Monday 30 September 2019

Comparison of manual pulse palpation, cardiac ultrasonography and Doppler ultrasonography to check the pulse in cardiopulmonary arrest patients

This study aimed to determine which method of pulse check is the best during CPR. Should we do the traditional manual pulse check, use our ultrasound to look at the heart (POCUS) or use a Doppler on the femoral artery.

Of course, to do such a study would require comparison against a gold standard and calculation of test performance by reporting sensitivity and specificity.

This study did none of this.

In addition, the manuscript is incredibly poorly presented and should not have been published in its current form (example below). Given the sloppiness of the paper, one should really question the veracity of the research conducted.

A more detailed USG was performed when the rhythm returned to normal or when the patient accepted exitus.

As this study looks to be fatally flawed, I should probably stop here… but I will mention a few things.

This study allegedly enrolled 137 patients in a single very busy Turkish ED. Two ED residents with a year of POCUS experience did all of the echo’s. All three methods to check the pulse were performed at the same time; at the start of resuscitation, at 15 minutes and at the end of efforts or ROSC. They tried to maintain blinding by curtain set up as seen in the picture.

They claim the echo’s only took 4 seconds to perform. Contrasted with doppler taking 8 seconds and manual palpation 10 seconds. This sounds impressive (and contrary to other published reports) until you consider the two ED residents were not blinded to the study aims. Nor did they mention how the times were measured.

The study claims the echo was the best (as it was always right by design) and there were a bunch of false positive and negatives with the Doppler and manual palpation.

I’m a big proponent of POCUS and have already incorporated echo as my default pulse check. I can get the images quickly and I feel a I get a better sense of cardiac contractility than with other methods. I occasionally find important pathology such as tamponade, RV strain, dissection, catastrophic valvular regurgitation or cardiac standstill.

AHA/ACC, ILCOR and ERC guidelines support POCUS in arrest, but caution it should not interfere with high quality CPR. To be fair, there has been little high-quality research. There is no doubt we should encourage further formal study with robust methods and design. 

We don’t want our patients to accept exitus.


Zengin S, Gumusboga H, Sabak M, et al. Comparison of manual pulse palpation, cardiac ultrasonography, and Doppler ultrasonography to check the pulse in cardiopulmonary arrest patients. Resusitation 2018;133:59-64. [link toarticle]

Pregnancy-Adapted YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism

There must be something in the coffee houses that make the Dutch so sensible.

Just like the HEART score, they have created another simple clinical decision instrument that has face validity (regardless if it is actually proven). This time, it’s for investigating potential PE in pregnancy.

This multicentre, international trial was conducted at 18 hospitals over 5 years. They included pregnant adults who had been referred to the ED or obstetrical ward with suspected PE.

They aimed to determine whether their pregnancy-adapted YEARS algorithm could be used to avoid diagnostic imaging in this at-risk population.

Simply put, the algorithm is as follows:

  • Three criteria were assessed in all patients; clinical signs of DVT, haemoptysis, whether PE was thought to be the most likely diagnosis. D-dimer was measured.
  • Patients with clinical signs of DVT underwent ultrasound.
  • If a patient did not meet any of the three YEARS criteria and the D-dimer was less than 1000ng/ml a diagnosis of PE was considered to be ruled out.
  • If a patient had any of the YEARS criteria and the D-Dimer was less than 500ng/ml then PE was ruled out.
  • All the remaining patients were referred for CTPA.

The primary outcome was the occurrence of symptomatic DVT or PE within 3 months. (Patients did not undergo routine screening.) Secondary outcome was the proportion of patients where CTPA was not indicated.


About 500 women were included. 20 (4%) of patients had a PE diagnosed at baseline. Only one patient (0.2%) was diagnosed with a DVT in the follow up period. There were no PE’s and no deaths. CTPA was avoided (not indicated) in about 40% of patients. The efficiency of the algorithm was better during the first trimester (65% avoided CTPA).

Major limitations?

