Friday, 18 April 2014

Welcome to EmergencyMedJC

The following posts are short and pertinent summaries of interesting articles discussed at our multi-disciplinary journal clubs in our area. We are a small Emergency Department located in regional Tasmania and as such we have the fortune of combining our meetings with other departments throughout the hospital. The different perspectives are worth their weight in gold and provide insight beyond the typical dedicated EM journal club. I thank my colleagues for their support and input. Much of what I post are the highlights from the discussion and certainly I cannot claim all of it as my own.

I endeavour to keep each post short and hit the key points. In order to maintain interest, I purposely do not mention every last detail of the methodology, statistics & results. Rather I have tried to filter out the best parts and hope readers find this educational and practical.  

I very much appreciate any feedback or suggestions. Enjoy!



Which blood test is the best at identifying serious bacterial infection (SBI) in febrile children without a source?

In the new era of widespread childhood immunization the rates of SBI in children has been plummeting. Hib and PCV7 vaccine have made our lives almost boring in the ED. When was the last time you saw a good case of pediatric epiglotitis? Have you even heard of buccal cellulitis? Well, at least vaccination has been good for kids.

But widespread immunization has also created a diagnostic problem for us. The prevalence of serious bacterial illness is now so low it is a kin to finding a needle in a haystack. Imperfect clinical acumen will certainly find more false positives than true positives. Or perhaps we will just get complacent and call everyone negative until it’s too late. We really don’t want to be missing something serious. I wish there was a blood test to help us.

Along comes a well done systematic review and meta-analysis published in the Annals of Emergency Medicine looking at the old favourites WBC, CRP and the new kid on the block procalcitonin. Which one is best at picking up SBI?

After a good systematic review, 8 studies were included for a total of 1,883 patients comparing the three blood tests. The primary outcome was the ability to detect SBI in children with fever without a source.

Right off the bat there is a problem with the definition of SBI. Included are some rare but serious conditions such as meningitis and sepsis. But also included are UTI, gastroenteritis, pneumonia and occult bacteremia. Cynics might proclaim, “If the bacteremia is so occult, then why should I care?” Do I really need a blood test to help me identify pneumonia, gastroenteritis or UTI’s? Shouldn’t I have picked up on this by other means? How many of the UTI’s were really false positive? As is the case in many of the studies of SBI, the majority had UTI as their “serious” illness.

In the end procalcitonin was the best of the worst. Its point estimate of sensitivity was 0.83 and specificity 0.69. Despite getting bigger numbers to crunch in this meta-analysis the confidence interval for sensitivity was as low at 0.70. CRP was hardly better. WBC was as good as flipping a coin. One might reasonably ask if this is good enough.

Another concern is these studies are performed in a heterogeneous population. These tests likely perform better at the more extreme spectrum of disease. I am not looking for a blood test to help me when it is quite clear one way or another if a child is sick. I want to know if it can help me when I’m on the fence. Therefore these tests may perform worse in the exact situation when I want to use them the most.

So what’s the take home point? At best these tests are a piece of the puzzle when evaluating the child without a source of fever. We should never use them in isolation or be overly reliant upon their ability to change our medical decision making. It is unusual for them sway my cognitive process in the ED. Believe it or not, I actually have the patient in front of me. Sometimes I can admit them or observe them for a period of time... crazy.


Yo Hc, Hsieh PS, Lee SH, et al. Comparison of the Test Characteristics of Procalcitonin to C-Reactive Protein and Leukocytosis for the Detection of Serious Bacterial Infections in Children Presenting With Fever Without a Source: A Systematic Review and Meta-analysis. Ann Emerg Med 2012;60:591-600.

Thursday, 17 April 2014

Single dose dexamethasone for asthma?

In the chaos of the Emergency Department, I love to keep things simple. Nothing makes me happier than to be able to give a single dose of a drug to cure a particular condition. No need for a prescription and no need to worry about medication non-compliance. Acute exacerbations of asthma are such a ubiquitous presentation that I have longed hoped that a single dose of dexamethasone would be sufficient to effect a cure in suitable outpatients. I have been looking for data to support my “hypothesis” for some time now. Perhaps we have found it in the form of a recent systematic review and meta-analysis published in the journal Pediatrics.

