Fentanyl-induced rigidity and unconsciousness in human volunteers. Incidence, duration, and plasma concentrations

Anesthesiology. 1993 Apr;78(4):629-34. doi: 10.1097/00000542-199304000-00003.


Background: Muscle rigidity frequently accompanies induction of anesthesia with opioids. The authors sought to determine whether unconsciousness and amnesia occur when humans develop rigidity and apnea after intravenous fentanyl (without other concomitant anesthetics).

Methods: The incidence and duration of rigidity and level of consciousness were evaluated and associated plasma concentrations of fentanyl were measured in 12 healthy adult male volunteers given only intravenous fentanyl. Fentanyl was infused at a rate of 150 micrograms/min until a total of 15 micrograms/kg had been administered. Arterial blood samples for fentanyl assay were drawn and responsiveness, heart rate (HR), and systolic and diastolic arterial blood pressures were determined at frequent intervals during and after infusion. If rigidity was accompanied by an Spo2 < 90%, positive pressure ventilation with 100% O2 with a mask was instituted until spontaneous ventilation resumed.

Results: The incidence of muscular rigidity was 50% (6/12). All subjects who developed rigidity were apneic, unresponsive, and had no recall of commands to breathe or of positive pressure ventilation. Subjects not developing rigidity remained awake and responsive. No subject developing rigidity required neuromuscular blockade to allow positive pressure ventilation and adequate oxygenation (Spo2 > 90%). When rigidity occurred, it started 3 +/- 0.9 (range 1-4) min after the peak plasma fentanyl concentration and lasted for 11.5 +/- 5.8 (range 7-23) min. Rigidity started at a plasma fentanyl concentration of 21.5 +/- 4.4 (range 16-28) ng/ml and ended at 6.9 +/- 1.5 (range 5.2-8.7) ng/ml. Baseline HR was less in the subjects who subsequently developed rigidity (56.7 +/- 7.8 vs. 67.2 +/- 7.8 P = 0.04). No differences in fentanyl plasma concentrations or predicted effect site concentrations for rigidity were detected between subjects who developed rigidity and those who did not.

Conclusions: These findings support the hypothesis that unconsciousness occurs in the unstimulated subject during fentanyl-induced apnea and rigidity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Fentanyl / adverse effects*
  • Fentanyl / blood
  • Fentanyl / pharmacokinetics
  • Heart Rate / drug effects
  • Humans
  • Male
  • Muscle Rigidity / chemically induced*
  • Unconsciousness / chemically induced*


  • Fentanyl