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CONTINUING MEDICAL EDUCATION
Continuing Medical Education Activity in Academic Emergency Medicine CME Editor: Hal Thomas, MD Authors: Asad E. Patanwala, PharmD, Courtney B. McKinney, PharmD, Brian L. Erstad, PharmD, and John C. Sakles, MD Article Title: Retrospective Analysis of Etomidate Versus Ketamine for First-pass Intubation Success in an Academic Emergency Department If you wish to receive free CME credit for this activity, please refer to the website: http://www.wileyhealthlearning.com/aem.
Accreditation and Designation Statement: Blackwell Futura Media Services designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit. Physicians should only claim credit commensurate with the extent of their participation in the activity. Blackwell Futura Media Services is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Educational Objectives After completion of this exercise the participant will be better able to identify the roles of ketamine and etomidate in emergent airway management. Activity Disclosures No commercial support has been accepted related to the development or publication of this activity. Faculty Disclosures: CME editor – Hal Thomas, MD: No relevant financial relationships to disclose. Authors Asad E. Patanwala, PharmD, Courtney B. McKinney, PharmD, Brian L. Erstad, PharmD, and John C. Sakles, MD: No relevant financial relationships to disclose. This manuscript underwent peer review in line with the standards of editorial integrity and publication ethics maintained by Academic Emergency Medicine. The peer reviewers have no relevant financial relationships. The peer review process for Academic Emergency Medicine is double-blinded. As such, the identities of the reviewers are not disclosed in line with the standard accepted practices of medical journal peer review.
Conflicts of interest have been identified and resolved in accordance with Blackwell Futura Media Services’s Policy on Activity Disclosure and Conflict of Interest. No relevant financial relationships exist for any individual in control of the content and therefore there were no conflicts to resolve. Instructions on Receiving Free CME Credit For information on applicability and acceptance of CME credit for this activity, please consult your professional licensing board. This activity is designed to be completed within an hour; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity during the valid credit period, which is up to two years from initial publication. Follow these steps to earn credit: • Log on to http://www.wileyhealthlearning.com • Read the target audience, educational objectives, and activity disclosures. • Read the article in print or online format. • Reflect on the article. • Access the CME Exam, and choose the best answer to each question. • Complete the required evaluation component of the activity. This activity will be available for CME credit for twelve months following its publication date. At that time, it will be reviewed and potentially updated and extended for an additional twelve months.
Retrospective Analysis of Etomidate Versus Ketamine for First-pass Intubation Success in an Academic Emergency Department Asad E. Patanwala, PharmD, Courtney B. McKinney, PharmD, Brian L. Erstad, PharmD, and John C. Sakles, MD
apid sequence intubation (RSI) is the mainstay of airway management in critically ill emergency department (ED) patients. With the possible exception of patients who are unconscious and unresponsive, all patients needing RSI require the use of a sedative agent prior to neuromuscular blockade. The intent of the sedative is to render the patient unconscious and unaware, while the paralytic facilitates passage of the tracheal tube via muscular relaxation. Most studies evaluating intubation conditions or success rates have traditionally focused on comparisons of neuromuscular blockers.1,2 However, the sedative used may also inﬂuence intubating conditions and success rates by potentiating the effect of the neuromuscular blocker;
reducing the time to maximal neuromuscular blockade; and affecting diaphragmatic, laryngeal, and pharyngeal reactivity to the intubation stimulus.3–5 In previous systematic reviews and registry studies, the effect of the paralytic on intubation conditions was modiﬁed based on the sedative used.2,5 This suggests that sedative selection could also inﬂuence intubation success, which is a more clinically relevant outcome compared to intubation conditions.6 A previous study by Jabre et al.,7 in which the primary focus was organ failure, reported intubation conditions and difﬁculty between etomidate and ketamine, but ﬁrst-pass intubation success has not been evaluated as an outcome. The complications related to intubation (such as hypoxemia,
