Friday 1 December 2017

Incorporating point-of-care ultrasound into ACLS: Does cardiac activity predict survival?

From the Journal of No Shit comes this study looking at whether cardiac activity on ultrasound during ACLS is associated with improved survival.

This observational study was conducted in 20 ED’s in North America in patients presenting to the ED in PEA or asystole. Ultrasound was performed at the beginning at the end of ACLS and they looked at several outcomes.

793 patients were enrolled. 13 (1.6%) patients survived to hospital discharge (no mention if they were neurologically intact.)

For what it is worth, cardiac activity on initial ultrasound was the variable with the strongest association with survival at every endpoint investigated. In addition, they found 34 pericardial effusions and some patients with suspected pulmonary embolism.

Caution is in order as 3 patients with no initial cardiac activity on ultrasound survived to hospital discharge.

Of course, there could have been some bias as the decision to terminate resuscitative efforts was probably influenced by the ultrasound. In today’s environment, I don’t think blinding the ultrasound would have been ethical.

I think the most valid conclusion is PEA and asystole are extremely terrible prognostic signs regardless. Ultrasound without cardiac activity is also dismal (but not 100% perfect).

I have wondered why so much time & effort was put into answering a research question that seemed so obvious. It’s kind of up there with the parachute study… But I guess point-of-care ultrasound is still in the stage of trying to prove itself worthy.


Intra-Articular Hematoma Block for Ankle Fracture Dislocation: an RCT

I recently listed to an episode of the Ultrasound Podcast featuring the guru of nerve blocks Dr Mike Stone. This guy sleeps with his ultrasound machine…

With this background, I was shocked to hear that he does not bother with using ultrasound or procedural sedation for reduction of ankle fracture dislocations. He just does a quick ankle hematoma block, “it’s what the orthopaedists would do…”

I’ve done hundreds of hematoma blocks of the distal radius but never considered the ankle. This prompted me to review the medical literature and find the best quality published evidence to support this practice.

Here we go…

This 2008 prospective RCT from New York City randomised patients with ankle fracture dislocations to either intra-articular block or procedural sedation.

What happened?

The authors concluded, “…an intra-articular lidocaine block provides a similar degree of analgesia and sufficient analgesia to achieve closed reduction of ankle fracture-dislocations.” In addition, the average time for reduction and stabilization was faster with the hematoma block.

So, ankle hematoma blocks are great!

Before we get too enthusiastic, consider the following limitations:
  • They only enrolled 42 patients. Yes, 42… Therefore, high risk for type II error and it cannot make adequate claims about safety.
  • It was sloppy; no specified primary outcome, no power calculation, CONSORT guidelines not followed, no mention of ethical approval, junior orthopaedic residents were “indirectly supervised,” some silly comments about “conscious sedation” etc.

So, this is really the best quality evidence we have?


However, there is a wealth of published literature on hematoma & intra-articular blocks elsewhere and I think it is reasonable to conclude they are generally safe.

Subsequently, I have tried this technique a couple of times and had great outcomes; complete and long-lasting analgesia with wide awake happy patients. All the while not requiring a resuscitation room and all the resources of a procedural sedation.  I have an “n” of two. More poor-quality evidence?

I would encourage researchers to publish more on ankle hematoma blocks. To be honest, an RCT is probably not necessary to answer this research question. A large prospective case series should be adequate.

So, get injecting and pulling! (Please don’t quote me out of context)

To read more about ankle hematoma blocks, see paper referenced below. To hear Mike Stone talk about this on the Ultrasound podcast, check the link below and go to about the 11 minute mark.


ECMO for refractory cardiac arrest: the Sydney experience

“Our study is the first multicentre study of ECPR outcomes in Australia. Thirty-seven patients between 2009 and 2016 underwent ECPR across two ECMO referral centres, with an overall survival rate of 35%, and excellent neurologic outcomes in survivors.”

Sounds great. Sign me up for ECMO!!!

But is there a downside?

This audit and medical record review took place over 7 years at two busy Sydney ED’s with a catchment area of 7 million. Both hospitals had developed ECMO response teams consisting of cardiothoracic surgery, anaesthetics, perfusionist and ICU personnel.

In the end, they had 13 good outcomes.

So, about 1 patient per year in each hospital…

In a system with limited healthcare resources, could these efforts been put to better use?

(Of course, ECMO can be used in other circumstances; support of cardiogenic shock post ROSC, overdose, hypothermia, etc.)

It is reasonable to conclude that ECMO currently is not ready for prime time in most centres. But perhaps we are in the ECMO infancy and it will become more feasible and important as the technology improves.

What do we conclude?

The current state of ECMO requires a lot of buck for little bang. It requires many resources and may have a role in the rare highly selected patient. But watch this space…



Shared decision making in patients with low risk chest pain: empowering patients to go home

In patients presenting to the ED with very low risk chest pain, can a structured approach to shared decision making provide some benefit? Specifically, does it improve general comprehension and decrease resource utilization all in a safe manner?

In this study, 898 patients in the USA were randomised to a shared decision making facilitated by a decision aid or to usual care.

Inclusion criteria were:
  • Adults presenting to the ED with chest pain
  • Non-ischemic ECG
  • Negative initial troponin
  • No known prior coronary artery disease
  • Treating doctor wanted to admit to an observation unit to get a stress test or CTCA

(Yes… in many countries most of these patients would never have been admitted in the first instance. There are clearly some issues of external validity.)


