How to get it wrong: Succinylcholine is associated with increased mortality when used for RSI in patients with severe traumatic brain injury

This is a fantastic study!

It is a fantastically bad study of how to perform research and come to wrong conclusions. It is so awful it makes one’s heart sink.

These authors performed a retrospect data-base review of patients who were intubated in their ED for traumatic brain injury. The main outcome was the difference in mortality when patients were intubated with either rocuronium or succinylcholine.

The results? No difference in mortality was found. Death occurred in 23% in each group.

Not satisfied with negative results, the authors conducted a post-hoc subgroup analysis and found that there was a difference in those with severe TBI. If you torture the data enough, it will talk.

Wooohooo... we can publish something!

They conclude, “in severely brain-injured patients undergoing RSI in the ED, succinlycholine was associated with increased mortality compared to rocurunium.”

This is totally nuts.

Regardless of the crazy analysis, all of the difference could easily be attributed to unmeasured confounding. This was not a randomized trial; therefore the patients given sux were very likely sicker.

Most experienced airway experts will tell you that they reach for sux when they want very rapid intubating conditions in sicker patients as compared to other neuromuscular blockers. Correcting for confounding (especially with a retrospective database) is far from an perfect science.

In the end, this is a small study with a high risk of bias that comes to unbelievable conclusions. Do we really believe a number needed to kill of 5 for succinylcholine in severe TBI!?!

There is so much I haven’t mentioned... the crazy power calculation, mixing association with causation, confusing subgroup analysis with stratification, neglecting the details of biological plausibility etc.

In 2005, John Ioannidis published his famous paper, “Why most published research findings are false.”

This study is a case in point. On so many levels, it is just wrong.

At best, it might raise a hypothesis for prospective testing. However, NOBODY should be changing their practice as a result of this paper.

Covering:

Patanwala AE, Erstad BL, Roe DJ, et al. Succinylchoine is associated with increased mortality when used for rapid sequence intubation of severely brain injured patients in the Emergency Department. Pharmacotherapy. 2016;36(1):57-63.

http://www.ncbi.nlm.nih.gov/pubmed/26799349

(Special thanks to Dr Mark Reeves, FANZCA and Dr Ryan Radeski for providing me with some of their insights. However they take no responsibility for the terrible nature of this post.) 

Efficacy of nasal cannula oxygen as a preoxygenation adjunct in emergency airway management in healthy volunteers

Who would have figured that giving patients more oxygen during simulated emergency airway management results in better oxygenation?

Ok... I’m being overly cynical.

Some clinicians provide extra oxygen through nasal cannula in addition to either a nonrebreather (NRB) or bag-valve mask (BVM) prior to RSI. But does this really matter? Or is it just an extra step in an otherwise stressful situation that could be avoided?

This Australian study randomized 60 young healthy volunteers to either a NRB or BVM with or without a supplemental nasal cannula running at 10L/min. In addition, they also investigated whether the addition of a simulated mask leak changed the results.

The primary outcome was a comparison of end-tidal oxygen between the groups.

Results?

The addition of a nasal cannula to a NRB or BVM did not seem to do much unless there was a mask leak. The BVM achieved higher oxygenation than the NRB. (I don’t think the actual numbers are important, but if you are interested then click on the link to the abstract below.)

The major limitations of this study are obvious. 

Unless you are sadistic, healthy volunteers are not the patients we typical intubate in the ED. The primary outcome was a surrogate marker and not necessarily a meaningful patient oriented one. Looking at real morbidity would have required a much larger study of actual patients.

What should we take from this?

The addition of a nasal cannula might be beneficial (or not) when performing RSI in the ED. This is not great evidence and it probably doesn’t matter in the vast majority of patients. Sure, give it a try when you really want to maximize pre-oxygenation. Also make sure you have a good mask seal.

Pedantic adherence to a supplemental nasal cannula adjunct during RSI is probably silly. But depending on the situation it might make sense and probably won’t hurt.

