Research Roundup – January 2026

The big paper of the month: ketamine vs etomidate for RSI

Casey JD, Seitz KP, Driver BE, et al. Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults. N Engl J Med. 2025 Dec 9. doi: 10.1056/NEJMoa2511420. Epub ahead of print. PMID: 41369227

On its face, this is a fairly simple pragmatic RCT comparing etomidate to ketamine as the induction agent in critically ill adults. It showed no difference in the primary outcome of mortality, but ketamine resulted in about 5% more “cardiovascular collapse” as the sole prespecified secondary outcome. However, I think there is a ton of nuance which makes interpretation of this trial somewhat difficult. The first question is whether this trial truly demonstrates equivalence when it comes to the mortality primary outcome. The whole reason for running this trial was that some people have been concerned that etomidate might be increasing mortality because of its known adrenal suppression. The trial is negative, but it was powered for an unheard of 5.2% absolute difference in morality. We therefore could have predicted, before even a single patient was enrolled, that this trial was going to be statistically negative. That doesn’t rule out a small but real increase in mortality from etomidate. Indeed, mortality was 1% worse with etomidate (29.1% vs 28.1%; risk difference adjusted for trial site, −0.8 percentage points; 95% CI −4.5 to 2.9; P = 0.65), so if you believed that etomidate was increasing mortality before this trial, you definitely shouldn’t change your opinion. (My personal guess is that these agents are likely close to equivalent.) The second major question is what to make of the “cardiovascular collapse” secondary outcome. I write extensively about this in the main post, but the primary outcome probably tells you everything you need to know: there is no change in mortality, so this “cardiovascular collapse” is pretty clearly a meaningless surrogate. If you want a little more detail, neither hypotension nor cardiac arrest were actually changed, so the only thing that “cardiovascular collapse” represents is the decision to start more patients on vasopressors. But if there wasn’t a difference in hypotension between the groups, why were they started on vasopressors? This outcome is almost certainly a biased artifact of an unblinded trial, but even if there is a real blood pressure drop with ketamine, we know for sure it it clinically unimportant as mortality outcomes are identical, and we should always be prepared to manage peri-intubation hypotension anyway.

More details can be found in the main post. 

Bottom line: This RCT, although underpowered, demonstrates no difference in mortality when etomidate is used instead of ketamine when intubating critically ill adult patients. Although it will be widely discussed, the “cardiovascular collapse” secondary outcome is almost certainly meaningless. 

An alternative bottom line might be: This data is most consistent with ketamine and etomidate having equivalent outcomes, but leaves open the possibility that etomidate results in a small but real increase in mortality, while there is essentially no chance that outcomes are worse with ketamine. Phrased that way, the clinical implications seem more obvious. 

Overdiagnosis and atrial fibrillation

Svendsen JH, Diederichsen SZ, Højberg S, Krieger DW, Graff C, Kronborg C, Olesen MS, Nielsen JB, Holst AG, Brandes A, Haugan KJ, Køber L. Implantable loop recorder detection of atrial fibrillation to prevent stroke (The LOOP Study): a randomised controlled trial. Lancet. 2021 Oct 23;398(10310):1507-1516. doi: 10.1016/S0140-6736(21)01698-6. Epub 2021 Aug 29. Erratum in: Lancet. 2021 Oct 23;398(10310):1486. doi: 10.1016/S0140-6736(21)02090-0. PMID: 34469766

The LOOP study randomized 6004 elderly (70-90 years) patients without known atrial fibrillation but at least one additional risk factor for stroke (hypertension, diabetes, prior stroke, etc.) to either an implantable loop recorder or standard care. Over about 5 years of follow up, 32% of the loop recorder group was diagnosed with atrial fibrillation as compared to 12% of the control group, resulting in a similar discrepancy in anticoagulation (30% vs 13%). Despite all that extra anticoagulation, stroke rates and arterial emboli rates in both groups were not statistically different (4.5 vs 5.6%). Major bleeding was also not statistically different (4.3% vs 3.5%), so the trial does not clearly demonstrate harm from this approach, but the trial may be underpowered for this outcome, and if there is no benefit, starting a bunch of asymptomatic people on anticoagulation will clearly cause harm. Screening for atrial fibrillation does not look good. 

