Effectiveness of Pharmacological Therapies for Intracranial Hypertension in Children With Severe Traumatic Brain Injury—Results From an Automated Data Collection System Time-Synched to Drug Administration

Abstract

Objective To describe acute cerebral hemodynamic effects of medications commonly used to treat intracranial hypertension in children with traumatic brain injury (TBI). Currently, data supporting the efficacy of these medications are insufficient. Design In this prospective observational study, intracranial hypertension (intracranial pressure [ICP] ≥ 20 mm Hg for > 5 min) was treated by clinical protocol. Administration times of medications for intracranial hypertension (fentanyl, 3% sodium chloride [HTS], mannitol and pentobarbital) were prospectively recorded and synchronized with an automated database that collected ICP and cerebral perfusion pressure (CPP) every 5 seconds. ICP crises confounded by external stimulation or mechanical ventilator adjustments were excluded. Mean ICP and CPP from epochs following drug administration were compared to baseline values using Kruskal-Wallis ANOVA and Dunn's test. Frailty modeling was used to analyze the time to ICP crisis resolution. Mixed effect models compared ICP and CPP 5min after the medication vs. baseline, and rates of treatment failure. Setting A tertiary care children's hospital. Patients Children with severe TBI (Glasgow Coma Scale score ≤ 8). Interventions None. Measurements and Main Results We analyzed 196 doses of fentanyl, HTS, mannitol and pentobarbital administered to 16 children (median: 12 doses/patient). Overall, ICP significantly decreased following fentanyl, HTS and pentobarbital. After controlling for administration of multiple medications, ICP was decreased following HTS and pentobarbital administration; CPP was decreased following fentanyl and was increased following HTS. After adjusting for significant covariates (including age, GCS score and ICP), HTS was associated with a two-fold faster resolution of intracranial hypertension than either fentanyl or pentobarbital. Fentanyl was significantly associated with the most frequent treatment failure. Conclusions ICP decreased after multiple drugs, but HTS may warrant consideration as the first-line drug for treating intracranial hypertension, as it was associated with the most favorable cerebral hemodynamics and fastest resolution of intracranial hypertension.

A Precision Medicine Approach to Cerebral Edema and Intracranial Hypertension after Severe Traumatic Brain Injury: Quo Vadis?

“…While not specifically in TBI, there are emerging data from pediatric critical illness suggesting a potential role of pharmacogenomic responses and polymorphisms in selection of the ideal agents—in the referenced study, ABC1 genotypes were associated with response to fentanyl/dose requirements [44]. Also, a recent direct comparison of fentanyl to hypertonic saline therapy for ICP spikes in children favored hypertonic saline [45]. …”

Pre-clinical models in pediatric traumatic brain injury—challenges and lessons learned

“…These types of collaborative investigators should be expanded. On the clinical front, studies of the epidemiology of severe TBI and the response to current therapies through investigations in the ADAPT trial [73–75] or via the use of big data [76] have great potential to begin to outline the most favorable approach to the management of severe pediatric TBI in the intensive care unit. Given the fact that its importance has only recently been recognized, pediatric models of mTBI and repetitive mTBI have only begun to be explored, and study of potential link between TBI in infants and children and long-term neurodegenerative diseases is another priority that must be addressed.…”

Current Medical Treatment of Severe Traumatic Brain Injury

“…3 Sedatif olarak sıklıkla kullanılan bir diğer ilaç; benzodiazepin türevi, anksiyolitik ve antikonvülzan özellikleri de olan midazolamdır. 9,10 Son yıllarda kritik hastalarda kullanımı artan deksmedetomidin selektif α2 adrenerjik agonist olup sedatif ve analjezik özelliklere sahip bir ilaçtır. Standart tedavilere ilave olarak kullanıldığında İKH'da faydalı olduğu, İKH epizodlarını ve HT ihtiyacını azalttığı ile ilgili yayınlar mevcuttur.…”

“…10,13 Analjezik olarak genellikle opioidler, bunlardan da sıklıkla fentanil kullanılmaktadır. 9,10 Geleneksel olarak İKH'u artırdığı ve kullanımının kontraendike olduğu kabul edilen ketaminin son yıllarda yayınlanan literatüre göre İKH'u artırıcı etkisi olmadığı hatta azaltıcı etkisinin olduğu belirtilmiştir. 14,15 Yukarıda bahsedilen tedaviler ve yeterli sedasyon-analjeziye rağmen İKH'un düşürülemediği hastalarda nöromüsküler bloke edici ilaçların kullanılabileceği belirtilmektedir.…”