Author: Ryan Radecki

Dexamethasone. Think About It.

Many aspects of medicine are simply based on momentum and routine.  One of those routines, in my anecdotal experience, is the use of 5-day courses of steroids for mild/moderate asthma exacerbations.  However, why give multiple doses when one will suffice?  Why not dexamethasone?

Unfortunately, this meta-analysis doesn’t really bring any new knowledge into play.  These authors attempt to pool the results from all the pediatric randomized trials comparing dexamethasone vs. short-course prednisone for the outpatient management of asthma with exacerbation.  No included individual trial showed a relapse rate with dexamethasone significantly worse than prednisone – and, unsurprisingly, the pooled results reflect that same finding.  The only recorded adverse effect – vomiting in the ED or at home – was seen less frequently with dexamethasone, although the overall incidence in both arms was minimal.

But, there are only six trials, most of which are fewer than 100 patients.  These trials are also a mix of oral and intramuscular, single and multiple dose, and dose ranges from 0.3 mg/kg to 1.7 mg/kg (“max 36 mg”!).  There were also methodologic problems with blinding, allocation, and other outcomes issues with each included study.

Based on this low-quality evidence, it would be reasonable to say dexamethasone use is not adequately described in the literature.  It would, likewise, be reasonable to go ahead and make use of dexamethasone in this setting, with the recognition of these limitations.  Personally, I fall on the dexamethasone side of the argument – for children, as well as adults.  When feasible, I use an approximately prednisone-equivalent oral dosing at 0.15 mg/kg up to a maximum dose of 12mg in both populations.

And I would love to see a high-quality trial to settle matter, once and for all.

“Dexamethasone for Acute Asthma Exacerbations in Children: A Meta-analysis”
http://www.ncbi.nlm.nih.gov/pubmed/24515516

Blood Pressure and ICH: The Beat Goes On….

A guest post by William Paolo (@paolomd1), the Program Director of Emergency Medicine at SUNY Upstate.

Spontaneous intracerebral hemorrhage (ICH) continues to carry a great deal of morbidity and mortality, with little hyperacute emergent patient interventions available to the treating physician.  For these reasons multiple avenues to alter patient prognosis have been explored, from continuous ICP monitoring to decompressive craniectomies, with little demonstrable patient benefit.  Elevations in blood pressure (BP) in all forms of measurement (SBP, DBP, MAP) have long been associated with worse outcomes in individuals with spontaneous ICH.  At issue is the nature of the association between ICH and a rise in BP, as it is not entirely clear that the subsequent elevation is directly responsible for causative harm rather than correlated poor outcomes.   As BP is a simple empirical data point, multiple studies have attempted to define the relationship between poor outcomes and BP to determine if acute BP lowering will result in net patient benefit.  It should be noted that the theoretical benefit of BP lowering in the face of ICH is counterbalanced by the potential for harm if elevations of MAP are in fact adaptive to allow for adequate cerebral and penumbral perfusion in the face of rising ICP.

In June of 2013 the New England Journal of Medicine published the INTERACT2 study in which individuals with spontaneous ICH were randomized into intensive BP lowering versus current guidelines based lowering.   The study assessed the proportion with poor outcomes (a composite of death and major disability) as its primary outcome, and a secondary outcome consisting of multiple measures of quality of life and death.  INTERACT2 found no difference in the primary outcome and discovered no difference between the hematoma growth across cohorts.  Only after conducting an ordinal analysis did the authors report a better functional primary outcome in the intensive BP lowering group, a result not fully supported by a principal analysis of the study’s raw findings. 

Continuing this work, The Lancet Neurology has published a post-hoc analysis of the INTERACT2 database in which it is hypothesized that variability in BP is predictive of poor outcomes in addition to total BP elevation.  The authors reanalyzed the INTERACT2 raw data looking for the association between variation in BP and patient outcomes.  Given multiple statistical assumptions and parsing of the initial data, the study determines that there is indeed an association between BP variation and poor outcomes.  The study concludes that the findings are in fact relevant to practice and should cause the provider not only to lower the BP acutely in ICH, but to aim for a smooth reduction in BP with little variability.  Unfortunately it is difficult to endorse the study’s findings given its multiple limitations and assumptions.  The entire INTERACT2 database was examined as a single cohort, lumping in together both treatment arms into a single evaluative group.  The authors posit that this demonstrates the robustness of the association, however it may in fact prove the opposite.  While it may be true that variability is predictive independent of treatment, it may also be true, given the grouped analysis, that treatment does not affect outcomes, and that BP across treatment groups predicts poor outcomes without the ability to positively intervene to change net patient results.  Further, the study is a post-hoc analysis in which a hypothesis is generated prior to the generation of data allowing only the demonstration of association.  No matter how robust the findings, clinical practice changes should not be recommended based on a study whose design can only generate new hypotheses from their discovered correlations to be confirmed with prospective evaluations.   Unfortunately, the debate will continue regarding BP management in ICH, as this study does not alter clinical practice nor change the negative findings of the INTERACT2 trial.

