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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 Maurice A. Baroody Bassam Barzangi (Iraq) Editors Chakib Ayoub Marie Aouad Sahar Siddik-Sayyid Izdiyad Bedran (Jordan) Dhafir Al-Khudhairi (Saudi Arabia) Mohammad Seraj (Saudi Arabia) Abdul-Hamid Samarkandi (Saudi Arabia) Mohamad Takrouri (Saudi Arabia) Emeritus Editor-In-Chief Anis Baraka Bourhan E. Abed (Syria) Honorary Editors Nicholas Greene Musa Muallem Mohamed Salah Ben Ammar (Tunis) Webmaster Rabi Moukalled M. Ramez Salem (USA) Secretary Alice Demirdjian [email protected] Elizabeth A.M. Frost (USA) Halim Habr (USA) Managing Editor Founding Editor Mohamad El-Khatib [email protected] Bernard Brandstater 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) 134 Kingdom of Saudi Arabiah National Guard Health Affairs CARDIAC SCIENCE DEPARTMENT 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: Consultant in Cardiac Critical Care and Assistant Consultants in Cardiac Critical Care Responsibilities include peri-operative care of critically ill cardiac patients. Our requirements in terms of academics and experience are as follows: • Consultant Cardiac Critical Care FRCS-Irish / UK, North American or Australian Boards coupled with minimum 3 years post Board experience in Anaesthesia and fellowship in Cardiac Anaesthesia and Critical Care desirable • Assistant Consultant Cardiac Critical Care FRCS-Irish / UK, North American, Australian Boards/Arab or Saudi Board/ MRCP or equivalent coupled with minimum 0-1 year post Board experience in Anaesthesia and fellowship in Cardiac Anaesthesia and Critical Care desirable We, in turn can offer a generous tax-free salary, generous holidays, annual flights and exceptional benefits. If you are interested please send your CV indicating which journal advert you are responding to, along 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. Your application will be treated in strictest of confidence and all initial enquiries or requests for more information are welcomed. For more information please visit our website at www.ngha.med.sa Middle East Journal of Anesthesiology Vol. 21, No. 3, October 2011 CONTENTS editorial Succinylcholine “The Gold Standard” For Rapid-Sequence Induction Of Anesthesia - Pro & Cons ��������������������������������������������������������������������������������������������������������������������������������������������������������������� Anis Baraka 323 scientific articles Prospective, Randomized Study To Assess The Role Of Dexmedetomidine In Patients With Supratentorial Tumors Undergoing Craniotomy Under �������������������������������������������������������� Rabie Soliman, Amira Hassan, Amr Rashwan and Ahmed Omar Anesthetic Challenges In Oro-Facial Cleft Repair In Ile-Ife, Nigeria ������������������������������������������������������������������ Anthony Adeneka, Aramide Faponle and Fadekemi Oginni Comparison Between Ropivacaine 1,5 MG ML-1 Plus Fentanyl 2 MF ML-1 And Ropivacaine 1,5 MG ML-1 Plus Clonidine 1 µg ML-1 As Analgesic Solution After Anterior Cruciate Ligament Reconstruction: A Randomized Clinical Trial ������������������������������������������������������������������������������������������������� Apostolos Kalakonas, Georgios Kotsovolis, Omiros Chalkeidis and Christos Triantafyllou The Influence Of Simulation-Based Physiology Labs Taught By Anesthesiologists On The Attitudes Of First-Year Medical Studnets Towards Anesthesiology ������������������������������������������������������� Samuel Demaria, Ethan Bryson, Carol Bodian, Yury Khelemsky, Alan Sim, Andrew Schwartz, Daniel Katz and Adam Levine Preemptive Analgesic Effect Of Diclofenac: Experimental Study In Rats �������������������������������������������������������������������������� Antigona Hasani, Marija Soljakova, Muharrem Jakupi and Serpil Ustalar-Ozgen Comparison Between Two Phenylephrine Infusion Rates With Moderate Co-Loading For The Prevention Of Spinal Anaesthesia- Induced Hypotension During Elective Caesarean Section ����������������������������������������������������������������������������������������� Tarek Ansari, Medhat Hashem, Ahmed Hassan, Ahmed Gamassy and Ayad Saleh Evaluation Of An Intraoperative Algorithm Based On Near-Infrared Refracted Spectroscopy Monitoring, In The Intraoperative Decision For Shunt Placement, In Patients Undergoing Carotid Endarterectomy ������������������������������������������������������������������� Ioannis Zogogiannis, Christos Iatrou, Miltiadis Lazarides, Theodossia Vogiatzaki, Mitchell Wachtel, Petros Chatzigakis and Vassilios Dimitriou Effects Of Preoperative Oral Carbohydrates And Trace Elements On Perioperative Nutritional Status In Elective Surgery Patients ���������������������������������������������������������������������������� Yoshimasa Oyama, Hideo Iwasaka, Keisuke Shiihara, Satoshi Hagiwara, Nobuhiro Kubo, Yutaka Fujitomi and Takayuki Noguchi Reduced Hemodynamic Responses To Tracheal Intubation By The Bonfils Retromolar Fiberscope: A Randomized Controlled Study ����������������������������������������� Abdulaziz Boker, Waleed Almarakbi, Abeer Arab and Adnan Almazrooa 319 325 335 341 347 355 361 367 375 385 M.E.J. ANESTH 21 (3), 2011 eFFecT oF prophylacTic dexameThaSone on nauSea and vomiTinG aFTer laparoScopic GynecoloGical operaTion: meTa-analySiS cecorrected in on-line version ������������������������������������������������������������������������������������������������������� Wang Bin, HE Kai-Hua, Jiang Meng-Bi, 397 Liu Chao and Min Su, eFFecT oF KeTamine on BiSpecTral index durinG propoFol- FenTanyl aneSTheSia: a randomized conTrolled STudy cecorrected in on-line version ���������������������������������������������������������������������������������Saikat Sengupta, Simantika Ghosh, Amitava Rudra, 391 P Kumar, Gaurab Maitra, Tanmoy Das CASE REPORTS venTilaTion diFFiculTy due To herniaTion oF inFlaTinG TuBe oF The cuFF inSide The endoTracheal TuBe ���������������������������������������������������������������������������������������������������������������������Oya Yalcin Cok, Melih Cekinmez, Pinar Ergenoglu and Anis Aribogan aneSTheSia For ceSarian SecTion in preGnanT Woman WiTh acuTe inTermiTTenT porphyria and hypoThyroidiSm ���������������������������������������������������������������������������������������������������������������������� Roberto Dumas, Elizabeth Silva, Marco Antonio Resende, Alberto Pantoja and Antonio Celso Barros “crime Scene inveSTiGaTion” aT an aneSTheTic cocKTail parTy WiTh aTriovenTricular diSSociaTion �������������������������������������������������������������������������������������������������� Christoph Schlimp and Franz Wiedermann leFT aTrial myxoma WiTh coronary arTery diSeaSe: an unexpecTed preoperaTive FindinG ��������������������������������������������������������������������Madan Maddali, Ahmed Abduraz, Prashanth Panduranga and Elizabeth Kurian 403 405 409 413 poST-operaTive reSpiraTory complicaTionS aFTer palaToplaSTy in a 19 monTh old Female WiTh cornelia de lanGe Syndrome: a caSe reporT ����������������������������������������������������������������������������������������������������������������� Brooke Ingram and Elizabeth Frost 419 WhaT iF The epidural caTheTer needS To Be Fixed more Than FiFTeen cenTimeTerS aT SKin? �������������������������������������������������������������������������������������������������������������������������������������������������������������� Vishal Uppal 423 exTreme inTraoperaTive hyperKalemia in a non dialySiS paTienT underGoinG Kidney TranSplanTaTion ���������������������������������������������������������������������������������������������������������������� Mia Kazanjian and Steven Neustein 425 SucceSSFul TreaTmenT oF early ropivacaine ToxiciTy WiTh inTralipid in a paTienT WiTh aTTenTion deFiciT hyperacTiviTy diSorder ����������������������������������������������������������������������������������������������������������������������������������������������������������Achir Al-Alami 427 chronic uSe oF oxyBuTynin and Spinal aneSTheSia: a caSe oF poSToperaTive urinary reTenTion and hemaTuria ����������������������������������������������������������������������������������������������������������������������������������������������������� Adriano Hobaika inFilTraTive anGiolipoma oF The necK ������� Abdul-Latif Hamdan, Laurice Mahfoud, Hani Rifai, Charbel Rameh and Nabil Fuleihan 431 433 cardiac arreST durinG elecTive orThopedic SurGery due To moderaTe hypoKalemia ����������������������������������������������������������������������������������������������������������������� Manuel Struck and Andreas Nowak 435 The aneSTheTic manaGemenT oF a paTienT WiTh dorFman- chanarin Syndrome �������������������������������������������������������������������� Azize Bestas, Esef Bolat, Mustafa Bayar and Omer Erhan 437 linGual Thyroid: a rare cauSe oF diFFiculT inTuBaTion ���������������������������������������������� Maroun Ghabash, Jean-Claude Stephan, May Matta and May Helou 441 320 letter to the editor Should Surgery Be Cancelled When Surreptitious Cocaine Use Is Discovered Before Elective Non-Cardiac Surgery? ��������������������������������������������������������� M. Chadi Alraies, Abdul Hamid Alraiyes and Franklin Michota 445 apparatus Automatic Endotracheal Tube Cuff Inflator And Continuous Pressure Monitor/ Controller ��������������������������������������������������������������������������������������������������Musa Muallem and Mohammad El- Khatib 321 447 M.E.J. ANESTH 21 (3), 2011 EDITORIAL Succinylcholine “The Gold Standard” For Rapid-Sequence Induction Of Anesthesia - Pro & Cons The neuromuscular effects of succinylcholine (SCh) were described1 by Bovet 1949. The drug was introduced into clinical anesthesia in the United States by Foldes et al 1952, who stated that “the advantages of succinylcholine as a muscular relaxant in anesthesiology far outweighed its disadvantages”2. Even today in the 6th decade of its use, SCh, despite complications, survived as the “gold standard” for rapid-sequence induction of anesthesia (RSI), against which other relaxants are compared3. The drug survived, despite the reported complications, because of the unique triad characterizing its neuromuscular block i.e. rapid onset, profound relaxation and short duration, which makes succinylcholine the drug of choice for rapid-sequence induction (RSI) of anesthesia in patients with full stomach, as well as the preferred relaxant for tracheal intubation in patients with a predicted difficult airway3-5. This characteristic triad of succinylcholine neuromuscular block can be attributed to the rapid hydrolysis of SCh by the normal plasma cholinesterase, as well as to its depolarizing action. In addition, the low molecular weight of SCh, and its simple molecular configuration consisting of two acetylcholine molecules attached together may contribute to its rapid onset of action by allowing the drug to pass directly from the blood to the endplate receptors prior to equilibration in the extracellular fluid. The hydrolysis of SCh by the normal plasma cholinesterase is very rapid, and the rate of hydrolysis is proportional to the substrate concentration. This rapid hydrolysis into succinylmonocholine and choline can allow us to use multiple ED95 doses (up to 5-10 ED95) which result in a very rapid onset of deep neuromuscular block, without a significant increase in the duration of action. The depolarization mechanism of SCh can also contribute to the rapid onset of block since we need to activate only 10-25% of the endplate receptors in order to achieve depolarization block. In contrast, non depolarizing relaxants need to block 75-90% of the receptors (i.e. the safety margin) in order to produce nondepolarizing neuromuscular block. Also, SCh can relax the fast-contracting muscles such as the vocal cords and the masseters more than the nondepolarizing relaxants which relax the slow-contracting muscles more than the fast-contracting muscles. In addition, the action of SCh is actually endplate-muscular and not neuro-muscular block which can result in profound muscular relaxation6. In conclusion, SCh stood the test of time as the “Gold Standard” relaxant for rapid-sequence induction of anesthesia because of its very rapid hydrolysis, its depolarizing mechanism of block, as well as to its simple and low molecular weight structure which can contribute to the triad characteristics of SCh block i.e. rapid onset, profound block and short duration of action. However, “there is no free dinner”. The characteristics contributing to the advantages of SCh as the “Gold Standard” for rapid sequence induction of anesthesia i.e. the very rapid hydrolysis and 323 M.E.J. ANESTH 21 (3), 2011 324 ANIS BARAKA its depolarizing action are the same factors that result in its side effects: I. The ultra-short action of SCh in the presence of normal plasma cholinesterase can change into a very prolonged block in the presence of homozygote atypical cholinesterase. This will be associated with gradual desensitization and change of block characteristics from depolarizing block (No tetanic fade and no post-tetanic facilitation) into phase II block (tetanic fade and post-tetanic facilitation). II. The depolarizing action of Sch can result in: 1. Post operative myalgia 2. Increase of intraocular pressure, intracranial pressure, intragastric pressure and intra abdominal pressure III. The autonomic effects of SCh can result following the initial dose in sympathomimetic side effects such as hypertension and tachycardia. In contrast, repeated doses of SCh may produce vagotonic bradycardia IV. In patients having neuromuscular disorders, depolarization by SCh can be complicated by serious hyperkalemia, rhabdomyolysis and malignant hyperthermia7. Now, is it time to say Good Bye Sux?! It seems not yet, until we can find an alternative non-depolarizing relaxant having similar characteristics i.e. rapid onset, short duration and profound neuromuscular block. However, because of the complications that can follow administration of SCh, I recommend the following: 1. To avoid SCh whenever contraindicated e.g. in patients having neuromuscular disorders 2. To use SCh only whenever indicated: e..g RSI in patients with full stomach4,5,8, and tracheal intubation in patients having predicted difficult airway. In addition, SCh as a single dose, may be indicated in procedures requiring profound relaxation for a short duration, such as electroconvulsive therapy, cardioversion, fracture setting3, and relief of laryngospasm. Also, SCh is the only relaxant which is effective following intramuscular injection. Anis Baraka, MD,FRCA(Hon) Emeritus Editor-in-Chief Middle East Journal of Anesthesiology Department of Anesthesiology American University of Beirut Medical Center References 1. Bovet D: Some aspects of the relationship between chemical constitution and curare-like activity. Annals of the New York Academy of Science; 1951, 54:407-37. 2. Foldes FF, McNall PG, Borrego-Hinojosa JM: Succinylcholine: a new approach to muscular relaxation in anesthesiology. New England Journal of Medicine; 1952, 247:596-600. 3. Lee C: Good bye Suxamethonium. Anaesthesia; 2009, 64 (Supp. 1), pp. 73-81. 4. Baraka A: Muscle relaxants for rapid-sequence induction of anesthesia. M E J Anesth; 2004, 17(4):557-568. 5. Baraka A: Rapid onset of suxamethonium block. Br J Anaesth; 1991, 66:733. 6. Baraka A: Neuromuscular block in different species. Acta Anaesth Scand; 1972, 16:132-139. 7. Baraka A, May J: Anesthesia and Myopathy. Current Opinion in Anaesthesiology; 2002, 15:371-376. 8. Siddik S, Jalbout M, Baraka A: Rapid sequence induction for cesarean section. M E J Anesth; 2004, 17(4):569-584. scientific articles PROSPECTIVE, RANDOMIZED STUDY TO ASSESS THE ROLE OF DEXMEDETOMIDINE IN PATIENTS WITH SUPRATENTORIAL TUMORS UNDERGOING CRANIOTOMY UNDER GENERAL ANAESTHESIA Rabie Nasr Soliman *, Amira Refaie Hassan*, Amr Madih Rashwan* and A hmed M ohamed O mar * Abstract Background: Preliminary data on the perioperative use of dexmedetomidine in patients undergoing craniotomy for brain tumor under general anaesthesia indicate that the intraoperative administration of dexmedetomidine is opioid-sparing, results in less need for antihypertensive medication, and may offer greater hemodynamic stability at incision and emergence. Dexmedetomidine, α 2 adrenoceptor agonist used as adjuvant to anaesthetic agents. Relatively recent studies have shown that dexmedetomidine is able to decrease circulating plasma norepinephrine and epinephrine concentration in approximately 50%, decreases brain blood flow by directly acting on post-synaptic α 2 receptors, decreases CSF pressure without ischemic suffering and effectively decrease brain metabolism and intracranial pressure and also, able to decrease injury caused by focal ischemia. Purpose: This prospective, randomized, double-blind study was designed to assess the perioperative effect of intraoperative infusion of dexmedetomidine in patients with supratentorial tumors undergoing craniotomy under general anaesthesia. Methods: Forty patients with CT- scanning proof of supratentorial tumors. The patients were classified equally into 2 groups (twenty patients in each group). Group A: - The dexmedetomidine was given as a bolus dose of 1 µg/kg in 20 minutes before induction of anaesthesia, followed by a maintenance infusion of 0.4 µg/kg/hr. The infusion was discontinued when surgery ended. Group B: - The patients received similar volumes of saline. Results: The heart rate and mean arterial blood pressure, decreased in patients of group A (dexmedetomidine group) more than group B (placebo group) with significant statistical difference between the two groups (P-value <0.05). No significant statistical difference between the two groups regarding the central venous pressure and arterial partial pressure of Carbon Dioxide (P-value >0.05). The intraoperative end-tidal sevoflurane (%) in patients of group A less than in patients of group B (P-value <0.05).The intracranial pressure decreased in patients of Group A more than group B (P-value <0.05). The Glasgow coma scale (GCS) improved in patients of group A and deteriorated in patients of Group B with significant statistical difference between the two groups (P-value <0.05).The Total fentanyl requirements from induction to extubation of patients * Lecturer of anaesthesia, Department of anaesthesia and neurosurgical ICU, Faculty of medicine, Cairo University, Egypt. E-mails: [email protected], [email protected],[email protected] 325 M.E.J. ANESTH 21 (3), 2011 326 increased in patients of group B more than in patients of group A (P-value <0.05). The total postoperative patients' requirements for antiemetic drugs within the 2 hours after extubation decreased in patients of group A more than group B (P-value <0.05). The postoperative duration from the end of surgery to extubation decreased significantly in patients of group A more than group B (P-value <0.05). The total urine output during the duration from drug administration to extubation of patients increased in patients of group A more than group B (P-value <0.05). Conclusions: Continuous intraoperative infusion of dexmedetomidine during craniotomy for supratentorial tumors under genera‑l anaesthesia maintained the haemodynamic stability, reduced sevoflurane and fentanyl requirements, decreased intracranial pressure, and improved significantly the outcomes. Key words: Dexmedetomidine - supratentorial Tumors - Craniotomy – Sevoflurane – Fentanyl Intracranial pressure - Neurosurgical intensive care unit. Introduction The intense surgical stimuli associated with craniotomy frequently engender sympathetic activation and marked changes in systemic arterial pressure, CBF, and ICP. Cerebrovascular responses may result in elevated ICP and reduction in cerebral perfusion pressure, especially in patients with impaired autoregulation and compromised cerebral compliance. Perioperative hypertension in neurosurgical patients is associated with intracranial bleeding and prolonged hospital stay1. Thus, the prevention and control of the hemodynamic response to nociceptive stimuli are of utmost importance to preserve cerebral homeostasis in neurosurgical patients. The antinociceptive, sympatholytic, and anaesthesia-sparing effects of α 2-agonists are well documented2,3. This spectrum of properties would be consistent with the important goals during neurosurgical anesthesia of intraoperative hemodynamic stability and modulation of intraoperative sympathetic responses to attenuate cerebrovascular and myocardial risks and avoid intracranial hemorrhage, and to allow immediate neurological evaluation upon emergence4-6. R. N. Soliman et. al Alpha-2-Adrenoreceptors are a subgroup of noradrenergic receptors distributed broadly within and outside the CNS. Alpha-2-Receptors in the brain are concentrated primarily in the pons and medulla, areas involved in transmitting sympathetic nervous system activation from higher brain centers to the periphery. Stimulation of presynaptic α 2-receptors reduces norepinephrine release, and activation of postsynaptic α 2-receptors hyper-polarizes neural membranes. Interaction between these receptors and norepinephrine thus acts as an inhibitory feedback loop in which excessive norepinephrine release actually reduces further release of the same neurotransmitter7,8. In the spinal cord, α 2-adrenergic receptors are located postsynaptically in the dorsal horn, and their stimulation inhibits nociceptive signal transmission9. In the periphery, α 2-receptors are found on vascular smooth muscle, in which their activation results in vasoconstriction8. Injectable dexmedetomidine was approved by the FDA in 1999 for use in the intensive care unit. Since its approval and clinical use, it has been utilized for sedation during surgery and postoperative periods10. Dexmedetomidine (DEX) is a highly selective α 2-adrenoreceptor agonist recently introduced to anaesthesia practice. It produces dose-dependent sedation, anxiolysis, and analgesia (involving spinal and supraspinal sites) without respiratory depression3,11. DEX enhances anaesthesia produced by other anaesthetic drugs and decreases blood pressure by stimulating central alpha2 and imidazoline receptors12,13. The use of DEX in neuroanaesthesia generate a reduction in the sympathetic tone and a decrease in peripheral noradrenaline release reducing hypertensive responses to neurosurgical patient stimulation during catheterization and head pin holder application14,15. The aim of our study to assess the perioperative effect of dexmedetomidine in patients with supratentorial brain tumors undergoing craniotomy under general anaesthesia. Patients and methods After obtaining informed consent and approval of local ethics and research committee, forty patients in Kasr El-Aini hospital, Cairo University with CTscanning proof of supratentorial brain tumor were PROSPECTIVE, RANDOMIZED STUDY TO ASSESS THE ROLE OF DEXMEDETOMIDINE IN PATIENTS WITH SUPRATENTORIAL TUMORS UNDERGOING CRANIOTOMY UNDER GENERAL ANAESTHESIA scheduled for craniotomy under general anaesthesia. The exclusion criteria were as follows: pregnant or nursing woman, morbid obesity, preoperative heart rate <45 beats/min, second or third degree AV block, antihypertensive medication with a-methyldopa, clonidine or other α 2-adrenergic agonist during the 28 days before scheduled study, EF <30% sleep problems, psychiatric diseases and renal or hepatic diseases. The surgery in all patients of both groups was elective. On arrival to operating room and under local anaesthesia, the central venous line was inserted in subclavian vein, left radial arterial cannulation was done and the intracranial pressure (ICP) was monitored by ventriculostomy catheter placed by the neurosurgeon through a burr hole into the lateral ventricle of the brain, preoperatively under local anaesthesia. Electronic monitoring of ICP was done by utilizing saline-filled tubing with a pressure transducer. The transducer should be zeroed as the same for arterial pressure (at the external auditory meatus) before induction of anaesthesia. The patients were randomized into 2 groups (twenty patients in each group). Group A; The dexmedetomidine group (The dexmedetomidine was supplied in 2-mL ampoules of 100 µg/ml concentration (Abbott, Chicago, IL, USA), and this volume was diluted with 98 mL of normal saline to yield a final concentration of 2 µg/ml), the patients were premedicated with dexmedetomidine (1 µg/kg) in 20 minutes followed by a maintenance infusion of 0.4 µg/kg/hr. The infusion was discontinued when surgery ended. Group B; The placebo group, the patients were received similar volumes of saline. All patients should be preoxygenated, and then intravenous thiopental (3-5mg/kg) followed by fentanyl (3-5µg/ kg) and atracurium 0.5 mg/kg as a bolus dose over 30 sec, while controlled hyperventilation with 100% oxygen was instituted. Before intubation an additional bolus of thiopental (2-3 mg/kg) was given. After induction, controlled mechanical ventilation was adjusted to maintain PaCO2 between 30 and 35 mmHg. The anaesthesia was maintained with sevoflurane 0.5 to 3%, atracurium was administered by intravenous infusion at a rate of 0.5 mg/kg/hr and fentanyl infusion (1 µg/kg/hr). Bolus doses of fentanyl (1-2 µg/kg) were given to control the increased heart rate and systemic hypertension during surgery according to the 327 need. Fluid resuscitation and maintenance fluids were provided with glucose free iso-osmolar crystalloid solutions 2-3 ml/kg/hr, and replacement of blood loss and urine output. Drugs such as corticosteroids, diuretics (1-2 mg/kg) and mannitol (1gm/kg) were given according to the need. The monitors used during anaesthesia included ECG, Pulse oximetry, non invasive blood pressure, invasive blood pressure from left radial artery cannula, continuously core temperature from nasopharyngeal probe, central venous pressure from subclavian vein, end tidal CO2, endtidal concentration of sevoflurane, urine output from urinary catheter every one hour, intracranial pressure (ICP) and arterial blood gases (ABG were done by AVL GRAZ OMNI 6 Modular system). Neurological assessment was done for all patients by Glasgow coma scale before induction of anaesthesia and after 2 hours of extubation. At the end of surgery, all patients were transferred to neurosurgical intensive care unit and monitored by the same monitors used intraoperatively. The data of patients was collected at the following timepoints, T0: The reading before administration of the study medication, T1: The reading after induction of anaesthesia, T2: The reading 2 hours after administration of study medication, T3: The reading at the of end surgery, T4: The reading on admission to the ICU, T5: The reading before extubation and T6: The reading 2 hours after extubation. The Statistical Paragraph in Material and Methods Data were statistically described in terms of range; mean ± standard deviation (± SD), median, frequencies (number of cases) and relative frequencies (percentages) when appropriate. Comparison of quantitative variables between the study groups was done using Mann Whitney U test for independent samples. For comparing categorical data, Chi square (χ2) test was performed. Exact test was used in stead when the expected frequency is less than 5. A probability value (p value) less than 0.05 was considered statistically significant. All statistical calculations were done using computer programs Microsoft Excel version 7 (Microsoft Corporation, NY, USA) and SPSS (Statistical Package for the Social M.E.J. ANESTH 21 (3), 2011 328 Science; SPSS Inc., Chicago, IL, USA) statistical program for Microsoft Windows. Results There were no significant statistical differences regarding the demographic data of patients (table 1). The types of supratentorial brain tumors in patients were similar as in (table 1).The heart rate (table 2 and fig. 1) and mean arterial blood pressure (table 3 and fig. 2) decreased in patients of group A more than in patients of group B with significant statistical difference between the two groups (P<0.05). Two patients of group A and Three patients of group B were received incremental doses of atropine(0.5 mg) and ephedrine (5 mg) as the heart rate decreased below 50 bpm and the mean arterial blood pressure decreased below 60mmHg (table 4). One patients of group A and four patients of group B were associated with elevated heart rate and mean arterial blood pressure and controlled by incremental doses of fentanyl and esmolol in addition to nitroglycerine infusion after opening of the dura matter (table 4). The central venous pressure decreased in patients of both groups, but there was no significant statistical difference between the two groups (table 5and figure 3). There was no significant statistical difference between the two groups regarding the arterial partial pressure of Carbon Dioxide (table 6 and fig. 4). The intracranial pressure decreased in patients of group A more than group B with significant statistical difference between the two groups (table 7 and fig. 5). The Glasgow coma scale (GCS) improved in patients of group A and deteriorated in patients of group B with significant statistical difference (P<0.05) between the two groups (table 8 and fig. 6). During extubation the conscious level was not fine in one patient of group A and four patients of group B. There was no significant statistical difference between the two groups regarding duration of the surgical procedures. Regarding the end-tidal sevoflurane % (table 9), there was significant statistical difference between the two groups (P<0.05). The total fentanyl requirements from induction to extubation of patients increased in patients of group B to control the elevated heart rate and arterial blood pressure more than in patients of group A with significant statistical difference (P<0.05) between the two groups (table 9). The total postoperative patients R. N. Soliman et. al requirements for antiemetic drugs (metoclopramide and ondansetron) within the 2 hours after extubation decreased in patients of group A more than group B with significant statistical difference (P<0.05) between the two groups (table 89). The postoperative duration from the end of surgery to extubation (table 9) decreased significantly in patients of group A more than group B with significant statistical difference between the two groups (P-value <0.05). The total urine output during the duration from drug administration to extubation of patients increased in patients of group A more than group B with significant statistical difference between the two groups (table 9). Table 1 Demographic data and types of supratentorial brain tumors in patients. Values are expressed as mean (SD) or % Item Group A ( n= 20) Group B ( n= 20) P-value Age ( year) 47.10 (13.345 ) 44.00 (14.220 ) 0.579 Weight (kg) 82.10 (11.229 ) 82.80 (12.007 ) 0.912 Sex (Male/Female) 9/11 12/8 40 30 Meningioma 40 45 Astrocytoma 20 25 Glioma Group A: Dexmedetomidine group and Group B: Placebo group. Table 2 Heart rate (bpm) in patients. Values are expressed as mean (SD) Item Group A (n = 20) Group B (n = 20) P-value T0 94.90 (6.887) 91.90 (5.859) 0.315 T1 T2 T3 T4 83.80 (5.453)† 73.60 (3.893)† 73.40 (3.777)† 73.40 (3.098)† 92.80 (2.616)+ 91.50 (4.116)+ 90.60 (5.016)+ 90.30 (4.228)+ 0.001* 0.000* 0.000* 0.000* T5 73.60 (2.797)† 89.10 (5.493)+ 0.000* † + T6 73.20 (2.530) 88.80 (6.494) 0.000* Group A: Dexmedetomidine group and Group B: Placebo group. T0: The reading before administration of the study medication. T1: The reading after induction of anaesthesia. T2: The reading 2 hours after administration of study medication.T3: The reading at the end of surgery.T4: The reading on admission to the ICU.T5: The reading before extubation. T6: The reading 2 hours after extubation. * Statistically significant (P-value < 0.05) Group A versus Group B. † P<0.0.05 versus baseline. + Statistically insignificant (P-value >0.05). PROSPECTIVE, RANDOMIZED STUDY TO ASSESS THE ROLE OF DEXMEDETOMIDINE IN PATIENTS WITH SUPRATENTORIAL TUMORS UNDERGOING CRANIOTOMY UNDER GENERAL ANAESTHESIA Fig. 2 The mean arterial blood pressure (mmHg) of patients in the two groups Fig. 1 The heart rate of patients in the two groups Mean arterial blood pressure of patients Group A Group B T0 T1 T2 T3 T4 T5 T6 Mean arterial blood pressure of patients ( mmHg ) Heart rate of patients ( bpm ) Heart rate of patients 100.00 90.00 80.00 70.00 60.00 50.00 40.00 30.00 20.00 10.00 0.00 Timepoints ( hours ) Table 3 Mean arterial blood pressure (mmHg) of patients. Values are expressed as mean (SD) Group A Group B (n = 20) (n = 20) T0 94.70 (8.957) 93.90 (8.863) 0.739 T1 90.30 (8.795) 99.70 (7.790) 0.019* T2 86.90 (7.564)† 96.80 (5.692)+ 0.003* T3 85.00 (6.549)† 96.10 (5.195)+ 0.001* T4 85.30 (5.889)† 94.00 (4.137)+ 0.002* T5 84.00 (6.037)† 84.00 (6.037)† 0.000* T6 83.00 (4.243)† 92.60 (3.950)+ 0.000* P-value Group A: Dexmedetomidine group and Group B: Placebo group. T0: The reading before administration of the study medication. T1: The reading after induction of anaesthesia. T2: The reading 2 hours after administration of study medication.T3: The reading at the end of surgery.T4: The reading on admission to the ICU.T5: The reading before extubation. T6: The reading 2 hours after extubation. * Statistically significant (P-value < 0.05) Group A versus Group B. † P<0.0.05 versus baseline. + Statistically insignificant (P-value >0.05). Item HR<50bpm MAP<60 mmHg HR>100bpm 120.00 100.00 80.00 Group A 60.00 Group B 40.00 20.00 0.00 T0 T0: baseline, T1: after induction, T2: 2 hours after administration of study medication, T3: at the end of surgery, T4: on admission to the ICU, T5: before extubation and T6: 2 hours after extubation. Group A: Dexmedetomidine group and Group B: Control group. Item 329 T1 T2 T3 T4 T5 T6 Timepoints ( hours ) T0: The reading before administration of the study medication. T1: The reading after induction of anaesthesia. T2: The reading 2 hours after administration of study medication.T3: The reading at the end of surgery.T4: The reading on admission to the ICU. T5: The reading before extubation. T6: The reading 2 hours after extubation. Group A: Dexmedetomidine group and Group B: Placebo group. Table 5 Central venous pressure (mmHg) of patients. Values are expressed as mean (SD) Item Group A Group B P-value (n = 20) (n = 20) T0 13.00 (1.155) 13.10 (1.197) 0.853 T1 12.40 (0.966) 1 2.50 (1.080) 0.796+ T2 9.90 (0.876) 10.30 (1.160) 0.481+ T3 9.00 (0.812) 9.80 (0.919) 0.075+ T4 8.80 (0.915) 9.60 (0.966) 0.105+ T5 9.50 (0.962) 9.30 (0.823) 0.684+ T6 9.00 (0.972) 9.00 (0.816) 1.000+ Group A: Dexmedetomidine group and Group B: Placebo group. T0: The reading before administration of the study medication. T1: The reading after induction of anaesthesia. T2: The reading 2 hours after administration of study medication.T3: The reading at the end of surgery.T4: The reading on admission to the ICU.T5: The reading before extubation. T6: The reading 2 hours after extubation. + Statistically insignificant (P-value >0.05). Table 4 Intraoperative drugs for haemodynamic disturbances Management Group A (n = 20) Group B (n = 20) 2 patients 3 patients Atropine 0.5 mg (Incremental doses) 2 patients 3 patients Ephedrine 5-10mg (Incremental doses) 1 patients 4 patients - Esmolol 0.mg/kg (Incremental doses) or infusion 50-200 μg /kg/ min if needed - Fentanyl 50-100μg(Incremental doses) MAP>100 mmHg 1 patients 4 patients - Nitroglycerine0/5-10 μg /kg/min after opening of dura matter or - Fentanyl 50-100μg(Incremental doses) Group A: Dexmedetomidine group and Group B: Placebo group. HR: Heart rate MAP: mean arterial blood pressure. M.E.J. ANESTH 21 (3), 2011 R. N. Soliman et. al Fig. 3 The central venous pressure (mmHg) of patients in the two groups Fig. 4 The arterial partial Pressure of Carbon Dioxide PaCO2 (mmHg) of patients in the two groups Central venous pressure of patients Arterial partial pressure of Carbon dioxide ( PaCO2 ) of patients 14.00 12.00 10.00 8.00 Group A 6.00 Group B 4.00 2.00 0.00 T0 T1 T2 T3 T4 T5 Arterial partial pressure of CO2 (mmHg ) Central venous pressure of patients ( mmHg ) 330 37.00 36.00 35.00 34.00 Group A 33.00 Group B 32.00 31.00 30.00 29.00 T0 T6 T1 T2 T0: The reading before administration of the study medication. T1: The reading after induction of anaesthesia. T2: The reading 2 hours after administration of study medication.T3: The reading at the end of surgery.T4: The reading on admission to the ICU. T5: The reading before extubation. T6: The reading 2 hours after extubation. Group A: Dexmedetomidine group and Group B: Placebo group. Table 6 Arterial partial Pressure of Carbon Dioxide PaCO2 (mmHg) of patients. Values are expressed as mean (SD) Item Group A Group B (n = 20) (n = 20) T3 T4 T5 T6 Timepoints ( hours ) Timepoints ( hours ) P-value T0: The reading before administration of the study medication. T1: The reading after induction of anaesthesia. T2: The reading 2 hours after administration of study medication. T3: The reading at the end of surgery. T4: The reading on admission to the ICU. T5: The reading before extubation. T6: The reading 2 hours after extubation. Group A: Dexmedetomidine group and Group B: Placebo group. Table 7 Intracranial pressure (mmHg) of patients. Values are expressed as mean (SD) Item Group A Group B (n = 20) (n = 20) P-value T0 22.30 (3.057) 22.10 (2.807) 0.739 T1 20.70 (2.669) 21.20 (2.300) 0.019 T0 35.80 (3.910) 35.50 (3.894) 0.315 T2 15.60 (1.578) † 18.90 (1.792) 0.003* T1 31.80 (1.687) 31.90 (1.595) 0.143+ T3 13.30 (1.636)† 17.30 (1.767) 0.001* T2 32.80 (1.676) 33.10 (1.197) 0.089+ T4 12.40 (1.265)† 16.40 (1.897)† 0.002* T3 34.90 (1.197) 34.80 (0.789) 0.912+ T5 11.80 (0.919)† 15.70 (1.636)† 0.000* T4 34.90 (2.601) 35.50 (1.354) 0.529+ T6 10.80 (1.135)† 15.10 (1.792)† 0.000* T5 36.50 (0.994) 36.30 (1.160) 0.579+ T6 35.60 (1.265) 36.10 (1.663) 0.435+ Group A = Dexmedetomidine group and Group B = Control group. T0: The reading before administration of the study medication. T1: The reading after induction of anaesthesia. T2: The reading 2 hours after administration of study medication.T3: The reading at the end of surgery.T4: The reading on admission to the ICU.T5: The reading before extubation. T6: The reading 2 hours after extubation. + Statistically insignificant (P-value >0.05). Group A: Dexmedetomidine group and Group B: Placebo group. T0: The reading before administration of the study medication. T1: The reading after induction of anaesthesia. T2: The reading 2 hours after administration of study medication.T3: The reading at the end of surgery.T4: The reading on admission to the ICU. T5: The reading before extubation. T6: The reading 2 hours after extubation. + Statistically insignificant (P-value >0.05). * Statistically significant (P-value <0.05) Group A versus Group B. † P<0.0.05 versus baseline. PROSPECTIVE, RANDOMIZED STUDY TO ASSESS THE ROLE OF DEXMEDETOMIDINE IN PATIENTS WITH SUPRATENTORIAL TUMORS UNDERGOING CRANIOTOMY UNDER GENERAL ANAESTHESIA Fig. 5 The intracranial pressure (mmHg) of patients in the two groups Intracranial pressure of patients ( mmHg ) 25.00 20.00 15.00 Group A 10.00 Group B 5.00 0.00 T0 T1 T2 T3 T4 T5 T6 Timepoints ( hours ) T0: The reading before administration of the study medication. T1: The reading after induction of anaesthesia. T2: The reading 2 hours after administration of study medication.T3: The reading at the end of surgery.T4: The reading on admission to the ICU. T5: The reading before extubation. T6: The reading 2 hours after extubation. Group A: Dexmedetomidine group and Group B: Placebo group. Table 8 Glasgow coma scale (GCS) of patients. Values are expressed as mean (SD) Timepoints Group A (n = 20) Group B (n = 20) P-value T0 12.10 (1.69) 12.20 (1.73) 1.000 T6 13.40 (1.31) 11.60 (1.34) 0.011* Group A: Dexmedetomidine group and Group B: Placebo group. T0: Glasgow coma scale before administration of the study medication and T6: Glasgow coma scale 2 hours after extubation. * Statistically significant (P-value <0.05) Group A versus Group B. Fig. 6 Glasgow coma scale (GCS) of patients in the two groups Glasgow coma score ( GCS ) of patients Glasgow coma score / 15 14.00 13.50 13.00 12.50 Group A 12.00 Group B 11.50 11.00 10.50 GCS before surgery Table 9 Intraoperative and postoperative data. Values are expressed as mean (SD) or % Item Intracranial pressure ( ICP ) of patients GCS after surgery Timepoints T0: Glasgow coma scale before administration of the study medication and T6: Glasgow coma scale 2 hours after extubation. Group A: Dexmedetomidine group and Group B: Placebo group. 331 Group A (n = 20) Group B (n = 20) P-value Surgical duration 239.3 (79.25) 236.1 0.1+ (min) (82.51) End-tidal 1.18 (0.209) 2.18 0.001* sevoflurane (%) (0.477) Total fentanyl doses 440.00 602.00 0.000* (µg) (42.164) (72.847) Patients' 50.0% 100.0% 0.016* metoclopramide requirement % Patients' 30.0% 80.0% 0.035* ondansetron requirement % Duration before 41.40 (6.310) 87.00 0.001* extubation (min) (16.533) Total fentanyl doses 440.00 602.00 0.000* (42.164) (72.847) Group A: Dexmedetomidine group and Group B: Placebo group. * Statistically significant (P-value <0.05) Group A versus Group B. + Statistically insignificant (P-value >0.05). Discussion The concept of neuroanaesthesia includes several principles, the haemodynamic stability perioperatively being one of utmost importance. During surgery, abrupt increases in arterial blood pressure may cause bleeding or edema in the operating field. Low arterial pressures on the other hand predispose the patients to cerebral ischaemia, because autoregulation of the cerebral blood flow (CBF) is often impaired near tumors or traumatized areas1. High concentrations of volatile anaesthetics can blunt the carbon dioxide response and render CBF pressure passively16. The haemodynamic responses to intracranial surgery are most often elicited at the beginning or the end of the procedure. Similarly, the manipulation of certain structures within the brain may produce cardiovascular changes. After surgery, hypertension may predispose the patient to postoperative intracranial haematoma1. Dexmedetomidine is a highly selective α2agonist that has been shown to have sedative, analgesic and anaesthetic sparing effects17-22. We investigated the effects of dexmedetomidine in neurosurgical patients in an attempt to find a clinically feasible combination of anaesthetics that M.E.J. ANESTH 21 (3), 2011 332 would ensure perioperative haemodynamic stability and fast recovery without respiratory depression. Such combination would reduce the required volatile anaesthetics, narcotics, sedatives and decrease the risk of affecting cerebral autoregulation. The present study showed that the dexmedetomidine significantly attenuated the haemodynamic responses to laryngoscopy, intubation, Mayfield three-pin head holder application surgical stimulation and extubation in patients undergoing supratentorial surgery and to control the haemodynamic responses in patients of the control group, higher doses of sevoflurane, fentanyl and esmolol were used before opening of the dura in addition to nitroglycerine after opening of the dura. In some earlier studies, oral clonidine (Alpha2-agent) premedication provided attenuation of the hypertensive response to laryngoscopy, intubation and head holder application in patients undergoing supratentorial surgery23,24. In patients undergoing general or gynaecological surgery, numerous studies have shown that dexmedetomidine blunts the cardiovascular responses to intubation25-27. Other studies shown that the haemodynamic responses to emergence from anaesthesia and extubation are blunted with dexmedetomidine28,29, and the centrally mediated sympatholytic effect has continued well into the postoperative period28. The intracranial pressure decreased significantly with dexmedetomidine group than in patients of the control group as the concentration of sevoflurane decreased and urine output increased in spite of fixed doses of diuretics. Many studies were done by to evaluate the effect of dexmedetomidine on the intracranial pressure and concluded that the dexmedetomidine decreased the intracranial pressure by the inhibition of the hypercapnic cerebral vasodilation30, and its potent venous vasoconstriction31. The extubation was happened more quickly in patient of group A and was R. N. Soliman et. al statistically significant in comparison to the patients in the group B. It may, however, reflect the lack of respiratory depression of dexmedetomidine and the uses of low doses of sevoflurane and fentanyl32. Dexmedetomidine has been shown to have minimal effects on respiration33,34, and ventilatory weaning and tracheal extubation has been successfully carried out in critically ill patients under continuing dexmedetomidine sedation35. The dose of fentanyl decreased significantly in group A in comparison to group B. A study done by Arain SR et al and Venn RM, et al who concluded that dexmedetomidine has been shown to consistently reduce opioid requirements by 30 to 50%36,37. The requirement for antiemetic drugs decreased in the group A as the doses of fentanyl and sevoflurane were decreased in comparison to the group B or due to the decreased intracranial pressure. A study done by Scott F et al involving patients undergoing abdominal hysterectomy and concluded that postoperative nausea was reduced by 77.5% when dexmedetomidine was employed as an intraoperative anesthetic adjuvant38. The amount of urine increased significantly in group A and this one of the factors that leads to decrease in the ICP. Many studies were done and showed that the dexmedetomidine seems to induce diuresis by ability to reduce efferent sympathetic outflow of the renal nerve39, in addition, dexmedetomidine has been shown to suppress antidiuretic hormone, with a resulting diuretic effect40, and finally, dexmedetomidine increases secretion of atrial natriuretic peptide, resulting in natriuresis41. Acknowledgements All anesthetists have the authority to read the paper. PROSPECTIVE, RANDOMIZED STUDY TO ASSESS THE ROLE OF DEXMEDETOMIDINE IN PATIENTS WITH SUPRATENTORIAL TUMORS UNDERGOING CRANIOTOMY UNDER GENERAL ANAESTHESIA 333 References 1. 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McPherson, R: Jack Cassingham, Intraoperative Dexmedetomidine Administration Reduces Postoperative Nausea and Vomiting. American Society Of Anesthesiologists; October 2007, 13-17. 39.Xu H, Aibiki M, Seki K, Ogura S, Ogli K: Effects of dexmedetomidine, an α2- adrenoceptor agonist, on renal sympathetic nerve activity, blood pressure, heart rate and central venous pressure in urethane- R. N. Soliman et. al anesthetized rabbits. J Auton Nerv Syst; 1998, 72:48-54. 40.Gellai M: Modulation of vasopressin antidiuretic action by renal α 2 -receptors. Am J Physiol; 1990, 259:F1-F8. 