Obviously, we don’t make a lot of decisions about implantable loop recorders. However, I am increasingly seeing patients present with asymptomatic smart watch detected atrial fibrillation. In general, the patients I am seeing are younger and lower risk than this cohort, which probably shifts the harm benefit ratio even further towards harm. Basically, I think this data likely suggests we should be ignoring asymptomatic smart watch identified arrhythmias. Sadly, as we have found over and over again with overtesting and overdiagnosis in medicine, this is almost impossible to do. Once we have the results of a test, even if those results are on a smart watch, those results are going to be acted upon. Perhaps the best advice is to just tell family and friends to disable this feature of their watches?

Bottom line: Don’t screen for atrial fibrillation. Ignore health gurus hawking smart watch screening. 

When I develop atrial fibrillation, can I still have my 8 cups of coffee a day?

Wong CX, Cheung CC, Montenegro G, Oo HH, Peña IJ, Tang JJ, Tu SJ, Wall G, Dewland TA, Moss JD, Gerstenfeld EP, Tseng ZH, Hsia HH, Lee RJ, Olgin JE, Vedantham V, Scheinman MM, Lee C, Sanders P, Marcus GM. Caffeinated Coffee Consumption or Abstinence to Reduce Atrial Fibrillation: The DECAF Randomized Clinical Trial. JAMA. 2025 Nov 9:e2521056. doi: 10.1001/jama.2025.21056. Epub ahead of print. PMID: 41206802

What is the impact of coffee consumption on atrial fibrillation? Do you counsel your patients about caffeine intake after cardioversion? This is an RCT of adult patients who underwent cardioversion by cardiologists, and then were randomized to either abstinence from caffeine, or the suggestion to drink 1 coffee every day and not otherwise change their caffeine intake. The quick answer is that coffee reduced the recurrence of atrial fibrillation. The longer answer is that there are a number of issues with the study. The biggest is probably the very select population they look at (most people just say no when you ask them to change their coffee habits). You had to be willing to stop drinking coffee to get into this trial, but anyone willing to stop drinking coffee is probably not drinking enough coffee to cause atrial fibrillation. Despite being “coffee drinkers” almost half of these patients were not drinking any coffee at the time of enrollment. Changing from 0 coffees a day to abstinence is not a very big change. 

Also, they decided to include atrial fibrillation identified by devices, so it isn’t clear whether any of these recurrences were actually clinically significant, especially considering the above results. In fact, it’s pretty clear the results aren’t important, as exactly 5 patients in each group ended up in the ED for atrial fibrillation. 

I don’t think we should be encouraging caffeine intake based on these results, and I am not sure we can even conclude that it is perfectly safe. However, there is a bunch of prior data on this topic, and the results seem to be consistent: coffee doesn’t provoke atrial fibrillation. Therefore, I think it is reasonable to counsel patients that coffee and caffeine consumption are not going to put them at a higher risk of atrial fibrillation recurrence, and that they should therefore live their lives as they please.

Bottom line: This RCT showed a reduced risk of atrial fibrillation recurrence with daily coffee consumption as compared to abstinence. There are numerous reasons to think these results are not true, but this probably is evidence that caffeine is not going to cause increased atrial fibrillation.

Full post here

To round out a fib month: What the heck is vernakalant?

