branch blocks, non-specific ST segment and T wave changes and prominent U waves3. Catecholamine cardiomyopathies are rare and are presumed to be associated with a longer duration of disease and exposure to catecholamines. In the most severe cases, these cardiomyopathies can lead to heart failure and death. The mechanism has not been fully delineated but persistent hypertension can cause a hypertrophic cardiomyopathy. Dilated cardiomyopathies are less common4. Other findings may include weight loss, carbohydrate intolerance due to decreased insulin production and increased hepatic glucose production. Orthostatic hypotension may be seen in as many as 70% of patients. The exact mechanism is unknown but may be due to desensitized alpha-adrenergic receptors or sympathetic reflexes from the high amount of circulating catecholamines or volume depletion related to hypertension4. Patients with pheochromocytomas in the bladder wall may present with hematuria and bladder spasms with polyuria. Diagnosis and Laboratory findings The first step in diagnosis is often made by measuring 24 hour urinary metanephrine and vanillylmandelic acid levels and plasma catecholamines. No test is perfect with each having different degrees of sensitivity and specificity. The sensitivity of plasma free metanephrines is approximately 96-100%. Specificity is lower, between 82-96%. In comparison, urine metanephrines and catecholamines have a greater specificity of 98% and a lower sensitivity of 90%5. Any of the biochemical markers could be negative despite positive clinical findings and the presence of a tumor. Conversely, there are several drugs that can lead to false positive results for 899 catecholamines and metanephrines, falsely suggesting a diagnosis of pheochromocytoma. The list includes antipsychotics, L-dopa, tricyclic antidepressants, clonidine, phenoxybenzamine, caffeic acid (found in decaffeinated coffee), ethanol, paracetamol and substantial physical stress5. The clonidine suppression test can be used to rule out a rise in catecholamines due to other causes6. Because a pheochromocytoma secretes catecholamines that are free from neurogenic control, administration of clonidine will not result in suppression. To confirm a diagnosis, imaging studies include CT scan, magnetic resonance imaging (MRI) and meta-iodobenzylguanidine scintiscan (MIBG). CT and MRI are comparable in sensitivity, 98% and 100% respectively but both have lower specificities, CT with 70% and MRI with 67%. MIBG has a specificity of 100% but a lower sensitivity of 78%7. All components of an evaluation must be taken into account to arrive at the correct diagnosis. Familial Pheochromocytomas in Association with Syndromes Five percent of pheochromocytomas are of familial origin, passed down as an autosomal dominant trait as an isolated finding or in association with a syndrome including VHL, Multiple Endocrine Neoplasia (MEN) type 2a and type 2b, and von Recklinghausen neurofibromatosis. For the anesthesiologist, pheochromocytoma is generally the most threatening component of both VHL and MENIIA/IIB8,9. Patients with any of these syndromes should be evaluated preoperatively for pheochromocytoma regardless of their medical history and whether or not they show any signs or symptoms of catecholamine secreting tumors. Von Hippel-Lindau Syndrome is an autosomal dominant disease that has variable expression and incomplete penetrance (Fig. 1). The disease was first described over 100 years ago. Eugen von Hippel described angiomas in the eye in 190410. Arvid Lindau described angiomas of the cerebellum and spine in 192711. M.E.J. ANESTH 20 (6), 2010 900 Fig. 1 Von Hippel-Lindau Syndrome is an autosomal dominant disease Findings include capillary hemangioblastomas of the retina (seen in 60-70% of patients), and hemangioblastomas of the central nervous system (CNS) (30-70% of patients). Most of the CNS lesions are located in the cerebellum. Less commonly, erythrocytosis, pancreatic and renal cysts, renal cell carcinoma and hypernephroma are seen. Pheochromocytoma occurs in about 10%12. and is more likely to be bilateral and to recur13. VHL patients tend to be younger at the age of diagnosis and have their pheochromocytomas diagnosed early, likely because of the higher level of suspicion for pheochromocytoma and its known association with VHL. VHL results from a mutation in the tumor-supressor gene on chromosome 3p25.314-19. As long as one copy of the VHL gene is producing functional VHL protein in each cell, tumors do not develop. If a mutation occurs in the second copy of the VHL gene during a person's lifetime, the cell has no working copies of the gene and produces no functional VHL protein. A lack of this protein allows tumors characteristic of von Hippel-Lindau syndrome to develop. Since both alleles need to be mutated for K. Dortzbach et. al the disorder to develop, it would be likely to conclude that the mutation is recessive. However, studying the patterns of heredity,VHL is, paradoxically, an autosomal dominant disorder because people who have already inherited one mutated copy of the gene have an extremely high probability of developing the second mutation. An inherited mutation of the VHL gene is responsible for about 80 percent of cases. In about 20 percent of