From the Department of Pharmacy Practice & Science (AEP, CBM, BLE) and the Department of Emergency Medicine (JCS), College of Pharmacy, University of Arizona, Tucson, AZ; and the Department of Pharmacy Services, Intermountain Medical Center (CBM), Salt Lake City, UT. Received May 6, 2013; revision received August 2, 2013; accepted August 2, 2013. Presented at the Society of Critical Care Medicine, Puerto Rico, January 2013. The authors have no relevant ﬁnancial information or potential conﬂicts of interest to disclose. Supervising Editor: Robert F. Reardon, MD. Address for correspondence and reprints: Asad E. Patanwala, PharmD; e-mail: [email protected]
ACADEMIC EMERGENCY MEDICINE • January 2014, Vol. 21, No. 1 • www.aemj.org
aspiration, bradycardia, and cardiac arrest) increase as the number of intubation attempts increase.6,8 Therefore, it is important that intubation success is achieved on the ﬁrst-pass, and studies are needed to ascertain if ketamine use is associated with a reduction in intubation success compared to etomidate before it can be routinely recommended. The primary goal of this study was to compare ﬁrstpass RSI success in ED patients who received etomidate versus ketamine. We hypothesized that there is no difference in ﬁrst-pass success between the two agents. METHODS Study Design This was retrospective analysis of prospectively collected data recorded in a quality improvement database between July 1, 2007, and December 31, 2012. The intent of the database is to evaluate resident performance, medications, and devices used for intubation in the ED. This study was granted exemption by the institutional review board. Study Setting and Population The study was performed in a 61-bed academic tertiary care ED with a census of approximately 75,000 patientvisits annually. Emergency physicians (EPs) primarily perform all intubations. During each intubation, physicians have access to a standardized intubation medication box containing the sedative etomidate, and the neuromuscular blockers succinylcholine, rocuronium, and vecuronium. Ketamine is available as an alternative agent via controlled access cabinets located in the ED. Sedative and neuromuscular blocker selection is primarily dependent on physician preference. All patients who underwent RSI in the ED were included. Patients were excluded if RSI was performed using a sedative other than etomidate or ketamine or if vecuronium was used for neuromuscular blockade instead of succinylcholine or rocuronium. Study Protocol The EP performing the intubation recorded data prospectively using a standardized data collection form, which was completed following the intubation. Pharmacy, billing, and admission records were used to identify any intubations performed without corresponding data forms, in which case the operators were contacted for form completion. Data collected included patient age, sex, trauma status (trauma or nontrauma), failure of prehospital intubation (failed or not attempted), presence of any difﬁcult airway characteristics (blood or vomit in the airway, short neck, cervical collar, small mandible, obesity, airway edema, facial trauma, or large tongue), laryngoscopy device used, reason for device selection (standard, anticipate difﬁcult airway, or educational reasons), reason for intubation (airway protection, respiratory failure, cardiac arrest, patient control, hypoxia), level of physician training (classiﬁed by postgraduate year [PGY] of residency training), medications used, and number of intubation attempts. The data were then entered into the electronic database program HanDBase 4.0 for the
iPad (DDH Software, Wellington, FL) with subsequent transfer to Excel for Windows 2010 (Microsoft, Redmond, WA). The primary outcome measure was ﬁrst-pass success. The deﬁnitions of intubation attempt and intubation success were similar to those used in previous investigations.9 An intubation attempt was deﬁned as the insertion and subsequent removal of the laryngoscopic device from the patient’s mouth, regardless of whether an attempt was made to pass a tracheal tube. Intubation success was deﬁned as correct placement of the tracheal tube into the trachea, which was conﬁrmed by end-tidal CO2 capnometry, pulse oximetry, chest auscultation, observation of chest excursion, absence of epigastric sounds, and misting of the endotracheal tube.9 Data Analysis Patients were categorized into two groups based on the sedative used for intubation: etomidate or ketamine. Demographic and intubation data were compared between the two groups. An unpaired Student’s t-test was used to compare continuous, normally distributed variables. Normality was determined by visually inspecting the data. Fisher’s exact test was used to compare categorical variables. A multivariate logistic regression analysis was performed to determine the effect of sedative agent on ﬁrst-pass success, after adjusting for confounders. Potential confounders that were included in the model were age, sex, paralytic used, trauma status, reason for intubation, device