Evaluating Clinical Effectiveness and Pharmacokinetic Profile of Atomized Intranasal Midazolam in Children Undergoing Laceration Repair.

BACKGROUND: Atomized intranasal midazolam is a common adjunct in pediatrics for procedural anxiolysis. There are no previous studies of validated anxiety scores with pharmacokinetic data to support optimal procedure timing. OBJECTIVES: We describe the clinical and pharmacokinetic profile of atomized intranasal midazolam in children presenting for laceration repair. METHODS: Children 11 months to 7 years of age and weighing <26 kg received 0.4 mg/kg of atomized intranasal midazolam for simple laceration repair. Blood samples were obtained at 3 time points in each patient, and the data were fit with a 1-compartment model. Patient anxiety was rated with the Observational Scale of Behavioral Distress. Secondary outcomes included use of adjunctive medications, successful completion of procedure, and adverse events. RESULTS: Sixty-two subjects were enrolled, with a mean age of 3.3 years. The median time to peak midazolam concentration was 10.1 min (interquartile range 9.7-10.8 min), and the median time to the procedure was 26 min (interquartile range 21-34 min). There was a trend in higher Observational Scale of Behavioral Distress scores during the procedure. We observed a total of 2 adverse events, 1 episode of vomiting (1.6%) and 1 paradoxical reaction (1.6%). Procedural completion was successful in 97% of patients. CONCLUSIONS: Atomized intranasal midazolam is a safe and effective anxiolytic to facilitate laceration repair. The plasma concentration was >90% of the maximum from 5 to 17 min, suggesting this as an ideal procedural timeframe after intranasal midazolam administration.

High-dose barbiturates for refractory intracranial hypertension in children with severe traumatic brain injury.

OBJECTIVES: To evaluate high-dose barbiturates as a second-tier therapy for pediatric refractory intracranial hypertension complicating severe traumatic brain injury. DESIGN: This is a retrospective cohort study of children with refractory intracranial hypertension treated with high-dose barbiturates. SETTING: A single center level I pediatric trauma from 2001 to 2010. PATIENTS: Thirty-six children with refractory intracranial hypertension defined as intracranial pressure greater than 20 mm Hg despite standard management treated with high-dose barbiturates after severe traumatic brain injury. INTERVENTIONS: High-dose barbiturates were administered for refractory intracranial hypertension for a minimum duration of 6 hours and monitored by continuous electroencephalography. MEASUREMENTS AND MAIN RESULTS: Exposure was control of refractory intracranial hypertension defined as > 20 mm Hg within 6 hours after starting barbiturates. Pediatric cerebral performance category scores at hospital discharge and at 3 months (or longer) follow-up were the primary outcomes. Ten of 36 patients (28%) had control of refractory intracranial hypertension. Neither demographic nor injury characteristics were associated with refractory intracranial hypertension control. Children who responded received barbiturates significantly later after injury (76 vs. 29 median hours). Overall, 14 children died, 13 without control of intracranial pressure. Survival was more common in those who responded compared with those who did not respond to high-dose barbiturates, although this did not reach statistical significance (relative risk of death 0.2; 95% confidence interval; [0.03-1.3]). Of the 22 survivors, 19 had an acceptable survival (pediatric cerebral performance category less than 3) at 3 months or longer after injury; however, only three returned to normal function. Among survivors, control of refractory intracranial hypertension was associated with significantly better pediatric cerebral performance category scores and over two-fold likelihood of acceptable long-term outcome (relative risk 2.3; 95% confidence interval [1.4-4.0]) compared with uncontrolled refractory intracranial hypertension despite high-dose barbiturates. CONCLUSIONS: Addition of high-dose barbiturates achieved control of refractory intracranial hypertension in almost 30% of treated children. Control of refractory intracranial hypertension was associated with increased likelihood of an acceptable long-term outcome.