cases, however, the altered gene is the result of a new mutation that occurs during the formation of reproductive cells (eggs or sperm) or early in fetal development. This is quite rare because the probability of a mutation occuring in a cell where both alleles are previously normal is quite small. Also, the first mutation must be followed by a second for the syndrome to develop. VHL may be diagnosed when one of its associated diseases causes discomfort20-26. Angiomatosis, hemangioblastomas, pheochromocytoma, renal cell carcinoma, pancreatic cysts and café au lait spots are all associated with VHL. Angiomatosis occurs in 37.2% of patients presenting with VHL and usually occurs in the retina, however other organs can be affected. As a result, loss of vision is very common. On average only about 20% of people with VHL get pheochromocytomas. The risk of developing such tumors (which are usually histologically benign) appears to hinge on the precise nature of the mutation responsible for VHL disease in a specific family. In kindreds with VHL who demonstrate a deletion or protein-truncating mutation of the VHL gene (type 1 VHL), the risk for pheochromocytoma is less than 10%. However, the risk is approximately 50% for pheochromocytoma development in kindreds with a missense mutation (type 2 VHL). There is a wide variation in the age of onset of the disease, the organ system affected and the severity of effect suggesting that the second mutation can occur in different types of cells and at various times of a person's life. If a patient with VHL has coexisting lesions or disorders that require surgical correction in addition to the removal of the pheochromocytoma, resection of the pheochromocytoma is prioritized. In patients with CNS lesions, potential complications exist. If the intracranial mass is addressed first, the anesthesiologist VARIANTS OF PHEOCHROMOCYTOMA AND THEIR ANESTHETIC IMPLICATIONS is faced with the potential for extreme hypertension leading to intracranial bleeding intraoperatively and postoperatively. If the decision is made to resect the pheochromocytoma first, required use of vasodilators to control hypertension may increase cerebral blood flow (CBF) and intracranial pressure which may be offset initially by hyperventilation, placement of an intraventricular drain or administration of mannitol and/or furosemide. This dilemma must be discussed with the operative team, to decide which procedure takes precedence27. Multiple endocrine neoplasias (MEN) comprise three different familial syndromes inherited as autosomal dominant traits8. MEN I does not have pheochromocytoma as part of its profile and therefore does not pertain to this case. MEN IIA (Sipple’s syndrome) includes medullary thyroid cancer (97%), pheochromocytoma (50%) and hyperparathyroidism (20%) and is thus more similar to VHL regarding the presentation of pheochromocytoma. MEN IIB, rarer than IIA, is associated with medullary thyroid cancer, pheochromocytoma and a Marfanoid body habitus and mucosal neuronal syndrome with mucosal neuromas and intestinal ganglioneuromas. Also, in MEN IIB, the tumor generally presents late and is rarely malignant or bilateral9. In the case of MEN IIA patients, if the pheochromocytoma is resected before removal of the parathyroid glands, the calcium level must be checked as most patients have asymptomatic hypercalcemia. Symptomatic patients may complain of fatigue, weakness in general or proximal muscle weakness, confusion, polyuria, and polydypsia. Patients may also have findings of hyporeflexia, pseudogout, anemia, subperiosteal bone resorption, and renal stones. Abnormal EKG findings include a shortened QT interval and prolonged PR interval8. Cardiac dysrhythmias are the most important potential complication of hypercalcemia. QT intervals do not necessarily correlate with changes in calcium concentrations, thus blood gas analyses must be done in conjunction with blood calcium levels. Management of hypercalcemia includes intravenous fluid administration with sodiumcontaining solutions, which dilute the calcium and inhibit renal reabsorption. Urine output must be closely monitored to assess renal dysfunction. Other concerns for the anesthesiologist in these 901 cases include muscle relaxant dosing, positioning of the patient and the potential for airway compromise. Muscle relaxant effects may be enhanced by hypercalcemia. Preoperative assessment of muscle weakness must be documented to record baseline and to tailor muscle relaxant administration to the patient’s requirements. Careful positioning of the patient with appropriate padding is important to avoid pathological fractures from osteoporosis8. Although bilateral tumors frequently occur with medullary thyroid cancer, they are rarely large enough to compress the airway. However, airway compromise must be considered and a difficult airway cart made available. For any patient with VHL or MENIIA/B presenting for surgery, the diagnosis of pheochromocytoma should be suspected even if the patient is asymptomatic. Additionally, patients who have had a previously resected pheochromocytoma, and are returning for surgery, should be screened for recurrences and/or for pheochromocytoma on the unresected side. Asymptomatic Pheochromocytoma A subset of pheochromocytomas