THE DOSE-RESPONSE PHARMACOLOGY OF INTRATHECAL SUFENTANIL IN FEMALE VOLUNTEERS

The pharmacologic effects of intrathecal sufentanil (ITS) beyond what is clinically administered (10 mu g) are not known. We observed 18 hea lthy, young, adult female volunteers who received 12.5, 25, or 50 mu g of ITS in a randomized, double-blind fashion for 11 h. Analgesia was assessed by pressure algometry at the tibia. Respiratory function was assessed by pulse oximetry, respiratory rate, arterial blood gas, the ventilatory response to CO2, and a respiratory intervention score (RIS ), The incidence and severity of side effects also were documented. Se rum sufentanil levels were measured for 4 h after ITS administration. We found that ITS produced statistically significant changes in algome try, doubling the pressure required to produce moderate pain. However, doses of ITS greater than 12.5 mu g failed to produce proportionate i ncreases in the duration or intensity of analgesia. All doses of ITS p roduced significant respiratory depression, but only the RIS was signi ficantly related to ITS dose. Neither respiratory rate nor sedation re liably predicted hypoxemia. Supplemental oxygen by nasal cannula consi stently prevented pulse oximeter readings below 90%. Serum sufentanil concentrations were related to ITS dose in a statistically significant manner, reached clinically significant concentrations, and followed a time course similar to analgesia and measures of respiratory depressi on. However, there was no significant increase in measured analgesia a ssociated with the increases in serum sufentanil concentrations. We co nclude that in our volunteer model of lower extremity pain, Administer ing ITS in doses larger than 12.5 mu g does not improve the speed of o nset, magnitude, or duration of analgesia and only causes dose-related increases in serum sufentanil concentrations, which may augment respi ratory depression.