Nalmefene for elective reversal of procedural sedation in children.

Nalmefene is a newer, long-acting opioid antagonist. Its use in children for the elective reversal of emergency department procedures has not been investigated. The objective was to evaluate the safety of nalmefene in children. An open-label pediatric clinical trial was performed. The study was conducted at the emergency department of an urban, university-affiliated children's hospital and consisted of children aged 6 months to 12 years who required procedural sedation where an opioid agent was administered. Patients were excluded if there was altered mental status, history of head trauma, history of opioid allergy, or the anticipated need for opioid agents for pain relief after the procedure. At the completion of the procedure, nalmefene was administered in a dose of 0.25 microg/kg increments (max 10 microg) until sedation was resolved, or to a maximum of 1.0 microg/kg (max 40 microg). Serial ECGs, vital signs, and oxygen saturation were recorded. Sedation was assessed using the Clinical Global Impression Scale (CGIS) at baseline, 2, 4, 6, 8, and 10 minutes after the initial nalmefene dose. The observer's assessment of alertness and sedation (OAA/S) was measured at baseline, 10, 30, 60, 90, and 120 minutes after the first dose of nalmefene. Episodes of resedation were recorded. All patients received follow-up by telephone at 4 and 24 hours after the initial dose of nalmefene to identify any potential late adverse effects. Over the study interval 15 patients were enrolled. Mean age was 59.1 +/- 41.5 months. Procedures involved fracture reduction (n=8), laceration repair (n = 4), abscess drainage (n = 2), and arthrocentesis (n = 1). All patients received IV fentanyl and midazolam. The mean dosage of fentanyl and midazolam was 3.21 +/- 1.03 microg/kg and 0.07 +/- 0.03 mg/kg, respectively. The mean dose of nalmefene at the time of complete response (CGIS = 1 or 2) was 0.55 +/- 0.29 microg/kg. The median number of nalmefene doses was 2. All but one patient (93%) had a complete response based on CGIS at 10 minutes after the initial dose of nalmefene was given. Nalmefene resulted in a significant improvement in CGIS (1.60 +/- 0.82 v 3.26 +/- 0.88, P =.001) and OAA/S (median score 5 v 4) when compared at baseline with 10 minutes after the initial dose of nalmefene. Nalmefene also resulted in increased diastolic blood pressure (62.6 +/- 10.5 v 55.8 +/- 10.7, P =.04) as well as improved oxygen saturation when compared at 120 minutes to baseline (99.5 +/- 0.74% v 98.5 +/- 0.4%, P =.03). There were no significant changes in pulse, systolic blood pressure, respiratory rate, and ECG. None of the patients became resedated after nalmefene was given. One patient developed nausea and vomiting within the first 2 hours after nalmefene; this resolved without intervention before discharge. No adverse events occurred in any of the patients at 4 and 24 hours postadministration. The results of this study showed that nalmefene is effective and safe for reversal of procedural sedation by opioids in children.

Bacteremia-associated pneumococcal pneumonia and the benefit of initial parenteral antimicrobial therapy.

OBJECTIVES: To describe clinical characteristics of patients with bacteremia-associated pneumococcal pneumonia (BAPP) and evaluate features that may distinguish these patients from those with uncomplicated pneumococcal bacteremia. To determine the impact of the route of initial antibiotic therapy on the clinical course of patients with BAPP. DESIGN/METHODS: Retrospective review of children with pneumococcal bacteremia comparing those with pneumonia to those without focal infections. RESULTS: We identified 110 patients with BAPP and 112 patients with pneumococcal bacteremia alone. Patients with pneumonia were significantly older (mean age, 34 vs. 19 months; P = 0.002) and more likely to present with cough/congestion (28% vs. 14%; P = 0.01) or difficulty breathing (12% vs. 4%; P = 0.047). There was no difference in mean temperature (39.5 vs. 39.7 degrees C; P = 0.3), mean white blood cell count WBC (21.9 vs. 22.6 x 1000/mm,3 P = 0.5) or presence of tachypnea (23% vs. 22%, P = 0.8). Sixty-one patients (55%) with pneumonia were discharged home from the initial visit in the emergency department. Those who received a parenteral antibiotic before discharge, when compared with the group who received an oral antibiotic alone, were more likely to have an improved condition (95% vs. 67%, P = 0.03) and were less likely to be admitted to the hospital (0% vs. 24%; P = 0.007) at follow-up. CONCLUSIONS: Children with bacteremia-associated pneumococcal pneumonia are older and more likely to complain of cough/congestion or difficulty breathing than those with uncomplicated pneumococcal bacteremia. The use of a parenteral antibiotic at the initial visit for children with bacteremia-associated pneumococcal pneumonia resulted in a lower admission rate and more likely parental report of improved condition at follow-up than those for children treated only with an oral antibiotic.