Etomidate RSI for Septic Patients in the ED
Search Strategy: As with most questions of therapy, you first turn to the Cochrane Database of Systematic Reviews where you see an incomplete protocol addressing this question. Thus, you grit your teeth and decide to pursue the question the “hard” way. Turning to PUBMED, you first conduct a broad/sensitive therapy clinical query using the term “Etomidate” (1948 citations). Next, you conduct a general PUBMED search of “sepsis” (103,374 citations). Finally, you combine these two searches to yield 48 citations including three of the four selections below (PGY II article noted as a “related article” on PUBMED when reviewing PGY I article).
You are working a busy shift in the Trauma/Critical Care area of the BJH Emergency Department when you receive the following page:
“48 yo f h/o BrCa, SOB/fever, 95% on 15L NRB, p 118, bp 70/0p, please pick a room to double book, ETA 5 minutes.”
The patient arrives, is diaphoretic and working to breath. Her temperature is 39.5°C and she has decreased lung sounds over the right pulmonary field at the base. She just completed a round of chemotherapy a few days ago. Her vital signs are significant for tachycardia (120), hypotension (70/40), tachypnea (30), and oxygen saturation 96% on15L NRB. A quick portable CXR shows a clear RML and RLL infiltrate and consolidation. Meanwhile, the patient is starting to tire from her increased work of breathing.
You and your critically care trained sensei Dr. Fuller, make a decision to intubate the patient and place a sepsis line. Quickly you review your approach to intubation including medications for rapid sequence intubation. Dr. Fuller stops you and says that Etomidate might not be ideal in septic patients, theoretically due to its adrenal suppression. You’ve used nothing but Etomidate since you started your residency training for these patients and this prompts a clinical question that could be answered with careful consideration of the literature.
Population: Emergency Department patients with sepsis requiring intubation
Intervention: Intubation with Etomidate as the induction agent
Comparison: Intubation with an induction agent other than Etomidate
Outcome:Sepsis-related mortality, all-cause mortality, ICU length of stay, intubation success and complication rates, adrenal insufficiency
Article 1: A Prospective Observational Study of the Effect of Etomidate on Septic Patient Mortality and Length of Stay, Acad Emerg Med 2009; 16: 11-14
Article 2: Rapid sequence induction in the emergency department: induction drug and outcome of patients admitted to the intensive care unit department: induction drug and outcome of patients admitted to the intensive care unit, EMJ 2009
Article 3: The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock, Intensive Care Med 2009; 35:1868–1876
Article 4: Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial, Lancet 2009; 374: 293-300
The evidence suggesting that etomidate is either safe (PGY I and PGY II articles) or dangerous (PGY III article) for emergency department RSI in septic patients is drawn from observational trials. Although observational trials often expand our knowledge and provide hypothesis-generating data, the medical literature is replete with compelling observational trials subsequently disproven by well-conducted randomized controlled trials including lung reduction surgery for emphysema (Flaherty 2001 vs. National Emphysema Treatment Trial Group 2001); inhaled nitric oxide for ARDS (Rossaint 1993 vs. Taylor 2004); naloxone for spinal cord injuries (Faden 1981 vs. Bracken 1990).
Whereas prognostic trials attempt to balance pre-existing prognostic inequalities between treatment groups via statistical manipulation (linear regression for continuous variables or logistic regression for dichotomous variables), controlled trials endeavor to randomly assign subjects to one treatment group or another within the constraints of trial inclusion or exclusion criteria. By randomly assigning subjects to treatment arms, clinical investigators provide the least biased estimate of true treatment effect by ensuring that prognostic parameters (both recognized and unrecognized) are equally distributed so as not to influence the trial’s outcome for reasons other than the treatment being tested. Fortunately, an RCT is underway (ClinicalTrials.gov Identifier NCT00441792) to compare etomidate to alternative induction agents for ED-based airway management. In the meantime, the current observational trials are the best available evidence and the PGY IV RCT provides one potential induction agent alternative if clinicians are concerned about using etomidate. One interesting research opportunity might be a meta-analysis of the multiple under-powered observational trials using the MOOSE guidelines to identify if the bulk of the evidence suggests a risk of harm with etomidate.
The data reviewed at this month’s Journal Club suggests that the use of etomidate for RSI of septic patients in the ED may increase median hospital LOS (8 days vs. 6.5 days) without impacting mortality. Another single-center airway registry analysis for 36-months of ED RSI in a critically ill population (median APACHE-II score 18.5 to 20) with a variety of acute disease processes (drug OD, seizure, sepsis, multiple trauma, head trauma, cerebral hemorrhage) did not identify etomidate use for RSI as an independent predictor of mortality. CORTICUS, a 52-ICU study suggests that etomidate exposure within the previous 72-hours in septic patients is associated independently with increased 28-day mortality that does not improve when hydrocortisone is administered a median of 14.5-hours after etomidate exposure. Etomidate exposure does not delay overall septic shock reversal or time-to-reversal. Despite stringent study guidelines advising against etomidate use, 20% of clinicians within the CORTICUS-institutions still choose to use it indicating significant equipoise remains about the risk vs. benefit of etomidate in septic shock patients.