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Comparison of etomidate and midazolam for prehospital Rapid-sequence intubation
COMPARISON
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ETOMIDATE AND MIDAZOLAM FOR PREHOSPITAL RAPID-SEQUENCE INTUBATION
Eric R. Swanson, MD, David E. Fosnocht, MD, Suzanne C. Jensen, MD Rapid-sequence intubation (RSI) is defined as the use of a sedative or induction agent and a neuromuscularblocking agent to facilitate intubation. Intubation success rates are improved by RSI in the air medical environment.1–4 Many sedatives are used for sedation or induction with RSI, but no single agent has emerged as clearly superior. Etomidate is an ultra-short-acting carboxylated imidazole sedative-hypnotic that was introduced in Europe in 1972 and approved for use in the United States in 1983.5 In recent years, etomidate has become popular for the RSI of emergency department (ED) patients.6–9 Etomidate and midazolam are the most commonly used sedative agents for RSI in the air medical setting. A recent survey of 196 air medical programs found that, out of the 114 respondents, 93% of the programs used RSI, and the most commonly used induction agents were midazolam (75%) and etomidate (44%).10 Etomidate is reported to be an effective agent for RSI in the air medical setting, with excellent hemodynamic stability.11,12 Although use of midazolam for RSI is common, it has not been well studied in the prehospital environment. One study reports that the use of midazolam for prehospital RSI is associated with a dose-related incidence of hypotension.13 Prehospital RSI remains a controversial subject, and many questions are yet unanswered in this evolving practice. Comparing the use of etomidate and midazolam for tendency to cause hypotension, poor intubating conditions, or difficulty in correct dosage selection will help define the utility of these agents for prehospital RSI programs. The purpose of this study was to compare etomidate with midazolam as sedative or induction agents for RSI in our air medical transport system. Outcome measures included the incidence of hypotension, percentage of change in heart rate (HR), percentage of change in systolic blood pressure (SBP), and success rate of intubation.
ABSTRACT Objective. This study compares etomidate with midazolam for prehospital rapid-sequence intubation (RSI). Methods. The authors conducted a retrospective review of consecutive intubations at a university-based air medical program from January 1995 to December 2000. Exclusion criteria were patients not undergoing RSI, age < 15 years, and incomplete chart data. Outcome measures included intubation success, incidence of hypotension, and percentage of change in heart rate (HR) and systolic blood pressure (SBP). Results. The intubation success rate was 110 out of 112 (98%) with etomidate, and 96 out of 97 (99%) with midazolam. Mean ages, patient gender distributions, and initial SBPs and HRs did not differ between the two groups. The mean dose of etomidate was 24 mg, the mean percentage of change in HR was ÿ1% (95% confidence interval [CI], ÿ6 to 4), and the mean percentage of change in SBP was 2% (95% CI, ÿ3 to 7). The mean dose of midazolam was 3.5 mg, the mean percentage of change in HR was 1% (95% CI, ÿ5 to 7), and the mean percentage change in SBP was 3% (95% CI, ÿ3 to 9). The number of hypotensive episodes with etomidate (7 out of 74) compared with midazolam (3 out of 56) did not differ significantly (Fisher’s exact test, p = 0.51). Conclusion. Intubation success rate was very high with both etomidate (98%) and midazolam (99%). There was no statistically significant mean percentage of change in SBP or HR with either agent. The authors found a low incidence of hypotension with both agents, although the mean dose of midazolam used was considerably less than typically recommended for induction. Key words: etomidate; midazolam; intubation; prehospital emergency care; air ambulances.
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Airway management with endotracheal intubation is an essential part of modern air medical transport. Challenges to intubation in the prehospital setting include awake or combative patients with intact airway reflexes, making intubation difficult or impossible. Received July 24, 2003, from the Division of Emergency Medicine and AirMed, University of Utah Health Sciences Center, Salt Lake City, Utah (ERS, DEF); and the Stanford-Kaiser Emergency Medicine Residency Program, Stanford, California (SCJ). Revision received December 16, 2003; accepted for publication December 20, 2003.
METHODS
Presented at the 2003 ACEP Research Forum, October 2003, Boston, Massachusetts.
Study Design
Address correspondence and reprint requests to: Eric R. Swanson, MD, Division of Emergency Medicine, 1150 Moran Building, 175 North Medical Drive, Salt Lake City, UT 84132. e-mail:.
This study was a retrospective review of a consecutive series of intubations performed by an air medical transport program based in a university hospital over a six-year period, from January 1995 to December 2000.
doi:10.1016/j.prehos.2003.12.026
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Population and Setting The air medical service is based at a university medical center that is a level-1 trauma facility and a major tertiary referral center. A nurse and paramedic flight crew perform all transports, with the exception of highrisk obstetric transports, which use a two-nurse team. The air medical program operates three rotor-wing and two fixed-wing aircraft, and transports approximately 1,600 patients per year. Flight nurses and flight paramedics perform intubations, operating under online medical command and written guidelines. The flight nurse is ultimately responsible for determining the need for RSI, as well as for making the choice of sedative and other medications used for RSI. Training in airway management for the flight crews consists of initial orientation, continuing education, and quality assurance feedback. Orientation includes a review of the program’s RSI and failed-intubation guidelines, the performance of at least ten intubations in the operating room (OR), skills training in animal models for intubation, training in cricothyrotomy and translaryngeal jet ventilation, and ten to 20 ride-along shifts with experienced crew members. Ongoing airway education includes yearly lectures on RSI and difficult-airway management, skills teaching in animal models, and laryngeal mask airway (LMA) and intubating laryngeal mask airway (I-LMA) training. The program conducts monthly manikin training and review of all difficult airway cases. Crew members are required to perform at least four intubations per month during patient care, on a manikin, or on an animal model. A standard RSI guideline is available, and deviation based on the clinical situation is inherent to the protocols. Lidocaine, atropine, and vecuronium are available for pretreatment. The choice of sedative agents was limited to midazolam from January 1995 to April 1998, but included both etomidate and midazolam from April 1998 to December 2000. The dose of etomidate recommended by our RSI guideline is 0.3 mg/kg, and the dose of midazolam is 0.1 mg/kg. Succinylcholine and vecuronium are the choices for neuromuscular blockade. At least one objective measure (end-tidal carbon dioxide [CO2] or esophageal detector device) in addition to clinical assessment is required for confirmation of endotracheal tube placement. The study was reviewed and approved by the university’s institutional review board and the requirement for written informed consent was waived.