With the decision aid, 15% more patients decided not to be admitted compared to usual care (52% vs. 37%).

Oh… and out of 898 patients, how many cardiac events were there?


This obviously begs the question as to why the vast majority of these patients could be sent home regardless of the decision aid.

Nevertheless, I think it does send the message that a structured approach to shared decision making may provide a better framework to educate our patients.


Wednesday 20 September 2017

Promising prognostic accuracy of Sepsis-3 criteria for in-hospital mortality among patients with suspected infection presenting to the emergency department

Thank goodness for the Third International Consensus Definition for Sepsis and Septic Shock! (Yes, this is an odd statement…) They have done away with the terrible SIRS criteria and put the sepsis back in sepsis.

Sepsis has reverted to “a life-threatening organ dysfunction caused by a dysregulated host response to infection.” This is always what we had thought it to be… not the young person with man-flu.

SIRS has been criticised for having poor test characteristics so now we have SOFA and the easier qSOFA

qSOFA is (0-3):

  • Hypotension (SBP less than 100)
  • Alterred mental status
  • Respiratory Rate >22

Yeeeeehaaaa... even I can remember 3 things!

The purpose of this study was to externally validate the qSOFA score among patients presenting to the ED and compare them to the old tools (SIRS, lactate, etc) to predict mortality.

This was a multicentre prospective cohort study mostly done in French ED’s that analysed 879 patients with sepsis. There was an overall 8% mortality rate.

How good was qSOFA?

Pretty darn good (if you believe this study to be valid).

If the qSOFA was less than 2, mortality was 2%. For 2 or greater it was 24%.

The area under the curve (AUC) is a plot of the true positives (sensitivity) on the y-axis and the false positives (1- specificity) on the x-axis. This is a great way to evaluate & compare diagnostic/prognostic tests that have continuous or ordinal values. An AUC of 0.5 would be a useless test (i.e. equal number of true to false positives). 1.0 would be perfect and of course does not exist.

What was the AUC for qSOFA?

0.80 (95%CI 0.74-0.85). This AUC would be considered excellent but certainly not perfect.

This was much better than SIRS which was marginal 0.65 (95% CI 0.59-0.70)

Of course, no study is without problems. This study used the worst qSOFA measurement during the patient's ED stay which increased the sensitivity. In the end, I doubt this tool is really that good.

Some aspects of qSOFA have face validity. I don’t need a decision instrument to tell me that patients with altered mental status and hypotension will do worse!

I also don’t know how this score will be in screening for sepsis. It strikes me as overly simplistic.

Sepsis is a complex and heterogeneous disease process. Clinical decision instruments have never been that useful in these circumstances. They often fail as no fancy regression analysis can account for all of the intricacies of complex disease and individual variability.

The good news is we can use experienced clinician judgement… go figure! In addition, you can incorporate aspects of SOFA in your decision making.  No doubt there will be more to come.

Tuesday 19 September 2017

Acupuncture for analgesia in the emergency department: Theatrical placebo vs. inadequate doses of analgesia



Was an RCT really done in multiple Australian ED’s investigating acupuncture for analgesia?

Why yes…

Anyway… This study aimed to assess analgesia from acupuncture alone or in combination with medications in ED patients with low back pain, migraine or ankle sprain. The primary outcome measure was pain at 1 hour.

There was no sham acupuncture arm and of course patients were not blinded to treatment allocation. 

Without going into too many details, they assessed 1964 patients and nothing seemed to work very well. Acupuncture was just as bad as pharmacotherapy. In addition, patients in the acupuncture group were almost twice as likely to require rescue analgesia.

Ok… perhaps I’m biased so I’ll quote “the implications” from the paper below

Acupuncture is safe, acceptable and has an analgesic effect comparable with that of pharmacotherapy, but none of the therapeutic strategies used provided optimal analgesia within one hour of presentation.

And a quote from the conclusion at the end of the manuscript

Our finding that acupuncture was safe and acceptable form of acute analgesia suggests it may be useful as an adjunct to pharmacotherapy or when pharmacotherapy is unsuitable.

There are no reputable high-quality studies of acupuncture show it is anything more than theatrical placebo. (The vast majority have small numbers, high risk of bias, and have conflicted researchers that want to prove it works.)When sham acupuncture and proper blinding is performed, it is no better than incantations, rain dances or Haitian Voodoo.

But this study was published in a highly regarded journal with a number of authors that are quite clever. So perhaps I’m wrong… and hopefully they don’t stab me with a voodoo doll.


Is it safe to routinely send patients home with topical tetracaine from the ED after corneal abrasion? A retrospective chart review

Simple corneal abrasions heal quickly but can be quite painful and irritating. Topical anaesthetics work like magic at relieving the pain. But tradition has told us sending patients home with this medication is a no-no. Your eyeballs will rot and fall out…

But recent literature has suggested this is probably all a myth. A New Zealand RCT performed by Waldman et al. in 2014 supported the safety of topical tetracaine.