used, failure of prehospital intubation, reason for device selection, difﬁcult airway parameters, and physician training. These were selected based on previous studies evaluating intubation success in this setting, and all variables were forced into the model.1,9 Age was categorized in the model as younger than 18, 18 to 65, and older than 65 years, since it did not meet the assumption of linearity in the log-odds. Difﬁcult airway characteristics were entered into the model as ordinal variables. The model was checked for interactions and model ﬁt was assessed by the HosmerLemeshow goodness-of-ﬁt test. No interactions were identiﬁed, allowing for all potential variables to be added in the same model. All statistical analyses were performed using Stata version 12 (StataCorp, College Station, TX) with signiﬁcance for all analyses deﬁned a priori as p < 0.05. RESULTS During the study period there were 2,258 RSIs performed in the ED. Of these, 113 were performed with sedatives other than etomidate or ketamine, 42 were performed with paralytics only, and ﬁve were performed with paralytics other than succinylcholine or rocuronium. Therefore, the ﬁnal cohort consisted of 2,098 intubations using either etomidate (n = 1,983) or ketamine (n = 115). Overall, most intubations were performed by EPs (n = 2,019), followed by medical students or paramedics (n = 59) and physicians from other specialties (n = 20). The mean (SD) patient age was 45.6 (22.5) years, 63.5% of the patients were male, and the proportion of trauma patients was 44.0%. Comparison of baseline patient demographics and intubation
Patanwala et al. • EFFECT OF SEDATIVES ON INTUBATION SUCCESS
Table 1 Demographics and Intubation Characteristics of Etomidate Versus Ketamine Groups
Characteristic Age group (yr)* <18 18 to 65 >65 Sex* Female Male Trauma* Medical Trauma Prehospital intubation Not attempted Failed Paralytic used Rocuronium Succinylcholine Reason for intubation* Airway protection Respiratory failure Cardiac arrest Patient control Hypoxia Device used* Direct laryngoscopy GlideScope C-MAC Other Reason for device selection* Standard Difficult Education Operator level of training Nonphysician (medical students and paramedics) PGY1 PGY2 PGY3 Attending Difficult airway characteristics* None 1 2 3 or more
PGY = postgraduate year. *Significant difference between groups.
parameters between the etomidate and ketamine groups is provided in Table 1. First-pass success occurred in 77.0% of patients in the etomidate group and 79.1% of patients in the ketamine group (difference = –2.1; 95% CI = –5.5 to 9.8). In the multivariate analysis, after the potential confounders and baseline differences were adjusted for, ketamine use was not associated with a reduction in ﬁrst-pass success (odds ratio = 0.89; 95% CI = 0.5 to 1.5; p = 0.632) compared to etomidate. The data ﬁt the model well (HosmerLemeshow goodness-of-ﬁt, p = 0.944). DISCUSSION First-pass intubation success is highly desirable because complications increase as the number of attempts increases.6,8 Previous studies have primarily focused on the effects of neuromuscular blockers, since they are
directly responsible for muscular relaxation for passage of the tracheal tube.1 However, the sedative used can affect this outcome by a variety of potential mechanisms. For instance, the response to the intubation stimulus, such as diaphragmatic movement and coughing, can be inﬂuenced by the sedative used.3 Also, the onset time of neuromuscular blockade can be modiﬁed by the sedative.4 This is particularly important in the context of our study because ketamine has a longer onset of effect compared to etomidate. Therefore, if intubation is attempted prior to maximal neuromuscular blockade, intubation success could be affected. Sivilotti et al.5 evaluated the effect of a wide range of sedatives on intubation success in a multicenter observational study. They found that collectively, thiopental, methohexital, and propofol were associated with improved ﬁrst-pass success, compared to other sedatives such as etomidate, ketamine, and benzodiazepines. They
ACADEMIC EMERGENCY MEDICINE • January 2014, Vol. 21, No. 1 • www.aemj.org
hypothesized that the former group of sedatives produce a deeper plane of anesthesia, thereby facilitating intubation before complete neuromuscular blockade is achieved with paralytics alone. However, these former agents are seldom used for emergency intubation because of the potential for adverse effects such as hypotension. Our study builds on the results of Sivilotti et al. by focusing on etomidate and ketamine, two of the most commonly used sedatives for this indication due to their favorable hemodynamic proﬁle. In addition, we included important confounders such as the intubation device used, which has recently been shown to be highly predictive of intubation success.10 Thus, our results are pertinent in an era in which video laryngoscopy is