Experimental Protocol The records of all adult and pediatric patients transported by the air medical program who required intubation during the six-year period from January
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1995 to December 2000 were reviewed. Exclusion criteria included patients who did not receive etomidate or midazolam and patients with incomplete chart data. One author abstracted data from the records of all patients intubated by the air medical program over the study period. For training purposes and to improve accuracy, the first 20 records also were reviewed by the primary author, and a standardized abstraction form was developed. Protocols were developed for the chart abstractor to ensure consistency in recording the timing of events such as intubation, medication administration, and vital sign measurement. In addition, a random sample of 26 charts was reabstracted by the primary author to determine interrater reliability of data recording. The chart abstractor was not blinded to the study purpose. The demographic information recorded for patients was limited to age and gender. Site of intubation (scene, air, referring facility, or receiving facility) and person intubating (flight nurse, flight paramedic, or other) were recorded. Data also included the medications used for pretreatment, sedation, and paralysis; the dosage of sedative medications; and the means of securing the airway, if not with endotracheal intubation. Vital signs recorded included systolic and diastolic blood pressures, HR, and oxygen saturation. Records were considered adequate for hemodynamic calculations if the vital signs were noted before RSI and at least one set was available within 10 minutes after intubation. Hypotension was defined as a SBP < 90 mm Hg, or a further decrease in SBP of 5 mm Hg or more, in patients who initially had had a SBP < 90 mm Hg.
Outcome Measures Primary outcome measures included the intubation success rate, percentage of change in HR, percentage of change in SBP, and incidence of hypotension when either etomidate or midazolam was used for RSI.
Analytical Methods Patient demographics, intubation details, and occurrence of adverse events are reported using descriptive statistics. The mean is expressed as 6 standard deviation (SD) with a 95% confidence interval (CI). Dichotomous variables are compared using the chisquare and Fisher’s exact test, with statistical significance set at p < 0.05. Interobserver agreement of the chart abstractors was measured with a kappa statistic.
RESULTS The flight program performed 372 intubations over the six-year period. Men comprised 71% of the patients (259 out of 366 with complete data). The average age of
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TABLE 1. Indications for Rapid-sequence Intubation and Person Intubating for All Patients Receiving Etomidate or Midazolam Etomidate Group (n = 113)
Midazolam Group (n = 97)
Indication Trauma Medical
84 (74%) 29 (26%)
76 (78%) 21 (22%)
Person intubating Flight nurse Flight paramedic Other
61 (54%) 46 (41%) 6 (5%)
51 (53%) 35 (36%) 11 (11%)
patients was 34 years (n = 358, SD 6 20; range four months to 89 years). Intubation occurred at the scene in 267 (72%) cases, at a referring facility in 89 (24%) cases, in the air in 13 (3%) cases, and in the receiving facility in two (0.5%) cases; the site could not be determined in one (0.3%) case. Etomidate or midazolam was used in 210 out of 372 (56%) intubations. Indications for intubation and the personnel performing the intubation are listed in Table 1. For the remaining intubations, no medications were used in 86 out of 372 (23%), a neuromuscular-blocking agent alone was used in 73 out of 372 (20%), and diazepam was used in three out of 372 (1%) instances. Before the introduction of etomidate as a sedative agent for RSI in our program, 193 intubations were performed from January 1995 to March 1998. Midazolam was used in 39% (75 out of 193) of cases. Midazolam was used alone in 18 cases, and in
FIGURE 1. Frequency of etomidate doses used in adult patients.
conjunction with a neuromuscular-blocking agent in 57 cases. Diazepam was used in one instance. After the introduction of etomidate, 179 intubations were performed from April 1998 to December 2000. Etomidate was used in 112 cases, midazolam in 22 cases, diazepam in two cases, and both etomidate and midazolam in one instance. Etomidate was used alone in nine cases, and in conjunction with a neuromuscular-blocking agent in 103 cases. Midazolam was used alone in one case, and in conjunction with a neuromuscular-blocking agent in 21 cases. During the entire six-year study period, 13 (3.5%) patients received atropine pretreatment, 33 (9%) had a defasciculating dose of vecuronium, and 79 (21%) received lidocaine pretreatment. Over the six-year period, 110 out of 112 (98%) who received etomidate and 96 out of 97 (99%) who received midazolam were successfully intubated. Two patients in the etomidate group could not be intubated orally. One patient had an endotracheal tube successfully placed through an I-LMA, and the other received a cricothyrotomy. The patient in the midazolam group who could not be intubated underwent successful cricothyrotomy. To calculate the average dose of etomidate, ten records of patients aged 14 years or less, five records with no age listed, one record with no dose listed, and one record of a patient who received both etomidate and midazolam were excluded, to yield a total of 96 patients. The average dose of etomidate in these 96 adult patients was 23 mg (range 5–40 mg). Most (77%) patients received 20, 25, or 30 mg of etomidate (Figure 1). To calculate the average dose of midazolam, 13
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FIGURE 2. Frequency of midazolam doses used in adult patients.
records of patients aged 14 years or less, two records with no age recorded, and five records with no dose recorded were excluded, to yield 77 patients. The average dose of midazolam in these 77 adult patients was 3.4 mg (range 1–10 mg). Most (82%) patients received 2.0, 2.5, or 5.0 mg of midazolam (Figure 2). Complete hemodynamic data were present for 74 of 96 (77%) of the adult patients who received etomidate, and 56 of 77 (73%) of the adult patients who received midazolam. These groups were used for all hemodynamic calculations. There were no clinically important differences in average age, gender, mean initial SBP, or mean initial HR between these two groups (Table 2). In the subgroup of 74 patients who received etomidate, the average dose was 24 mg, the average percentage of change in HR was ÿ1% (95% CI, ÿ5.5 to 3.5), and the average percentage of change in SBP was 1.8% (95% CI, ÿ3.3 to 6.9). In the 56 patients who received
midazolam, the average dose was 3.5 mg, the average percentage of change in HR was 0.84% (95% CI, ÿ4.9 to 6.6), and the average percentage of change in SBP was 2.9% (95% CI, ÿ3.0 to 8.8) (Table 3). Four patients were hypotensive (SBP = 80, 54, 88, and 78 mm Hg) when they received etomidate. All four of these patients had subsequent increases in SBP to above 90 mm Hg after administration of etomidate. One of these patients became hypotensive again 15 minutes after etomidate was administered. Seven (9%) patients who were initially not hypotensive developed hypotension after administration of etomidate. One of these patients had a transient decrease in SBP, and three patients did not become hypotensive until 15 minutes after etomidate was given. Three patients were hypotensive (SBP = 85, 80, and 84 mm Hg) when they received midazolam. All three of these patients had subsequent increases in SBP to above 90 mm Hg after
TABLE 2. Demographic Data for Hemodynamic Calculation Subgroup of Adult Patients with Complete Records
TABLE 3. Hemodynamic Comparisons for Adult Patients with Complete Records
Demographic Data
Age, years, mean 6 SD % Male Initial systolic blood pressure, mm Hg, mean 6 SD Initial heart rate, beats/min, mean 6 SD *Chi-square.
