Category: Pediatrics

Procalcitonin, Still Auditioning For a Role in Neonatal Sepsis

A single test to rule out bacteria infection would be a lovely invention.  But, in the absence of such, we’ll settle for a test to rule out serious bacterial infection.  But, alas, procalcitonin – despite its sponsored proponents – is not that test.

This is a systematic review and meta-analysis pooling 2,317 patients from seven studies evaluating its use in detection of SBI in a neonatal population of less than 91 days of life.  Most commonly, the discriminatory value reported used was 0.3 ng/mL, with five studies reporting this data and the other two providing this data upon request.  All told, infants with PCT >0.3 ng/mL had a 42.7% prevalence of SBI, while those with PCT below the cut-off had a 12.5% prevalence.

So, this works out to a relative risk of 3.97 (95% CI 3.41 to 4.62) given a PCT greater than the cut-off.  Unfortunately, a prior review of the “Rochester criteria” for infants aged 29 to 90 days noted this cohort of low-risk patients had a prevalence of SBI of only 2.7%, with a RR for SBI of 30.6 (95% CI 7.0-68.13).  Noting 2.7% to be superior to 12.5% as a rule-out mechanism, it would seem prudent to retain the Rochester criteria rather than rely on PCT.

It may be reasonable to incorporate PCT into future decision instruments for risk-stratification, but such validated rules are not yet available.

“Use of Serum Procalcitonin in Evaluation of Febrile Infants: A Meta-Analysis of 2,317 Patients”
http://www.ncbi.nlm.nih.gov/pubmed/25281186

The Most Dangerous Holiday!

Here in the United States, it is Labor Day – a Federal holiday established in 1886 by U.S. President Grover Cleveland.  We, apparently, have Canada to thank for this innovation.

But, what was actually news to me – Labor Day is actually the highest-volume holiday for pediatric trauma, outpacing all other holidays.  I’d have thought 4th of July – with it’s various explosive devices – would be the most popular pediatric trauma holiday, but, between 1997 and 2006, Labor Day takes the lead, followed by Memorial Day, and 4th of July as a close third.  Halloween, Easter, Thanksgiving, New Year’s and Christmas round out the list, in that order.

Most common documented products associated with injuries on Labor Day included:  Football, bicycles, stairs/ramps, playgrounds, and beds.  Contrast with Christmas:  Stairs, beds, skiing, tables, knives, and sofas.  And the article provides lists of appropriately seasonal injury mechanisms for each other holiday.

So – beware Labor Day!  The most dangerous holiday of the year!

“Epidemiology of Pediatric Holiday-Related Injuries Presenting to US Emergency Departments”
http://www.ncbi.nlm.nih.gov/pubmed/20368316

Emergency Department or Return-to-Daycare Department?

Have you ever seen a child brought to the Emergency Department for pinkeye?  Not only that, but specifically to fulfill the requirement they receive a prescription for antibiotic ointment in order to return to daycare?  You would not be alone, my friends.

In this convenience sample of 303 surveyed parents, 26% reported taking their child to an Urgent Care, and 25% reported taking their child to an Emergency Department, rather than primary care, for minor ailments – including pinkeye.

These parents were also asked several questions regarding how they dealt with illness in children outside the home, where they would take the child for care, and what sort of requirements were placed upon them by daycare.  Most parents would send their children to daycare with a minor upper respiratory infection, but, fever, ringworm, and gastroenteritis were not accepted.  Most parents would either keep the child at home or seek primary care, but at least 10% of those surveyed would utilize some urgent or emergent services.  Significant predictors of utilizing emergency services for minor pediatric ailments were requirements for a “return to daycare” note or a parent “work excuse”, African American ethnicity, single/divorced parents, and those with tenuous job situations.

As such, the authors recommend improved guideline adoption by child care facilities to allow improved management of infectious disease – and reduced resource utilization from harried parents.

“Emergency Department and Urgent Care for Children Excluded From Child Care”
http://www.ncbi.nlm.nih.gov/pubmed/24958578

Hypoxia & Overtreatment in Bronchiolitis

“Treat the patient, not the number” works for many things in medicine – asymptomatic hypertension, hyperglycemia, and anemia, among others.  However, hypoxia is less frequently dismissed as clinically irrelevant.

And, that perfectly explains the results in this study, which evaluated clinician dependence on oxygen saturation to guide disposition in pediatric bronchiolitis.

Bronchiolitis, a viral process of large airway inflammation, can be challenging to treat.  For the most part, the disease simply must run its course, and it’s a matter of the secondary effects of the infection determining need for admission – work of breathing and hydration status.  Clinicians have been encouraged to accept low oxygen saturations (>90%) in the absence of other sequelae as part of their decision-making process leading to safe discharge home.