Six randomized trials were identified after an explicitly defined search of Medline looking at dexamethasone vs. prednisone/prednisolone for the outpatient treatment of asthma. The primary outcome was return visits or hospital readmissions. As is the potential weakness of meta-analysis, there was some heterogeneity in the studies identified. Dexamethasone was given as a single IM dose in 3 studies, as a single oral dose in 1 study and as multiple oral doses in 2 studies. Therefore combining them may be problematic.

Nevertheless, there were no differences in relative risk in the primary outcome and the conclusion was “practitioners should consider single or 2-dose regimens of dexamethasone as a viable alternative to 5 days of prednisolone/prednisone.”

The whole point of a meta-analysis is to combine similar smaller studies in order to have greater statistical power to detect differences between groups. In addition, this greater number gives you better point estimates, narrow confidence intervals and allows you to look at subgroups that may have been impossible had the studies not been combined. Unfortunately this meta-analysis only included ONE small study with 117 patients that gave a single dose of oral dexamethasone (0.6mg/kg up to 18mg). Perhaps the jury is still out.

Whats the bottom line? I like the conclusion. I like the fact that it is printed in pretty font in a high impact journal. This may provide me with greater confidence (perhaps bravado) when prescribing a single dose of dexamethasone for outpatient asthma. But the monkey on my back has me worried that there still is a lack of high quality evidence to support this practice. A single large good quality RCT will trump a meta-analysis any day. Can someone please chuck a banana to the monkey and conduct a large RCT?


Keeney, GE, Gray MP, Morrison AK, et al. Dexamethasone for Acute Asthma Exacerbations in Children: A Meta-analyisis. Pediatrics 2014;133:493-499

Tympanostomy tube and otorrhea. Which treatment is best?

This well done open label randomized published in the NEJM comes to us from the Netherlands. Parts of Europe and Scandinavia have long had a more enlightened & conservative approach to acute otitis media. But this condition is a little different. I think we have all had the young child with tubes (grommets) in their ears who now has fluid (or pus) discharging from the ear. Should we put them on oral antibiotics, topical drops or adopt a wait and watch approach? This is a useful question to answer.

This study randomized children in a 1:1:1 fashion to hydrocortisone-bacitracin-colistin ear drops, or augmentin (think diarrhea) or initial observation. The primary outcome measure was the presence of otorrhea at 2 weeks as determined by otoscopy by a study investigator.

There were 230 patients enrolled. The results showed a fantastic treatment effect of the topical drops. At 2 weeks only 5% of the children randomized to drops had otorrhea as compared to 44% in the Augmentin group and 55% in initial observation.

There are perhaps a few issues of external validity when interpreting this paper. The specific ear drops studied are only available in the Netherlands and France. Nevertheless, there likely are similar drops around the world that do not contain ototoxic aminoglycosides. The study protocol involved quite a lot of home visits which may have provided extra insensitive for medication compliance.

The primary outcome is interesting and of dubious importance. The reason for placement of typmanostomy tubes is to allow for the drainage of the middle ear. Therefore drainage could be considered a normal and perhaps desirable process in the setting of otitis media. Of course one might be concerned about prolonged otorrhea and inflammation. But it is hard to know if this is a meaningful outcome.

I think the biggest issue of concern is the general caution that should come when looking at small studies showing dramatic treatment effects. These are almost always shown to be less impressive on subsequent study.

What are the take home points? Despite some of the above concerns, this is a compelling study. I doubt that the drops really work as well as this small study suggests. But now I find myself searching for the appropriate drops the next time I see that kid with tympanostomy tubes and pus flowing from ear.


M.A. va Dongen T, J.M.G. van der Heijden G, Vanekamp RP, et al. A Trial of Treatment for Acute Otorrhea in Children with Tympanostomy Tubes. N Eng J Med 2014;270:723-33.


Cough and Cold? Getting a better nights sleep with Vick's Vapo Rub?

