alvimopan-anhydrous and Pain--Postoperative

Alvimopan, a trans-3,4-dimethyl-4-(3-hydroxy-phenyl) piperidine, is a selective, peripherally acting micro-opioid receptor antagonist that is available for short-term use in hospitalized patients who have undergone bowel resection. The efficacy of alvimopan in the management of postoperative ileus has been evaluated in five phase III trials; four conducted in North America and one conducted in Europe/Australasia. Patients who had undergone partial large or small bowel resection surgery with primary anastomosis were randomized to receive alvimopan 12 mg or placebo as a single oral pre-operative dose followed by twice-daily administration for up to 7 days postoperatively. In the five phase III trials, alvimopan was significantly more effective than placebo in reducing the time to recovery of upper and lower gastrointestinal (GI) function, as assessed using a two-component endpoint (GI2) comprising time to tolerance of solid food and first bowel movement. The mean time to reach the GI2 endpoint was 11-26 hours sooner with alvimopan than with placebo. In the phase III trials conducted in North America, the time to writing the hospital discharge order was 13-21 hours sooner with alvimopan than with placebo. Alvimopan did not reduce opioid-induced analgesia and/or increase the amount of opioids administered postoperatively. Short-term alvimopan was generally well tolerated in adults undergoing bowel resection.

Topics: Analgesics, Opioid; Animals; Digestive System Surgical Procedures; Gastrointestinal Agents; Gastrointestinal Diseases; Gastrointestinal Motility; Half-Life; Humans; Pain, Postoperative; Piperidines; Receptors, Opioid, mu

The adverse effects of opioids are well documented. Because opioid receptors have a wide-ranging anatomic distribution, the effects subsequent to opioid binding, both good and bad, occur centrally and in the periphery. Postoperative strategies to reduce opioid burden, therefore, are in the patient's best interest. Multimodal analgesia is the key towards balancing the need for opioids while simultaneously reducing their burden. Alternative anesthesia and analgesia options such as regional anesthesia, nonsteroidal anti-inflammatory drugs, or cyclooxygenase-2 enzyme inhibitors should be considered part of multimodal protocols. Familiarity of where these drugs are active in the body and how they can be employed is imperative for all surgical team members. Optimal implementation of multimodal approaches can reduce hospital stay and improve clinical outcomes, including patient satisfaction. Finally, strategies that may help reduce rates of hospital readmission also contribute to overall improved outcome. New peripherally acting mu-opioid-receptor antagonists represent significant progress in the ability of perianesthesia nurses to play an even greater role in achieving these goals. In contrast to older opioid-receptor antagonists, these agents specifically target an important aspect of the multifactorial etiology of postoperative ileus (POI), mu-opioid-receptor-mediated activity in the GI tract. In addition, they do not pass the blood-brain barrier or diminish opioid-mediated analgesia. Advanced clinical trials have already demonstrated the ability of one of these agents, alvimopan, to reduce POI and improve other postoperative outcomes while maintaining adequate analgesia. Combined with other options aimed at reducing opioid burden, alvimopan and similar drugs in development hold promise as part of multimodal protocols to optimize pain management while minimizing postoperative morbidities.

Topics: Analgesia; Analgesics, Opioid; Anesthesia; Anesthesiology; Anti-Inflammatory Agents, Non-Steroidal; Attitude of Health Personnel; Blood-Brain Barrier; Clinical Trials, Phase III as Topic; Humans; Ileus; Length of Stay; Naltrexone; Narcotic Antagonists; Nurse's Role; Outcome Assessment, Health Care; Pain, Postoperative; Patient Satisfaction; Piperidines; Postanesthesia Nursing; Postoperative Care; Postoperative Complications; Quaternary Ammonium Compounds; Receptors, Opioid, mu; Risk Factors

