Prolonged tachycardia following analytically confirmed cyclizine ingestion

To the Editor:

Cyclizine is an antihistamine used as an antiemetic, and to treat vertigo, motion sickness and labyrinthine disorders. Overdose has been reported only rarely. Over the last 45 years, there have been seven reports of cyclizine poisoning not involving co-ingestion with dipipanone.^1–7 Two reported the clinical course of 44 patients who ingested an overdose of cyclizine either accidentally or intentionally^1,2; two papers reported 125 individuals who were abusing oral cyclizine (and other agents)^3,4; and three publications reported three fatalities involving cyclizine predominantly without giving clinical details.^5–7 None of the 169 patients who survived had analytical confirmation of the diagnosis.

We report a patient with analytically confirmed cyclizine poisoning who developed a persistent sinus tachycardia and three episodes of transient supraventricular arrhythmias in the absence of other anticipated muscarinic features of toxicity except mydriasis.

A 32-year-old pharmacology graduate presented to hospital after ingesting 500-mg cyclizine, together with 1200-mg ibuprofen and unknown quantities of 30-mg lansoprazole tablets. The patient had a medical history of irritable bowel syndrome, polycystic ovarian syndrome, mood-related cognitive impairment and transverse myelitis. On admission, she was tachycardiac with a pulse rate of 160 bpm, a blood pressure of 155/109 mm Hg, a respiratory rate of 12 per min, oxygen saturation of 98% on air, a temperature of 37°C and mydriasis. Her mental state was normal and remained so throughout her admission. Following presentation, her blood pressure fell to normal values within 2 h though her pulse remained elevated (> 100 bpm). Twenty-four hours post ingestion, her heart rate was 110 bpm; at 40 h post ingestion, it was 88 bpm, and at 46 h was 101 bpm. The patient suffered three episodes of fast heart rate lasting less than a minute at 47 h (blood pressure transiently, 170/85 mm Hg), 49 h and 52 h (blood pressure, 130/75 mmHg) post ingestion, during which she complained of palpitations and chest tightness. Taking account of the rapid onset of the arrhythmias, their spontaneous termination, and of the ECG traces on the monitor, the tachycardias were considered to be supraventricular in origin. The patient denied having previous episodes of palpitations or chest tightness. Seventy-two hours post ingestion when her pulse was 103 bpm, the patient decided to discharge herself against medical advice. Her detailed haematological and biochemical profiles, including thyroid function tests, were normal. The cyclizine concentration (measured using HPLC with diode array detection) some 8 h after ingestion was 590 μg/L, at 11 h was 550 μg/L, at 53 h was 180 μg/L, and at 66 h post ingestion was 200 μg/L.

Typically, sinus tachycardia, hypertension, mydriasis, excitement, agitation, disorientation, tremor, incoordination, slurred speech, ataxia, athetoid movements, hyperkinetic extrapyramidal features, convulsions, confusion and hallucinations occur in cyclizine poisoning.^1–4 Rarely, respiratory failure has been observed.² Although sinus tachycardia is commonly observed, there are no reports of this persisting for several days in the absence of other features of poisoning.^1–4 In a review of 42 teenagers admitted to hospital after taking cyclizine (for reasons of abuse), the mean heart rate was 117 bpm on presentation; 52% had a heart rate greater than 115 bpm. Fifty-five percentage of these patients were discharged after a mean observation time of 3.2 h.⁴ In another report of three teenage boys who each ingested 750 mg cyclizine to get “high”, a sinus tachycardia (120–140 bpm) was present about 4 h post ingestion; the heart rate returned to normal some 6 h after ingestion.³

In our patient, the cyclizine concentration some 8 h after ingestion was 590 μg/L, which is approximately 9 times higher than the median (IQR) steady-state cyclizine concentration of 65 μg/L (49–93 μg/L) found in 12 palliative care patients prescribed with oral cyclizine 75–150 mg/24 h⁸ and that found 2 h after a single dose of cyclizine 50 mg (69 μg/L).⁹ The episodes of self-terminating tachyarrhythmia occurred between 47 and 52 h after cyclizine ingestion (plasma cyclizine concentration at 53 h was 180 μg/L). The cyclizine concentration was still higher than therapeutic concentrations 66 h post ingestion. The peak cyclizine concentration in our patient was very substantially less than the concentrations found at post-mortem (80,000 μg/L⁵ and 15,000 μg/L⁶) in two patients who ingested cyclizine predominantly.

We report the first patient with analytically confirmed cyclizine poisoning whose clinical course was characterized by mydriasis, prolonged sinus tachycardia and episodes of transient supraventricular arrhythmias in the absence of other anticipated muscarinic features.