Waldman et al. has been on a roll down in Invercargill. Their RCT changed local practice in the ED and they started discharging patients with simple corneal abrasions with a take home pack of tetracaine (3 plastic 0.5ml commercially available vials or approximately 50 drops. They could use it as often as every 30 minutes for 24 hours)

They did a retrospective medical records review to see if this practice was safe.

During the study period, tetracaine was used 459 times for corneal abrasion. How many serious complications did they find?


Sounds like a slam dunk. Send home patients with topical anaesthetic. Boy… that was easy.

Or maybe not…

To be fair, this is poor quality evidence. Retrospective record reviews suffer from poor quality data that was never collected with the intention to be included in a study. Much may be incomplete, missing or wrong.

In addition, the surrogate measures for “safety” are problematic. ED rechecks and ophthalmology clinic referrals were thought to suggest complications. But were they? We don’t know.

The authors conclusions and editors capsule summary are appropriately cautious. They mention wide confidence intervals, some increased risk for complicated corneal abrasions and large prospective studies are needed to confirm safety. Sure…

But it is probably true that no eyeballs went rotten or fell out… so I’m tempted to believe it. This may be poor quality evidence but it has face validity anyway. It also adds to an evolving body of literature that is pretty much telling us the same thing.

Send them home with topical anaesthetic… it’s ok.


Sunday 17 September 2017

Ketamine as an adjunct to opioids for acute pain in the ED: a peer review fail

Another ketamine for acute pain in the ED study…

Unfortunately there are numerous problems with the way in which this paper is presented that makes me genuinely concerned about the integrity of the data (I'll get to this... shame…)

Anyway… adult patients were eligible for enrollment if they reported pain greater than 6/10 and had a dose of intravenous opioid analgesia (about 5mg morphine I think… but half got hydromorphone).

Patients were randomized to 0.1mg/kg of ketamine vs. placebo. At 30 minute intervals they were asked their pain level and if they needed more pain medication.

The primary outcome was pain control over 120 minutes. (Really they claimed two primary outcomes which you can’t do in an RCT… did a power calculation then decided to do a different power calculation later… oh boy…)

In the end, they had 63 people in the placebo group and 53 in the ketamine group. (Block randomisation should have prevented substantially extra patients in one group so I’m not sure how they explain this. In addition, their CONSORT flow diagram shows 32 and 34 patients in each group, sloppy…)

I think most patients had abdominal or flank pain. (But it is really unclear as 20% of patients are unaccounted for in the descriptor of chief complaint on Table 2. Slop slop)

Without going into too many details, the authors claim that ketamine as an adjunct to opioid therapy was more effective at reducing pain.

If you look at the pain reduction over time, it looks like the ketamine worked best at 120 minutes; long after it should have worn off. I’m sure someone could come up with some biological plausibility for this, but it does seem odd.

50% of the ketamine group had patient reported side effect. But “no patient had side effects lasting longer than 6 minutes.” I find this very difficult to believe.

So in the end, a study claiming a low dose of ketamine 0.1mg/kg had quite an analgesic effect. This is of course discounting the low total dose of opioids given, changing research methods, numerous figures & tables that were wrong and some dispensing of belief. 

Opioids have been around for a long time. They are reasonably safe, predictable & effective with a reversal agent.

Researchers have been furiously looking how we can “spare opioids.” How about more research on how we can "spare ketamine!"

Ok... perhaps I've overstated things. There probably is a role for low dose ketamine when adequate doses of first line analgesia are contraindicated or not working. But unfortunately this paper does not really add much to our knowledge.


Monday 31 July 2017

What is the purpose of log roll examination in the unconscious adult trauma patient?

I often wonder what we are trying to accomplish by performing log roll examination in patients with trauma. Will our magical fingers exclude spinal fractures?

Ok, I’ll acknowledge it clearly is useful in penetrating trauma, finding wounds, and foreign bodies. (Interestingly, the most interesting foreign body I ever found was a sawed-off shotgun. But this is another story…)

This retrospective cohort study conducted at the Alfred Hospital aimed to assess the utility of the log roll examination in unconscious (GCS <8) trauma patients for the diagnosis of soft tissue and thoracolumbar spine injury.

Examination findings as documented in the medical record were compared to the CT and/or MRI reports.

The had 402 cases that met inclusion criteria with 35% having thoracolumbar fracture. Yes, quite a banged-up cohort.

The sensitivity of log roll?


Specificity was found to be reasonable at 91%. The log-roll also found soft tissue injury, open wounds, burns and glass but no firearms.

Of course, there are several issues with this paper. The retrospective data charted in the medical record was likely incomplete. There was only a single data abstractor not blinded to the study intentions and a few other problems.

But I’m willing to believe the conclusions.

“Where CT is available, we recommend examination during log roll be limited to visual inspection only, in unconscious trauma patients.”

Some might argue… well, what’s the harm? Fair enough, but palpating is clearly a waste of time in a cohort getting CT anyway.

So, you’ll have to find another place to stick those magical fingers... Just sayin'


The fist bump: A more hygienic alternative to the handshake?

No, I don’t subscribe to the American Journal of Infection Control. This study was brought to my attention by a very recent blurb in our local newspaper the Mercury.

Should we be fist bumping rather than shaking hands? Does this reduce the spread of bacteria? For all the craziness promulgated by infection control authorities, I wonder how they have missed this breakthrough!?!

