Sixteen clinical indicators were created to represent measures of adherence with recommendations within the Pediatric Guidelines (Supplemental Digital Content - Table 1). The number and type of study indicators for each treatment location was determined a priori by the study group. While we initially derived indicators from the Pediatric guidelines 2003, we had to operationalize some variables. This was an iterative process involving the project investigators. The effect of adherence was unable to be examined for the subset of indicators with close to 100% adherence (Supplemental Digital Content - Table 4). The indicators examined at each treatment location are given in Supplemental Digital Content - Table 1.
The number of indicators does not map directly to the Guidelines due to duplication of indicators across some chapters and involvement of multiple indicators in others (Supplemental Digital Content - Table 1). Since patients may undergo surgery either before or after admission to the ICU, intracranial pressure (ICP) monitoring and cerebral perfusion pressure (CPP) indicators were collected for both the OR and ICU. Five indicators were collected for the PH setting, 5 for the ED, 10 for the OR, and 14 for the ICU. For some indicators, we added a time component based on time-dependent effect on patient outcomes. Each clinical indicator was examined for conditionality; clinical indicators were considered relevant for patients who had underlying conditions that would have qualified for given treatments. We examined ICP in a number of ways. First, we have defined high ICP (intracranial hypertension) as presence of cerebral herniation (unequal pupils, or hypertension & bradycardia, as determined clinically) or administration of mannitol and/or hypertonic saline, or ICP > 20mmHg if ICP monitor was placed. These definitions were used in each treatment location (Prehospital [PH; includes EMS & Index hospital], ED, OR and ICU; Supplemental Digital Content - Table 1). We also examined the effect of ICP on CPP (MAP – ICP) as part of examining hyperventilation as opposed to normoventilation in the presence of cerebral herniation, and as part of the decompressive craniectomy indicator. Lastly, we examined ICP effects in the context of barbiturate use in the absence of hypotension for refractory high ICP and use of hypertonic saline to treat high ICP.
The main outcome was the association of adherence across all treatment locations with mortality and discharge Glasgow Outcome Scale (GOS) score. Secondary outcomes were the association with the location-specific adherence to indicators. For both summary measures, we included only those indicators with a protective point risk estimate after adjustment for all confounding variables. Summary measures were defined as the sum of indicators to which care was adherent divided by the number of relevant adherence indicators for a given patient at a given treatment location or across all locations.