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.