Prokinetic Agents for Gastric Intolerance

First-Line Agents

The American College of Gastroenterology recommends eritromicina intravenosa (100-250 mg three times a day) as the most effective first-line prokinetic agent for gastric intolerance in critically ill patients, with superior evidence compared to other agents 1, 2
The recommended dose is 100-250 mg three times a day by intravenous route, with a significant efficacy (RR 0.58, CI 0.34-0.98, p=0.04) in improving enteral feeding tolerance 1, 2
However, its effectiveness decreases to one-third after 72 hours due to tachyphylaxis, so it should be discontinued after 2-4 days 1, 2
It does not affect the incidence of pneumonia according to available studies 1

Metoclopramida may be used as an alternative prokinetic therapy, although with lower evidence of efficacy 1
The recommended dose is 10 mg two to three times a day by intravenous route 1, 3
Adverse effects are reported in 11-34% of patients, including somnolence, restlessness, and extrapyramidal reactions 4, 5
The American Academy of Pediatrics establishes that there is no sufficient evidence to support the routine use of metoclopramida in infants or children with gastroesophageal reflux disease (GERD) 4, 5

Prucaloprida is a high-affinity selective 5-HT4 receptor agonist without the cardiac risks of cisaprida or tegaserod 3
It does not affect the QT interval, unlike older agents 3
It is primarily indicated for constipation in severe intestinal dysmotility 3
It represents a safer alternative for long-term therapy compared to dopaminergic agents 3, 6

Cisaprida was historically the most effective prokinetic agent for GERD, but it was withdrawn from the market due to the risk of fatal cardiac arrhythmias by QT interval prolongation 3, 4, 5
Domperidona is a selective peripheral D2 dopaminergic receptor antagonist, but it has a black box warning for potentially irreversible tardive dyskinesia, especially with prolonged use 3, 7
It requires electrocardiographic monitoring due to QTc prolongation, especially with long-term use 3, 7

Metoclopramide is the sole United States FDA‑approved prokinetic for gastroparesis; its use must be limited to ≤ 12 weeks because of a black‑box warning for potentially irreversible tardive dyskinesia. 8

In cancer patients with early satiety after constipation has been addressed, metoclopramide can improve satiety, but central‑nervous‑system adverse effects (somnolence, depression, hallucinations, extrapyramidal symptoms) limit its routine use. 9
Domperidone is used internationally for early satiety and other upper‑GI motility disorders; it does not cross the blood‑brain barrier, resulting in fewer CNS side effects compared with metoclopramide. 9
Domperidone carries a black‑box warning for QTc prolongation and torsade de pointes; ECG monitoring is required, especially with intravenous bolus dosing. 9
For feeding intolerance in sepsis or septic shock, metoclopramide is a weakly recommended second‑line agent when enteral nutrition is interrupted and other prokinetics are unsuitable. 10

Velusetrag, a selective 5‑HT4 agonist, accelerated gastric emptying in a phase 2 randomized controlled trial of patients with gastroparesis, indicating moderate‑level efficacy evidence. 8
Velusetrag is not yet FDA‑approved for any indication. 8