Selective Postoperative Inhibition of Gastrointestinal Opioid Receptors

Taguchi, Akiko; Sharma, Neeraj; Saleem, Rao; Sessler, Daniel I.; Carpenter, Randall L.; Seyedsadr, Mahmoud; Kurz, Andrea

doi:10.1056/nejmoa010564

Cited by 294 publications

(208 citation statements)

References 19 publications

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“…Surgical manipulation of the bowel leads to POI1,2. It has been theorized that endogenous stimulation of opioid receptors can contribute to this neurally mediated reflex3–5.…”

Section: Introductionmentioning

confidence: 99%

“…Opioids exacerbate and prolong POI by binding to µ-opioid receptors in the gut, resulting in decreased propulsive peristaltic waves and delayed intestinal transit1,2,6,8,9. Conventional treatments, including nasogastric suction, prokinetic agents, early enteral feeding, and the use of minimally invasive surgical techniques, have not been proven effective in preventing or alleviating POI1.…”

Section: Introductionmentioning

confidence: 99%

“…However, because it crosses the blood–brain barrier, it also reverses the analgesic effect of opioid treatments and produces withdrawal symptoms2,13. Methylnaltrexone, a peripheral µ-opioid receptor antagonist, is a quaternary derivative of naltrexone (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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Randomized placebo-controlled study of intravenous methylnaltrexone in postoperative ileus

Viscusi

Rathmell

Fichera

et al. 2013

Journal of Drug Assessment

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ObjectiveThis phase 2 study evaluated the safety and activity of intravenous methylnaltrexone on the duration of postoperative ileus in patients undergoing segmental colectomy.MethodsAdults (aged 18 years or older) with American Society of Anesthesiologists physical status of I, II, or III who underwent segmental colectomy, including partial colectomy, sigmoidectomy, cecectomy, or anterior proctosigmoidectomy, via laparotomy with general anesthesia, received intravenous methylnaltrexone 0.30 mg/kg or placebo every 6 h beginning within 90 min after end of surgery. Treatment continued until 24 h after the patient tolerated solid foods, was discharged, or for 7 d maximum. Efficacy endpoints included measures of gastrointestinal recovery and time to discharge eligibility.ResultsA total of 65 patients (methylnaltrexone, n = 33; placebo, n = 32) were randomized. Mean time to first bowel movement was accelerated by 20 h (p = 0.038) and time to discharge eligibility was accelerated by 33 h (p = 0.049) with methylnaltrexone vs placebo. Opioid use was similar between groups until postoperative day 4, then fluctuated in the placebo group. Methylnaltrexone was generally well tolerated.ConclusionsIn this study, intravenous methylnaltrexone significantly decreased time to postoperative bowel recovery and eligibility for hospital discharge by ∼1 d, with an adverse event profile similar to placebo. These were two of several exploratory endpoints; not all efficacy endpoints showed a significant difference between methylnaltrexone and placebo. The efficacy results in this trial were not seen in two subsequent large-scale studies.

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“…Surgical manipulation of the bowel leads to POI1,2. It has been theorized that endogenous stimulation of opioid receptors can contribute to this neurally mediated reflex3–5.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Randomized placebo-controlled study of intravenous methylnaltrexone in postoperative ileus

Viscusi

Rathmell

Fichera

et al. 2013

Journal of Drug Assessment

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“…Unlike naxolone, these peripherial mu-opioid receptor antagonists do not antagonise the analgesic effects of analgesia and induce withdraw effects [46] . Alvimopan, a peripheral µ-opioid receptor antagonist, has been shown to counteract the inhibitory effect of opiate on small bowel motility [47] and significant reduce both the time to bowel recovery and time to discharge from hospital in patients with abdominal surgery [48] . The efficacy of alvimopan in the management of feed intolerance during critical illness, however, has not been formally assessed and warranted further evaluation.…”

Section: Gastrointestinal Side Effectsmentioning

confidence: 99%

Pharmacological therapy of feed intolerance in the critically ills

Nguyen¹

2014

WJGPT

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Feed intolerance in the setting of critical illness is associated with higher morbidity and mortality, and thus requires promptly and effective treatment. Prokinetic agents are currently considered as the first-line therapy given issues relating to parenteral nutrition and postpyloric placement. Currently, the agents of choice are erythromycin and metoclopramide, either alone or in combination, which are highly effective with relatively low incidence of cardiac, hemodynamic or neurological adverse effects. Diarrhea, however, can occur in up to 49% of patients who are treated with the dual prokinetic therapy, which is not associated with Clostridium difficile infection and settled soon after the cessation of the drugs. Hence, the use of prokinetic therapy over a long period or for prophylactic purpose must be avoided, and the indication for ongoing use of the drug(s) must be reviewed frequently. Second line therapy, such as total parenteral nutrition and post-pyloric feeding, must be considered once adverse effects relating the prokinetic therapy develop.© 2014 Baishideng Publishing Group Inc. All rights reserved. Key words: Adverse effects; Critical illness; Enteral feeding; Feed intolerance; Prokinetic therapyCore tip: Feed intolerance during critical illness must be promptly recognized and treated due to the associated morbidity and mortality. The current first line treatment for feed intolerance is prokinetic therapy with erythromycin and metoclopramide (alone or in combination), which are highly effective and free of significant adverse effects. Although diarrhoea occurs commonly after combination prokinetic therapy, it is not associated with Clostridium difficile colitis and settled shortly after stopping the treatment. The use of prokinetic therapy over a long period or for prophylactic purpose, therefore, must be avoided and the indication for ongoing use of the drug(s) should be frequently reviewed.Nguyen NQ. Pharmacological therapy of feed intolerance in the critically ills.

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“…Although the molecule has been investigated for its efficacy in both opioid induced constipation and acute postoperative ileus, the focus in development has been primarily towards the latter. In patients who developed postoperative ileus after undergoing bowel resection and hysterectomy (Cochrane data, n = 2225) [4], alvimopan administration reduced the time to first bowel movement or flatus, or total time to pass flatus when compared with placebo [8][9][10][11][12]. Patients in the alvimopan group also showed a reduced requirement for postoperative X-ray and nasogastric tube insertion compared with placebo [4].…”

Section: Peripheral Opioid Antagonismmentioning

confidence: 99%