Gold standard screening tests were not performed to look for subsequent DVT or PE. Much like it is hard to find a fever if you don’t take a temperature, it is hard to find VTE if you are not testing for it. But they reportedly did look if patients had symptoms… which is the practical and ethical approach in this RCT.

It is hard for this study to claim safety regarding mortality as death from PE in pregnancy is reasonably low. It will never be feasible to enrol enough patients in an RCT to asses mortality benefit.

What’s the take home?

Using clinical gestalt (i.e. the 3 YEARS criteria) and a pregnancy adjusted D-dimer is a sensible approach. 


Van der Pol LM, Tromeur C, Bistervels IM, et al. Pregnancy-Adapted YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism. N Engl J Med 2019;380:1139-49. [link to article]

Sunday 29 September 2019

IV cefazolin plus probenecid vs oral cephalexin for the treatment of skin and soft tissue infections

It is traditionally thought that IV antibiotics are superior to those given orally. But IV administration comes with extra time, cost, resources, and possibly not necessary.

To answer the question, these authors designed an elegant bias-busting study. It was a prospective, multicentre, double-dummy blind, randomised non-inferiority trial conducted in two Canadian ED’s.

However, the authors soon learned valuable lessons in performing an RCT; feasibility and generalisability.

They had quite strict inclusion and exclusion criteria that hindered patient recruitment. In addition, this also made any conclusions rather difficult to generalise to a broader patient population.

They included adult patients who had what they thought was mild to moderate cellulitis (a bit subjective). They excluded very mild patients, those with renal disease, prior MRSA, prior antibiotic use in the preceding 7 days, infections requiring I&D or debridement, two or more signs of SIRS, bites, PVD, perioperative wounds, etc, etc.

They even excluded patients with BMI greater than 30. That’s most of Canada!

Arguably defeating the whole purpose of the study, participants were brought back to the ED every day for 7 days of treatment. This is hardly decreasing resources and simulating real conditions.

The primary outcome was failure rate at 72 hours. About 300 patients were thought needed to power the study to a 10% non-inferior margin.

Why 72 hours? A great pearl… 

“This end point is beyond the clinical extension of redness that may be seen in the first 24-48 hours of therapy which would not typically represent treatment failure.”


Over 4 years, they screened 2855 patients for eligibility but finally gave up after randomising 206 patients.

The proportion of patients failing therapy at 72 hours was not statistically different and about 5% in both groups. The authors conclude cephalexin is just as good as IV cefazolin for mild to moderate cellulitis.

It is probably true that we overdo IV antibiotics for many infectious disease processes. But it is disappointing to see such a well-designed study design ultimately unable to provide us with much useful information.


Dalen D, Fry A, Campbell, S, et al. IV cefazolin plus probenecid vs oral cephalexin for the treatment of skin and soft tissue infections. Emerg Med J 2018;35:492-429 [link to article]

Friday 27 September 2019

Duration of ECG monitoring of ED patients with Syncope

How long do we need to monitor patients after an episode of syncope? What a great question…

These authors used data that came from a large multicentre study that developed the Canadian Syncope Risk Score (CSRS). They enrolled consecutive adult patients who presented within 24 hours of a simple syncopal episode.

They collected data on baseline characteristics and were eventually able to risk stratify patients by using their newly derived syncope score into low, intermediate and high-risk groups.

The primary outcome was serious arrhythmic conditions (arrhythmias, interventions for arrhythmias, and unexplained death) over 30 days.

The 30 day follow up was a tremendous undertaking. They had structured review of all available medical records, subsequent visits, hospitalisations, and deaths. They performed a scripted telephone follow up at 30 days and they looked at administrative records for subsequent visits.

A whopping 5581 patients were analysed. As expected, only a small number 7.5% had serious outcomes. The syncope score seemed to work pretty well. The low risk group had 0.4% 30-day arrhythmic outcomes. The intermediate and high risk were 8% and 25% respectively.

The authors state that one-half of arrhythmic events were identified within 2 hours of ED arrival in low risk patients and within 6 hours in the intermediate and high-risk patients.

