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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: Bikhazi George Assem Abdel-Razik (Egypt) Executive Editors Mohamad El-Khatib Editors Chakib Ayoub Marie Aouad Ghassan Kanazi Sahar Siddik-Sayyid Mohamad El-Khatib [email protected] Bassam Barzangi (Iraq) Izdiyad Bedran (Jordan) Dhafir Al-Khudhairi (Saudi Arabia) Mohammad Seraj (Saudi Arabia) Abdul-Hamid Samarkandi (Saudi Arabia) Mohamad Takrouri (Saudi Arabia) Bourhan E. Abed (Syria) Mohamed Salah Ben Ammar (Tunis) Managing Editor Assistant Iman Jaafar M. Ramez Salem (USA) Webmaster Rabi Moukalled Elizabeth A.M. Frost (USA) Secretary Alice Demirdjian [email protected] Halim Habr (USA) Managing Editor Founding Editor Bernard Brandstater Emeritus Editor-In-Chief Anis Baraka Honorary Editors Nicholas Greene Musa Muallem 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 Middle East Journal of Anesthesiology Vol. 23, No. 1, February 2015 CONTENTS editorial «Routine» Preoxygenation ��������������������������������������������������������������������������������������������������������������������������������� Anis Baraka 5 review article The Impact Of Endotracheal Tube Vs Laryngeal Mask Airway On The Incidence Of Postoperative Nausea And Vomiting: A Systemic Review And Meta-Analysis ������������������������������������������������������������� Jahan Porhomayon, Sina Davari Farid, Ali A. El-Solh, Ghazaleh Adlparvar, Nader D. Nader 9 scientific articles Renal Protection In The Cardiac Surgery Patient: Peri-Operative Sodium Bicarbonate Infusion (Posbi) Or Not? ��������������������������������������������������������������������Hassan H. Amhaz, Deepak Gupta, Larry Manders, George McKelvey, Marc S. Orlewicz, Romeo N. Kaddoum Effect Of Ultrasound-Guided Subsartorial Approach For Saphenous Nerve Block In Cases With Saphenous Nerve Entrapment In Adductor Canal For Controlling Chronic Knee Pain �������������������������������������������������������������������������� Arman Taheri, Maryam Hatami, Majid Dashti, Alireza Khajehnasiri, Mahsa Ghajarzadeh Comparison Of The Effects Of Oral Vs. Peritonsillar Infiltration Of Ketamine In Pain Reduction After Tonsillectomy: A Randomized Clinical Trial ������������������������������������������������������������������������������������������������Afsaneh Norouzi, Abolfazl Jafari, Hamid Reza Khoddami Vishteh, Shahin Fateh The Impact Of Anesthetic Techniques On Cognitive Functions After Urological Surgery 17 25 29 ����������������������������������������������������������������������������������������Mahtab Poor Zamany Nejat Kermany, Mohammad Hossein Soltani, Khazar Ahmadi, Hoora Motiee, Shermin Rubenzadeh, Vahid Nejati Comparison Between C-Mac® Video-Laryngoscope And Macintosh Direct Laryngoscope During Cervical Spine Immobilization ��������������������������������������������������������������������������������������������Shahir H.M. Akbar, Joanna SM Ooi 43 Effects Of Memantine On Pain In Patients With Complex Regional Pain Syndrome-A Retrospective Study �������������������������������������������������������Mohammad-Hazem I. Ahmad-Sabry, Gholamreza Shareghi 51 Effects Of Dexamethasone And Pheniramine Maleate On Hemodynamic And Respiratory Parameters After Cementation In Cemented Partial Hip Prosthesis ������������������������������������������������������������������������������������������������������������������������ Abdulkadir Yektaş 55 Effect Of Preoperative Oral Pregabalin On Postoperative Pain After Mastectomy �������������������������������������������������������������������� Mardhiah Sarah, Harnani Mansor, Choy Yin Choy 1 35 63 M.E.J. ANESTH 23 (1), 2015 Consumption Trends Of Rescue Anti-Psychotics For Delirium In Intensive Care Units (Icu Delirium) Show Influence Of Corresponding Lunar Phase Cycles: A Retrospective Audit Study From Academic University Hospital In The United States ������������������������������������������������������������������� Deepak Gupta, Vinay Pallekonda, Ronald Thomas, George Mckelvey, Farhad Ghoddoussi Ultrasound-Guided Sciaticoliteal Nerve Block: A Comparison Of Separate Tibial And Common Peroneal Nerve Injections Versus Injecting Proximal To The Bifurcation �������������������������������������������������������������� Alberto E. Ardon, Roy A. Greengrass, Upasna Bhuria, Steven B. Porter, Christopher B. Robards, Kurt Blasser Subtenon bupivacaine injection for postoperative pain relief following pediatric strabismus surgery: A randomized controlled double blind trial ����������������������������������������������������������������������������������� Radwa H Bakr and Hesham M Abdelaziz 69 81 91 case reports Straight To Video: Tonsillar Injury During Elective Glidescope-Assisted Pediatric Intubation ��������������������������������������������������������������������� Jason D. Rodney, Zulfiqar Ahmed, Deepak Gupta, Maria Markakis Zestos Percutaneous Balloon Compression Of Gasserian Ganglion For The Treatment Of Trigeminal Neuralgia: An Experience From India ��������������������������������������������������������������������� Anurag Agarwal, Vipin Dhama, Yogesh K. Manik, M. K. Upadhyaya, C. S. Singh, V. Rastogi Bedside Retianed Radial Artery Catheter Removal In A Hemodynamically Unstable Neurocritically-Ill Patient: A Case Report ����������������������������������������������������������������������������� Christa O’Hana V. San Luis, Athir H. Morad 101 105 111 Esophageal Perforation Following Orogastric Suction Catheter Insertion In An Elderly Patient ������������������������������������������������������������������Roland N. Kaddoum, Fadi Farah, Rita W. Saroufim, Salah M. Zeineldine 117 letter to the editor Pediatric Endotracheal Intubation ��������������������������������������������������������������������������������������������������������������������������Claude Abdallah 2 123 LIFE ON WHEELS Triumph over the agony of pain and sadness; admission of the ways of the creator and “happy to be alive”; optimism with brilliant accomplishments from a wheelchair and “breathing happiness”, are but few of the accomplishments of faculties endowed on Alon P. Winnie , Professor and Chairman of the Department of Anesthesiology of the University of Illinois. Fig1. Dr. Winnie among his colleagues ; Dr. Baraka (far left) & Dr. Raj (far right). In his own words, Dr. Winnie writes « Dear Anis*… To fulfill my promise to you, the following… Let me preface it by telling you that it was written from the viewpoint of a rocking bed after I had been given my first wheelchair, for which I had waited for an eternity of months while physiotherapy tried to rid me of the rigidity left behind when the pain of the muscle spasms finally subsided… It was the middle of winter and I had a beautiful view of the slum section of the city just behind the hospital…The first half obviously representing the translation of my impression at night and the second during the day… The sad white eye of this new night Cries myriads of auto tears That criss-cross over its many streeted face; The freckles of which glow dimly * Dr. Anis Baraka, Department of Anesthesiology, American University of Beirut, Beirut, Lebanon. MEJA 3: 240, 1972. 3 M.E.J. ANESTH 23 (1), 2015 4 And disappear One by one As an angry lock of cloud Slips down And covers sad eye rendered sadder By the loss of legs, Yet soon The bright orange eye of the day Combs back the clouds Revealing life and lives Breathing happiness In little gray-blue puffs From the cigarette chimneys As the city yawns As a sleepy but happy to be alive yawn And readies itself For this new day Of life on wheels…” Fig 2. Dr. Alon Winnie EDITORIAL “ROUTINE” PREOXYGENATION It is a fact of great clinical importance that the body oxygen stores are so small, and if replenishment ceases, they are normally insufficient to sustain life for more than a few minutes. Breathing oxygen causes a substantial increase in the total oxygen stores; most of the additional oxygen is accommodated in the alveolar space (functional residual capacity) from which 80% may be withdrawn without the PaO2 falling below the normal vale. This concept is the basis of the preoxygenation technique1. In 1955, Hamilton and Eastwood demonstrated that denitrogenation of the functional residual capacity of the lung is 95% complete within 2-3 minutes, if a subject is breathing at a normal tidal volume form a circle anesthesia system using an oxygen flow of 5 l/min2. These studies led to the recommendation of preoxygenation as a standard practice before rapid sequence induction of general anesthesia in patients with full stomach. “Routine” preoxygenation has become a new “minimum standard” of care not only during induction of anesthesia and tracheal intubation, but also during emergence from anesthesia and tracheal extubation1. The original American Society of Anesthesiologists (ASA) difficult airway algorithm made no mention of preoxygenation. However, in an updated report of the ASA Task Force on “Management of the Difficult Airway” 2003, the topic of face mask preoxygenation before initiating management of the difficult airway was added3. Preoxygenation before induction of anesthesia was also recommended in patients with low functional residual capacity of the lung, associated with a high oxygen consumption. This category includes the neonates, the pregnant and the morbidly obese patients who rapidly decrease their oxygen saturation during apnea while breathing room air4. Preoxygenation is also recommended in patients with decreased oxygen delivery (Cardiac output x Hb conc x% saturation x 1.34) which include patients with low cardiac output or pulmonary disease, as well as patients with low or abnormal hemoglobin such as methemoglobin. Before induction of general anesthesia, preoxygenation can be achieved either by tidal volume breathing of 100% oxygen for 3-5 minutes using an oxygen flow of 5 l/min as described by Hamilton and Eastwood2, or by the 8 deep breaths technique for 60 seconds using an oxygen flow of 10 L/ min as described by Baraka et al5. The mean time to decrease of hemoglobin oxygen saturation from 100% to 99% is significantly longer during the subsequent apnea following the 8-deep breaths technique of preoxygenation than following the traditional tidal volume preoxygenation technique5. As suggested by Benumof, the 8 deep breaths technique may be considered the best method of preoxygenation for both efficacy and efficiency6. The high efficiency of preoxygenation by the deep breaths technique may be attributed to a relatively larger minute volume, and/or to 5 M.E.J. ANESTH 23 (1), 2015 6 Dr Baraka possible expansion of any collapsed alveoli by the deep breathing technique. The beneficial effect of preoxygenation by tidal volume or deep breathing, can be further extended during subsequent apnea by the apneic diffusion oxygenation7-9. The technique of ADO has been advantageous not only in patients with a difficult airway or pulmonary disease, but also in children, the pregnant and the morbidly obese patients who have a high oxygen consumption associated with a relatively low FRC4. ADO has been also used to maintain oxygenation during bronchoscopy7, and one-lung ventilation10. Apneic diffusion oxygenation (ADO) is achieved by preoxygenation by tidal volume2, or deep breathing technique5, to be followed by insufflations of high flow of 100% oxygen by a catheter into the pharynx via an open airway. During ADO, the increase in time to hemoglobin desaturation achieved by increasing the FIO2 from 0.9 to 1.0 is greater than that caused by increasing the FIO2 from 0.21 to 0.99. During ADO, CO2 is not exhaled because of the mass movement of oxygen down the trachea. The alveolar CO2 concentration (PACO2) shows an initial rise of 8-16 mmHg during the first minute, followed by a subsequent fairly linear increase of about 3 mmHg/ min. Thus, the ADO can maintain oxygenation for a prolonged period. However, the increase of PaCO2 will limit the period of apnea. In conclusion, preoxygenation has been initially recommended for rapid-sequence induction of anesthesia in patients with full stomach, as well as in patients with predicted difficult airway. However, the technique is nowadays recommended as a routine during induction, as well as during recovery from general anesthesia, since difficult airway may be unpredicted. Preoxygenation, followed by apneic diffusion oxygenation is indicated in patients who desaturate rapidly during apnea such as the neonate, the obese and the pregnant patients who have a relatively low FRC associated with a high oxygen consumption. ADO is also advantageous in patients with decreased oxygen delivery such as the elderly, cardiac and pulmonary diseased patients. The technique is also used to maintain oxygenation during certain procedures such as bronchoscopy, and one-lung ventilation. “Routine” preoxygenation with 100% oxygen is considered a “safety” measure during anesthetic induction and emergence from anesthesia, and is advantageous in critically-ill patients requiring airway management. However, it must be used as an adjunct rather than an alternative to a sequence of fundamental precautions that minimize adverse sequelae1. Anis Baraka, MD, FRCA (Hon) Emeritus Professor of Anesthesiology American University of Beirut “ROUTINE” PREOXYGENATION 7 References 1. Baraka AS, Salem MR: Preoxygenation: In Benumof and Hagberg’s Airway management, Third Edition 2013, Chapter 13, pp. 280-297. 2. Hamilton W, Eastwood D: A study of denitrogenation with some inhalation anesthetic systems. Anesthesiology; 1955, 16:861-867. 3. Practice guidelines for management of difficult airway: An updated report by the American Society of Anesthesiologists Task force on the management of the difficult Airway. Anesthesiology; 2003, 98:1269-1277. 4. Baraka AS, Taha SK, Siddik SM et al: Supplementation of oxygenation in morbidly obese patients using nasopharyngeal oxygen insufflation. Anaesthesia; 2007, 62:769-773. 5. Baraka AS, Taha SK, Aouad MT, El-Khatib MF, Kawkabani NI: Preoxygenation: Comparison of maximal breathing and tidal volume breathing techniques. Anesthesiology; 1999, 91(3):612-616. 6. Benumof JL: Preoxygenation: Best method for both efficacy and efficiency. Anesthesiology; 1999, 91(3):603-605. 7. Holmdahl MH: Pulmonary uptake of oxygen, acid-base metabolism, and circulation. Acta Chir Scand; 1956, 212(supp):1-128. 8. Framery AD, Roe PG: A model to describe the folre of oxyhemoglobin desaturation during apnea. Br J Anaesth; 1996, 76:284-291. 9. McNamara MJ, Harman JG: Hypoxemia during open airway apnea. A computational modeling analysis. Anaesthesia; 2006, 60:741-746. 10.Baraka A, Aouad M, Taha S, El-Khatib M, et al: Apnea-induced hemoglobin desaturation during one-lung vs two-lung ventilation. Can J Anaesth; 2000, 47(1):58-61. M.E.J. ANESTH 23 (1), 2015 REVIEW ARTICLE The Impact of Endotracheal Tube vs. laryngeal Mask Airway on the Incidence of Postoperative Nausea and Vomiting: A Systemic Review and Meta-analysis Jahan Porhomayon*, Sina Davari Farid** Ali A. El-Solh***, Ghazaleh Adlparvar**** and Nader D. Nader***** Abstract Objective: To investigate the impact of Endotracheal tube (ETT) vs. Laryngeal Mask Airway (LMA) on postoperative nausea and vomiting (PONV) in patients undergoing surgery with general anesthesia. Methods: Key words searching from databases such as Medline, Embase, and Cochrane library provided 14 studies focusing on the use of EET vs. LMA for general anesthesia. Pooled estimate of relative risk with 95% confidence interval using random effect model was conducted. Results: 14 studies were selected for meta-analysis with a total of 1866 patients. 9 studies focused on the outcome of PONV in adult patients. It showed incidence of PONV with of LMA and ETT in adult of about 204/690 (30%) and 145/725 (20%) respectively with [Odds Ratio (OR) = 1.69, 95% CI, 0.76-3.75, P = 0.20]. Heterogeneity was high (I2 = 87%). Five studies focused on the outcome of PONV in pediatric patients with PONV in LMA and ETT group of 85/229 (37%) and 72/222 (32%) respectively with (OR = 1.30, 95% CI, 0.61-2.76, P = 0.50). Heterogeneity was moderate at (I2 = 53%). When all patients were combined heterogeneity was high at 81% with OR = 1.56, 95% CI, 0.87-2.79, P = 0.14. Conclusion: Risk of PONV shows an increase trend toward the use of LMA. Larger randomized trials are needed to assess the impact of airway devices on PONV. Keywords: Postoperative, Nausea and Vomiting, Endotracheal Tube, Laryngeal Mask Airway. *MD, FCCP. Associate Professor of Anesthesiology and Critical Care Medicine VA Western New York Healthcare System, Division of Critical Care Medicine, Department of Anesthesiology, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York. **MD. Anesthesiology Research Fellow VA Western New York Healthcare System, Division of Critical Care Medicine, Department of Anesthesiology, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York. ***MD, MPH. Professor of Medicine, Anesthesiology and Preventive Medicine VA Western New York Healthcare System, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York. **** MA, BA. Research Assistant Department of Science University at Buffalo, MCC College, Rochester, New York. ***** M.D., Ph.D., FCCP. Professor of Anesthesiology, Surgery and Pathology VA Western New York Healthcare System, Division of Cardiothoracic Anesthesia and Pain Medicine, Department of Anesthesiology, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York. Corresponding author: Jahan Porhomayon MD, FCCP, VA Medical Center, Rm 203C, 3495 Bailey Ave, Buffalo, NY 14215. Tel: 716 862-8707, Fax 716 862-8707. E-mail: [email protected] 9 M.E.J. ANESTH 23 (1), 2015 10 Introduction PONV remain a common problem occurring in in 20-30% of surgical population, and can be as high as 70-80% in the high risk population1. It increases cost, and delays discharge, and decreases patient satisfaction2. In this analysis, nausea is defined as uncomfortable feeling of stomach which might lead to the eagerness to vomit, while vomiting refers the actual motion of throwing up. PONV could lead to pulmonary aspiration of gastric content and may lead to aspiration pneumonia with potentially fatal consequences. Our current knowledge outlines several well-established risk factors for the occurrence of PONV3,4. These risk factors include: patient, anesthesia and surgical risk specific risk factors. The patient specific risk factors include, female gender, history of PONV or motion sickness, non-smoking status, age greater than or equal to three, and family history of PONV in children. Anesthesia related risk factors include volatile anesthetics, use of Nitrous oxide, and opioid use3,5. There is also a dose relation between volatile anesthetics and opioids. Surgical risk factors include duration of surgery and type of procedure, in particular strabismus correction in children and laparoscopic procedures. In addition to these well-established risk factors, there are other etiologies for development of PONV such as, the lower American society of anesthesiology (ASA) classification, the use of large doses of neostigmine (>2.5mg), restrictive vs. liberal intraoperative fluid strategy, ventilation mode, starvation nausea, heartburn, anxiety, depression, Hepatitis C, P450 inducers/suppressors (medications and food), migraines, and ethnicity6. However, the role of airway devices and its impact on the incidence of PONV remains controversial. Therefore, the following systematic review was conducted to study the influence of airway devices on the incidence of PONV. Materials and Methods We conducted databases searches from Embase, Cochrane, Medline with the term “Laryngeal mask AND Endotracheal tube AND Post-operative AND Nausea AND Vomiting”. Abstracts were reviewed Porhomay on Jahan et. al and only prospective RCTs included7. A total of 6568 articles were identified. 5967 were excluded because it was not related to risk factors or airway device. 601 relevant articles related to PONV risk factors and airway device were screened. 584 were excluded because they were either review, duplicate and nonrelevant duplications. 17 articles were assessed for eligibility with additional 3 articles excluded due to its retrospective nature and low quality. Finally, 14 articles included for final analysis [Figure 1]. Compared to Yu3, we included newer studies published since, as well as pediatric studies. We also included RCTs with the use of non-depolarizers muscle relaxant and Neostigmine usage in the ETT group. RCTs with regional techniques were also excluded8. Data Extraction Timing of PONV reporting varied among studies. Some studies reported PONV in the post-anesthesia Fig. 1 Endotracheal tube vs LMA for PONV 11 recovery unit (PACU) while others reported PONV on the first postoperative day. When confronted with multiple data points, data extracted for analysis with earliest time for PONV was reported. This was an effort to reduce confounding factors such as, rescue anti-emetics given after surgery. Furthermore, PACU treatment for PONV was not always standardized and was often based on individual patient variables and anesthesiologist preference. Characteristics of each study was extracted, which included last name of first author, publication year, patient age range, procedure type, usage of anesthetics and prophylactic antiemetics. The following outcomes were also extracted including the incidence of PONV for both ETT and LMA group. After data searching and study selection, 14 studies were included in our meta-analysis. Study characteristics and demographics were shown in Table 1. 12 studies reported postoperative vomiting as the primary outcome and 10 reported postoperative nausea as the primary outcome. One study did not differentiate between nausea and vomiting. Results were shown in Table 2. Table 1 Studies Included Joshi 199717 Adult ASA 1or 2; Succinylcholine or non-depolizer + Neostigmine sometimes used in ET group; Higher overall fentanyl dose in intra-op ETT group; post-op pain management unstated Patel 201013 Age 3-10; ProSeal LMA vs ETT; lower abdominal procedures; no opioids given intraop; caudal injection with GA with Sevo + N2O; universal OG tube use Klockgether 199614 Age 4-14, strabismus surgery, identical induction (Propofol, Vecuronium, Alfentanil), identical maintenance (67% N2O, Propofol, Alfentanil). PONV incidence by 24 hours reported Doksrod 201015 Age 3-16 tonsillectomy & adenoidectomy; prophylactic Dexamethasone used; nausea and vomiting not reported separately Gulati 200416 Age 1-12 ophthalmologic procedures; greater duration of surgery and more strabismus procedures in LMA group Hohlrieder 2007a7 Adult 18-75, standardized induction and maintenance with oral midazolam, propofol, fentanyl, and Neostigmine in both groups. ProSeal LMA used along with ETT; Universal use OG tube placement and decompression; No prophylactic anti-emetics Cork199420 Adult outpatient peripheral orthopedic procedures; Non-depolarizers and Neostigmine used in both groups; no sig differences in patient population or duration or opioids intra-op; greater morphine post-op in ET group Hohlrieder 2007b8 Adult female 18-75 for laparoscopic gynecological surgery; iv induction after oral midazolam, ProSeal LMA used along with ETT; Universal OG placement + Dexamethasone 4mg + Tropisetron 2mg prophylactic dose administered Quinn 199618 Adult 18-64; Nasal ET with Mivacurium vs. none for LMA group; no prophylactic anti-emetics Swann 1993 Adult laparoscopic gynecological surgeries; ASA 1-2 single blinded RCT LMA vs ET. Atracurium and Neostigmine 2.5mg given in ET group only; controlled ventilation with ETT vs intermittent manual assistance to maintain ETCO2 in LMA group 21 Griffiths 201310 Adult ASA 1-2 Laparoscopic gynecological procedures. Single blinded RCT ProSeal LMA vs ET: same induction; Dexamethasone prophylaxis; universal reversal with Neostigmine 2.5mg Idrees 200019 Adult ASA 1-2 Limb surgery. Single blinded RCT ProSeal LMA vs ETT; Standardized induction + maintenance; Dexamethasone prophylaxis; Gul 201211 Age 1-12 strabismus surgery; ProSeal LMA vs. ETT; inhaled induction, 50% N2O, Atracurium in both groups. Universal OG tube and gastric decompression Porhomayon12 Adult, mostly male, undergoing general anesthesia with N2O in knee surgery M.E.J. ANESTH 23 (1), 2015 12 Porhomay on Jahan et. al Table 2 Outcomes on Postoperative Vomiting and Nausea Author Postoperative Vomiting Postoperative Nausea ETT LMA ETT LMA Joshi 199717 8/174 (4.6%) 15/207 (7.2%) 23/174 (13.2%) 28/207 (13.5%) Patel 201013 1/30 (3.3%) 0/30 (0) NR NR Klockgether 199614 24/50 (48%) 16/50 (32%) 14/50 (28%) 8/50 (16%) Doksrod 201015 NR NR 36/69 (52.2%) 37/62 (59.7%) Gul 201211 NR NR 4/40 (10%) 2/40 (5%) 2/30 (6.7%) 5/30 (16.7%) NR NR 18/100 (18%) 4/100 (4%) 45/100 (45%) 13/100 (13%) Cork199420 1/22 (4.5%) 1/22 (4.5%) 3/22 (13.6%) 5/22 (22.7%) Hohlrieder 2007b8 6/50 (12%) 1/50 (2%) 10/50 (20%) 2/50 (4%) Quinn 199618 3/50 (6%) 2/50 (4%) 13/50 (26%) 9/50 (18%) Swann 199321 4/30 (13.3%) 8/30 (26.7%) 6/30 (20%) 15/30 (50%) Griffiths 201310 27/57 (47.4%) 28/59 (47.5%) NR NR Porhomayon12 25/157 (15%) 12/157(7%) 25/157 12/157 50/3(1.6%) 50/12(4%) NR NR Gulati 200416 Hohlrieder 2007a7 Idrees19 Statistical Analysis RevMan 5.2 was used to calculate the odds ratio for the incidence of PONV. Subgroup analysis including only adult or pediatric patients was also performed. I2 was used to assess heterogeneity with a value below 30% standing for low heterogeneity, a value between 30% and 50% standing for moderate heterogeneity and a value above 50% standing for high heterogeneity. Random effect model was used in all analyses. A p value of <0.1 was significant. Results A total of 1899 patients were included. The incidence of PONV with of LMA and ETT was 289/919 (31%) and 217/947 (22%) respectively. In all patients heterogeneity was high at 81% with OR = 1.56, 95% CI, 0.87-2.79, P = 0.14 [Figure 2, 3]. Meta-analysis of subgroups In terms of PONV in subgroups of adults and pediatric patients, the incidence of PONV was higher in adults’ patients. PONV in adult with the use of LMA and ETT was about 204/690(30%) and 145/725(20%) respectively with (OR = 1.69, 95% CI, 0.76-3.75, P = 0.20). In pediatric population PONV in the LMA and the ETT group was 85/229(37%) and 72/222 (32%) respectively with (OR = 1.30, 95% CI, 0.612.76, P = 0.50). Overall, LMA was associated with higher incidence of PONV. Statistical heterogeneity for adult and pediatric patients was 87% and % 53 % respectively. Test for subgroup difference was not statistically significant with p value of 0.64 and I2 = 0. Discussion The impact of the airway device on PONV remains unresolved. Previous models included the influence of airway devices on development of PONV, Endotracheal tube vs LMA for PONV 13 Fig. 2 Study or Subgroup 1.1.1 Adult cork Griffiths Hohlrieder Hohlrieder1 Idrees Joshi porhomayon quinn swann Subtotal (95% CI) LMA ETT Events Total Events Total Weight 4 27 63 16 12 31 25 16 10 22 57 100 50 50 174 157 50 30 690 6 28 17 2 3 43 12 11 23 22 59 100 50 50 207 157 50 30 725 6.1% 8.4% 8.6% 5.8% 6.4% 9.0% 8.4% 7.9% 7.1% 68.0% Odds Ratio M-H, Random, 95% CI Odds Ratio M-H, Random, 95% CI 0.59 [0.14, 2.48] 1.00 [0.48, 2.07] 8.31 [4.29, 16.10] 11.29 [2.44, 52.38] 4.95 [1.30, 18.81] 0.83 [0.49, 1.38] 2.29 [1.11, 4.74] 1.67 [0.68, 4.08] 0.15 [0.05, 0.47] 1.69 [0.76, 3.75] 145 204 Total events Heterogeneity: Tau² = 1.22; Chi² = 60.13, df = 8 (P < 0.00001); I² = 87% Test for overall effect: Z = 1.29 (P = 0.20) 1.1.2 Pediatric Doksrod Gul Gulati Klockgether Patel Subtotal (95% CI) 36 4 6 38 1 69 40 40 50 30 229 37 4 7 24 0 62 40 40 50 30 222 8.5% 6.0% 6.9% 8.0% 2.4% 32.0% 0.74 [0.37, 1.47] 1.00 [0.23, 4.31] 0.83 [0.25, 2.74] 3.43 [1.46, 8.06] 3.10 [0.12, 79.23] 1.30 [0.61, 2.76] 72 85 Total events Heterogeneity: Tau² = 0.36; Chi² = 8.45, df = 4 (P = 0.08); I² = 53% Test for overall effect: Z = 0.67 (P = 0.50) Total (95% CI) 919 947 100.0% 217 289 Total events Heterogeneity: Tau² = 0.92; Chi² = 69.58, df = 13 (P < 0.00001); I² = 81% Test for overall effect: Z = 1.48 (P = 0.14) Test for subgroup differences: Chi² = 0.22, df = 1 (P = 0.64), I² = 0% 1.56 [0.87, 2.79] 0.01 0.1 1 LMA ETT 10 100 The graph favors ETT with less PONV. but failed to show sufficient independent significance to be included in the final models. But we continue to see investigators including PONV as a variable outcome difference between LMA and ETT. Two prospective randomized control trials (RCT) by Holhreidner reported statistically significant reduction of PONV with the use of Pro-Seal LMA7,8. A recent meta-analysis of RCTs in 2010 by Yu9 looked at the risk of airway complications between the LMA and ETT. Since the primary goal of Yu study was to look at the airway complications, he failed to show statistical significance in the incidence of PONV between the two devices. Additionally, pediatric studies were excluded due to differences in airway anatomy between adult and children. This systematic review and meta-analysis includes 14 total studies focusing on the incidence of PONV comparing the different airway devices including ETT and LMA. Overall, no statistically significant difference was noted between airway devices, although a trend towards higher incidence was noted with the use of LMA group. Subgroup analysis included only children and adult, showed similar trend with stronger association in adult patients. Compared with previously meta-analysis by Yu9, we included 3 newer studies10-12 and 5 pediatric RCTs1317 . Therefore, our final analysis was more reliable. Of the studies included, only the four by Holhreider7,8, Quinn, Idrees and Klockgether-Radke14,18,19 showed a M.E.J. ANESTH 23 (1), 2015 14 Porhomay on Jahan et. al Fig. 3 0 SE(log[OR]) 0.5 1 1.5 2 0.01 OR 0.1 1 10 100 Subgroups Adult Pediatric statistically significant reduction in PONV with LMA. Of note, the studies by Holhreider7 were conducted with Pro-Seal LMA and universal oro-pharyngeal tube placement with gastric decompression. Therefore gastric decompression may have a role in preventing PONV. The study by Joshi, Swann, Doksrod and Cork15,20,21 indicated higher PONV with the use of ETT. One hypothesis leading to the difference in the incidence of PONV between the airway devices may be related to greater stimulation with the use of ETT requiring higher doses of anesthetics and opioids3 when compared to the LMA group6. Opioids and volatile anesthetics have also a role in the development of PONV with a dose dependent effect on the development of PONV. Alteration in barometric pressure was demonstrated by Nader et al22 when LMA was used in comparison to ETT. Although the authors of that article did not demonstrate a statistically significant difference in PONV between the ETT and LMA, they showed a higher trend of PONV in the LMA group. This study was underpowered and additional trials are necessary to address this hypothesis. Limitations Due to nature of meta-analysis, results were analyzed from wide variety of RCTs with differing anesthetic techniques, types of surgery, anesthesiologist experience, various types of LMA, and time when outcome was measurement. Heterogeneity was high due to different anesthetic techniques23, type of surgeries and heterogeneous population. However, with RCT there was standardization of anesthetic techniques between two groups to minimize confounding factors. Those without standardization between two groups were excluded from the trial. Despite standardization of anesthetic techniques, there were differences in duration of anesthesia and intra-operative opioid usage. There were statistically significant differences Endotracheal tube vs LMA for PONV in patient selection as well as type of procedure within some of the RCTs. Additionally; patient Characteristics relevant to the risk of PONV was not always reported. Consistent with previously performed metaanalysis9 studying the same outcome, we were able to identify only a limited number of studies addressing the influence of airway device on PONV. Furthermore, many of the RCTs had small sample sizes limiting reliability in concluding the incidence PONV between the two groups. Furthermore, two large retrospective studies24,25 were identified, but were not included in the final analysis due to high degree of variability in anesthetic techniques. 15 Conclusion Further research and additional randomized controlled trials are needed to precisely identify the influence of airway device on PONV. These trials should provide essential information for the design, conduct, and presentation of these studies. When comparing group, comparability should be based on well-proven risk factors. And lastly, interpretation of results should take into account the study hypothesis, sources of potential bias or imprecision, and the difficulties associated with multiplicity of analysis and outcome. M.E.J. ANESTH 23 (1), 2015 16 Porhomay on Jahan et. al References 1.Apfel CC, Philip BK, Cakmakkaya OS, Shilling A, Shi YY, Leslie JB, et al: Who is at risk for postdischarge nausea and vomiting after ambulatory surgery? Anesthesiology; 2012, 117:475-486. 2.Habib AS, Chen YT, Taguchi A, Hu XH, Gan TJ: Postoperative nausea and vomiting following inpatient surgeries in a teaching hospital: a retrospective database analysis. Curr Med Res Opin; 2006, 22:1093-1099. 3.Gan TJ: Risk factors for postoperative nausea and vomiting. Anesthesia and analgesia; 2006, 102:1884-1898. 4.Gan TJ, Meyer TA, Apfel CC, Chung F, Davis PJ, Habib AS, et al: Society for Ambulatory Anesthesia guidelines for the management of postoperative nausea and vomiting. Anesthesia and analgesia; 2007, 105:1615-1628, table of contents. 5.Wilkins CJ, Cramp PG, Staples J, Stevens WC: Comparison of the anesthetic requirement for tolerance of laryngeal mask airway and endotracheal tube. Anesth Analg; 1992, 75:794-797. 6.Apfel CC, Heidrich FM, Jukar-Rao S, Jalota L, Hornuss C, Whelan RP, et al: Evidence-based analysis of risk factors for postoperative nausea and vomiting. British journal of anaesthesia; 2012, 109:742-753. 7.Hohlrieder M, Brimacombe J, Eschertzhuber S, Ulmer H, Keller C: A study of airway management using the ProSeal LMA laryngeal mask airway compared with the tracheal tube on postoperative analgesia requirements following gynaecological laparoscopic surgery. Anaesthesia; 2007, 62:913-918. 8.Hohlrieder M, Brimacombe J, Von Goedecke A, Keller C: Postoperative nausea, vomiting, airway morbidity, and analgesic requirements are lower for the ProSeal laryngeal mask airway than the tracheal tube in females undergoing breast and gynaecological surgery. British journal of anaesthesia; 2007, 99:576-580. 9.Yu SH, Beirne OR: Laryngeal mask airways have a lower risk of airway complications compared with endotracheal intubation: a systematic review. J Oral Maxillofac Surg; 2010, 68:2359-2376. 10.Griffiths JD, Nguyen M, Lau H, Grant S, Williams DI: A prospective randomised comparison of the LMA ProSeal versus endotracheal tube on the severity of postoperative pain following gynaecological laparoscopy. Anaesth Intensive Care; 2013, 41:4650. 11.Gul R, Goksu S, Ugur BK, Sahin L, Koruk S, Okumus S, et al: Comparison of proseal laryngeal mask and endotracheal tube for airway safety in pediatric strabismus surgery. Saudi Med J; 2012, 33:388-394. 12.Porhomayon J, Wendel PK, Defranks-Anain L, Leissner KB, Nader ND: Do the choices of airway affect the post-anesthetic occurrence of nausea after knee arthroplasty? A comparison between endotracheal tubes and laryngeal mask airways. Middle East J Anesthesiol; 2013, 22:263-271. 13.Patel MG, Swadia V, Bansal G: Prospective randomized comparative study of use of PLMA and ET tube for airway management in children under general anaesthesia. Indian J Anaesth; 2010, 54:109-115. 14.Klockgether-Radke A, Gerhardt D, Muhlendyck H, Braun U: [The effect of the laryngeal mask airway on the postoperative incidence of vomiting and sore throat in children]. Anaesthesist; 1996, 45:1085-1088. 15.Doksrod S, Lofgren B, Nordhammer A, Svendsen MV, Gisselsson L, Raeder J: Reinforced laryngeal mask airway compared with endotracheal tube for adenotonsillectomies. Eur J Anaesthesiol; 2010, 27:941-946. 16.Gulati M, Mohta M, Ahuja S, Gupta VP: Comparison of laryngeal mask airway with tracheal tube for ophthalmic surgery in paediatric patients. Anaesth Intensive Care; 2004, 32:383-389. 17.Joshi GP, Inagaki Y, White PF, Taylor-Kennedy L, Wat LI, Gevirtz C, et al: Use of the laryngeal mask airway as an alternative to the tracheal tube during ambulatory anesthesia. Anesth Analg; 1997, 85:573-577. 18.Quinn AC, Samaan A, McAteer EM, Moss E, Vucevic M: The reinforced laryngeal mask airway for dento-alveolar surgery. Br J Anaesth; 1996, 77:185-188. 19.Idrees A, Khan FA: A comparative study of positive pressure ventilation via laryngeal mask airway and endotracheal tube. J Pak Med Assoc; 2000, 50:333-338. 20.Cork RC, Depa RM, Standen JR: Prospective comparison of use of the laryngeal mask and endotracheal tube for ambulatory surgery. Anesth Analg; 1994, 79:719-727. 21.Swann DG, Spens H, Edwards SA, Chestnut RJ: Anaesthesia for gynaecological laparoscopy--a comparison between the laryngeal mask airway and tracheal intubation. Anaesthesia; 1993, 48:431434. 22.Nader ND, Simpson G, Reedy RL: Middle ear pressure changes after nitrous oxide anesthesia and its effect on postoperative nausea and vomiting. Laryngoscope; 2004, 114:883-886. 23.Klockgether-Radke A, Piorek V, Crozier T, Kettler D: Nausea and vomiting after laparoscopic surgery: a comparison of propofol and thiopentone/halothane anaesthesia. Eur J Anaesthesiol; 1996, 13:3-9. 24.Ayala MA, Sanderson A, Marks R, Hoffer M, Balough B: Laryngeal mask airway use in otologic surgery. Otol Neurotol; 2009, 30:599-601. 