Category: Pediatrics

The Rate of Resuscitation in Pediatric DKA

A few children experience cognitive impairment and cerebral edema following the resuscitation phase of diabetic ketoacidosis. For many years, there has been suspicion the rapid volume replacement with isotonic crystalloids precipitated cerebral edema, leading to protocols requiring conservative rates of fluid administration.

Probably unnecessarily so.

This 2×2 randomized trial tested “fast” versus “slow” fluid resuscitation, as well as isotonic 0.9% saline versus 0.45% saline. “Fast” resuscitation repleted a 10% body weight fluid deficit with half of the fluid in the first 12 hours, while the “slow” resuscitation repleted a 5% fluid deficit at a steady rate over 48 hours. A little more than three hundred patients were included in each arm, with the primary outcome being a decline in mental status as measured by the Glasgow Coma Score. Persistent cognitive impairment, “clinically apparent brain injury”, and other adverse events were tracked as secondary outcomes.

Effectively, there is no discernable difference in outcomes between the four groups. Deterioration of mental status and clinically apparent brain injury were rare – occurring, essentially, around the expected 0.5-1.0% rate regardless of resuscitation speed or fluid selection. Serious adverse events were uncommon and similar across groups, without reliable signals of inferiority to any specific resuscitation strategy.

Whatever you’ve been doing these last few years, at least, hasn’t been “wrong”. Unfortunately, having failed to identify this as a preventable trigger for cerebral injury in DKA, the search for its cause must go on.

“Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis”
https://www.nejm.org/doi/full/10.1056/NEJMoa1716816

Snacking Before Bedtime

How long before a procedural sedation is fasting required? You know, of course, the American Society of Anesthesiologists guidelines specify: a mini- mum fasting period of 2 hours for clear liquids, 4 hours for breast milk, 6 hours for infant formula and light meals, and 8 hours for solids containing meat or fatty foods.

Of course, anecdotally – if anecdotally means hundreds of thousands of safe sedations – Emergency Physicians have known these restrictions are nonsense.

But, guidelines are best written off published evidence – so, we have a pre-planned analysis of the relationship between fasting time and vomiting from a Canadian cohort study of pediatric sedation. With 6,295 sedations included in their analysis, almost half of whom did not meet solids fasting guidelines, these authors found no relationship between fasting time and vomiting. There were, even, only six instances of intra-procedure vomiting, and fasting duration ranged from 1.7 hours to 17.5 hours – but they all received ketamine. None of the intra-procedure, or ~300 peri-procedural episodes of vomiting, resulted in pulmonary aspiration. No relationship was found between fasting time and any other type of adverse event, either.

So, another useful piece of literature to wave around in committee meetings – both to eliminate any fasting restrictions, and, again, to help demonstrate the safety of EP-performed procedural sedation.

“Association of Preprocedural Fasting With Outcomes of Emergency Department Sedation in Children”
https://jamanetwork.com/journals/jamapediatrics/article-abstract/2680050

The Penicillin Allergy Lie

This is a short follow-up study that touches upon a ubiquitous subject of which we’re mostly familiar – most patients with a stated allergy to penicillin do not actually have a true, IgE-mediated reaction. In the original study, these authors performed a standard 3-tier allergy testing on 100 patients with “low-risk” reported allergy symptoms, all of whom tested negative and ultimately passed a 500mg amoxicillin challenge dose.  Now, in this study, these authors re-contacted the patients and the primary care physicians to determine the downstream communication, effects of the allergy testing notification, and any adverse events related to prescribing after removal of the allergy from the patient’s chart.

Without going into much detail, there was a huge disconnect – most parents reported relaying the information, most physicians reported no information was relayed, and about half the patients had the allergy still listed in their chart. Regardless, 26 patients filled at least one prescription for a pencillin-derivative medication within the year, and one child developed a rash attributed to the amoxicillin.

The authors use this narrow experience to estimate cost savings attributed to using penicillin derivatives versus cephalosporins or clindamycin, and determine their allergy testing resulted in $1,368.13 in savings. Across the 6,700 reported penicillin allergies annually in their ED, they estimate accurate allergy information and delabeling could save nearly $200k each year.

