methylnaltrexone and Postoperative-Complications

Peripherally acting mu-opioid receptor antagonists methylnaltrexone and alvimopan are a new class of drugs designed to reverse opioid-induced side-effects on the gastrointestinal system without compromising pain relief. This article gives an overview of the pharmacology, the efficacy, and adverse effects of these drugs. Both compounds seem to be generally well tolerated and effective for the treatment of opioid-related bowel dysfunction and postoperative ileus. Methylnaltrexone recently received approval by the US Food and Drug Administration (FDA) and the European Medicines Agency for treatment of opioid-related bowel dysfunction in patients with advanced illness. Alvimopan was recently approved by the FDA for treatment of postoperative ileus, but the use of the drug is restricted to inpatients because it has been associated with an increased rate of myocardial infarction. Further research should assess the effectiveness and safety of these drugs in clinical practice.

Topics: Analgesics, Opioid; Blood-Brain Barrier; Drug Approval; Europe; Humans; Ileus; Myocardial Infarction; Naltrexone; Narcotic Antagonists; Patient Selection; Piperidines; Postoperative Complications; Quaternary Ammonium Compounds; Research Design; Safety; United States; United States Food and Drug Administration

The duration of postoperative ileus following abdominal surgery is quite variable, and prolonged postoperative ileus is an iatrogenic phenomenon with important influence on patient morbidity, hospital costs and length of stay in hospital. Adequate treatment for prolonged postoperative ileus is important to improve patient morbidity and clinical efficiency. Both clinical and pharmacological management strategies have improved rapidly over the last decade, and appropriate and timely management using multimodal techniques should be used for optimal care. In this review, we define postoperative ileus, describe the pathogenesis and briefly discuss clinical management before detailing potential pharmacologic management options.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Anti-Inflammatory Agents, Non-Steroidal; Bisacodyl; Cathartics; Cisapride; Dihydroergotamine; Humans; Ileus; Inflammation; Naltrexone; Neostigmine; Parasympathomimetics; Piperidines; Postoperative Complications; Propranolol; Quaternary Ammonium Compounds; Receptors, Opioid, mu; Serotonin Receptor Agonists

Constipation is a common problem associated with opiates and opioid compounds used for the treatment of pain and other medical conditions, and can influence patient quality of life. Methylnaltrexone appears effective in the therapy of opioid-induced constipation and will be useful for patients failing to respond to traditional laxative regimens.

Topics: Analgesics, Opioid; Clinical Trials as Topic; Constipation; Dose-Response Relationship, Drug; Drug Interactions; Gastrointestinal Transit; Half-Life; Humans; Infusions, Intravenous; Infusions, Subcutaneous; Laxatives; Naltrexone; Narcotic Antagonists; Postoperative Complications; Quaternary Ammonium Compounds

Progenics Pharmaceuticals Inc and Wyeth Pharmaceuticals are developing methylnaltrexone, a micro-receptor opioid antagonist derived from naltrexone by the addition of a methyl group. The intravenous formulation of methylnaltrexone is currently in phase III clinical trials for the potential treatment of postoperative ileus.

Topics: Analgesics, Opioid; Gastrointestinal Motility; Humans; Ileus; Naltrexone; Postoperative Complications; Postoperative Nausea and Vomiting; Quaternary Ammonium Compounds; Receptors, Opioid, mu; Urinary Retention

Methylnaltrexone and alvimopan are two new and potentially useful agents in the management of opioid-induced bowel dysfunction and prevention of postoperative ileus. Both agents have promising prokinetic properties and appear to be capable of reversing the effects of opioids on delayed gastrointestinal transit. This article reviews currently available published literature to provide an overview of the clinical trials and to provide insight for the potential use of these agents for patients requiring opioid based analgesia. These compounds represent a new class of compounds that may impact the therapeutics for opioid induced bowel dysfunction as well as postoperative ileus.

