Pamela J. Okada

Comparison of hypothermia and normothermia after severe traumatic brain injury in children (Cool Kids): a phase 3, randomised controlled trial

BACKGROUND On the basis of mixed results from previous trials, we assessed whether therapeutic hypothermia for 48-72 h with slow rewarming improved mortality in children after brain injury. METHODS In this phase 3, multicenter, multinational, randomised controlled trial, we included patients with severe traumatic brain injury who were younger than 18 years and could be enrolled within 6 h of injury. We used a computer-generated randomisation sequence to randomly allocate patients (1:1; stratified by site and age [<6 years, 6-15 years, 16-17 years]) to either hypothermia (rapidly cooled to 32-33°C for 48-72 h, then rewarmed by 0·5-1·0°C every 12-24 h) or normothermia (maintained at 36·5-37·5°C). The primary outcome was mortality at 3 months, assessed by intention-to-treat analysis; secondary outcomes were global function at 3 months after injury using the Glasgow outcome scale (GOS) and the GOS-extended pediatrics, and the occurrence of serious adverse events. Investigators assessing outcomes were masked to treatment. This trial is registered with ClinicalTrials.gov, number NCT00222742. FINDINGS The study was terminated early for futility after an interim data analysis on data for 77 patients (enrolled between Nov 1, 2007, and Feb 28, 2011): 39 in the hypothermia group and 38 in the normothermia group. We detected no between-group difference in mortality 3 months after injury (6 [15%] of 39 patients in the hypothermia group vs two [5%] of 38 patients in the normothermia group; p=0·15). Poor outcomes did not differ between groups (in the hypothermia group, 16 [42%] patients had a poor outcome by GOS and 18 [47%] had a poor outcome by GOS-extended paediatrics; in the normothermia group, 16 [42%] patients had a poor outcome by GOS and 19 [51%] of 37 patients had a poor outcome by GOS-extended paediatrics). We recorded no between-group differences in the occurrence of adverse events or serious adverse events. INTERPRETATION Hypothermia for 48 h with slow rewarming does not reduce mortality of improve global functional outcome after paediatric severe traumatic brain injury. FUNDING National Institute of Neurological Disorders and Stroke and National Institutes of Health.

The safety of etomidate for emergency rapid sequence intubation of pediatric patients

Objective To determine whether pediatric patients given etomidate for rapid sequence intubation (RSI) in the ED develop clinically important hypotension or adrenal insufficiency. Methods Retrospective review of 100 consecutive patients younger than age 10 years given etomidate for RSI in the ED at two academic medical centers. Data were abstracted from ED and in-patient medical records. Clinically important hypotension was defined as a decrease in systolic blood pressure (BP) measurement to below one standard deviation (SD) of mean normal for age. Clinically important adrenal insufficiency was defined as the need for exogenous corticosteroid replacement for suspected adrenal insufficiency at any time during hospitalization. Results BP measurements before and within 20 minutes after etomidate administration for RSI were recorded on 84 intubations (84%). The mean change in BP between pre-intubation and post-intubation measurements was a decrease of 1 mmHg (95% CI: −6 mmHg to +7 mmHg, P = 0.83). When expressed as a percentage of normal BP for age, the mean change in BP was a decrease of 1% (95% CI: −7% to +6%, P = 0.82). Four patients (4.8%; 95% CI: 1.3–11.7%) had a systolic BP decrease to below one SD of mean normal for age. Fourteen patients received corticosteroids during hospitalization, but none (0/99, 95% CI: 0–3.7%) for suspected adrenal insufficiency. Conclusions We found no evidence of clinically important adrenocorticoid suppression and a low incidence of clinically important hypotension when using etomidate for emergent pediatric RSI. Because other induction agents may also result in hypotension, prospective comparison studies are needed to further evaluate the safety of etomidate in this patient population.

Lorazepam vs Diazepam for Pediatric Status Epilepticus: A Randomized Clinical Trial

