Complete atrioventricular block due to ingestion of Visine eye drops

Abstract

Visine eye drops are a commonly used topical drug for irritation of the eye. The active component in Visine eye drops is tetrahydrozoline. Tetrahydrozoline is an imidazoline derivative found in several ophthalmic and nasal decongestants. Exposure is common in young children, who unintentionally ingest it, but cases have been rising in the adult population. The main systemic effects are bradycardia and hypotension due to activation of the central alpha-adrenergic receptors. In this case report, a 76-year-old man presents with bradycardia after 24 hours following ingestion of 120 mL of 0.05% tetrahydrozoline (eight bottles of Visine eye drops) in a suicide attempt. His initial ECG demonstrated complete heart block and QT prolongation. Subsequent ECGs showed unremitting first-degree atrioventricular block and QT prolongation. Here, we are presenting the first case of complete heart block following tetrahydrozoline consumption.

Background

Tetrahydrozoline is an imidazoline derivative that is found in many commonly used over-the-counter ophthalmic and nasal decongestants, most notably Visine eye drops. Documented intentional and unintentional ingestion of this substance has led to severe toxic effects.¹ Tetrahydrozoline works primarily as a central alpha-adrenergic agonist.² Side effects of overdose include: lethargy, hypotension, bradycardia and respiratory depression.¹ Tetrahydrozoline toxicity is well established in paediatric case reports due to its increased propensity for unintentional ingestion.³ However, cases of adult tetrahydrozoline toxicity have been rising over the last decade.^{4 5} As a result, the consequences of tetrahydrozoline ingestion in the adult population require more attention. While reports have been published on the cardiovascular effects of tetrahydrozoline,^1–3 there are no prior reports of first-degree and third-degree atrioventricular (AV) block following tetrahydrozoline ingestion.

Case presentation

A 76-year-old man with a medical history significant for bullous emphysema and major depressive disorder presented to the emergency department (ED) approximately 24 hours after ingesting eight bottles of Visine eye drops (120 mL of 0.05% tetrahydrozoline) mixed in wine. At the time, the patient was suicidal and read on the internet that this would be a quick and painless method of committing suicide. He denied taking any other substances nor any of his medications. He quickly fell asleep and woke up the next day confused. The patient felt dizzy and off balance with movement. Fortunately, the patient was no longer suicidal and immediately called emergency medical services to report his suicide attempt and request transportation to the hospital.

On arrival to the ED, the patient was alert and oriented to person, place and time. His heart rate was irregular and bradycardic at 54 beats per minute (bpm). During his X-ray, the patient’s heart rate dropped to 30 bpm, which required immediate intervention with atropine. His heart rate following administration was 70 bpm. He was normotensive with a blood pressure of 115/72 mm Hg. His pupils were equal at 3 mm and reactive bilaterally. The rest of his physical examination was unremarkable.

Basic metabolic panel showed hyponatraemia (131 mmol/L) with a high anion gap metabolic acidosis (15 mmol/L) and a serum bicarbonate of 19 mmol/L. His troponin was found to be elevated at 30 ng/L. He was also hyperglycaemic with a blood glucose of 394 mg/dL. Complete blood count showed a mild leucocytosis of 12.1. The liver function tests were within normal limits.

Prior to admission, previous ECGs were unremarkable. In the ED, a 12-lead ECG (figure 1) was performed and revealed third-degree/complete AV block at a rate of 37 bpm and a prolonged corrected QT interval (QTc=452 ms). Following these findings, the patient was admitted to the medical intensive care unit (MICU).

Figure 1.

Complete atrioventricular block, 37 beats per minute (bpm) and a prolonged corrected QT interval (QTc=452 ms).

Investigations

In the MICU, a second ECG (figure 2) was conducted 20 min later showing sinus bradycardia at a rate of 52 bpm, QT interval prolongation (QTc=530) and first-degree AV block (PR=252 ms). Serial troponins (from 30 ng/L to 26 ng/L) were downtrending. Echocardiogram obtained showed a left ventricular ejection fraction of 55%–60% with no regional wall motion abnormalities, ventricular dysfunction or pericardial effusion. Given the patient’s symptoms and signs, lack of other ischaemic changes on the ECG and no regional wall motion abnormalities on the echocardiogram, there was no concern for acute coronary syndrome or myocarditis. Troponin elevation was attributed to demand ischaemia. Cardiology was on board and only recommended further monitoring of the patient’s rhythm on telemetry and with ECGs, without the need for further ischaemic work-up. Subsequent ECGs (total of 21) over the next 4 days demonstrated sinus rhythm with first-degree AV block (PR=226–258 ms) and QT interval prolongation (QTc=464–509 ms).

Figure 2.

Sinus bradycardia, 52 beats per minute (bpm), QT interval prolongation (corrected QT interval (QTc)=530) and first-degree atrioventricular block (PR=252 ms).