Etomidate Group (n = 74) (95% CI)
Midazolam Group (n = 56) (95% CI)
36 6 19 (32–40) 64 138 6 34 (130–146)
35 6 17 (31–40) 73 (p = 0.20)* 136 6 28 (129–143)
101 6 30 (94–108)
109 6 29 (102–117)
Hemodynamic Parameter
% Change in heart rate mean 6 SD % Change in systolic blood pressure, mean 6 SD Number of hypotensive episodes *Fisher’s exact test.
Etomidate Group (n = 74) (95% CI)
Midazolam Group (n = 56) (95% CI)
ÿ1 6 20 (ÿ5.5–3.5)
0.84 6 22 (ÿ4.9–6.6)
1.8 6 22 (ÿ3.3–6.9)
2.9 6 22 (ÿ3.0–8.8)
7
3 (p = 0.51)*
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administration of midazolam. Three (5.4%) patients who were initially not hypotensive developed hypotension after administration of midazolam. One patient did not become hypotensive until 15 minutes after midazolam was administered. There was no statistically significant difference in the number of hypotensive episodes with etomidate compared with midazolam (Fisher’s exact test, p = 0.51). The chart abstractor and the primary author had excellent agreement on the categorical variables compared. The site of intubation recorded (scene, air, referring facility, or receiving facility) were identical for 26 out of 26 records (kappa = 1). The groups of vitals signs used were identical in 25 out of 26 records (kappa = 0.98) for preintubation vital signs, and identical in 24 out of 26 records (kappa = 0.838) for postintubation vital signs.
DISCUSSION The ideal sedative for RSI has rapid onset, short duration, and minimal side effects. Etomidate and midazolam are both frequently used agents for RSI in the prehospital air medical setting.10 Midazolam provides excellent sedation and amnesia for RSI. There is variability in the dosing requirements among patients for midazolam, and the recommended induction dose for RSI is 0.1–0.3 mg/kg.14 The use of midazolam for prehospital RSI has been shown to be associated with dose-dependent hypotension.13 A recent multicenter study on ED intubations reported that midazolam is frequently underdosed when used as an induction agent for RSI.15 Previous studies on midazolamfacilitated intubation and midazolam sedation for RSI in the prehospital setting have used protocols for administration of midazolam at or significantly below the minimum recommended dose of 0.1 mg/kg.13,16–19 Our program’s guideline for administering midazolam at doses of 0.1 mg/kg for RSI is also at the minimum recommended induction dose. Etomidate is reported to be a safe and effective induction agent for RSI in the ED6,20 with no clinically important adrenocortical dysfunction after a single bolus dose.21 Etomidate is the most hemodynamically stable of all the currently available induction agents, at doses of 0.2–0.3 mg/kg.22 It has the added benefit of decreasing underlying elevated intracranial pressure (ICP) as well as attenuating the increase in ICP associated with laryngoscopy and intubation by decreasing the cerebral metabolic oxygen demand and cerebral blood flow without adversely affecting cerebral perfusion pressure.23 Etomidate is reported to be a useful agent for RSI in virtually any shock state, and offers a protective effect against cerebral or coronary ischemia.5 Etomidate used for RSI in the air medical
277 setting has been shown to be effective and offer excellent hemodynamic stability.11,12 We found very high intubation success rates with both midazolam (99%) and etomidate (98%). Despite this high success rate with both agents, etomidate was used five times more frequently than midazolam after it became available to our program. This may be because flight crews perceived a risk of hypotension with midazolam, as well as a broad dose–response relationship. The popularity of etomidate for RSI in other settings would suggest that it was not just enthusiasm for a new agent that was responsible for its increased usage. The percentage of patients receiving a sedative for intubation (alone or with a neuromuscular-blocking agent) increased from 39% to 75% after the introduction of etomidate. The reason for this dramatic increase in sedative use is unclear; however, flight crews may have been more willing to use etomidate because of its perceived hemodynamic stability. Etomidate and midazolam as administered in our study had very stable hemodynamic profiles. There was no statistically significant percentage of change in HR or SBP after administration of either etomidate or midazolam. However, the percentage of change in HR and SBP may be less important than identifying episodes of hypotension after RSI. The numbers of hypotensive episodes following RSI were not significantly different between the etomidate and midazolam groups. We attempted to capture all hypotensive events in our study and included transient decreases in SBP as well as decreases in SBP that occurred up to 15 minutes after administration of the sedative agents. Other factors such as concomitant medication administration, hypovolemia, and underlying patient condition may be responsible for hypotension, and it is likely that the actual number of hypotensive episodes causally related to etomidate or midazolam administration was less than we reported. The lack of clinically important hemodynamic changes and hypotensive episodes after midazolam administration in our study may be related to the low doses used. Although we did not record patient weights, and the doses given were based on flight crews’ estimation of patient weights, the average dose of 3.5 mg used in the subgroup of adult patients used for hemodynamic calculations would be much less than the recommended induction dose of 0.1–0.3 mg/kg for a 70-kg adult. This dose is also lower than the 0.1-mg/kg dose recommended by our RSI guideline. All but one patient was administered 5 mg or less of midazolam. This likely represents a deviation from our RSI guideline, as it is doubtful that all of the patients administered midazolam weighed 50 kg or less. The flight crews in our program also commonly use midazolam as a sedative for procedures, for control of
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agitated patients, and in treatment of seizures at much lower doses than are recommended for induction. This familiarity with lower doses of midazolam may have contributed to underdosing for RSI. The packaging of midazolam in 2-mg and 5-mg vials may also be partly responsible for the low doses used for RSI. Midazolam was administered in 2.0-mg, 2.5-mg, or 5.0-mg doses in 82% of the patients who received midazolam in our study. Higher dosages of midazolam than used in our study may result in greater hypotension. By contrast, the average dose of etomidate in the subgroup of adult patients used for our hemodynamic calculations was 24 mg, which is very close to the recommended induction dose of 0.3 mg/kg for an average 70-kg patient. Etomidate is packaged in 40-mg vials and is not used for any other purpose than RSI by our program. This may have resulted in better adherence to the etomidate dose recommended by our program’s RSI guideline.