Stiell IG, Taljaard M, Eagles D, Yadav K, Vadeboncoeur A, Hohl CM, Archambault PM, Birnie D, Brown E, Campbell SG, Chen Y, Clement CM, Cournoyer A, de Wit K, Emond M, Macle L, McRae AD, Mercier E, Morris J, Mohamad G, Nemnom MJ, Nicholls SG, Pare D, Parkash R, Sivilotti M, Thavorn K, Perry JJ. Vernakalant versus procainamide for rapid cardioversion of patients with acute atrial fibrillation (RAFF4): randomised clinical trial. BMJ. 2025 Nov 11;391:e085632. doi: 10.1136/bmj-2025-085632. PMID: 41218981

This paper talks about it as if it is widely used in Canada, but I have never heard of vernakalant. I guess the drug reps start with the big influential academic centers. Cardioversion is obviously widely used in Canada, and despite being the best option available, we all know procainamide sort of sucks. It is only moderately successful at best, it has to be used slowly, and has a relatively long list of adverse events. This RCT out of 12 Canadian emergency departments asks: might vernakalant be a better option? Patients with acute atrial fibrillation who were guideline appropriate for cardioversion were randomized to either vernakalant or procainamide. (See the main post for details about inclusion criteria as well as dosing.) Vernakalant looks better across the board. Their primary outcome was conversion and maintenance of sinus rhythm, and it occurred in 62% of the vernakalant group, as compared to 48% of the procainamide group (adjusted ARR 15.0% 95%CI 4.6-25.0%, p=0.005). Fewer patients in the vernakalant group underwent attempted electrical cardioversion (34% vs 44%). Time to successful cardioversion was faster with vernakant (22 vs 45 minutes). Adverse events were not statistically different, but the difference was big enough to be potentially clinically important (17.4% with vernakalant vs 25.0% with procainamide). Of course, seeing as being in sinus rhythm does actually impact long term outcomes for patients, we might be tricking ourselves here. The outcomes that the patient really saw were: no differences in the rate of discharge to home (96.1% with vernakalant vs 97.7% with procainamide) and very similar total time in the hospital (8.9 vs 9.2 hours). The biggest problem with this study is that it was open label, although conversion to sinus rhythm is a pretty objective outcome. It is also too small to comment on rare harms, which are still a big enough concern that the FDA has refused to license this drug in the United States. (Does the FDA still have any credibility in 2026?) That being said, I have looked through the data available, and I don’t see anything in the multiple RCTs available that indicate a safety issue to me. Vernakalant is significantly more expensive than procainamide, but I do wonder what the overall expenses will be if you factor in the 10% reduction in need for sedation and electrical cardioversion. Personally, I have a hard time acting on this trial, because I generally use electrical rather than chemical cardioversion. How does vernakalant compare to a strategy of just sedating and using electricity immediately? I know for sure that my patients are discharged home way before the 9 hours seen here. However, if you are currently using procainamide as your first line, in this trial, the numbers look better for vernakalant across the board. The only question is whether you should change to a more expensive option after one open label RCT?

Bottom line: This open label RCT shows better cardioversion rates and perhaps fewer adverse events when vernakalant is used instead of procainamide to cardiovert atrial fibrillation. 

Emotional Analgesia and the Decline of Rational Decision Making

Stewart D. Emotional Analgesia and the Decline of Rational Decision Making in Emergency Medicine. Emerg Med Australas. 2025 Dec;37(6):e70180. doi: 10.1111/1742-6723.70180. PMID: 41305908

I have been accused of using a pen name to write this article; or perhaps of acting as a ghost writer. It is true that I can imagine myself writing this exact article, which makes me think that Dr. Daniel Stewart must be a very bright chap, indeed. It is only a 2 page article, so I strongly suggest taking 5 minutes and reading it for yourself. Essentially, Dr. Stewart accuses us of ordering tests not for diagnostic purposes, or medical purposes, or rational purposes, but to soothe our frayed emotions. The CRP, he says, is not dissimilar to your toddler’s favourite blankie, or stuffy, or soother. Inside, you are crying, dismayed by the uncertainty of day to day emergency medicine, and instead of stepping up and being a doctor, you act like a child, reaching for the closest object of comfort: more tests. We are practicing “relief-seeking decision making”. “The results are predictable. Overtesting leads to overdiagnosis, and clinicians are diverted down low-or no-value diagnostic pathways.” “The central concern is not the unnecessary test itself, but the thinking it displaces.” Preach, brother.

