Friday, 14 August 2020

Propofol for migraine in the ED: A pilot controlled trial

Migraine – characteristics, recommended treatment


This was an open label pseudo-randomized trial of propofol (1mg/kg) vs. standard therapy for migraine in a single busy ED in Melbourne. 

Patients were included if the treating doctor thought they would require intravenous medication.

Patients were excluded if there was not a resuscitation bay available and a few other things.

The primary outcome was time to discharge from the ED or short stay unit. This is obviously not a patient-oriented outcome and subject to bias due to lack of blinding.


Over 28 months they enrolled 30 patients (one excluded in analysis due to missing data).

The time to discharge was about 5 hours in the propofol arm and 9 hours in the usual care arm. (P=0.021). The authors conclude that patients go home quicker.

There are some MAJOR problems with this study, mostly to do with study design, safety, efficacy, feasibility, and ethics.

There are substantial challenges to using propofol for migraine. It requires a set up for deep procedural sedation. It needs senior clinicians, airway nurses, and a resuscitation room for probably 30 minutes at a minimum. What are the harms to all the other patients in the ED that we are now potentially neglecting?

It is self-evident that the clinicians considered this as they were only able to enroll one patient a month for a common condition in a busy tertiary hospital.

In addition, with only 30 patients enrolled it cannot make any claims about efficacy or safety. Of the 15 patients who got propofol, six patients required additional medications. Two patients required airway maneuvers to maintain oxygenation & ventilation.

I am a bit surprised this study was granted ethical approval. But obviously there are differing opinions.

For now, please do NOT give propofol for migraine!



Mitra B, Roman C, Mercier E, et al. Propofol for migraine in the emergency department: A pilot randomised controlled trial. Emerg Med Aus 2020;32:542-547. [link to article]




Dexamethasone in Hospitalized Patients with COVID-19- Preliminary Report

COVID-19 and the cheap, old, boring drug that could treat it

Beyond supportive care, we currently don’t have much to treat COVID-19. Remdesivir might decrease hospital length of stay. But we have found no medications that save lives.

The unprecedented RECOVERY trial involves 176 NHS organizations in the UK and are answering clinical questions at an lightning pace. This adaptive RCT has been looking at the use of dexamethasone, hydroxychloroquine, lopinovir/rotonavir, tocilizumab, and convalescent plasma.

This “preliminary report” is publishing the data on dexamethasone.

The background is COVID-19 often results in some immune mediated lung injury. Could steroids mitigate this? Or might they may cause harm by inducing immunosuppression?

6425 hospitalized patients with COVID-19 were randomized in a 1:2 fashion to dexamethasone vs. usual care.

The primary outcome was all-cause mortality at 28 days. They had a bunch of prespecified secondary outcomes.

The dose of dexamethasone was 6mg/day for 10 days.


Mean age was 66. Median days from symptom onset was 8 days. 16% of them were intubated and 60% were getting supplemental oxygen. 24% had no oxygen requirements.

Overall, 23% of patients randomized to dexamethasone died while 25% died in the usual care group for a number needed to treat (NNT) of about 35. (Rate ratio 0.83, 95% CI 0.75-0.93; P less than 0.001)

But it seemed to work the best in the sickest patients. Those who were intubated had an absolute mortality reduction of 12% for an NNT of 8. Those only on supplemental oxygen derived small benefit at a 3% reduction.

Unfortunately, it appears there is a trend toward harm in patient not requiring oxygen with a number needed to kill of about 26.

With the multitude of crap quality studies being rushed to publication, this is an absolute breath of fresh air. Prior to the final manuscript, this study has already changed the guidelines around the world.

Bottom line?

Intubated patients should get dexamethasone. We should probably give it to sicker patients on oxygen, but avoid it in everyone else.

Of course, this could all change tomorrow…



Horby P, Lim WS, Emberson JR, et al. Dexamethasone in Hospitalized Patients with COVID-19- Preliminary Report. NEJM. 2020,  DOI: 10.1056/NEJMoa2021436 [link to full text article]


Thursday, 13 August 2020

Five-year follow-up of antibiotic therapy for uncomplicated appendicitis in the APPAC Randomized Clinical Trial

Long term outcomes are important when trying to understand the usefulness of a non-surgical approach to appendicitis. If all the patients eventually fail and have an appendicectomy, then what is the point?

The Appendicitis Acuta (APPAC) trial out of Finland randomized 530 patients with CT proven uncomplicated acute appendicitis to antibiotics vs. open appendicectomy. Now we have some 5-year data.