LIMITATIONS The primary limitation of this study is the retrospective nature of the data collection. This method of data collection depends on the accuracy of the air medical transport chart. Real-time charting of information for critically ill patients in the air medical environment is hard to achieve. However, the hemodynamic data that were recorded and timed by portable monitors are more likely to be accurate than the timing of other adverse events and complications. An attempt was made to limit bias in retrospective data retrieval by having chart abstraction training, strict criteria for data entry, and confirmation of interrater reliability. The variety of indications and clinical settings in which RSI was performed, and the nonrandom assignments to treatment with either etomidate or midazolam are also limitations. These factors and the inability to control the variety of other medications used in combination with etomidate and midazolam produce a diverse population for data comparison, which could limit internal validity. However, this disparity of patient population and clinical scenarios is likely to represent the reality of practice in the air medical setting. A third limitation is the lack of complete hemodynamic data for 22 patients who received etomidate and 21 patients who received midazolam. Hemodynamic changes in these excluded patients may have altered the conclusions of the study. However, 18 of the 22 patients in the etomidate group and 13 of the 21 patients in the midazolam group were excluded because their charts lacked only preintubation SBP and HR. Only two of the 18 patients in the etomidate group and one of the 13 patients in the midazolam group with no preintubation vital signs developed
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hypotension on subsequent measurements. If these patients are included in the analysis, 92 out of 96 (96%) patients receiving etomidate and 69 out of 77 (90%) patients receiving midazolam had at least postintubation vital sign measurements recorded. The incidence of postsedative hypotension in this group was nine out of 92 (10%) patients receiving etomidate and four out of 69 (6%) patients receiving midazolam, which is not statistically significant (Fisher’s exact test, p = 0.40).
CONCLUSION Etomidate and midazolam appear to be excellent agents for RSI in the air medical setting. The intubation success rate was very high for both etomidate (98%) and midazolam (99%). There was no statistically significant mean percentage change in SBP or HR with either agent. We found a low incidence of hypotension with both etomidate and midazolam, although the doses of midazolam used were considerably less than typically recommended for induction. The introduction of etomidate increased the use of appropriate doses of sedative agents for RSI without increasing the incidence of adverse hemodynamic events. The authors thank N. Clay Mann, PhD, for his statistical assistance.
References 1. Vilke GM, Hoyt DB, Epperson M, Fortlage D, Hutton KC, Rosen P. Intubation techniques in the helicopter. J Emerg Med. 1994;12:217–24. 2. Sing RF, Reilly PM, Rotondo MF, Lynch MJ, McCans JP, Schwab CW. Out-of-hospital rapid-sequence induction for intubation of the pediatric patient. Acad Emerg Med. 1996;3:41–5. 3. Rose WD, Anderson LD, Edmond SA. Analysis of intubations. Before and after establishment of a rapid sequence intubation protocol for air medical use. Air Med J. 1994;13:475–8. 4. Ma OJ, Atchley RB, Hatley T, Green M, Young J, Brady W. Intubation success rates improve for an air medical program after implementing the use of neuromuscular blocking agents. Am J Emerg Med. 1998;16:125–7. 5. Bergen JM, Smith DC. A review of etomidate for rapid sequence intubation in the emergency department. J Emerg Med. 1997; 15:221–30. 6. Smith DC, Bergen JM, Smithline H, Kirschner R. A trial of etomidate for rapid sequence intubation in the emergency department. J Emerg Med. 2000;18:13–6. 7. Sokolove PE, Price DD, Okada P. The safety of etomidate for emergency rapid sequence intubation of pediatric patients. Pediatr Emerg Care. 2000;16:18–21. 8. Sakles JC, Laurin EG, Rantapaa AA, Panacek EA. Airway management in the emergency department: a one-year study of 610 tracheal intubations. Ann Emerg Med. 1998;31:325–32. 9. Sivilotti MLA, Filbin MR, Slasor P, Walls RM. Factors involved in the selection of induction agent during emergency rapid sequence intubation [abstract]. Ann Emerg Med. 2000;35:S52. 10. Wydro G, Yeh E, Walters W, Hamel M. Current practices in advanced airway management by air medical programs [abstract]. Prehosp Emerg Care. 2002;6:169–70.
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11. Swanson ER, Fosnocht DE, Neff RJ. The use of etomidate for rapid-sequence intubation in the air medical setting. Prehosp Emerg Care. 2001;5:142–6. 12. Deitch S, Davis DP, Schatteman J, Chan TC, Vilke GM. The use of etomidate for prehospital rapid-sequence intubation. Prehosp Emerg Care. 2003;7:380–3. 13. Davis DP, Kimbro TA, Vilke GM. The use of midazolam for prehospital rapid-sequence intubation may be associated with a dose-related increase in hypotension. Prehosp Emerg Care. 2001;5:163–8. 14. Walls RM. Airway management. In: Marx JA, Hockberger R, Walls RM (eds). Emergency Medicine: Concepts and Clinical Practice. Philadelphia: Harcourt Health Sciences, 2002. 15. Sagarin MJ, Barton ED, Sakles JC, Vissers RJ, Chiang V, Walls RM. Underdosing of midazolam in emergency endotracheal intubation. Acad Emerg Med. 2003;10:329–38. 16. Dickinson ET, Cohen JE, Mechem CC. The effectiveness of midazolam as a single pharmacologic agent to facilitate endotracheal intubation by paramedics. Prehosp Emerg Care. 1999;3:191–3. 17. Wang HE, O’Connor RE, Megargel RE, et al. The utilization of midazolam as a pharmacologic adjunct to endotracheal
18.
19.
20.
21.
22. 23.
intubation by paramedics. Prehosp Emerg Care. 2000;4: 14–8. Lauder CT, Megargel RE, Barnes TA, Schnyder M, O’Connor RE. Comparison of midazolam and etomidate as pharmacologic adjuncts to endotracheal intubation [abstract]. Ann Emerg Med. 2001;38:S9. Ochs M, Davis D, Hoyt D, Bailey D, Marshall L, Rosen P. Paramedic-performed rapid sequence intubation of patients with severe head injuries. Ann Emerg Med. 2002;40:159–67. Woodard LL, Wolfson AB, Iorg EC, Peitzman AB. Hemodynamic effects of etomidate for rapid sequence intubation in emergency department trauma patients [abstract]. Acad Emerg Med. 1995;2:406. Schenarts CL, Burton JH, Riker RR. Adrenocortical dysfunction following etomidate induction in emergency department patients. Acad Emerg Med. 2001;8:1–7. Miller RD. Nonbarbiturate intravenous anesthetics. In: Miller RD (ed). Anesthesia. New York: Churchill Livingstone, 1994:247–89. Schneider RE, Sedatives and Induction Agents. In: Walls RM (ed). Manual of Emergency Airway Management. Philadelphia: Lippincott Williams & Wilkins, 2000:129–34.
