The pharmacokinetics and pharmacodynamics of cisatracurium in critically ill patients with severe sepsis
Date
2012
Authors
Liu, X.
Kruger, P.S.
Weise, M.
Roberts, M.S.
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Journal article
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British Journal of Clinical Pharmacology, 2012; 73(5):741-749
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Abstract
Aim: To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of cisatracurium in critically ill patients with severe sepsis.
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.
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.
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Copyright 2011 The Authors; British Journal of Clinical Pharmacology copyright 2011 The British Pharmacological Society