This study looked at the transfer of E. coli during a standard handshake, high five, fist bump and man hugs. (Ok… I made the last one up.)

The figure clearly shows we should be taking Barack Obama's lead and go fist bumping.

Image result for fist bump barack obama michelle

Alright… I’ll acknowledge this is a surrogate marker and there are many other methodologic issues. But I don’t care.

Peace… Doyle out!


Every minute counts: Time to delivery of initial massive transfusion cooler and its impact on mortality. A misleading observational study.

This study was a planned subanalysis of the PROPPR trial. If you can remember, this was an RCT looking at a blood products transfusion ratio of 1:1:1 vs. 1:1:2 (platelets, plasma, PRBC’s) in trauma patients with exsanguinating haemorrhage. There was no difference in the primary outcome.

But the PROPPR trial also collected observational data on time to massive transfusion (MT) activation and time to blood product cooler arrival. Could mortality and other outcomes be predicted by these times? Time for some subanalysis…

I’ll start with the conclusion of this observational study;

“…every minute from time of massive transfusion protocol activation to time of initial cooler arrival increases odds of mortality by 5%.”

You will very likely hear this quoted in the future. Unfortunately, it is not only misleading but likely wrong.

First, it is not absolute mortality but rather “odds.” This concept of “odds” is challenging to comprehend and relies on relative numbers.

In addition, there was very likely residual confounding that was responsible for the differences in mortality. The timing of MT activation and cooler arrival was not randomized.

The authors did make attempts at a few adjusted analyses for some identified confounders such as injury severity, physiology etc. and this was a bit hit and miss. There were some statistical differences and some trends. But nothing very clear. Of course, these adjustments are always difficult and are based on many assumptions.

The authors then go on to discuss how their results may be analogous to STEMI teams, door-to-balloon time, stroke teams etc. All of this is a bit silly.

I don’t have an issue with recognizing the need for massive transfusion quickly and getting blood products to the bedside as fast as possible when needed. But this is based on common sense and not this study.

So, when you hear “it is proven that there is a 5% increase in the odds of mortality for each minute delay…” you can shake your head in either a 1:1:1 or 1:1:2 fashion.


Sunday 30 July 2017

Prevalence and Clinical Import of Thoracic Injury Identified by Chest CT but not Chest X-ray in Blunt Trauma: Multicentre Descriptive Study

Uuuggggh… this paper was hard to digest. The writing and presentation of the manuscript was more complicated than playing Twister in a hot-tub. 

Case in point; the abstract alone has 629 words.  Screw the Annals of Emergency Medicine limit of 250 words in their instructions to authors.

I’ll try to distil it for you…
  • In patients with blunt trauma, how many more injuries does a chest CT find over a plain film?
  • Are these injuries clinically significant?
  • Does finding these occult injuries result in major intervention?

This was a secondary analysis of data collected for NEXUS chest and chest CT studies collected at 10 level 1 trauma centres in the USA. (So, good data in...)

Inclusion criteria were patients >14 years old with blunt trauma who had both a chest x-ray and chest CT. (98% of the time, the chest x-rays were portable supine films.)

Occult injury was defined as those seen on CT but not on plain film. These included pneumothorax, hemothorax, sternal or scapula fracture, >2 rib fractures, pulmonary contusion, T-spine fracture, diaphragm injury.


Of 14,553 patients in the NEXUS database, 5,912 met inclusion getting both plain film and chest CT. Of these, 2048 had chest injury.

What was the rate of occult injury?


What proportion of occult injuries required major intervention? (as defined by surgery, chest tube, or mechanical ventilation for pulmonary contusion).


This sounds rather impressive until you realize the great majority of these interventions were chest tubes for occult injury! 

In the end, 48 patients (08%) out of 5912 had major intervention (excluding chest tubes). A few of these were clearly nasty injuries including diaphragm rupture and major vessel injury.

Could many of these interventions been of no patient benefit and/or harmful? Could these injuries have been detected after a period of observation?

Of course.

Did over-diagnosis with CT cause harm with increased downstream intervention and resource utilization?

Quite possible.

What about the addition of point-of-care ultrasound? We know that portable supine chest x-rays are awful at finding pneumothorax and haemothorax.

This was ignored.

What are we to make of all of this?

The biggest caution is the interpretation.

You will probably hear it quoted that chest x-ray misses 70% of all injuries compared to CT without mention of the details above.


Also, remember the included patients got both plain film and CT at the discretion of the ED doctors. So, this is not all comers with blunt trauma… This was a sicker group that the doctors were worried about.

In the end, I think this paper provides more questions than answers. If you use a bigger microscope, you will find more injury. But does this help or harm patients?

The answer is still uncertain.

I think I need a dip in that hot-tub.


Mortality rates of severe TBI: impact of direct vs. non-direct transfer

There are potential benefits to transfer patients with suspected severe traumatic brain injury (TBI) directly to a trauma centre and bypass smaller local hospitals. The tertiary centres likely have more experience and expertise to manage these patients well.

But of course, this must be balanced by potential harm of prolonged transportation prior to hospital evaluation and resource implications.  

This study sought to answer which strategy is best for these patients; go to the small centres first or direct transfer to the trauma centre?

