Jill M. Baren

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.

Primary Varicella in Adults: Pneumonia, Pregnancy, and Hospital Admission☆☆☆★

STUDY OBJECTIVE To define the rate of complications of adult varicella, including pneumonia, and to determine the association of such complications with pregnancy. METHODS Retrospective, descriptive case series of consecutive adult emergency department patients with primary varicella seen over a 31-month period in an urban county hospital. RESULTS A total of 130 patients were identified, with a mean age of 23.9 +/- 6.1 years; 69 (53%) were female. Thirteen patients (10.0%) had pneumonia; 6 of these were hospitalized. Two patients admitted with pneumonia had significant underlying comorbid disease and expired from respiratory failure. The remaining 4 admitted patients recovered uneventfully. Four of the 7 patients discharged with pneumonia were known to have recovered uneventfully. Twenty-eight (41%) of the 69 female study patients were pregnant; 7 of these (25%) were admitted, with admission diagnoses of pneumonia (1), active labor (2), and pregnancy with varicella (4). Incidence of pneumonia in pregnant patients was 3.6% (1 of 28; 95% confidence interval, 1% to 18.3%). All 7 admitted pregnant patients and the 19 (of 21) discharged pregnant patients who were contacted recovered uneventfully. No congenital anomalies or perinatal complications were noted in the infants of the 26 mothers with documented follow-up. CONCLUSION Hospital admission should be considered for adults with varicella pneumonia, especially if they have significant comorbid disease. It does not appear that pregnant women are at increased risk of developing varicella pneumonia.

Children's mental health emergencies-part 1: Challenges in care: Definition of the problem, barriers to care, screening, advocacy, and resources

Objective: At a time when there has been a reduction in mental health resources nationwide, the incidence of mental health disorders in children has seen a dramatic increase for many reasons. Methods: A review of the literature was done to identify the epidemiology, barriers to care, useful emergency department (ED) screening methods, and resources regarding pediatric mental health disorders in the ED. Results: Although there are many challenges to the provision of care for children with mental health emergencies, some resources are available. Furthermore, ED screening and intervention may be effective in improving patient outcomes. Conclusions: Collaborative efforts with multidisciplinary services can create a continuum of care, promote better identification of children and adolescents with mental health disorders, and promote early recognition and intervention, which are key to effective referral and treatment.

Implementation of the Exception From Informed Consent Regulations in a Large Multicenter Emergency Clinical Trials Network: The RAMPART Experience

Clinical trials investigating therapies for acutely and critically ill and injured patients in the earliest phases of treatment often can only be performed under regulations allowing for exception from informed consent (EFIC) for emergency research. Implementation of these regulations in multicenter clinical trials involves special challenges and opportunities. The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), the first EFIC trial conducted by the Neurological Emergencies Treatment Trials (NETT) network, combined centralized resources and coordination with retention of local control and flexibility to facilitate compliance with the EFIC regulations. Specific methods used by the NETT included common tools for community consultation and public disclosure, sharing of experiences and knowledge, and reporting of aggregate results. Tracking of community consultation and public disclosure activities and feedback facilitates empirical research on EFIC methods in the network and supports quality improvements for future NETT trials. The NETT model used in RAMPART demonstrates how EFIC may be effectively performed in established clinical trial networks.

A Clinical Decision Rule to Identify Infants With Apparent Life-Threatening Event Who Can Be Safely Discharged From the Emergency Department

Objective This study aimed to formulate a clinical decision rule (CDR) to identify infants with apparent-life threatening event (ALTE) who are at low risk of adverse outcome and can be discharged home safely from the emergency department (ED). Methods This is a prospective cohort study of infants with an ED diagnosis of ALTE at an urban children’s hospital. Admission was considered warranted if the infant required significant intervention during the hospital stay. Logistic regression and recursive partitioning were used to develop a CDR identifying patients at low risk of significant intervention and thus suitable for discharge from the ED. Results A total of 300 infants were enrolled; 228 (76%) were admitted; 37 (12%) required significant intervention. None died during hospital stay or within 72 hours of discharge or were diagnosed with serious bacterial infection. Logistic regression identified prematurity, abnormal result in the physical examination, color change to cyanosis, absence of symptoms of upper respiratory tract infection, and absence of choking as predictors for significant intervention. These variables were used to create a CDR, based on which, 184 infants (64%) could be discharged home safely from the ED, reducing the hospitalization rate to 102 (36%). The model has a negative predictive value of 96.2% (92%–98.3%). Conclusions Only 12% of infants presenting to the ED with ALTE had a significant intervention warranting hospital admission. We created a CDR that would have decreased the admission rate safely by 40%.

Pharmacokinetics of Intravenous Lorazepam in Pediatric Patients with and without Status Epilepticus

OBJECTIVE To evaluate the single dose pharmacokinetics of an intravenous dose of lorazepam in pediatric patients treated for status epilepticus (SE) or with a history of SE. STUDY DESIGN Ten hospitals in the Pediatric Emergency Care Applied Research Network enlisted patients 3 months to 17 years with convulsive SE (status cohort) or for a traditional pharmacokinetics study (elective cohort). Sparse sampling was used for the status cohort, and intensive sampling was used for the elective cohort. Non-compartmental analyses were performed on the elective cohort, and served to nest compartmental population pharmacokinetics analysis for both cohorts. RESULTS A total of 48 patients in the status cohort and 15 patients in the elective cohort were enrolled. Median age was 7 years, 2 months. The population pharmacokinetics parameters were: clearance, 1.2 mL/min/kg; half-life, 16.8 hours; and volume of distribution, 1.5 L/kg. On the basis of the pharmacokinetics model, a 0.1 mg/kg dose is expected to achieve concentrations of approximately 100 ng/mL and maintain concentrations >30 to 50 ng/mL for 6 to 12 hours. A second dose of 0.05 mg/kg would achieve desired therapeutic serum levels for approximately 12 hours without excessive sedation. Age-dependent dosing is not necessary beyond using a maximum initial dose of 4 mg. CONCLUSIONS Lorazepam pharmacokinetics in convulsive SE is similar to earlier pharmacokinetics measured in pediatric patients with cancer, except for longer half-life, and similar to adult pharmacokinetics parameters except for increased clearance.