known as adrenal incidentalomas is clinically silent. These tumors likely make a substantial contribution to the statistic that fifty percent of pheochromocytomas are discovered post-mortem6. With advancements in imaging, these lesions are estimated at a prevalence of almost 3% in middle age to nearly 10% in the elderly13. These pheochromocytomas may be hormonally active or inactive and therefore may not be detected during screening12. While incidentalomas may secrete catecholamines at a level that leaves the patient asymptomatic, the lesions are not benign. There has been an increasing trend to treat these subclinical tumors given the uncertainty of their association with increased morbidity. The undiagnosed pheochromocytoma suspected intraoperatively during surgery for another medical condition can have devastating consequences. The mortality rate is as high as 80%, during anesthesia. Any hypertensive patient not taking antihypertensive medications presenting for surgery who complains of orthostatic hypotension, should be tested for a diagnosis of pheochromocytoma. As many as 10% of cases of orthostatic hypotension may be due to M.E.J. ANESTH 20 (6), 2010 902 pheochromocytomas6,28. Also any patient for surgery to remove an adrenal mass must be evaluated for pheochromocytoma. Preoperative Management Part of the key to avoiding intraoperative complications in the removal of pheochromocytomas is to ensure preoperative optimization. The most important goal is to achieve blood pressure control prior to surgery. The alpha adrenergic blocker, phenoxybenzamine is first line therapy. Phenoxybenzamine is a non-selective alpha blocker targeting both alpha 1 and alpha 2 receptors. The blockade is noncompetitive and irreversible. Phenoxybenzamine can be started at least two weeks prior to the scheduled surgery on an outpatient basis to allow for maximal alpha blockade and restoration of blood volume given that chronic alpha constriction causes volume depletion. The protocol for preoperative alpha blockade requires initially phenoxybenzamine 40 mg per day followed by a gradual increase to 80 to 120 mg per day. Postural hypotension is the most common side effect. While this relatively simple intervention cannot promise the prevention of fluctuations in blood pressure intraoperatively, it has been estimated to decrease perioperative mortality from 45% to 3%6. Even patients without cardiovascular symptoms despite the diagnosis of pheochromocytoma may benefit from alpha blockade treatment. Apparent preoperative hemodynamic stability does not preclude severe intraoperative hemodynamic fluctuations including increased systemic vascular resistance following induction of anesthesia and hypotension following tumor resection. Calcium channel blockers have shown benefit in patients who are generally normotensive but with paroxysmal hypertension8. The advantage is that they do not cause orthostatic hypotension; however alpha blockers are still considered preferable in preoperative management. Beta blockade is the second component to preoperative preparation if the patient has tachycardia, arrhythmias, or a history of coronary artery disease. Alpha-adrenergic block must be established prior to beta-blockade. If beta-blocking agents are given first, unopposed alpha-blockade and its consequential vasoconstriction could lead to a life threatening hypertensive crisis. To ensure optimization K. Dortzbach et. al for surgery, it is highly recommended that the patient meet the Roizen criteria for sufficient alpha blockade (Table 1)29. Table 1 Roizen’s Criteria for Appropriate Preoperative Alpha Blockade and Surgical Optimization • No in hospital pre-surgical blood pressures measuring higher than 165/90 24 hours prior to surgery. • No orthostatic hypotension with blood pressure measuring lower than 80/45. • No EKG showing ST-T changes one week prior to surgery. • No more than one premature ventricular contraction every five minutes. An echocardiogram should be performed preoperatively to assess catecholamine related cardiomyopathy. In patients with cardiomyopathy, a longer period of preoperative preparation, while not always practical (some have suggested that as long as six months treatment with alpha-blockade is necessary) may help reverse myocardial dysfunction30. Untreated, a heart stressed by high levels of circulating catecholamines and arterial hypertension may not compensate for postoperative hypotension due to catecholamine withdrawal. Intraoperative Management Surgical resection cures 90% of patients. Laparoscopic removal of pheochromocytomas has become increasingly common, provided there is no local invasion and the mass is less than 6cm. Large, recurrent or invasive pheochromocytomas should be removed by laparotomy31. While the laparoscopic approach results in a shorter recovery time, both laparoscopic and open approaches are equal in terms of overall survival7. Neither approach has been proven superior regarding anesthetic management. The greatest intraoperative concern is the release of catecholamines leading to life-threatening hypertension. Hypertensive crises can cause myocardial infarction, heart failure, dysrhythmias, and cerebral hemorrhage. Severe hypertension can occur at any time throughout the surgery but