This was a registry review of patients (with no chart extraction methods reported) presenting to a level 1 trauma centre in New York. 171 patients with GCS<8 (severe TBI) were directly transferred as compared to 92 that were transferred after going to a local hospital.

The primary outcome was mortality. Can’t argue with this outcome…


There was an observed 19% mortality rate for direct transfer vs. 36% for secondary transfer.  To be clear, this was an absolute difference of 16% or a NNT of 6 for mortality.

The only thing that springs to my mind is, “holy shit!”

But wait…

This is sounds too good to be true. So, what’s wrong?

This was not a randomized trial. Therefore, this observational study will inevitably have some underlying confounders between the groups. Did they make any attempt at controlling or analysing for confounding?


To be fair, they did mention that the patients undergoing direct transfer had higher injury severity scores (ISS) but this is only a single measure and far from perfect.

I strongly suspect the cohort of patients undergoing secondary transfer were vetted at the local centres and found to be genuinely quite sick. Many likely had complete primary surveys and pan-scans. They kept the patients that were ok and only transferred the sickest ones. So of course, this group was going to have worse outcomes than those who were not screened by doctors.

But, for many reasons I could be wrong.

Unfortunately, a good RCT would be very tricky to undertake. In addition, it would arguably fail on feasibility, ethics and issues of external validity.

What should we conclude?

This study does not add much to our understanding of this complex question. It has the capacity to be grossly misinterpreted. 

Great one for journal club… but afterward you might feel like you have your own TBI.


Sunday 2 July 2017

Early Secondary Neurologic Deterioration After Blunt Spinal Trauma: Are the collars really necessary?

“Keep them still! Don’t let them move… if they turn their head an inch, they’ll be paralysed.”
-Dr Longheld Dogma

Protection of the cervical spine has been a bedrock of trauma care. This has traditionally been accomplished by strapping patients to backboards and the application of properly fitted cervical collars.

But these collars are uncomfortable, have potential harms and can make cooperative patients rather uncooperative.

Of course we can rest easy in the knowledge that  the original randomised controlled trials (RCT's) of the cervical collar took this all into account. 

What…there is no good quality evidence that the c-collars do anything?!?

Surely there must at least be a large body of observational literature to suggest they work? Heck, we’ve been using them for decades!

These authors sought to definitively answer the latter question.

They conducted a thorough literature review to find cases of neurologic deterioration in the early care of blunt spinal trauma.

In the end, they found only 41 cases from 12 papers. The quality of the evidence was “extremely low.” They conclude the following:

No reports were found of sudden, movement-provoked deterioration during the prehospital interval; this remains an unpublished phenomenon if not a medical myth. Overall, since many of these events described are consistent with the natural history of disease, it is unclear how often deterioration may be causally linked with patient movement and furthermore whether such events are preventable by motion restriction.

On the flip side, one might argue that lack of evidence does not equate to lack of efficacy. After all, these collars have not truly been studied. In addition, there may have been negative reporting bias of bad outcomes.

What should we conclude? I think you can make up your own mind… hopefully not while strapped to a collar.


Saturday 1 July 2017

Outcomes After Out-of-Hospital Cardiac Arrest Treated by BLS vs. ALS: polishing a pig

There is a developing rationale that giving ALS care during out-of-hospital cardiac arrest (OHCA) might actually be harmful. The reasons often include potential harm by trying to establish an advanced airway, drugs have never been shown to improve meaningful outcomes, and the extra time it takes. This delay may distract from other beneficial interventions.

Thus far, the best quality data comes from Captain Ian Stiell’s OPALS study out of Canada. This was a before and after design and concluded no benefit to ALS over BLS with a focus on rapid defibrillation.

Obviously a properly done RCT with allocation concealment would be ideal to answer this research question. But there are questionable ethical hurdles and genuine issues of feasibility.

These authors sought to answer the question with another hypothesis raising observational study. 

Unfortunately, it has several fatal flaws and probably should not be read beyond the abstract.

They looked at patients with OHCA who had ALS or BLS dispatched in non-rural counties in the USA. They identified the variables by Medicare billing and coding data.

This study was not randomised and there could be very good reason why one type of dispatch was chosen over another. Could the ALS cohort have been sicker?

To try to correct for this confounding by indication, the authors tried the usual propensity matching based on all kinds of variables that may or may not have been measured correctly.

In short, this study was based on a multitude of assumptions and dubious statistical analysis of poor quality billing data. There is no doubt they tried hard and put in a lot of effort. But there is only so much one can do to polish a pig. In the end, it’s still swine.


Sanghavi P, Jena A, Newhouse J, et al. Outcomes After Out-of Hospital Cardiac Arrest Treated by Basic vs. Advanced Life Support. JAMA Intern Med. doi:10.1001/jamainternmed.2014.5420

Friday 30 June 2017

Prehospital administration of TXA in trauma patients: a hypothesis raising study

The CRASH-2 trial put tranexamic acid on the map for patients with trauma at risk for significant haemorrhage. Although the reported 1.5% absolute mortality reduction was impressive, there are some concern as most of the data was obtained in resource poor countries. Is this externally valid to us? Perhaps not.

So, more data is needed.

This German study was a retrospective look at a database and registry to try to determine if TXA could be helpful when given prehospital. It sought to compare sick trauma patients who happened to get TXA vs. those that did not. They looked at a whole lot of outcome measures.

