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Three Part Question

In [adult patients with nausea in the Emergency Department]
Is [nasally inhaled isopropyl alcohol effective]
At [improving symptoms of nausea]

Clinical Scenario

You are a clinician working in a busy Emergency Department overnight. A 35 year-old woman presents feeling very nauseous, and requests medications to alleviate symptoms while awaiting results of her investigations. You prescribe an appropriate antiemetic, but note that the nurses are busy dealing with a number of other patients. You therefore anticipate a delay in administration of the antiemetic and wonder whether there is anything you can offer in the short term. You recall an anaesthetic colleague talking about how they ask patients to smell alcohol-containing wipes to treat post-operative nausea. You wonder whether there is any evidence to support similar practice in the Emergency Department.

Search Strategy

Ovid MEDLINE 1946-2020 database:

(Isopropyl alcohol.mp.) AND (Nausea/)

The Cochrane Library:

(“Isopropyl alcohol”) AND (nausea)

Search Outcome

Ovid MEDLINE yielded 7 results. 2 papers were identified as being relevant to question.
The Cochrane Library yielded 1 result. 0 papers were identified as being relevant to the question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Beadle et al. 2015 USA	Adult patients presenting to San Antonia Military Medical Centre ED with a chief complain of nausea or vomiting (of 3 or more out of 10 on verbal numeric response scale). Randomised to inhale either isopropyl alcohol swab or saline swab. Subjects inhaled from pad at study start, 2 minutes and 4 minutes. Self-reported pain and nausea measured at study start and 2,4,6 and 10 minutes post-intervention.	Randomised, placebo-controlled trial. Study investigators visually blinded to allocations. Subjects visually blinded to allocation. 80 patients.	Nausea verbal numeric response scale at 10mins post-intervention (0-10)	Significantly greater reduction in 10 minute nausea score in isopropyl alcohol group (p<0.05)	1) Subjects and investigators were not blinded to scent, giving rise to a risk of performance bias 2) Short study time - limited information regarding the medium-long term efficacy of isopropyl alcohol. There is also limited information regarding the medium-long term harmful effects. 3) Convenience sampling may give rise to selection bias. Population from military medical centre may not be representative of general ED patient population. 4) Verbal numeric response scale is a subjective measure.
			Pain verbal numeric response scale at 10mins post-intervention (0-10)	No significant difference in 10 minute pain scores
			Patient satisfaction verbal response scale at 10mins post-intervention (0-5)	Isopropyl alcohol group reported higher patient satisfaction scores (no p value quoted)
			Need for rescue anti-emetics	No significant difference in patients receiving rescue anti-emetics
April et al. Feb 2018 USA	Adults presenting to the Emergency Department (ED), with chief complaint of nausea or vomiting (of 3 or more out of 10 on verbal numeric response scale). Randomised to one of three arms: inhaled isopropyl alcohol and 4mg oral ondansetron; inhaled isopropyl alcohol and oral placebo; inhaled saline placebo solution and 4mg oral ondansetron.	Prospective placebo-controlled RCT – 122 patients	Change in nausea on Visual Analogue Scale (VAS) at 30 minutes, comparing inhaled isopropyl alcohol to oral Ondansetron, or both	Inhaled isopropyl alcohol significantly reduced reported nausea VAS than compared to inhaled placebo. Addition of oral Ondansetron to inhaled isopropyl alcohol did not significant improve nausea compared to placebo	1) VAS is a subjective outcome measure by definition, and given the difficulty blinding isopropyl alcohol inhalations, there is a risk of performance bias 2) Participants were only eligible if they did not have intravenous access (IV), meaning findings are less generalisable to those with more severe symptoms who will have likely needed IV access 3) Majority of presumed aetiology of patients was infectious gastroenteritis (64%) – the efficacy in nausea/vomiting of other causes less clear due to small individual numbers of each 4) Ondansetron has limited evidence for efficacy over placebo in unselected aetiology of nausea, and did not represent a gold-standard treatment for nausea 5) Short study time (30min) may not have given ondansetron adequate time to take effect
			Vomiting, use of rescue antiemetic, admission to hospital, ED length of stay	No significant improvement in vomiting, rescue antiemetic use, admission or ED length of stay

Comment(s)

The 2 randomised placebo-controlled trials that we have reviewed provide evidence that nasal inhalation of isopropyl alcohol in ED produces statistically significant reduction in patient-rated nausea scores compared to placebo. These studies complement an existing body of evidence for the use of inhaled isopropyl alcohol post-operatively(1). The aetiology of this effect is unclear - mechanisms that have been proposed included olfactory distraction and controlled breathing(2,6). Studies in animal models have demonstrated safety of inhaled isopropyl alcohol (3,4), and there are no reports of adverse events in human trials (1). There are few contraindications, such as those with allergy/intolerance or those taking medications that interact with alcohol (e.g. Metronidazole, Disulfiram). Both studies have a number of limitations. The short study times mean that we cannot comment on the medium to long-term efficacy of isopropyl alcohol inhalation. Furthermore, the inclusion/exclusion criteria of the studies may have precluded generalisation of results to those with the more severe symptoms of nausea and/or vomiting. Difficulties with appropriately blinding the study participants to the inhaled therapy may have given rise to performance bias which may have affected the reported effect size. Nonetheless, there does appear to be a clinically and statistically significant short-term anti-emetic effect of isopropyl alcohol inhalation. Importantly, they have no known harmful side effects, are cheap and widely available. This could give potential utility to alcohol pads as ‘bridging’ therapy in ED, where there are often delays in administration of prescribed medications due to clinical pressures. The therapeutic benefit has been shown to be short-lived, and there is no evidence to suggest that inhaled isopropyl alcohol reduces ongoing requirement for traditional anti-emetics.

Clinical Bottom Line

There is sufficient evidence to support the use of inhaled isopropyl alcohol wipes as a ‘bridging’ anti-emetic in the Emergency Department. They are, cheap, widely available in ED, and safe to use in the short term. We therefore feel that it would be appropriate to offer our 35-year-old female patient this therapy whilst she is waiting for her anti-emetics.

References

1. Beadle KL, Helbling AR, Love SL, April MD, Hunter CJ Isopropyl Alcohol Nasal Inhalation for Nausea in the Emergency Department: A Randomized Controlled Trial Ann Emerg Med 2016;68(1):1-9.e1.
2. April MD, et al. Aromatherapy Versus Oral Ondansetron for Antiemetic Therapy Among Adult Emergency Department Patients: A Randomized Controlled Trial. Ann Emerg Med. 2018;72(2):184-193
3. Hines S, Steels E, Chang A, et al. Aromatherapy for treatment of postoperative nausea and vomiting. Cochrane Database Syst Rev. 2012;(4):CD007598.
4. Anderson LA, Gross JB. Aromatherapy with peppermint, isopropyl alcohol, or placebo is equally effective in relieving postoperative nausea. J Perianesth Nurs. 2004;19:29-35.
5. Gill MW, Burleigh-Flayer HD, Strother DE, et al. Isopropanol: acute vapor inhalation neurotoxicity study in rats. J Appl Toxicol. 1995;15:77-84.
6. Ohashi Y, Nakai Y, Ikeoka H, et al. An experimental study on the respiratory toxicity of isopropyl alcohol. J Appl Toxicol. 1988;8:67-71.