Tuesday 26 February 2019

Does POCUS improve outcomes in ED patients with undifferentiated hypotension? Hocus pocus; how the SHoC-ED trial got it so wrong.

This study recruited a convenience sample of patients from six ED’s with undifferentiated hypotension. They were randomised to early point-of-care ultrasound (POCUS) vs standard care without POCUS.

The primary outcome measure was a 10% reduction in mortality. Secondary outcomes included length of stay, rates of CT scanning, use of inotropes, fluid administration, etc.

In the end, they could not find any difference. POCUS doesn’t work for undifferentiated hypotension!?

So how did this study get it so wrong?

Two primary reasons.

First, their primary outcome measure was wrong. It is preposterous to expect this diagnostic test would result in a 10% reduction in mortality. But I won’t belabour this point…

Second, and much more important, they excluded patients who stood the most to benefit from ultrasound. This merits further explanation.

“… they excluded patients who stood the most to benefit from ultrasound.”

They excluded patients who were pregnant as they thought it would be unethical to miss an early diagnosis of ruptured ectopic. They also excluded patients with trauma or suspected ruptured AAA for similar reasons.

They only included only an extraordinarily selected group of non-consecutive patients. Only 273 patients were enrolled from 6 ED’s over 4 years! That’s just over one patient per month per ED. Obviously most patients with hypotension were not included.

Even in “undifferentiated hypotension” there are still varying degrees of working diagnosis and clinical suspicion.

If I was a doctor considering enrolling a patient with undifferentiated hypotension in this study, would I be comfortable if my working diagnosis included patients at risk for pericardial tamponade, tension pneumothorax, or massive pulmonary embolism? Would I enrol them if I really wanted a good look at their lungs or IVC?

Put simply; would I enrol them if I really thought the early ultrasound was needed?

Of course not.

One only needs to look at their recruitment to see this ring true. About half had sepsis. Only about 4% had a diagnosis where early ultrasound could have had made a substantial benefit.

To say that I am annoyed by this study is an understatement. It is misleading and may result in substantial harm when it is bound to be misinterpreted. This study is hocus pocus!

I believe early POCUS for undifferentiated hypotension has face validity. It is one of the first things I do as it narrows the differential diagnosis and potentially guides treatment. It is quick and non-invasive. On occasion, it picks up a “can’t miss” diagnosis and saves lives. Misleading studies are not going to change this.


Atkinson PR, Milne J, Diegelmann L, et al. Does Point-of-Care Ultrasound Improve Clinical Outcomes in Emergency Department Patients with Undifferentiated Hypotension? An International Randomized Controlled Trial From the SHoC-ED Investigators. Ann Emerg Med 2018;72:478-489. [link to abstract]

Monday 25 February 2019

Effect of Cricoid Pressure Compared with a Sham Procedure in the RSI of Anaesthesia: Old habits are dying hard

The use of cricoid pressure to prevent aspiration during intubation was never based on high quality evidence. Recently, it has been dying a slow death with many ED doctors abandoning this practice. But there still is controversy, and our anaesthetics counterparts are having trouble letting go.

Pulmonary aspiration during endotracheal intubation is exceedingly uncommon. The study of rare events requires enrolment of lots of patients to have the statistical power to come to an answer. As such it has not been feasible to get high quality RCT’s to inform practice.

These authors tried… but we are still not totally clear.

This was a double blind RCT non-inferiority trial conducted in 10 academic centres in France. 

Patients undergoing RSI in the operating theatre (not the ED) were randomised to proper cricoid vs. sham cricoid (hand was put in place, but no pressure applied).

The primary endpoint was aspiration and they also looked at several secondary outcomes.

They considered sham to be “non-inferior” if the incidence of aspiration was not more than 50% higher (i.e. relative risk of 1.5).


After enrolling 3472 patients they only had 10 cases of aspiration in the cricoid group vs. 9 in the sham. This gives a relative risk of 0.9.

Sham wins!?!

Not officially…

With such tiny numbers of aspiration, it is no surprise that the confidence intervals are rather wide. The 95% confidence interval was 0.33-2.38. This is greater than the non-inferiority margin of 1.5 and as such this is officially a negative study… i.e. they failed to demonstrate the non-inferiority of the sham procedure in preventing pulmonary aspiration.

From a purist EBM standpoint this may be a negative study, but many interpret this as another nail in the coffin for cricoid pressure. Outcomes were rare regardless. A look at the secondary outcomes shows worse laryngoscopic view and greater time to intubate with cricoid. There was really nothing to suggest any benefit from cricoid pressure.

If someone happened to “invent” cricoid pressure today, we would never take it up. But tradition, culture and "eminence-based" medicine is hard to kill.

