Tuesday 16 August 2016

Isopropyl Alcohol Nasal Inhalation for Nausea in the ED?

Wouldn’t it be great to have something quick, safe, ubiquitous, non-invasive and cheap to give patients with nausea in the ED? How about getting them to sniff on an alcohol wipe?

Yes, you heard me correctly.

But unfortunately, it is probably no better than proper placebo and may cause downstream harm.

There have been some prior studies of alcohol nasal inhalation in the post-operative literature. In addition, aromatherapy has been used in other studies investigating treatments for nausea. So why not bring it to the ED?

This was a randomized double blind, placebo controlled trial performed in a single military ED in Texas. Inclusion criteria were patients aged 18 to 65 with a chief complaint of nausea >3/10 on a numerical rating scale (NRS).

Patients were randomized to hold either an alcohol prep pad or sterile saline wipe about 2.5cm from their nose. They were instructed to nasally inhale deeply for no more than 60 seconds and told to stop if the nausea was completely relieved. This was repeated at the 2 and 4 minute mark if they did not have success.

The primary outcome measure was nausea as reported on the NRS at 10 minutes.

Results? Only 80 patients were recruited but it didn’t matter because there was a huge treatment effect. At ten minutes, the NRS for the alcohol arm dropped from 6 to 3. The placebo had no effect at all. This is great stuff!

But not so fast…

For a placebo to have no effect for nausea is astounding. The vast majority of studies quote about a 30% reduction in nausea when using placebo. The results of this study would have been remarkably different had they used a proper placebo.

Another interesting piece of data was the use of subsequent antiemetics. They were given in only 72% of the placebo group but were required in 89% of the alcohol group. This 17% (95%CI -0.5 to 34.8) increase was not statistically significant but quite clearly worrisome. Could the alcohol sniffing cause paradoxical increased antiemetic requirements?

Probably the biggest argument for skepticism is simple methodology. Small studies demonstrating large treatment effects are usually proven wrong. In statistical speak, this is very likely a type I error.

Despite what you may have heard on the social media echo-chamber of the underqualified, we should not be getting our patients to sniff alcohol. This is unless it is a beautiful glass of Penfolds Grange Hermitage.  

Bon appetit!


Propofol vs. Ketofol for deep procedural sedation in the ED; which is better?

Ketofol exploded on the scene with great enthusiasm over the past decade. But is all the hype worth it?


Most anaesthetists are loath to combine fixed strength drugs in the same syringe. This is akin to combining salt and pepper in the same shaker. (Don’t think about it… I’ve already got the patent.)

Ketofol, a fixed mixture of ketamine and propofol, is theoretically meant to have the advantage of mitigating the side effects of either drug when used alone. So why not.

This Australian double blind randomized controlled trial went far to try to answer the question. They included adults requiring deep procedural sedation supervised by a FACEM.

The primary outcome looking for “respiratory events” was arguably a bit irrelevant. To be fair, researchers try to come up with a feasible question to study. Sometimes the primary outcome is a compromise. But fortunately, they did look at secondary outcomes that are more important.

Results? 573 patients were randomized to propofol or ketofol. 5% in the propofol group and 3% in the ketofol group met the primary outcome. So, no statistical difference.

More patients had self-limited hypotension with propofol. But recovery times were shorter by about 9 minutes.

However, there was a 5% incidence of “severe emergence delirium” in the ketofol group vs. 2% in those that got propofol. 1 in 20 seems concerning to me and probably enough for me to abandon ketofol. 

In the end, I wonder what we are trying to accomplish with ketofol. Either drug works fine when used alone. Procedural sedation is incredibly safe when properly administered. There are times when we should use propofol and times we should use ketamine.

So keep the salt out of the pepper shaker and use either drug alone.  


Does Amiodarone or Lidocaine work for Out-of-Hospital Cardiac Arrest?


Despite advanced life support protocols, there is little evidence that drugs do very much to improve meaningful outcomes after cardiac arrest.

Along with this comes a tremendous effort and trial published in the New England Journal of Medicine. Unfortunately it may not help us too much but, it does provide us with some interesting data to ponder.  

This was a randomized, double blind placebo controlled trial in adults with shock refractory VF or VT that took place in 10 sites in the USA and Canada. (Ian Stiell is one of the authors of course. One cannot conduct a large trial in Canada without his approval.)

The primary outcome was survival to hospital discharge. It was powered to find a 6.3% absolute difference. This was done by a per-protocol analysis rather than intention-to-treat which was fine in this case. They also looked at more important secondary outcomes. You could probably guess what they are…

Results? 37,889 patients were screened for eligibility (holy smokes) and about 3000 patients ultimately randomized to amiodarone, lidocaine or placebo. 70% of the arrests were witnessed and the time to EMS arrival was just over five minutes.

Between the groups, there was no difference in the primary outcome. The absolute difference between amiodarone and placebo was 3.2% (95% CI 0.4 to 7.0.) p=0.08. Nevertheless, this is quite an eyebrow raising trend.

In the pre-specified subgroup of witnessed arrest, the drugs seem to work. At least it was statistically significant with a 5% increase in survival to hospital discharge.

As expected, the conclusion as printed in the NEJM is very measured and reported as a negative trial. However, I’m sure this study will be interpreted in many different ways.

We know that the best predictors of successful outcomes in out-of-hospital cardiac arrest are; witnessed arrest, bystander CPR, and an initial shockable rhythm. It makes sense that an intervention will be more successful in this particular group. So perhaps we should be aggressive.

I don’t think we should be throwing away our drugs quite yet. In fact, I interpret this trial as supporting the existing protocols and use of amiodarone in selected patients. The press release from the NIH seems to agree. However, we could ultimately be proven wrong.