Guest Skeptic: Meghan Groth (@EMPharmGirl). Meghan is the emergency medicine pharmacy specialist at the University of Vermont Medical Center, and an adjunct professor of pharmacy at the Albany College of Pharmacy and Health Sciences.
Case: A 34-year-old male presents to your emergency department with complaints of severe nausea for the past 24 hours. He’s vomited a number of times at home and on a scale of zero to ten (ten being the worst nausea he’s ever experienced), he rates his current nausea at an eight. As the triage nurse brings him back to get settled into his room, you observe him holding an emesis basin and dry heaving. He has no significant past medical history and no known drug allergies.
Background: Nausea and vomiting is a very common complaint for patients presenting to the emergency department, accounting for almost five million visits in the US each year.
Currently available antiemetic treatments include ondansetron, droperidol, metoclopramide, promethazine, and prochlorperazine. Ondansetron is the most commonly administered medication in US emergency departments. Despite this, it takes about 30 minutes for intravenous ondansetron to work, which isn’t ideal in patients on the verge of vomiting.
There are studies showing commonly used antiemetic drugs are not superior to placebo in undifferentiated emergency department patients. We covered one of those studies with Eve Purdy on SGEM#101 called Puke – Antiemetics in Adult Emergency Department Patients.
A number of studies have evaluated the use of isopropyl alcohol inhalation for nausea, but these have primarily been in the postoperative setting. A recent Cochrane Review by Hines et al found that isopropyl alcohol inhalation was more effective than placebo in reducing the number of subjects requiring rescue anti-emetics but not as effective as standard anti-emetic therapy.
That Cochrane review also found that other aromatherapies like peppermint oil did not have any good evidence to support their use in treating postoperative nausea and vomiting.
Clinical Question: Does nasally inhaled isopropyl alcohol reduce nausea in adult emergency department patients?
Reference: Beadle, et al. Isopropyl alcohol nasal inhalation for nausea in the emergency department: a randomized controlled trial. Ann Emerg Med 2015
Population: Adult patients presenting to an urban tertiary care emergency department with chief complaint of nausea or vomiting.
Exclusion: Patients with an allergy to isopropyl alcohol, were unable to inhale through the nares, if they were unable to read or write in English, or had altered mental status (including intoxication). Other exclusions included patients who had received an antiemetic (including nasally inhaled isopropyl alcohol) or psychoactive drug or a medication known to potentially produce nausea when exposed to alcohol (eg, disulfiram, metronidazole, cefoperazone).
Intervention: Nasal inhalation of an isopropyl alcohol pad for no more than 60 seconds (at study start, after two minutes and after four minutes). If nausea was relieved at any time, subjects were instructed to not further inhale.
Comparison: Nasal inhalation of a pad saturated in normal saline
Primary outcome: Nausea score at 10 minutes post treatment using an 11-point verbal numeric response scale (0 being “no nausea” to 10 being “worst nausea imaginable”).
Secondary outcomes: Patient satisfaction scores on a 5-point Likert scale (1 being “very unsatisfied” to 5 being “very satisfied”), pain verbal numeric response scale score at 10 minutes post-intervention, and receipt of subsequent rescue antiemetics.
Author’s Conclusions: “We found that nasally inhaled isopropyl alcohol achieves increased nausea relief compared with placebo during a 10-minute period.”
Quality Checklist for Randomized Clinical Trials:
The study population included or focused on those in the ED. Yes
The patients were adequately randomized. Yes
The randomization process was concealed. Yes
The patients were analyzed in the groups to which they were randomized. Yes
The study patients were recruited consecutively (i.e. no selection bias). No
The patients in both groups were similar with respect to prognostic factors. Yes
All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Unsure
All groups were treated equally except for the intervention. Yes
Follow-up was complete (i.e. at least 80% for both groups). Yes
All patient-important outcomes were considered. No
The treatment effect was large enough and precise enough to be clinically significant. Unsure
Key Results: Eighty patients were enrolled in this study and underwent randomization (37 to treatment and 43 to control).
Primary Outcome: The isopropyl alcohol arm had lower verbal numeric response scale nausea scores at 10 minutes than placebo (Median score of 3 vs. 6 on an 11 point scale, p<0.001). This gave an effect size of 3 (95% CI 2 to 4).
Secondary Outcomes: No significant difference between groups in median pain verbal numeric response scale scores or subsequent receipt of rescue antiemetics. Patients randomized to the isopropyl alcohol arm reported higher satisfaction scores. Median satisfaction score was 4 in the isopropyl alcohol arm vs. 2 in the placebo arm. This gave an effect size of 2 (95% CI 2 to 2). There were no serious adverse events were documented in either group.
This paper, although small, is the first to evaluate this intervention in an emergency department population of patients presenting with nausea and vomiting-related complaints.
Isopropyl alcohol inhalation may affect neurotransmission at sites affecting the chemoreceptor trigger zone, and represents an inexpensive and safe intervention for the treatment of nausea, a common presentation to the emergency department.