41.Menegaz RG, Kapusta DR, Mauad H, de Melo Cabral A: Activation of α2- adrenoreceptors in the rostral ventrolateral medulla evokes natriuresis by arenal nerve mechanism. Am J Physiol; 2001, 218:R98-R101. ANESTHETIC CHALLENGES IN ORO-FACIAL CLEFT REPAIR IN ILE-IFE, Nigeria Anthony Taiwo Adenekan*, Aramide Folayemi Faponle**, Fadekemi Olufunmilayo Oginni*** Abstract Background and Methods: A retrospective review of all patients with oro-facial lip defects operated at the Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria over an 18 month period was undertaken with a view to determine: the pattern of presentation; associated clinical problems and congenital anomalies; perioperative complications; anaesthetic techniques used and outcomes; and the determinants of outcome. Results: Of the 80 patients treated, 74 were managed under general anaesthesia but the case records of only 60 (81%) of these patients were available for review. The ages ranged between 3 months and 59 years. The male to female ratio was 1:1. Eighty percent of all cases studied were cleft lip (CL) ± cleft palate (CP). Of these, 65% were left sided CL, 23% were right sided while 12% were bilateral. All patients had ASA score 1 or 2 at the time of surgery. Halothane in O2 induction was employed in 60% of the patients while 40% had IV induction. Intubation was facilitated with muscle relaxant in 63.3% of these patients. Naso-tracheal intubation was performed in 82% of all cleft palate repairs. Preoperative complications were encountered in 18% of the patients. Associated congenital anomalies were noted in 5% of the cases. One case each of difficult intubation and failed intubation were encountered. Intra-operative dysrrhythmia was noted in 5% of cases; no life-threatening complication was encountered peri-operatively. Conclusions: There is a dramatic increase in the number of patients presenting for care due to improved awareness of the population. Peri-operative attention to detail is essential in handling the challenges posed by the condition. Introduction Oro-facial cleft is a common congenital deformity with a worldwide incidence of 1 in 7-800 live births1. The actual aetiology is largely unknown2. Oro-facial cleft is associated with facial disfigurement, feeding difficulty, and speech and dental development problems. It is accompanied with significant psychosocial consequences. However, patients with oro-facial cleft can achieve their ultimate potential through aesthetic and functional treatment. In recent times, surgical treatment of patients with oro-facial cleft has been facilitated by the SmileTrain, USA globally. This has led to an increasing number of patients presenting for care in Nigeria. * ** *** MBBS, DA, FWACS, Consultant, Dept. of Anaesthesia. BSc, MBChB, FWACS, FMCA, Consultant, Dept. of Anaesthesia. BChD, FMCDS, FWACS, Consultant, Dept. of Oral and Maxillofacial Surgery. Correspondence to: Dr. A.T. Adenekan, Department of Anaesthesia, Obafemi Awolowo University, Ile-Ife, Nigeria. Tel: +2348033855903, E-mail: [email protected] 335 M.E.J. ANESTH 21 (3), 2011 336 A. T. Adenekan et al. The occurrence of these congenital defects in Nigeria has been documented by previous reports3,4. Orofacial cleft can be repaired within the first year of life. In limited resourced economies, many of the patients present much later probably due to ignorance, poverty, and limited available material and human resources5,6. However, little is known about the anaesthetic challenges in oro-facial cleft repair in Nigeria. of attempts, intubation aids, outcome and analgesic used were noted. Details of intraoperative monitoring, critical incidents, recovery room complications, and postoperative complications were documented. Data were analysed using SPSS version 12.0.1 and summarized into tables and relationships tested using the Chi-square test at 5% level of significance. This study was undertaken to assess: the pattern of presentation of oro-facial cleft; associated clinical problems and congenital anomalies; perioperative complications; anaesthetic techniques used and outcomes; and the determinants of outcome. Results Method A retrospective review of anaesthesia for all orofacial cleft repairs performed over an 18 month period (between January 2006 to June 2007) at the Obafemi Awolowo University Teaching Hospital, Ile-Ife, was undertaken. The hospital is a tertiary health facility located in South-western Nigeria with referral from over 200 kilometres radius. The theatre records were reviewed to identify all cases of oro-facial clefts operated during the period. The case records of the patients identified were then reviewed. The data retrieved include demographic details of the patients, diagnosis (including the type of cleft, medical diagnosis, additional craniofacial deformities), proposed surgery, preoperative packed cell volume (PCV), pre-induction vital signs, premedication used, anaesthetic technique, induction technique and relaxant use for intubation. Also, the intubation route, number Eighty patients were treated during the study period. They were all Nigerians residing in Ile-Ife and its environs. Of these, seventy four patients (92.5%) were managed under general anaesthesia (GA) while the rest (7.5%) were operated under local anaesthesia (LA). However, the case records of only sixty patients (81%) managed under GA were available for review at the time of this study. Table 1 shows the age distribution of the patients. The ages ranged between 3 months and 59 years with a mean of 10.08 ± 11.60 years. Majority (86.7%) of the patients presented after the first year of life, while 7 patients (11.7%) presented after the age of 20 years. No gender predilection was observed. Table 1 Age and Gender Distribution of Patients Age 1-4 Months 5-12 Months 1-10 Years 10-20 Years >20 Years Total Male No (%) Female No (%) No of Pts No (%) % 3 2 19 3 3 30 0 3 14 9 4 30 3 (5.0) 5 33 12 7 60 5.0 8.3 55.0 20.0 11.7 100.0 Table 2 Cleft Deformity type by Gender Type of Cleft Gender Side Male No (%) Female No (%) Right No (%) Left No (%) Total (%) Cleft lip only 17 (54.8) 14 (45.2) 7 (22.6) 24 (77.4) 31 (51.7) Cleft lip and palate 7 (63.6) 4 (36.4) 4 (36.4) 7 (63.6) 11 (18.3) Cleft palate alone 6 (54.5) 5 (45.5) - - 11 (18.3) - 1 - - 1 (1.7) Bilateral Transverse Bilateral cleft Lip Total - 6 - - 6 (10) 30 (50%) 30 (50%) 11(26.2%) 31(73.8%) 60 (100) ANESTHETIC CHALLENGES IN ORO-FACIAL CLEFT REPAIR IN ILE-IFE, Nigeria Type of defect by gender in this series is shown in Table 2. Isolated cleft lip, isolated cleft palate and combined cleft lip and palate were commoner in males than females (17: 14, 7:4, and 6:5 respectively). Bilateral cleft lip (n = 6) and bilateral transverse cleft lip (n = 1) observed in this series were exclusively in females. However, the difference observed is not statistically significant (p = 0.43). The PCV ranged from 26-44% and mean was 32.78 ± 3.76%. Table 3 shows the pattern of distribution of medical complications among the patients. Preoperative complications were noted in 18% of cases (n = 11). Anaemia was the commonest, occurring in 11.7% (n = 7). One 6 month old child with cleft lip had severe anaemia and was transfused before presentation for anaesthesia. Others were under-nutrition (5%, n = 3), delayed developmental milestone with growth retardation (1.7%, n = 1), upper respiratory tract infection (1.7%, n = 1) and chronic suppurative otitis media (1.7%, n = 1). Besides the cleft palate patient with chronic suppurative otitis media and another with anaemia, the remaining patients (n = 9) were cases of cleft lip with or without associated cleft palate. However, there was no statistically significant relationship between the type of oro-facial cleft and medical complications (p = 0.88). Table 3 Distribution of medical complications among oro-facial cleft patients Clinical complications Cleft lip ± Cleft cleft palate palate Anaemia 3 1 Anaemia + Transfused before surgery 1 - Anaemia + Severe undernutrition 2 - Under-nutrition 1 - Delayed dev milestone + growth retardation 1 - Upper Respiratory Tract Infection 1 - Chronic suppurative otitis media - 1 Nil 41 8 Total 50 10 337 Three patients (5%) had associated congenital abnormalities. Two of these (3.4%) were craniofacial abnormalities while one (1.7%) was cardiovascular. One of the patients with craniofacial abnormalities had Wolf-Hirschhorn syndrome7 (- a one year old girl with a combination of microcephaly, low set ears, hypertelorism, growth retardation, delayed developmental mile stones in addition to a right complete cleft lip and incomplete cleft palate). The other was a case of complete cleft palate with lower lip pits. The third patient had congenital cardiac disease (membranous ventricular septal defect) with left complete cleft lip. All patients were either ASA physical status-1 (77%) or ASA-2 (23%) at the time of surgery. Eighty five percent had IV atropine premedication to dry their airway; six (10%) patients who had intravenous induction with ketamine also had IV diazepam premedication in addition. Induction with halothane in oxygen was employed in 60% of the patients while 40% had intravenous induction (thiopentone or ketamine). All cases had endotracheal intubation with halothane ± N2O in O2 for maintenance. Intubation was facilitated with muscle relaxant (suxamethonium) in 63.3% of these patients. Naso-tracheal intubation was performed in 18% of all cases (but 82% of all cleft palate repairs). Respiration was assisted in all patients less than 2 years old. Ketamine anaesthesia either in form of intermittent boluses or total intravenous anaesthesia was not employed in this case series. One case of difficult intubation was noted in a 5-month old boy with cleft lip. After multiple unsuccessful attempts during the initial presentation, he was rescheduled and successfully intubated at representation for anaesthesia and surgery two weeks later. Failed intubation occurred in one patient. This was in the child with Wolf-Hirschhorn syndrome. The patient has not been represented for anaesthesia as at the time of this review. Intraoperative dysrrhythmia was noted in three (5%) of the patients. Delayed recovery was experienced in 2 (3.4%) cases. These patients were induced with ketamine. Postoperative complications noted were palatal fistula in one patient and palatal fistula with bifid uvula in another. There was no perioperative mortality. M.E.J. ANESTH 21 (3), 2011 338 Discussion In this review, 80 patients were treated over a 1½ year period. An earlier report from the same centre 12 years ago8 reported an average of 7 patients presenting over 18 months or 4.4 patients per year (57 cases over 13 years period). The current report represents over 1000% increase in the number of patients presenting for care in about 1 decade. In contrast with earlier reports4,8 majority (86.7%) of the patients in this series presented after the first year of life. This is particularly unlike the findings of Ugboko et al8 where 90% of the patients presented within the first year of life while only 1.7% reported in adulthood. The pattern of presentation observed in this study suggests positive attitude towards oro-facial cleft surgeries. There was equal number of male and female in this review in agreement with earlier reports including that of Sullivan among black patients in the United States2,9. It however differs from the findings in some other Nigerian studies5,10 which showed female preponderance and others8,11,12 which showed male preponderance. Anaemia was the commonest preoperative complications noted in this series (11.7%). Undernutrition (5%) and growth retardation with delayed developmental milestones (1.7%) were also observed. These are usually due to feeding problems. Cleft lip defect interferes with lip closure and sucking while cleft palate patients have swallowing difficulties. Repeated infections could also be contributory and these complications can be prevented by early presentation and repair of the defects13. Chronic rhinorrhoea is common in oro-facial cleft and patients may present with recurrent upper respiratory tract infection (URTI). Surgical repair reduces rhinorrhoea and URTI. Therefore, the risks of anaesthesia and adverse respiratory events should be individually balanced against the benefits of the surgery14. URTI was noted in 1.7% of the patients but no adverse respiratory event was observed. Atropine premedication can be administered to dry the airway particularly when difficult intubation is anticipated or ketamine induction is to be used. Difficult laryngoscopy occurs in up to 10% of patients with oro-facial cleft and the incidence rises in those with A. T. Adenekan et al. associated syndrome15. The incidence of associated abnormalities with or without recognized syndrome is quoted to be 10-60%16. Craniofacial abnormalities are the most common and these may affect intubation outcome. The only case of failed intubation encountered was in the child with Wolf-Hirschhorn syndrome. It is hoped that intubation outcome will be good during representation at which time the child would have been older. Congenital cardiac disease occurs in 5-10% of patients with oro-facial cleft16. One (1.6%) of the patients in this series had ventricular septal defect. The anaesthesia was however uneventful. Naso-tracheal intubation was used in 82% of all cleft palate repairs in this series. This reflects the surgeons’ preference as against oro-tracheal intubation which is often used. Besides providing greater access to the mouth, the risk of kinking of endotracheal tube following application mouth gag is removed. The risk of inadvertent extubation or endobronchial intubation may also be less with this route. However, naso-tracheal intubation requires greater expertise and is associated with the risk of damage to nasal mucosa and bleeding. Disruption of palatal repair during extubation may also be a remote complication. The possible role of this technique in the two cases of postoperative palatal fistula observed out of 15 cases of palatoplasty in this series cannot be established. Intraoperative dysrrhythmia was noted in three (5%) of the patients. Possible causes include inadequate depth of anaesthesia, hypercapnia and halothane in the presence of cathecolamines. The risk of dysrrhythmia is much lower with the use of isoflurane, enflurane, or desflurane. However, halothane because of its affordability remains the primary inhalational anaesthetics in Nigeria. Delayed recovery was experienced in 2 patients (3.3%). This might be related to diazepam premedication and ketamine induction used in these cases. Conclusion There has been a dramatic increase in the number of patients presenting for care particularly adults. Increased support from donor organizations and training of appropriate manpower will help to clear the backlog of patients with oro-facial cleft. ANESTHETIC CHALLENGES IN ORO-FACIAL CLEFT REPAIR IN ILE-IFE, Nigeria Early presentation and repair may help in reducing the incidence of preoperative complications. Airway management challenges are not uncommon; however, anaesthesia for oro-facial cleft repair can be given 339 relatively safely in developing countries with attention to detail and the careful use of available facilities and anaesthetic agents. References 1.Hatch DJ: Airway management in cleft lip and palate. Br J Anaesth; 1996, 76:755-756. 2.Omovie EE, Shepherd JP: Cleft lip and Palate. Africa Health; 1994, 22-24. 3.Akpata O, Ojo MA, Eroje BM and Ohre O: Congenital Cleft lip, cleft palate and lip fistulae (Van Der Woude Syndrome) in two Nigerian families. The Saudi Dental Journal; 1995, 7:40-44. 4.Iregbulem LM: The incidence of cleft lip and palate in Nigeria. Cleft Palate J; 1982, 19:201-204. 5.Olasoji HO, Dogo D, Obiano SK and Yawe T: Cleft lip and Palate in North Eastern Nigeria. Nig Ot J Hosp Med; 1997, 7:209-213. 6.Paul AM, Spauwen PHM, Spronk CA and Niemeijer RPE: Cleft lip and palate treatment in Bangladesh. European Journal of Plastic Surgery; 2007, 29 (6):267-270. 7.Butler MG, Hayes BG, Hathaway MM and Begleiter ML: Specific Genetic Diseases at Risk for Sedation/Anesthesia Complications. Anesth Analg; 2000, 91:837-855. 8.Ugboko V, Owotade F, Otuyemi O and Adejuyigbe O: experience with cleft lip and palate patients seen in a Nigerian Teaching Hospital. Paediatric dental Journal; 1997, 7:41-44. 9.Sullivan WG: Cleft lip with and without cleft palate in Black. An analysis of 81 patients. Plast Reconstr Surg; 1989, 84:406-408. 10.Adekeye EO: Occurrence of cleft lip and palate in Kaduna. Nigerian Dental Journal; 1982, 3(1):19-25. 11.DeMey A, Vadoud-Seyedi J, Demol F and Govaerts M: Early postoperative complications in primary cleft lip and palate surgery. Eur J Plast Surg; 1997, 20:77-79. 12.Calnan JS: Recent Advances in surgery. 6th Edition. Ed Swelyn Taylor pg 356. J and A Churchill London, 1964. 13.Tung MK, Yau CK, Lau DWC, Kwock CL, Mak ASY and Lui WWK: Cleft lip and palate management. J Hong Kong Med Assoc; 1994, 46(4):274-281. 14.Kotur PF: Surgical repair of cleft lip and palate in children with upper respiratory tract infection. Indian J Anaesth; 2006, 50(1):5859. 15.Gunawardana RH: Difficult laryngoscopy in cleft lip and palate surgery. Br J Anaest; 1996, 76:757-759. 16.Rawlinson E: Anaesthesia for cleft lip and palate. Update in Anaesthesia; 2002, 14:27-30. M.E.J. ANESTH 21 (3), 2011 COMPARISON BETWEEN ROPIVACAINE 1,5 MG ML -1 PLUS FENTANYL 2 ΜG ML -1 AND ROPIVACAINE 1,5 MG ML -1 PLUS CLONIDINE 1 ΜG ML -1 AS ANALGESIC SOLUTION AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION: A RANDOMIZED CLINICAL TRIAL * Kalakonas Apostolos, Kotsovolis Georgios, Chalkeidis Omiros and Triantafyllou Christos Abstract Backround: Ropivacaine is commonly used as local anesthetic for postoperative analgesia through an epidural catheter. Data show that several adjuvants influence the analgesic effect of local anesthetic potency. Objective: The aim of the study was to compare fentanyl and clonidine as adjuvants to 1,5 mg ml-1 ropivacaine in terms of motor blockade, pain relief and side effects. Methods: In this single center, randomized, clinical trial, 52 patient scheduled for arthroscopic anterior cruciate ligament reconstruction were radomly allocated in two groups. At twenty-six patient a solution with ropivacaine 1,5 mg ml-1 plus fentanyl 2 μg ml-1 (group F) was administered through patient controlled epidural analgesia (PCEA) as postoperative analgesia and ropivacaine 1,5 mg ml-1 plus clonidine 1 μg ml-1 (group C) was administered at the remaining twenty-six patients. The VAS score, the Bromage scale and total solution consumption were documented and compared between the two groups for 24 hours after the end of the operation. Results: The mean patient control consumption of the solution was higher at group C respect group F (p = 0,007). At the 8th hour after the operation we register a statistical significant difference at the mean VAS score between the two groups (p<0, 05) with clonidine group achieving a higher score. At the 8th and 12th hour clonidine group register a lower Bromage score than fentanyl group (p<0,005 and p = 0,002). Conclusion: Ropivacaine 1,5 mg ml-1 plus fentanyl 2 μg ml-1 administred through PCEA compared with ropivacaine 1,5 mg ml-1 plus clonidine 1 μg ml-1 h guarantee higher quality analgesia after ACL reconstruction. Keywords: Ropivacaine, fentanyl, clonidine, anterior cruciate ligament. Conflict of interest: The study has been supported solely from the departmental sources. * Department of Anaesthesiology 424 Teaching Military Hospital Thessaloniki, Periferiaki Odos N.Eukarpia 56421, Greece. Corresponding Author: Kalakonas Apostolos MD, 424 Teaching Military Hospital Thessaloniki, Periferiaki Odos N.Eukarpia 56421, Greece. Tel: +302310381954, Fax: +302310381010. E-mail: [email protected] 341 M.E.J. ANESTH 21 (3), 2011 342 Introduction Placement of an epidural catheter allows to provide better postoperative analgesia for abdominal and lower extremity surgery respect parenteral opioid administration1. Several studies comparing PCEA over conventional epidural continuous infusion have found several benefits, including better analgesia and superior patient satisfaction2. Ropivacaine and bupivacaine are the most common local anesthetics administrated for epidural anlgesia. Usually adding adjuvants such opioids, a2adrenergic agonist, neostigmine, ketamine reduce side effects of local anesthetics and increase the analgesic propriety of the mixture3. The aim of this study was to compare motor blockade, pain relief, drug consumption and side effects during patient controlled epidural analgesia (PCEA) with ropivacaine 1,5 mg ml-1 plus fentanyl 2 μg ml-1 versus ropivacaine 1,5 mg ml-1 plus clonidine 1 μg ml-1. Methods After thorough explanation of the parameters of the study 52 ASA 1-2 patients agreed to sign the consent form and participate in our study.These patients were scheduled for arthroscopic anterior cruciate ligament (ACL) reconstruction. After the admission of the patient in the operating room, adequate monitoring for each patient was commenced. To all patients 2,8 ml of heavy bupivacaine 5 mg ml-1 was administrated intrathecally for surgical anesthesia. We used a kit of combined spinal epidural anesthesia and an epidural catheter was advanced 3cm into the epidural space for postoperative analgesia. The puncture level was L2-L3 or L3-L4. All the patients were operated by the same surgeon. The epidural infusion was started in the recovery room. Every patient was randomized (sealed and opaque envelopes) in one of the two groups. 26 patients for fentanyl (F) and 26 patients for clonidine (C). The study solution was prepared by an anaesthesia nurse, who was not involved in the treatment of the patients. In group F the epidural mixture consisted of ropivacaine 1,5 mg ml-1 plus 2 μg ml-1 fentanyl and in group C was ropivacaine 1,5 mg ml-1 plus 1 μg ml-1 clonidine. The infusion rate postoperatively was 5ml K. Apostolos et al. h-1 for either solutions regulated by an electronic pump. All the patients were instructed to self administrate epidural bolus doses of 5 ml on demand using the same pump. The lockout interval was 20min. An investigator blinded to the identity of the solution visited every patient 2, 4, 8, 12, 24 hours after the operation. At every visit he examined the motor blockade using the Bromage scale (modified Bromage’s score: 0 = no motor block, 1 = hip blocked, 2 = hip and knee blocked, 3 = hip, knee and ankle blocked) and pain using VAS score. Solution consumption, urination, hypotension, nausea and vomiting were also recorded. If any patient wasn’t content from the analgesic regiment (suffered pain VAS>6) automatically was excluded from the trial and another pain rescue regiment was started additionally. Statistical analysis was performed using the SPSS 15.0. Continuous variable were evaluated with t-test. The Mann-Whitney test was used if data were not normally distributed. A p value less than 0, 05 was considered statistically significant. Results A total of 2 patients were excluded from the statistical analyses. Reasons for withdrawal are presented in Table 1. There were no significant differences between the two groups in the demographic data. (Table 2) Hypotension and vomiting was rare. The first urination timing between the two groups was statistically insignificant too (Table 3). There was a statistical difference at the mean patient control consumption of the solution. The mean patient control consumption of the solution was higher at group C respect group F (p = 0,007) (Table 3). The pump indication during the 24 hours was statistical different except the 4th hour (p<0, 05). In fact at the 2nd hour group F consumed more solution than group C. At the rest measuring hours (8th, 12th, 24th) group C consumed more (Fig. 1). At the 8th hour after the operation we register a statistical significant difference at the mean VAS score between the two groups (p<0, 05) with group C achieving a higher score (Fig. 2). At the 8th and 12th hour group C register a lower Bromage score than group F (p<0,005 and p = 0,002 respectively) (Table 4). COMPARISON BETWEEN ROPIVACAINE 1,5 MG ML -1 PLUS FENTANYL 2 ΜG ML -1 AND ROPIVACAINE 1,5 MG ML -1 PLUS CLONIDINE 1 ΜG ML -1 AS ANALGESIC SOLUTION AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION: A RANDOMIZED CLINICAL TRIAL 2,50 2,00 Group Fentanyl Clonidine Mean VAS score Table 1 Reason for withdrawal Patient group Reason for Comment withdrawal Group F Insufficient Replace with a more dense analgesia epidural solution Group C Technical Epidural catheter problem dislocation 343 1,50 1,00 Table 2 Demographic characteristics Groups Age Weight Height BMI Fentanyl 27,4 (4,28) 85,04 (8,43) 180 (5,66) 26,24 (2,4) Clonidine 28,76 (4,43) 81,88 (7,68) 178,76 (5,87) 25,59 (1,73 0,50 0,00 2 4 8 12 24 Time Values in parentheses indicate standard deviation. * VAS score in Group 1(Fentanyl) different than 2(Clonidine) [p<0,05] Table 3 Patient controlled local anesthetic consumption, time of first urination and cases of hypotension and vomiting Groups Hypotention Vomit PCEA Yes No Yes No 2h 4h 8h 12h 24h No 25 0 25 0 11 6 3 4 1 Clonidine 27,80 (26,22)* 3 22 1 24 6 7 11 1 0 0 - Values in PCEA column indicate the extra mean patientcontrolled local anesthetic consumption in addition to the base dose (5 ml h-1) and values in parentheses indicate standard deviation. - Values in other columns indicate frequency. * Statistical difference between the groups. Fig. 1 Mean pump indication in 24 hours 150,00 Mean Pump indication Group Fentanyl Clonidine 100,00 50,00 2 4 8 12 24 Time * Pump indication in Group 1(Fentanyl) different than 2(Clonidine) [p<0,05] Fig. 2: VAS score of the patients Time Group score Urination Fentanyl 13,40 (14,629) 0 0,00 Table 4 Bromage level of kinetic blockade 2 4 8 12 24 F/C F/C F/C F/C F/C 0 3/2 4/7 4/18 12/21 22/25 1 11/6 14/11 16/4 10/4 0/0 2 11/17 7/7 5/3 3/0 3/0 3 0/0 0/0 0/0 0/0 0/0 Discussion Epidural analgesia is more effective for postoperative pain relief respect other regiments4. But pain relief isn’t the only goal for a successful postoperative outcome. Other variants such as early mobilization and fewer side effects from the analgesic regiment are some aspects. With this study we compare two analgesic solutions trying to achieve excellent pain relief without any motor blockade and no side effects. Ropivacaine is an amide local anesthetic with a high pKa (8.1). At the same concentration ropivacaine produce less motor block than bupivacaine5. Opioids used epidurally, and especially fentanyl, as adjuvant to local anesthetics reduce the dose and side effects of both drugs and achieve better analgesia. Opioids mediate their analgesic effect by acting at their receptors in the substantia gelatinosa of the spinal cord6,7. These results have been underlined by Berti et al where a combination of ropivacaine and opioid were M.E.J. ANESTH 21 (3), 2011 344 K. Apostolos et al. administered epiduraly for postoperative analgesia after anterior cruciate ligament repair8. ml-1 fentanyl as adjuvant in epidural solutions seems to be free of side effects too18,19,20. Clonidine is another drug that is frequently used as adjuvant to local anesthetics for epidural analgesia and significantly enhances the duration of analgesia of epidurally administered ropivacaine9. This α2 agonist mediates its analgesic effect by activating postsynaptic α2 receptors in the gelatinous substance of the spinal cord, mimicking the activation of descending inhibitory pathways10,11,12. De Kock et al have used clonidine as the sole agent administrated epidurally for postoperative analgesia13. We register a higher consume from Group C than Group F. Sides effects at both groups were statistically insignificant. Patient comfort was higher at Group F than Group C if we evaluate the VAS score. Even if at Group C the legs sensibility and mobility return earlier the greatest patient’s fear is pain. There are no similar studies with such low ropivacaine concetration after ACL reconstruction operation in order to compare the postoperative analgesia and patient comfort. Several studies had already proposed different concentration for epidural ropivacaine. When used alone 2 mg ml-1 seems to be the optimal concentration14,15,16. But sometimes with excessive motor block. Although Tetsuya et al propose 0.5 mg ml-1 as the favorable concentration in order to reduce local anesthetics side effect, in our study we conclude that even in higher concentration up to 1,5 mg ml-1 ropivacaine was also free of side effects17. Concentration of 1 μg ml-1 clonidine and 2 μg In conclusion, we consider that ropivacaine 1,5 mg ml-1 plus fentanyl 2 μg ml-1 administred through PCEA is safe, without side effects and can provide excellent postoperative analgesia after ACL reconstruction. Acknowledgement The study has been supported solely from departmental sources. COMPARISON BETWEEN ROPIVACAINE 1,5 MG ML -1 PLUS FENTANYL 2 ΜG ML -1 AND ROPIVACAINE 1,5 MG ML -1 PLUS CLONIDINE 1 ΜG ML -1 AS ANALGESIC SOLUTION AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION: A RANDOMIZED CLINICAL TRIAL 345 References 1. Block BM, Liu SS,Rowlingson AJ, Cowan Jajr, Wu CL: Efficacy of postoperative epidural analgesia: a meta analysis. JAMA; 2003, 290:2455-63. 2.Liu SS, Allen HW, Olsson GL: Patient-controlled epidural analgesia with bupivacaine and fentanyl on hospital wards: prospective experience with 1,030 surgical patients. Anesthesiology; 1998, 88:688-95. 3.Forster JG, Rosenberg PH: Clinically useful adjuvants in regional anaesthesia. Curr Opin Anaesthesiol; 2003, Oct;16(5):477-86. 4.Schug SA, Fry RA: Continuous regional analgesia in comparison with intravenous opioid administration for routine postoperative pain control. Anaesthesia; 1994, 49:528-32. 5.Leland L, Raj S, Kayet DA: Local anesthetics in: Textbook of Regional Anesthesia, P. Prithvi Raj MD Edition Churchill Livingstone, 2003. 6. Liu SS, Moore JM, Luo AM et al: Comparison of three solutions of ropivacaine /fentanyl for operative patient-controlled epidural analgesia. Anesthesiology; 1999, 90:727-33. 7. Lee WK, Li CH, Lee LS et al: Epidural ropivacaine for postoperative analgesia in Taiwanese patients. Acta Anaesthesiol Sin; 2003, 41:215. 8. Berti M, Danelli G, Antonino FA, Moizo E, Vinciguerra F, Casati A: 0.2% ropivacaine with or without sufentanil for patientcontrolled epidural analgesia after anterior cruciate ligament repair. Minerva Anestesiol; 2005 Mar, 71(3):93-100. 9. Engel JM, Hussmann R, Gurtler KH, Menges T, Hempelmann G: Dose-response relationship of clonidine with epidural administration of ropivacaine in orthopedic procedures of the lower extremities. Anaesthesist; 1998 Jul, 47(7):565-70. 10.Vadalouca AN: Adjuvant Drugs in: Textbook of Regional Anesthesia P. Prithvi Raj MD Edition Churchill Livingstone, 2003. 11.Duggan AW, Morton CR: Tonic descending inhibition and spinal nociceptive transmission. Prog Brain Res; 1988, 77:193-211. 12.Bernard JM, Hommeril JL, Passuti N, Pinaud M: Postoperative analgesia by intravenous clonidine. Anesthesiology; 1991, 75:57782. 13.De Kock M, Wiederkher P, Laghmiche A, Scholtes JL: Epidural clonidine used as the sole analgesic agent during and after abdominal surgery: a dose-response study. Anesthesiology; 1997, 86:285-92. 14.Scott DA, Chamley DM, Mooney PH Et Al: Epidural ropivacaine infusion for postoperative analgesia after major lower abdominal surgery: a dose finding study. Anesth Analg; 1995, 81:982-6. 15.Turner G, Blake D, Buckland M et al: Continuous extradural infusion of ropivacaine for prevention of postoperative pain after major orthopaedic surgery. Br J Anaesth; 1996, 76:606-10. 16.Schug SA, Scott DA, Payne J et al: Postoperative analgesia by continuous extradural infusion of ropivacaine after upper abdominal surgery. Br J Anaesth; 1996, 76:487-91. 17.Iijima T, Ishiyama T, Kashimoto S, Yamaguchi T, Andoh T, Hanawa K, Tanzawa I, Kawata K, Hanawa T, Hiejima Y: Comparison of Three Different Concentrations of Ropivacaine with Fentanyl for PatientControlled Epidural Analgesia. Anesth Analg; 2007, 105:507-11. 18.Huang YS, Lin LC, Huh BK, Sheen MJ, Yeh CC, Wong CS, Wu CT: Epidural Clonidine for Postoperative Pain After Total Knee Arthroplasty: A Dose-Response Study. Anesth Analg; 2007, 104:1230-5. 19.Scott DA, Beilby DS, Mcclymont C: Postoperative analgesia using epidural infusions of fentanyl with bupivacaine. A prospective analysis of 1,014 patients. Anesthesiology; 1995, 83:727-37. 20.Sveticic G, Gentilini A, Eichenberger U, Zanderigo E, Sartori V, Lunginbuhl M, Curatolo M: Combinations of bupivacaine, fentanyl, and clonidine for lumbar epidural postoperativeanalgesia: a novel optimization procedure. Anesthesiology; 2004 Dec;101(6):1381-93. M.E.J. ANESTH 21 (3), 2011 THE INFLUENCE OF SIMULATION-BASED PHYSIOLOGY LABS TAUGHT BY ANESTHESIOLOGISTS ON THE ATTITUDES OF FIRST-YEAR MEDICAL STUDENTS TOWARDS ANESTHESIOLOGY Samuel DeMaria Jr*, Ethan O. Bryson*, Carol Bodian**, Yury Khelemsky*, Alan J. Sim***, Andrew D. Schwartz****, Daniel Katz**** and Adam I. Levine***** Abstract Background: The development of medical students’ perceptions of different medical specialties is based on many factors and influences their career choices and appreciation of other practitioners’ knowledge and skills. The goal of this study was to determine if participation in a series of anesthesiologist-run, simulation-based physiology labs changed first year medical students’ perceptions of anesthesiologists. Methods: One hundred first-year medical students were surveyed at random three months before completion of a simulation-based physiology lab run by anesthesiologists. All participants received the same survey instrument, which employed a 5-point Rating Scale to rate the appropriateness of several descriptive terms as they apply to a particular specialist or specialty. A post-simulation survey was performed to track changes in attitudes. Results: Response rates to the survey before and after the simulation labs were 75% and 97% (of the initial cohort responding), respectively. All students who filled out the post-simulation surveys had been exposed to anesthesiologists in the prior three months whereas none had interacted with surgeons in the interim. Nearly all had interacted with internal medicine specialists in that time period. No changes in the medical students’ perceptions of surgeons or internal medicine specialists were evident. Statistically significant changes were found for most descriptors of anesthesiologists, with a trend towards a more favorable perception after the simulation program. Conclusions: Using a survey instrument containing descriptors of different medical specialists and specialties, we found an improved attitude towards anesthesiology after medical students participated in an anesthesiologist-run simulation-based physiology lab series. Given the importance of providing high quality medical education and attracting quality applicants to the field, integrati‑on of anesthesiology staff into medical student courses at the non-clinical level appears useful. * Assistant Professor, Department of Anesthesiology, Mount Sinai Medical Center, New York, NY. ** Associate Professor, Department of Anesthesiology, Mount Sinai Medical Center, New York, NY. *** Fellow, Department of Anesthesiology, Mount Sinai Medical Center, New York, NY. **** Resident, Department of Anesthesiology, Mount Sinai Medical Center, New York, NY. *****Associate Professor and Residency Program Director, Department of Anesthesiology. Associate Professor, Structural and Chemical Biology, Mount Sinai Medical Center, New York, NY. Corresponding Author: Samuel DeMaria Jr., Department of Anesthesiology, One Gustave L. Levy Place, Box 1010, New York, NY 10029. Tel: (212) 241-7475, Fax: (212) 426-2009. E-mail: [email protected] 347 M.E.J. ANESTH 21 (3), 2011 348 Disclosures: This study was funded by the department of anesthesiology, Mount Ainai Medical Center. Acknowledgements The authors wish to acknowledge the medical students who agreed to participate in this study and Basil Hans, PhD, of the physiology department at the Mount Sinai School of Medicine. Introduction The influences on medical students’ attitudes toward different medical specialties are varied and have been studied extensively1,2,3,4. These attitudes may affect medical students’ career choices as well as their respect and appreciation of physicians in other fields once they enter practice. Early exposure to clinicians in the basic science years has been identified as one factor that can alter students’ perceptions5. While work has been done regarding patients’ perceptions of anesthesiologists, mostly revealing pervasive misconceptions about their roles, training and abilities6,7,8,9 little has been done regarding students’ perceptions towards anesthesiologists. In order to uphold the goals of the specialty and attract high quality applicants, a good public relations initiative is important to the field of anesthesiology. Indeed, the American Society of Anesthesiologists (ASA) is actively engaged in studying and improving the profile of anesthesiologists through its newly launched Lifeline Campaign10. While patients and practicing clinicians of other specialties are the main targets of this campaign, clinicians at their earliest stages seem an equally important demographic to address. One way the perception of anesthesiologists might be improved is through the active participation of anesthesiologists in medical education during the basic science years where their unique scope of practice makes them particularly suited to teaching human physiology. The use of high fidelity simulation, in particular, allows students to meet anesthesiologists in an environment where their knowledge and skills can enhance the students’ educational experience. In this setting, medical students might be surprised to see Samuel DeMaria et al. that anesthesiologists have an exceptional command of physiologic and pharmacologic principles and can be effective communicators and enthusiastic educators. The simulation team from the Department of Anesthesiology at the Mount Sinai Medical Center has been conducting simulator-based physiology labs for the Mount Sinai School of Medicine (MSSM) for approximately fifteen years. The current course covers the cardiovascular, respiratory and autonomic nervous systems over three weeks and has been unchanged since 1999. Prior to this time, truncated simulations had been performed. This course has allowed students access to anesthesiologists early in their schooling. Indeed, it is likely that in most institutions medical students will at best have a mandatory 3rd year anesthesia rotation of variable length or an elective during their 4th year when match application deadlines have either passed or are looming. Anecdotally, our team has observed that students’ attitudes toward the practice of anesthesiology and anesthesiologists seem to improve dramatically after completing the simulation series with many students asking to “shadow” a faculty member after the experience. This survey was conducted to determine whether the prevailing attitude towards anesthesiology and anesthesiologists changed after first-year medical students participated in a simulator–based physiology lab conducted solely by anesthesiologists. Materials and Methods Study Design After obtaining institutional review board approval and exemption from written informed consent from the Mount Sinai Hospital Program for the Protection of Human Subjects, a 60-item questionnaire was developed. The questionnaire was designed to elicit data from first-year medical students regarding their perceptions of anesthesiology, but other medical specialties were included to make the purpose appear to be one of more general interest and mask the principle goal of the study. Also, we believed that it was important to prove that the opposite of the study goal was true. Namely, if no exposure occurred, we posited that attitudes should not change. Ten descriptive terms and three medical fields were included in the survey, THE INFLUENCE OF SIMULATION-BASED PHYSIOLOGY LABS TAUGHT BY ANESTHESIOLOGISTS ON THE ATTITUDES OF FIRST-YEAR MEDICAL STUDENTS TOWARDS ANESTHESIOLOGY which takes approximately 5-10 minutes to complete (Appendix 1). A 5-point rating scale was employed so that students could rate their level of agreement or disagreement with the applicability of an available descriptive term to the specialists (as people) or specialty (as a field). Appendix 1 Survey instrument regarding perceptions of different specialists and specialties Please rank the appropriateness (in your honest opinion) of the following descriptions as they apply to the typical specialist in each field by placing the appropriate number between 1 and 5 in each box. 1 – strongly disagree 2 – disagree 3 – neither agree nor disagree 4 – agree 5 – strongly agree Internist Surgeon Anesthesiologist devoted intelligent compassionate hard-working approachable focused confident dexterous/ skillful influential/ leader problem-solver Please rank the appropriateness of the following descriptions as they apply to each specialty by placing the appropriate number between 1 and 5 in each box 1 – strongly disagree 2 – disagree 3 – neither agree nor disagree 4 – agree 5 – strongly agree Internal Surgery Anesthesiology Medicine stimulating prestigious/ respected hands-on rewarding good life style competitive/ rigorous patient-centered intellectual boring my possible career 349 Student subjects from the Mount Sinai School of Medicine (MSSM) class of 2012 were recruited during a physiology lecture in November of 2008. This class has 140 students enrolled. On the day the class was to be surveyed, one hundred students were present. Each student received a survey and was asked to return it to a study group member once completed. The study group members did not identify themselves as members of the department of anesthesiology. Three months later, after completing a simulation-based physiology lab series, the 75 students who completed the initial survey were again surveyed. In addition to the core survey, students were asked if they had any exposure to members of the three medical specialties before and during the time since the initial survey. Exposure was defined as an instructive interaction such as a didactic or “shadowing” experience. Simulation Course The simulation-based physiology lab series is an integral mandatory component of the first-year physiology course at the MSSM. Students participate in three different two-hour simulation-based laboratories taught by a team of 2-3 anesthesiologists (residents and attendings) in groups of 10-15 students per session. The first lab covers cardiovascular physiology, the second covers respiratory physiology and the final session is a trauma scenario/autonomic nervous system lesson. During these fundamental laboratories the simulator serves as a means to demonstrate normal and deranged physiology. In the final session, students apply principles of basic cardiovascular and pulmonary physiology to successfully resuscitate a simulated hypotensive trauma patient. Full environment simulation (FES) is staged for each session using a METI (Medical Education Technologies Inc.) Human Patient Simulator (HPS). The HPS has full drug recognition capabilities and monitoring data are displayed on a large 50-inch plasma cell with Smartboard overlay capability (SMART Technologies Inc.). The overlay affords the ability to operate any Windows based (Microsoft Corporation) program from the plasma cell or write directly on the screen via a blackboard function. The facilitators rapidly change the display between physiologic data and blackboard in order to review key physiologic M.E.J. ANESTH 21 (3), 2011 350 Samuel DeMaria et al. concepts as the scenarios unfold. The experience is Socratic and the students are expected to apply physiologic concepts learned in the classroom in order to interpret clinically relevant patient care issues. Each scenario is stopped and started as needed to discuss the application of classroom knowledge to the clinical situation and to allow participants time to develop diagnostic and therapeutic plans. Anesthesiology is not discussed, per se, though the scenario facilitators do introduce themselves as anesthesiologists and discuss the relevance of basic physiologic concepts to the practice of acute care medicine typically encountered in the emergency room, operating room, or critical care bay. Statistical Analysis Returned surveys were reviewed and data entered in an Excel file. Categorical variables are described as frequency and percentage, and continuous variables as means. In order to maintain anonymity, no attempt was made to identify the respondents by name from pre to post surveys. The pre- and post-simulation survey responses to each question were compared using Wilcoxon Two-Sample Tests. Results Of the 100 surveys that were distributed prior to the simulation program, a total of 75 (75%) were returned. Seventy-three surveys (97%) were returned in the post-simulation group by the cohort of 75 participants. Table 1 shows the demographic distribution of study participants. Table 1 Participants by age and gender Pre-Simulation Post-Simulation (n = 75) (n‑ = 73) Mean Age (SD, Range) 24 (20-32) 24 (20-33) Women (%) 45 (60) 44 (60) Caucasian Race (%) 49(65) 49(67) Before the simulation labs, 12% and 20% of students had been exposed to anesthesiologists and surgeons as teachers, respectively. Forty-three percent of students had been exposed to physicians from internal medicine before the labs and 95% had been exposed by the time of the last survey. During the period between the two surveys, 100% of the students in the final cohort had exposure to anesthesiologists through the physiology labs. The group had no comparable exposure to surgeons in that time period. The results of the surveys for specialists (Table 2) and specialties (Table 3) are shown below. In almost every category, the post-simulation anesthesiology scores were significantly higher than their pre-simulation counterparts, whereas no significant differences were noted for the surgery or internal medicine scores. The one negative attribute, “boring”, decreased in the post-simulation scores. The anesthesiology match rates for MSSM are included in Table 4. Table 2 Pre and post-simulation perceptions of surgeons, internists and anesthesiologists Surgeon Anesthesiologist Mean score Mean score pre-sim post-sim Devoted 4.2 4.3 Intelligent 4.4 4.4 Compassionate 2.9 3.0 Hard-working 4.6 4.7 Approachable 2.7 2.7 Focused 4.5 4.6 Confident 4.7 4.8 Dexterous 4.7 4.8 Influential/ leader 4.1 4.3 Problem-solver 4.0 4.2 p-value 0.60 0.48 0.94 0.35 0.99 0.64 0.42 0.37 0.13 0.30 Mean score Mean score pre-sim post-sim 3.6 4.0 4.2 4.5 3.1 3.6 3.7 4.1 3.4 3.9 4.2 4.3 4.1 4.4 4.1 4.5 3.4 3.8 4.0 4.4 p-value 0.018 0.024 0.002 0.02 0.0003 0.71 0.04 0.03 0.012 0.006 Internist Mean score Mean score p-value pre-sim post-sim 4.3 4.3 0.98 4.2 4.2 0.62 4.3 4.3 0.69 4.3 4.1 0.18 4.3 4.3 0.77 4.2 3.9 0.06 4.1 3.9 0.15 3.7 3.6 0.42 3.7 3.6 0.48 4.4 4.5 0.46 Pre and post-simulation scores are reported as mean scores on a Likert Scale. P-values are based on Wilcoxon 2-sample test comparisons of pre and post-simulation survey data. THE INFLUENCE OF SIMULATION-BASED PHYSIOLOGY LABS TAUGHT BY ANESTHESIOLOGISTS ON THE ATTITUDES OF FIRST-YEAR MEDICAL STUDENTS TOWARDS ANESTHESIOLOGY 351 Table 3 Pre and post-simulation perceptions of surgery, internal medicine and anesthesiology Surgery Anesthesiology Internal Medicine Mean Mean score p-value Mean score Mean score p-value Mean score Mean score p-value score pre- post-sim pre-sim post-sim pre-sim post-sim sim Stimulating 4.2 4.3 0.89 3.2 3.9 <0.0001 3.8 3.8 0.62 Prestigious 4.7 4.8 0.61 3.7 4.0 0.046 3.3 3.3 0.91 Hands-on 4.8 4.8 0.65 3.6 4.3 <0.0001 4.0 3.8 0.29 Rewarding 4.1 4.2 0.64 3.3 3.9 0.0002 4.1 4.0 0.31 Good lifestyle 2.3 2.5 0.23 4.1 4.3 0.49 3.3 3.3 0.89 Competitive 4.7 4.7 0.64 3.9 4.3 0.03 3.2 3.1 0.34 Patient-centered 2.9 3.1 0.104 3.1 3.3 0.12 4.7 4.7 0.77 Intellectual 3.8 3.8 0.55 3.6 4.1 0.012 4.3 4.2 0.56 Boring 2.1 2.1 1.0 3.3 2.5 <0.0001 2.5 2.6 0.48 Possible career 2.7 3.0 0.17 2.2 3.1 <0.0001 3.4 3.2 0.46 Pre and post-simulation scores are reported as mean scores on a Likert Scale. P-values are based on Wilcoxon 2-sample test comparisons of pre and post-simulation survey data. Table 4 Comparison of anesthesiology match rates of medical students at MSSM++ and nationwide Year MSSM (%) National (%)* 1991+ 6.9 6.3 1992+ 9.2 6.5 1993 3.9 5.8 1994 4.3 4.9 1995** 1.5 2.9 1996** 0.7 1.2 1997+ 2.5 1.7 1998+ 4.1 2.6 1999** 2.3 2.8 2000+ 5.9 3.7 2001 1.8 4.7 2002+ 6.7 5.9 2003+ 14.5 6.0 2004 4.6 5.8 2005+ 8.7 5.9 2006+ 9.9 6.5 2007+ 12.3 6.3 2008+ 7.3 6.5 2009+ 10.9 6.7 + Greater percentage placement than national average. * Derived from National Residency Matching Program website: www.nrmp.org/index.html ++ Mount Sinai School of Medicine. ** The cardiovascular lab was introduced in 1995, the respiratory lab in 1996 and the complete course in 1999. Discussion Misconceptions of anesthesiology are common amongst other medical specialists and patients6,7,8,9. Similar inaccurate perceptions amongst medical students may deter them from choosing anesthesiology as a specialty or cause them to have an inaccurate opinion of anesthesiologists as professional colleagues in the future. It makes implicit sense that resources invested by members of academic anesthesiology departments in the form of medical student teaching might help improve the attitudes of these budding clinicians towards the field. This is important not just for recruitment of strong applicants to the field, but for strong professional relationships amongst practitioners which are based on mutual respect and appreciation of each others’ roles and abilities. This, ultimately, fosters the teamwork which is so important to safe medical care. In this study, we showed that exposure of firstyear medical students to anesthesiology resident and attending physicians in a series of simulation-based physiology labs improved their attitudes towards the field. Exposure to internal medicine specialists in a more traditional setting (lectures and shadowing opportunities) did not have a similar effect on attitudes. In particular, marked positive improvements (p<0.001) were found for the following domains: “approachable”, “stimulating”, “hands-on”, “rewarding”, “boring” and “my possible career”. None of the students surveyed had been exposed to surgeons and their views of these clinicians did not change. This is important in corroborating the data gathered for anesthesiology, as no change would be expected if no exposure occurred. Most had been exposed to practitioners from internal medicine through lectures and shadowing experiences, yet their overall attitudes did not change significantly. M.E.J. ANESTH 21 (3), 2011 352 It is possible that attitudes towards internal medicine did not change because expectations of that field were more in line with reality. While our results are limited by several factors (e.g., relatively low initial response rate, p-values not adjusted for the influence of doing many significance tests in a survey-based design) the trends we observed are compelling. It is possible that although we attempted to feign that anesthesiology was the principal study subject we were unsuccessful in doing so. This may have led participants to give favorable ratings to anesthesiologists once the course facilitators were identified as such. Additionally, the results of this study may be heavily influenced by selection bias since those more interested in the simulation labs or in anesthesiology may have been more likely to return the surveys. Indeed, the study was done for one course and one class by one group at only one medical school. Also, a lack of subject identifier use means that no individual shifts in attitude could be determined and this negatively impacts the statistical significance of our data. It is also impossible to tell whether the observed shift in attitudes towards anesthesiologists was due to faculty skill or the educational environment. The current design does not allow the necessary comparisons to identify the sources of the change or the relative weight of either factor. Future work should be done to more effectively determine the importance of faculty skill versus environment in improving attitudes. We are currently investigating whether this change in perception is sustained or manifests as a higher number of students ultimately pursuing anesthesiology as a career. Each year, the simulation labs are rated very highly by students. In this most recent cycle, 98.5% of students (138 completers of 140 total students) rated the course as “excellent” and all respondents agreed that the course should continue Samuel DeMaria et al. to be integrated into the physiology curriculum. The course in its current form was first introduced in 1999 and effects, if any, would be expected from 2002 to present assuming normal graduation pathways. We have accordingly seen a significant percentage of the graduating class entering anesthesiology since the introduction of the complete course, with rates higher than the national average in 7 out of the past 8 years (Table 4). However, this is a correlation not based on rigorous data gathering and is certainly the result of many confounding factors. Other than this brief exposure to anesthesiologists in the first year, students have a 1-week mandatory clerkship in their 3rd year. We believe that respect for anesthesiologists fostered in students’ first year simulation course may result in students entering this brief clerkship with positive expectations and that this potentially explains the high rate of placement in anesthesia programs. We propose it is crucial for anesthesiologists to maintain a strong presence in the basic science curriculum to enrich the educational experience of students and potentially foster interest in and respect for the specialty. Most simulation centers are run by or have anesthesiologists on staff. The simulated environment allows students to learn basic science in a unique way and also see anesthesiologists “in action” and dynamically applying basic physiologic concepts to patient care. In this fashion, students get a high quality educational experience and gain an appreciation of the knowledge and scope of practice of anesthesiologists. Anesthesiologists should therefore take a more active role in the education of medical students at even the earliest stages. In this fashion, simulation serves not just as a powerful educational tool, but a recruiting tool as well. This effect may be true for other specialties as well, such as nursing, emergency medicine and critical care. THE INFLUENCE OF SIMULATION-BASED PHYSIOLOGY LABS TAUGHT BY ANESTHESIOLOGISTS ON THE ATTITUDES OF FIRST-YEAR MEDICAL STUDENTS TOWARDS ANESTHESIOLOGY 353 References: 1. Levin KJ, Friedman CP, Scott PV: Anesthesiology and the graduating medical student: a national survey. Anesth Analg; 1979, 58(3):201-7. 