Should we stop prescribing metoclopramide as a prokinetic drug in critically ill patients?

Abstract

Regulatory agencies in North America and Europe recently re-evaluated the safety of metoclopramide. This re-evaluation resulted in recommendations and restrictions in order to minimise the risk of neurological and other adverse reactions associated with the use of metoclopramide. In the ICU, off-label prescription of metoclopramide is common. We have reviewed the evidence for safety, effectiveness and dosing of metoclopramide in critically ill patients. Furthermore, tachyphylaxis is addressed and alternatives are summarised. Finally, recommendations are presented not to abandon use of metoclopramide in ICU patients, because metoclopramide is considered effective in enhancing gastric emptying and facilitating early enteral nutrition.

Barriers and Solutions to Delivery of Intensive Care Unit Nutrition Therapy

“…Furthermore, prokinetic agents, such as metoclopramide or erythromycin, may also be considered when clinically appropriate to help manage elevated GRV, although these medications are not approved by the U.S. Food and Drug Administration for management of EN intolerance and may be associated with serious side effects . In 2014, a European regulatory agency recommended limiting the duration of prokinetic use to no more than 5 days, lowering the maximum daily dose, and avoiding their use in patients with chronic conditions such as gastroparesis to minimize the risk for neurologic and cardiac adverse reactions . Alternative strategies to promote gastric emptying include achieving adequate blood glucose control to prevent gastroparesis, promoting regular bowel movements, and minimizing the use of opioids.…”

Metoclopramide-induced Serotonin Syndrome

“…Metoclopramide has multiple mechanisms of action such as antagonism/inhibition of pre-and post-synaptic dopamine-2 (D2) receptors in the gut wall, stimulation of presynaptic 5-HT4 receptors and releasing acetylcholine from cholinergic neurons, inhibition of D2 and 5-HT3 receptors in the chemoreceptor trigger zone [8]. Metoclopramide contributes to serotonin syndrome by impairing its reuptake from the synaptic cleft into the presynaptic neuron [9]. Metoclopramide is metabolized through the liver and excreted in urine.…”

High exposure compared with standard exposure to metoclopramide associated with a higher risk of parkinsonism: a nationwide population‐based cohort study

“…In 2009, the Food and Drug Administration issued safety alerts concerning the hazards associated with high‐dose and/or long‐duration use of metoclopramide . Accordingly, to reduce the potential risk of neurological side effects, such as parkinsonism, in 2013 the European Medicines Agency (EMA) enacted restrictions on using metoclopramide that limited the maximum dose to 30 mg per day and the duration to 5 days . Based on the 2013 report of a postmarket surveillance system in Taiwan, metoclopramide has been listed among the top five causes of adverse drug reactions, including parkinsonism .…”

“…In 2009, the Food and Drug Administration issued safety alerts concerning the hazards associated with high-dose and/or long-duration use of metoclopramide [13,14].…”