The pharmacokinetics and pharmacodynamics of cisatracurium in critically ill patients with severe sepsis

Abstract

Aim 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 8h after a single bolus dose of cisatracurium 0.1mgkg -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±71mlkg -1 and plasma clearance was 5.2±1.8mlmin -1kg -1 in these patients with greater inter-patient variability compared with other populations. The time to maximum block (8.3±2.9min) and delay time of transferring from central to effect compartment (17.2min) 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±58ngml -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. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.