2. Samra SK, Davis W, Pandit SK, Cohen PJ: The effect of a clinical clerkship on attitudes of medical students toward anesthesiology. J Med Educ; 1983, 58(8):641-7. 3. Henderson E, Berlin A, Fuller J: Attitude of medical students towards general practice and general practitioners. Br J Gen Pract; 2002, 52(478):359-63. 4. Hauer KE, Durning SJ, Kernan WN et al: Factors associated with medical students' career choices regarding internal medicine. JAMA; 2008, 300:1154-1164. 5. Grayson MS, Klein M, Franke KB: Impact of a first-year primary care experience on residency choice. J Gen Intern Med; 2001, 16(12):860-3. 6. Klafta JM, Roizen MF: Current understanding of patients’ attitudes toward and preparation for anesthesia: a review. Anesth Analg; 1996, 83:1314-21. 7. Ho RY, Wong DT: Anesthesiology: the misunderstood occupation! Can J Anaesth; 2005, 52(2):208-9. 8. Garcia-Sanchez MJ, Prieto-Cuelar M, Galdo-Abadin JR, Palacio-Rodriguez MA: Can we change the patient’s image of the anesthesiologist? (Spanish). Rev Esp Anestesiol Reanim; 1996, 43:204-7. 9. Huang Y, Yang K, Ren H, Luo A: A survey of elective surgical patients’ attitudes toward anesthesia in PUMC hospital. Chin Med Sci J; 2002, 17:77-80. 10.http://lifelinetomodernmedicine.com/ accessed September 30, 2009. M.E.J. ANESTH 21 (3), 2011 PREEMPTIVE ANALGESIC EFFECT OF DICLOFENAC: EXPERIMENTAL STUDY IN RATS Antigona S. Hasani*, Marija Soljakova**, Muharrem H. Jakupi*** and S erpil Z. U stalar -O zgen **** Abstract Background: Preemptive analgesia is an antinociceptive treatment that prevents central sensitization. Antinociceptive effects of diclofenac are well-known. The aim of this study was to investigate preemptive analgesic effects of intraperitoneally administrated diclofenac, before and after acute and inflammatory induced pain in rat model. Methods: Forty eight male Sprague Dawley rats were included in the study. The rats are divided in five groups (n = 8 per each group); Group A, diclofenac at 10 mg/kg given ip, 30 min before the nociceptive stimulus realized with hot plate test; Group B, diclofenac at 10 mg/kg given ip, 5 min after the nociceptive stimulus, realized with hot plate test; Group C, diclofenac at 10 mg/kg given ip, 30 min before the nociceptive stimulus realized with formalin test, and; Group D, diclofenac at 10 mg/kg given ip, 5 min after the nociceptive stimulus, realized with formalin test. Saline was used as a control. Paw movements in response to induced pain with hot plate test and formalin test were measured during 60 minutes. Results: Preemptive analgesic effect was significant in both groups when diclofenac was administrated before the pain stimuli (P<0.01 and P<0.001). The significant decrease in paw movements started in 15 min after pain stimuli in group A and in 25 min, in group C. Conclusion: Intraperitoneally administered diclofenac had preemptive analgesic effects on acute thermal, and inflammatory induced pain in rats. Our results contain the preemptive analgesic effect of systematically administrated diclofenac. Keywords: diclofenac, preemptive analgesia, hot plate test, formalin test. Introduction Preemptive analgesia suggests that the application of analgesic in prior to proceeding of noxious stimuli prevent the sensibility of the central nervous system, which provokes the pain. Pain associated with tissue damage results in prolonged modulation of the somatosensory system, with increased responsiveness of both peripheral and central pain pathways1. Experimental evidence proposes that to ‘prevent’ or ‘preempt’ the noxious input to the CNS, may be more effective than treatment. The idea of preemptive analgesia was first introduced into clinical practice by Crile * Assistant Professor, Department of Anesthesiology & Reanimation, University Clinical Centre of Kosovo, Pristina, Kosovo. ** Professor, Department of Anesthesiology & Reanimation, Medical Faculty”Sv. Kiril Metodij” Skopje, Macedonia. *** Professor, Institute of Clinical Pharmacology, Medical Faculty, Pristina, Kosovo. **** Assistant Professor, Department of Anesthesiology & Reanimation, Ozel Acibadem Universitesi, Istanbul, Turkey. Corresponding Author: Dr. Antigona Hasani, Department of Anesthesiology & Reanimation, University Clinical Centre of Kosovo, Pristina, Kosovo; Address: Arberia, rr. Zagrebit no. 5, 10000 Pristina, KOSOVO. Tel: 0037744402781, Fax: +38138243838, E-mail: [email protected] 355 M.E.J. ANESTH 21 (3), 2011 356 Antigona S. Hasani et al. in 19132 and further developed by Wall3 and Woolf4. The definition of preemptive analgesia was formed by Kissin5. According to him, preemptive analgesia is “treatment that prevents establishment of central sensitization caused by incisional and inflammatory injuries; it starts before incision and covers both the period of surgery and the initial postoperative period. Preemptive analgesia prevents pathologic pain that is different from physiologic pain”, which means: prevention or reversal of central and peripheral sensitization. Diclofenac sodium, 2-[(2,6-dichlorophenyl) amino] benzene acetic acid, is a non-steroidal antiinflammatory drug (NSAID), with an approximate relative COX-1⁄COX-2 specificity ratio of one6. NSAIDs inhibit the cyclo-oxygenase enzymes (COX), and decrease peripheral and central prostaglandin production. To reduce the inflammation that accompanies tissue injury, decreasing prostaglandin production attenuates the response of the peripheral and central components of the nervous system to noxious stimuli and reduce the pain occurred in response to following noxious stimuli7. These properties would seem to make NSAIDs ideal drugs to use in a preemptive approach. Preemptive analgesic effect of diclofenac is discussed in many studies, but the results are still controversy8-14. In the present study the preemptive analgesic properties of systemically administered diclofenac sodium were investigated in a rat model of acute and inflammatory pain. Materials and Methods After Institutional Ethics Committee approval, 48 male (8 for each group) Sprague Dawley rats, weighing 250-300g (60-70 days after birth), were included in the study. The animals were housed in a cage at 20-25ºC under diurnal light condition and allowed to access food and water ad libitum. All experiment was done in accordance with the Guide for the Care and Use of Laboratory Animals published by the United States National Institutes of Health (NIH Publication No. 8023, revised 1996). Diclofenac sodium (Proanalysis-Merck, Germany) was dissolved in normal saline to achieve solutions of 10 mg/kg for intraperitoneally (ip) administration. The total injected volume was adjusted to 10 ml/kg in each rat. Diclofenac was used for ip injection at 1-ml syringe with a 23-G needle. The rats are divided in five groups; Group A, diclofenac at 10 mg/kg given ip, 30 min before the nociceptive stimulus realized with hot plate test; Group B, diclofenac at 10 mg/kg given ip, 5 min after the nociceptive stimulus, realized with hot plate test; Group C, diclofenac at 10 mg/kg given ip, 30 min before the nociceptive stimulus realized with formalin test, and; Group D, diclofenac at 10 mg/kg given ip, 5 min after the nociceptive stimulus, realized with formalin test. Saline group, (1ml/kg), normal saline given ip, was used as a control. The acute thermal pain was realized with hot plate test. The hot plate test was performed at 55ºC on the paw of each rat. Animals were placed on the heated smooth surface and observations began and continued for the next 60 minutes (Fig. 1a. and 1b). To prevent the tissue injury the rats were removed from the hot plate test after 30 sec. Hot plate tests were performed 10 min before or 30 min after ip drug injection, and repeated every 10 min during 60 min. Fig. 1a Hot plate test PREEMPTIVE ANALGESIC EFFECT OF DICLOFENAC: EXPERIMENTAL STUDY IN RATS Fig. 1b Paw movements 357 catatonic excitement and flaccidity) were observed in animals during the study. Statistical analysis was performed using SPSS version 15. Data are expressed as the mean ± SD or 95% confidence interval (CI). The experimental groups were compared by the nonparametric Kruskal-Wallis test. Multiple comparisons after the Kruskal-Wallis test were performed using the two-tailed Dunn test. A P value less than 0.05 were considered significant. Results Fig. 1c Formalin test Preemptive analgesic effect, in groups before and after diclofenac sodium administration, was shown in hot plate test with significant decrease in paw movements in group A, when diclofenac sodium was administrated before the pain stimuli with hot plate test (P<0.01) (Fig. 2). Fig. 2 Paw movements after ip administration of diclofenac before and after the pain stimuli and control group in hot plate test. Data are presented as mean ± SD. * significant difference The formalin test, model of inflammatory pain, was performed ten minutes after drug administration. Fifty microlitres of 10% formalin was injected subcutaneously into the dorsal surface of the right hind paw with a 30-G needle (Fig. 1c). Immediately after injection, the rat was placed in an open surface, and their paw response was observed at ten minutes intervals for a period of one hour. The number of movements was counted for one minute. Two phases were observed: phase 1 for the first six minutes after injection; and phase 2 beginning after about ten minutes. The paw movements were measured every 10 minutes during 60 minutes. A nociceptive score was determined by measuring the 4 behavioural categories: 0, the position and posture of the hind paw is indistinguishable from the contralateral paw; 1, the paw has little or no weight placed on it; 2, the paw is elevated and is not in contact with any surface; 3, the paw is licked, bitten or shaken. Significant decrease of paw movements was shown in formalin test as well, in groups before administration of diclofenac sodium (group C) (P<0.001) (Fig. 3). Fig. 3 Paw movements after ip administration of diclofenac before and after the pain stimuli and control group, with formalin test. Data are presented as mean ± SD. * significant difference Behavioral side effects (agitation, allodinia, M.E.J. ANESTH 21 (3), 2011 358 Antinociceptive effects in the hot plate test, group before (group A) started in 15 min after diclofenac administration and continue to decrease during followed 60 minutes. In the formalin test group before (group C) significantly increased paw movements, antinociceptive effects continue to decrease in 25 min and up to 60 min. Diclofenac decrease the number of paw movement in both phases of formalin test, in group C (P<0.05). Antinociceptive effects of diclofenac administrated before pain stimuli were higher in group C, than the corresponding group A (P<0.01 vs. P<0.001, respectively) (Fig. 4). Fig. 4 Paw movements after ip administration of diclofenac before and after the pain stimuli and control group, in hot plate test and formalin test. Data are presented as mean ± SD. * significant difference Antigona S. Hasani et al. In our study, we used before versus after design; we applied diclofenac before and after pain stimuli. It is evident that pain processing may be reduced by preadministration of various agents (e.g. opioids, local anesthetics, NSAID etc.) leading to the concept of preemptive analgesia. Due to their mode of action, competing with arachidonic acid for binding to cyclo-oxygenase and decreasing the formation of prostaglandins, treatment with NSAIDs should be started as early as possible. The treatment should be initiated before the input of nociceptive stimuli; however, the clinical value of this technique remains still uncertain15. Instrumentation of the uterus and Fallopian tubes during laparoscopy or surgery leads to prostaglandin release and, the prostaglandins released play a role in pain following laparoscopy16. Inhibition of prostaglandin production by the NSAIDs both peripherally and centrally should, therefore, decrease postoperative discomfort and reduce opioid requirement17. Woolf and colleagues showed no difference with preoperative diclofenac from postoperative diclofenac in patients undergoing laparoscopic tubal ligation18. Both before and after ip administration of diclofenac decrease the number of paw movements after pain stimuli performed by hot plate or formalin, in comparison with control saline group (P<0.001) (Fig. 2, 3, 4). No behavioural side effects were observed in any animal. Discussion In this recent study, we demonstrated that intraperitoneally administered diclofenac had preemptive analgesic effects in the hot plate test and formalin test in rats. Preemptive analgesia can reduce both the acute and inflammatory pain and in this way can reduce peripheral and central sensitization. However, Buggy et al. and Gillberg et al. demonstrate that preoperative administration of ketorolac, piroxicam and diclofenac did reduce postoperative pain in patients undergoing laparoscopy19,20. Our findings support these results as well. There are two systematic reviews published in recent years; one of them supports the clinical value of preemptive analgesia, whereas the other one is the opposite. Firstly, Moiniche et al21 published a systematic review of 80 studies, with 3761 patients, based on before versus after design. They show that the trials of single-dose epidural analgesia resulted with an improvement in pain control in 7 of 11 studies, but that validity and clinical relevance of the effect of epidural analgesia were uncertain. They concluded that the preemptive use of analgesics is not resulted in better postoperative pain relief. However, three years later, Ong et al. in their review analyzed 66 studies with data from 3261 patients and concluded that preemptive epidural analgesia, preemptive local wound infiltration and NSAID administration improve postoperative PREEMPTIVE ANALGESIC EFFECT OF DICLOFENAC: EXPERIMENTAL STUDY IN RATS pain scores22. Comparing the two reviews, Ong et al. suggested that 10 additional new trials from 2001– 2003, not included in the review by Moiniche et al. Our study shows that ip administered diclofenac has preemptive and antinociceptive effects in acute thermal and inflammatory induced pain. The hot plate test evaluates supraspinal antinociceptive effects, and it reflects activity in thermally sensitive afferent fibers and activity of Aδ and C fibers25. Responses in the formalin test are mediated by both the spinal and supraspinal sites. The phase 1 response of the formalin test is caused by the direct stimulation of nociceptors by formalin or tissue damage, and is thought to be an acute pain reaction. This reflects activity that is prominent in Aβ, Aδ and high-threshold C nociceptor afferent fibers. The phase 2 response is caused by inflammation after formalin injection and central sensitization related to C activity. It reflects activity in mechanically insensitive afferent fibers and activity of Aδ and C fibers26. Sensory fibers respond to physical and chemical stimuli producing mediators with origin from tissue injury and inflammation. These inflammatory mediators activate or sensitize afferent fibers, and the neural impulses originated from nociceptors are transmitted via peripheral nerves to the spinal cord and with cranial nerves to cranial nerve ganglia. Prostaglandins are among the most important mediators of inflammatory pain. During inflammation prostaglandin formation is induced by COX enzymes. NSAIDs block COX enzymes production and produce analgesia27. Studies have highlight that NSAIDs do not increase the pain threshold in animal model such as tail-flick and hotplate tests, but they normalize the pain behavior, which is observed after tissue injury and inflammation mechanism28,29. However, diclofenac 359 cause dose dependant analgesia. The ED50 values for diclofenac are 7.20 mg/kg (3.95 ± 13.30)30. We assume that the inadequate administered doses of drug may decrease the concentration in peripheral nociceptive terminals and antinociceptive response may fail. The intraperitoneally administrated dose of diclofenac sodium, in our study, was 10 mg/kg, the optimal dose to cause antinociceptive response in rats. The analgesic action of NSAIDs is generally considered to be related to an inhibition of the enzyme cyclo-oxygenase and to involve a peripheral site of action. Recent studies have demonstrated the central antinociceptive mechanism of action of the NSAIDs31-36. Bjorkman studied the site and nature of the antinociceptive effect of diclofenac and paracetamol in the central nervous system. He observed the antinociceptive effect of diclofenac engage with central nervous component in different areas of central nervous system30. Herrero and colleagues31 studied the central antinociceptive effect of NSAID ketoprofen in two experiment models in rats and conclude that ketoprofen has central while peripheral analgesic activity. The present results suggest that intraperitoneally administered diclofenac has few effects at the level of the spinal cord and antinociceptive effects in the periphery and the brain. However the available preoperative trials of preemptive NSAID use have modest or unclear results and it may be due to controversy associated with the definition of preemptive analgesia. Even though, NSAIDs may have an ability to induce a preemptive analgesic effect. Our study suggests how the preoperative use of diclofenac was more effective. It is expected that NSAIDs will play an increasing role in preemptive analgesia and pain relief in general. M.E.J. ANESTH 21 (3), 2011 360 Antigona S. Hasani et al. References 1. Woolf CJ, Chong MS: Preemptive analgesia-treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg; 1993, 77:362-379. 2. Crile GW: The kinetic theory of shock and its prevention through anoci-association. Lancet; 1913, 185:7-16. 3. Wall PD: The prevention of postoperative pain. Pain; 1988, 33:289290. 4. Woolf CJ: Central mechanisms of acute pain. In Bond MR, Charlton JE, Woolf CJ (eds) Proc. 6th World Congr on Pain; 1991, Amsterdam: Elsevier, 25-34. 5. Kissin I: Preemptive analgesia. Anesthesiology; 2000, 93:1138-43. 6. Van Der Marel CD, Anderson BJ, Romsing J, Jacqz-Aigrain E, Tibboel D: Diclofenac and metabolite pharmacokinetics in children. Paediatr Anaesth; 2004, 14:443-51. 7. Kokki H: Nonsteroidal anti-inflammatory drugs for postoperative pain: a focus on children. Paediatr Drugs; 2003, 5:103-123. 8. Riad W, Moussa A: Preoperative analgesia with rectal diclofenac and/or paracetamol in children undergoing inguinal hernia repair. Anaesthesia; 2007, 62:1241-1245. 9. Tuzuner AM, Ucok C, Kucukyavuz Z, Alkis N, Alanoglu Z: Preoperative diclofenac sodium and tramadol for pain relief after bimaxillary osteotomy. J Oral Maxillofac Surg; 2007, 65:2453-8. 10.Alexander R, El-Moalem HE, Gan TJ: Comparison of the morphine-sparing effects of diclofenac sodium and ketorolac tromethamine after major orthopedic surgery. J Clin Anesth; 2002, 14:187-92. 11.Yukawa Y, Kato F, Ito K, Terashima T, Horie Y: A prospective randomized study of preemptive analgesia for postoperative pain in the patients undergoing posterior lumbar interbody fusion continuous subcutaneous morphine, continuous epidural morphine, and diclofenac sodium. Spine; 2005, 30:2357-61. 12.Jakobsson J, Rane K, Davidson S: Intramuscular NSAIDS reduce post-operative pain after minor outpatient anaesthesia. Eur J Anaesthesiol; 1996, 13:67-71. 13.Joshi A, Parara E, Macfarlane TV: A double-blind randomised controlled clinical trial of the effect of preoperative ibuprofen, diclofenac, paracetamol with codeine and placebo tablets for relief of postoperative pain after removal of impacted third molars. Br J Oral Maxillofac Surg; 2004, 42:299-306. 14.Oztekin S, Hepaguslar H, Kar AA, Ozzeybek D, Artikaslan O, Elar Z: Preemptive diclofenac reduces morphine use after remifentanil-based anaesthesia for tonsillectomy. Paediatr Anaesth; 2002, 12:694-699. 15.Mccrory CR, Lindahl SG: Cyclooxygenase inhibition for postoperative analgesia. Anesth Analg; 2002, 95:169-76. 16.Wang ZH, Wu R, Ge X: Relationships between pelvic pain and prostaglandin levels in plasma and peritoneal fluid collected from women after sterilization. Contraception; 1992, 45:67-71. 17.Mccormack K: Non-steroidal anti-inflammatory drugs and spinal nociceptive processing. Pain: 1994, 59:9-43. 18.Woolf CJ, Chong MS: Preemptive analgesia – treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg; 1993, 77:362-79. 18.Buggy DJ, Walll C, Carton EG: Preoperative or postoperative diclofenac for laparoscopic tubal ligation. Br J Anaesth; 1994, 73:767-70. 19.Gillberg LE, Harsten AS, Stahl LB: Preoperative diclofenac sodium reduces post-laparoscopy pain. Can J Anaesth; 1993, 40:406-8. 20.Moiniche S, Kehlet H, Dahl JB: A Qualitative and quantitative systematic review of preemptive analgesia for postoperative pain relief. The role of timing of analgesia. Anesthesiology; 2002, 96:725-741. 21.Ong CK, Lirk P, Seymour RA, Jenkins BJ: The efficacy of preemptive analgesia for acute postoperative pain management: a meta-analysis. Anesth Analg; 2005, 100:757-73. 22.Espejo EF, Mir D: Structure of the rat's behaviour in the hot plate test. Behav Brain Res; 1993, 30, 56:171-6. 23.Tjolsen A, Berge OG, Hunskaar S, Rosland JH, Hole K: The formalin test: an evaluation of the method. Pain; 1992, 51:5-17. 24.Dray A: Inflammatory mediators of pain. Br J Anaesth; 1995, 75:125-131. 25.Bjorkam R, Hedner J, Hedner T, Henning M: Central, naloxonereversible antinociception by diclofenac in the rat. Naunyn Schmiedebergs Arch Pharmacol; 1990, 342:171-6. 26.Miranda HF, Lopez J, Sierralta F, Correa A, Pinard G: NSAID antinociception measured in chemical and a thermal assay in mice. Pain Res Manage; 2001, 6:190-196. 27.Miranda HF, Sierralta F, Pinard G: Neostigmine interactions with non steroidal anti-inflammatory drugs. Br J Pharmacol; 2002, 135:1591-7. 28.Bjorkman R: Central antinociceptive effects of non-steroidal antiinflammatory drugs and paracetamol. Experimental studies in the rat. Acta Anaesthesiol Scand; Suppl. 1995, 103:1-44. 29.Herrero JF, Parrado A, Cervero F: Central and peripheral actions of the NSAID ketoprofen on spinal cord nociceptive reflexes. Neuropharmacology; 1997, 36:1425-31. 30.Yaksh TL, Dirig DM, Conway CM, Svensson C, Luo ZD, Isakson PC: The acute antihyperalgesic action of nonsteroidal, antiInflammatory drugs and release of spinal prostaglandin E2 is mediated by the inhibition of constitutive spinal cyclooxygenase-2 (COX-2) but not COX-1. J. Neurosci; 2001, 21:5847-5853. 31.Mccormack K: The spinal actions of nonsteroidal anti-inflammatory drugs and the dissociation between their anti-inflammatory and analgesic effects. Drugs; 1994, 47 Suppl 5:28-45. 32.Jurna I: Central analgesic effects of non-steroidal anti-rheumatic agents. Z Rheumatol; 1991, 50 Suppl 1:7-13. 33.Bjorkman RL, Hedner T, Hallman KM, Henning M, Hedner J: Localization of the central antinociceptive effects of diclofenac in the rat. Brain Res; 1992, 590:66-73. Comparison between two phenylephrine infusion rates with moderate co-loading for the prevention of spinal anaeshtesia- induced hypotension during elective * caesarean section Tarek Ansari, Medhat M. Hashem, Ahmed A. Hassan, Ahmed Gamassy and Ayad Saleh Abstract Background: Phenylephrine induces maternal bradycardia in 50% of mothers when used for prevention and treatment of spinal anaesthesia-induced hypotension during caesarean delivery. Rapid fluid administration immediately after initiation of the spinal block (co-loading) may have a vasopressor sparing effect. The aim of this study was to evaluate the hypothesis that when using rapid crystalloid co-loading, an infusion of 50 mcg/minute of PE could be as effective as 100 mcg/minute in preventing maternal hypotension but with minimal maternal bradycardia and an acceptable fetal outcome. Methods: 117 mothers scheduled for elective caesarean section were recruited in this randomized controlled trial. Co-loading with 10 ml/kg of Hartmann’s solution started immediately after a standard spinal anaesthesia. Parturients were then randomly allocated into two groups. Group 50 (n = 54) received phenylephrine infusion at 50 μg/min, and group 100 (n = 63) 100 μg/ min. Rescue phenylephrine boluses (50 mcg) were administered if needed to maintain systolic blood pressure between 80-100% of its baseline values. Results: Systolic blood pressure was not different between mothers in both groups during the study period. All neonatal Apgar scores at 1 minute were ≥7 and at 5 minutes were ≥ 9. No mother had umbilical arterial pH <7.2. Umbilical arterial and venous blood gas and acid base values were not different between both groups except the umbilical arterial PCO2 that was significantly higher in group 100. There were more frequent episodes of maternal bradycardia in Group 100 than in Group 50 (eleven and one parturients respectively). There was no difference in the incidence of nausea and vomiting in both groups. Conclusion: In combination with rapid co-loading, an infusion rate of 50 µg/min of PE is as adequate as 100 µg/min in prevention of spinal anaesthesia-induced hypotension during elective caesarean section. Both infusions are associated with a similar neonatal outcome. PE infusion of 50 µg/min is associated with significantly less maternal bradycardia than 100 µg/min. Keywords: Phenylephrine, Spinal Aneasthesia, Caesarean section, Hypotension, Co-loading. * Department of Anaesthesia, Corniche Hospital, Abu Dhabi, United Arab Emirates. Corresponding Author: Dr Medhat M. Hashem, Consultant Anaesthetist, North East London NHS Treatment Centre, King George Hospital,Barley Lane, Ilford, Essex, IG3 8YY, UK. Tel +(44) 08450524175, Fax: +(44) 02085984605. E-mail: [email protected] 361 M.E.J. ANESTH 21 (3), 2011 362 Introduction During elective caesarean section, maternal hypotension is the most frequent complication of spinal anaesthesia with an incidence approaching 100%1. Among its multifactorial aetiology is profound vasodilatation secondary to complete sympathetic denervation that is often accentuated by a variable degree of aortocaval compression. Many strategies are currently used to minimize hypotension including maternal left tilt, leg wrappings2, sympathomimetic drugs3, and intravenous fluid loading whether before (pre-loading)4 or with (co-loading) induction of spinal anaesthesia. Co-loading may be more effective than preloading in terms of reducing the dose of vasopressor prior to delivery5. Recent work suggests that prophylactic continuous infusion of the <alpha>-adrenergic agonist phenylephrine (PE) is superior to ephedrine in prevention of spinal anaesthesia induced hypotension. Major postulated benefits are a reduction in the incidence of nausea and vomiting, and less fetal acidosis6,7. But when PE was used on its own to maintain maternal systolic blood pressure at 100% of baseline, the incidence of hypotension was still 29%8. A Cochrane systematic review concluded that no one method on its own is effective, and that combining more than one measure should be investigated9. PE induces bradycardia in up to 50% of mothers, in a dose-related manner, via a secondary baroreceptor response to induced-hypertension11. The aim of the study was to evaluate the hypothesis that when using rapid crystalloid co-loading, PE infusion of 50 mcg/ minute could be as effective as 100 mcg/minute in preventing maternal hypotension with similar foetal outcome but with minimal maternal bradycardia. Methods Following Corniche hospital Ethics Committee approval (Abu Dhabi United Arab Emirates) and informed written consent, 117 mothers scheduled for elective caesarean section were recruited. All mothers had normal singleton pregnancy at 37 week gestation or more. Exclusion criteria were American Society of Tarek Ansari et al. Anaesthetists (ASA) Class 3 or more, height <150 or >180 cm, or body mass <60 or >100 kg, pre-eclampsia, known fetal abnormality, or any contraindication to spinal anaesthesia. Oral ranitidine (150 mg) was given on the evening before and the morning of surgery. In the preparation room, oral sodium citrate 0.3 M (30 ml) was given. Three measurements of non-invasive blood pressure at one minute interval were taken after the mothers were allowed a 5 minute rest period in the supine position with left lateral tilt. The average of the 3 readings of systolic blood pressure (SBP) was used as a baseline. Following skin infiltration with 2% lidocaine, a 16G IV catheter was inserted and intravenous fluid was started at a minimal rate to keep the vein open. Mothers were randomized into Group 50 (PE 50 µg/ ml) or Group 100 (PE 100 µg /ml) using closed similar envelops labeled with either of the two designated concentration of PE. An anaesthetist, who was not involved in the case management, prepared a 20 ml syringe for PE infusion with the designated concentration. Both the patient and the anaesthetist in charge of the case were blinded to the concentration of PE in the syringe. In the operating theatre, after the skin was infiltrated with 2% lidocaine, subarachnoid injection of 3 ml (15 mg) hyperbaric bupivacaine 0.5% and preservative-free fentanyl 20 µg was performed in the sitting position using a 26G atraumatic spinal needle (RapidTM, Portex, UK) at the L3-4 or L4-5 interspace. With the operating table leveled, mothers were positioned supine with left lateral tilt and 2 pillows supporting the head and shoulders. Monitoring consisted of a continuous 3 lead electrocardiograph, noninvasive blood pressure measurement every minute, and pulse oximetry. Intraoperative haemodynamic data, from the time of induction of spinal anaesthesia until the delivery of the baby, were downloaded from the monitor (IntelliVue MP70, Phillips Medical Ltd, Germany) for off-line analysis. Five minutes after induction of anaesthesia, the upper sensory level of anaesthesia was assessed using loss of cold stimulus discrimination. Oxygen (5 L/min) by a clear facemask was given only if pulse oximetry reading was less than 95%. Comparison between two phenylephrine infusion rates with moderate co-loading for the prevention of spinal anaeshtesia- induced hypotension during elective caesarean section Immediately after spinal anaesthesia, both PE infusion and co-loading were commenced. An intravenous bolus of warm Hartmann's solution (10 ml/kg) was administered as rapidly as possible, with the aid of a pressure bag inflated at 200 mmHg, followed by a reduction of the rate to a minimal flow. PE infusion was commenced at a rate of 60 ml/h for the first three minutes and stopped if SBP was greater than 120% of the baseline. After the first three minutes, the infusion was continued at the same rate if SBP was between 80-100% of baseline, until the time of delivery. PE infusion was discontinued if the SBP was more than 100% of the baseline value. A rescue dose of PE (50 µg) was given if blood pressure decreased to below 80% of the baseline for two consecutive readings despite PE infusion. If bradycardia (heart rate <50/min) developed without hypotension, PE infusion was discontinued for one minute. Intravenous glycopyrronium (200 µg) was used to treat bradycardia associated with hypotension (SBP<80% of baseline). After delivery, an intravenous bolus of oxytocin (5 IU) was slowly administered. Apgar score was assessed at 1 and 5 minutes after delivery by the attending paediatrician, who was unaware of the dose of PE used. With the umbilical cord double clamped, umbilical venous and arterial blood samples were drawn for gas and acid base analysis. The primary outcome of the study was the incidence of maternal hypotension, defined as a drop in SBP to less than 80% of baseline. The incidence of hypotension was 29% in a previous study8. A priori 363 sample size of 58 mothers in each group was deemed sufficient to detect a 5% difference (α = 0.05, β = 0.8). Another 10% was added to compensate for drop outs. Secondary outcomes were maternal bradycardia, the total dose of PE used pre-delivery, the incidence of nausea and vomiting, Apgar scores at 1 and 5 minutes, and umbilical arterial and venous blood gases and base deficits. Normally distributed numerical data were described in terms of mean and standard deviation and compared using unpaired t-test and one way ANOVA. Non-normally distributed data were compared using Mann-Whitney test. Categorical data were analysed using Chi square and Fischer Exact tests where appropriate. Statistical analysis was performed using SPSS 14.0 for windows (Statistical Package for Social Sciences). Statistical significance was assumed at a P value of <0.05. Results One hundred and twenty eight mothers were originally enrolled in this trial with eleven dropouts due to different reasons. Two mothers had inadequate block and subarachnoid injection was repeated. Trial design was not strictly followed in four mothers. Five umbilical blood gas results had technical problems. One hundred and seventeen full-term parturients undergoing elective caesarean section completed the study. None of them complained of intraoperative pain nor was intraoperative supplementation with analgesics or sedatives required (Table 1). Table 1 Mothers’ characteristics, block height and surgical times in both groups Group 50 (n = 54) Group 100 (n = 63) P Age (years) 32.7 (4.6) 32.8 (5.3) 0.92 Weight (Kg) 74.0 (9.1) 75.5 (9.9) 0.41 Height (cm) 158.4 (4.8) 159.0 (6.6) 0.56 Gestational age (weeks) 38.4 (1.0) 38.2 (0.9) 0.26 T4 (T2-T6) T4 (T2-T6) 1.0 Induction to delivery time (minutes) 14.5 (2.7) 14.0 (3.5) 0.35 Uterine incision to delivery time (seconds) 65.5 (36.9) 72.0 (55.8) 0.47 Block height at 5 minutes (dermatome) All values are mean (SD) except block height: median (range). M.E.J. ANESTH 21 (3), 2011 364 Tarek Ansari et al. Table 2 Intraoperative haemodynamic data and side effects Group 50 (n = 54) Incidence of hypotension (systolic blood pressure less than 80% of 8 (14.8) baseline) Incidence of hypertension (systolic blood pressure more than 120%) 2 (3.7) Phenylephrine dose used (micrograms) 546.9 (211.3) Number of mothers that received at least one rescue dose of 7 (12.9) phenylephrine Incidence of bradycardia (heart rate less than 50/min) 1 (1.8 %) Number of mothers that received glycopyrronium 0 Co-loading volume (ml) 759 (95) Incidence of nausea and vomiting 3 (5.5) Values are number (%) except phenylephrine dose and co-loading volume: mean (SD). * denotes a significant difference (p<0.05). Intraoperative haemodynamic data and side effects are shown in table 2. Systolic blood pressure was not different statistically at any time during the study period (Fig. 1). Fig. 1 Mean systolic blood pressure in both groups None of the neonates in both groups had an umbilical artery pH <7.2 (Table 3). All neonatal Apgar scores at 1 minute were ≥7 and at 5 minutes were ≥9. P Group 100 (n = 63) 3 (4.7) 0.12 10 (15.8) 913.5 (361.4) 1 (1.5) 0.063 <0.001* 0.023* 11 (17.4 %) 1 (1.5 %) 775 (107) 1 (1.5) 0.005* 0.46 0.39 0.33 All umbilical arterial and venous blood gas values were not different between neonates in both groups except the umbilical arterial PCO2 that was significantly higher in neonates in group 100 (p<0.05). Discussion In this trial, we found that when using rapid crystalloid co-loading, PE infusion of 50 mcg/min would maintain SBP at near normal values, similar to PE infusion of 100 mcg/min that was suggested in previous trial.10 This trial failed to detect a difference in the incidence of hypotension although it was powered to detect it. Also, there was no difference in the incidence of hypertensive episodes between both groups. Blood pressure was measured non-invasively every minute in this study. Invasive arterial blood pressure monitoring would have been more sensitive but it lacks clinical justification. There was no significant difference in Table 3 Neonatal outcome in both groups Group 50 (n = 54) Group 100 (n = 63) P 7.31 (0.04) 52.5 (6.7) 13.8 (5.0) -0.15 (2.5) 7.30 (0.04) 55.4 (7.1) 12.7 (5.4) 0.26 (1.9) 0.14 0.02* 0.24 0.26 7.36 (0.03) 43.1 (4.2) 23.8 (5.5) -1.5 (1.6) 7.35 (0.03) 44.4 (5.2) 24.4 (6.1) -1.3 (1.6) 0.29 0.13 0.64 0.29 Umbilical arterial blood gases pH PCO2 (mmHg) PO2 (mmHg) Base excess (mmol Litre-1) Umbilical venous blood gases pH PCO2 (mmHg) PO2 (mmHg) Base excess (mmol Litre-1) Values are mean (SD), * denotes a significant difference (p<0.05). Comparison between two phenylephrine infusion rates with moderate co-loading for the prevention of spinal anaeshtesia- induced hypotension during elective caesarean section the incidence of nausea and vomiting between both groups. Crystalloid preloading before spinal anaesthesia for caesarean section, as a sole measure, is not effective in preventing hypotension12. This is probably due to its rapid redistribution and the stimulation of atrial natriuretic peptide secretion that lead to peripheral vasodilatation and diuresis13. Starting fluid loading immediately after induction of spinal anaesthesia (coloading) is a more rational approach as intravascular volume expansion coincides with sympathetic blockade-associated vasodilatation5,14. Rapid crystalloid co-loading with 20 ml/kg was associated with less ephedrine requirement than with preloading suggesting that co-loading has a vasopressor-sparing effect5. In non-obstetric patients, co-loading, with 12 ml/kg, was associated with a significant increase in cardiac output as compared to preloading and no loading, with no difference in the incidence of hypotension15. In a recent Cochrane systematic review, no conclusions were reached with respect to the optimum intravenous fluid loading volume9. In this trial, coloading relied on a body weight-based moderate volume of Hartmann’s solution (10 ml/kg). This moderate co-loading would minimize any deleterious effect of sudden intravascular volume expansion. This volume was used previously in a similar study16. To achieve an optimum response to co-loading, the preset Hartmann's volume was infused as rapidly as possible, aided with a pressure bag inflated at 200 mmHg, through a standard 16 gauge venous catheter. Gravity was the driving force in previous co-loading trials5,10. Further studies are needed to quantify the vasopressorsparing effect of different co-loading volumes. All vasopressors share the same adverse effects that include anaphylaxis, hypertension and cardiac dysrhythmia17. There is also a potential for impaired utero-placental perfusion secondary to vasoconstriction. Among the currently used vasopressors, PE is gaining popularity in preventing spinal anaesthesia-induced hypotension in mothers undergoing caesarean section. Contrary to previous beliefs, it is now suggested that maintaining utero-placental perfusion pressure by PE outweigh its potential utero-placental vasoconstriction effect18. This is evident by higher UApH in mothers 365 receiving PE as compared to ephedrine19. Although some studies showed that PE was not associated with maternal or foetal morbidity, the high incidence of maternal bradycardia is still a concern20. The recommended infusion dose of PE ranges from 30 to 180 mcg/min. according to blood pressure response21. This wide dose range may precipitate high plasma concentrations that might precipitate hypertension and bradydysrhythmia. Ventricular bigeminy was previously reported in a mother having a caesarean section under spinal anaesthesia while receiving PE boluses of 100 μg/min22. We believe that a user-friendly infusion regimen that can be adopted easily even by less experienced practitioners is needed. PE infusion protocol in this study was simple. PE infusion (60 ml/h) commenced immediately after subarachnoid injection for 3 minutes. After 3 minutes, the anaesthetist will either discontinue or continue PE infusion at the same rate to maintain maternal SBP within 20% of its baseline. If maternal SBP dropped below 80% of baseline, PE infusion will restart at the same rate (60 ml/h). In this trial, only one mother in group 50 developed one or more episodes of sinus bradycardia (1.8%) as compared to eleven mothers in group 100 (17.4%). The difference was highly significant (p = 0.005). The incidence of bradycardia in group 100 is comparable to that of Ngan kee et al, 16.9% when used a similar dose of PE10. Two different mechanisms could instigate sinus bradycardia during spinal anaesthesia; sympathetic cardiac denervation and baroreceptor response to PE induced hypertension. In this trial, the technique of spinal anaesthesia was the same in all mothers. The dose of bupivacaine used (15 mg) was within the recommended dose range18,23. As there was no detectable difference in block height between both groups, we can assume that the difference in the incidence of sinus bradycardia is attributed to the significant difference between the doses of PE. In this trial, glycopyrrolate was given if bradycardia persists despite PE discontinuation or if bradycardia was associated with hypotension. There was no difference in the use of glycopyrrolate between both groups as apparently discontinuation of PE infusion promptly eliminated sinus bradycardia. All babies in both groups had an Apgar score M.E.J. ANESTH 21 (3), 2011 366 of >7 at one minute and >9 at 5 minutes. The UA pH was ≥7.3 for all babies in both groups. There was no statistical significant difference between both groups’ UA and UV blood gas and acid-base values except UA PCO2. The UA PCO2 was significantly higher in group 100 as compared to group 50. Although the difference in UA PCO2 was statistically significant, it was not clinically relevant. It was previously suggested that a higher UA PCO2 might indicate foetal respiratory acidaemia secondary to acute uteroplacental insufficiency24. We believe that any attempt Tarek Ansari et al. to associate this with the higher dose of PE (100 mcg/ minute) would be speculative. We conclude that, in combination with rapid co-loading, an infusion rate of 50 µg/min of PE is as adequate as 100 µg/min in prevention of spinal anaesthesia-induced hypotension during elective caesarean section. PE infusion of 50 µg/min is associated with significantly less maternal bradycardia than 100 µg/min. Both infusions are associated with a similar neonatal outcome. References 1. May L: Epidural is an outmoded form of regional anaesthesia for elective caesarean section. Int J Obstet Anesth; 1995, 4:34. 2. Van Bogaert L: Prevention of post spinal hypotension at elective caesarean section by wrapping of the lower limbs. Int J Gynecol Obstet;1998, 61:233. 3. Kang Y, Abouleish E And Caritis S: Prophylactic intravenous ephedrine infusion during spinal anesthesia for cesarean section. Anesth Analg;1982, 61:839. 4. Wollman S And Marx G: Acute hydration for prevention of hypotension of spinal anesthesia in parturients. Anesthesiology;1968, 29:374, 1968. 5. Dyer R, Farina Z, Joubert I, Toit P, Meyer M, Torr G, Wells K And James M: Crystalloid preload versus rapid crystalloid administration after induction of spinal anaesthesia (coload) for elective Caesarean section. Anaesth. Intensive Care; 2004, 32:351. 6. Cooper D, Carpenter M, Mowbray P, Desira W, Ryall D And Kokri M: Fetal and maternal effects of phenylephrine and ephedrine during spinal anesthesia for Cesarean delivery. Anesthesiology; 2002, 97:1582. 7. Ngan Kee W, Lee A, Khaw K, Ng F, Karmakar M And Gin T: A randomized double-blinded comparison of PE and ephedrine infusion combinations to maintain blood pressure during spinal anesthesia for Caesarean delivery: the effects on fetal acid-base status and hemodynamic control. Anesth Analg; 2008, 107:1295. 