Forty-eight hours of postoperative pain relief after total hip arthroplasty with a novel, extended-release epidural morphine formulation

Anesthesiology. 2005 May;102(5):1014-22. doi: 10.1097/00000542-200505000-00022.


Background: Epidural morphine has proven analgesic efficacy in the postoperative period and is widely used. This study evaluated the efficacy of extended-release epidural morphine (EREM; DepoDur; Endo Pharmaceuticals Inc., Chadds Ford, PA; SkyePharma, Inc., San Diego, CA) in providing pain relief for 48 h after surgery.

Methods: Patients (n = 200) scheduled to undergo total hip arthroplasty were randomized to receive a single dose of 15, 20, or 25 mg EREM or placebo. After surgery and after asking for pain medication, patients had access to intravenous patient-controlled analgesia fentanyl for breakthrough pain as needed. Postoperative intravenous patient-controlled analgesia fentanyl use, time to first postoperative fentanyl use, pain intensity at rest and with activity, patient and surgeon ratings of pain control, and adverse events were recorded.

Results: All EREM dosages reduced the mean (+/- SD) fentanyl use versus placebo (510 +/- 708 vs. 2,091 +/- 1,803 microg; P < 0.0001) and delayed the median time to first dose of fentanyl (21.3 vs. 3.6 h; P < 0.0001). All EREM groups had significantly improved pain control at rest through 48 h postdose (area under the curve [0-48 h]) compared with placebo (P < 0.0005). More EREM-treated patients rated their pain control as good or very good compared with placebo (at 24 h: 90 vs. 65%, P < 0.0001; at 48 h: 83 vs. 67%, P < 0.05). No supplemental analgesia was needed in 25% of EREM-treated patients and 2% of placebo-treated patients at 48 h (P < 0.05). The safety profile of EREM was consistent with that of other epidurally administered opioid analgesics.

Conclusions: EREM provided significant postoperative pain relief over a 48-h period after hip surgery, without the need for indwelling epidural catheters.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesia, Epidural*
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use*
  • Arthroplasty, Replacement, Hip*
  • Delayed-Action Preparations
  • Double-Blind Method
  • Female
  • Fentanyl / administration & dosage
  • Fentanyl / therapeutic use
  • Humans
  • Liposomes
  • Male
  • Middle Aged
  • Morphine / administration & dosage*
  • Morphine / adverse effects
  • Morphine / therapeutic use*
  • Pain, Postoperative / drug therapy*
  • Treatment Outcome


  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Liposomes
  • Morphine
  • Fentanyl