Based on this, the authors suggest either 2 or 6 hours of cardiac monitoring is enough after syncope but outpatient cardiac monitoring for 15 days in higher risk patients.

There were a few problems…

Only 11% of the patients were hospitalised and the median ED length of stay was only 4 hours. It is no surprise that they found half of the events early on when they were actually looking. It is quite possible that many events were missed when the patients were not being monitored at home. However, they should have at least they should have picked up on mortality.

Remember the extraordinary work they did in assessing the 30-day outcomes? Unfortunately, quality of data is often inversely proportional to the effort and complexity in obtaining it. In other words, they may have been making conclusions based on bad data.  It’s hard to know.

There have been several attempts at creating a clinical decision instrument for syncope. Unfortunately, these instruments don’t tend to work in complex disease processes. The CSRS has not  been externally validated nor compared to clinician gestalt.

What’s the take home point?

From an evidence-based medicine standpoint, I don’t believe this single study is enough to justifiably change practice. But in our hearts, we all know that low risk patients probably don’t need to be watched very long… and high-risk patients need to be monitored longer. 2 or 6 hours? Who knows…


Thiruganasambandamooooorhylinglangadong, V, Rowe B, Sivilotti M, et al. Duration of Electrocardiographic Monitoring in Emergency Department Patients with Syncope. Circulation 2019;139:1396-1406. [link to article]

Saturday 24 August 2019

Decreased facial expression variability in patients with serious cardiopulmonary disease in the emergency care setting

Could “normal affect variation” be a new physical examination finding that predicts severity of illness?

Dr Jeff Kline thinks it might be. He’s the preeminent PE researcher who brought us the PERC rule. He has conducted this pilot study that suggests we might be on to something.

This was a prospective study of a convenience sample of patients presenting to the ED with dyspnea and chest pain. 50 patients looked at 3 stimulus slides on a laptop computer that recorded their facial expressions. Did their faces move when viewing the slides?

Two independent blinded observers reviewed the recordings and scored the change in facial expression using a coding system. The main analysis compared the results of the score to the patient’s presence of disease (predefined yes/no serious cardiopulmonary disease.)

How well did the change in facial expression perform?

It seemed to be ok.

The expression of surprise had the largest difference between yes/no disease with an area under the receiver operating curve (AUC) of 0.75. But given the low numbers, the confidence intervals were rather wide (95% CI 0.52 to 0.87).

Perhaps the biggest limitation to the study beyond the small numbers was the gold standard. How do we quantify “how sick” someone is? The authors acknowledge several patients did not meet their predefined determination of “serious cardiopulmonary disease” but were likely sick due to other pathology.

To be fair, Dr Kline points out that we consciously or unconsciously use affect variation as part of our gestalt assessment anyway. How many times have you heard an experienced clinician say, “the patient just looks sick…” But this study is a step towards standardisation and/or quantification of this implicit process.

Could artificial intelligence be the next step… perhaps. Dr Kline co-founded the company BreathQuant Medical Systems Inc that has many patents for medical devices. Perhaps we’ll have “affect variationometer” soon.


Kline JA, Neumann D, Huang MA, et al. Decreased facial expression variability in patients with serious cardiopulmonary disease in the emergency care setting. Emerg Med J 2015;32:3-8. [link to article]

Femoral Nerve Catheters Improve Home Disposition and Pain in Hip Fractures... maybe

There has been a push to perform nerve blocks for femoral neck fractures. Typically, these are single injections with a long acting anaesthetic. But continuous infusions through a femoral nerve catheter may supply better and longer lasting analgesia. Perhaps this could decrease complications from parenteral medications, allow for earlier mobilisation and get patients home faster?

This group from Stanford retrospectively reviewed health records of all geriatric hip fractures during a 4-hour period. About halfway through this time, this hospital started a hip fracture protocol that involved insertion of an ultrasound guided indwelling continuous female nerve catheter (CFNC).

They compared the before group that got standard analgesia vs. the CFNC. They sought to answer three questions; do CFNC improve home disposition rates, do they decrease pain scores & narcotic consumption, and does it decrease opioid-related side effects.  