induction, intubation and tumor palpation tend to be the times of greatest catecholamine release. VARIANTS OF PHEOCHROMOCYTOMA AND THEIR ANESTHETIC IMPLICATIONS Premedication with an anxiolytic such as midazolam decreases the stress response activating the sympathetic nervous system. After entering the operating room and placing standard ASA monitors, obtaining intravenous access, preferably at two reliable sites is desirable. Arterial cannulation is necessary and should be in place prior to induction. The use of central venous monitoring and pulmonary artery catheterization depends upon the clinical condition and should be used in cases of cardiomyopathy and documented preoperative cardiac compromise. Induction agents should be titrated slowly to maintain normotension. A short acting narcotic such as fentanyl, with its minimal myocardial depression, in combination with a sedative/hypnotic is preferable to a sedative/hypnotic agent alone. It is important to achieve an adequate depth of anesthesia such that the patient does not respond to the stimulus of intubation8,31. Vecuronium or rocuronium may be used for muscle relaxation as these agents have few if any cardiovascular effects. Pancuronium should be avoided because of its sympathomimetic effects. Histamine release caused by atracurium can increase the release of catecholamines. Succinylcholine should theoretically be avoided because of its possible potentiation of catecholamine release from contracting skeletal muscle6,8. Inhalational agents (isoflurane, sevoflurane, desflurane) may be used with or without intravenous agents. Intraoperatively, alpha blockade is continued with phentolamine. Phentolamine is a competitive alpha 1 and alpha 2 receptor blocker32 and is the single best antihypertensive treatment in managing hypertensive crises due to pheochromocytoma. Its most common side effect is reflex tachycardia due to the baroreceptor reflex following alpha 2 blockade. Labetalol should be used to control tachycardia. Calcium channel blockers and nitroprusside, while sporadically helpful in controlling hemodynamic fluctuations, do not have the same success as phentolamine. Based upon the anesthesiologist’s preference, intravenous nitroprusside (1-2 mcg/kg) and sublingual nifedipine can be used as second line therapies. However, the combination of phentolamine and labetalol ideally render unnecessary the use of other antihypertensives8. 903 Phentolamine should be titrated in 5 mg increments intravenously. One technique is to inject phentolamine 5mg after induction, and before the tumor is mobilized. With close communication between the surgeon and anesthesiologist, the surgeon is asked to stop if necessary so that more phentolamine can be administered. Thus, blood pressure control is maintained during tumor resection8. Over administration of phentolamine may lead to transient hypotension. Cardiovascular instability may be such that treatment of hypotension with a pressor such as ephedrine or other beta adrenergic agents may rarely lead to significant ventricular irritability including ventricular tachycardia or even fibrillation. Thus, careful dosing of phentolamine is extremely important, however at times very difficult given the unexpected extreme rises in blood pressure. Transient hypotension induced by phentolamine may be treated best with fluid administration and watchful waiting for a natural rise and return of blood pressure to normal. In severe symptomatic cases, a magnesium infusion can be used in addition to phentolamine and labetalol. Maintaining plasma levels < 2ug/ml (not to potentiate muscle relaxation) decreases catecholamine levels and hemodynamic fluctuations and blunts the effects of stimulation during intubation6. Following ligation of the vein draining the pheochromocytoma, intravenous fluid administration is essential for volume expansion. The sudden drop in catecholamines can lead to significant hypotension, requiring aggressive fluid replacement with a combination of crystalloids and colloids. Pressors may be necessary to maintain blood pressure in severe hypotension but they are best avoided and contraindicated if the patient is hypovolemic. Often the hypotension of pheochromocytoma is refractory to agents such as norepinephrine, epinephrine, and dopamine because of the desensitization of sympathetic receptors to the previously persistently high levels of catecholamines8. Throughout the case, aggressive intravenous fluid resuscitation is important to account for chronic volume depletion, hypotension following catecholamine withdrawal, and intraoperative blood loss, which is usually minimal with a laparoscopic approach. The anesthesiologist should also monitor for M.E.J. ANESTH 20 (6), 2010 904 K. Dortzbach et. al glycemic changes. Hyperglycemia associated with increased catecholamine secretion may require insulin. It almost always resolves with removal of the tumor. Hypoglycemia may follow tumor resection because of rebound hyperinsulinism without the inhibitory effect of norepinephrine on insulin secretion. Medications That Trigger Catecholamine Release Several medications have been shown to trigger the release of catecholamines from pheochromocytomas (Table 2). The pressor effects of metoclopramide are well established. Although