Articles of the month (July 2016)

Another month and another edition of the articles of the month. However, this time I have some very exciting news. I have teamed up with Casey Parker (the brilliant, smooth-talking Australian physician, not the adult film star) to produce an audio version of these summaries. You will be able to find this podcast on, a great FOAM website that everyone should probably be following anyway. This is the first edition, and we will likely tweak the format with time, so if you have any feedback (hopefully more constructive than, “Justin, you have the perfect voice for silent films”), we would love for you to get in touch.

The podcast is here:

Who needs a doctor? Just light ‘em up

Sierink JC, Treskes K, Edwards MJ. Immediate total-body CT scanning versus conventional imaging and selective CT scanning in patients with severe trauma (REACT-2): a randomised controlled trial. Lancet (London, England). 2016. PMID: 27371185

We aren’t a trauma center, so the concept of a ‘pan scan’ isn’t part of our daily vernacular. That being said, every ED sees trauma, and sometimes we do end up CTing patients that don’t obviously need trauma center activation. This is a non-blinded, multi-center RCT looking at 1403 adult patients with potentially severe injuries comparing immediate whole body CT (pan-scan) to selective CT scanning. Selective scans were decided on based on protocols. For the primary outcome of mortality, there was no difference between the two groups 15.9% vs 15.7%, p=0.92. As a secondary outcome, it should not be surprising that radiation was increased in the pan-scan group (although maybe not clinically significantly.) Really, the selective CT group still wasn’t very selective (46% of this group still got a whole body CT). There is an interesting artifact in the data. The pan-scan group looks sicker when you look at the ISS scores. However, as Rory Spiegel has pointed out, when you do a whole body CT you do end up finding more injuries, but often those injuries aren’t clinically important. However, every injury you find will increase the ISS score. So the elevated ISS probably doesn’t represent unbalanced groups. It is an artifact of increased scanning.

Bottom line: Routine, thoughtless testing is never the answer. Not for trauma. Not for anything.

Read more: EMNerd, (and even more on EMNerd), The Bottom Line, EM Lit of Note, St Emlyn’s

The ongoing saga of ondansetron for nausea and vomiting in pregnancy

Fejzo MS, MacGibbon KW, Mullin PM. Ondansetron in pregnancy and risk of adverse fetal outcomes in the United States. Reproductive toxicology (Elmsford, N.Y.). 62:87-91. 2016. PMID: 27151373

There seems to be a lot of conflicting data on this topic. I think the most honest answer at this point is simply “we don’t know”.  This is a retrospective cohort comparing 1070 pregnancies exposed to ondansetron with 2 groups who were not exposed (women with and without hyperemesis gravidarum). There was no difference in teratogenicity. Overall, the rate was 3.4% in the ondansetron group and 3.4% in the ondansetron negative group (p=1.0). With regards to ventricular septal defects in particular, the recent concern, there were 2/952 with ondansetron and 4/1286 with no ondansetron (no difference). However, the ondansetron group had less miscarriages, fewer terminations, and higher rates of live births. These are very important considerations in the overall balance of harm to benefit that are often overlooked.

Bottom line: We can’t know for sure. Ondansetron may increase birth defects, although if it does, the rates will likely be low. However, we don’t know if any of the other options are actually safer.  

Maybe ondansetron is worse for your heart after you are born? (Or not)

Krammes SK, Jacobs T, Clark JM, Lutes RE. Effect of Intravenous Ondansetron on the QT Interval of Patients’ Electrocardiograms. Pediatric emergency care. 2016. PMID: 27261956

Another quick one on ondansetron. We have heard for a while that ondansetron is probably not much different from droperidol in terms of the dreaded QT prolongation that earned droperidol its black box. This an observational study looking at 100 pediatric patients (aged 6 months to 18 years) receiving ondansetron for vomiting in the emergency department. They measured QTs at baseline, at ondansetron’s peak effect (3 minutes when given IV), and 1 hour later. There was no statistically significant change in the QT interval. There also wasn’t a clinically significant increase in QT interval (mean increase of 3 milliseconds at 3 minutes). Of course, we already knew this, as we give millions of doses of this medication safely every year. However, a study this small can’t really prove safety, or rule out significant QT prolongation in a small number of patients.

Bottom line: All medications have side-effects. We should only prescribe them when they are needed. But come one – ondansetron is clearly safe and effective.

Platelets to reverse antiplatelets?

Baharoglu MI, Cordonnier C, Al-Shahi Salman R. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial. Lancet (London, England). 387(10038):2605-13. 2016. PMID 27178479

This is an open-label, multicenter RCT comparing platelet transfusion to no transfusion in adult patients with acute intracranial hemorrhage who had been on antiplatelet therapy in the prior 7 days. They enrolled 190 patients. The primary outcome, death or disability on a modified Rankin score using an ordinal analysis, was worse in the transfusion group (adjusted OR 2.05; 95% CI 1.18 – 3.56; p = 0.01). 3 month mortality was also worse in the transfusion group (68% vs 77%), although the difference was not statistically significant. There were a few problems with this trial, including its small size, lack of blinding, and baseline differences between the two groups, but it is the best trial we have on this topic to date.