This hardly represents all the benefits of delabeling, as the antibiotics avoided are also typically broader-spectrum, with greater contributions to antibiotic resistance. Clearly, a simpler, accepted pathway to expedite penicillin allergy delabeling would be of great value.

“Antibiotic Use After Removal of Penicillin Allergy Label”

http://pediatrics.aappublications.org/content/early/2018/04/18/peds.2017-3466

Don’t Give NEXUS II Much Thought For Kids

Into the the world of PECARN, CHALICE, and CATCH, we add NEXUS II. Why? Good question.

This is a planned secondary analysis of the NEXUS Head CT decision instrument among enrolled patients less than 18 years of age. Like most decision instruments, this rule classifies patients into “high risk” or “low risk”, with “low risk” being free of any mandated imaging. Their rule, which I will not recount, was tested in 1,018 blunt head trauma patients, and their rule picked up all 27 of those who required neurosurgical intervention. Unfortunately, it also only classified 330 patients as “low-risk” – for an abysmal 33% specificity.

The authors state it may yet have value, despite this poor specificity, as a one-way decision rule. Unfortunately, one-way decision rules are fraught with peril, as the inability to classify a patient as “low risk” is difficult to ignore.  This leads clinicians to ultimately use the one-way instrument as a two-way, despite the bleak positive predictive value. This rule also missed one of 49 patients with “significant intracranial injuries”, meaning it is reasonable to expect it may not actually be 100% sensitive.  Considering clinical judgement is vastly superior to this product, and there are enough alternative options, it is reasonable not to give this product another thought.

“Validation of the Pediatric NEXUS II Head CT Decision Instrument for Selective Imaging of Pediatric Patients with Blunt Head Trauma”
https://www.ncbi.nlm.nih.gov/pubmed/29665151

The Elephant in the PECARN/CHALICE/CATCH Room

A few months ago, I wrote about the main publication from this study group – a publication in The Lancet detailing a robust performance comparison between the major pediatric head injury decision instruments. Reading between the lines, as I mentioned then, it seemed as though the important unaddressed result was how well physician judgment performed – only 8.3% of the entire cohort underwent CT.

This, then, is the follow-up publication in Annals of Emergency Medicine focusing on the superiority of physician judgment. Just to recap, this study assessed 18,913 patients assessed to have had a mild head injury. Of these, 160 had a clinically important traumatic brain injury and 24 underwent neurosurgery. The diagnostic performance of these decision instruments is better detailed in the other article but, briefly, for ciTBI:

  • PECARN – ~99% sensitive, 52 to 59.1% specific
  • CHALICE – 92.5% sensitive, 78.6% specific
  • CATCH – 92.5% sensitive, 70.4% specific

These rules, given their specificity, would commit patients to CT scan rates of 20-30% in the case of CHALICE and CATCH, and then an observation or CT rate of ~40% for PECARN. But how did physician judgment perform?

  • Physicians – 98.8% sensitive, 92.4% specific

Which is to say, physicians missed two injuries – each detected a week later in follow-up for persistent headaches – but only performed CTs in 8.3% of the population. As I highlighted in this past month’s ACEPNow, clinical decision instruments are frequently placed on a pedestal based on their own performance characteristics in a vacuum, and rarely compared with clinician judgment – and, frequently, clinician judgment is as good or better. It’s fair to say these head injury decision instruments, depending on the prevalence of injury and the background level of advance imaging, may actually be of little value.

“Accuracy of Clinician Practice Compared With Three Head Injury Decision Rules in Children: A Prospective Cohort Study”
http://www.annemergmed.com/article/S0196-0644(18)30028-3/fulltext

When Seizures Return

This one isn’t precisely hot-off-the press, but, in having just discovered it, it’s hot to me!

This study aims to inform the guidance we provide to families after a child presents with a first-time, unprovoked seizure. Interestingly enough, the data for this analysis is dredged back up from a prospective cohort study from 2005 to 2007, in which patients with first-time seizures were being evaluated for abnormal neuroimaging. However, following discharge from the hospital or Emergency Department, patients also received short- and long-term telephone follow-up.