the mechanism by which it does this is unclear, metoclopramide can cause a serious or even fatal hypertensive crisis. It should be avoided not only in patients with pheochromocytomas but also in all patients with particularly labile blood pressure that could very rarely be due to this tumor. Table 2 Medications Reported to Trigger the Release of Catecholamines in Pheochromocytomas • Metoclopramide. • Pentazocaine. • Droperidol. • Atracurium. • SSRIs. • MAO inhibitors. • Imipramine. • Beta-blockers. • Opioids. • Curare. Many of the above medications particularly beta-blockers and opioids have been used in cases with pheochromocytomas without incidence. Patients must be treated on an individual basis. Pentazocaine and droperidol can also increase release and circulating levels of catecholamines. Droperidol additionally inhibits the reuptake of catecholamines into nerve terminals. Any medications that induce histamine release should be avoided, including morphine and atracurium. Even small amounts of histamine can lead to large release of catecholamines from pheochromocytomas, although practitioners have used morphine and atracurium without repercussions. Selective serotonin reuptake inhibitors (SSRI), monoamine oxidase (MAO) inhibitors, imipramine, and curare have all been implicated in provoking the release of catecholamines12,33. Conclusion In the case of our 23 year-old male, post mortem examination revealed an incidentaloma. It is possible that the patient had episodes of postoperative pain, not controlled by patient controlled analgesia, which caused the release of catecholamines. These catecholamines could have then caused either a hypertensive crises or cardiac arrhythmias in turn leading to the patient’s demise. Thus, an undiagnosed pheochromocytoma should be included as one of the causes of the patient’s death. It was not seen on radiographic images and the patient had not been screened for biochemical markers given he was asymptomatic and had had a history of prior resection of bilateral pheochromocytomas. This case raises the question of fully evaluating for pheochromocytomas in every patient with VHL or with MENIIA/B regardless of symptomatology or previous history of pheochromocytoma. Such evaluation is not a universally accepted standard of care but should be considered. Pheochromocytomas have variable ways in which they may present beyond the well known text book case. Clinicians must be prepared to identify and treat patients with such atypical presentations, particularly with the aging population and their increased incidence of these tumors. In instances where anesthesiologists find great lability in perioperative blood pressures, there should be a higher level of suspicion for pheochromocytoma. Our case especially emphasizes the need for careful post-operative monitoring, possibly in an intensive care unit setting for 24-48 hours. VARIANTS OF PHEOCHROMOCYTOMA AND THEIR ANESTHETIC IMPLICATIONS 905 References 1. Williams DT, Dann S and Wheeler MH: Pheochromocytomaviews on current management. European Journal of Surgical Oncology; 2003, 29:483-490. 2. Landsberg and Young JB: Pheochromocytoma. Harrison’s Principles in Internal Medicine. 14th edition. 1998. TR Harrison. McGraw-Hill. New York, 2057-2060. 3. Roizen MF: Anesthetic Implications of Concurrent Diseases. Anesthesia. 5th edition. 2000. RD Miller. Churchill Livingstone. New York, 924-925. 4. Munakata M, Aihara A, Imari Y, Noshiro T, Ito S, and Yoshinaga K: Altered sympathetic and vagal modulations of the cardiovascular system in patients with pheochromocytoma. American Journal of Hypertension; 1999, 12:572-580. 5. Tahrani AA and Macleod AF: A diagnostic dilemma in diagnosing and managing an incidental phaeochromocytoma. Exp Clin Endocrinol Diabetes; 2006, 114:204-207. 6. Myklejord DJ: Undiagnosed pheochromocytoma: the anesthesiologist nightmare. Clinical Medicine & Research; 2004, 2:59-62. 7. Bravo EL: Pheochromocytoma: current perspectives in the pathogenesis, diagnosis, and management. Arq Bras Endocrinol Metabol; 2004, 48:746-50. 8. Grant F: Anesthetic considerations in the multiple endocrine neoplasia syndromes. Current Opinion in Anaesthesiology; 2005, 18:345-352. 9. Ailun L, Xiangyang G, Hongzhi R, Yuguang H, and Tiehu Y: Clinical features and anesthetic management of multiple endocrine neoplasia associated with pheochromocytoma. Chinese Medical Journal; 2003, 116:208-211. 10.von Hippel E: Ueber eine sehr seltene Erkrankung der Netzhaut. Albrecht von Graefes Arch Ophthal; 1904, 59:83-106. 11.Lindau A: Zur Frage der Angiomatosis Retinae und Ihrer Hirncomplikation. Acta Ophthal; 1927, 4:193-226. 12.Gurunathan U and Korula G: Unsuspected pheochromocytoma: von Hippel-Lindau disease. Journal of Neurosurgical Anesthesiology; 2004, 16:26-28. 13.Amar L, Servais A, Gimenez-Roqueplo AP, Zinzindohour F, Chatellier G and Plouin PF: Year of diagnosis features at presentation, and risk of recurrence in patients with pheochromocytoma or secreting paraganglioma. The Journal of Clinical Endocrinology & Metabolism; 2005, 90:2110-2116. 14.Wong WT, Agrón E, Coleman HR, et al: "Genotype-phenotype correlation in von Hippel-Lindau disease with retinal angiomatosis". Archives of ophthalmology; 2007, 125 (2):239-45. 