Etomidate Versus Thiopental Sodium with Rocuronium for Rapid Sequence Induction

Original Article

Two Forgotten Induction Agents; Etomidate versus Thiopental Sodium with Rocuronium for Rapid Sequence Induction

Syeda Asma Khalid, Syed Hamid Ali, Sadqa Aftab, Waqar H. Kazmi

Abstract

Objective: To assess the effect on intubating conditions and haemodynamic response on intubation of two different induction agents etomidate and thiopental sodium with rocuronium during rapid sequence induction. Methods: This prospective quasi experimentalstudy was conducted in Department Of Anaesthesia, SICU and Pain Management, Dow Medical College, Civil Hospital Karachi and Abbasi Shaheed Hos- pital Karachi Medical and Dental College over a period of one year. Total 120 American Society of Anaesthesiologists (ASA) physical class I and II, adult patients of either gender, aged between 18 to 60 years, undergoing elective surgery were allocated randomly into two equal groups to receive either intravenous thiopental sodium (Group NTR) or etomidate(Group NER) for rapid sequence induction. Group NER was given nalbuphine 0.1mg/kg, induction agent etomidate 3 mg/kg with muscle relaxant rocuronium 1.0 mg/kg while in group NTR induction agent thiopental sodium was given in the dose of 4 mg/kg with nalbuphine and rocuronium in the same doses. After sixty seconds, laryngoscopy was done. Intubating condition was assessed using the criteria of Cooper and colleagues: ease of intubation, condition of vocal cords and response to intubation. Cardiovascular response on intubation in terms of systolic and diastolic blood pressure and heart rate was evaluated at 0,1, 3 and 5 minutes. Results: Demographic data were comparable between the groups. Intubating conditions which were assessed in terms of ease of laryngoscopy, condition of vocal cords at intubation and intubation response coughing, bucking and diaphragmatic movement were significantly better in the group NER (p<0.05). Similarly, arterial blood pressure remained close to base line in NER group but there was significant fall in both systolic and diastolic blood pressure in group NTR. However, there was no significant difference in change in the heart rate in the groups. Conclusion: Etomidate-rocuronium is better than thiopental-rocuronium in terms of intubating conditions and haemodynamic stability during rapid sequence induction in non-septic surgical patients in emergency department. Keywords: Etomidate, thiopental sodium, nalbuphine intubation, rocuronium, laryngoscopy. (ASH & KMDC 19(2):79;2014).

Introduction properties. Nothing had yet replaced succinylcholine in the scenarios of difficult intubation before but with Rapid sequence induction (RSI) is the advent of rocuronium antagonist (ORG-25969, standard anaesthetic technique and the depol- sugamedax) that chelates the drug and act as the arizing neuromuscular agent succinylcholine has reversal agent, rocuronium can also be used in been the drug of choice for RSI and anticipated difficult intubation situations in RSI. However, difficult intubations for its short and rapid acting ______rocuronium is the suitable alternative, equally rapid Department of Anaesthesia, acting muscle relaxant in the recommended doses Abbasi Shaheed Hospital, KMDC, Karachi for RSI (2or3xED95) where succinylcholine is Correspondance: Dr. Syeda Asma Khalid relatively contraindicated, like in the patients with Assistant Professor, Department of Anaesthesia, SICU and Pain Management. hyperkalemia or known family history of abnormal Abbasi Shaheed Hospital, Karachi Medical and Dental 1,2 cholinesterase enzyme activity . In addition, College, Cell # 03002411812 Email:[email protected] rocuronium being monoquatnary amino steroidal