But, apparently, we’re still married to “normal” numbers.  In this study, researchers in Ontario randomized patients to the pulse oximeter providing either a true oxygen saturation, or an “altered oxygen saturation” – altered, specifically, to display 3% higher than the true value.  Over four years, 345 patients in respiratory distress with a clinical diagnosis of bronchiolitis met screening criteria, although only 213 agreed to participate.  As you might expect, patients with the true oxygen saturation were much more likely to be hospitalized than the patients with the falsely elevated oxygen saturation – 41% vs 25%.  Patients whose true oxygen saturation was displayed also tended to have increased resource utilization within 72-hours.  Zero adverse patient-oriented outcomes were observed in either group.

This is a small, single-center study, so, strictly speaking, its generalizability is limited.  However, it probably accurately reflects practice in many settings – where hypoxia, independent of more important clinical factors, is inappropriately sufficient cause for admission or observation.  This is a worthy reminder of such a flaw in our practice as respiratory viral season begins to ramp up this fall.

“Effect of Oximetry on Hospitalization in Bronchiolitis: A Randomized Clinical Trial”
http://jama.jamanetwork.com/article.aspx?articleid=1896981

The BATiC Score for Pediatric Trauma – Promising, But Not Prime-Time

Excluding significant intra-abdominal trauma on the basis of clinical evaluation is a lost art in the realm of zero-miss.  Nowhere is this more important than in a pediatric population, considering the small, but real, potential from harms due to exposure to ionizing radiation from CT.

This is the Blunt Abdominal Trauma in Children (BATiC) score, derived in 2009 by a Swiss group.  This rule promotes use of clinical exam, ultrasonographic findings, and laboratory results to determine need for CT.  In this study, authors from the Netherlands retrospectively applied the rule to 216 pediatric trauma patients presenting in a four-year span between 2006 and 2010.  All told, this cohort contained 18 patients for whom intra-abdominal injury were identified, and a BATiC score cut-off of 6 would have a sensitivity of 100% and specificity of 87%, with an AUC of 0.98.  So, this all sounds splendid.

But, only 34 of these patients even received a CT scan as part of their evaluation – and, with the standard outcome definition being injuries diagnosed on CT or as part of hospitalization, there is potential for a fair number of missed diagnoses.  A reasonable case may be made whether any missed injuries were clinically significant, given lack of observed morbidity, but it would be difficult to have confidence based on such as small sample.  Furthermore, just as a simple cultural issue, trauma surgeons in the U.S. tend to feel any injury is clinically significant.

Then, 18.5% of observations used to validate this rule were missing from the retrospective data collection and required imputation.  The extent of this missing data further degrades the reliability of the observed diagnostic characteristics.  No confidence intervals are presented along with their results – but, rest assured, they are quite wide.  Ultimately, this decision-instrument may indeed be valid – but requires specific prospective evaluation.

As an interesting Costs of Care side note, the additional charge for a such a trauma encounter including a CT scan in the Netherlands?  A mere 148 euros.

“External validation of the Blunt Abdominal Trauma in Children (BATiC) score: Ruling out significant abdominal injury in children”
http://www.ncbi.nlm.nih.gov/pubmed/24747461

Bizarrely Alarmist Pediatric URI Study

In our new Gawker and Buzzfeed-fueled, short-attention span reality, attention-grabbing headlines are essential.  So, let me come up with the modern headline for news coverage of this latest article, published in Pediatrics:  “Is your child’s next cold a killer?”

Seriously, as covered by Medscape (subscription required):

“As many as 1 in 3 children seeking treatment in the emergency department for influenza-like illnesses (ILI) at the peak of influenza season are at high risk of suffering severe complications, such as pneumonia.”

But, that’s hardly the case.  The study upon which they report is an observational cohort of ILI presenting to a tertiary children’s hospital.  To be eligible for inclusion, children needed to have ILI, defined as fever + cough/sore throat, and have “moderate to severe” symptoms.  However, their definition of “moderate to severe” is not based on any specific clinical criteria – it’s based off the surrogate of whether a clinician judged venipuncture and viral testing necessary.

So, 125,940 children were screened during the study period, and this cohort comprises the, presumably, sickest 241 of those.  Of those 241, over half had one of a predefined list of high-risk conditions: asthma, neurologic/neuromuscular disease, respiratory disease, heart disease, or immunosuppression.  And, yes, about 40% of each cohort developed a complication – most frequently pneumonia.  But, it should not be concluded there are killer viruses everywhere – rather, the sickest ILI, particularly those children who presumably appeared ill despite lacking underlying chronic illness, are the tiny cohort at higher risk of subsequent complication.

