Can metoclopramide cause bradycardia?/nA 33-year-old man, unconscious due to massive cerebral infar

Fråga: Can metoclopramide cause bradycardia?

A 33-year-old man, unconscious due to massive cerebral infarction, was treated with metoclopramide, both intravenously and by suppositories, to prevent aspiration. Initially, he had a heart rate of about 60, which gradually decreased to around 40 after two days treatment.

Sammanfattning: Bradycardia and asystole have rarely been described in direct connection to intravenously administered metoclopramide, especially in severely ill patients. In the present case, the connection seems less clear, but metoclopramide cannot be excluded as a contributing factor to bradycardia.

Svar: Metoclopramide is a procaineamide derivative, used as a prokinetic and anti-emetic agent. It acts both centrally, as a dopamine-2 receptor antagonist, and peripherally, posssibly by an action on 5-HT receptors on presynaptic muscarinic neurons in the gut (1).

Metoclopramide is generally considered to have few side-effects, with extrapyrimidal symptoms being the main concern. As for cardiovascular side-effects, hypertension has rarely been reported (1, 2). Patients with pheocromocytoma have had hypertensive crises following metoclopramide administration, and one such case has previously been described in Drugline (3). Other cardiovascular effects are not mentioned in pharmacological handbooks.

However, a literature search has revealed a total of 10 case-reports, describing bradycardia and/or asystole, following intravenous by administrated metoclopramide. The majority of these reports refer to severly ill patients, with malignancies or acute brain damage, who have reacted with bradycardia, and in four cases cardiac arrest, promptly after metoclopramide injection. Several of the patients also had similar reactions to the drug at least twice (4-12). The most recently published report describes a 41-year-old man with a subarachnoidal bleeding, who, upon recovery, was prescribed metoclopramide 10 mg intravenously, three times daily. During the following 48 hours he had five episodes of asystole after metclopramide injections. The medication was stopped, and no further episodes occurred (12).

In the case-reports cited above, it is speculated on possible direct effects of metoclopramide on the heart (Class I antiarrhythmic properties), facilitated acetylcholin release, mimicking enhanced vagal stimulation, or drug interactions, e.g with dopamine or ondansetron, as contributing factors (12).

In the present case, there seems to be no direct connection in time between bradycardia and metoclopramide administration and dosage is somewhat unclear. Arrhythmia is also known to occur during the acute phase after cerebral bleeding (12). However, it cannot be excluded that metoclopramide have contributed to the bradycarida, and it is suggested that the metoclopramide administration is stopped, at least temporarely. 1 Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999

2 Drugline no 04277 (year 1984)
3 Swedis (The Swedish Drug Information System) (cited 2003-04-17)
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6 Hughes RL. Hypotension and dysrhythmia following intravenous metoclopramide. Anaesthesia 1984;39:720.
7 Withington DE. Dysrhythmias following intravenous metoclopramide. Intensive Care Med 1986;12:378-9.
8 Midttun M, Öberg B. Total heart block after intravenous metoclopramide. Lancet 1994;343:182-3.

9 Malkoff MD, Ponzillo JJ, Myles GL, Gomez CR, Cruz-Flores S. Sinus arrest after administration of intravenous metoclopramide. AnnPharmacother 1995;29:381-3. 10 Baguley WA, Hay WT, Mackie KP, Cheney FW, Cullen BF. Cardiac dysrhythmias associated with the intravenous administration of ondansetron and metoclopramide. Anesth Analg 1997;84:1380-1. 11 Campo MM del, Martinez PG et al. Paro sinusal tras la administracion de metoclopramida intravenosa. Med Clin (Barc) 2001;117:238-9. 12 Bentsen G, Stubhaug A. Cardiac arrest after intravenous metoclopramide - a case of five repeated injections of metoclopramide causing five episodes of cardiac arrest. Acta Anaesthesiol Scand 2002;46:908-10.