Therapeutic Mild Hypothermia and the Pharmacokinetics of Drugs in Trauma Brain Injury (TBI) Patients with a Focus on Sedation, Anticonvulsant and Antibiotic Therapy

Abstract

Background: Therapeutic hypothermia may alter both the pharmacokinetic (PK) and dynamics (PD) of the commonly used drugs in critical care. To achieve maximum benefit, medication dosage and schedules should be optimized. Objective: To review the existing scientific evidence showing the effect of therapeutic hypothermia on the pharmacokinetics of drugs commonly used in the care of patients after Trauma Brain Injury (TBI); particularly including sedatives, anticonvulsants and antibiotics. Data Sources: Computerized searches of OVID MEDLINE, OVID EMBASE, Cochrane Clinical Trials Register to August 2013 and hand searching of references of retrieved articles and proceedings of meetings; associated reference lists; and articles identified by experts in the field. Study Selection: Inclusion criteria were as follows: a) population- humans or animals undergoing therapeutic hypothermia b) design-prospective, randomized controlled trial, c) intervention-hypothermia; measurement of PD and PK of different drugs. Data Extraction: A data extraction form was used and authors (CB & SP) reviewed all trials. Data Synthesis: We reviewed 30 trials that documented changes in PD and PK of sedatives (propofol and midazolam), opioids (fentanyl, remifentanil, alfentil and morphine), anticonvulsants (phenytoin) and antibiotics (aminoglycosides) conducted in human or animal models undergoing therapeutic hypothermia. Conclusion: Data show that therapeutic hypothermia significantly alters the pharmacokinetics of commonly used agents. Particular care should be taken to reduce sedatives once target temperature is reached. Further clinical studies are required to clarify the effect of hypothermia on the PD and PK of therapeutic agents to optimize the benefits of therapeutic hypothermia in the treatment of TBI patients.