Bottom line: Platelets don’t seem to help in patients with intracranial hemorrhage who have been taking antiplatelet medications – although this trial is not strong enough to definitely settle the issue.

Read more: REBEL EM, EM lit of note

The pain-free ED – minimizing children’s pain

Ali S, McGrath T, Drendel AL. An Evidence-Based Approach to Minimizing Acute Procedural Pain in the Emergency Department and Beyond. Pediatric emergency care. 32(1):36-42; quiz 43-4. 2016. PMID: 26720064

This is a nice quick review that goes over the evidence behind the things we can do to limit procedural pain in kids (although, really, we should be applying these concepts to adult patients as well). Sucrose is there, although I still think that real pain medication is better than placebo (sugar) for children. We should use topical anesthetics for needles and IVs. They talk about various distraction techniques, such as music, toys, or watching cartoons. Parental presence helps kids as does allowing them to breastfeed during the procedure. For lacerations, we should be buffering our lidocaine with bicarb, and when possible using skin adhesives. One thing I didn’t know and might change practice for people is that venipuncture is significantly less painful than heel lance. The only thing that wasn’t mentioned, but I think is an essential tool, is intranasal analgesia and sedation.

Bottom line: These are all techniques that we should be applying routinely

Epinephrine in digital blocks – the benefits

Welch JL, Cooper DD. Should I Use Lidocaine With Epinephrine in Digital Nerve Blocks? Annals of emergency medicine. 2016. PMID: 27125816

I’ve discussed papers that indicated epinephrine is safe in digital blocks before, but that always raised the question of why you would want to use epinephrine. This is a systematic review looking at RCTs comparing lidocaine plus epinephrine to lidocaine alone in digital nerve blocks. One study looked at duration of anesthesia: it was a median of 3.2 hours longer in the epinephrine group (95%CI 2.5-3.9). 2 studies looked at bleeding: it was also less in the epinephrine group (RR 0.35, 95%CI .02-0.7). There were no adverse events. Of course, these are small studies, but we know epinephrine has these advantages when used elsewhere in the body, so why not in the digits?

Bottom line: Not only is epinephrine safe in digital blocks, but there may be some advantage to using it as well.

The elbow fat pad: could this really be another example of dogma?

Jie KE, van Dam LF, Hammacher ER. Isolated fat pad sign in acute elbow injury: is it clinically relevant? European journal of emergency medicine : official journal of the European Society for Emergency Medicine. 23(3):228-31. 2016. PMID: 26153882

Orthopedics is one area of emergency medicine that seems to be rife with dogma. I was taught to cast buckle fractures and Salter-Harris 1 injuries, but no longer do either. I was told I should never use NSAIDs in patients with fractures, but think that is probably a myth. However, for some reason, it had never occurred to me that this could be a myth: the fat pad sign in the elbow is a clear indication of a fracture, or serious injury. This is a subset of a prospective observational trial, in which 587 adults with acute isolated elbow injuries all had x-rays done. This study looked at the 111 (19%) that had an isolated fat pad (anterior sail sign and/or posterior fat pad) but no other injuries seen on the x-ray. The standard practice for these patients was an elastic bandage and a sling, with orthopedics follow-up in 1 week. (Where I work, children generally get a plaster splint, as we are concerned about occult supracondylar fractures.) At the 1 week follow up, there were no significant injuries identified, although they did not routinely get follow-up x-rays. Only 1 patients was transitioned to a cast because of ongoing pain. Unfortunately, they did lose 17% of the patients to follow-up at 1 week. They had long term follow up (phone calls 22 months later) on 90% of the patients, and there were no patients with persistent symptoms that prevented them from carrying out their daily activities.

Bottom line: The classic teaching that an elbow fat pad signs indicates an occult fracture could be wrong

Another pediatric ortho myth?

Schuh AM, Whitlock KB, Klein EJ. Management of Toddler’s Fractures in the Pediatric Emergency Department. Pediatric emergency care. 32(7):452-4. 2016. PMID: 26087443

This is another paper about a potential pediatric orthopedics myth – although without much in the way of evidence. Perhaps the most interesting part of the paper is the reference to prior orthopedics literature that argues that toddler’s fractures almost never displace, so there may not be any real reason to immobilize these children for prolonged lengths of time. The study  is a retrospective chart review, looking at all the children aged 9 months to 3 years diagnosed with a toddler’s fracture (undisplaced spiral fracture of the tibia) based on x-ray at their single tertiary pediatric emergency department. Interestingly, 9% of children with spiral fractures on x-ray were managed without any immobilization at this center. 24% were given a removable boot, and the remaining 67% were splinted or casted. Unfortunately, we don’t have any information on pain control, short term, or long term functionality, so we really can’t conclude anything except that there are pediatric specialists out there managing toddler’s fractures without immobilization. Somewhat concerningly, 17% of their cohort ended up with skin breakdown from their cast or splint, so there is probably a legitimate question about whether the benefits of immobilization outweigh harms in a condition where displacement is essentially unheard of..