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ETOMIDATE AND MIDAZOLAM FOR PREHOSPITAL RAPID-SEQUENCE INTUBATION
Eric R. Swanson, MD, David E. Fosnocht, MD, Suzanne C. Jensen, MD Rapid-sequence intubation (RSI) is defined as the use of a sedative or induction agent and a neuromuscularblocking agent to facilitate intubation. Intubation success rates are improved by RSI in the air medical environment.1–4 Many sedatives are used for sedation or induction with RSI, but no single agent has emerged as clearly superior. Etomidate is an ultra-short-acting carboxylated imidazole sedative-hypnotic that was introduced in Europe in 1972 and approved for use in the United States in 1983.5 In recent years, etomidate has become popular for the RSI of emergency department (ED) patients.6–9 Etomidate and midazolam are the most commonly used sedative agents for RSI in the air medical setting. A recent survey of 196 air medical programs found that, out of the 114 respondents, 93% of the programs used RSI, and the most commonly used induction agents were midazolam (75%) and etomidate (44%).10 Etomidate is reported to be an effective agent for RSI in the air medical setting, with excellent hemodynamic stability.11,12 Although use of midazolam for RSI is common, it has not been well studied in the prehospital environment. One study reports that the use of midazolam for prehospital RSI is associated with a dose-related incidence of hypotension.13 Prehospital RSI remains a controversial subject, and many questions are yet unanswered in this evolving practice. Comparing the use of etomidate and midazolam for tendency to cause hypotension, poor intubating conditions, or difficulty in correct dosage selection will help define the utility of these agents for prehospital RSI programs. The purpose of this study was to compare etomidate with midazolam as sedative or induction agents for RSI in our air medical transport system. Outcome measures included the incidence of hypotension, percentage of change in heart rate (HR), percentage of change in systolic blood pressure (SBP), and success rate of intubation.
ABSTRACT Objective. This study compares etomidate with midazolam for prehospital rapid-sequence intubation (RSI). Methods. The authors conducted a retrospective review of consecutive intubations at a university-based air medical program from January 1995 to December 2000. Exclusion criteria were patients not undergoing RSI, age < 15 years, and incomplete chart data. Outcome measures included intubation success, incidence of hypotension, and percentage of change in heart rate (HR) and systolic blood pressure (SBP). Results. The intubation success rate was 110 out of 112 (98%) with etomidate, and 96 out of 97 (99%) with midazolam. Mean ages, patient gender distributions, and initial SBPs and HRs did not differ between the two groups. The mean dose of etomidate was 24 mg, the mean percentage of change in HR was ÿ1% (95% confidence interval [CI], ÿ6 to 4), and the mean percentage of change in SBP was 2% (95% CI, ÿ3 to 7). The mean dose of midazolam was 3.5 mg, the mean percentage of change in HR was 1% (95% CI, ÿ5 to 7), and the mean percentage change in SBP was 3% (95% CI, ÿ3 to 9). The number of hypotensive episodes with etomidate (7 out of 74) compared with midazolam (3 out of 56) did not differ significantly (Fisher’s exact test, p = 0.51). Conclusion. Intubation success rate was very high with both etomidate (98%) and midazolam (99%). There was no statistically significant mean percentage of change in SBP or HR with either agent. The authors found a low incidence of hypotension with both agents, although the mean dose of midazolam used was considerably less than typically recommended for induction. Key words: etomidate; midazolam; intubation; prehospital emergency care; air ambulances.
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Airway management with endotracheal intubation is an essential part of modern air medical transport. Challenges to intubation in the prehospital setting include awake or combative patients with intact airway reflexes, making intubation difficult or impossible. Received July 24, 2003, from the Division of Emergency Medicine and AirMed, University of Utah Health Sciences Center, Salt Lake City, Utah (ERS, DEF); and the Stanford-Kaiser Emergency Medicine Residency Program, Stanford, California (SCJ). Revision received December 16, 2003; accepted for publication December 20, 2003.
METHODS
Presented at the 2003 ACEP Research Forum, October 2003, Boston, Massachusetts.
Study Design
Address correspondence and reprint requests to: Eric R. Swanson, MD, Division of Emergency Medicine, 1150 Moran Building, 175 North Medical Drive, Salt Lake City, UT 84132. e-mail:
This study was a retrospective review of a consecutive series of intubations performed by an air medical transport program based in a university hospital over a six-year period, from January 1995 to December 2000.
doi:10.1016/j.prehos.2003.12.026
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Population and Setting The air medical service is based at a university medical center that is a level-1 trauma facility and a major tertiary referral center. A nurse and paramedic flight crew perform all transports, with the exception of highrisk obstetric transports, which use a two-nurse team. The air medical program operates three rotor-wing and two fixed-wing aircraft, and transports approximately 1,600 patients per year. Flight nurses and flight paramedics perform intubations, operating under online medical command and written guidelines. The flight nurse is ultimately responsible for determining the need for RSI, as well as for making the choice of sedative and other medications used for RSI. Training in airway management for the flight crews consists of initial orientation, continuing education, and quality assurance feedback. Orientation includes a review of the program’s RSI and failed-intubation guidelines, the performance of at least ten intubations in the operating room (OR), skills training in animal models for intubation, training in cricothyrotomy and translaryngeal jet ventilation, and ten to 20 ride-along shifts with experienced crew members. Ongoing airway education includes yearly lectures on RSI and difficult-airway management, skills teaching in animal models, and laryngeal mask airway (LMA) and intubating laryngeal mask airway (I-LMA) training. The program conducts monthly manikin training and review of all difficult airway cases. Crew members are required to perform at least four intubations per month during patient care, on a manikin, or on an animal model. A standard RSI guideline is available, and deviation based on the clinical situation is inherent to the protocols. Lidocaine, atropine, and vecuronium are available for pretreatment. The choice of sedative agents was limited to midazolam from January 1995 to April 1998, but included both etomidate and midazolam from April 1998 to December 2000. The dose of etomidate recommended by our RSI guideline is 0.3 mg/kg, and the dose of midazolam is 0.1 mg/kg. Succinylcholine and vecuronium are the choices for neuromuscular blockade. At least one objective measure (end-tidal carbon dioxide [CO2] or esophageal detector device) in addition to clinical assessment is required for confirmation of endotracheal tube placement. The study was reviewed and approved by the university’s institutional review board and the requirement for written informed consent was waived.