The authors also try to single out H1N1 influenza as an independent risk factor for subsequent complications.  11/29 patients with H1N1 influenza developed pneumonia, compared with 1/20 patients without, leading to their conclusion H1N1 confers particular risk.  However, 22/29 of patients diagnosed with H1N1 carried high-risk comorbidities, compared with only 10/20 in the non-H1N1 influenza cohort.  Yes, H1N1 probably increases risk of respiratory complications, but these data may not reliably support their conclusion.

“Severe Complications in Influenza-like Illnesses”
http://pediatrics.aappublications.org/content/early/2014/07/29/peds.2014-0505.abstract

VUR, Renal Scarring and other Fictitious Maladies

A guest post by Rory Spiegel (@EMNerd_) who blogs on nihilism and the art of doing nothing at emnerd.com.

As Emergency Physicians, one of the more vexing tasks asked of us is to identify the otherwise well appearing patient who has an occult illness that, if not identified, will lead to poor outcomes. With this in mind, we now turn our attention to the well appearing febrile infant and our unfounded obsession with urine. The fear that these children are quietly infarcting their nephrons is one of the more far fetched tales in emergency medicine.



In a recent NEJM article published by the RIVUR Trial Investigators, the authors examined whether prophylactic antibiotics for children with voiding cystourethrogram (VCUG) confirmed vesicoureteral reflux(VUR) were effective in preventing recurrent infections and more importantly, decreasing the extent of renal scarring (as per DMSA scan). Patients were randomized to either daily trimethoprim-sulfamethoxazole (TMP-SMX) suspension or placebo for one year. Authors found that children treated with prophylactic antibiotics had an absolute decrease in the recurrence of urinary tract infections by 12%. Meaning, you would have to treat 8 children for 12 months to prevent one case of recurrent UTI. More importantly the rate of renal scaring at follow up was identical.

  Among the children who experienced their first recurrent UTI, the rates of E. coli resistance to to TMP-SMX was 63% in the active group vs 19% in the controls.

Though this trial fails to address the futility of our quixotic attempts to diagnose and treat every UTI, clearly the utility of searching for and diagnosing VUR in febrile children in the hopes of preventing future renal scarring is a flawed concept. Furthermore it is unclear whether the surrogate endpoint of renal scarring, as seen on DMSA, is clinically relevant.  Not only are we most likely treating a fictitious disease process, but as the RIVUR authors demonstrated we are doing so ineffectively.

“Antimicrobial Prophylaxis for Children with Vesicoureteral Reflux.” http://www.ncbi.nlm.nih.gov/pubmed/24795142

Head Injury Showdown: PECARN Wins!

Most are familiar with the Pediatric Emergency Care Applied Research Network (PECARN) decision instrument for children with mild traumatic brain injury.  While they enrolled the largest number of patients in their derivation, they’re not alone:  the Canadian Assessment of Tomography for Childhood Head Injury (CATCH) and Children’s Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) address similar clinical questions.

And, now that you know about them, you might as well forget about them.

This is a prospective validation of each of the three decision instruments at Denver Health, enrolling 1,009 children with blunt head injury and GCS 13 or greater.  52 patients had head injuries on CT, 21 of which were judged clinically significant, and 4 required neurosurgical intervention.  Based on the 90% of their cohort for whom they had complete outcome data, the PECARN rule was 100% sensitive and 62% specific, CATCH was 91% sensitive and 44% specific, and CHALICE was 84% sensitive and 85% specific.  Therefore it is most defensible to use the PECARN decision instrument in a setting concerned with maximal sensitivity.

However, what’s most interesting in this study – only 188 children underwent CT, and physician practice had 100% sensitivity.  All told, the PECARN instrument classified 47 as “high risk” and 335 as “intermediate risk”.  The original derivation publication states this intermediate cohort may be eligible for observation vs. CT, depending on provider comfort level.  Ultimately, the management of “intermediate risk” is the key to this instrument’s role in reducing resource utilization.  In many settings, such as this one, if the “intermediate risk” group predominantly undergoes CT rather than observation, resource utilization will increase, rather than decrease.

However, the Denver Health expertise is not generalizable to most institutions – but provides an interesting perspective on the performance of PECARN to expert clinical judgment.