common. In a recent randomized controlled trial by Jabre at al.,7 655 patients who required emergency intubation were given either etomidate or ketamine for induction. There was no difference between groups with regard to the development of organ failure, which was the primary outcome. Although intubation success was not an outcome in this study, the difﬁculty of intubation was measured and was found to be comparable between the two groups. However, since this was not the focus of the study, important confounders were not measured. Our study is unique because we measured ﬁrst-pass success, which was our primary outcome. We were unable to measure adverse effects, which is an important consideration in terms of sedative selection. However, the much larger study by Jabre et al.7 did not show differences in adverse effects, and these agents are considered to have similar safety proﬁles. Thus, given the fact that multiple intubation attempts are associated with an increase in adverse effects, we felt that ﬁrst-pass success was the most important outcome to study. LIMITATIONS The study has a few limitations related to its design. The results should be extrapolated with caution to nonacademic EDs. There is a possibility for measurement bias because physicians performing each intubation completed the data forms themselves. Ideally, an independent observer would collect this information. However, our main outcome variable was intubation attempts, and it is very unlikely that this variable would be erroneously documented. Some data collection forms were not completed immediately after the intubations and required the senior investigator (JCS) to contact individual physicians as part of a quality improvement process. Although this was done as quickly as possible, the delay in recording information in these cases could have led to recall bias. Nonetheless, the senior investigator veriﬁed information provided against medical records to ensure accuracy of documentation. It is possible that there was selection bias with regard to ketamine and etomidate. There were many more patients in the etomidate group, but we included all patients to minimize the potential for selection bias. Ideally, a randomized controlled trial would overcome this bias. However, we adjusted for differences between groups and performed the necessary model diagnostics. In addition, there could be individual variation between
operators, but we could not stratify the results by operator because there were more than 150 operators in the database. Also, operator success could improve with number of previous intubations. Nonetheless, we included level of training as a surrogate for operator skill. We did not have dosing information of the paralytics, which could inﬂuence intubation conditions. There were several baseline differences between groups. However, we adjusted for this in our multivariate model. Finally, it is possible that there are additional confounders that were not included in our model. However, we have included the most likely variables, based on previous studies that could affect our outcome. CONCLUSIONS Etomidate and ketamine were associated with equivalent ﬁrst-pass success in this retrospective review. A prospective randomized trial of ﬁrst-pass success is needed to conﬁrm these ﬁndings. References 1. Patanwala AE, Stahle SA, Sakles JC, Erstad BL. Comparison of succinylcholine and rocuronium for ﬁrst-attempt intubation success in the emergency department. Acad Emerg Med. 2011;18:10–4. 2. Perry JJ, Lee JS, Sillberg VA, Wells GA. Rocuronium versus succinylcholine for rapid sequence induction intubation. Cochrane Database Syst Rev. 2008 (2):CD002788. 3. Fuchs-Buder T, Sparr HJ, Ziegenfuss T. Thiopental or etomidate for rapid sequence induction with rocuronium. Br J Anaesth. 1998;80:504–6. 4. Gill RS, Scott RP. Etomidate shortens the onset time of neuromuscular block. Br J Anaesth. 1992;69:444– 6. 5. Sivilotti ML, Filbin MR, Murray HE, Slasor P, Walls RM. Does the sedative agent facilitate emergency rapid sequence intubation? Acad Emerg Med. 2003;10:612–20. 6. Sakles JC, Chiu S, Mosier J, Walker C, Stolz U. The importance of ﬁrst pass success when performing orotracheal intubation in the emergency department. Acad Emerg Med. 2013;20:71–8. 7. Jabre P, Combes X, Lapostolle F, et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009; 374:293–300. 8. Mort TC. Emergency tracheal intubation: complications associated with repeated laryngoscopic attempts. Anesth Analg. 2004;99:607–13. 9. Mosier J, Chiu S, Patanwala AE, Sakles JC. A comparison of the GlideScope video laryngoscope to the C-MAC video laryngoscope for intubation in the emergency department. Ann Emerg Med. 2013;61: 414–20. 10. Sakles JC, Mosier JM, Chiu S, Keim SM. Tracheal intubation in the emergency department: a comparison of GlideScope(R) video laryngoscopy to direct laryngoscopy in 822 intubations. J Emerg Med. 2012;42:400–5.