Estimated reading time: 6 minutes
Just a quick review this week as this is a paper published back in December that has been superbly reviewed already over on the SGEM. However, it’s an interesting topic and one that has been a matter of some debate here in Virchester for many years.
When I originally trained (admittedly some time ago) Etomidate was the drug of choice for the induction of anaesthesia in the unstable patient. This is still the case for some clinicians in Virchester, although they are diminishing as most have moved over to using Ketamine as the drug of choice.
Etomidate fell out of favour for many reasons, with one being the concerns around adrenal suppression (but that’s not really an issue as a single dose). Personally, I use Ketamine most of the time but occasionally use Thiopentone for isolated head pathology (trauma, SAH) or Etomidate for some cardiac patients. Now, I know that people will have views on that, and there are great arguments for using other approaches, but I’m just telling you what I do. One of my colleagues, whom I have the highest regard for is a strong advocate for Etomidate as an induction agent.
I used to use a lot of Etomidate, but changed over time, eventually being fairly convinced following the publication of the KSS experience with prehospital induction of anaesthesia that implied better outcomes with Ketamine (though this was an observational study only).
To be clear. For the vast majority of anaesthetics conducted by emergency clinicians in Virchester we use Ketamine/Rocuronium/Fentanyl. However, there is still a degree of variation in practice amongst some of the senior clinicians for specific cases.
Having said that, I would freely admit that my personal evidence base for my decisions is not that strong, and that some of it is simply custom and practice. What we need is a trial putting the options of Ketamine and Etomidate against each other, and that’s what we have this week. The abstract is below, but as we always say, read the paper for yourself and come to your own conclusions.
What kind of paper is this?
It’s a randomised controlled trial which is exactly what we want to see when comparing two clinical interventions, in this case that’s a comparison between using Etomidate or Ketamine as an induction agent.
Tell me about the patients.
This was a single centre trial in an urban US hospital. The patients were anaesthetised by a dedicated airway team from the department of anaesthesiology. The inclusion criteria were quite broad including patients over the age of 18 requiring induction agents (excluding pregnancy, known allergies etc.).
It is interesting to note that 11952 patients were screened and of those, 309 were excluded for a different induction agent , and 396 were excluded for unknown reasons including clinician preference. Clearly these were not consecutive patients and it’s likely that there was some degree of clinician selection into the trial. This may well bias the results.
801 patients were randomised in the trial. 10 later withdrew.
Patients were pretty similar at baseline with shock and acute resp failure being the major reasons for intubation. There were smaller numbers of trauma patients in this trial (roughly 15%).
What about the intervention?
The doses used in this trial were fairly standard to UK practice: etomidate 0.2–0.3 mg/kg intravenous; ketamine 1–2 mg/ kg IV. The intervention was not blinded. All other aspects of airway care were up to the airway team, within their usual scope of practice.
What about the outcomes?
The main outcome was survival at day 7. This is a hard endpoint and certainly relevant to patients. Secondary endpoints included day 28 survival, adrenal suppression, ventilation, ICU stay SOFA scores etc. There was less of a focus on immediate haemodynamic change, which is perhaps the factor that influences our decisions as emergency physicians more (rightly or wrongly). However, these exploratory endpoints were recorded in the study.
The trial was powered to detect a 10% difference in outcome (day 7 survival) which is rather ambitious in my opinion. It’s unlikely that an induction agent would be responsible for a 10% difference in survival and perhaps this trial could be considered clinically underpowered.
Survival alone is a bit blunt, and in many trials of critically unwell/injured patients we are now seeing outcomes that include functional outcomes. It would be good to see that in a trial of this kind.
What did they find?
In terms of the main outcome, 7-day survival, there was a significant benefit to the use of ketamine (85.1%) as compared to etomidate (77.3%). This was the primary outcome of the study (p=0.005).
By day 28 the difference in outcome had diminished, survival with etomidate was (64.1%) vs. ketamine (66.8%).
In terms of the ‘exploratory’ outcomes around haemodynamics and other characteristics around the time of intubation there was not a huge amount of difference, although the authors note a higher rate of cardiovascular collapse in the ketamine group (17.4% for etomidate vs. 25.1% for ketamine). This seems high, but may just reflect use of inotropes in a sick group of patients (which I think is in the Vanderbilt definition).
So what does this mean?
We need to be a bit cautious in changing practice on this paper. It is unblinded, single centre, it’s not EM patients and the construction of the airway team/process is somewhat different to the UK.
In terms of the primary outcome Ketamine performed better than Etomidate in this cohort of critically unwell patients. This benefit is not sustained statistically through to day 28, but ketamine is still better at that time point. So on balance Ketamine appears to be the better option here as we should consider the secondary and exploratory outcomes as hypothesis generating.
My take-away is that this paper reinforces my current practice which is to use Ketamine as my first option. However, the limitations and patient selections in this trial mean that there may still be the occasional patient in whom I (and colleagues) use Etomidate in.
There is a nice infographic from Kirsty Challen below.
If you have not done so already then please do visit the SGEM and review Ken Milne’s take on this paper.
Significant modification of traditional rapid sequence induction improves safety and effectiveness of pre-hospital trauma anaesthesia https://pubmed.ncbi.nlm.nih.gov/25879683/
Critical Appraisal Nuggets: Randomisation. https://www.stemlynsblog.org/critical-appraisal-nuggets-the-st-emlyns-can-podcast/
SGEM#356: DRUGS ARE GONNA KNOCK YOU OUT – ETOMIDATE VS. KETAMINE FOR EMERGENCY ENDOTRACHEAL INTUBATION
Etomidate versus ketamine for emergency endotracheal intubation: a randomized clinical trial. Intensive Care Med . 2022 Jan;48(1):78-91. doi: 10.1007/s00134-021-06577-x. Epub 2021 Dec 14