There were a number of limitations:
Single Center: This was done at the San Antonio Military Medical Center. It serves active-duty military personnel, retirees and beneficiaries. The mean age was in the mid thirties and about 2/3 were women. This may or may not reflect your patient population presenting to your emergency department with nausea and vomiting.
Convenience Sample: These were not consecutive patients presenting with nausea and vomiting but a convenience sample. This could introduce selection bias. They tried to minimize this potential bias by having study personnel available to recruit patients at varying times (days, nights, and weekends).
Blinding: The investigators tried hard to blind the subjects and evaluators. This included obscuring the two types of pads with opaque brown tape, holding the packages at arms length from the investigators and telling the patients not to describe the pad scent. Despite these efforts, I think there probably was some un-blinding. Because isopropyl alcohol provides a stronger olfactory stimulation compared to normal saline it could trigger a placebo effect. This would bias the study toward the treatment group. The authors could have addressed this in the study design by having three groups; isopropyl alcohol, placebo (normal saline pad) and sham group (peppermint oil). The investigators could then inform patients about the possibility of being randomized into a placebo group. After the study, patients and investigators could be asked which group they felt they were assigned. This would serve two purposes. It would help minimize the olfactory component associated with the isopropyl alcohol and confirmed if blinding was maintained.
Patient Oriented Outcomes: A decrease in nausea scores at 10 minutes is important but there are other possibly important patient oriented outcomes. It would have been nice to see how many patients in each group actually vomited after the intervention. Receiving an antiemetic and the number of doses are indirect markers for the patient-oriented outcome that really matters (i.e. did you vomit?). The primary outcome of nausea scores on a verbal rating scale is certainly a subjective measure, but measuring individual episodes of vomiting may have provided a more objective endpoint to measure. Additionally, the duration of the study period was relatively short at 10 minutes. You wouldn’t necessarily expect that the effectiveness of isopropyl alcohol nasal inhalation to last longer than 10 minutes, but further detail evaluating what happened to these patients further on in their emergency department stay might have been valuable to measure and describe. The onset of action for many of our commonly used anti-emetics isn’t immediate; ondansetron takes around 30 minutes to have a notable effect on nausea. So if you have a patient who is acutely nauseous in front of you, the use of isopropyl alcohol via nasal inhalation might in theory represent a “bridge” therapy until the other anti-emetics can kick in. However, when prophylactic isopropyl alcohol was evaluated along with ondansetron versus ondansetron alone for postoperative nausea and vomiting, the study investigators weren’t able to detect a benefit (Radford et al).
Harm: This study is too small and too short a time period (10min) to give any strong statement about safety. It is a common mistake to assume the lack of evidence of harm equals evidence of safety. I am not saying that nasal inhalation of isopropyl alcohol is harmful but the conclusion cannot be that it is safe. The authors seem to acknowledge this limitation.
Comment on author’s conclusion compared to SGEM Conclusion: We agree that isopropyl alcohol nasal inhalation appears to transiently decrease nausea compared with placebo.
SGEM Bottom Line: For patients presenting to the emergency department with complaints of nausea and vomiting, a nasal inhalation of isopropyl alcohol is a quick, inexpensive way that may transiently improve symptoms without evidence of harm.
Case Resolution: While emergency department staff are settling your patient in his room, gowning him up, and establishing intravenous access, you open up an isopropyl alcohol swab and ask him to take a few deep inhalations. After a period of about 10 minutes, the patient reports that he’s still a bit nauseous, but on a 0 to 10 scale his score has decreased to a 4 (from an 8 he reported in triage).
Clinical Application: Emergency department physicians may consider using isopropyl alcohol nasal inhalation as a very inexpensive intervention for transient relief of nausea symptoms for patient presenting to the emergency department.
What do I tell my patient? It sounds like you’re experiencing some pretty severe nausea and discomfort. I would like you take a few deep breaths of this alcohol swab. There is some evidence it can help with nausea. This will give us 10 minutes to set up an IV and start you on some IV fluids and other medications for your nausea.
ALiEM: Trick of the Trade: Isopropyl Alcohol Vapor Inhalation for Nausea and Vomiting
Keener Kontest: Last weeks’ winner was Mario Pinoli from Lubbock Texas. He knew Motorola was the company credited for making the first commercially available handheld mobile phone.
Listen to the podcast for this weeks’ keener question. If you know the answer then send an email to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.
If you have a paper you want Meghan to review then go to the Hot or Not function on the SGEM website and submit an article.
Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.
Cotton J, Rowell L, Hood R, et al. A comparative analysis of isopropyl alcohol and ondansetron in the treatment of postoperative nausea and vomiting from the hospital setting to the home. AANA J. 2007; 75(1):21-6
Winston A, Rinehart R, Riley G, et al. Comparison of inhaled isopropyl alcohol and intravenous ondansetron for treatment of postoperative nausea. AANA J. 2003; 71(2):127-32
Radford KD, et al. Prophylactic isopropyl alcohol inhalation and intravenous ondansetron versus ondansetron along in the prevention of postoperative nausea and vomiting in high-risk patients. AANA J 2011;79(4 Suppl):S69-74