Its design included some fancy matching of cohorts and some complex propensity scoring.

Without reading any further, it is obvious this design could never claim cause & effect. At best it would be hypothesis generating. Too many assumptions, confounding and making decisions based on poor quality registry data.

For what it’s worth, they found a big early mortality difference with TXA. It was 5.8% vs. 12.4%. Let’s face it, this is too good to be true. More believable was overall hospital mortality that was similar in both groups with an absolute trend of 1.5% benefit in the TXA group… Wait a minute, where have we seen this before? CRASH-2 anyone?

The authors conclude, “until further evidence emerges, the results of this study support the use of TXA during prehospital treatment of severely injured patients.”

This conclusion is a stretch if only looking at this paper. But given other data on TXA, I think the overall message is reasonable.

Good news; we will probably be getting much better data soon. The PATCH trial is estimated to wrap up in December of this year. This large multi-centre double blind RCT of TXA is what we genuinely need to answer the question.

So why did we need to raise the hypothesis?


Wafaisade A, Lefering R, Bouillon B, et al. Prehospital administration of tranexamic acid in trauma patients. Crit Care. 2016;20:143.

A meta-analysis of amiodarone or lidocaine for cardiac arrest: when crunching numbers is not appropriate

No anti-arrhythmic drugs have been proven to result in increased meaningful outcomes after cardiac arrest. Sure, a larger proportion of patients arrive at the hospital alive but they all die anyway.

A recent RCT of 3026 patients published in 2016 reported about a 3% trend towards improved survival to hospital discharge with amiodarone or lidocaine as compared to placebo. If this trend was true, it would be rather important. A NNT of 33 for survival is nothing to shake a stick at!

Perhaps a systematic review & meta-analysis with more statistical power give us the answer? Why not.

These well intended authors conducted such a study.

As is often the case, their search found tons of papers but in the end only 3 RCT’s.

One RCT had 3026 patients… sound familiar?

The other two only enrolled 347 and 304 patients respectively. To be clear, 80% of the data comes from one study.

So, the authors quit here and acknowledged they shouldn’t go much further until such time more evidence became available.

Just joking…

Of course they crunched some numbers and came to some conclusions. As expected, it didn’t really provide us with any new information.

To be fair, their overall methods were good as was the discussion. I thought their advocacy for the reconsideration of lidocaine was interesting and probably correct. It’s great when things come full circle.

In the end, the jury is still out. But we knew this already… with no need for crunching.


Monday 24 April 2017

Do you shenfu? Shenfu injection for septic shock.

There is probably better quality evidence for shenfu injection for sepsis than the recent craze over Vitamin C… pretty sad considering this awful paper.


It’s a “well-known traditional Chinese formulation restoring Yang from collapse, tonifying Qi for relieving desertion…” (It’s made from ginseng and aconite.)

So if you need your Yang restored and your Qi tonified then Shenfu is for you! Especially if you are feeling a bit septic?

Back to this randomized placebo controlled trial…

157 patients with sepsis were randomized to either shenfu injection vs. placebo in addition to usual care.

Inclusion criteria relied on the Third International Consensus Definition for sepsis and septic shock published in 2016… even though this study was conducted from June 2010 to November 2012. Perhaps shenfu makes you see into the future…?

The primary outcome was lots of things… something to do with cellular immunity, CD4, CD8 counts, mHLA-DR expression, ex-vivo endotoxin LPS induced TNF, IL 6 and IL 10 cytokines, length of ICU stay, vasopressor use, illness severity, etc.

Why didn’t they just measure the Yang and Qi?

Believe it or not, the authors state the study was powered to the secondary outcome of mortality at 28 days. They were looking for a “holy shit!” difference of 20% and as such only needed low numbers of patients.  (Could it be they changed their original primary outcome to a secondary one after no difference was found? No….)


Shenfu was great! (except for mortality… but who cares)

The authors conclude, “these findings suggest that shenfu injection can enhance the cellular immunity of patients with septic shock and could be a promising adjunctive treatment for patients with septic shock.”

So for all of you out there giving Vitamin C for sepsis, perhaps you should mix it with a little shenfu… shouldn’t hurt?


Geckos & Watermelons: Association Between Tracheal Intubation During Adult In-Hospital Cardiac Arrest and Survival

Generally speaking, what do you get when you perform an observational study based on registry data?

Not much.

Nevertheless, this study does pose an interesting research question. Is intubation beneficial for in-hospital cardiac arrest? Or should we just use other means of ventilation and resuscitate accordingly.

To really answer this question, one would ideally like to see a randomized trial so that confounders are equal amongst the two groups. Otherwise we might be comparing geckos to watermelons.

Back to the study...

This was an observational cohort study of patients who had in-hospital cardiac arrest. The primary outcome was survival to hospital discharge.

Of 71,615 patients who were intubated in the first 15 minutes, 60% were matched to a patient not intubated in the same minute.

Survival was lower among patients who were intubated 16.3% vs those not intubated 19.4% (RR=0.84; 95% CI 0.81-0.87; p<.001)

So this was a huge study with a pretty p value… so it must be right?!


A few things...

You can’t overpower bias with big numbers.

This study relied on registry data which is notoriously of poor quality. Garbage in, garbage out. No amount of fancy statistics can make up for this.

