A multicenter, randomized, double-blind study of ulimorelin and metoclopramide in the treatment of critically ill patients with enteral feeding intolerance: PROMOTE trial.

PURPOSE: Enteral feeding intolerance (EFI) is a frequent problem in the intensive care unit (ICU), but current prokinetic agents have uncertain efficacy and safety profiles. The current study compared the efficacy and safety of ulimorelin, a ghrelin agonist, with metoclopramide in the treatment of EFI. METHODS: One hundred twenty ICU patients were randomized 1:1 to ulimorelin or metoclopramide for 5 days. EFI was diagnosed by a gastric residual volume (GRV) ≥ 500 ml. A volume-based feeding protocol was employed, and enteral formulas were standardized. The primary end point was the percentage daily protein prescription (%DPP) received by patients over 5 days of treatment. Secondary end points included feeding success, defined as 80% DPP; gastric emptying, assessed by paracetamol absorption; incidences of recurrent intolerance (GRV ≥ 500 ml); vomiting or regurgitation; aspiration, defined by positive tracheal aspirates for pepsin; and pulmonary infection. RESULTS: One hundred twenty patients were randomized and received the study drug (ulimorelin 62, metoclopramide 58). Mean APACHE II and SOFA scores were 21.6 and 8.6, and 63.3% of patients had medical reasons for ICU admission. Ulimorelin and metoclopramide resulted in comparable %DPPs over 5 days of treatment (median [Q1, Q3]: 82.9% [38.4%, 100.2%] and 82.3% [65.6%, 100.2%], respectively, p = 0.49). Five-day rates of feeding success were 67.7% and 70.6% when terminations unrelated to feeding were excluded, and there were no differences in any secondary outcomes or adverse events between the two groups. CONCLUSIONS: Both prokinetic agents achieved similar rates of feeding success, and no safety differences between the two treatment groups were observed.

Prophylactic antiemetic treatment with ondansetron in children undergoing tonsillectomy.

BACKGROUND: Children undergoing tonsillectomy are at high risk for postoperative vomiting. This study was undertaken to compare ondansetron with metoclopramide and droperidol for the prevention of postoperative vomiting after tonsillectomy. METHODS: Two hundred fifty-six pediatric patients, ages 2-12 years, scheduled for outpatient tonsillectomy were enrolled in a prospectively randomized, double-blinded investigation and assigned to one of four treatment regimens: placebo (saline), ondansetron 0.15 mg.kg-1, metoclopramide 0.5 mg.kg-1, or droperidol 0.075 mg.kg-1. Study drugs were administered intravenously after inhalation induction of anesthesia with halothane, nitrous oxide, and oxygen. No premedication or neuromuscular blocking agents were used. Tracheal extubation was performed while patients were still deeply anesthetized. Acetaminophen and meperidine were given for postoperative pain. Patients were observed in the recovery room for a minimum of 4 h before discharge. Parents were contacted by telephone 24 h later for follow-up. RESULTS: Ondansetron reduced the incidence of postoperative emesis from 62% to 27% (relative risk 0.45, 95% confidence interval 0.29 to 0.70, P < 0.001). Metoclopramide and droperidol had no significant effect on postoperative vomiting. CONCLUSIONS: The intravenous administration of ondansetron 0.15 mg.kg-1 is highly effective in reducing postoperative emesis in children undergoing tonsillectomy. Metoclopramide and droperidol at the doses tested are ineffective in this population.

Comparison of metoclopramide and erythromycin in the treatment of diabetic gastroparesis.

OBJECTIVE: To compare the effects of erythromycin and metoclopramide on gastric emptying and symptoms of gastroparesis in diabetic patients with delayed gastric emptying. RESEARCH DESIGN AND METHODS: The study group consisted of 13 patients with symptoms of severe gastroparesis and delayed gastric emptying. Gastric emptying was evaluated using a radionuclide method, and gastrointestinal symptoms were scored. The patients were given either erythromycin (250 mg 3 times/day) or metoclopramide (10 mg 3 times/day) in random order for 3 wk, and after a washout period of 3 wk they were crossed-over to the other medication for another 3 wk. Parameters of gastric emptying were assessed before treatment and after both erythromycin and metoclopramide administration. RESULTS: The half-time of gastric emptying in diabetic subjects was 110 (77-120) min before treatment. At 60 and 90 min, the median value of residual isotope activity was 66.5 (55-83.5) and 55% (43-74.3), respectively. The half-time decreased to 55 min (28.6-115) after 3 wk of treatment with erythromycin and percentages of meal retention in the stomach at 60 and 90 min were 49.9 (38.4-70) and 40.5% (29.7-60), respectively. After taking metoclopramide, the median value of half-time was 67 min (15-115) and percentages of meal retention at 60 and 90 min were 51 (34.5-93.9) and 42% (24-71.2), respectively. When compared with baseline values a significant difference in gastric emptying parameters was found after both erythromycin and metoclopramide. A significant improvement of the total score for gastrointestinal symptoms was observed with both drugs, but this improvement was more pronounced with erythromycin. CONCLUSIONS: Erythromycin, a macrolide antibiotic and a motilin receptor agonist, appears to stimulate intestinal motility and seems to be an alternative agent for the treatment of gastroparesis caused by diabetic autonomic neuropathy.