Pharmacokinetic Alterations by Patient Status

Patient age may influence the physiologic disposition of local anesthetics. The half-life of lidocaine after intravenous administration averaged 80 minutes in human volunteers ranging in age from 22 to 26 years, whereas volunteers aged 61 to 71 years demonstrated a significantly prolonged lidocaine half-life that averaged 138 minutes.^[110]

Newborn infants have immature hepatic enzyme systems and prolonged elimination of lidocaine and bupivacaine.^{[111] [112]} Prolonged elimination is particularly an issue for continuous infusions of local anesthetics in infants, and seizures have been associated with rapid bupivacaine infusion rates.^{[113] [114]} Based on analysis of these cases, a maximum infusion rate of 0.4 mg/kg/hr for prolonged bupivacaine infusions has been proposed for children and adults, whereas prolonged infusion rates for neonates and young infants should not exceed 0.2 mg/kg/hr.^[115] Even at 0.2 mg/kg/hr, plasma bupivacaine concentrations were found to be rising toward a toxic range in some younger infants after 48 hours.^[116] Similarly, prolonged lidocaine infusions in neonates should not exceed 0.8 mg/kg/hr. Chloroprocaine may offer unique advantages for epidural infusion in neonates because it is cleared rapidly from plasma, even in preterm neonates.^[117]

Decreased hepatic blood flow or impaired hepatic enzyme function can produce substantially elevated blood levels of the aminoamide local anesthetics. An average lidocaine half-life of 1.5 hours was reported in volunteers with normal hepatic function, whereas patients with liver disease had an average half-life of 5.0 hours.^[118] The rate of lidocaine disappearance from blood has also been shown to be markedly prolonged in patients with congestive heart failure.^[119]