Postoperative ileus (POI) is defined as the impairment of bowel motility that occurs almost universally after major open abdominal procedures, as well as other abdominal and nonabdominal procedures. For the majority of affected patients, POI generally lasts approximately three to five days, but longer duration is not uncommon. The causes of POI are multifactorial, but can be broadly categorized into two groups: those related to the surgical procedure and those related to pharmacologic interventions (opioids). The fact that POI is generally transient and therefore self-limited should not deter the surgical team from seeking improved ways to mitigate its associated adverse effects, which can be substantial and immensely uncomfortable for the patient, and can have far-reaching implications regarding overall hospitalization costs for many types of surgeries. Optimization of POI management and prevention efforts is a responsibility of all members of the surgical team and can drastically affect the overall clinical outcome of major abdominal surgery. Depending on the individual team member's role, different perspectives and strategies may be used to achieve improved outcomes, including but not limited to hospitalization costs related to care and length of stay, resource utilization, and, perhaps most critically, patient quality of life not only immediately after surgery but also after discharge. The ability to reliably and significantly decrease the duration of POI should be readily recognized as an important objective in the management of this condition. Opioids will continue to be a mainstay of postoperative care regimens, but new agents such as peripherally acting mu-opioid-receptor antagonists may offer a unique clinical advantage by helping to reduce the adverse gastrointestinal effects of opioids while preserving their desired benefits for postoperative analgesia.

Topics: Analgesics, Opioid; Causality; Cost of Illness; Hospital Costs; Humans; Ileus; Incidence; Laparotomy; Length of Stay; Naltrexone; Narcotic Antagonists; Nurse's Role; Outcome Assessment, Health Care; Pain, Postoperative; Patient Care Team; Patient Satisfaction; Piperidines; Postanesthesia Nursing; Postoperative Care; Postoperative Complications; Professional Role; Quaternary Ammonium Compounds; Time Factors; Total Quality Management

The current use of multimodal analgesia for the management of postoperative pain has resulted in reduced side effects and improved pain relief. Limitations of the technology associated with current pump- or catheter-based systems have prompted the development of continuous delivery systems and extended-duration techniques for pain relief. Among these are morphine sulfate sustained-release liposome injection (Morphine SR, DepoMorphine) and the patient-controlled transdermal system (PCTS, E-TRANS). Morphine SR utilizes the novel DepoFoam technology, a novel delivery system that allows the drug to be gradually released into the surrounding epidural space. Morphine SR is compatible with anticoagulation therapy and eliminates interference from pump and intravenous (IV) equipment. Administration of Morphine SR during hip arthroplasty significantly reduced patients' postoperative consumption of fentanyl. E-TRANS fentanyl PCTS is a transdermal system attached to the patient's arm or upper chest; a button on the device is controlled by the patient to deliver doses of fentanyl. In a study comparing fentanyl HCl PCTS with conventional IV-patient-controlled analgesia (PCA) morphine, PCTS was found to be as safe and effective as PCA for the treatment of postoperative pain. Novel delivery systems that are less invasive, that are compatible with anticoagulation regimens, and that provide continuous delivery, thus preventing analgesic gaps, will facilitate rehabilitation and recovery and ultimately improve patient outcomes.

Topics: Analgesia, Epidural; Analgesia, Patient-Controlled; Analgesics, Opioid; Drug Therapy, Combination; Fentanyl; Humans; Length of Stay; Liposomes; Morphine; Orthopedic Procedures; Pain, Postoperative; Piperidines

Alvimopan is a peripherally acting mu-opioid receptor (PAM-OR) antagonist for accelerating gastrointestinal recovery after surgery.. 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).. 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.. Alvimopan (6 or 12 mg) accelerates GI recovery and is well tolerated in patients undergoing open laparotomy.

Topics: Abdomen; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Double-Blind Method; Female; Gastrointestinal Tract; Humans; Hysterectomy; Ileus; Laparotomy; Male; Middle Aged; Pain Measurement; Pain, Postoperative; Pelvis; Piperidines; Proportional Hazards Models; Receptors, Opioid, mu; Recovery of Function; Survival Analysis; Treatment Outcome

ADL-8-2698 is a novel peripherally restricted opioid antagonist that may selectively prevent opioid-induced gastrointestinal effects without reversing analgesia. Gastrointestinal transit time (lactulose hydrogen breath test) was measured in 14 volunteers with oral and intravenous placebo, oral placebo and intravenous morphine (0.05 mg x kg(-1)), and oral ADL 8-2698 (4 mg) and intravenous morphine (0.05 mg x kg(-1)) in a double blind, cross-over study. Morphine prolonged gastrointestinal transit time from 69 to 103 minutes (P = .005); this was prevented by ADL 8-2698 (P = .004). Postoperatively, 45 patients were randomly assigned in a double-blind fashion to receive ADL 8-2698 (4 mg) or placebo and intravenous morphine (0.15 mg/kg) or to receive oral and intravenous placebo. Analgesia and pupil constriction were measured. Morphine analgesia and pupil constriction were unaffected by ADL 8-2698 and differed from placebo (P < .002). We conclude that ADL 8-2698 prevents morphine-induced increases in gastrointestinal transit time by means of selective peripheral opioid anitagonism without affecting central opioid analgesia.

