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