title: Vancomycin pharmacokinetic parameters in patients with acute brain injury undergoing controlled normothermia, therapeutic hypothermia, or pentobarbital infusion.
abstract: BACKGROUND
  Therapeutic strategies that cause an alteration in patient temperature, such as controlled normothermia (CN), therapeutic hypothermia (TH), and pentobarbital infusion (PI), are often used to manage complications caused by acute brain injury. The purpose of this study was to evaluate pharmacokinetic (PK) parameters of vancomycin in patients with acute brain injury undergoing temperature modulation.
  
  
  METHODS
  This was a retrospective cohort study of adult patients with acute brain injury admitted between May 2010 and March 2014 who underwent CN, TH, or PI and received vancomycin. Predicted PK parameters based on population data were compared with calculated PK parameters based on serum concentrations.
  
  
  RESULTS
  Seventeen CN patients and 10 TH/PI patients met inclusion criteria. Traumatic brain injury and aneurysmal subarachnoid hemorrhage accounted for the majority of admitting diagnoses. In the CN group, the median dose was 16.7 (15.5-18.4) mg/kg. The median calculated elimination rate constant [0.155 (0.108-0.17) vs. 0.103 (0.08-0.142) hr(-1); p = 0.04] was significantly higher than the predicted value. The median measured trough concentration [8.9 (7.7-11.1) vs. 17.1 (10.8-22.3) υg/mL; p = 0.004] was significantly lower than predicted. In the TH/PI group, the median dose was 15.4 (14.7-17.2) mg/kg. No significant differences were found between the median calculated and predicted elimination rate constant [0.107 (0.097-0.109) vs. 0.112 (0.102-0.127) hr(-1); p = 0.41] and median measured and predicted trough concentration [14.2 (12.7-17.1) vs. 13.1 (11-17.8) υg/mL; p = 0.71].
  
  
  CONCLUSIONS
  Patients who underwent TH/PI did not exhibit PK alterations when compared to predicted PK parameters based on population data, while patients who underwent CN experienced PK alterations favoring an increased elimination of vancomycin.
authors.affiliation: Division of Practice Advancement and Clinical Education, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 115 Beard Hall, Campus Box 7574, Chapel Hill, NC, 27599, USA.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Morbitzer
authors.forename: J Dedrick
authors.initials: JD
authors.lastname: Jordan
authors.forename: Denise H
authors.initials: DH
authors.lastname: Rhoney
mesh_terms: D000328:Adult; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology*; D001930:Brain Injuries / Q000188:drug therapy / Q000628:therapy*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010424:Pentobarbital / Q000008:administration & dosage*; D012189:Retrospective Studies; D014640:Vancomycin / Q000493:pharmacokinetics*
chemical_list: D006993:Hypnotics and Sedatives; D014640:Vancomycin; D010424:Pentobarbital