methylnaltrexone and Critical-Illness

Gastrointestinal dysmotility and dysfunction underlie our difficulties in providing adequate nutrition by the enteral route to our critically ill patients.. Recent studies have quantified gastric emptying and nutrient absorption. Slow gastric emptying is common and probably mediated by cholecystokinin and reduced active ghrelin concentrations. The cause of impaired nutrient absorption is not yet fully understood but may be related to small intestinal blood flow and/or mucosal factors. The absorption of the different macronutrients may be affected in different ways both by critical illness and by therapies. A better understanding of this may optimize the design of nutrient formulations in the future. New treatment modalities for gastrointestinal dysfunction are being investigated and include small intestinal feeding, nonpharmacological options such as acupuncture, and drugs including novel motilin receptor agonists, and opioid antagonists.. We are gradually developing a better understanding of how the gut works during critical illness, which has implications for optimizing the delivery of nutrition and thereby improving nutritional and clinical outcomes.

Topics: Cholecystokinin; Critical Illness; Enteral Nutrition; Evidence-Based Medicine; Gastric Emptying; Gastrointestinal Agents; Gastrointestinal Diseases; Ghrelin; Humans; Intestine, Small; Motilin; Naltrexone; Quaternary Ammonium Compounds; Randomized Controlled Trials as Topic

Opioid-induced constipation (OIC) may occur in up to 81% of critically ill patients and can lead to many complications. Opioid antagonists are a reasonable approach and may be used for managing OIC.. The purpose of this study was to assess the efficacy of enteral naloxone (NLX) versus subcutaneous methylnaltrexone (MNTX) for the management of OIC in critically ill patients.. A retrospective analysis was conducted on adult patients who received NLX or MNTX and a continuous opioid infusion for at least 48 hours. The primary end point was time to resolution of constipation, defined as hours to first bowel movement (BM) after the first dose of an opioid antagonist. Reversal of analgesia was assessed by comparing the total number of morphine milligram equivalents (MME) 24 hours preopioid and postopioid antagonist administration. Univariate and multivariate analyses were conducted to assess treatment response within 48 hours.. The time to first BM was shorter with enteral NLX. Both NLX and MNTX appear to be effective for the management of OIC without causing reversal of analgesia. Future controlled, prospective trials comparing these agents are warranted.

Topics: Adult; Analgesics, Opioid; Constipation; Critical Illness; Humans; Naloxone; Naltrexone; Narcotic Antagonists; Opioid-Induced Constipation; Pain; Prospective Studies; Quaternary Ammonium Compounds; Retrospective Studies

Opioid-induced constipation (OIC) is common in critically ill patients; it leads to complications that can increase hospital stay and, rarely, bowel perforation. Opioid antagonists are considered a logical approach to treat OIC; however, the agent of choice has yet to be determined.. To assess the effectiveness and safety of enteral naloxone (NTX) versus subcutaneous methylnaltrexone (MNTX) for the treatment of OIC in the medical intensive care unit.. This retrospective review evaluated patients who received fentanyl continuous infusions for at least 72 hours and were initiated on NTX or MNTX. Active colitis, mechanical gastrointestinal obstruction, and inability to receive NTX orally were exclusion criteria. The primary outcome was time to first bowel movement (BM). Secondary outcomes included total number of BMs within 48 hours, opioid requirements after NTX or MNTX, and change in any of the following after the opioid antagonist: heart rates, mean arterial pressures, and level of sedation. A post hoc subgroup analysis of patients on vasopressors was conducted.. Baseline characteristics were similar between patients receiving NTX (n = 52) and MNTX (n = 48), except the MNTX group required a higher median norepinephrine dose (0.22 vs 0.1 µg/kg/min, P = 0.001). The median times to first BM for NTX and MNTX were 30 and 24 hours ( P = 0.165). There was no difference in the primary outcomes for patients on vasopressors. Both groups did not require additional fentanyl equivalents, as evidenced by stable vitals and opioid requirements during treatment.. Both agents appear to be effective and safe for the treatment of OIC; however, future controlled prospective trials are warranted.

Topics: Adult; Analgesics, Opioid; Constipation; Critical Illness; Electronic Health Records; Female; Fentanyl; Heart Rate; Humans; Intensive Care Units; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Prospective Studies; Quaternary Ammonium Compounds; Retrospective Studies

Topics: Abdominal Pain; Analgesics, Opioid; Child; Constipation; Critical Illness; Defecation; Humans; Infant; Laxatives; Male; Morphine; Naltrexone; Narcotic Antagonists; Quaternary Ammonium Compounds; Treatment Outcome

Peripheral-acting mu opiate receptor antagonists have been extensively studied for the treatment of opiate-induced constipation in advanced illness for the prophylaxis of postoperative ileus. We document the first intensive care patient to receive methylnaltrexone in an attempt to facilitate enteral nutrition. Gastric residuals markedly decreased and enteral feeding increased after administration of i.v. methylnaltrexone. The patient's ileus resolved coincident with the first injection.

Topics: Adult; Analgesics, Opioid; Burns; Critical Illness; Enteral Nutrition; Gastric Emptying; Humans; Male; Naltrexone; Narcotic Antagonists; Quaternary Ammonium Compounds