Unravelling sources of variability on rocuronium pharmacokinetics:
implications for prolonged recovery in older patients
Abstract
Residual neuromuscular blockade (RNB) commonly occurs when using
neuromuscular blockers and increases the risk for pulmonary
complications, such as airway obstruction and severe hypoxemia, in
extubated patients. Rocuronium exhibits a high variability in recovery
time, contributing to an increased risk for RNB. This study aimed to
identify and characterize the sources of variability in rocuronium
exposure and response via a population pharmacokinetic/pharmacodynamic
(PK/PD) analysis and to apply the developed PK/PD model to investigate
clinical implications. A nonlinear mixed-effect model was developed for
rocuronium in patients undergoing general anaesthesia, using doses of
0.3–1.2 mg/kg. Plasma concentrations and the neuromuscular block
[train of four ratio] were assessed up to 6 h after dosing. The
influence of age, body mass index, renal function, and sex on PK and PD
was explored. Simulations were performed to predict the recovery time. A
two-compartment model with linear elimination and an indirect sigmoid
I-max model was used to describe PK and PD. The transfer rate into the
periphery increases with age. The predicted recovery time was
significantly longer in older subjects compared to young adults
following single bolus administrations of doses ≥ 0.7 mg/kg. Our
findings suggest that geriatric patients take slightly longer to recover
than younger adults due to an age-dependent increase in tissue uptake.
However, a priori dose adjustments for rocuronium in elderly patients
are not feasible, since age contribution is overshadowed by the overall
variability in the recovery time.