Christopher M. Pruitt

Interpretation of Cerebrospinal Fluid White Blood Cell Counts in Young Infants With a Traumatic Lumbar Puncture

Study objective We determine the optimal correction factor for cerebrospinal fluid WBC counts in infants with traumatic lumbar punctures. Methods We performed a secondary analysis of a retrospective cohort of infants aged 60 days or younger and with a traumatic lumbar puncture (cerebrospinal fluid RBC count ≥10,000 cells/mm3) at 20 participating centers. Cerebrospinal fluid pleocytosis was defined as a cerebrospinal fluid WBC count greater than or equal to 20 cells/mm3 for infants aged 28 days or younger and greater than or equal to 10 cells/mm3 for infants aged 29 to 60 days; bacterial meningitis was defined as growth of pathogenic bacteria from cerebrospinal fluid culture. Using linear regression, we derived a cerebrospinal fluid WBC correction factor and compared the uncorrected with the corrected cerebrospinal fluid WBC count for the detection of bacterial meningitis. Results Of the eligible 20,319 lumbar punctures, 2,880 (14%) were traumatic, and 33 of these patients (1.1%) had bacterial meningitis. The derived cerebrospinal fluid RBCs:WBCs ratio was 877:1 (95% confidence interval [CI] 805 to 961:1). Compared with the uncorrected cerebrospinal fluid WBC count, the corrected one had lower sensitivity for bacterial meningitis (88% uncorrected versus 67% corrected; difference 21%; 95% CI 10% to 37%) but resulted in fewer infants with cerebrospinal fluid pleocytosis (78% uncorrected versus 33% corrected; difference 45%; 95% CI 43% to 47%). Cerebrospinal fluid WBC count correction resulted in the misclassification of 7 additional infants with bacterial meningitis, who were misclassified as not having cerebrospinal fluid pleocytosis; only 1 of these infants was older than 28 days. Conclusion Correction of the cerebrospinal fluid WBC count substantially reduced the number of infants with cerebrospinal fluid pleocytosis while misclassifying only 1 infant with bacterial meningitis of those aged 29 to 60 days.

Lidocaine Pretreatment Reduces the Discomfort of Intranasal Midazolam Administration: A randomized, double-blind, placebo-controlled trial

OBJECTIVE Intranasal (IN) midazolam is a commonly prescribed medication for pediatric sedation and anxiolysis. One of its most frequently encountered adverse effects is discomfort with administration. While it has been proposed that premedicating with lidocaine reduces this undesirable consequence, this combination has not been thoroughly researched. The objective of our study was to assess whether topical lidocaine lessens the discomfort associated with IN midazolam administration. METHODS This was a double-blind, randomized, placebo-controlled trial performed in an urban, academic pediatric emergency department. Children 6-12 years of age who were receiving IN midazolam for procedural sedation received either 4% lidocaine or 0.9% saline (placebo) via mucosal atomizer. Subjects were subsequently given IN midazolam in a similar fashion and then rated their discomfort using the Wong-Baker FACES Pain Rating Scale (WBS). The primary endpoint of WBS score was analyzed with a two-tailed Mann-Whitney U-test, with p < 0.05 considered statistically significant. RESULTS Seventy-seven patients were enrolled over a consecutive 8-month period. One child was excluded from analysis due to a discrepancy in recording the drug identification number. Study groups were similar in regard to demographic information and indication for sedation. Subjects who received IN lidocaine reported less discomfort with IN midazolam administration (median WBS = 3, interquartile range [IQR] = 0-6) than those who received placebo (median WBS = 8, IQR = 2-9; p = 0.006). CONCLUSIONS Premedication with topical lidocaine reduces the discomfort associated with administration of IN midazolam (ClinicalTrials.gov, NCT02396537).