79 Annals Abbasi Shaheed Hospital & Karachi Medical & Dental College Syeda Asma Khalid, Syed Hamid Ali, Sadqa Aftab, Waqar H. Kazmi

drug, does not cross placenta therefore can safely lar dysfunction; it does not cause haemodynamic be used in obstetrical surgeries where risk of instability. The circulatory factor that determines 3-5 regurgitation requires rapid sequence induction . the intravenous anaesthetic etomidate proportionally effects the distribution of rapid acting muscle relax- The most popular hypnotic agents for RSI in ant; hence supporting the better intubating condition emergency cases in South Asia have been intrave- in shortest period of time for rapid sequence induc- nous thiopental sodium, ketamine, propofol and tion13-16 etomidate. Thiopental sodium, a short acting . thiobarbiturate, is considered a gold standard and The aim of this study is to determine the ef- has been widely used induction agent even for RSI fect on intubating conditions and haemodynamic re- in the past. However, it causes reduction in arterial sponse on intubation of two almost forgotten but blood pressure and reflex tachycardia in the pres- available and well proven different anaesthetic induc- ence of hypovolemia by abolishing the sympathetic tion agents, etomidate and thiopental sodium, with compensation with rapid induction. Regardless of a rapid acting muscle relaxant rocuronium in emer- its side effects thiopental sodium had long been gency department. used with pre-induction pharmacological optimiza- tion and intravenous fluids resuscitation. It sup- Patients and Methods presses neuronal activity, making it a useful This study was conducted in department of induction agent in haemodynamically stable pa- anaesthesia, Civil Hospital Karachi, Dow University tients with conditions that can elevate intracranial of Health Sciences and Abbasi Shaheed Hospital pressure including seizures, intracranial bleeding, or after approval from concerned ethics committee, de- trauma. However, its use as induction agent is now partmental permission and informed consents from limited due to unavailability in western part of world all the patients, from Nov 2011 to Dec 2012. This and the advent of newer hypnotics like propofol4-7, 9 . was a prospective quasi experimental study, in- Propofol, a phenol derivative, attenuates intuba- cluded 120 adult patients of either gender, aged be- tion response the most as compare to all other in- tween 18 and 80 years,having American Society of duction agents, but it can cause marked Anaesthesiologists(ASA) physical class I and II, un- hypotension and bradycardia with rapid induction in dergoing emergency surgeries, including general, compromised emergency situations4,14. Ketamine, a orthopaedic, plastic and neurosurgeries were allo- dissociative anaesthetic poorly attenuates the intu- cated randomly into two equal groups to receive ei- bation response, is favorable in situation where ther intravenous thiopental sodium (Group NTR) or marked cardiovascular decompensation is antici- etomidate (Group NER) as induction agent with pated after induction, provided the endogenous cat- muscle relaxant rocuronium for rapid sequence in- echolamine stores are not depleted as in critically duction. ill patients. On the contrary, it can cause hyperten- The patient with anticipated difficult laryngos- sion and marked tachycardia that can be deleteri- copy and intubation, allergy to any study medica- ous in hypertensive patients with left ventricular tions, receiving any other sedatives, acute upper air dysfunction2,4, 11-13 . way disease causing hyperreactive airway, pharyn- Etomidate, an imidazole compound, produces geal or laryngeal disease and having any neuromus- sedation and amnesia through α amino butyric acid cular dysfunction, severe sepsis were excluded (GABA)inhibitory neurotransmitter system. Its onset from the study. of action is rapid and comparable to propofol and The patients were randomly grouped using odd thiopental sodium that is 15-20 seconds. It has a and even method, patient with odd serial numbers superior profile in terms of cardiovascular stability were grouped to receive thiopental sodium with even when used in patients with severe left ventricu-

Volume No. 19 (2), December 2014 80 Two Forgotten Induction Agents; Etomidate versus Thiopental Sodium with Rocuronium for Rapid Sequence Induction