The cumulative incidence of appendicitis was 27% at year one, 34% year two, 35% year three, 37% year four and finally 39% by 5 years.

The five year overall surgical complication rate (SBO, surgical infection, incisional hernias, and abdominal pain) was 24%.

These are good statistics to consider when considering shared decision-making.

But there are a few things to remember.

  • All patients got CT prior to randomization to ensure uncomplicated illness. (i.e no perforation, abscess, appendicolith or suspicion of tumor.)
  • They excluded children and adults over the age of 60
  • They used some crazy C diff inducing doses of antibiotics including an IV carbapenem for 3 days followed by an oral fluoroquinolone and metronidazole. (But Augmentin has been used in other studies.)
  • Patients had open appendicectomies. Laparoscopic surgery would be expected to have a lower surgical complication rate.

What’s the take home?

There is now more and more literature consistently demonstrating the decent efficacy of antibiotic therapy for uncomplicated appendicitis. Decades of surgical tradition is hard to change. But it is getting to the point where patients will need to participate in discussions regarding treatment options.



Salminen P, Tuominen R, Paajanen H, et al. Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial. JAMA. 2018;320:1259-65. [link to article]

 How to Tell If That Pain Is Your Appendix – Health Essentials from  Cleveland Clinic

Monday, 13 July 2020

Electrical vs pharmacological cardioversion for ED patients with acute atrial fibrillation

This was in fact two RCT’s.

The primary one was comparing conversion to sinus rhythm between a drug-before-shock strategy vs. shock only for cardioversion of acute (<48 hours) atrial fibrillation. The second was a nested RCT comparing anterioposterior vs. anterolateral pad placement.

They enrolled about 400 patients. Half were randomised to procainamide infusion before an attempt at DC cardioversion. The other half got matching placebo followed by DC cardioversion.

Both strategies were highly effective in conversion to sinus rhythm at 96% with drug/shock vs. 92% for shock only (95%CI 0-9; p=0.07). Pad placement didn’t matter.

Of note, the procainamide worked for half of the patients and they were able avoid electricity and procedural sedation.

But not emphasized in the paper was the success of doing nothing. Many patients self-reverted during their ED stay and even with placebo infusion. Perhaps we should adopt a wait-and-see approach as suggested by the Dutch and Doyle?

There are a few things to note.

They reported no adverse events at follow up. (But there was one case of “cardiac arrest” when they forgot to hit the sync button… woops!) As per prior similar studies, it looks safe.

The cohort was a bit younger (mean age 60) and most had AF for less than 12 hours. Therefore, care should be taken when extrapolating this study to older patients with longer duration of AF.

11% of patients returned to the ED with recurrent AF within 14 days. This very likely underrepresents the amount of recurrence. Which begs the question of why bother…

There was a trend towards efficacy with the drug shock group with NNT of 25 for more successful overall conversion. This makes physiological sense.

Of course, the biggest issue is procainamide is not officially available in Australia and in some other countries. The authors suggest other antiarrhythmics might be useful.

Overall, I think this is compelling evidence to a consider a drug/shock strategy. But I still think doing nothing might be even better. Time for shared decision making.



Steill I, Sivlotti M, Taljaard M, et al. Electrical vs pharmacological cardioversion for emergency department patients with acute atrial fibrillation (RAFF2): a partial factorial RCT. Lancet 2020;395:339-49. [link to article]

SGEM#260: Quit Playing Game with My Heart – Early or Delayed ...

Multicenter Emergency Department Validation of the Canadian Syncope Risk Sore

Syncope Rules?

We all love syncope with its ubiquity and complexity. Most causes are benign but the needle in the haystack may be fatal. Wouldn’t it be nice to have a good clinical decision instrument to help us out?

These researchers sought to validate the Canadian Syncope Risk Score (see below) among 3819 patients that presented across 9 ED’s in Canada.

The risk score is mostly a quantification of what we evaluate already. History, ECG, ED diagnosis and troponin (if performed). Score ranges from -3 to 11 and patients are put into one of five categories; very low, low, medium, high or very high risk.

The primary outcome was “30-day serious outcomes” as determined during medical record review, telephone follow up, return visits, and coroners’ database.


The proportion of patients with serious outcomes increased from 0.3% in the very low risk group to 51% in the very high risk group.

This seems ok but I’m not so sure this “rule” will gain traction.

First, it’s too complicated to commit to memory. We would need to refer to MDCalc which will decrease its utility.