Herpes simplex virus infection in infants undergoing meningitis evaluation

In this study, HSV infection was identified in 0.42% of 26 533 encounters in 0 to 60-day-old infants being evaluated by LP for CNS infection. BACKGROUND: Although neonatal herpes simplex virus (HSV) is a potentially devastating infection requiring prompt evaluation and treatment, large-scale assessments of the frequency in potentially infected infants have not been performed. METHODS: We performed a retrospective cross-sectional study of infants ≤60 days old who had cerebrospinal fluid culture testing performed in 1 of 23 participating North American emergency departments. HSV infection was defined by a positive HSV polymerase chain reaction or viral culture. The primary outcome was the proportion of encounters in which HSV infection was identified. Secondary outcomes included frequency of central nervous system (CNS) and disseminated HSV, and HSV testing and treatment patterns. RESULTS: Of 26 533 eligible encounters, 112 infants had HSV identified (0.42%, 95% confidence interval [CI]: 0.35%–0.51%). Of these, 90 (80.4%) occurred in weeks 1 to 4, 10 (8.9%) in weeks 5 to 6, and 12 (10.7%) in weeks 7 to 9. The median age of HSV-infected infants was 14 days (interquartile range: 9–24 days). HSV infection was more common in 0 to 28-day-old infants compared with 29- to 60-day-old infants (odds ratio 3.9; 95% CI: 2.4–6.2). Sixty-eight (0.26%, 95% CI: 0.21%–0.33%) had CNS or disseminated HSV. The proportion of infants tested for HSV (35%; range 14%–72%) and to whom acyclovir was administered (23%; range 4%–53%) varied widely across sites. CONCLUSIONS: An HSV infection was uncommon in young infants evaluated for CNS infection, particularly in the second month of life. Evidence-based approaches to the evaluation for HSV in young infants are needed.

Impact of Enteroviral Polymerase Chain Reaction Testing on Length of Stay for Infants 60 Days Old or Younger

Objective To determine the impact of a cerebrospinal fluid enterovirus polymerase chain reaction (PCR) test performance on hospital length of stay (LOS) in a large multicenter cohort of infants undergoing evaluation for central nervous system infection. Study design We performed a planned secondary analysis of a retrospective cohort of hospitalized infants ≤60 days of age who had a cerebrospinal fluid culture obtained at 1 of 18 participating centers (2005–2013). After adjustment for patient age and study year as well as clustering by hospital center, we compared LOS for infants who had an enterovirus PCR test performed vs not performed and among those tested, for infants with a positive vs negative test result. Results Of 19 953 hospitalized infants, 4444 (22.3%) had an enterovirus PCR test performed and 945 (21.3% of tested infants) had positive test results. Hospital LOS was similar for infants who had an enterovirus PCR test performed compared with infants who did not (incident rate ratio 0.98 hours; 95% CI 0.89–1.06). However, infants PCR positive for enterovirus had a 38% shorter LOS than infants PCR negative for enterovirus (incident rate ratio 0.62 hours; 95% CI 0.57–0.68). No infant with a positive enterovirus PCR test had bacterial meningitis (0%; 95% CI 0–0.4). Conclusions Although enterovirus PCR testing was not associated with a reduction in LOS, infants with a positive enterovirus PCR test had a one‐third shorter LOS compared with infants with a negative enterovirus PCR test. Focused enterovirus PCR test use could increase the impact on LOS for infants undergoing cerebrospinal fluid evaluation.

Correction of Cerebrospinal Fluid Protein in Infants with Traumatic Lumbar Punctures

In our multicenter cohort of infants ⩽60 days of age, we identified 2646 infants with a traumatic lumbar puncture, of which 31 (1.2%) had bacterial meningitis. For every 1000 cerebrospinal fluid red blood cells/mm3, cerebrospinal (cerebrospinal fluid) protein increased 1.1 mg/dL (95% confidence interval: 1.0–1.2 mg/dL).

Epidemiology and Etiology of Invasive Bacterial Infection in Infants ≤60 Days Old Treated in Emergency Departments

Objectives To help guide empiric treatment of infants ≤60 days old with suspected invasive bacterial infection by describing pathogens and their antimicrobial susceptibilities. Study design Cross‐sectional study of infants ≤60 days old with invasive bacterial infection (bacteremia and/or bacterial meningitis) evaluated in the emergency departments of 11 childrens hospitals between July 1, 2011 and June 30, 2016. Each sites microbiology laboratory database or electronic medical record system was queried to identify infants from whom a bacterial pathogen was isolated from either blood or cerebrospinal fluid. Medical records of these infants were reviewed to confirm the presence of a pathogen and to obtain demographic, clinical, and laboratory data. Results Of the 442 infants with invasive bacterial infection, 353 (79.9%) had bacteremia without meningitis, 64 (14.5%) had bacterial meningitis with bacteremia, and 25 (5.7%) had bacterial meningitis without bacteremia. The peak number of cases of invasive bacterial infection occurred in the second week of life; 364 (82.4%) infants were febrile. Group B streptococcus was the most common pathogen identified (36.7%), followed by Escherichia coli (30.8%), Staphylococcus aureus (9.7%), and Enterococcus spp (6.6%). Overall, 96.8% of pathogens were susceptible to ampicillin plus a third‐generation cephalosporin, 96.0% to ampicillin plus gentamicin, and 89.2% to third‐generation cephalosporins alone. Conclusions For most infants ≤60 days old evaluated in a pediatric emergency department for suspected invasive bacterial infection, the combination of ampicillin plus either gentamicin or a third‐generation cephalosporin is an appropriate empiric antimicrobial treatment regimen. Of the pathogens isolated from infants with invasive bacterial infection, 11% were resistant to third‐generation cephalosporins alone.

