XXXX and @entity1363 Are Ineffective in Reducing @entity428 in Severe Pediatric @entity131 .

@entity1 @entity131 @entity101 @entity428 @entity3575 @entity1363 @entity130
OBJECTIVE: To evaluate the clinical effectiveness of bolus-dose @entity3575 and @entity1363 to treat @entity428 in @entity1 with severe @entity131 . DESIGN: Retrospective cohort. SETTING: PICU in a university-affiliated @entity1 's hospital level I @entity130 center. @entity1 : Thirty-one @entity1 0-18 years of age with severe @entity131 (Glasgow Coma Scale score of  <= 8) who received bolus doses of @entity3575 and/or @entity1363 for treatment of @entity428 . INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The area under the curve from high-resolution intracranial pressure-time plots was calculated to represent cumulative intracranial @entity101 exposure: area under the curve for intracranial pressure above 20 mm Hg (area under the curve-intracranial @entity101 ) was calculated in 15-minute epochs before and after administration of @entity3575 and/or @entity1363 for the treatment of @entity428 . Our primary outcome measure, the difference between predrug and postdrug administration epochs (  area under the curve-intracranial @entity101 ), was calculated for all occurrences. We examined potential covariates including age, injury severity, mechanism, and time after injury; time after injury correlated with   area under the curve-intracranial @entity101 . In a mixed-effects model, with @entity1 as a random effect, drug/dose combination as a fixed effect, and time after injury as a covariate, intracranial @entity101 increased after administration of @entity3575 and/or @entity1363 (overall aggregate mean   area under the curve-intracranial @entity101 = +17 mm Hg * min, 95% CI, 0-34 mm Hg * min; p = 0.04). The mean   area under the curve-intracranial @entity101 increased significantly after administration of high-dose @entity3575 (p = 0.02), low-dose @entity1363 (p = 0.006), and high-dose @entity3575 plus low-dose @entity1363 (0.007). Secondary analysis using age-dependent thresholds showed no significant impact on cerebral perfusion pressure deficit (mean   area under the curve-cerebral perfusion pressure). CONCLUSIONS: Bolus dosing of @entity3575 and @entity1363 fails to reduce the intracranial @entity101 burden when administered for @entity428 . Paradoxically, we observed an overall increase in intracranial @entity101 burden following drug administration, even after accounting for within-subject effects and time after injury. Future work is needed to confirm these findings in a prospective study design.