8. Ngan Kee W, Kkaw K and Ng F: Comparison of phenylephrine infusion regimens for maintaining maternal blood pressure during spinal anaesthesia for Caesarean section. Br J Anaesth; 2004, 92:469. 9. Cyna A, Andrew M, Emmett R, Middleton P and Simmons S: Techniques for preventing hypotension during spinal anaesthesia for caesarean section (Review). The Cochrane Library; 2009, Issue 1. Art. No: CD002251. 10.Ngan Kee W, Khaw K and Ng F: Prevention of hypotension during spinal anaesthesia for Caesarean delivery. Anesthesiology; 2005, 103:744. 11.Thomas D, Robson S, Redfern N, Hughes D and Boys R: Randomised trial of bolus phenylephrine or ephedrine for maintenance of arterial pressure during spinal anaesthesia for Caesarean section. Br J Anaesth; 1996, 76:61. 12.Husaini S and Russell I: Volume preload: lack of effect in the prevention of spinal induced hypotension at Caesarean section. Int J Obstet Anesth;1998, 7:76. 13.Pouta A, Karinen J, Vuolteenaho O and Laatikainen T: Effect of intravenous fluid preload on vasoactive peptide secretion during Caesarean section under spinal anaesthesia. Anaesthesia; 1996, 51:128. 14.Mojica J, Melendez H and Bautista L: The timing of intravenous crystalloid administration and incidence of cardiovascular side effects during spinal anesthesia: the results from a randomized controlled trial. Anesth Analg; 2002, 94:432. 15.Kamenik M and Paver-Erzen V: The effects of lactated Ringer’s solution infusion on cardiac output changes after spinal anesthesia. Anesth Analg; 2001, 92:710. 16.Loughrey J, Yao N, Datta S, Pian-Smith M and Tsen L: Hemodynamic effects of spinal anesthesia and simultaneous intravenous bolus of combined phenylephrine and ephedrine versus ephedrine for Cesarean delivery. Int J Obstet Anesth; 2005, 14:43. 17.Monthly Index of Medical Specialties, MIMS Annual 19th Edition, 1995, 836-7. 18.Macarthur A And Riley E: Obstetric anesthesia controversies: vasopressor choice for post spinal hypotension during Cesarean delivery. Int Anesthesiol Clin; 2007, 45:115. 19.Riley E: Spinal anaesthesia for Caesarean delivery: keep the pressure up and don't spare the vasoconstrictors. Br J Anaesth; 2004, 92:469. 20.Lee A, Ngan Kee W and Gin T: A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for Cesarean delivery. Anesth Analg; 2002, 94:920. 21.British National Formulary, BMJ Group and RPS Publishing, London, September 2010, 124-125. 22.LAI F And JENKINS J: Ventricular bigeminy during phenylephrine infusion used to maintain normotension during Caesarean section under spinal anaesthesia. Int J Obstet Anesth; 2007, 16:288. 23.Stoneham M, Eldridge J, Popat R and Russel R: Oxford positioning technique improves haemodynamic stability and predictability of block height of spinal anaesthesia for elective caesarean section. Int J Obstet Anesth; 1999, 8:242. 24.Thorp J and Rushing R: Umbilical cord blood gas analysis. Obstet Gynecol Clin North Am; 1999, 26:695. EVALUATION OF AN INTRAOPERATIVE ALGORITHM BASED ON NEAR-INFRARED REFRACTED SPECTROSCOPY MONITORING, IN THE INTRAOPERATIVE DECISION FOR SHUNT PLACEMENT, IN PATIENTS UNDERGOING CAROTID ENDARTERECTOMY Ioannis D. Zogogiannis*, Christos A. Iatrou**, Miltiadis K. Lazarides***, Theodossia D. Vogiatzaki****, Mitchell S. Wachtel*****, Petros K. Chatzigakis****** and Vassilios K. D imitriou ******* Abstract Background: We evaluated whether the use of an intraoperative algorithm based on cerebral oximetry with near-infrared refracted spectroscopy (NIRS) monitoring, could aid in the intraoperative decision for shunt placement, in patients undergoing carotid endarterectomy (CEA). Methods: In this prospective, randomized, controlled study were included 253 patients who underwent CEA under general anesthesia. They were randomly allocated in Group A (n = 83) using NIRS monitoring and the suggested algorithm, Group B (n = 84) using NIRS monitoring without the algorithm and Group C (n = 86) who served as controls. Shunt placement criterion for Group A and B was 20% drop in ipsilateral regional saturation from the baseline value recorded before surgery. Primary endpoint of the study was to evaluate the use of the intraoperative algorithm based on NIRS monitoring, in the intraoperative decision for shunt placement, in patients undergoing carotid endarterectomy. Additionally, we examined whether this might affect the rate of postoperative neurologic deficits. Results: When compared with Group A, Group B and Group C had 3.7 times (99% c.i 1.59.5) and 70.6 times (99% c.i. 15-724.3) respectively, greater likelihood of having a shunt placed. When compared with Group B, Group C had 19.4 times (99% c.i. 4.3-191.2) greater likelihood of having a shunt placed. Regarding the rate of postoperative neurologic deficits no significant difference was found between the three groups. Conclusions: The use of a specific algorithm based on NIRS monitoring, in patients undergoing CEA, may aid in the intraoperative decision for shunt placement. * ** Consultant Anesthetist, «G Gennimatas» General Hospital of Athens, Greece. Associate Professor of Anesthesia, Department of Anesthesia, Democritus University of Thrace Medical School, Greece. *** Professor of Vascular Surgery, Medical School, Democritus University of Thrace, Greece. **** Assistant Professor of Anesthesia, Medical School, Democritus University of Thrace, Greece. ***** Associate Professor, Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA. ****** Consultant Vascular Surgeon, Department of Vascular Surgery, «G Gennimatas» General Hospital of Athens, Greece. ******* Associate Professor of Anesthesia, Head of Department of Anesthesia, «G Gennimatas» General Hospital of Athens, Greece. Corresponding Author: Vassilios K Dimitriou, Associate Professor of Anesthesia, Head of Department of Anesthesia, «G Gennimatas» General Hospital of Athens, 154 Mesogion Avenue, 11527 Athens, Greece. Fax: +302132032212. E-mail address: [email protected] 367 M.E.J. ANESTH 21 (3), 2011 368 Keywords: Carotid endarterectomy, monitoring, cerebral oximetry. I. D. Zogogiannis et al. shunt, Financial competing interests - We have not received financial support (reimbursements, fees, funding, or grants) from an organization that may in any way gain or lose financially from the publication of this manuscript. - We do not have any other financial competing interests. Introduction Hypoperfusion during carotid endarterectomy (CEA) due to clamping of the internal carotid artery may result in cerebral ischemia or further aggravate a preexisting brain damage1-4. The complications reported in the NASCET and ECST studies, included a 5.8% and 7.5% major stroke rate and 2.1% and 3.2% mortality rate, respectively1,3. Previous studies have showed the risks for postoperative neurologic deficits during common carotid artery (CCA) cross clamping and embolic events due to vascular surgical manipulations5,6. Vascular surgeons estimate the risk adequacy of the collateral flow by measuring the stump pressure7-10. Recently, the introduction of cerebral Near-Infrared Refracted Spectroscopy (NIRS) monitoring has been associated with shorter recovery and hospital stay in noncardiac surgery11 and with a decrease in major organ dysfunction after cardiac surgery12. Furthermore, Denault et al. have suggested an algorithm based on NIRS monitoring to optimize cerebral oxygenation during surgery13. However, there are not extensive studies for the intraoperative use of NIRS and/or NIRS based intraoperative strategies during carotid endarterectomy. In this prospective study, we evaluated whether the use of an intraoperative algorithm based on NIRS monitoring, could aid the intraoperative decision for shunt placement, in patients undergoing carotid endarterectomy. Methods This prospective, controlled, randomized study was conducted in two Greek institutions from December 2007 to January 2010, and included 253 patients American Society of Anesthesiologists physical status II-III, aged 42-82 years who underwent carotid endarterectomy. The study was in conformation with the principles outlined in the Declaration of Helsinki and was approved by the Institutional Ethics Committee. The criteria for carotid endarterectomy were symptomatic carotid artery stenosis greater than 70% and asymptomatic carotid artery stenosis greater than 80% with coexisting risk factors14. The degree of stenosis was evaluated by means of vascular ultrasound and invasive angiography. Preoperatively, all patients underwent a complete clinical neurologic evaluation followed by a brain computed tomography (CT) scan. Anesthetic management was standardized. Anesthesia was induced with fentanyl and propofol. Neuromuscular blockade was achieved with cisatracurium. Maintenance was with remifentanil infusion, sevoflurane in oxygen and nitrous oxide. Heparin 100U/kg was administered five minutes before carotid cross clamping (CCC). Stump pressure was measured using a transducer system connected to 22G catheter. Thirty minutes before emergence morphine was administered for postoperative analgesia. Standard monitoring in all patients included electrocardiography (ECG), end tidal carbon dioxide (EtCO2), invasive blood pressure (IBP) and pulse oximetry (SpO2). Patients were randomly allocated by using closed envelopes into three groups. In the first and second group (group A and group B respectively), in addition to the above mentioned monitoring, cerebral oximetry with near-infrared refracted spectroscopy (INVOS 4100, Somanetics Inc., Troy MI) was used. Patients in the third group (Group C) underwent routine CEA without INVOS monitoring and served as control group. In groups A and B, the cerebral oximetry sensors (rSO2) were placed on the forehead over the eyebrows monitoring the ipsilateral and contralateral hemispheres. Baseline rSO2 values were obtained before induction and without any medication administered and from that point continuous recording every 10 seconds was established. Cerebral oximetry changes were recorded when the patient entered the operating room without any medication (T1), 2min before CCC (T2), 2min after CCC (T3), 2min after end of patching during reperfusion (T4), 10min after reperfusion (T5) and after emergence (T6). The change from the baseline (ΔrSO2) taken before induction EVALUATION OF AN INTRAOPERATIVE ALGORITHM BASED ON NEAR-INFRARED REFRACTED SPECTROSCOPY MONITORING, IN THE INTRAOPERATIVE DECISION FOR SHUNT PLACEMENT, IN PATIENTS UNDERGOING CAROTID ENDARTERECTOMY was recorded in percentage. The rSO2 values were recorded as averages. A 20% drop from the baseline was considered as a cutoff value for ischaemia and the surgeon was notified. This value has been well established from previous studies15-17. During the above time points vital signs (MAP, HR, EtCO2) were recorded in all patients. Patients in group A were managed according to the algorithm developed by Denault et al13 for patients undergoing cardiac surgery, which was adjusted for patients undergoing carotid surgery by our team (Fig. 1). On the other hand, in patients of group B cerebral oximetry values were recorded but anesthesia management was not based upon the aforementioned algorithm. Patients who exhibited new neurologic deficits postoperatively that persisted for more than 24 hours underwent a followup brain CT scan. Fig. 1 The suggested intraoperative algorithm based on cerebral oximetry with near-infrared refracted spectroscopy 369 Primary end point of the study was to evaluate whether the use of the intraoperative algorithm based on NIRS monitoring might affect the intraoperative decision for shunt placement, in patients undergoing carotid endarterectomy. Additionally, the possible effect of the above algorithm upon the rate of postoperative short-term neurologic deficits was examined. Statistical Analysis Categorical variables were evaluated by twotailed Fisher exact tests, with odds ratio estimates for 2 x 2 tables being conditional maximum likelihood estimates. Continuous variables were evaluated by twotailed Welch's t tests, with natural logarithms of ratios being taken. Because three statistical assessments were performed for many variables, alpha was adjusted such that null hypotheses were rejected when P < 0.5/3 ≈ 0.015. Power analysis was performed with Power And PrecisionTM (Biostat, Inc., Englewood, NJ). Other statistical analyses were performed on R2.10.1 (R Development Core Team (2009). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, URL http://www.R-project.org). All remaining analyses had results that might have been due to chance (P > 0.015, for each analysis); power analysis revealed all would have been able to detect moderate sized differences. Seventy patients per patient group detects as significant moderately-sized differences for χ² tests of 2 x 2 contingency tables and two-tailed t tests in 81% of studies with alpha = 0.01. Table 1 Demographic and clinical characteristics Group A Group B Group C (n = 83) (n = 84) (n = 86) P-values Fisher exact test, two-tailed A vs B A vs C B vs C Gender (M/F) 57/26 68/16 Mean (range) 60/26 0.20 0.87 0.12 Age (yrs) BMI (kg/m2) 69.1 (50-82) 27.7 (23.1-33.1) 68.3 (48-80) 26.9 (21.5-33.8) N (%) 68.4 (48-81) 28.2 (22-33.1) 0.28 0.15 0.28 0.31 0.40 0.0057 Hyperlipidemia Hypertension Diabetes mellitus Coronary artery disease 42/83 (50.6%) 45/83 (54.2%) 21/83 (25.3%) 32/83 (38.5%) 41/84 (48.8%) 47/84 (55.9%) 21/84 (25%) 31/84 (36.9%) 40/86 (46.5%) 46/86 (53.4%) 24/86 (27.9%) 33/86 (38.3%) 0.71 0.68 0.87 0.7 0.3 0.85 0.7 0.75 0.56 0.65 0.71 0.7 Hemodialysis 4/83 (4.8%) 5/84 (5.9%) 5/86 (5.8%) 0.85 0.88 0.88 M.E.J. ANESTH 21 (3), 2011 370 I. D. Zogogiannis et al. Table 2 Preoperative neurologic status Group A Group B Group C (n = 83) (n = 84) (n = 86) Asymptomatic 56/83 (67.4%) 56/84 (66.7%) 58/86 (67.4%) Symptomatic 27/83 (32.5%) 27/84 (32.1%) 27/86 (31.3%) Stroke 11/83 (13.2%) 13/84 (15.4%) 14/86 (16.2%) TIAs 9/83 (10.8%) 10/84 (11.9%) 10/86 (11.6%) Amaurosis fugax 7/83 (8.4%) 5/84 (5.9%) 4/86 (4.6%) Differences between groups were not statistically significant (Fisher’s test), TIAs: Transient Ischemic Attacks. Results Patients were randomly allocated to three groups: group A (n = 83) and group B (n = 84) in which NIRS monitoring was applied and group C (n = 86) in which only standard anesthesia monitoring was used (control group). There were no differences between groups with respect to demographic and clinical characteristics (Table 1). There were not statistically significant differences in the preoperative neurologic status between the three groups (Table 2). Table 3 shows data from the monitoring of intraoperative vital signs. MAP values taken two minutes after the opening of the CCA (T4) were decreased in all groups as compared to values taken two minutes before CCA cross clamp (T2). Chronological alterations in MAP between the above two time points (MAP T4/T2 ratios) were significantly increased in both groups A and B as compared to controls, which means that accordingly there was a smaller amount of reduction in MAP values in groups A and B as compared to controls (Table 3). EtCO2 values taken two minutes after the opening of the CCA (T4) were increased in groups A and B, while decreased in controls, as compared to values taken two minutes before CCA cross clamp (T2) (Table 3). Finally, chronological alterations in rSO2 values between two minutes after CCA cross clamp and two minutes before CCA cross clamp, as described by the rsO2 T3/T2 ratio, showed an increase of the above ratio in group A as compared to group B (Table 3). Table 4 describes significant differences concerning shunt placement that were recorded between groups. Specifically, patients in groups B and C exhibited 3.7 times (99% c.i 1.5 - 9.5) and 70.6 times Table 3 Intraoperative monitoring data Group A (n = 83) MAP T3/T2 MAP T4/T2 0.85 (0.6-1.14) 0.86 (0.58-1.2) Group B Group C (n = 84) (n = 86) Log mean (range) 0.87 (0.54-1.2) 0.83 (0.65-1.1) 0.96 (0.74-1.4) 0.78 (0.57-1.35) P-values Welch's t test, two-tailed, on logs A vs B A vs C B vs C 0.57 0.31 0.11 < 0.001 0.002 < 0.001 MAP T5/T2 0.81 (0.6-1.27) 0.92 (0.65-1.3) 0.77 (0.6-1.04) < 0.001 0.07 < 0.001 HR T3/T2 0.97 (0.68-1.9) 1.0 (0.66-1.5) 0.96 (0.65-1.5) 0.39 0.76 0.20 HR T4/T2 1.01 (0.75-1.7) 1.03 (0.57-1.5) 0.98 (0.6-1.5) 0.50 0.46 0.19 HR T5/T2 1.01 (0.75-1.5) 1.0 (0.60-1.5) 1.04 (0.8-1.6) 0.85 0.36 0.30 etCO2 T3/T2 1.03 (0.90-1.2) 1.01 (0.92-1.1) 0.95 (0.8-1.2) 0.015 < 0.001 < 0.001 etCO2 T4/T2 1.05 (0.94-1.4) 1.02 (0.92-1.1) 0.93 (0.8–1.0) 0.006 < 0.001 < 0.001 etCO2 T5/T2 1.03 (0.9-1.3) 1.03 (0.97-1.1) 0.90 (0.8–1.0) 0.87 < 0.001 < 0.001 rSO2 T3/T2 0.91 (0.73-1.1) 0.85 (0.6-1.1) § < 0.001 § § rSO2 T4/T2 1.04 (0.9-1.2) 1.02 (0.82-1.2) § 0.11 § § rSO2 T5/T2 1.04 (0.9-1.2) 1.03 (0.83-1.2) § 0.43 § § MAP: mean arterial pressure, HR: heart rate etCO2: end-tidal carbon dioxide, rSO2: cerebral oximeter measured regional hemoglobin saturation in cerebral tissue ipsilateral to the operated carotid artery. MAP, HR, et CO2 and rSO2 ratios reference ratios of measurements taken at different time points: T2 - two minutes before common carotid artery cross clamp; T3 - two minutes after common carotid artery cross clamp; T4 - two minutes after opening common carotid artery; T5 - ten minutes after opening common carotid artery. § rSO2 values were not recorded in the control group. EVALUATION OF AN INTRAOPERATIVE ALGORITHM BASED ON NEAR-INFRARED REFRACTED SPECTROSCOPY MONITORING, IN THE INTRAOPERATIVE DECISION FOR SHUNT PLACEMENT, IN PATIENTS UNDERGOING CAROTID ENDARTERECTOMY (99% c.i. 15 - 724.3), respectively, greater likelihood of having a shunt placed, as compared with patients in group A. When compared with Group B, Group C had 19. 4 times (99% c.i. 4.3 - 191.2) greater likelihood of having a shunt placed. Table 4 Intraoperative shunt placement Shunt Not placed Placed p-value Fisher's exact test Group C 0 (0%) 86 (100%) <0.001 Group A 60 (72.3%) 23 (27.7%) <0.001 Group B 34 (40.5%) 50 (59.5%) <0.001 There were no significant differences between the three groups regarding postoperative neurologic deficits (Table 5). Thirty two out of the total 253 patients (12.6%) experienced neurologic deficits postoperatively and only 13 out of the total 253 patients (5.1%) suffered a permanent deficit confirmed by a CT scan as an ischemic region. Finally, seven out of the total 253 patients (2.7%), (group A n = 1, group B n = 2 and group C n = 4) exhibited evidence of cardiovascular ischemia, as assessed by clinical and laboratory examinations; while 2 out of the total 253 patients (0.8%), one in group B and one in group C, expired due to cardiovascular events, postoperatively. Table 5 Postoperative neurologic deficits between groups Neurologic deficit Group A Group B Group C No 73 (87.9%) 73 (86.9%) 75 (87.3%) Yes 10 (12.1%) 11 (13.1%) 11 (12.7%) P-value Fisher's exact test 0.89 Discussion We demonstrated that the use of an intraoperative algorithm based on NIRS monitoring, in patients undergoing carotid endarterectomy, may aid in the intraoperative decision for shunt placement. The latter during carotid endarterectomy is a surgical practice that may minimize the risk of perioperative cerebral ischemia18. However, definite benefits from this intraoperative practice have not been published yet. Additionally, there is no consensus whether routine shunting is superior to selective shunting during carotid endarterectomy19. The present data suggested that in patients in whom 371 an intraoperative algorithm based on NIRS monitoring was used (group A), the rate of shunt placement was reduced as compared to patients in whom even though NIRS monitoring was applied the specific algorithm was not utilized (group B). Additionally, no significant differences between the three groups concerning the rate of postoperative neurologic deficits were recorded. Postoperatively, 12.6% of patients presented with new neurologic deficits, and only 5.1% of patients were diagnosed with permanent deficits. These findings are in agreement with the NASCET and ECST studies1,2. During surgery the identification of possible hypoperfusion may aid in the intraoperative decision for the necessity of shunt placement. Intraoperative stroke accounts for 15–20% of the perioperative strokes, due to hypoperfusion during cross-clamping or thromboembolism20,21. Intraoperative neurological deficit is most often associated with carotid artery dissection or clamp release (83%) and only rarely (17%) with cross-clamping22. Mental status evaluation during carotid crossclamping in the awake patient remains the gold standard with which other methods of monitoring should be compared23,24. Monitoring of the conscious patient provides a unique opportunity to determine the time of onset of a neurological deficit and to deduce the likely cause25,26. In patients under general anesthesia monitoring with electroencephalography (EEG) is oftentimes applied27, however this method can not reliably detect cerebral ischaemia and therefore provide a clear guide to shunting. Recent data reported a 82% rate of shunting in patients who underwent CEA under general anesthesia28, which is significantly higher compared with the 28.4% recorded rate in our patients in whom the specific intraoperative algorithm based on NIRS monitoring was used. Cerebral oximetry with near-infrared spectroscopy (NIRS) allows for continuous monitoring of changes in cerebral oxygenation (rSO2) through adhesive sensors on the patients’ forehead16,29,30. NIRS was evaluated under regional anesthesia in patients undergoing CEA by previous studies (16, 31). In these studies rSO2 values showed an intersubject variability in the pre-clamp period. Specifically, Samra et al16 considered a decrease in rSO2 of 20%, or an absolute reading of less than 50%, as indicative of cerebral M.E.J. ANESTH 21 (3), 2011 372 I. D. Zogogiannis et al. ischaemia, resulting in a false-negative rate of 2.6% and a false-positive rate of 66.7%. Roberts et al31 used a decrease of ≥ 27% in rSO2 as indication for a shunt and had no false-negative or false-positive results in 45 patients. A possible explanation was the shorter duration of cross-clamping, and it was demonstrated that permanent sequelae result from a combination of both the magnitude and duration of ischaemia31. the study groups postoperatively. Therefore placement of shunt may not be of the major criteria to avoid neurological complications. It may be the patient's integrity of circle of Willis and collateral circulation to compensate the acute ischemia during carotid cross clamp. From this point of view cerebral oximetry with near-infrared spectroscopy may be a useful and effective monitoring. Our study implemented the use of NIRS monitoring along with a series of interventions such as intraoperative adjustments of MAP, CO2, FiO2 and pertinent modifications in the depth of anesthesia in order to provide a safe guide for shunting. Our study exhibits several limitations. First, embolic insult is a significant factor in determining patient outcome and no published studies have demonstrated that NIRS can detect emboli. On the other hand, neither EEG nor SEP can detect emboli and even the usage of transcranial Doppler is rather problematic in detecting emboli32-34. Additionally, NIRS is highly regional in nature and monitoring is limited to a small but critical area of the watershed between the middle and anterior cerebral arteries territories. In the present study a 20% drop in rSO2 was used as a cutoff value indicative of cerebral ischemia, which is comparable to previous reports16,31. Interestingly, we found that chronological alterations in between and two minutes before CCA cross clamp, as described by the rsO2 T3/T2 ratio, showed an increase of the above ratio in group A as compared to group B. Hence, two minutes after CCA cross clamp rSO2 values were increased in group A as compared to group B. This might be attributed to the fact that intraoperative adjustments of MAP, CO2, FiO2 and pertinent modifications in the depth of anesthesia, according to the suggested algorithm, were applied only in patients of group A. However, no significant differences in the rate of new neurologic deficits were recorded between Conclusions We found that the use of an intraoperative algorithm based on NIRS monitoring, in patients undergoing carotid endarterectomy, may aid in the intraoperative decision for shunt placement. However, no significant effect of the above method upon the rate of postoperative neurologic deficits was observed. EVALUATION OF AN INTRAOPERATIVE ALGORITHM BASED ON NEAR-INFRARED REFRACTED SPECTROSCOPY MONITORING, IN THE INTRAOPERATIVE DECISION FOR SHUNT PLACEMENT, IN PATIENTS UNDERGOING CAROTID ENDARTERECTOMY 373 References 1. North American Symptomatic Carotid Endarterectomy Trial Collaborators: Beneficial effect of carotid endarterctomy in symptomatic patients with high grade carotid stenosis. N Engl J Med; 1991, 325:445-453. 2. Executive Committee for the Carotid Atherosclerosis Study: Endarterectomy for asymptomatic carotid artery stenosis. JAMA; 1995, 273:1421-1428. 3. European Carotid Surgery Trialists' Collaborative Group. MRC European Carotid Surgery Trial: Interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. Lancet; 1991, 337:1235-1243. 4. Batnett HJ, Taylor DW, Eliasziw M et al: Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. N Engl J Med; 1998, 339:1415-1425. 5. Cantelmo NL, Babikian VL, Samaraweera RN et al: Cerebral microembolism and ischemic changes associated with carotid enderterectomy. J Vasc Sur; 1998, 27:1024-1031. 6. Jansen C, RamosLMP, van Heesewijk JPM et al: Impact of microembolism and hemodynamic changes in the brain during carotid endarterectomy. Stroke; 1994, 25:992-997. 7. Michal V, Hejnat L, Firt P: Temporary Shunts in vascular surgery. Thoraxchir Vask Chir; 1966, 14(1):35-43. 8. Kelly JJ, Callow AD, O'Donnell TF et al: Failure of carotid stump pressures. Its incidence as a predictor for a temporary shunt during carotid endarterectomy. Arch Surg; 1979, 114 (12):1361-1366. 9. Kwaan JH, Peterson GJ, Connolly JE: Stump pressure: an unreliable guide for shunting during carotid endarterectomy. Arch Surg; 1980, 115(9):1083-86. 10.Cherry KJ Jr, Roland CF, Hallett JW Jr et al: Stump pressure, the contralateral carotid artery, and electroencephalographic changes. Am J Surg; 1991, 162(2):185-189. 11.Casati A, Fanelli G, Pietropaoli P, et al: Continuous monitoring of cerebral oxygen saturation in elderly patients undergoing major abdominal surgery minimizes brain exposure to potential hypoxia. 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ANESTH 21 (3), 2011 Effects of preoperative oral carbohydrates and trace elements on perioperative nutritional status in elective surgery patients Yoshimasa Oyama*, Hideo Iwasaka*, Keisuke Shiihara*, Satoshi Hagiwara*, Nobuhiro Kubo**, Yutaka Fujitomi***, Takayuki Noguchi* Abstract Purpose: In order to enhance postoperative recovery, preoperative consumption of carbohydrate (CHO) drinks has been used to suppress metabolic fluctuations. Trace elements such as zinc and copper are known to play an important role in postoperative recovery. Here, we examined the effects of preoperatively consuming a CHO drink containing zinc and copper. Methods: Subjects were 122 elective surgery patients divided into two groups (overnight fasting and CHO groups); each group was further divided into morning or afternoon surgery groups. Subjects in the CHO group consumed 300 mL of a CHO drink the night before surgery, followed by 200 ml before morning surgery or 700 ml before afternoon surgery (≥2 hours before anesthesia induction). Blood levels of glucose, nonesterified fatty acids (NEFA), retinol-binding protein, zinc, and copper were determined. Results: One subject in the CHO group was excluded after refusing the drink. There were no adverse effects from the CHO drink. NEFA levels increased in the fasting groups. Although zinc levels increased in the CHO group immediately after anesthesia induction, no group differences were observed the day after surgery. Conclusion: Preoperative consumption of a CHO drink containing trace elements suppressed preoperative metabolic fluctuations without complications and prevented trace element deficiency. Further beneficial effects during the perioperative period can be expected by adding trace elements to CHO supplements. * ** *** M.D. Ph.D, Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita, Japan. M.D, Ph.D, Department of Surgery, Oita Kouseiren Tsurumi Hospital, Oita, Japan. M.D., Ph.D, Department of Breast Surgery, Oita Kouseiren Tsurumi Hospital, Oita, Japan. Corresponding Author: Yoshimasa Oyama M.D, Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka-Hasamamachi, Yufu City, Oita 879-5593, Japan. Tel: +81-97-586-5943, Fax: + 81-97-586-5949. E-mail: [email protected] 375 M.E.J. ANESTH 21 (3), 2011 376 Introduction In the last decade, the customary practice of overnight fasting before elective surgery has been reconsidered, and a shorter fasting time has been advised. Intake of water, black coffee, tea, or fruit juice without pulp up to 2 to 3 h before anesthesia induction does not increase the risk of pulmonary aspiration and is recommended by anesthesiology societies in many countries1-4. However, while thirst, unfitness, and malaise prior to surgery can be improved by preoperative intake of such drinks5, metabolism is unchanged because the drinks contain few calories. In recent years, preoperative management has focused on maintaining physiologic function and enhancing postoperative recovery. The Enhanced Recovery After Surgery (ERAS) critical care protocol recommends the preoperative consumption of a carbohydrate (CHO) drink6, which helps maintain the nutritional state and suppress catabolism due to surgical stress7. Furthermore, it has been reported to enhance recovery and reduce the duration of hospitalization8. Many nutrients are important for postoperative recovery, including the trace elements zinc (Zn) and copper (Cu), which are important in wound healing. Zn is required by enzymes involved in cell division and proliferation, and Cu is required for initiate the cross-linking of elastin and collagen9,10. Surgical stress increases Zn and Cu consumption11, increases their excretion in urine and discharge through drains12-14, and causes their direct loss by bleeding. Moreover, the demand for these elements increases during the postoperative assimilation phase, resulting in perioperative Zn and Cu deficiencies. Low preoperative concentrations of Zn have been observed in patients with delayed postoperative wound healing15, and satisfactory outcomes have been obtained for burn patients by early administration of trace elements16. However, studies evaluating the effects of preoperative supplementation of trace elements in elective surgery patients have not been reported. In order to evaluate the nutritional state resulting from preoperative nutrition management, a dynamic index capable of detecting subtle changes is needed. Generally, a protein with a short half-life is used for this purpose. Among such proteins, retinol-binding protein (RBP) is considered a good indicator of Y. Oyama et al. daily nutritional changes17, and is well-suited for evaluating nutritional states that may be influenced by preoperative nutrition management. Preoperative oral CHO administration is used effectively throughout Europe and the United States. However, conventional overnight fasting is still used as standard practice in some nations18,19. The aim of this study was to evaluate the effects of an 18% CHO drink containing trace elements on preoperative nutritional state and trace element levels as compared with a conventional fasting protocol. Methods This study was conducted between May and August 2009. The study protocol was approved by the Medical Ethics Committee of Oita Kouseiren Tsurumi Hospital, and was carried out in accordance with the Helsinki Declaration. For all subjects, we provided a full explanation of the aims and methods of the study and obtained their informed consent. Patients Subjects were 122 elective surgery patients. Selection criteria were: scheduled surgery; age, 20-89 years; body mass index (BMI), 18-35; and American Society of Anesthesiologists (ASA) physical status (PS) classification, 1-3. Exclusion criteria were: diabetes, abnormal glucose tolerance, upper gastrointestinal disease (gastroesophageal reflux, hiatal hernia), ileus, use of drugs that cause delayed gastric emptying, and patients that needed to begin fasting two days before surgery. One subject in the CHO consumption group refused the CHO drink after we obtained consent, and was therefore excluded. Patients were divided into two groups according to the period of study: 1) The first 2-month period involved the conventional overnight fasting protocol at this hospital (fasting group, n = 61); 2) the next 2-month period used the new protocol of preoperative CHO drink supplementation (CHO group, n = 60). Both groups were further divided into morning surgery (AM group, 9:30-10:00 surgery suite entry) and afternoon surgery (PM group, 14:00-16:00 surgery suite entry). Patient characteristics are shown in Table 1. Effects of preoperative oral carbohydrates and trace elements on perioperative nutritional status in elective surgery patients 377 Table 1 Patient characteristics and demographic data AM fasting PM fasting AM CHO PM CHO n = 26 n = 35 n = 27 n = 33 9/17 17/18 7/20 15/18 Age (y) 62 ± 11 61 ± 18 59 ± 12 61 ± 15 Height (cm) 157 ± 9 159 ± 9 159 ± 9 157 ± 9 Weight (kg) BMI (kg/m2) 59 ± 12 60 ± 12 61 ± 10 58 ± 9 24 ± 4 24 ± 4 24 ± 3 24 ± 3 ASA (I/II/III) 4/22/0 5/29/1 6/20/1 7/25/1 Sex (M/F) 178 ± 81# Duration of surgery (min) 132 ± 64 135 ± 60 132 ± 72 Data are presented as absolute numbers or mean ± SD. CHO = carbohydrate, M = male, F = female, BMI = body mass index, ASA # = classification of illness according to the American Society of Anesthesiology. P <0.05 vs. PM fasting, AM CHO, and PM CHO groups (ANOVA). Study protocol For all patient groups, the final meal before surgery was at 18:00. The fasting group began their fast at 21:00 on the night before surgery. The CHO group ingested a CHO drink (IsocalTM, Arginaid® drink, Nestle) the CHO drink and then waited 2-3 hours before surgery: AM surgery group (300 ml from 21:00 throughout the night before surgery and 200 ml from 6:30 to 7:30 on the day of surgery), and PM surgery group (300 ml from 21:00 throughout the night before surgery, and on the day of surgery, 200 ml from 6:30 to 7:30, 300 ml from 9:00 to 10:00, and 200 ml from 11:00 to 12:00) (Fig. 1). The contents of the Arginaid® drink are shown in Table 2. In the fasting group, intravenous crystalloid fluid solution without sugar was initiated at 9:00 for morning and afternoon surgeries. In the CHO group, intravenous crystalloid fluid solution without sugar was initiated at 9:00 for morning surgeries and 13:00 for afternoon surgeries. Blood samples for measuring blood glucose, nonesterified fatty acid (NEFA), RBP, Zn, Cu, blood urea nitrogen (BUN), and creatinine were collected immediately after anesthesia induction, and blood samples for Zn and Cu measurements were also collected the following morning. To assess patient discomfort before surgery, we asked questions regarding thirst, hunger, and anxiety using a questionnaire immediately after they entered the surgery suite. Responses were given using a 5-point Likert scale (1: not at all, 2: hardly, 3: neither, 4: somewhat, 5: very much). Fig. 1 Timeline of perioperative carbohydrate (CHO) drink consumption Table 2 Contents of the preoperative carbohydrate drink suppleent (ISOCAL® Arginaid® drink) Typical contents per 100 ml Carbohydrates 18 g Protein 2g L-arginine 2g Phosphorus 18 mg Zinc 8 mg Copper 0.8 mg Anesthesia and surgery No premedication was administered, and patients walked into the surgery suite. If there were no contraindications, patients received an epidural catheter at an appropriate location before general anesthesia in thoracic surgery, orthopedic surgery of the lower limbs, or urinary tract surgery. Epidural anesthesia was initiated before general anesthesia with mepivacaine. When combined with epidural anesthesia, general anesthesia was induced with propofol (2 mg/kg) and vecuronium (0.1 mg/kg), M.E.J. ANESTH 21 (3), 2011 378 and maintained by sevoflurane (1%3%-). When not combined with epidural anesthesia, general anesthesia was induced with propofol (1.5 mg/kg), vecuronium (0.1 mg/kg), and remifentanil (0.5 µg/kg/min); sevoflurane (1%-3%) and remifentanil (0.2-0.5 µg/ kg/min) were used for maintenance. Heart rate and blood pressure were recorded at the following time periods: immediately before anesthesia induction, and 1, 2, and 5 minutes after anesthesia induction. The anesthesiologist maintained normovolemia throughout the surgery and gave a single injection of ephedrine (4 mg) as a vasopressor to maintain mean systolic blood pressure at 60-70 mmHg. When the target blood pressure could not be maintained, the anesthesiologist initiated continuous infusion of dopamine (2-5 µg/kg/min). Assessment of gastric content volume To determine residual gastric content, a doublelumen gastric tube was inserted immediately after anesthesia induction. Insertion into the stomach was confirmed by auscultation and aspiration. The gastric tube was moved several times, and gastric juice was aspirated at several locations. The amount of gastric juice was then measured. Biochemical analysis Blood glucose levels were measured immediately after collection by the glucose oxidase method using a blood gas analyzer (ABL-555, Radiometer, Copenhagen, Denmark). Blood samples for measuring NEFA, RBP, Zn, Cu, BUN, and creatinine were centrifuged immediately after collection and stored at -20˚C until analysis. NEFA levels were determined by enzymatic methods (SRL, Tokyo, Japan), and RBP levels were determined with nephelometric methods (SRL, Tokyo, Japan). Serum BUN (urease-glutamate dehydrogenase method), creatinine (sarcosine oxidase-peroxidase method), Zn (5-Br-PAPS colorimetric method; reference range118-66 µg/dl), and Cu (3,5-DiBrPAESA colorimetric method; reference range 71-132 µg/dl) were determined by an automated analyzer (TBA-200FR; Toshiba Medical Systems, Tokyo, Japan) and commercial kits (Shino-Test, Tokyo, Japan for creatinine, Zn, and Cu; SYSMEX, Hyogo, Japan for BUN). Y. Oyama et al. Statistical analysis Parametric data are expressed as mean ± standard deviation (SD); group differences were determined by one-way ANOVA or Student’s t-test, and differences in repeated measurements by Fisher’s protective leastsquares difference and paired samples t-test. Nonparametric data are expressed as medians and quartiles; group differences were determined by the Kruskal-Wallis test and differences in repeated measurements by the Mann-Whitney U-test. P <0.05 was considered significant. Statistical analysis was carried out with StatView for Windows, version 5.0 (SAS Institute Inc.). Results Demographic data Of the 122 elective surgery patients, one subject in the CHO group refused the CHO drink after we obtained consent and was thus excluded; 121 subjects completed the study. There were no differences in patient characteristics before surgery; however, surgery duration for the AM fasting group was longer than that of the other patient groups (Table 1). The types of surgery performed are shown in Table 3. Thoracic surgeries were lobectomies and partial lobectomies, breast surgeries were mastectomies and breast preservations, gastrointestinal surgeries were laparoscopic cholecystectomies, plastic surgeries were body surface surgeries, orthopedic surgeries were joint replacement and spinal surgeries as well as osteosynthesis of broken limbs, and urinary tract surgeries were prostatectomies and bladder removal. Given the hospital’s surgery schedule, no orthopedic or urinary surgeries were performed in the morning (AM) surgery groups. Table 3 Surgical procedures AM fasting PM fasting AM CHO PM CHO n =26 n =35 n =27 n =33 Thoracic, n Breast, n Digestive, n Urologic, n Plastic surgery, n Orthopedic, n CHO = carbohydrate. 8 11 4 0 3 0 2 6 3 5 8 11 8 7 5 0 7 0 2 8 2 5 9 7 Effects of preoperative oral carbohydrates and trace elements on perioperative nutritional status in elective surgery patients 379 Table 4 Preoperative patient characteristics AM fasting n =26 Glucose (mg/dl) PM fasting n =35 102 ±14 93 ±11 AM CHO n =27 PM CHO n =33 104 ±16 105 ±11 §§ # 475 ±278 ** 589 ±357 †† NEFA (µEq/L) 679 ±237 927 ±317 RBP (mg/dl) 4.1 ±1.4 3.7 ±1.1 3.8 ±0.9 5.0 ±6.6 BUN (mg/dl) 15 ±7 14 ±4 14 ±3 16 ±4 Creatinine (mg/dl) 0.8 ±0.4 0.7 ±0.2 0.7 ±0.1 0.8 ±0.2 Data are presented as mean ± SD. CHO = carbohydrate, NEFA = nonesterified fatty acids, RBP = retinol binding protein. §§P <0.01 vs. AM fasting, AM CHO, and PM CHO groups; #P <0.05 vs. AM fasting; **P <0.01 vs. AM fasting; † †P <0.01 vs. PM fasting. Preoperative fasting duration was 751 ± 6 min for AM fasting and 1013 ± 13 min for PM fasting. The time from final CHO drink consumption to anesthesia was 201 ± 4 min for the AM CHO group and 209 ± 11 min for the PM CHO group. In the CHO groups, the time from the final meal excluding drink consumption was 754 ± 9 min for AM CHO and 1023 ± 15 min for the PM CHO group, which did not differ significantly from fasting durations in the fasting groups. Effects of CHO consumption on preoperative biochemical data As shown in Table 4, blood glucose levels immediately after anesthesia induction were lower in the PM fasting group than in other patient groups. However, NEFA increased more in the PM fasting group (927 ± 54 µEq/L) than the AM fasting group (679 ± 46 µEq/L; P = 0.022), and was lower in the AM CHO group (475 ± 54 µEq/L) than the AM fasting group (679 ± 46 µEq/L; P = 0.016). Likewise, there was a significant decline in the PM CHO group (589 ± 62 µEq/L) compared with the PM fasting group (927 ± 54 µEq/L; P <0.001). In contrast, RBP, BUN, and creatinine levels did not differ among patient groups. Effects of CHO on serum trace element levels Table 5 shows that, immediately after anesthesia induction, serum levels of Zn were higher in the CHO groups than in the fasting groups (AM fasting vs. AM CHO: 67 ± 2 μg/dl vs. 105 ± 4 μg/dl, P <0.001; PM fasting vs. PM CHO: 69 ± 2 μg/dl vs.100 ± 4 μg/dl, P <0.001). However, on postoperative day 1, Zn levels had decreased in the CHO groups and were not significantly different from the fasting groups. Serum levels of Cu did not differ among groups immediately after anesthesia induction or on postoperative day 1. However, in the CHO group, Cu levels on postoperative day 1 were lower than those observed immediately after anesthesia induction. Table 5 Trace elements AM fasted PM fasted AM CHO PM CHO n =26 n =35 n =27 n =33 67 ± 9 69 ± 10 105 ± 19** 62 ±10 ## 59 ±15 ## 65 ±10 ## 65 ±21 ## 96 ±16 96 ±17 93 ±16 # 96 ±15 102 ±23 95 ±21 ## Zn (μg/dl) Anesthesia induction Day 1 Cu (μg/dl) Anesthesia induction Day 1 Data are presented as mean ± SD. CHO = carbohydrate. anesthesia induction; ##P <0.01 vs. anesthesia induction. 95 ±14 ** P <0.01 versus AM fasting; 96 ±16 †† 100 ± † 21† P <0.01 vs. PM fasting; ## P <0.01 vs. M.E.J. ANESTH 21 (3), 2011 380 Effects of CHO on preoperative discomfort Answers to the questionnaire evaluating thirst, hunger, and anxiety before anesthesia induction did not differ significantly among groups (Table 6). Effects of CHO on perioperative clinical data Heart rate and blood pressure at each time periods did not differ significantly across groups. At 1, 2, and 5 minutes after anesthesia induction, heart rate and blood pressure were lower than those observed immediately before anesthesia induction (Table 7). During the anesthesia induction period, inotrope requirements did not differ across groups. For PM surgeries, preoperative intravenous fluid replacement was lower in the CHO groups than the fasting groups due to protocol differences; however, no differences in intravenous fluid replacement amounts were observed among patient groups during surgery. We did not observe a single case of pulmonary aspiration or other adverse event associated with CHO drink consumption. Mean gastric juice volumes immediately after anesthesia induction were low, and did not differ among groups (Table 8). Maximum volumes of gastric juice were 83 ml (AM fasting), 60 ml (PM fasting), 71 ml (AM CHO), and 33 ml (PM CHO). Discussion The present study shows that preoperative supplementation of a CHO drink containing trace elements suppresses preoperative increases in NEFA levels and decreases in Zn levels. The CHO drink was a hypertonic solution containing protein and trace elements; therefore, gastric retention time may have been prolonged compared with that of an isotonic CHO drink. Henriksen et al. reported that preoperative supplementation with a drink containing 12.5% CHO and 3.5% protein did not increase gastric juice volume. Likewise, we did not observe increased gastric juice volume or pulmonary aspiration, demonstrating the safety of this perioperative protocol. The CHO group took more water during the preoperative period than did the fasting group. However, during the anesthesia induction period, heart Y. Oyama et al. rate and blood pressure did not differ significantly across groups, indicating that the balance of bodily fluids did not differ significantly. We also observed no group-dependent differences in intraoperative fluid volume or urinary volume. These observations may indicate that dehydration caused by overnight fasting as well as that caused by CHO drink replacement is within a normal range of homeostasis, and is mainly regulated by renal function. In the CHO groups, preoperative NEFA levels were low compared to those of the fasting groups due to lipolysis suppression, which is consistent with previous reports by Soope et al. and Henriksen et al.7,20. Elevated NEFA levels suppress phosphoinositide 3-kinase in muscle cells, thereby lowering glucose uptake and promoting insulin resistance21. Accordingly, glucose oxidation and nonoxidative glucose disposal have been prevented by intravenous administration of lipids to healthy adults22. Preoperative consumption of a CHO drink has also been shown to attenuate insulin resistance23, possibly by reducing NEFA levels. RBP changes were not observed in the present study. The half-life of RBP is 10 to 20 h, suggesting that RBP would respond to subtle differences in the nutritional state caused by brief perioperative fasting or CHO drink consumption. Fasting times were 12 to 17 h, which may have been too short to be captured by RBP changes. Deteriorating renal function can also increase RBP [24], but no differences in renal function were observed in the study. Wound repair is an important postoperative process, and delayed wound healing is a serious problem. The trace elements Zn and Cu are important in wound healing. Zn is essential for cell division and proliferation, and demand for Zn increases after surgery. In a state of deficiency, Zn is supplied by bone, muscle, and the liver, which generally store Zn. In the present study, we observed that preoperative serum Zn concentrations were decreased to the lower end of the reference range in the fasting groups, which reflects the notion that serum Zn is taken from storage. However, surgical stress increases Zn demand11 as well as depletes it through draining12-14 and bleeding. Thus, Zn deficiencies are likely during the perioperative period. In contrast, we observed higher serum Zn concentrations in the CHO groups. This suggests Effects of preoperative oral carbohydrates and trace elements on perioperative nutritional status in elective surgery patients 381 Table 6 Preoperative discomfort evaluated by 5-point Likert scale AM fasting n = 26 PM fasting n = 35 AM CHO n = 27 PM CHO n = 33 Thirst 2.5 (0.5-4.5) 3 (1-5) 2 (0-4) 2 (0.75-3.25) Hunger 2.5 (0.5-4.5) 4 (2-6) 3 (1-5) 3 (1-5) Anxiety 2 (1-3) 2 (1-3) 1 (0-2) 2 (1-3) Data are presented as median (interquartile range: 25 -75 percentiles) CHO = carbohydrate. th th Table 7 Time course of changes in heart rate, blood pressure during anesthesia induction HR (beats/min) SBP (mmHg) DBP (mmHg) T0 T1 T2 T5 T0 T1 T2 T5 T0 T1 T2 T5 AM-fasted 71 ± 18 61 ± 19* 58 ± 18* 55 ± 16* 133 ± 21 91 ± 21* 80 ± 19* 75 ± 16* 73 ± 12 48 ± 10* 43 ± 11* 40 ± 10* PM-fasted 71 ± 12 63 ± 13* 59 ± 11* 57 ± 13* 144 ± 21 103 ± 20* 91 ± 19* 82 ± 18* 77 ± 11 56 ± 11* 50 ± 11* 45 ± 9* AM-CHO 70 ± 14 61 ± 15* 58 ± 14* 57 ± 12* 123 ± 18 90 ± 17* 82 ± 15* 76 ± 15* 70 ± 11 50 ± 10* 45 ± 10* 42 ± 9* PM-CHO 71 ± 13 62 ± 12* 59 ± 12* 58 ± 12* 140 ± 24 95 ± 23* 86 ± 17* 83 ± 18* 75 ± 15 53 ± 13* 45 ± 13* 45 ± 13* Data are presented as mean ± SD. CHO = carbohydrate, HR = Heat rate, SBP = systolic blood pressure, DBP = diastolic blood pressure, T0 = immediate before anesthesia induction, T1 = 1 min after anesthesia induction, T2 = 2 min after anesthesia induction, T5 = 5min after anesthesia induction. *P <0.05 vs. T0. Table 8 Perioperative clinical data AM fasting n = 26 PM fasting n = 35 AM-CHO n = 27 Preoperative fluid (ml) 161 ± 49 357 ± 159 140 ± 52 191 ± 96 Intraoperative fluid (ml) 1082 ± 493 1237 ± 629 798 ± 290 1130 ± 936 Blood loss (ml) 91 ± 136 172 ± 253 46 ± 64 138 ± 253 Urine (ml) 395 ± 318 303 ± 289 281 ± 175 194 ± 133 12 ± 22 11 ± 16 13 ± 18 10 ± 12 Gastric fluid volume (ml) Data are presented as mean ± SD. CHO = carbohydrate. PM-CHO n = 33 ** ** P <0.01 vs. PM fasting. M.E.J. ANESTH 21 (3), 2011 382 that ingesting a CHO drink with trace elements may maintain not only serum Zn concentrations, but also its storage in bone, muscle, and the liver, which may help increase Zn demand during the perioperative period. We observed lower Zn concentrations the day after surgery in all groups, but group-related differences did not exist. We did not administer any trace elements postoperatively, as this yields a decrease in Zn concentrations, as demonstrated in the fasting groups immediately after anesthesia induction. Acute stress induces metallothionein, which has a strong affinity for Zn25 and redistributes Zn to the liver and other tissues for protein synthesis, thereby reducing serum Zn levels26. Zorrilla et al. reported that low preoperative serum Zn concentrations were predictive of delayed wound healing following total hip replacement15. Maintaining preoperative serum Zn concentrations may help redistribute Zn to the wound, which improves wound healing. Many metalloenzymes contain copper that reacts with oxygen. In particular, monoamine oxidase and lysyl oxidase are necessary for cross-linking elastin and collagen in wound healing5,6. In the present study, we observed postoperative changes in Cu levels in the PM surgery group. Berger et al. reported that trauma causes little change in Cu concentration, and that recovery is fast10. Our findings are consistent with those results. Although differences in thirst, hunger, or anxiety before anesthesia induction were not significant, preoperative CHO drink supplementation appeared to slightly reduce patient discomfort. Using a visual analog scale, Hausel et al. reported that thirst and hunger were reduced by preoperative consumption of a CHO drink5. Shorter fasting times can reduce discomfort associated with a surgical procedure; thus preoperative drink supplementation can mitigate, even if only slightly, the stress experienced by patients before surgery. Y. Oyama et al. In the present study, patients received the preoperative drink containing 18% CHO, amino acids, and trace elements. All patients tolerated the drink well. Preoperative consumption of a drink containing 12.5% CHO has been reported to suppress surgical stress-induced catabolism, thereby attenuating insulin resistance23. Furthermore, this treatment enhanced postoperative recovery and shortened hospital stays8. Preoperative consumption of a drink containing 18% CHO, such as the one used in the present study, may also enhance postoperative recovery. Given that this study was carried out at a single facility, there are a number of limitations. By grouping subjects according to morning or afternoon surgery, seasonal fluctuations in metabolism may have influenced the results. In addition, the postoperative observation period was short, so the long-term effects of CHO consumption (days hospitalized, wound healing) were not assessed. To confirm our findings, long-term studies at multiple institutions will be needed. In conclusion, compared to conventional preoperative fasting, preoperative consumption of a CHO drink containing trace elements suppressed preoperative metabolic fluctuations without causing adverse effects, and trace element deficiency was circumvented. Further, the drink appears to reduce patient anxiety. Additional benefits during the perioperative period can be expected by adding trace elements to the preoperative CHO drink supplementation protocol. Acknowlegements The authors thank nurse Kenji Maeda, nureses at Oita Kouseiren Turumi Hospital and laboratory technicians Tugio Kudo and Tomonori Waki for their excellent nursing and technical assistance, dietitian Megumi Maruo for invaluable help. Effects of preoperative oral carbohydrates and trace elements on perioperative nutritional status in elective surgery patients 383 References 1.Eriksson LI, Sandin R: Fasting guidelines in different countries. Acta Anaesthesiol Scand; 1996, 40:971-4. 