IMPORTANCE Benzodiazepines are considered first-line therapy for pediatric status epilepticus. Some studies suggest that lorazepam may be more effective or safer than diazepam, but lorazepam is not Food and Drug Administration approved for this indication. OBJECTIVE To test the hypothesis that lorazepam has better efficacy and safety than diazepam for treating pediatric status epilepticus. DESIGN, SETTING, AND PARTICIPANTS This double-blind, randomized clinical trial was conducted from March 1, 2008, to March 14, 2012. Patients aged 3 months to younger than 18 years with convulsive status epilepticus presenting to 1 of 11 US academic pediatric emergency departments were eligible. There were 273 patients; 140 randomized to diazepam and 133 to lorazepam. INTERVENTIONS Patients received either 0.2 mg/kg of diazepam or 0.1 mg/kg of lorazepam intravenously, with half this dose repeated at 5 minutes if necessary. If status epilepticus continued at 12 minutes, fosphenytoin was administered. MAIN OUTCOMES AND MEASURES The primary efficacy outcome was cessation of status epilepticus by 10 minutes without recurrence within 30 minutes. The primary safety outcome was the performance of assisted ventilation. Secondary outcomes included rates of seizure recurrence and sedation and times to cessation of status epilepticus and return to baseline mental status. Outcomes were measured 4 hours after study medication administration. RESULTS Cessation of status epilepticus for 10 minutes without recurrence within 30 minutes occurred in 101 of 140 (72.1%) in the diazepam group and 97 of 133 (72.9%) in the lorazepam group, with an absolute efficacy difference of 0.8% (95% CI, -11.4% to 9.8%). Twenty-six patients in each group required assisted ventilation (16.0% given diazepam and 17.6% given lorazepam; absolute risk difference, 1.6%; 95% CI, -9.9% to 6.8%). There were no statistically significant differences in secondary outcomes except that lorazepam patients were more likely to be sedated (66.9% vs 50%, respectively; absolute risk difference, 16.9%; 95% CI, 6.1% to 27.7%). CONCLUSIONS AND RELEVANCE Among pediatric patients with convulsive status epilepticus, treatment with lorazepam did not result in improved efficacy or safety compared with diazepam. These findings do not support the preferential use of lorazepam for this condition. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00621478.

Febrile Infants With Urinary Tract Infections at Very Low Risk for Adverse Events and Bacteremia

BACKGROUND: There is limited evidence from which to derive guidelines for the management of febrile infants aged 29 to 60 days with urinary tract infections (UTIs). Most such infants are hospitalized for ≥48 hours. Our objective was to derive clinical prediction models to identify febrile infants with UTIs at very low risk of adverse events and bacteremia in a large sample of patients. METHODS: This study was a 20-center retrospective review of infants aged 29 to 60 days with temperatures of ≥38°C and culture-proven UTIs. We defined UTI by growth of ≥50 000 colony-forming units (CFU)/mL of a single pathogen or ≥10 000 CFU/mL in association with positive urinalyses. We defined adverse events as death, shock, bacterial meningitis, ICU admission need for ventilator support, or other substantial complications. We performed binary recursive partitioning analyses to derive prediction models. RESULTS: We analyzed 1895 patients. Adverse events occurred in 51 of 1842 (2.8% [95% confidence interval (CI): 2.1%–3.6%)] and bacteremia in 123 of 1877 (6.5% [95% CI: 5.5%–7.7%]). Patients were at very low risk for adverse events if not clinically ill on emergency department (ED) examination and did not have a high-risk past medical history (prediction model sensitivity: 98.0% [95% CI: 88.2%–99.9%]). Patients were at lower risk for bacteremia if they were not clinically ill on ED examination, did not have a high-risk past medical history, had a peripheral band count of <1250 cells per μL, and had a peripheral absolute neutrophil count of ≥1500 cells per μL (sensitivity 77.2% [95% CI: 68.6%–84.1%]). CONCLUSION: Brief hospitalization or outpatient management with close follow-up may be considered for infants with UTIs at very low risk of adverse events.

A comparison of the influence of hospital-trained, ad hoc, and telephone interpreters on perceived satisfaction of limited English-proficient parents presenting to a pediatric emergency department

Background: Latinos are the fastest growing minority group in the United States with a significant percentage of this population having limited English proficiency. Objective: To determine whether mode of interpretation influences satisfaction of limited English-proficient parents presenting to a tertiary care pediatric emergency department. Design: One hundred eighty parents of patients presenting to a pediatric emergency department were surveyed after receiving services from one of the following interpreters: hospital-trained, ad hoc, or telephone. An English-proficient comparison group of 60 parents of any ethnicity was also surveyed (total N = 240). Results: Parents were significantly more satisfied (P < 0.001) with hospital-trained interpreters. While no significant difference was found in overall visit satisfaction, there were significant differences in several other outcome variables. When hospital-trained interpreters were used, parents were significantly more satisfied (P < 0.001) with their physicians and nurses. With regard to the ability to communicate with pediatric emergency department personnel, parents using hospital-trained interpreters averaged significantly higher scores (P < 0.001) than the telephone group. Quality-of-care scores were significantly higher (P < 0.001) for parents assigned to hospital-trained interpreters than for the other forms of interpretation. English-proficient parents scored highest in the following categories: ability to communicate, quality of care, and overall visit satisfaction. Parents using hospital-trained interpreters scored higher than English-proficient parents when questioned about physician and nursing satisfaction. Conclusion: Hospital-trained interpreters are a valuable and needed resource to facilitate communication with limited English-proficient patients and families. Other interpretation services are useful but have limitations.

