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Canadian Journal of Anesthesia 50:333-335 (2003)
© Canadian Anesthesiologists' Society, 2003
General Anesthesia

Asystolic cardiac arrest: an unusual reaction following iv metoclopramide

[L’asystolie : une réaction inhabituelle à l’administration iv de métoclopramide]

Yvan Grenier, MD and Pierre Drolet, MD

From the Department of Anesthesiology, University of Montreal, Montreal, Quebec, Canada.

Address correspondence to: Dr. Yvan Grenier, Département d’anesthésiologie, Hôpital Maisonneuve-Rosemont, 5415, boul. de l’Assomption, Montréal, Québec H1T 2M4, Canada. Phone: 514-252-3426; Fax: 514-252-3542; E-mail: y_grenier{at}videotron.ca


   Abstract
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 Abstract
Introduction
 Case report
 Discussion
 References
 
Purpose: To describe a case of sinus arrest after iv metoclopramide.

Clinical features: A 66-yr-old diabetic female with no cardiovascular disease was anesthetized for a partial mastectomy. While in the postanesthesia care unit, she suffered two episodes of asystole after iv metoclopramide 10 mg. The first episode lasted ten seconds and corrected spontaneously while the second episode, lasting less than one minute required closed chest massage and atropine iv 0.8 mg. The cardiac investigation that followed was inconclusive for ischemia and the patient did not experience any other episodes of dysrhythmia. No formal investigation was done to disclose diabetic autonomic neuropathy. However, based on the results of dipyridamole myocardial single photon emission computed tomography, if diabetic autonomic neuropathy was present, it was very mild.

Conclusion: The patient sustained two episodes of asystole after iv metoclopramide 10 mg in the immediate postoperative period in the absence of any predisposing cardiac history or medication. Diabetes, even without overt autonomic neuropathy, may have been a predisposing factor for sinus arrest after iv metoclopramide.


   Introduction
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 Abstract
 Introduction
Case report
 Discussion
 References
 
METOCLOPRAMIDE is widely used to prevent or treat postoperative nausea and vomiting. Although it is generally considered safe, problems have been reported following its administration to patients with cardiac abnormalities.1,2 We report a case of repeated episodes of asystole after two iv boluses of metoclopramide to a patient without known cardiac disease.


   Case report
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 Abstract
 Introduction
 Case report
Discussion
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The patient was a 66-yr-old female with no previous history of dysrhythmia, coronary disease, syncope, or postural dizziness. She suffered from type II diabetes that was treated with metformin for the past three years. She had a previous partial mastectomy two years ago without any reported adverse event and was returning for a second partial mastectomy. The electrocardiogram (ECG) done a few minutes before surgery showed a normal sinus rhythm at a rate of 92 beats•min-1, a PR interval of 124 msec and a QT interval of 370 msec. Her preoperative blood pressure was 120/70. Anesthesia was induced with iv fentanyl 250 µg, thiopental 400 mg, and rocuronium 50 mg followed by isoflurane for maintenance. She did not require reversal of neuromuscular blockade at the end of the one hour procedure.

Upon arrival in the postanesthesia care unit (PACU), the patient’s pulse, blood pressure, and oxygen saturation were 41 beats•min-1, 175/80 mmHg, and 97% respectively. Thirty-three minutes later, her pulse rate was 80 beats•min-1 and she received metoclopramide 10 mg iv for treatment of nausea. One minute later, the patient experienced ten seconds of asystole without loss of consciousness. The PACU nurse summoned the attending anesthesiologist, who requested a cardiology consultation, an ECG and a chest roentgenogram. By this time, the patient had reverted to a normal sinus rhythm at 81 beats•min-1 with a PR interval of 156 msec and a QT interval of 370 msec. While the cardiologist was in the PACU, 53 min postoperatively, the patient complained of nausea again and received another dose of metoclopramide 10 mg iv. Eight minutes later, she experienced a second episode of asystole. Closed cardiac massage was initiated and atropine 0.8 mg iv was given. Again the episode lasted less than a minute. A transcutaneous pacemaker was applied and kept on standby. The patient was transferred to the coronary care unit (CCU) for further surveillance. She had no further episodes of bradycardia or asystole while in the CCU.

Subsequent cardiac investigation failed to identify a cause. Repeated cardiac enzyme levels were not elevated. Repeated ECGs were all described as normal, as was an echocardiogram. The exercise stress ECG was suspicious for ischemia, with 0.9 to 1.5 mm ST-depression or downsloping in the inferior leads, when the heart rate and blood pressure were 147 beats•min-1 and 185/70 mmHg respectively. Dipyridamole myocardial single photon emission computed tomography (SPECT), done after hospital discharge, was inconclusive for ischemia with a resting heart rate of 102 beats•min-1 and a peak heart rate of 167 beats•min-1 (peak-basal heart rate ratio 1.64).