15.Abbott MA, Nathanson KL, Nightingale S, Maher ER and Greenstein RM: The von Hippel-Lindau (VHL) germline mutation V84L manifests as early-onset bilateral pheochromocytoma. Am J Med Genet A; 2006, 140:685-90. 16.Beroud C, Joly D, Gallou C, Staroz F, Orfanelli MT and Junien C: Software and database for the analysis of mutations in the VHL gene. Nucleic Acids Res; 1998, 26:256-8. 17.Bryant J, Farmer J, Kessler LJ, Townsend RR, and Nathanson KL: Pheochromocytoma: the expanding genetic differential diagnosis. J Natl Cancer Inst; 2003, 95:1196-204. 18.Glasker S: Central nervous system manifestations in VHL: genetics, pathology and clinical phenotypic features. Fam Cancer; 2005, 4:37-42. 19.Maher ER and Eng C: The pressure rises: update on the genetics of phaeochromocytoma. Hum Mol Genet; 2002, 11:2347-54. 20.Molino D, Sepe J, Anastasio P and De Santo NG: The history of von Hippel-Lindau disease. J Nephrol; 2006, 19 Suppl, 10:S119-23. 21.Kreusel KM: Ophthalmological manifestations in VHL and NF 1: pathological and diagnostic implications. Fam Cancer; 2005, 4:437. 22.Kreusel KM, Bechrakis NE, Krause L, Neumann HP and Foerster MH: Retinal angiomatosis in von Hippel-Lindau disease: a longitudinal ophthalmologic study. Ophthalmology; 2006, 113:1418-24. 23.Maher ER, Iselius L, Yates JR, Littler M, Benjamin C, Harris R, Sampson J, Williams A, Ferguson-Smith MA and Morton N: Von Hippel-Lindau disease: a genetic study. J Med Genet; 1991, 28:4437. 24.Molino D, Sepe J, Anastasio P and De Santo NG: The history of von Hippel-Lindau disease. J Nephrol; 2006, 19 Suppl, 10:S119-23. 25.Wanebo JE, Lonser RR, Glenn GM and Oldfield EH. The natural history of hemangioblastomas of the central nervous system in patients with von Hippel-Lindau disease. J Neurosurg; 2003, 98:8294. 26.Webster AR, Maher ER and Moore AT: Clinical characteristics of ocular angiomatosis in von Hippel-Lindau disease and correlation with germline mutation. Arch Ophthalmol; 1999, 117:371-8. 27.Umgawar M, Rajender Y, Purohit A, Sastry RA, Sundaram C and Rammurti S: Anesthetic management of von Hippel-Lindau syndrome for excision of cerebellar hemangioblastoma and pheochromocytoma surgery. Anesthesia & Analgesia; 1998, 86:673674. 28.Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y and Bornstein SR: The clinically unapparent adrenal mass: update in diagnosis and management. Endocrine Reviews; 2004, 25:309-340. 29.Roizen MF, Schreider BD and Hassan SZ: Anesthesia for patients with pheochromocytoma. Anesthesiol Clin North Am; 1987, 5:26975. 30.Shupak RC: Difficult anesthetic management during pheochromocytoma surgery. Journal of Clinical Anesthesia; 1999, 11:247-250. 31.Pederson LC and Lee JE: Pheochromocytoma. Current Treatment Options in Oncology; 2003, 4:329-37. 32.Mycek MJ, Harvey RA and Chaupe PC: Lippincott’s Illustrated Reviews Pharmacology, 2nd edition. Lippincott-Raven. Philadelphia; 1992, pp. 71-71. 33.Anon: Phaeochromocytoma unmasked by drug therapy. Prescrire int; 2003, 12:181-2. M.E.J. ANESTH 20 (6), 2010 ANESTHETIC MANAGEMENT OF ACHONDROPLASTIC DWARF UNDERGOING CESAREAN SECTION - A Case Report Banu Çevik* and Serhan Çolakoğlu* Abstract There are more than 100 different types of dwarfism. Achondroplasia is the most common of these conditions. The aim of this report is to describe the anesthetic management of these patient, discussing the anesthetic considerations and emphasizing the difficulties encountered. A 32-year-old achondroplastic parturient underwent cesarean section under general anesthesia. We did not encounter problems related with airway management. The operation went without any complication. There are risks for both regional and general anesthesia in achondroplastic patients. The most important point is the careful preoperative assessment. Anesthesia plan should be specified to individual basis. Introduction Various uncommon disorders present in pregnant women can create a dilemma for obstetricians and obstetric anesthesists as to how to best manage these patients. Achondroplastic dwarfism is one of these disorders and the clinical management remains controversial1. Achondroplasia is the commonest form of dwarfism, in which a large number of cases resulted from spontaneous mutation. The incidence varies between 4 and 15 per 100,000 live births. Females are affected more frequently than males2. Achondroplastic patients present several problems for both general and regional anesthesia. We describe a patient with achondroplasia undergoing Cesarean section and discuss the anesthetic considerations in achondroplastic individuals. Case Report A 32-yr-old primagravid achondroplastic dwarf presented for elective Cesarean section at 37 weeks’ gestation. She had no previous history of anesthesia and her pregnancy had been uneventful. Her history included no relevant conditions. She was taking prenatal vitamins and had no known allergies. Physical examination revealed a 49-kg, 135 cm, normal intelligent female with large head, short limbs and mild kyphoscoliosis. She had short neck, large tongue, protruded chin, full set of teeth. Mouth opening was adequate with Mallampati II airway and neck extention was not limited. Examination of cardiorespiratory system revealed no problems and there was no neurological abnormalities. Preoperative hemoglobin and electrolyte concentrations