Factors Associated with Adverse Outcomes among Febrile Young Infants with Invasive Bacterial Infections

Objective To determine factors associated with adverse outcomes among febrile young infants with invasive bacterial infections (IBIs) (ie, bacteremia and/or bacterial meningitis). Study design Multicenter, retrospective cohort study (July 2011‐June 2016) of febrile infants ≤60 days of age with pathogenic bacterial growth in blood and/or cerebrospinal fluid. Subjects were identified by query of local microbiology laboratory and/or electronic medical record systems, and clinical data were extracted by medical record review. Mixed‐effect logistic regression was employed to determine clinical factors associated with 30‐day adverse outcomes, which were defined as death, neurologic sequelae, mechanical ventilation, or vasoactive medication receipt. Results Three hundred fifty infants met inclusion criteria; 279 (79.7%) with bacteremia without meningitis and 71 (20.3%) with bacterial meningitis. Forty‐two (12.0%) infants had a 30‐day adverse outcome: 29 of 71 (40.8%) with bacterial meningitis vs 13 of 279 (4.7%) with bacteremia without meningitis (36.2% difference, 95% CI 25.1%‐48.0%; P < .001). On adjusted analysis, bacterial meningitis (aOR 16.3, 95% CI 6.5‐41.0; P < .001), prematurity (aOR 7.1, 95% CI 2.6‐19.7; P < .001), and ill appearance (aOR 3.8, 95% CI 1.6‐9.1; P = .002) were associated with adverse outcomes. Among infants who were born at term, not ill appearing, and had bacteremia without meningitis, only 2 of 184 (1.1%) had adverse outcomes, and there were no deaths. Conclusions Among febrile infants ≤60 days old with IBI, prematurity, ill appearance, and bacterial meningitis (vs bacteremia without meningitis) were associated with adverse outcomes. These factors can inform clinical decision‐making for febrile young infants with IBI.

Time to Pathogen Detection for Non-ill Versus Ill-Appearing Infants ≤60 Days Old With Bacteremia and Meningitis

OBJECTIVES We sought to determine the time to pathogen detection in blood and cerebrospinal fluid (CSF) for infants ≤60 days old with bacteremia and/or bacterial meningitis and to explore whether time to pathogen detection differed for non-ill-appearing and ill-appearing infants. METHODS We included infants ≤60 days old with bacteremia and/or bacterial meningitis evaluated in the emergency departments of 10 childrens hospitals between July 1, 2011, and June 30, 2016. The microbiology laboratories at each site were queried to identify infants in whom a bacterial pathogen was isolated from blood and/or CSF. Medical records were then reviewed to confirm the presence of a pathogen and to extract demographic characteristics, clinical appearance, and the time to pathogen detection. RESULTS Among 360 infants with bacteremia, 316 (87.8%) pathogens were detected within 24 hours and 343 (95.3%) within 36 hours. A lower proportion of non-ill-appearing infants with bacteremia had a pathogen detected on blood culture within 24 hours compared with ill-appearing infants (85.0% vs 92.9%, respectively; P = .03). Among 62 infants with bacterial meningitis, 55 (88.7%) pathogens were detected within 24 hours and 59 (95.2%) were detected within 36 hours, with no difference based on ill appearance. CONCLUSIONS Among infants ≤60 days old with bacteremia and/or bacterial meningitis, pathogens were commonly identified from blood or CSF within 24 and 36 hours. However, clinicians must weigh the potential for missed bacteremia in non-ill-appearing infants discharged within 24 hours against the overall low prevalence of infection.