   Discussion
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 Abstract
 Introduction
 Case report
 Discussion
References
 
Metoclopramide treats vomiting by blocking dopaminergic receptors in the central nervous system (CNS) and by direct action on the digestive tract, possibly by the peripheral release of acetylcholine.3 Although its molecular structure resembles procainamide, metoclopramide seems devoid of any significant antiarrhythmic or local anesthetic activity.4 Hence, most reported side effects (extrapyramidal symptoms, drowsiness, agitation and anxiety) reflect CNS activity.5–8 Hypotension9 and ventricular bigeminy10 have been reported following prophylactic metoclopramide administration during general anesthesia. Hypotension, associated with metoclopramide, have been described also in healthy, conscious volunteers.11

Cardiac dysrhythmias associated with metoclopramide have been reported in the critical care, perioperative, and emergency room settings (TableGo). Withington reported a case of asystole and bradycardia in a jaundiced postoperative patient receiving dopamine.1 Jaundice was suggested as the predisposing factor. Midttun and Øberg described two cases of complete heart block after iv metoclopramide.2 The first patient had been treated with digoxin for atrial fibrillation and the second patient had been treated for circulatory failure. Other authors have reported supraventricular dysrhythmias following the administration of metoclopramide.12,13 Baguley et al. reported two cases of perioperative dysrhythmias after combined administration of metoclopramide and ondansetron and warned against this combination.14 Malkoff et al. reported a case of sinus arrest after iv metoclopramide in a woman with Guillain-Barré syndrome and severe dysautonomia and suggested that autonomic dysfunction could be a risk factor for metoclopramide-associated dysrhythmias.15


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  		TABLE Previous case reports of metoclopramide and cardiac dysrhythmias
 
Our patient did not have any predisposing cardiac history nor did she receive any cardiac medications prior to her episodes of asystole. She had not received ondansetron. Her only potential predisposing factor was diabetes. Diabetes is associated with autonomic neuropathy and cardiovascular involvement.16 The clinical and laboratory characteristics of diabetic autonomic neuropathy have been reviewed elsewhere.17 A peak-basal heart rate ratio less than 1.2 on dipyridamole myocardial SPECT has been suggested as an indicator of cardiac autonomic dysfunction in diabetes.18 Our patient did not undergo standardized diagnostic tests for diabetic autonomic neuropathy or any formal assessment of her heart rate variability. Her peak-basal heart rate ratio on SPECT was well above the suggested threshold for cardiac autonomic dysfunction. Still, in the absence of other tests, the possibility of autonomic neuropathy cannot be completely excluded.

In summary, we report a case of repeated asystole after iv metoclopramide in the immediate postoperative period. Diabetic autonomic neuropathy could be a contributing factor.

Revision received December 2, 2002. Accepted for publication May 23, 2002.


   References
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
1 Withington DE. Dysrhythmias following intravenous metoclopramide. Intensive Care Med 1986; 12: 378–9.[Medline]

2 Midttun M, Øberg B. Total heart block after intravenous metoclopramide (Letter). Lancet 1994; 343: 182–3.[Medline]

3 Brunton LL. Agents affecting gastrointestinal water flux and motility, digestants and bile acids. In: Goodman LS, Gilman AG, Gilman A (Eds). Pharmacological Basis of Therapeutics, 8th ed. New York: McGraw-Hill Inc; 1990: 926–9.

4 Thorburn CW, Sawton E. The haemodynamic effects of metoclopramide. Postgrad Med J 1973; 49(Suppl. 4): suppl. 4: 22–5.

5 Robinson OPW. Metoclopramide – side effects and safety. Postgrad Med J 1973; 49(Suppl. 4): suppl. 4: 77–80.[Medline]

6 Galland MC, Rodor F, Gratecos LA, Bourdillon N, Gailhaguet AM, Jouglard J. Le métoclopramide. Bilan des effets secondaires et toxiques relevés au Centre de Pharmacovigilance et de Toxicologie Clinique de Marseille. Thérapie 1983; 38: 465–73.[Medline]

7 Allen RW. Metoclopramide – a safe antiemetic? (Letter). S Afr Med J 1990; 77: 219.[Medline]

8 Caldwell C, Rains G, McKiterick K. An unusual reaction to preoperative metoclopramide. Anesthesiology 1987; 67: 854–5.[Medline]

9 Pegg MS. Hypotension following metoclopramide injection (Letter). Anaesthesia 1980; 35: 615.

10 Hughes RL. Hypotension and dysrhythmia following intravenous metoclopramide (Letter). Anaesthesia 1984; 39: 720.[Medline]

11 Park GR. Hypotension following the intravenous injection of metoclopramide (Letter). Anaesthesia 1981; 36: 75–6.[Medline]

12 Shaklai M, Pinkhas J, De Vries A. Metoclopramide and cardiac arrhythmias (Letter). BMJ 1974; 2: 385.

13 Bevacqua BK. Supraventricular tachycardia associated with postpartum metoclopramide administration. Anesthesiology 1988; 68: 124–5.[Medline]

14 Baguley WA, Hay WT, Mackie KP, Cheney FW, Cullen BF. Cardiac dysrhythmias associated with the administration of ondansetron and metoclopramide. Anesth Analg 1997; 84: 1380–1.[Medline]

15 Malkoff MD, Ponzillo JJ, Myles GL, Gomez CR, Cruz-Flores S. Sinus arrest after administration of intravenous metoclopramide. Ann Pharmacother 1995; 29: 381–3.[Abstract]

16 Emanuele NV, Emanuele MA. Diabetic neuropathy: therapies for peripheral and autonomic symptoms. Geriatrics 1997; 52: 40–9.[Medline]

17 Ewing DJ. Diabetic autonomic neuropathy and the heart. Diabetes Res Clin Pract 1996; 30(suppl.): S31–6.

18 Lee KH, Yoon JK, Lee MG, Lee SH, Lee WR, Kim BT. Dipyridamole myocardial SPECT with low heart rate response indicates cardiac autonomic dysfunction in patients with diabetes. J Nucl Cardiol 2001; 8: 129–35.[Medline]




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