“Blood pressure variability and outcome after acute intracerebral haemorrhage: a post-hoc analysis of INTERACT2, a randomised controlled trial.”

Splicing Up PECARN

The PECARN study is the largest of the prospective evaluations of children with minor head injury for clinically important traumatic brain injury.  The derived prediction instruments, for children aged <2 years of age and for children aged 2 to 18 years, generate “very low risk” cohorts whose incidence of important injury is negligible.  However, the overall incidence of cTBI was quite low in the entire study – meaning each positive predictor still only raises the risk of cTBI from negligible to tiny.

One of the predictors, vomiting, is an element in the decision instrument for children aged 2 to 18 years.  The management recommendation for patients with vomiting, then, defaults to “do as is your wont” – and studies suggest most folks are going ahead with CT, rather than using the “observation” option.

This study goes back and looks specifically at the vomiting component – and tries to tease out whether “isolated” or “non-isolated” prior to enrollment provided additional information.  Of the 5,392 enrolled patients with complete data, 815 had a single episode of vomiting – with 0.2% having cTBI.  The remaining 4,577 with non-isolated vomiting had a 2.5% incidence of cTBI.  The article goes further into the details of the data set, noting patients with vomiting who received CT were more likely to have cTBI – but also had other concomitant comorbid injury.

This is, unfortunately, not terribly profound – and of debatable utility.  The joy – what there is – of PECARN is its use as a decision-instrument with which to simplify medical decsion-making.  Mining the details of individual +LR and -LR provides more patient-specific information, but increases the complexity of knowledge translation – and ultimately decreases the contextual acceptability of the product.  The cTBI is heterogeneously distributed throughout the PECARN set – but the existing rule cannot be improved upon until better tools emerge to offload the cognitive demand required for for precision medicine-type applications.

“Association of Traumatic Brain Injuries With Vomiting in Children With Blunt Head Trauma”
http://www.ncbi.nlm.nih.gov/pubmed/24559605

Still Muddling Through Massive Hemorrhage

The last few years have given way to a paradigm shift in the resuscitation of traumatic hemorrhage.  Using observational data from military settings, resuscitation strategies utilizing reactive correction of coagulopathy have given way to strategies mimicking whole blood transfusion.  Limited evidence suggests PRBC:FFP:Platelet ratios nearing 1:1:1 may be beneficial in resuscitation from traumatic hemorrhage.

This observational study of trauma patients followed lactate levels and measures of coagulopathy during the acute resuscitative phase from major trauma.  106 patients with median Injury Severity Score of 34 received a median of 8 units of PRBCs, 6 units of FFP, and a smattering of platelets and cryoprecipitate transfusions.  Lactate levels, as compared by median and IQR, did not significantly normalize following the initial transfusion, requiring a full day of therapeutic intervention to improve.  Likewise, measures of coagulopathy did not reflect improvement in the acute phase, tending to normalize only after a full day.  It did not matter whether patients received a small, moderate, or large amount of resuscitation.

This study only comments on surrogate outcomes – serum lactate, markers of coagulopathy – and not patient-oriented outcomes, but it serves as a reminder the science is clearly not settled regarding the optimal, cost-effective fashion to resuscitate patients from traumatic hemorrhage.  While many centers have fully adopted whole blood-style resuscitation strategies, it would be incorrect to conclude we have any sort of certainty in the matter.

“Hemostatic resuscitation is neither hemostatic nor resuscitative in trauma hemorrhage”
http://www.ncbi.nlm.nih.gov/pubmed/24553520

Kids with Tubes and Otitis Media Get Drops not Pills

A guest post by Anand Swaminathan (@EMSwami) of EM Lyceum and Essentials of EM fame.

Over the last decade, researchers have sought to determine the usefulness, or lack there of, for systemic antibiotics in a number of infectious etiologies previously thought to require antibiotics for resolution. This includes strep throat, sinusitis, bronchitis and, more recently, diverticulitis. Acute otitis media (AOM) has long been a target for such studies and recently, the guidelines have changed. The American Academy of Pediatrics now endorses a “wait and see” approach for many children with AOM while also recommending a more stringent definition of the disease.

