The Hemodynamics of RSI: Ketamine vs. Etomidate

Rapid sequence intubation (RSI) is an emergency procedure frequently performed in the prehospital setting. Induction with sedating agents is an important step in this process. The use of etomidate for this purpose has long been a standard of practice. When I studied RSI during my postgraduate training, one article simply stated, “Etomidate is the gold standard for induction in RSI.”¹ Indeed, data from the National Emergency Airway Registry demonstrated that from 2002 to 2012, etomidate was used in over 90% of RSI interventions, compared with just 1% that used ketamine.^2,3 

Over the past decade, ketamine has gained traction as an alternative to etomidate, partially due to a transient shortage of etomidate in 2011.⁴ One area of particular interest is the question of how ketamine compares to etomidate’s favorable hemodynamics in the peri-intubation period. Currently there are limited studies that compare ketamine against etomidate in this context, and the data demonstrate mixed results. 

Some new studies coming from the prehospital and emergency department settings may help shine light on this topic. One example is the recent research done by Kevin Collopy, MHL, FP-C, NRP, CMTE, and colleagues. These researchers published a retrospective study comparing the peri-intubation hemodynamics of ketamine and etomidate. Along with Collopy, coinvestigators Lucy Stanke, PharmD, BCPS, BCCCP, and Steven Nakajima, PharmD, BCCCP, agreed to be interviewed for this article. 

Currently in press with Air Medical Journal, their study is titled “Hemodynamic Effects of Ketamine Versus Etomidate for Prehospital Rapid Sequence Intubation” and represents the first U.S.-based study to compare ketamine and etomidate for RSI in both air medical and ground emergency medical transport services.⁵

Study Design

The study is a retrospective review following a protocol change for a regional emergency transport service. Per the protocol, providers could choose between etomidate and ketamine for induction at standard doses of 0.3 mg/kg and 1–2 mg/kg, respectively. The review looked at data from December 2015 to January 2017. Vital signs (heart rate, systolic blood pressure, diastolic blood pressure, and respiratory rate), indication for intubation, time of intubation, number of intubation attempts, induction agent and dose, adjunctive sedatives, pain medications, vasopressors, and fluids were recorded, as well as mean arterial pressure and shock index. 

Hypotension was defined as a 20% decrease in systolic blood pressure within 15 minutes of receiving ketamine or etomidate. “That [threshold] came through us reviewing the literature around peri-intubation hypotension, and it mainly stems from anesthesia literature,” says Stanke. 

Adds Nakajima, “We wanted to be sure we defined [it] as a clinically significant drop and make sure we were looking at clinically significant hypotension.”

Study Findings

After identifying and analyzing 113 patients, their results showed no statistically significant differences in pre- or post-intubation hemodynamics in the 15 minutes following intubation when comparing patients sedated with ketamine to those sedated with etomidate. Hypotension after induction (defined as a decrease of 20% or more in SBP from baseline) occurred in 16% of the etomidate group and 18% of the ketamine group, but this difference was not statistically significant. 

The authors then performed subgroup analyses to detect any differences in hypotension after induction, grouping patients by age (over 60, over 70, and over 80), indication for RSI, and shock index but again found no statistically significant differences. Finally they evaluated the use of medications following intubation, such as traditional sedatives (midazolam and propofol) and analgesics (fentanyl, morphine, and hydromorphone) within 30 minutes of RSI, as well as vasopressors within 15 minutes, antihypertensive agents, fluids, and blood products, with no statistically significant differences found between groups.

Limitations, Further Research

This was a retrospective review and unfortunately didn’t reach the necessary number of ketamine patients to meet power calculations. This is important, because power is a factor in a study’s ability to detect false negatives—or the lack of significant differences.

Additionally, there was no specific preference in the EMS protocol for which drug to use, which may have subjected the decision to selection bias.

The retrospective study was used as a platform to pursue a prospective study, which involved a larger number of patients and included both prehospital and ED arms. The prospective study data have been presented in poster and abstract form but have yet to be published as a manuscript.⁶ 

In contrast to the retrospective study, the prospective data revealed that ketamine did show a statistically significant increase in the rate of hypotension following its use for RSI, both in the prehospital (high shock index subgroup) and ED settings. 

“For a person in a shock state, when you’ve already depleted your internal catecholamine stores, the additional norepinephrine you might have at the synapse is [gone],” Nakajima says, “so patients in a shock state, with no catecholamines left, are not going to be protected from [the hypotension associated with ketamine].”

Additionally, studies using National Emergency Airway Registry (NEAR) data have shown ketamine has an increased risk of peri-intubation hypotension.^7,8

Take-Home Point

While there have been varying results comparing the impact on peri-intubation hypotension with ketamine and etomidate (for example, the retrospective study referenced above), other data procured from recent investigations have shown an increased risk of hypotension with ketamine. Further studies will likely be needed to fully elucidate the clinical implications of the current data, but in the meantime caregivers should be aware of the potential for hypotension with ketamine as compared to etomidate in the peri-intubation period.  

Sidebar: Collaboration

As a pharmacist with a strong interest in optimizing prehospital pharmacological interventions, I was pleased to see this collaboration between prehospital caregivers and ED-crit pharmacists. “I think it’s incumbent on any EMS system to find [a pharmacist] to do this with,” says Collopy, “so we make sure we’re providing medicine that makes sense not just from a prehospital perspective but also from a pharmacological perspective.” 

Adds Nakajima, “I think it’s a huge opportunity for improvement for patients across the continuum. We can get therapies started prehospital or in interhospital transport much earlier.” 

Healthcare exists across a continuum, and increased collaboration between caregivers is a worthy endeavor with the ultimate goal of improving patient care.

References

1. Hampton JP. Rapid-sequence intubation and the role of the emergency department pharmacist. Am J Heal Pharm, 2011; 68(14): 1,320–30.

2. Upchurch CP, Grijalva CG, Russ S, et al. Comparison of Etomidate and Ketamine for Induction During Rapid Sequence Intubation of Adult Trauma Patients. Ann Emerg Med, 2017; 69: 24–33.

3. Brown CA, Bair AE, Pallin DJ, Walls RM. Techniques, success, and adverse events of emergency department adult intubations. Ann Emerg Med, 2015; 65(4): 363–70.

4. Price B, Arthur AO, Brunko M, et al. Hemodynamic consequences of ketamine vs etomidate for endotracheal intubation in the air medical setting. Am J Emerg Med, 2013; 31(7): 1,124–32.

5. Stanke L, Nakajima S, Zimmerman LH, Collopy K, Fales C, Powers W. Hemodynamic Effects of Ketamine Versus Etomidate for Prehospital Rapid Sequence Intubation. Air Med J, 2021; 40(5): 312–6.

6. Nakajima S, Taylor K, Zimmerman LH, Collopy K, Fales C, Powers W. Hemodynamic Effects of Ketamine Versus Etomidate During Rapid Sequence Intubation in an ED. Crit Care Med, 2019; 47: 403.

7. Mohr NM, Pape SG, Runde D, et al. Etomidate Use Is Associated With Less Hypotension Than Ketamine for Emergency Department Sepsis Intubations: A NEAR Cohort Study. Acad Emerg Med, 2020; 27(11): 1,140–9.

8. April MD, Arana A, Schauer SG, et al. Ketamine Versus Etomidate and Peri-intubation Hypotension: A National Emergency Airway Registry Study. Acad Emerg Med, 2020; 27(11): 1,106–15.

Daniel Hu, PharmD, BCCCP, has Doctor of Pharmacy degree and is a critical care and emergency medicine pharmacist. He is a frequent speaker at conferences and has many publications in peer-reviewed journals.