2.Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: application to healthy patients undergoing elective procedures: a report by the American Society of Anesthesiologist Task Force on Preoperative Fasting. Anesthesiology; 1999, 90:896-905. 3.Søreide E, Eriksson LI, Hirlekar G, Eriksson H, Henneberg SW, Sandin R, Raeder J: Task Force on Scandinavian Preoperative Fasting Guidelines, Clinical Practice Committee Scandinavian Society of Anaesthesiology and Intensive Care Medicine. Preoperative fasting guidelines: an update. Acta Anaesthesiol Scand; 2005, 49:1041-7. 4.Søreide E, Fasting S, Raeder J: New preoperative fasting guidelines in Norway. Acta Anaesthesiol Scand; 1997, 41:799. 5.Hausel J, Nygren J, Lagerkranser M, Hellström PM, Hammarqvist F, Almström C, Lindh A, Thorell A, Ljungqvist O: A carbohydrate-rich drink reduces preoperative discomfort in elective surgery patients. Anesth Analg; 2001, 93:1344-50. 6.Fearon KCH, Ljungqvist O, Von Meyenfeldt M, Revhaug A, Defong CHC, Lassen K, Nygren J, Hausel J, Soop M, Anderson J, Kehlet H: Enhanced recovery after surgery: a Consensus review of clinical care for patients undergoing colonic resection. Clin Nutr; 2005, 24:466-77. 7.Soop M, Nygren J, Myrenfors P, Thorell A, Ljungqvist O: Preoperative oral carbohydrate treatment attenuates immediate postoperative insulin resistance. Am J Physiol Endocrinol Metab; 2001, 280:E576-83. 8.Noblett SE, Watson DS, Huong H, Davison B, Hainsworth PJ, Horgan AF: Preoperative oral carbohydrate loading in colorectal surgery: a randomized controlled trial. Colorectal Dis; 2006, 8:5639. 9.Jonas J, Burns J, Abel EW, Cresswell MJ, Strain JJ, Paterson CR: Impaired mechanical strength of bone in experimental copper deficiency. Ann Nutr Metab; 1993, 37:245-52. 10.Rucker RB, Kosonen T, Clegg MS, Mitchell AE, Rucker BR, Uriu -Hare JY, Keen CL: Copper, lysyl oxidase, and extracellular matrix protein cross-linking. Am J Clin Nutr; 1998, 67:S996-1002. 11.Hallbook T, Hedelin H: Zinc metabolism and surgical trauma. Br J Surg; 1977, 64:271-3. 12.Askari A, Long CL, Blakemore WS: Urinary zinc, copper, nitrogen, and potassium losses in response to trauma. JPEN J Parenter Enteral Nutr; 1979, 3:151-6. 13.McClain CJ, Twyman DL, Ott LG, Rapp RP, Tibbs PA, Norton JA, Kasarskis EJ, Dempsey RJ, Young B: Serum and urine zinc response in head-injured patients. J Neurosurg; 1986, 64:224-30. 14.Berger MM, Cavadini C, Chiolero R, Dirren H: Copper, Selenium, and Zinc Status and Balances after Major Trauma. J Trauma; 1996, 40:103-9. 15.Zorrilla P, Gómez LA, Salido JA, Silva A, López -Alonso A: Low serum zinc level as a predictive factor of delayed wound healing in total hip replacement. Wound Repair Regen; 2006, 14:119-22. 16.Berger MM, Binnert C, Chiolero RL, Taylor W, Raffoul W, Cayeux MC, Benathan M, Shenkin A, Tappy L: Trace element supplementation after major burns increases burned skin trace element concentrations and modulates local protein metabolism but not whole-body substrate metabolism. Am J Clin Nutr; 2007, 85:1301-6. 17.Mears E: Outcomes of Continuous Process Improvement of a Nutritional Care Program Incorporating Serum Prealbumin Measurements. Nutrition; 1996, 12:479-84. 18.Shime N, Ono A, Chihara E, Tanaka Y: Current practice of preoperative fasting: a nationwide survey in Japanese anesthesiateaching hospitals. J Anesth; 2005, 19:187-192. 2002 May; 102(5):36-44; quiz 45. 19.Crenshaw JT, Winslow EH: Preoperative fasting: old habits die hard. Am J Nurs; 2002 May, 102(5):36-44; quiz 45. 20.Henriksen MG, Hessov I, Dela F, Hansen HV, Haraldsted V, Rodt SA: Effects of preoperative oral carbohydrates and peptides on postoperative endocrine response, mobilization, nutrition and muscle function in abdominal surgery. Acta Anaesthesiol Scand; 2003, 47:191-9. 21.Dresner A, Laurent D, Marcucci M, Griffin ME, Dufour S, Cline GW, Slezak LA, Andersen DK, Hundal RS, Rothman DL, Petersen KF, S hulman GI: Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest; 1999, 103:253-9. 22.Bonadonna RC, Zych K, Boni C, Ferrannini E, De-Fronzo RA: Time dependence of the interaction between lipid and glucose in humans. Am J Physiol Endocrinol Metab; 1989, 257:E49-E56. 23.Nygren J: The metabolic effects of fasting and surgery. Best Pract Res Clin Anaesthesiol; 2006, 20:429-38. 24.Bosin E, Monji N: Analysis of serum and urinary retinol binding protein in hepato-renal syndrome. Clin Biochem; 1987, 20:47-51. 25.Karin M, Imbra RJ, Heguy A, Wong G.: Interleukin 1 regulates human metallothionein gene expression. Mol Cell Biol; 1985, 5:2866-9. 26.Walther LE, Winnefeld K, Sölch O: Determination of iron, copper, zinc, magnesium and selenium in plasma and erythrocytes in neurosurgical patients. J Trace Elem Med Biol; 2000, 14:92-5. M.E.J. ANESTH 21 (3), 2011 REDUCED HEMODYNAMIC RESPONSES TO TRACHEAL INTUBATION BY THE BONFILS RETROMOLAR FIBERSCOPE: A RANDOMIZED CONTROLLED STUDY Waleed A. Almarakbi**, Abeer A. Arab*** and A dnan A. A lmazrooa **** Abdulaziz Boker*, Abstract The Bonfils retromolar intubation fiberscope is a rigid endoscope designed to enable glottic visualization and facilitate intubation under endoscopic vision. Theoretically, avoiding direct-vision laryngoscopy and thus could produce less stimulation during intubation than the conventional direct laryngoscopic procedure. This prospective randomized study was designed to compare the effect of tracheal intubation with direct vision laryngoscopy (Macintosh blade) and the Bonfils retromolar intubation fiberscope on the hemodynamic responses in ASA I patients. Forty patients scheduled for elective surgery and requiring endotracheal intubation were randomly allocated to one of two groups according to the intubating tool under sevoflurane nitrous oxide Anaesthesia (n = 20 each). The retromolar group received tracheal intubation with the Bonfils retromolar fiberscope, while the direct laryngoscopy group received tracheal intubation by the direct vision laryngoscope (Macintosh blade). Heart rate and arterial blood pressure (systolic BP, diastolic BP, mean ABP) were recorded before induction of Anaesthesia, 3 minutes after induction of Anaesthesia (before intubation) and 5 successive recordings at one-minute interval after intubation. All the systolic BP, diastolic Bp, mean ABP and heart rate values in the direct laryngoscopy group were significantly higher in the 5 successive minutes after intubation in comparison with the retromolar group (P = 0.00). This might be attributed to the gentle intubating technique, by the Bonfils retromolar fiberscope, which allows quick endotracheal intubation without manipulations of the base of the tongue or epiglottis. Financial Support/Conflict of interest Authors have no commercial association with financial involvement that might pose a conflict of interest in connection with the results of the submitted article. The study was supported by the department of Anesthesia, King Abdulaziz University, Jeddah, Saudi Arabia. No other source of funding to disclose. * MBBS, Med, FRCPC, Assistant Professor, Consultant, Department of Anesthesia & Critical Care, Chairman, Medical Education Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. ** MD, Department of Anesthesiology and Intensive Care Medicine, Ain Shams University, Cairo, Egypt. *** MBBS, FRCPC, Department of Anesthesia and Critical Care, Faculty of Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia. **** FFA, CPE, Associate Professor, Consultant, Department of Anesthesia and Critical Care, Vice President, King Abdulaziz University, Jeddah, Saudi Arabia. Corresponding Author: Dr. Abdulaziz Boker, Department of Anesthesia & Critical Care, Chairman, Medical Education Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. P. O. Box Address: P. O. Box: 80215, Jeddah 21589, Tel/Fax: +96626408335. E-mail: [email protected] 385 M.E.J. ANESTH 21 (3), 2011 386 A. Boker et al. Introduction Tracheal intubation via direct laryngoscopy produces a marked stress response1. Although these hemodynamic responses are short lived and tolerated by most of the patients, they might provoke detrimental effect, on the coronary and cerebral circulation particularly in high-risk patients2. Several pharmacological agents have been suggested to attenuate these stress responses to laryngoscopic intubation such as the use of variety of anesthetic agents, sympatholytics, vasodilators, local anesthetics and magnesium3,4,5,6,7. In principle, tracheal intubation techniques that avoid or minimize oropharyngeal stimulation might attenuate the hemodynamic stress response. However, published studies have provided little or conflicting evidence for an attenuated response for a variety of non-laryngoscopic intubation devices8,9,10,11,12. Bonfils retromolar intubation fiberscope (Karl Storz, Gmb and Co, KG, TuttLingen, Germany) is 3.55.0mm optical stylet that allows a retromolar approach to the larynx. It is designed to position a 6.5mm I.D. or larger endotracheal tube directly between the vocal cords into the trachea with minimal or no manipulation of the epiglottis which is richly innervated13. The aim of this study was to compare the effect of tracheal intubation with direct vision laryngoscopy (Macintosh blade) and the Bonfils retromolar fiberscope on the hemodynamic responses in American Society of Anesthesiologist (ASA) physical status I patients. Materials and Methods After obtaining approval from our institutional research committee and informed consent from each patient, forty, ASA I patients scheduled for, less than two hours, elective surgery requiring tracheal intubation were solicited in this prospective, randomized, unblinded study. Exclusion criteria were age <18 yr or >60 yr old, history gastroesophageal reflux, a history of difficult intubation or intercisal distance <3 cm, patients in whom tracheal intubation time was more than 30 seconds or the oropharyngeal (Guedel) airway was used to facilitate face-mask ventilation. All patients were premedicated with diazepam 5mg PO and ranitidine 150mg PO 2 hrs before induction of Anaesthesia. Also, Mallampati score, thyromental, and sternomental distances were measured and recorded. In the pre-induction room, an IV cannula was inserted with infusion of lactated ringer at a rate of 15 mL.kg-1.hr- throughout the operation. In the operating room, patients received standard anesthetic monitors, including noninvasive blood pressure, electrocardiogram lead II, and pulse oximeter (Zeus, Drager, Germany). Heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) were recorded as baseline values. Anaesthesia was induced with xylocaine 0.5 mg/ kg with venous retention for 30 seconds to minimize propofol pain, propofol 3mg/kg IV, and cisatracrium 0.1 mg/kg IV. Anaesthesia was then maintained with sevoflurane 2% in oxygen and nitrous oxide 50%. After 3 minutes of manual ventilation, arterial blood pressure (SBP, DBP, MAP), heart rate, end tidal CO2 and sevoflurane concentrations were recorded. Both the Bonfils retromolar fiberscope and direct laryngoscope (Macintosh Blade) were ready to use on the anesthetic tray. Patients were assigned on a random number basis (using the sealed envelope method) into 2 groups: Group D, (n = 20) in which intubation was done by the direct vision laryngoscopy with Macintosh blade (Karl Storz, Germany) no.3 or 4 for female patients and no. 4 or 5 for male patients while in Group R, (n = 20) patients were intubated by the Bonfils retromolar fiberscope (Karl Storz, Gmb and Co, KG, TuttLingen, Germany). Cuffed Portex tracheal tubes (SIMS Portex, Inc., Keene NH) with internal diameter of 7 mm for female patients and 8mm for male patients were used after lubrication by K-Y Jelly. As soon as the trachea was intubated and confirmed by positive end tidal CO2, arterial blood pressure (SBP, DBP MAP) and heart rate were recorded for 5 successive recordings at one-minute interval. The intubation time was recorded from the time the device passed into the oropharynx to the time of reconnection of the ventilator tubing system to the endotracheal tube. A single anesthetist experienced with the direct larygoscopy and the Bonfils retromolar fiberscope techniques performed all tracheal intubations. The Cromack and Lehane14 grade without REDUCED HEMODYNAMIC RESPONSES TO TRACHEAL INTUBATION BY THE BONFILS RETROMOLAR FIBERSCOPE: A RANDOMIZED CONTROLLED STUDY external laryngeal pressure was recorded in Group D. Intraoperative complications were recorded by an unblinded observer e.g. mucosal injury (blood detected on the intubation device after use), dental injury and lip injury. 387 significant changes among the groups as regards MAP or heart rate (P = 0.00) (Graph 1, 2). Graph 1 Heart Rate Changes at Different Phases of Induction of Anesthesia Also, postoperative sore throat was assessed 12 hrs after surgery by using the visual analogue scale that ranges from zero (no Pain) to ten (the worst imaginable pain). Statistical Analysis Statistical analyses were performed with the Stat View SE Package (Abacus Concepts, CA, USA) on a Power Macintosh 7200 (Apple Computer Inc., CA, USA). Patients’ characteristics were compared using student’s-t-test. Between group differences were compared using analysis of variance (ANOVA) for factors. If significant differences were observed, Scheffe F was used for post hoc analysis. Data are presented as mean (SD). P<0.05 was considered statistically significant. Results There were no significant differences between the two groups in terms of age, sex, weight, or height (table 1). End tidal CO2 and sevoflurane concentrations immediately before intubation were also similar between the two groups (table 1). Table 1 Patients Demographic Data, Airway Assessment and Intubation Data Group D: Direct Laryngoscopy group, Group R: Retromolar group. * P<0.05. Graph 2 Mean Arterial Blood Pressure Changes at Different Phases of Induction of Anesthesia Group D: Direct Laryngoscopy group, Group R: Retromolar group. * P<0.05. Both MAP and heart rate values in Group D were significantly higher in the 5 successive minutes after intubation in comparison with Group R (P = 0.00) (Graph 1, 2). As regards the intubation time, it was significantly higher in Group D than Group R (P = 0.00) (table1). In Group D, one case was recorded to have mucosal injury and another one for lip injury while no cases were recorded for intraoperative complications in Group R (table 2). Regarding the post-operative sore throat, it was significantly higher in Group D than Group R (P = 0.00) (table 2). Table 2 Intra and Postoperative complications Group D: Direct Laryngoscopy group, Group R: Retromolar group. * P<0.05 Before induction, there were no significant differences between the two groups as regards MAP and heart rate (Graph 1, 2). Furthermore, after induction and immediately before intubation, there were no Group D: Direct Laryngoscopy group, Group R: Retromolar group, VAS: visual analogue scale (0-10). * P<0.05. M.E.J. ANESTH 21 (3), 2011 388 Discussion This prospective study showed that tracheal intubation by Bonfils retromolar fiberscope produced lower level of hemodynamic responses in healthy patients. As an Anesthesiologist become more curious to use the new tools available, which are helping in management of the difficult airway, Bonfils retromolar intubation fiberscope is one of these new instruments that recently introduced to daily anesthetic practice as it permits clear visualization of the glottic area. Additionally, it has a unique option of direct oxygen insufflation through a side-port that disperses the secretions, prevents fogging of the view and allows oxygenation in cases of difficult ventilation during the intubation trials. Also, it facilitates tracheal intubation in trauma patients with immobilized cervical spine15 and being introduced through the retromolar space, it prevents teeth damage in vulnerable patients as caused by the direct vision laryngoscope. Only few studies were done to evaluate the Bonfils retromolar fiberscope as intubating tool16,17,18,19,20. Orotracheal intubation using the direct vision laryngoscopy needs elevation of the epiglottis for laryngeal exposure. In order to elevate the epiglottis and to put the glottic aperature in one axis with the anesthetist eye, a forward and upward movement of the laryngoscope blade exerted along the axis of the laryngoscope handle, which may results in hemodynamic response21. In our study we anticipated that orotracheal intubation through a gentle intubating technique using the Bonfils retromolar fiberscope would cause less hemodynamic responses. The study showed a significant increase in heart rate, SBP, DBP and MAP in the direct laryngoscopy group when compared with the retromolar group (P<0.005) in the 5 successive minutes after intubation. During orotracheal intubation using the direct vision laryngoscopy sympathetic activation occurs due to two possible causes; the direct contact of the blade to the tongue especially the posterior third and the vallecula with a force to elevate the epiglottis, while the second cause is the introduction of the endotracheal tube in the trachea. In our study, the hemodynamic responses were lower in the retromolar A. Boker et al. group as one of the causes of sympathetic activation is minimized which is the oropharyngeal stimulation. The introduction of the retromolar fiberscope into the oropharynx is under vision, through a camera connected to the fiberscope and a screen, which gives us the opportunity to direct the endotracheal tube into the larynx with minimal or no contact with the epiglottis. Furthermore, in order to make a clear passage in the oropharynx for introduction of the retromolar fiberscope, upward chin lift is achieved by grasping the jaw with the anesthetist thumb and index finger to separate the tongue and epiglottis away from the posterior pharyngeal wall. Shinji et al22 showed that hemodynamic changes are likely to occur because of direct tracheal irritation rather that direct stimulation of the larynx in their study, which contained 3 groups, the light wand group received tracheal intubation with Trachlight®, the laryngoscope intubation group received tracheal intubation with a direct vision laryngoscope (Macintosh blade), and the laryngoscope alone group received the laryngoscope alone without intubation. The maximum heart rate and systolic blood pressure were significantly higher in both Trachlight® and Macintosh laryngoscope group than those in the laryngoscope alone group. On the contrary, the study of Hirabayashi et al11 showed non-significant changes in mean arterial blood pressure and heart rate to tracheal intubation with using either the light wand or the Macintosh laryngoscope. They attributed the cause of similarity in hemodynamic response of the light wand group to Macintosh laryngoscope group to the technique for light wand intubation in which the jaw is grasped and lifted upward using the thumb and index finger of the intubator’s hand to facilitate passage of the endotracheal tube to the larynx, which considered by them a sufficient stimulus to cause circulatory responses. We concur that chin lift stimulus may cause stress response but, in our opinion, not to the same degree as the Macintosh blade laryngoscope does. Although we used a similar technique of chin lift, the difference lies in using the retromolar fiberscope instead of the light wand. The light wand technique is a blind one in which the endotracheal tube may touch the tongue base, vallecula, epiglottis or the piriform fossa during the introduction trials. That may be an added cause to the chin lift to increase the hemodynamic response. Alternatively, the retromolar REDUCED HEMODYNAMIC RESPONSES TO TRACHEAL INTUBATION BY THE BONFILS RETROMOLAR FIBERSCOPE: A RANDOMIZED CONTROLLED STUDY fiberscope introduces the endotracheal tube to the larynx under vision to avoid touching and stimulating the oropharyngeal structures with subsequent minimization of the circulatory responses. However, Nishikawa et al23 showed in their study attenuated hemodynamic changes in the light wand technique in comparison to the laryngoscopic technique. In their study, they had different anesthetic technique as induction of general Anaesthesia was by fentanyl 2 mcg/kg followed after 3 minutes by IV propofol and vecronium. Fentanyl could attenuate the hemodynamic responses associated with tracheal intubation24,25,26. Prolongation of the duration of intubation has been reported to increase hemodynamic changes after tracheal intubation27. Nishikawa et al28 concluded that tracheal intubation using a light wand is more effective than flexible fiberoptic intubation in attenuating hemodynamic changes after tracheal intubation in normotensive elderly patients. They attributed the cause to the rapidity of intubation; the intubation times in the light wand group were significantly shorter that those in the fiberoptic group. In our study, the intubation time was significantly shorter in the retromolar group (P<0.05) thus, sharing in causes of attenuation of the hemodynamic responses during intubation with the Bonfils retromolar fiberscope. Another contributing factor in the hemodynamic response to direct vision laryngoscopy using the Macintosh blade is the degree of force applied to elevate the tongue base and epiglottis as revealed by the study of McCoy et al29 in which the stress response was less marked with the use of McCoy blade than the Macintosh blade due to reduction of force necessary to obtain clear view of the larynx by the McCoy blade. Hassan et al30 reported that, by activating proprioceptors, direct laryngoscopy 389 induces stress responses proportional to the intensity of the stimulus exerted against the base of the tongue. Therefore, the retromolar group in our study experienced lower hemodynamic responses than the direct laryngoscopy group as there was not any force applied to the base of the tongue or epiglottis during introduction of the Bonfils Fiberscope towards the larynx which also was reflected on the lower incidence of sore throat (VAS = 1.5 ± 0.5) than in the direct laryngoscope group (VAS = 4.8 ± 0.8) (P<0.05). Our study has limitations. First, it lacks the double blinding, which is not practical to do. Second, only normotensive patients were included in this study so hemodynamic responses to tracheal intubation by the Bonfils fiberscope in hypertensive patients could not be predicted. Collectively, we recommend a further study to evaluate the hemodynamic effect of intubation by the Bonfils fiberscope in hypertensive patients. Third, patients anticipated to have difficult intubation and whom intubation time exceeds 30 seconds were excluded from the study. Consequently, we could not assess the hemodynamic responses in repeated trials and prolonged intubation times. Finally, we measured the hemodynamic parameters as an indicator for stress response to intubation without measuring the serum catecholamine levels as it is of high cost and also, the study of Michal et al31 concluded that catecholamine levels do not correlate with the hemodynamic changes during their comparative study between the direct vision laryngoscopy and fiberoptic bronchoscopy as regards the stress response. In summary, tracheal intubation by the Bonfils retromolar fiberscope caused hemodynamic responses significantly lower than tracheal intubation by the direct laryngoscope (Macintosh blade) in ASA I patients. M.E.J. ANESTH 21 (3), 2011 390 A. Boker et al. References 1. AM Forces and FG Dally, Acute hypertension during induction of Anaesthesia and endotracheal intubation in normotensive man. Br J Anaesth; 1970, 42:618-624. 2. Hung, Orlando: Understanding hemodynamic responses to tracheal intubation. Can J Anesth; 2001, 48:723-726. 3. Kautto UM: Effect of combinations of topical Anaesthesia, fentanyl, halothane or N2O on circulatory intubation response in normo and hypertensive patients. Acta Anesthesiol Scand; 1983, 27:245-51. 4. Lui PL Gatts, Gugino LD, Mallampati Sr, Govino BG: Esmolol for control of increases in heart rate and blood pressure during tracheal intubation after thiopentone and succinyl choline. Can Anaesth Soc J; 1986, 33:556-62. 5. Stoelting RK: Attenuation of blood pressure response to laryngoscopy and tracheal intubation with sodium nitroprusside. Anesth Analg; 1979, 58:116-9. 6 Hamill JF, Bedford RF, Weaver DC, Colohan AR: Lidocaine before endotracheal intubation: intravenous or laryngotracheal? Anesthesiology; 1981, 55:578-81. 7. Puri GD, Marudhachalam KS, Chari P, Suri RK: The effect of magnesium sulphate on hemodynamics and its efficacy in attenuating the response to endotracheal intubation in patients with coronary artery disease. Anesth Analg; 1998, 87:808-11. 8. Finfer SR, Mackenzie SI, Saddler JM, Watkins: Cardiovascular responses to tracheal intubation: a comparison of direct laryngsocopy and fiberoptic intubation. Anaesth Intensive Care; 1989, 17:44-8. 9. Imai M, Matsumura C, Hanaoka Y, Kemmotsu O: Comparison of Cardiovascular responses to airway management: using a new adaptor, laryngoscopic intubation. J Clin Anesth; 1995, 7:14-8. 10.Pernestorfer T, Krafft P, Fitzgerald RD et al: Stress response to tracheal intubation: direct laryngoscopy compared with blind oral intubation. Anaesthesia; 1995, 50:17-22. 11.Hirabayashi Y, Hirata M, Kawakami T et al: Effect of lightwand (Trachlight® compared with direct laryngsocopy on circulatory responses to tracheal intubation. Br J Anaesth; 1998, 81:253-5. 12.Joo HS, Rose DK: The intubating laryngeal mask airway with and without fiberoptic guidance. Anesth Analg; 1999, 88:662-6. 13.Liancai MU, Ira Sanders: Sensory nerve supply of the human oro - and laryngopharynx: A preliminary study. The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology. March 2000, 258:406-420. 14.Cromack RS, Lehane J: Difficult tracheal intubation in obstetrics. Anaesthesia; 1984, 39:1105-11. 15.Byhahn C, Meiniger D, Walcer F, Hofstetter C, Zwissler B: prehospital emergency endotracheal intubation using the Bonfils intubation fiberscope. Eur j Emerg Med; 2007, 14:43-6. 16.Halligan M, Charters P: Learning curve for the Bonfils intubation fiberscope. Br J Anaesth; 2003, 90:826. 17.Halligan M, Weldon B, Charters P: A Clinical appraisal of the Bonfils intubating fiberscope. Br J Anaesth; 2002, 89:671-2. 18.Halligan M, Charters P: A clinical evaluation of the Bonfils intubation fiberscope. Anaesthesia; 2003, 58:1087-91. 19.Maybauez MO, maier S, Thierbach AR: An unexpected difficult intubation: Bonfils rigid fiberscope. Anesthetist; 2005, 54:35-40. 20.Bein B,. Yan M. Tonner PH, Scholz J, Steinfath M,. Dorgers V: Tracheal intubation using the Bonfils intubation fiberscope after failed direct laryngoscopy. Anaesthesia; 2004, 59:1207-9. 21.Shribman AJ, Smith G and Achola KJ: Cardiovascular and catecholamine responses to laryngoscopy with and without tracheal intubation. Br J Anaesth; 1987, 59:295-299. 22.Shinji T, Taro M, Masayuki M and Hidenori T: Hemodynamic responses to tracheal intubation with laryngoscope versus lightwand intubating device (Trachelight®) in adults with normal airway. Anesth Analg; 2002, 95:480-484. 23.Nishikawa K, Omote K, Kawana S, Namiki A: A comparison of hemodynamic changes after endotracheal intubation by using the light wand device and the laryngoscope in normotensive and hypertensive patients. Anesth Analg; 2000, 90:1203-7. 24.Dahlgren N, Messeter K: Treatment of stress response to laryngoscopy and intubation with fentanyl. Anaesthesia; 1981, 36:1022-6. 25.Martin DE, Rosenberg H, Aukburg SJ et al: Low-dose fentanyl blunts circulatory responses to tracheal intubation. Anesth Analg; 1982, 61:680-4. 26.KO SH, Kim DC, Han YJ, Song HS: Small dose fentanyl: optimal time of injection for blunting the circulatory responses to tracheal intubation. Anesth Analg; 1998, 86:658-61. 27.Stoelting RK: Circulating changes during direct laryngoscopy and tracheal intubation: influence of duration of laryngoscopy with and without prior Lidocaine. Anesthesiology; 1977, 47:381-3. 28.Nishikawa,Kohki, Kawamata, Mikito, Namiki and Akiyoshi: Light wand intubation is associated with less hemodynamic changes than fiberoptic intubation in normotensive, but not in hypertensive patients over the age of 60. Can J Anesth; 2001, 48:1148-53. 29.McCoy EP, Mirakhur RK and McCloskey BV: A comparison of the stress response to laryngoscopy. Anaesthesia; 1995, 50:943-946. 30.Hassan HG, El-Sharkawy TY, Renck H et al: Hemodynamic and catecholamine responses to laryngoscopy with and without endotracheal intubation. Acta Anesthesiol Scand; 1991, 35:442-7. 31.Mochal B, Avishai Z, Avital G, Sophie L, Beno R. Hemodynamic and catecholamine response to tracheal intubation: direct laryngoscope compared with fiberoptic intubation. Journal of Clinical Anaesthesia; 2003, 15:123-136. EFFECT OF KETAMINE ON BISPECTRAL INDEX DURING PROPOFOL - FENTANYL ANESTHESIA: A * RANDOMIZED CONTROLLED STUDY Saikat Sengupta, Simantika Ghosh, Amitava Rudra, Palash Kumar, Gaurab Maitra, Tanmoy Das Abstract Background: The Bispectral Index (BIS) helps in the assessment of the depth of hypnosis. N-methyl-D-aspartic acid antagonist, ketamine, has been used in various doses to decrease postoperative morphine consumption. The purpose of our study was to compare the effects of two different doses (0.5 mg/kg and 0.2 mg/kg) of ketamine on BIS values. Methods: Forty-five ASA I or II patients undergoing general anesthesia were included in this double-blind, prospective, control trial and randomly allocated into three groups. After induction of anesthesia and tracheal intubation, a propofol infusion was started and titrated to attain BIS values of around 40. After five minutes of stable BIS values and in the absence of any surgical stimulus, patients received either 0.5 mg/kg of ketamine (Group K1) or 0.2 mg/kg of ketamine (Group K2) or normal saline (Group N) as bolus intravenously. BIS values were recorded for the next 15 minutes, at five-minutes interval. Results: Mean BIS values were significantly increased in Group K1 (63.5) while Group K2 (42.0) failed to show any significant rise. BIS values in Group K2 were comparable to those in Group N. Conclusion: Thus, under stable propofol anesthesia, a bolus of ketamine 0.5 mg/kg increases BIS values while ketamine 0.2 mg/kg does not. Introduction Ketamine is an intravenous anesthetic with analgesic properties in subanesthetic doses. It is a non-competitive antagonist of the N-methyl - D - aspartic acid (NMDA) receptor that participates in excitatory neurotransmission in the central nervous system. Although analgesia produced by ketamine alone does not seem to be equivalent to that produced by opioid analgesics1-4, ketamine can prevent the development of opioid tolerance via NMDA receptors5-8 (Fig. 1). Opioid tolerance is a major concern when postoperative pain requires large doses of opioids, such as in major abdominal and thoracic surgeries and in cancer patients with chronic opioid intake. In such patients, Ketamine has proved to be a useful adjuvant for the management of pain9-11. * Department of Anesthesiology, Perioperative Medicine and Pain, Apollo Gleneagles Hospitals. Corresponding Author: Saikat Sengupta, MD DNB MNAMS, Senior Consultant & Academic Coordinator, Department of Anesthesiology, Perioperative Medicine and Pain, Apollo Gleneagles Hospitals, 58, Canal Circular Road, Kolkata-700058. Tel: +91 9830179539. E-mail:[email protected] 391 M.E.J. ANESTH 21 (3), 2011 392 S. Sengupta et al. Fig. 1 Pain pathway and action of Ketamine Strong pain Opioids µ receptors Ketamine NMDA receptors Increased glutanate synaptic effectiveness range of ketamine doses (between 0.15 and 1 mg/Kg) used intravenously16-18. We undertook this study to determine the dose of ketamine which would provide analgesia but be devoid of its paradoxical effects on BIS. Specifically, the study aims to compare the effect of ketamine on BIS when given at two different doses as i.v. bolus: 0.2 mg/Kg and 0.5mg/Kg. Hyperexcitability of dorsal root neurons Methods • Central Sensitization • Wind-up phenomenon • Pain memory Among the three components of the triad of anesthesia (hypnosis, areflexia, analgesia) hypnosis is perhaps the most difficult to measure and monitor. The importance of measuring hypnosis or depth of anesthesia lies in the prevention of awareness, which can be a very unpleasant experience and result in tragic consequences for both the patient and the anesthesiologist. Several non-continuous clinical scales for describing sedation levels in adults have been devised, such as the Observer’s Assessment of Alertness and Sedation (OAAS) and the Ramsay Scales. However, these have proved inadequate in measuring the depth of anesthesia and have paved the way for processed EEG monitors. ECG monitors provide a continuous measure that encompasses the full range of sedation levels measured by the discontinuous scales. In October 1996, the Food and Drug Administration (Rockville, MD) approved the Bispectral Index (BIS) monitor (Aspect Medical Systems, Newton, MA) as an accepted measure of the hypnotic effect of anesthetics and sedative drugs12. BIS was derived by empirically estimating the EEG parameters that best predicted OAAS measurements and may be described as a “probability of state” measure, reflecting the complex nature of consciousness13. Today, BIS is widely used to monitor the hypnotic component of anesthesia and guide the administration of volatile and intravenous anesthetics. Several studies have reported an increase in BIS values, despite a deepening level of hypnosis when ketamine 0.5 mg/Kg is administered as a rapid bolus during general anesthesia14-15. Perioperative use of ketamine for acute postoperative pain involves a wide After approval from the Institutional Review Board, and obtaining written informed consent, 45 patients, ASA I or II, aged 18-65 years, posted for surgeries under general anesthesia were enrolled in this prospective, double-blind, randomized control trial. Selection criteria included the absence of any neurological or psychiatric disease, obesity and arterial hypertension, as well as complete abstinence from illicit drugs and alcohol. Upon arrival in the operating theatre, noninvasive blood pressure monitoring, continuous electrocardiography and pulse oximetry were instituted in all patients. BIS was monitored using a Quatro TM sensor applied appropriately to the patient’s forehead. Premedication consisted of midazolam 0.02 mg/ Kg and glycopyrrolate 0.04 mg/Kg. General anesthesia was induced with propofol titrated to attain a BIS value just below 40 and fentanyl 2 µg/Kg. Tracheal intubation was facilitated with rocuronium 0.6 mg/ Kg and maintenance of anesthesia was achieved with propofol infusion titrated to attain BIS values below 40 and air in oxygen (50% inspired fraction). The propofol infusion was continuously titrated to maintain stable BIS of ~ 40. After 5 minutes of stable BIS and in the absence of any surgical or noxious stimulus, patients received randomly (using closed enveloped technique), in double-blind fashion either a bolus of ketamine 0.5 mg/Kg diluted to 5 ml (Group K1; n = 15) or ketamine 0.2 mg/Kg diluted to 5 ml (Group K2; n = 15) or normal saline 5 ml (Group N; n = 15) (Fig. 2). The solution was prepared by an independent anesthesiologist unaware of the study protocol. Non-invasive arterial pressure, heart rate, pulse oximetry, end tidal CO2 and BIS values were recorded automatically, before the start of the drug administration until the end of the study period of 15 minutes in the absence of any surgical stimulation. EFFECT OF KETAMINE ON BISPECTRAL INDEX DURING PROPOFOL - FENTANYL ANESTHESIA: A DOMIZED CONTROLLED STUDY Fig. 2 Study Methodology 5 minutes of stable BIS + Absence of any surgical or noxious stimulus 393 Kg) although Group K2 (ketamine 0.2 mg/Kg) showed no such increase (Table 2) (Fig. 4). Vital parameters, however, did not vary significantly among the groups. Fig. 4 Graphical Representation of study results Closed Envelope Technique I.V. Bolus of ketamine 0.5 mg/Kg I.V. Bolus of ketamine 0.2 mg/Kg I.V. Bolus of normal saline 5 ml Group K1 n =15 Group K2 n =15 Group N n =15 Results SPSS software version 11.5 was used for statistical analysis. Power analysis yielded a sample size of 43 when the confidence level was fixed as 95% to achieve an α error of 0.05 and a β error of 0.2. On analysis of demographic data using Chi-square test, no statistically significant differences were noted among the 3 study groups (Table 1). BIS values were expressed as mean (SD) and analyzed using two-way analysis of variance (ANOVA). Compared to the control group (normal saline 5 ml), statistically significant increase in BIS values was noted in Group K1 (ketamine 0.5 mg/ Discussion Review of relevant literature showed that doses of ketamine administered perioperatively varied almost seven-fold, from 0.15 to 1 mg/Kg i.v. No consensus seems to be present on a specific and systematic administration regimen of ketamine in the context of its preemptive anti-hyperalgesic effects. Table 1 Demographic Characteristics of Study Sample K1 K2 N 0.5 mg/kg 0.2 mg/kg Normal saline 15 45 ± 2* 8 (53.3)* 15 44 ± 2# 7 (46.7)# 15 43 ± 4 8 (53.3) K1 K2 N 0.5 mg/kg 0.2 mg/kg Normal saline 0 Min (Baseline) 58.4 (3.5) 59.0 (1.69) 60.3 (1.49) 5 Mins (After Induction) 41.2 (3.99) 40.9 (1.66) 41.5 (1.60) No. of Patients Age (Yrs.) Males (Nos.) (%) * P value > 0.05 compared to N. # P value > 0.05 compared to N. 10 Mins (After Stabilization of BIS) 15 Mins (5 Mins after Bolus) * P value < 0.05 compared to N. # P value > 0.05 compared to N. 420 Table 2 BIS Values as Mean (SD) 40.2 (0.77) 40.2 (0.77) 40.1 (0.80) 63.5 (2.03)* 42.0 (0.75)# 40.8 (1.01) M.E.J. ANESTH 21 (3), 2011 394 In 1969, Corssen et al19 reported that ketamine 1 mg/Kg increases the activity of the EEG spectrum. In more recent studies, ketamine shifted the alpha peak of bicoherence induced by propofol to higher frequencies, but did not block their formation20-22. Hirota et al23 showed that a bolus of ketamine 0.4 mg/Kg significantly increases the BIS values during propofol-fentanyl anesthesia. Vereecke et al15 showed the same effects on the BIS after a bolus injection of ketamine 0.4 mg/Kg followed by a continuous infusion of 1 mg/Kg/h. During sevoflurane anesthesia, Hans et al14 showed that a bolus of 0.5 mg/Kg ketamine also significantly increases the BIS values. Lauretti and Azevedo24 have demonstrated the efficacy of 0.2 mg/ Kg of ketamine on the decrease of rescue analgesic drug requirement for postoperative pain therapy after vaginoplasty. Faraoni et al25 showed that under stable propofol and remifentanil TCI anesthesia, a slow bolus infusion of ketamine 0.2 mg/Kg administered over a 5 min period did not increase the BIS value over the next 15 min. With such a wide spectrum of used doses, we decided to evaluate the effect of two different doses of ketamine on BIS values – 0.5 mg/Kg and 0.2 mg/Kg. Although 0.5mg/Kg of ketamine has been proved to increase BIS values when given as an i.v bolus under sevoflurane anesthesia14, 0.2 mg/Kg of ketamine has been shown to have no effects on BIS when given as an infusion over 5 minutes25. Does this hold true when 0.2 mg/Kg ketamine is administered as a bolus? Can the use of a propofol infusion for maintenance of anesthesia alter the effects of 0.5mg/Kg of ketamine on BIS? We sought the answers to these questions through our study. The results of our study corroborate the findings of Hans et al14 as well as Faraoni et al25 in that a bolus of 0.5 mg/Kg of ketamine significantly increases BIS values but 0.2 mg/Kg does not, inspite of differences in the study protocol. Faraoni et al25 have used propofol and remifentanil TCI anesthesia while we have used propofol infusion titrated according to BIS alongwith fentanyl. Ketamine was administered as a bolus in our study but Faraoni et al25 administered a slow bolus infusion over a 5 min period. The hypnotic effect of ketamine is characterized by a dissociative mechanism and an increase in Ө activity of EEG. The increase in BIS in response to ketamine is paradoxical in that the level of anesthesia S. Sengupta et al. is deepened by the administration of an additional anesthetic agent. Thus, BIS must be considered to reflect cortical activity rather than the level of consciousness26. Ketamine administered in patients anaesthetized with GABAergic agents that depress cortical activity, induces a change in the EEG pattern towards higher frequencies and desynchronisation (Fig. 3). This modification is reflected in an increase in BIS and has no relationship with the depth of anesthesia. Anesthesiologists unaware of this paradox will inadvertently administer additional hypnotic agents in order to decrease BIS values, ultimately landing the patient in an over dose of hypnotic agents which may have profound effects on the perioperative outcome. Once aware, the anesthesiologist will use his clinical skills to determine the depth of anesthesia and thus refrain from chasing the BIS values and causing an over dose of hypnotic agents and better perioperative outcomes. Fig. 3 Ketamine and its effect on BIS GABAergic AGENTS + KETAMINE EEG DESYNCHRONIZATION ↑ FREQUENCY ↑ BIS VALUES UNRELATED TO ANAESTHETIC DEPTH The reason of increase in BIS values with a low dose of ketamine remains unclear. We also did not evaluate the effects of ketamine on postoperative analgesia, 24 hour morphine consumption or on the incidence of PONV. In conclusion, a bolus dose of ketamine 0.2 mg/Kg does not affect BIS values during propofol anesthesia whereas higher doses of 0.5 mg/kg increase BIS values despite a deepening level of anesthesia. This increase modifies the relationship between BIS and the hypnotic component of anesthesia. Ignoring this effect could lead to inadvertent over dose of hypnotic agents and thus calls for increased awareness EFFECT OF KETAMINE ON BISPECTRAL INDEX DURING PROPOFOL - FENTANYL ANESTHESIA: A DOMIZED CONTROLLED STUDY 395 among anesthesiologists. References 1. Owen H, Reekie RM, Clements JA, Watson R, Nimmo WS: Analgesia from morphine and ketamine: a comparison of infusions of morphine and ketamine for postoperative analgesia. Anaesthesia; 1987, 42:1051-6. 2. Mankowitz E, Downing JW, Brock-Utne JG, Maharaj RJ, Morrel DF: Total intravenous anaesthesia using low-dose ketamine infusion for caesarean section: a comparison with a standard inhalation anaesthetic technique. S Afr Med J; 1984, 65:246-50. 3. Kawana Y, Sato H, Shimada H, Fujita N, Veda Y, Hayashi A, Araki Y: Epidural ketamine for postoperative pain relief after gynecologic operations: a double – blind study and comparison with epidural morphine. Anesth Analg; 1987, 66:735-8. 4. Peat SJ, Bras P, Hanna MH: A double – blind comparison of epidural ketamine and diamorphine for postoperative analgesia. Anaesthesia; 1989, 44:555-8. 5. Kissin I, Bright CA, Bradley EL Jr: The effect of ketamine on opioid – induced acute tolerance: can it explain reduction of opioid consumption with ketamine – opioid analgesic combinations? Anesth Analg; 2000, 91:1483-8. 6. Celerier E, Rival C, Jun Y, Laulin JP, Larcher A, Reynier P, Simmonet G: Long – lasting hyperalgesia induced by fentanyl in rats: preventive effect of ketamine. Anesthesiology; 2000, 92:46572. 7. Laulin JP, Maurette P, Corcuff JB, Rivat C, Chauvin M, Simmonet G: The role of ketamine in preventing fentanyl – induced hyperalgesia and subsequent acute morphine tolerance. Anesth Analg; 2002, 94:1263-9. 8. Rivat C, Laulin JP, Corcuff JB, Celerier E, Laure P, Simmonet G: Fentanyl enhancement of carrageenan – induced long – lasting hyperalgesia in rats: prevention by the N-methyl - D - aspartate receptor antagonist ketamine. Anesthesiology; 2002, 96:381-91. 