Topics: Analgesics, Opioid; Gastrointestinal Transit; Humans; Ileus; Intestinal Diseases; Naltrexone; Narcotic Antagonists; Piperidines; Postoperative Complications; Quaternary Ammonium Compounds

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

Postoperative ileus (POI) is frequently experienced by many patients undergoing abdominal operations and other surgical procedures. Postoperative ileus causes physical discomfort and may increase risk for prolonged hospital length of stay. Despite its prevalence, there is currently no accepted standard definition of POI and, consequently, no standardized mode of prevention or treatment; it is no wonder that a variety of management approaches for POI have been developed. Some of these include alternative surgical techniques such as laparoscopic or endoscopic procedures to minimize trauma and help lessen the release of endogenous mediators of POI. Others have evaluated alternate analgesic regimens such as thoracic epidural anesthetics to avoid stimulating opioid receptors in the gut. These approaches have had varying results. Other pharmacologic attempts to reduce POI have focused on the blockade of opioid receptors to prevent opioid-induced GI-related adverse effects. A new class of agents, peripherally acting mu-opioid-receptor antagonists such as methylnaltrexone and alvimopan, may improve the pharmacologic management of POI and reshape the current paradigm of multimodal management of POI. Protocols that incorporate these agents may offer yet another avenue to mitigate the adverse effects of POI, and thus help improve surgical outcomes. To date, alvimopan has been shown in phase 3 clinical trials to significantly reduce the duration of POI while maintaining satisfactory analgesia and reducing length of hospital stay. Combinations of strategies with demonstrated effectiveness such as early feeding, epidural analgesia, laparoscopic surgery, and peripherally acting mu-opioid-receptor antagonists may help transform the management of POI into an effective multimodal paradigm that targets the diverse etiologic factors leading to this common clinical problem. Clearly, all surgical team members are crucial in the optimal implementation of such multimodal approaches.

Topics: Analgesia, Epidural; Analgesics, Opioid; Attitude of Health Personnel; Choice Behavior; Enteral Nutrition; Evidence-Based Medicine; General Surgery; Humans; Ileus; Intubation, Gastrointestinal; Laparoscopy; Laparotomy; Length of Stay; Naltrexone; Narcotic Antagonists; Outcome Assessment, Health Care; Patient Care Team; Patient Selection; Piperidines; Postoperative Care; Postoperative Complications; Practice Guidelines as Topic; Quaternary Ammonium Compounds; Risk Factors

Opioid treatment for postoperative or chronic pain is frequently associated with adverse effects, the most common being dose-limiting and debilitating bowel dysfunction. Postoperative ileus, although attributable to surgical procedures, is often exacerbated by opioid use during and following surgery. Postoperative ileus is marked by increased inhibitory neural input, heightened inflammatory responses, decreased propulsive movements and increased fluid absorption in the gastrointestinal tract. The use of opioids for chronic pain is characterised by a constellation of symptoms including hard dry stools, straining, incomplete evacuation, bloating, abdominal distension and increased gastroesophageal reflux. The current management of opioid-induced bowel dysfunction among patients receiving opioid analgesics consists primarily of nonspecific ameliorative measures. Intensive investigations into the mode of action of opioids have characterised three opioid receptor classes -mu, delta and kappa- that mediate the myriad of peripheral and central actions of opioids. Activation of mu-opioid receptors in the gastrointestinal tract is responsible for inhibition of gut motility, whereas receptors in the central nervous system mediate the analgesic actions of opioids. Blocking peripheral opioid receptors in the gut is therefore a logical therapeutic target for managing opioid-induced bowel dysfunction. Available opioid antagonists such as naloxone are of limited use because they are readily absorbed, cross the blood-brain barrier, and act at central opioid receptors to reverse analgesia and elicit opioid withdrawal. Methylnaltrexone and alvimopan are recently developed opioid antagonists with activity that is restricted to peripheral receptors. Both have recently shown the ability to reverse opioid-induced bowel dysfunction without reversing analgesia or precipitating central nervous system withdrawal signs in non-surgical patients receiving opioids for chronic pain. In addition, recent clinical studies with alvimopan suggest that it may normalise bowel function without blocking opioid analgesia in abdominal laparotomy patients with opioid-related postoperative ileus.