Who will participate in acute stroke trials

Background: Despite the high incidence of acute stroke, only a minority of patients are enrolled in acute stroke treatment trials. We aimed to identify factors associated with participation in clinical trials of novel therapeutic agents for acute stroke. Methods: Prospective survey of patients with acute stroke <72 hours from onset. A structured interview was administered to the patient or primary decision-maker. If offered participation in an actual acute treatment trial, questions focused on decisions about that trial; otherwise a similar mock trial was proposed. The primary outcome was whether the subject agreed to participate in the proposed trial. Results: A total of 200 subjects (47% patients, 53% proxies) completed the survey: mean age 63 ± 14 years, 47% women, 44% white, 50% black. A real acute trial was offered to 22%; others were offered a mock trial. Overall, 57% (95% confidence interval: 50%–64%) of respondents stated they would participate in the proposed acute treatment trial. There were no differences with respect to age, sex, race, educational level, self-assessed stroke severity or stroke type, vascular risk factors, or comorbidities. Misconceptions about key research concepts were found in 50% but did not impact participation. Participation was associated with the perceived risk of the proposed trial intervention (p < 0.001), prior general attitudes about research (p < 0.001), and influences attributed to family, religion, and other personal beliefs (p < 0.001). Patients were more likely to participate than proxy decision-makers (p = 0.04). Conclusions: Demographic factors, clinical factors, and prior knowledge about research have little impact on the decision to participate in acute stroke clinical trials. Preexisting negative attitudes and external influences about research strongly inhibit participation. Patients are more inclined to participate than their proxy decision-makers.

Community Views on Neurologic Emergency Treatment Trials

STUDY OBJECTIVE We improve our understanding of the community consultation process for acute neurologic emergency trials conducted under the federal regulations for Exception From Informed Consent (EFIC) for emergency research. METHODS We performed a qualitative study using focus groups to collect data from patients with a previous stroke or brain injury and their families and from young men at risk for traumatic brain injury. Discussions were transcribed, coded, and analyzed for major themes and subthemes. RESULTS Five focus groups, involving 40 participants, were convened. Major themes included the awareness and understanding of key clinical trial concepts, including prominent concerns about placebo and therapeutic misconception; inability to obtain informed consent and acceptable surrogate decision-making; EFIC in emergency research and whether existing regulations are acceptable; specific trial design problems, including comparison to standard of care versus 2 competing active therapies; and community consultation and representation. CONCLUSION In this study sample, EFIC trials were deemed appropriate and acceptable for acute neurologic emergency research. Education, along with open discussion about basic clinical research concepts, disease- and trial-specific information, and potential surrogate decision-making, was essential to determine the acceptability of an EFIC trial. Approval by institutional review boards was highly regarded as a means of human protection and effective community consultation for such trials. A data repository of information gained from similar qualitative research may help investigators and regulators who wish to plan, conduct, review, and provide oversight for acute neurologic emergency trials under EFIC regulations.

Serious Bacterial Infections in Infants Who Have Experienced an Apparent Life-Threatening Event

STUDY OBJECTIVE We determine the incidence of serious bacterial infection in infants presenting to the emergency department (ED) with an apparent life-threatening event. METHODS This was a prospective cohort study of infants younger than 12 months who were treated at an urban childrens hospital ED during 1 year and who met standard criteria for an apparent life-threatening event. Sociodemographic data, presenting features, diagnostic testing, hospital course, and final diagnosis were collected. Follow-up information was obtained 4 weeks after the visit. RESULTS Of the 198 infants enrolled, 44 (22.2%) had evaluation for serious bacterial infection: urine culture 36 (18%), blood culture 38 (19%) and cerebrospinal fluid culture 18 (9%). No infant (0/198; 95% confidence interval 0% to 1.8%) was found to have bacteremia, urinary tract infection, or bacterial meningitis, which was confirmed at the 4-week interview (99% ascertainment). Two infants were found to have enteroviral meningitis. CONCLUSION The incidence of serious bacterial infection in this cohort was extremely low. Infants presenting with an apparent life-threatening event need not be subjected to a full serious bacterial infection evaluation routinely.

The future of emergency medicine: an evolutionary perspective.

Emergency medicine (EM) has grown rapidly over the past 50 years, evolving from a specialty defined by its locational identity—a hospital receiving room—to the specialty picked fourth-most-frequently by graduating U.S. medical students and to being the focal point of clinical care and of research on time-sensitive medical conditions. The authors review the forces that led to the growth of EM and those that will shape its future—in particular, cost, quality, and technology. A balancing of cost and quality considerations will likely drive EM education and research endeavors. The future of the field will be determined in part by resolution of the tension between the current inefficient conditions of emergency departments (EDs), which are crowded because of the temporary boarding of admitted patients for whom a bed is not yet ready, and the desired provision of quality care under emergent conditions. That is, patients with stroke, myocardial infarction, sepsis, or severe injuries from trauma require a working diagnosis and interventions that are initiated shortly after presentation, but ED personnel distracted by the demands of caring for boarded patients are unable to deliver optimal ED care. The reduction or elimination of boarding will enhance education and research within EDs and will contribute to an efficient system of high-quality EM services.