Fentanyl Blood Concentration-Analgesic Response Relationship in the Treatment of Postoperative Pain

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Abstract
The inter-and intrasubject variability in blood concentration-analgesic response relationship for fentanyl were investigated using the technique of patient-controlled analgesia (PCA) in30 consenting patients scheduled for surgical procedures involving an abdominal incision (15 upper and 15 lower abdominal incisions). All patients had a thiopental, nitrous oxide/oxygen, pancuronium anesthetic with 200 μg fentanyl intraoperatively. Postoperative pain relief was providedwith fentanyl from a Janssen On-Demand Analgesic Computer (ODAC) set to provide a basal infusionrate of 20 μg/hr, a bolus “demand” dose of 20 μg, and a lockout period of 5 minutes. Frequent blood samples were collected immediately before patients demanded doses, and these were taken asan estimate of the minimum effective concentration (MEC). A mean of 22 samples (range 12 to 45) were collected per patient over a mean study duration of 50 hours (range 24 to 72). The patients required larger hourly fentanyl doses in the first 6-hour period (83.9 ± 30.1 μg/hr) than in any other 6-hour period (mean values varied from 37.3 to 63 pg/hr). The mean (± SD) hourly fentanyl dose rate and total cumulative dose were 55.8 ± 22 μg/hr (range 28.8to 136 μg/hr) and 2739 ± 1191 μg (range 900 to 6260 μg), respectively. The mean (± SD) MEC was 0.63 ± 0.25 ng/ml (five-fold range from 0.23 to 1.18) and the mean intrapatient coefficient of variation in MEC was 30.2% (range 16 to 46%). The MEC values remained relatively constant in all patients over the 48-hour study period. The small intrapatient variation in MEC over the study period supports a relationship between blood fentanyl concentration and the extent of pain relief. Therefore, the large fluctuations in the hourly fentanyl dose rate do not accurately reflect the relatively constant blood concentration-analgesic effect relationship. These data emphasize the care necessary in the use of mean hourly fentanyl dose requirements as derived from PCA infusions as indexes of pharmacodynamic effects, especially pain relief. A similarsituation may exist for the other opioids used in PCA infusion pumps. Psychological factors werefound to have some predictive value for MEC and maintenance dose requirements.

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