Topics: Constipation; Digestive System; Gastrointestinal Motility; Gastrointestinal Transit; Humans; Intestinal Obstruction; Naltrexone; Narcotic Antagonists; Narcotics; Postoperative Complications; Quaternary Ammonium Compounds; Receptors, Opioid; Water-Electrolyte Balance

Postoperative ileus (POI) is a common complication with no proven prophylactic measures in place. While perioperative opioid use has been implicated in POI development, current treatments fail to target this disease mechanism. Methylnaltrexone (MNTX) has been used to prevent the effects of opioids on the bowel and could reduce the incidence of POI when administered preoperatively.. In this phase IIb randomized controlled trial, we assessed the effect of perioperative MNTX on time-to-first-bowel movement following spinal arthrodesis surgeries.. 82 patients were randomly selected in a 1:1 ratio to be included in either the treatment or placebo groups. Comparison of relevant factors of included patients to patients who refused to participate (n = 21) and to a prior retrospective series (n = 241) revealed no differences in age, male sex, liver disease, and number of surgical levels. Overall treatment fidelity (98% adherence) and retention (100% at one-month follow-up) were high. The predicted POI incidence (9.3-11.1%) was also equivalent to a prior retrospective series. However, the overall observed POI incidence (3.7%) was lower than expected, which could reflect a superimposed 'trial effect' related to standardized care in a research setting.. Since exposure to significant opioid doses represents a barrier to enhanced recovery after surgery, the results of this innovative trial may provide further guidance for the peri-operative use of opioid-receptor blockers. Here, we show that MNTX can be effectively administered in the peri-operative period with appropriate follow-up achieved in a representative population of patients undergoing spinal surgery.. Clinicaltrials.gov - NCT03852524 and Institutional Review Board - 2018H0260.

Topics: Adult; Arthrodesis; Feasibility Studies; Humans; Ileus; Male; Naltrexone; Postoperative Complications; Quaternary Ammonium Compounds; Retrospective Studies

Methylnaltrexone is a peripheral opioid receptor antagonist that does not cross the blood-brain barrier; so without interference with pain relief, it could reverse the peripheral opioid side effects such as constipation, pruritus, postoperative ileus, and urinary retention. This study has been designed to evaluate the effect of methylnaltrexone on postoperative side effects of intrathecal morphine. In seventy-two 18- to 55-year-old patients scheduled for elective orthopedic operations under spinal anesthesia, neuraxial blockade was achieved using 10 mg 0.5% hyperbaric bupivacaine and 0.1 mg preservative-free morphine sulfate. The first group (M) received 12 mg methylnaltrexone, while the second group (P) received normal saline, subcutaneously, immediately after spinal block in a randomized, double-blind fashion. There was a significant decrease in the rate of nausea and vomiting in group M, but there was no significant difference in the rate of pruritus or urinary retention between the two groups. Pain score was significantly lower in group M. Respiratory depression or decreased level of consciousness was not reported in any patient. Subcutaneous administration of methylnaltrexone was not effective in decreasing postoperative urinary retention and pruritus, but lowered the rate of nausea and vomiting and pain score after intrathecal bupivacaine and morphine.

Topics: Adult; Analgesics, Opioid; Anesthesia, Spinal; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphine; Naltrexone; Narcotic Antagonists; Orthopedic Procedures; Pain, Postoperative; Postoperative Complications; Quaternary Ammonium Compounds; Young Adult

Intrathecal morphine-induced pruritus is a very common side-effect that is difficult to prevent or treat. Central and peripheral mechanisms are believed to be involved. The aim of this study was to determine if a peripherally acting, μ-opioid antagonist would reduce morphine-induced pruritus.. We conducted a multicentre, randomized, blinded, placebo-controlled trial of women having elective Caesarean section under spinal anaesthesia with intrathecal morphine 100 μg. After delivery, participants received either subcutaneous methylnatrexone bromide 12 mg (MNTX group, n=69) or saline (placebo group, n=68). Pruritus, nausea, pain, analgesic use, and side-effects were assessed at 2, 4, 8, and 24 h. The primary outcome was the severity of pruritus (0-10 score).. One hundred and thirty-seven women completed the study, with five major protocol violations. There was no statistically significant difference between the MNTX and placebo groups for the median (IQR) pruritus AUC scores [24 (9-47) vs 36 (11-68), median difference 8.5, 95% confidence interval (CI) 0-20, P=0.09] or the worst pruritus score [3 (2-7) vs 5 (2-6), median difference 1, 95% CI 0-2, P=0.24]. The incidence of pruritus was 84% in the MNTX group and 88% in the placebo group (P=0.48). Analgesic and gastrointestinal outcomes did not significantly differ between the groups.. A single dose of subcutaneous methylnaltrexone bromide 12 mg did not reduce the overall severity or incidence of pruritus. In this study, treatment with a peripherally acting μ-opioid antagonist was generally ineffective against intrathecal morphine-induced pruritus, but a small clinical effect cannot be excluded.. Australian New Zealand Clinical Trials Registry (ACTRN12611000345987).

