title: The pharmacokinetics and pharmacodynamics of cisatracurium in critically ill patients with severe sepsis.
abstract: OBJECTIVE
  To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of cisatracurium in critically ill patients with severe sepsis.
  
  
  METHODS
  Blood samples were collected before and over 8 h after a single bolus dose of cisatracurium 0.1 mg kg(-1) . Neuromuscular block was assessed by accelerometric peripheral nerve stimulation (TOF Watch). Plasma concentration and neuromuscular block data were fitted using population analysis.
  
  
  RESULTS
  Steady-state volume of distribution was determined to be 111 ± 71 ml kg(-1) and plasma clearance was 5.2 ± 1.8 ml min(-1) kg(-1) in these patients with greater inter-patient variability compared with other populations. The time to maximum block (8.3 ± 2.9 min) and delay time of transferring from central to effect compartment (17.2 min) was much longer, while the maximum block (95.0 ± 6.3%) was less compared with those in other patient populations. The effect compartment concentration resulting in 50% of maximum effect (128 ± 58 ng ml(-1)) was larger than previously described.
  
  
  CONCLUSIONS
  This study suggests that standard dosing of cisatracurium in patients with severe sepsis results in a slower patient response with a reduced effect. Use of a larger dose may overcome this reduced delayed response.
authors: Therapeutics Research Centre, School of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
authors: Xin
authors: X
authors: Liu
authors: Peter S
authors: PS
authors: Kruger
authors: Michael
authors: M
authors: Weiss
authors: Michael S
authors: MS
authors: Roberts
mesh_terms: D000328:Adult; D000368:Aged; D001279:Atracurium / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D016638:Critical Illness; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009466:Neuromuscular Blocking Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism*; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D009466:Neuromuscular Blocking Agents; D001279:Atracurium; C101584:cisatracurium