Once again, this was not a randomized trial so the groups were very likely different from the start. The outcomes could very well be due to one group being sicker than the other. The authors tried to correct for this confounding by some clever propensity matching. But it must be emphasized that this is far from an exact science.

So what’s the take home?

Probably not much. But this study does lay the foundations for a proper randomized trial… hopefully only including geckos.


Andersen LW, Granfeldt A, Calloway CW, et al. Association Between Tracheal Intubation During Adult In-Hospital Cardiac Arrest and Survival. JAMA 2017;317(5):494-506.

Trial of Pregabalin for Acute and Chronic Sciatica… Show me the money!

It seems half of the patients I see in the ED are taking Lyrica (pregabalin). Therefore, it was no surprise to me to see it at number 13 on the list of the biggest blockbuster drugs of 2015 making billions of dollars for Pfizer.  

But I was equally surprised to see a negative high quality RCT of pregabalin published in the highest impact journal on the planet!

Surely Pfizer was crazy when they funded and performed this study? Well… of course they weren’t… it was some other crazy authors.

This Australian NHMRC funded double-blind controlled trial randomized 209 participants to either pregabalin or placebo. The primary outcome was a leg-pain intensity score at the 8 week mark.

How much did the pregabalin help?

Zero, zip, zilch, nada…

There was no statistical improvement in the primary or any of the secondary outcomes. About the only thing we are sure of is the incidence of adverse events was significantly higher in the pregabalin group.

Although this was a small study (i.e. risk for Type II error), it probably had adequate power to detect a clinically meaningful difference in pain scores. And the results trended a favour towards placebo anyway.

Of course, no study is perfect. If I was working for Pfizer, I would point out that only a minority of the participants were likely to have neuropathic pain as measured on the PainDETECT score. So of course my drug wouldn’t work… while I sit on my horse made of gold.

As an aside…

I’ve been dubious of these neuopathic pain drugs. A disturbing study published in the NEJM demonstrated what looks like systematic research misconduct with gabapentin which is very closely related to pregabalin. This only was discovered during litigation and release of internal company documents. (This is probably my favourite journal club paper of all time…)

So what’s the take home message for the emergency docs?

Pregabalin probably does not help sciatica. But I would also be sceptical as to the benefits in a wide range of other indications… Especially with industry sponsored research.


Wednesday 19 April 2017

Risk for Clinically Relevant Adverse Cardiac Events (CRACE) in very low risk chest pain patients admitted to hospital (in the USA)

Move over MACE and say hello to CRACE!

These high profile authors from the USA sought to determine the incidence of short term life threatening events in low risk chest pain patients admitted to hospital.

Their concern was a lack of benefit from admission balanced with the potential harm (false positives, over-diagnosis, hospital acquired infections, VTE, iatrogenic etc.).

They reviewed a large database from 3 hospitals in the US Midwest from 2008-2013. They identified admitted patients that had negative serial biomarkers (old school troponins), normal vital signs and non-ischemic ECGs.

Interestingly, these authors picked a different outcome measure for this study from the traditional MACE that we have seen in many previous studies. They created “CRACE” defined as:
  • Life-threatening arrhythmia (VF, symptomatic bradycardia, or treated brady or tachy arrhythmias)
  • Inpatient STEMI
  • Cardiac or respiratory arrest
  • Death

(Noticeably absent from CRACE is non-STEMI or longer term outcomes beyond hospitalization.)

What did they find?

Of course this group was very low risk… but could you have guessed a CRACE rate of only 0.06% (4 of 7266 patients)!

As is usually the case, there were some methodological issues with this study and the reported rate is probably not a complete reflection of the truth. However this makes a compelling argument that this is an extremely low risk group that may derive more net harm from admission.

The authors are careful to mention that this study does not mean patients derive no utility from further investigation and management after the ED evaluation. But suggest this may be done as an outpatient and might provide a framework for shared decision making.

My guess is the Australians would never admit many of these low risk patients anyway. In addition, these patients would be even lower risk with the high sensitive troponin assays.

Take home? Perhaps we can sleep a little better knowing that low risk patients truly are very low risk. Hope this doesn’t seem to CRACEy…


Wednesday 22 March 2017

An RCT of Single Dose Dexamethasone vs. 5 days of Prednisone for Acute Adult Asthma... making life simple

Many emergency doctors have traditionally given a 5 day course of prednisone (prednisolone) for acute asthma. However, can the long duration of action (up to 72 hours) of dexamethasone replace a course of prednisone in a single dose? Certainly this would lead to less prescriptions and greater compliance.

The authors from Oakland, California enrolled 376 patients in a single ED with mild to moderate asthma. This was essentially defined as well enough to go home. They were randomized to either a single dose of dexamethasone 12mg or five days of prednisone 60m.

The primary outcome was “relapse” defined as an unscheduled return visit to a health care provider for asthma within 14 days. This was determined by telephone interview.

It was powered to a non-inferiority margin of 8%. In other words, if the results of the two treatment arms were within 8% then they were considered to be equivalent.  Why 8% you ask...? Ok, it’s a bit arbitrary.


So close...

Relapse rate for dex was 12% and pred was 10%. The absolute difference 2.3%. BUT the 95% confidence interval just scraped above 8%. Therefore this was a statistical fail.