Unfortunately, this study has the possibility of being misleading. Years from now, I imagine it will be casually mentioned as evidence in favour of cricoid pressure. This is precisely why it is good to dissect these papers, take the pressure off (pun intended) and to find the hidden truth.


Birenbaum A, Hajage D, Roche S, et al. Effect of Cricoid Pressure Compared with a Sham-Procedure in the Rapid Sequence Induction of Anesthesia. The IRIS Randomized Clinical Trial. Jama Surg 2019;154:9-17. [link to article]

Saturday 23 February 2019

ED Discharge of Patients with Pulmonary Embolism; Marketing Rivaroxaban

Do PE patients discharged from the ED on rivaroxaban have a shorter length stay than those admitted to hospital?

Yes, you read the question correctly…

This was essentially the aim of a recent study published in Academic Emergency Medicine.

This RCT conducted at 35 hospitals (yes 35… but they planned on 57!) enrolled 114 subjects randomised to early discharge on rivaroxaban vs. “standard of care” (generally admission to hospital). Primary outcome was length of stay.

It turns out the early discharge had a much shorter length of stay at 4.8 hours vs 33 hours for standard care.


Why would anyone conduct an RCT to answer such an obvious research question (Notwithstanding, it is considered unethical to conduct an RCT without clinical equipoise… oh well…)



All 11 of the authors disclosed conflict of interest in taking money from Janssen. Guess what drug they make…

Two of the authors were employed by the drug company and declared that they were involved in the study concept, design, analysis, interpretation and revision of the manuscript.

One other important aspect may have slipped your attention.

Was this a “seeding trial?”


As per Sax HC & Rennie D, Seeding Trials: Just Say “No” (Ann Intern Med. 2008;149:279-280)

Why would a drug company go to the expense and bother of conducting a trial involving hundreds of practitioners- each recruiting a few patients- when a study based at a few large medical centres could accomplish the same scientific purposes much more efficiently? The main point of a seeding trial is not to get high-quality scientific information: It is to change the prescribing habits of large numbers of physicians. A secondary purpose is to transform physicians into advocates for the sponsor’s drug. The company flatters a physician by selecting him because he is “an opinion leader” and incorporates him in the research team with the title of “investigator.” Then, it pays him good money: a consulting fee to advise the company of the drug’s use and another fee for each patient he enrols. The physician becomes invested in the drug’s future and praises its good features to patients and colleagues. Unwittingly, the physician joins the sponsor’s marketing team. Why do companies pursue this expensive tactic? Because it works.

Without internal company documents, we’ll never know the true reason for this study. But I highly doubt it was to advance great research.


Peacock WF, Coleman CI, Diercks DB. et al. Emergency Department Discharge of Pulmonary Embolism Patients. Acad Emerg Med 2018;25:995-1003. [full text link]

Thursday 21 February 2019

Ketamine for severe ethanol withdrawal?

Ketamine seems to be good for everything; procedural sedation, induction of anaesthesia, pain management, depression and now severe alcohol withdrawal?

These authors from the heavily drunk city of Pittsburgh point out that there is a good reason why ketamine might work. Ethanol, like ketamine is also an NMDA receptor antagonist. I didn’t know that…

We have traditionally only targeted the GABA receptor. But perhaps there could be some benefit with also hitting the neglected NMDA.

This was a chart review comparing outcomes in 29 patients before and 34 patients after a guideline for ketamine infusion was instituted in their ICU. The infusion was at 0.15-0.3mg/kg/hour continuously until the delirium resolved. This is about 10-20mg/hr in an a 70kg adult… not very much.


Ketamine worked great!

Mean ICU days were almost halved. There were shorter mean hospital days, less benzodiazepine use and the rate of intubations plummeted (see table below for more details).

But before we get too enthusiastic, we need to remind ourselves this is very low-quality evidence.

There were no methods to their chart review, and they did not appear to use prespecified outcome measures. Retrospective data can be of poor quality etc.

But the biggest issue is the retrospective nature of this study. The small before and after groups could have been rather different to start with… like comparing apples to oranges. Therefore, the observed differences may have had nothing to do with ketamine.

Some would say the evidence of ketamine in severe alcohol withdrawal is as weak as vitamins for sepsis!


In the end, what would I do?

I could easily be proven wrong, but I might consider this low dose ketamine infusion if I had a suitable patient with severe ethanol withdrawal… and I would also give them some vitamins.


Pizon AF, Lynch MJ, Benedict NJ, et al. Adjunct Ketamine Use in the Management of Severe Ethanol Withdrawal. Crit Care Med 2018;46(8):e768-e771. [Free full text link]