What about for patients with tympanostomy tubes who present with signs of AOM? These patients typically present with otorrhea (pus from the tympanostomy tube). Is the presence of drainage adequate to treat or should these patients be placed on oral or topical antibiotics? Small trials have shown good efficacy of topical antibiotics but Pediatricians and Emergency Physicians continue to prescribe oral antibiotics in the face of inadequate evidence.

The researchers here attempt to answer this question. They performed a fairly large study of 230 children who were randomized to either observation, oral antibiotics or topical antibiotic-glucocortocoid drops in an open-label fashion. The primary endpoint was resolution of otorrhea at 2 weeks. The results are surprising. Resolution was seen in 95% in the group given drops, 56% in the oral antibiotic group and 45% in the observation group. These numbers yield a miniscule NNT = 3 for resolution of otorrhea with topical antibiotics-glucocortocoids vs. oral antibiotics.

A couple of notes are important. All of the patients had otorrhea for up to 7 days prior to entering the study and the presence of a fever excluded them from the study. Additionally, tubes couldn’t be recently placed (< 2 weeks) there couldn’t be recent antibiotic use (< 2 weeks) or otorrhea (< 4 weeks).

As evidence mounts to the harms of inappropriate and unnecessary systemic antibiotic use, it’s important to tailor therapy based on the available literature. Many patients with tympanostomy tubes that develop otorrhea will resolve with simple observation. However, treatment with topical antibiotic-glucocortocoid drops should be the first line treatment as they are superior to oral antibiotics with fewer side effects.

“A trial of treatment for acute otorrhea in children with tympanostomy tubes.” 

Sources of Nonmedical Opiates

Making an even three consecutive posts on opiate abuse makes a week of it; this ought to be the last, unless further profound insights are hot-off-the-presses.

This study – actually a minor Research Letter in JAMA Internal Medicine – evaluates self-reported behavioral patterns in nonmedical drug use in the United States.  This accompanies another study looking at the risk factors for unintentional opiate-related deaths, which, helpfully, adds a little context.

This survey extrapolates out to approximately 12 million nonmedical opiate users aged greater than 12 years in the United States.  A slight majority of users were male, and most had annual incomes less than USD$50,000.  Most interesting, however, is Table 2, which describes how the source of opiates varies with increasing frequency of use.  Individuals who reported nonmedical use of opiates fewer than 30 days out of the year received their opiates predominantly for free from a friend or relative.  As frequency of use increased, opiates were less frequently received from a friend for free – and more likely to be received from a physician or purchased from friends, family, or drug dealers.  As the accompanying study notes, increasing prescription and increasing mean daily use of opiates were associated with increased risk of death – so it would appear the population at highest risk of death also has the greatest extent of physician contact for opiates.

But, just as important as it may be to evaluate an individual risk for opiate misuse when prescribing, it is also important to note the majority of nonmedical use was obtained via diversion activities.  Every opiate prescribed enters an ecosystem of illicit exchange – presumably under-recognized by physicians, else I would expect far fewer prescriptions.  Judicious – and sparing – use of opiates is far more likely to benefit society than harm.

“Sources of Prescription Opioid Pain Relievers by Frequency of Past-Year Nonmedical Use: United States, 2008-2011”
http://archinte.jamanetwork.com/article.aspx?articleid=1840031

Nonsensical Opiate Overuse in Adolescent Headache

The title says it all.

This is an observational cohort analysis of linked medical and pharmacy records for commercially insured patients across 14 health plans.  Patients were identified by age 13-17 with, allegedly, new-onset atraumatic headache from claims database abstraction – limited, of course, by the nature of querying such a database.  8,373 patients were identified from their two year study period as meeting these criteria.

And 46% were prescribed opiates.

52% of those received more than one prescription for opiates, including 11% who received 5 or more prescriptions for opiates during the study period.

This study came about because the insurer contacted the American Academy of Pediatrics with a query regarding the appropriate frequency of use of opiates for headache.  The answer ought to be a tiny fraction, as third-line or rescue therapy.

Considering all the problems this country has with prescription opiate abuse, it is maddening to see physicians inoculating such a vulnerable population with medication whose harms almost certainly outweigh the benefits.