Topics: Adult; Analgesia, Obstetrical; Analgesics, Opioid; Anesthesia, Spinal; Australia; Cesarean Section; Female; Humans; Middle Aged; Morphine; Naltrexone; Narcotic Antagonists; Postoperative Complications; Pregnancy; Pruritus; Quaternary Ammonium Compounds; Singapore; Treatment Outcome; United States; Young Adult

Postoperative ileus contributes to surgical morbidity and is associated with prolonged hospitalization and increased health care costs. The efficacy and safety of the peripherally acting μ-opioid receptor antagonist methylnaltrexone in shortening the duration of postoperative ileus following segmental colectomy was evaluated.. Two identically designed, multicenter, double-blind, parallel-group, placebo-controlled studies randomly assigned patients undergoing segmental colectomy (study 1, N = 515; study 2, N = 533) to receive 12 or 24 mg of methylnaltrexone intravenously or placebo every 6 hours starting within 90 minutes of surgery completion, continuing for up to 10 days or up to 24 hours after gastrointestinal recovery. The primary efficacy end point was the time from the end of surgery to the first bowel movement. Safety was evaluated via standard assessments (ie, adverse events and related withdrawals, physical examinations, laboratory tests, vital signs, electrocardiograms) and assessment of surgical complications.. The primary and secondary efficacy outcomes (time to discharge eligibility, time to hospital discharge, and clinically meaningful events of nausea and vomiting following segmental colectomy) did not differ significantly between patients treated with either a dose of methylnaltrexone or with placebo. Rates of adverse events and serious adverse events were comparable across all treatment groups in both studies. The most commonly observed adverse events were nausea, pyrexia, and vomiting.. Although the efficacy of methylnaltrexone in reducing the duration of postoperative ileus was not demonstrated in these studies, intravenous methylnaltrexone at doses of 12 mg and 24 mg was safe, in general, and well tolerated in postcolectomy patients. The utility of intravenous methylnaltrexone in treating postoperative ileus remains unproven.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Colectomy; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Ileus; Injections, Intravenous; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Postoperative Complications; Quaternary Ammonium Compounds; Retrospective Studies; Treatment Outcome; Young Adult

We examined the effect of methylnaltrexone on the incidence of postoperative nausea and vomiting in a prospective double-blind placebo controlled study. One hundred and twenty female patients undergoing laparoscopic major gynecological surgery were allocated randomly to receive either 20 mg methylnaltrexone or placebo IV at the end of surgery. Postoperative nausea and vomiting was evaluated for 6 h after admission to the PACU and assessed by number of episodes and degree of severity. The incidences of nausea and vomiting for the placebo group were 27 and 18 percent, respectively. The corresponding values for the methylnaltrexone group were 20 and 10 percent. We conclude that methylnaltrexone did not prevent nor significantly reduced the incidence and severity of postoperative nausea and vomiting following a balanced anesthetic technique in gynecological procedures.

Topics: Adult; Antiemetics; Double-Blind Method; Female; Humans; Middle Aged; Naltrexone; Narcotic Antagonists; Nausea; Postoperative Complications; Prospective Studies; Quaternary Ammonium Compounds; Vomiting

Postoperative ileus (POI) is a surgical complication resulting in increased morbidity and length of stay (LOS). Usual care for POI includes bowel rest and gastric decompression. It has been questioned if methylnaltrexone (MNTX), a peripheral opioid antagonist, could be used as treatment for POI. The purpose of this study was to determine if MNTX is effective and safe for POI treatment.. This single-center, retrospective cohort study included patients ⩾ 18 years with a POI. Patients with acute colonic pseudo-obstruction, small bowel obstruction, and gastrointestinal malignancy were excluded. The intervention was MNTX administration. The primary outcome was time to ileus resolution. Secondary outcomes included LOS, duration of nasogastric tube, total parenteral nutrition requirement, and incidence of gastrointestinal perforations.. 110 patients were included in the analysis; 28 received MNTX. Time to ileus resolution was 9.9 days for the MNTX group and 11.4 days for the control group (. For the treatment of POI, MNTX did not significantly reduce time to resolution of ileus, LOS, duration of gastric decompression, or TPN requirements. However, no gastrointestinal perforations were seen, indicating that MNTX may be safely used in these patients.