Effect of clarithromycin on cytokines and chemokines in children with an acute exacerbation of recurrent wheezing: a double-blind, randomized, placebo-controlled trial

BACKGROUND Clarithromycin is postulated to possess immunomodulatory properties in addition to its antimicrobial activity. OBJECTIVE To evaluate the effect of clarithromycin on serum and nasopharyngeal cytokine and chemokine concentrations in children with an acute exacerbation of recurrent wheezing. METHODS Children with a history of recurrent wheezing or asthma and who presented with an acute exacerbation of wheezing were enrolled in a double-blind, randomized trial of clarithromycin vs placebo. Concentrations of tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, RANTES, eotaxin, macrophage inflammatory protein 1alpha, macrophage inflammatory protein 1beta, and monocyte chemoattractant protein 1 were measured in serum and/or nasopharyngeal aspirates before, during, and after therapy. Mycoplasma pneumoniae and Chlamydophila pneumoniae infection were evaluated for by polymerase chain reaction and serologic testing. RESULTS Nasopharyngeal concentrations of TNF-alpha, IL-1beta, and IL-10 were significantly and persistently lower in children treated with clarithromycin compared with placebo. There tended to be a greater effect of clarithromycin on nasopharyngeal cytokine concentrations in patients with evidence of M. pneumoniae or C. pneumoniae infection. No significant differences were detected in serum cytokines for children treated with clarithromycin compared with placebo. CONCLUSION Clarithromycin therapy reduces mucosal TNF-alpha, IL-1beta, and IL-10 concentrations in children with an acute exacerbation of recurrent wheezing.

Bedside ketone determination in diabetic children with hyperglycemia and ketosis in the acute care setting

Objective:  Diabetic ketoacidosis (DKA) is a serious complication of diabetes mellitus marked by characteristic biochemical derangements. Diagnosis and management involve frequent evaluation of these biochemical parameters. Reliable bedside equivalents for these laboratory studies may help reduce the time to treatment and reduce costs.

Capnometry for noninvasive continuous monitoring of metabolic status in pediatric diabetic ketoacidosis

ObjectiveTo determine the utility of continuous noninvasive capnometry for monitoring pediatric patients with diabetic ketoacidosis as assessed by the agreement between end-tidal carbon dioxide (Petco2) and Pco2. DesignClinical, prospective, observational study. SettingUniversity affiliated children’s hospital. InterventionsPatients with diabetic ketoacidosis were monitored with an oral/nasal carbon dioxide (CO2) sampling cannula while in the emergency department. Laboratory studies were ordered per protocol. Petco2values were correlated with respiratory rate, Pco2, and pH. Measurements and Main ResultsOne hundred twenty-one patients were monitored for 5.9 ± 0.32 hrs. The average (mean ± sd) initial values for pH were 7.08 ± 0.18; respiratory rate, 35.1 ± 9.1 breaths/min; Petco2, 18.6 ± 10.8 torr; and venous Pco2, 20.2 ± 10.6 torr. At the conclusion of the observation period, averages were pH, 7.29 ± 0.05; respiratory rate, 22.4 ± 3.7 breaths/min; Petco2, 35.3 ± 5.8 torr; and venous Pco2, 36.8 ± 5.3 torr. For all 592 observations, the correlations between Petco2 and venous Pco2 (r = .92, p = .0001), Petco2 and pH (r = .88, p = .0001), Petco2 and respiratory rate (r = −.79, p = .0001), and respiratory rate and pH (r = −.80, p = .0001) were statistically significant and the correlations with respiratory rate were inversely related to pH and Petco2. The difference scores were not related to the average scores for initial readings (r = −.073, p = .43), final readings (r = −.124, p = .18), and overall readings (r = .057, p = .17). Limits of agreement between the two methods were established with Petco2 lower than venous Pco2 with 95% limits of agreement 0.8 ± 8.3 (2 sd) torr. ConclusionsPetco2 monitoring of patients with diabetic ketoacidosis provides an accurate estimate of Pco2. Noninvasive Petco2 sampling may be useful in patients with diabetic ketoacidosis to allow for continuous monitoring of patients.