43% of the patients getting CFNC were discharged home compared to 7% of the standard group. In addition, the patients with nerve catheters had lower pain scores, less opioids, and less side effects.

Sounds great!

But unfortunately, there are some big limitations.

They only included 29 patients. (I find it hard to believe that this was “all” patients with fractures at Stanford over 4 years… selection bias?) So, 43% vs. 7% is really 6 vs. 1 patient. This is hardly strong evidence.

Chart reviews are always problematic, and it does not look like this one followed the usually recommended methods. Of course, patients were not randomised. As such, there may have been some further selection bias.

I also wonder if the new protocol introduced other aspects of care that led to improvements. Perhaps this is why the “after” group looked better.

Nevertheless, I think the idea of femoral nerve catheters is quite compelling. Hopefully we can get further data to inform our practice.  


Arsoy D, Huddleston JI, Amanatullah DF, et al. Femoral Nerve Catheters Improve Home Disposition and Pain in Hip Fractures Treated with Total Hip Arthroplasty. J Arthro 2017;32:3434-3437. [link to full text]

Friday 23 August 2019

Behavioral Changes in Children After ED Procedural Sedation

Image result for dumb and dumber
It is unusual to see such an awful paper published in a reasonably respected journal. This addition to the medical literature has only made us dumber.

The purpose of this study was to determine the proportion of children undergoing procedural sedation for fracture reduction in the ED that have negative behaviours afterwards. With this information, the authors claim that we could possibly improve things by treating the child’s anxiety prior to sedation. (But this aspect was not studied).

This was a prospective cohort study of a convenience sample of kids getting IV ketamine for reduction of (mostly) broken arms. The child’s anxiety was measured on a scale prior to the procedure. Negative behaviours were measured by parents on another scale 1-2 weeks after discharge. There was no control or comparator group.

82 patients were analysed. 33 kids were “highly anxious” before sedation and 18 had negative behaviours after ED discharge.

The authors clearly imply that the procedural sedation itself was causal to the negative behaviours.


What about the traumatic event that caused the fracture, the pain from the injury, the wait to be seen by a doctor in a chaotic ED, the visible worry of the parents, the disruption to sleep, play, and activity from injury & plaster. Could they have potentially caused some anxiety afterward?

Evidently not… it must have been the ketamine from the procedural sedation.

This paper is shameful.

It is VERY likely the ketamine was protective of negative behaviours and changing this would have resulted in worse outcomes. When used correctly, ketamine is a wonderful drug for procedural sedation. It is incredibly safe, provides pain relief, amnesia and excellent conditions for procedures.


Pearce Ji, Brousseau DC, Yan K, et al. Behavioral Changes in Children After Emergency Department Procedural Sedation. Acad Emerg Med 2019;25:267-274. [link to article]

C-MAC vs Direct Laryngoscopy for Rapid Sequence Intubation in the ED

Prior studies have clearly proven a video laryngoscopes (VL) generally provide a better view of the chords. But does this translate into improved first pass success rates of intubation?

This study tried to determine which is ultimately better; a C-MAC or old fashion direct laryngoscopy (DL)? This is probably a decent research question.

150 ED patients undergoing RSI in a single ED in Zurich were randomised to either C-MAC vs. DL.  

For "ethical reasons" they excluded patients that they thought would be difficult to intubate. The primary outcome measure was first pass success rate. It was powered to find a 14% difference between the groups.

Unfortunately, all intubations were performed by one of three “very experienced” anaesthetic consultants.

Can you guess the first pass success rate for “very experienced” anaesthetists for simple intubations?

Yes, you guessed it… 100% in both groups. (Well, just about.)

This study was never going to find a difference and I wonder why they went to so much effort in the first place. Seems like it was always going to be a waste of time.

We already know that video laryngoscopes are taking over. But what do you do when the scope fails, unavailable, or needs rescue?

Learn both.


