methylnaltrexone and Pain--Postoperative

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 is a major barrier to gastrointestinal recovery following surgery. Opioid analgesics likely play an important causative role, particularly in spinal or orthopedic surgeries not involving bowel manipulation. Methylnaltrexone, a peripherally-acting µ-opioid receptor antagonist, is a potential prophylactic treatment.. To assess the influence of perioperative subcutaneous methylnaltrexone administration on gastrointestinal recovery following short-segment lumbar arthrodesis surgeries.. This is a randomized, double-blind, controlled trial.. Eligible patients undergoing posterior short-segment lumbar arthrodesis surgeries at a single institution between February 2019 and April 2021 were enrolled in this study.. The primary outcome measure was time-to-first bowel movement. Secondary outcome measures included time-to-discharge/discharge eligibility. Exploratory outcome measures included daily postoperative opioid consumption and pain scores.. In this study, eligible patients were enrolled to receive either methylnaltrexone or placebo perioperatively. Time-to-bowel movement, time-to-discharge/discharge eligibility, intra and postoperative analgesic administration, and pain scores were recorded and compared.. Eighty two patients in total were enrolled; 41 to the methylnaltrexone and 41 to the placebo group. Both groups were similar in their baseline characteristics. There was no difference in median (range) time-to-bowel movement between the 2 groups [61.8 hours (35.7-93.6) versus 50.7 hours (17.8-110.8), p = .391]. There was also no difference in time-to-discharge/discharge eligibility [105.0 hours (81.0 - 201.3) versus 90.7 (77.5 - 184.5), p=.784]. Finally, there were no differences in either postoperative opioid consumption or numeric rating scores for back, leg, or abdominal pain on postoperative days 0 to 4 (p>.05).. Methylnaltrexone did not accelerate gastrointestinal recovery and did not affect opioid consumption or pain scores following short-segment spinal surgery as compared to placebo. Additional studies will be needed to identify effective opioid receptor antagonist dosing regimens for patients undergoing either short- or long-segment spinal arthrodesis procedures.

Topics: Analgesics, Opioid; Arthrodesis; Double-Blind Method; Humans; Naltrexone; Narcotic Antagonists; Pain, Postoperative; Quaternary Ammonium Compounds; Treatment Outcome

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

Experimental studies suggest that a large proportion of opioid analgesia can be mediated by peripheral opioid receptors. This trial examined the contribution of such receptors to clinical analgesia induced by intravenous morphine. We hypothesized that the selective blockade of peripheral opioid receptors by methylnaltrexone (MNX) would increase the patients' demand for morphine to achieve satisfactory postoperative pain relief. In a double-blind, placebo-controlled, sequential 2-center trial, 50 patients undergoing knee replacement surgery were randomized (1:1) to receive either subcutaneous MNX (0.9 mg/kg) (hospital I: n=14; hospital II: n=11) or saline (hospital I: n=13; hospital II: n=12) at the end of surgery. The primary endpoint was the cumulative amount of intravenous morphine administered during the first 8 hours. Secondary endpoints were pain scores at rest and during movement (by numerical rating scale and McGill Questionnaire), vital signs, adverse side effects, and withdrawal symptoms. After MNX, demands for morphine were strongly (by about 40%) increased (hospital I: 35.31 ± 12.99 mg vs 25.51 ± 7.92 mg, P=0.03; hospital II: 35.42 ± 11.73 mg vs 24.80 ± 7.84 mg, P=0.02; pooled data: P<.001; means ± SD). Secondary endpoints were similar in all groups (P>.05). Thus, a significant proportion of analgesia produced by systemically administered morphine is mediated by peripheral opioid receptors. Drugs that selectively activate such receptors should have the potential to produce powerful clinical pain relief.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesia, Patient-Controlled; Analgesics, Opioid; Arthroplasty, Replacement, Knee; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphine; Naltrexone; Narcotic Antagonists; Pain Measurement; Pain, Postoperative; Quaternary Ammonium Compounds; Young Adult

Opioid pain medications have detrimental side effects including analgesic tolerance and opioid-induced hyperalgesia (OIH). Tolerance and OIH counteract opioid analgesia and drive dose escalation. The cell types and receptors on which opioids act to initiate these maladaptive processes remain disputed, which has prevented the development of therapies to maximize and sustain opioid analgesic efficacy. We found that μ opioid receptors (MORs) expressed by primary afferent nociceptors initiate tolerance and OIH development. RNA sequencing and histological analysis revealed that MORs are expressed by nociceptors, but not by spinal microglia. Deletion of MORs specifically in nociceptors eliminated morphine tolerance, OIH and pronociceptive synaptic long-term potentiation without altering antinociception. Furthermore, we found that co-administration of methylnaltrexone bromide, a peripherally restricted MOR antagonist, was sufficient to abrogate morphine tolerance and OIH without diminishing antinociception in perioperative and chronic pain models. Collectively, our data support the idea that opioid agonists can be combined with peripheral MOR antagonists to limit analgesic tolerance and OIH.

Topics: Analgesia; Analgesics, Opioid; Animals; Chronic Pain; Disease Models, Animal; Drug Tolerance; Gene Deletion; Hyperalgesia; Long-Term Potentiation; Mice; Mice, Knockout; Microglia; Morphine; Naltrexone; Nociception; Nociceptors; Pain, Postoperative; Quaternary Ammonium Compounds; Receptors, Opioid, mu; Signal Transduction; Spinal Cord

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