Neurointensive Care of Children with Severe Traumatic Brain Injury : Studies of barbiturate coma treatment, intracranial compliance, pressure autoregulation and optimal cerebral perfusion pressure

Abstract: Traumatic brain injury (TBI) is among the most common causes of death and acquired disability during childhood. Management guidelines for pediatric patients are usually extrapolated from adults. Specific pediatric studies are warranted to improve the TBI management in children. A modern neurointensive care (NIC) unit, with standardized care and advanced computerized multimodality monitoring and data collection systems, offers an unique platform for explorative research.The general aims of this thesis were to increase the knowledge on barbiturate coma treatment (BCT) for refractory intracranial hypertension (RICH) and on cerebral pressure autoregulation (CPA) of cerebral blood flow, in pediatric TBI.  Paper I - Twenty-one children were included with severe TBI who developed RICH despite first-tier therapy. BCT proved to be effective in lowering ICP without causing severe side effects, when used in a modern NIC setting. BCT resulted in relatively good long-term outcome. Paper II - High resolution (100 Hz) monitoring data were analyzed in 17 TBI children with RICH. BCT reduced ICP significantly and improved intracranial compensatory reserve (RAP-index) while cerebral perfusion pressure (CPP) was maintained. Paper III - High resolution (100 Hz) monitoring data from 57 children with TBI were analyzed for assessment of CPA status according to the pressure reactivity index (PRx), calculation of  optimal CPP (CPPopt) and  assessment of deviations from CPPopt (ΔCPPopt). Impaired CPA was related to poor outcome and actual CPP below the CPPopt level contributed significantly to unfavorable outcome in children < 15 years. CPPopt appeared to be higher after a few days when CPA was most impaired. Paper IV - The metabolic state of the brain was assessed in 21 children with cerebral microdialysis (CMD) and related to actual CPP levels, PRx, CPPopt and ΔCPPopt. Increased levels of CMD lactate and the lactate/pyruvate ratio (LPR) (markers of ischemia) were related to disturbed CPA (higher PRx), actual CPP levels ≥70 mmHg and when actual CPP was above CPPopt, respectively.The findings in this thesis indicate that BCT may be an effective option for treatment of RICH in pediatric TBI and that  individualized CPA guided CPP management may be beneficial, at least in younger TBI children.