9. Bell R, Eccleston C, Kalso E: Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database Syst Rev; 2003, 1:CD003351. 10.McQueen AL, Baroletti SA: Adjuvant ketamine analgesia for the management of cancer pain. Ann Pharmacother; 2002, 36:1614-9. 11.Kannan TR, Saxena A, Bhatnagar S, Barry A: Oral ketamine as an adjuvant to oral morphine for neuropathic pain in cancer patients. J Pain Symptom Manage; 2002, 2:60-5. 12.Dahaba AA: Different conditions that could result in the Bispectral Index indicating an incorrect hypnotic state. Anesth Analg; 2005, 101:765-73. 13.Crick F, Koch C: A framework for consciousness. Nat Neurosci; 2003, 6:119-26. 14.Hans P, Dewandre P-Y, Brichant J-F, Bonhomme V: Comparative effects of ketamine on bispectral index and spectral entropy of the electroencephalogram under sevoflurane anaesthesia. Br J Anaesth; 2005, 94:336-40. 15.Vereecke HEM, Struys MRF, Mortierand EP: A comparison of bispectral index ARX–derived auditory evoked potential index measuring the clinical interaction between ketamine propofol anaesthesia. Anaesthesia; 2003, 58:957-61. 16.Subramaniam K, Subramaniam B, Steinbrook RA: Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review. Anesth Analg; 2004, 99:482-95. 17.Elia N, Tramer MR: Ketamine and postoperative pain – a quantitative systematic review of randomized trials. Pain; 2005, 113:61-70. 18.Bell RF, Dahl JB, Moore RA, Kalso E: Peri-operative ketamine for acute postoperative pain: a quantitative and qualitative systematic review (Cochrane review). Acta Anaesthesiol Scand; 2005, 49:140528. 19.Corssen G, Domino EF, Bree RL: Electroencephalographic study of children during ketamine administration. Anesth Analg; 1969, 48:1. 20.Tsuda N, Hayashi K, Hagihira S, Sawa T: Ketamine, an NMDA – antagonist, increases the oscillatory frequencies of α – peaks on the electroencephalographic power spectrum. Acta Anaesthesiol Scand; 2007, 51:472-81. 21.Hayashi K, Tsuda N, Sawa N, Hagihira S: Ketamine increases the frequency of electroencephalographic bicoherence peak on the alpha spindle area induced by propofol. Br J Anaesth; 2007, 99:389-95. 22.Sakai T: The effect of ketamine on clinical endpoints of hypnosis and EEG variables during propofol infusion. Acta Anaesthesiol Scand; 1999, 43:212-6. 23.Hirota K, Kubota T, Ishihara H, Matsuki A: The effects of nitrous oxide and ketamine on bispectral index and 95% spectral edge frequency during propofol-fentanyl anaesthesia. Eur J Anaesthesiol; 1999, 16:779-83. 24.Lauretti GR, Azevedo VMS: Intravenous ketamine or fentanyl prolongs postoperative analgesia after intrathecal neostigmine. Anesth Analg; 1996, 83:766-70. 25.Faraoni D, Salengros J-C, Engelman E, Ickx B, Barvais L: Ketamine has no effect on bispectral index during stable propofolremifentanil anaesthesia. Br J Anaesth; 2009, 102:336-9. 26.Sleigh JW, Barnard JP: Entropy is blind to nitrous oxide. Can we see why? Br J Anaesth; 2004, 92:159-61. M.E.J. ANESTH 21 (3), 2011 Effect of prophylactic dexamethasone on nausea and vomiting after laparoscopic gynecological operation: meta-analysis Jiang Wang Bin*, HE Kai-Hua**, Meng-Bi*, LIU Chao* and MIN Su** Abstract Keywords: dexamethasone; postoperative nausea and vomiting; laparoscopic gynecological operation; meta-analysis Background: Sex of female and laraproscopic surgery are both risk factors related to postoperative nausea and vomiting, and dexamethasone is used as anti-emetic in some operations. A meta-analysis of randomized trials was performed to determine the effect of prophylactic dexamethasone administration on postoperative nausea and vomiting, pain and complications in patients undergoing laparoscopic gynecological operation. Methods: A systematic literature search was conducted to identify all randomized clinical trials. The primary outcome was the incidence and severity of postoperative nausea and vomiting. The secondary outcomes include postoperative pain and complications. Results: Totally 1801 patients were enrolled in 11 eligible randomized trials comparing effect of prophylactic dexamethasone administration on postoperative nausea and vomiting with placebo. The pooled incidence of nausea, vomiting, nausea and vomiting, and rescue anti-emetic was significantly lower in dexamethasone group than placebo group during post-anesthesia care unit (10.5% vs 18.2%, OR 0.51, 95% CI 0.31-0.84; 6.5% vs 17.1%, OR 0.31, 95% CI 0.17-0.56; 17.0% vs 35.4%, OR 0.33, 95% CI 0.21-0.50; 6.7% vs 23.3%, OR 0.22, 95% CI 0.10-0.49, P<0.00001) and within the first postoperative 24 hours (25.2% vs 40.3%, OR 0.46, 95% CI 0.32-0.66; 14.4% vs 36.6%, OR 0.27, 95% CI 0.19-0.40; 33.0% vs 69.0%, OR 0.18, 95% CI 0.13-0.26; 21.0% vs 51.1%, OR 0.26, 95% CI 0.16-0.41, P<0.00001). No significant difference was found about the incidence of rescue analgesia between dexamethasone group and placebo group (48.5% vs 56.4%, OR 0.68, 95% CI 0.40-1.18, P=0.17). Conclusion: Prophylactic dexamethasone administration decreases the incidence of nausea and vomiting after laparoscopic gynecological operations during post-anesthesia care unit and within the first postoperative 24 hours. (286 words) Postoperative nausea and vomiting are the most common complications after anesthesia and surgery, and both sex of female and type of laparoscopic operation are risk factors1. It is certain of a remarkably high incidence after laparoscopic gynecological surgery, which is reported as nearly 70% within the first postoperative 24 hours2. It is very important to find an effective treatment to alleviate postoperative nausea and vomiting. * ** PhD, Department of Anesthesiology, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. Professor, Department of Anesthesiology, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. Correspondence to: MIN Su, Department of Anesthesiology, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China (Tel: 86-023-89011068. Fax: 86-023-89011068. E-mail: [email protected]). 397 M.E.J. ANESTH 21 (3), 2011 398 Wang Bin et al. Dexamethasone was first used as an antiemetic in patients receiving chemotherapy for cancer treatment by a central mechanism involving endogenous prostaglandin and opioid production3,4. And then some trials showed that dexamethasone alone or combination with traditional anti-emetics may decrease the incidence and severity of postoperative nausea and vomiting5,6. Furthermore, perioperative dexamethasone administration may decrease postoperative pain by modulationg the systemic physiologic response in favor of antiinflammatory mediators. Researchers have reviewed the pathophysiologic effects and clinical implications of perioperative dexamethasone administration, but the variability in surgical procedures has precluded definitive conclusions regarding the effectiveness of dexamethasone5. The outcome of interest included the incidence and severity of postoperative nausea and vomiting, and one or more of pain, postoperative complications. The incidence and severity of postoperative nausea and vomiting were evaluated using these four variables: the incidence of (1) nausea, (2) vomiting, (3) PONV (nausea + vomiting), and (4) rescue anti-emetic used. And retching was considered as vomiting. Furthermore, the incidence and severity of postoperative nausea and vomiting included two time interval: during post-anesthesia care unit (PACU) and within the first postoperative 24 hours. Postoperative pain was assessed as the incidence of rescue analgesia. The present meta-analysis was conducted to determine the effect of prophylactic dexamethasone administration on postoperative nausea and vomiting, pain, and complications after laparoscopic gynecological operation. Studies were selected and data were extracted independently by two reviewers. Disagreements were resolved by consensus. We referred to the guidelines of the Cochrane handbook for systematic reviews of interventions 4.2 for our meta-analysis. Methods Statistical methods Criteria for study selection Randomized clinical trials that investigate effect of prophylactic dexamethasone administration on postoperative nausea and vomiting in patients undergoing laparoscopic gynecological operations were included. Data sources and search strategy We carried out this meta-analysis in accordance with the standard protocol recommended by the quality of reporting of meta-analyses group and the guidelines of Cochrane handbook of systematic reviews of interventions 4.2. We searched Pubmed, EMBASE, ISI Web of Science and the Cochrane Central Register of Controlled Trials for randomized trials investigate impact of prophylactic dexamethasone administration on postoperative nausea and vomiting in patients undergoing laparoscopic gynecological operations. We included following terms: laparoscopic, gynecological operation, steroid, dexamethasone, nausea, vomiting. Searches were restricted to the period from January 1, 1998 to December 31, 2009 and language of English. Classification of outcome and definitions Data abstraction and assessment of quality Binary outcomes from individual studies were analyzed according to the Mantel–Haenszel model to compute individual odds ratios (ORs) with pertinent 95% confidence intervals (CIs), and a pooled summary effect estimate was calculated by means of fixed effect. Statistical heterogeneity and inconsistency was measured using, respectively, Cochran Q tests and I2 values. Computations were performed with SPSS 11.0 (SPSS, Chicago, IL) and RevMan 4.2 (a freeware available from The Cochrane Collaboration). All P values were two-sided, and P<0.05 was considered as statistically significant. Results Description of included studies Overall 11 randomized double-blind 7-17 investigate effect of prophylactic clinical trials dexamethasone administration on postoperative nausea and vomiting in patients undergoing laparoscopic gynecological operations were identified, in which 1801 patients were involved, and all belonged to Effect of prophylactic dexamethasone on nausea and vomiting after laparoscopic gynecological operation: meta-analysis 399 Table 1 Prophylactic dexamethasone administration Trial Dexamethasone administration Rescue-antimetic Rescue analgesia Chu dexamethasone 5 mg, iv 15 min after induction Ondansetron 4 mg iv Ketorolac 30 mg iv Fujii Dexamethasone 4 mg/8 mg, iv At end of the sugery Not mentioned 50 mg indomethacin rectally Michael Dexamethasone 4 mg/2mg, iv At end of the sugery Prochlorperazine 12.5 mg iv, followed by Not mentioned droperidol 1 mg iv as necessary Yuksek Dexamethasone 8 mg, iv 2 min before induction Metroclopramide 10 mg, iv 3 mg morphine first, and 50 μg fentanyl repeated if necessary Maddali Dexamethasone 8 mg, iv 2 min before induction Not mentioned Not mentioned Lee Dexamethasone 8 mg, iv 2 min before induction Metoclopramide 10 mg, iv Ketorolac 15 mg iv Eliana Dexamethasone 8 mg, iv 2 min before induction Ondansteron 4 mg iv Tramadol 50 mg iv Huang Dexamethasone 5 mg, iv After tracheal intubation Ondansteron 4 mg iv Not mentioned wang Dexamethasone 10 mg, iv at induction Ondansteron 4 mg iv Not mentioned Rajeeva Dexamethasone 8 mg, iv after induction Metoclopramide 0.15 mg/kg, iv 75mg diclofenac im Rothenberg Dexamethasone 0.017 mg/kg, iv, Not mentioned just prior to abdominal incision Ketorolac 30-60 mg iv, then morphine 1-2 mg iv if necessary ASA(America Society of Anethesiologists) grade I or II. Laparoscopic operations included tubal ligation, myonectomy, hysterectomy, salpingo-oophorectomy, oophorocysterctomy and diagnostic laparoscopy. All of the studies administered a single dose of dexamethasone intravenously, with the timing of administration ranging from immediately before anesthesia induction to the end of the surgery (Table Fig. 1 Forest plot for the comparison of incidence of nausea, vomiting, PONV, and need for rescue anti-emetic during PACU between dexamethasone group and placebo group. Fig 2 Forest plot for the comparison of incidence of nausea, vomiting, PONV, and need for rescue anti-emetic within 24 h between dexamethasone group and placebo group. M.E.J. ANESTH 21 (3), 2011 400 Wang Bin et al. Table 2 Baseline characteristics of patients Trial Chu n 372 Age (y) * Weight (kg)* 43.1(4.7) 57.2(9.2) MS (%) 17 Previous PONV (%) 7 Smoker (%) ---- To (min)* 91.9(24.8) Ta (min)* 114.5(29.0) Fujii 90 35.6(6.4) 53.0(7.0) 0 0 27 85.3(33.1) 123.0(34.6) Michael 614 32.5(6.3) 64.0(6.8) ---- 16 38 --- 40.0(18,1) Yuksek 60 31.1(5.2) 61.9(7.3) 0 ---- ---- 57.3(10.6) 71.7(16.4) Maddali 120 29.1(7.2) 62.8(12.6) ---- ----- ---- 62.9(24.6) ---- Lee 164 39.3(8.0) 56.9(6.8) 0 0 0 113.8(23.0) 137.9(21.9) Eliana 40 30.5(6.5) 60.5(10.1) 0 0 ---- 62.0(37.7) 88.5(37.6) Huang 115 34.0(6.4) 55.0(7.7) 0 0 ---- 42.0(12.2) 65.0(17.3) wang 81 33.0(6.2) 55.0(8.1) --- ---- ---- 44.0(11.8) 66.5(17.3) Rajeeva 51 28.7(4.8) 49.8(6.7) 0 0 Rothenberg 94 32.0(5.5) 66.1(7.8) 12 8 * mean(sd); MS: motion sickness; To: time of operation; Ta: time of anesthesia 1). All the studies measured incidence of postoperative nausea and vomiting, and a substantial proportion measured pain. Not enough reported complications, health-related quality of life or hospital length of stay to allow us to pool the results. The baseline characteristics revealed a relatively young and healthy population, and a relatively short time of anesthesia and operation (Table 2). Effect of prophylactic dexamethasone administration on postoperative nausea and vomiting The incidence of nausea, vomiting, PONV, and need for rescue anti-emetic was significantly lower in dexamethasone group than in placebo group during PACU (10.5% vs 18.2%, OR 0.51, 95% CI 0.31-0.84; 6.5% vs 17.1%, OR 0.31, 95% CI 0.17-0.56; 17.0% vs 35.4%, OR 0.33, 95% CI 0.21-0.50; 6.7% vs 23.3%, OR 0.22, 95% CI 0.10-0.49, P<0.00001) (Fig. 1) and within the first postoperative 24 hours (25.2% vs 40.3%, OR 0.46, 95% CI 0.32-0.66; 14.4% vs 36.6%, OR 0.27, 95% CI 0.19-0.40; 33.0% vs 69.0%, OR 0.18, 95% CI 0.13-0.26; 21.0% vs 51.1%, OR 0.26, 95% CI 0.16-0.41, P<0.00001) (Fig. 2). Effect of prophylactic dexamethasone administration on postoperative pain The incidence of rescue analgesia in dexamethasone group was lower than in placebo group ---- 28.7(4.0) ---- ---- 41.8(12.7) ---- (48.5% vs 56.4%, P=0.17), which suggest a trend toward less need for rescue analgesia in dexamethasone group although the CI was wide (OR 0.68, 95% CI, 0.40-1.18) (Fig. 3). Discussion This meta analysis identified 11 randomized and double-blind trials, which investigate the effect of prophylactic dexamethasone administration on postoperative nausea and vomiting in patients undergoing laparoscopic gynecological operations. Although the trials varied with different other antiemetics, every trial compared dexamethasone with placebo, and presented data for us to pool the results. The pooled results showed that prophylactic dexamethasone administration decreased incidence and severity of postoperative nausea and vomiting during PACU and within the first postoperative 24 hours. Fig. 3 Forest plot for the comparison of rescue analgesics between dexamethasone group and placebo group. Effect of prophylactic dexamethasone on nausea and vomiting after laparoscopic gynecological operation: meta-analysis Prophylactic dexamethasone was administered at different time, varied from 2 minutes before induction to at the end of the operation. Most trials administered dexamethasone soon before or after induction, while just one trial prior to the abdominal incision, and two at the end of the surgery. The optimal timing of dexamethasone administration is still unclear because there was no significant difference between trials with different time of administration. 8 mg or more dexamethasone was administered in 8 trials, and 5 mg or less dexamethasone was administerd in 3 trials. Any dose can decrease incidence and severity of postoperative nausea and vomiting compared with placebo. 8 mg or more dexamethasone was more effective than 5 mg or less on prevention PONV (32% vs 38%). And so 8 mg or more dexamethasone was suggested. This meta-analysis showed lower incidence of rescue analgesia in dexamethasone group than in placebo group, but the difference was not significantly, which was not consistent with other studies18. With repeated reading the trials, all the trials paid more attention to postoperative nausea and vomiting, while only a few trials investigated pain simultaneously, and so a relatively less data about pain could be collected. Another aspect should be taken account that 354 401 patients underwent diagnostic laparoscopic operation, which was minimal invasive and hardly induced pain. And so it was sure that there was a trend a less need for rescue analgesia in dexamethasone group. All the trials did not report serious adverse events after prophylactic dexamethasone administration, which suggested its safety. Furthermore, dexamethasone was very cheap compared with other types of anti-emetics. That is to say, dexamethasone is both safe and economic drug to prevent postoperative nausea and vomiting. Certainly, there are several limitations in this meta-analysis. First, it suffers from inherent limitations of any analysis of aggregate data from published reports to lump study ourcomes rather than data from individual patients. Second, the conclusion of our metaanalysis can not be confined to all patients undergoing laparoscopic gynecological operations, since all the trials excluded obese patients. In fact, there are more and more obese patients. At the same time, our metaanalysis just included trials reported in English. In conclusion, prophylactic dexamethasone decreases the incidence of nausea and vomiting after laparoscopic gynecological operations during PACU and within the first postoperative 24 hours. M.E.J. ANESTH 21 (3), 2011 402 Wang Bin et al. Reference 1. Fujii Y: Postoperative nausea and vomiting and their sex differences. Masui; 2009, 58:59-66. 2. McKeen DM, Arellano R, O'Connell C: Supplemental oxygen does not prevent postoperative nausea and vomiting after gynecological laparoscopy. Can J Anaesth; 2009, 56:651-7. 3. Aapro MS, Alberts DS: Dexamethasone as an antiemetic in patients treated with cisplatin. N Engl J Med; 1981, 305:520. 4. Callery MP: Preoperative steroids for laparoscopic surgery. Ann Surg; 2003, 238:661-662. 5. Holte K, Kehlet H: Perioperative single-dose glucocorticoid administration: pathophysiologic effects and clinical implications. J Am Coll Surg; 2002, 195:694-712. 6. Fujii Y, Nakayama M: Dexamethasone for the reduction of postoperative nausea and vomiting and analgesic requirements after middle ear surgery in adult Japanese patients. Methods Find Exp Clin Pharmacol; 2009, 31:337-40. 7. Chin-Chen Chu, Ja-Ping Shieh, Jann-Inn Tzeng, Jen-Yin Chen, Yi Lee, Shung-Tai Ho, et al: The prophylactic effect of haloperidol plus dexamethasone on postoperative nausea and vomiting in patients undergoing laparoscopically assisted vaginal hysterectomy. Anesth Analg; 2008, 106:1402-1406. 8. Y Fujii, M Nakayama: Dexamethasone for reduction of nausea, vomiting and analgesic use after gynecological laparoscopic surgery. Inter J Gyn and Obst; 2008, 100:27–30. 9. Michael J Paech, Matthew WM Rucklidge, Jennifer Lain, Philip H: Dodd, Emma-Jane Bennett, Dorota A. Doherty. Ondansetron and dexamethasone dose combinations for prophylaxis against postoperative nausea and vomiting. Anesth Analg; 2007, 104:808814. 10.MS Yuksek, HA Alici, AF Erdem, M Cesur: Comparison of prophylactic anti-emetic effects of ondansetron and dexamethasone in women undergoing day-case gynaecological laparoscopic surgery. J Inte Med Res; 2003, 31:481-488. 11.Maddali MM, Mathew J, Fahr J, Zarroug AW: Postoperative nausea and vomiting in diagnostic gynaecological laparoscopic procedures: comparison of the efficacy of the combination of dexamethasone and metoclopramide with that of dexamethasone and ondansetron. J Postgrad Med; 2003, 49:302-306. 12.Yi Lee, Hsien-Yong Lai, Pei-Chin Lin, Shen-Jer Huang, YouhSheng Lin: Dexamethasone prevents postoperative nausea and vomiting more effectively in women with motion sickness. Can J Anesth; 2003, 50:232–237. 13.Eliana Marisa Ganem, Fernanda B Fukushima, Daniela S Medeirosda Silva, Giane Nakamura, Yara Marcondes Machado Castiglia, Pedro Thadeu Galvão Vianna: Efficacy of propofol and propofol plus dexamethasone in controlling postoperative nausea and vomiting of gynecologic laparoscopy. Rev Bras Anestesiol; 2002, 52:394-401. 14.Jeng-Chai Huang, Ja-Ping Shieh, Chao-Shun Tang, Jann-Inn Tzeng, Koung-Shing Chu, Jhi-Joung Wang: Postoperative nausea and vomiting after ambulatory laparoscopic surgery. Can J Anesth; 2001, 48:973-977. 15.JJ Wang, ST Ho, HS Liu, CM Ho: Prophylactic antiemetic effect of dexamethasone in women undergoing ambulatory laparoscopic surgery. Br J Anesth; 2000, 84:459-462. 16.V Rajeeva, N Bhardwaj, YK Batra, LK Dhaliwal: Comparison of ondansetron with ondansetron and dexamethasone in prevention of PONV in diagnostic laparoscopy. Can J Anesth; 1999, 46:40-44. 17.DM Rothenbergr, J Mccarthyc, C Peng, DA Normoyle: Nausea and vomiting after dexamethasone versus droperidol following outpatient laparoscopy with a propof ol-based general anesthetic. Acfn Aizaesfkesiol Scand; 1998, 42:637-642. 18.Korb K, Scherer M, Chenot JF: Steroids as adjuvant therapy for acute pharyngitis in ambulatory patients: a systematic review. Ann Fam Med; 2010, 8:58-63. VENTILATION DIFFICULTY DUE TO HERNIATION OF INFLATING TUBE OF THE CUFF INSIDE THE ** ENDOTRACHEAL TUBE Oya Yalcin Cok, Melih Cekinmez, Pinar Ergenoglu and A nis A ribogan The complications due to airway equipments remain to be one of the most challenging situations for the anesthesiologists. Any part of an endotracheal tube may cause a risk when it leads to an obstruction in the airway. Here, we present an increased airway pressure due to herniation of inflating tube of the cuff inside an armored (wire reinforced) endotracheal tube during neurosurgery in prone position. A 34 years old, female patient was scheduled for 6th thoracic vertebraectomy and bilateral transpedinculer fixation after vertebrae fracture and dislocation. The patient was intubated uneventfully with an armoured tube (I.D. 7.5 mm, O.D. 17 mm, Mallinckrodt, St. Louis, USA). The tube level was checked by auscultation and taped at 19 cm. The initial airway pressure was between 14 - 16 cm H2O with a tidal volume of 450 ml and 11 breaths/min. The anesthesia was maintained by isoflurane and nitrous oxide/O2 (50%/50%). The endotracheal tube checked again for an unintentional malpositioning of the tube after prone positioning and confirmed by auscultation and airway pressure which remained between 18 and 20 cm H2O. After two hours, air leakage was suspected from the tube and the cuff was inflated with 1 ml of air and the leakage was ended. Airway pressure started to rise during rod placement after transpedinculer screws insertion at the 3rd hour, and the neurosurgeons were informed about the problem assuming that the rise in airway pressure might be related to the surgical procedure as the manipulations due to the reduction for obtaining thoracic lordosis could be the cause of increased airway pressure. We tried to aspirate through the endotracheal tube with a 14 Ch aspiration catheter. However, we couldn’t insert the catheter more than 5 cm inside the tube. The manual ventilation was started until suturation since the airway pressure and PaCO2 peaked at 60 cm H2O and 70 mmHg, respectively. After a rapid closure of the surgical site, the patient positioned supine, however airway pressure still remained high and the suctioning was impossible. When we inspected inside the tube, we noticed a transparent projection obstructing ½ of the inner diameter of the endotracheal tube (Fig. 1). Immediately, we removed the obstructed tube and replaced it with a standard 7.5 mm tube. The airway pressure returned into normal and increase in PaCO2 resolved quickly. The patient was extubated uneventfully. * * Baskent University, Faculty of Medicine, Ankara, Turkey. Corresponding Author: Dr. Oya Yalcin Cok, Baskent University, Department of Anesthesiology and Reanimation, Adana Research and Education Center, Yuregir Adana/Turkey. Tel: +90 322 3272727-1469, Fax: +90 322 3271274. E-mail: [email protected] 403 M.E.J. ANESTH 21 (3), 2011 404 Oya Yalcin Cok et al. Fig. 1 The photograph of the obstruction inside the endotracheal tube Nitrous oxide may diffuse into the potential spaces in the structure of armoured tubes as they are manufactured in layers3. This may cause a layer separation leading to an obstructing projection inside the tube.4 However, in our case, the obstructing projection was originated from inflating tube of the cuff (Fig. 2). Inflating the tube cuff during the operation exacerbated the obstruction as the pressure was increased both because of the diffused nitrous oxide and additional air volume. We observed that deflating the pilot balloon and the cuff resolved the obstruction after we replaced it with a new tube. It is important to emphasize that this was not inspected in the routine examination of the tube before intubation. We suggest that armoured tubes may require a more careful examination as they are more likely to cause unusual complications. Fig. 2 Diagram of the herniation of inflating tube of the cuff References 1. Yapici D, Atici S, Birbicer H, Oral U: Manufacturing defect in an endotracheal tube connector: risk of foreign body aspiration. J Anesth; 2008, 22:333-4. 2. Gettelman TA, Morris GN: Endotracheal tube failure: undetected by routine testing. Anesth Analg; 1995, 81:1313. 3. Hansen D, Dopjans D, Syben R: [Obstruction of a spiral anesthesia tube in a pediatric circuit system]. Anaesthesist; 1995, 44:884-6. 4. Kopp KH, Wehmer H: [Nitrous oxide induced intraluminal tube obstruction during endotracheal intubation with armored tubes (author's transl)]. Anaesthesist; 1981, 30:577-9. ANESTHESIA FOR CESARIAN SECTION IN PREGNANT WOMAN WITH ACUTE INTERMITTENT PORPHYRIA AND HYPOTHYROIDISM - Case Report* - Roberto P. Dumas, Elizabeth F. V. Silva, Marco Antonio C. Resende, Alberto V. Pantoja and A ntonio C elso G. S. B arros F. Abstract Acute intermittent porphyria (AIP) is a rare autosomal dominant metabolic disorder¹ affecting the production of heme, the oxygen-binding prosthetic group of hemoglobin². It is characterized by a deficiency of the enzyme hydroxymethylbilane synthase; without this cytoplasmic enzyme, heme synthesis cannot finish, and the metabolite porphobilinogen accumulates in the cytoplasm³. Some additional factors must also be present such as drugs, hormones, dietary changes, infections diseases and surgery that trigger the appearance of symptoms, which include neurological disorders, abdominal pain, constipation, and muscle weakness. We present a perioperative course of a pregnant woman with porphyria in association with hypothyroidism and its anesthetic management. Case Report A 30 yr-old, 67 Kg female woman was admitted with history of 42 weeks of gestational age and proposal to hold an emergency cesarean section for cephalo-pelvic disproportion. Past medical history included diagnosis of AIP (without sequelae and with no history of acute crisis of last 2 years) and hypothyroidism with hormone replacement to 75 mcg of levothyroxine daily. His airway classification was Mallampati 2 and her ASA status was PIIE. After completion of the venipuncture with an 18G catheter and monitoring with ECG, NIBP, pulse oximetry and urine output hourly, carried spinal anesthesia with the patient in the left lateral position with a 27G Quincke tip and, by median, L3-L4 interspace and injection of 12 mg of heavy bupivacaine combined with 50 mcg of morphine. At the fifth minute of the blockade, the sensory level was at T4. After the birth of male fetus (Apgar 9/10), was administered 10 IU of oxytocin. The volume replacement was given with 500 ml of dextrose 5% and 1000 ml of Ringer's lactate; had diuresis of 150 ml during the procedure. The patient remained stable throughout the procedure, which lasted about 75 minutes. * Dept. of Surgery. Hospital Universitário Antônio Pedro – Universidade Federal Fluminense. Corresponding Author: Antonio Celso G. S. Barros F, Dept. of Surgery. Hospital Universitário Antônio Pedro – Universidade Federal Fluminense. Rua Marquês de Paraná, 303. Centro. Niterói-RJ. CEP 24220-300. Tel: 55-21-26299000 Ramal 9090. E-mail: [email protected] 405 M.E.J. ANESTH 21 (3), 2011 406 R. P. Dumas et al. Discussion The AIP management includes high-carbohydrate diet; in severe attacks, a glucose 10% infusion is recommended, which may aid in recovery. Infection is one of the causes of attacks and requires treatment. Pain is extremely severe and almost always requires the use of analgesic drugs and should be treated early as medically possible. Nausea and vomiting can be severe. Hematin and heme arginate are the drugs of choice and need to be given very early in an attack to be effective. They are not curative drugs, but can shorten attacks and reduce the intensity of an attack. Patients with a history of acute porphyria are recommended to wear an identification at all times in case they develop severe symptoms, a result of which may be that they cannot explain to healthcare professionals about their condition and the fact that some drugs are absolutely contraindicated. An attack of acute intermittent porphyria may be precipitated by one of the "four Ms": medication, menstruation, malnutrition, maladies. If drugs have caused the attack, discontinuing the offending substances is essential. Patients that experience frequent attacks can develop chronic neuropathic pain. This is thought to be due to axonal nerve deterioration in affected areas of the nervous system. Depression and seizures often accompanies the disease and is best dealt with by treating the offending symptoms and, the judicious use of anti-depressants and anti-convulsant drugs. Most seizure medications exacerbate this condition. Urine from a person experiencing an acute attack may be red or "port wine" in color because of the presence of porphyrins. In obstetrics, the main factors triggering the acute crisis of porphyria are hyperemesis gravidarum, fasting pre and post-operative, hormonal changes, infections, surgery and anesthesia. The anesthetic management must include a careful selection of drugs, hydration with glucose solution, diet-based carbohydrates, prophylaxis of bronchial aspiration and evaluation of liver function. Regional anesthesia is preferred, because they are many unknown and unsafe anesthetic drugs, which can be seen in the Table 1. However, regional anesthesia should be avoided in cases where there is a neurological injury suspect or indefinite. Worsening of porphyria during pregnancy may be between 50% and 90%, with maternal mortality ranging from 2% to 40%, fetal mortality from 13% to 40%. In conclusion, AIP and its association with hypothyroidism in a pregnant patient can be catastrophic. The main complicating factors in this case are the association of exposure to surgical stress, drugs and anesthetic procedure itself. Table 1 Common Used Anesthetic Drugs Classification DRUGS SAFE UNKNOWN UNSAFE HYPNOTICS Midazolam, Propofol, Lorazepam Ketamin, Diazepam Barbiturates, Etomidate INHANALATED Nitrous Oxide, Desflurane Isoflurane, Halothane, Sevoflurane Enflurane OPIOIDS Fentanyl, Morfine Alfentanyl, Sufentanyl MUSCLE RELAXANTS Succinylcholine, Vecuronium Atracurium, Pancuronium LOCAL ANESTHETICS Bupivacaine Lidocaine ANOTHER DRUGS Neoestigmine Steroids ANESTHESIA FOR CESARIAN SECTION IN PREGNANT WOMAN WITH ACUTE INTERMITTENT PORPHYRIA AND HYPOTHYROIDISM 407 References 1. Whatley SD, Roberts AG, Llewellyn DH, Bennet CP, Garret C, Elder GH: "Non-erythroid form of acute intermittent porphyria caused by promoter and frameshift mutations distant from the coding sequence of exon 1 of the HMBS gene". Hum Genet; 2000, 107(3):243-8. 2. Baker S and Taylor B: Anaesthesia is also risky in patients with porphyria. BMJ; 2006, 321:1023-1023. 3. Aarsand AK, Petersen PH, Sandberg S: “Estimation and application of biological variation of urinary delta-aminolevulinic acid and porphobilinogen in healthy individuals and in patients with acute intermittent porphyria". Clinical Chemistry; 2006, 52(4):650656. 4. JAMES MFM and HIFT RJ.: Porphyrias. Br J Anaesthesia; 2000, 85:143-153. 5. Jensen NF, Fiddler DS, Striepe V: Anesthetic considerations in porphyrias. Anesth Analg; 1995, 80:591-599. 6. Yamashita AM, Gozzani JL: Anestesia em Obstetrícia. 2 Edição. São Paulo. Editora Atheneu, 2007. 7. James WD, Berger TG et al: Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier, 2006. 8.American Porphyria Foundation. "About Porphyria: Acute Intermittent Porhyria", 2007. 9. Marcucci L: PathCards. Baltimore, MD: Lippincott Willians & Wilkins, 2004, pp. 105-106. M.E.J. ANESTH 21 (3), 2011 “CRIME SCENE INVESTIGATION” AT AN ANESTHETIC COCKTAIL PARTY WITH ATRIOVENTRICULAR DISSOCIATION Christoph J. Schlimp* and Franz J. Wiedermann** Abstract A healthy 21-year old female patient received midazolam, propofol, fentanyl, rocuronium, nitrous oxide in oxygen, ranitidine, diclofenac, neostigmine and glycopyrrolate during the anesthetic process for elective knee arthroscopy and developed a complete AV dissociation with a P-wave frequency of 40 and a “small” QRS-complex frequency of 55 beats/min. Based on this typical case of poly-pragmatic anesthetic drug administration causing a complete atrioventricular dissociation in a young healthy patient we will discuss the possible pharmacodynamic mechanisms of all used drugs with regard to the cardiac conduction system. Keywords: atrioventricular heart block, general anesthesia, midazolam, fentanyl, propofol, ranitidine, neostigmine, rocuronium, glycopyrrolate, nitrous oxide. Financial support and conflict of interest: None. Introduction Poly-pragmatic drug administration during balanced anesthesia is commonly used to reduce high doses and side effects of one drug or to antagonize (side) effects of other drugs. Typically used poly-pragmatic anesthetic drug administrations are e.g. different hypnotics: benzodiazepines for pre-medication, barbiturates for induction and a volatile anesthetic for sustaining anesthesia; or e.g. different opioids: fentanyl for induction of anesthesia, remifentanyl for accurate controllable analgesia during the operation and a less potent agent like morphin or piritramid for postoperative analgesia. In addition to hypnotics and opiods, neuromuscular blocking agents and their antagonist (acetyl-cholinesterase inhibitor again combined with its own vegetative antagonist: an anticholinergic) are commonly used. Histaminic H2-receptor antagonists are also often administered to minimize gastric volume and for gastric protection in combination with non-steroidal anti inflammatory drugs. However, the advantages of this poly-pragmatic drug administration may lead to difficult allocation of possible side effects due to the higher potential of drug interaction. Based on a “crime scene” of a complete atrioventricular (AV) dissociation after administration of nine different drugs in a young healthy patient we will investigate and discuss the scene and review the possible pharmacodynamic mechanisms of all used drugs with regard to its influence on the AV conduction system. * ** Dept. of Anesthesiology and Critical Care Medicine, Trauma Hospital Klagenfurt, Austria. Associate Professor. Dept. of Anesthesiology and Critical Care Medicine, Medical University Innsbruck, Austria. Corresponding Author: Dr. Christoph Schlimp, Department of Anesthesiology and Critical Care Medicine, Trauma Hospital Klagenfurt, Waidmannsdorferstrasse 35, A-9021 Klagenfurt, Austria. Tel: +43-463-5890-1035, Fax: +43-4635890-1038. E-mail: [email protected] 409 M.E.J. ANESTH 21 (3), 2011 410 “Crime Scene” A 21-year-old woman, 65 kg and 168 cm, ASA status I, presented for an elective knee arthroscopy of about 45 min anesthesia. Medical history and physical examination were without pathological findings, the patient took no medication, and preoperative routine laboratory results were within the normal range. The following drugs were given to the patient during the anesthetic process: midazolam (7.5 mg orally), propofol (200 mg bolus + 400 mg/h), fentanyl (0.15 mg), rocuronium (25 mg), nitrous oxide (66%) in oxygen (33%), ranitidine (50 mg), diclofenac (75mg), neostigmine (3.2 mg) and glycopyrrolate (0.6 mg). Suddenly the monitoring ECG showed a complete AV dissociation, with a P-wave frequency of 40 and a “small” QRS-complex frequency of 55 beats/min, hemodynamical stable and resolving during emergence. C.S.I. “Crime Scene Investigation” Investigator: At the scene currently under investigation, we saw the appearance of a complete AV dissociation during anesthesia. Nine drugs (midazolam, fentanyl, propofol, rocuronium, nitrous oxide, ranitidine, diclofenac, neostigmine, glycopyrrolate) have been spotted on the scene. Which drug used has the potential to elicit AV dissociation? Anesthesia Expert: Midazolam was reported to have a dose-dependent depressing effect on the AV node in isolated guinea pig hearts1. Fentanyl is known to have central vagal effects and might probably posses direct depressing effects on the AV conduction2. Clinical evaluation of cardiac electrophysiological effects of midazolam combined with fentanyl, however, did not show significant changes in the electrophysiological variables3. Propofol’s mechanism of action on the AV conduction system is not completely known and literature is quite dissolute on this topic. Propofol is supposed to have a central vagotonic and/or sympatholytic mechanism4 and was held responsible for the occurrence of a second degree AV Mobitz I block5-7 reversible by anticholinergic drug administration. In a child, a single bolus of propofol elicited a complete AV block, but this child was suffering from Ondine’s curse, characterized by a generalized disorder of autonomic function8. The combination of propofol and neostigmine in a patient also caused a complete heart block9. In all of the cases described above, the AV block was thought to be caused by a vagotonic (cholinergic) mechanism. Recently, propofol was associated with antiarrhythmic properties in the cardiac conduction system10, but the indirect vagotonic or direct influence of propofol on the electrophysiological properties of the heart are controversial and may depend on the species investigated and the specific conditions of study. The negative dromotropic effects of propofol in the isolated guinea pig heart were suggested to be mediated by muscarinic M2-receptors11, an idea which would be supported by a study that found no direct effect of propofol on the canine cardiac conduction system under autonomic blockade12. This is in contrast with the results of a study of isolated rabbit hearts, in which under complete autonomic blockade at clinically relevant propofol doses, a direct frequencydependent effect on the AV node was found13. A study in closed chest pigs showed that propofol causes a dose-related depression of the sinus node and the His-Purkinje system but has no effect on the AV node function14 whereas studies in isolated guinea pig heart revealed dose-or frequency-dependent AV nodal effects of propofol1,15. On the cellular level, propofol suppressed directly the sodium, calcium and potassium currents in rabbit heart myocytes16. However, clinical studies have shown that propofol does not affect the effective refractory periods of the AV node in patients with Wolff-Parkinson-White syndrome17 and children undergoing radiofrequency ablation18. Ranitidine blocks histaminic H2-receptors and inhibits the G-protein mediated rise in cyclic adenosine monophosphate, and thus decreases the heart rate. Furthermore, by blocking competitively H2-receptors, free histamine molecules can now activate more H1receptors leading to a G-protein- mediated rise in calcium decreasing cardiac dromotropy. Extremely rare cardiovascular side effects are reported to occur especially after rapid infusion19, and it has been mentioned in association with AV block20,21. Neostigmine, a peripheral acetyl-cholinesterase inhibitor is strongly parasympathomimetic by increasing the acetyl-cholin concentration also at the muscarinic M2-receptor in the heart, Therefore, neostigmine was reported to cause AV conduction 411 depression in several cases9,22-24. Investigator: What effects do the other drugs exert on the cardiac conduction system? Anesthesia Expert: Glycopyrrolate, a peripheral blocking drug at the muscarinic M2-receptor in the heart, enhances parasympatholytic effects and therefore is a cardiac conduction-stimulatory agent. Rocuronium is also known to have weak parasympatholytic activity25. Nitrous oxide was mentioned in a case of AV dissociation with AV junctional rhythm26 but its influence on the heart’s automaticity and conduction is not easy to define and might rather be a change in sympathetic nervous activity27. Diclofenac is not known to have any direct impact on cardiac arrhythmia, besides the possible hyperkalemia after non-steroidal anti-inflammatory drug-induced renal dysfunction28. Investigator: What do you think was the combined effect of all these drugs and which drug should be held most responsible regarding the onset of AV dissociation in this patient? Anesthesia Expert: Probably minor complices on the scene but inevitably present in almost all anesthetic scenes were midazolam and fentanyl. Due to its previously discussed properties, propofol is a very interesting possible culprit present during the whole act. Another potential offender present and to be considered is ranitidine. All these drugs were finally toped up with neostigmine. We have previously discussed, that midazolam, fentanyl, propofol, ranitidine and neostigmine have all depressing effects on the AV conduction and may therefore conclude in the first place that their combination might have elicited this AV dissociation. Timing of the appearance of neostigmine shortly before the onset of the AV dissociation would also suggest that it played the major role in this act. Furthermore, due to the well known parasympathomimetic effect of neostigmine to induce bradycardia, it is usually combined with glycopyrrolate a parasympatholytic. Some would now advocate that the simplest explanation for the heart block in this patient is a relatively high dose of neostigmine and a relatively low dose of glycopyrrolate. Rocuronium that has weak vagolytic side effects was apparently not much of a help to support glycopyrrolate in this case. We do, however, not know whether a higher dose of glycopyrrolate would have made any difference in the occurrence of the AV dissociation and can conclude that midazolam, fentanyl, propofol and ranitidine had at least a very high potential for enhancing this side effect of neostigmine. Investigator: Well, then is there anything, that could have prevented AV dissociation? Anesthesia Expert: With regard to this patient, it is of interest that post-operative evaluation of preoperative existing electrocardiography (ECG) showed a borderline AV block grade I with a PQ interval of 212 ms. Pre-operative consideration of this fact would probably have changed the poly-pragmatic drug administration in this case, but routine ECG evaluation in young patients is not common and its outcome and cost effectiveness with regard to the prevention of such adverse events would be subject to further discussion and investigation? However its knowledge might lead to a more critical use of the previously discussed agents in such patients. Furthermore, routine use of intraoperative relaxometry might help to reduce or avoid the routine use of acetyl-cholinesterase inhibitors and their mentioned side effects. Routine use of ranitidine in every patient should be carefully considered and restricted to especially indicated cases. Maybe, where possible, regional anesthesia would be preferable reducing drug interaction and its potential to cause AV dissociation in such patients. Final pleading The combination of many drugs routinely used during general anesthesia may have caused the complete AV dissociation in this scene. It appears that the cardiac conduction-stimulatory agent glycopyrrolate was not effective enough to compensate for the cardiac conduction-depression, provoked by the cumulative drug interaction due to combination of midazolam, fentanyl, propofol, ranitidine and neostigmine. Anesthetists should be aware of the cardiac conduction side effects of routinely used drug cocktails and should adapt poly-pragmatic drug administration with regard to possible AV conduction abnormalities evident on available ECGs even in young healthy patients. Current poly-pragmatic drug administration should be generally reconsidered. M.E.J. ANESTH 21 (3), 2011 412 References 1. Stowe DF, Bosnjak ZJ, Kampine JP: Comparison of etomidate, ketamine, midazolam, propofol, and thiopental on function and metabolism of isolated hearts. Anesth Analg; 1992, 74:547-58. 2. Bovill JG, Sebel PS, Stanley TH: Opioid analgesics in anesthesia: with special reference to their use in cardiovascular anesthesia. Anesthesiology; 1984, 61:731-55. 3. Lau W, Kovoor P, Ross DL: Cardiac electrophysiologic effects of midazolam combined with fentanyl. Am J Cardiol; 1993, 72:177-82. 4. Cullen PM, Turtle M, Prys-Roberts C, Way WL, Dye J: Effect of propofol anesthesia on baroreflex activity in humans. Anesth Analg; 1987, 66:1115-20. 5. Ganansia MF, Francois TP, Ormezzano X, Pinaud ML, Lepage JY: Atrioventricular Mobitz I block during propofol anesthesia for laparoscopic tubal ligation. Anesth Analg; 1989, 69:524-5. 6. Elhairy A, Seguier JC, Sinda P: Auriculo-ventricular conduction disorder following a continuous administration of propofol. Apropos of a case. Cah Anesthesiol; 1992, 40:417-9. 7.El Hairy M: Mobitz I atrioventricular block during propofol anesthesia. Ann Fr Anesth Reanim; 1993, 12:606. 8. Sochala C, Deenen D, Ville A, Govaerts MJ: Heart block following propofol in a child. Paediatr Anaesth; 1999, 9:349-51. 9. James MF, Reyneke CJ, Whiffler K: Heart block following propofol: a case report. Br J Anaesth; 1989, 62:213-5. 10.Kannan S, Sherwood N: Termination of supraventricular tachycardia by propofol. Br J Anaesth; 2002, 88:874-5. 11.Alphin RS, Martens JR, Dennis DM: Frequency-dependent effects of propofol on atrioventricular nodal conduction in guinea pig isolated heart. Mechanism and potential antidysrhythmic properties. Anesthesiology; 1995, 83:382-4; discussion 24A. 12.Ikeno S, Akazawa S, Shimizu R et al: Propofol does not affect the canine cardiac conduction system under autonomic blockade. Can J Anaesth; 1999, 46:148-53. 13.Wu MH, Su MJ, Sun SS: Age-related propofol effects on electrophysiological properties of isolated hearts. Anesth Analg; 1997, 84:964-71. 14.Pires LA, Huang SK, Wagshal AB, Kulkarni RS: Electrophysiological effects of propofol on the normal cardiac conduction system. Cardiology; 1996, 87:319-24. 15.Napolitano CA, Raatikainen MJ, Martens JR, Dennis DM: Effects of intravenous anesthetics on atrial wavelength and atrioventricular nodal conduction in guinea pig heart. Potential antidysrhythmic properties and clinical implications. Anesthesiology; 1996, 85:393402. 16.Wu MH, Su MJ, Sun SS: Comparative direct electrophysiological effects of propofol on the conduction system and ionic channels of rabbit hearts. Br J Pharm; 1997, 121:617-24. 17.Sharpe MD, Dobkowski WB, Murkin JM, Klein G, Yee R: Propofol has no direct effect on sinoatrial node function or on normal atrioventricular and accessory pathway conduction in WolffParkinson-White syndrome during alfentanil/midazolam anesthesia. Anesthesiology; 1995, 82:888-95. 18.Lavoie J, Walsh EP, Burrows FA, Laussen P, Lulu JA, Hansen DD: Effects of propofol or isoflurane anesthesia on cardiac conduction in children undergoing radiofrequency catheter ablation for tachydysrhythmias. Anesthesiology; 1995, 82:884-7. 19.Vial T, Goubier C, Bergeret A, Cabrera F, Evreux JC, Descotes J: Side effects of ranitidine. Drug Saf; 1991, 6:94-117. 20.Allegri G, Pellegrini K, Dobrilla G: First-degree atrioventricular block in a young duodenal ulcer patient treated with a standard oral dose of ranitidine. Agents Actions; 1988, 24:237-42. 21.Patterson LJ, Milne B: Latex anaphylaxis causing heart block: role of ranitidine. Can J Anaesth; 1999, 46:776-8. 22.Lonsdale M, Stuart J: Complete heart block following glycopyrrolate/neostigmine mixture. Anaesthesia; 1989, 44:448449. 