were within normal limits. Ultrasonic measurements in utero suggested that the fetus was normally developed. * MD, Department of Anesthesiology and Reanimation, Dr. Lütfi Kirdar Kartal Training and Research Hospital, Istanbul, Turkey. Correspondong author: Banu Çevik, MD, Bağdat Cad., Noter Sok, Yazicioğlu Apt. 10/12 Erenköy/Istanbul/Turkey. Phone: (0216) 4413900/1298, E-mail: [email protected] 907 M.E.J. ANESTH 20 (6), 2010 908 The patient was very anxious and she did not desire to be awake during procedure. Therefore, after discussion of potential risk and written informed consent, it was decided to performe the operation under genral anesthesia. Appropriate sized facemasks, tracheal tubes, stillettes, laryngeal mask airways (LMATM) and intubating laryngeal mask airways (ILMATM) were prepared for possible difficulty in intubation. No premedication was given and she was monitored by non-invasive arterial pressure, electrocardiogram (ECG) and pulse oxymetry on arrival in the operating room. Anesthesia was induced with thiopenthal and neuromuscular blockade was achieved with succinylcholine. Trachea was intubated at the first attempt with a 7.0-mm ID endotracheal tube. Lower segment cesarean section proceeded and a live baby was delivered weighing 3200 grams with APGAR scores of 8 and 9 at the first and the fifth minutes respectively. Maintenance of anesthesia was provided by sevoflurane in 50% oxygen-nitrous oxide mixture. Muscle relaxation was achieved with vecuronium the patient was given oxytocin and fentanyl after the umbilical cord was clamped. No other medication was given during the procedure. The total duration of anesthesia was 1h and all monitored parameters (ECG, pulse oxymetry, endtidal CO2 and non-invasive blood pressure) remained stable. At the end of the operation, neuromuscular blockade was reversed with neostigmine 0.05 mg.kg-1 and atropine 0.02 mg.kg-1 and the trachea was extubated when the patient was fuly awake. The patient was taken to postanesthesia care unit and administered 5 l.min-1 of oxygen through a face mask until transferring to the ward. The postoperative period was uneventful and the patient and neonate were discharged on the fifth day. Discussion Achondroplastic dwarfs characteristically have low fertility rates; however, they often require delivery by cesarean section because the normal-sized fetal head and smaller than normal maternal pelvic diameter result in cephalopelvic disproportion during the later stages of pregnancy3. These patients have a number of anatomic and physiological abnormalities that contribute to problems with the administration of B. Çevik & S. Çolakoğlu obstetric anesthesia. Achondroplastic patients have facial features that alert the anesthesists to potential problems in airway management4. They have narrow nasal passages and pharyngeal and maxillary hypoplasia. Maintenance of a patent upper airway may be difficult because of the presence of a large tongue and mandible. The base of the skull is shorted (because of early fusion of constituent bones) and angulated, yielding a limited extension and making endotracheal intubation potentially difficult1,5. On the other hand, not all authors have encountered difficulties. Mayhew et al.6 reported no difficulty in airway management or direct laryngoscopy in a series of 27 patients undergoing 36 anesthetic procedures. They also suggested that is tracheal intubation was required, a small tracheal tubes should have been selected. There are reports describing the achondrplastic patients with classical symptoms and signs of upper airway obstruction but no difficulty encountered7-11. We elected to use general anesthesia for two reasons. First of all, the patient wanted to be asleep because of her anxiety. Secondly, preoperative examination suggested no possibility of a difficult airway. Consequently, the intubation was completed in the first attempt without any undesirable effects. Several anatomical abnormalities found in achondroplasia may complicate regional techniques. Difficulties may result from kyphoscoliosis and other spinal abnormalities, included narrowing of the vertebral canal, shortening of the pedicles, reduced interpedicular distance (particularly in the lower lumbar spine) and osteophyte formation. Spinal stenosis may impair cerebrospinal fluid flow, such that identification of dural puncture is more difficult. Also the presence of narrow epidural space make insertion of catheter difficult12. Engorged epidural veins increase the risk of venous puncture either by the Tuohy needle or the catheter, and result in an unpredictable spread of local anesthetic within the space13. We found reports related with achondroplasia which had successfully managed by regional anesthesia. These are spinal14-17, epidural3,5,13,18-20 or combined spino-epidural (CSE) techniques4. In these reports, technically challenging problems owing to skeletal abnormalities and the appropriate ANESTHETIC MANAGEMENT OF ACHONDROPLASTIC DWARF UNDERGOING CESAREAN SECTION dose of drugs were discussed. Ravenscroft et al.16 were successful in one patient with the spinal anesthetic dose decreased by 30%. DeRenzo et al.17 also reduced the intracheal dose of bupivacaine from 12 to 10 mg with the addition of 0.2 mg morphine for the relief