Sulser S, Ubmann D, Schlaepfer, et al. C-MAC videolaryngoscope compared with direct laryngoscopy for rapid sequence intubation in an emergency department. Eur J Anaesthesiol 2016;33:1-6. [link to article]

Saturday 29 June 2019

Buddy taping vs. Plaster for Neck of 5th Metacarpal (Boxer’s) Fractures

I love saving time in the ED. Much of this can come from avoiding procedures that don’t provide benefit to the patient.

Should we dump plaster casting for Boxer’s fractures?

This was an RCT from Queensland, Australia. Evidently, they do a lot of punching in Queensland.

They included patients between 18-70 years old, simple closed fractures without rotation and an angulation of less than 70 degrees. Yes, you read that correctly, they tolerated up to 70 degrees.

126 patients were randomised to buddy taping or plaster cast immobilisation.

The primary outcome was hand function at 12 weeks using the quickDASHquestionnaire. They also looked at pain, satisfaction, return to work or sport, and quality of life.

As expected with this cohort of patients, there were quite a few lost to follow up and 97 patients underwent intention to treat analysis.


At twelve weeks, both groups were the same on the quickDASH questionnaire. Those randomised to buddy taping returned to work earlier than those in the plaster group. Other measures were also similar. Ultimate fracture angle at follow up was similar at about 30 degrees.

The authors conclude, “we advocate a minimal intervention such as buddy taping for uncomplicated boxer’s fractures.”

However, there were several limitations to this study. It was not blinded which could have introduced bias. The study design should have really been a non-inferiority trial.

But there may have been a bigger issue.

The quality of the conclusion is only as good as the validity of the primary outcome measure. I’m not convinced that the quickDASH questionnaire is robust enough to reliably measure the big picture. In addition, capture of data may not have been the most discerning; thus pushing the conclusions towards the null hypothesis.

In the end, our referring doctors (ortho, plastics, or hand specialists) are going to dictate their preferences to us. Given the overall quality of the evidence, I don’t have a problem doing what they like.

My local hand specialists have asked us to continue with plaster immobilisation. They feel you can get a better reduction using the Jahss technique, have less initial pain, less narcotic use and possibly require less operative reduction. Of course, this is an eminence-based recommendation. If I moved to Queensland, I will probably be buddy taping... and watching my back. 


Pellatt R, Fomin I, Pienaar C, et al. Is Buddy Taping as Effective as Plaster Immobilization for Adults With an Uncomplicated Neck of Fifth Metacarpal Fracture? A Randomized Controlled Trial. Ann Emergency Med. 2019; 74:22-97. [link to article]

Early vs. Delayed Cardioversion in Recent onset of Atrial Fibrillation

We know from prior studies that acute atrial fibrillation will frequently spontaneously revert. So, when patients arrive to the ED, which is better? Immediate cardioversion or a “wait-and-see" approach.

To attempt to answer this question, these Dutch investigators conducted a multicentre randomised noninferiority trial. They enrolled stable patients with recent onset (less than 36 hours) to early cardioversion vs. wait-and-see.

The wait-and-see approach involved giving rate control medications and eventual cardioversion if the AF was not resolved by 48 hours.  

The primary endpoint was the presence of sinus rhythm at 4 weeks. However, there were other important secondary measures they captured such as rate of spontaneous resolution, resource utilisation, recurrence of AF, safety etc.


By 4 weeks both groups were about the same and within their prespecified non-inferiority margin. Sinus rhythm was present in 91% of the delayed group vs. 94%.

So, it doesn’t matter?

Perhaps it does… In the delayed group, the rate of spontaneous resolution was 70%! This begs the question, why do we bother with such an early aggressive approach to AF when it very often spontaneously resolves.  Can we limit the potential harms of antiarrhythmic medications and procedural sedations and let nature take its course?

These findings are consistent with prior researchDoyle B et al. Heck, I may not ever get published in the NEJM but at least I have been referenced! 

What do I do?

This is the time for shared decision making. Pull up a chair and have a chat to the patient.  It also depends on how symptomatic the patient is, their prior experiences, rates of recurrence, and dare I say, a busy department.

Quick… don’t just do something, stand there!


