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Opioid analgesia impairs gastrointestinal motility. Enteral administration of naloxone theoretically allows selective blocking of intestinal opioid receptors caused by extensive presystemic metabolism. Therefore, we studied the effect of enteral naloxone on the amount of gastric tube reflux, the frequency of pneumonia, and the time until first defecation in mechanically ventilated patients with fentanyl analgesia.Prospective, randomized, double-blinded study.University hospital intensive care unit.Eighty-four mechanically ventilated, fentanyl-treated patients without gastrointestinal surgery or diseases.Patients were assigned to receive 8 mg naloxone or placebo four times daily via a gastric tube during fentanyl administration.Thirty-eight patients received naloxone and 43 placebo; three patients were excluded because of protocol violation. Median gastric tube reflux volume (54 vs. 129 mL, p = .03) and frequency of pneumonia (34% vs. 56%, p = .04) were significantly lower in the naloxone group. In both groups, time until first defecation, ventilation time, and length of intensive care unit stay did not differ. There was no difference in fentanyl requirements between the naloxone and the placebo group (7 vs. 6.5 μg/kg/hr, p = .15).Our results provide evidence that the administration of enteral opioid antagonists in ventilated patients with opioid analgesia might be a simple—and possibly preventive—treatment of increased gastric tube reflux and reduces frequency of pneumonia.