Topics: Female; Humans; Ileus; Intestinal Perforation; Intubation, Gastrointestinal; Length of Stay; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Parenteral Nutrition; Postoperative Complications; Quaternary Ammonium Compounds; Retrospective Studies; Time Factors; Treatment Outcome

To assess the impact of N-methylnaltrexone, a peripherally acting mu-opioid receptor antagonist, on the post-operative recovery of patients undergoing robotic-assisted radical cystectomy for bladder cancer.. We retrospectively reviewed patients undergoing robotic-assisted radical cystectomy by a single surgeon (KC) prior to (control group) and after (treatment group) the routine use of N-methylnaltrexone. Kaplan-Meier curves and the log-rank test were used to quantify time to flatus, bowel movement, and discharge. Daily mean opioid use, daily pain assessment rating, and episodes of severe pain (7-10/10) were compared. Gastrointestinal-related complications, including ileus, emesis, and/or need for post-op nasogastric tube placement, and 30-day readmissions were also compared between groups. Charge capture data were compared between groups to analyze cost impact.. 29 patients each in the control and treatment group met inclusion criteria. Patients receiving N-methylnaltrexone had reduced length of stay compared with no N-methylnaltrexone (median 4 vs. 7 days, p < 0.01). Time to flatus and bowel movement, however, were similar. In a multivariable analysis controlling for possible confounders, however, the improvement in length of stay associated with N-methylnaltrexone use did not reach statistical significance (p = 0.11). Episodes of severe pain and composite gastrointestinal-related complications were reduced in the N-methylnaltrexone group (44.8% vs. 10.3%, p < 0.01). The reduction in length of stay was associated with approximately $10,500 in cost savings per patient.. In this study, N-methylnaltrexone was associated with reduced length of stay, fewer episodes of severe pain, and reduced costs. These results provide the impetus for further study.

Topics: Aged; Cystectomy; Female; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Postoperative Complications; Postoperative Period; Quaternary Ammonium Compounds; Retrospective Studies; Robotic Surgical Procedures; Treatment Outcome; Urinary Bladder Neoplasms

Pain management with opioids is often limited by medication side effects. One of the most common and distressing side effects is opioid-induced constipation (OIC), a syndrome that is now getting significant national attention. We report the case of an opioid-dependent 56-year-old man who underwent lumbar decompression for spinal stenosis. Postoperatively, he developed OIC and Ogilvie syndrome, then following treatment with methylnaltrexone experienced an acute bowel perforation. We briefly review the recommended management of OIC as well as indications and contraindications of methylnaltrexone and similar new medications.

Topics: Analgesics, Opioid; Colonic Pseudo-Obstruction; Constipation; Decompression, Surgical; Humans; Hydromorphone; Intestinal Perforation; Low Back Pain; Male; Methadone; Middle Aged; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Oxycodone; Postoperative Complications; Quaternary Ammonium Compounds; Spinal Stenosis

