Pharmacokinetics and pharmacodynamics of rocuronium in young adult and elderly patients undergoing elective surgery

Abstract

Abstract Objective To evaluate the impact of advanced age on rocuronium kinetic disposition in ASA I–III patients undergoing elective surgeries. Methods Young adult (20–50 years, n = 15) and elderly patients (65–85 years, n = 14) submitted to surgery under general anaesthesia were investigated. All patients were induced with individual intravenous doses of midazolam, rocuronium, fentanyl and propofol. Rocuronium-induced neuromuscular block was monitored by train of four stimulations of the adductor muscle of the thumb on the ulnar nerve. The pharmacokinetic parameters were calculated by non-compartmental analysis. The relationship between rocuronium plasma concentration and the neuromuscular blockade was described by a sigmoidal Emax model. Key-findings Elderly patients presented decreased Cl (2.1 ml/kg per min vs 2.8 ml/kg per min; P = 0.0123); increased AUC/dose (507.8 μg min/ml (mg/kg) vs 392.2 μg min/ml/(mg/kg); P = 0.0168) and reduced volume of distribution (285.4 ml/kg vs 435.6 ml/kg, P = 0.0434) compared to young adults. The concentrations required to achieve 50% of maximum neuromuscular block (EC50) were similar for young adult (338.8 ng/ml) and elderly (462.7 ng/ml) patients (P > 0.05). Conclusions Elderly patients showed increased AUC/D and reduced total Cl compared to young adult patients due to the age-related reduced renal function. Differences in the PK-PD properties of rocuronium in elderly population are due to changes in drug disposition rather than to alterations in the sensitivity to the drug.