rocuronium while patient on even serial were 18 patients which had thiopental sodium as the in- grouped in to have etomidate and rocuronium for duction agent NTR (p=0.002), shown in Fig 1.The RSI. The anaesthetists, who intubated and as- vocal cords seen open in statistically significant pa- sessed the effect of drugs in terms of intubating tients on laryngoscopy, were 56 patients in NER condition and haemodynamics, were more than versus 38 patients in the other group (p=0.036) three year in experience and were blinded for the whereas in group NTR 8 and 12 patients had clos- study drugs. The primary investigator prepared the ing and moving vocal cords respectively at the time anaesthetic drugs and ensured the blinding with of intubation (Fig. 2). No patient from either group screen from intubating anaesthetist. All patients had had severe coughing and bucking. However 12 pa- standard monitoring including non-invasive blood tients in group NTR showed mild coughing versus 4 pressure, SpO2, ECG, capnography and tempera- patients in the group NER. Slight diaphragmatic ture monitoring. Baseline blood pressure, heart rate movement was also noticed in 26 patients which were noted in all the patients. was higher than found in group NER (p=0.007), (Table 2.). There was statistically significant differ- Group NTR was given intravenous analgesia In- ence in the mean of addition of all the scores i.e. jection Nalbuphine 0.1 mg/kg, induction agent thio- 6.84 ± 1.41 in group NTR compared to 8.44 ± 1.04 pental sodium 4 mg/kg and muscle relaxant in group NER (p=0.0001). injection rocuronium 0.6mg/kg (2xED 95), while in group NER, induction was done with intravenous For haemodynamic changes, there was no sta- etomidate 0.3 mg/kg with same doses of nalbuphine tistically significant difference in terms of baseline and rocuronium as in group NTR. After sixty sec- heart rate, systolic and diastolic blood pressures onds of the administration of rocuronium, laryngos- between the groups. Also, there was no significant copy was done, trachea intubated. Intubating change in heart rates from baseline after 1, 3, and conditions were assessed using the criteria of Coo- 5 minute in both groups. However, the systolic and per and colleagues; ease of laryngoscopy (0=im- diastolic blood pressure were significantly higher in possible, 1=difficult, 2=fair, 3=easy), condition of group NER recorded on the given intervals (p<0.05), vocal cords (0=closed, 1=closing, 2=moving, (Table 3). 3=open) and response to intubation9. Discussion The cardiovascular response on intubation in both the groups was recorded in terms of systolic The ease in performing endotracheal intubation and diastolic blood pressure and heart rate at depends on the type and degree of muscle relax- baseline 0,1,3,5 minutes. All the data were recorded ation, depth of anaesthesia and the skill of the on proforma. anaesthesiologist. In this study we used the steroidal non depolarizing muscle relaxant rocuronium for Statistical analysis of categorical variable was facilitation of intubation with two different intrave- done using chi square test and fisher exact test nous induction agents: etomidate and thiopental so- white continuous data was evaluated by student t- dium. We found it suitable alternative for historically test (p<0.05) was taken as significant. used depolarizing muscle relaxant succinylcholine, in situations where its use is relatively or absolutely Results contraindicated. The rapid onset of adequate paraly- Demographic characteristics were comparable sis for endotracheal intubation was achieved with in- between the groups except the ASA status (Table. travenous bolus of rocuronium bromide after one 1). In group NTR 44 patient were ASA1 while 48 in minute. Group NER. Laryngoscopy was found easier in 56 patients in those induced by etomidate NER versus

81 Annals Abbasi Shaheed Hospital & Karachi Medical & Dental College

Two Forgotten Induction Agents; Etomidate versus Thiopental Sodium with Rocuronium for Rapid Sequence Induction