Experimental Protocol The records of all adult and pediatric patients transported by the air medical program who required intubation during the six-year period from January
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1995 to December 2000 were reviewed. Exclusion criteria included patients who did not receive etomidate or midazolam and patients with incomplete chart data. One author abstracted data from the records of all patients intubated by the air medical program over the study period. For training purposes and to improve accuracy, the first 20 records also were reviewed by the primary author, and a standardized abstraction form was developed. Protocols were developed for the chart abstractor to ensure consistency in recording the timing of events such as intubation, medication administration, and vital sign measurement. In addition, a random sample of 26 charts was reabstracted by the primary author to determine interrater reliability of data recording. The chart abstractor was not blinded to the study purpose. The demographic information recorded for patients was limited to age and gender. Site of intubation (scene, air, referring facility, or receiving facility) and person intubating (flight nurse, flight paramedic, or other) were recorded. Data also included the medications used for pretreatment, sedation, and paralysis; the dosage of sedative medications; and the means of securing the airway, if not with endotracheal intubation. Vital signs recorded included systolic and diastolic blood pressures, HR, and oxygen saturation. Records were considered adequate for hemodynamic calculations if the vital signs were noted before RSI and at least one set was available within 10 minutes after intubation. Hypotension was defined as a SBP < 90 mm Hg, or a further decrease in SBP of 5 mm Hg or more, in patients who initially had had a SBP < 90 mm Hg.
Outcome Measures Primary outcome measures included the intubation success rate, percentage of change in HR, percentage of change in SBP, and incidence of hypotension when either etomidate or midazolam was used for RSI.
Analytical Methods Patient demographics, intubation details, and occurrence of adverse events are reported using descriptive statistics. The mean is expressed as 6 standard deviation (SD) with a 95% confidence interval (CI). Dichotomous variables are compared using the chisquare and Fisher’s exact test, with statistical significance set at p < 0.05. Interobserver agreement of the chart abstractors was measured with a kappa statistic.
RESULTS The flight program performed 372 intubations over the six-year period. Men comprised 71% of the patients (259 out of 366 with complete data). The average age of
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TABLE 1. Indications for Rapid-sequence Intubation and Person Intubating for All Patients Receiving Etomidate or Midazolam Etomidate Group (n = 113)
Midazolam Group (n = 97)
Indication Trauma Medical
84 (74%) 29 (26%)
76 (78%) 21 (22%)
Person intubating Flight nurse Flight paramedic Other
61 (54%) 46 (41%) 6 (5%)
51 (53%) 35 (36%) 11 (11%)
patients was 34 years (n = 358, SD 6 20; range four months to 89 years). Intubation occurred at the scene in 267 (72%) cases, at a referring facility in 89 (24%) cases, in the air in 13 (3%) cases, and in the receiving facility in two (0.5%) cases; the site could not be determined in one (0.3%) case. Etomidate or midazolam was used in 210 out of 372 (56%) intubations. Indications for intubation and the personnel performing the intubation are listed in Table 1. For the remaining intubations, no medications were used in 86 out of 372 (23%), a neuromuscular-blocking agent alone was used in 73 out of 372 (20%), and diazepam was used in three out of 372 (1%) instances. Before the introduction of etomidate as a sedative agent for RSI in our program, 193 intubations were performed from January 1995 to March 1998. Midazolam was used in 39% (75 out of 193) of cases. Midazolam was used alone in 18 cases, and in
FIGURE 1. Frequency of etomidate doses used in adult patients.
conjunction with a neuromuscular-blocking agent in 57 cases. Diazepam was used in one instance. After the introduction of etomidate, 179 intubations were performed from April 1998 to December 2000. Etomidate was used in 112 cases, midazolam in 22 cases, diazepam in two cases, and both etomidate and midazolam in one instance. Etomidate was used alone in nine cases, and in conjunction with a neuromuscular-blocking agent in 103 cases. Midazolam was used alone in one case, and in conjunction with a neuromuscular-blocking agent in 21 cases. During the entire six-year study period, 13 (3.5%) patients received atropine pretreatment, 33 (9%) had a defasciculating dose of vecuronium, and 79 (21%) received lidocaine pretreatment. Over the six-year period, 110 out of 112 (98%) who received etomidate and 96 out of 97 (99%) who received midazolam were successfully intubated. Two patients in the etomidate group could not be intubated orally. One patient had an endotracheal tube successfully placed through an I-LMA, and the other received a cricothyrotomy. The patient in the midazolam group who could not be intubated underwent successful cricothyrotomy. To calculate the average dose of etomidate, ten records of patients aged 14 years or less, five records with no age listed, one record with no dose listed, and one record of a patient who received both etomidate and midazolam were excluded, to yield a total of 96 patients. The average dose of etomidate in these 96 adult patients was 23 mg (range 5–40 mg). Most (77%) patients received 20, 25, or 30 mg of etomidate (Figure 1). To calculate the average dose of midazolam, 13
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FIGURE 2. Frequency of midazolam doses used in adult patients.
records of patients aged 14 years or less, two records with no age recorded, and five records with no dose recorded were excluded, to yield 77 patients. The average dose of midazolam in these 77 adult patients was 3.4 mg (range 1–10 mg). Most (82%) patients received 2.0, 2.5, or 5.0 mg of midazolam (Figure 2). Complete hemodynamic data were present for 74 of 96 (77%) of the adult patients who received etomidate, and 56 of 77 (73%) of the adult patients who received midazolam. These groups were used for all hemodynamic calculations. There were no clinically important differences in average age, gender, mean initial SBP, or mean initial HR between these two groups (Table 2). In the subgroup of 74 patients who received etomidate, the average dose was 24 mg, the average percentage of change in HR was ÿ1% (95% CI, ÿ5.5 to 3.5), and the average percentage of change in SBP was 1.8% (95% CI, ÿ3.3 to 6.9). In the 56 patients who received
midazolam, the average dose was 3.5 mg, the average percentage of change in HR was 0.84% (95% CI, ÿ4.9 to 6.6), and the average percentage of change in SBP was 2.9% (95% CI, ÿ3.0 to 8.8) (Table 3). Four patients were hypotensive (SBP = 80, 54, 88, and 78 mm Hg) when they received etomidate. All four of these patients had subsequent increases in SBP to above 90 mm Hg after administration of etomidate. One of these patients became hypotensive again 15 minutes after etomidate was administered. Seven (9%) patients who were initially not hypotensive developed hypotension after administration of etomidate. One of these patients had a transient decrease in SBP, and three patients did not become hypotensive until 15 minutes after etomidate was given. Three patients were hypotensive (SBP = 85, 80, and 84 mm Hg) when they received midazolam. All three of these patients had subsequent increases in SBP to above 90 mm Hg after
TABLE 2. Demographic Data for Hemodynamic Calculation Subgroup of Adult Patients with Complete Records
TABLE 3. Hemodynamic Comparisons for Adult Patients with Complete Records
Demographic Data
Age, years, mean 6 SD % Male Initial systolic blood pressure, mm Hg, mean 6 SD Initial heart rate, beats/min, mean 6 SD *Chi-square.
