Episode 32- Drug shortage debacle: Methohexital or ketamine for RSI

Hello and welcome to Episode 32 of ER-Rx. In this “Fresh Fruit” series, we look at an article published in October 2020 in the Journal of Emergency Medicine entitled “A comparison of etomidate, ketamine, and methohexital in emergency department rapid sequence intubation.”

Rapid sequence intubation (RSI) is used frequently in the ER for emergent airway management. During this procedure, we give an agent that induces general anesthesia, followed by a paralytic (such as rocuronium or succinylcholine). Studies show that RSI is successful on the first attempt at least 75% of the time. Obviously, this can vary depending on the site, the experience of the intubator, and other patient-related factors. We also know that multiple attempts can increase the risk of complications.

When we talk about induction agents, we use mostly etomidate, ketamine, propofol, midazolam, and much less commonly- methohexital. Etomidate tends to be our gold standard. It’s almost 100% hemodynamically neutral. It has a very quick onset (30-60 seconds) and a short duration (5-10 minutes) with minimal side effects. It’s no surprise that this agent is most frequently used at my site, and probably most sites in the US.

Ketamine has almost identical onset and durations as etomidate. Ketamine may actually increase blood pressure and heart rate, making it a good agent for hypotensive patients or those with reactive airway disease due to its bronchodilatory effects.

Propofol has almost identical onset and duration as the other two agents. But it isn’t used as much because it can cause hypotension.

Midazolam has a longer onset (60-90 seconds) and a longer duration than the other agents. This one also isn’t frequently used due to the risk of hypotension, and when it is used it is commonly under-dosed. Remember that the dose here is 0.1-0.3 mg/kg-which most people tend to forget.

Lastly, we come to Methohexital (Brevital), and this is one I have never used before. Methohexital is a barbiturate agent that comes with similar risks of hypotension as midazolam and propofol, and it can also cause bronchospasm. To top it off, it requires reconstitution prior to administration- so nurses and pharmacists will probably hate it even more. It does, however still retain the rapid onset and short durations that are characteristic of etomidate, ketamine, and propofol.

Research shows that any of these agents can be effective for RSI, and therefore it’s hard to determine which is the best agent in terms of intubation success rates and time to intubation. So why did the authors even do this study? Well, I actually think its genius and very timely. With COVID surging and ER and ICUs being at full capacity in many areas across the US and the world, drug shortages are always something that the pharmacy world is considering. What if we run out of etomidate? Or ketamine? Or propofol? This is nightmare fuel for hospital administration, providers, and pharmacists, since we know that using alternative agents that everyone is less familiar with during drug shortages can often lead to adverse events, inferior therapy, and more medication errors.

Fearing a worsening shortage of our first-line agents for RSI, the authors of this study looked back to their ER practice from 2012, during an actual etomidate shortage, where they had to use more ketamine or methohexital. They wanted to describe the effectiveness and safety of RSI with ketamine or methohexital as compared to our gold standard etomidate to help guide us in the future should a drug shortage like this occur again.

This study was a retrospective, observational study in patients undergoing RSI between May and August 2012 (during the etomidate shortage). They left out RSI performed by the difficult airway response team or by anesthesiology. Their study site was a 496-bed urban, academic, Level I trauma center. This trauma center was staffed 24-hours per day by attending physicians as well as emergency medicine residents. It was also staffed about 8-12 hours per day by an ER pharmacist.

This study Included 82 patients overall: 47 that received etomidate, 9 who received ketamine, and 26 that received methohexital, and all of these patients had similar baseline characteristics. Not surprisingly, ketamine was used most often in pts with lower blood pressures and in patients being intubated due to respiratory distress. All 82 patients were successfully intubated, but more patients in the etomidate and methohexital groups were intubated on the first attempt compared to ketamine (~ 74% vs 55%). But remember that the ketamine group was too small with only 9 patients to draw any real conclusions from. Also, remember that this rate was slightly lower than some studies that have shown upwards of 80 % or even 90 % first attempt success rates by emergency physicians, but this study included intubation attempts by PGY-1 through PGY-3 EM residents. So it could have brought the rates down a little bit. The authors found that there were similar times to intubation, with etomidate being the shortest at 3.8 minutes, but this probably wasn’t clinically significant, as the other agents had a time of 4.3 minutes. There were also no patients who experienced dental or airway trauma, esophageal intubation, or seizures.

In conclusion this is yet another addition to the growing pool of research that shows that there is no superior induction agent in the setting of RSI. It also showed that providers preferred methohexital to ketamine, and it didn’t appear that the need for reconstitution was as off-putting to the team as I thought. This agent also didn’t cause any hypotension in this cohort, but many of their patients did not have vital signs recorded.

All in all, this and other studies show that ketamine, and the very unfamiliar methohexital are safe alternatives to etomidate should a drug shortage occur. The authors also give some practical advice. Since both methohexital and ketamine come in 500 mg, single use vials, much of the drug gets wasted after RSI. The authors recommend preparing 100 mg prefilled medication syringes of ketamine and methohexital, both of which have extended stability after reconstitution, and then putting these syringes in automated dispensing machines in the ER. This could cut down on preparation time and waste.

As always, thank you so much for your time. Please remember to check out the website, errxpodcast.com, and sign up for our newsletter for your chance to win some prizes.