“Opioid Use Among Adolescent Patients Treated for Headache”
http://www.jahonline.org/article/S1054-139X(13)00834-3/abstract

Gently Euthanizing the Elderly

It is well-known the elderly are at higher risk for medication adverse effects.  It is, likewise, recognized opiates are one of the most dangerous prescription medications in use.  Therefore, the prudent thing to do would be avoid opiate use in the elderly – and, certainly, not be irresponsible regarding multiple, concurrent prescriptions for opiates.

However, as this 20% random sample of Medicare beneficiaries demonstrates, an estimated 5.2M Americans covered by this insurance source received opiates – with approximately 85% of this cohort aged greater than 55.  Most patients who received opiates filled more than one prescription – including a full 7% who received >4 prescriptions, from >4 different providers.  This last group received a mean number 15 opiate prescriptions in a single calendar year.  Unsurprisingly, increased opiate prescriptions were associated with increased subsequent hospitalizations.  While there is no mortality data in this report, I don’t think it’s a stretch to speculate the illness-adjusted outcomes would be much poorer.

The use of opiates for pain control for acute and chronic illness is a necessary evil, particularly in the elderly.  This study, given its limitations, cannot precisely elucidate whether the opiates provided represented irresponsible prescribing – but it supports much of what we anecdotally observe regarding the fragmented healthcare process.  Whether the magnitude of the problem is as great as these authors seem to suggest, there should be no argument we have plenty of room for improvement in treating some of our most vulnerable patients.

“Opioid prescribing by multiple providers in Medicare: retrospective observational study of insurance claims”
http://www.bmj.com/content/348/bmj.g1393

Outpatient Management of Large Pneumothorax

A guest post by Justin Mazzillo, a community doc in New Hampshire.
“Okay Mr. Smith now that your chest tube is in we’re going to go ahead and discharge you.  Just come back to the Emergency Department if you have any problems.”

That’s pretty much what these investigators set out to do…with a few minor differences. Instead of following the more common practice of aspirate and observe or place a chest tube and admit, the authors’ goal was to demonstrate that patients with large primary and secondary pneumothorax can be managed as outpatients with pigtail catheters. This prospective case series of 132 patients aimed to evaluate the success rate of outpatient management, as well as the one-year recurrence rate, pain medication use, safety and cost of this approach.

Patients who presented to this French hospital with large primary or secondary pneumothoraces had a pigtail catheter placed, were observed for two hours without a confirmatory chest radiograph and then discharged. Patients were seen in follow-up clinic on days 2 and 4 and admitted to the hospital on day 4 if the pneumothorax failed to resolve.

Of the 132 patients, 78% were managed entirely as outpatients. Patients with primary and secondary pneumothoraces had similar success rates, although the latter group was considerably smaller.  Two patients had mechanical catheter issues that were addressed as outpatients on their follow-up visit on day 2. The recurrence rate at one-year was 26%. The average cost of being managed as an outpatient in this study was $926 vs. $4,276 for the conventional inpatient approach.

This seems like an attractive and safe option as health care costs continue to skyrocket and more patients are managed in the ambulatory setting.  
“Ambulatory Management of Large Spontaneous Pneumothorax With Pigtail Catheters”


ABCD3 – Better, But Good Enough?

The ABCD2 score for the prediction of stroke after TIA was initially touted as a possible risk-stratification tool geared towards determining which patients could undergo delayed evaluation for modifiable risk factors.  Unfortunately, the “low risk” cohort generated by the ABCD2 score still has an unacceptably high risk of stroke at 7 days, with poor predictive and discriminative power.

These authors try to take it to the next level – the ABCD3 score and the ABCD3-I score.  Derived retrospectively from the Kyoto Stroke Registry, the third element of D3 is “Dual TIA” – which is having had another TIA within the prior 7 days.  Then, the “I” is dependent upon having a positive MRI DWI lesion associated with concurrent ipsilateral carotid artery stenosis.

In their retrospective application of ABCD2, ABCD3, and ABCD3-I, as expected, the ABCD2 score showed minimal utility for the outcome of interest for the Emergency Department – the 7 day risk of stroke in the low-risk cohort was ~6%.  The low-risk ABCD3 and ABCD3-I cohort, however, had a ~1 to 2% risk at 7 days.  If verified prospectively, this begins to approach reliable utility for discharge decision-making in the ED.  Given the ABCD2 score’s checkered past, I would certainly wait for the next bit of evidence.

“ABCD3 and ABCD3-I Scores Are Superior to ABCD2 Score in the Prediction of Short- and Long-Term Risks of Stroke After Transient Ischemic Attack”
http://stroke.ahajournals.org/content/45/2/418.full