Off-label uses of the peripheral μ-opioid receptor antagonists alvimopan and methylnaltrexone are reviewed.. Alvimopan is approved by the Food and Drug Administration (FDA) for postoperative ileus after surgeries that include partial bowel resection with primary anastomosis, while methylnaltrexone is approved for the treatment of opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care. Literature describing the off-label use of alvimopan in the treatment of OIC and of methylnaltrexone in postoperative ileus was reviewed and included retrospective studies and prospective Phase II-IV trials. Randomized controlled trials did not demonstrate consistent benefit of alvimopan in OIC nor of methylnaltrexone in postoperative ileus. A greater proportion of patients receiving alvimopan for OIC experienced severe adverse cardiovascular events, leading to a risk evaluation and mitigation strategy and discontinuation of its study in this condition. Data are limited and unreplicated for the off-label use of alvimopan for postoperative ileus in patients undergoing abdominal hysterectomy. Individual studies suggest benefit with methylnaltrexone for OIC in unlabeled populations, including patients with non-cancer-related pain, opioid dependence, opioid sedation, and opioid use after orthopedic surgery; however, confirmatory evaluations have not been performed.. Trials of alvimopan in the FDA-approved use of methylnaltrexone (OIC) indicate potentially serious cardiovascular safety concerns and conflicting findings of efficacy. Similarly, trials of methylnaltrexone in the FDA-approved use of alvimopan (postoperative ileus) consistently showed no benefit. Evaluations of both drugs in their labeled conditions in populations not endorsed in their product labeling have been limited and largely unreplicated.

Topics: Analgesics, Opioid; Constipation; Gastrointestinal Agents; Humans; Ileus; Naltrexone; Narcotic Antagonists; Off-Label Use; Piperidines; Postoperative Complications; Quaternary Ammonium Compounds

Postoperative ileus, a temporary cessation in bowel motility, is a common and significant complication of major surgery. Consequences of postoperative ileus include increased patient discomfort, delayed time to adequate nutrition, prolonged length of stay, and increased cost to the patient and healthcare system. The traditional, multi-modal approach to the resolution of postoperative ileus includes opioid minimization, early ambulation, and early feeding. Newer medications, such as methlynaltrexone and alvimopan (which are peripherally acting mu opioid receptor antagonists), have become available and have proven beneficial for use with postoperative ileus.

Topics: Combined Modality Therapy; Exercise Therapy; Gastrointestinal Agents; Humans; Ileus; Naltrexone; Narcotic Antagonists; Piperidines; Postoperative Complications; Quaternary Ammonium Compounds

Transient impairment of bowel function is a frequent and distressing problem in neonates on opioid-induced analgesia. Methylnaltrexone, a peripheral-acting μ-opioid receptor antagonist, has been studied in adults for the treatment of opioid-induced constipation in advanced illness and has been suggested as a promising therapeutic concept for reducing postoperative ileus. Here, we report on a newborn infant on fentanyl analgesia after major abdominal surgery with aggravated ileus. After 8 days of quiescent bowel, the patient's intestinal dysmotility resolved within 15 minutes after intravenous administration of methylnaltrexone (0.15 mg/kg body weight). Methylnatrexone was repeated daily until cessation of fentanyl administration. There were no signs of pain or opioid withdrawal.

Topics: Aortic Arch Syndromes; Coronary Disease; Extracorporeal Membrane Oxygenation; Fatal Outcome; Female; Fentanyl; Humans; Infant, Newborn; Intestinal Pseudo-Obstruction; Naltrexone; Narcotic Antagonists; Narcotics; Pain, Postoperative; Postoperative Complications; Quaternary Ammonium Compounds; Remission Induction

One of the most common undesired effects of analgesic opioid use and addiction is constipation. Numerous pharmacologic agents have been used to treat opioid-induced bowel hypomotility with limited success. Methylnaltrexone bromide (MNTX) selectively targets the peripheral adverse effects of opioids while preserving the central analgesic effects of opioid agonist treatment.. While it is indicated for use in nonsurgical patients in the palliative care setting, here we report the use of MNTX for the alleviation of postoperative ileus in a heroin user with recurrent cervical cancer undergoing diverting colostomy and urinary conduit placement.. Results suggest that MNTX may accelerate postoperative gastrointestinal recovery in opioid-dependent patients. Further studies are warranted to evaluate its role in the pharmacologic management of postoperative ileus.

Topics: Analgesics, Opioid; Female; Heroin Dependence; Humans; Ileus; Injections, Subcutaneous; Middle Aged; Naltrexone; Narcotic Antagonists; Postoperative Complications; Quaternary Ammonium Compounds

Topics: Analgesics, Opioid; Anesthetics; Gastrointestinal Agents; Humans; Intestinal Pseudo-Obstruction; Intubation, Gastrointestinal; Naltrexone; Piperidines; Postoperative Complications; Preoperative Care; Quaternary Ammonium Compounds

We observed a patient with incomplete, cervical paraplegia and opioid-induced constipation who developed a resistance to laxatives after 15 years of treatment. The constipation-induced reduction in the patient's quality of life was improved using 12 mg methylnaltrexone, a peripheral mu-opioid receptor antagonist, administered subcutaneously twice a week.