In a Cochrane meta analysis of 58 clinical tri- changes in hearts where comparable that is in- als, 0.6 mg/kg (2xED) to 1.2 mg/kg (3xED95) creased from baseline in after intubation(Table 3). doses of rocuronium have been compared with succinylcholine and found comparable intubating con- Our results of the study are consistent with ditions with 1 mg/kg dose of rocuronium with 1 the previous trials that compared induction agent mg/kg of depolarizing muscle relaxant1. Patanwala etomidate for intubating condition and cardiovascular AE, after a retrospective evaluation of 327 patients stability in emergency situations where risk of aspi- also concluded that succinylcholine and ration hypoxia and emergency surgeries were the rocuronium are comparable in regard to first-at- indications for intubation in rapid sequence induc- tempt intubation success in the emergency depart- tion. The controversy with etomidate regarding its 2 ment using equivalent doses of both the drugs . use in septic patients has always been there but However, we used 0.6 mg/kg, a lowest dose and some researcher found it safe when it is as a achieved good intubation conditions with etomidate. single bolus in septic or trauma patients. The re- If a higher dose is chosen i.e. 1 mg/kg, it may fur- searchers concluded that a bolus dose of ther improve the intubation condition in terms of etomidate for RSI was not associated with in- ease of laryngoscopy, vocal cords conditions and response on intubation1-4. creased morbidity and mortality compared to ketamine in critically ill patients but suggested that In addition to a neuromuscular blocking agent, 18-23 ketamine is a safe alternative . to achieve optimal intubating conditions, choice of As there is no randomized control trial in our the anaesthetic induction agent and dose most ap- population regarding the use of etomidate in severe propriate for the clinical situation is an important sepsis and we did not evaluated serum cortisol lev- component of RSI for haemodynamic stability1,5,8,9 . els to determine the adrenal insufficiency in any pa- The induction agent may influence the rate of tient, we recommend cautious administration in onset of advocate relaxation required for satisfac- patients with evolving or established septic shock, tory intubating conditions3,6,13 The haemodynamic etomidate should be deferred for other options like . thiopental sodium and ketamine21 However, in pa- stability related to the induction anaesthetics pro- . tients where haemodynamic instability is not an is- portionally effect the time of the distribution of sue, use of thiopental sodium has been a gold muscle relaxant. We compared etomidate with thio- standard and in the presence of hypotension, it pental sodium and had more haemodynamic stabil- should be preferred over commonly used induction ity in terms of diastolic and systolic blood agent propofol that is known to be associated with pressures (p=0.0001). Different trials have evaluated hypotension and bradycardia. Moreover, in our part the relation between the onset of block and the of the world where thiopental and etomidate are change in mean arterial pressure; onset of block easily available for use, we should not limit our was shortest when anaesthesia was induced with choices of induction agents that compromise 9 patient’s safety in terms of hemodynamic stability6. Etomidate compared with thiopental and propofol . The induction agent also effect intubating condition American society has shown great concerns over by attenuating laryngeal and pharyngeal response the unavailability of thiopental and its absence is of laryngoscopy and intubation,among all propofol being considered as a risk to their patients’ safety 25 attenuates these responses better than the two we in USA and other European countries . used, but when muscle relaxant is used this prop- So, we recommend that the two forgotten an- erty of propofol does not outweigh the aesthetic induction agents, etomidate and thiopen- cardiodepressent effect like bradycadia and hy- tal should be brought in current anaesthesia potension which is the major concern with the use practice for the safety of our patients especially in of propofol4. However, between the two we com- emergency situations where haemodynamic insta- pared, etomidate was associated with more sus- bilities are frequently encountered. We also recom- tained diastolic and systolic blood pressures while mend that rocuronium is equally effective muscle