Bottom line: Not nearly enough to change practice, but certainly thought provoking

I am unsure exactly what to do with this paper

Wray CM, Loo LK. The Diagnosis, Prognosis, and Treatment of Medical Uncertainty. Journal of graduate medical education. 7(4):523-7. 2015. PMID: 26692960

This is an nice editorial reviewing uncertainty in medicine that is worth reading. They point out that no matter how much information we are able to gather, the inherent complexity of human life, the variability of presentations, and the fact that we cannot predict the future will always leave us with an intrinsic uncertainty. They point out the problem in medical education in that we value certainty from our students, and present them with black and white multiple choice exams that don’t well represent the grey of real life medicine. They close with an excellent quote from Sir William Osler: “A distressing feature in the life of which you are about to enter … is the uncertainty which pertains not alone to our science and art, but the very hopes and fears which make us men. In seeking out the absolute truth we aim for the unattainable, and must be content with finding broken portions.’’

Bottom line: Every doctor must be comfortable and quick to admit “I don’t know”

Enough flip-flopping to make you think Cochrane is running for office

Gagyor I, Madhok VB, Daly F. Antiviral treatment for Bell’s palsy (idiopathic facial paralysis). The Cochrane database of systematic reviews. 2015. PMID: 26559436

This whole topic is a mess and I don’t think I can sort it out for you. The prior cochrane review on this topic demonstrated no benefit to the use of antiviral medications for the treatment of Bell’s palsy. This updated review adds 3 new trials and a total of 300 patients and they came to a different conclusion. However, this is a revised version of the review. The same author group published the same review earlier in 2015. At that point it included 1 more trial (of 500 patients) and their conclusions were that there was no significant benefit to adding antivirals to corticosteroids for the treatment of Bell’s palsy. That trial (Abdelghany et al 2013) has been removed, because they are questioning the reliability of the data, and now it does look like antivirals might help. For what is is worth, incomplete recovery and ‘crocodile tears’ were both better with antivirals (RR 0.61 95%CI 0.39-0.97 and RR 0.56 95%CI 0.36-0.87 respectively.) Honestly, I am not sure what to make of these results. The fact that you couldn’t see a benefit with 2000 patients in the prior Cochrane review means any benefit is likely to be small. The quality of a meta-analysis is dependent on the quality of the included studies – which leaves us with just a bunch of poor quality data here. A single large, high quality RCT would overrule all of this data. Probably the most important point for me is that these trials do not adequately report harms (with only 3/10 mentioning adverse events), so there is no way to know is the small potential benefit outweighs the harms.

Bottom line: It’s a positive Cochrane review, so I wouldn’t blame you if you used it to change your practice, but personally I think there are way too many issues with this data and will continue not suggesting antivirals in Bell’s palsy

Another knock against amiodarone

Ortiz M, Martín A, Arribas F. Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study. European heart journal. 2016. PMID: 27354046

This is a multicenter, randomized trial comparing amiodarone (5mg/kg over 20 minutes) to procainamide (10mg/kg over 20 min) in 74 adult patients with hemodynamically stable ventricular tachycardia. The results will be surprising to anyone who has listened to drug reps or the AHA over the last 15 years, but probably not surprising to anyone who has read the prior amiodarone literature. Procainamide was better. The primary outcome of cardiac adverse events (mostly hypotension requiring cardioversion), occurred in 9% of the procainamide group and 41% of the amiodarone group (odds ratio 0.1, 95%CI 0.03-.06, p=0.006). In terms of stopping the v.tach, procainamide worked 67% of the time as compared to only 38% with amiodarone (OR = 3.3; 95% CI 1.2-9.3; P = 0.026). Unfortunately, the trial was originally designed to include 300 patients, but they stopped it early because of slow recruitment. However, this comparison may not be all that relevant to you if, like me, you prefer to go straight to electricity in these patients.