Pluymaekers N, Crazy Dutch Name, Dudink J, Luermans J, et al. Early or Delayed Cardioversion in Recent-Onset of Atrial Fibrillation. N Engl J Med 2019;380:1499-1508. [link to article]

Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke: how fragile can we be?

The biggest, baddest controversy in Emergency Medicine just got worse.

Yes, it’s stroke lysis.

This multicentre RCT enrolled adult patients in whom alteplase or placebo could be given between 4.5 to 9 hours after onset of stroke or on awakening with stroke symptoms. A prerequisite for inclusion was a perfusion deficit (area of ischemic but not infarcted brain) on CT or MRI.

The primary outcome was a score of 0-1 on a modified Rankin scale (mRS) adjusted for age and baseline severity of stroke. Of course, they looked at many secondary outcomes including the classic ordinal shift analysis and some safety measures.

They estimated a sample size of 400 patients would be needed in order to have 80% to detect a difference of 15% in the primary outcome.

Recruitment was slow going. They only enrolled 225 patients over 8 years in in 28 centres! That’s about one patient per centre per year! Yikes. No wonder they called it quits early. They claimed the WAKE-UP trial published in May 2018 caused them to lose clinical equipoise and they terminated early. I think they probably had enough anyway…


40 (35%) patients in the alteplase group were mRS 0-1 vs. 33 (29.5%) in the placebo group (adjusted risk ratio, 1.44 95% confidence interval 1.01 to 2.06; P=0.04). Symptomatic ICH was 6% vs. 1%.

Thrombolysis is a winner!??!!

Unfortunately, it is not so clear.

There was no statistical difference in the primary outcome when they used their originally proposed logistic regression modelling rather than a different method introduced during recruitment. The unadjusted analysis; no difference. There was no difference in the ordinal shift analysis (which ironically was touted as the saviour of IST-3). But most of all, the results are just plain fragile.


The fragility index was less than one. Put another way, if one less patient in the alteplase group did not meet the primary outcome, the trial would have been negative. This seems far from a definitive trial.

The authors claim that “further trials of thrombolysis in this time window are required.” This seems rather contradictory when they claim to have stopped their trial due to lack of clinical equipoise.

What to think?

If I was calling the shots, I would not extend my window. But at the same time, others may interpret this study differently. 

However, much of this might be a storm in a teacup. The vast majority of patients in this window derive neither harm nor benefit from thrombolysis (NNT 17 if you believe the results). In addition, clot retrieval is all the rage now.  


Ma H, Campbell BCV, Parsons MW, et al. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke. N Eng J Med 2019;380:1795-803.[link to article]

Wednesday 24 April 2019

Changing target temperature from 33 to 36 in the ICU management of OHCA: a before and after study

I’ve always been skeptical of the original studies claiming efficacy of therapeutic hypothermia for out-of-hospital cardiac arrest (OHCA).

Image result for the alfred hospital
Two small studies published in 2002 demonstrated a profound treatment effect that caused most of the world to change practice.

Anytime you see a small RCT claiming results that are too good to be true, you need to think that the results are exactly that. Medical reversal is common and much of what is published in the medical literature turns out to be wrong.

Along came Nielsen’s study of Targeted Temperature Management (TTM) in 2013 and most of us reversed back to normothermia. However, several studies have indicated that it is difficult to keep patients at this warmer temperature and there are concerns about fever & possible worse outcomes.
The Alfred Hospital in Melbourne conducted a retrospective before and after study after they changed their targeted temperature from 33 to 36 degrees. They describe their experience and try to compare outcomes.

Over a 30-month period they had 76 patients with OHCA due to ventricular fibrillation. There were 24 in the before group and 52 in the after.

After the TTM change, less patients got active cooling (100% vs. 70%), less time was spent at the target temperature (87% vs. 50%) and fever rates went up from zero to 19%.

The authors compare the before and after outcomes and state there was a trend towards better outcomes with the before group.