But hold your horses.

There is one important point to emphasize... The study investigators gave the patients the prednisone tablets (or placebo) to take home from the ED. This nullified the prescription filling issue and certainly increased compliance. This biased the study to the prednisone arm.

I think the results are compelling and provide us with ongoing evidence that a single dose of dexamethasone is probably sufficient to treat mild to moderate asthma. This is on the back of numerous similar studies in the pediatric literature. Consistency is a powerful message.

For me, dexamethasone is close enough.


Saturday 11 February 2017

Should we give a lower dose of ketorolac for treating acute pain in the ED?

Ok, ketorolac is a little bit funny...

For some reason, it was never granted TGA approval in Australia for intravenous use although it is used all over the world in this manner. (Therefore it is perfectly fine for giving it IV off-label).

Second, it is probably the only drug where it is recommended to give a lower oral dose (10mg) than parenteral (30mg).

But now that 30mg IV dose is being challenged.

These authors from New York suggest the “ceiling dose” of ketorolac is probably 10mg and postulate that higher doses can cause more harm than good.

They performed a RCT of three different doses of IV ketorolac monotherapy; 10, 15 and 30mg. Inclusion criteria were adults with undifferentiated pain (most had acute flank, abdominal, musculoskeletal pain and headache). They had to have a numerical rating (NRS) of pain >5 not having had any previous pain medication.

The primary outcome was reduction in pain score at 30 minutes.

It was powered to find a 1.3 difference and as such 80 patients in each arm were enrolled.


The pain score dropped about 2.5 in both the 10 & 15mg doses of ketorolac. It dropped by 3.0 in the 30mg dose. This was not statistically significant.

The authors boldly conclude, “The results of our study provide a basis for changes in practice patterns and guidelines in ED care, supporting use of the 10mg intravenous ketorolac dose.

Unfortunately this conclusion is inappropriate.

Despite the decent design and blinding of this study, there were significant problems such that one cannot make any decent conclusions.

Any time one does not see a dose response with a particular drug then one must seriously consider if it is having any effect at all. This is pharmacology 101. I very much imagine that placebo (i.e. a ketorolac dose of zero) would have given similar results in this heterogeneous group of patients with these study methods.

I give ketorolac in patients in whom I think it will have a greater benefit. This is usually part of a cocktail of medications and not monotherapy. It works extremely well in patients with renal colic but less so in those with abdominal pain and headache. So extrapolating the results of this study to the individual patient is problematic.

A key foundation of this study is predicated on the theoretical harm with a higher dose of ketorolac. Otherwise this whole discussion is moot. I would seriously question if a single dose at the higher range would cause clinically important problems. In addition, we can pick and choose which patients get higher doses. An 85 year old 40kg woman with chronic renal failure would probably never get ketorolac in the first place.

In summary, we don’t know if a lower dose of ketorolac is appropriate at the moment. A single administration of ketorolac at the standard dose would be extremely unlikely to cause clinically significant problems.

It is always wise to be sceptical of small single centre studies. In the end they are often proven wrong. Nevertheless, this study could provide foundation for future study and clinical equipoise for inclusion of a placebo dose of ketorolac.

Watch this space but don’t change you dose of ketorolac just yet.

(Addendum: Please see lead authors reply to this post under the comments section)


Friday 10 February 2017

Midazolam-Droperidol, Droperidol, or Olanzapine for Acute Agitation in the ED. An Australian RCT

What is the best drug for treatment of acute agitation in the ED?

Generally speaking we know the real answer to such questions is, “it depends...” And this is often followed by an emphatic explanation of the clinician’s beliefs based on eminence based medicine.

This study at least makes an attempt to enter some high quality evidence into the discussion.

This randomized, controlled, double blind, triple-dummy (who you callin’ dummy?) clinical trial enrolled adult patients requiring IV sedation for acute agitation in 2 ED’s. They randomized 349 patients to either:

·         Group 1: Midazolam 5mg + Droperidol 5mg or
·         Group 2: Droperidol 10mg or
·         Group 3: Olanzapine 10mg

If patients were not adequately sedated by five minutes they could get further pre-specified study drug.

The primary outcome was adequate sedation by 10 minutes.

If you have any knowledge of pharmacodynamics of the study drugs, you can probably guess the results.

Yes, the midazolam group did better. By the 10 minute mark, about 75% were adequately sedated vs. 50% in the groups that got monotherapy with droperidol or olanzapine.

Once again, the results of this study are not a surprise. Intravenous midazolam works within seconds of IV administration whereas the antipsychotics take several minutes.

I personally (eminence based medicine anyone?) rapidly titrate midazolam in combination with a single dose of antipsychotic. I have most of this done well before the 10 minute mark with the attendants already wiping the sweat off their brow.

Of course we have made no mention of safety. This study was not powered for safety outcomes. Nevertheless it is quite clear that drugs in combination require extra care; especially benzodiazepines.

What’s the take-home point?

Combination therapy with IV midazolam plus an antipsychotic is probably the best strategy if the goal is rapid sedation of the acutely agitated patient. But really, therapy should be tailored to the individual patient and adequate precautions taken.

This is a great triple dummy RCT... but whatever you do, “don’t call me stupid.”