Covering:

Hayes-Bradley C, Lewis A, Burns B, et al. Efficacy of Nasal Cannula Oxygen as a Preoxygenation Adjunct in Emergency Airway Management. Ann Emerg Med. 2015; Dec 31 [ePub]

http://www.ncbi.nlm.nih.gov/pubmed/26747218

An RCT of ultrasound guided hematoma block vs. procedural sedation for distal radial fracture reduction

This study sought to compare the efficacy of ultrasound guided hematoma block vs. procedural sedation (midazolam/fentanyl) for reduction of distal radius fractures in the ED.

The “primary” outcome was pain on a numerical rating scale recorded at 5, 10 and 15 minutes after reduction. Secondary outcomes looked at satisfaction, early/late complications and time to discharge from the ED.

I liked this paper, but it is impossible to overlook some of their sloppy methods and statistical analysis.  For example, “We don’t need no stinkin power calculation...”

Results?

They randomised 143 patients in to the two groups. In the end, the pain scores were quite similar. But time to discharge was significantly lower in the hematoma block group. And there were more adverse events in the procedural sedation group.

The limitations are several. Single site, only one type of procedural sedation, the outcome measures was perhaps dubious, and given small numbers we definitely can’t make conclusions about rare adverse events (i.e. infections.)

What do we take from this?

Effective hematoma blocks are probably just fine for the reduction of distal radius fractures. They are quicker, simpler, and avoid the nuisance of procedural sedation. (In my opinion, if you can do an “in-plane” ultrasound guided nerve block, then you should have no trouble using the same technique to do a hematoma block.)

Although not addressed in this paper, lots of ED’s in Australia are doing Bier’s blocks. There is no doubt they are highly effective in the reduction of pain. But they probably carry just as much, if not more hassle than a procedural sedation.

So the hematoma block? When done properly it is simple, quick & pretty darn effective. So break a leg (or arm) and give it a try... 

Covering: 

Fathi M, Moezzi M, Abbasi S, et al. Ultrasound-guided hematoma block in distal radial fracture reduction: a randomised clinical trial. Emerg Med J. 2015;32:474-477. 

http://www.ncbi.nlm.nih.gov/pubmed/25016389

Getting back to common sense with an acute pain titration protocol: “Do you want more pain medication?”

The Joint Commission (TJC) is the peak hospital accreditation body in the USA. In the year 2000, they mandated screening pain assessments.  Since then, pain has been considered the “fifth vital sign” and the numerical rating scale (NRS) has taken over ED’s around the world. “Rate your pain 0 to 10?” often bellows through the corridors of the ED. But is this practice asking the wrong question?

Out of the ashes of all this mess comes an interesting study from the Bronx, New York. Hey... fagitaboutit. As can be imagined, this is a very busy and underserved emergency department. So perhaps a pain protocol might be more effective in this setting.

They devised a prospective cohort study of adults with acute severe pain defined as requiring IV opiods. The protocol called for an initial 1mg of hydromorphone (equivalent to 7mg of morphine). About 30 minutes later they asked, “Do you want more pain medication?” This was repeated until they reached a maximum of 4mg of the drug.

They considered the protocol a success if at any time they declined the offer of more pain medication. If they got all 4mg and still wanted more, they failed.

As would be predicted, the success rate was very high. 205 of 207 (99%; 95%CI 97% to 100%) subjects achieved satisfactory analgesia. There were only very few adverse events.   

But this is not why I liked this paper...

They also explored the relationship to a request for more pain mediation with their reported pain score on the NRS.

Perhaps the most interesting part of this study was the results of this comparison. They plotted the relationship graphically. This showed large variability in pain scores when patients requested and declined additional pain medication.

So what are we to take home from all of this?

I think Dr Steve Green sums it up best in the accompanying editorial entitled, “The Numerical Scoring of Pain: This Practice Rates a Zero out of Ten.”