23.Tanaka H, Murata K, Sera A, Horibe M, Izumi H, Tsuchiya T: Conversion to 2nd degree from 1st degree atrioventricular (AV) block by the reversal of neuromuscular blockade. Masui; 1991, 40:616-21. 24.Webb MD: Type I second-degree AV block after neostigmine administration in a child with renal failure. Anesth Prog; 1995, 42:21-2. 25.Wierda JM, Schuringa M, van den Broek L: Cardiovascular effects of an intubating dose of rocuronium 0.6 mg kg-1 in anaesthetized patients, paralysed with vecuronium. Br J Anaesth; 1997, 78:586-7. 26.Roizen FR, Plummer GO, Lichtor JL: Nitrous oxide and Dysrhythmias. Anesthesiology; 1987, 66:427-31. 27.Stowe DF, Monroe SM, Marijic J, Rooney RT, Bosnjak ZJ, Kampine JP: Effects of nitrous oxide on contractile function and metabolism of the isolated heart. Anesthesiology; 1990, 73:1220-6. 28.Alva JP, Kotian G: Diclofenac induced renal dysfunction presenting as cardiac arrhythmia. J Assoc Physicians India; 2001, 49:749-52. LEFT ATRIAL MYXOMA WITH CORONARY ARTERY DISEASE: AN UNEXPECTED PREOPERATIVE FINDING - Case Report - Madan Mohan Maddali*, Ahmed Mohammed Abduraz**, Prashanth Panduranga*** and Elizabeth Kurian**** Abstract We describe the case of a 54-year-old man with no symptoms of a cardiac disease who, in the preoperative assessment for eye surgery was diagnosed to have a left atrial myxoma coupled with coronary artery disease. After thorough investigations, the patient underwent resection of the left atrial tumor and coronary artery bypass grafting with a succesful outcome. The histopathological examination revealed a myxoma. This case report highlights the importance of preoperative evaluation in patients with unsuspected coexisting cardiac diseases, treatment options and the anesthetic concerns. Keywords: Myxoma; heart atria left; Myxoma/surgery; Coronary Disease/surgery. Atrial myxomas are the most common benign primary tumours of the heart and sudden deaths probably related to coronary embolization have been described1,2. This report is unusual on account of a rarely described concomitant presence of a left atrial {LA} myxoma with coronary artery disease [CAD] in an otherwise asymptomatic patient. The objective of this report is to highlight the importance of a through preoperative evaluation in the diagnosis of cardiac ailments even in asymptomatic patients. In addition, this report draws attention to conundrums like: a) Could the CAD be secondary to embolization from the LA myxoma b) What are the therapeutic options? When should coronary artery bypass surgery [CABG] be performed and c) What are the anesthetic challenges? Case History A large LA mass was incidentally found during a transthoracic echocardiography [TTE] examination when an asymptomatic 54 year old man with electrocardiogram [ECG] changes was undergoing a routine preoperative cardiological assessment for eye surgery. He was a diabetic with sedentary habits and belonged to ASA class III physical status [BMI >30]. All his hematological * Senior Consultant in Anesthesia,Royal Hospital, Muscat, Sultanate of Oman. ** Senior Specialist in Cardiology, Royal Hospital, Muscat, Sultanate of Oman. *** Senior Specialist in Anesthesia, Royal Hospital, Muscat, Sultanate of Oman. ****Resident in Anesthesia, Oman Medical Specialty Board, Sultanate of Oman. Address for correspondence: Dr. Madan Mohan Maddali, Senior Consultant in Anesthesia, Royal Hospital, P.B. No: 1331, P.C: 111, Seeb, Muscat, Sultanate of Oman. Tel/Fax: 00 968 24499759. E-mail: [email protected] 413 M.E.J. ANESTH 21 (3), 2011 414 and biochemical markers were within normal limits except that he had dyslipedemia as well as an elevated fibrinogen level {4.31g/L[normal: 1.5 to 4.2]}. ECG showed a sinus rhythm with left axis deviation, left ventricular hypertrophy with strain and a QS pattern in III,AVF. Chest radiography showed cardiomegaly with minimal left basal effusion. Transesophageal echocardiography (TEE) confirmed a large LA mass [5 cm x 3.5 cm] attached to fossa ovalis with specks of calcification. The mass was prolapsing into mitral valve during diastole [Fig. 1] and the mitral valve was normal. LA appendage had no thrombus but there was a 4 mm layered atheroma in the descending aorta. Considering patients age, diabetic status, ECG showing old inferior wall myocardial infarction (MI) pattern and left ventricular dysfunction, a coronary angiography was performed which demonstrated an isolated 70% occlusion of the left anterior descending [LAD] artery. Under general anesthesia with standard ASA monitoring intraoperative TEE guidance, the patient underwent resection of the LA mass and coronary artery bypass grafting with an anastomosis between the left internal mammary artery and the LAD artery on cardiopulmonary bypass [CPB]. Tables 1 and 2 show perioperative hemodynamic data and blood gas Fig. 1 Transesophageal echocardiography in long-axis view showing a large left atrial myxoma attached at fossa ovalis and prolapsing into left ventricle during diastole M. M. Maddali et al. parameters. The postoperative course was uneventful. The specimen weighed 47 grams (gms) and on histopathological analysis confirmed the diagnosis of a myxoma. Discussion Fifty percent of all primary cardiac tumors are myxomas with a majority arising in the LA3,4. Approximately 10% of patients with atrial myxomas may be completely asymptomatic1. Most often a thorough preoperative evaluation detects the underlying pathology in these asymptomatic patients when they undergo incidental non cardiac or cardiac surgery. Awareness of the clinical signs and symptoms produced by myxomas is essential to raise the suspicion of their presence. Atrial myxomas can produce obstructive, constitutional, and embolic symptoms when they weigh greater than 70 gms5. As the myxoma in our patient weighed less probably he was asymptomatic. Obstruction of mitral valve can mimic mitral stenosis6. Systemic manifestations like weight loss, arthralgias, fever, anemia etc might occur before obstructive or embolic events and might be due to microembolism or due to the triggering of immunologic responses by tumor fragmentation7. LEFT ATRIAL MYXOMA WITH CORONARY ARTERY DISEASE: AN UNEXPECTED PREOPERATIVE FINDING 415 Table 1 Perioperative hemodynamic parameters 8:00 8:30 8:30 am 9:00 am PAP [mm Hg] 9:00 9:30 am 9:30 -10:00 am 10:30 -11:00 am 11:30 12:00 am 11:00 -11:30 am 12:00 12:30 am 25/15 26/14 CVP [mm Hg] 8 7 7 ETCO2[mm Hg] 32 32 34 SaO2 100 100 100 150/80 100/65 105/ 65 Arterial Blood pressure[mm Hg] 10:00 -10:30 am 8 9 34 34 100 100 100 125/55 125/ 60 105/ 50 CPB Started at 9:42 am Ended at 11:10 am Table 2 Blood gas analysis values of arterial and mixed venous blood Arterial Blood Gas / Electrolytes arterial sample [8:42am] venous sample [9:40am] venous sample [10:30am] arterial sample [10:32am] venous sample [10:56am] venous sample [11:35am] PH (7.35 - 7.45) 7.548 7.435 7.404 7.431 7.375 7.460 PCO2 mmHg 35.6 38.5 38.4 36.4 39.2 36.4 PO2 mmHg 174.7 41.7 47.5 190.9 42.6 37.3 HCO3 std mmol/L 23.5 23.8 23.4 23.2 22.1 21.9 tCO2 mmol/L 19.9 24.4 24.6 23.4 23.6 21.3 Base Excess -1.3 -0.4 -1.1 -1.5 -2.5 -2.7 Na+ (135.0 - 148.0mmol/L) 134.6 135.5 136.8 138.6 135.2 139.7 K+ (3.5 – 5.3 mmol/L) 3.14 3.14 4.36 4.34 4.2 3.48 Ca++ (1.13 – 1.32mmol/L) 0.8 0.8 1.11 1.10 1.11 0.94 Cl(98 – 106 mmol/L) 106 101 107 107 107 105 Anion Gap [mmol/L] 12.5 14.3 4.7 5.6 6.0 10.7 Screening for myxomas should involve a thorough history, physical examination and echocardiography [TTE: 95% sensitivity, TEE: 100% sensitivity]8. The age at presentation and the symptoms of atrial myxomas and CAD can be similar. At times, the two lesions coexist as seen in our patient. A high index of suspicion remains the key element in making a combined diagnosis9. Is the CAD in this patient secondary to embolization from the myxoma or a coexisting condition secondary to atherosclerosis or both? Coronary artery embolization, albeit a lethal complication of atrial myxomas, is extremely rare [0.6%]10. The low rates might be because emboli are less likely to enter the coronary arteries11. There is a tendency for embolism into the right coronary artery due to its conducive M.E.J. ANESTH 21 (3), 2011 416 position. Villous or polypoidal myxomas are fragile and embolize easily12. Tumors with an irregular and friable surface have a higher incidence of embolization7. Even though, the myxoma in this patient was not villous, it could have been the source of right coronary artery embolization with subsequent recanalization. This was seen as QS waves in the inferior wall leads in the ECG as well as an akinetic segment on TTE. But, coronary angiography that was performed a few days later revealed a normal right coronary artery suggesting a possible recanalization. The rate of recanalization is high for coronary embolism from myxomas13,14,15. We believe that the CAD in this patient was due to both atherosclerotic disease as well as due to a previous tumour emboli. As regards the therapeutic options, in cases of atrial myxoma presenting with acute MI, coronary angiography is mandatory12. Thrombolytic therapy usually is not recommended for patients with cardiac myxomas and MI, because of the risk of tumor embolisation16,17. Following diagnosis of an atrial myxoma, immediate operative removal is advisable. Patients with associated CAD should undergo CABG during tumor removal. If the excision of the myxoma is to be delayed in patients with atrial myxoma and MI, it would be advisable to repeat coronary angiography M. M. Maddali et al. immediately before the operation, because of the tendency for spontaneous recanalization. The anesthetic concerns for patients with a LA myxoma are similar to those with mitral stenosis. Occasionally, atrial fibrillation might warrant heart rate control with pharmacologic therapy perioperatively. Postural hypotension can occur due to prolapse of the tumor mass into a valve orifice. Entrapment of the myxoma in the mitral valve during the course of anesthesia can result in a cardiac arrest. Placing the patient in the right lateral decubitus position with a head down tilt and vigorously shaking the chest might aid in dislodging the tumor from the mitral valve18. In conclusion, patients with atrial myxoma are either asymptomatic or often present with non specific symptoms that are often overlooked in the absence of a supporting cardiac history. This makes an early diagnosis challenging. Although atrial myxomas are very rare, their presence should be considered, particularly in young patients without cardiac risk factors who present with either acute or old MI. Echocardiography is a reliable diagnostic tool that helps in the differential diagnosis and decisionmaking. Surgery should not be delayed in patients with polypoid-type LA myxomas because of the high incidence of embolism. For patients aged above 40 years and without cardiovascular risk factors, it is advisable to perform coronary angiography preoperatively to identify the presence of a concomitant CAD. LEFT ATRIAL MYXOMA WITH CORONARY ARTERY DISEASE: AN UNEXPECTED PREOPERATIVE FINDING 417 References 1. Percell RL Jr, Henning RJ, Siddique Patel M: Atrial myxoma: case report and a review of the literature. Heart Dis; 2003, 5:224-30. 2. Li AH, Liau CS, Wu CC, Chien KL, Ho YL, Huang CH et al: Role of coronary angiography in myxoma patients: a 14-year experience in one medical center. Cardiology; 1999, 92:232-35. 3. Ha JW, Kang WC, Chung N, Chang BC, Rim SJ, Kwon JW et al: Echocardiographic and morphologic characteristics of left atrial myxoma and their relation to systemic embolism. Am J Cardiol; 1999, 83:1579-82, A8. 4. Lamparter S, Moosdorf R, Maisch B: Giant left atrial mass in an asymptomatic patient. Heart Journal; 2004, 90:24-26. Percell RL Jr, Henning RJ, Siddique Patel M. Atrial myxoma: case report and a review of the literature. Heart Dis; 2003, 5:224-30. 5. O'sRourke F, Dean N, Mouradian MS, Akhtar N, Shuaib A: A trial myxoma as a cause of stroke: case report and discussion. CMAJ; 2003, 169:1049-51. 6. Goswami KC, Shrivastava S, Bahl VK, Saxena A, Manchanda SC, Wasir HS: Cardiac myxomas: clinical and echocardiographic profile. Int J Cardiol; 1998, 63:251-59. 7. Demir M, Akpinar O, Acarturk E: Atrial myxoma: an unusual cause of myocardial infarction. Tex Heart Inst J; 2005, 32:445-47. 8. Engberding R, Daniel WG, Erbel R, Kasper W, Lestuzzi C, Curtius JM et al: Diagnosis of heart tumours by transoesophageal echocardiography: a multicentre study in 154 patients. Eur heart J; 1993, 14:1223-1238. 9. Kejriwal NK, Tan J, Ullal RR, Alvarez JM: Atrial Myxoma with Coexistent Coronary Artery Disease: A Report of Two Cases. Heart Lung and Circulation; 2003, 12:108−111. 10.Lehrman KL, Prozan GB, Ullyot D: A trial myxoma presenting as acute myocardial infarction. Am Heart J; 1985, 110:1293-95. 11.Panos A, Kalangos A, Sztajzel J: Left atrial myxoma presenting with myocardial infarction. Case report and review of the literature. Int J Cardiol; 1997, 62:73-75. 12.Braun S, Schrotter H, Reynen K, Schwencke C, Strasser RH: Myocardial infarction as complication of left arterial myxoma. Int J Cardiol; 2005, 101:115-121. 13.Hashimoto H, Takahashi H, Fujiwara Y, Joh T, Tomino T: Acute myocardial infarction due to coronary embolization from atrial myxoma. Jpn Circ J; 1993, 57:1016-1020. 14.Rath S, Har-Zahav Y, Battler A, Agranat O, Neufeld HN: Coronary arterial embolus from left atrial myxoma. Am J Cardiol; 1984, 54:1392-1393. 15.Soejima Y, Niwa A, Tanaka M, Doi M, Nitta M, Takamoto T et al: A left atrial myxoma complicated with acute myocardial infarction. Intern Med; 1997, 36:31-34. 16.Abascal VM, Kasznica J, Aldea G, Davidoff R: Left atrial myxoma and acute myocardial infarction. A dangerous duo in the thrombolytic agent era. Chest; 1996, 109:1106-1108. 17.Roudaut R, Labbe T, Lorient-Roudaut MF, Gosse P, Baudet E, Fontan F et al: Mechanical cardiac valve thrombosis. Is fibrinolysis justified? Circulation; 1992, 86:II8-15. 18.Kapoor MC, Singh S, Sharma S: Resuscitation of a patient with giant left atrial myxoma after cardiac arrest. J Cardiothorac Vasc Anesth; 2004, 18:769-71. M.E.J. ANESTH 21 (3), 2011 POST-OPERATIVE RESPIRATORY COMPLICATIONS AFTER PALATOPLASTY IN A 19 MONTH OLD FEMALE WITH CORNELIA DE LANGE SYNDROME - A Case Report - Brooke Ingram*, Elizabeth AM Frost Abstract Cornelia De Lange syndrome is a rare genetically heterogeneous and sporadic syndrome, with an estimated prevalence of 1 in 10,000 to 30,000. The disorder may present many complications during anesthesia due to cardiac, gastrointestinal and airway anomalies. We report a case of an ex premature toddler presenting for repair of a cleft palate. Postoperatively she had respiratory distress, successfully treated by the anesthetic care team Causes for the complication are discussed. Case Report A 19 month old former 34-week gestational age female with a history of Cornelia De Lange Syndrome presented for closure of a cleft palate. Additional past medical history was significant for reflux disease treated by Nissen fundoplication, failure to thrive managed with G-tube placement, and hearing loss for which she had undergone left myringotomy tube placement. Previous anesthetic records indicated she was easily ventilated with an oral airway but a Grade 3 view was achieved during prior intubation attempts with a Miller 1 blade. On examination, with a deep bite, her lower front incisors bit into her malformed palate. Induction of anesthesia was achieved with sevoflurane and nitrous oxide in oxygen. A WIS blade 1.0 revealed an anterior airway with a grade 3 view which improved to a grade 2 view with cricoid pressure. The first attempt to pass a 4.0 endotracheal tube failed. The next attempt with a 3.5 cuffed tube was successful. Intravenous access was secured. Anesthesia was maintained with isoflurane in oxygen plus intermittent fentanyl. At the conclusion of surgery, the patient’s mouth and gastric tube were suctioned; she was moving spontaneously. The trachea was extubated and she was given blow-by oxygen. Her oxygen saturation remained satisfactory for approximately five minutes. She was then moved to her hospital bed at which time acute desaturation to the 60s occurred. The patient was moved back to the OR table and ventilated with 100% inspired oxygen. She remained otherwise hemodynamically stable. Dexamethasone 4 mg and glycopyrrolate 30 mcg were given in addition to albuterol nebulization. An oral airway was placed with the surgeon’s approval and mask ventilation with continuous positive pressure reestablished. No upper airway obstruction or swelling could be observed, but auscultation of her lungs revealed rhonchi bilaterally. After approximately one hour, the inspired oxygen was decreased from 100% with assisted ventilation to blow-by oxygen. At time of transport, she remained hemodynamically stable * Department of Anesthesiology, Mount Sinai Medical Center, New York, NY. Contact information: E-mail: [email protected], [email protected]. Phone: (212) 241-1518, Fax: (212) 4262009. 419 M.E.J. ANESTH 21 (3), 2011 420 with oxygen saturations above 92%. Over the next few hours, the oxygen saturation improved to 99%. There were no further episodes of desaturation. Chest X-ray was clear. She was discharged to home after 3 days. B. Ingram & E. A. Frost autosomal dominant. Discussion Cornelia de Lange syndrome (CdLS) was first documented by Brachman in 19161 and later by a Dutch pediatrician, Cornelia de Lange in 19332,3. The syndrome consists of multiple congenital anomalies resulting in a distinctive facial appearance, prenatal and postnatal growth deficiency (95%), feeding difficulties (reflux in 90%), psychomotor delay, behavioral problems, and associated malformations that mainly involve the upper extremities (80% have clinodactyly, bradydactyly or olidactylyl). Congenital heart disease occurs in 20-30% and hearing loss in 60%4,5. The most diagnostic aspect of the disease are the facial characteristics which include: confluent eyebrows, long curly eyelashes, low anterior and posterior hairline, underdeveloped orbital arches, well-defined arched eyebrows (as though they had been penciled), long philtrum, thin lip, depressed nasal bridge, high arched/cleft palate, and micrognathia (Fig. 1). A gene responsible for CdLS-NIPBL on chromosome 5-was discovered in 2004 jointly by researchers at the Children’s Hospital of Philadelphia, USA and researchers at Newcastle University, UK6,7. In 2006, a second gene-SMCIA on the X chromosonewas found by Italian scientists. A third gene discovery was announced in 2007. The gene SMC3 is on chromosone 10 and was also discovered by the research team in Philadelphia. The latter two genes seem to correlate with a milder form of the syndrome. NIPBL and SMC3 have autosomal dominance and SMCIA, an X linked dominant pattern of inheritance. All genes are involved in sister chromatid cohesion. There is no known cure but the syndrome can be managed by treating associated clinical symptoms. Sixty six percent of CdLS individuals die during the first year of life. Mortality occurs primarily from aspiration in infancy and from infection and bowel obstruction there after4,5. However, some children live until adulthood.The vast majority of cases are due to spontaneous mutations, although the defected gene can be inherited from either parent, making it Anesthetic concerns include high risk of aspiration, upper airway obstruction and difficult intubation, unpredictable response to drugs due to endocrine disorders and renal failure, and adverse effects of pulmonary hypertension or congenital cardiac anomalies. Pulmonary hypoplasia also predisposes the patient to respiratory infection post operatively. The etiology of our patient’s postoperative respiratory distress was probably multifactorial. She may have had undiagnosed sleep apnea and thus was extremely susceptible to sedatives. There may also have been residual effects of prematurity as she remained very small for her age at the time of surgery. Opioid-induced respiratory depression and residual inhalational anesthetic effects are other possibilities. As prolonged surgery was performed in the area, postoperative edema of the oropharynx may also have had some additive effect. Most likely, it was a combination of these factors. The importance of close communication between all members of the perioperative team and careful monitoring of vital signs, especially oxygenation, is emphasized. These patients should not be candidates for day care surgery or anesthetic management in an out patient facility, including a dental office. In an attempt to identify patients and learn more about the syndrome, the Cornelia de Lange Syndrome (CdLS) Foundation was established as a nonprofit, family support organization based in Connecticut, USA. It provides materials for public education and information. In addition to Reaching Out, a bi-monthly newsletter, the Foundation produces and distributes POST-OPERATIVE RESPIRATORY COMPLICATIONS AFTER PALATOPLASTY IN A 19 MONTH OLD FEMALE WITH CORNELIA DE LANGE SYNDROME several other publications on the syndrome, as well as a video The foudation can be reached at info@cdlsusa. 421 org Ph:001 860-676-8166 860-676-8255 Toll-Free Support Lines: 800-753-2357 (United States) References 1.Brachmann, W: Ein Fall von symmetrischer Monodaktylie durch Ulnadefekt, mit symmetrischer Flughautbildung in den Ellenbeugen, sowie anderen Abnormitaeten (Zwerghaftigkeit, Halsrippen, Behaarung) (A case of symmetrical monodactyly, representing ulnar deficiency, with symmetrical antecubital webbing and other abnormalities, (dwarfism, cervical ribs, hirsutism)). Jahrbuch fuer Kinderheilkunde und physische Erziehung; 1916, 84:225-235. 2. de Lange, C: Sur un type nouveau de degenerescence (typus Amstelodamensis). Arch. Med. Enfants; 1933, 36:713-719. 3.http://www.whonamedit.com/synd.cfm/1080.html 4.Deardorff M, Yaeger D, and I Krantz: "Cornelia de Lange Syndrome". National Center for Biotechnology Information; 2006. Available at: www.ncbi.nlm.nih.gov. 5.Parker, P: Cornelia de Lange Syndrome-A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers. ICON Group International; 2007. 6.Krantz ID, McCallum J, DeScipio C, et al (2004): "Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B". Nat. Genet; 36(6):631-5. doi:10.1038/ng1364. PMID 15146186. 7.Tonkin E, Wang TJ, Lisgo S, Bamshad MJ, Strachan T (2004): "NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome". Nat. Genet. 36(6):636–641. doi:10.1038/ng1364. PMID 15146185. M.E.J. ANESTH 21 (3), 2011 WHAT IF THE EPIDURAL CATHETER NEEDS TO BE FIXED MORE THAN FIFTEEN CENTIMETRES AT SKIN? Vishal Uppal* Epidural catheters inserted 8 cm within the epidural space are more likely to result in intravenous cannulation and unilateral block1. Epidural catheters inserted 2 or 4 cm within the epidural space are more likely to be dislodged than epidural catheters inserted 6 or 8 cm.1 Obese patients are at particular risk of epidural catheter displacement2. It is recommended that epidural catheters should be inserted 5 or 6 cm into the epidural space when prolonged labour or caesarean delivery is likely1,3. Epidural catheters do not have cm markings between 15 and 20 cm marks. I would like to report an inconvenient situation caused by absence of these markings and a method of dealing with it. A 26 year old, morbidly obese primigravida requested an epidural in the first stage of labour. Her booking BMI and body weight were recorded as 66 kg.m-2 and 175 kg respectively. After failing to reach epidural space with a standard 10.5 cm, 18 gauge Portex Epidural needle, a Portex extra length (13.5 cm) Tuohy needle was used. On the fourth attempt, the epidural space was located using loss of resistance to saline technique with the Tuohy needle at 11 cm to skin. An 18 gauge epidural catheter was inserted via the Tuohy needle beyond the 20 cm mark and the Tuohy needle was withdrawn with care. I intended to leave the epidural catheter 6 cm into the epidural space to minimise risk of catheter dislodgement. This implied that the epidural catheter would need to be 17 cm at the skin. But, as mentioned earlier, there are no cm marking on epidural catheter between 15 and 20 cm marks. However, Portex extra length Tuohy needles have markings every cm starting from the tip of the needle. So, I used the Tuohy needle markings to measure 3 cm from 20 cm mark on the epidural catheter. Using the Tuohy as a guide, I pulled the epidural catheter out from 20 cm to 17 cm at skin for fixation. The parturient had a good bilateral epidural block for labour analgesia. The same epidural catheter was later used to provide successful regional anaesthesia for an emergency caesarean delivery. I have described a simple and accurate method of measuring catheter length if the epidural catheter needs to be fixed more than 15 cm at skin. However, care must be taken not to shear the catheter with the tip of the epidural needle while measurement. From the Department of Anaesthesia, Princess Royal Maternity Hospital, Glasgow, UK. * DA, FRCA, Speciality Registar in Anaesthesia, Glasgow Royal Infirmary, Glasgow, UK Correspondence to: Dr. Vishal Uppal, FRCA, Speciality Registar in Anaesthesia, Princess Royal Maternity Hospital, Glasgow Royal Infirmary, Glasgow, UK. Tel: +44 01412114620, Fax: +44 01412111191. E-mail: drvishal76@rediffmail. com 423 M.E.J. ANESTH 21 (3), 2011 424 V. Uppal References 1.D'Angelo R, Berkebile BL, Gerancher JC: Prospective examination of epidural catheter insertion. Anesthesiology; 1996, 84:88-93. 2.Hamilton CL, Riley ET, Cohen SE : Changes in the position of epidural catheters associated with patient movement. Anesthesiology; 1997, 86:778-84. 3.Beilin Y, Bernstein HH, Zucker-Pinchoff B: The optimal distance that a multiorifice epidural catheter should be threaded into the epidural space. Anesth Analg; 1995, 81:301-4. EXTREME INTRAOPERATIVE HYPERKALEMIA IN A NON DIALYSIS PATIENT UNDERGOING KIDNEY TRANSPLANTATION Mia Kazanjian and Steven M. Neustein** Abstract The majority of patients who present for kidney transplantation have end stage renal disease and are on dialysis. Those patients are known to be at risk for the development of hyperkalemia. A patient who has not required dialysis, and with stable potassium levels would not be expected to acutely develop intraoperative hyperkalemia. Presented here is an unusual case in which a 61-yearold man with chronic renal disease but no history of dialysis developed severe intraoperative hyperkalemia during a renal transplant. Case Report A 61-year-old man with end stage renal disease secondary to polycystic kidney disease presented for right sided living unrelated renal transplant. Past medical history was also significant for hypertension and hyperlipidemia, and past surgical history revealed bilateral cataract repair. The patient had no history of dialysis. Home medications included atenolol, enalopril, and simvastatin. Physical examination revealed a well developed, well nourished man weighing 78 kg and measuring 176 cm; it was otherwise unremarkable. Preoperative EKG was normal. Preoperative comprehensive metabolic panel revealed a BUN of 70 mg/dl, a creatinine of 5.3 mg/ dl, and a potassium of 5.1 mEq/L. Review of past potassium levels revealed a level of 5.4 mEq/L 5 days prior to surgery, and an earlier level of 5.5mEq/L. He had nothing per orem (NPO) after midnight on the night prior to surgery. In the operating room, standard American Society of Anesthesiologists monitors were applied to the patient. Initial vital signs included heart rate of 52 beats/min with normal sinus rhythm and blood pressure of 135/88 mmHg. Following induction of general anesthesia with 2 mg of midazolam, 200 mg of propofol, 200 mcg of fentanyl, and 10 mg of vecuronium, an endotracheal was placed and anesthesia was maintained with desflurane. An arterial line was placed following the induction of anesthesia, and an arterial blood gas (ABG) shortly after the start of surgery revealed pH 7.28, paCO2 39 mmHg, paO2 284 mmHg, bicarbonate 18 mEq/L, glucose 94 mg/dL, and potassium 7.5 mEq/L. The electrocardiogram (ECG) revealed peak T waves. Repeat arterial blood gas confirmed elevated potassium at 7.4 mEq/L. Fifty mEq of sodium bicarbonate was given, followed by 25 g of dextrose, 1000 mg of CaCl2, and 10 units of regular insulin. When a subsequent ABG showed potassium 6.9 mEq/L and 244 mg/dL of glucose, 1000 mg of CaCl2 and 5 units of regular insulin were given. The next ABG taken 30 minutes later showed potassium = 5.2 mEq/L and glucose = 87 mg/dL, after which 12.5 g of dextrose was infused. Subsequent ABGs during the procedure revealed potassium levels <5 mEq/L and glucose levels in the 50s to 80s, Corresponding Author: Steven M. Neustein, Associate Professor of Anesthesiology Mount Sinai Medical Center, 1 Gustave L. Levy Place, Box 1010, Dept. of Anesthesiology, New York, NY 10029-6574 Tel: (212) 241-7467, Fax: 212-426-2009. E-mail: [email protected] 425 M.E.J. ANESTH 21 (3), 2011 426 prompting a total of 37.5 g of dextrose to be given. The peaked T waves resolved as the potassium level became normalized. Two L of .9% NaCl, and 4 L of 45% NaCl, each with 75 mEq of bicarbonate, were administered intravenously (IV). Urine output was 2800cc. The kidney was transplanted successfully into the right iliac fossa with minimal blood loss. Total surgery time was 5 hours 9 minutes. Postoperative potassium level was 3.8 mEq/L. For the remainder of the hospital stay, it remained <5 mEq/L. The patient made an uneventful recovery, the transplanted kidney functioned well with consistently adequate urine output, and he was discharged home on POD 3. Discussion This case is of particular interest in that the patient had no history of dialysis and had a record of past stable potassium levels in the range of low to mid 5 mEqs/L. Cases of intraoperative hyperkalemia may be attributable to RBC transfusions, extensive muscle dissection, metabolic acidosis, use of angiotensin receptor blockers (ARBs) or angiotensin converting enzyme (ACE) inhibitors, use of succinylcholine, and propofol infusion syndrome (1-3). In our patient with chronic renal disease, there is not a clear explanation for the acute and dramatic rise in potassium during this procedure. He did not receive any blood during the procedure, there was limited muscle dissection, and there was no propofol infusion. There was no potassium in the intravenous fluid at any time. Possible M. Kazanjian and S. M. Neustein causes for his hyperkalemia include consequence of intraoperative metabolic acidosis which was apparent by the low bicarbonate level, administration of enalapril prior to surgery, and coincidental worsening of renal failure. It could have possibly been related to the ingestion of foods containing potassium, and then subsequent dehydration from the standard maintenance of NPO status preoperatively. Patients with a history of chronic renal failure, especially those on ACEIs/ARBs, should be routinely monitored for potassium and creatinine levels. Raebel et al2 analyzed the characteristics of patients on ACEIs/ARBs that were predictive of compliance with routine potassium and creatinine monitoring. They found that risk factors of older age, comorbid chronic renal disease, heart failure, or diabetes, recent hospitalization, higher number of outpatient visits, and therapy with diuretics, potassium supplements, or digoxin increased the likelihood of monitoring. Intraoperative treatment relied on administration of medications to actively lower potassium; this entailed giving sodium bicarbonate, insulin, and calcium. In addition, switch of fluids to 45% NaCl with sodium bicarbonate after diagnosis of hyperkalemia sought to prevent further rise in potassium by providing alkaline IV fluid instead acidic fluid. With continual insulin boluses, glucose levels were monitored to avoid hypoglycemia. In all kidney transplantation cases, the electrolyte levels should be assessed on the day of surgery. An arterial line should be placed and levels sampled intraoperatively in order to assess for acute changes and monitor treatments. References 1. Mali AR, Patil VP, Pramesh CS, Mistry RC: “Hyperkalemia during surgery: is it an early warning of propofol infusion syndrome?” Journal of Anesthesia; 2009, 23:421-423. 2. Raebel MA, McClure DL, Simon SR, Chan KA, Feldstein A, Andrade SE, Lafata JE, Roblin D, Davis RL, Gunter MJ, Platt R: “Laboratory monitoring of potassium and creatinine in ambulatory patients receiving angiotensin converting enzyme inhibitors and angiotensin receptor blockers”. pharmacoepidemiology and drug safety; 2007, 16:55-64. 3. Suzuki S, Kashiwagi G, Nakasone Y, Tomioka A, Saito S: “Case of unexpected intraoperative hyperkalemia”. Masui; 2009, Aug, 58(8):1014-6. SUCCESSFUL TREATMENT OF EARLY ROPIVACAINE TOXICITY WITH INTRALIPID IN A PATIENT WITH ATTENTION DEFICIT HYPERACTIVITY DISORDER Achir A. Al-Alami* Case Report A 16 year old male underwent right shoulder arthroscopy and Bankart procedure. The patient weighed 58 Kg and had a BMI of 19.6. He had a history of attention deficit hyperactive disorder (ADHD) treated with atomoxetine, a newer drug that works by selectively inhibiting the re-uptake of norepinephrine (1). We planned for a general endotracheal anesthetic with interscalene block for postoperative analgesia. Monitors were applied in the preoperative block room including: ECG, non-invasive blood pressure, and pulse oximeter. Nasal oxygen was administered at 2 L/ min. Sedation was provided with 2 mg of midazolam IV. The patient was positioned in right lateral decubitus. After sterile preparation of the skin with chlorhexidine, a high frequency US probe 1215 Hz (HD 11 XE, Phillips, Bothell, WA, USA) was used to localize the brachial plexus roots. A nerve stimulator was set at 0.4 mA with a frequency of 2 Hz and 0.3 ms. Skin and subcutaneous tissue anesthesia was obtained with injection of 3 ml of 1% lidocaine. Using a posterior approach, the interscalene block was performed in plane, using a 90 mm 21 guage nerve stimulator needle (Arrow, StimuQuik, Reading, PA, USA). The C6 root stimulation was confirmed with a biceps twitch, and 20 ml of 0.75% ropivacaine was injected after negative aspiration and negative test dose (D5W with 1:200,000 epinephrine, 3 ml). The C5 root stimulation was confirmed with a brisk deltoid twitch, and 20 ml of 0.75% ropivacaine was injected after negative aspiration and negative test dose. A total of 40 ml of 0.75% ropivacaine was given. Ten minutes after the block, the patient became slightly confused, reported visual hallucinations (purple spots), and was noted to have slower and slightly slurred speech. He also had an intention tremor in his left arm when asked to move it, but no obvious tremor at rest. Cranial nerves 2-12 were grossly intact, but he did have some non-coordinated tremor in his tongue on protrusion. His respiratory rate increased to 25. His heart rate steadily increased from 75 to 156 bpm over 5-7 minutes. He remained in sinus rhythm. His blood pressure increased from 112/62 to 140/80. Suspecting ropivacaine toxicity, we infused 1.5 mg/kg Intralipid 20% (Fresenius Kabi, Uppsala, Sweden) as a bolus over 4-5 minutes. His heart rate and breathing declined rapidly. We then administered 0.5 mg midazolam IV. Intralipid infusion was continued at 0.25 mg/kg/min over 3 hours. After 20-30 minutes of observation, his motor twitching ceased, his speech became more coherent, and his hallucinations were gone. He had a full motor and sensory block of the operative arm. He was taken to the operating room and underwent an uneventful general anesthetic with endotracheal intubation. He was maintained on propofol (150-200 mcg/kg/min) and sevoflurane 1.2% in air: oxygen mixture of 1:1. * Correspondence: Achir A Al-Alami, Regional Anesthesia Fellow, University of Iowa Hospital and Clinics, 200 Hawkins Dr, Iowa City, IA, 52242, USA. E-mail: [email protected] 427 M.E.J. ANESTH 21 (3), 2011 428 The postoperative course was uneventful; he reported minimal pain in his elbow. He had some recollections of the events, including remembering the purple spots he had seen. A month after the surgery the patient was called and he reported that he was doing well. Discussion Ropivacaine has been shown to be a safe longacting local anesthetic. In both animal studies and case reports, investigators have shown that ropivacaine cardiac toxicity is more responsive to standard ACLS recommended resuscitation procedures in comparison with other local anesthetics2,3. The estimated incidence of ropivacaine-induced toxic events is 6-8 in 1000,000 patients4. The manufacturer’s maximum recommended dose of ropivacaine (300 mg) for brachial plexus blockade is not evidence based5,6. Total dose is an important consideration, but we must weigh it against other factors such as the pharmacokinetics of the drug, block site, patient characteristics and drug interactions. Used collectively, these considerations provide the greatest margin of safety against local anesthetic toxicity6,7. In our case, direct intravascular injection is unlikely as the block was performed under visualization with ultrasound, there was no blood visualized after aspiration, the HR did not change with test dose, and signs and symptoms of local anesthetic toxicity occurred10 minutes after completion of the block. We believe that the observed symptoms were the result of ongoing systemic absorption of the drug. The administered dose of ropivacaine was 5.3 mg/ kg which can be considered in the toxic range for a brachial plexus block (4-8 mg/kg)7-12. Other factors may have played a role in the development of toxicity Achir A. Al-Alami in our patient. These include the high vascularity associated with the interscalene approach, the lean body mass of the patient and potentially his ADHD diagnosis. There is a bidirectional relationship between ADHD and epilepsy. In one study children diagnosed with ADHD have been shown to have greater incidence of EEG abnormalities in comparison to general population (6.1% vs 3.5%). In another study of children with ADHD, 30.1% of them were found to have pathological EEG findings13,14. If we consider that his ADHD was a contributing factor to the development of CNS symptoms, the cardiovascular and respiratory symptoms we observed may have been due to sympathetic stimulation from global CNS excitation15. It is also likely that these symptoms can be explained as direct cardiac toxicity resulting from the excessive local anesthetic in the blood. There have been two reported cases of early CNS symptoms induced by local anesthetic toxicity successfully treated by lipid infusion16,17. Our case highlights the concept that early administration of Intralipid for treatment of local anesthetic-induced early CNS toxicity prior to development of seizure and cardiac arrest is a safe and viable option for anesthesiologists. Our case also highlights the diversity of symptoms that may be present in patients with local anesthetic toxicity. These symptoms may be different or masked in populations with ongoing mental disease or in those taking pharmaceuticals for those diseases. The patient’s BMI, associated co-morbidities and type of block are important in determining local anesthetic dosage. Furthermore, we found Intralipid infusion was safe and successful in reversing local anesthetic-induced early CNS and cardiac abnormalities when administered early prior to the development of seizure and cardiac arrest. SUCCESSFUL TREATMENT OF EARLY ROPIVACAINE TOXICITY WITH INTRALIPID IN A PATIENT WITH ATTENTION DEFICIT HYPERACTIVITY DISORDER 429 References 1. Chang K, Nayar D, Howe M, Rana M: Atomoxetine as an adjunct therapy in the treatment of co-morbid attention-deficit/hyperactivity disorder in children and adolescents with bipolar I or II disorder. J Child Adolesc Psychopharmacol; 2009, 19 (5):547-51. 2. Finucane BT: Ropivacaine cardiac toxicity-not as troublesome as bupivacaine. Can J Anesth; 2005, 52(5):449-53. 3. Ohmura S, Kawada M, Ohta T et al: systemic toxicity and resuscitation in bupivacaine, levobupivacaine, or ropivacaineinfused rats. Anesth Analg; 2001, 93:743-48. 4. Periodic safety update report: Naropin, Astra Zeneca; 2000, May, 17. 5. Hickey R, Blanchard J, Hoffman J, Sjovall J, Ramamurthy S: Plasma concentrations of ropivacaine given with or without epinephrine for brachial plexus block. Can J Anaesth; 1990, 37:87882. 6. Rosenberg H, Veering B, Urmey WF: Maximum recommended doses of local anaesthtics: A multifactorial concept. Region Anesth Pain Med; 2004, 29(6):546-75. 7. Spofford C, Menhusen MJ: Possible Bupropion interaction with ropivacaine: setting the stage for seizure? Region Anesth Pain Med; 2008, 33(2):193. 8. Eldejam JJ, Gros T, Viel E, Mazoit JX, Bassoul B: Ropivacaine overdose and systemic toxicity. Anaesth Intensive care; 2000, 28:705-7. 9. Satsumae T, Tanaka M, Saito S, Inomata S: Convulsions after ropivacaine 300 mg for brachial plexus block. Br J Anaesth; 2008, 101(6):860-2. 10.Litz RJ, Popp M, Stehr SN, Koch T: Successful resuscitation of a ptient with ropivacaine-induced asystole after axillary plexus block using lipid infusion. Anaesthesia; 2006, 61:800-01. 11.Mardirosoff C, Dumont I: Conculsions after the administration of high dose ropivacaine following an interscalene block. Can J Anaesth; 2000, 47:1263. 12.Ala-Kokko TI, Löppönen A, Alahuhta S: Two instances of central nervous system toxicity in the same patient following repeated ropivacaine-induced brachial plexus block. Acta Anaesth Scand; 2000, 44:623-26. 13.Wernicke JF, Chilcott Holdridge KC, Jin L, Edison T, Zhang S, Bangs ME, Allen AJ, Ball S, Dunn D: Seizure risk in patients with attention-deficit-hyeractivity disorder treated with atomoxetine. Dev med child neurol; 2007, 49:498-502. 14.Hamoda HM, Guild DJ, Gumlak S, Travers BH, GonzalezHeydrich J: Association between attention-deficit/hyperactivity disorder and epilepsy in pediatric populations. Expert rev neurother; 2009, 9(12):1747-54. 15.Sevcencu C, Struijk JJ: Autonomic alterations and cardiac changes in epilepsy. Epilepsia; 2010, Jan, 7. 16.Spence AG: Lipid reversal of central nervous system symptoms of Bupivacaine toxicity. Anesthesiology; 2007, 107:516-7. 17.Esponet AJ, Emmerston MT: The successful use of Intralipid for treatment of local anesthetic-induced central nervous system toxicity. Clin J Pain; 2009, 25(9):808-809. M.E.J. ANESTH 21 (3), 2011 CHRONIC USE OF OXYBUTYNIN AND SPINAL ANESTHESIA: A CASE OF POSTOPERATIVE URINARY RETENTION AND HEMATURIA Adriano BS Hobaika* Overactive bladder is a disorder characterized by micturition urgency with or without incontinence and with an increased urinary frequency and nocturia. Oxybutynin is the most common medication used in the treatment owing to having more tolerable side effects1. This drug has not been described as a risk factor to develop postoperative urinary retention. Male, 61 years old, 84 kg and using simvastatin in order to control hypercholesterolemia and oxybutynin to control overactive bladder. Preoperative examinations were normal. He was scheduled to varicectomy of the lower limbs on outpatient basis. Spinal anesthesia (L3/L4 interspace) with bupivacaine, 12.5 mg plus intrathecal fentanyl, 15 mcg was administered in addition to an intravenous sedation with midazolam and sufentanyl. Intravenous saline (2000 ml) and ephedrine (15 mg) was administered in order to treat hypotension during a two-hour procedure. Seven hours after the end of the procedure, the patient complained of a strong pelvic pain, dysuria, hematuria and clot elimination. He also presented a very painful urinary retention on palpation. There was an immediate symptom relief when bladder catheter was used and blood clots were seen in urine. The catheter was withdrawn and the patient was discharged on the following day, urinating with no problems but with a slight hematuria. Oxybutynin acts as an anticholinergic agent with an antimuscarinic action and, particularly, an antispasmodic action in the vesical smooth muscle. As a consequence, there is an increased vesical capacity, reduced micturition frequency and inhibition of the initial micturition stimulus. In an experimental model, urinary frequency was reduced in a situation of induced-hemorrhagic cystitis and there was a remarkable decrease in the detrusor muscle contraction strength when compared to the normal control2. Intrathecal opioid administration causes urinary retention via µ- and/or δ-receptors3. In an animal model, cholinomimetic agents and α-adrenergic agonists aggravate the increase of morphine-induced intravesical pressure4. This patient, possibly, presented urinary retention arising out of the additive association of two pathophysiological mechanisms. Bladder distension may have caused an increase of the intravesical pressure which led to the rupture of vessels from the bladder or prostate with hematuria. In a recent review, Baldini et al recommends that surgical outpatients with low risk for post-operative urinary retention can be sent home without voiding5. According to these authors, the patient of this case is classified as a high risk patient. In surgical outpatients using oxybutynin, it should be considered the non-administration of opioids in the neuroaxis. Moreover, it seems prudent to wait them for voiding before home discharge. * Master of Science in Medicine, Co-responsible for the Anesthesiology Teaching and Training Center Santa Casa de Belo Horizonte, Staff anesthesiologist of Mater Dei Hospital. Adress: Rua Des. Jorge Fontana, 336/1701, Belvedere. Phone: 31-55-92134969. [email protected] 431 M.E.J. ANESTH 21 (3), 2011 432 A. BS Hobaika References 1. Abrams P, Andersson KE: Muscarinic receptor antagonists for overactive bladder. BJU Int; 2007, 100:987-1006. 2. Mizuma EK, Takeshita MS, Suaid HJ, Martins ACP, Tucci JR S, Cologna AJ, Gonçalves MA: Efeito do cloridrato de oxibutinina na hiperatividade vesical conseqüente a cistite hemorrágica. Acta Cir Bras; 2003, 18 suppl, 24-27. 3. Dray A: Epidural opiates and urinary retention: New models provide new insights. Anesthesiology; 1988, 68:323-324. 4. Durant PAC, Yaksh TL: Drug effects on urinary bladder tone during spinal morphine-induced inhibition of the micturition reflex in unanesthetized rats. Anesthesiology; 1988, 68:325-334. 