There were 475 patients enrolled in the original study, and differing numbers were appropriate for inclusion at their various timeframes of follow-up, depending on whether anti-epileptic therapy was started, or whether follow-up could be obtained. All told, seizure recurrence rates were:

  • 48 hours – 21/38 (5.4%)
  • 14 days – 51/359 (14.2%)
  • 4 months – 102/335 (30.4%)

These are extremely non-trivial numbers, and they surprised me. Risk facotrs associated with increased seizure incidence were recurrent seizures at initial presentation, younger age (<3 years), and presence of focal neurologic findings on initial examination. Regardless, however, even absent any of these predictors, the incidence of subsequent seizure is certainly high enough parents should be counseled they ought arrange for prompt neurology evaluation in follow-up.

“Early Recurrence of First Unprovoked Seizures in Children”

https://www.ncbi.nlm.nih.gov/pubmed/29105207

Is the Urinalysis Reliable in Young Infants?

The evaluation of the very young infant with a fever is complex, with multiple competing factors including the rarity of serious illness, the severity of serious illness, and the cost of the intensive evaluation frequently required. The most commonly identified bacterial source for fever is a urinary tract infection, and our bedside test in the Emergency Department is the urinalysis.

So, how reliable and accurate is that test?

This is an analysis of prospectively collected data from the PECARN network, looking at the evaluation of febrile infants fewer than 60 days of age. Of 4,147 patients enrolled, 289 patients had UTIs by a 50,000 CFUs/mL definition on the subsequent urine culture. Only 27 patients had bacteremia and a UTI. The news is generally mixed: using the 50,000 CFUs/mL cut-off, any abnormality on the UA was 94% sensitive for UTI and 91% specific, but was 100% sensitive for a UTI associated with bacteremia.

The authors also do analyses including different cut-offs for UTI based down to 10,000 CFUs/mL and, as you might expect, the sensitivity for any UTI diminishes. While the interpretation of the urine culture result is less applicable to the initial Emergency Department evaluation, the subsequent threshold for diagnosis is relevant to the ongoing follow-up care for the febrile infant, particularly if an initial decision involved observation without antibiotics and the infant remains symptomatic without another source.

Overall, it is reasonable to suggest – if the UA is negative, a serious bacterial illness is unlikely to be present. Some consideration should be made to the duration of illness, and natural course of delayed onset of development of cystitis or pyuria in the urine. A positive UA, however, despite the apparent high specificity, does not reliably indicate a true positive for UTI, owing to the low prevalence. This should also be taken into consideration regarding whether additional invasive evaluation is indicated.

“Accuracy of the Urinalysis for Urinary Tract Infections in Febrile Infants 60 Days and Younger”
http://pediatrics.aappublications.org/content/early/2018/01/12/peds.2017-3068

The HSV Meningitis Question

This is one of those questions that always crops up when evaluating an infant for sepsis and meningitis – should we test and/or empirically cover for herpes simplex virus infection? Just how frequently is this diagnosis made?

The answers, as described in this retrospective, multi-center study, are complex. First, the basics: 26,533 total encounters analyzed, with 112 children ultimately diagnosed with HSV meningitis. Then, it’s basically chaos. The percent of patients whose CSF was tested for HSV ranged from 12.5% to 70.9% across hospitals included, along with empiric coverage with acyclovir ranging from 4.2% to 53.0%. Rates of positive HSV results were unrelated to overall institutional testing or empiric acyclovir coverage rates, excepting in the sense that HSV infection was more frequent in younger infants – and younger infants were more likely to be tested and empirically treated, in general.  A handful of patients with ultimate diagnoses of HSV meningitis were not treated or tested initially, and were found on a subsequent visit.

The authors go into some detail regarding the questionable value of empiric treatment, citing a number needed to treat of 152 for infants 0-28 days and an NNT of 583 for infants from 29-60 days. Generally speaking, these authors agree with a prior cost-effectiveness analysis recommending waiting for the initial CSF cell count, and empirically treating those with a CSF pleocytosis. Consequently, these authors would therefore recommend testing only those ultimately treated empirically – but this is naturally a pragmatic consideration, rather than a statistically modeled balance between sensitivity and specificity.

