title: The influence of targeted temperature management on the pharmacokinetics of drugs administered during and after cardiac arrest: a systematic review.
abstract: OBJECTIVE
  Pharmacokinetic parameters of drugs are widely investigated under normothermic conditions and normal hemodynamic parameters. The European Resuscitation Council recommends the use of targeted temperature management (TTM) with a target temperature of 34 °C in cardiac arrest (CA) patients. The aim of this literature review is to investigate the influence of CA combined with TTM on the pharmacokinetics of drugs. Results of preclinical and clinical studies are compared with each other. Only the most important drugs, administered during CA in emergency setting, were studied.
  
  
  METHODS
  A literature search was conducted within PubMed and Google Scholar. The search terms included 'therapeutic hypothermia', 'TTM', 'drug metabolism', 'pharmacokinetics during hypothermia', 'cardiac arrest/etiology'. In Pubmed, MeSH-terms were also included: 'myocardial infarction/therapy', 'heart arrest/complications' and 'hypothermia'. To search for preclinical studies: the search terms 'pigs' and 'swine' were used. After the primary shift of relevant findings, further articles were found through references of these (snowballing method), as well as through related articles as suggested by the databases.
  
  
  RESULTS
  Due to the reduced cardiac output during TTM, most of the distribution volume ([Formula: see text]) of drugs included in this literature study is decreased. Only the [Formula: see text] of chlorzoxazone in CA rats and midazolam in non-CA patients are significantly increased during respectively deep and mild hypothermia. The renal, hepatic and biliary clearance of drugs administered during CA/TTM/hypothermia are decreased.
  
  
  CONCLUSIONS
  The combination of a decreased [Formula: see text] and a decrease in the metabolization/excretion of drugs during CA/TTM result in higher plasma concentrations compared to the plasma concentrations during CA without TTM.
authors.affiliation: a Faculty of Medicine and Health Sciences , Ghent University , Ghent , Belgium.
authors.forename: Tessa
authors.initials: T
authors.lastname: Crombez
authors.affiliation: a Faculty of Medicine and Health Sciences , Ghent University , Ghent , Belgium.|b Department of Emergency Medicine , Ghent University Hospital , Ghent , Belgium.
authors.forename: Said
authors.initials: S
authors.lastname: Hachimi-Idrissi
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006323:Heart Arrest / Q000188:drug therapy*; D006801:Humans; D007036:Hypothermia, Induced
chemical_list: D002317:Cardiovascular Agents
keywords: Cardiac arrest; Pharmacokinetics; Targeted temperature management; Therapeutic hypothermia