Pharmacokinetics and pharmacodynamics of alfentanil infusions during general anesthesia

The pharmacokinetic and pharmacodynamic properties of alfentanil were studied in 64 surgical patients. Alfentanil was administered as a loading infusion (25-130 micrograms/kg) followed by a maintenance infusion (0.25-1.3 micrograms X kg-1 X min-1) as part of a nitrous oxide-narcotic-muscle relaxant technique. Although alfentanil doses of at least 50 micrograms/kg (in combination with thiopental, 2 mg/kg) were required to prevent hemodynamic changes during intubation, apnea or chest wall rigidity frequently occurred with alfentanil loading infusions exceeding 75 micrograms/kg. The alfentanil clearance rate was significantly lower in patients with liver dysfunction (2.3 +/- 1.3 vs 4.2 +/- 2.0 ml X kg-1 X min-1, mean +/- SD). In addition, the patients who required opioid antagonists to reverse postoperative respiratory depression had lower clearance rates (1.5 +/- 0.7 vs 4.1 +/- 1.9 ml X kg-1 X min-1) and longer elimination half-life values (406 +/- 304 vs 87 +/- 53 min). For maintenance of hemodynamic stability during superficial and intraabdominal operations, alfentanil serum concentration-response curves revealed ED95 values exceeding 300 ng/ml and 400 ng/ml, respectively. Our study also demonstrated a wide range of clinical responses to fixed doses of alfentanil. At equivalent doses, some patients required supplemental anesthetics, whereas others required an opioid antagonist. Careful titration of the alfentanil maintenance infusion is recommended to minimize the possibility of postoperative respiratory depression.