25.Anderson BJ, Pearce S, McGann JE, Newson AJ, Holford NH: Investigations using logistic regression models on the effect of the LMA on morphine induced vomiting after tonsillectomy. Paediatr Anaesth; 2000, 10:633-638. SCIENTIFIC ARTICLES Renal Protection in the Cardiac Surgery Patient: Peri-Operative Sodium Bicarbonate Infusion (POSBI) or Not? Hassan H. Amhaz*, Deepak Gupta**, Larry Manders**, George McKelvey***, Marc S. Orlewicz** and R omeo N. K addoum ** Abstract Background: Acute renal failure following cardiac surgery is not uncommon and carries a high level of morbidity and mortality. The aim of our study was to determine whether perioperative sodium bicarbonate infusion (POSBI) would decrease acute kidney injury in cardiac surgery patients and improve post-operative outcomes. Methods: A retrospective analysis of 318 cardiac surgery patients from 2008-2011 was performed. Clinical parameters were compared in patients receiving POSBI versus sodium chloride. Serum creatinine levels were measured in the first five post-operative days. The primary outcome measured was the number of patients developing post-operative renal injury. Secondary outcomes included three-month mortality, intensive care unit and hospital length of stay. Results: Patients given POSBI showed no significant differences compared to the normal saline cohort in regards to increases in serum creatinine [<25% rise in Cr: 93% vs 94%; >25% rise in Cr: 6% vs 6%; >50% rise in Cr: 1% vs 1%; >100% rise in Cr: 1% vs 0%, all with p-value >0.99]. There were fewer patients with AKIN stage 1 renal failure receiving POSBI [8% vs 28%, p = 0.02] however there was no difference between POSBI and sodium chloride cohorts in AKIN stages 2 and 3 renal failure. Mortality, duration of hospitalization and ICU stay were not statistically significant. Conclusions: POSBI resulted in fewer patients developing AKIN stage 1 renal failure. Despite this, there appears to be little benefit in the prevention of acute kidney injury after 48 hours or mortality reduction in cardiac surgery patients. *MD, MS. **MD. ***PhD. Affiliation: Department of Anesthesiology, Wayne State University, Detroit Medical Center; Detroit, Michigan, United States. Corresponding author: Romeo N. Kaddoum, MD. Assistant Professor; Wayne State University, Detroit Medical Center; 3990 John R, Rm 2901; 2-Hudson, Detroit, MI 48201, United States. Office: 1-313-745-7233, Fax: 1-313-993-3889. E-mail: [email protected] 17 M.E.J. ANESTH 23 (1), 2015 18 Introduction Acute kidney injury (AKI) in patients undergoing cardiac surgery is a common and serious occurrence with an incidence ranging between 3% and 50% of patients and is associated with significant morbidity and mortality rates as high as 38%1,2,3. Of these patients, 1% will require dialysis, with associated mortality rates in this group as high as 60%-70%4,5,6. There are numerous factors that contribute to postoperative renal failure, including ischemia, drugs, generation of reactive oxygen free radicals, hemolysis and activation of inflammatory and complement pathways1,4,6. Additionally, numerous independent risk factors have been found to be predictive of post-operative AKI following cardiac surgery4,6-10. Although some studies have shown sodium bicarbonate to ameliorate postoperative kidney injury, its use in cardiac surgery remains controversial. We present a retrospective multi-centered study of 318 patients undergoing cardiac surgery to evaluate whether peri-operative sodium bicarbonate infusion (POSBI) would reduce post-operative AKI. Material and Methods After institutional review board approval (Wayne State University IRB committee, IRB#065611M1E), a retrospective analysis of 318 post-cardiac surgery patients, from two institutions within our medical center over a four-year period (2008-2011) was performed. Biochemical and clinical parameters were compared in patients receiving POSBI versus sodium chloride. Inclusion and exclusion criteria of the study are listed in Table 1. Serum creatinine levels were measured in the first five post-operative days in patients who received sodium bicarbonate and those receiving sodium chloride. Starting in 2009, our medical center instituted a sodium bicarbonate infusion protocol for patients undergoing cardiac surgery due to new literature showing possible benefit from POSBI. Previously, patients received normal saline at a rate of 1-1.5cc/ kg/hr from the start of surgery for a total of 24 hours. The sodium bicarbonate infusion protocol simply added 3 Amps (150mEq) of sodium bicarbonate in 1 Romeo Kaddoum et. al liter of D5W. The protocol was to infuse the sodium bicarbonate at a rate of 1-1.5cc/kg/hr starting from the beginning of surgery for a total of 24 hours as normal saline was previously done. Table 1 Study Inclusion and Exclusion Criteria* Inclusion criteria Exclusion criteria Age 18-80 End Stage Renal Disease (ESRD) CABG +/- valve surgery, intracardiac surgery Emergency cardiac surgery Redo cardiac surgery Use of intra-aortic balloon pump (IABP) Pre-operative plasma creatinine concentration >1.3 mg/dL Currently enrolled in another study NYHA class III/IV Known blood-borne Infectious disease Left Ventricle EF <35% Chronic corticosteroid therapy * Cardiac surgery patients having one or more of the listed criteria To determine a sample size for the study a Chi-squared power analysis was chosen to obtain an alpha error probability of 0.05 and a power of 0.95. A sample size of 300 patients (at least 150 in each group; effect size d=0.2 small -medium) was deemed to give the study sufficient power. Repeated Measures Analysis of Variance (ANOVA) and T-tests (Unpaired; two sided) were used where appropriate to measure continuous variables between the 2 patient groups with post hoc differences measured using the StudentNeuman-Keuls test. Comparisons between study groups on proportional differences were examined using a non-parametric Fisher’s Exact Chi-square test, when applied to 2X2 tables. A p-value of <0.05 was considered significant. Of note, the 318 patients that were included in our study were patients of only two cardiothoracic surgeons who used sodium bicarbonate consistently following the protocol implementation in 2009. Hence, when data before 2009 was obtained for patients not receiving POSBI we used the patients from only these two surgeons. For this reason, the 318 cardiac surgery patients only represent a smaller fraction of total cardiac surgery patients at our institution. This was done to minimize surgeon bias and to exclude surgeons Renal Protection in the Cardiac Surgery Patient who did not consistently use POSBI. The primary outcome measured was the number of patients who developed post-operative renal injury following cardiac surgery. Kidney injury was defined into four categories which were based on baseline serum creatinine levels to those on the fifth postoperative day: serum creatinine increases <25%, an increase greater than 25%, greater than 50%, and greater than 100% from baseline. The proportion of kidney injury between these groups as defined by the AKIN criteria was also compared, Table 2. Other Characteristics 19 secondary outcomes that were measured included intensive care unit (ICU) and hospital length of stay, and three-month mortality rates. Table 2 Acute Kidney Injury Network (AKIN) Classification Criteria Classes Serum Cr (sCr) Criteria 1 sCr increase x 1.5 - 2 (50%-100%) or sCr increase >0.3 mg/dL from baseline 2 sCr increase x 2 - 3 (101%-200%) from baseline 3 sCr increase x 3 (>201%) or sCr >4 mg/dL with increase >0.5 mg/dL Table 3 Patient pre-operative characteristics Sodium Bicarbonate Demographic data Age, yr, mean (SD) Gender Males, n (%) Females, n (%) Race African Americans, n (%) Non - African Americans, n (%) Comorbidities Hypertension, n (%) Chronic kidney disease, n (%) Peripheral vascular disease, n (%) Hypercholesterolemia, n (%) Chronic obstructive pulmonary disease, n (%) Diabetes Mellitus, n (%) Left ventricular ejection fraction, percent (SD) Hemodialysis, n (%) Medications Beta-blockers, n (%) ACE inhibitors or angiotensin blockers, n (%) HMG-CoA reductase inhibitor, n (%) Pre-operative creatinine levels Cr <1.0, n (%) 1.0 <Cr <1.3, n (%) 1.4 <Cr <1.6, n (%) 1.7 <Cr <1.9, n (%) Cr >2, n (%) Pre-operative Ejection Fraction (EF) EF <15%, n (%) 15% <EF <25%, n (%) 25% <EF <35%, n (%) 35% <EF <45%, n (%) 45% <EF <55%, n (%) EF >55%, n (%) Sodium Chloride p-value 62 (11) 63 (12) 0.56 0.01 119 (68) 56 (32) 77 (54) 66 (46) 118 (67) 57 (33) 103 (72) 40 (28) 158 (90) 47 (27) 28 (16) 146 (83) 57 (33) 77 (44) 49 (15) 13 (7) 133 (93) 38 (27) 40 (28) 114 (80) 39 (27) 65 (45) 49 (15) 17 (12) 0.42 >0.99 0.01 0.47 0.33 0.82 0.83 0.18 137 (78) 86 (49) 144 (82) 86 (60) 83 (58) 96 (67) 0.0005 0.12 0.003 0.17 60 (34) 68 (39) 22 (13) 3 (2) 21 (12) 56 (38) 48 (33) 11 (8) 7 (5) 23 (16) 0 (0) 16 (9) 16 (9) 21 (13) 34 (20) 90 (49) 3 (2) 11 (7) 15 (10) 21 (15) 29 (20) 73 (48) 0.39 0.47 M.E.J. ANESTH 23 (1), 2015 20 Romeo Kaddoum et. al Results Three hundred and eighteen patients underwent cardiac surgery at our institutions from 2008 thru 2011. There were 175 patients who received POSBI and 143 patients received only sodium chloride. Preoperative patient characteristics of the study are listed in Table 3. Patient characteristics were fairly matched between POSBI and normal saline groups with the exception that recipients of POSBI were more likely to be male and be on β-blockers and statins. However, more peripheral vascular disease was seen in patients receiving normal saline. New institutional mandates regarding patients receiving preoperative β-blockers, around the same time the sodium bicarbonate infusion protocol was instituted, is a likely reason for why the sodium bicarbonate group received more β-blockers. Regarding the surgery type, no significant differences were seen between groups with the exception that more patients who underwent mitral valve repair received POSBI. However, when considering all valve surgeries combined, there was no significant difference seen between the POSBI and normal saline groups. Although aortic clamp times did not differ between the groups, cardiopulmonary bypass (CPB) time was slightly lower in the sodium bicarbonate group, Table 4. Serum creatinine levels measured on the fifth post-operative compared to baseline were divided into four categories: <25%, >25%, >50%, and >100%. There were no significant differences between patients receiving POSBI versus normal saline, Table 5. When renal dysfunction was defined using the AKIN criteria, creatinine levels 48 hours post-operatively compared to baseline, patients receiving POSBI had fewer patients with AKIN stage 1 renal failure. However, no significant differences were observed between the two groups in regards to AKIN stage 2 and 3, Table 6. The Table 4 Type of surgery and patient intra-operative characteristics Characteristics Sodium Bicarbonate Sodium Chloride Cardiac surgery p-value 0.08 Valve surgery only, n (%) 58 (33) 41 (27) 0.29 Aortic valve replacement, n (%) 25 (14) 18 (12) 0.57 Mitral valve replacement, n (%) 14 (8) 16 (10) 0.39 Mitral valve repair, n (%) 12 (7) 3 (2) 0.04 Double valve surgery, n (%) 7 (4) 4 (3) 0.52 100 (57) 80 (54) 0.56 17 (9) 22 (14) 0.16 Cardiopulmonary bypass time, mins (SD) 106 (38) 119 (57) 0.02 Aortic clamp time, mins (SD) 86 (32) 93 (52) 0.16 CABG only, n (%) Valve and CABG surgery, n (%) Table 5 Post-operative sCr changes in patients receiving POSBI vs Normal Saline Sodium Bicarbonate Normal Saline p-value <25% sCr Rise 163 (93%) 134 (94%) >0.99 >25% sCr Rise 10 (6%) 8 (6%) >0.99 >50% sCr Rise 1 (1%) 1 (1%) >0.99 >100% sCr Rise 1 (1%) 0 (0%) >0.99 175 143 Post-operative sCr change Total Renal Protection in the Cardiac Surgery Patient 21 Table 6 Post-operative AKIN stage in patients receiving POSBI vs Normal Saline Sodium Bicarbonate Normal Saline p-value 148 (85%) 110 (62%) 0.09 AKIN Stage 1 14 (8%) 24 (28%) 0.02 AKIN Stage 2 7 (4%) 5 (3%) >0.99 AKIN Stage 3 6 (3%) 4 (3%) >0.99 175 143 Post-operative AKIN stage Normal Total Table 7 Secondary outcomes measured Secondary outcomes Sodium Bicarbonate p-value Normal Saline Mortality, n (%) 27 (15) 25 (16) 0.76 Intensive Care Unit stay, days (SD) 9.2 (8.6) 10 (9.2) 0.39 Duration of hospitalization, days (SD) 10.7 (9.9) 12 (8.7) 0.22 secondary outcomes that were measured in the study included 30-day mortality, length of hospitalization and ICU stay, Table 7. Our average ICU length of stay was higher than other studies secondary to several patients in each cohort with ICU stays longer than one month. However, total hospital length of stay was consistent with other published studies1. No significant differences were seen between groups in regards to 30day mortality, length of hospitalization or ICU stay. Discussion Acute kidney injury (AKI) is a common and serious complication following cardiac surgery with an incidence ranging from 3% to 50%1,7. AKI following cardiac surgery carries a significant cost burden and is an independent predictor of mortality. Pre-operative serum creatinine levels are the most important predictive factor for post-operative AKI7,10. Approximately 10% to 20% of patients with baseline creatinine levels between 2mg/dL and 4mg/dL will require dialysis and those with creatinine levels greater than 4mg/dL will require dialysis 30% of the time7. Patients requiring post-operative dialysis have a mortality rate of 60-70%. To date, no treatment including peri-operative sodium bicarbonate infusion has been shown to be effective in preventing renal failure after cardiac surgery1,7,9. Only a few prospective randomized control trials have been done to evaluate the role of sodium bicarbonate or other adjuvant therapies (N-acetylcysteine and fenoldopam) in the prevention of acute kidney injury following cardiac surgery. Haase et al1, conducted a pilot double-blinded, randomized control trial of 100 cardiac surgery patients. The patients underwent treatment to see if POSBI can attenuate postoperative increases in serum creatinine. Their primary outcome was reaching a serum creatinine of >25% above baseline within the first five postoperative days. They found a statistical significance using bicarbonate in patients with creatinine increases >25% however there was no difference in patients with creatinine increases of either >50% and >100%. There was no statistical significance found when acute kidney injury was defined by the AKIN criteria. No mortality benefit was seen in patients receiving POSBI. Furthermore, other large RCT studies looking at N-acetylcysteine, fenoldopam and statins failed to show a clear benefit in postoperative renal protection. Post-operative renal failure is multifactorial: ischemia-reperfusion injury seen from hemodynamic instability and aortic cross clamping, low cardiac output states, loss of pulsatile flow while on bypass, nephrotoxic drugs, generation of reactive oxygen free radicals, and the activation of neutrophils, inflammatory and complement pathways7,10,11. Furthermore, mechanical and shear forces on red blood cells seen in cardiopulmonary bypass is associated with levels of free hemoglobin which exceeds the capacity of haptoglobin. Thus, longer bypass times are M.E.J. ANESTH 23 (1), 2015 22 Romeo Kaddoum et. al Table 8 Major Risk Factors for Developing Acute Kidney Injury Patient Risk Factors Surgical Risk Factors Age Pre-operative use of an IABP Female CABG, Valve or combined procedures Pre-operative serum creatinine CPB duration EF <35% Hemodilution during CPB Insulin Dependent Diabetes Mellitus Emergency surgery Chronic obstructive pulmonary disease associated with increased free hemoglobin exposure and can theoretically worsen kidney injury. Under acidic conditions increased free iron release from hemoglobin occurs which catalyzes the Haber-Weiss reaction promoting hydroxyl radical formation. The alkalinizing effects of sodium bicarbonate on the urine are thought to provide some degree of renal protection due to the reduction in hydroxyl radical formation from free iron and tubular cast formation1,7,10,11. study showed that 1.1% of these patients had AKI after surgery, and the mortality in this group was 63.7%. The end result of the study was that cardiac surgery was an independent risk factor for developing AKI, and was associated with a high mortality rate. The rate of AKI and AKI-related mortality could not be explained by comorbidities alone12. In addition to cardiac surgery, cardiopulmonary bypass itself was found to be an independent risk factor for the development of AKI6. Classification of renal injury, as with AKIN, does not provide insight into the nature of the injury. Typically, the window for therapeutic intervention has passed once serum creatinine levels begin to rise4. As a result, biomarkers for the early detection of renal injury have been sought after. Neutrophil gelatinaseassociated lipocalin (NGAL), cystatin C, IL-18, kidney injury molecule-1 (KIM-1) and many more have all been studied1,4,7,10. Urinary NGAL levels are virtually undetectable in patients with normal kidney function and serve as a marker of oxidative stress. Urinary NGAL levels greater than 100ng/mL two hours following cardiopulmonary bypass predict acute kidney injury (sensitivity, 82%; specificity, 90%); much higher than other studied biomarkers1,10. In a study by Haase et al1, the use of sodium bicarbonate does not appear enough to thwart the acute kidney injury seen following cardiac surgery despite a significant attenuation in urinary NGAL. Although there appears to be a beneficial effect of POSBI within the literature there are several important factors that must be considered. First, the definition of “AKI”, an increase in serum creatinine >25%, is quite liberal. This equates to less than a 0.1mg/dL/day increase in serum creatinine over the first five post-operative days5. Mehta and colleagues13 convened in an international meeting to develop a uniform system for the diagnosis and classification of acute kidney injury, which is formally known as the AKIN criteria, Table 2. When AKI is defined as an increase in serum creatinine >50%, no difference is found between POSBI and normal saline groups seen in the prospective pilot study1,5. Regardless of stage, no significance was found when the AKIN criteria were used5. Although we found a lower incidence of AKIN stage 1 renal failure in patients receiving POSBI, it appears that by the fifth post-operative day these benefits are no longer seen. Several risk factors have been identified that are associated with AKI in cardiac surgery patients, Table 84,6-10. Chertow et al12, conducted a large cohort study of 42,273 patients undergoing coronary artery bypass graft (CABG) or valvular heart surgery. This The use of sodium bicarbonate and its resulting alkalemia is not benign. Mortality, CO2 retention and associated hypoxia from impaired oxygen delivery are all potential complications of POSBI5. Haase et al1, showed considerable group differences from baseline Renal Protection in the Cardiac Surgery Patient to 24 hours post-operatively in plasma bicarbonate concentration, base excess, and pH levels. Therefore, careful monitoring of plasma pH and bicarbonate levels would be warranted in instances where large amounts of sodium bicarbonate are being administered. Our study has several limitations that should be noted. Although retrospective, pre-operative patient characteristics between cohorts were fairly matched however if we were to match for every characteristic the overall numbers would be low and the study underpowered. Additionally, we did not include patients with new-onset hemodialysis requirements following cardiac surgery. Numerous patients have multiple uncontrolled comorbidities with baseline renal dysfunction that may have contributed to the extended ICU length of stay compared to other studies however overall length of hospitalization remained consistent1. 23 Conclusion We present a retrospective multicenter study comparing the use of POSBI to that of sodium chloride in patients undergoing cardiac surgery to prevent postoperative renal failure. Despite a lower incidence of patients developing AKIN stage 1 renal failure in the POSBI cohort, the benefit does not persist through the fifth post-operative day. With no reduction in mortality, hospital or ICU length of stay, there currently appears to be no benefit with the use of POSBI in cardiac surgery patients. Acknowledgments Dimitrios Apostolou, MD - cardiothoracic surgeon of patients in study Ali Kafi, MD - cardiothoracic surgeon of patients in study M.E.J. ANESTH 23 (1), 2015 24 Romeo Kaddoum et. al References 1. Haase M, Haase-Fielitz A, Bellomo R, et al: Sodium bicarbonate to prevent increases in serum creatinine after cardiac surgery: a pilot double-blind, randomized controlled trial. Crit Care Med; 2009, Jan; 37(1):39-47. 2. Adabag AS, Ishani A, Bloomfield HE, Ngo AK, Wilt TJ: Efficacy of N-acetylcysteine in preventing renal injury after heart surgery: a systematic review of randomized trials. Eur Heart J; 2009, Aug; 30(15):1910-7. 3. Liakopoulos OJ, Choi YH, Haldenwang PL, et al: Impact of preoperative statin therapy on adverse postoperative outcomes in patients undergoing cardiac surgery: a meta-analysis of over 30,000 patients. Eur Heart J; 2008, Jun; 29(12):1548-59. 4. Coleman MD, Shaefi S, Sladen RN: Preventing acute kidney injury after cardiac surgery. Curr Opin Anaesthesiol; 2011, Feb; 24(1):706. 5. Weisberg L: Sodium bicarbonate for renal protection after heart surgery: let’s wait and see. Crit Care Med; 2009, Jan; 37(1):333-4. 6. Stallwood M, Grayson A, Mills K, Scawn N: Acute renal failure in coronary artery bypass surgery: independent effect of cardiopulmonary bypass. Ann Thorac Surg; 2004, Mar; 77(3):96872. 7. Mariscalco G, Lorusso R, Dominici C, Renzulli A, Sala A: Acute kidney injury: a relevant complication after cardiac surgery. Ann Thorac Surg; 2011, Oct; 92(4):1539-47. Epub 2011, Aug 27. Review. 8. McCullough PA, Wolyn R, Rocher LL, Levin RN, O’Neill WW: Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med; 1997, Nov; 103(5):368-75. 9. Ranucci M, Soro G, Barzaghi N, et al: Fenoldopam prophylaxis of postoperative acute renal failure in high-risk cardiac surgery patients. Ann Thorac Surg; 2004, Oct; 78(4):1332-7; discussion 1337-8. 10.Kumar A, Suneja M. Cardiopulmonary bypass-assicated acute kidney injury. Anesthesiology; 2011, Apr; 114(4):964-70. 11.Haase M, Haase-Fielitz A, Bagshaw SM, Ronco C, Bellomo R: Cardiopulmonary bypass-associated acute kidney injury: a pigment nephropathy? Contrib Nephrol; 2007, 156:340-53. 12.Chertow GM, Levy EM, Hammermeister KE, Grover F, Daley J: Independent association between acute renal failure and mortality following cardiac surgery. Am J Med; 1998, Apr; 104(4):343-8. 13.Mehta RL, Kellum JA, Shah SV, et al: Acute Kidney Injury Network. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care; 2007, 11(2):R31. Effect of ultrasound-guided subsartorial approach for saphenous nerve block in cases with saphenous nerve entrapment in adductor canal for controlling chronic knee pain. Arman Taheri*, Maryam Hatami**, Majid Dashti***, Alireza Khajehnasiri**** and Mahsa Ghajarzadeh***** Abstract Background: Saphenous nerve neuropathy is one of the causes of chronic pain of the knee. Blockade of saphenous nerve under sonographich guide has been used for controlling pain in recent years. The goal of this study was to evaluate the effect of saphenous nerve block for controlling pain in patients with chronic knee pain. Method: Thirty five patients with chronic knee pain referred to Amir Alam hospital during June 2012-June 2013 were enrolled in this study. Under sonographic approach, subsartorial blockade of saphenous nerve conducted and patients were followed up for 3 months after treatment. Demographic data, ASA (American Society of Anesthesiologists) category, weight, height, complications of intervention and pain scores were recorded. Results: In 54%, the NRS was zero 30 minutes after intervention. In one patient (2.8%) all NRSs were 0 after intervention. We observed no sensory dysfunction in enrolled cases. Conclusion: the result of current study showed that ultrasound guided subsartorial approach is moderately effective in blockade of saphenous nerve in cases with saphenous nerve entrapment in adductor canal for controlling chronic knee pain. Keywords: ultrasound-guided block, knee pain, pain management. Introduction Saphenous nerve is a terminal branch of the femoral nerve which innervates medial, anteromedial, and posteromedial aspects of the lower extremity1. Saphenous nerve entrapment is one of the causes of chronic knee pain (especially at medial site) which could mimic orthopedic disorders of the knee or L4 radiculopathy2. * FIPP, Assistant professor of Anesthesiology, Iran section of World Institute of Pain Director, Chairman of Tehran University of Medical Science Fellowship Program, Department of Anesthesia & Pain Management Amiralam Hospital, Tehran University of Medical sciences, Tehran, Iran. ** Pain fellowship, Department of Anesthesia & Pain Management, Tehran University of Medical Sciences, Tehran, Iran. *** Cardiac anesthesia fellowship, department of anesthesia, Shahid rajaee hospital, Tehran University of Medical Sciences, Tehran, Iran. ****Assistant Professor of Anesthesiology and Pain, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. *****Brain and Spinal Injury Repair Research Center, Tehran University of Medical Sciences, Tehran, Iran. Corresponding author: Maryam Hatami MD. E-mail: [email protected] 25 M.E.J. ANESTH 23 (1), 2015 26 Maryam Hatami et. al Blockage of saphenous nerve could be applied for procedures on the medial aspect of the distal leg3. Different approaches could be applied for blockage of saphenous nerve such as perifemoral, trans-sartorial, block at the medial femoral condoyle, below-the-knee field block, and blockade at the level of the medial malleolus. Benzon et al found that trans-sartorial approach was the best approach for complete sensory blockade4. located. After negative aspiration, 10 cc Bupivacaine 25% and 40 mg methyl prednisolone sulphate under the sonography guidance were injected. Maximal NRS was recorded after 30 minutes, one week, one month and three months after intervention. The Numeric Rating Scale (NRS) is a 10-point scale for patient selfreporting of pain. Zero means ‘No pain’ and 10 means ‘Worst possible pain’. In recent years, blockade of the saphenous nerve under the guidance of ultrasound has been considered as an acceptable approach. Tsai et al reviewed the medical records of 39 cases who underwent subsartorial saphenous nerve block for lower extremity surgery and found that this technique was successful in 77% of cases5. Demographic data, ASA, weight, height, and complication of intervention were recorded. The aim of the study is to evaluate effect of saphenous nerve block in cases with saphenous nerve entrapment in adductor canal for controlling chronic knee pain. Method and material In this cross sectional study which conducted between June 2012-June 2013 in Amir Alam hospital (affiliated hospital of Tehran university of medical sciences), patients with chronic knee pain (pain more than 3 months), Numeric rating scale ≥7 and tenderness in adductor canal were enrolled. Patients with previous surgery of lower extremities, recent trauma to the knee, consumption of anti-coagulant agents, drug abuse, severe osteoarthritis (according to radiologic findings), allergy to local anesthetic agents, psychologic disorders, and active infection were excluded. For blockade, patients were placed in supine position, with the lower extremity rotated externally at the hip, and the knee slightly flexed. The midthigh area was prepped and 8-12 MHz linear probe was placed at the proximal aspect of the leg (10 cm proximal to medial condyle) to obtain a cross-sectional view of the femoral artery in short-axis. The saphenous nerve was defined as a highly hyperechoic structure medial to femoral artery. The needle was inserted lateral to femoral artery then proceeded to the medial aspect of the artery where the saphenous nerve was Official approval from ethics committee of TUMS was obtained for the study and all the patients gave informed consent. Statistical analyses were performed with SPSS software version 18.0 (Statistical Product and Service Solutions, SSPS Inc., Chicago). Results are presented as mean ± SDs, and frequencies. The Student’s t test was used for continuous variables, and the Pearson x2 test with Fisher’s exact test was applied for categorical variables. Repeated measure ANOVA was used to compare mean NRS during study period. P value <0.05 was considered statistically significant. Results Thirty five cases enrolled in this study. Mean age of all cases was 54.6 ± 12.8 years. Twenty four cases (68.6%) were female and 11 (31.4%) were male. Twenty there (65.7%), 9 (25.7%), and 3 (8.6%) patients were ASA class I,II, and III respectively. Only the left knew was affected in 9 patients (25.7%), only the right knee was affected in 11 patients (31.4%) while both knees were affected in 15 patients (42.9%). Mean BMI, and pre-intervention NRS were 25.1 ± 2.3 (kg/m2) and 8 ± 0.8 (7-10) respectively. Repeated measure ANOVA showed that mean NRS significantly decreased throughout the evaluation time (p <0.001) (Table 1). In nineteen patients (54%), the NRS was zero at 30 minutes after intervention (Table 2). Only one patient (2.8%) had a NRS of 0 throughout the study period. We observed no sensory dysfunction in in all enrolled cases. saphenous nerve block in knee pain 27 Table 1 (mean ± SD) NRS during evaluation time NRS before intervention 8 ± 0.8 NRS after 30 minutes NRS after one week NRS after one month NRS after 3 months P value 0.7 ± 0.8 1.5 ± 1.3 2.2 ± 1.8 5.2 ± 2.6 <0.001 Table 2 Success rates during follow up Success rate Reduction of NRS scores to 0 after 30 minutes 19 (54.3%) Reduction of NRS scores to 0 after one week 7(20%) Reduction of NRS scores to 0 after one month 4(11.4%) Reduction of NRS scores to 0 after 3 months 3 (8.6%) Discussion The result of this study showed that ultrasoundguided sub-sartorial blockade of saphenous nerve in cases with saphenous nerve entrapment in adductor canal is a successful method for controlling pain during post intervention period in patients with chronic knee pain. We observed that pain NRS became zero 30 minutes after intervention in 54% of cases and pain eradicated in 2.8% of patients who suffer from chronic knee pain. However, this success rate is lower that the rates in previous studies. Romanoff et al evaluated 30 patients with saphenous nerve entrapment in adductor canal who underwent series of nerve blockade (mean 1.9 of blockade). They reported VAS score of 6.4 at baseline and 2.8 at the end of the study. Eighty seven of cases had improved at the final stage of the study6. Their findings along with our results show that saphenous nerve blockade in cases with saphenous nerve entrapment in adductor canal is effective for controlling pain. In Tsai et al study the success rate of saphenous nerve blockade in cases who underwent lower extremity surgery was 77% and in Benzon et al study the success rate was 70%4-5. In their study saphenous nerve block was performed in conducted for patients who were candidate for menisectomy. In another studyby Manickam, et al, blockade of the saphenous nerve at the distal part of adductor canal for patients who underwent ankle or foot surgery resulted in 100% success rate7. The lower success rate in the current study could be attributed due to our first experiment in doing subsartorial blockade of saphenous nerve. During follow up we found that NRS decreased significantly and then increased but the mean score at the end of follow up was lower than pre intervention score. It could show that this approach is useful for reducing pain for a short time and it is not applicable for eradicating pain. May be continuous blockades or other methods such as radio frequency (RF) is necessary for eradicating pain in cases with chronic knee pain. Chronic knee pain is a disabling condition which affects quality of life of the patients and limits daily activity8. Different underlying diseases such as osteoarthritis, rheumatoid arthritis, bursitis, chondromalacia patella, baker’s cyst and jumper’s knee are among common causes of chronic knee pain. This study has some limitations. First, the sample size was low and the follow up period was short. Larger studies with long follow up periods are recommended. Conclusion: The results of the current study showed that ultrasound guided subsartorial approach is moderately effective in blockade of saphenous nerve in cases with saphenous nerve entrapment in adductor canal for controlling chronic knee pain. M.E.J. ANESTH 23 (1), 2015 28 Maryam Hatami et. al References 1.Horn J-L, Pitsch T, Salinas F, Benninger B: Anatomic basis to the ultrasound-guided approach for saphenous nerve blockade. Reg anesth pain med; 2009, 34(5):486-9. 2.Brad McKechnie D: Saphenous Nerve Entrapment Neuropathy. Dynamic Chiropractic; May 22, 1995, 13(11):1-3. 3.Akkaya T, Ersan O, Ozkan D, Sahiner Y, Akin M, Gümüş H, et al: Saphenous nerve block is an effective regional technique for post-menisectomy pain. Knee Surgery, Sports Traumatology. Arthroscopy; 2008, 16(9):855-8. 4.Benzon HT, Sharma S, Calimaran A: Comparison of the different approaches to saphenous nerve block. Anesthesiology; 2005, 102(3):633-8. 5.Tsai PB, Karnwal A, Kakazu C, Tokhner V, Julka IS: Efficacy of an ultrasound-guided subsartorial approach to saphenous nerve block: a case series. Can J Anesth; 2010, 57(7):683-8. 6.Romanoff ME, Cory PC, Kalenak A, Keyser GC, Marshall WK: Saphenous nerve entrapment at the adductor canal. Am J Sports Med; 1989, 17(4):478-81. 7.Manickam B, Perlas A, Duggan E, Brull R, Chan VW, Ramlogan R: Feasibility and efficacy of ultrasound-guided block of the saphenous nerve in the adductor canal. Reg anesth pain med; 2009, 34(6):578-80. 8. Ikeuchi M, Ushida T, Izumi M, Tani T: Percutaneous Radiofrequency Treatment for Refractory Anteromedial Pain of Osteoarthritic Knees. Pain Med; 2011, 12(4):546-51. 9. Tsui BC, Özelsel T: Ultrasound-guided transsartorial perifemoral artery approach for saphenous nerve block. Reg anesth pain med; 2009, 34(2):177-8. 10.Krombach J, Gray AT: Sonography for saphenous nerve block near the adductor canal. Reg anesth pain med; 2007, 32(4):369-70. 11.Mansour N: Sub-sartorial saphenous nerve block with the aid of nerve stimulator. Reg anesth; 1992, 18(4):266-8. 12.Bouaziz H, Benhamou D, Narchi P: A new approach for saphenous nerve block. Reg anesth; 1996, 21(5):490. 13.Gray AT, Collins AB: Ultrasound‐Guided Saphenous Nerve Block. Reg anesth pain med; 2003, 28(2):148. Comparison of the effects of oral vs. peritonsillar infiltration of ketamine in pain reduction after tonsillectomy: a Randomized Clinical Trial Afsaneh Norouzi*, Abolfazl Jafari**, Hamid Reza Khoddami Vishteh*** and S hahin Fateh **** Abstract Background: Although oral ketamine has been used in some cases to reduce pain in children, the use of this drug to reduce pain after tonsillectomy has not been studied yet. Methods: This double-blind clinical trial was conducted in 2009 in 92 children who were aged three to nine years old, met ASA I or II criteria, and were candidate for tonsillectomy. Patients were divided randomly into two groups. Half an hour before general anesthesia, 5 mg/kg ketamine mixed in 2 cc/kg apple juice was given to the children in oral ketamine group and 2 cc/kg of apple juice alone was given to the children in the peritonsillar group. After general anesthesia and three minutes before surgery 1 cc of 0.9% normal saline in the oral group and 1cc of ketamine (0.5 mg/ kg) in the peritonsillar group was injected to the tonsil bed of patients. Results: There was no difference between the two groups in terms of sex, age, and weight. Duration of surgery was significantly shorter in the peritonsillar group (P <0.001) and the severity of postoperative bleeding was significantly higher in peritonsillar group (P = 0.022). However, postoperative bleeding recurred in 25 patients (27%) and there was no statistically significant difference between the two groups. The level of pain in children six hours after surgery according to CHEOPS criteria was significantly lower in the peritonsillar group (0.9 ± 0.8) than in the oral group (2.6 ± 1) (P <0.001). Conclusions: The finding of this study showed that, compared with the peritonsillar infiltration of ketamine, the use of oral ketamine before general anesthesia was less effective in reducing postoperative pain of tonsillectomy in children. Keywords: tonsillectomy, adenotonsillectomy, postoperative pain, ketamine. *Assistant Professor (MD), Department of Anesthesiology and Intensive Care Medicine, Arak University of Medical Sciences, Arak, Iran. **Assistant Professor (MD), Department of Otolaryngology, Arak University of Medical Sciences, Arak, Iran. *** General Practitioner, Arak University of Medical Sciences, Arak, Iran. ****Assistant Professor (MD), Thoracic surgeon, Department of Surgery, Arak University of Medical Sciences, Arak, Iran. Corresponding author: Afsaneh Norouzi, Assistant Professor (MD), Department of Anesthesiology and Intensive Care Medicine, Arak University of Medical Sciences, Arak, Iran. Address: Valiasr hospital, Arak, Markazi province, Iran. Tel: +989181611365, Fax: +988613137474. E-mail: [email protected], [email protected] 29 M.E.J. ANESTH 23 (1), 2015 30 Afsaneh Norouzi et. al Introduction Materials and Methods Adenotonsillectomy is one of the most common ear, nose, and throat surgeries in children and postoperative pain is one of its important complications. Inadequate control of postoperative pain leads to different complications such as poor nutrition, dehydration, sleep disorders, behavioral changes, nausea, and vomiting1; moreover, it can increase the length of hospitalization and consequently increase healthcare costs2. Despite the high prevalence of pain after tonsillectomy and adenotonsillectomy3, 4 and the presence of different analgesics and assessment tools for measuring age-related pain5, the choice of appropriate analgesic to be used after tonsillectomy operation is still controversial6. This double-blind clinical trial was conducted in 2009 on 92 children aged three to nine years old who were referred to Amir Kabir hospital in Arak City. Inclusion criteria were: being aged three to nine years old, meeting ASA I or II criteria, and candidate for tonsillectomy surgery. Exclusion criteria were: the presence of an underlying disease, and the presence of contraindications to the use of ketamine including upper airway active infection, increased intracranial pressure, open eyes surgery, and seizures. The study was approved by the Ethics Committee of the Arak University of Medical Sciences. To reduce pain after tonsillectomy in children, different groups of drugs (oral paracetamol, opioids, NSAIDs, and local anesthetics) have been studied. Although paracetamol is a safe and effective analgesic, when it is used alone it cannot achieve an appropriate analgesic effect after tonsillectomy7. Opiates may reduce upper airway tone, suppress the cough reflex, cause sedation and respiratory depression (especially in unintended outpatient surgery), and also lead to postoperative nausea and vomiting4. Although NSAIDs are an alternative to opioids, they may increase the risk of postoperative bleeding and reoperation8. In addition, local anesthetics are associated with vasoconstriction9. N-methyl-D-aspartate (NMDA) receptors in the dorsal horn of the spinal cord are involved in central sensitization to painful stimuli10. Ketamine is a noncompetitive antagonist of NMDA receptors which has analgesic effects at sub-anesthetic doses10. Safari et al showed that the use of ketamine reduced the need for postoperative opioids and other analgesics in children undergoing tonsillectomy11. Intravenous injection12, peritonsillar infiltration13, rectal14, spray at the site of surgery15, continuous infusion16 and subcutaneous injection11 of ketamine have been investigated for pain reduction after tonsillectomy, too. To our knowledge, no previous studies have evaluated the role of oral ketamine for pain reduction after tonsillectomy. The aim of the current study is to compare oral ketamine to peritonsillar ketamine infiltration for pain relief after tonsillectomy. After explaining the procedures of the study to parents and obtaining their informed consent, patients who met inclusion criteria were divided randomly into two groups. In order to double-blind study, injectable medications were tagged using similar labels and oral ketamine was also given to patients mixed in apple juice by a medical student. Anesthesiologist and ENT specialists were unaware of the patient group and used apple juices and injectable medications for patients, respectively. Anesthesia was started using fentanyl and atropine as premedication and then anesthesia was induced using sodium thiopental 6 mg/kg and atracurium 0.5-1 mg/kg and it was sustained with isoflurane 1%, NO2 and O2 with a ratio of 50%. All patients were intubated and to prevent entering blood to the throat, which is of the factors causing nausea, gauze was placed in the throat. Half an hour before general anesthesia, 5 mg/kg ketamine mixed in 2 cc/kg apple juice was given to the children in oral ketamine group and 2 cc/kg of apple juice alone was given to the children in the peritonsillar group. After the induction of general anesthesia and three minutes before surgery 1 cc of normal saline 0.9% in the oral group and 1cc of ketamine (0.5 mg/ kg) in the peritonsillar group was injected to the each tonsil bed of patients (a total of 2 cc injections for each child). Injection was performed by an ENT specialist. Age, sex, weight, duration of surgery, intraoperative blood loss, postoperative bleeding (in the recovery room), nausea, vomiting, and postoperative bleeding recurrence six hours after surgery were recorded by the medical student who was unaware of Oral ketamine vs. peritonsillar infiltration in tonsillectomy 31 patient group. In order to measure the pain six hours after surgery, Modified Scoring CHEOPS criterion was used (Table 1). The range for this criterion is from 0 to 10 where a higher score indicates greater pain17. order to compare the two groups, chi-square test and Mann-Whitney U test were used. P-value less than 0.05 was considered as a significant level. Power calculations had indicated that 46 children would be required per group to detect a difference of 30% in facial CHEOPS pain scoring with a power of 85% and α =0.05 . SPSS 13 software was used for data analysis. Qualitative variables were described using frequencies and percentages and quantitative variables were described using mean and standard deviation. In Results There were no differences between the two groups in terms of sex, age, and weight (Table 2). Table 3 shows the comparison of the characteristics of surgeries and postoperative complications between the two groups. Duration of surgery was ≤20 minutes in Table 1 Modified CHEOPS scoring Score 0 1 2 Cry No cry Crying, moaning Scream Facial Smiling Neutral Grimace Verbal Positive statement Negative statement Suffering from pain, another complaint Torso Neutral Variable, taut, upright Stretched Legs Neutral Kicking Stretched, continuous move Table 2 Comparison of demographic characteristics between groups Oral group (N = 46) Peritonsillar group (N = 46) Male 37 (80%) 9 (20%) Female 30 (65%) 16 (35%) ≤5 yr 9 (20%) 12 (26%) 6-7 yr 18 (39%) 11 (24%) Sex Age group Weight ≥8 yr 19 (41%) 23 (50%) ≤20 Kg 18 (39%) 18 (39%) 21-24 Kg 18 (39%) 12 (26%) ≥25 Kg 10 (22%) 16 (35%) P value 0.101 0.278 0.275 Table 3 Comparison of surgery time and side effects between groups Surgery time Peritonsillar group (N = 46) P-value 0 (0%) 19 (41%) 21-29 min 18 (39%) 7 (15%) ≥30 min 28 (61%) 20 (44%) Mild 9 (20%) 14 (30%) Moderate 37 (80%) 27 (59%) 0 (0%) 5 (11%) Post-op bleeding recurrence 9 (20%) 16 (35%) 0.101 Nausea & Vomiting 0 (0%) 2 (4%) 0.153 Post-op bleeding ≤20 min Oral group (N = 46) Severe <0.001 0.022 M.E.J. ANESTH 23 (1), 2015 32 Afsaneh Norouzi et. al 19 patients (21%), 21-29 minutes in 25 patients (27%), and ≥30 minutes in 48 patients (52%). The durations of surgeries were significantly shorter in the peritonsillar group than in the oral group (P <0.001). The severity of postoperative bleeding was mild in 23 patients (25%), moderate in 64 patients (70%), and severe in five patients (5%); overall, the incidence of postoperative bleeding was significantly higher in peritonsillar group than in the oral group (P = 0.022). Postoperative bleeding recurred in 25 patients (27%) and there was no statistically significant difference between the two groups. Only two patients had postoperative nausea and vomiting, and there was no significant difference between the two groups. The level of pain in children six hours after surgery according to CHEOPS criteria was significantly lower in the peritonsillar group (0.9 ± 0.8) than in the oral group (2.6 ± 1) (P <0.001). Table 4 shows the characteristics of pain in each item. All the children in the peritonsillar group had neutral facial expression; however in the oral group only half the children had neutral facial expression (P <0.001). In the peritonsillar group, 39% of children were suffering from pain, whereas 76% of patients in the oral group were suffering from pain (P <0.001). The leg condition was neutral in all children in the peritonsillar group, while only 30% of children in the oral group had neutral condition (P <0.001). There was no significant difference between the two groups in terms of children cry and their body shape (Torso). Discussion The findings of this study showed that, compared with oral ketamine, the peritonsillar infiltration of ketamine after general anesthesia and immediately before tonsillectomy shortened the duration of operation and reduced the severity of postoperative pain. Although postoperative bleeding was more in the ketamine peritonsillar group, the recurrent bleeding, nausea, and vomiting after surgery was not significantly different between the two groups. Thus, it seems that, compared to peritonsillar infiltration, the use of oral ketamine 5 mg/kg is less effective in reducing pain in children after tonsillectomy. Ketamine is a noncompetitive antagonist of the NMDA receptor. These receptors are located in the dorsal horn of the spinal cord and play an important role in the development of central sensitization to painful peripheral stimuli. Seemingly, hyperexcitability of the central nervous system appears to be the cause of the Table 4 Comparison of pain based on CHEPOS between groups Cry Oral group (N = 46) Peritonsillar group (N = 46) No cry 28 (61%) 36 (78%) Crying, moaning 18 (39%) 10 (22%) 0 (0%) 0 (0%) Scream Facial Verbal Torso Legs Smiling 0 (0%) 0 (0%) Neutral 23 (50%) 46 (100%) Grimace 23 (50%) 0 (0%) 0 (0%) 16 (35%) Negative statement 11 (24%) 12 (26%) Suffering from pain, another complaint 35 (76%) 18 (39%) Neutral Positive statement 46 (100%) 46 (100%) Variable, taut, upright 0 (0%) 0 (0%) Stretched 0 (0%) 0 (0%) Neutral 14 (30%) 46 (100%) Kicking 0 (0%) 0 (0%) 32 (70%) 0 (0%) Stretched, continuous move P-value 0.070 <0.001 <0.001 1.000 <0.001 Oral ketamine vs. peritonsillar infiltration in tonsillectomy wind-up phenomenon and subsequent hyperalgesia in the place of injury18. The goal of preemptive analgesia is to prevent the afferent impulses to the spinal cord that is causing such a phenomenon. Hence, preemptive analgesia may prevent pain memory in the central nervous system and reduce the need for analgesics in the postoperative period19. It has been shown that ketamine’s effects on these receptors can reduce pain in humans20. Ketamine has been used in different ways, at different doses and different times as an analgesic after tonsillectomy surgery, but the reported results were not consistent have been various. Some studies failed to show the effect of ketamine on reducing pain after tonsillectomy. O’Flaherty et al’s study which compared the effects of the administration of intravenous ketamine with that of placebo4 and Van Elstraet et al’s study which examined the effect of ketamine on pain after tonsillectomy in adults21 did not show a positive effect in reducing pain after tonsillectomy. However, other studies reported that using ketamine was effective in reducing pain following tonsillectomy. Murray et al showed that a low-dose of intravenous ketamine may be effective in reducing pain after tonsillectomy22. Marcus et al23 and Elhakim et al24 stated that the intramuscular ketamine can be used as an alternative analgesic for tonsillectomy. Erhan et al. reported that ketamine injection in the tonsillar area was more effective than placebo in reducing pain without inducing sedation or nausea25. Dal et al. reported that intravenous or peritonsillar infiltration of ketamine before adenotonsillectomy surgery could reduce postoperative pain and reduce the need for analgesics without causing any adverse effects26. More recent studies have also suggested the effect of ketamine on reducing pain after tonsillectomy. Sizer et al12 showed that intravenous ketamine was effective in reducing pain following tonsillectomy. According to a study by Siddiqui et al. peritonsillar infiltration of 33 ketamine with doses of 0.5 or 1 mg/kg reduced pain after tonsillectomy, compared to control13. Our study also showed that peritonsillar infiltration of ketamine could be a useful method for reducing pain following tonsillectomy in children. Although ketamine has been used via different methods to reduce pain after tonsillectomy, oral method, however, has not been used yet for this purpose. Filatov et al. have compared oral ketamine as premedication with rectal diazepam/diclofenac in adenoidectomy surgery and reported that oral ketamine group had slightly higher pain scores than other group27. However, they conclude that oral ketamine is not suitable for premedication in upper airway surgeries27. Oral ketamine has been effective in children for controlling pain in different cases such as abdominal malignancy surgery, sickle cell crisis, and chronic pains28-30. It has also been used for anesthetic premedication in children in surgeries such as dental, ophthalmic and minor surgeries31-33. In addition, oral ketamine is effective in postoperative agitation in children34. In the present study we examined the effects of oral ketamine in reducing pain after tonsillectomy and compared it with peritonsillar ketamine. Although Ketamine reduced postoperative bleeding, overall it was associated with more pain in children than peritonsillar infiltration. Thus, it seems that oral ketamine with a dose of 5 mg/kg is less effective in reducing pain in children after tonsillectomy compared to peritonsillar infiltration. Conclusions The finding of this study indicated that, compared with the use of oral ketamine before tonsillectomy, the peritonsillar infiltration of ketamine after general anesthesia and immediately before tonsillectomy was more effective in reducing postoperative pain in children. M.E.J. ANESTH 23 (1), 2015 34 Afsaneh Norouzi et. al References 1.Sutters KA and Miaskowski C: Inadequate pain management and associated morbidity in children at home after tonsillectomy. J Pediatr Nurs; 1997, 12(3):178-185. 