It is great to see the eye’s of science peer down on a consumer product as old and ubiquitous as Vicks Vapo Rub. A recent randomized trial in the journal Pediatrics looked at the effect of vapor rub, petrolatum (petroleum jelly), or no treatment for children with nocturnal cough symptoms. As the parent of small children who currently have colds, I want to know the answer. Which works best?

Surveys (6 questions on a 7 point Likert scale) were administered to parents on 2 consecutive days. The first was done on the day of presentation to a pediatric clinic before medication was given. Children were randomised to get one of the above treatments. Then the next survey was completed the following day by the parent self report who hopefully had a better night’s sleep

I already know what you are thinking? How did they blind Vapo Rub? Believe it or not, the study design cleverly asked parents to place Vapo Rub below their nose before opening the study packet which contained the randomised medication. (I wonder how many actually performed this requested step!? ) In addition, they asked the children not to disclose to their parents whether the treatment had an odor. Despite these efforts, the parents were able to accurately identify the actual treatment arm 90% of the time.

The results? 138 children completed the trial. Vicks Vapo Rub consistently scored the best and no treatment was the worst.

Unfortunately it is hard to really get a sense of how much the Vapo Rub actually works given the nature of the complex Likert scale utilized as the outcome measure.

Obviously there could have been some bias introduced due to lack of blinding. Do smelly placebos work better? Once again, this was a self completed survey by the parent.

In addition, this study was industry funded! It was supported by an unrestricted grant from Procter & Gamble and the lead author has been a paid consultant for company. Is nothing else sacred in this world?

This study is far from definitive. I would be disappointed but not overly surprised if I saw direct to consumer advertisements for Vapor Rub stating it is “clinically proven” to decrease nocturnal cough and cold symptoms in children.

What will I do with my kids? I’m busting out the Vapo Rub! Yes the science isn’t perfect but if the parents said they all slept better than what am I to do. If my evidenced based sceptical head is sleeping on a pillow made of placebo, then so be it.


Paul IM, Beiler JS, King TS et al. Vapor Rub, Petrolatum, and No Treatment for Children With Nocturnal Cough and Cold Symptoms. Pediatrics 2010;126;1092-1099.

How much IV fluids should we be giving children in DKA in order to avoid cerebral oedema (CE)?

The pathogenesis of CE in children with DKA is controversial. There are those who propose that it is caused by excessive administration of IV fluids and cerebral osmotic shifts. Alternatively it might be caused by cerebral hypoperfusion and reperfusion during DKA treatment. Should we be giving more fluid or less fluid… Who knows?

In an ideal world, we would answer this question by conducting a large randomized control trial in the sickest subset of children. These are the kids who develop CE. We would randomize two groups. One gets lots of fluids and the other not so much. The primary outcome would be death as this is usually caused by cerebral oedema. Unfortunately such a study would be near impossible to conduct given the rarity of clinical apparent CE in children with DKA.

The authors of this paper perhaps tried the next best thing. They conducted an RCT using 2 different rehydration protocols (but some would argue were not that different). In the end, one group got 60ml/kg and the other 40ml/kg in the first 8 hours. They used the “apparent diffusion coefficient” on serial MRI’s as a surrogate marker to look for cerebral oedema.  All of kids recovered well.

The conclusion of the paper? Cerebral oedema does not appear to be substantially affected by the rate of IV fluid administration.

But hold on a minute… There were only 18 children included in this study. Clearly there would have only been enough statistical power to find very large differences in the study arms. In addition, one might question the validity of the surrogate marker looking for subclinical CE. The conclusion as written in the paper clearly overstates any reasonable interpretation of this study.

In the end, this paper raises more questions than it answers. It certainly would raise the hypothesis (again) calling for a large RCT which will probably never happen.

Before we get too critical, we should remember that the lead author, Dr Nicole Glaser, a professor of pediatric endocrinology at UC Davis has done some fantastic work well over the past decade looking at this subject. (Remember NEJM 2001;344(4):264-269?) This is a very challenging niche of research and we see look forward to see more of her work.



Glaser NS, Wootton-Gorges SL, Buonocore MH et al. Subclinical Cerebral Edema in Children With Diabetic Ketoacidosis Randomized to 2 Different Rehydration Protocols. Pediatrics 2013;131;e73-e80.