“Comparison of PECARN, CATCH, and CHALICE Rules for Children With Minor Head Injury: A Prospective Cohort Study”
http://www.ncbi.nlm.nih.gov/pubmed/24635987

Procalcitonin in Serious Bacterial Infection: Spoiler Alert – It Doesn’t Help Here Either

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

Over the years, numerous studies have been published attempting to show the benefit for serum markers in diagnosing sepsis or other infections. These markers include ESR, CRP and more recently, procalcitonin (PCT). Despite the reams of literature published, no study has shown a true patient centered outcome benefit to using these markers. Instead of doing an in depth review here of the literature on PCT, I recommend reading Rory Spiegel’s post here.

This recent article from Academic Emergency Medicine attempts to use PCT as an indicator of serious bacterial infection (SBI) in children under 3 years of age. They basically compared PCT with WBC, absolute neutrophil count (ANC) and absolute band count. PCT had the largest area under the curve (0.80 vs. 0.76 for WBC, 0.73 for ANC and 0.67 for absolute band count). Overall, the study found that all of these tests suffered from poor sensitivities but that specificity for PCT (92.7% at a cutoff of 0.6 ng/ml) coupled with its sensitivity (51.6% at the same cutoff) yielded the best positive likelihood ratio of any of these tests (+LR = 7.04). Based on this finding, the investigators conclude that PCT is a “more accurate marker than white blood count, absolute neutrophil count or absolute band count in identifying young febrile infants and children with serious bacterial infections.”
But, are we asking the right question? This study, as with many of the others, tries to use PCT to identify patients that we would otherwise miss as having a serious infection. However, they don’t compare PCT to physician clinical judgment. Or, more importantly, they do not investigate if PCT adds to clinical judgment. Instead, they compare it to markers we know are seriously lacking in their ability to predict (WBC, ANC and absolute band count).
Additionally, the investigators focus on the positive likelihood ratio and the high specificity. But we aren’t concerned about overworkup in febrile kids. As with all bad diseases, we want high sensitivity to make sure we miss as few SBIs as possible and a low negative likelihood ratio to aid in risk stratification. With a strong negative likelihood ratio (-LR < 0.10) we could use a PCT < 0.5 ng/ml to risk stratify patients to a low or very low risk of SBI and potentially send them home with follow up. Here, a PCT < 0.5 ng/ml had a – LR = 0.52. In this study, 13.3% (30/226) patients ultimately had an SBI. If you started with a pretest probability of 13.3% and apply a – LR of 0.52 using the Fagan Nomogram (below) you’d get a post-test probability of around 10%. This is nowhere near low enough for us to stop our workup.
Where does this leave us? Biomarkers will continue to be pushed since there are strong industry interests. Additionally, we want something concrete, objective and tangible to help us with our clinical decision-making. Future studies, though should focus on the additional benefit of markers to the clinician’s assessment and gestalt instead of looking at the biomarker in a vacuum. Show us this and we’ll all sit up and take notice. Until then, procalcitonin is simply another test without a clear indication.

Special thanks to Rory Spiegel (@CaptainBasilEM) and Mike Mojica for the help with this post.

Focused Evaluation for “Lethargy & Poor Feeding”

As these authors note, infants are evil.

Well, more specifically, they note infants with non-specific complaints as benign as “crying” can be harboring serious pathologic diagnoses.  Therefore, the diagnostic work-up for such complaints as “lethargy” or “poor feeding” varies widely by clinician and comfort level.

These authors retrospectively reviewed charts for 352 infants 0 – 6 months with presenting complaint of “lethargy” or “poor feeding”.  They exclude the chronically ill/premature, abnormal vital signs, and those with recent trauma, and review the laboratory testing and ultimate diagnoses for each remaining patient.  Of the 272 remaining, 34 patients ultimately had a diagnosis requiring intervention or monitoring.  These included hematologic disorders, dehydration, intracranial bleeding and SBI.  Of these 34, 26 were otherwise well-appearing.  However, these authors note each of the well-appearing patients had some obvious focal finding on physical examination – mostly jaundice, leading to treatment for hyperbilirubinemia – leading to directed testing.  They conclude, therefore, a well-appearing infant with a reassuring examination does not need any specific testing or monitoring.

This study is limited by its retrospective nature, as well the lack of comprehensive follow-up.  That said, their algorithm for focused evaluation of “lethargy” and “poor feeding” is probably reasonable.  Fishing expeditions in the otherwise well infant are certain to be costly and low-yield, with continued caregiver observation and follow-up a more prudent plan.

“Diagnostic Findings in Infants Presenting to a Pediatric Emergency Department for Lethargy or Feeding Complaints“
http://www.ncbi.nlm.nih.gov/pubmed/24583575