Bottom line: It is time to grow up, and stop using tests as emotional crutches.

Healthcare systems everywhere are failing their patients

Trainee Emergency Research Network (TERN). Understanding corridor and escalation area care in 165 UK emergency departments: a multicentre cross-sectional snapshot study. Emerg Med J. 2025 Dec 27:emermed-2025-215301. doi: 10.1136/emermed-2025-215301. Epub ahead of print. PMID: 41365687

This is a retrospective look at 165 emergency departments in the United Kingdom in the spring of 2025, and it found that almost 18% of patients were receiving care in “escalation areas” aka the hallway or other repurposed areas. About 10% of these sites were doubling up patients in single cubicles. The number of sites that had no available resuscitation cubicles ranged from 11 to 27%. Of course, to people working in the emergency department, none of this is surprising at all. Human dignity has long since been abandoned in most emergency departments. I don’t usually include articles that state the obvious, but I think there is a tendency to assume that one’s local health system is the problem. People are always trying to blow up their own models in favour of others. In Canada, people blame the single payer government model for all our problems, but I think it is important to acknowledge that the exact same problems exist in almost all systems. It doesn’t matter who controls the money: healthcare systems, and especially emergency departments, are underfunded and understaffed worldwide. The people in charge have never understood emergency capacity. They aim to staff us for the average number of visits for the year, so that every year during flu season we have cancer patients lying for days at a time in the hallway with no privacy. It is disgusting, and unfortunately will never change as long as the people in charge of hospital budgets and their families are treated as VIPS, skipping the line for hospital beds when they are sick. Every hospital CEO everywhere should have to sign a pledge to be treated exactly the same as every patient in the hospital if they were to become ill. If so, I think we would see rapid changes to the way emergency departments were funded. 

“Expired” or “best before”?

Charlton N, Berry DC, Kannan V, Yee R, Carlson JN, Orkin AM. The use of expired resuscitation medications for life-threatening first aid conditions: a systematic search and narrative review. Resusc Plus. 2025 Sep 23;26:101110. doi: 10.1016/j.resplu.2025.101110. PMID: 41142213

You are on a small propeller plane making a journey over the Andes and one of your fellow passengers develops anaphylaxis. The flight attendant finds a first aid kit in the back of one of the overhead bins. You have to wipe a layer of cobwebs off to even find the zipper. To your amazement, there is an epipen in the kit, but the plastic is so faded the words are hard to read. It looks like it was made in the 1980s. Do you use it?

I have covered medication expiry dates in the past. Although we need to maintain high quality standards for drugs (if you haven’t read the book “Bottle of Lies”, I recommend it), there is also an overlay of conflict of interest, where drug companies profit tremendously by having us throw out perfectly good drugs and buy replacements. This is a review that looked at 4 important first aid drugs: aspirin, epinephrine, albuterol, and naloxone. The short answer is that all 4 retain a high percentage of their active ingredient well after “expiry”, with no harmful byproducts identified. One study found that albuterol retained 98% of its active drug, with less than 0.5% impurities, 20-30 years after the stated expiry. Aspirin had 97% of active drug levels at 9 months and 90% by 30-40 years, and degradation did not result in harmful products. Naloxone had 100% active drug levels at 19 months and ‘high levels’ of active drug up to 27 years. Epinephrine might be the worst, with levels between 55-75% after 10 years of regular storage. (There are prior studies showing much higher epinephrine levels, but with autoinjectors stored in climate controlled warehouses. This is real life data.) The primary limitation is that these studies are all looking at the chemical ingredients, but not clinical efficacy. For a ventolin inhaler, for example, I could imagine the propellant or delivery mechanism might fail, which would make the high percentage of active drug sort of irrelevant. If you asked a lay person, they might worry about a drug that only has 90% of its active dose. However, we know that almost all drug doses are completely made up, and so slight changes for most medications are probably irrelevant. (There are a few exceptions, such as levothyroxine, where small dose changes really matter, but these rare exceptions really highlight how little precise doses matter with most of our medications.) To me, it seems pretty obvious that expired medications will remain effective. Especially when we are talking about drugs with immediate effect, like albuterol, epinephrine, or naloxone, where you can just give more if the first dose isn’t working. The only question would be harm from degradation products.

