Case of low dose clenbuterol toxicity

Abstract

We present a case of acute clenbuterol toxicity following ingestion of 20 μg of clenbuterol, resulting in symptoms of sympathetic activation, sinus tachycardia and electrolyte derangement. The patient was managed conservatively with fluid resuscitation, electrolyte replacement and monitoring, and discharged following a 5-day stay in hospital.

Background

Toxicity following clenbuterol is a rarely reported syndrome, and this case suggests that toxicity can occur at relatively low doses of clenbuterol. As use of anabolic agents becomes more frequent, this is likely to be a more frequently observed presentation to emergency departments.

Case presentation

A 25-year-old Caucasian man with no medical history of note was seen in the emergency department following ingestion of the β2-agonist, clenbuterol. At 7:30 that morning, he had taken one tablet equating to 20 μg of clenbuterol; 90 min after ingestion, he developed sudden onset palpitations associated with some central chest pain, nausea, sweating and anxiety. He then presented to his general practitioner (GP), who found the patient's heart rate to be elevated at 140 bpm and a labile blood pressure, with one recording in excess of 220 mm Hg systolic, followed soon after by a reading of 80/20 mm Hg. The GP urgently sent the patient to the emergency department.

On further questioning, the patient admitted to having regularly taken the same dose of clenbuterol up until 3 weeks previously, with no adverse effect. He denied concurrently taking any other illicit drugs or alcohol. He was a regular gym-goer and was using clenbuterol as an anabolic agent. There was no relevant family history.

In the emergency department, the patient was found to be tachycardic, with a heart rate of 130 and blood pressure of 132/41. He had a raised respiratory rate of 24 with normal saturations. He was afebrile. Examination revealed a muscular man. He was warm, sweaty and tremulous. He had a bounding peripheral pulse and a hyperdynamic apex beat. Heart sounds included a loud ejection systolic murmur. Examination was otherwise unremarkable.

Investigations

Twelve-lead ECG (figure 1) showed a sinus tachycardia with inferolateral ST segment depression and a corrected QTc of 529 ms.

Figure 1.

Twelve-lead ECG taken on arrival at accident and emergency demonstrating sinus tachycardia with inferolateral ST depression. The corrected QT interval is 529 ms.

Blood tests on admission (table 1) demonstrated hypokalaemia, hypophosphataemia, hyperglycaemia, and raised lactate and troponin. These resolved prior to discharge. Thyroid function was normal.

Table 1.

Blood test	Day 0	Day 2
Sodium (mmol/L)	141	141
Potassium (mmol/L)	2.9	4.6
Urea (mmol/L)	6.6	3.5
Creatinine (µmol/L)	129	93
Phosphate (mmol/L)	0.51	0.98
Magnesium (mmol/L)	0.83	1.02
Troponin T (ng/mL)	128	123
Lactate (mmol/L)	9	1.0
Haemoglobin (g/L)	137	142
Glucose (mmol/L)	15.0	6.3
Thyroid-stimulating hormone (U/mL)	2.0	–

Bedside echocardiogram demonstrated a hyperkinetic left ventricle with an ejection fraction of 80%, but otherwise normal.

Urine toxicology screening was negative for abuse of other drugs.

Serum clenbuterol levels were not available for testing.

Differential diagnosis

Differential diagnosis of clenbuterol toxicity includes thyrotoxicosis, phaeochromocytoma and ingestion of stimulants such as cocaine, amphetamines and other β agonists.

Treatment

The patient was admitted to intensive care due to his cardiovascular instability and electrolyte disturbance. He was treated with 2 L of intravenous crystalloid with potassium supplementation. He was observed for several days.

Outcome and follow-up

The heart rate gradually reduced over 48 h to 70 bpm, with correction of the ST segment changes and prolonged QT interval. Repeat troponin was 123 ng/mL. The patient's electrolytes normalised. He was discharged with a repeat echocardiogram booked as an outpatient and GP to review.