of postcesarean section pain21. In that report, the patient had experienced discomfort, requiring iv sedation for forty minutes after delivery. The suggested that decreasing the intracheal dose was not unreliable. It’s suggested that epidural anesthesia was theoretically preferable to spinal anesthesia because of ability to titrate the level of block. Incremental doses of anesthesia could be required due to maternal short stature and kyphoscoliosis1,4. Trikha et al.4 preffered CSE over a spinal or epidural technique because it 909 combines the rapid onset of spinal anesthesia with the implantation of epidural catheter. This approach provided prolonged anesthesia and excellent postoperative analgesia. DeRenzo et al.17 also reported that titratable techniques such as epidural, CSE, continuous spinal would have been beter suited for these paitents. In conclusion, the risks of both regional and general anesthesia in achondroplastic patients are known. With the above factors taken into consideration, a complete history and physical examination before administration of anesthesia can help to reduce risks. The anesthesia plan should be based on each indivdual case and the potential risks must be discussed with the patient. M.E.J. ANESTH 20 (6), 2010 910 B. Çevik & S. Çolakoğlu References 1. Kuczkowski KM: Labor analgesia for the parturient with an uncommon disorder: A common dilemma in the delivery suite. Obstet Gynecol Surv; 2003, 58(12):800-3. 2. Eisenach JC: Orthopedic disease. In: Obstetrical Anesthesia: The Complicated Patient (James FM, Wheeler AS, Dewan DM eds) 2dn ed. FA Davis Company. Philadelphia 1998, p. 239. 3. Brimacombe JR, Caunt JA: Anaesthesia in a gravid achondroplastic dwarf. Anaesthesia; 1990, 45(2):132-4. 4. Trikha A, Goyal K, Sadera GS, Singh M: Combined spinal epidural anaesthesia for vesicovaginal fistula repair in an achondroplastic dwarf. Anaesth Intensive Care; 2002, 30(1):96-8. 5. Morrow MJ, Black IH: Epidural anaesthesia for caseran section in an achondroplastic dwarf. Br J Anaesth; 81(4):619-21. 6. Mayhew JF, Katz J, Miner M, Leiman BC, Hall ID: Anaesthesia for the achondroplastic dwarf. Can J Anaesth; 1986, 33(2):216-21. 7. Krishnan BS, Eipe N, Korula G: Anaesthetic management of a patient with achondroplasia. Paediatr Anaesth; 2003, 13(6):547-9. 8. Kalla GN, Fening E, Obiaya MU: Anaesthetic management of achondroplasia. Br J Anaesth; 1986, 58(1):117-9. 9. Monedero P, Garcia-Perdajas F, Coca I, Fernandez-Liesa JI, Panadero A, de los Rios J: Is management of anesthesia in achondroplastic dwarfs really a challenge? J Clin Anesth; 1997, 9:208-12. 10.Huang J, Babins N: Anesthesia for cesarean delivery in an achondroplastic dwarf: a case report. AANAJ; 2008, 76(6):435-6. 11.Ghumman S, Goel N, Rajaram S, Singh KC, Kansal B, Dewan P: Pregnancy in an achondroplastic dwarf: a case report. J Indian Med Assoc; 2005, 103(10):536-8. 12.Berkowitz ID, Raja SN, Bendor KS, Kopits SE: Dwarfs: Pathophysiology and anesthetic implications. Anesthesiology; 1990, 73:739-59. 13.Wardall GJ, Frame WT: Extradural anaesthesia for Cesarean section in achondroplasia. Br J Anaesth; 1990, 64(3):367-70. 14.Crawford M, Dutton DA: Spinal anaesthesia for caeserean section in an achondroplastic dwarf. Anaesthesia; 1992, 47(11):1007. 15.McGlothlen S: Anesthesia for cesarean section for achondroplastic dwarf: a case report. AANA J; 2000, 68(4):305-7. 16.Ravenscroft A, Govender T, Rout C: Spinal anesthesia for emergency cesarean section in an achondroplastic dwarf. Anaesthesia; 1998, 53:1236-7. 17.DeRenzo JS, Vallejo MC, Ramanathan S: Failed regional anesthesia with reduced spinal bupivacaine dosage in a parturient with achondroplasia presenting for urgen cesarean section. Int J Obstet Anesth; 2005, 14(2):175-8. 18.Cohen SE: Anesthesia for cesarean section in achondroplastic dwarfs. Anesthesiology; 1980, 52(3):264-6. 19.Carstoniu J, Yee I, Halpern S: Epidural anaesthesia for cesarean section in an achondroplastic dwarf. Can J Anaesth; 1992, 39(7):708-11. 20.Waltz IF, Finerman G, Wyatt GM: Anaesthesia for dwarfs and other patients of pathological small stature. Can J Anaesth; 1975, 22(6):703-9. 21.Abboud TK, Dror A, Mosaad P et al: Mini-dose intracheal morphine for the relief of post-cesarean section pain: safety, efficacy and ventilatory responses to carbon dioxide. Anesth Analg; 1988, 67:137-43. GUIDELINES FOR AUTHORS The Middle East of Anesthesiology publishes original work in the fields of anesthesiology, intensive care, pain, and emergency medicine. This includes clinical or laboratory investigations, review articles, case reports and letters to the Editor. Submission of manuscripts: The Middle East Journal of Anesthesiology accepts electronic submission of manuscripts as an e-mail attachment only. Manuscripts must attachment to: be submitted via email Editor-In-Chief, Department of Anesthesiology, American University of Beirut Medical Center Beirut, Lebanon E-mail: [email protected] Human Subjects Manuscripts describing investigations performed in humans must state that the study was approved by the appropriate Institutional Review Board and written informed consent was obtained from all patients or parents of minors. Language: Articles are published in English. 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