There are a few more nuances within the paper with regard to their gold standard for diagnosis of HSV meningitis, limitations with regard to selection of patients undergoing testing, and generalizability from these tertiary referral settings, but it is still generally an interesting snapshot of data. Unfortunately, their ultimate conclusion is still back at square one – reiterating a call for specific clinical and laboratory data to help guide clinicians in selecting patients for HSV testing and empiric treatment. In the meantime, we’ll just keep doing our best to differentiate the ill child at the bedside based on gestalt and the culture of our practice setting.

“Herpes Simplex Virus Infection in Infants Undergoing Meningitis Evaluation”
http://pediatrics.aappublications.org/content/early/2017/12/29/peds.2017-1688

Treatment Failure, or is Treatment the Failure?

Acute respiratory tract infections – otitis media, streptococcal pharyngitis, and sinusitis – comprise virtually a laundry list for antibiotic overuse in self-limited conditions. Certainly, a subset of each of these conditions are true bacterial infections and, again, a subset of these have their resolution hastened by antibiotics – and, finally, a subset of those would have clinically important worsening if antibiotics were not used. Conversely, the harms of antibiotics are generally well-recognized,though not necessarily routinely appreciated in clinical practice.

This patient-centered outcomes study, with both retrospective and prospective portions, enrolled children diagnosed with the aforementioned “acute respiratory tract infections” and evaluated outcomes differences between those receiving “narrow-spectrum” antibiotics and those receiving “broad-spectrum antibiotics”. Before even delving into their results, let’s go straight to this quote from the limitations:

Because children were identified based on clinician diagnosis plus an antibiotic prescription to identify bacterial acute respiratory tract infections, some children likely had viral infections.

“Some children likely had viral infections” is a strong contender for understatement of the year.

So, with untold numbers of viral infections included, it should be no surprise these authors found no difference in “treatment failure” between narrow-spectrum and broad-spectrum antibiotics. Nor, in their prospective portion, did they identify any statistically difference in surrogates for wellness, such as missed school, symptom resolution, or pediatric quality of life. However, adverse events were higher (35.6% vs. 25.1%, p < 0.001) in the broad-spectrum antibiotic cohort, and this accompanied smaller, but consistent, differences favoring narrow-spectrum antibiotics on those wellness measures.

So, the takeaway: broad-spectrum antibiotics conferred no advantage, only harms. If you’re using antibiotics (unnecessarily), use the cheapest, most benign ones possible.

“Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections”

https://jamanetwork.com/journals/jama/article-abstract/2666503

Why Are Children Dizzy?

Vertigo presentations in adults are nearly always benign – with cerebral ischemia generally the most worrisome diagnosis in the differential. But, what about children? With a much lower risk for stroke, but also spared the other decay and decrepitude of aging, ought we be more or less concerned?

The short answer: mostly no. However, the etiologies of pediatric vertigo are almost certainly different.

In this short systematic review comprised of 24 studies and 2,726 children, the vast majority of cases resulted from generally benign etiologies. The most common diagnosis was ascribed to “vestibular migraine”, at about a quarter of the cases, followed by a smattering of peripheral vertigo and labyrinthitis-spectrum disorders. Not until diagnostic prevalence approached ~1% of cases did the most serious underlying etiologies begin to manifest, with central nervous system tumors, demyleninating disease, and ototoxic medication effects at the top of the lists of infrequent findings.

The limitations of this analysis include lack of generalizability to the Emergency Department, as several of the included articles are drawn from outpatient subspecialty case series review. A reasonable takeaway from these data, at least, as in adults, is serious underlying etiologies are very infrequently, and isolated vertigo need not be particularly worrisome absent other important neurologic findings.

“The Differential Diagnosis of Vertigo in Children: A Systematic Review of 2726 Cases”
https://www.ncbi.nlm.nih.gov/pubmed/29095392