2. Aydin ON, Ugur B, Ozgun S, Eyigor H and Copcu O: Pain prevention with intraoperative ketamine in outpatient children undergoing tonsillectomy or tonsillectomy and adenotomy. J Clin Anesth; 2007, 19(2):115-9. 3. Bazin V, Bollot J, Asehnoune K, Roquilly A, Guillaud C, Windt De A, Nguyen J-M and Lejus C: Effects of perioperative intravenous low dose of ketamine on postoperative analgesia in children. Eur J Anaesthesiol; 2010; 27(1):47-52. 4. O’Flaherty JE and Lin CX: Does ketamine or magnesium affect posttonsillectomy pain in children? Paediatr. Anaesth; 2003, 13(5):413-21. 5. Hain RD: Pain scales in children: a review. Palliat Med; 1997, 11(5):341-350. 6. Ugur KS, Karabayirli S, Demircioglu RI, Ark N, Kurtaran H, Muslu B and Sert H: The comparison of preincisional peritonsillar infiltration of ketamine and tramadol for postoperative pain relief on children following adenotonsillectomy. Int J Pediatr Otorhinolaryngol; 2013, 77(11):1825-9. 7. Rømsing J, Østergaard D, Drozdziewicz D, Schultz P and Ravn G: Diclofenac or acetaminophen for analgesia in paediatric tonsillectomy outpatients. Acta Anaesthesiol Scand; 2000, 44(3):291-295. 8. Warltier DC, Marret E, Flahault A, Samama C-M and Bonnet F: Effects of postoperative, nonsteroidal, antiinflammatory drugs on bleeding risk after tonsillectomy meta-analysis of randomized, controlled trials. Anesthesiology; 2003, 98(6):1497-1502. 9. Møiniche S, Rømsing J, Dahl JB and Tramer MR: Nonsteroidal antiinflammatory drugs and the risk of operative site bleeding after tonsillectomy: a quantitative systematic review. Anesth Analg; 2003, 96(1):68-77. 10.Kochs E, Scharein E, Mollenberg O, Bromm B and Esch JS: Analgesic efficacy of low-dose ketamine: Somatosensory-evoked responses in relation to subjective pain ratings. Anesthesiology; 1996, 85(2):304-314. 11.Safavi M, Honarmand A, Habibabady MR, Baraty S and Aghadavoudi O: Assessing intravenous ketamine and intravenous dexamethasone separately and in combination for early oral intake, vomiting and postoperative pain relief in children following tonsillectomy. Med Arh; 2012, 66(2):111-5. 12.Sizer C, Kara I, Topal A and Celik JB: A comparison of the effects of intraoperative tramadol and ketamine usage for postoperative pain relief in patients undergoing tonsillectomy. Agri; 2013, 25(2):47-54. 13.Siddiqui AS, Raees US, Siddiqui SZ and Raza SA: Efficacy of preincisional peritonsillar infiltration of ketamine for post-tonsillectomy analgesia in children. J Coll Physicians Surg Pak; 2013, 23(8):533-7. 14.Heidari SM, Mirlohi SZ and Hashemi SJ: Comparison of the preventive analgesic effect of rectal ketamine and rectal acetaminophen after pediatric tonsillectomy. Int J Prev Med; 2012, 3(Suppl 1):S150-5. 15.Hosseini Jahromi SA, Hosseini Valami SM and Hatamian S: Comparison between effect of lidocaine, morphine and ketamine spray on post-tonsillectomy pain in children. Anesth Pain Med; 2012, 2(1):17-21. 16.Quibell R, Prommer EE, Mihalyo M, Twycross R and Wilcock A: Ketamine. J Pain Symptom Manage; 2011, 41(3):640-649. 17.McGrath PJ, Johnson G, Goodman JT, Schillinger J, Dunn J and Chapman J: CHEOPS: a behavioral scale for rating postoperative pain in children. Adv Pain Res Ther; 1985, 9:395-402. 18.Woolf CJ and Thompson SW: The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain; 1991, 44(3):293-299. 19.McQuay HJ and Dickenson AH: Implications of nervous system plasticity for pain management. Anaesthesia; 1990, 45(2):101-102. 20.Arendt-Nielsen L, Petersen-Felix S, Fischer M, Bak P, Bjerring P and Zbinden A: The effect of N-methyl-D-aspartate antagonist (ketamine) on single and repeated nociceptive stimuli: a placebo-controlled experimental human study. Anesth Analg; 1995, 81(1):63-68. 21.Van Elstraete AC, Lebrun T, Sandefo I and Polin B: Ketamine does not decrease postoperative pain after remifentanil-based anaesthesia for tonsillectomy in adults. Acta Anaesthesiol Scand; 2004, 48(6):756-60. 22.Murray WB, Yankelowitz SM, le Roux M and Bester HF: Prevention of post-tonsillectomy pain with analgesic doses of ketamine. S Afr Med J; 1987, 72(12):839-42. 23.Marcus RJ, Victoria BA, Rushman SC and Thompson JP: Comparison of ketamine and morphine for analgesia after tonsillectomy in children. Br J Anaesth; 2000, 84(6):739-42. 24.Elhakim M, Khalafallah Z, El-Fattah HA, Farouk S and Khattab A: Ketamine reduces swallowing-evoked pain after paediatric tonsillectomy. Acta Anaesthesiol Scand; 2003, 47(5):604-9. 25.Erhan OL, Goksu H, Alpay C and Bestas A: Ketamine in posttonsillectomy pain. Int J Pediatr Otorhinolaryngol; 2007, 71(5):735-9. 26.Dal D, Celebi N, Elvan EG, Celiker V and Aypar U: The efficacy of intravenous or peritonsillar infiltration of ketamine for postoperative pain relief in children following adenotonsillectomy. Paediatr Anaesth; 2007, 17(3):263-9. 27.Filatov SM, Baer GA, Rorarius MG and Oikkonen M: Efficacy and safety of premedication with oral ketamine for day-case adenoidectomy compared with rectal diazepam/diclofenac and EMLA. Acta Anaesthesiol Scand; 2000, 44(1):118-24. 28.Bredlau AL, McDermott MP, Adams HR, Dworkin RH, Venuto C, Fisher SG, Dolan JG and Korones DN: Oral ketamine for children with chronic pain: a pilot phase 1 study. J Pediatr; 2013, 163(1):194-200.e1. 29.Jennings CA, Bobb BT, Noreika DM and Coyne PJ: Oral ketamine for sickle cell crisis pain refractory to opioids. J Pain Palliat Care Pharmacother; 2013, 27(2):150-4. 30.Ugur F, Gulcu N and Boyaci A: Oral ketamine for pain relief in a child with abdominal malignancy. Pain Med; 2009, 10(1):120-1. 31.Khattab AM, El-Seify ZA, Shaaban A, Radojevic D and Jankovic I: Sevoflurane-emergence agitation: effect of supplementary lowdose oral ketamine premedication in preschool children undergoing dental surgery. Eur J Anaesthesiol; 2010, 27(4):353-8. 32.Darlong V, Shende D, Subramanyam MS, Sunder R and Naik A: Oral ketamine or midazolam or low dose combination for premedication in children. Anaesth Intensive Care; 2004, 32(2):246-9. 33.Astuto M, Disma N and Crimi: Two doses of oral ketamine, given with midazolam, for premedication in children. Minerva Anestesiol; 2002, 68(7-8):593-8. 34.Kararmaz A, Kaya S, Turhanoglu S and Ozyilmaz MA: Oral ketamine premedication can prevent emergence agitation in children after desflurane anaesthesia. Paediatr Anaesth; 2004, 14(6):477-82. The Impact of Anesthetic Techniques on Cognitive Functions after Urological Surgery Mahtab Poor zamany Nejat kermany*, Mohammad Hossein Soltani**, Khazar Ahmadi***, Hoora Motiee***, Shermin Rubenzadeh*** and Vahid N ejati *** Abstract Background: Postoperative cognitive dysfunction (POCD) is a well-recognized complication of cardiac and noncardiac surgery. However, contradictory results concerning postoperative mental function have been reported. The aim is to determine the effect of anesthetic techniques (general or spinal) on cognitive functions using more sensitive neuropsychological tests in patients undergoing urological surgery. Material and Methods: A total of thirty patients were enrolled in the study and assigned to receive either general (n=15) or spinal (n=15) anesthesia. A battery of neuropsychological tests including Wisconsin Card Sorting Test, Iowa Gambling Task, Stroop Color-Word Test, N-back Task and Continuous Performance Test was performed preoperatively and three days later. Results: The two experimental groups were similar at baseline assessment of cognitive function. Although there were no statistically significant differences between general and spinal anesthetic groups with respect to Wisconsin Card Sorting Test and Iowa Gambling Task, a significant intergroup difference between pre-and postoperative N-back scores was detected in the general anesthesia group (p=0.001&p=0.004). In addition, patients within this group had significantly higher error rates on the Stroop Color-Word (p=0.019) and Continuous Performance Tests (p=0.045). In contrast, patients receiving spinal anesthesia exhibited little change or marginal improvement on all subscales of the battery. Conclusions: Our findings indicate significant decline in specific aspects of mental function among patients who were administered general anesthesia compared with the other technique. It seems that spinal anesthesia contributes to lower disturbance after surgery. Key word: Anesthesia - Cognitive function - Urology. * Anesthesiology Department of Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, I.R. Iran. ** Urology Department of Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, I.R. Iran. *** Neuroscience department of Shahid Beheshti University of Medical Sciences (SBMU), Tehran, I.R. Iran. Address: No#99, 9th Boston St., Pasdaran Ave, Tehran, Iran.Tel & Fax: 0098-21-22588016 . Corresponding author: Vahid Nejati , Urology Department of Shahid Labbafinejad Medical Center, Email : v_nejati@sbu. ac.ir 35 M.E.J. ANESTH 23 (1), 2015 36 Introduction Postoperative cognitive dysfunction (POCD) is a common complication in adult patients undergoing surgical procedures which refers to decline in variety of neuropsychological domains such as verbal or visual memory, executive functioning, language comprehension, attention and concentration1. Although primarily observed after cardiac surgery, it has also been detected following major noncardiac surgeries2,3. While POCD is presumed to be transient and the longterm effects are considered uncertain4,5, recent studies suggest that the symptoms of neurocognitive change may persist long after the operation6,7 and diminish quality of life. Patients with POCD are more likely to withdraw from employment and social activities that will lead to premature dependency8,9. The ISPOCD 1 study (International Study of Post-Operative Cognitive Dysfunction) of 1,218 elderly patients (60 yr or older) scheduled for major noncardiac surgery showed that cognitive impairment was present in 25.8% patients one week after the operation and in 9.9% of them after 3 months10. Furthermore, postoperative cognitive decline has been associated with significantly higher risks of postoperative morbidity and mortality, particularly in elderly11. A similar study revealed that patients with POCD at hospital discharge were more likely to die whitin 3 months of the discharge12. In general, the rate of cognitive dysfunction has been positively correlated with mortality risk. Several studies show an increased risk of early mortality in elderly individuals with cognitive deterioration13,14. The etiology of POCD is likely multifactorial with type of surgical procedure (due to differences in duration) metabolic/endocrine stress response, imbalance of neurotransmitter system (particularly acetylcholine and serotonin), hypoxia and hospitalization, all potentially playing a role15. Advanced age, history of cerebral vascular accident with no residual impairment, lower educational level, evidence of cognitive dysfunction at hospital discharge and alcohol abuse also contribute to the pathogenesis of POCD12,16. With further identification of preoperative risk factors for POCD, patients and healthcare providers can be better informed before making a decision to proceed with major surgery. Mahtab poor zamany Nejat kermany et. al It has been speculated that POCD risk could be reduced by performing certain surgical procedures under regional anesthesia. Results of a study indicated that the maintenance of mental function in an elderly population was better following spinal anesthesia when compared with general anesthetic technique17. Similarly, another report showed that the incidence of cognitive deterioration was lower after epidural anesthesia18. A recent study found that general anesthesia posed a significant risk for the occurrence of early POCD in elderly patients that could persist for 3 days after surgery19. However, review of the existing literature has not revealed a significant difference between the two intraoperative anesthetic techniques20,21. The heterogeneity of procedures used to measure cognitive deficits and methodological inconsistencies make the limited literature on POCD difficult to interpret22,23. Most of these tests are subsets of test banks used to assess the memory and intelligence of adults. The use of more sensitive neuropsychological tests may elucidate more prolonged damage to cognitive performance. In addition, the majority of previous investigations have primarily focused on elderly patients, a population with an increased vulnerability to neurological deterioration after exposure to anaesthesia24,25. As a result, the cognitive effects of anesthesia and surgery in young and middle-aged adults are poorly understood. The objective of this study was to evaluate post-operative mental function of patients who had undergone general or spinal anesthesia for a urologic surgery, and to compare the effect of these two anesthetic techniques on mental function. Material and Methods From July to September 2011, 30 patients undergoing urological surgery following either general or spinal anesthesia were participated in the study at Shahid Labbafinezhad Hospital. Written informed consent was taken from all patients and university ethics committee approved the study structure. Entry criteria included age (24+ yr), normal mental status, speaking and reading fluency in the Persian language and the absence of any serious vision or hearing impairment that would preclude neuropsychological testing. Participants were excluded if they had any Impact of anesthesia on cognitive function prior history of dementia, central nervous system disease, psychiatric disorders, alcoholism and drug abuse. In addition, any patients with history of allergy to anesthetic drugs were also excluded. Information about the demographic status, medical history, education and occupational history of the subjects were documented. Anesthetic techniques and agents All patients received 5cc/kg normal saline serum before anesthesia. In the group of patients who underwent general anesthesia, the following agents were used for the induction of anesthesia: Fentanyl (2µ/kg), Midazolam (1mg), Lidocain (1.5mg/kg), Propofol (2mg/kg) and Atracurium (0.5mg/kg). For maintenance phase of general anesthesia, Propofol (100-200µ/kg) and Remifentanil (0.1 µ/kg/min) were used. Spinal Anesthesia was done by injection of 2.5 to 3 cc bupivacaine 0.5% (Marcaine®) in the subarachnoid space. For post-operative pain control, intravenous pethidine (25-50 mg) was administrated in the recovery room and Diclofenac 100mg suppository was given in the ward as needed. Neuropsychological Assessment The cognitive function evaluation was performed in an undisturbed room with only the patient and the psychometrician present. Patients completed the tests one day prior to surgery and at hospital discharge (three days after the operation). The psychological measures included Wisconsin Card Sorting Test, Stroop ColorWord Task, Continuous Performance Test, N-Back Task and Iowa Gambling Test that were administered in about 30 minutes. These measures primarily focus on executive functions and memory, elaborated as follows: Wisconsin Card Sorting Test is commonly regarded as “the gold standard executive function task”26,27. Patients were asked to match response cards to reference cards according to three dimensions of sorting principle (color, form and number)28. Stroop Color-Word Test estimates the patient’s ability to concentrate and ignore distracting stimuli29. Continuous Performance Test (CPT) requires subjects 37 to maintain vigilance and react to the presence or absence of specific stimuli within a continuously presented set of distracters30,31. N-Back Task is one of the most popular experimental paradigms for studies of working memory, in which subjects are asked to monitor the identity or location of a set of verbal or nonverbal stimuli and to indicate when the currently presented stimulus is the same as the one presented in trials previously32,33. Iowa Gambling Task evaluates decision-making under initially ambiguous conditions. It simulates real-life decision making by testing the ability of subjects to learn to sacrifice immediate rewards in favor of long-term gains34,35. Statistical Analysis Given the large number of dependant variables, comparison of the cognitive function between the two anesthesia groups was performed with multivariate analysis of covariance (MANCOVA) using SPSS (version 18). Follow-up tests were conducted when warranted by multivariate results with ANOVA and paired t-tests. Pre-test scores were considered to be covariate variables in order to control for the practice effect. The customary two-tailed α level of significance was set at 0.05. Results Thirty patients (13 women and 17 men) were recruited. The subjects had a mean age of 44.6 (±12.66). 36.6% subjects were classified as young (24-39yr), 53.33% were middle-aged (40-59) and 10% were elderly (60-65). General anesthesia was used in 15 patients (50%), and the remaining subjects received spinal anesthesia. The baseline characteristics of the patients included in the study are listed in table 1. Data analysis revealed that the two groups did not differ in preoperative scores. However, statistically significant differences were observed when postoperative scores were compared with the baseline levels. Results indicated significant association between general anesthetic technique and damage to particular domains of cognitive functions. Although subtests of the Wisconsin Card Sorting Test and Iowa Gambling Task did not change significantly M.E.J. ANESTH 23 (1), 2015 38 Mahtab poor zamany Nejat kermany et. al between the two groups, separate univariate analysis and paired t-test showed that patients were more likely to have worse 1-and 2-back test performance after general anesthesia (p=0.001& p=0.004). These patients also had significantly higher omission error score on the Continuous Performance Task (p=0.045) and considerable error rates on the 3rd part of the Stroop Color-Word Test (p=0.019). It is worth noting that patients receiving spinal anesthesia showed little change or slight improvement on all subscales of the battery. The mean pre-and postoperative neuropsychological test scores are exhibited in Table 2. Discussion This study is one of the few investigations of postoperative cognitive function that includes younger population. In the current study, we used some of the most popular neuropsychological tasks to assess executive functions. Comparison of the two arms of the study was based on MANCOVA which provided more statistical power. Our data revealed that general anesthesia was associated with weaker performance in the memory and concentration domains. These results are in accordance with the findings of Chung et al, who found that patients receiving general anesthesia performed worse on digit-symbol substitution for 2-3 days after surgery36. Herbert and colleagues also noted that choice reaction time was impaired for 36hours after administration of general anesthesia37. Findings of another study indicated that general anesthesia patients perceived residual impairment of their cognitive faculties after 3 days38. Previous research addressing the role of anesthesia on cognitive deterioration has yielded conflicting results. The absence of a consistency regarding the operational definition of POCD may contribute to this issue. Our findings are inconsistent with the vast majority of existing evidence demonstrating no significant difference between intraoperative regional and general anesthesia in preserving postoperative Table 1 General characteristics of the patients, compared in two groups (general vs. spinal anesthesia.) General Anesthesia Spinal Anesthesia Total P value 46.9 42.26 44.6 0.614 24-39 (Young) 6 5 11 0.120 40-59 (Middle-aged) 8 8 16 60 and above (Elderly) 1 2 3 Male 7 10 17 Female 8 5 13 Less than High school 4 7 11 High School 6 4 10 More than High school 5 4 9 Lithotripsy 4 1 5 Intravesical injection 1 2 3 Radical Nephrectomy 2 0 2 Varicocelectomy 2 3 5 Bladder Stone Removal 2 2 4 TUL 1 5 6 TURT 1 2 3 Mean Age Age Groups Sex Education Type of surgery 0.211 0.340 0.151 Impact of anesthesia on cognitive function 39 Table 2 Pre-and postoperative (at hospital discharge) test results Preoperative Postoperative General Spinal General Spinal (n-15) (n-15) (n-15) (n-15) Achieved Clusters 1.66±0.61 1.60±0.63 1.66±0.72 2.00±0.84 Number of Total Errors 37.93±6.39 38.2±5.79 37.53±6.01 36.26±7.53 Perseverative Errors 15.46±3.62 14.86±2.13 14.8±3.66 12.00± Iowa Gambling Task 25.20±2.48 23.53±3.29 26.20±1.97 23.46±3.99 1-back 19.93±6.71 16.26±6.30 16.20±5.99* 17.73±6.41 2-back 8.13±3.29 8.73±3.97 5.60±2.55* 10.33±3.90 Omission Error 16.06±8.67 16.33±8.10 19.20±7.93* 13.60±6.56 Commission Error 1.064±0.51 1.157±0.94 1.11±0.35 1.151±0.56 Hit Reaction Time 0.548±0.06 0.562±0.04 0.606±0.1 0.541±0.05 Error Rates 1 1.33±0.97 1.40±0.82 1.60±1.88 0.66±0.61 Reaction Time 1 0.46±0.45 0.33 ±0.37 0.42±0.54 0.25±0.32 Error Rates 2 0.53±0.74 0.53±0.63 2.13±1.95 0.26±0.59 Reaction Time 2 0.34±0.55 0.27±0.34 0.79±0.81 0.22±0.46 Error Rates 3 17.40±7.91 19.33±7.006 22.06±6.94* 16.60±6.99 Reaction Time 3 1.85±0.93 1.34±0.55 2.11±0.91 1.53±0.61 Wisconsin Card Sorting Test N-Back Task Continuous Performance Test Stroop Color-Word Task Values are given as mean±SE. “*” mark indicates significant difference in the assigned group before and after the operation. cognitive function. For instance, in a prospective, randomized study, Williams-Russo et al, compared the effect of epidural versus general anesthesia on the incidence of POCD in patients undergoing elective unilateral total knee replacement and found no significant difference postoperatively20. In another randomized trial, no significant differences were found in the postoperative mental abilities between patients who received general, regional or combined anesthetic techniques39. O’Hara et al, observed no clinically important impacts on major outcomes in patients who were administered general or spinal anesthetic techniques after the hip surgery40. In a systematic review, Wu et al, found that intraoperative neuraxial anesthesia does not decrease the incidence of POCD when compared with general anaesthesia41. Detection of POCD requires two crucial elements: a sensitive battery of tests and controlling for the practice effect. We used some of the well-known psychological measurements to determine more subtle defects. The enhancement observed in this trial cannot be attributed to practice effect. In as much as, pretest scores were considered as covariate variables. There may be several factors that might have a negative impact on cognitive function after general anesthesia. Some agents that are used to induce and maintain anesthesia may deteriorate cognition and memory10. In addition, there may be a possibility of hemodynamic instability, hypoxia and stress induced response due to prolonged intubation; the factors that are not commonly related to regional anesthesia15. M.E.J. ANESTH 23 (1), 2015 40 This study was limited by two major factors. Firstly, patients were not allocated randomly to the general or spinal anesthesia groups. Secondly, we were unable to include a control group of healthy volunteers matched with the experimental groups in the present study. Hospitalized patients not undergoing surgery or any other intervention were also considered as a better control group, but a sufficient sample size for comparison could not be attained due to lack of participation. Our findings should therefore be interpreted with caution. A more extensive study with follow-up testing is required to determine the precise profile of the postoperative cognitive impairment. In conclusion, our results suggest a linkage between general anesthesia and weaker postoperative Mahtab poor zamany Nejat kermany et. al mental function. Local anesthesia might have an advantage over general anesthesia in terms of neuropsychological functioning. Acknowledgments The authors thank the hospital staff and patients for taking part in this study. Their assistance was essential for data collection and the coordination of the research protocol. Conflict of interest: The authors have no conflict of interest. Impact of anesthesia on cognitive function 41 References 1. 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Comparison between C-MAC ® video-laryngoscope and Macintosh direct laryngoscope during cervical spine immobilization Shahir HM Akbar* and Joanna SM Ooi** Abstract Background: Video-laryngoscopes have gained popularity in the recent years and have shown definite advantages over the conventional Macintosh direct laryngoscopes. However, there is still insufficient evidence comparing the C-MAC® with the Macintosh for patients during manual inline stabilization (MILS). Methods: This prospective, randomized, single blind study was carried out to compare tracheal intubation using the C-MAC® video-laryngoscope and Macintosh laryngoscope in patients during MILS. Ninety consented patients, without features of difficult airway, who required general anesthesia and tracheal intubation were recruited. Intubation was performed with either the C-MAC® video-laryngoscope or the Macintosh laryngoscope by one single investigator experienced with both devices. Various parameters which included Cormack and Lehane score, time to intubate, intubation attempts, optimization maneuvers, complications and hemodynamic changes were recorded over the initial period of 5 minutes. Results: C-MAC® video-laryngoscope performed significantly better with lower Cormack and Lehane grades, shorter time to intubate of 32.7 ± 6.8 vs. 38.8 ± 8.9 seconds (p=0.001) and needed less optimization maneuvers. There were no significant differences seen in the intubation attempts, complications or hemodynamic status of the patients with either device. Conclusion: The C-MAC® video-laryngoscope was superior to the Macintosh laryngoscope for patients requiring intubation when manual inline neck stabilization was applied. Keywords: C-MAC® laryngoscope, Macintosh laryngoscope, intubation, neck immobilization, manual inline stabilization. Introduction Securing the airway with tracheal intubation in a patient suspected or known to have a cervical spine injury has always been a challenge regardless of whether it is conducted in a controlled operating room environment, in a busy critical zone of the emergency department or in an out-of-hospital setting. This has been recognized since the early 1950’s and by the early 1980’s the standard of care to overcome this scenario was to use the time tested formulae of direct laryngoscopy with tracheal intubation using manual inline stabilization (MILS)1 with a Macintosh laryngoscope. MILS is a maneuver that ensures a neutral alignment and motionless cervical spine * MBBS, Master in Medicine (Anesthesiology). ** MD, Master in Medicine (Anesthesiology). Corresponding author: Professor Dr. Joanna Su Min Ooi. Address: Department of Anesthesiology and Intensive Care, University Kebangsaan Malaysia Medical Center, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. Tel: +0193207265, Fax: +60391456585. E-mail: [email protected] 43 M.E.J. ANESTH 23 (1), 2015 44 during the intubation process and is carried out by a healthcare personnel who places a hand on each side of the patients neck with fingers pressed on each mastoid process and the hands then pressed firmly into the operating table2. While the practice of MILS was considered to be the standard care with regards to prevention or worsening of any neurological morbidity, it has been found that MILS produced significantly worse laryngoscopy view upon direct laryngoscopy for tracheal intubation3-5. The delay in or a failed tracheal intubation could potentially result in hypoxia leading to worse outcomes and is a leading cause of morbidity and mortality for patients in both the operative setting and in an emergency situation5,6. With due consideration to the above, advances in technology have provided alternatives to the conventional Macintosh laryngoscope to perform direct laryngoscopy during a MILS scenario. Considerable development has occurred especially in the field of indirect laryngoscopy using videoassisted techniques producing devices such as the Glidescope® (Saturn Biomedical System Inc., Burnbaby, Canada) and the Airwayscope® laryngoscope (Pentax Corporation, Tokyo, Japan). These new devices have been shown to have definite advantages over the conventional Macintosh direct laryngoscopy in scenarios where MILS was applied. These included better glottic visualization, less optimizing maneuvers needed for a successful intubation and more favorable hemodynamic profiles during the intubation itself7-10. The C-MAC® (Karl Storz, Tuttlingen, Germany), a portable video-laryngoscope is unique as it offers an original Macintosh blade shape with an approximately 80° angle of view and practically eliminated fogging of the camera11. Owing to its similar design to the Macintosh blade, there would not be very much of a learning curve to using it by most anesthetic doctors. An initial study showed great promises in it being able to obtain good view of the glottis on the first attempt in all patients12. At this point of time the question of whether any video-laryngoscope is definitely better in MILS is yet to be answered convincingly3. The aim of this study was to compare laryngoscopic views (based on Cormack and Lehane grading) during tracheal intubation when using either J.Su Min Ooi et. al the C-MAC® video-laryngoscope or the Macintosh laryngoscope during MILS. The time taken to intubate (seconds), number of intubation attempts, optimization maneuvers required, complications encountered and the changes in hemodynamic parameters of the patients being intubated were also compared. Methods This study design was based on a prospective, randomised, single-blinded clinical trial that was done following approval of the Dissertation Committee of the Department of Anesthesiology and Intensive Care, Universiti Kebangsaan Malaysia Medical Center (UKMMC) and the Research Ethics Committee of UKMMC (Research No. FF-024-2011). After obtaining written informed consent, ninety patients between 18 and 60 years of age with American Society of Anesthesiology (ASA) physical status I or II, scheduled for elective surgery under general anesthesia that required tracheal intubation were enrolled in the study. Those patients who had features of difficult airway (e.g. Mallampati grade >III, thyromental distance <6cm or a Body Mass Index >35kg/m2), pregnant or had other conditions associated with an increased risk of pulmonary aspiration were excluded from the study. Likewise patients who had pre-existing cervical neck pathologies, hypertensive individuals and those with allergies or contraindications to medications used for general anesthesia were excluded as well. The selected patients were then randomised into two arms. Group 1 patients were intubated with the C-MAC® video-laryngoscope whereas patients in Group 2 were intubated with the Macintosh (MAC) laryngoscope. This randomisation process was done using ‘Random Numbers Tables’ that were computer generated. In the operating room, all patients received a standardized general anesthetic. Both groups of patients were started on IV fluid of Lactated Ringer’s solution. Induction of anesthesia with the administration of 100% oxygen at 6 liters/min, IV fentanyl (2 mcg/kg) and IV propofol (up to 2 mg/kg) was carried out to induce unconsciousness defined as loss of eyelash reflex. Subsequently manual C-MAC® video-laryngoscope during manual inline stabilization ventilation was initiated with sevoflurane (2.0%) in oxygen as test ventilation, before administration of IV rocuronium (0.6 mg/kg) as a muscle relaxant. Standard anesthetic monitoring which included ECG, noninvasive blood pressure (NIBP), oxygen saturation (SpO2), end tidal carbon dioxide (EtCO2) and a multigas analyzer were provided to both groups of patients. After full muscle relaxation was confirmed with a nerve stimulator, the patient’s neck was immobilized utilizing MILS technique. The MILS was performed by another medical officer who stood at the right side of the patient caudal to the intubator and the patient’s airway. The assistant placed a hand on each side of the patient’s neck with fingers pressed on each mastoid process and the hands were then pressed firmly into the operating table ensuring neutral alignment and a motionless cervical spine as described in Advanced Trauma Life Support2. Intubation was then performed with one of the two devices (both with blade #3) as per the group that the patient was in . A tracheal tube size #7.5 - 8 for males and #7 - 7.5 for females was used. Once the vocal cords were visualized they were graded using the Cormack and Lehane (CL) grading. After successful tracheal intubation in all patients, mechanical ventilation was commenced for the duration of the procedure with anesthesia being maintained with sevoflurane (1.0 MAC) and air-oxygen mixture (FiO2 0.5). In each group, tracheal intubation was considered a failure if it could not be established with three attempts, within three minutes or desaturation of SpO2 <92%. In the event of such an incident, MILS was abandoned and intubation was performed using the Macintosh blade with optimal patient head and neck positioning. Any additional instruments to aid intubation were used if deemed necessary. All intubations were performed by the investigator SH, an anesthetic trainee whose previous experience includes >30 intubations with the C-MAC® and more than 5 years frequent use of the Macintosh laryngoscope. Data collected included CL score, time to intubate in seconds (defined as when either of the blades was inserted beyond the lip until first appearance of the capnograph waveform) and number of intubation attempts. In addition, the nature of optimisation maneuvers done such as the use of a gum elastic 45 bougie (GEB), external laryngeal manipulation (ELM) or presence of a second assistant were also recorded. Complications including fogging of lens, local trauma (mucosal/lip/dental), hypoxia (SpO2 <92%) and failed intubation were recorded. Recording of the patient’s baseline mean arterial pressure (MAP) and heart rate (HR) along with repeat recordings at fixed one minute time intervals for 5 minutes were done. No other medications were administered, or procedures performed during the 5-minute data collection period after tracheal intubation. Subsequent management was left to the discretion of the anesthetist providing care for the patient. The sample size was obtained using the computer software: “Power and Sample Size Calculations Version 3.0.14, January 2009” otherwise known as PS2. (http://bisotat.mc.vanderbilt.edu/powersamplesize ). The alpha error was set at 5% (p<0.05) and a beta error of 20% (power = 0.8). The p0 was set at 0.2 from a previous study with the Macintosh laryngoscope using MILS where 20% of patients obtained CL grade 1 views9. Since the C-MAC® video-laryngoscope has not been studied previously in this manner, the probability of obtaining a CL grade 1 view was estimated as 50% from a preliminary study12. Thus the p1 was set at 0.5 and the results calculated using the sample size software as discussed previously. The sample size required was found to be 38 patients, which was rounded up to 40 patients on each arm. A dropout rate of 10% was factored in to give a sample size of 45 patients in each arm and thus a total sample size of 90 patients. Data analysis was done using Chi-square test for non-parametric data and Student’s t-test for parametric data. A p value of less than 0.05 was considered as statistically significant. All analysis was performed using SPSS for Windows (version 12.0, Chicago, IL). Results A total of 90 patients were enrolled into the study with 45 patients in each group. There were no significant differences in the patient characteristics such as age, gender, ASA physical status, BMI and Mallampati grades between the two groups as shown in Table 1. M.E.J. ANESTH 23 (1), 2015 46 J.Su Min Ooi et. al Table 1 Demographic and patient characteristics. Values expressed as Mean ± SD or number (%) Gender 32.7 ± 6.8* 38.8 ± 8.9 1 44 (97.8) 39 (86.7) 2 1 (2.2) 4 (8.9) 3 0 2 (4.4) 13 (28.9) None 38 (84.4)** 27 (60.0) 25 (55.6) 22 (48.9) GEB 3 (6.7) 1 (2.2) 20 (44.4) 23 (51.1) ELM 3 (6.7) 14 (31.1) ELM + GEB 1 (2.2) 3 (6.7) Second assistant 0 0 Blade size change 0 0 Failed intubation 0 2 (4.4) Lip trauma 0 1 (2.2) Esophageal intubation 0 0 Dental trauma 0 0 SpO2<92% 0 0 40.8 ± 15.1 41.6 ± 14.8 Female 22 (48.9) 24 (53.3) Male 23 (51.1) 21 (46.7) 26.2 ± 4.7 26.9 ± 3.7 I 30 (66.7) 32 (71.1) II 15 (33.3) I II BMI (kg/m ) Mallampati MAC (n=45) MAC (n = 45) 2 ASA C-MAC® (n=45) C-MAC® (n = 45) Age (years) Table 2 Intubation characteristics. Values are expressed as Mean ± SD or numbers (%) The CL grade was significantly better in Group 1 using the C-MAC® producing a CL Grade I for 67% of the study population compared to Group 2 with only 38% of the sample having CL Grade I as shown in FIGURE 1 (p <0.05). None of the patients in Group 1 had CL Grade IV whereas there was one patient in Group 2 with CL grading of IV. The majority of patients intubated with the MAC (56%) were found to have a CL Grade of II. The CL grading correlated well with the time to intubate (TTI) which was found to be significantly shorter in Group 1 with a mean time of 32.7 ± 6.8 vs. 38.8 ± 8.9 seconds for Group 2 (p = 0.001) as shown in Table 2. The number of intubation attempts required in the two groups however was found to be not significantly different. The majority of patients in both Fig. 1 Cormack and Lehane grades obtained in the two groups * p <0.05 TTI ( seconds) Intubation attempts Optimization maneuvers Complications * p = 0.01, ** p <0.05. C-MAC® video-laryngoscope during manual inline stabilization groups were able to be intubated in the first attempt. Optimisation maneuvers were found to be commonly required for patients in Group 2 with 31% of them requiring ELM and 7% required both ELM and GEB. In contrast 84% of Group 1 patients required no such measures for successful tracheal intubation and only 7% of patients needed the help of either a GEB or ELM (p =0.01). There were no reported complications in patients from Group 1. In Group 2, there were two cases of failed intubation and one case of minor lip trauma. However on statistical analysis these results were not significant. Additionally, there was no occurrence of oxygen desaturation or esophageal intubation encountered on both the study arms. On a side note, we experienced fogging occurring in 11% of the cases on the C-MAC® arm but this was not severe enough to impair the performance of the device. This was likely 47 due to the presence of a built in software system that initiates pre-warming of the optical system by the camera light12. Both groups had similar trends of MAP and HR over the 5-minute data collection period as shown in Figures 2 and 3. There were no recorded increases of more than 20% of their respective baseline values of these two parameters. However at one point of time (T +1: one minute post intubation) Group 2 had a higher MAP of 93.5 ± 16.0 vs. 86.9 ± 10.4 mmHg for Group 1(p<0.05). The rest of the data points were not statistically different between the groups. Discussion From this study, we found that using the C-MAC® video-laryngoscope would be of benefit in patients with Fig. 2 Changes in MAP during tracheal intubation. Values are expressed as Mean ± SD * p <0.05 Fig. 3 Changes in mean heart rate following tracheal intubation. Values are expressed as Mean ± SD M.E.J. ANESTH 23 (1), 2015 48 MILS due to its superiority in various aspects compared to the Macintosh laryngoscope. The C-MAC® was able to obtain better CL scores with a majority of them being CL Grade I without requiring additional optimization maneuvers. The Macintosh laryngoscope on the other hand had majority of CL II grades. Poor laryngoscope views in the setting of MILS is a known factor that will complicate intubation in this group of patients1. The limited neck movement from the MILS made direct laryngoscopy become more challenging mainly due to difficulties in aligning the oral, pharyngeal and laryngeal axis which was required for a successful tracheal intubation10. In order to overcome this situation, having an indirect laryngoscope such as the C-MAC® with a camera mounted on the blade capturing live images and projecting them onto a video screen dramatically reduces the line of sight required which in turn resulted in the much improved CL scores as seen occurring in our study. This advantage was also noted by McElwain and Laffey where 35 % of patients intubated with the C-MAC® had a CL Grade 1 vs. the Macintosh which produced CL Grade 1 in 19% of their study sample10. The mean difference of 18 seconds reduction in TTI for the C-MAC® obtained in our study may initially seem unremarkable at its face value especially since the lengthened period of apnea for the Macintosh group was not associated with desaturation or other hemodynamic changes. However, in an emergency airway management situation where the patient is at risk of hypoxia, any reduction in the TTI could be a very crucial factor. In a similar study the TTI recorded however was longer although insignificantly for the C-MAC® [TTI of 27secs IQR 18, 47] vs. Macintosh [TTI of 23 sec IQR 14, 47]10. A point to note in that study was that the measurement of TTI was not standardized. The investigators measured the TTI from the time the laryngoscope blade passed the lips up till they visualized the ETT passing the vocal cords and in cases where the ETT was not visualized, the appearance of capnograph tracing was taken as the end point. In our study the TTI was standardized and recorded for all intubations from the time the laryngoscope blade passed the lips till the appearance of the capnograph. J.Su Min Ooi et. al Using the C-MAC® also resulted in less need for additional optimization maneuvers compared to the Macintosh Group. In our study we found that the Macintosh group required the use of ELM in 61% of patients which was similarly seen in other studies as well9,10. The main reason behind this was because of the need for the intubator to obtain a best line of sight by aligning the intubation axis as has been discussed earlier. This however is not needed when using the C-MAC® as the vocal cords are readily visualized due to the blade mounted camera and 80° angle of view12. During the course of our intubations, we did not require a change in blade size or use of second assistant for either of the groups and blade size #3 was used for both devices. Patients from both groups had no significant complications. Oxygenation was well maintained despite the variation in intubation times due to the process of preoxygenation that was conducted in our study. There may possibly have been hypoxemia if this crucial step was omitted highlighting once again its importance especially in emergency airway management. The lack of significant airway trauma in both groups as observed in our study arise possibly because of the similar shape and structure of the two laryngoscope blades that results in similar mechanical forces and movements during intubation when using either of the devices. These similarities in the low occurrence of airway trauma was also observed in other studies as well10,13. There are a few limitations that can be identified in our study. Firstly, it is not possible to blind the investigator about the device being used. The performance of the device is highly dependent on the capabilities of the operator. However due to the overall similar design of the two blades this would be quite unlikely to affect performance markedly. Nevertheless all the intubations were carried out by a single investigator (SH) so that the variability in technique and operator bias could be minimized. The other issue lies with the subjectivity of the CL scoring. Once again by utilizing a single operator we hope that this can be overcome as well. One important factor to keep in mind is that this study was conducted on adequately fasted, pre-oxygenated patients with no difficult airway C-MAC® video-laryngoscope during manual inline stabilization management anticipated. These patients underwent elective surgery exclusively. Thus the situation would be expected to be very different in the post-trauma patients presenting to the emergency department or operating room for emergency airway management. Further well planned studies will be required to assess how the C-MAC® performs in these situations. 