Second, it hasn’t formally been compared to what we already do… which is gestalt. (However, some may argue that it is already heavily reliant on gestalt.) It is possible that following the rule could make things worse. 

Third, we know rules tend to perform less well in complex disease processes. This is why doctors have not been replaced by robots… yet.

How might I use the rule?

Probably how we use most rules; something we can write in the medical record to support a decision we have already made. This might sound cynical, but gestalt is probably the best rule.



Thiruganasambandamoorthy V, Sivilotti M, Le Sage N, et al. Multicenter Emergency Department Validation of the Canadian Syncope Risk Score. JAMA Intern Med. 2020;180:737-44. [link to article]

You passed out, Eh?- The Canadian Syncope Risk Score and its use ...



Saturday, 11 July 2020

Apixaban for the Treatment of DVT/PE Associated with Cancer

Most DVT’s and PE’s in patients with cancer are treated with low molecular weight heparin. As if the malignancy was not enough, now they will get painful daily injections often for the rest of their life.

Seems cruel… why not just use a DOAC?

In turns out, there was no good evidence that they could be used in this population and there was some concern about increased bleeding.

Sounds like a good reason for a clinical trial?

These authors performed a randomized open-label noninferiority trial comparing apixaban to daltiparin in over 1000 patients in 119 centres in Europe, Israel and the USA.

They excluded patients with any CNS malignancy, leukemia, basal and squamous cell skin cancers, or if they were high risk of bleeding.

The primary outcome was recurrent DVT/PE during the trial period.


Recurrent DVT/PE occurred in 5.6% of the apixaban group and 7.9% of the daltiparin group. This met their non-inferiority margin but was not quite enough to claim superiority (p=0.09). Major bleeding was the same in both groups.

All good?!?


There was a trend towards more “clinically relevant” non-major bleeding with apixaban at 9% compared to 6% . This should lead to some caution as they already excluded those with high risk of bleeding.

Although the authors claim this was an “investigator-initiated” trial, it was funded by a “Bristol-Myers Sqibb-Pfizer Alliance.” In addition, there is an impressive list of author conflicts of interest- lecture & consulting fees, grant money, travel expenses, advisory board fees, etc. etc.

Either way, this trial published in the NEJM will be considered “high quality evidence” and will change the guidelines. Hopefully it's right.


Agnelli G, Becattini C, Meyer G, et al. Apixaban for the Treatment of Venous ThromboemolismAssociated with Cancer. N Engl J Med 2020;382:1599-607. [Link to article]

Thursday, 21 May 2020

Early self-proning in awake, non-intubated patients in the ED: A single ED’s Experience during the COVID-19 pandemic

This pilot study was carried out at the crazy Lincoln Medical Center, New York City. Located in the Bronx, it is the third busiest ED in the United States. In the grips of a pandemic, it is the perfect place to study potential treatments of COVID-19.

Awake proning has been shown to be beneficial in patients with ARDS and anecdotal reports have suggested it may be helpful for patients with coronavirus.

This pilot study enrolled a convenience sample of 50 patients who presented to their ED with hypoxia without resolution despite supplemental oxygen and who were capable of self-proning. They excluded patients who were NFR, getting NIV or intubated in the prehospital setting. All were eventually confirmed as COVID positive.

They termed these patients the “happy hypoxemics” as they generally looked quite well without respiratory distress despite having low oxygen saturation.


The median SpO2 at triage was 80% and this improved to 84% with supplemental oxygen. After 5 minutes of proning the saturation increased to 94%!

18 of the 50 patients eventually required intubation; 13 of those (24%) within the first 24 hours.

This pilot study has lots of limitations; no control group, no idea if proning resulted in meaningful patient-oriented outcomes. Nevertheless, it has adequately raised the hypothesis for a clinical trial.  A search of shows there are now several in progress.

Could there be harm from self-proning? It is possible. But these authors recommend proning until we get better quality evidence to inform practice. They have typical protocols whereby patients are asked to rotate about every 30 to 120 minutes.

Proning support cushions are already being sold in the USA. You can get one for US$164! I would not be surprised if a device manufacturer comes out with a human rotisserie device. No joke… watch this space!


Caputo ND, Strayer R, Levitan R. Early Self-Proning in Awake, Non-intubated Patients in the Emergency Department: A Single ED’s Experience during the COVID-19 Pandemic. Acad Emerg Med. 2020;27(5):375-378 [link to full text article]