5. Baldini G, Bagry H, Aprikian A, Carli F: Postoperative Urinary Retention: Anesthetic and Perioperative Considerations. Anesthesiology; 2009, 110:1139-1157. INFILTRATIVE ANGIOLIPOMA OF THE NECK Abdul-Latif Hamdan*, Laurice Mahfoud**, Hani Rifai**, Charbel Rameh**, Nabil Fuleihan* Introduction Lipomas are the most common mesenchymal tumors of the body. They can occur in any soft tissue ranging from subcutaneous fat to the parosteal areas adjacent to bone. They are usually asymptomatic masses easily diagnosed on radiological imaging1. Angiolipoma is a variant of lipoma with proliferation of its vascular component. These tumors occur on the trunk and extremities of young adults with the forearm being the most common site of involvement. Documented sites of occurrence in the head and neck region include cheek, palate, neck, jaw, nose, eyelid, parotid, tongue, paranasal sinuses and parapharynx. Only 4 cases have been described in the neck, with 75% of these being infiltrative2. We would like to present the fifth case of infiltrative angiolipoma of the neck. Case presentation A 23y old male patient, previously healthy, presented with a four month history of a slowly growing, painless neck mass that was not associated with skin changes, fever, recent infection or trauma. No history of contact with patients with tuberculosis. Physical examination revealed a well circumscribed soft left postero-lateral neck mass, 5 × 5 cm, non tender and non pulsatile. Patient had normal muscle power in his upper extremities and normal pulses. A fine needle aspiration revealed an acellular specimen. Magnetic resonance imaging of the head and neck showed a heterogeneous 5 × 4 × 4 cm, well-circumscribed mass with a prominent vascular component, underneath the trapezius and longus colli muscles. The mass enhanced on T1 and T2 weighted images. The patient underwent resection of the posterior neck mass through a cervical approach incision. Intraoperatively the mass was found to be infiltrating the adjacent muscles. Histopathologic examination revealed proliferation of small mostly capillary sized vessels and adipose tissue between muscle fibers In a pseudo-infiltrative type (Fig. 1). The diagnosis was consistent with angiolipoma of the neck the infiltrative type. Discussion Lipomas occur in regions such as back and shoulders, with the head and neck region being rarely the site of origin. Histologically, they are classified into five categories; 1) lipoma; 2) hybernoma; 3) heterotopic lipoma; 4) lipomatoses syndrome; and 5) histologic variants of lipoma * MD, FACS, Clinical Associate Professor, Otolaryngology Department, American University of Beirut Medical CenterLebanon. ** MD, Resident, Otolaryngology Department, American University of Beirut Medical Center-Lebanon. Corresponding Author: Abdul-latif Hamdan, MD, FACS, Clinical Associate Professor, Otolaryngology Department, American University of Beirut Medical Center-Lebanon, Tel/Fax: 961-1746660, P.O. Box: 110236 Beirut-Lebanon. E-mail: [email protected], [email protected] 433 M.E.J. ANESTH 21 (3), 2011 434 Abdul-Latif Hamdan Fig. 1 H&E staining (X100 magnification) shows proliferation of small mostly capillary sized vessels and adipose tissue between muscle fibers in a pseudo-infiltrative type. The vessels have plump nuclei with well formed lumina. Mitotic figures are not seen. There is no atypia. Findings are constant with angiolipoma such as angiolipoma. Angiolipomas constitute 6%17% of all lipomas with only 20 cases being reported in the literature. They are suspected whenever the lesion becomes painful or tender and at times leading to muscular pain and or neural deficits. This is more common when the tumor is infiltrative and lacks an identifiable capsule, as in our case3,4. Histopathologic characteristics of angiolipomas include 1) gross evidence of tumor formation; 2) microscopic evidence of more than 50% of mature lipocytes in the tumor and 3) microscopic evidence of angiomatous proliferation. These were the findings in our case. Because of their extensive vascular component and their tendency to locally recur, they have often been classified under benign vascular lesions such as intramuscular hemangiomas. The differential diagnosis includes hemangioma, lymphangioma, kaposi’s sarcoma and angiosarcoma. Liposarcomas can be differentiated by the presence of embryonal adipose tissue, pleomorphism, increased number of mitosis and metastasis1,2. The non fatty vascular component of angiolipomas makes these tumors radiologically distinct with Magnetic resonance imaging (MRI) being the most sensitive imaging technique. These tumors tend to show high signal intensity on T1-weighted sequences and T2weighted fast spin echo-MRI sequences. Analyzing the nonfatty regions of these atypical lipomas invariably provides the clue for distinguishing them from well differentiated liposarcomas. These later tend to have thick nodular septa that enhance variably on contrast enhancement images. These findings were not present in our case. MRI is also used for the assessment of the neighboring structures and the extent of infiltration3-5. Treatment consists of complete surgical excision. In the infiltrative type, wider resection that includes the adjacent involved soft tissues is recommended in view of the high incidence of local recurrence. Adjuvant radiation therapy may be recommended in cases of incomplete resection. References 1.Alvi A, Garner C, Thomas W: Angiolipoma of the head and neck. J Otolaryngol; 1998, 27:100-3. 2.Ozer E, Shuller D: Angiolipoma of the neck. Otolaryngol Head Neck Surg; 2006, 135:643-644. 3.Enzinger FM, Weiss SW: Benign lipomatous tumors. In: Enzinger FM, Weiss SW. eds. Soft tissue tumors. 3rd Edition. St. Louis: Mosby; 1995, 381-430. 4.Munk PL, Lee MJ, Janzen DL, et al: Lipoma and liposarcoma: evaluation using CT and MR imaging. AJR Am J Roentgenol; 1997, 169:589-94. 5.Kim JY, Park JM, Lim GY, et al: Atypical benign lipomatous tumors in the soft tissue: Radiographic and pathologic correlation. J Comp Assisted Tomography; 2002, 26(6):1063-1068. CARDIAC ARREST DURING ELECTIVE ORTHOPEDIC SURGERY DUE TO MODERATE HYPOKALEMIA Manuel F. Struck*, Andreas Nowak* Abstract We report the case of a perioperative cardiac arrest (ventricular fibrillation) of a patient undergoing elective orthopedic surgery due to moderate hypokalemia (serum potassium 2,8 mmol/l), whereas preoperative levels were normal. He was successfully resuscitated without neurological deficits and underwent postoperative intensive care monitoring. In times of increasing populations of elderly people presenting with considerable co-morbidity, clinicians should be aware of possible rapid changes of electrolyte levels resulting in perioperative cardiac arrhythmia. Introduction Perioperative cardiac arrhythmias are common complications, which, in most cases, do not affect hemodynamic stability and not always require antiarrhythmic therapy. Life-threatening arrhythmias with a sudden and unexpected onset during non-cardiac surgery are rare1. Electrolyte imbalances such as a low serum potassium level may be one possible underlying cause2. This condition is commonly defined as moderate (3-2.5 mmol/l) or severe hypokalemia (<2.5 mmol/l). Reasons for a hypokalemia in the perioperative setting may be previous medication, hypoglycemia (transcellular shift of potassium from serum into cells), and renal or gastrointestinal losses. Case Report We report the case of a 71-year-old man with a medical history of arterial hypertension, arterial obstructive disease, both without medication, borderline diabetes mellitus, treated with dietary measures, hypercholesterolemia, treated with simvastatin, alcohol and nicotine use, and no allergies. He was scheduled for amputation of his left lower thigh due to necrotic erysipelas and osteomyelitis for which he had been treated with clindamycin and levofloxacin. Further medication included palladon for pain therapy. Preoperative examination showed a 72 kg, 178 cm man. Noninvasive blood pressure was 143/85 mmHg, heart rate was 78/min and ECG revealed no cardiac pathology. Preoperative laboratory values included hemoglobin (Hb) of 5.8 mmol/l and serum potassium of 3.9 mmol/l. The patient underwent anesthetic induction and endotracheal intubation with intravenous sufentanil (40 µg), propofol (100 mg) and rocuronium (50 mg) after implementation of standard monitoring. He was started on intravenous ketamine via infusion pump (5 mg/h) and received a bolus application of 25 mg for postoperative pain therapy. Anesthesia was maintained with 40% * MD, Department of Anesthesiology, Friedrichstadt Hospital, Dresden, Germany. Correspondence: Manuel Florian Struck, Department of Anesthesiology, Friedrichstadt Hospital, Dresden, Germany, Friedrichstr. 41, 01067 Dresden, Germany. Phone: 0049(0)3514801170, Fax: 0049(0)3514801179. E-mail: manuelstruck@ web.de 435 M.E.J. ANESTH 21 (3), 2011 436 oxygen, 60% air, and sevoflurane (0.7-1.3% endtidal concentration). Surgery then commenced and was uneventful. An arterial blood sample to assess the blood loss revealed anemia (Hb 5.0 mmol/l) and moderate hypokalemia (serum potassium 2.9 mmol/l). About one minute later, the ECG monitor alarmed and displayed an artefact-like pattern that frequently occurs when surgeons use electrocoagulation devices, whereas this was not the case. The immediate check of the ECG electrodes revealed no mislocation, and the palpation of both carotid arteries revealed pulselessness. Surgery was abandoned, and chest compressions were performed immediately. The first defibrillation had no effect, whereas the second resulted in asystole. After total administration of 2 mg adrenaline (aliquots of 1 mg each), return of spontaneous circulation (ROSC) was evident by palpable pulses of both carotid arteries and the ECG showed a heart rate of 87/min. The first available BP was 160/90 mmHg. The time from onset of ventricular fibrillation to ROSC was 9 minutes. Surgery was than completed, and the patient was transferred to the intensive care unit, where he received correction of hypokalemia and anemia. He was successfully weaned off the ventilator and.extubated 4 hours after ROSC. Subsequent neurological examination revealed no deficits. Laboratory measures, ECG, echocardiography and chest radiography did not show evidence of cardiac ischemia, valvular pathology or pulmonary embolism. After three further days of monitoring, the patient was discharged to the regular ward. M. F. Struck & A. Nowak Discussion In this patient, there was no high-risk medication for a hypokalemia such as diuretics or insulin, whereas his antibiotic medication have rarely been reported to cause electrolyte imbalances2. Other possible causes for a perioperative cardiac arrest may be iatrogenic by anesthetic agents or insufficient pain therapy. However, the analysis of five prospective cohort studies, covering 6253 non-cardiac surgery patients, revealed postoperative cardiac arrhythmia in 7.84%3. The occurrence of atrial fibrillation was by far the most frequent type of arrhythmia (4.41%), whereas VF was a very rare complication (0.02%). In another large review, the overall frequency of perioperative cardiac arrest was 4,3 per 10.0004. Most arrests were not due to anesthesia-related causes, and most patients experiencing anesthesia-related arrest survived to hospital discharge. Conclusion We conclude that ventricular fibrillation and cardiac arrest may suddenly occur perioperatively probably due to unrecognized moderate electrolyte imbalances even patients presenting with a lower risk profile. In a future demography of increasing age and morbidity it may hardly be possible to identify this kind of risk factor in any patients scheduled for surgery. Therefore, clinicians may be confronted more frequently with similar complications requiring appropriate attention and immediate response measures for successful management. References 1.Thompson A, Balser JR: Perioperative cardiac arrhythmias. Br J Anaesth; 2004, 93:86-94. 2.Alfonzo AV, Isles C, Geddes C, Deighan C: Potassium disordersclinical spectrum and emergency management. Resuscitation; 2006, 70:10-25. 3.Walsh SR, Tang T, Wijewardena C, Yarham SI, Boyle JR, Gaunt ME: Postoperative arrythmias in general surgical patients. Ann R Coll Surg Engl; 2007, 89:91-95. 4.Sprung J, Warner ME, Contreras MG, Schroeder DR, Beighley CM, Wilson GA, Warner DO: Predictors of survival following cardiac arrest in patients undergoing noncardiac surgery: a study of 518,294 patients at a tertiary referral center. Anesthesiology; 2003, 99:259-269. THE ANESTHETIC MANAGEMENT OF A PATIENT WITH DORFMAN-CHANARIN SYNDROME Azize Beştaş*, Esef Bolat**, Mustafa K. Bayar***, Ömer L. Erhan*** Abstract Dorfman-Chanarin syndrome (DCS), which is also known as neutral lipid storage disease, is a rare autosomal recessive inherited lipid storage disease with congenital ichthyotic erythroderma. Since the Dorfman-Chanarin syndrome is a multisystemic disease the choice of drugs and the conduct of anesthesia in these patients are important. Preoperative evaluation should be performed in detail and anesthetic method and drugs to be used should be chosen carefully in accordance with affected system, overall state of patient and characteristics of the operation, in order to decrease perioperative morbidity rates in these patients. We report the anesthetic management of a child with DCS operated for correction of strabismus under general anesthesia. Keywords: Dorfman-Chanarin syndrome, anesthesia. Introduction Dorfman-Chanarin syndrome (DCS), which is also known as neutral lipid storage disease, is a rare autosomal recessive inherited lipid storage disease with congenital ichthyotic erythroderma1. Peripheral blood smears showing lipid vacuoles in neutrophils (Jordans’ anomaly) in patients with ichthyosis leads to the diagnosis2. Other organ systems, such as liver, muscle, central nervous system, ears and eyes are frequently involved1,3. Therefore, patients with DCS may present anesthetic challenges to the anesthesiologist. To our best knowledge, there is no information available on the anesthetic management of a patient with DCS. Here, we report the anesthetic management of a child with DCS operated for correction of strabismus under general anesthesia. Case Report A 5-year-old, 18 Kg, 108 cm (at 25th-50th percentiles) girl with DCS was scheduled for elective strabismus surgery. Review of the previous medical records revealed that the patient had presented with ichthyosis since birth. At age 16 months, she had demonstrated hepatomegaly, hepatosteatosis, elevated liver enzymes, renal parenchymal hypertrophy and motor-mental retardation. After observing the peripheral blood smears showing lipid vacuoles in neutrophils (Jordans’ anomaly) she had been diagnosed with DCS. The patient’s preoperative physical examination revealed * ** *** Associate Professor, Firat University School of Medicine Department of Anesthesiology and Reanimation, 23119-ELAZIG, TURKEY. Assistant Professor, Bozok University School of Medicine Department of Anesthesiology and Reanimation, YOZGAT, TURKEY Professor, Firat University School of Medicine Department of Anesthesiology and Reanimation, 23119-ELAZIG, TURKEY. Corresponding Author: Dr. Azize BESTAS, Fırat Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimation AD, 23119 Elazıg-TURKEY, Tel: +90 532 3402332, Fax: +90 424 2388096. E-mail: [email protected]; [email protected] 437 M.E.J. ANESTH 21 (3), 2011 438 generalized squamatous skin lesions and horizontal strabismus in the right eye. The liver was palpable to 2 cm below the costal margin, smooth and firm, but the spleen was not palpable. She also had slight motor-mental retardation. Other systemic examination was normal. Results of laboratory studies showed a normal blood count, lipid profile, serum electrolytes, urea, creatinine, total protein, albumin, globulin, total bilirubin, direct bilirubin, indirect bilirubin, glucose, prothrombin time, activated partial thromboplastin time, INR and urinanalysis. The liver functions were deranged with elevated enzymes [serum aspartate aminotransferase (AST): 122 U/L, alanine aminotransferase (ALT): 145 U/L, alkaline phosphate (ALP): 312 U/L, gammaglutamyl transferase (GGT): 36 U/L]. The muscle enzyme, serum creatine phosphokinase (CPK) has also been increased (CPK: 722 U/L). However, there were no myopathy evidence clinically and she was electromyographically normal. Ultrasound of the abdomen showed hepatomegaly with grade II hepatosteatosis, splenomegaly and bilateral grade I renal parenchymal hypertrophy. A chest x-ray showed a normal heart size, and clear lung fields. Liver biopsy showed 80% fatty changes, minimal portal fibrosis with mixed type inflammatory infiltrates. Skin biopsy revealed marked hyperkeratosis and sporadic acanthosis. The peripheral blood smear showed lipid vacuoles in the cytoplasm of leucocytes consistent with Jordans’ anomaly, characteristic of DCS. Lipid vacuoles were also found in cells of the myeloid series in bone marrow smear. The patient received no preoperative medication. In the operating room, electrocardiography, heart rate, non-invasive arterial blood pressure, temperature, pulse oximetry and end-tidal (ET) CO2 were monitored. In addition, neuromuscular function was monitored by using a peripheral nerve stimulator (TOF Watch SX Monitor, Organon, Oss. Holland). Heating blanket was used and room temperature was kept at normal limits, in case of a possibility of hypothermia development. Anesthesia was induced with sevoflurane in 50% nitrous oxide (N2O) and oxygen (O2). After induction of anesthesia, intravenous access was established and TOF Watch SX Monitor was calibrated. Then, endotracheal intubation was performed easily without using muscle relaxants, at the first attempt. Following tracheal intubation, anesthesia was maintained with A. Beştaş et al. isoflurane 1.0-1.5% in a combination of 50% N2O and O2. Ventilation was controlled mechanically and was adjusted to maintain an ET CO2 at 30-40 mmHg. Muscle relaxants were not used, since the patient had not moved during surgical operation, which was completed in 50 minutes, and the operation had been performed easily. After stopping the administration of anesthetic agents the patient waked up rapidly, began to breathe spontaneously; she could raise her head and grasp forcefully. Her trachea was extubated uneventfully. In recovery room, patient was evaluated with “Modified Aldrete Scoring System”. When her Modified Aldrete Score reached to 10 she was transported from recovery room to the ward. Patient’s hemodynamic variables, SpO2 and body temperature were within normal limits both during the operation and in recovery room. There were no differences in laboratory values on the second day postoperatively compared with preoperatively. The patient was discharged successfully on the third day postoperatively. Discussion Since the Dorfman-Chanarin syndrome is a multisystemic disease the choice of drugs and the conduct of anesthesia in these patients are important. Extracutaneous manifestations variably include fatty liver, myopathy, cataracts, hearing impairment, mental retardation and a variety of neurologic symptoms1,3,4. In this presented case, the perioperative anesthetic care has been performed by considering the ichthyosis, hepatosteatosis, hepatic disfunction and raised serum CPK, present in the patient. There is a tendency to increased skin fragility in the ichthyotic patients, therefore adhesive pads or electrodes can cause trauma during application or removal. However, the fixation of endotracheal tube and ECG monitor electrodes to the skin was well tolerated by the patient. It is very important to maintain normothermia during surgery, because patients with ichthyosis have risk of developing inadvertent hypothermia during anesthesia5. Using of heating blanket and at normal room temperature, the intraoperative body temperature of the patient could be maintained at a normal level during operation. THE ANESTHETIC MANAGEMENT OF A PATIENT WITH DORFMAN-CHANARIN SYNDROME Patients with liver disease are at risk for perioperative morbidity and mortality. General anesthesia can reduce total hepatic blood flow and hence can increase the present parenchymal damage6. Therefore drugs decreasing the hepatic blood flow, hypotension and hypercapnia should be avoided. Isoflurane and desflurane may be the most appropriate for use in patients with liver disease, as they seem to decrease liver blood flow less than the other volatiles, and have a low degree of metabolism7. In the present case, we preferred isoflurane in maintenance of anesthesia, stabilized the hemodynamic variably and adjusted the ventilation to maintain normocapnia. Besides, since hepatic dysfunction affects the distribution, metabolism and excretion of anesthetic drugs8, drug doses and dosing schedules should be set accordingly. The coagulopathy, associated with liver disease, may cause bleeding of friable nasopharyngeal structures, such as application of an endotracheal tube. Abnormally high levels of serum CPK can be reflect an occult myopathy9. Patients with myopathy are very sensitive to paralyzing agents. If a muscle relaxant had been required in these patients, a shortacting non-depolarizing muscle relaxant should be administered carefully, using small incremental doses and under close monitoring of neuromuscular function, since some reports have described prolonged effect 439 of neuromuscular blocking agents in patients with myopathy10,11. Furthermore, use of succinylcholine should also be avoided because of risk of severe hyperkalemia development or malign hyperthermia12. Although she is clinically and electromyographically normal, we monitored the neuromuscular function, since serum CPK level was high in our case. We did not use muscle relaxants for endotracheal intubation, since sevoflurane could provide sufficient muscle relaxation. Moreover, we did not use neuromuscular blocking agents during surgery, because the surgical operation did not require further muscle relaxation and the patient was sufficiently anesthetized with volatil anesthetic agent. Although strabismus correction in children is associated with a high incidence of postoperative nausea and vomiting (PONV) without prophylactic antiemetic medication13 PONV was not occurred in our patient. Anesthesia for these patients should be carried out carefully, because DCS is a multisystemic lipid storage disease. Preoperative evaluation should be performed in detail and anesthetic method and drugs to be used should be chosen carefully in accordance with affected system, overall state of patient and characteristics of the operation, in order to decrease perioperative morbidity rates in these patients. M.E.J. ANESTH 21 (3), 2011 440 A. Beştaş et al. References 1. CIesek S, Hadem J, Manns MP, FIscher J, Strassburg CP: A rare cause of nonalcoholic fatty liver disease. Annals of Internal Medicine; 2006, 145:154-155. 2. Rozenszajn L, Klajman A, Yaffe D, EfratI P: Jordans’ anomaly in white blood cells. Report of case Blood; 1966, 28:258-265. 3. Akiyama M, Sawamura D, Nomura Y, Sugawara M, Shimizu H: Truncation of CGI-58 protein causes malformation of lamellar granules resulting in ichthyosis in Dorfman-Chanarin Syndrome. The Journal of Investigative Dermatology; 2003, 121:1029-1034. 4. Chanarın I, Patel A, Slavın G, Wılls EJ, Andrews TM, Stewart G: Neutral-lipid storage disease: A new disorder of lipid metabolism. British Medical Journal; 1975, 1:553-555. 5. Kubota R, Miyake N, Nakayama H, ArIta H, Hanaoka K: Anesthetic management of a patient with non-bullous congenital ichthyosiform erythroderma. Masui; 2003, 52:1332-1334. 6. Keegan MT, Plevak DJ: Preoperative assessment of the patient with liver disease. American Journal of Gastroenterology; 2005, 100:2116-2127. 7. Green DW, Ashley EMC: The choice of inhalation anaesthesia for major abdominal surgery in children with liver disease. Paediatric Anaesthesia; 2002, 12:665-673. 8. Hanje AJ, Patel T: Preoperative evaluation of patients with liver disease. Nature Clinical Practice Gastroenterology & Hepatology; 2007, 4:266-276. 9. Isaacs H, Barlow MB: Malignant hyperpyrexia during anaesthesia: possible association with subclinical myopathy. British Medical Journal; 1970, 1:275-277. 10.Schmidt J, Muenster T, Wick S, Forst J, Schmitt HJ: Onset and duration of mivacurium-induced neuromuscular block in patients with Duchenne muscular dystrophy. British Journal of Anaesthesia; 2005, 95:769-772. 11.Wick S, Muenster T, Schmidt J, Forst J, Schmitt HJ: Onset and duration of rocuronium-induced neuromuscular blockade in patients with Duchenne muscular dystrophy. Anesthesiology; 2005, 102:915919. 12.Sullivan M, Thompson WK, Hill GD: Succinylcholine-induced cardiac arrest in children with undiagnosed myopathy. Canadian Journal of Anaesthesia; 1994, 4:497-501. 13.Kuhn I, Scheıfler G, Wıssıng H: Incidence of nausea and vomiting in children after strabismus surgery following desflurane anaesthesia. Paediatric Anaesthesia; 1999, 9:521-526. LINGUAL THYROID: A RARE CAUSE OF DIFFICULT INTUBATION Maroun Badwi Ghabash*, Jean-Claude M. Stephan**, May Semaan Matta*** and May Radi Helou**** Abstract This case report is about a patient with an oropharyngeal mass presenting to our hospital for biopsy under general anesthesia. Because of the great risk of failure of mask ventilation and direct laryngoscopy, an awake fiberoptic intubation was performed successfully. The biopsy revealed a thyroid tissue leading to the diagnosis of ectopic lingual thyroid. Introduction Managing a patient with difficult airway is among the most challenging and stressful tasks in anesthesia1. The inability to provide adequate ventilation and to perform tracheal intubation is associated with major morbidity and mortality2. Lingual thyroid, first described in 1869 by Hickman3, is located at the base of the tongue between the circumvallate papillae and epiglottis. This ectopic variation has an incidence of 1:1000004. Its position and size may cause obstruction of the laryngeal pathway leading to ventilation and intubation difficulties with a potential dramatic risk of hemorrhage during attempts of intubation. This case report describes the successful management of a patient with symptomatic lingual thyroid undergoing surgery under general anesthesia. Case Report A 42-year-old woman presented to our hospital for biopsy of an oropharyngeal mass under general anesthesia. The pre-operative anesthetic evaluation revealed a patient with 55 Kg body weight, 155 cm height, non-smoker, with a negative past medical and surgical history, and absence of weight loss; She was only complaining of dyspnea and dysphonia. Airway examination for difficult intubation was insignificant; Normal mobility of the neck, Mallampati score of 1, thyromental distance of 6 cm, mouth opening of 4 cm and inability of visualization of the mass. Pre-operative investigation included normal hematology tests, coagulation profile, chemistry, TSH, free T3 and T4 and a normal chest X-ray. A CT-scan of the neck showed an evidence of a large well defined 5 cm heterogeneous mass lesion at the base of the tongue extending to the oropharynx * MD, Anesthesiologist, Chairman of Anesthesia, Haddad Hospital for the Rosary Sisters Gemayze-Beirut-lebanon, chargé d’enseignement at the Lebanese University-Medical School. ** MD, Third Year Resident of Anesthesia, Department of Anesthesia Lebanese University-Medical School. *** MD, Anesthesiologist, Haddad Hospital for the Rosary Sisters Gemayze-Beirut-Lebanon. **** MD, Anesthesiologist, Chairman of Anesthesia and ICU Department at the Lebanese University-Medical School. Corresponding Author: Maroun Ghabash, MD, Anesthesiologist, Chairman of Anesthesia, Haddad hospital for the Rosary Sisters, Gemayze, Beirut-Lebanon. Tel: 03-451882, E-mail:[email protected] 441 M.E.J. ANESTH 21 (3), 2011 442 and causing marked narrowing of the oropharyngeal airway mainly on the left side (Fig. 1). M. B. Ghabash et al. Fig. 2 The mass as visualized by the fiberscope Fig. 1 The mass at the base of the tongue as visualized by the scan Embryology The patient had been explained about the hazards of intubation in her case and that an awake fiberoptic intubation will be performed. No premedication was given preoperatively. In the induction room, a standard monitoring was applied on the patient and an intravenous access was established. A solution of lidocaine 5% and phenylephrine nasal was sprayed in both nostrils. The fiberscope, Olympus P40, lubricated and threaded through the lumen of an ETT size 6.5, was inserted in the right nostril and was navigated into the oral pharynx. The mass was visualized (Fig. 2) and was completely obscuring the epiglottis and the larynx. The fiberscope was guided through a narrow passage on the right side of the lesion then was flexed anteriorly to enter between the vocal cords into the trachea. Once reaching the carina, the ETT was railroaded over the fiberscope. Intubation was reconfirmed by the presence of EtCO2 and anesthesia was induced with propofol and was maintained with rocuronuim, sevoflurane and remifentanyl. Surgery underwent uneventfully and the patient was extubated. Embryologically, the thyroid gland develops as an endodermal diverticulum between the first and the second pharyngeal pouches. At the seventh week of embryonic life, it passes from the base of the tongue in front of the hyoid bone to settle ultimately anterior to the trachea. Incomplete caudal migration of the gland may lead to lingual thyroid as a developmental anomaly5. The etiology of this embryonic defect is not yet understood, but maternal antibodies against thyroid antigens have been incriminated6. Discussion Management of the difficult airway in the general surgical population has been widely studied, and several algorithms have been established7. However, the incidence of difficult ventilation and endotracheal intubation in lingual thyroid surgery has rarely been reported. Clinically, the lingual thyroid presents as a pink and firm mass at the base of the tongue. Most of the cases are asymptomatic, but frequently encountered symptoms are due to mass effect: dysphonia, dysphagia, lump in throat sensation, dyspnea, chronic cough and bleeding. Surgical intervention is indicated LINGUAL THYROID: A RARE CAUSE OF DIFFICULT INTUBATION in symptomatic cases or as prophylactic due to the risk of malignant transformation. Lingual thyroid surgery under general anesthesia is a risky challenge due to its location, size and bleeding tendency. This paper presents the case of an expected difficult airway due to a symptomatic mass sized 5cm in the oropharynx (Figure 1). The approach to the airway was based on two targets. The first was to keep a spontaneous breathing: we avoided the use of sedative drugs that can cause apnea and posterior displacement of the soft palate, base of the tongue or epiglottis; thus majoring the already narrowed pharynx by the mass leading to difficulty and inability of mask 443 ventilation. In addition, any attempt to insert a guedel airway, LMA, or fast track can easily injure the fragile tissue leading to bleeding with a fatal outcome. The second target was to visualize the vocal cord and to intubate the patient under direct vision without traumatizing the surrounding tissue. On the other hand, performing a direct classical laryngoscopy can also cause hemorrhage and catastrophic compromise of the airway. As a result, an awake fiberoptic intubation was the only choice to successfully secure the airway in this case. References 1. Kheterpal S, Martin L, Shanks A and Tremper K: Prediction and outcomes of impossible mask ventilation. Anesthesiology; 2009, 110:891-7. 2. Caplan R, Posner K, Ward R and Cheney F: Adverse respiratory events in anesthesia: a closed claims analysis. Anesthesiology; 1990, 72:828-33. 3. Hickman W: Congenital tumor of the base of the tongue, pressing down the epiglottis on the larynx and causing the death by suffocation sixteen hours after birth. Trans pathology Soc London; 1869, 20:160-63. 4. Douglas P and Baker A: Lingual thyroid. Br J Oral Maxillofac Surg; 32:123-4. 5. Abdallah-Matta M, Dubarry P, Pessy J and Caron P: Lingual thyroid and hyperthyroidism: a new case and review of the literature. J Endocrinol Invest Mar; 2002, 25(3):264-7. 6. Van Der Gaag R, Drexhage H and Dussault J: Role of maternal immunoglobulins blocking TSH induced thyroid growth in sporadic forms of congenital hypothyroidism. Lancet; 1985, 1:1246-50. 7. American Society of Anesthesiologists Task Force of Management of Difficult Airway.Practice guidelines for management of the difficult airway. Anesthesiology; 2003, 98:1269-77. M.E.J. ANESTH 21 (3), 2011 SHOULD SURGERY BE CANCELLED WHEN SURREPTITIOUS COCAINE USE IS DISCOVERED BEFORE ELECTIVE NON-CARDIAC SURGERY? M. Chadi Alraies MD FACP*, Abdul Hamid Alraiyes MD**, Franklin Michota MD FACP* Answer: Patients presenting for elective non-cardiac surgery requiring general anesthesia who test positive for cocaine but are asymptomatic and clinically nontoxic are at no greater risk for surgical complications than cocaine-free patients. Routine cancellation of surgery for these patients is unwarranted. Such patients need careful preoperative history and physical examination along with screening electrocardiogram (ECG) looking for QT prolongation. Patients who display signs of acute cocaine intoxication or those with a prolonged QT interval will need to have elective surgery delayed. However, there is paucity in literature and no guidelines supporting this practice and clinician practicing perioperative medicine and anesthesia should be vigilant till more prospective studies are done to support this practice. Discussion One of the goals of the preoperative evaluation is to ensure that the surgical patient is optimized for the stress of surgery. In the patient with a history of cocaine use, it is reasonable to avoid the combined stress of acute cocaine exposure and surgery; however, postponing surgery well beyond the time cocaine is physiologically active may be unnecessary and cause a delay in patient care. Cocaine blocks the reuptake of norepinephrine, dopamine, and serotonin at the synaptic junctions producing an excess of transmitter at the postsynaptic receptor sites1. Signs include an increase in systolic, diastolic and mean arterial blood pressure, heart rate, body temperature and the potential for coronary artery vasospasm and arrhythmias. Cocaine toxicity is a clinical diagnosis, as signs of toxicity do not correlate well to measured blood concentrations of cocaine2,3. The most reliable supporting evidence for cocaine toxicity is a confirmed history of active use4. Many cocaine abusers are not going to admit to it5. Patients with surreptitious cocaine abuse may manifest feelings of excitation, report weight loss, anxiety, requests for sedatives and pain medicine and complain of digestive problems. Cocaine abusers should be asked for timing, amount, route of cocaine in the last 24 hours, and length of addiction6. Cocaine users are known to experience a higher cardiac related mortality associated with arrhythmia and coronary artery disease7. The mechanism for the induction of these arrhythmias is a combination of coronary artery vasospasm and cocaine-induced sodium and potassium channel blockade that causes lengthening of the QTc interval as well8. * ** MD, Cleveland Clinic, Cleveland, Ohio, USA. MD, Tulane University, New Orleans, Luisiana, USA. Corresponding author: Clinical Assistant Professor of Medicine, Cleveland Clinic Lemer College of Medicine of Case Western Reserve University, Staff, Department of Hospital Medicine, Institute of Medicine, Cleveland Clinic, 9500 Euclid Ave. A13, Cleveland, OH 44195, Office: (216) 445-1472, Fax: (216) 445-1767. E-mail: [email protected] 445 M.E.J. ANESTH 21 (3), 2011 446 Cocaine has a short half-life in plasma (30-90 minutes) and is rapidly hydrolysed into metabolites by plasma and liver esterases9. Cocaine metabolites pose no cocaine-like stimulation effects and have long half-life which is responsible for positive urine testing for 6 to 14 days after cocaine ingestion. As a result, urine tests for cocaine are poor markers of acute intoxication, but may reflect surreptitious cocaine abuse in the past10,11. The cancellation of surgery among patients who screen positive for cocaine use is a common practice in many surgical centers. However, there is paucity in literature studying the management of these patients going for urgent or elective surgery. We found two studies that addressed this issue. Ryb GE et al12, studied cocaine-positive patients (n = 465) undergoing surgery and compared those patients with recent (<24 hours) cocaine use vs. patients who did not use cocaine M. C. Alraies et al. immediately before injury (>24 hours). Outcomes were similar for mortality (3% vs. 4%), infectious (18% and 19%) and neurologic (2% vs. 1%) complications. Another study investigated the role of screening ECG as a safety protocol among patients going for elective surgery (N =13)40 . No significant differences in episodes of ST segment elevation/depression >1 mm, recovery room stay, intraoperative body temperature, duration of anesthesia and total anesthesia/analgesic dose, were found when compared with controls that did not have a positive cocaine urine test. We should be careful in interpreting these two studies giving the small sample size. In summary, surreptitious perioperative cocaine use does occur. Patients with a normal ECG and without clinical signs of cocaine toxicity may proceed safely with surgery. However, larger prospective studies are needed to support this practice. References 1.Ritz MC: Cocaine inhibition of ligand binding at dopamine, norepinephrine and serotonin transporters: a structure-activity study. Life Sci; 1990, 46:635-45. 2.Karch SB: Relating cocaine blood concentrations to toxicity: an autopsy study of 99 cases. J Forensic Sci; 1998, 43:41-45. 3.Karch SB: Cocaine cardiovascular toxicity. South Med J; 2005, 98:794-799. 4.Stephens BG: National Association of Medical Examiners Position Paper on the Certification of Cocaine-related Deaths. Am J Forensic Med Pathol; 2004, 25:11-13. 5.Skerman JH: The cocaine-using patient: perioperative concerns. Middle East J anesthesiol; 2005 Feb, 18(1):107-22. 6.Frost EA: Preanesthetic assessment of the of the drug abuse patient. Anesthesiology Clinics of North America; 1990, 8:829-841. 7.Bauman JL: Cocaine related sudden cardiac death: a hypothesis correlating basic science and clinical observations. J Clin Pharmacol; 1994, 34:902-11. 8.Kimura S: Early after depolarizations and triggered activity induced by cocaine. Circulation; 1992, 85:2227-35. 9.Cheng D: Perioperative care of the cocaine-abusing patient. Can J Anaesth; 1994, 41:10, pp. 883-7. 10.Jatlow PI: Drug abuse profile: cocaine. Clin Chem; 1987, 33:66B-71B. 11.Brownlow HA, Pappachan J: Pathophysiology of cocaine abuse. Eur J Anaesthesiol; 2003, 19:395-414. 12.Ryb GE, Cooper C: Outcomes of cocaine-positive trauma patients undergoing surgery on the first day after admission; 2008 Oct, 65(4):809-12. 13.Hill GE: General anesthesia for the cocaine abusing patient. Is it safe? Br J Anaesth; 2006, 97:654-657. AUTOMATIC ENDOTRACHEAL TUBE CUFF INFLATOR AND CONTINUOUS PRESSURE MONITOR/CONTROLLER Musa Muallem*, Mohamad F. El-Khatib** Background Endotracheal tube cuff pressure over 30 cm of water has been found to occur in about 50% of cases where cuff inflation was performed without monitoring, using pilot balloon palpation, minimal leak, or minimal occlusive volume techniques1. The incidence of post operative respiratory complications such as cough, sore throat, hoarseness, blood-streaked expectoration, and even tracheal stenosis is increased with increase of cuff pressure over 30 cm of water2. Mandatory continuous monitoring and control of the endotracheal tube cuff pressure have been recommended to minimize such complication. Anesthesiologists continue to ignore the above important recommendation in many institutions because they do not have easy access to devices that monitor and control cuff pressure, and because continuous intracuff pressure control and measurement using a device are not yet mandate or standard of care for anesthesia practice. Intermittent checking of the cuff pressure during anesthesia is not good enough and has a very poor compliance. Ideally, the cuff pressure should be monitored and controlled at the required level continuously and automatically without concern from the anesthesiologist. This situation prompted us to design and develop cuff inflator and cuff pressure monitor/ regulator that is simple and practical. Description of the apparatus The cuff inflator/monitor is operated by an oxygen line from the auxiliary outlet of the anesthesia machine at a pressure of 50 psi. The oxygen line is connected to the inlet of a Butane gas reducing valve available commercially in the market and which operate at an inlet pressure of five bars and an outlet pressure variable from 15 to 45 cm of water. This reducing valve fits the requirements of a reducing valve suitable for building a cuff inflator monitor/controller. The oxygen comes out from the Butane reducing valve at a maximum pressure of 45 cm of water and can be further reduced to 15 cm of water by the valve pressure controlling knob. The oxygen from the reducing valve outlet is connected by plastic tubings to: 1- Outlet nipple that connect through an oxygen plastic tube, via a luer tap at the distal end, to the ET tube cuff pilot balloon (Fig. 1, 2). * Emeritus Professor. **Professor. Department of Anesthesiology, American University of Beirut Medical Center, Beirut 1107-2020 Lebanon. Correspondence to: Dr. Mohamad El-Khatib. E-mail: [email protected] 447 M.E.J. ANESTH 21 (3), 2011 448 M. Muallem & M. F. El-Khatib Fig 1 Schematic Diagram the valve outlet plastic tube to reduce the oxygen flow rate to a minimum, yet enough to inflate the cuff in few seconds. While the venting needle valve and the outlet to the tube cuff are closed, the outlet pressure of the Butane reducing valve is set at 45 cm H2O, by the valve controlling pressure knob or by a screw driver. Then the venting needle valve knob is turned to open and pressure set at 30 cm H2O. When the cuff inflator/ controller is connected to the tube cuff, the cuff will be inflated instantly and its pressure is maintained constant at 30 cm of water or as set by the user. The pressure of the cuff can be increased or decreased by the needle valve that increases or decreases the gas vented out, as each case may require, and depending on the inflating pressure required to inflate the lung. Usually the cuff pressure is set at 30 cm of water or slightly higher than the lung inflating pressure required. Fig 2 Back view The cuff inflator/controller described above (Fig. 3) has been used successfully for many years in the department of anesthesiology at the American University of Beirut Medical center during anesthesia and in chronically intubated and ventilated patients, without complications or failure, provided all connections are tight with no leaks. Fig 3 Front View 2- Airway pressure gauge graduated from 0 to 60 cm H2O (figure 1, 2). 3- Needle valve that is vented to atmosphere. A brass insert with a very small hole is placed in AUTOMATIC ENDOTRACHEAL TUBE CUFF INFLATOR AND CONTINUOUS PRESSURE MONITOR/CONTROLLER 449 References 1.Kim Z Rokamp, Niels H Secher, Ann M Moller and Henning B Nielsen: Tracheal tube and laryngeal mask cuff pressure during anaesthesia-Mandatory monitoring is in need. BMC Anesthesiology; 2010, 10:20doi:10.1186/1471-2253-10-20. 2.Liu J, Zhang X, Gong W, Li S, Wang F, Fu S, Zhang M, Hang Y: Correlations between controlled endotracheal tube cuff pressure and post procedural complications: a multicenter study. Anesth Analg; 2010 Nov, 111(5):1133-7. Epub 2010 Aug 24. M.E.J. ANESTH 21 (3), 2011 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. Manuscript Preparation Manuscript format required: Double-spaced lines Wide margins (1.5 inches or 3.8 cm) Page numbers start on title page Word count should reflect text only (excluding abstract, references, figures and tables). Editorial 1500 Abstract 250 (General articles) 100 (Case Reports) Clinical or laboratory investigations: The following structured format is required: 1. Cover Letter 7. Discussion 2. Title page 8. Acknowledgements 3. Abstract 9. References 4. Introduction 10. Tables 5. Methods 11. Figures 6. Results 1. Cover Letter Manuscripts must be accompanied by a cover letter, signed by all authors and stating that: - All authors have contributed intellectually to the manuscript and the manuscript has been read and approved by all the authors. - The manuscript has not been published, simultaneously submitted or accepted for publication elsewhere. 2. Title Page Starts at page 1 and includes: - A concise and informative title (preferably less than 15 words). Authors should include all information in the title that will make electronic retrieval of the article both sensitive and specific. - Authors listing: first name, middle initial and last name with a superscript denoting the academic degrees as footprints. - The name of the department(s) and institutions(s) to which the work should be attributed. - The name, address, telephone, fax numbers and e-mail address of the corresponding author. - Disclose sources of financial support (grants, equipment, drug etc…). - Conflict of interest: disclosure of any financial relationships between authors and commercial interests with a vested interest in the outcome of the study. - A running head, around 40 characters. - Word count of the text only (excluding abstract, acknowledgements, figure legends and references). Review article 4000 Original article 3000 Case Reports 800 3. Abstract Letter to Editor 500 Abstract should follow the title page. It should be structured with background, methods, results and conclusion. M.E.J. ANESTH 21 (3), 2011 It should state, the specific purpose of the research or hypotheses tested by the study, basic procedures, main findings and principal conclusions. Provide separate word count for the abstract. 4. Introduction Provide the nature of the problem and its significance. State the specific purpose or research objectives or hypothesis tested. Provide only directly pertinent references and do not include data or conclusions from the work being reported. 5. Methods A. Selection and description of participants: - Describe selection of participants (including controls) clearly, including eligibility and exclusion criteria. B. Technical information: -Identify the methods, apparatus (give the manufacturer’s name and address in parentheses), and procedure in sufficient detail to allow others to reproduce the results. Give references to established methods. Provide references and brief descriptions for methods that have been published. Identify precisely all drugs and chemicals used, including generic names(s), dose(s) ands routes(s) of administration. C. Statistics-describe statistical methods with enough detail to enable a knowledgeable reader with access to the original date to verify the reported results. Define statistical terms, abbreviations and most symbols. Specify the computer software used. Provide a power analysis for the study. 6. Results Present your results in logical sequence in the text, tables and illustrations, giving the main or most important findings first. Do not repeat all the data in the tables or illustrations in the text: emphasize or summarize only the most important observations. Extra or supplementary materials and technical details can be placed in an appendix. 7. Discussion Emphasize the new and important findings of the study and the conclusions that may be drawn. Do not repeat in details data or other information given in the Introduction or the Results sections. For experimental studies, it is useful to begin the discussion by summarizing briefly the main findings, then explore possible mechanisms or explanations for these findings, compare and contrast the results with other relevant studies. State the limitations of the study, and explore the implications of the findings for future research and for clinical practice. Link the conclusions with the goals of the study, but avoid unjustified statements and conclusions not adequately supported by the data. 8. Acknowledgements They should be brief. Individuals named must be given the opportunity to read the paper and approve their inclusion in the acknowledgments. 9. References - References should be indicated by Arabic numerals in the text in the form of superscript and listed at the end of the paper in the order of their appearance. Please be accurate, giving the names of all authors and initials, the exact title, the correct abbreviation of the journal, year of publication, volume number and page numbers. - The titles of journals should be abbreviated according to the style used in the list of Journals Indexed for MEDLINE. Example: (1) from a journal (2) from a book. 1.SHAWW: AND ROOT B: Brachial plexus anesthesia Comparatives study of agents and techniques. Am. J. Surg.; 1951, 81:407. 2. ROBINSON JS: Modern Trends in Anaesthesia, Evans and Gray Ch. 8, Butterworth Pub. Co., London 1967. 10. Tables Tables capture information concisely and display it efficiently: They also provide information at any desired level of details and precision. Including data in tables rather than text frequently makes it possible to reduce the length of the text. - Type or print each table with double spacing on a separate sheet of paper. - Number tables consecutively in the order of their first citation in the text. - Supply a brief title for each. - Place explanatory matter in footnotes, not in the heading. - Explain all nonstandard abbreviations in footnotes. - Identify statistical measures of variations, such as standard deviation and standard error of the mean. 11. Figures - Figures should be submitted in JPEG or TIFF format with a minimum of 150 DPI in resolution. - Colored data if requested by author is chargeable. - If a figure has been published previously, acknowledge the original source and submit written permission from the copyrights holder to produce the figure. Abbreviations and symbols: - Use only standard abbreviations. - Avoid abbreviations in the title of the manuscript. -The spelled-out abbreviations followed by the abbreviation in parenthesis should be used in first mention. Printed by Arab Scientific Publishers Ain Al-Tineh, Beirut, Lebanon Telefax: + 961 (1) 785107 / 8 Email: [email protected] www.asp.com.lb