Topics: Adult; Analgesics, Opioid; Double-Blind Method; Drug Interactions; Female; Gastrointestinal Diseases; Gastrointestinal Transit; Humans; Male; Molar, Third; Morphine; Narcotic Antagonists; Pain Measurement; Pain, Postoperative; Piperidines; Tooth Extraction; Tooth, Impacted

Postoperative recovery of gastrointestinal function and resumption of oral intake are critical determinants of the length of hospital stay. Although opioids are effective treatments for postoperative pain, they contribute to the delayed recovery of gastrointestinal function.. We studied the effects of ADL 8-2698, an investigational opioid antagonist with limited oral absorption that does not readily cross the blood-brain barrier, on postoperative gastrointestinal function and the length of hospitalization. We randomly assigned 79 patients--including 1 whose surgery was canceled--to receive one capsule containing 1 mg or 6 mg of ADL 8-2698 or an identical-appearing placebo capsule two hours before major abdominal surgery and then twice daily until the first bowel movement or until discharge from the hospital. Data were analyzed for 26 patients in each of the three groups; all received opioids for postoperative pain relief. Observers who were unaware of the group assignments evaluated the outcomes.. Fifteen patients underwent partial colectomy and 63 underwent total abdominal hysterectomy. Patients given 6 mg of ADL 8-2698 had significantly faster recovery of gastrointestinal function than those given placebo. The median time to the first passage of flatus decreased from 70 to 49 hours (P=0.03), the median time to the first bowel movement decreased from 111 to 70 hours (P=0.01), and the median time until patients were ready for discharge decreased from 91 to 68 hours (P=0.03). Effects in the group that received 1 mg of ADL 8-2698 were less pronounced.. Selective inhibition of gastrointestinal opioid receptors by an antagonist with limited oral absorption that does not readily cross the blood-brain barrier speeds recovery of bowel function and shortens the duration of hospitalization.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Colectomy; Defecation; Digestive System; Female; Flatulence; Humans; Hysterectomy; Intestinal Obstruction; Length of Stay; Male; Meperidine; Middle Aged; Morphine; Narcotic Antagonists; Pain, Postoperative; Piperidines; Postoperative Complications; Receptors, Opioid; Time Factors

Radical cystectomy is associated with significant morbidity, with rates of gastrointestinal complications as high as 30%. Alvimopan is a mu opioid receptor antagonist that has been shown in randomized control trials to accelerate gastrointestinal recovery in patients undergoing bowel resection with primary anastamosis. We report our experience with gastrointestinal recovery for patients undergoing cystectomy with urinary diversion treated with alvimopan.. Between January 2008 and August 2011, 50 consecutive patients underwent radical cystectomy with urinary diversion at our institution. The first 27 patients in our study did not receive alvimopan preoperatively. The latter 23 patients received perioperative alvimopan and were without postoperative nasogastric decompression. Return of bowel function, initiation of diet, and gastrointestinal complications were evaluated.. Times to first flatus (3.1 versus 5.6 days, p < 0.001, 95% CI 1.66-3.26) and bowel movement (3.8 versus 6.0 days, p < 0.001, 95% CI 1.35-2.99) were significantly shorter in those patients who received alvimopan. Additionally, the initiation of clear liquid diet (4.1 versus 6.3 days, p < 0.001, 95% CI 1.20-3.12), regular diet (5.7 versus 7.3 days, p = 0.023, 95% CI 0.57-2.63) and hospital discharge (7.4 versus 9.5 days, p = 0.04, 95% CI 0.03-4.21) were accelerated in the alvimopan cohort. There were no incidences of prolonged ileus in patients who received perioperative alvimopan (0% versus 25.9%, p = 0.012).. In our experience, the use of alvimopan perioperatively significantly accelerates the rate of gastrointestinal recovery and hospital discharge, eliminates the need for nasogastric tube decompression, and reduces the incidence of postoperative ileus in patients following radical cystectomy and urinary diversion.

Topics: Aged; Analgesics, Opioid; Cystectomy; Eating; Female; Gastrointestinal Agents; Gastrointestinal Tract; Humans; Ileus; Intubation, Gastrointestinal; Length of Stay; Male; Pain, Postoperative; Piperidines; Receptors, Opioid, mu; Recovery of Function; Retrospective Studies; Time Factors; Urinary Diversion