A randomized study of the serum pharmacokinetics of lower thoracic extended-release epidural morphine (DepoDur) after lidocaine-epinephrine test dose administration in patients undergoing upper abdominal surgery.

OBJECTIVE: The primary objective was to evaluate the serum pharmacokinetic profile of a single 15-mg dose of extended-release epidural morphine (EREM) administered at the lower thoracic epidural space alone or following a lidocaine-epinephrine test dose in patients undergoing major upper abdominal surgery. MATERIALS AND METHODS: This randomized, open-label study recruited men and women > or = 18 years of age scheduled for major upper abdominal surgery. Patients were randomly assigned to 1 of 5 treatment groups and were administered a single 15-mg dose of EREM or EREM preceded by a 3 ml lidocaine (1.5%)/epinephrine (1 : 200,000) test dose with or without a saline flush: EREM alone; test dose + flush + 3-minute wait + EREM; test dose + flush + 10-minute wait + EREM; test dose + flush + 15-minute wait + EREM; or test dose + 3-minute wait + EREM. EREM was administered at the lower thoracic epidural intervertebral space (T8 - T12) approximately 30 minutes before the surgical incision. Noncompartmental pharmacokinetic parameters were determined based on the serum concentration-time profiles of morphine and morphine metabolites. Effectiveness and safety were also assessed. RESULTS: The intent-to-treat and safety populations included 39 patients; the pharmacokinetic population included 37 patients. Administration of EREM 3 minutes after a lidocaine-epinephrine test dose, with or without a flush, resulted in an increased mean maximum serum concentration of morphine (Cmax; flush, 30.2 +/- 8.5 ng/ml; no flush, 25.6 +/- 10.1 ng/ml; EREM alone, 11.5 +/- 7.3 ng/ml) and a decreased median time to Cmax (tmax; flush, 0.2 h; no flush, 0.2 h; EREM alone, 2.0 h) compared with administration of EREM alone, without affecting relative morphine bioavailability. Flushing the catheter and waiting 15 minutes normalized the Cmax (11.4 +/- 6.4 ng/ml) but not the median tmax (0.5 h). There were no significant group differences in safety, tolerability, or analgesic effectiveness. CONCLUSIONS: The interaction between EREM and a lidocaine-epinephrine test dose administered at T8 - T12 can be minimized by waiting 15 minutes after test dose administration. The overall safety and effectiveness of 15 mg EREM administered at the lower thoracic epidural intervertebral space in patients undergoing major upper abdominal surgery appears similar to that observed in previous studies assessing lumbar administration. ClinicalTrials.gov Identifier: NCT00728832.

Alvimopan, a peripherally acting mu-opioid receptor antagonist, compared with placebo in postoperative ileus after major abdominal surgery: results of a randomized, double-blind, controlled study.

BACKGROUND: Alvimopan is a peripherally acting mu-opioid receptor (PAM-OR) antagonist for accelerating gastrointestinal recovery after surgery. METHODS: Patients undergoing open laparotomy (bowel resection, n = 418; hysterectomy, n = 197) were randomized to receive alvimopan 6 or 12 mg or placebo orally > or = 2 h before surgery and then b.i.d. until hospital discharge (up to 7 days). The primary efficacy endpoint was time to gastrointestinal (GI) recovery (measured by toleration of solid food and passage of flatus/stool; GI-3). Secondary endpoints included time to GI-2 recovery (toleration of solid food and passage of stool) and hospital discharge order written (DCO). RESULTS: Alvimopan did not significantly accelerate GI-3 compared with placebo [6 mg: hazard ratio (HR) = 1.20, p = 0.080; 12 mg: HR = 1.24, p = 0.038). However, after adjustment for significant covariates (sex/surgical duration), benefits were significant for both doses (6 mg: HR = 1.24, p = 0.037; 12 mg: HR = 1.26, p = 0.028). Alvimopan also significantly accelerated time to GI-2 (6 mg: HR = 1.37, p = 0.008; 12 mg: HR = 1.33, p = 0.018) and DCO (6 mg: HR = 1.31, p = 0.008; 12 mg: HR = 1.28, p = 0.015). Adverse events were similar between groups. CONCLUSIONS: Alvimopan (6 or 12 mg) accelerates GI recovery and is well tolerated in patients undergoing open laparotomy.

Epidural analgesia compared with intravenous morphine patient-controlled analgesia: postoperative outcome measures after mastectomy with immediate TRAM flap breast reconstruction.

BACKGROUND AND OBJECTIVES: Epidural analgesia has been shown to provide superior pain control compared with intravenous (IV) opioids after major surgical procedures. In this study, we compared the effect of epidural analgesia and IV morphine patient-controlled analgesia (PCA) on pain relief, duration of hospitalization, oral nutrition, ambulation, and side effects in patients undergoing a major surgical procedure (i.e., unilateral mastectomy with immediate transverse rectus abdominis musculocutaneous flap reconstruction). METHODS: Eighteen patients were prospectively randomized to receive either epidural analgesia or PCA during the postoperative period. The intensity of pain was assessed daily by a 100-mm visual analog scale. The total length of hospital stay, time to ambulation, and time to oral nutrition were recorded. RESULTS: The epidural group had significantly lower pain scores at 3 evaluation times through postoperative day number 4 (P < .05). The total length of hospitalization for the epidural group (median, 101 hours) was significantly less than the PCA group (median, 126 hours; P = .0498). The time to first ambulation, time to first bowel sounds, time to tolerating oral nutrition, incidence of nausea/vomiting or pruritus, and time to first flatus were not statistically different between the groups. CONCLUSIONS: These results show that epidural analgesia compared with PCA offered improved pain control after breast reconstruction with immediate transverse rectus abdominis musculocutaneous flap reconstruction. It also resulted in a 25-hour reduction in time of hospitalization.