49 Conclusion In conclusion, our study demonstrated that the C-MAC® video-laryngoscope was superior for patients being intubated during manual inline neck stabilization when compared to the standard Macintosh laryngoscope. M.E.J. ANESTH 23 (1), 2015 50 J.Su Min Ooi et. al References 1. Manoach S, Paladino L: Manual In-Line Stabilisation For Acute Airway Management Of Suspected Cervical Spine Injury: Historical Review And Current Questions. Ann Emerg Med; 50:236-45 2007. 2. Committee on Trauma, American College of Surgeons. ATLS: Advanced Trauma Life Support Program for Doctors (8th ed.). Chicago: American College of Surgeons, 2008. 3. Calder I and Pearce A: Core Topics in Airway Management. 9780521111881. 2nd Edition. 248. Cambridge; Cambridge University Press, 2010. 4. Nolan JP, Wilson ME: Orotracheal intubation in patients with potential cervical spine injuries. An indication for the gum elastic bougie. Anesthesia; 1993, 48:630-3. 5. Heath KJ: The effect of laryngoscopy of different cervical spine immobilisation techniques. Anesthesia; 1994, 49:843-5. 6. Mort TC: Emergency tracheal intubation: complications associated with repeated laryngoscopy attempts. Anaesth Analg; 2004, 99:60713. 7. SUN DA, WARRINER CB, PARSONS DG, et al: The Glidescope® video-laryngoscope: randomised clinical trial in 200 patients. Br J Anaesth; 2005, 95:381-4. 8. Enomoto Y, Asai T, Arai T, et al: Pentax-AWS®, a new video- laryngoscope, is more effective than the Macintosh laryngoscope for tracheal intubation in patients with restricted neck movements: a randomised comparitive study. Br J Anaesth; 2008, 100:544-8. 9. Malik MA, Maharaj CH, Harte BH, et al: Comparison of Macintosh, Trueview EVO2®, Glidescope®, and Airwayscope® laryngoscope use in patients with cervical spine immobilisation. Br J Anaesth; 2008, 101:723-30. 10.Mcelwain J and Laffey JG: Comparison of the C-MAC®, Airtraq®, and Macintosh laryngoscopes in patients undergoing tracheal intubation with cervical spine immobilisation. Br J Anaesth; 2011, 107(2):258-264. 11.Thierbach A, Piepho T: Emergency Airway Management. Tuttlingen, Germany: Endo PressTM 2009. 12.Cavus MD, Kieckhaefer J, Doerges V, et al: The C-MAC® videolaryngoscope: first experiences with a new device for videolaryngoscopy guided intubation. Anaesth Analg; 2010, 110:473-7. 13.Maharaj CH, Buckley E, Harte BH, et al: Endotracheal intubation in patients with cervical spine immobilisation. A comparison of Macintosh and Airtraq laryngoscope®. Br J Anaesth; 2007, 107:53-9. Effects of Memantine on Pain in Patients with Complex Regional Pain Syndrome-A Retrospective Study Mohammad-Hazem Ahmad-Sabry* and G holamreza S hareghi ** Abstract Introduction: Memantine was discovered in 1968 and is used as a treatment for Alzheimer’s disease. We evaluated the use of memantine to treat complex regional pain syndrome in this retrospective study. Patients and methods: 56 patients with CRPS, who were treated with trial of memantine for at least two months with 40mg QHS from 2007 until 2009. Results: 34 females and 22 male patients. Age-46.0+/-9.7 years. Number of years with CRPS-9.24 ± 5.7 years. Mean age-46.0+/-9.7 years. Memantine was started at 5 or 10mg QHS, before being increased by 5 or 10mg every 4-7 days, as tolerated, to a maximumdose of 40mg60mg, as tolerated. In all, 13 patients showed complete remission from CRPS with VAS 0 and the disappearance of allodynea for at least nine months after the use of memantine. In addition, 18 patients showed partial improvement of VAS and allodynea. Eight patients showed no improvement even after continuous use of memantine at a dose of 40mg QHS for two months. Seven patients could not take more than 5mg of memantine per day and had to stop it due to side effects. In terms of subjective improvement in short-term memory, nine patients showed much improvement, 14 patients showed some improvement, three patients showed no changes and one patient didnot answer the questionnaire. Regarding subjective feelings of a having better quality of life, 17 patient answered yes, three did not feel any changes, six could not give an answer and two did not fill out the questionnaire. Conclusions: Memantine is a promising option for the treatment of CRPS. A randomised controlled study is needed to evaluate its efficacy*. Introduction Bowsher (1991) found that neuropathic pain affected 25-50% of chronic pain patients in most pain clinics1. Richards (1967) reported the history of CRPS and its terminology2. Although previous descriptions were of single cases, Weir Mitchell, Morehouse and Keen (1864) first described the condition in full in the book “Gunshot Wounds and other Injuries of Nerves”. The * MB, ChB MSc FRCPC MD ABPM. ** MD, PhD, DABIPP. Department of Anesthesia and Surgical Intensive Care, Alexandria Faculty of Medicine, Alexandria University, Alexandria, Egypt, Advanced Pain Therapeutics of Knoxville, Knoxville, TN, USA. Correspondence author: Mohammad-Hazem I. Ahmad-Sabry MB, ChB MSc FRCPC MD ABPM, Alexandria Faculty of Medicine, Khartoum Square, Shalalat, Alexandria, EGYPT, 21111. Tel: +2016-271-8827 or +203-487-0509, Fax: +203-4842236. Email:[email protected] 51 M.E.J. ANESTH 23 (1), 2015 52 Ahmad-Sabry et. al authors described the condition as a burning pain, which Weir Mitchell later described as causalgiain 1872 in the Merck Manual for Health Professionals3. Thomas and Grossberg explained the multimodal therapies and treatments used for Alzheimer’s disease, including memantine which was discovered 19684. Siniset al. (2007) published his preliminary report on the use of memantine in complex regional pain syndrome with promising results5. Scheleyet al.’s (2007) experiment with memantine in patients with phantom limb pain, in combination with continuous brachial plexus blocks, showed a decrease in phantom pain up for to six months6. However, treating CRPS remains an off-label use for memantine. In this study, we evaluated the use of memantine in patients with complex regional pain syndrome. hallucinations, wild dreams, and psychotic ideations were the frequent complaints while on memantine. The mean age of the participants was 46.0 ± 9.7 years. The average number of years since the participants’ diagnoses of CRPSwas9.24 ± 5.7 years. Memantine was started at 5 or 10mg QHS, before being increased by 5 or 10mg every 4-7 days, as tolerated, up to a maximum level of 40mg, or 60mg if a better response was achieved with no side effects. No changes were made in any of the patients’ current poly-pharmacy treatment plans for CRPS during the experiment until the patients asked for to stop or decrease their non-experimentalmedications. Before the starting memantine, all of our patients had been taking a large variety of CRPS treatments including: Several diagnostic/therapeutic sympathetic blocks (all patients), and/or continuous sympathetic blocks (if possible, some patients). Patients and methods We reviewed the charts of patients with diagnosed with CRPS that were treated in our clinic from 2007 until 2009. In all, 56 CRPS patients (52 CRPS I, four CRPS II) were treated with memantine, including 34 females and 22 males. Retrospective, open label data and results were gathered from treating our patients during at least two years of follow-up after beginning memantine. All patients consented to the off label use of memantine for the treatment of CRPS. Table 2 Paired Samples Statistics Std. Error Mean Std. Deviation N Mean .20065 1.40456 49 8.1633 VASB 0.44134 3.08937 49 3.5510 VASA .29776 2.08432 49 7.7755 Burn B .41853 2.92973 49 3.7143 Burn A Table 1 Patient Demographics Percentage Frequency 42.9 21 Male 57.1 28 Female 100.0 49 Total Patients received a minimum dose of 40mg/day60mg/day, as long as a better response was achieved with no side effects. Seven patients were excluded from the study because they did not tolerate a memantine dose of even 5 mg a day. Five of the seven patients had already been diagnosed with bipolar affective disorder at least two years prior to their CRPS diagnosis and were on antipsychotic medications and mood stabilisers prior to receiving the memantine. Severe A number of months of proper physical therapy. Psychological therapy, if needed. Extensive poly-pharmacy therapy: membrane stabilisers, NSAIDS, anti-depressants, muscle relaxants, alpha-2 agonists, alpha-1 antagonists, steroids, opioids and/or biphosphonats. A few had intrathecal delivery systems ([opioids/ baclofen/clonidine/local anaesthetic] combinations). A few had epidural Dorsal Column Stimulation for pain modulation. A few had a combination of treatments five and six. Each patient was encouraged to maximise participation in daily living activities. Effects of Memantine on Pain in Patients with Complex Regional Pain Syndrome-A Retrospective Study All patients received a monthly evaluation for signs of changes in: Allodynia Burning pain Short-term memory loss Anger level Normalcy in everyday life To assess for burning pain, the following assessments were used: • • • • • 1) Quantitative Visual Analog Scale (VAS) before and after six months on the full dose of memantine. 2)Quantifying the number of exaggerated burning attacks per month on the primary CRPS extremity (patients voted to call these “a 10/10 Fire Storm”). Allodynia was assessed according to the following: 1) Percentage of decrease of the disgusting unpleasing feelingsrelated tosoft touch of the skin of the area affected by CRPS. 2)For the patients that enjoyed taking a shower prior to the development of CRPS,the time spent in the shower from before and after six months on memantine. To assess for CRPS-related migraine headaches, a quantitative decrease in the numberof migraine attacks/ monthbefore and after six months on memantine was examined. We followed the patients for at least two years after the start of the memantine. Results In all, 56 patients were enrolled in the study, and ultimately, seven were excluded, as they did not tolerate the memantine. Of the patients that were excluded, six were females and one was male. Five of the seven patients had been already diagnosed with bipolar affective disorder at least two years prior to the CRPS diagnosis, and were on antipsychotic medications and mood stabilisers prior to beginning memantine. Severe hallucinations, wild dreams, and psychotic ideations were the frequent complaints related to side effects while on memantine. Out of the 49 patients that continued to use memantine, 21 were male (42.9%) and 27 were female (57.1%). 53 The mean VAS was 8.1633 (SD: 1.40456) before the use of memantine and 3.5510 (SD: 3.08937) after the use of memantine, which was statistically significant at p <0.001. Those that responded positively to the memantine did not ask for any increase in other pain medications, and instead, asked for the dosages of the other medications to be decreased. The mean burning pain was 7.7755 (SD: 2.08432) before the use of memantine and 3.7143 (SD: 2.92973) after the use of memantine, which was statistically significant at p <0.000. Out of 49 patients, 13 (26.5%) showed a complete disappearance of the pain, burning and allodynea. Discussion Memantine is a drug with the ability to block NMDA receptors in the brain. Juliato Piovesan et al. (2008) suggested that memantine was much more potent inhibitor of central and peripheral sensitisation than were non-NMDA antagonists7. Park et al. (2012) tested the drug on trigeminal pain in rats8. Belozertseva and Bespalov (1998), as well as Popik and Kozela (1999), showed that memantine could attenuate the tolerance to morphine in animal models9,10. Davidson and Carlton’s (1998) experiment demonstrated that the local use of memantine in attenuating pain in animal modelswas comparable to the use of dexmethorphan and ketamine11. Eisenberg et al. (1998) failed to find clinical benefits of using memantine for post-herpetic neuralgia when using doses of 10-20mg/day12. Nikolajsen et al. (2000), in a randomised cross-over study,could not find any difference when using 20mg/ day of memantine after amputation or nerve injury surgery13. Siniset al. (2007) published preliminary results in human patients with CRPSthat had good responsesto the medication when using 20 mg/day5. Scheleyet al. (2007) found a decrease in the medication requirements, as well as in the phantom limb pain, when using memantine at doses of 20-30mg/day compared to those people that did not use the drug6. Grande et al. reported the use of memantine with small doses of ketamine for opioid tolerant oncology patients, demonstrating less opioid consumption at memantine doses of 20mg a day, and recommended more studies be done in this area14. Thomas and Grossberg (2009) M.E.J. ANESTH 23 (1), 2015 54 recommended the use of memantine for Alzheimer’s disease and other neuropsychiatric diseases due toits level of safety4. Olivan-Blázquezet al. (2014) found promising results for memantine use at doses of 20g/ day when used for fibromyalgia15. We used the memantine in our practice for resistant cases of CRPS and used largerdoses than what was recommended for use in patients with Alzheimer’s disease (40mg/day), which could be why other studies results did not show the same benefits. Also, in our study, the pathology was different than in Ahmad-Sabry et. al the other studies, which might also contribute to the conflicting results. Our study was limited in the lack of randomisation with a controlled group that used aplacebo. However, in our study, we compared the same patient before and after the use of memantine, using the patients’ data before the treatment as the control. We concluded that memantine is effective and is a promising option for the treatment of CRPS. More studies are needed using blinding, randomisation and possibly placebo procedures. References *. Partially published as an abstract presentation in the 8th Congress of European Federation of IASP Chapter (EFIC) October 9-12, 2013 in Florence, Italy. 1. Bowsher D: (1991) Neurogenic pain syndromes and their management. Brit Med Bull; 1991, (47):644-666. 2. Richards RL: (1967) The term causalgia. Medical History; 11(1):8690. 3. Russell K, Portenoy: (Feb 2012) Neuropathic pain. Merck Manual for Healthcare Professionals. 4. Thomas S, Grossberg T: (2009) Memantine: A review of studies into its safety and efficacy in treating Alzheimer’s disease and other dementias. ClinInterv Aging; 4:367-377. 5. Sinis N, Birbaumer N, Gustin S, Schwarz A, Bredanger S, Becher ST, Unertl K, Schaller HE, Haerle M: (2007) Memantine treatment of CRPS, A preliminary report of 6 cases. Clin J Pain; 23:237-243. 6. Scheley M, Topfner S, Wiech K, Schaller H, Konrad C, Schmelz M, Birbaumer N: (2007) Continuous brachial plexus blockade in combination with the NMDA receptor antagonist memantine prevents phantom pain in acute traumatic upper limb amputees. Eur J Pain; 2007, Apr: 11(3):299-308. Epub 2006 May 22. 7. Piovesan EJ, Randunz V, Utiumi M, Lange MC, Kowacs PA, Mulinari RA, Oshinsky M, Vital M, Sereniki A, Fernandes AF, Silva LL, Werneck LC: (2008) Influence of NMDA and non-NMDA antagonists on acute and inflammatory pain in the Trigeminal territory. Arq Neuropsiquiatr; 66(4):837-843. 8. Park J, Suh J, Shin H, Park G: (2012) Influence of memantine on nociceptive responses of the trigeminocervical complex after formalin injection. Cephlalgia; 2012 Mar, 32(4):308-16. 9. Belozertseva I, Bespalov A: (1998) Effects of NMDA receptor channel blockers, dizocilpine and memantine, on the development of opiate analgesic tolerance induced by repeated morphine exposures or social defeats in mice. Nauyn Schmiedergs Arch Pharmacol; 358(2):270-4. 10.Popik P, Kozela E: (1999) Clinically available NMDA antagonist, memantine, attenuates tolerance to analgesic effects of morphine in a mouse tail flick test. Pol J Pharmacol; 1999 May-Jun, 51(3):22331. 11.Davidson E, Carlton S: (1998) Intraplantar injection of dextrorphan, ketamine or memantine attenuates formalin-induced behaviors. Brain Res;1998 Feb, 23:785(1):136-42. 12.Eisenberg E, Kleiser A, Dortort A, Haim T, Yarnitsky D: (1998) The NMDA (N-methyl-D-aspartate) receptor antagonist memantine in the treatment of postherpetic neuralgia: A double-blind, placebocontrolled study. Eur J Pain; 2(4):321-327. Nikolajsen L, Gottrup H, Kristensen A, Jensen T: (2000) 13. Memantine (a N-Methyl-D-Aspartate receptor antagonist) in the treatment of neuropathic pain after amputation or surgery: A randomized, double-blinded, cross-overstudy. Anesth Analg; 91:960-6. 14.Grande L, O’Donnell B, Fitzgibbon D, Terman G: (2008) Ultralow dose ketamine and memantine treatment for pain in an opioidtolerant oncology patient. Anesth Analg; 107:1380-3. 15.Olivan-Blázquez B, Herrera-Mercadal P, Puebla-Guedea M, Pérez-Yus MC, Andrés E, Fayed N, López-Del-Hoyo Y, Magallon R, Roca M, Garcia-Campayo J: (2014) Efficacy of memantine in the treatment of fibromyalgia: A double-blind, randomised, controlled trial with 6-month follow-up. Pain; 2014 Dec, 155(12):2517-25. Effects of dexamethasone and pheniramine maleate on hemodynamic and respiratory parameters after cementation in cemented partial hip prosthesis Abdulkadir Yektaş*, Funda Gümüş*, Tolga Totoz*, Nurten Gül*, Kerem Erkalp* and Ayşin Alagöl* Summary Purpose: To prevent hemodynamic and respiratory changes that are likely to occur during cementation in partial hip prosthesis by prophylactic use of pheniramine maleate and dexamethasone. Methods and Materials: The study included 40 patients aged between 60 and 85 years with an American Society of Anesthesiologists (ASA) grade of II-III who underwent partial hip prosthesis. Just after spinal anesthesia, 4 mL normal saline was pushed in patients in Group S, whereas 45.5 mg pheniramine maleate and 8 mg dexamethasone mixture was pushed intravenously in a total volume of 4mL in patients in Group PD. Results: Amounts of atropine and adrenaline administered after cementation were significantly higher in Group S than in Group PD (P <0.05). There was a significant difference between SpO2 values before and after cementation in Group S; SpO2 value was lower after cementation (P <0.05) except for 1. min after cementation. SpO2 value increased 1 min after cementation (P = 0.031) Conclusion: Prophylactic use of pheniramine maleate and dexamethasone in partial hip prosthesis led to an increase in SpO2 value and a decrease in the utilization of adrenaline and atropine after cementation. Keywords: Methylmethacrylate, partial hip prosthesis, bone cement implantation syndrome, pheniramine maleate, dexamethasone. Introduction Partial hip arthroplasty is usually performed in elderly population in whom concomitant diseases may enhance the likelihood of a more progressive BCIS (Bone Cement Implantation Syndrome). BCIS is the most important cause of intraoperative morbidity and mortality in patients undergoing cemented hip arthroplasty, and rarely, hypoxia and confusion may be encountered in the postoperative period. Intraoperative mortality rate is 0.43 % for cemented partial hip prosthesis in patients with or without femur fracture1. Although the etiology and pathophysiology of BCIS have not been understood clearly, few mechanisms including monomer-mediated model, embolic model, histamine release and hypersensitivity, complement activation, and multimodal model *Anesthesiology and Reanimation Clinic, Bagcilar Training and Research Hospital, Istanbul, TURKEY. Corresponding author: Abdulkadir Yektas. Address: Bagcilar Egitim ve Arastirma Hastanesi Anesteziyoloji ve Reanimasyon Klinigi 34200 Bagcilar, Istanbul, TURKEY, Tel: + 90 505 388 18 84, Fax: + 90 212 488 69 63. E-mail: [email protected] 55 M.E.J. ANESTH 23 (1), 2015 56 have been suggested. In a study, blockade of histamine receptors by clemastine and cimetidine (H1 and H2 antagonists) was reported to have protective effects3. Pheniramine maleate is an H1 receptor antagonist. H1 receptor antagonists have been successfully used before drug infusion to prevent and for acute treatment of type I hypersensitivity9. Dexamethasone is a synthetic glucocorticosteroid. In animal studies, this glucocorticosteroid has been demonstrated to inhibit airway eosinophilia in the presence of antigen by inhibiting interleukin-5 synthesis and to be successfully used for the prophylaxis of type I hypersensitivity reaction10,11. The aim of the present study is to assess the effect of pheniramine maleate and dexamethasone on incidence of hypotension, bradycardia and hypercarbia associated with BCIS. Methods and Materials After obtaining approval from the Ethical Committee of Bağcılar Training and Research Hospital and written informed consents of the patients, 40 patients aged between 60 and 85 years with an American Society of Anesthesiologists (ASA) grade of II-III who underwent partial hip prosthesis with cement due to femur neck fracture under spinal anesthesia were included in the study. The present study was designed as a prospective, randomized and double-blinded study. Data of the patients regarding age, height, weight, gender, concomitant diseases, medications, smoking status, ASA classification and surgery duration of surgery were recorded. Patients with allergic diseases, those using antiallergic medications or corticosteroids, who have deep venous thrombosis and lower extremity venous insufficiency, those with cardiac disease likely to cause atrial fibrillation or thromboembolism, or paraplegiahemiplegia, who were immobile before fracture (i.e., bedridden patients), those with previous cardiac surgery, and those having a contraindication for regional anesthesia were excluded from the study. The patients did not receive any premedication. The patients were positioned with the hip that would be A.Yektas et. al operated being on top, and an 18 G intravenous canula was placed into a pheripherial vein in the dorsal aspect of the hand opposite to the surgery side and 0.9% NaCl was administreted at a rate of 10 mL kg-1 h-1 for first hour and than 5 mL kg-1 h-1. In order to obtain blood sample for blood gas analysis, an intra-arterial catheter was inserted into the radial artery of the arm on the surgery side via a 20-gauge intravenous catheter, and it was washed with heparinized fluid and closed using a three-way tap. The patients were administrated oxygen at a rate of 2 L/min through a free oxygen mask which was fixed hole in any side of the free oxygen mask in which the free end of end-tidal CO2 (ET-CO2) line. All patients underwent electrocardiography, non-invasive arterial blood pressure measurement, peripheral pulse oximetry and end-tidal CO2 monitoring. All patients underwent spinal anesthesia. Patients in both groups were positioned laterally with the leg that would be operated being on top, and spinal anesthesia was performed via a 27-gauge Quincke-type needle after performing cutaneous-subcutaneous infiltration anesthesia using 2 mL of 2% lidocaine through L4L5 space. After observing cerebrospinal fluid (CSF) outflow, 1 mL (5 mg) isobaric bupivacaine and 25 µg (0.5 mL) fentanyl were administered in a total volume of 1.5 mL. Spinal anesthesia was performed by a specialist in both groups. The patients in whom spinal anesthesia was unsuccessful three times were excluded from the study. Then the patient were randomly divided into the following two groups using sealed envelopes: 1) Group S (n = 20) patients were administrated 4 mL of normal saline, 2) Group PD (n = 20) patients were administrated 45.5 mg pheniramine maleate and 8 mg dexamethasone. Prior to spinal anesthesia, basal values of arterial blood pressure, heart rate, oxygen saturation by pulse oximeter (SpO2), end-tidal CO2 (ETCO2), and blood gases were recorded. Pre-prepared syringes were used; thus, both the anesthesiologist and the patient were blinded to the content. Cephazoline sodium 1 g was administered iv approximately 30 to 60 min prior to surgery for prophylaxis. Values of arterial blood pressure, heart rate, SpO2, end-tidal CO2, and blood gases were recorded for all patients prior to surgical procedure and at 10min intervals until the first minute before cementation. Dexamethasone & pheniramine in hip prosthesis 57 Amount of bleeding, amount of crystalloid administered by IV route, and, if used, doses of atropine and adrenaline were also recorded until the first minute before cementation. Those parameters were recorded at 1-min intervals in the first 5 min after cementation and then every 5 minutes. Measurements were discontinued at the 25th min after cementation. Amount of administered crystalloid throughout the surgical procedure and amount of bleeding were recorded. Arterial blood gases were analyzed before spinal anesthesia, just before cementation, and at the 10th and 25th min after cementation. of bleeding throughout surgery before and after cementation, amount of crystalloid, amount of atropine and adrenaline were compared between the groups by an independent-t test.. Data analyses were performed using the Statistical Package for the Social Sciences (SPSS, Inc. Chicago, IL, USA) version 11.5. A P value <0.05 was considered statistically significant. A 5 µg adrenalin was pushed via venous route in the following conditions: 1) a decrease in mean blood pressure more than 30% of the initial value until cementation, 2) after cementation, a more than 30% decrease in the blood pressure value measured before cementation. In case of a decrease in heart rate below 50 beats/min, 0.5 mg atropine was injected. Patients in whom amount of bleeding before cementation exceeded 400 mL were excluded from the study (bleeding before cementation exceeded 400 mL in any of the patients), and blood loss was replaced by normal saline. When the surgical procedure was completed and following postoperative observation, patients with a modified Aldrete score of ≥9 were transferred to the clinic. Statistical Analysis Based on a preliminary study performed in 10 patients, we estimated that a sample size of 20 patients in each group would be sufficient with a 5% error and a statistical power of 80% assuming that the mean arterial pressure on the 25th min would be 92 ± 15 mmHg in Group PD and 85 ± 15 mmHg in Group S. Descriptive statistics of data were expressed as mean ± standard deviation. Normal distribution of variables was tested by Kolmogorov Smirnov test. Comparison of data regarding age, height, weight, gender, type of surgery, duration of surgery, time elapsed from spinal anesthesia to cementation, and ASA grades were performed using the Chi square test. Heart rate, arterial blood pressure values, SpO2, end-tidal CO2 and blood gas measurements, amount Results Distributions of age, weight, height, type of surgery, duration of surgery, duration of cementation, ASA grades and gender in the study groups are presented in Table 1. There were no statistically significant differences between the groups in terms of age, weight, height, type of surgery, duration of surgery, duration of cementation, ASA grade and gender. Table 1 Distribution of age, weight, height, type of surgery, duration of surgery, duration of cementation, the American Society of Anesthesiologists grades and gender in the study groups. Data are presented as mean ± SD Group S (n = 20) Group PD (n = 20) P Age (years) 80.50 ± 7.05 76.85 ± 9.31 0.198 Weight (kg) 70.75 ± 11.14 70.60 ± 10.45 0.989 Height (cm) 168.45 ± 8.40 166.35 ± 5.65 0.462 Duration of surgery (min) 79.30 ± 27.29 84.55 ± 18.01 0.579 Duration of cementation (min) 61.60 ± 22.87 64.35 ± 10.55 0.968 ASA (II/III) 14/6 13/7 0.708 Gender (F/M) 11/9 12/8 0.061 SD: standard deviation; ASA: the American Society of Anesthesiologists; F: female; M: male Doses of atropine and adrenaline and the amounts of intravenous fluid and bleeding in the study groups are presented in Table 2. The dose of adrenaline used M.E.J. ANESTH 23 (1), 2015 58 A.Yektas et. al Table 2 Distribution of amounts of atropine, adrenaline, and intravenous fluid, and the amount of bleeding in the study groups. Numbers are presented as mean ± SD. Group S (n = 20) Group PD (n = 20) P Adrenaline after cementation (µg) 4.50 ± 11.34 0.75 ± 1.83 0.022 Atropine after cementation (mg) 0.25 ± 0.91 0.00 ± 0.00 0.014 Intravenous crystalloid before cementation (mL) 560.50 ± 206.33 480.00 ± 176.51 0.345 Intravenous crystalloid surgical procedure (mL) 890.00 ± 282.65 827.50 ± 181.71 0.274 Amount of bleeding before cementation (mL) 184.25 ± 96.99 158.75 ± 77.01 0.243 Total amount of bleeding (mL) 228.75 ± 118.73 211.00 ± 77.50 0.059 administered throughout SD: standard deviation after cementation was significantly higher in Group S than in Group PD (P = 0.022). The dose of atropine used after cementation was significantly higher in Group S than in Group PD (P = 0.014). pH (P = 0.102), PaCO2 (P = 0.063), PaO2 (P = 0.175) and end-tidal CO2 values (P = 0.448) and 25th min pH (P = 0.193), PaCO2 (P = 0.186), PaO2 (P = 0.084) and endtidal CO2 values (P = 0.054) min after cementation. Comparison of the study groups in terms of systolic diastolic and mean arterial pressures, heart rate and SpO2 before and after cementation are presented in Table 3. There were no statistically significant differences between the groups in terms of systolic/ diastolic and mean arterial pressure, heart rate and SpO2. Heart rate increased significantly 2 min after cementation in Group PD when compared to before (p = 0.008) (Table 3). One patient in Group S developed cardiopulmonary arrest at the 1st min after cementation and accepted as dead after performing cardiopulmonary resuscitation (CPR) for 45 min. Blood gas values and end-tidal CO2 values of this case was not consistent with pulmonary embolus. In Group S, SpO2 increased 1 min after cementation (P = 0.031), and were significantly lower at the rest of all times when compared to the value before cementation (P = 0.003, P = 0.003, P <0.001, P = 0.003, P = 0.001, P = 0.001, P = 0.001, P = 0.004, respectively) (Table 3). There were no significant differences between Group S and Group PD in terms of PH (P = 0.168), partial arterial carbon dioxide pressure (PACO2) (P = 0.067), partial arterial oxygen pressure (PAO2) (P = 0.056) and end-tidal CO2 values before cementation and at the 10th (P = 0.067) and 25th (P = 0.152) min after cementation. In addition, there were no significant differences in both groups in terms of pH, PaCO2, PaO2 and endtidal CO2 values before cementation, and at the 10th min All patients were transferred to the clinic after observing postoperatively in recovery room for 2 hours and then all patients were discharged. None of the patients developed postoperative hypoxia or confusion. Discussion Respiratory and cardiovascular changes during partial hip replacement seriously affect the prognosis of patients. These changes exist in a wide spectrum of disorders ranging from temporary hypoxia to cardiac rhythm disorders and even cardiac arrest12,13. Several mechanisms have been suggested in the etiology and pathophysiology of BCIS including monomer-mediated model, embolic model, histamine release and hypersensitivity, complement activation, and multimodal model2. A study has shown that implantation of methacrylic bone cement into the femur may increase plasma histamine level by more than 1 ng/mL. Temperate histamine release may cause severe, 97.2 ± 2.4 97.5 ± 2.8 S PD 84.4 ± 18.7 76.4 ± 13.0 S PD 85.4 ± 21.8 93.8 ± 20.7 S PD 71.8 ± 16.5 PD 76.4 ± 21.0 S 96.3 ± 2.9 97.8 ± 2.8 87.1 ± 21.8 79.4 ± 18.9 81.7 ± 16.9 83.1 ± 22.1 69.8 ± 15.6 69.9 ± 17.7 125.6 ± 22.1 124.0 ± 26.0 137.4 ± 27.0 127.2 ± 28.3 1.min PD S Before C 95.9 ± 3.2 92.6 ± 21.9* 95.1 ± 24.5* 76.1 ± 23.9 81.7 ± 16.9 88.3 ± 20.7 67.0 ± 14.3 73.6 ± 17.4 118.8 ± 27.6 128.2 ± 24.4 2.min 96.0 ± 3.0 92.1 ± 21.9* 86.9 ± 22.2 75.7 ± 24.0 78.9 ± 17.4 87.9 ± 25.3 67.8 ± 13.6 74.3 ± 21.8 121.1 ± 22.9 127.2 ± 25.9 3.min 5.min 10.min 87.6 ± 19.3 74.4 ± 23.1 81.9 ± 15.8 89.5 ± 20.6 68.0 ± 13.6 74.0 ± 20.1 87.3 ± 17.9 75.1 ± 25.7 87.7 ± 15.8 91.8 ± 26.3 70.9 ± 12.4 74.2 ± 21.4 95.8 ± 2.8 95.9 ± 2.8 95.6 ± 2.9 92.2 ± 21.9* 92.7 ± 21.9* 92.7 ± 21.9* 88.3 ± 18.7 74.7 ± 24.6 79.5 ± 16.2 91.6 ± 27.2 67.9 ± 15.4 74.3 ± 23.1 122.1 ± 22.7 119.9 ± 34.1 132.8 ± 20.3 130.3 ± 28.3 131.5 ± 25.5 135.3 ± 24.3 4.min 87.1 ± 17.5 87.41 ± 7.9 93.4 ± 9.8 95.5 ± 3.3 96.0 ± 2.6 92.7 ± 22.0* 81.5 ± 27.5 85.2 ± 19.9 84.4 ± 13.9 81.2 ± 27.2 92.4 ± 25.3 68.4 ± 12.1 69.1 ± 11.6 89.9 ± 18.5 70.6 ± 20.8 72.2 ± 19.01 92.2 ± 21.9* 92.5 ± 21.9* 88.4 ± 20.3 79.7 ± 25.1 90.8 ± 14.9 93.2 ± 26.1 70.7 ± 11.8 72.9 ± 21.4 131.6 ± 22.2 134.6 ± 23.5 131.6 ± 23.9 25.min 133.6 ± 26.1 20.min 130.2 ± 28.4 135.1 ± 24.1 15.min SAP: Systolic Arterial Pressure; DAP: Diastolic Arterial Pressure; MAP: Mean Arterial Pressure; HR: Heart Rate; SpO2: Peripheral Oxygen Saturation; Group; S: Saline; Group; PD: pheniramine maleate-dexamethasone; Before C: Before cementation. There is no statistical difference between groups (P >0.05) * P <0.05 when compared with Before Cementation. SpO2 HR MAP DAP SAP Group Table 3 Systolic, Diastolic and Mean Arterial Pressure, Heart Rate and Peripheral Oxygen Saturation (Mean ± SD) Dexamethasone & pheniramine in hip prosthesis 59 M.E.J. ANESTH 23 (1), 2015 60 sometimes fatal, cardiovascular complications in very old patients in case they have signs of hypovolemia or cardiac diseases3. Cardiac problems defined to date have been mostly about wall motion and rhythm disorders, with no remarkable changes in heart rate14,15. We also found no significant difference between heart rates before and after cementation; heart rate at the 2nd min after cementation was higher than before cementation only in Group PD. In Group S, as compared with before cementation, heart rate decreased by 0.40% at the 2nd min, 1% at the 3rd min, 2.5% at the 4th min and 3.1% at the 5th min, but thereafter returned to the normal values. The dose of atropine administered was significantly higher in Group S than in Group PD. However, as heart rate was recorded with 5-min intervals, such decrements in HR were not reflected in the statistical analysis. In Group PD, an increase in the heart rate was observed by 12.73% at the 2nd min (P <0.05), 3% at the 3rd min, 4.62% at the 4th min and 3.79% at the 5th min. Potential causes of hypotension, one of the parameters of BCIS, include histamine release and type I hypersensitivity reaction, or hemodynamic impairment caused by pulmonary air or by fat embolism and reflex mechanisms responsive to this16,17. An experimental study has demonstrated that methylmethacrylate monomers influence intracellular and extracellular calcium mobilization, resulting in direct relaxation in venous and arterial smooth muscles18,19. Nevertheless, this hypothesis has not been verified by in vivo animal experiments and it has been determined that plasma methylmethacrylate concentration after cemented hip arthroplasty is lower than the concentration that is likely to cause pulmonary or cardiovascular effects20,21. A clinical study evaluating plasma concentrations revealed that maximum levels of serum methylmethacrylate was measured 30 s after cementation and this was thought to cause a decrease in arterial blood pressure20. Another study compared non-cemented hip arthroplasty with cemented hip arthroplasty using transesophageal echocardiography and demonstrated a higher embolic load in the cemented hip arthroplasty group22. The authors concluded that, embolism might also cause hypotension due to increase in pulmonary arterial pressure together with decrease in right ventricular function23. In the present A.Yektas et. al study, there were no significant differences between the groups in terms of the amounts of crystalloid and bleeding before cementation and throughout the surgical procedure. The amount of adrenaline administered in Group S was significantly higher than that administered in Group PD; however, as blood pressure was measured at specific time intervals, such variations in blood pressure had no impact on the statistical outcomes. A patient in Group S developed hypotensive bradycardic arrest at the 1st min after cementation, which was not responsive to CPR. There were no significant differences in PaO2, pH, PaCO2 and endtidal CO2 values of this patient before cementation and during CPR performed after cementation; this ruled out the possibility of massive embolism. In the present study, despite oxygen provided through a free oxygen mask at a rate of 2 L/min in both groups, there was a significant difference between SpO2 values before and after cementation in Group S. An increase by 0.25% at the 1st min after cementation and a decrease by 7.1% at the 2nd min after cementation were observed, and this decrease continued until the end of surgery in the same manner. Various studies have demonstrated hypoxia development during hip and knee arthroplasty24,25. This has been thought to result from pulmonary embolism or pulmonary vasoconstriction due to cement toxicity21,26. In the present study, there was no significant difference between SpO2 values before and after cementation in Group PD; this suggests that dexamethasone and pheniramine maleate prevented bronchospasm resulted from pulmonary vasoconstriction caused by cement toxicity and pulmonary embolism. Studies performed after observation of intraoperative deaths occurred during cemented arthroplasty have demonstrated the presence of bone marrow embolism, fat embolism and bone embolism and methylmethacrylate particles in the lungs27,28,29. Medulla residue may cause embolism in the lungs, heart or paradoxically in the brain and coronary arteries30,31. This suggests that hypotension occurs due to characteristic hypoxia and right ventricular dysfunction as the consequence of pulmonary embolism21. However, a definite correlation could not be established in the literature between the degree of embolism detected by performing transesophageal Dexamethasone & pheniramine in hip prosthesis echocardiography and the severity of hypoxia22. It has been reported that blood cement monomer levels do not reach high concentrations that likely can cause toxicity in human32, in which both mechanisms are considered to play a role. Among anaphylatoxins, C3a and C5a are potent mediators that lead to vasoconstriction and bronchoconstriction33. The levels of C3a and C5a have been observed to increase in cemented hemiarthoplasties by complement activation33. In human studies, high dose (2g) methylprednisolone have been demonstrated to reduce hypoxia and complement activation. The decreases in anaphylatoxin release and oxygen saturation are reduced by methylprednisolone33. However, whether methylmethacrylate particles or embolus material causes complement activation is not clear. Complement 61 levels were not studied in the present study. We thought that complement activation might have been prevented by dexamethasone, due to the less decrease in hemodynamic values-although no statistically difference was found, but clinically important-1 min after cementation and lack of desaturation in Group PD In conclusion, the dose of adrenaline and atropine used after cementation was significantly lower and, SpO2 values were stable after cementation in Group PD; on the other hand, in Group S, SpO2 values decreased after cementation, except for 1. min after cementation. SpO2 value increased 1 min after cementation. This suggests that prophylactic administration of pheniramine maleate and dexamethasone may minimize the clinical symptoms of BCIS. M.E.J. ANESTH 23 (1), 2015 62 A.Yektas et. al References 1. Parvizi J, Holiday AD, Ereth MH, Lewallen DG: The Frank Stinchfield Award. Sudden death during primary hip arthroplasty. Clin Orthop Relat Res; 1999, 309:39-48. 2. Donaldson AJ, Thomson HE, Harper NJ, Kenny NW: Bone cement implantation syndrome. Br J Anaesth; 2009, 102:12-22. 3.Tryba M, Linde I, Voshage G, Zenz M: Histamine release and cardiovascular reactions to implantation of bone cement during total hip replacement (in German with English abstract). Anaesthetist; 1991, 40:25-32. 4. Lamadé WR, Friedl W, Schmid B, Meeder PJ: Bone cement implantation syndrome. A prospective randomised trial for the use of antihistamine blockade. Arch Orthop Trauma Surg. 114: 335– 339, 1995. 5. Mitsuhata H, Saitoh J, Saitoh K, Fukuda H, Hirabayasi Y, Shimizu R, Hasegawa J, Matsumoto S, Enzan K: Methylmethacrylate bone cement dose not release histamine in patients undergoing prosthetic replacement of femoral head. Br J Anaesth; 1994, 73:779-781. 6. Fries IB, Fisher AA, Salvati EA: Contact dermatitis in surgeons from methylmethacrylate bone cement. J Bone Joint Surg Am; 1975, 57:547-548. 7. Jensen JS, Trap B, Skydsgaard K: Delayed contact hypersensitivity and surgical glove penetration with acrylic bone cements. Acta Orthop Scand; 1991, 62:24-28. 8. Rumpf KW, Rieger J, Jansen J, Scherer M, Seubert S, Seubert A, Sellin HJ: Quincke’s edema in a dialysis patient after administration of acrylic bone cement: possible role of ethylene oxide allergy. Arch Orthop Trauma Surg; 1986, 105:250-252. 9. DE Silva HA, Pathmeswaran A, Ranasinha CD, Jayamanne S, Samarakoon SB, Hittharage A, Kalupahana R, Ratnatilaka GA, Uluwatthage W, Aronson JK, Armitage JM, Lalloo DG, De Silva HJ: Low-dose adrenaline, promethazine, and hydrocortisone in the prevention of acute adverse reactions to antivenom following snakebite: a randomised, double-blind, placebo-controlled trial. PLos Med; 2011, 8: e1000435. 10.Eum SY, Créminon C, Hailé S, Lefort J, Vargaftig BB: Inhibition of airways inflammation by dexamethasone is followed by reduced bronchial hyperreactivity in BP2 mice. Clin Exp Allergy; 1996, 26:971-979. 11.Fürll M, Wujanz G, Strauch A, Drechsel J: Anaphylactic shock in swine. 5. Studies on the prophylactic effect of dexamethasone and dexamethasone-metapyrine combination (in German with English abstract). Arch Exp Veterinarmed; 1986, 40:445-452. 12.Fallon KM, Fuller JG, Morley-Forster P: Fat embolization and fatal cardiac arrest during hip arthroplasty with methylmethacrylate. Can J Anaesth; 2001, 48:626-629. 13.Duncan JA: Intra-operative collapse or death related to the use of acrylic cement in hip surgery. Anaesthesia; 1989, 44:149-153. 