Dr Green’s conclusion is so good that I dare not paraphrase:

The numeric rating scale is helpful for pain research but is inaccurate and counterproductive for standard patient care. TJC mandates that pain be identified and addressed but does not specifically require pain scoring. What happened to the old-fashioned question such as “Are you in pain?” and “Do you want pain medication?” Pain scoring in electronic medical records could be more appropriately replaced with a single yes/no checkbox per encounter: “Was pain evaluated and addressed?” As noted by Walid et al, “The use of the 0-to-10 pain scale... as a sole measure of pain assessment undercuts compassionate communication.” Let’s evaluate pain as the complex, nuanced symptom that it is, rather than oversimplifying it as a single integer of dubious merit. Routine pain scoring is a proven failure and should be abandoned.

Wow... perhaps he should tell us what he really thinks.

Covering:

Chang, AK, Bijur PE, Holden L, et al. Efficacy of an Acute Pain Titration Protocol Driven by Patient Response to a Simple Query: Do You Want More Pain Medication? Ann Emerg Med. 2016;67:565-72.

http://www.ncbi.nlm.nih.gov/pubmed/26074387

A single dose of oral dexamethasone is probably just as good as 5 days of oral prednisolone for acute asthma

Oh... this would make life simpler, so I hope it works.

Dexamethasone has a duration of action up to 72 hours. Therefore several researchers have considered it as a potential agent to streamline the treatment of asthma.

This was a triple blind “non-inferiority” trial looked at single dose of dexamethasone 12mg vs. the usual five days of prednisone (prednisolone can be considered the same). Included patients were adults with mild to moderate asthma discharged home from the ED.

The primary outcome measure was relapse as defined by an unscheduled return to a health care provider within 14 days.  (Ok... this outcome measure is not perfect but probably represented a pragmatic compromise in the design of the study.)

It was powered to an 8% difference between groups.

Why 8%?

Yes, it’s fairly arbitrary. And they provided some nebulous justification. 

Results?

They kind-of, sort-of, almost met inferiority. There was a 2.3% (95% CI -4.1% to 8.6%) absolute difference in the primary outcome of relapse at 14 days, but the confidence interval just barely crossed their pre-specified arbitrary margin of non-inferiority.

So this officially is a negative study. But I don’t really think so. Nor do the study investigators.

I’ll bet the authors are kicking themselves for not ensuring the proper statistical power in order to narrow down their confidence interval. Statistically speaking, the probability of the truth is always closer to the point estimate.  

I also bet the authors are disappointed they didn’t pick a non-inferiority margin higher than 8%!

Either way, I think this is more evidence to suggest that a single dose of dexamethasone is probably just as good as the usual course of prednisone. As we get more evidence, we will surely get a better idea of the true efficacy.

For now, stock up on the dex!

Covering:

Rehrer MW, Liu B, Rodriguez M, et al. A Randomized Controlled Noninferiority Trial of Single Dose of Oral Dexamethasone Versus 5 Days of Oral Prednisone in Acute Adult Asthma. Ann Emerg Med. 2016;67:593-601.

http://www.ncbi.nlm.nih.gov/pubmed/27117874

Intramuscular Ketamine as a Rescue Treatment for Acute Behavioural Disturbance (after getting droperidol) in the ED

This Australian study looked at the use of a knockout dose of ketamine (4-6mg/kg) for the sedation of acute behavioural disturbance in the Emergency Department.

Their protocol generally called for a couple doses of droperidol. This was followed by ketamine if sedation was not adequate.

Out of 1296 patients, they only had to resort to ketamine in 53 (4%) patients.

The ketamine seemed to work and the authors liked it.

The few failures were put down to inadequate low doses of ketamine. There were only very few minor adverse events.

The authors conclude ketamine appears to be a reasonable third-line agent in the sedation of patients with acute behavioural disturbance.

