title: Opioids inhibit febrile responses in humans, whereas epidural analgesia does not: an explanation for hyperthermia during epidural analgesia.
abstract: 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 microg/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. h on the control day, to 3.8 +/- 3.0 degrees C. 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.
  
  
  CONCLUSIONS
  These data support the authors' proposed mechanism for hyperthermia during epidural analgesia. Fever during epidural analgesia should thus not be considered a complication of the anesthetic technique per se.
authors.affiliation: Department of Anesthesia, University of California-San Francisco, USA.
authors.forename: C
authors.initials: C
authors.lastname: Negishi
authors.forename: R
authors.initials: R
authors.lastname: Lenhardt
authors.forename: M
authors.initials: M
authors.lastname: Ozaki
authors.forename: K
authors.initials: K
authors.lastname: Ettinger
authors.forename: H
authors.initials: H
authors.lastname: Bastanmehr
authors.forename: A R
authors.initials: AR
authors.lastname: Bjorksten
authors.forename: D I
authors.initials: DI
authors.lastname: Sessler
mesh_terms: D000328:Adult; D015360:Analgesia, Epidural / Q000009:adverse effects*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D001831:Body Temperature; D016207:Cytokines / Q000097:blood; D005283:Fentanyl / Q000494:pharmacology*; D005334:Fever / Q000209:etiology* / Q000517:prevention & control; D006801:Humans; D008297:Male
chemical_list: D000701:Analgesics, Opioid; D016207:Cytokines; D005283:Fentanyl