14.Propst JW, Siegel LC, Schnittger I, Foppiano L, Goodman SB, Brock-Utne JG: Segmental wall motion abnormalities in patients undergoing total hip replacement: correlations with intraoperative events. Anesth Analg; 1993, 77:743-749. 15.Vazeery AK, Skeie S, Anda O: Changes in cardiac output and systemic arterial pressure after insertion of acrylic cement during trimetaphan, sodium nitroprusside and glycerol trinitrate-induced hypotension. A comparison with changes during normotension. Br J Anaesth; 1983, 55:783-790. 16.Rinecker H: New clinico-pathophysiological studies on the bone cement implantation syndrome. Arch Orthop Trauma Surg; 1980, 97:263-74. 17.Dahl EO: Cardiorespiratory and vascular dysfunction related to major reconstructive orthopedic surgery. Arch Orthop Scand; 1997, 68:607-614. 18.Karlsson J, Wendling W, Chen D, Zelinsky J, Jeevanandam V, Hellman S, Carlsson C: Methylmethacrylate monomer produces direct relaxation of vascular smooth muscle in vitro. Acta Anaesthesiol Scand; 1995, 39:685-689. 19.Peebles DJ, Ellis RH, Stride SD, Simpson BR: Cardiovascular effects of methylmethacrylate cement. Br Med J; 1972, 1:349-351. 20.Svartling N, Pfäffli P, Tarkkanen L: Methylmethacrylate blood levels in patients with femoral neck fracture. Arch Orthop Trauma Surg; 1985, 104:242-246. 21.Orsini EC, Byrick RJ, Mullen JB, Kay JC, Waddell JP: Cardiopulmonary function and pulmonary microemboli during arthroplasty using cemented or non-cemented components. The role of intramedullary pressure. J Bone Joint Surg Am; 1987, 69:822832. 22.Ereth MH, Weber JG, Abel MD, Lennon RL, Lewallen DG, Ilstrup DM, Rehder K: Cemented versus noncemented total hip arthroplasty--embolism, hemodynamics, and intrapulmonary shunting. Mayo Clin Proc; 1992, 67:1066-1074. 23.Urban MK, Sheppard R, Gordon MA, Urquhart BL: Right ventricular function during revision total hip arthroplasty. Anesth Analg; 1996, 82:1225-1229. 24.Lewis RN: Respiratory complications of bone cement insertion during total hip replacement under spinal anaesthesia. Eur J Anaesthesiol; 1997, 14:52-54. 25.Nolan JP: Arterial oxygenation and mean arterial blood pressure in patients undergoing total hip replacement: cemented versus uncemented components. Anaesthesia; 1994, 49:293-299. 26.Taira M, Nakao H, Matsumoto T, Takahashi J: Cytotoxic effect of methyl methacrylate on 4 cultured fibroblasts. Int J Prosthodont; 2000, 13:311-315. 27.Sevitt S: Fat embolism in patients with fractured hips. Br Med J; 1972, 2:257-262. 28.Byrick RJ, Mullen JB, Mazer CD, Guest CB: Transpulmonary systemic fat embolism. Studies in mongrel dogs after cemented arthroplasty. Am J Respir Crit Care Med; 1994, 150:1416-1422. 29.Wheelwright EF, Byrick RJ, Wigglesworth DF, Kay JC, Wong PY, Mullen JB, Waddell JP: Hypotension during cemented arthroplasty. Relationship to cardiac output and fat embolism. J Bone Joint Surg Br; 1993, 75:715-723. 30.Lafont ND, Kalonji MK, Barre J, Guillaume C, Boogaerts JG: Clinical features and echocardiography of embolism during cemented hip arthroplasty. Can J Anaesth; 1997, 44:112-117. 31.Ries MD, Lynch F, Rauscher LA, Richman J, Mick C, Gomez M: Pulmonary function during and after total hip replacement. Findings in patients who have insertion of a femoral component with and without cement. J Bone Joint Surg Am; 1993, 75:581-587. 32.Bengtson A, Larsson M, Gammer W, Heideman M: Anaphylatoxin release in association with methylmethacrylate fixation of hip prostheses. J Bone Joint Surg Am; 1987, 69:46-49. 33.Gammer W, Bengtson A, Heideman M: Inhibition of complement activation by high-dose corticosteroids in total hip arthroplasty. Clin Orthop Relat Res; 1998, 236:205-209. Effect of preoperative oral pregabalin on postoperative pain after mastectomy Mardhiah Sarah Harnani Mansor and C hoy Y in C hoy ** Abstract Background: This was a randomized, double-blinded clinical trial to study the effects of a single oral dose of pregabalin 150 mg in postoperative pain management after mastectomy. Methods: Design: forty nine patients ASA I or II, aged between 20-60 years, scheduled for mastectomy with or without axillary lymph nodes dissection (ALND) were recruited into this study. They were randomized into two groups, placebo (n = 24) or pregabalin (n = 25) receiving either oral pregabalin 150 mg or placebo when called to operation theatre (OT). The assessment of pain score were performed at recovery, 2, 4, 6 and 24 hours postoperatively at rest and on movement, using the verbal numeral rating score (VNRS). Results: VNRS scores for pain at rest were lower in the pregabalin group at 2 (p = 0.024), 4 (p = 0.006) and 6 (p = 0.003) hours postoperatively, and also at 4 (p = 0.005) and 6 (p = 0.016) hours postoperatively on movement compared to the placebo group. Incidences of dizziness were common, however, side effects such as nausea and vomiting, headache, somnolence and visual disturbance were low and comparable in both groups. Conclusion: a single dose of 150 mg pregabalin given preoperatively compared to placebo significantly reduced postoperative pain scores after mastectomy. Keywords: pregabalin, postoperative pain, mastectomy, opioid. Introduction Preventive analgesia is a treatment approach that aims to reduce the development of central sensitization in the postoperative period by reducing peripheral nociceptive input into the central nervous system, thus reducing postoperative pain and analgesics consumption. The concept of preventive analgesia includes multimodal antinociceptive techniques with analgesics that exceed the expected duration of action and also attenuate peripheral or central hypersensitivity2,3,4. Effective methods include systemic NSAIDs, single dose epidural analgesia, systemic NMDA receptor antagonists, systemic opioids and local anaesthetic infiltration. Gabapentin and pregabalin have been proven to be effective medications in serving these purposes. Pregabalin was originally developed as an antiepileptic drug with an improved pharmacological profile when compared to that of its predecessor gabapentin5. Although gabapentin and pregabalin were first identified as useful in the treatment for neuropathic pain, recent reviews showed that they reduced postoperative acute pain and analgesic consumption as well. Gabapentin has been shown to be an effective analgesic for tonsillectomy, mastectomy and knee arthroplasty6,7,8, * Department of Anaesthesiology and Intensive Care, Universiti Kebangsaan Malaysia Medical Centre. Corresponding author: Choy Yin Choy, e-mail: [email protected] 63 M.E.J. ANESTH 23 (1), 2015 64 however pregabalin appears to be a better option when compared with gabapentin as it has better analgesic efficacy and an improved pharmacokinetic profile9. Pregabalin and gabapentin bind to the α2δ sub-unit of pre-synaptic voltage-gated calcium channels in the spinal cord and brain1,2,3,4,5. By altering calcium currents, it reduces or modulates the release of several excitatory neurotransmitters including glutamate, norepinephrine, substance P and calcitonin generelated peptide, producing inhibitory modulation of ‘over-excited’ neurons and returning them to a normal state. One advantage of pregabalin in clinical use is that it has higher bioavailability when giving orally with linear pharmacokinetics property compared to gabapentin. It is rapidly and extensively absorbed after oral dosing in the fasting state with maximal plasma concentration occurring within 1 hour after single or multiple doses9. Absorption of gabapentin is limited by saturable, active and dose dependent transport in gastrointestinal tract but absorption of pregabalin is not saturable, resulting in a linear pharmacokinetic profile with bioavalability exceeding 90% and independent of dose3,5. In recent years, pregabalin has been introduced as an adjunct in multimodal management of postoperative analgesia in many studies because of its favourable pharmacokinetics10-15. The aim of this study was to compare the effect of single-dose 150 mg oral pregabalin to placebo on postoperative pain after mastectomy for breast cancer. Methods This randomized, double-blinded clinical trial was done following approval of the Dissertation Committee of the Department of Anaesthesiology and Intensive Care, Universiti Kebangsaan Malaysia Medical Centre (UKMMC) and the Research Ethics Committee of UKMMC (Research No. FF–444-2012). Forty nine, ASA I or II patients, aged 20 to 60 years who were scheduled for elective mastectomy with or without axillary lymph nodes dissection (ALND) were included in the study. Informed and written consent was obtained from all patients during preoperative anaesthetic assessment a day before surgery. Exclusion criteria included, known contraindication to Mardhiah Sarah Harnani Mansor and Choy Yin Choy medication use in the study, patients with chronic pain or on daily intake of analgesic and impaired kidney function (creatinine level >80 µmol/L). Patients were randomized using computer-generated randomized numbers to receive either pregabalin (Lyrica®) or placebo (vitamin B complex). Information regarding the study and the verbal numerical rating scale (VNRS) range from 0 – 10 was explained to the patients. On the day of surgery, all patients were given premedication of oral midazolam 7.5 mg with either oral pregabalin 150 mg (in 2 tablets) or oral vitamin B complex (in 2 tablets) one hour before being sent to operating room. Patients were instructed to close their eyes before given the test drug to swallow. In the operation theatre, basic monitoring included electrocardiogram (ECG), oxygen saturation (SpO2) and non invasive blood pressure (NIBP). General anesthesia was induced with IV propofol 1.5 – 2.5 mg/kg and IV fentanyl. After the patient was adequately anaesthetized, a supraglottic airway device was inserted. Anaesthesia was maintained with sevoflurane in 50% O2 / 50% air mixture maintaining minimum alveolar concentration (MAC) of 0.8–1.0. Intraoperatively, patients were given IV morphine 0.1– 0.2 mg/kg as an analgesic. Additional IV parecoxib 40 mg was given at the time of skin suturing. Adequate local anesthetic infiltration of levobupivacaine up to 2 mg/kg was given by the surgeon at the incision site. Pain was assessed by independent observer in the recovery area, 2, 4, 6 and 24 hours postoperatively using the VNRS at rest and on movement. In the ward, all patients received oral etoricoxib 120 mg daily with oral paracetamol 1g every 6 hours as a standard analgesic. If the pain score was rated 5 or more, intravenous tramadol 50 mg was given as a rescue medication. Any incidence of side effects such as nausea, vomiting, headache, somnolence, dizziness and visual disturbance were documented. Based on previous study13, with the power of 0.8, alpha value of 0.05 and dropout rate of 10%, the sample size calculated was 60. Statistical analysis and calculations was performed using SPSS for Windows Version 12.0. VNRS pain score and amount of intraoperative morphine used were analysed using Mann-Whitney U-test. Categorical variables such as number of patients needed rescue analgesic and Effect of preoperative oral pregabalin on postoperative pain after mastectomy 65 Table 1 Demographic data values are expressed as mean± SD or number(percentage) Age Placebo (n=24) Pregabalin (n=25) 52.0 ± 8.4 51.5 ± 9.6 Weight (kg) 62.4 ± 8.0 60.2 ± 5.0 Height (cm) 156.9 ± 3.0 156.2 ± 2.8 Race Malay Chinese Indian 12 (50) 8 (33.3) 4 (16.7) 17 (68) 5 (20) 3 (12) ASA I II 12 (50) 12 (50) 15 (60) 10 (40) Type of operation Mastectomy Mastectomy with ALND 6 (25) 18 (75) 6 (24) 19 (76) * p value = 0.024. “ p value = 0.006. ‘ p value = 0.003. incidence of side effects were evaluated with X2 test or Fischer’s exact test. A p value of <0.05 was considered statistically significant. Results Forty nine patients were recruited in this study in which 24 patients were in the placebo group and 25 patients were in the pregabalin group. There were no statistical differences with regards to age, weight, height, race, ASA and type of operation (Table 1). Figure 1 showed VNRS at rest in pregabalin group compared to placebo. There were statistically significant differences at 2, 4 and 6 hours postoperatively. Figure 2 showed VNRS on movement in Fig. 1 postoperative VNRS. values are expressed as mea * p value = 0.024. “ p value = 0.006. ‘ p value = 0.003. M.E.J. ANESTH 23 (1), 2015 66 Mardhiah Sarah Harnani Mansor and Choy Yin Choy Fig. 2 postoperative VNRS. values are expressed as mean * p value = 0.005. “ p value = 0.016. pregabalin group compared to placebo. There were statistically significant differences at 4 and 6 hours postoperatively. There was no statistically significant difference in the mean intraoperative morphine consumption in both placebo group and pregabalin group. Six patients from the placebo group and three patients in the pregabalin group needed tramadol as a rescue drug postoperatively, however the difference was statistically not significant. There was no difference in postoperative oral analgesic consumption for both groups. Adverse effects postoperatively in both groups, which was statistically not significant are presented in table 2. There was no documented incidence of somnolence or visual disturbances in any of the patients. Table 2 Incidence of side effects Placebo n = 24 Pregabalin n = 25 Nausea/vomiting 17 19 Headache 8 7 Dizziness 9 16 Discussion In this current study, we found that preoperative single dose of oral pregabalin 150 mg was effective in reducing both the resting and on movement postoperative pain in patients undergoing mastectomy with or without ALND. Spreng et al, showed a reduction of postoperative pain at rest and morphine consumption from 4 up to 24 hours postoperatively after lumbar discectomy with a single dose of oral pregabalin 150 mg10. In another study, Agarwal et al used a single dose of oral pregabalin 150 mg and effectively reduced postoperative pain and fentanyl consumption in patients undergoing laparoscopic cholecystectomy up to 24 hours11. Jokela et al used oral pregabalin 150 mg preoperative for day-case gynecological laparoscopic surgery and had better analgesia during the early recovery but not sustained up to 24 hours12. A study by Kim et al where mastectomy patients received oral pregabalin 75 mg twice a day showed that there was reduced postoperative pain and analgesic consumption respectively13. That study also showed the ability of divided doses of pregabalin to reduced pain after 48 hours up to 1 week after surgery. Ittichaikulthol et al used a higher dose of oral pregabalin 300 mg preoperatively and showed reduction of pain scores and morphine consumption Effect of preoperative oral pregabalin on postoperative pain after mastectomy for abdominal hysterectomy with or without salphingooophorectomy up to 24 hours post operatively14. However a study by Paech et al using a lower dose of oral pregabalin 100 mg preoperatively was unable to reduce acute pain or improve recovery after minor gynecological surgery15. Most of these studies also showed comparable rescue analgesic needed similar with the current study. A meta analysis on efficacy of pregabalin in acute postoperative pain by Zhang et al concluded that postoperative opioid consumption and opioid related side effects were reduced but pain scores were not reduced. These conflicting results could possibly be due to differences in dosage, dosing regimen, type of surgery, the use of other analgesic regimes such as opioid or non opioids, different anesthetic technique and surgical procedure16. Most studies showed pregabalin to be well tolerated and associated with dose dependent adverse effects that are mild to moderate and usually transient11-15. Different doses of pregabalin have been used in the literature and doses ranging from 75 mg to 300 mg11-17. It has been shown that higher doses 67 are associated with increased frequencies of side effects. The common adverse effects of pregabalin are nausea and vomiting, visual disturbances, headache, dizziness and somnolence. Most of the studies showed no significant adverse effects when a lower dose of pregabalin was used10-14. Nausea and vomiting were the common side effects in the current study followed by headache and dizziness. There were no documented side effects of somnolence or visual disturbances. There are a few limitations in study. The pain score was assessed immediately in the postoperative period in the recovery area which makes it difficult to assess the effects of pregabalin at that point of time. Another confounding factor is the use of IV tramadol as a rescue drug which may affect the assessment of pain score postoperatively and incidence of side effects. Conclusion In conclusion, single dose of 150 mg pregabalin given preoperatively compared to placebo significantly reduced the postoperative pain scores after mastectomy. M.E.J. ANESTH 23 (1), 2015 68 Mardhiah Sarah Harnani Mansor and Choy Yin Choy References 1. Buvanendran A and Kroin JS: Multimodal analgesia for controlling acute postoperative pain. Current Opinion in Anaesthesiology; 2009, 22:588-593. 2. Dahl, JB, Mathiesen O and Moiniche S: ‘Protective premedication’: an option with gabapentin and related drugs? A review of gabapentin and pregabalin in the treatment of post operative pain. Acta Anaesthesiologica Scandinavica; 2004, 48:1130-1136. 3. Tiippana EM, Hamunen K, Kontinen VK and Kalso E: Do surgical patient benefit from perioperative gabapentin/pregabalin? A systematic review of efficacy and safety. Anesthesia & Analgesia; 2007, 104(6):1545-1556. 4. Pogatzki-Zahn EM and Zahn PK: From preemptive to preventive analgesia. Current Opinion in Anaesthesiology; 2006, 19:551-555. 5. Gajraj NM: Pregabalin: Its pharmacology and use in pain management. Anesthesia & Analgesia; 2007, 105:1805-1815. 6. Mikkelsen S, Hilsted KL, Andersen PJ, Hjortso NC, Enggaard TP, Jorgensen DG, Hansen M, Henriksen J and Dahl JB: The effect of gabapentin on postoperative pain following tonsillectomy in adults. Acta Anaesthesiologica Scandinavica; 2006, 50:809-815. 7. Dirks J, Fredensborg BB, Christensen D, Fomsgaard JS, Flyger, H and Dahl JB: A randomized study of the effect of single dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy. Anaesthesiology; 2002, 97:560-564. 8. Clarke H, Pereira S, Kennedy D, Gilron I, Katz J, Gollish J and Kay J: Gabapentin decreases morphine consumption and improves functional recovery following total knee arthroplasty. Pain Research & Management; 2009, 14:217-222. 9. Gilron I: Gabapentin and pregabalin for chronic neuropathic and early postsurgical pain: current evidence and future directions. Current Opinion in Anaesthesiology; 2007, 20:456-472. 10.Spreng UJ, Dahl V and Raeder J: Effect of a single dose of pregabalin on postoperative pain and preoperative anxiety in patients undergoing discectomy. Acta Anaesthesiologica Scandinavica; 2011, 55:571-576. 11.Agarwal A, Gautam S, Gupta D, Agarwal S, Singh PK and Singh U: Evaluation of a single preoperative dose of pregabalin for attenuation of postoperative pain after laparoscopic cholecystectomy. British Journal of Anaesthesia; 2008, 101:700-704. 12.Jokela R, Ahonen J, Tallgren M, Haanpaa M and Korttila K: Premedication with pregabalin 75 or 150 mg with ibuprofen to control pain after day-case gynaecological laparoscopic surgery. British Journal of Anaesthesia; 100(6):834-840. 13.Kim SY, Song JW, Park B, An YJ and Shim YH: Pregabalin reduces postoperative pain after mastectomy: a double-blind, randomized, placebo-controlled study. Acta Anaesthesiologica Scandinavica; 2011, 55:290-296. 14.Ittichaikulthol W, Virankabutra T, Kunopart M, Khamhom W, Putarawuthicai P and Rungphet S: Effects of pregabalin on postoperative morphine consumption and pain after abdominal hysterectomy with/without salphino-oophorectomy: A randomized, double-blind trial. Journalof the Medical Association of Thailand; 2009, 10(92):1318-1323. 15.Paech MJ, Goy R, Chua S, Scott K, Christmas T and Doherty DA: A randomized, placebo-controlled trial of preoperative oral pregabalin for postoperative pain relief after minor gynaecological surgery. Anesthesia & Analgesia; 2007, 105:1449-1453. 16.Zhang J, Ho KY and Wang Y: Efficacy of pregabalin in acute postoperative pain: a meta-analysis. British Journal of Anaesthesia; 2011, 106(4):454-462. 17.Engelman E and Cateloy F: Efficacy and safety of perioperative pregabalin for post-operative pain: a meta-analysis of randomizedcontrolled trials. Acta Anaesthesiologica Scandinavica; 2011, 55:927-943. Consumption Trends of Rescue Anti-Psychotics for Delirium in Intensive Care Units (ICU Delirium) show influence of Corresponding Lunar Phase Cycles: A Retrospective Audit Study from Academic University Hospital in the United States Deepak Gupta**, Vinay Pallekonda*, Ronald Thomas**, George Mckelvey** and Farhad Ghoddoussi** Abstract Background: The etiology of delirium in intensive care units (ICU) is usually multi-factorial. There is common “myth” that lunar phases affect human body especially human brains (and minds). Objective: In the absence of any pre-existing studies in ICU patients, the current retrospective study was planned to investigate whether lunar phases play any role in ICU delirium by assessing if lunar phases correlate with prevalence of ICU delirium as judged by the corresponding consumptions of rescue anti-psychotics used for delirium in ICU. Materials and Methods: After institutional review board approval with waived consent, the daily census of ICU patients from the administrative records was accessed at an academic university’s Non-Cancer Hospital in a Metropolitan City of United States. Thereafter, the ICU pharmacy’s electronic database was accessed to obtain data on the use of haloperidol and quetiapine over the two time periods for patients aged 18 years or above. Subsequently the data was analyzed for whether the consumption of haloperidol or quetiapine followed any trends corresponding to the lunar phase cycles. Results: A total of 5382 pharmacy records of haloperidol equivalent administrations were analyzed for this study. The cumulative prevalence of incidents of haloperidol equivalent administrations peaked around the full moon period and troughed around the new moon period. As compared to male patients, female patients followed much more uniform trends of haloperidol equivalent administrations’ incidents which peaked around the full moon period and troughed around the new moon period. Further sub-analysis of 70-lunar cycles across the various solar months of the total 68-month study period revealed that haloperidol equivalent administrations’ incidents peaked around the full moon periods during the months of November-December and around the new moon periods during the month of July which all are interestingly the major holiday months (a potential confounding factor) in the United States. Conclusion: Consumption trends of rescue anti-psychotics for ICU delirium revealed an influence by lunar phase cycles particularly that of full moon periods on female patients in the ICU. Introduction * *MD. **PhD. Corresponding author: Vinay Pallekonda MD, Department of Anesthesiology, Wayne State University, School of Medicine. Box No 162, 3990 John R, Detroit, MI 48201. Tel: 313-745-7233, Facsimile: 313-993-3889. E-mail: [email protected] 69 M.E.J. ANESTH 23 (1), 2015 70 Critically ill patients in the Intensive Care Units (ICUs) frequently experience delirium which is an acute reversible dysfunction of the brain. The etiology of ICU delirium is usually multi-factorial1. There is common “myth” that lunar phases affect human body especially human brains (and minds). This “myth” has often been studied in various scenarios including automobile accidents and injury accidents2, suicides3, peri-operative blood loss4, clustering of seizures5, mental status changes in schizophrenics6, and human and animal behavior and physiology7. The results of these studies reveal much ambiguity of the issue due to poorly understood underlying mechanisms; and hence results of various studies have either supported5-7 or refuted2-4 this norm/”myth” altogether. The common thread of this “myth” is that as lunar phases affect the oceans (tidal forces), these phases may affect the human body because it is composed of 70% water (fluids) that may result in “human tidal waves” generated by lunar influences8. Based on this background and in the absence of any pre-existing studies in the ICU patients, the current retrospective study was planned to investigate whether lunar phases have any role in ICU delirium by assessing if lunar phases correlate with prevalence of ICU delirium as judged by the corresponding consumptions of rescue anti-psychotic medications used for delirium in ICU. Materials and Methods After institutional review board approval with waived consent, the daily census of ICU patients from the administrative records was accessed at an academic university’s Non-Cancer Hospital in a Metropolitan City of United States. Thereafter, the ICU pharmacy’s electronic database was accessed to obtain data on the use of haloperidol and quetiapine over the two time periods for patients aged 18 years or above. Haloperidol and quetiapine are the two rescue anti-psychotic medications primarily used to manage ICU delirium in our hospital. The two time periods analyzed in this study were: 2008-2012 (five year period before the standardized protocol for ICU delirium was instituted in our hospital) and March 2013-October 2013 (eight month period after the standardized protocol for ICU Gupta Deepak et. al delirium was instituted in our hospital). Since March 2013, our hospital’s standardized protocol for ICU delirium include (a) daily screening for delirium with Intensive Care Delirium Screening Checklist (ICDSC) to recognize patients with positive ICDSC scores ≥4 followed by (b) their initial non-pharmacological management with sleep promotion, ambient noise reductions during night-time, early and aggressive ambulation, and circadian rhythm cycle promotion, and thereafter reserving (c) pharmacological treatment for intractable cases in form of haloperidol 2.5mg every 6hrs as needed intravenous boluses (maximum single dose 5mg and maximum daily dose 40mg) or quetiapine 25-50mg by mouth every 12hrs (maximum dose 200mg every 12hrs) besides ensuring maximization of pain management strategies and minimization of benzodiazepine use among the ICU delirium patients. Subsequently, the day-to-day lunar phases (from new moon to first quarter to full moon to third quarter) for these time periods were accessed from the freely available public domain web-address http:// www.timeanddate.com/calendar/moonphases.html. Thereafter, the daily prevalence of ICU delirium was adjudged by recording the daily percentage of ICU patients who had received haloperidol or quetiapine. Subsequently, the data was analyzed for whether the incidents of haloperidol or quetiapine administrations followed any medication consumption trends corresponding to the lunar phase cycles (any timesensitive-trends across the 29-plus days of a standard lunar cycle as described in Table 1). Additionally, the data was compared for patients’ age and sex, and their actual haloperidol/quetiapine usage. For uniformity during comparisons, all anti-psychotic usage was equated to per mg oral haloperidol equivalents as per the below-mentioned explanations for bio-equivalence. Using a multiplication factor of 1.6, intravenous haloperidol dose was converted to oral haloperidol equivalent as per the recommendations of the freely available public domain web-address http://www. globalrph.com/haloperidol_dilution.htm. Similarly, 9 although Woods (2003) advised using a conversion of 75mg quetiapine as equivalent to 2mg oral haloperidol, Andreasen et al (2010)10 described the changing arena of patients’ requirements for very Rescue anti-psychotics for delirium in ICU 71 Table 1 Nomenclature of Lunar Phases for the Study Popular Nomenclature Popular Explanation Nomenclature for Explanation for This Study This Study New Moon Time when 0% Visible Moon New Moon Period First Quarter Time after New Moon when 50% NOT STUDIED Moon becomes Visible NOT APPLICABLE Full Moon Time when 100% Visible Moon 24-hr period in either direction of Full Moon’s Time (Total 48-hr Period) Last Quarter (also known as Third Quarter) Time after Full Moon when 50% Moon NOT STUDIED remains Visible NOT APPLICABLE Waxing Crescent Over 7-8 days when Moon becomes Lunar Phase 1 Visible from 0% to 50% Time Zone from New Moon’s Time to First Quarter’s Time Waxing Gibbous Over 7-8 days when Moon becomes Lunar Phase 2 Visible from 50% to 100% Time Zone from First Quarter’s Time to Full Moon’s Time Waning Gibbous Over 7-8 days when Moon looses Lunar Phase 3 Visibility from 100% to 50% Time Zone from Full Moon’s Time to Last Quarter’s Time Waning Crescent Over 7-8 days when Moon looses Lunar Phase 4 Visibility from 50% to 0% Time Zone from Last Quarter’s Time to New Moon’s Time high doses of quetiapine for efficacy and hence calculated and recommended the changed equivalent doses as 151.97mg quetiapine equivalent to 2 mg oral haloperidol. Therefore, for our retrospective study, we followed the latest 2010 recommendations and used 76 mg quetiapine per mg oral haloperidol equivalent for study results analysis. For statistical analysis, ANOVA (Analysis of Variance) tests (Repeated measures 2 way ANOVA treatment) were used to compare the continuous data. Fisher exact test and Chi square analysis were used to compare categorical data. For post-hoc analyses, the Student Newman-Keuls test was used. P-values <0.05 were considered statistically significant. Results As described in the CONSORT Diagram (Figure 1), a total of 5382 pharmacy records of haloperidol equivalent administrations were analyzed for this study (4734 administrations during 2008-2012 period and 648 administrations during 8-month period in 2013). The time-trends analysis for these administrations Full Moon Period 24-hr period in either direction of New Moon’s Time (Total 48-hr Period) were tabulated based on a minimally modified popular nomenclature of lunar phases (Table 1) where the focus was comparisons between new moon period vs. full moon period; and inter-phase comparisons among the four lunar phases. As shown in Table 2, although there were variations for ICU delirium incidence among lunar cycles with the widest values ranging from one-in-four ICU patients to one-in-nine ICU patients receiving haloperidol equivalents (P <0.001), most commonly every 5th or 6th ICU patient based on daily ICU census was receiving haloperidol equivalent during 2008-2013 combined period irrespective of lunar cycle phase. However, the cumulative prevalence of incidents of haloperidol equivalent administrations (Table 2; Figure 2) were significantly different in both study periods (2008-2012 and 8-month 2013) wherein the incidents of haloperidol equivalent administrations peaked around the full moon period and troughed around the new moon period. There was a significant difference between the incidents of haloperidol equivalent administrations based on the patients’ sex (Table 3; Figure 3) wherein as compared to male patients, female patients followed much more uniform M.E.J. ANESTH 23 (1), 2015 72 Gupta Deepak et. al Table 2 At any given time-point, each instance of haloperidol equivalent administration was representative as following LUNAR PERIOD Percentage Incidence of Haloperidol Equivalent Administration per Daily Census Incidence of Haloperidol Equivalent Administration per Daily Census On Average P Value (F-Test) COMBINED 2008-2013 Cumulative Prevalence of Incidents of Haloperidol Equivalent Administrations P Value (F-Test) COMBINED 2008-2013 New Moon Period 16.7% ±16.6% 1-in-6 Patients 0.88 n=337 Full Moon Period 16.9% ±14.7% 1-in-6 Patients Lunar Phase 1 18.3% ±18.3% 1-in-5 Patients Lunar Phase 2 17.6% ±16.2% 1-in-6 Patients n=1453 Lunar Phase 3 17.5% ±14.5% 1-in-6 Patients n=1427 Lunar Phase 4 18.7% ±19.2% 1-in-5 Patients n=1308 0.006 n=412 0.18 2008-2012 n=1194 <0.001* 2008-2012 New Moon Period 16.1% ±15.0% 1-in-6 Patients <0.001 n=309 Full Moon Period 17.8% ±15.4% 1-in-6 Patients New Moon Period 23.8% ±28.3% 1-in-4 Patients n=28 Full Moon Period 10.7% ±5.2% 1-in-9 Patients n=51 0.03 n=361 2013 2013 2008-2012 0.008 2008-2012 Lunar Phase 1 18.8% ±18.6% 1-in-5 Patients Lunar Phase 2 18.3% ±17.1% 1-in-5 Patients n=1269 Lunar Phase 3 17.9% ±15.0% 1-in-6 Patients n=1248 Lunar Phase 4 19.6% ±20.0% 1-in-5 Patients n=1166 2013 0.16 n=1051 <0.001* 2013 Lunar Phase 1 14.1% ±15.1% 1-in-7 Patients n=143 Lunar Phase 2 12.9% ±6.1% 1-in-8 Patients n=184 Lunar Phase 3 14.6% ±9.1% 1-in-7 Patients n=179 Lunar Phase 4 11.8% ±6.5% 1-in-8 Patients n=142 0.02* *All pair-wise post-hoc comparisons are significantly different (P<0.05) when compared to their expected frequencies trends of haloperidol equivalent administrations’ incidents which peaked around the full moon period and troughed around the new moon period during both study periods (2008-2012 and 8-month 2013). On further analysis of the actual administered haloperidol mg equivalent doses, the statistical significance for differences in the administered doses across lunar cycle phases were only observed when the patientdoses were compared across the combined 2008-2013 period (Table 4: section B); and even though there was a statistical significance, the average clinical doses were 0.6-0.7 haloperidol mg equivalent per daily ICU census across all the lunar cycle phases (Table 4: section B). Further sub-analysis of 70-lunar cycles across the various solar months of the total 68-month study period (Figure 4) revealed that haloperidol equivalent administrations’ incidents peaked around the full moon periods during the months of NovemberDecember and around the new moon periods during the month of July; however, interestingly, the actual administered haloperidol mg equivalent average doses were highest around the new moon periods during the months of November-December. Rescue anti-psychotics for delirium in ICU 73 Fig 1 CONSORT Diagram Discussion To summarize the key points of the study results: (a) ICU delirium events, as adjudged by haloperidol equivalent administrations’ incidents, occurred on an average in approximately 20% of ICU patients daily at our hospital during 2008-2013; (b) ICU delirium events peaked around full moon; (c) ICU delirium events trended similarly across the lunar cycles during pre-standardized protocol time period (2008-2012) as well as during post-standardized protocol time period (2013); (d) as compared to male patients, ICU delirium events in female patients more uniformly followed lunar cycle trends; (e) after removing patients’ age as confounding factor, haloperidol mg equivalent doses’ trends were statistically different (though differences were clinically inconspicuous) in relation to lunar cycle phases; and (f) ICU delirium events happening in relation to lunar cycle phases were more common in the solar months of July, November and December which are interestingly the major holiday months (a potential confounding factor) in the United States besides July being first month-in-training for new resident/fellow ICU physicians and November-December being severe winter weather months in our Metropolitan city. The moon and its effects on animal and human M.E.J. ANESTH 23 (1), 2015 74 Gupta Deepak et. al Table 3 Demographics of Patients who received Haloperidol Equivalent Administrations LUNAR PERIOD Age (Mean ±SD) in years P Value (F-Test) Cumulative Prevalence of Incidents of Haloperidol Equivalent Administrations Gender Distribution of Incidents of Haloperidol Equivalent Administrations P Value (F-Test) COMBINED 2008-2013 New Moon Period 57.8 ±13.5 Full Moon Period 59.1 ±14.2 Lunar Phase 1 58.3 ±13.7 Lunar Phase 2 0.2 n=337 Females 39% Males 61% n=412 Females 54% Males 46% n=1194 Females 43% Males 57% 57.6 ±15.2 n=1453 Females 50% Males 50% Lunar Phase 3 57.5 ±13.7 n=1427 Females 51% Males 49% Lunar Phase 4 58.5 ±13.8 n=1308 Females 45% Males 55% n=309 Females 39% Males 61% n=361 Females 53% Males 47% n=28 Females 50% Males 50% n=51 Females 63% Males 37% n=1051 Females 41% Males 59% 0.15 <0.001 <0.001 2008-2012 New Moon Period 57.2 ±13.5 Full Moon Period 59.0 ±14.0 0.09 <0.001 2013 New Moon Period 65.0 ±11.6 Full Moon Period 60.1 ±16.0 0.16 0.34 2008-2012 Lunar Phase 1 57.9 ±13.6 0.09 Lunar Phase 2 56.9 ±15.3 n=1269 Females 48% Males 52% Lunar Phase 3 57.4 ±13.9 n=1248 Females 49% Males 51% Lunar Phase 4 58.2 ±14.1 n=1166 Females 45% Males 55% n=143 Females 57% Males 43% <0.001 2013 Lunar Phase 1 61.3 ±14.5 0.009 Lunar Phase 2 62.9 ±13.5 n=184 Females 60% Males 40% Lunar Phase 3 58.4 ±12.6 n=179 Females 63% Males 37% Lunar Phase 4 61.2 ±10.5 n=142 Females 47% Males 53% 0.03 Rescue anti-psychotics for delirium in ICU 75 Table 4 Haloperidol mg Equivalent-Strength Administration Dose Per Daily Intensive Care Unit Census Lunar Period Characteristic that Acted as Confounding Factor/Covariate Study Period 2008-2012 A Number of Administrations (n) New Period Moon 309 Haloperidol mg Equivalent (Mean ±SD) P Value (F-Test) Study Period 2013 Number of Administrations (n) Haloperidol mg Equivalent (Mean ±SD) 0.6 ±1.0 28 0.4 ±0.7 Full Moon Period 361 0.6 ±0.7 51 0.4 ±0.4 Lunar Phase 1 1051 0.6 ±0.9 143 0.4 ±0.6 Lunar Phase 2 1269 0.6 ±1.0 184 0.4 ±0.5 Lunar Phase 3 1248 0.6 ±0.8 179 0.5 ±0.6 Lunar Phase 4 1166 0.7 ±1.1 142 0.4 ±0.7 Patient’s Age as Co-Variate B Number of Administrations (n) New Period Moon 337 Haloperidol mg Equivalent (Mean ±SD) 0.6 ±1.0 Full Moon Period 412 0.6 ±0.7 Lunar Phase 1 1194 0.6 ±0.9 Lunar Phase 2 1453 0.6 ±0.9 Lunar Phase 3 1427 0.6 ±0.8 Lunar Phase 4 1308 0.7 ±1.1 Patient’s Sex: Female C Number of Administrations (n) Haloperidol mg Equivalent (Mean ±SD) 0.85 0.27 P Value (F-Test) 0.006 0.001 Patient’s Sex: Male Number of Administrations (n) Haloperidol mg Equivalent (Mean ±SD) New Period Moon 133 0.4 ±0.5 204 0.6 ±1.2 Full Period Moon 223 0.5 ±0.7 189 0.6 ±0.7 Lunar Phase 1 509 0.5 ±0.8 685 0.6 ±0.9 Lunar Phase 2 721 0.6 ±0.9 732 0.6 ±1.0 Lunar Phase 3 728 0.6 ±0.8 699 0.6 ±0.8 Lunar Phase 4 591 0.6 ±0.9 717 0.7 ±1.2 P Value (F-Test) 0.17 0.74 M.E.J. ANESTH 23 (1), 2015 76 Fig. 2 Graphical Presentation of Haloperidol Equivalent Administrations’ Incidents across the Whole Study Period: New Moon vs. Full Moon AND Lunar Phases 1-4 (Comparative P-Values reported in Table 2) Fig. 3 Graphical Presentation of Haloperidol Equivalent Administrations’ Incidents’ Distribution per Patients’ Sex/ Gender: New Moon vs. Full Moon AND Lunar Phases 1-4 (Comparative P-Values reported in Table 3) Gupta Deepak et. al Rescue anti-psychotics for delirium in ICU 77 Fig. 4 Graphical Presentation of Haloperidol Equivalent Administrations’ Incidents across the 68-Solar Month Study Period: New Moon vs. Full Moon (F-Test P-Value <0.001 for Overall Solar Month Trends’ Effect) AND Lunar Phases 1-4 (F-Test P-Value <0.001 for Overall Solar Month Trends’ Effect) behavior have fascinated mankind since ancient times. Similarly, the medical profession has not been naive or immune to these discussions. Thakur and Sharma (1984)8 observed that crime rates in three different cities in India during 1978-1982 increased threefold from new moon period to full moon period; and the authors explained this effect secondary to “human tidal waves” in human physiology as similar to gravitational effects of moon on the oceans. However, Laverty and Kelly (1998)2 reviewed a nine-year period with almost 300,000 accidents and observed periodic changes secondary to calendar changes and season changes but no relationship was apparent in relation to lunar cycle phases including full moon period. Barr (2000)6 revisited the historical aspect of term “lunacy” wherein during pre-modern times, mentally ill patients were supposedly displaying behavior changes in accordance to the changes in moon (“lunar”) phases. Among 100 patients who were followed for two-and-half years, Barr6 observed significant changes during full moon period in the schizophrenic patients as compared to the non-schizophrenic patients; and concluded that further investigations were required to validate the findings. Zimecki (2006)7 further expanded these discussion by reviewing the lunar phase effects on the animal kingdom in regards to phylogenesis, fishes’ fertility cycles, hormonal level changes in birds, sensory system of rats, and human reproduction. Zimecki7 tried to explain lunar effects on animal physiology as due to possible induction of changes in electromagnetic milieu around animals due to the periodic changes in the moon. Around same time, Polychronopoulos et al (2006)5 reported neurology emergency department experience over five year-period that as compared to 21.4% epileptic seizures that occurred during new moon period, 34.2% epileptic seizures occurred during full moon period. They re-iterated5 the possibility of epileptic seizures induction secondary to deprived sleep behavior during the full moon periods as an evolutionary learned behavior in response to increased night-time ambient light during the full moon period. Recently, Voracek et al (2008)3 reviewed over 65,000 suicides in Austria from 1970-2006. They M.E.J. ANESTH 23 (1), 2015 78 did not find any significant difference in completed suicides’ incidence between new moon period vs. full moon period, and the completed suicides’ incidence was equally divided among the four lunar phases. Voracek et al (2008)3 suggested that as compared to their almost four-decade long study period, other researchers’ short duration study periods can be the reason for other studies reporting lunar effects on human behavior events because they themselves also observed new moon as well as full moon sporadically affecting completed suicide rates during a few individual years among their cumulative 37-year long study period. Similarly, Schuld et al (2011)4 questioned the idea of patients scheduling their elective major surgeries in accordance to avoid lunar phases like full moon period because their analysis of emergency surgeries’ tenyear data revealed absence of statistical significance in regards to any differences in peri-operative blood loss and complications when measured in concurrence to lunar phases. The limitations of our study are that (a) it is a retrospective analysis, (b) it measured primarily the action (rescue anti-psychotics use) and assumed the corresponding cause (ICU delirium), (c) it puts forth only our observations but does not provide evidence for the interpretation how (if any) lunar phases affect ICU Gupta Deepak et. al delirium, and (d) it does not differentiate the effects of lunar phases (if any) on the ICU delirium patients vs. their medical care providers who had diagnosed ICU delirium and decided to administer haloperidol equivalents. Conclusion In summary, consumption trends of rescue antipsychotics for ICU delirium revealed an influence by lunar phase cycles particularly that of full moon periods on female patients in the ICU. Acknowledgement The authors are deeply indebted to the appreciative efforts of Ms. Connie Tourangeau, Pharmacist, and Mr. Xavier Bell, Field Engineer, Department of Pharmacy, Harper Hospital, Detroit Medical Center, Detroit, Michigan, United States in regards to their retrospective enlisting of the ICU patients according to the medications that they had received per their databases. The authors are also grateful to Ms Sapna Parmar, Information Systems Division Application Staff, for her help in enlisting daily ICU patients’ census data for our retrospective study period. Rescue anti-psychotics for delirium in ICU 79 References 1. Banh HL: Management of delirium in adult critically ill patients: an overview. J Pharm Pharm Sci; 2012, 15:499-509. 2. Laverty WH, Kelly IW: Cyclical calendar and lunar patterns in automobile property accidents and injury accidents. Percept Mot Skills; 1998, 86:299-302. 