Fortunately, the conclusion in the manuscript is appropriately measured:

After the change from a TTM target of 33 to 36 we report low compliance with target temperature, higher rates of fever, and a trend towards clinical worsening in patient outcomes. Hospitals adopting the 36 target temperature need to be aware that this target may not be easy to achieve and requires adequate sedation and muscle relaxant to avoid fever.

I would go a step further.

A small retrospective before and after study can be rather problematic. With such small numbers it is very likely the groups were different; akin to comparing apples to oranges. No amount of adjustment for confounding factors will fix this.

So, I don’t think we should be taking anything away from the trend toward benefit. Much better-quality evidence from the TTM trial shows there is none.

There are also some potential harms noted in this study. They note patients in the 33 degree arm were intubated a full day longer, experienced more shivering, bleeding requiring transfusion and pneumonia.

What’s the take home message?

Overall this was a small study in a single centre that is poor quality evidence to inform practice. It demonstrates it is more difficult to keep patients at a higher target temperature. Whether this has any impact on real patient outcomes is not known but I think unlikely.


Bray J, Stub D, Bloom JE, et al. Changing target temperature from 33 to 36 degrees in the ICU management of out-of-hospital cardiac arrest: A before and after study. Resus 2017;113:39-43. [link to article]

Coronary Angiography after Cardiac Arrest without STEMI

Well regarded guidelines recommend immediate coronary angiography in patients who present with STEMI and cardiac arrest. But what about those that don’t have STEMI? Should they also go to the cath lab?

This RCT conducted in 19 centres in the Netherlands attempted to answer this question.

These researchers randomised 552 patients to immediate vs. delayed angiography.

The inclusion criteria were comatose survivors of out-of-hospital cardiac arrest (OHCA) that had shockable rhythms and return of spontaneous circulation. Patients were excluded if they had STEMI in the ED, shock, or an obvious non-cardiac cause of arrest.

The study was powered to detect a whopping 40% difference between the groups. Of course, it is quite ambitious to think immediate angiography would be so efficacious. Therefore, the study had an “adaptive design” that allowed for an increase in sample size if they detected a trend towards benefit during an interim analysis of the first 400 patients. (Kinda sounds like cheating… but I get it)


Those Dutch know how to conduct a study (must be something in the Heineken).

Adherence to protocol was fantastic. Median time to angiography was about 45 minutes in the immediate group and about 5 days in the delayed.

Acute thrombotic occlusion of a coronary vessel was found in a small minority of patients. Only 3.4% in the immediate and vs. 7.6% in the delayed. As such PCI and CABG was performed less than a third of the time.

I think you know where this is going… this was a negative study.

At 90 days 64% of the immediate group and 67% of the delayed group were alive.
So what should we conclude?

I think it is safe to say that we should not send all patients with OHCA without STEMI to the cath lab.

But one of the major challenges with evidence-based medicine is extrapolating the results of a study to the individual patient in front of us. 

What about the patient with some degree of hemodynamic or electrical instability? Or what about lots of dynamic ST and T wave changes on the ECG (of course this could also come from intracranial catastrophe)? What if they just smell like a coronary occlusion?

In summary, don’t send all patients to the cath lab. But I think we should still consider it on an individual basis. Now back to my Grolsch...


Lemkes JS, Janssens GN, van der Hoeven NW, et al. Coronary Angiography after Cardiac Arrest without ST-Segment Elevation. N Engl J Med 2019;380:1397-1407. [link to article]

Effect of a Resuscitation Strategy Using Capillary Refill Time vs. Lactate in Patients with Septic Shock: The ANDROMEDA-SHOCK Trial

Related image

Can capillary refill time (CRT) replace serum lactate as a resuscitation target in septic shock?

Leave it to the South Americans to try to figure this one out… ¡Vamonos Amigos!

This was an RCT conducted in 28 ICU’s in Chile, Argentina, Uruguay, Ecuador and Colombia. (¿Valididad externa?)

424 adult patients were randomised to a resuscitation protocol aimed at either normalising CRT vs. normalising or decreasing lactate levels.