What happens to the “good saves”?

Physicians who care for patients who suffer out-of-hospital cariac arrest (OHCA) are often left to wonder how their patients do, articularly if they are discharged from the hospital with a seemngly good recovery. Do they continue to do well? Or have we imply delayed an unfavorable, or an ultimately inevitable, outome? In this issue of the journal, Nehme and colleagues attempt to ddress the question of recurrent OCHA – namely, what factors are ssociated with recurrence? [1] Although prior studies have estabished the importance of implantable cardioverter-defibrillators ICDs) for patients with cardiac etiologies of their OHCA [2,3], he current study comprises a more heterogeneous population, ith only a quarter of the study population with initial shockable hythms. In examining a broader cohort of patients, the authors ttempt to tackle a question that has been previously addressed nly by more indirect means. Using the Victorian Ambulance Cardiac Arrest Registry, a regiser encompassing a rather exhaustive list of field data from one f the largest EMS systems in the world [4],the authors examned patients with OHCA over a consecutive 15-year period. State ortality records were cross-referenced to ensure comprehenive capture. Without delving into much detail, as a whole, the ethodology of the current study was comprehensive and robust, articularly the means of matching cases of initial OHCA with those hat might represent recurrence. Two hundred fourteen (6.0%) of their patient cohort suffered ecurrent OHCA within the study period, with a median time to ecurrence of 5 years. Stated otherwise, over 25% of survivors of nitial OHCA died from recurrence during the time of the study. nfortunately, there was no decline in recurrent OHCA over the 5-year study period. The paucity of data on recurrent OHCA render contextualizaion of these findings difficult. Previous studies – again, focused n cardiac etiologies for the arrests – have demonstrated widely ariable rates of recurrent arrest [5,6]. The present study demontrated that patients with an index arrest due to primary respiratory r toxicologic etiologies were significantly associated with recurence. This is rather unsurprising in light of existing literature on ong-term survival rates following arrest episodes of non-cardiac tiology [7,8]. Perhaps of more importance is the finding that patients with cer-

When will we get there? The quandary of investigation in pediatric out-of-hospital cardiac arrest

Although out-of-hospital cardiac arrest (OHCA) is rare in chilren, it often results in death or considerable morbidity.1–3 ntuitively, recent data suggest that adherence to established uidelines for pediatric OHCA in the pre-hospital setting is assoiated with improved survival.4,5 Less is known about factors ssociated with survival for children with OHCA who are admitted ith return of spontaneous circulation (ROSC). In this issue of the journal, Scholefield and colleagues present heir data on children with OHCA collected through a prospective ntensive care unit database (PICANet) in the United Kingdom and epublic of Ireland.6 Their primary aim was to establish the prevaence of these cases within their 33-center network. Secondarily, hey sought to analyze the clinical factors linked with mortality in he pediatric intensive care unit (PICU). The prevalence of PICU admissions with OHCA and ROSC was 1%, which translates to a population estimate of 1.3 children er 100,000 person-years in their setting. This number is lower han those published elsewhere,2,3,7 leading the authors to reasonbly conclude that performing a prospective clinical trial for OHCA ithin their network is likely infeasible. PICANet is a robust, prospectively-collected database for PICU atients in the United Kingdom.8 As the authors acknowledge, owever, its design is not for resuscitation data, and many tstein-type variables are missing for this cohort. Perhaps more roblematically, a “probable cause for arrest” could not be ttributed for nearly 50% of subjects. While other large studies ave had even greater rates of unknown cause for arrest,3 only 12% f children in the recent study by Moler et al. had an unknown ause.9 To the authors’ credit, their attempted delineation of cause or arrest was more granular than that found in other studies. oreover, being that data were extracted retrospectively, this coniderable rate of unknown cause speaks to their caution against ver-speculation. The other limitation of the study that bears consideration s the authors’ selection of endpoint. When studying OHCA, uch thought goes into the selection of clinically meaningful ndpoints.10 Here, we are again limited by the database, as hisorical factors and interventions are analyzed in terms of survival o discharge from the PICU – not neurologic outcome, long-term urvival, or even survival to hospital discharge. This renders the onclusions more narrowly applicable than similar studies. The factors associated with survival to PICU discharge do, howver, present some beneficial points of discussion. Echoing prior