3. Voracek M, Loibl LM, Kapusta ND, Niederkrotenthaler T, Dervic K, Sonneck G: Not carried away by a moonlight shadow: no evidence for associations between suicide occurrence and lunar phase among more than 65,000 suicide cases in Austria, 1970-2006. Wien Klin Wochenschr; 2008, 120:343-349. 4. Schuld J, Slotta JE, Schuld S, Kollmar O, Schilling MK, Richter S: Popular belief meets surgical reality: impact of lunar phases, Friday the 13th and zodiac signs on emergency operations and intraoperative blood loss. World J Surg; 2011, 35:1945-1949. 5. Polychronopoulos P, Argyriou AA, Sirrou V, Huliara V, Aplada M, Gourzis P, Economou A, Terzis E, Chroni E: Lunar phases and seizure occurrence: just an ancient legend? Neurology; 2006, 66:1442-1443. 6. Barr W: Lunacy revisited. The influence of the moon on mental health and quality of life. J Psychosoc Nurs Ment Health Serv; 2000, 38:28-35. 7. Zimecki M: The lunar cycle: effects on human and animal behavior and physiology. Postepy Hig Med Dosw (Online); 2006, 60: 1-7. 8. Thakur CP, Sharma D: Full moon and crime. Br Med J (Clin Res Ed); 1984, 289:1789-1791. 9. Woods SW: Chlorpromazine equivalent doses for the newer atypical antipsychotics. J Clin Psychiatry; 2003, 64:663-667. 10.Andreasen NC, Pressler M, Nopoulos P, Miller D, Ho BC: Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs. Biol Psychiatry; 2010, 67:255-262. M.E.J. ANESTH 23 (1), 2015 The Use of Paravertebral Blockade for Analgesia after Anterior-Approach Total Hip Arthroplasty. Alberto E. Ardon* MD MPH, Roy A. Greengrass* MD, Upasna Bhuria* MBBS, Steven B. Porter* MD, Christopher B. Robards* MD and Kurt Blasser** MD Abstract Background: Anterior approaches for total hip arthroplasty (ATHA) are becoming increasingly popular. We postulated that the use of PVB of the T12, L1, and L2 roots would provide adequate analgesia for ATHA while allowing motor sparing. Methods: The medical records of 20 patients undergoing primary ATHA were reviewed. T12, L1 and L2 paravertebral blockade was accomplished with 3-4ml of 1% ropivacaine with epinephrine 1:200,000 and 0.5mg/ml of preservative-free dexamethasone per level. Primary outcomes were mean opioid consumption in intravenous morphine equivalents and worst recorded visual analog scale (VAS) pain scores during postoperative days 0 to 2 (POD 0 to 2). Results: Mean opioid consumption was 8.4mg on POD0, 16.6mg on POD1, and 9.8mg on POD2. Median worst VAS scores were 2 for all time intervals except POD 0, which had a median value of 0. All patients had full hip motor strength the evening of POD0. 19 patients were able to ambulate the afternoon of POD1. Conclusion: T12-L2 PVB, when utilized as part of a multimodal analgesic regimen, results in moderate opioid consumption, low VAS scores, preservation of hip motor function, and may be an effective regional anesthesia technique for ATHA. Keywords: Paravertebral blockade1, anterior total hip arthroplasty, multimodal analgesia, opioid consumption. Introduction Anterior approaches for total hip arthroplasty are becoming increasingly popular due to advantages of less muscle trauma, resulting in enhanced convalescence1. *Department of Anesthesiology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224. **Department of Orthopedic Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224. Corresponding author: Alberto E. Ardon, Department of Anesthesiology, Mayo Clinic, Jacksonville, FL 4500 San Pablo Road, Jacksonville, FL 32224. Tel: 904-766-0738; 225-773-4407, Fax: 904-956-3332. E-mail: [email protected] Present academic appointment and address: Assistant Professor, University of Florida-Jacksonville, 2nd Floor, Clinical Center, Department of Anesthesiology, 655 West 8th Street, C72, Jacksonville, FL 32209. Tel: 904-244-4195; 225-7734407, Fax: 904-244-4908. E-mail [email protected]; [email protected] 1. PVB: paravertebral blockade. ATHA: anterior total hip arthroplasty. POD: postoperative day. VAS: visual analog scale. 81 M.E.J. ANESTH 23 (1), 2015 82 Unfortunately, similar to posterior approaches, anterior total hip arthroplasty (ATHA) is associated with significant pain requiring moderate to large doses of opioids with attendant side effects. Multimodal analgesia including regional analgesic techniques such as posterior lumbar plexus block (psoas compartment block) have been utilized to treat the pain of total hip arthroplasty with encouraging results2. However, the motor weakness associated with psoas compartment block may limit ambulation and decrease effective physiotherapy, possibly increasing the risk of falls3. It is felt by many surgeons that motor sparing analgesic techniques would be of benefit to patients. While opioids are commonly used for postoperative analgesia in hip arthroplasty patients, the use of these medications is associated with a significant negative side effect profile that includes nausea and vomiting, respiratory depression, prolonged recovery room stay, increased healthcare burden, and decreased patient satisfaction4. Consequently, the use of a regional anesthetic technique as a part of a multimodal analgesic plan aimed at reducing postoperative opioid consumption would be advantageous. The paravertebral block (PVB) is a block of the mixed nerve soon after it exits the intervertebral foramen5. It provides intense unilateral analgesia of long duration and has become the primary anesthetic for many applications6,7. We postulated that the use of PVB of the T12, L1 and L2 roots would provide adequate analgesia for ATHA while allowing motor sparing. In this study we present our initial expanded case series of 20 patients who received PVB for ATHA. Methods The Institutional Review Board (IRB) approved this study. From June 2013 to February 2014, the medical records of 20 patients undergoing primary ATHA were reviewed. No patient had preoperative motor deficit or opioid consumption requiring longacting opioids. After a preoperative interview, informed consent for both surgical anesthesia and peripheral nerve blockade was obtained by an anesthesiologist. All blocks were performed in the preoperative area in a sterile fashion after placement of American Society of Alberto Ardon et. al Anesthesiologists standard monitors and verification of patient identity and laterality of the procedure. Sedation was at the discretion of the attending anesthesiologist, and included sedative doses of midazolam, fentanyl, ketamine, and/or propofol. For PVB placement, patients were positioned in the sitting position. The T12, L1 and L2 spinous processes were identified in the sitting position either by counting from the L4 spinous process at the level of iliac crest and/or from the T7 spinous process at the level of lower border of the scapulae. Needle entry points were marked 2.5 cm lateral to the spinous process as described previously by Greengrass et al5. After skin infiltration with 2% lidocaine with epinephrine 1:200,000 at the marked sites, a sterile 22 G, 10 cm Tuohy needle (B Braun, Melsungen, DE) was introduced perpendicular to the skin until the transverse process was contacted. The needle was then redirected in a caudad direction and advanced 1-1.5 cm. After negative aspiration, 3-4 ml of 1% ropivacaine with epinephrine 1:200,000 and 0.5mg/ml of preservative free dexamethasone were injected per level. Injections were repeated at the other two levels. Sensory deficit in the distribution of T12, L1 and L2 dermatomes were confirmed with ice testing prior to surgical anesthesia. Absence of motor blockade upon hip flexion, assessed with the modified Bromage scale, was also confirmed preoperatively. The modified Bromage scale is defined as follows: 1 = unable to move foot or knee; 2 = able to move foot only; 3 = just able to move knee; 4 = full flexion of knee; 5 = no detectable weakness of hip flexion while supine. One patient required an additional injection at all levels to establish appropriate sensory deficit. Surgical anesthesia was achieved with an intrathecal injection of 12.5 to 13mg of preservativefree isobaric 0.5% bupivacaine. The same surgeon performed all surgeries utilizing a modified SmithPeterson anterior approach. No patients had intraoperative complications. At the discretion of the surgeon, patients received an intra-articular injection consisting of morphine 10mg, ketorolac 30mg, and epinephrine 200mcg. Daily opioid and non-opioid analgesic consumption, visual analog scale (VAS) pain scores, and length-of-stay data were extracted from the electronic medical record. Paravertebral block for hip arthroplasty 83 Table 1 Patient characteristics Pt ID Age ASA Sex Operative Side Consistent Preoperative opioid, if any Day of Discharge 1 82 2 64 3 F Right No POD 3 2 M Right No POD 2 3 72 3 F Right No POD 3 4 56 1 M Right No POD 2 5 74 3 M Left No POD 3 6 76 2 F Left No POD 3 7 81 3 M Left No POD 3 8 65 2 M Left Oxycodone POD 3 9 72 2 M Right No POD 2 10 71 2 M Left No POD 3 11 69 2 M Left Oxycodone POD 2 12 61 2 F Right No POD 2 13 77 2 M Left No POD 3 14 91 3 M Right No POD 3 15 67 2 F Left No POD 3 16 70 2 F Right No POD 3 17 64 2 F Right Hydrocodone POD 3 18 70 3 M Right No POD 3 19 72 3 M Left No POD 3 20 83 3 M Left No POD 2 Postoperatively, patients received scheduled intravenous acetaminophen every 6 hours for the first 24 hours, and thereafter on an as-needed basis. All patients received oral celecoxib 200mg twice daily. Primary Outcomes Mean opioid consumption in intravenous morphine equivalents during the time intervals of postoperative day 0 (POD 0, defined as the period of time from surgical incision until 07:00 on postoperative day 1), postoperative day 1 (POD 1, defined as 07:00 until 07:00 on POD2), and postoperative day 2 (POD 2, defined as .)07:00 on POD2 until 18:00 Worst recorded visual analog scale (VAS) pain scores, rated from 0 - 10, during time intervals from POD 0 .to 2 Secondary Outcomes Secondary outcomes included maximum opioid consumption, non-opioid analgesic consumption, ability to ambulate, and distance ambulated. Results Patient characteristics are shown in Table 1. A total of 20 patients were included, all of whom received a spinal anesthetic. Mean operative time was 78 minutes. Three patients had documented preoperative opioid consumption with short-acting agents. However, none of these patients consumed more than 30mg of oral morphine equivalents per day. The remaining patients denied use of preoperative opioids. No patients developed complications from the paravertebral blocks while hospitalized. No falls M.E.J. ANESTH 23 (1), 2015 84 Alberto Ardon et. al Table 2 Opioid consumption in IV morphine equivalents (mg) Patient ID 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Mean Median POD 0 4 10 10 15 0 5 12 10 9 0 10 10 5.3 3.3 20.3 10 21.7 16.7 0 0 8.4 9.5 POD 1 12 10 10 10 15 33.3 42.3 20 11.3 20 15 25 4 13.3 18.3 15 36.7 10 0 0 16.6 15 POD 2 9 5 5 10 0 30 15.6 15 5 15 10 10 13.3 7.5 5.3 10 30 0 0 0 9.8 9.5 Table 3 Visual analog pain scores Patient ID 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 n/a: not recorded secondary to lack of record or patient discharge Worst VAS POD 0 to 19:00 0 0 5 0 0 0 2 0 0 0 5 4 0 6 4 2.5 6 0 0 0 Worst VAS POD 0-1 overnight 0 4 2 8 1 7 2 4 0 3 5 2 2 5 2 2 4 6 0 0 Worst VAS POD 1 AM Worst VAS POD 1 PM 0 2 0 3 0 3 2 1 0 3 2 3 2 3 2 0 6 2 0 0 0 2 0 3 n/a 1 0 2 0 2 2 3 0 3 3 2 4 0 0 0 Worst VAS POD 1-2 overnight 0 4 0 3 3 5 7 2 0 2 2 1 0 3 3 0 5 4 0 1 Worst VAS POD 2 AM Worst VAS POD 2 PM 2 2 2 2 0.5 0 0 2 0 2 5 1 0 0 2 0 4 2 1 2 2 n/a 3 n/a 1 4 4 0 2 2 4 n/a n/a 0 3 1.5 3 2 0 n/a Paravertebral block for hip arthroplasty occurred during hospitalization. Six patients were discharged on POD 2. Opioid consumption in IV morphine equivalents by patient is shown in Table 2. Mean opioid consumption was 8.4mg on POD0, 16.6mg on POD1, and 9.8mg on POD2. Median opioid consumption was 9.5mg, 15mg, and 9.5mg for POD0, POD1, and POD2, respectively. Maximum opioid consumption was 21.7mg on POD0, 42.3mg on POD1, and 30mg on POD2. The three patients with documented preoperative opioid use had postoperative opioid consumption greater than the median on POD 0, 1 and 2. Worst VAS scores recorded for each patient are shown in Table 3; values ranged from 0 to 8. Median worst VAS scores, shown in Table 4, were 2 for all time intervals except POD0, which had a median value of 0. Table 4 Median worst visual analog pain scores (minimum, maximum) POD0 to 19:00 0 (0,6) POD 0-1 overnight 2 (0,8) POD1 AM 2 (0,6) POD1 PM 2 (0,4) POD 1-2 overnight 2 (0,7) POD2 AM 2 (0,5) POD2 PM 2 (0,4) Regarding non-opioid analgesics, median acetaminophen and celecoxib doses are shown in Table 5. Median acetaminophen dose was highest on POD 0 (4000mg), while median celecoxib dose was higher on POD1 and POD2 (400mg). Table 5 Median acetaminophen and celecoxib consumption among patients (mg) Acetaminophen Consumption POD 0 4000 POD 1 2650 POD 2 1000 Celecoxib Consumption POD 0 200 POD 1 400 POD 2 400 85 All patients had modified Bromage scores of 5 the evening of POD 0; 2 patients were able to ambulate at that time. On the morning of POD 1, 15 patients were able to ambulate, while 19 were able to do so by that afternoon (Table 6). Median distances ambulated on the morning and afternoon of POD1 were 30 feet and 80 feet, respectively. Table 6 Ambulation among study patients, with distance ambulated in feet [median (range)] # of patients ambulated POD0 2 # of patients ambulated POD1 AM 15 # of patients ambulated POD1 PM 19 Distance ambulated POD1 AM 30 (1, 500) Distance ambulated POD1 PM 80 (5, 980) Discussion Although the concept of the paravertebral block (PVB) originated in the early 20th century, its popularity has waxed and waned. Recently, a renewed interest in the technique has developed, as it has been found to be an effective analgesic technique that minimizes hemodynamic compromise8,9. The injection of local anesthetic in the paravertebral space blocks conduction in the dorsal and ventral rami of the exiting spinal nerve root. Paravertebral blockade also inhibits conduction through the sympathetic chain, resulting in only a unilateral sympathectomy. At the levels of thoracic vertebrae, the paravertebral space is a wedge shaped space defined anterolaterally by the parietal pleura, posteriorly by the superior costotransverse ligament, and medially by the vertebral, vertebral disk, and intervertebral foramina. The superior and inferior borders are provided by the heads of the ribs. In the lumbar vertebrae, the inter-transverse ligament provides the posterior border of the paravertebral space. As explained by Greengrass et al, the paravertebral space provides an area where exiting spinal nerves are not tightly enveloped by fascia, possibly facilitating nerve blockade5. Paravertebral blockade is commonly used for breast surgery, video-assisted thoracic surgery, minimally invasive cardiac surgery, herniorrhaphy, and hand-assisted laparoscopic nephrectomy7,8,9. To our M.E.J. ANESTH 23 (1), 2015 86 knowledge, use of this analgesic technique in anteriorapproach hip arthroplasty has not been described in the literature. While the use of PVB was reported by Bogoch and colleagues in 2002 for postoperative analgesia following total hip and knee arthroplasty, the technique described suggests a psoas compartment blockade, not a true paravertebral block, as the initial needle approach was made 4cm lateral to the spinous process rather than 2.5cm10. Lee et al reported excellent analgesia in two patients who patients received L1/ L2 paravertebral blocks along with local anesthetic infiltration of the joint for hip arthroscopy11. Wardhan and colleagues described continuous L2 paravertebral blockade to be slightly inferior to a lumbar plexus catheter when comparing opioid consumption in posterior approach total hip arthroplasty patients, with no motor strength advantage12. However, patients in that study received 15ml of local anesthetic during placement of the paravertebral catheter. Injection of a large amount of local anesthetic in the paravertebral space may result in epidural and/or unpredictable spread5,13,14. In one radiographic study, 25% of patients who received 20ml injectate at a single paravertebral level had epidural spread evident on MRI13. Thus, observed weakness in PVB patients after a large volume injection could be secondary to neuraxial or extensive paravertebral spread of local anesthetics. In our current study, we have limited the injectate to a maximum of 4ml per level, which we believe minimizes the risk of these complications. In our case series, no patient had a modified Bromage score less than 5 the evening of POD 0. Additionally, no patient was noted by physical therapy as having significant ipsilateral lower extremity weakness that prevented full participation in physical activity. Studies addressing opioid consumption among patients who undergo anterior approach total hip arthroplasty are limited. In a prospective study by Barrett et al, ATHA patients consumed a mean of 32.2mg, 50.7mg, and 33.7mg IV morphine equivalents on POD 0, 1 and 2, respectively15. Another study by Restrepo describes POD0, POD1, and POD2 mean intravenous morphine consumption as 11.2mg, 13.9mg, and 6.82mg, respectively. However, patients in this study received intrathecal morphine as part of their analgesic plan, thus our results are not directly comparable1. Additionally, the risk of postoperative Alberto Ardon et. al respiratory depression after an intrathecal opioid injection is unnecessary when non-opioid modalities are available. Bogoch et al’s study which used a single-injection lumbar plexus block showed an opioid consumption of 18.7mg of morphine equivalents in the first 8 hours after surgery, which is significantly higher than our results10. Some studies contend that there is little difference in opioid consumption or pain scores when comparing an anterior approach hip arthroplasty to a classic posterior approach. Rodriguez et al found no difference in either metric when comparing the two surgical methods16. Even with a lumbar plexus catheter in place, opioid consumption may be high in the classic posterior approach. For example, Wilson et al documented a mean opioid consumption of 54.67mg of IV morphine equivalents in the first 24 hours after THA, even with a properly functioning lumbar plexus catheter17. If indeed little difference in opioid consumption exists between the two surgical techniques, our results suggest that multimodal analgesia including a PVB at T12-L2 may decrease opioid consumption significantly in ATHA patients. During the time intervals studied, all median VAS scores were 2 or less. Reports of perioperative VAS scores for the ATHA patient population are limited. One study described mean POD 0, 1, and 2 VAS scores to be (4.2 ± 1.4), (4.0 ± 1.0) and (3.8 ± 1.1), respectively15. The low median VAS scores in our study, combined with moderate opioid consumption, are thus encouraging. The potential efficacy of paravertebral blockade in this study may be explained on anatomic grounds. First, the cutaneous analgesia provided by paravertebral blocks at T12, L1 and L2 is suited for coverage of the surgical incision. Second, as described by Wetheimer in 1952, the peripheral nerve innervation of the hip joint is provided by the obturator nerve, femoral nerve, and branches of the sacral plexus18. The spinal nerves at the levels of T12, L1 and L2 provide sensory fibers to the iliohypogastric, ilioinguinal, genitofemoral, lateral femoral cutaneous, femoral and obturator nerves. Thus, a significant proportion of the sensory fibers to the hip joint are affected by T12-L2 paravertebral blockade. Lastly, the bony innervation of the hip joint may indeed be affected by this paravertebral approach. Although osteotomal anatomy of the hip Paravertebral block for hip arthroplasty joint is much less well defined, Brown and colleagues describe L2 as providing innervation to the medial midshaft femur, iliac crest, and anterior superior iliac spine; L3 provides innervation to the femoral neck and acetabulum19. In our study we did not conduct an L3 block so as to decrease the total anesthetic dose and minimize the risk of motor block. Based on our results, separate blockade of L3 may indeed not be required for adequate analgesia after ATHA. Femoral nerve fibers arise from L2, L3, and L4 nerve roots. Blockade with moderate volume only at L2, while giving sensory block in that dermatomal distribution and having limited caudal spread, may allow full motor function of the femoral nerve. We recognize, however, that until further studies delineating osteotomal hip innervation are conducted, the exact contribution of PVB analgesia to the hip joint may not be well defined. The patients in this case series received both acetaminophen and celecoxib as part of a multimodal approach to postoperative analgesia. Acetaminophen use was highest on POD0-1, which may have contributed to the low opioid consumption and very low median worst VAS of zero. Likewise, twice-daily celecoxib administration may also have contributed to decreasing the total opioid consumption among these patients. While the exact contribution of acetaminophen and celecoxib in reducing opioid requirements in these anterior hip arthroplasty patients is not known, previous studies in total knee and posterior-lateral approach hip arthroplasty suggest that multimodal analgesia reduces opioid burden20,21. The low overall pain scores and opioid consumption in this case series certainly suggest that the use of multimodal analgesia may contribute to the analgesic efficacy of paravertebral blockade. All but two of the study patients were able to participate in physical therapy to some degree by the evening of their surgical day. The two patients who did not were limited by a late discharge from the recovery room, as they were both mid-afternoon cases. By the morning of POD1, 15 of the 20 patients were able to ambulate. Median distance ambulated during the morning physical therapy session was 30 feet. By the afternoon of postoperative day 1, 19 patients were ambulating, with a median distance of 80 feet. These results, when considered in the context of low median 87 VAS scores on POD1, suggest that paravertebral blockade may provide significant analgesia to facilitate ambulation during the first 24 hours after surgery. As mentioned previously, 13 patients received intraarticular morphine, ketorolac and epinephrine. The evidence supporting the use of these medications within the articular space without local anesthetic, however, is not robust. While some studies do suggest that the use of intraarticular local anesthetic may enhance postoperative analgesia22,23,24, the analgesic properties of intra-articular morphine or epinephrine without local anesthetic are yet to be supported by data. To our knowledge, there are no studies regarding the analgesic properties of sole epinephrine when injected into an articulation. Regarding opioids, one murine-model study suggests that subcutaneous administration of morphine may have some analgesic properties at the site of injection, but these effects have not been validated in the intra-articular space in humans25. Another study in patients undergoing knee surgery showed no difference in postoperative opioid consumption when morphine is added to intraarticular bupivacaine in the presence of a femoral nerve block26. The efficacy of ketorolac when injected into a joint without local anesthetic has also not been studied extensively. One small study by Vintar et al studied the impact of 10mg ketorolac on an ondemand intraarticular bolus of 25mg ropivacaine and 2mg morphine available every 60 minutes. Patients who received intraarticular ketorolac had decreased opioid use 24 hours postoperatively27. However, another study showed that patients who only received intraarticular ketorolac had higher pain scores and shorter time to first analgesic request compared to patients who only received intraarticular bupivacaine28. In our study, when patients who did not receive this intra-articular injection are analyzed separately, mean and median opioid consumption are similar to those of the overall cohort (Table 7). Thus, given these results and the paucity of evidence for the efficacy of this intra-articular mixture, we do not believe this modality affected our primary outcome. However, as shown in Table 8, median worst VAS scores did seem to be slightly higher in those patients. Thus, we realize that the theoretical possibility of a combined analgesic effect cannot entirely be discounted. M.E.J. ANESTH 23 (1), 2015 88 Alberto Ardon et. al Table 7 Mean and median opioid consumption in mg IV morphine equivalents, patients who did not receive intra-articular injection Mean Median POD 0 8.96 10 POD 1 12.43 10 POD 2 7.04 5 Table 8 Median visual analog pain scores (minimum, maximum), patients who did not receive intra-articular injection POD0 to 19:00 0 (0,5) POD 0-1 overnight 5 (0,9) POD1 AM 0 (0,3) POD1 PM 2 (0,6) POD 1-2 overnight 4 (0,6) POD2 AM 5 (0,8) POD2 PM 6 (0,7) The limitations in our case series include the retrospective nature of the study, the small number of patients, and the lack of randomization. Additionally, the VAS scores were recorded by ward nursing staff per regular protocol, without mention of activity status during the patient’s self-assessment of pain. However, since we have collected the worst recorded VAS rather than the entire range of pain scores, we hope to capture as many VAS scores associated with activity as possible. We also recognize that while appropriate sensory deficit was confirmed preoperatively, the duration of this sensory deficit was not documented. Thus, we can only speculate on the exact duration of the paravertebral block. Given the steady level of opioid requirements throughout postoperative day 2, though, we suspect that the analgesia associated with nerve blockade continued to some degree during this time period. Conclusion T12 through L2 paravertebral blockade, when utilized as part of a multimodal pain management plan, results in low VAS scores, preservation of hip motor function, moderate opioid consumption, and may be an effective analgesic modality for patients undergoing anterior approach total hip arthroplasty. The outcomes of our retrospective case series are encouraging. Prospective studies are warranted. Paravertebral block for hip arthroplasty 89 References 1. Restrepo C, Parvizi J, Pour AE, Hozack WJ: Prospective randomized study of two surgical approaches for total hip arthroplasty. J of Arthroplasty; 2010, 25(5):671-80. 2. Horlocker TT: Pain management in total joint arthroplasty: a historical review. Orthopedics; 2010, 33(9):supplement. 3. Ilfeld BM, Mariano ER, Madison SJ, Loland VJ, Sandhu NS, Suresh PJ, Bishop ML, Kim TE, Donohue MC, Kulidjian AA, Ball ST: Continuous femoral versus posterior lumbar plexus nerve blocks for analgesia after hip arthroplasty: a randomized, controlled study. Anesth Analg; 2011, 113(4):897-903. 4. Greenberg C: Practical, cost-effective regional anesthesia for ambulatory surgery. J of Clinical Anesthesia; 1995, 7:614-21. 5. Greengrass RA, Duclas R: Paravertebral blocks. International Anesthesiology Clinics; 2012, 50(1):56-73. 6. Akcaboy EY, Akcaboy ZN, Gogus N: Ambulatory inguinal herniorrhaphy: paravertebral block versus spinal anesthesia. Minerva Anestesiologica; 2009, 75(12):684-691. 7. Schnabel A, Reichl SU, Kranke P, Pogatzki-Zahn EM, Zahn PK: Efficacy and safety of paravertebral blocks in breast surgery: a metaanalysis of randomized controlled trials. British J of Anesthesia; 2010, 105(6):842-52. 8. Eason MJ, Wyatt R: Paravertebral thoracic block: a re-appraisal. Anesthesia; 1979, 34(7):638-42. 9. Clendenen SR, Wehle MJ, Rodriguez GA, Greengrass RA: Paravertebral block provides significant opioid sparing after handassisted laparoscopic nephrectomy: an expanded case report of 30 patients. J of Endourology; 2009, 23(12):1979-83. 10.Bogoch ER, Henke M, Mackenzie T, Olschewski E, Mahomed NN: Lumbar paravertebral nerve block in the management of pain after total hip and knee arthroplasty. J of Arthroplasty; 2002, 17(4):398401. 11.Lee EM, Murphy KP, Ben-David B: Postoperative analgesia for hip arthroscopy: combined L1 and L2 paraverterbral blocks. J of Clinical Anesthesia; 2008, 20:462-465. 12.Wardhan R, Auroux AM, Ben-David B, Chelly JE: Is L2 paravertebral block comparable to lumbar plexus block for postoperative analgesia after total hip arthroplasty? Clin Orthop Rel Res; 2014, 472(5):1475-81. 13.Marhofer D, Marhofer P, Kettner SC, Fleischmann E, Prayer D, Schernthaner M, Lackner E, Willschke H, Schwetz P, Zeitlinger M: Magnetic resonance imaging analysis of the spread of local anesthetic solution after ultrasound-guided lateral thoracic paravertebral blockade. Anesthesiology; 2013, 118(5):1106-12. 14.Richardson J, Jones J, Atkinson R: The effect of thoracic paravertebral blockade on intercostal somatosensory evoked potentials. Anesth Analg; 1998, 87:373-6. 15.Barrett WP, Turner SE, Leopold JP: Prospective randomized study of direct anterior vs postero-lateral approach for total hip arthroplasty. J of Arthroplasty; 2013, 28:1634-38. 16.Rodriguez JA, Deshmukh AJ, Rathod PA, Greiz ML, Deshmane PP, Hepinstall MS, Ranawat AS: Does the direct anterior approach in THA offer faster rehabilitation and comparable safety to the posterior approach? Clin Orthop Rel Res; 2014, 472:455-63. 17.Wilson SH, Auroux AM, Eloy JD, Merman RB, Chelly JE: Ropivacaine 0.1% versus 0.2% for continuous lumbar plexus nerve block infusions following total hip arthroplasty: a randomized, double blinded study. Pain Medicine; 2014, 15:465-472. 18.Wertheimer LG: The sensory nerves of the hip joint. J of Bone and Joint Surgery; 1952, 34(2):477-87. 19.Brown DL, Boezaart AP, Galway UA, Rosenquist RW, Rathmell JP, Sites BD, Spence BC: Atlas of Regional Anesthesia. 4th Ed. Philadelphia: Saunders Elsevier; 2010. 20.Ittichaikulthol W, Prachanpanich N, Kositchaiwat C, Intapan T: The postoperative analgesic efficacy of celecoxib compared with placebo and parecoxib after total hip or knee arthroplasty. J Med Assoc Thai; 2010, 93(8):937-42. 21.Peters CL, Shirley B, Erickson J: The effect of a new multimodal perioperative anesthetic regimen on postoperative pain, side effects, rehabilitation, and length of hospital stay after total joint arthroplasty. J of Arthroplasty; 2006, 21(6 Suppl 2):132-8. 22.Chen LH, Huang QW, Wang WJ, He ZR, Ding WL: The applied anatomy of anterior approach for minimally invasive hip joint surgery. Clinical Anatomy; 2009, 22:250-55. 23.Dobrydnjov I, Anderberg C, Olsson C, Shapurova O, Angel K, Bergman S: Intraarticular versus extraarticular ropivacaine infusion following high-dose local infiltration analgesia after total knee arthroplasty: a randomized double-blind study. Acta Orthopaedica; 2011, 82(6):692-98. 24.Axelsson K, Gupta A, Johanzon E, Berg E, Ekback G, Rawal N, Enstrom P, Nordensson U: Intraarticular administration of ketorolac, morphine and ropivacaine combined with intraarticular patient-controlled regional anesthesia for pain relief after shoulder surgery: a randomized, double-blind study. Anesth Analg; 2008, 106:328-33. 25.Desroches J, Bouchard JF, Gendron L, Beaulieu P: Involvement of cannabinoid receptors in peripheral and spinal morphine analgesia. Neuroscience; 2014, 261:23-42. 26.McCarty EC, Spindler KP, Tingstad E, Shyr Y, Higgins M: Does intraarticular morphine improve pain control with femoral nerve block after anterior cruciate ligament reconstruction? American J of Sports Med; 2001, 29(3):327-33. 27.Vintar N, Rawal N, Veselko M: Intraarticular patient-controlled regional anesthesia after arthroscopically assisted anterior cruciate ligament reconstruction: ropivacaine/morphine/ketorolac versus ropivacaine/morphine. Anesth Analg; 2005, 101:573-8. 28.Reuben SS, Connelly NR: Postoperative analgesia for outpatient arthroscopic knee surgery with intraarticular bupivacaine and ketorolac. Anesth Analg; 1995, 80:1154-7. M.E.J. ANESTH 23 (1), 2015 Subtenon bupivacaine injection for postoperative pain relief following pediatric strabismus surgery: A randomized controlled double blind trial Radwa H Bakr** and Hesham M Abdelaziz* Abstract Background: Strabismus surgery in children is often associated with undesirable intraoperative and postoperative side effects including pain, postoperative nausea and vomiting (PONV), and occulocardiac reflex (OCR). Systemic analgesics have side effects and are contraindicated in some cases. We hypothesized that the preoperative subtenon injection of bupivacaine would reduce postoperative pain and the incidence of side effects adverse effects. Methods: Sixty children (2 to 6 years of age, ASA status I to II) were randomized to receive either subtenon bupivacaine 0.5% or a saline injection before the beginning of surgery in a doubleblind manner. Pain scores using the Face, Legs, Cry, Activity, and Consolability (FLACC) scale, incidence of OCR and PONV, requirement of additional systemic analgesia, and time to discharge from the recovery room were compared. Results: The pain scores were significantly lower in the subtenon bupivacaine group at 0 min (p = 0.0056) and at 30 min (p = 0.013). There was no significant difference between the two groups at the other time intervals. There was a significant reduction in the incidence of occulocardiac reflex and the incidence of vomiting in the subtenon bupivacaine group. Eight of the 27 patients in the subtenon bupivacaine group required additional systemic analgesia compared to 19 of 29 controls. The time to discharge from recovery room was lower in the subtenon bupivacaine group. Conclusion: These data provide some evidence that a preoperative subtenon block with bupivacaine combined with general anesthesia allows efficient control of postoperative pain as well as a reduction in the incidence of OCR and PONV in young children undergoing strabismus surgery. Keywords: Bupivacaine, Pain, Pediatrics, Strabismus surgery, Subtenon anesthesia. Introduction Following strabismus surgery children often experience severe discomfort and are unable to open the operated eye. The surgical manipulation of the medial rectus muscle causes severe bradycardia because of the occulocardiac reflex1. The postoperative period is marked by frequent obvious discomfort, caused by a high frequency of postoperative nausea and vomiting and pain. Pain after strabismus correction is thought to be in the conjunctival area, but Tenon’s capsule, sclera, and stretched muscles may also contribute to its intensity1. This pain represents a source of distress to the child and the parents. Different modalities of treatment have been proposed and found to be variably effective. Opioids are helpful but carry the risk of nausea, vomiting, and drowsiness. * MD. Department of anesthesia and intensive care, Faculty of Medicine, Ain Shams University, Cairo, Egypt. ∗ 91 M.E.J. ANESTH 23 (1), 2015 92 Non-steroidal anti-inflammatory drugs (NSAIDs) remain controversial in small children. The side effects of these agents are particularly undesirable in the ambulatory surgery setting or are contraindicated in many children. Regional anesthesia has been proposed for management of postoperative pain following strabismus surgery. Topical amethocaine 1% drops and subconjunctival infiltration with bupivacaine 0.5% administered at the conclusion of strabismus surgery have been shown to be effective in reducing postoperative pain2,3,4. Retrobulbur and peribulbar block have been explored in children with varying degrees of success5. Among the different techniques, the subtenon eye block is widely used for anterior and posterior segment surgery in adults. A small quantity of local anesthetic is injected in the subtenon space by use of a smooth cannula after surgical incision of the conjunctiva. This technique ensures adequate postoperative analgesia in adults6,7 although it has not been sufficiently explored when used before the start of surgery in children. We performed a prospective, randomized, double-blind, controlled study to determine the efficacy of subtenon’s bupivacaine injection at reducing postoperative pain, the incidence of postoperative complications, and the requirements of postoperative analgesics in pediatric patients undergoing strabismus surgery. Patients and Methods Approval to perform the study was granted by the Institutional Review Board. Informed written consent was obtained from the parents prior to their children’s enrollment in the study. Sixty children aged 2-6 years of age with ASA status I to II scheduled for primary surgical correction of unilateral or bilateral strabismus were included in the study. Patients were randomly allocated to one of 2 equal groups. The inclusion criteria were: age 6 years or under, unilateral or bilateral surgery, primary surgery or reoperation, horizontal, vertical, or oblique muscle surgery. Exclusion criteria were: known drug sensitivity or body weight less than 8 kg. A standard anesthetic protocol was used for all children included in the studyMidazolam (0.3 mg/kg) Radwa Bakr et. al and atropine (10 μg/kg) were given rectally 30 minutes before anesthesia. EMLA (eutectic mixture of local anesthetics) cream was applied 30 min before anesthesia over two potential venipuncture sites. Induction was by sevoflurane inhalation and maintenance was by spontaneous ventilation of sevoflurane in oxygen and nitrous oxide via laryngeal mask airway. Intraoperative analgesia was in the form of rectal paracetamol 20 mg/kg. Patients were monitored intraoperatively by electrocardiography, pulse oximetry, noninvasive blood pressure, and end-tidal CO2 measurements. Heart rate and blood pressure were recorded before induction and every 5 minutes during anesthesia and surgery until the end of the procedure. After induction, bupivacaine 0.5% or a placebo saline solution were slowly injected in the subtenon space with a curved, blunt 25-mm 20 gauge cannula introduced through a small conjunctival and subtenon limbal aperture. The dose of bupivacine was titrated according to the child’s body weight to ensure a subtoxic dose of less than 2.5 mg/kg. The efficacy of the block was judged satisfactory if the pupil was widely dilated and fixed, thus confirming ciliary ganglion blockade. The anesthesiologist, surgeon, and nurses were blinded to the nature of the injected solution. All operations were performed by the same surgeon. Surgery was started 5 minutes after the subtenon injection. The surgical protocol was standardized; for surgery on the vertical rectus muscles the conjunctiva was opened over the insertion. The inferior oblique was approached via limbal peritomy if surgery on the lateral rectus was also being performed, or via a circumferential conjunctival incision 10 mm from the limbus if not. The conjunctiva was closed with 6-0 or smaller Vicryl®. All patients received 1 drop of amethocaine 1% onto the operated eye at the conclusion of surgery. After emergence from anesthesia patients were transferred to the recovery ward. On arrival in the recovery room, the patient›s behavior was assessed by a nurse who was not aware of the nature of the solution injected in the subtenon space. The pain scale used for assessment was the Face, Legs, Activity, Cry, Consolability scale (FLACC)8 (Table 1). This behavioral pain assessment scale is widely accepted as a method of assessment for pain in children by direct observation. The scale consists of 5 categories. Each category is scored on a 0-2 scale, which results in a total score of 0-10. A score Subtenon bupivacaine for pediatric strabismus surgery 93 Table 1 FLACC (face, legs, activity, cry, consolability) scale Face Legs 0 1 2 No particular expression or smile Occasional grimace or frown, withdrawn, disinterested Frequent to constant frown, clenched jaw, quivering chin 0 1 2 Normal position or relaxed Uneasy, restless, tense Kicking or legs drawn up Activity Cry Consolability Lying quietly, normal position, Squirming, shifting back and forth, moves easily tense Arched, rigid or jerking 0 1 2 No cry (awake or asleep) Moans or whimpers Crying steadily, screams or sobs, frequent complaint 0 1 2 Content, relaxed Reassured by touch Difficult to console or comfort The FLACC scale can be used in children up to 7 years and in children with cognitive impairment. Each of the five categories (faces, legs, activity, cry, consolability) is scored 0-2, and the scores are added to yield a total from 0 to 10. Each section above is scored and a total obtained. of 0 means relaxed and comfortable, 1-3 indicates mild discomfort, 4-6 indicates moderate pain, and 7-10 indicates severe discomfort or pain or both. Pain assessment was performed after the removal of the laryngeal mask, and then at 30 min intervals until discharge from the recovery ward. Children with a FLACC score equal to or higher than 4 were given 20 mg/kg rectal paracetamol. The following parameters were collected in the recovery room: Pain scores, at 0 min, 30 min, 1hr, 2hrs, 3hrs, incidence of occurrence of Occulo-cardiac reflex (indicated by a sudden decrease of the heart rate higher than 20% and concomitant with muscular traction), incidence of postoperative nausea and vomiting, number of patients requiring additional systemic analgesia, and the mean time to first analgesia. Statistical analysis was done using SPSS (version 14.0, SPSS Inc., Chicago, IL, USA). Continuous data, such as age, weight, anesthetic duration, time to discharge from the recovery ward and time to eye opening, were expressed as mean and SD and were analyzed using Student’s t-test. A chi-squared test was performed for the comparison between qualitative variables. A Mann-Whitney U test allowed intergroup comparison between quantitative variables. A P value < 0.05 was considered as significant. Results were expressed as mean ± SD. Confidence intervals of 95% are provided for statistically significant results. Results Fifty six children completed the study. One child in the control group and three in the treatment group were excluded after recruitment due to incomplete data. 46 (82.0%) underwent unilateral and 10 (18.0%) underwent bilateral surgery. 45 operations (81.1%) were primary procedures and 11 (18.9%) were reoperations. 