Efficacy and Safety of Enteral Erythromycin Estolate in Combination With Intravenous Metoclopramide vs Intravenous Metoclopramide Monotherapy in Mechanically Ventilated Patients With Enteral Feeding Intolerance: A Randomized, Double‐Blind, Controlled Pilot Study

Abstract

Background In this pilot study, we aimed to determine the efficacy and safety of enteral erythromycin estolate in combination with intravenous metoclopramide compared to intravenous metoclopramide monotherapy in mechanically ventilated patients with enteral feeding intolerance. Methods This randomized, double‐blind, controlled pilot study included 35 mechanically ventilated patients with feeding intolerance who were randomly assigned to receive 10‐mg metoclopramide intravenously every 6–8 hours in combination with 250‐mg enteral erythromycin estolate (study group) or placebo every 6 hours for 7 days. The primary outcome was an administered‐to‐target energy ratio of ≥80% at 48 hours, indicating a successful feeding. Secondary, prespecified outcomes were daily average gastric residual volume (GRV), total energy intake, administered‐to‐target energy ratio, hospital length of stay, in‐hospital mortality, and 28‐day mortality. Results The rate of successful feeding was not significantly different between the study and placebo groups (47.1% and 61.1%, respectively; P = .51). The average daily GRV was significantly lower in the study group than in the placebo group (β = 91.58 [95% Wald CI, −164.35 to −18.8]), determined by generalized estimating equation. Other secondary outcomes were comparable, and the incidence of adverse events was not significantly different between the 2 groups. One common complication was cardiac arrhythmia, which was mostly self‐terminated. Conclusion Although the combination therapy of enteral erythromycin estolate and intravenous metoclopramide reduced GRV, the successful feeding rate and other patient‐specific outcomes did not improve in mechanically ventilated patients with feeding intolerance.

The efficacy and safety of itopride in feeding intolerance of critically ill patients receiving enteral nutrition: a randomized, double-blind study

“…In our study, nutrition risk and illness severity were high similar to results of a recent randomized controlled trial [25] while they were evidently higher than those in previous study [41].…”

“…Likewise, to the results of our study, a recent RCT reported that intravenous metoclopramide caused significantly higher accumulative GRV than another prokinetic (erythromycin estolate) combined with metoclopramide when used for EFI in critically ill patients [25].…”

“…[3] however, a GRV of 250 mL is defined as the threshold for the early detection of feeding intolerance and prompt initiation of therapy. Similarly, to our study, several other studies used ≥ 250 mL as an indication of high GRV [6,[24][25][26].…”

Association between Domperidone Administered via Feeding Tube and Feeding Success in Critically Ill Patients with Enteral Feeding Intolerance

“…Patients with EFI received either domperidone (10 mg administered via tube feeding every 8 h) or metoclopramide (10 mg administered as a 50-mL IV infusion over 30 min every 8 h) [ 11 ]. The dose of IV metoclopramide was 50% of normal dose in patients with creatinine clearance ≤40 mL/min and 25% in patients with clearance ≤10 mL/min or undergoing dialysis or continuous renal replacement techniques [ 30 ].…”

Use of prokinetic agents in hospitalised adult patients: A scoping review

“…The most studied prokinetic agent in both ICU and non-ICU settings was metoclopramide (49%) followed by erythromycin (31%). 18,20,21,24,25,28,33,34,36,[40][41][42]45,46,49,52,56,59,60,67,69,70,[72][73][74]84,93,96,[100][101][102]105,106,109,113,114 Other agents included serotonin receptor agonists (cisapride, mosapride, prucalopride, TAK-954) (18%) and dopamine antagonists (domperidone and itopride) (10%). Five studies investigated alternative interventions as prokinetic agents, for example, three studies investigated acupuncture.…”