Intensive care treatment of uncontrolled status epilepticus in children: systematic literature search of midazolam and anesthetic therapies*.

OBJECTIVE: A systematic literature search and review of the best evidence for intensive care treatment of refractory status epilepticus in children using continuous infusion of midazolam or anesthetic agents. DESIGN: MEDLINE and EMBASE search before December 2013 using key words and/or Medical Subject Headings identified English-language citations that were screened for eligibility and used if 1) the study was about high-dose benzodiazepine or anesthetic agent for children; 2) the treatment protocol was described and used for refractory status epilepticus; 3) the outcomes included seizure control; and 4) the series included at least five children. MAIN RESULTS: Sixteen studies (645 patients) were identified, including midazolam (nine studies), barbiturate (four studies), and other anesthetic approaches (three studies). When midazolam was used as the initial agent for refractory status epilepticus, the rate of clinical seizure control was 76%, which was achieved on average 41 minutes after starting the infusion. When midazolam was used in conjunction with continuous electroencephalography, the time to seizure control was much longer and the mean dose required for seizure control was 10.7 µg/kg/min compared with a lower dose (2.8 µg/kg/min) in the studies not using this form of monitoring, suggesting that continuous electroencephalography provided additional targets for treatment. Barbiturates were usually used after midazolam failed and treatment was started, on average, 66 hours after refractory status epilepticus onset with the goal of electroencephalography burst suppression, which was achieved, on average, 22.6 hours later. Among patients failing midazolam, barbiturate infusion was effective in 65%. Inhaled anesthetics, ketamine, and hypothermia were generally used after prior therapy with midazolam and barbiturates had failed, usually several days after seizure onset. CONCLUSIONS: The data on intensive care treatment of pediatric refractory status epilepticus are of poor quality, yet they show a hierarchy in strategies: early midazolam, then barbiturates, and then trial of other anesthetic strategies. In addition, using a solely clinical endpoint for seizure control may be missing significant seizure burden in pediatric refractory status epilepticus.

Measuring Critical Care Unit Performance Using a Postoperative Mechanical Ventilation Quality Metric.

BACKGROUND: Safely minimizing postoperative mechanical ventilation duration after congenital heart surgery could be a cardiac intensive care unit (CICU) quality measure. We aimed to measure CICU performance using duration of postoperative mechanical ventilation and identify organizational factors associated with this metric. METHODS: Observational analysis of 16,848 surgical hospitalizations of patients invasively ventilated on admission from the operating room from 26 Pediatric Cardiac Critical Care Consortium CICUs. We fitted a multivariable model to predict duration of postoperative mechanical ventilation adjusting for pre- and postoperative factors to measure CICU performance accounting for postoperative illness severity. We used our model to calculate observed-to-expected (adjusted) ventilation duration ratios for each CICU, describe variation across CICUs, and characterize outliers based on bias-corrected bootstrap 95% CIs. We explored associations between organizational characteristics and patient-level adjusted ventilation duration by adding these as independent variables to the model. RESULTS: We observed wide variation across CICUs in adjusted ventilation duration ratios, ranging from 0.7 to 1.7. Nine of 26 CICUs had statistically better than expected ventilation duration, while 10 were significantly worse than expected. Organizational characteristics associated with shorter adjusted ventilation duration included mixed (60%-90%) staffing by critical care or anesthesia-trained attendings, lower average attending-to-patient ratio, average CICU daily occupancy 80% to 90%, and greater nurse staffing ratios and experience. CONCLUSIONS: CICU performance in postoperative duration of mechanical ventilation varies widely across Pediatric Cardiac Critical Care Consortium centers. Several potentially modifiable organizational factors are associated with this metric. Taken together, these findings could spur efforts to improve ventilation duration at outlier hospitals.

Neonatal herpes virus infection and extracorporeal life support.

OBJECTIVES: To investigate outcomes among neonates with herpes virus infection reported to the Extracorporeal Life Support Organization (ELSO) Registry and analyze factors associated with death before hospital discharge with this virus. Currently, scant data exist regarding extracorporeal membrane oxygenation support in neonates with herpes virus infection. DESIGN: Retrospective analysis of ELSO Registry data set from 1985 to 2005. SETTING: A total of 114 extracorporeal membrane oxygenation centers contributing data to the ELSO Registry. PATIENTS: Patients, 0 to 31 days of age, with herpes simplex virus infection supported with extracorporeal membrane oxygenation and reported to the ELSO Registry. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical characteristics, outcomes, and factors associated with death before hospital discharge were investigated for patients in the virus group. Kaplan-Meier estimates of survival to hospital discharge according to virus type were investigated. Newborns with herpes simplex virus infection requiring extracorporeal membrane oxygenation support demonstrated much lower hospital survival rates (25%). Clinical presentation with septicemia/shock was significantly associated with mortality for the herpes simplex virus group on multivariate analysis. There was no difference in herpes simplex virus mortality when comparing two eras (> or =2000 vs. <2000). CONCLUSIONS: In this cohort of neonatal patients with overwhelming infections due to herpes simplex virus who were supported with extracorporeal membrane oxygenation, survival was dismal. Patients with disseminated herpes simplex virus infection presenting with septicemia/shock are unlikely to survive, even with aggressive extracorporeal support.

Pediatric intensive care treatment of uncontrolled status epilepticus.

The critically ill mechanically ventilated child with ongoing seizures that are refractory to any treatment presents a distinct challenge in pediatric neurocritical care. The evidence base from randomized controlled trials on which anti-epileptic drug (AED) strategy should be used is inadequate. This review of refractory and super-refractory status epilepticus summarizes recent pediatric case series regarding definitions, the second-tier AED therapies once initial anticonvulsants have failed, and the experience of high-dose midazolam, barbiturate anesthesia, and volatile anesthetics for uncontrolled status epilepticus.