27 children (48.6%) were randomized to the treatment group and 29 (51.4%) were randomized to the control group. The groups were similar with regards to age, weight, sex, proportions having bilateral surgery or reoperations, and number of muscles operated upon (Table 2). The pain scores at each time interval are summarized in Table (3). The treatment group experienced significantly less pain than the control at the 0-h observation (P = 0.005) and at 30 min (P = 0.013). There was no significant difference between the two groups at the other time intervals. There was a significant reduction in the incidence of occurrence of occulocardiac reflex that required a temporary interruption of traction on the muscles and the injection of atropine in the study group (5 patients) compared to (11 patients) in the control group. The incidence of nausea was not significantly decreased in the study group (3 patients compared to 4 patients in M.E.J. ANESTH 23 (1), 2015 94 Radwa Bakr et. al Table 2 Patient characteristics: Data is presented as mean ± SD Subtenon Group (N = 27) Mean (SD) Control Group (N = 29) Mean (SD) P-value Age (years) 3.27 ± 1.69 3.37 ± 1.71 0.38 Weight (kg) 17.6 ± 3.6 17.9 ± 3.9 0.54 12:15 11:18 0.62 Sex ratio (male: female) ASA I:II 18:1 18:1 1 Unilateral: Bilateral surgery 22:5 24:5 0.9 Primary surgery: reoperations 21:6 22:8 0.69 Number of operated muscles 2.2 ± 0.8 2.2 ± 0.8 1 Length of the operation 35.5 ± 10 36 ± 10.2 0.63 the control group); however, the incidence of vomiting was significantly lower in the study group (6 patients) than the control group (10 patients) (Table 4). Eight of the 27 patients in the subtenons group required additional systemic analgesia (30%) compared to 19 of 29 controls (65%). This difference was borderline with regards to statistical significance (P = 0.052). The median time to first analgesia was 2hrs 45min in the control group compared to 1 hour in the study group (Table 5). The length of stay in the recovery room was reduced to a significant degree in the bupivacaine group; two hours after the removal of the LMA, 22 of 29 children recruited in the control group were still present in the recovery room in contrast to 4 of the 27 children in the study group. Discussion Strabismus surgery in children is frequently performed as an outpatient procedure. A large proportion of children experience clinically significant pain after strabismus surgery9. Additionally, Pediatric strabismus surgery often leads to postoperative behavioral problems during the recovery period as a result of pain, visual disturbances, nausea and vomiting, and separation from parents. A study demonstrated that altered behavior was encountered on emergence in 44% of operated children, and that 20% of them exhibited complex symptoms simulating delirium10. Symptoms such as PONV and pain are the main cause of delayed discharge, contact with the hospital after discharge, and hospital readmission after outpatient surgery for these children11. Pain after strabismus surgery may be caused by sectioning and traction exerted on the extraoccular muscles. Many strategies have been proposed for treatment of the pain experienced by these children. Topical analgesia using drops containing a NSAID was efficient in some studies12, but not effective in others13,14. Table 3 Summary of pain scores, Mean ± SD Subtenon Group (N = 27) Control Group (N = 29) P-value 0 min 1.77 ± 1.12 3.41 ± 1.12 0.005 30 min 1.66 ± 1 3.17 ± 1.04 0.013 1 hr. 2.11 ± 0.89 2.14 ± 0.1 0.91 2 hrs. 2.55 ± 0.89 2.86 ± 1.41 0.57 3 hrs. 3.04 ± 1.4 2.72 ± 1.47 0.38 Subtenon bupivacaine for pediatric strabismus surgery 95 Table 4 Incidence of side effects: Data is presented as n(%) Subtenon Group (N = 27) Control Group (N = 29) P-value OCR 5 (18%) 11 (38%) 0.003 Incidence of nausea 3 (11%) 4 (14%) 0.575 Incidence of vomiting 6 (22%) 10 (34%) 0.048 Opioid analgesia is frequently used to reduce postoperative pain after strabismus surgery; however, these drugs often cause nausea, vomiting, and drowsiness. A study showed that opioid analgesia is associated with more prolonged recovery times after anesthesia, a longer stay in hospital, and delayed return to normal activity when compared to other analgesics15. Intravenous NSAID such as ketorolac have been shown to be as effective as morphine and pethidine for the relief of pain after strabismus surgery in children, and with a lower incidence of postoperative nausea and vomiting16,17. Other studies showed that systemic NSAIDs such as ketoprofen were efficient in reducing pain after strabismus surgery in children when compared to placebo18,19. On the other hand certain NSAIDs such as ibuprofen and simple analgesics such as paracetamol were shown to be less effective20. Asthma occurs in 30% to 40% of children, 20% of those are sensitive to aspirin and other NSAIDs21,22. In addition, reactions to NSAIDs include urticaria, angioedema, rhinitis23, and exacerbation of asthma or bronchospasm24-27, which may be fatal28. These side effects occur after administration in common ophthalmic procedures and have been shown to occur with NSAIDs such as ibuprofen, diclofenac, and ketorolac28. Therefore the use of NSAIDs may not be appropriate for many children undergoing strabismus surgery. Different techniques of regional anesthesia combined with general anesthesia have been proposed for the young child undergoing strabismus surgery. In addition to controlling postoperative pain, it has been suggested that suppression of the trigeminal reflex by regional anesthesia may correlate with a decrease in the incidence of vomiting29. These techniques have yielded conflicting reports. Postoperative topical tetracaine compared with topical saline in pediatric strabismus surgery was shown to provide a short-lived but significantly better pain relief as judged by both pain score and analgesic requirement30. Topical amethocaine 1% drops and subconjunctival infiltration with bupivacaine 0.5% administered at the conclusion of strabismus surgery have been shown to be equally effective in reducing postoperative pain31, although another study did not show any additional analgesic effect of either of these interventions when compared to placebo32. Similarly, a study showed that the subconjunctival injection of bupivacaine 0.5% as compared with a placebo decreased postoperative pain scores in 36 young children. Another study compared subconjunctival bupivacaine to topical tetracaine in children undergoing squint surgery, with both giving effective analgesia. Table 5 Requirements of additional systemic analgesia Number of patients requiring additional systemic analgesia n (%) Median time to first analgesia Subtenon Group (N = 27) Control Group (N = 29) P-value 8 (30%) 19 (65%). 0.052 2 hours 45 minutes 1 hour 0.05 M.E.J. ANESTH 23 (1), 2015 96 However, some investigators found no difference in pain score after pediatric squint surgery using postoperative topical saline, topical tetracaine or subconjunctival bupivacaine. Although subconjunctival local anesthetics have had some success in the relief of postoperative pain, the source of pain after strabismus surgery is believed to be receptors in tenon’s fascia and muscle tendons as well as conjunctival receptors. Regional blocks have also been explored in children. Retrobulbar anesthesia by the administration of 2 mL of bupivacaine 0.5% before surgery was as effective as a subconjunctival injection given after the operation in 10 children5. However the block reduced the incidence of OCR from 60% (control group) to 4% in children3. Similarly, a study proved that peribulbar block (0.3 mL/kg of a bupivacaine 0.5% and lidocaine 2% mixture) reduced postoperative pain in 25 children 5 to 14 years of age to a significant degree; two thirds of these children were operated on for strabismus33,34. The authors also reported a major reduction in the incidence of occulocardiac reflex and postoperative nausea and vomiting compared with the control group treated with pethidine35,36. However, when comparing different eye blocks in children, subtenon anesthesia seems to offer some advantages over retrobulbar or peribulbar blocks in pediatric strabismus surgery; All these techniques require the cooperation of patients by asking them to move their eyes laterally to exclude perforation of the globe or nerve injury during the procedure37. Small children are unable to cooperate in this way, which leads to performance of the block under general anesthesia, with poor clinical control. Thus, in the current study, we elected to perform subtenon anesthesia in pediatric patients undergoing squint surgery. Subtenon’s anesthesia results in excellent anesthesia and akinesia and is widely used for adult anterior and posterior segment surgery38. The anesthetic agent is delivered into the subtenon’s space posterior to the globe’s equator using a blunt cannula inserted through a conjunctival incision, usually located in the inferonasal quadrant. The drug spreads rapidly through the subtenon’s space and anesthetizes the long and short ciliary nerves as they pierce Tenon’s capsule around the optic nerve39. Radwa Bakr et. al These nerves carry sensory fibers from the sclera, cornea, and uveal tract. Spread of the drug into the muscle sheaths and eyelids results in anesthesia of these structures40. The surgery is then started through the same conjunctival incision which allows access to extraocular muscles. Therefore, application of anesthetics is no more invasive than the operation itself. Moreover, the required volume of local anesthetics to provide adequate analgesia is less important and limits the risks of damage caused by rapid injection or myotoxicity from the anesthetic solution. Complications after subtenons anesthesia are uncommon but orbital hemorrhage41, extraocular muscle injury42,43, and globe perforation with scissors during dissection of the subtenons space44 have all been reported. There is also a risk of damage to structures crossing the subtenons space during rapid or high volume injection, and of myotoxicity from the anesthetic agent, but neither of these has yet been reported after subtenons administration. This was fully explained to parents at the time of consent. There were no complications resulting from subtenon injection in this study. We chose to administer the block preoperatively rather than postoperatively since regional blocks are associated with fewer episodes of bradycardia and hypertension intraoperatively caused by the occulocardiac reflex which results from the traction on the extraoccular muscles45, this was evident in our study where a significant difference in the occurrence of occulocardiac reflex was observed. Preoperative administration also offered the advantage of facilitation of surgical dissection and delivery of a controlled volume. The administration of local anesthetic, postoperatively is usually associated with protrusion of Tenon fascia and leakage of anesthetic through the incision. The administration of a preoperative subtenon block did not result in any surgical difficulty from tissue distortion. In this study we looked at the administration of a long acting anesthetic; bupivacaine has an onset of action of approximately 20 min45, preoperative administration ensures analgesic effectiveness as the general anesthetic wears off. We, found significant reduction in postoperative pain score as measured by Subtenon bupivacaine for pediatric strabismus surgery the FLACC score. Similar results have been obtained in a randomized controlled trial that investigated the postoperative use of sub-Tenon lignocaine in 111 children undergoing squint surgery. Pain was reduced significantly in the first hour after surgery, but thereafter there was no effect46. Lignocaine is a shorter-acting anesthetic with a duration of 1-2h when given as a sub-Tenon block, while the effect of bupivacaine lasts for 3-3.5h45. Our findings are also similar to those obtained by Steib et al. who explored the preoperative administration of bupivacaine in 40 children the authors found a significant reduction in pain scores in the study group. The incidence of occulocardiac reflex and postoperative nausea and vomiting were also reduced in the study group47. On the other hand, in a study by Morris et al the authors used preoperative levobupivacaine to perform subtenon block in 27 children undergoing strabismus surgery and found no significant reduction in pain scores in the study group49. However, their study had several limitations; a placebo was not used in the control group, and not all patients received exactly the same general anesthetic agents or additional analgesia these two factors may have influenced the results obtained by these investigators. These factors were avoided in our study which may explain our favorable results. However, the results obtained by these authors matched previous results obtained by Carden et al33. 97 No data in the literature suggests the optimal volume to inject in the pediatric population. Use of a large volume to produce akinesia is not essential, as general anesthesia is always used with young children, which allows satisfactory operating conditions by itself49-52. A significant reduction in PONV was observed in our study during the recovery period. This undesirable effect after strabismus surgery is caused by pain, traction of the muscles, and perioperative use of opioids. A similar reduction in PONV was also encountered in the study conducted by Steib et al47. In conclusion, a preoperative subtenon block with bupivacaine combined with general anesthesia allowed efficient control of postoperative pain as well as a reduction in the incidence of OCR and PONV in young children undergoing strabismus surgery. We recommend that further studies be conducted to determine the optimal volume to inject in the subtenon space and to compare different local anesthetics. Acknowledgements The authors sincerely acknowledge the support of the Ain Shams University Ophthalmology Department in supporting this anesthesiology research. The authors also acknowledge the efforts of Mr. Deepak Gupta in the statistical calculations and analysis. M.E.J. ANESTH 23 (1), 2015 98 Radwa Bakr et. al References 1. Ruta U, Gerding H, Möllhoff T: Einfluss von local appliziertem Lidocain auf die Ausprägung des okulokardialen Reflexes. Ophtalmologe; 1997, 94:354-359. 2. Watson DM: Topical amethocaine in strabismus surgery Anaesthesia, 46 (1991), pp. 368-370. 3. El-Kasaby HT, Habib NE, Marczak AM: Subconjunctival bupivacaine in strabismus surgery Eye, 7 (1993), pp. 346-349. 4. Habib NE, El-Kasaby HT, Marcza, Hsuan J: Subconjunctival bupivacaine versus topical amethocaine in strabismus surgery Eye, 7 (1993), pp. 757-759. 5. Ates Y, Unal N, Cuhruk H, Erkan N: Postoperative analgesia in children using preemptive retrobulbar block and local anesthetic infiltration in strabismus surgery. Reg Anesth Pain Med; 1998, 23:569-574. 6. Verma SR, Makker RH: Sub-tenon eye block: Approaching the ideal? Anesthesiology; 2001, 94:376-377. 7. Walters G, Stewart OG, Bradbury JA: The use of subtenon ropivacaine in managing strabismus with adjustable sutures. JAAPOS; 2001, 5:95-97. 8. Merkel SI, Voepel-Lewis T, Shayevitz JR et al: The FLACC: a behavioral scale for scoring postoperative pain in young children. Pediatr Nurs; 1997, 23:293-297. 9. Finlay GA, McGrath PJ, Forward SP, McNeill G, Fitzgerald P: Parents’ management of children’s pain following ’minor’ surgery. Pain; 1996, 64:83-7. 10.Rawal N: Analgesia for day-case surgery. 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Ophthalmology; 1997,104:419-24. 16.Munro HM, Riegger LQ, Reynolds PI, Wilton NCT, Lewis IH: Comparison of the analgesic and emetic properties of ketorolac and morphine for paediatric outpatient strabismus surgery. Br J Anaesth; 1994, 72:624-8. 17.Shende D, Das K: Comparative effects of intravenous ketorolac and pethidine on perioperative analgesia and postoperative nausea and vomiting (PONV)for paediatric strabismus surgery. Acta Anaesthesiol Scand; 1999, 43:265-9. 18.Mikawa K, Nishina K, Maekawa N, Shigh M, Obara H: Dose response of flurbiprofen on postoperative pain and emesis after pediatric strabismus surgery. Can J Anaesth; 1997, 44:95-8. 19.Kokki H, Homan E, Tuovinen K, Purhonen S: Peroperative treatment with IV ketoprofen reduces pain and vomiting in children after strabismus surgery. Acta Anaesthesiol Scand; 1999, 43:13-8. 20.Morrison NA, Repka MX: Ketorolac versus acetaminophen or ibuprofen in controlling postoperative pain in patients with strabismus. Ophthalmology; 1994, 101:915-8. 21.Taussig LM, Landau LI: Pediatric respiratory medicine. St Louis, Mosby; 1999, pp. 3, 918. Levy S, Volans G: The use of analgesics in patients with asthma. 22. Drug Safety; 2001, 24:829-41. 23.Jenkins C: Recommending analgesics for people with asthma. Am J Therapeutics; 2000, 7:55-61. 24.Sharir M: Exacerbation of asthma by topical diclofenac. Arch Ophthalmol; 1997, 115:294-5. 25.Sitenga GL, Ing EB, Van Dellen RG, Younge BR, Leavitt JA: Asthma caused by topical application of ketorolac. Ophthalmology; 1996, 103:890-2. 26.Hebert WG, Scopelitis E: Ketorolac precipitated asthma. South Med J; 1994, 87:282-3. 27.Chen AH, Bennett CR: Ketorolac induced bronchospasm in an aspirin-intolerant patient. Anesth Progress; 1994, 41:102-7. 28.Antonicelli L, Tagliabracci A: Asthma death induced by ibuprofen. Monaldi Arch Chest Dis; 1995, 50:276-8. 29.Allen LE, Sudesh S, Sandramouli S, et al: The association between the oculocardiac reflex and post-operative vomiting in children undergoing strabismus surgery. Eye; 1998, 12:193-6. 30.Dalens B: Regional anaesthesia in infants, children, and adolescents. London, England: Waverly Europe; 1995, pp. 162-3. 31.Habib NE, El-Kasaby HT, Marczak AM, Hsuan J: Subconjunctival bupivacaine versus topical amethocaine in strabismus surgery. Eye; 1993, 7:757-9. 32.Watson DM. Topical amethocaine in strabismus surgery. Anaesthesia; 1991, 46:368-70. 33.Carden SM, Colville DJ, Davidson AJ, et al: Adjunctive intraoperative local anaesthesia in paediatric strabismus surgery: a randomised controlled trial. Austral NZ J Ophthalmol; 1998, 26:289-97. 34.Burton H: Somatosensory sensation from the eye. In: Moses RA, ed. Adler’s physiology of the eye: clinical applications. 7th edn. St Louis: CV Mosby, 1981, p. 74. 35.Kaline RE, Orcutt JC: Ocular and periocular pain. In: Bonica JJ, ed. The management of pain. 2nd edn, vol. 1. Philadelphia: Lea & Febiger; 1990, pp. 759-68. 36.Deb K, Subramaniam R, Dehran M, Tandon R, Shede D: Safety and efficacy of peribulbar block as adjunct to general anaesthesia for paediatric ophthalmic surgery. Paediatr Anaesth; 2001, 11:161-167. 37.Ruschen H, Bremner FD, Carr C: Complications after sub-tenon’s eye block. Anesth Analg; 2003, 96:273-277. 38.Roman SJ, Chong Sit DA, Boureau CM, Auclin FX, Ullern MM: Subtenons anesthesia: an efficient and safe technique. Br J Ophthalmol; 1998, 81:673-6. 39.Winder S, Walker SB, Atta HR: Ultrasonic localization of anesthetic fluid in subtenons, peribulbar, and retrobulbar techniques. J Cataract Refract Surg; 1999, 25:56-9. 40.Ripart J, Metge L, Prat-Pradal D, Lopez FM, Eledjam JJ: Medial canthus single injection episcleral (subtenon anesthesia): computed tomography imaging. Anesth Analg; 1998, 87:42-5. 41.Olitsky SE, Juneja RG: Orbital hemorrhage after the administration of subtenons infusion anesthesia. Ophthalmic Surg Lasers; 1997, 28:145-6. Subtenon bupivacaine for pediatric strabismus surgery 42.Jaycock PD, Mather CM, Ferris JD, Kirkpatrick JN: Rectus muscle trauma complicating subtenons local anesthesia. Eye; 2001, 15:583-6. 43.Spierer A, Schwalb E: Superior oblique muscle paresis after subtenons anesthesia for cataract surgery. J Cataract Refract Surg; 1999, 25:144-5. 44.Frieman BJ, Friedberg MA: Globe perforation associated with subtenons anesthesia. Am J Ophthalmol; 2001,131:520-1. 45.Tuckley JM: The pharmacology of local anaesthetic agents. Update Anaesth; 1994, 4:1-3. 46.Sheard RM, Mehta JS, Barry JS, et al: Subtenon’s lidocaine injection for postoperative pain relief after strabismus surgery in children: a prospective randomized controlled trial. J AAPOS; 2004, 8:314-17. 47.Steib A, Karcenty A, Calache E, Franckhauser J, et al: Effects of Subtenon Anesthesia Combined With General Anesthesia on perioperative analgesic requirements in pediatric strabismus surgery. Regional Anesthesia and Pain Medicine; 2005, 30(5):478-483. 99 48.Morris B, Watts P, Zatman T, Absolom M, Haider S, Hall J: Pain relief for strabismus surgery in children: a randomised controlled study of the use of preoperative sub-Tenon levobupivacaine. Br J Ophthalmol; 2009, 93:329-332. 49.Calendar E, Murrain M, Quentin JC, Brassier G: Subtenon infiltration or classical analgesic drugs to relieve postoperative pain. Clin Experimental Ophthalmol; 2004, 32:154-158. 50.Kumar CM, Odds C: Evaluation of the Greenbaum sub-Tenon’s block. Br J Anaesth; 2001, 87:631-633. 51.Tokuda Y, Oshika T, Amano S, Yoshitomi F, Inouye J: Anesthetic dose and analgesic effects of sub-Tenon’s anesthesia in cataract surgery. J Cataract Refract Surg; 1999, 25:1250-1253. 52.Nouvellon E, L’hermite J, Chaumeron A, Mahamat A, Mainemer M, Charavel P, Mahiou P, Dupeyron G, Bassoul B, Dareau S, Eledjam JJ, Ripart J: Ophthalmic regional anesthesia: Medial canthus episcleral (sub-tenon) single injection block. Anesthesiology; 2004, 100:370-374. M.E.J. ANESTH 23 (1), 2015 CASE REPORTS Straight to Video: Tonsillar Injury During Elective GlideScope Ò-Assisted Pediatric Intubation Jason D. Rodney*, Zulfiqar Ahmed*, Deepak Gupta*, and M aria M arkakis Z estos * Abstract Airway management in pediatric patients presenting for tonsillectomy and adenoidectomy may prove challenging given the enlarged upper airway structures. Video Laryngoscopy (VL) can be very helpful but it does not come without risks. In this case report, we report an unfavorable outcome of VL in a pediatric patient with adenotonsillar hypertrophy. Introduction Airway management in pediatric patients presenting for tonsillectomy and adenoidectomy may prove challenging given the enlarged upper airway structures. Video Laryngoscopy (VL) as a modality of airway instrumentation has the potential to facilitate an unobstructed view of the vocal cords in situations where the oral, pharyngeal and laryngeal axes are difficult to align. Such may be the case due to body habitus, trauma or neoplasm, among other indications. For this reason, VL is an important tool in the anesthesiologist’s armamentarium. It has been suggested that VL has earned a place high up in an algorithm for dealing with a difficult airway, particularly in a “can’t intubate/can’t ventilate” patient scenario1-4. VL may also be considered in patients where minimizing the force required during laryngoscopy is desirable such as a patient with loose teeth. Even though VL can be very helpful, it does not come without risks. There have been numerous case reports describing injury to various oropharyngeal structures. Hereby, we report an unfavorable outcome of VL in a pediatric patient with adenotonsillar hypertrophy undergoing tonsillectomy and adenoidectomy. Case Presentation A 6-year old female with comorbidities of sickle cell disease and a history of numerous blood transfusions presented for elective tonsillectomy-adenoidectomy due to obstructive sleep apnea. Preoperative airway examination revealed Mallampati Class I with full range of neck *MD. Corresponding author: Maria Markakis Zestos, MD, Chief of Anesthesiology, Children’s Hospital of Michigan, Associate Professor, Wayne State University, 3901 Beaubien St, Suite 3B-17, Detroit Michigan 48201, United States. Office: 1-313745-5535, Fax: 1-313-745-5448. E-mail: [email protected] 101 M.E.J. ANESTH 23 (1), 2015 102 and jaw mobility, adequate thyro-mental distance, and as expected, enlarged tonsils. In addition to tonsillar hypertrophy, it was noted that the patient had loose upper incisors about which the parent was very concerned. The anesthesia team decided to use GlideScopeÒ Cobalt AVL for endotracheal intubation in an effort to avoid inadvertent pressure or traction on the loose teeth. After the induction of anesthesia, endotracheal intubation was attempted by the anesthesiology resident with the GlideScopeÒ. A Cormack Lehane grade I laryngoscopic view was easily achieved with a size 2 GlideScopeÒ blade. A 6.0 internal diameter (ID) oral RAE endotracheal tube, without stylet, was unsuccessfully introduced to the oropharynx. The rigid GlideRiteÒ stylet was not used during the initial attempts to pass the endotracheal tube because when inserted into the endotracheal tube, the tip of the stylet protruded beyond the end of the oral RAE endotracheal tube. The RAE endotracheal tube of ID 6.0 mm was removed, and it was noted that blood was present on the tip of the endotracheal tube. Mask ventilation was resumed with oxygen and sevoflurane and at this time, it was much more difficult to manually ventilate than during induction despite head-tilt-chin-lift and jaw thrust maneuvers. A subsequent attempt at VL by the supervising anesthesiologist revealed that the tonsils were almost completely obstructing the laryngoscopic view. Further attempts at intubation were withheld, and assistance was sought from the otorhinolaryngology surgical team due to the apparent injury to the enlarged tonsils during the initial intubation attempt. The examination by the otorhinolaryngologist revealed Brodsky Grade 4+ tonsils with one partially detached tonsil having minimal mucosal bleeding. Endotracheal intubation was achieved by an attending physician with a Miller 2 blade with no observable effect to the loose teeth. At this time, the decision was made to proceed with the tonsillectomyadenoidectomy as planned. After discussion with the concerned parent, the loose tooth was removed by the attending dentist. The remainder of the peri-operative course was unremarkable. J.Rodney et. al Discussion Even though VL has been shown to improve the ability of novices to obtain laryngeal exposure when compared to Direct Laryngoscopy (DL) in adults5, there is evidence for and against ease of use with respect to pediatric patients. Fonte et al6 demonstrated that pediatric residents, who were unfamiliar with VL, failed at tracheal intubations at a higher rate while using VL than when performing DL with a Miller blade in pediatric patients with a normal airway or tongue edema. Ilies et al7 found no difference between an attending physician’s and an experienced resident’s ability to obtain an improved view of vocal cords using VL after DL. Despite a perceived disadvantage to using VL for tracheal intubation by novices, it has been shown that in the hands of experienced anesthesiologists, VL does improve the ability to successfully intubate pediatric patients8-10. VL may prove to be a useful tool in obtaining laryngeal exposure, but there have been numerous reports of injury to various oropharyngeal structures in adults including abrasion, perforation and laceration of tonsils, palatopharyngeal wall, lingual nerve as well as dental injury11-18. It has been suggested that both the blind insertion and pathway of the endotracheal tube and the rigid stylet may be contributing factors to oropharyngeal injury during VL19-20. Although the decision for airway instrument choice was ultimately influenced by the patient’s dentition rather than a perceived difficult airway (even though the loose tooth was eventually removed by a dentist), this case shows one instance wherein use of GlidescopeÒ for pediatric endotracheal intubation may have contributed to more harm than good. Even if the rigid stylet is not used to facilitate intubation, there is an inherent risk of oropharyngeal injury when using the video laryngoscope due to the inability to visualize the endotracheal tube passing from the opening of the mouth to the point where it enters the field of focus of the camera lens. The GlidescopeÒ has become a popular tool among peri-operative, critical care and emergency room care providers. Few would dispute that it has earned a place in the American Society of Anesthesiologists’ Difficult Airway Algorithm21 which Injury with GlideScope pediatric intubation states that providers managing difficult airway should give appropriate considerations to the comparative benefits vs. workability potential of options including VL as the initial intubation attempt3. In the presence of a known pharyngeal mass it may be worth considering DL, flexible fiberoptic (FFO) bronchoscope or a combination of VL and FFO used in conjunction as described by Weissbrod and Merati22. We would also recommend caution when using the video laryngoscope for educational purposes. Although VL may facilitate both trainer and trainee to visualize the vocal cords in pediatric patients, its use may increase 103 the risk of oropharyngeal injury or failed intubation in inexperienced hands. Conclusion In summary, operators’ tendency to direct and focus their attention ‘Straight To Video’ in VL should be cautioned against in order to avoid potential oropharyngeal injuries along the route of blind insertion of the endotracheal tube from the angle of the mouth until it becomes visible on the screen of the VL. M.E.J. ANESTH 23 (1), 2015 104 J.Rodney et. al References 1. Caldiroli D, Cortellazzi P: A new difficult airway management algorithm based upon the El Ganzouri Risk Index and GlideScope® videolaryngoscope: a new look for intubation? Minerva Anestesiol; 2011, 77:1011-1017. 2. Frova G: Do videolaryngoscopes have a new role in the SIAARTI difficult airway management algorithm? Minerva Anestesiol; 2010, 76:637-640. 3. Saxena S: The ASA difficult airway algorithm: is it time to include video laryngoscopy and discourage blind and multiple intubation attempts in the nonemergency pathway? Anesth Analg; 2009, 108:1052. 4. Weiss M, Engelhardt T: Proposal for the management of the unexpected difficult pediatric airway. Paediatr Anaesth; 2010, 20:454-464. 5. Cooper RM, Pacey JA, Bishop MJ, Mccluskey SA: Early clinical experience with a new videolaryngoscope (GlideScope) in 728 patients. Can J Anaesth; 2005, 52:191-198. 6. Fonte M, Oulego-Erroz I, Nadkarni L, Sánchez-Santos L, Iglesias-Vásquez A, Rodríguez-Núñez A: A randomized comparison of the GlideScope videolaryngoscope to the standard laryngoscopy for intubation by pediatric residents in simulated easy and difficult infant airway scenarios. Pediatr Emerg Care; 2011, 27:398-402. 7. Ilies C, Fudickar A, Thee C, Dütschke P, Hanss R, Doerges V, Bein B: Airway management in pediatric patients using the Glidescope Cobalt®: a feasibility study. Minerva Anestesiol; 2012, 78:10191025. 8. Kim JT, Na HS, Bae JY, Kim DW, Kim HS, Kim CS, Kim SD: GlideScope video laryngoscope: a randomized clinical trial in 203 paediatric patients. Br J Anaesth; 2008, 101:531-534. 9. Redel A, Karademir F, Schlitterlau A, Frommer M, Scholtz LU, Kranke P, Kehl F, Roewer N, Lange M: Validation of the GlideScope video laryngoscope in pediatric patients. Paediatr Anaesth; 2009, 19:667-671. 10.Xue FS, Liu HP, Liu JH, Liao X, Zhang YM: Facilitating endotracheal intubation using the GlideScope video laryngoscope in children with difficult airways. Paediatr Anaesth; 2009, 19:918-919. 11.Cross P, Cytryn J, Cheng KK: Perforation of the soft palate using the GlideScope videolaryngoscope. Can J Anaesth; 2007, 54:588589. 12.Cooper RM: Complications associated with the use of the GlideScope videolaryngoscope. Can J Anaesth; 2007, 54:54-57. 13.Choo MK, Yeo VS, See JJ: Another complication associated with videolaryngoscopy. Can J Anaesth; 2007, 54:322-324. 14.Chin KJ, Arango MF, Paez AF, Turkstra TP: Palatal injury associated with the GlideScope. Anaesth Intensive Care; 2007, 35:449-450. 15.Malik AM, Frogel JK: Anterior tonsillar pillar perforation during GlideScope video laryngoscopy. Anesth Analg; 2007, 104:16101611. 16.Vincent RD JR, Wimberly MP, Brockwell RC, Magnuson JS: Soft palate perforation during orotracheal intubation facilitated by the GlideScope videolaryngoscope. J Clin Anesth; 2007, 19:619-621. 17.Hsu WT, Tsao SL, Chen KY, Chou WK: Penetrating injury of the palatoglossal arch associated with use of the GlideScope videolaryngoscope in a flame burn patient. Acta Anaesthesiol Taiwan; 2008, 46:39-41. 18.Leong WL, Lim Y, Sia AT: Palatopharyngeal wall perforation during Glidescope intubation. Anaesth Intensive Care; 2008, 36:870-874. 19.Dupanovic M: Maneuvers to prevent oropharyngeal injury during orotracheal intubation with the GlideScope video laryngoscope. J Clin Anesth; 2010, 22:152-154. 20.Magboul MM, Joel S: The video laryngoscopes blind spots and possible lingual nerve injury by the Gliderite rigid stylet-case presentation and review of literature. Middle East J Anesthesiol; 2010, 20:857-860. 21.Apfelbaum JL, Hagberg CA, Caplan RA, Blitt CD, Connis RT, Nickinovich DG, Hagberg CA, Caplan RA, Benumof JL, Berry FA, Blitt CD, Bode RH, Cheney FW, Connis RT, Guidry OF, Nickinovich DG, Ovassapian A: American Society of Anesthesiologists Task Force on Management of the Difficult Airway: Practice guidelines for management of the difficult airway: an updated report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology; 2013, 118:251-270. 22.Weissbrod PA, Merati AL: Reducing injury during video-assisted endotracheal intubation: the “smart stylet” concept. Laryngoscope; 2011, 121:2391-2393. Percutaneous Balloon Compression of Gasserian Ganglion for the treatment of Trigeminal Neuralgia: An Experience from India Dr. Anurag Agarwal*, Dr. Vipin Dhama**, Dr. Yogesh K. Manik**, Dr. M. K. Upadhyaya**, Dr. C. S. Singh**and Dr. V. Rastogi** Abstract Trigeminal neuralgia (TN) is characterized by unilateral, lancinating, paroxysmal pain in the dermatomal distribution area of trigeminal nerve. Percutaneous balloon compression (PBC) of Gasserian ganglion is an effective, comparatively cheaper and simple therapeutic modality for treatment of TN. Compression secondary to PBC selectively injures the large myelinated A-alfa (afferent) fibers that mediate light touch and does not affect A-delta and C-fibres, which carry pain sensation. Balloon compression reduces the sensory neuronal input, thus turning off the trigger to the neuropathic trigeminal pain. In this current case series, we are sharing our experience with PBC of Gasserian Ganglion for the treatment of idiopathic TN in our patients at an academic university-based medical institution in India. During the period of August 2012 to October 2013, a total of twelve PBCs of Gasserian Ganglion were performed in eleven patients suffering from idiopathic TN. There were nine female patients and two male patients with the age range of 35-70years (median age: 54years). In all patients cannulation of foramen ovale was done successfully in the first attempt. In eight out of eleven(72.7%) patients ideal ‘Pear-shaped’ balloon visualization could be achieved. In the remaining three patients (27.3%), inflated balloon was ‘Bullet-shaped’. In one patient final placement of Fogarty balloon was not satisfactory and it ruptured during inflation. This case was deferred for one week when it was completed successfully with ‘Pear-shaped’ balloon inflation. During the follow up period of 1-13 months, there have been no recurrences of TN. Eight out of eleven patients (72.7%) are completely off medicines (carbamazepine and baclofen) and other two patients are stable on very low doses of carbamazepine. All patients have reported marked improvement in quality of life. This case series shows that percutaneous balloon compression is a useful minimally invasive intervention for the treatment of trigeminal neuralgia. Introduction Trigeminal neuralgia (TN) is characterized by unilateral, lancinating, paroxysmal pain in the dermatomal distribution area of trigeminal nerve1. According to International Headache Society (IHS) and International Association for Study of Pain (IASP) trigeminal neuralgia is *MD, PDCC. **MD. Corresponding author:Anurag Agarwal, MD, PDCC, Pain Specialist & Associate Professor, Dept. of Anesthesiology & Pain Medicine, Lala Lajpat Rai Memorial Medical College, Meerut, Uttar Pradesh, India. Tel: 00-91-73889-70385. E-mail ID: [email protected] 105 M.E.J. ANESTH 23 (1), 2015 106 painful, unilateral affliction of face, characterized by brief, electric shock like pain limited to one or more divisions of trigeminal nerve, commonly evoked by trivial stimuli like shaving, talking, washing of face but may also occur spontaneously with abrupt onset and termination2. Exact cause of TN is not known, and multiple treatment options are available but there is no ideal treatment available for all patients3. Severity of pain can result in poor health and deterioration of dayto-day functional status4,5. According to IHS, TN can be classified as classical or idiopathic and symptomatic or secondary6,7. In 2003, Burchiel classified TN on the basis of clinical features: Type 1 TN which is predominantly episodic and sharp; and Type 2 TN which is constant, dull, and burning in nature8. The American Academy of Neurology (AAN) and the European Federation of Neurological Societies (EFNS) Guidelines on TN treatment (2008) recommend medical treatment with carbamazepine and oxcarbazepine or lamotrigine and baclofen as first option for TN7. In patients refractory to medical treatment or in whom side effects of medications are intolerable, other surgical treatments are recommended. Various modalities of surgical treatment are possible, from major intracranial operation to minimally invasive percutaneous techniques. Because of the achievable longest duration of pain relief, microvascular decompression (MVD) is recommended as the first option, but it is a major intracranial operation, which may not be suitable for older, debilitated patients. MVD is also complicated with the risk of major neurological morbidity and mortality. Due to their minimally invasive nature and possibility to repeat, percutaneous procedures are widely used for the surgical treatment of TN, mostly in the patients who are not eligible for MVD, are not willing to have MVD or are refractory to previous surgical treatments. One of these procedures is percutaneous balloon compression (PBC) of Gasserian ganglion which was first introduced by Mullan and Lichtor in 19839. PBC is an effective, comparatively cheaper and simple therapeutic modality for treatment of TN. Compression secondary to PBC selectively injures the large myelinated A-alfa (afferent) fibers that mediate light touch and does not affect A-delta and C-fibres, Anurag agarwal et. al which carry pain sensation. Balloon compression reduces the sensory neuronal input, thus turning off the trigger to the neuropathic trigeminal pain. PBC is not as selective for pain originating from a particular trigeminal division as radiofrequency thermocoagulation (RFTC) is10,11. In this current case series, we are sharing our experience with PBC of Gasserian ganglion for the treatment of idiopathic TN in our patients at an academic university-based medical institution in India. Case Series During the period of August 2012 to October 2013, a total of twelve PBCs of Gasserian Ganglion were performed in the Department of Anesthesiology and Pain Medicine at Lala Lajpat Rai Memorial Medical College, Meerut, India in eleven patients suffering from idiopathic TN. There were nine female patients and two male patients with the age range of 35-70years (median age: 54years). All the patients were suffering from Burchiel Type 1 TN with the classical features of idiopathic TN i.e., electric shocklike lancinting pain in the territory of trigeminal nerve (CN V). Two patients had involvement of both maxillary (V2) and mandibular (V3) divisions of Cranial Nerve V; three patients had involvement of V2 division only and remaining six patients had TN alongV3 division only. The duration of the disease ranged from 2.5-12 years. Only three patients could undergo a magnetic resonance imaging because of financial constraints; all other patients were screened for any intra-cranial pathology by computerized tomography scanning. None of our patients had bilateral TN; five patients had involvement of right side CN V and six patients had left-sided involvement. All patients had been treated with carbamazepine and baclofen as part of failed medical management prior to PBC. One patient had already undergone retrogasserian glycerol rhizotomy, which provided pain relief for only five months. One patient underwent PBC on two occasions secondary to non-satisfactory placement of balloon inside the Meckel’s cave followed by rupture of balloon and venous bleeding. The case was deferred and performed again after one week with satisfactory results. Compression in Gasserian ganglion in trigeminal neuralgia Procedural Details of PBC: All the procedures were performed under conscious sedation using two dimensional C-arm fluoroscopic guidance. Patients were placed in supine position with slight extension of neck. C-arm fluoroscope was aligned to take a ‘Modified sub-mental view’, in which foramen ovale was visualized between mandible on the lateral side and maxilla on the medial side (Figure 1). In this view, a 14-gauge cannula with blunt trocar was used to enter the foramen ovale to reach the Meckel’s cave where the Gasserian ganglion is situated (Figure 2). Once entry was confirmed in the Meckel’s cave, lateral view was obtained wherein 4-Fr Fogarty catheter was gently threaded in to the Meckel’s cave up to the clivus. After confirmation of correct position of the balloon in anterio-posterior and lateral views, Fogarty balloon was inflated with 0.8-1 ml of water soluble contrast dye (Omnipaque-240, GE Healthcare) for 1.5-3minutes. After completion of the intervention, Fogarty balloon was deflated and removed along with the cannula; and manual digital pressure was applied for five minutes against the maxilla to stop any bleeding and cerebrospinal fluid drainage. A small dressing was applied on the skin puncture site and patients were transferred to postanesthesia care unit for observation. After regaining full consciousness, patients were examined for relief in pain, facial sensation and corneal reflex; and, after two to four hours, patients were discharged home on oral antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs). Fig. 1 Submental View showing Foramen Ovale 107 Fig. 2 Modified Submental View with cannula in Foramen ovale Procedural Results of PBC: In all patients cannulation of foramen ovale was done successfully in the first attempt. In eight out of eleven(72.7%) patients ideal ‘Pear-shaped’ balloon visualization could be achieved (Figures 3-4). In the remaining three patients (27.3%), inflated balloon was ‘Bullet-shaped’. In one patient final placement of Fogarty balloon was not satisfactory and it ruptured during inflation. This case was deferred for one week when it was completed successfully with ‘Pear-shaped’ balloon inflation. In one patient, venous bleeding was detected on removal of trocar from cannula that ceased after placement of Fogarty catheter and successful PBC. In another patient, who had not been pre-medicated with atropine, there was sudden asystole on entering in to the foramen ovale, which responded to Inj. atropine 1.2mg intravenous bolus with no post-operative sequelae. In all other patients, no episode of major bradycardia occurred due to pre-medication with atropine 0.4mg intravenously. All patients had complete relief of neuralgic pain in the immediate post-operative period. In nine out of eleven patients (81.81 %), there was mild to moderate facial hypoesthesia, which was more prominent with longer compression-duration (3 minutes vs. 1.5 minutes). This hypoesthesia improved within 6-8 weeks and did not cause appreciable discomfort to these patients. Five out of eleven patients (45.4%) complained about mild facial dysesthesias (continuous burning sensation in CN V distribution), which improved in 6-8 weeks with the use of neuro-modulatory drugs such as pregabalin. One patient complained of malocclusion of mandible and difficulty in chewing on the operated side, which M.E.J. ANESTH 23 (1), 2015 108 Anurag agarwal et. al Fig. 3 Ideal Pear shaped balloon in Lateral View Fig. 4 Anterio-Posterior view with Pear shaped balloon Discussion also improved in four weeks without any treatment. Four out of eleven (36.36%) patients revealed mild to moderate asymptomatic masseteric weakness on postoperative physical examination that also improved in 4-6 weeks. None of the patients had loss of corneal reflex and/or anesthesia dolorosa. In two out of eleven (18.2%) patients, there was eruption of herpes labialis on the ipsilateral side, which was treated with anti-viral drugs with resolution of the lesions within two weeks. All patients complained of temporal headache in the immediate post-operative period, which improved in 24-48 hrs with the use of NSAIDs and ice fomentation. None of the patients had any major complication such as corneal ulcer, 4th or 6th cranial nerve palsy, meningitis or death. During the follow up period of 1-13 months, there have been no recurrences of TN. Eight out of eleven patients (72.7%) are completely off medicines (carbamazepine and baclofen) and other two patients are stable on very low doses of carbamazepine. All patients have reported marked improvement in quality of life. Minimally invasive pain interventions have found a niche among the available treatments for many intractable, chronic painful conditions such as TN. PBC has been found to be an effective intervention in many studies3,6,10,12. PBC has an advantage of sparing the corneal reflex over other percutaneous methods. It has a unique mechanism of action of selective injury to large myelinated A-alfa and A-beta fibers and relative sparing of small, unmyelinated C-fibers and poorly myelinated A-delta fibers13. So it may be the best technique for addressing ophthalmic division (V1) pain of TN6 and this observation has been confirmed by Brown et al12. Initially PBC was advocated for older age group and for those who were unfit for major surgical procedure. Now it has been found useful even in many young patients, especially those who do not have any evidence of vascular malformation and/or are unwilling to undergo major surgery. Strojnik and Smigoc9 and Natrajan14 have used this technique in patients with aberrant basilar artery as well as in young patients. In our study, there was a female patients preponderance, most patients were of advanced age and there was almost equal distribution of right side vs. left side involvement, although some authors have found preponderance of right sided involvement9. In all our patients, modified Mullan’s technique was used9,11 for PBC. Though ‘Pear-shaped’ balloon is considered to be the best in some studies9,10,15,16,17, this shape was achieved in only eight out of eleven patients in our series but we did not find any differences in the outcome, possibly due to shorter follow-up in our study (1-13 months). Same can be true in regards to the compression-duration wherein practitioners have used compression time ranging from 1-20 minutes; some authors have reported correlation between the duration of compression and duration of pain relief but with longer duration of compression, more complications like facial dysesthesias9,15,18have been reported. Compression in Gasserian ganglion in trigeminal neuralgia 109 Because there is no consensus on the optimal duration of compression during PBC, in our practice we have used the compression times of 1.5 minutes and 3 minutes; and we have found that although the pain relief was complete with both compression-duration, incidence and magnitude of facial hypoesthesia and dysesthesia was more in patients who had received compression for longer duration. operative sequelae. Therefore, it is our suggestion to ensure premedication with atropine prior to penetration of foramen ovale before all percutaneous procedures including PBC. Though review of medical literature elicits rare incidences of anesthesia dolorosa, intracranial fistula formation and cranial nerve injury, corneal ulceration and death during PBC, we did not encounter any such adverse effect. Prolonged masticatory weakness due to masseter-pterygoid weakness has been reported after PBC11,15. We also encountered malocclusion on ipsilateral jaw in one patient and mild masseteric weakness in four patients, which was not bothersome to the patients because pre-procedure, they were not chewing from that side any way due to the precipitation of their neuralgic pain. In all patients, this weakness completely recovered in 4-6 weeks without any intervention. In all patients in our series, complete relief from neuralgic pain was observed, which is similar to other studies9,11,14. Autonomic changes such as bradycardia and hypotension have been reported on entering the foramen ovale in more than 50% of cases14,19 which was not observed in our series because of pre-medication with atropine. Though no mortality has been reported during PBC in the literature, Natrajan had reported an incidence of intra-operative myocardial infarction which was managed successfully14. We also encountered a case of sudden asystole on foramen ovale penetration in a patient who was not given atropine pre-operatively in spite of our policy. It was recognized immediately due to continuous electrocardiography and was managed successfully with rescue dose of atropine with no post- Recurrence of pain after successful PBC and initial pain relief has been reported very widely in the literature, Baabor and Perez-Limonte20had reported 15% recurrence after 3 years, and Skirving and Dan17 had reported 31.9% recurrence in 20-years duration. In our moderate follow-up period of 1-13 months, we have not found any recurrence so far. The major limitations in the present study were retrospective nature of the case series, small number of patients (n=11) and short duration of follow-up (1-13months). Conclusion This case series shows that percutaneous balloon compression of Gasserian ganglion is a useful minimally invasive intervention for the treatment of trigeminal neuralgia. If performed appropriately with the help of anatomical landmarks and radiological guidance, it is a low risk procedure with high success rate. Due to very low incidence of corneal anesthesia and anesthesia dolorosa, we recommend PBC as first choice among percutaneous interventions for TN especially involving V1division as well as in multidivisional pain. M.E.J. ANESTH 23 (1), 2015 110 Anurag agarwal et. al References 1. Edlich RF, Winters KL, Britt L, Long WB 3rd: Trigeminal neuralgia. J Long Term Eff Med Implants; 2006, 16:185-192. 