Sick of Ondansetron? Sniff some alcohol instead…

 

Tim Minchin is famous for a number of reasons, chiefly for being a brilliant Aussie musician, lyricist and comedian. He also holds a special place in my heart for a particular quote, or rather expository snippet, regarding evidence based medicine from his beat poem, Storm :

 ‘By definition’, I begin, ‘alternative medicine’, I continue, ‘has either not been proved to work, or been proved not to work. Do you know what they call alternative medicine that’s been proved to work? Medicine.’

(Seriously, if you haven’t listened to this, watched the animated short film, or read the graphic novel / illustrated book adaptation, do yourself a favour.)

The context was that of explaining to a clueless hippy at a dinner party the concept of evidence based medicine. In the Emergency Department, I tend to find myself spending a not inconsiderable amount of time (politely) explaining to patients why complementary therapy xyz is a steaming pile of stuff a dung beetle would be very excited about, and the evidentiary basis for the real medical treatment option I am suggesting or offering in lieu. From a broader perspective, we also find ourselves explaining to junior doctors, and various colleagues, the basis for dropping a longstanding practice from our medical armamentarium (e.g. PPI infusions for upper GI bleeding, clopidogrel and morphine in acute coronary syndromes, etc). In a happy reversal of fortune, very occasionally we get to do as Tim Minchin suggests, and rather than demote a previously cherished treatment, someone produces some decent quality evidence that suggests we might, and perhaps should, elevate something that at first glance sounds a bit… shall we say chiropractic*… to the status of actual, real, bona fide medicine.

This, my friends is, dare I suggest, just such an occasion.

Way back in the mists of time… well, okay, the late 1990’s… various folk started publishing papers looking at non-standard options for reducing post-operative nausea and vomiting (PONV). Most of these were small case series, observational studies, or underpowered not well-controlled sort-of-trials. Among the contenders for antiemetic of the year were ginger extract, peppermint oil, carbohydrate-rich beverages, and various acupuncture or acupressure points that were (according to TCM principles) most likely to alleviate nausea. None of those worked. But, like a phoenix rising from the ashes of the complementary and alternative therapy compost heap, one treatment did seem to do something useful. Quite useful. And, surprisingly, quite consistently. This feisty underdog was aromatherapy!

Yes, aromatherapy to the rescue. But to be clear, we’re not talking about randomly selected essential oils here (we all know what an essential amino acid is, and there are indeed essential oils or lipids we need in our diet, too, but I’ve never quite figured out what’s “essential” about the smelly ones?). No cute little ceramic things with tea candles are involved. The feng shui of your hospital bed doesn’t matter so much. And neither the presence of crystals nor the alignment of any pyramids in the room seem to play an outcome-altering role here, either. The salient feature is in the inhalation, via simple sniffing, of a volatile agent… isopropyl alcohol (IPA).

IPA-768x643

The exact origin story of this practice is lost to modern historians, but seems to have stemmed from quaint folk practices taking place in the mysterious environment of the pre & post-op anaesthetic and recovery rooms of the world, where nursing and anaesthetic staff presumably noticed a correlation between solvent-sniffing patients sequestering large quantities of alco-wipes and a decreased incidence of PONV. One surprising anecdote in the tea room led to another, and another, until it evolved into a cliché, finally attaining enough spatial and temporal distance from its origin to become received wisdom and embed itself permanently in peri-operative management as a Thing We Know™. Such is the way of medicine. Interestingly, most of these studies used “time to 50% reduction in nausea” as an outcome measure, rather than “Did they chuck again?”, but nonetheless, sniffing IPA consistently won the day.

But we don’t work in theatres, so who cares, right? Well, finally, someone with enough enthusiasm, curiosity, and statistical / study design skills picked up the gauntlet, and dared to ask “What about ED? Surely there’s a better option than just putting ondansetron in the drinking water?”  And thus, two studies of interest to us were born…

Beadle et al. 2016, Ann Emerg Med, “Isopropyl Alcohol Nasal Inhalation for Nausea in the Emergency Department: A Randomized Controlled Trial”

April et al. 2018, Ann Emerg Med, “Aromatherapy Versus Oral Ondansetron for Antiemetic Therapy Among Adult Emergency Department Patients: A Randomized Controlled Trial”

Beadle & Co. essentially did the important preliminary work of demonstrating that sniffing isopropyl alcohol (IPA) is more effective than sniffing a placebo. April & Friends went on to do the hard yards, and in a well-designed and elegant piece of 3-armed BRCT work showed that sniffing IPA is at least as good as ondansetron for improving nausea, and much better than ondansetron at reducing the need for further doses of anti-emetics while in ED.

So what did they do?

Beadle 2016 – IPA vs placebo

  • n = 84 (80 completed the study for data collection) adults in ED with nausea/vomiting
  • Blinded RCT with a convenience sample
  • Primary outcome = 11-point verbal scale of nausea before & 10 mins post Rx
  • Secondary outcome = 5-point Likert scale of patient satisfaction
  • Results
    • Primary – nausea score of 3 vs 6 for IPA vs placebo
    • Secondary – satisfaction score of 4 vs 2 for IPA vs placebo

April 2018 – IPA vs ondansetron(4mg PO/SL) vs placebo

  • n = 122 (120 completed the study for data collection) adults in ED with nausea/vomiting
  • Blinded RCT with a convenience sample
  • Primary outcome = mean nausea reduction on 100mm visual analogue scale (VAS) 30 mins post Rx
  • Secondary outcome = incidence of requiring further / rescue anti-emetic(s) in ED
  • Results
    • Primary
      • IPA + ondansetron = 30 mm reduction
      • IPA + placebo = 32 mm reduction
      • Placebo + ondansetron = 9 mm reduction
    • Secondary
      • IPA + ondansetron = 27.5 %
      • IPA + placebo = 25 %
      • Placebo + ondansetron = 45 %

Now, these are relatively small sample sizes, but even so, the magnitude of the differences is impressive, both subjectively and statistically, and more importantly almost certainly represent a clinically significant difference worthy of our interest. The 2018 study by April is particularly compelling, and while the sensible among us are usually hesitant to advocate a change in practice based on a single study (NINDS, anyone?) in this case it is a high quality study with a very large treatment effect, and no known or reasonably expected harm involved in introducing the new treatment.

SUMMARY

  • Sniffing an isopropyl alcohol (IPA) swab is more effective than ondansetron for reducing nausea in adult ED patients.

  • Sniffing an IPA swab (with or without an initial dose of ondansetron) roughly halves the rate of having to give any further dose of anti-emetic.

AlcoWipes-768x432

PRACTICE POINTS

  • The BLUE alco-wipes in the IV starter kits are 70% IPA, with nothing else in them.
  • The YELLOW “Prep pads” ones loose in the IV trolleys have 70% IPA + 2% chlorhexidine in them. Keeping in mind the amount of chlorhexidine in mouthwash, gargled anaesthetic agents, etc. it is pathophysiologically inconceivable that the presence of the chlorhex should matter.
  • Don’t let anyone lock the alco-wipes up in a Pyxis, because now they’re a “drug” (EMLA / LMX, anyone?)
  • Beware the overly-enthusiastic patient – don’t let them aspirate the swab!

[*noun, synonym: quackery]

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