Episode 42- What is the most effective antiemetic in the ER setting?

Hello and welcome to Episode 42 of ER-Rx. This week, we answer the question; “which antiemetic works best to control nausea and vomiting in the ER?” We’ll also briefly discuss dosing, administration, and safety of the most commonly used agents. Nausea and vomiting accounts for more than 4 million ER visits per year, and antiemetic agents are one of the most ordered medications in the ER. Although we have a lot of data regarding the use of these agents in the oncology and post-op settings, there isn’t much to go off of for our ER population.

Unfortunately, the fact is that none of the agents we use are very effective for treating nausea and vomiting. In most studies, metoclopramide was shown to be no more effective than placebo. It also comes with a risk of akathisia- especially if it is given as an IV bolus, and it also has a Black Box Warning for the risk of tardive dyskinesia when used long-term. The dose is typically 10 mg, ideally given as an IVPB in at least 50 mLs over 15 minutes to reduce this risk of akathisia (when compared to the same dose given over 2 mins (5.8 % vs 24.7 %, P <0.001)).

Phenothiazines such as prochlorperazine and promethazine also come up short when compared to placebo. In one study, the two agents were compared to each other and prochlorperazine came out on top, but the study was not adequately powered to show a difference in akathisia rates between the groups. Prochlorperazine has a high affinity for D2 receptors and in other trials has shown akathisia rates of up to 44%. Similar to metoclopramide, prochlorperazine should be given as a 10 mg IVPB over 15 minutes to reduce the risk of akathisia.

In the same study, promethazine was associated with more sedation, but on the flip side it is expected to have lower rates of akathisia. However, it comes with a Black Box Warning for severe tissue injury, and in 2006, the Institute for Safe Medication Practices (ISMP) issued an alert on the use of IV promethazine, citing cases where blood vessel damage at the site of infusion resulted in necrosis and even amputations. Promethazine can be given IM or it can also be further diluted in 50 mLs and given slowly in a large vein to help reduce the chance of extravasation. Still, it should not be considered a first-line agent. Following the ISMP’s recommendations from 2009, my institution has actually removed this agent from formulary.

Serotonin receptor antagonists such as ondansetron are considered first-line agents due to their relatively small risk of side effects and perceived efficacy compared to other agents. High doses (of 8 mg or higher) are used for the prevention of nausea and vomiting due to chemotherapy, but this is only because of the mechanism of chemo-induced nausea. On the other hand, the recommended dose for post-op nausea and vomiting is only 4 mg, given as a slow IV push. Most of the studies in the ER setting also used 4 mg- but we still consistently see higher doses being ordered. It’s not uncommon to try a second, or even a third dose, but remember this will not help your patient and will only increase the risk of side effects. Also keep in mind it’s QT prolonging effects, which typically occurs within 1-2 hours, but can also develop within 15 minutes after the dose.

Droperidol, as much as I consider it my favorite drug in the ER setting, also doesn’t have the best data to back up its use for nausea and vomiting. However, in one study, droperidol was significantly better at reducing nausea at 30 minutes than metoclopramide, prochlorperazine, and placebo. But this came at a greater risk of akathisia at 24-hour follow-up (71.4 % vs 23.5%). Droperidol does have a Black Box Warning for QT prolongation- but this warning is, in most people’s opinions, drastically overstated.

A Cochrane review published in 2018 set out to provide evidence on the efficacy and safety of antiemetic agents in the ER setting, searching registries for randomized controlled trials in any language dating back to 1955. In the end, the review included only 8 trials in over 900 patients. They found that the differences in nausea severity scores from baseline to 30 minutes were no different between placebo and metoclopramide, prochlorperazine, promethazine, or ondansetron. However, one small trial did show significantly greater efficacy of droperidol versus placebo. But once again, no other larger trial showed that any other agent worked better than placebo. Further, when compared to active controls, there was no evidence of one agent being better than any another agent.

There was overall no difference in rescue medication use, hospital admission, and best of all, no difference in patient satisfaction scores in the studies that reported these outcomes. The authors concluded that there is “no evidence to support the superiority of any one drug over any other drug, or the superiority of any drug over placebo.” If you absolutely have to use an antiemetic or if you are still not convinced, give one that the patient prefers and one that minimizes patient-specific risks of side effects – which will vary on a case-by-case basis.

In conclusion, the answer to the question at the top of the episode is; none of the agents is the “the best,” and based on the current evidence we have in the ER setting, they are all equally “the worst”. The fact of the matter is that your patient’s nausea will usually decrease by a similar and clinically significant amount in about 30 minutes- whether you give them an antiemetic or not. This is potentially due to the other things that we are doing for the patient such as removing the trigger, giving IV fluids, and treating their pain.

Of course, there are probably things that this review and other studies are missing, such as actually measuring reductions in episodes of vomiting, or tailoring the agent to the specific cause of the nausea. But still, these agents should not be considered emergent. Even when they do work, most of them have an onset of at least 5-10 minutes with peak effects usually taking 30-60 minutes. If there is a risk of side effects or of worsening QT prolongation- consider holding off.

As always, thank you so much for your time. We recently hit a big milestone with over 20,000 downloads worldwide! Thank you again for tuning in, and please leave a review of the show on Apple Podcasts—I’ll post a direct link on errxpodcast.com and in the Show Notes.