Opioids Inhibit Febrile Responses in Humans, Whereas Epidural Analgesia Does Not: An Explanation for Hyperthermia during Epidural Analgesia

Background: Epidural analgesia is frequently associated with hyperthermia during labor and in the postoperative period. The conventional assumption is that hyperthermia is caused by the technique, although no convincing mechanism has been proposed. However, pain in the "control" patients is inevitably treated with opioids, which themselves attenuate fever. Fever associated with infection or tissue injury may then be suppressed by opioids in the "control" patients while being expressed normally in patients given epidural analgesia. The authors therefore tested the hypothesis that fever in humans is manifested normally during epidural analgesia, but is suppressed by low-dose intravenous opioid.

Methods: The authors studied eight volunteers, each on four study days. Fever was induced each day by 150 IU/g intravenous interleukin 2. Volunteers were randomly assigned to: (1) a control day when no opioid or epidural analgesia was given; (2) epidural analgesia using ropivacaine alone; (3) epidural analgesia using ropivacaine in combination with 2 [mu]g/ml fentanyl; or (4) intravenous fentanyl at a target plasma concentration of 2.5 ng/ml.

Results: Fentanyl halved the febrile response to pyrogen, decreasing integrated core temperature from 7.0 +/- 3.2[degrees]C [middle dot] h on the control day, to 3.8 +/- 3.0[degrees]C [middle dot] h on the intravenous fentanyl day. In contrast, epidural ropivacaine and epidural ropivacaine-fentanyl did not inhibit fever. The fraction of core-temperature measurements that exceeded 38[degrees]C was halved by intravenous fentanyl, and the fraction exceeding 38.5[degrees]C was reduced more than fivefold.