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.

Results?

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. 


Covering:

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.

Results?

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!


Covering:

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…

Results?

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.

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.  


Covering:

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.


Covering:

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)

Results?

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...


Covering:

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


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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.

¿Resultados?

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.

¡OlĂ©!


Covering

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


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“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.

Results?

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.

Yikes! 

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.


Covering:

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]