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 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.

© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Figures

Figure 1

Schematic of PK/PD link model showing the link between the three compartment PK model and sigmoid Emax PD model

Figure 2

Plasma concentration − time profile of each patient after a single bolus injection of cisatracurium. The solid line represents the fitting curve for the data obtained from first assessment. Δ measured data from first assessment, measured data from second assessment, ○ measured data from third assessment

Figure 2

Plasma concentration − time profile of each patient after a single bolus injection of cisatracurium. The solid line represents the fitting curve for the data obtained from first assessment. Δ measured data from first assessment, measured data from second assessment, ○ measured data from third assessment

Figure 3

Pharmacodynamic profile [T1 suppression (%) vs. time] of each patient after a single bolus injection of cisatracurium. The solid line represents the fitting curve for the data obtained from first assessment. Δ measured data from first assessment, measured data from second assessment, ○ measured data from third assessment