A chest X-ray was only significant for bullous emphysema, one of the patient’s chronic problems. The patient also had a urine drug screen and analysis with gas chromatography mass spectrometry, and it confirmed the presence of tetrahydrozoline in his urine. No other substances were found.

Treatment

In the ED, the patient received 0.5 mg of intravenous atropine for his sinus bradycardia. The patient was also given a 1 L bolus of normal saline and 5 units of regular insulin to address his metabolic acidosis and hyperglycaemic state.

Outcome and follow-up

Administration of 0.5 mg intravenous atropine improved the patient’s sinus bradycardia. Furthermore, the regular insulin corrected the patient’s metabolic acidosis and hyperglycaemic state. In the MICU, the patient was monitored and remained stable for 24 hours. The patient was then transitioned to inpatient floors and had no acute events for 8 days. He was then transferred to inpatient psychiatry to address his suicidal attempt and depression. He completed 4 days of individualised psychotherapy and group therapy with no haemodynamic instability. He was discharged with the addition of sertraline 50 mg to his medication list and instructed to follow up with his primary care physician within 1–2 weeks.

Discussion

It is well documented that acute ingestion of over-the-counter tetrahydrozoline triggers severe cardiovascular and respiratory effects.^{1–3 6} This case reports an elderly patient who presented with complete heart block followed by unremitting first-degree AV block 24 hours after ingestion of eight bottles of Visine eye drops. Like other imidazoline derivatives, tetrahydrozoline activates peripheral and central alpha-adrenergic receptors. Peripheral activation of alpha-1-adrenergic receptors causes vasoconstriction, which initially leads to transient hypertension.² Bradycardia can also occur through a negative feedback mechanism due to hypertension. Over time, hypotension and bradycardia predominate through stimulation of the central alpha-2-adrenergic receptors.³

Abnormalities of cardiac conduction can also result from overdoses of central alpha agonists, particularly clonidine, and can lead to sinus node dysfunction, first-degree AV block, 2:1 AV block and complete AV block.^{7 8} Jones et al document a case of tetrahydrozoline cardiotoxicity that interrupted atrial activity and lead to transient sinoatrial node arrest that resolved spontaneously after 24 hours.⁹ While tetrahydrozoline has a similar mechanism to clonidine, no previous reports have shown complete AV block following ingestion. The persistent effects of tetrahydrozoline on our patient past 24 hours are also notable. Our patient’s first-degree AV block and QT prolongation required follow-up to ensure they resolved spontaneously. This residual effect of tetrahydrozoline was also seen in another report: Spiller and Griffith describe a case of prolonged bradycardia and hypotension that lasted for 36 hours after ingestion.¹⁰ Nevertheless, cases that are symptomatic primarily occur within 2 hours and resolve within a day.³

Most exposures to small amounts of tetrahydrozoline remain asymptomatic; however, the response can be variable. In one report, a 1-year-old girl showed signs of respiratory depression and bradycardia after consumption of 2.5–5 mL of 0.05% tetrahydrozoline.² Nonetheless, cases that require hospitalisations are infrequent and require only supportive treatment.^3–5 Haemodynamic instability with significant bradycardia as in this case can be treated with atropine. It is important to surveil the patient’s blood pressure following administration as significant hypertension can result from increasing heart rate.³

While the effects of tetrahydrozoline intoxication on the paediatric population are well documented, adult poisoning is a growing problem in the USA that has received limited coverage. According to the most recent American Association of Poison Control Centers’ data, despite a decrease in total tetrahydrozoline exposure, the percentage of adult (ages ≥20 years) cases has increased from 17% (N=1238) in 2012 to 30% (N=853) in 2018.^{4 5} It is unclear why the number of cases has grown in the adult population, but it may stem from malicious intent. Some reports have shown that tetrahydrozoline has been used to adulterate beverages in cases of sexual assault and suicidal attempts.^{3 11} Since products containing this compound are so accessible and can be used for harm, it is important that the range of toxic effects be made clear to physicians for appropriate treatment.

To the best of our knowledge, this is the first reported case of complete heart block after tetrahydrozoline consumption. Our patient was fortunate to receive medical assistance and avoid more serious complications after his suicide attempt. Healthcare professionals should be aware of this potential side effect following Visine eye drops ingestion.

Patient’s perspective.

I did it because I was depressed. My friends who I used to go fishing and golf with all died from the coronavirus. And my daughter, she just had a baby, and I can’t see him. I can’t see my grandson because of the coronavirus. I didn’t know what to do. I am glad I am still alive, but I am ashamed to tell my family. Please don’t tell my daughter.

Learning points.

• Visine eye drops contain a toxic compound called tetrahydrozoline that can have serious health complications if ingested.

• It is well established that tetrahydrozoline works by activating central alpha-2 receptors, which can lead to lethargy, hypotension, bradycardia and respiratory depression.

• Based on our case report, clinicians should also be aware that tetrahydrozoline can trigger first-degree and third-degree atrioventricular block to treat patients appropriately.