Bottom line: If your choice is between doing nothing and using an expired medication in a life threatening medical emergency, you use the expired medication every time. 

Is it time for doctors to write “dying certificates”?

Brindley PG, Morgan M. Diagnosing dying: is it time for doctors to write “dying certificates”? BMJ. 2024 Jun 4;385:q1167. doi: 10.1136/bmj.q1167. PMID: 38834200

Like many of the essays I include here, my summary cannot possibly do justice to the original. This is a one page article that you should probably just read. They point out how bad most physicians are at communicating about the end of life. “Instead of 30 minutes of conversation we default to two weeks on machines.” We use euphemisms like, “the prognosis is guarded”, instead of direct language. I like their suggestion of “they are sick enough to die.” They point out that dying is a life event we all will face, and should be a moment for family and community. Instead, “at a time when community and connection matter most, we too often default to high-tech and low-touch. Moreover, misguided heroism on the part of medicine can mean whisking people away from those they love, and from the

homes, and familiarity that they deserve.” They want us to be better in communicating about the end of life to improve the process for our patients and their families. “A “dying certificate,” or at least unequivocal communication, helps everyone understand that the end is approaching and is likely unavoidable. If a certificate seems too dramatic, too certain, then at least let us commit to speaking and writing more clearly.” “Nowadays, dying hides in plain sight. It is institutionalised, technologically-mediated, and obscured by monitors and Latin words. In hospitals, the tea, cake and pets are frequently banned, and family visitation is policed. Doctors still claim expertise because we know the pills and machines. However, let’s admit our amateur status when it comes to helping families make sense, connections, and meaning. Dying should be nurtured by society, instead it has been highjacked by “big medicine.”

The monthly ‘what is Justin smoking’ paper

Apostolov A, Bradley A, Dreher S, Dwyer C, Edwards J, Evans ME, Gu N, Hansen J, Lewis JD, Mashburn AT, Miller K, Richardson E, Roller W, Stark A, Swift J, Zuniga O, Lesch R. Tracking domestication signals across populations of North American raccoons (Procyon lotor) via citizen science-driven image repositories. Front Zool. 2025 Oct 2;22(1):28. doi: 10.1186/s12983-025-00583-1. PMID: 41039604

Last month I had a ridiculous rhinoceros paper. This month, I changed my attention to the raccoon – widely loved and/or hated across the city of Toronto. We often think of domestication as a purely human led endeavour, but anyone who reads the news these days should probably intuit that that might be giving humans too much credit. This paper discusses the broader theory that suggests domestication must start long before humans are actively involved, as animals and humans become habituated to each other when living in the same environment. Humans generate a lot of refuse, and so there is a strong selective pressure on wild animals to adapt to the human environment. This would require the animals to become less afraid of humans, and also perhaps for humans to become more accepting of the animals. To this point, I am completely on board with this paper, but then they move into basically animal phrenology, with the theory that all domestic animals share common skull traits as part of a general “domestication syndrome”. They used images collected by regular people on an app to compare the appearance of raccoons based on how far they lived from human population centers. Although the data looks like a mostly random scatter to me, they find a 3.5% reduction in snout length between rural and urban raccoons, which could support their hypothesis. As far as I know, this type of research isn’t preregistered, so it is hard to know whether this was truly their primary hypothesis, or whether p-hacking might be at play. Obviously, this is already far too many words to spend on a paper about raccoon evolution. However, this is the area of PubMed where I now seem to be spending my time, so you can probably expect at least one truly bizarre article to skip over each month. Is there any relevance to your practice of medicine? Perhaps only insofar as staying scientifically curious will make you a more rounded physician.