The study was powered to detect an absolute reduction of 28-day mortality by 15%. Of course, this is crazy… nothing would be expected to work this well. As such, this study was always at a high risk of a type II error (i.e. not finding a difference when one truly exists). ¿Vamonos?

Out of interest, the CRT involved training and standardisation as follows

...CRT was measured by applying firm pressure to the ventral surface of the right index finger distal phalanx with a glass microscope slide. The pressure increased until the skin was blank and then maintained for 10 seconds. The time for return of the normal skin color was registered with a chronometer, and refill time greater than 3 seconds was defined as abnormal.

Once again, the primary outcome was all cause mortality at 28 days. There were lots of prespecified secondary outcome measures.


By day 28, a total of 35% in the CRT group vs 43 % in the lactate group had died (hazard ratio, 0.75 [95% IC, 0.55 to 1.02]; P=.06; risk difference, -8.5% [95% CI, -18.2% to 1.2%]

P value was 0.06. Therefore, a negative study…

This highlights the silly dichotomous nature that we attribute to P values. Less than 0.05 means “something important” whereas above 0.05 means nothing… totalmente loco amigo.

0.05 has always been a single arbitrary cut-off of probability. It tells us nothing about the effect size, whether a study was powered correctly or whether the outcomes are clinically important. It doesn’t tell us about bias, confounding, reverse causality or if the correct statistical analysis was used. The reverence we hold to P values must stop!

In the end, this study produces quite a bit of noise in favour of capillary refill time as a target for resuscitation. But perhaps it highlights the lack of utility of lactate. To be fair, we would never use a single marker in isolation. So perhaps this is all a bit silly… almost as silly as the title, ANDROMEDA-SHOCK trial.



Hernandez G, Ospina-Tascon G Damiani LP, et al. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients with Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA. 2019;321:654-64. [link to article]

Tuesday 23 April 2019

Bag-Mask Ventilation during Tracheal Intubation of Critically Ill Adults: A tack in the coffin of RSI

Related image

“Rapid sequence induction” is intended to decrease pulmonary aspiration during endotracheal intubation. Classily it requires a period of apnoea during which time we wait for the paralytic agent to take effect. No breaths are given for fear of insufflating the stomach and increasing the risk of aspiration.

But what if this period of apnoea is worse that the theoretical risk of aspiration? Herein lies a decent research question.

But spoiler… this was not fully addressed with this study.

This RCT in 7 ICU’s in the USA randomised 401 adult patients to BVM or no ventilation between induction and laryngoscopy. They excluded patients at high risk for aspiration (i.e. ongoing emesis, bowel obstruction, haematemesis etc.)

The primary outcome was lowest oxygen saturation. They also looked at many secondary outcomes and rates of pulmonary aspiration.


Those that got BVM had lower rates of hypoxemia. Rates of severe hypoxemia (sats less than 80%) were 11% in the BVM group but 23% in the no-ventilation group. This is hardly surprising but ultimately is not a patient-oriented outcome.

As expected, the incidence of pulmonary aspiration was quite low. It was noted in 5 (2.5%) patients in the BVM group vs. 8 (4%) in the apnoea group. With such small numbers, obviously this is not statistically significant.

The authors state the following:

Given the low incidence of operator-reported aspiration during tracheal intubation of critically ill adults, determining whether bag-mask ventilation increases the relative risk of aspiration by 50% would require a trial enrolling approximately 4000 patients.


I don’t think we’ll see this trial anytime soon.

There were a number of limitations in this trial. It was performed only in ICU’s, high risk patients were excluded, no blinding, the gold standard for aspiration is problematic, etc.

Do we have an answer? Is RSI dead?

Not really. But perhaps this is a tack (but not a nail) in the coffin of RSI.

Ultimately, I think we can use our common sense and cater to the individual patient. Those that are hypoxic are probably fine to have some BVM. Hold off on those where oxygenation is ok and/or high risk for aspiration.


Casey JD, Janz DR, Russell DW, et al. Bag-Mask Ventilation during Tracheal Intubation of Critically Ill Adults. N Engl J Med 2019;380:811-21. [link to article]

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]