83 Annals Abbasi Shaheed Hospital & Karachi Medical & Dental College Syeda Asma Khalid, Syed Hamid Ali, Sadqa Aftab, Waqar H. Kazmi relaxant in situation where succinylcholine is con- 11. Masoudifar M, Beheshtian E. Comparison of cardiovascular response to laryngoscopy and tra- sidered unsafe and contraindicated. cheal intubation after induction of anesthesia by Propofol and Etomidate. J Res Med Sci 2013;18:870-4. Conclusion 12. El-Beheiry H, Kim J, Milne B, Seegobin R. Prophy- Induction agents etomidate and thiopental are laxis against the systemic hypotension induced by propofol during rapid-sequence intubation. Can J safe for rapid sequence induction in emergency sur- Anaesth 1995;42:875-8. geries and etomidate provides better intubating con- 13. Harsten A, Gillberg L. Intubating conditions pro- ditions and haemodynamic stability than thiopental. vided by propofol and alfentanil acceptable, but Moreover, nondepolarizing muscle relaxant rocuro- not ideal. ActaAnaesthScand 1997;41:985-7. nium can be an acceptable alternative whenever 14. Gill RS, Scott RP.Etomidateshortend the onset of succinylcholine is contraindicated, provided intuba- time of neuromuscular block. Br J Anesth 1992;69:444-6. tion is not anticipated difficult. 15. Jackson WL Jr. Should we use etomidate as an induction agent for endotracheal intubation in pa- References tients with septic shock? a critical appraisal. Chest 2005;127:1031-8. 1. Perry JJ, Lee JS, Sillberg VAH, Wells GA. Rocuronium versus succinylcholine for rapid se- 16. Kelly-Smith C, Hohl C, Should emergency physi- quence induction intubation. Cochrane Database cians use etomidate for rapid sequence intuba- of Syst Rev 2008;16:2. tion? CJEM 2011;13:44-7. 2. Patanwala AE. Comparison of Succinylcholine 17. Smith DC, Bergen JM, Smithline H, Kirschner R. A and Rocuronium for First-attempt Intubation Suc- trial of etomidate for rapid sequence intubation in cess in the Emergency Department. AcadEmerg the emergency department.. J Emerg Med Med 2010;18:11-4. 2000;18:13-6. 3. Shahnawaz M, Shahjahan B, Sarwar SS. Evalua- 18. Choi YF, Wong TW, Lau CC. Midazolam is more tion of intubating conditions after rocuronium bro- likely to cause hypotension than etomidate in mide in adults induced with propofol or emergency department rapid sequence intuba- thiopentone sodium. J Anaesthesiol Clin tion. Emerg Med J 2004;21:700-2. Pharmacol 2011;27:215-9. 19. Murray H, Marik PE. Etomidate for endotracheal 4. OglesbyAJ.Should etomidate be the induction intubation in sepsis: acknowledging the good agent of choice for rapid sequence intubation in while accepting the bad. Chest 2005;127:707-9. the emergency department? Emerg Med J 2004;21:655-9. 20. ScherzerD, Leder M, Tobias JD. Pro-Con Debate: etomidate or ketamine for rapid sequence intuba- 5. Ching KY, Baum CR. Newer agents for rapid se- tion in pediatric patients. J PediatrPharmacolTher quence intubation: etomidate and rocuronium. 2012;17:142-9. Pediatr Emerg Care 2009;25:200-7. 21. Walls RM, Murphy MF. Clinical controversies: 6. Khan TH. Availability of essential drugs in Paki- etomidate as an induction agent for endotracheal stan. Anaesth Pain and Intensive Care 2009;13:1- intubation in patients with sepsis: continue to use 3. etomidate for intubation of patients with septic shock. Ann Emerg Med 2008;52:13-4. 7. AnisSB, Sayyid, Sahar S, Assaf, Boutros A. Thio- pental-rocuronium versus ketamine-rocuronium 22. Cherfan AJ, Arabi YM, Al-Dorzi HM, Kenny for rapid-sequence intubation in parturients un- LP.Advantages and disadvantages of etomidate dergoing cesarean Section. Anesthesia & Analge- use for intubation of patients with sepsis. Phar- sia 1997;5:1104-7. macotherapy 2012;32:475-82. 8. WilliamsonRM, Mallaiah S, Barclay P. Rocuronium 23. Zed PJ, Mabasa VH, Slavik RS, Abu-Laban RB. and sugamedax for rapid sequence induction of Etomidate for rapid sequence intubation in the obstetric general anaesthesia; Acta Anaesthesiol emergency department: is adrenal suppression a Scan 2011;55:694-9. concern? CJEM 2006;8:347-50. 9. Fuchs-Buder T, Sparr HJ, Ziegenfuss T. Thiopen- 24. Cuthbertson BH, Sprung CL, Annane D, Chevret tal or etomidate for rapid sequence induction with S, Garfield M, Goodman S, et al. The effects of rocuronium? Br J Anesth 1998;80:504-6. etomidate on adrenal responsiveness and mortality in patients with septic shock. Intensive Care 10. AU-Jellish WS, Riche H, Salord F, Ravussin P, Medicine 2009;35:1868-76. Tempelhoff RS. Etomidate and thiopental-based anesthetic induction: comparisons between differ- 25. Mediscape medical news: Anesthesiologists ask ent titrated levels of electrophysiological cortical FDA to okay importation of thiopental sodium depression and response to laryngoscopy. J [Internet]. Available from: http://www.med- ClinAnesth 1997;9:36. scape.com/viewarticle/737303.

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