Topics: Aged; Cervical Vertebrae; Constipation; Fecal Impaction; Humans; Injections, Subcutaneous; Male; Naltrexone; Narcotic Antagonists; Narcotics; Paraplegia; Postoperative Complications; Quaternary Ammonium Compounds; Spinal Cord Compression

Postoperative ileus (POI), a transient impairment of bowel function, is considered an inevitable response after open abdominal surgery. It leads to significant patient morbidity and increased hospital costs and length of stay. The pathophysiology is multifactorial, involving neurogenic, hormonal, inflammatory and pharmacologic mediators. Several treatments have been shown to reduce the duration of POI, and a multimodal approach combining several of these interventions seems to be the most effective treatment option. Various drug therapies have been evaluated for the treatment of POI, although most have not shown any benefit. Peripherally active mu-opioid receptor antagonists are a new class of compounds that selectively block the peripheral (i.e., gastrointestinal [GI]) effects of opioids while preserving centrally mediated analgesia. Recently, alvimopan was approved in the US for the treatment of POI after abdominal surgery with bowel resection. Methylnaltrexone is a peripherally active mu-opioid receptor antagonist that has been shown to antagonize the inhibitory effects of opioids on GI transit without impairing analgesia. Phase II data indicated that methylnaltrexone was effective for improving GI recovery, reducing POI and shortening the time to discharge readiness in patients who underwent segmental colectomy. Two Phase III trials have been completed, and one is underway at present. Preliminary results from the two completed trials indicate that methylnaltrexone was not better than placebo for the primary or secondary outcomes. Further analyses of these data, clinical trial designs and the various dosage forms are necessary to determine the potential role of methylnaltrexone in the treatment of POI.

Topics: Animals; Clinical Trials as Topic; Drug Evaluation; Humans; Ileus; Naltrexone; Postoperative Complications; Quaternary Ammonium Compounds; Receptors, Opioid, mu

Postoperative ileus (POI) is often exacerbated by opioid analgesic use during and following surgery, since mu opioid receptor activation results in a further delay of gastrointestinal (GI) transit. The effects of alvimopan, a novel, selective, and peripherally acting mu opioid receptor antagonist, and the reference compound methylnaltrexone, upon POI were investigated in rats. Under isoflurane anesthesia, POI was induced by laparotomy with intestinal manipulation. Immediately after the surgery, the rats received (51)Cr by gavage. Three hours after the surgery, the rats were sacrificed and GI transit was estimated using the geometric center (GC) of (51)Cr. Alvimopan (0.1-3 mg/kg) or methylnaltrexone (100 mg/kg) were administered by gavage either before or after the surgery, with or without morphine administration (1 mg/kg). GI transit was delayed by intestinal manipulation (GC = 2.92 +/- 0.17). Alvimopan (1 and 3 mg/kg) significantly reversed this delayed GI transit when administered 45 min prior to surgery. However, the effects of alvimopan were less pronounced when administered following surgery. Morphine administration further delayed GI transit induced by intestinal manipulation (GC = 1.97 +/- 0.11). Under these conditions, alvimopan (1 and 3 mg/kg) also significantly improved delayed GI transit when administered before surgery. Methylnaltrexone was inactive under all experimental conditions. These data suggest that mu opioid receptors play a role in the pathogenesis of POI, and that the clinical benefit reported to be afforded by alvimopan may be in part mediated via inhibition of an endogenous opioid release as well as blockade of the unwanted GI actions of analgesic agents.

Topics: Analgesics, Opioid; Analysis of Variance; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Gastrointestinal Transit; Ileus; Laparotomy; Male; Naltrexone; Narcotic Antagonists; Piperidines; Postoperative Complications; Quaternary Ammonium Compounds; Rats; Rats, Sprague-Dawley

Topics: Humans; Intestinal Obstruction; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Postoperative Complications; Postoperative Nausea and Vomiting; Quaternary Ammonium Compounds