Etomidate Group (n = 74) (95% CI)
Midazolam Group (n = 56) (95% CI)
36 6 19 (32–40) 64 138 6 34 (130–146)
35 6 17 (31–40) 73 (p = 0.20)* 136 6 28 (129–143)
101 6 30 (94–108)
109 6 29 (102–117)
Hemodynamic Parameter
% Change in heart rate mean 6 SD % Change in systolic blood pressure, mean 6 SD Number of hypotensive episodes *Fisher’s exact test.
Etomidate Group (n = 74) (95% CI)
Midazolam Group (n = 56) (95% CI)
ÿ1 6 20 (ÿ5.5–3.5)
0.84 6 22 (ÿ4.9–6.6)
1.8 6 22 (ÿ3.3–6.9)
2.9 6 22 (ÿ3.0–8.8)
7
3 (p = 0.51)*
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administration of midazolam. Three (5.4%) patients who were initially not hypotensive developed hypotension after administration of midazolam. One patient did not become hypotensive until 15 minutes after midazolam was administered. There was no statistically significant difference in the number of hypotensive episodes with etomidate compared with midazolam (Fisher’s exact test, p = 0.51). The chart abstractor and the primary author had excellent agreement on the categorical variables compared. The site of intubation recorded (scene, air, referring facility, or receiving facility) were identical for 26 out of 26 records (kappa = 1). The groups of vitals signs used were identical in 25 out of 26 records (kappa = 0.98) for preintubation vital signs, and identical in 24 out of 26 records (kappa = 0.838) for postintubation vital signs.
DISCUSSION The ideal sedative for RSI has rapid onset, short duration, and minimal side effects. Etomidate and midazolam are both frequently used agents for RSI in the prehospital air medical setting.10 Midazolam provides excellent sedation and amnesia for RSI. There is variability in the dosing requirements among patients for midazolam, and the recommended induction dose for RSI is 0.1–0.3 mg/kg.14 The use of midazolam for prehospital RSI has been shown to be associated with dose-dependent hypotension.13 A recent multicenter study on ED intubations reported that midazolam is frequently underdosed when used as an induction agent for RSI.15 Previous studies on midazolamfacilitated intubation and midazolam sedation for RSI in the prehospital setting have used protocols for administration of midazolam at or significantly below the minimum recommended dose of 0.1 mg/kg.13,16–19 Our program’s guideline for administering midazolam at doses of 0.1 mg/kg for RSI is also at the minimum recommended induction dose. Etomidate is reported to be a safe and effective induction agent for RSI in the ED6,20 with no clinically important adrenocortical dysfunction after a single bolus dose.21 Etomidate is the most hemodynamically stable of all the currently available induction agents, at doses of 0.2–0.3 mg/kg.22 It has the added benefit of decreasing underlying elevated intracranial pressure (ICP) as well as attenuating the increase in ICP associated with laryngoscopy and intubation by decreasing the cerebral metabolic oxygen demand and cerebral blood flow without adversely affecting cerebral perfusion pressure.23 Etomidate is reported to be a useful agent for RSI in virtually any shock state, and offers a protective effect against cerebral or coronary ischemia.5 Etomidate used for RSI in the air medical
277 setting has been shown to be effective and offer excellent hemodynamic stability.11,12 We found very high intubation success rates with both midazolam (99%) and etomidate (98%). Despite this high success rate with both agents, etomidate was used five times more frequently than midazolam after it became available to our program. This may be because flight crews perceived a risk of hypotension with midazolam, as well as a broad dose–response relationship. The popularity of etomidate for RSI in other settings would suggest that it was not just enthusiasm for a new agent that was responsible for its increased usage. The percentage of patients receiving a sedative for intubation (alone or with a neuromuscular-blocking agent) increased from 39% to 75% after the introduction of etomidate. The reason for this dramatic increase in sedative use is unclear; however, flight crews may have been more willing to use etomidate because of its perceived hemodynamic stability. Etomidate and midazolam as administered in our study had very stable hemodynamic profiles. There was no statistically significant percentage of change in HR or SBP after administration of either etomidate or midazolam. However, the percentage of change in HR and SBP may be less important than identifying episodes of hypotension after RSI. The numbers of hypotensive episodes following RSI were not significantly different between the etomidate and midazolam groups. We attempted to capture all hypotensive events in our study and included transient decreases in SBP as well as decreases in SBP that occurred up to 15 minutes after administration of the sedative agents. Other factors such as concomitant medication administration, hypovolemia, and underlying patient condition may be responsible for hypotension, and it is likely that the actual number of hypotensive episodes causally related to etomidate or midazolam administration was less than we reported. The lack of clinically important hemodynamic changes and hypotensive episodes after midazolam administration in our study may be related to the low doses used. Although we did not record patient weights, and the doses given were based on flight crews’ estimation of patient weights, the average dose of 3.5 mg used in the subgroup of adult patients used for hemodynamic calculations would be much less than the recommended induction dose of 0.1–0.3 mg/kg for a 70-kg adult. This dose is also lower than the 0.1-mg/kg dose recommended by our RSI guideline. All but one patient was administered 5 mg or less of midazolam. This likely represents a deviation from our RSI guideline, as it is doubtful that all of the patients administered midazolam weighed 50 kg or less. The flight crews in our program also commonly use midazolam as a sedative for procedures, for control of
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agitated patients, and in treatment of seizures at much lower doses than are recommended for induction. This familiarity with lower doses of midazolam may have contributed to underdosing for RSI. The packaging of midazolam in 2-mg and 5-mg vials may also be partly responsible for the low doses used for RSI. Midazolam was administered in 2.0-mg, 2.5-mg, or 5.0-mg doses in 82% of the patients who received midazolam in our study. Higher dosages of midazolam than used in our study may result in greater hypotension. By contrast, the average dose of etomidate in the subgroup of adult patients used for our hemodynamic calculations was 24 mg, which is very close to the recommended induction dose of 0.3 mg/kg for an average 70-kg patient. Etomidate is packaged in 40-mg vials and is not used for any other purpose than RSI by our program. This may have resulted in better adherence to the etomidate dose recommended by our program’s RSI guideline.
