Dr. Harrison Pidgeon

Background:

We see nausea all the time in the Emergency Department (ED). Providers have different preferences on what agents they use as anti-emetics. But when put through the best evidence based tests (randomized controlled trials), ondansetron/Zofran, metoclopramide/Reglan, and prochlorperazine/Compazine fail to prove better than placebo for undifferentiated nausea. These agents are used because they have a proven benefit in chemotherapy associated nausea.

Personally, ondansetron has been my go-to agent of choice. Besides its small QTc prolongation, there aren’t many side effects. It avoids the restlessness or akathisia feeling that I have seen with metoclopramide and prochlorperazine. But is there something better?

Thanks to our anesthesia colleagues, we have research backing another class of agents: aromatherapy. There is literature to support aromatherapy for post-op nausea1-3, which some smart folks used to back their research showing it can also work within 10 minutes for undifferentiated nauseated patients in the ED4.

Study Question:

How does aromatherapy (isopropyl alcohol) compare to ondansetron for antiemetic therapy among adult ED patients?

Design:

3 groups: 1) inhaled isopropyl alcohol + oral ondansetron, 2) Inhaled isopropyl alcohol + oral placebo, and 3) inhaled placebo plus oral Zofran.

Zofran dose was 4mg in 5ml solution.

Primary outcome: Nausea on a 0-100 visual analog scale (VAS) (100= most nausea imaginable) at baseline compared to at 30 minutes.

Secondary outcomes: Rescue medications, vomiting episodes, VAS score at other time points, overall satisfaction, admission, ED length of stay, nausea score at time of disposition.

Results:

Primary outcome of reduction in VAS baseline to 30 minutes:

  • 30: alcohol + ondansetron
  • 32: alcohol + placebo
  • 9: placebo + ondansetron

Secondary outcomes: lower VAS for inhaled alcohol groups at disposition and better overall satisfaction. There was no demonstrated difference in rescue medications and need for admission.

Discussion:

There were a bunch of strengths to this study. It was a well-designed randomized controlled trial. The groups were well balanced. It was double blinded with some quality assurance (QA) imbedded in the study. Most importantly to me, it was clinically meaningful. A 30+ point versus 9 point decrease on an 100 point scale (aka 3 points on my typical 10 point scale) is like bringing someone’s nausea from a 6 to a 3 or from a 6 to a 5. I’ll take that any day!

Every study has limitations. This was only done at one hospital so it’s hard to say how generalizable this is or if there are other unaccounted for confounders. They excluded patients with PICC lines or ports which means cancer patients or those receiving long term antibiotics were mostly excluded. They used a convenience sample which leaves the study open to selection bias. The patients here had moderate nausea (average baseline around 50 out of 100), so we can’t know if these results are as applicable to more severe nausea. I also have a hard time believing they were able to blind the providers and participants to the inhaled agent. Alcohol smells very different from saline. The QA seemed to suggest they were relatively successful but I still have my doubts. Probably the biggest weakness here was the primary endpoint being 30 minutes after the baseline. Most sources cite ondansetron’s onset of action as between 30 and 120 minutes so it just may not have given ondansetron long enough to take full effect.

This study is a huge win for aromatherapy in our current body of literature. No, it is not going to replace our standard anti-emetics overnight but this does give me some legitimate backing to have my next nauseous patient sniff an alcohol pad until the ondansetron they got/will get can take effect. Plus an alcohol pad is something within arm’s reach of nearly every patient encounter I have. Patients love when I can give them something to immediately address their needs.

The authors briefly discussed some proposed mechanisms of why this may work. One is about olfactory distraction which is to say we get our brains focused on something other than our nausea. Another theory is that as we are intentionally smell something, we use controlled breathing similar to a mindfulness or meditation. Either way, the aromatherapy maybe does not have to be isopropyl alcohol. I’m hoping our administration has some lavender or peppermint essential oils in the next order…

Take Away:

Inhalation of isopropyl alcohol reduces nausea in the first 30 minutes better than oral ondansetron.

Reference:

  • April MD, Oliver JJ, Davis WT, et al. Aromatherapy Versus Oral Ondansetron for Antiemetic Therapy Among Adult Emergency Department Patients: A Randomized Controlled Trial [published correction appears in Ann Emerg Med. 2019 May;73(5):552]. Ann Emerg Med. 2018;72(2):184‐193. doi:10.1016/j.annemergmed.2018.01.016
  • Hines S, Steels E, Chang A, et al. Aromatherapy for treatment of postoperative nausea and vomiting. Cochrane Database Syst Rev. 2012;(4):CD007598.
  • Teran L, Hawkins JK. The effectiveness of inhalation isopropyl alcohol vs. granisetron for the prevention of postoperative nausea and vomiting. AANA J. 2007;75:417-422.
  • Pellegrini J, DeLoge J, Bennett J, et al. Comparison of inhalation of isopropyl alcohol vs promethazine in the treatment of postoperative nausea and vomiting (PONV) in patients identified as at high risk for developing PONV. AANA J. 2009;77:293-299.
  • Beadle KL, Helbling AR, Love SL, et al. Isopropyl alcohol nasal inhalation for nausea in the emergency department: a randomized controlled trial. Ann Emerg Med. 2016;68:1-9.e1.

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