2. Merskey H, Bogduk N: Classification of chronic pain. Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. Seattle: IASP Press; 1994, 59-71. 3. Tattli M, Satici O, Kanpolat Y, Sindou M: Various surgical modalities for trigeminal neuralgia: literature study of retrospective long-term outcomes. ActaNeurochirurgica; 2008, 150:243-255. 4. Pollock BE, Stein KJ: Surgical management of trigeminal neuralgia patients with recurrent or persistent pain despite three or more prior operations. World Neurosurgery; 2010, 73:523-528. 5. Tölle T, Dukes E, Sadosky A: Patient burden of trigeminal neuralgia: results from a cross-sectional survey of health state impairment and treatment patterns in six European countries. Pain Practice; 2006, 6:153-160. 6. Campos WK, Linhares MN: A prospective study of 39 patients with trigeminal neuralgia treated with percutaneous balloon compression. ArqNeuropsiquiatr; 2011, 69:221-226. 7. Cruccu G, Gronseth G, Alksne J, Argoff C, Brainin M, Burchiel K, Nurmikko T, Zakrzewska JM: AAN-EFNS guidelines on trigeminal neuralgia management. European Journal of Neurology; 2008, 15:1013-1028. 8. Burchiel J: A new classification for facial pain. Neurosurgery; 2003, 53:1164-1167. 9. Strojnik T, Ŝmigoc T: Percutaneous Trigeminal Ganglion Balloon Compression Rhizotomy: Experience in 27 Patients. The Scientific World Journal; Article ID 328936, 2012,6 pages. 10.Linderoth B, Bergenheim AT:The predictive power of balloon shape and change of sensory functions on outcome of percutaneous balloon compression for trigeminal neuralgia: clinical article. Journal of Neurosurgery; 2010, 113:498-507. 11.Mullan S, Lichtor T: Percutaneous microcompression of the trigeminal ganglion for trigeminal neuralgia. Journal of Neurosurgery; 1983, 59:1007-1012. 12.Brown JA, McDaniel MD, Weaver MT, Burchiel KJ, Young RF:Percutaneous trigeminal nerve compression for treatment of trigeminal neuralgia: results in 50 patients. Neurosurgery; 1993, 32:570-573. 13.Brown JA, Hoeflinger B, Long PB, Gunning WT, Rhoades R, Bennett-Clarke CA, Chiaia NL, Weaver MT:Axon and ganglion cell injury in rabbits after percutancous trigeminal balloon compression. Neurosurgery; 1996, 38:993-1004. 14.Natarajan M: Percutaneous trigeminal ganglion balloon compression: experience in 40 patients. Neurol India; 2000, 48:330. 15.Kouzounias K, Schechtmann G, Lind G, Winter J, Linderoth B:Factors that influence outcome of percutaneous balloon compression in the treatment of trigeminal neuralgia. Neurosurgery; 2010, 67:925-934. 16.Park SS, Lee MK, Kim JW, Jung JY, Kim IS, Ghang CG:Percutaneous Balloon Compression of Trigeminal Ganglion for the Treatment of Idiopathic Trigeminal Neuralgia: Experience in 50 Patients. J Korean NeurosurgSoc; 2008, 43:186-189. 17.Skirving DJ, Dan NG:A 20-year review of percutaneous balloon compression of the trigeminal ganglion. Journal of Neurosurgery; 2001, 94:913-917. 18.Lichtor T, Mullan JF: A 10-year follow-up review of percutaneous microcompression of the trigeminal ganglion. J Neurosurg; 1990, 72:49- 54. 19.Brown JA, Preul MC: Trigeminal ganglion compression for trigeminal neuralgia: experience in 22 patients and review of the literature. J Neurosurg; 1989, 70:900-904. 20.Baabor MG, Perez-Limonte L: Percutaneous balloon compression of the gasserian ganglion for the treatment of trigeminal neuralgia: personal experience of 206 patients. ActaNeurochirurgicaSupplementum; 2011, 108:251-254. Bedside retained radial artery catheter removal in a hemodynamically unstable neurocritically-ill patient: a case report. Christa O’Hana V. San Luis* and Athir H. Morad* Abstract Radial artery insertion is a common procedure in intensive care units. We describe a case of a critically-ill 73-year-old man in the neurocritical care unit with a subarachnoid hemorrhage whose radial arterial catheter tip was transected from the main line and was successfully managed with bedside retrieval of the catheter. Introduction Radial artery insertion is usually done in the neurocritical care unit (NCCU) for the purposes of blood pressure monitoring and arterial blood sampling. Several complications are known such as temporary occlusion, thrombosis, pseudoaneurysm formation, hematoma formation, abscess, cellulitis, median nerve involvement and air embolism. Retained radial artery catheter is rare but has been reported in literature. Several causes have been mentioned such as accidental transection, repeated catheterization and repeated wrist movements. Several modalities have been mentioned to confirm the location of the arterial catheter as well as different methods to remove the catheter. We describe a case of a 73-year-old man who presented with aneurysmal subarachnoid hemorrhage due to an anterior communicating aneurysm and underwent aneurysmal clipping. His course was complicated by cardiopulmonary instability. On his first post-operative day, the radial arterial catheter tip on his left wrist was fractured from the main line as it was being removed. He then underwent a bedside vascular exploration and removal of the foreign body. We also present a review and summary of the available literature regarding retained radial catheters and the available modes of image confirmation and options for treatment. Case A 73-year-old man was admitted in our Neurosciences critical care unit (NCCU) for an aneurysmal subarachnoid hemorrhage (ASAH), Hunt and Hess 3, Modified Fischer Scale 3. He underwent aneurysmal clipping after a four vessel angiogram revealed a 3-millimeter irregular and superiorly projecting anterior communicating artery aneurysm. Post-operatively day 1, he was very agitated and his left radial arterial catheter was discontinued due to very poor waveform. As it was being pulled out, the nurse noticed that the long portion of the distal cannula was not there. It was highly suspected that it was still in the vessel. Pulses and perfusion distally were adequate. A *M.D, Department of Anesthesia and Critical Care Medicine, Division of Neurosciences critical care, Johns Hopkins University School of Medicine Baltimore, MD 21287, USA. Corresponding author: Christa O’Hana V. San Luis, M.D, 600 N Wolfe Street, Phipps 455, Baltimore, MD, 21287. Tel: (949)8780490, Fax: (410)6147903. [email protected] 111 M.E.J. ANESTH 23 (1), 2015 112 stat portable 3-view X-ray of the wrist and hand done visualized a 4cm catheter fragment in the anterolateral soft tissue aspect of the distal forearm proximal to the left wrist (Figure 1). A vascular surgery consult was placed and surgical removal and exploration was planned the following day. His family was informed of the incident and consented for the procedure. On the day of the planned exploration, the patient had acute respiratory failure further complicated by an asystolic event. He was immediately resuscitated and was started on norepinephrine, dopamine, epinephrine to maintain his mean arterial pressure. The surgical procedure was postponed due to hemodynamic instability. Three days after, it was deemed that due to the patient’s continued hemodynamic instability, he was not a good surgical candidate to transport to the operating room. The bedside exploration of the left radial artery and the removal of the distal catheter tip were then done with local anesthesia under ultrasound guidance. The incision was made at the top of the radial artery on the left forearm. The catheter was identified right at the entry site of the radial artery. DeBakey pickups were used to extract the catheter out of the radial artery (Figure 2). The radial artery was found to be thrombosed at that location. Dopplers were performed after the procedure to assure adequate pulses and perfusion distally. The procedure was tolerated well and perfusion was maintained throughout the hospital stay. Fig. 1 Plain left hand and wrist x-ray. Panel A is the PA (posteroanterior) view. Panel B is the lateral view. Encircled in red is the retained radial artery catheter fragment Christa San Luis et. al Fig. 2 Proximal part of the radial arterial catheter without the retained distal catheter tip Discussion The radial arterial line for this patient was for strict blood pressure monitoring which is one of the most common reasons for its placement1,2. The reason for the radial artery catheter breakdown in this patient is unclear. Several reasons for this type of breakdown have been reported in the past including accidental transection while separating the arterial line from the intravenous line3, possible damage to the catheter sheath due to repeated catheterization attempts4, transection while suturing5, shearing off of the cannula due to repeated wrist movement postoperatively during recovery6-8, reinsertion of the stylet needle9, accidental cutting during suture removal10,11 and dressing removal12. In our case, our suspicion is that the patient was probably moving his wrist repeatedly during his post-operative agitation. Prompt vascular surgery consult for possible exploration is very important to prevent the possibility of distal embolization and distal migration with thrombosis. There is also a possibility of proximal migration4 and the use of ultrasound to confirm the location of the catheter preoperatively is recommended. Described by Aslam et al.1, this proximal migration, although unlikely, may occur because of arterial spasm distally. Several imaging modalities may be used to confirm the location of the retained fragment (Table 1). In this patient, the most rapid way to confirm the imaging late at night was a plain radiograph. With the vascular surgery team Bedside retained radial artery catheter removal 113 Table 1 Summary of causes, diagnostic imaging and approach to removal of retained radial artery catheters (CT = computed tomography, OR = operating room) Source Patient characteristic Cause of cannula transection Diagnostic procedure for confirmation Consulting service/ Procedure for removal 7.5 MHz highfrequency ultrasonography, 3-D CT Plastic surgery/OR Surgical exploration and removal of fragment by microforceps Outcome Recovered, no residual sequelae Moon et al.3 69 y.o., Male Accidental transection by scissors while separating intravenous and arterial catheter Lee SY et al.4 69 y.o., Male Wrist CT Reinsertion may have damaged the catheter sheath, manufacturing defect of angiocatheter is suggested Service not mentioned/OR surgical exploration and removal of fragment Ho KS et al.6 20 y.o., Female Repeated wrist movement Not mentioned Vascular surgery/OR surgical exploration under local anesthesia Aslam M et al.1 63 y.o., Female Not mentioned ultrasound Vascular surgery/OR surgical exploration under local anesthesia Shah U.S. et al.5 72 y.o., Female Transected while securing the arterial catheter with suture. none Vascular surgery/OR surgical exploration simultaneous with planned indicated surgery Bengezi OA et al.7 58 y.o., Male Hypothesized to be repeated flushing and manipulation created a vulnerable point along the catheter length Plain X-ray of wrist and hand with ultrasound confirmation pre- and intraoperatively Vascular surgery/OR surgical exploration with arteriotomy Kim IS et al.9 74 y.o., Male Portable X-ray Reinsertion of stylet needle through the embedded catheter sheath intraoperatively for pleural decortication Recovered Unclear if vascular surgery involved/OR Exploration and uneventful removal during scheduled primary surgery Moody C et al.10 Unknown elderly Accidental cutting of the plastic cannula Ultrasound imaging pre-and intraoperatively Surgical team involved/OR exploration with arteriotomy and removal of catheter Recovered uneventful Ferguson E et al.11 62 y.o., Male Accidental cutting of catheter fragment Portable X-ray Vascular surgery/OR arteriotomy and removal of catheter Uneventful Mayne D and Kharwar F8 64 y.o., Male Repeated flexion and extension Portable X-ray Unclear if vascular surgery involved/Unclear if OR Exploration and removal or bedside Uneventful Hamid et al.12 unknown Accidental transection with dressing removal Sonosite, X-ray Percutaneous approach using a snare Some spasm on angiography however no complications after removal Recovered, no residual sequelae Excellent flow with good capillary refill in all fingers. M.E.J. ANESTH 23 (1), 2015 114 on board, they were able to perform their bedside ultrasound localization both preoperatively and during the surgery itself. Ideally, patients are taken to the operating room for surgical exploration and removal of the fragment with generally good outcome (Table 1). However that is not always possible as in our case. The patient was hemodynamically unstable and was unable to tolerate repeated position changes even just for transportation. However, as soon as the patient was deemed able to tolerate the surgical exploration at bedside, it was immediately arranged and another ultrasound was performed preoperatively. The procedure was performed in our NCCU. Retained radial artery catheter is rare but has been reported. Clinicians should be aware of the various Christa San Luis et. al mechanisms by which the catheter may be transected so precautions can be observed. Appropriate wrist stabilization, careful suture placement and removal and avoidance of multiple stylet needle reinsertion are the suggested ways to prevent this complication. Prompt confirmation of the location of the retained fragment is indicated with simultaneous vascular surgery consultation for timely exploration and removal. Intraoperative confirmation of the catheter may be needed. If the patient is unable to tolerate transport to the operating room, it is feasible to perform the procedure at bedside. To the authors’ knowledge this is the first report of a bedside surgical exploration for a retained radial arterial catheter in a hemodynamically unstable patient. Bedside retained radial artery catheter removal 115 References 1. Aslam M, Sarker B, Bhattacharya V: A Rare Complication of Radial Artery Cannulation. J Med Ultrasound; 2012, 20(3):183-185. 2. Scheer BV, Perel A and Pfeiffer U: Clinical review: Complications and risk factors of peripheral arterial catheters used for haemodynamic monitoring in anaesthesia and intensive care medicine. Crit Care; 2002, 6(3):199-204. 3. Moon S, Gong J, Kim J, Lee KC, K HY, Choi EK and Lee MJ: A retained catheter fragment in radial artery caused by accidental catheter transection during arterial catheter removal. J Anesth; 2012, 26:625-626. 4. Lee S, Na H, Kim M, Kim C, Jeon Y, Hwang J and Do S: A Sheared catheter fragment in the wrist after arterial cannulation attempt-a case report. Korean J Crit Care Med; 2010, 25:118-21. 5. Shah US, Downing R and Davis I: An iatrogenic arterial foreign body. Br J Anaesth; 1996, 77:430-431. 6. Ho KS, Chia KH and Teh LY: An unusual complication of radial artery cannulation and its management: a case report. J Oral Maxillofac Surg; 2003, 61:955-7. 7. Bengezi OA, Dalcin A, Al-Thani H and Bain J: Unusual complication of radial artery cannulation. Can J Plast Surg; 2003, 11(4): 213-215. 8. Mayne D and Kharwar F: Another complication of radial artery cannulation. Anaesthesia; 1997 Jan, 52(1):89-90. 9. Kim IS, Shin HK and Dae YK: Iatrogenic catheter sheath shearing during radial artery cannulation. Korean J Anesthesiol; 2013 Dec, 65(6 Suppl):S12-S13. 10.Moody C, Bhimarasetty C and Deshmukh S: Ultrasound guided location and removal of retained arterial cannula fragment. Anesthesia; 2009 Mar, 64(3):338-9. 11.Ferguson E, Baumgartner P and Hamilton M: Accidental transection of radical artery cannula. Anaesth and Intensive Care; 2005 Feb, 33(1):142-3. 12.Hamid UI, Collins A, McConkey C and Sidhu P: Accidental transection of a radial artery cannula. BMJ Case Reports; 2012, doi:10.1136/bcr-2012-006753. M.E.J. ANESTH 23 (1), 2015 Esophageal perforation following orogastric suction catheter insertion in an elderly patient Roland N. Kaddoum*, Fadi Farah**, Rita W. Saroufim*** and S alah M. Z eineldine **** Abstract Esophageal rupture has been described following iatrogenic manipulation. In this report, we present an elderly lady admitted to the operative theater for laparoscopic cholecystectomy. Multiple intra-operative attempts to place a flexible orogastric tube were unsuccessful because of failure to advance. Post-operatively, the patient developed sepsis and a right pleural effusion. She was transferred to the Intensive Care Unit and she was treated with antibiotics. Radiologic evaluation confirmed an esophago-pleural fistula. Surgical repair was urgently performed for closure of fistula and lung decortication. The patient recovered and was discharged home. Introduction Esophageal perforation is a serious complication of procedures performed on or around the esophagus and is mainly iatrogenic1,2. Esophageal perforation is most frequently encountered during endoscopic procedures3 but also during nasogastric tube placement4-9, endotracheal intubation10-14, stricture dilation15,16 and during the use of oesophageal bougies17. This complication has a poor prognosis with inadequate management3. While providing anesthesia to surgical patients, anesthesists frequently insert esophageal dilators, nasogastric tubes or orogastric tubes/suction catheters. Such interventions may cause trauma to soft tissue structures. We describe a case of esophageal perforation secondary to the orogastric insertion of a simple 14 french suction catheter used routinely to deflate the stomach during laparoscopic cholecystectomy. To our knowledge, this is the first case report describing esophageal perforation following the insertion of a flexible orogastric 14Fr suction catheter in an adult patient undergoing laparoscopic cholecystectomy. * MD, Assistant Professor of Anesthesiology, American University of Beirut Medical Center, Department of Anesthesiology, Beirut, Lebanon (Riad Solh 1107-2020). ** MD, Anesthesiology resident, Formerly of: American University of Beirut Medical Center, Department of Anesthesiology, Beirut Lebanon (Riad Solh 1107-2020). Current Department: St. Elizabeth's Medical Center, Department of Anesthesiology, Critical Care and Pain Medicine, 736 Cambridge Street, #213, Brighton, MA 02135. ***Medicine III student, Bachelor degree in Biology, American University of Beirut Medical Center, Department of Anesthesiology, Beirut, Lebanon (Riad Solh 1107-2020). ****MD, Assistant Professor of Clinical Medicine, American University of Beirut Medical Center, Department of Internal Medicine, Beirut, Lebanon (Riad Solh 1107-2020). Corresponding author: Salah M. Zeineldine, MD, Assistant Professor of Clinical Medicine, American University of Beirut Medical Center, Department of Internal Medicine, Beirut, Lebanon (Riad Solh 1107-2020). Tel: +961-1-350 000 x 4706, Fax: +961-1-744 489. E-mail: [email protected] 117 M.E.J. ANESTH 23 (1), 2015 118 Roland Kaddoum et. al Case Report was uneventful. The patient was transferred to the recovery room. She was fully awake and asymptomatic. A 79 year old, 70 kg lady known hypertensive and dyslipidemic presented for laparoscopic cholecystectomy and intraoperative cholangiogram secondary to an acute cholecystitis. The patient denied any symptoms or history of dysphagia, odynophagia, gatroesophageal reflux or chest pain. Difficult intubation was anticipated due to short neck and a glidescope assisted intubation was planned. On post-op day one, the patient complained of dry cough and dyspnea after her first meal. On physical exam, she had scattered wheezes and right field crakles. She was afebrile. Chest X ray (CXR) revealed opacification on the right lower and right middle fields. A diagnosis of pulmonary aspiration was suspected and Solumedrol, Combivent, pulmicort and Tazocin were started. The CXR improved in the afternoon. However, clinically the patient was getting worse the following day with progressive desaturation down to 90% and became hypotensive with systolic pressure of 80 mmHg. The patient was transferred to the intensive care unit and Tazocin was shifted to broad spectrum antibiotic coverage consisting of Meropenem, Levofloxacin and Metronidazole. The patient symptoms improved, however the cough and wheezes persisted. A CT chest was done on post op day 7 revealing an air pocket posterior to the carina in continuity with the right lower lobe. A diagnosis of esophageo-pleural fistula in the lower esophagus was suspected and was confirmed with Gastrograffin swallow. On post-op day 9, a thoracotomy for right lung decortication and closure of fistula was performed. The patient was kept intubated and extubation was done on the following day. Antibiotics were continued for 14 days post-op. The radiological findings on CXR resolved on post-op day 17. In the operating room, after lung denitrogenation with 100% oxygen, rapid sequence induction was performed using lidocaine 100 mg (1.5 mg/kg), propofol 140 mg (2 mg/kg) and succinylcholine 100 mg (1.5 mg/kg) intravenously. No bag ventilation was performed. The trachea was intubated by an endotracheal tube (ETT) size 8.0 using the Glidesscope and a 10Fr intubating stylet (Unomedical). Several attempts to insert a well lubricated 14 Fr suction catheter failed (Bicakcilar, suction catheter w/ vakon connector ideal tip 4.7 mm x 600mm). The catheter would not advance even with an index finger inserted in the patient mouth guiding the catheter into the pharynx. After multiple attempts using the laryngoscope to have better visualization, the insertion of the orogastric tube was not successful. During the procedure, the surgeon noted that the stomach was inflated and insisted on the placement of an orogastric tube to suction the stomach. We elected then to place an ETT size 7.0 that we advanced in the esophagus and inserted the orogastric tube through it. The advancement of the catheter would always stop at the same level as previously tried with or without the laryngoscope attempts. The resistance upon the insertion of the catheter was encountered at a distance of about 25 cm from the lips. No forceful maneuvers were performed and no blood was recovered over the suction catheter. We decided to abort the placement of the orogastric tube and the surgeon was advised so. His concern was a fully inflated stomach that he is showing us on the video camera. We explained that placement of orogastric tube was difficult, and will treat his concern by extubating the trachea when the patient is fully awake. After the surgical procedure ended, extubation A repeated gastrograffin swallow was performed on post-op day 20 showing an outpouching at the level of the fistula but no leak. Another gastrograffin swallow was performed on post-op day 27 showed no leak. The patient was discharged from the hospital on post-op day 33. Discussion Perforation of the esophagus due to instrumentation in the adult is a rare yet potentially devastating event associated with high morbidity and mortality3. The mortality has decreased from 38.7% in the 1970s to 8.3% today18. The leading cause of Esophageal perforation in laparoscopy esophageal perforation is mainly iatrogenic with perforations at the thoracic level being the highest19. Most of perforations occur during instrumentation of the esophagus i.e. endoscopy procedures, transesophageal echocardiography, esophageal varices sclrerotherapy, stricture dilatation, using relatively large stiff probes (endoscope, TEE probe, SengstakenBlakemore (SB) tube, bougie). Several risk factors have been described for esophageal perforation such as pre-existing esophageal abnormalities (carcinoma, stricture, diverticuli)20 and cervical osteophytes21. Esophagogastroduodenoscopy was the most commonly litigated procedure, followed by intubation and Nissen fundoplication22. But there have been few reported cases of iatrogenic esophageal perforations by a flexible nasogastric tube occurring mainly in neonates or infants4-6,9,23. In our patient the perforation occurred after multiple attempts at inserting the orogastric suction catheter where the obstruction was faced at 25cm distal to the lips. The most common areas of instrumental esophageal perforation are the relatively narrow portions at the distal esophagus. The perforation is complicated by an inflammatory process and communication with the pleura in 80% of the cases24. The thin mediastinal pleura is ruptured by the inflammatory process, producing contamination of the pleural space and a pleural effusion. Then, gastric contents and fluids are drawn into the pleural space by the negative intrathoracic pressure resulting in further inflammation and fluid sequestration, hypovolemia, and the early appearance of tachycardia and systemic sepsis. In our patient the CXR revealed opacifications which reflect consolidation of the lungs that is due to an accumulation of fluids that is most probably edema and inflammation. This explains the scattered wheezes and crackles that were heard on post op day one. In addition, esophageal perforation allows bacteria, usually polymicrobia flora to spread into the mediastinum and subphrenic space leading to mediastinitis18,25-27. This explains the septic picture of our patient that was revealed by hypotension and progressive oxygen desaturation. Literature showed a better outcome with primary surgical closure if diagnosed in less than 24 hours. 119 However if delayed diagnosis beyond 48h was made, no patient with esophageal perforation should be deprived from surgical repair28. Mortality is decreased in surgical repair versus conservative treatment29, for that reason, our patient underwent thoracotomy for fistula closure and repair of esophageal tear. In any patient with a recent history of esophageal instrumentation, the diagnosis of esophageal injury should be suspected in the presence of any of the symptoms encountered by our patient. Also, the absence of gastric content on naso/orogastric tube or the presence of blood on the catheter elicit a possible diagnosis of perforation. Nevertheless blood was not noted on the suction catheter in our case. For the first 24 hours following the laparoscopic cholecystectomy, our patient’s only complain was pain over the incision and a mild shoulder pain attributed to the laparoscopic procedure. This pain was controlled by analgesics. She denied any complain or history of dysphagia, odynophagia, dysphonia or dyspnea. However, after her first meal she complained of sudden dry cough and severe dyspnea. Taking into consideration the fact that the patient was extubated with a distended stomach, pulmonary aspiration was the most probable diagnosis. It was the persistence of the cough and dyspnea and the worsening of these symptoms following meals, along with a problematic naso/orogastric tube insertion that made the suspiscion of esophageal perforation high. Because of the failure of insertion of the orogastric catheter and the occurrence of resistance at 25 cm from the lips, an intrathoracic esophageal injury in our case was suspected. The CT chest showed an air pocket adjacent to the carina in continuity with the right lower lobe. This prompted us to perform esophagogram to confirm the diagnosis of esophageal perforation. The presence of underlying esophageal pathology could explain the difficulty in advancing the orogastric tube. As anesthesiologists we are the experts in inserting orogastric tubes or suction catheters, a maneuver that we perform almost every day in our practice. The advancement of the catheter was impossible past 25cm of the lips despite so many attempts. This could be M.E.J. ANESTH 23 (1), 2015 120 explained by a pre-existing esophageal pouch that the patient is unaware of or by an osteophytic compression of the esophagus due to the patient age, which made the advancement of the catheter impossible. Forcing the catheter insertion through multiple attempts lead to the perforation. On another note, the deviation from our current practice of inserting a suction catheter through an ETT placed in the esophagus is a very rare maneuver that we perform in extreme situations. This also could be the reason of the perforation. Roland Kaddoum et. al Conclusion The lesson taken from this case report is not to force the advancement of an orogastric/nasogstric suction catheter especially when different techniques and multiple attempts fail. The other lesson taken is to have a very high threshold inserting an ETT in the esophagus to facilitate the suction catheter insertion by advancing the catheter through the ETT since this could also be a risk factor for esophageal perforation. Esophageal perforation in laparoscopy 121 References 1. Gupta NM, Kaman L: Personal management of 57 consecutive patients with esophageal perforation. American journal of surgery; 2004,187(1):58-63. 2. Bhatia P, Fortin D, Inculet RI, Malthaner RA: Current concepts in the management of esophageal perforations: a twenty-seven year Canadian experience. The Annals of thoracic surgery; 2011, 92(1):209-15. 3. Chirica M, Champault A, Dray X, Sulpice L, Munoz-Bongrand N, Sarfati E, et al: Esophageal perforations. Journal of visceral surgery; 2010, 147(3):e117-28. 4. Ahmed A, Aggarwal M, Watson E: Esophageal perforation: a complication of nasogastric tube placement. The American journal of emergency medicine; 1998, 16(1):64-6. 5. de Dominicis F, Rekik R, Merlusca G, Deguines JB, Gamain J, Berna P: [Esophageal perforation during nasogastric tube insertion in a patient with right-sided aortic arch and thoracic aorta. Pathophysiology and surgical implications]. Journal de chirurgie; 2009, 146(5):499-502. 6. Gasparella M, Schiavon G, Bordignon L, Buffo M, Benetton C, Zanatta C, et al: Iatrogenic traumas by nasogastric tube in very premature infants: our cases and literature review. La Pediatria medica e chirurgica. Medical and surgical pediatrics; 2011, 33(2):85-8. 7. Gruen R, Cade R, Vellar D: Perforation during nasogastric and orogastric tube insertion. The Australian and New Zealand journal of surgery; 1998, 68(11):809-11. 8. Hutchinson R, Ahmed AR, Menzies D: A case of intramural oesophageal dissection secondary to nasogastric tube insertion. Annals of the Royal College of Surgeons of England; 2008, 90(7):W4-7. 9. Jackson RH, Payne DK, Bacon BR: Esophageal perforation due to nasogastric intubation. The American journal of gastroenterology; 1990, 85(4):439-42. 10.Dubost C, Kaswin D, Duranteau A, Jehanno C, Kaswin R: Esophageal perforation during attempted endotracheal intubation. The Journal of thoracic and cardiovascular surgery; 1979, 78(1):4451. 11.Jougon J, Cantini O, Delcambre F, Minniti A, Velly JF: Esophageal perforation: life threatening complication of endotracheal intubation. European journal of cardio-thoracic surgery. Official Journal of the European Association for Cardio-thoracic Surgery; 2001, 20(1):710; discussion-1. 12.Ku PK, Tong MC, Ho KM, Kwan A, van Hasselt CA: Traumatic esophageal perforation resulting from endotracheal intubation. Anesthesia and analgesia; 1998, 87(3):730-1. 13.Norman EA, Sosis M: Iatrogenic oesophageal perforation due to tracheal or nasogastric intubation. Canadian Anaesthetists’ Society journal; 1986, 33(2):222-6. 14.Ranchere JY, Gordiani B, Lupo C, Serror PM, Bobin JY: [Perforation of the esophagus during attempted endotracheal intubation]. Annales francaises d’anesthesie et de reanimation; 1992, 11(1):100-2. 15.Gander JW, Berdon WE, Cowles RA: Iatrogenic esophageal perforation in children. Pediatric surgery international; 2009, 25(5):395-401. 16.Garey CL, Laituri CA, Kaye AJ, Ostlie DJ, Snyder CL, Holcomb GW, 3rd, et al: Esophageal perforation in children: a review of one institution’s experience. The Journal of surgical research; 2010, 164(1):13-7. 17.Theodorou D, Doulami G, Larentzakis A, Almpanopoulos K, Stamou K, Zografos G, et al: Bougie insertion: A common practice with underestimated dangers. International journal of surgery case reports; 2012, 3(2):74-7. 18.Liu J, Zhang X, Xie D, Peng A, Yang X, Yu F, et al: Acute mediastinitis associated with foreign body erosion from the hypopharynx and esophagus. Otolaryngology--head and neck surgery. Official Journal of American Academy of OtolaryngologyHead and Neck Surgery; 2012, 146(1):58-62. 19.Eroglu A, Turkyilmaz A, Aydin Y, Yekeler E, Karaoglanoglu N: Current management of esophageal perforation: 20 years experience. Diseases of the esophagus. Official Journal of the International Society for Diseases of the Esophagus/ISDE; 2009, 22(4):374-80. 20.Ghogomu NT, Kallogjeri D, Nussenbaum B, Piccirillo JF: Iatrogenic esophageal perforation in patients with head and neck cancer: evaluation of the SEER-Medicare database. Otolaryngology-head and neck surgery. Official Journal of American Academy of Otolaryngology-Head and Neck Surgery; 2010, 142(5):728-34. 21.Wright RA: Upper-esophageal perforation with a flexible endoscope secondary to cervical osteophytes. Digestive diseases and sciences; 1980, 25(1):66-8. 22.Svider PF, Pashkova AA, Vidal GP, Mauro AC, Eloy JA, Chokshi RJ: Esophageal perforation and rupture: a comprehensive medicolegal examination of 59 jury verdicts and settlements. Journal of gastrointestinal surgery. Official Journal of the Society for Surgery of the Alimentary Tract; 2013, 17(10):1732-8. 23.Su BH, Lin HY, Chiu HY, Lin HC: Esophageal perforation: a complication of nasogastric tube placement in premature infants. The Journal of pediatrics; 2009, 154(3):460, e1. 24.Bjerke HS: Boerhaave’s syndrome and barogenic injuries of the esophagus. Chest surgery clinics of North America; 1994, 4(4):81925. 25.Katsetos MC, Tagbo AC, Lindberg MP, Rosson RS: Esophageal perforation and mediastinitis from fish bone ingestion. Southern medical journal; 2003, 96(5):516-20. 26.Kerschner JE, Beste DJ, Conley SF, Kenna MA, Lee D: Mediastinitis associated with foreign body erosion of the esophagus in children. International journal of pediatric otorhinolaryngology; 2001, 59(2):89-97. 27.Cole S, Kearns D, Magit A: Chronic esophageal foreign bodies and secondary mediastinitis in children. The Annals of otology, rhinology, and laryngology; 2011, 120(8):542-5. 28.Mahmodlou R, Abdirad I, Ghasemi-Rad M: Aggressive surgical treatment in late-diagnosed esophageal perforation: a report of 11 cases. ISRN surgery; 2011:868356. 29.Hasimoto CN, Cataneo C, Eldib R, Thomazi R, Pereira RS, Minossi JG, et al: Efficacy of surgical versus conservative treatment in esophageal perforation: a systematic review of case series studies. Acta cirurgica brasileira/Sociedade Brasileira para Desenvolvimento Pesquisa em Cirurgia; 2013, 28(4):266-71. M.E.J. ANESTH 23 (1), 2015 LETTER TO THE EDITOR Pediatric Endotracheal Intubation Claude Abdallah* Dear Editor, I have read with interest the manuscript: ”Simulation training in endotracheal intubation in a pediatric residency” M. E. J. Anesth 22(5) 2014, by Drs. Sharara-Chami, Taher, Kaddoum, Tamim and Charafeddine. The authors are to be congratulated for taking the time to analyze and publish the study, the discussion highlights interesting points. Tracheal intubation in pediatric patients is an essential tool in anesthesiology, traditionally acquired in a clinical setting. Factors related to the patient such as the age of the patient and the level of experience of the trainee may be determinant factors in the decision of the anesthesiologist to make a first attempt at tracheal intubation. Learning curves exist for practical skills and despite useful tools to monitor the learning process; competency is difficult to assess by the anesthesiologist in the absence of adequate exposure with the trainee or a previous documentation of the level of execution of involved skills. Literature review shows the advantage of preparing trainees outside the operating room so that clinical training opportunities can be used most effectively when they arise. Scientific reports documenting the effects of simulation training on learning and updating knowledge about airway management showed improvement in decision-making, communication capabilities1-4 and a better learning of crisis management and endotracheal intubation5. Residents achieve proficiency levels in a smaller number of elapsed days of training and in a smaller number of trials in the operating room6. Simulation would represent also an additional tool for assessing the performance of procedures in anesthesia, such as rapid sequence induction, since it represents more clearly behaviors used in clinical practice than is possible to demonstrate using evaluation by questionnaires7. This may be particularly interesting since theoretical lectures and standard mannequin-based driven workshops have shown to improve overall theoretical knowledge but not to translate to practical skill during realistic mannequin-based simulations8. As discussed by the authors, future studies pertaining to documentation of the trainee’s perspective when faced with a pediatric tracheal intubation with teaching of pediatric endotracheal intubation with and without simulation training would be useful to perform. * MD, MSc, Children’s National Medical Centre, Division of Anesthesiology, 111 Michigan Ave. NW, Washington DC, 20010 USA, (202) 476-2407. E-mail: [email protected] 123 M.E.J. ANESTH 23 (1), 2015 124 Claude Abdallah References 1. Russo SG, Eich C, Barwing J, Nickel EA, Braun U, Graf BM, Timmermann A: Self-reported changes in attitude and behaviour after attending a simulation-aided airway management course. J Clin Anesth; 2007, 19:517-22. 2. Schaefer JJ 3rd: Simulators and difficult airway management skills. Paediatr Anaesth; 2004, 14:28-37. 3. Owen H, Plummer JL: Improving learning of a clinical skill: the first year’s experience of teaching endotracheal intubation in a clinical simulation facility. Med Educ; 2002, 36:635-42. 4. Rowe R, Cohen RA: An evaluation of a virtual reality airway simulator. Anesth Analg; 2002, 95:62-6. 5. Ti LK, Tan GM, Khoo SG, Chen FG: The impact of experiential learning on NUS medical students: our experience with task trainers and human-patient simulation. Ann Acad Med Singapore; 2006, 35:619-23. 6. Abrahamson S, Denson JS, Wolf RM: Effectiveness of a simulator in training anesthesiology residents. Qual Saf Health Care; 2004, 13:395-7. 7. Zausig YA, Bayer Y, Hacke N Sinner B, Zink W, Grube C, Graf BM: Simulation as an additional tool for investigating the performance of standard operating procedures in anaesthesia. Br J Anaesth; 2007, 99:673-8. 8. Wiel E, Lebuffe G, Erb C Assez N, Menu H, Facon A, Goldstein P: Mannequin-based simulation to evaluate difficult intubation training for emergency physicians. Ann Fr Anesth Reanim; 2009, 28:542-8. Erratum The correct spelling name of the first author of the Letter-to-Editor entitled “Anesthetic management of a patient after functional hemispherectomy using bilateral bispectral index monitoring” and published in the October 2014 issue of the Middle East Journal of Anesthesiology (pp. 627-628) is “Shinichiro Kira” and not “Shinichiri Kira”. 125 M.E.J. ANESTH 23 (1), 2015 GUIDELINES FOR AUTHORS The Middle East of Anesthesiology publishes original work in the fields of anesthesiology, intensive care, pain, and emergency medicine. 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