title: The concentration-effect relationship of the respiratory depressant effects of alfentanil and fentanyl.
abstract: The relative potencies of fentanyl and alfentanil for respiratory depression were determined in eight healthy male volunteers in a double-blinded, randomized study with a cross-over design. The drugs were delivered by computer-driven infusion with logarithmically ascending plasma concentrations until the respiratory rate reached 2/min and/or oxygen saturation decreased below 85% with subjects breathing room air. Ventilation was measured with respiratory inductive plethysmography, indirect calorimetry, and arterial blood gas analysis, and plasma drug concentrations were determined. Pharmacodynamic modeling was performed using a fractional E(max) model for minute volume and respiratory rate and the concentrations producing 50% depression (i.e., apparent 50% effective concentration [EC(50)] values) were determined. Both drugs decreased ventilation in a similar manner, and drug infusions were terminated at mean +/- SD measured plasma concentrations of 254 +/- 88 ng/mL and 5.1 +/- 1.7 ng/mL for alfentanil and fentanyl, respectively. Alfentanil decreased minute volume from baseline by 54% +/- 19% and respiratory rate by 40% +/- 11% with EC(50) values of 234 +/- 57 ng/mL and 195 +/- 101 ng/mL. The respective decreases for fentanyl were 50% +/- 11%, 41% +/- 15%, and the estimated EC(50) values were 6.1 +/- 1.4 ng/mL and 3.5 +/- 1.4 ng/mL, respectively. Using the apparent EC(50) values, the calculated potency ratio for alfentanil:fentanyl was (mean and 95% confidence interval) 1:39 (1:31-1:46) for minute volume and 1:51 (1:34-1:68) for respiratory rate. This is analogous to the analgesic effect studied earlier. The findings support the notion of parallel analgesic and respiratory depressant effects of alfentanil and fentanyl. Therefore equianalgesic concentrations of both drugs will lead to equally pronounced respiratory depression.
  
  
  CONCLUSIONS
  This double-blinded, randomized study evaluated the potency ratio of alfentanil and fentanyl-induced respiratory depression. The findings support the notion of parallel analgesic and respiratory depressant effects of alfentanil and fentanyl. Therefore equianalgesic concentrations of both drugs will lead to equally pronounced respiratory depression.
authors.affiliation: Department of Anesthesia and Intensive Care, Helsinki University Hospital, Helsinki, Finland. leena.mildh@hus.fi
authors.forename: L H
authors.initials: LH
authors.lastname: Mildh
authors.forename: H
authors.initials: H
authors.lastname: Scheinin
authors.forename: O A
authors.initials: OA
authors.lastname: Kirvelä
mesh_terms: D000328:Adult; D015760:Alfentanil / Q000494:pharmacology*; D000465:Algorithms; D000701:Analgesics, Opioid / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002153:Calorimetry, Indirect; D018592:Cross-Over Studies; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D005283:Fentanyl / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010991:Plethysmography; D015656:Respiratory Mechanics / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid; D015760:Alfentanil; D005283:Fentanyl