LIMITATIONS The primary limitation of this study is the retrospective nature of the data collection. This method of data collection depends on the accuracy of the air medical transport chart. Real-time charting of information for critically ill patients in the air medical environment is hard to achieve. However, the hemodynamic data that were recorded and timed by portable monitors are more likely to be accurate than the timing of other adverse events and complications. An attempt was made to limit bias in retrospective data retrieval by having chart abstraction training, strict criteria for data entry, and confirmation of interrater reliability. The variety of indications and clinical settings in which RSI was performed, and the nonrandom assignments to treatment with either etomidate or midazolam are also limitations. These factors and the inability to control the variety of other medications used in combination with etomidate and midazolam produce a diverse population for data comparison, which could limit internal validity. However, this disparity of patient population and clinical scenarios is likely to represent the reality of practice in the air medical setting. A third limitation is the lack of complete hemodynamic data for 22 patients who received etomidate and 21 patients who received midazolam. Hemodynamic changes in these excluded patients may have altered the conclusions of the study. However, 18 of the 22 patients in the etomidate group and 13 of the 21 patients in the midazolam group were excluded because their charts lacked only preintubation SBP and HR. Only two of the 18 patients in the etomidate group and one of the 13 patients in the midazolam group with no preintubation vital signs developed
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hypotension on subsequent measurements. If these patients are included in the analysis, 92 out of 96 (96%) patients receiving etomidate and 69 out of 77 (90%) patients receiving midazolam had at least postintubation vital sign measurements recorded. The incidence of postsedative hypotension in this group was nine out of 92 (10%) patients receiving etomidate and four out of 69 (6%) patients receiving midazolam, which is not statistically significant (Fisher’s exact test, p = 0.40).
CONCLUSION Etomidate and midazolam appear to be excellent agents for RSI in the air medical setting. The intubation success rate was very high for both etomidate (98%) and midazolam (99%). There was no statistically significant mean percentage change in SBP or HR with either agent. We found a low incidence of hypotension with both etomidate and midazolam, although the doses of midazolam used were considerably less than typically recommended for induction. The introduction of etomidate increased the use of appropriate doses of sedative agents for RSI without increasing the incidence of adverse hemodynamic events. The authors thank N. Clay Mann, PhD, for his statistical assistance.
References 1. Vilke GM, Hoyt DB, Epperson M, Fortlage D, Hutton KC, Rosen P. Intubation techniques in the helicopter. J Emerg Med. 1994;12:217–24. 2. Sing RF, Reilly PM, Rotondo MF, Lynch MJ, McCans JP, Schwab CW. Out-of-hospital rapid-sequence induction for intubation of the pediatric patient. Acad Emerg Med. 1996;3:41–5. 3. Rose WD, Anderson LD, Edmond SA. Analysis of intubations. Before and after establishment of a rapid sequence intubation protocol for air medical use. Air Med J. 1994;13:475–8. 4. Ma OJ, Atchley RB, Hatley T, Green M, Young J, Brady W. Intubation success rates improve for an air medical program after implementing the use of neuromuscular blocking agents. Am J Emerg Med. 1998;16:125–7. 5. Bergen JM, Smith DC. A review of etomidate for rapid sequence intubation in the emergency department. J Emerg Med. 1997; 15:221–30. 6. Smith DC, Bergen JM, Smithline H, Kirschner R. A trial of etomidate for rapid sequence intubation in the emergency department. J Emerg Med. 2000;18:13–6. 7. Sokolove PE, Price DD, Okada P. The safety of etomidate for emergency rapid sequence intubation of pediatric patients. Pediatr Emerg Care. 2000;16:18–21. 8. Sakles JC, Laurin EG, Rantapaa AA, Panacek EA. Airway management in the emergency department: a one-year study of 610 tracheal intubations. Ann Emerg Med. 1998;31:325–32. 9. Sivilotti MLA, Filbin MR, Slasor P, Walls RM. Factors involved in the selection of induction agent during emergency rapid sequence intubation [abstract]. Ann Emerg Med. 2000;35:S52. 10. Wydro G, Yeh E, Walters W, Hamel M. Current practices in advanced airway management by air medical programs [abstract]. Prehosp Emerg Care. 2002;6:169–70.
Swanson et al.
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11. Swanson ER, Fosnocht DE, Neff RJ. The use of etomidate for rapid-sequence intubation in the air medical setting. Prehosp Emerg Care. 2001;5:142–6. 12. Deitch S, Davis DP, Schatteman J, Chan TC, Vilke GM. The use of etomidate for prehospital rapid-sequence intubation. Prehosp Emerg Care. 2003;7:380–3. 13. Davis DP, Kimbro TA, Vilke GM. The use of midazolam for prehospital rapid-sequence intubation may be associated with a dose-related increase in hypotension. Prehosp Emerg Care. 2001;5:163–8. 14. Walls RM. Airway management. In: Marx JA, Hockberger R, Walls RM (eds). Emergency Medicine: Concepts and Clinical Practice. Philadelphia: Harcourt Health Sciences, 2002. 15. Sagarin MJ, Barton ED, Sakles JC, Vissers RJ, Chiang V, Walls RM. Underdosing of midazolam in emergency endotracheal intubation. Acad Emerg Med. 2003;10:329–38. 16. Dickinson ET, Cohen JE, Mechem CC. The effectiveness of midazolam as a single pharmacologic agent to facilitate endotracheal intubation by paramedics. Prehosp Emerg Care. 1999;3:191–3. 17. Wang HE, O’Connor RE, Megargel RE, et al. The utilization of midazolam as a pharmacologic adjunct to endotracheal
18.
19.
20.
21.
22. 23.
intubation by paramedics. Prehosp Emerg Care. 2000;4: 14–8. Lauder CT, Megargel RE, Barnes TA, Schnyder M, O’Connor RE. Comparison of midazolam and etomidate as pharmacologic adjuncts to endotracheal intubation [abstract]. Ann Emerg Med. 2001;38:S9. Ochs M, Davis D, Hoyt D, Bailey D, Marshall L, Rosen P. Paramedic-performed rapid sequence intubation of patients with severe head injuries. Ann Emerg Med. 2002;40:159–67. Woodard LL, Wolfson AB, Iorg EC, Peitzman AB. Hemodynamic effects of etomidate for rapid sequence intubation in emergency department trauma patients [abstract]. Acad Emerg Med. 1995;2:406. Schenarts CL, Burton JH, Riker RR. Adrenocortical dysfunction following etomidate induction in emergency department patients. Acad Emerg Med. 2001;8:1–7. Miller RD. Nonbarbiturate intravenous anesthetics. In: Miller RD (ed). Anesthesia. New York: Churchill Livingstone, 1994:247–89. Schneider RE, Sedatives and Induction Agents. In: Walls RM (ed). Manual of Emergency Airway Management. Philadelphia: Lippincott Williams & Wilkins, 2000:129–34.