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Cardiac Dysrhythmias Associated with the Intravenous Administration of Ondansetron and Metoclopramide

1997; Lippincott Williams & Wilkins; Volume: 84; Issue: 6 Linguagem: Inglês

10.1097/00000539-199706000-00038

1526-7598

William A Baguley, William T. Hay, Ken Mackie, Frederick W. Cheney, Bruce F. Cullen,

Ion channel regulation and function

Ondansetron and metoclopramide are often administered as prophylaxis, either when severe postoperative nausea and vomiting would be detrimental to the patient or when the patient is at high risk of nausea and vomiting. We report two cases of cardiac dysrhythmias associated with the intravenous (IV) administration of ondansetron and metoclopramide. Case 1 A 37-yr-old woman who had injured her leg several months earlier presented for advancement of a thigh flap. Her only medication was occasional oxycodone. She occasionally smoked and drank alcohol. She was ambulatory and denied significant pulmonary or cardiac disease. She received several general anesthetics after her injury. The only complication was severe postoperative nausea and vomiting treated with ondansetron and metoclopramide. Her physical examination was unremarkable, and her only laboratory abnormality was a hematocrit level of 24%. Because of the patient's history of postoperative nausea and vomiting, she received ondansetron (4.0 mg) and metoclopramide (10.0 mg) IV in the preoperative holding area. En route to the operating room, she complained of feeling light-headed and nauseated and of having a headache. She vomited once. After she was assisted onto the operating room table, an electrocardiogram (ECG) monitor showed bigeminy, which converted spontaneously to a sinus rhythm within 10 s. Arterial blood pressure (BP) was normal. Subsequently, the ECG showed marked ST segment depression. Coincidentally, the patient complained of chest heaviness and a tightness in her throat. Oxygen was administered by mask, and fentanyl 25 micro g was given IV. A 12-lead ECG revealed T-wave inversion with ST segment depression on the inferior, anterior, and lateral leads. BP remained normal. The procedure was canceled, and the patient's symptoms and ECG abnormalities resolved within 5 min without further intervention. She was admitted to a cardiac unit and subsequently ruled out for a myocardial infarction. A subsequent dipyridamole thallium study was normal. Case 2 A 34-yr-old man had had reduction of bilateral calcaneal fractures 6 mo previously and had hardware removed from the left calcaneus 4 mo earlier. He now presented for hardware removal from his right calcaneus. The patient was healthy but reported a 10- to 20-s episode of palpitations 3 mo earlier. He had been taking naproxen until 2 wk prior to the scheduled operation. Two previous general anesthetics were complicated only by severe postoperative nausea and vomiting. The physical examination was unremarkable, and the preoperative hematocrit level was 42%. Anesthesia was induced with propofol 200 mg, lidocaine 50 mg, fentanyl 150 micro g, and succinylcholine 120 mg IV. The trachea was intubated, and he was placed in a left lateral position. Cefazolin 1 g was administered just prior to incision. Anesthesia was maintained with desflurane (approximately 4% end-tidal), N2 O 40% and O2 70%. Oxygen saturation was greater than 96% for the entire procedure, and ventilation was controlled to keep ETCO2 at 35-40 mm Hg. Ten minutes after incision, metoclopramide 10 mg was administered IV. Approximately 20 min later, ondansetron 2 mg was given IV. At that time, the BP was 120/75 mm Hg, and heart rate was 65 bpm. Immediately after the administration of ondansetron, the ECG showed sinus bradycardia with a heart rate approximately 50 bpm, which then progressed to a junctional rhythm of less than 30 bpm with ventricular escape beats. The BP was 100/45 mm Hg. Atropine 1.2 mg was given in divided doses, and the fraction of inspired oxygen (FIO (2)) increased to 1.0. Short runs of ventricular tachycardia (3-6 beats) were superimposed on the junctional rhythm and treated with lidocaine 80 mg. Subsequently, there was a brief episode of accelerated junctional rhythm (100 bpm) and then a sustained supraventricular tachycardia (SVT) (165 bpm). The total time from initial sinus bradycardia to SVT was approximately 3 min. The SVT lasted approximately 8 min and was associated with hypertension (BP 220/130 mm Hg), which was treated with increasing concentrations of desflurane. No change in rhythm followed carotid sinus massage, application of positive end-expiratory pressure, or administration of adenosine (6 and 12 mg). The SVT stopped after administration of esmolol 45 mg with conversion to sinus tachycardia (P = 102 bpm). Arterial blood drawn at the onset of SVT (FIO2 = 0.4) yielded PaO2 87 mm Hg, PaCO2 36 mm Hg, pHa 7.44, and normal serum sodium, potassium, calcium, and glucose. The patient experienced no further dysrhythmias. A postoperative chest radiograph showed mild unilateral subsegmental atelectasis. A lower extremity duplex scan showed no evidence of deep vein thrombosis. The patient was observed overnight in the hospital and required no follow-up cardiac evaluation. Discussion These two patients had dysrhythmias that were temporally associated with the IV administration of ondansetron and metoclopramide. One patient had bigeminy with ST segment depression, the other patient had sinus bradycardia followed by a slow junctional rhythm with ventricular escape beats. A review of the literature produced only one letter that postulated an association between ondansetron and cardiovascular complications. Ballard et al. [1] describe seven cases of cardiac symptoms during chemotherapy and ondansetron administration. All of the patients were elderly, some had cardiac disease, and the association of dysrhythmias with the administration of ondansetron was not well established. Ondansetron is a serotonin (5-hydroxytryptamine3; 5-HT3) receptor antagonist. The family of serotonin (5-HT) receptors is large and diverse. However, in the clinical setting, ondansetron is a specific antagonist for 5-HT3 receptors [2-4]. 5-HT3 receptors are ligand-gated ion channels that mediate fast, depolarizing responses. They are widely expressed in the autonomic nervous system, located on presynaptic terminals, and their activation enhances neurotransmission [3]. Pertinent to the cases presented above, 5-HT3 receptors influence various aspects of cardiac function, including inotropy, chronotropy, and coronary arterial tone [5]. These effects are mediated by both the parasympathetic and the sympathetic nervous systems. Thus, in any given patient, blockade of 5-HT3 receptors by ondansetron will produce effects dependent on the preexisting serotonergic activity in both arms of the autonomic nervous system. Clinical trials of ondansetron demonstrated no significant effects on BP or heart rate [6]. The incidence of myocardial infarction in patients who receive ondansetron with cancer chemotherapy is no greater than the incidence in patients who receive other antiemetics or placebo, and overdoses as large as 145 mg have not produced ECG changes [7]. A randomized, double blind study of the effects of ondansetron in women prior to surgery was unable to demonstrate any significant effect on BP or heart rate over a seven-minute observation period [8]. A possible confounding factor in these two cases is that both patients received the nonspecific dopamine receptor antagonist, metoclopramide. Its administration has, on rare occasion, been associated with dysrhythmias [9]. Metoclopramide enhances catecholamine release in patients with pheochromocytomas [10] and with "essential" hypertension [11], perhaps by blocking presynaptic autoreceptors. Its less well characterized actions include enhancement of muscarinic cholinergic neurotransmission [12] and blockade of 5-HT3 receptors [13]. Thus, it is possible that the concurrent (Case 1) or prior (Case 2) administration of metoclopramide contributed to the dysrhythmias seen in our patients. While the cause of the dysrhythmias in these patients is not clear, it seems prudent to monitor the ECG when ondansetron and metoclopramide are administered rapidly IV within a few minutes of one another.