Which is fair enough, but…

This study was not exactly high science or great quality evidence of anything. But at least it demonstrates that the practice of using ketamine for behavioural disturbance is not entirely a fringe concept.

The numbers are small and cannot make claims about safety. This would require much larger numbers to find rare adverse events. Nevertheless, the EM community has had vast experience with ketamine and we generally regard it as being very safe.

Would adjunctive benzodiazepines changed things? A good number of the patients with behavioural disturbance are amped up on psychostimulants and respond well to benzo, benzo, benzo. So who knows?

The fantastic accompanying editorial by Dr Steve Green was entitled, “Let’s Take ‘Em Down witha Ketamine Blow Dart.” Dr Green (aka Dr Ketamine) is largely regarded as the world’s expert on ED use of this drug. He seems to think this is reasonable and it is difficult to argue with such an intellectual badass.

So bring on the knockout dose (4-6mg/kg IM) of ketamine. To emphasize, it should NOT be a first line agent. But it may represent the best option where there truly is a significant risk to patient and caregivers and other options have failed.

Covering:

Isbester GK, Calver LA, Downes MA, et al. Ketamine as a Rescue Treatment for Difficult-to-Sedate Acute Behavioral Disturbance in the Emergency Department. Ann Emerg Med. 2016;67:581-587.

http://www.ncbi.nlm.nih.gov/pubmed/26899459

A 1-hour rule out MI protocol in the era of high sensitive troponin assays; ready for prime time

Studies of the high sensitive troponin assays all demonstrate the same thing. Patients will rule-in for MI much quicker compared to the old conventional assays. The vast majority will do so within a few hours of onset of symptoms.

The lead author of this study, Dr Tobias Reichlin has been working his way down the impact factor ladder with his ongoing research. His most recent offer has been published in the Canadian Medical Association Journal. But don’t let this fool you. This study is important and the final nail in the coffin for the 3 or 6 hour rule-out. 

This multicentre study enrolled 1320 patients presenting to the ED with suspected MI. The algorithm they attempted to validate used a baseline and 1 hour high sensitive troponin T. They looked at the absolute values in addition changes at one hour. Two independent cardiologists adjudicated the final diagnosis with access to all of the information (including troponin values... so ok, there was some incorporation bias with the gold standard.)

Results: The sensitivity and the negative predictive value for ruling out MI was 99.6% and 99.9% respectively. This made up about 60% of their cohort. The rule-in rate was 17%. They also had an indeterminate category that only made up one quarter of the patients overall. I have cut and pasted the algorithm below.

These results are one in a long line of studies demonstrating the same thing. Consistency in the literature is always compelling. The time has come to change our local protocols to allow for the safe rapid rule-out strategy in suitable patients.

Having said this, there is one strong word of caution. Beware the early presenters. Common sense would dictate that the person developing chest pain in the parking lot of the hospital should not undergo a one hour rule-out.

Unfortunately, the manuscript of this paper did a terrible job of describing the proportion of the early presenters. A vague and unhelpful mention was made in the on-line only appendix.

Another contention was the “data snooped” cut-off’s of 12ng/ml and 52ng/ml as their low and high cut-off’s for rule-out or rule-in MI. Of course this came from the earlier derivation study, but I think that 14ng/ml and 50ng/ml should be just fine. This certainly should make it more user friendly without having a substantial impact on test characteristics. Of course this is just my opinion, so there might be differing opinions.

If you are waiting for the AHA/ACC to provide updated guidelines then don’t hold your breath. The Americans have been very slow adopters of the high sensitive troponin assays. It is now up to us to determine what is clearly ready for prime time.

Covering:

Reichlin T, Twerenbold R, Wildi K, et al. Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high sensitive cardiac troponin T assay. Can Med Ass J 2015;187:1-10. doi: 10.1503/cmaj.141349

http://www.ncbi.nlm.nih.gov/pubmed/25869867

Link to the algorithm:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4435896/figure/f1-187e243/