Bottom line: Amiodarone is definitely not as good as cardiologists think it is

The vital signs are better – this couldn’t be PE

Kline JA, Corredor DM, Hogg MM, Hernandez J, Jones AE. Normalization of vital signs does not reduce the probability of acute pulmonary embolism in symptomatic emergency department patients. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 19(1):11-7. 2012. PMID: 22251189 [free full text]

This is a good study, but I worry that the results could be misinterpreted to the detriment of our patients. This is a prospective, single center diagnostic accuracy study, looking at whether normalization of initially abnormal triage vital signs lowered the chance of pulmonary embolism in adult emergency department patients. (Any single center that Jeff Kline works at might be very different from other centers in terms of PE diagnosis, potentially limiting generalizability.) These were non-consecutive patients who were identified because the treating clinicians ordered a CTPA (the key to interpreting this data). The overall rate of positive CTs in this cohort is 5%. Change in vital signs did not predict PE and the vital signs changed the same amout in both the PE positive and negative groups. However, this was only in patients for whom the physician was concerned enough to order a CT scan. There might be a large group of patients whose vital signs normalized, and the physicians actually used that information to rule-out PE, and so never ordered the CT. If they were included, it is possible that changing vital signs would be predictive. I have never used normalizing vital signs as a way to eliminate PE, but I do worry about this data being taken too far. (And I have seen some overreaching interpretations on Twitter). A healthy young person with a heart rate of 65 at the time that I am seeing them is unlikely to have a clinically significant PE, even if when they nervously walked up to triage their heart rate was 105. A single abnormal number does not overrule your clinical judgement. People with no pretest probability of a PE should not be getting a D-dimer sent just because of a single abnormal heart rate at triage.

Bottom line: Normalizing vital signs do not rule out PE in patients who you are still concerned enough about PE to order a CT scan

Apparently babies don’t need oxygen

Principi T, Coates AL, Parkin PC, Stephens D, DaSilva Z, Schuh S. Effect of Oxygen Desaturations on Subsequent Medical Visits in Infants Discharged From the Emergency Department With Bronchiolitis. JAMA pediatrics. 170(6):602-8. 2016. PMID: 26928704

This is one of a number of recent publications that downplay the importance of oxygen saturation in bronchiolitis. If true, this might be helpful, as even if the sats are a little low, there isn’t anything I can do to help these kids aside from admitting them to hospital for oxygen therapy, which seems like overkill in a self-limited, generally safe viral disease. However, I am not sure that any of these studies are looking at the outcomes we should care about. This is a prospective cohort from a single center (Sick Kids in Toronto) of 118 healthy infants (aged 6 weeks to 12 months) who were discharged home from the ED with acute bronchiolitis. They sent the children home attached to a continuous oxygen saturation monitor, but the display was turned off. They found that 64% of the children had at least 1 desaturation event (O2 sat less than 90% for at least 1 minute). The median length of desaturation was 3 minutes and 22 seconds (interquartile range 1:54 to 8:50). 50% of children had desaturations to 80% or lower for more than one minute, and 25% had desaturations of 70% or lower. The primary outcome of unscheduled medical visits was the same whether or not you had a desaturation, so the authors conclude that pulse oximetry is not an effective tool. However, this is clearly not the most appropriate primary outcome when talking about oxygen saturation. I worry about a low sat because you are starting to fall off the hemoglobin dissociation curve. It isn’t follow up visits that I care about, but death – but that is such a rare outcome, that a study this small has no chance of telling us is these desaturations are safe. Also, if you are desaturating for longer than 8 minutes, I am worried about your brain cells, but we are going to need some very long and intensive studies to determine if there are any changes there.

Bottom line: There is a push to lower your oxygen goals in bronchiolitis, and I am always for doing less in medicine, but none of the evidence to date is strong enough to prove safety.  

Surprisingly, a medication that doesn’t decrease pain was shown not to decrease pain

Friedman BW, Cabral L, Adewunmi V. Diphenhydramine as Adjuvant Therapy for Acute Migraine: An Emergency Department-Based Randomized Clinical Trial. Annals of emergency medicine. 67(1):32-39.e3. 2016. PMID: 26320523

Is diphenhydramine part of your cocktail for managing migraines? This is a randomized, double-blind RCT comparing metoclopramide 10mg IV, either with diphenhydramine 50mg IV or placebo in 208 adult emergency patients with migraines. There was no difference in the primary outcomes of sustained headache relief at 48 hours (40 vs 37%). There was also no difference at 1 hour. However, I think this represents a misunderstanding of why diphenhydramine is used. It is not used to treat pain, but rather to prevent the extra-pyramidal side effects of other migraine medications we use. (Although, I think it makes more sense to just wait and give it to the few patients that need it, rather than just treating everyone prophylactically.)

Bottom line: Diphenhydramine was never going to decrease pain, if anyone thought that it did

Cheesy Joke of the Month

What did the pony say when it had a sore throat?

I apologize, I am a little horse!

Author: Justin Morgenstern

Community emerg doc, FOAM enthusiast, evidence junkie “One special advantage of the skeptical attitude of mind is that a man is never vexed to find that after all he has been in the wrong.” - William Osler

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