Pharmacokinetics of intravenous morphine in balanced anesthesia: studies in children.

Intravenous morphine in combination with muscle relaxants, nitrous oxide, and oxygen in so-called balanced anesthesia is commonly used in children between the ages of 0 and 5 yr during surgery. We define dosing rules for a loading dose followed by a continuous intravenous infusion of morphine sulfate to achieve a serum morphine concentration of 75 micrograms/L. This concentration is well above the minimum serum morphine concentration of 50 micrograms/L for moderate analgesic effects in adults. It also exceeds the concentration of 65 micrograms/L claimed to provide adequate analgesia in children during surgery. The clearance of morphine in 8 children between 0 and 5 yr of age was 20.5 +/- 2.8 mL/kg/min (means +/- SD). This result is threefold larger than the clearance value obtained after a single intravenous dose and 1.5 times greater than clearance values found after multiple intravenous doses of morphine, previously reported by others in children between the ages of 1 and 15 yr. Having established a dosing regimen that achieves a steady-state serum morphine concentration of approximately 75 micrograms/L, we plan to investigate the relationship between morphine serum concentration and pharmacologic effect. Intraoperatively the action of morphine at its receptor site will be assessed according to a scoring system including EEG changes, heart rate, blood pressure, response to sensory stimuli, and maintenance of vital functions. The effect of intravenous morphine will further be estimated according to the postanesthetic scoring system described in this report. Using intraoperative and postanesthetic scores to evaluate the pharmacodynamics of morphine for anesthesia in relation to morphine serum concentration will lead to a better understanding and improvement in use of intravenous morphine in young children.