Target-controlled infusion of rocuronium in infants, children, and adults: a comparison of the pharmacokinetic and pharmacodynamic relationship.

UNLABELLED: Target-controlled infusion (TCI) of rocuronium can be used to maintain a stable blood concentration (Cp). At steady-state, the pharmacokinetics (PK) are compensated for by TCI, and a stable effect can be observed. The theoretical Cp may represent effect-site concentration (EC). We used the EC-effect relationship to study pharmacodynamics (PD) in infants, children, and adults. After giving their written, informed consent, 14 infants, 23 children, and 21 adults scheduled for elective surgical procedures received 3 to 6 ascending Cp targets of TCI rocuronium according to PD data. Just before each increase of TCI, venous blood samples were taken to measure Cp. Neuromuscular block was evaluated acceleromyographically. Individual effect data and measured Cp were fitted to the Hill equation. Maximum block during TCI targets-1000, 1300, and 1600 ng/mL-was smaller in children in comparison with infants and adults. The concentration in the effect compartment associated with a 50% drug effect (EC(50)) was significantly smaller in infants (mean [SD]) (652 [215] ng/mL) than in adults (954 [276] ng/mL) and was the largest in children (1200 [295] ng/mL). Calculated mean EC(90) values were 1705, 2230, and 2035 ng/mL, respectively, in infants, children, and adults. TCI rocuronium established steady-state PK/PD at different TCI targets and allowed us to define PK/PD relationships in a standardized way. Steady-state TCI rocuronium revealed the most potency of rocuronium in infants and the least in children.

IMPLICATIONS: Target-controlled infusion (TCI) of rocuronium in infants, children, and adults was used to analyze the pharmacokinetic/pharmacodynamic relationship. Steady-state TCI rocuronium revealed the most potency of rocuronium in infants and the least in children.