Discussion

Clenbuterol is increasingly being used as a drug of abuse among athletes, mainly for its anabolic and lipolytic properties.^{1 2} It is listed as a banned substance by the International Olympic Committee in inhaled and oral form.³ There have been several reports of competitive athletes who have been disqualified due to its use. Clenbuterol is similar in structure and effect to other sympathomimetic drugs such as salbutamol and isoprenaline, although it is far more potent than either.⁴ Clenbuterol mediates its effects via stimulation of β2 adrenergic receptors. This has been shown to induce lipolysis, reduce adipogenesis,¹ as well as mediating the anabolic effects such as skeletal myocyte hypertrophy.⁵ It is used in certain countries as a treatment for asthma (the patient in the case above obtained his from Russia), with a typical dose of 20–40 μg daily. In the UK, its main legal use is in livestock, helping to relax the uterus of cattle during parturition.⁶ It is widely available online and its current price equates to 22 pence per 20 μg tablet.⁷ Doses used by bodybuilders vary from 20 to 200 μg one to three times per day.

Following ingestion, onset of action is within 30 min and peak effect is seen at 3 h.⁸ Therapeutic duration is roughly 12 h; however, the half life is longer at 25–39 h.⁹ Features of toxicity are similar to those seen with excessive adrenergic stimulation including nausea, vomiting, agitation, headache, tremor, convulsions, tachycardia and tachypnoea.¹⁰ Specific cardiovascular effects include labile blood pressure, prolonged QT interval, chest pain, myocardial ischaemia and tachyarrhythmia including supraventricular tachycardia, atrial fibrillation and ventricular tachycardia.^9–11 There is at least one report of clenbuterol use leading to myocardial infarction.¹¹ These cardiovascular effects are mainly mediated by direct β-2 receptor stimulation of the cardiac myocyte as well as on adrenergic nerve terminals in the myocardium.^{12 13} Commonly seen metabolic disturbances include hyperglycaemia, hypokalaemia, hypomagnesaemia and hypophosphataemia.¹⁰ These can exacerbate cardiac rhythm disturbance seen in acute clenbuterol toxicity.

Management of clenbuterol toxicity centres around recognition and treatment of the cardiovascular and metabolic consequences aforementioned. Tachycardia with haemodynamic compromise should be treated with short-acting β-blockers such as esmolol and metoprolol.^{9 10} Electrolyte disturbances should be cautiously corrected. If problematic, benzodiazepines can be used to treat severe agitation.¹⁰ All patients should be monitored for 4–8 h after exposure to clenbuterol.¹⁰

To our knowledge, 20 μg is the lowest reported dose of clenbuterol exposure leading to toxicity. This case reinforces the need for medical practitioners to be aware of the potential for severe toxicity at low doses. It is interesting to note that the patient had previously taken the same dose of clenbuterol without experiencing any toxicity, raising the suspicion that the patient ingested a higher dose of clenbuterol than he claimed. Unfortunately, serum clenbuterol levels are not routinely available for testing.

Data regarding the recreational use of anabolic and lipolytic agents are fairly limited, making it difficult to fully appreciate the extent of the problem. Data from the British Crime Survey suggest that the number of people who have ever used anabolic steroid use has increased between 2006/2007 and 2014/2015 from 37 000 to 66 000, respectively.¹⁴ Furthermore, data from needle exchange centres suggests that the number of new steroid users between 1996 and 2010 has increased 10 times and the total number of steroid users has increased 20 times in the same period.^15–17 As a result, we feel that emergency department attendances resulting from the use of anabolic and lipolytic agents are likely to increase in the coming years, making it all the more important to be aware of the clinical presentation and management of toxicity.

Learning points.

• Clenbuterol toxicity can result in profound metabolic and haemodynamic compromise.

• Management of clenbuterol toxicity is largely supportive.

• This case reinforces the need for medical practitioners to be aware of the potential for severe toxicity at low doses of clenbuterol ingestion.

• Although rarely reported, acute toxicity from the use of anabolic and lipolytic agents such as clenbuterol is likely to become more common in emergency departments across the UK.