Ketamine vs Etomidate in severe traumatic brain injury
Myron Yaster MD, Ethan Sanford MD, and Shawn Jackson MD PhD
An all too frequent clinical management conundrum: a patient presents with an acute traumatic brain injury and requires intubation to protect the airway, prevent hypoxemia, and to allow targeted control of ventilation (CO2). The patient’s level of consciousness and Glascow coma scale are high enough that an IV induction agent is required to facilitate the intubation. What induction drug should you use? To prevent hypotension, you decide against propofol (or in Europe maybe a barbiturate) and wonder which is safer: etomidate or ketamine? Each has drawbacks and benefits. In today’s PAAD, Mansvelder et al.1 present their mortality data from the Dutch ADULT BRAIN-PROTECT database2 of patients with severe TBIs, who were intubated in the field with either etomidate or S (+) ketamine prior to transport via helicopter to a regional center.
Almost 2 years ago (April 12, 2022), Drs. Vanessa Mazandi and Justin Lockman from the Children’s Hospital of Philadelphia discussed/dispelled many of the myths surrounding (racemic) ketamine and its effects on intracranial pressure and seizures in their PAAD entitled ‘Traumatic brain injury: another bubbameisa (old wives tale)’. It was and remains one of the most read PAADs in our history. Because so many of you joined the PAAD community since the publication of that PAAD, I am going to repost it in its entirety tomorrow. Myron Yaster MD
Original article
Mansvelder FJ, Bossers SM, Loer SA, Bloemers FW, Van Lieshout EMM, Den Hartog D, Hoogerwerf N, van der Naalt J, Absalom AR, Peerdeman SM, Bulte CSE, Schwarte LA, Schober P; BRAIN-PROTECT collaborators. Etomidate versus Ketamine as Prehospital Induction Agent in Patients with Suspected Severe Traumatic Brain Injury. Anesthesiology. 2024 Apr 1;140(4):742-751. doi: 10.1097/ALN.0000000000004894. PMID: 38190220.
In the Netherlands, prehospital treatment of patients with traumatic brain injuries3 involves securing the airway with the use of sedative/hypnotic/analgesic drugs such as etomidate or S(+) ketamine prior to helicopter transport. The goal of tracheal intubation is to protect the airway and facilitate neuroprotective measures (including normoxia, normocarbia, normothermia, and normotension) Because of their hemodynamic stability and minimal effects on cerebral flow and intracranial pressure, the most commonly used pre-hospital induction drugs used in the Netherlands are etomidate and S (+) ketamine.
Before reviewing their results, a few words about S (+) ketamine. S (+) ketamine has been in the news because, as a nasal spray, it very effectively treats major depression unresponsive to other treatment modalities.4 Its IV formulation is not FDA approved for use in the United States. On the other hand, in Europe and many other countries outside of the United States, IV S (+) ketamine has largely replaced racemic ketamine because it has fewer unwanted psychotomimetic/hallucinatory effects compared to the racemic formulation. The pharmacology is straight forward: S (+) ketamine exhibits a higher affinity at the N-methyl-d-aspartate receptor binding site and has approximately four times higher anesthetic potency compared to the R(−) enantiomer.4 Equianalgesic doses of the S(+) enantiomer and the racemic mixture result in comparable increases in blood pressure and catecholamine concentrations. Will the results of this study be the same if the racemic version of ketamine is used? The authors state: “given the fact that racemic ketamine contains about 50% S(+)-ketamine, which is the pharmacologically more active component, and given the similar pharmacologic effects of the S(+) enantiomer and the racemate regarding hemodynamics and cerebral blood flow and metabolism, there is no compelling reason to believe that the conclusions would differ when comparing racemic ketamine and etomidate.”1
Ok, what did they find? In this observational study, “there was no evidence of differences in mortality after 30 days, in postinduction blood pressure, Glasgow Outcome Scale at discharge, or length of ICU stay in patients who received either etomidate or S (+) ketamine. Only for the length of hospital stay, a statistically significant albeit rather small difference was found in favor of etomidate for patients who survived to hospital discharge.” Thus, there is no advantage of using one drug over the other. Importantly, the outcome of this study was mortality. This result is meaningful as prior studies suggest an association of etomidate with worsened mortality in patients with sepsis and those requiring emergent intubation in the emergency department. However, if small changes in cerebral autoregulation and perfusion pressure are caused by each agent, is it possible that minor or major neurologic outcomes are different? We think this is unlikely, but we don’t know because this wasn’t studied. Studies of smaller pediatric populations have shown no negative effects of ketamine on short term neurologic outcomes.5 As the authors conclude, further studies are warranted “to explore potential associations with other important clinical endpoints, such as long-term functional outcomes.”1Furthermore, a prospective trial (such as a randomized control trial) would help to eliminate concerns about confounding. In the meantime, it seems either agent is acceptable for intubating after acute traumatic brain injury.
What do you think and which drug to you use to facilitate intubation in traumatic brain injury? Have you utilized ketamine more frequently over the past few years after it has been ‘exonerated’ from an adverse effects perspective? Have recent concerns about the safety of etomidate6 affected your use of the medication? Send your results to Myron who will post in a Friday reader response.
Original article
1. Mansvelder FJ, Bossers SM, Loer SA, et al. Etomidate versus Ketamine as Prehospital Induction Agent in Patients with Suspected Severe Traumatic Brain Injury. Anesthesiology 2024;140(4):742-751. DOI: 10.1097/aln.0000000000004894.
2. Bossers SM, Boer C, Greuters S, et al. Dutch Prospective Observational Study on Prehospital Treatment of Severe Traumatic Brain Injury: The BRAIN-PROTECT Study Protocol. Prehosp Emerg Care 2019;23(6):820-827. (In eng). DOI: 10.1080/10903127.2019.1587126.
3. Bossers SM, Verheul R, van Zwet EW, et al. Prehospital Intubation of Patients with Severe Traumatic Brain Injury: A Dutch Nationwide Trauma Registry Analysis. Prehosp Emerg Care 2023;27(5):662-668. (In eng). DOI: 10.1080/10903127.2022.2119494.
4. Paul R, Schaaff N, Padberg F, Möller HJ, Frodl T. Comparison of racemic ketamine and S-ketamine in treatment-resistant major depression: report of two cases. World J Biol Psychiatry 2009;10(3):241-4. (In eng). DOI: 10.1080/15622970701714370.
5. Mazandi VM, Lang SS, Rahman RK, et al. Co-administration of Ketamine in Pediatric Patients with Neurologic Conditions at Risk for Intracranial Hypertension. Neurocrit Care 2023;38(2):242-253. DOI: 10.1007/s12028-022-01611-2.
6. Kotani Y, Piersanti G, Maiucci G, et al. Etomidate as an induction agent for endotracheal intubation in critically ill patients: A meta-analysis of randomized trials. J Crit Care 2023;77:154317. (In eng). DOI: 10.1016/j.jcrc.2023.154317.