Can novice sonographers accurately locate an endotracheal tube with a saline-filled cuff in a cadaver model? A pilot study.

BACKGROUND No single confirmatory device can accurately distinguish between endotracheal, endobronchial, and esophageal intubation. Bedside ultrasound (US) shows promising potential for endotracheal tube (ETT) verification. Image acquisition depends on the approach used and the experience of the sonographer. Air within the trachea remains a challenge for interpretation of US images. Insufflation of the ETT cuff with saline helps overcome this difficulty and allows easy visualization of the cuff. This novel approach has not been studied in ETT verification among novice sonographers. OBJECTIVES The objective was to evaluate the accuracy of novice sonographers in identifying proper ETT location and depth using US visualization of a saline-filled cuff. METHODS Eight pediatric emergency medicine (PEM) fellows without prior training in airway bedside US participated in this prospective pilot study. Baseline US knowledge was assessed using a pretraining questionnaire. Fellows received a 20-minute didactic training session focused on airway US, followed by a 30-minute practice session. Using a linear US probe placed at the suprasternal notch, fellows identified the saline-filled cuff of an ETT in both the trachea and the esophagus. Following training, the ETT was placed in either the esophagus or the trachea of the cadaver model by the principal investigator. ETT depth (adequacy) was confirmed by chest radiograph. Each PEM fellow, blinded to the placement of the ETT, used bedside US to determine ETT location and depth. If placement was determined to be tracheal, the fellow was asked to comment on adequacy of tube placement. Adequate placement was defined as complete visualization of the ETT cuff within the trachea at the suprasternal notch. This was used as a surrogate for correct depth. This study sequence was repeated five times for each trainee, following varying placement of the ETT in the trachea or esophagus. RESULTS The PEM fellows displayed limited baseline knowledge of US prior to receiving the training module (average score of 50% on pretest questionnaire). None had any prior airway bedside US experience. Following training, PEM fellows correctly identified ETT location in 39 of 40 scans, with a sensitivity of 96% (23 of 24) for identifying tracheal location. The tube depth was correctly identified in 22 of 23 scans identified as tracheal intubations. CONCLUSIONS PEM fellows, lacking formal airway bedside US training, were able to identify the location and depth of a saline-filled ETT above or at the suprasternal notch in an adult cadaver model following a 50-minute teaching module. Filling the ETT cuff with saline allowed novice sonographers to accurately visualize the ETT within the trachea.

Sterile cerebrospinal fluid pleocytosis in young febrile infants with urinary tract infections.

OBJECTIVES To determine the prevalence of and to identify risk factors for sterile cerebrospinal fluid (CSF) pleocytosis in a large sample of febrile young infants with urinary tract infections (UTIs) and to describe the clinical courses of those patients. DESIGN Secondary analysis of a multicenter retrospective review. SETTING Emergency departments of 20 North American hospitals. Patients Infants aged 29 to 60 days with temperatures of 38.0°C or higher and culture-proven UTIs who underwent a nontraumatic lumbar puncture from January 1, 1995, through May 31, 2006. MAIN EXPOSURE Febrile UTI. OUTCOME MEASURES Presence of sterile CSF pleocytosis defined as CSF white blood cell count of 10/μL or higher in the absence of bacterial meningitis and clinical course and treatment (ie, presence of adverse events, time to defervescence, duration of parenteral antibiotic treatment, and length of hospitalization). RESULTS A total of 214 of 1190 infants had sterile CSF pleocytosis (18.0%; 95% confidence interval, 15.9%-20.3%). Only the peripheral white blood cell count was independently associated with sterile CSF pleocytosis, and patients with a peripheral white blood cell count of 15/μL or higher had twice the odds of having sterile CSF pleocytosis (odds ratio, 1.97; 95% confidence interval, 1.32-2.94; P = .001). In the subset of patients at very low risk for adverse events (ie, not clinically ill in the emergency department and without a high-risk medical history), patients with and without sterile CSF pleocytosis had similar clinical courses; however, patients with CSF pleocytosis had longer parenteral antibiotics courses (median length, 4 days [interquartile range, 3-6 days] vs 3 days [interquartile range, 3-5 days]) (P = .04). CONCLUSION Sterile CSF pleocytosis occurs in 18% of young infants with UTIs. Patients with CSF pleocytosis at very low risk for adverse events may not require longer treatment with antibiotics.