Clenbuterol toxicity

Reviewed and revised 24 May 2014

OVERVIEW

  • Clenbuterol is a long acting beta-2-adrenergic agonist used in veterinary medicine and as a banned doping agent in athletes
  • veterinary uses: equine bronchodilator and bovine tocolytic agent
  • previously used for anabolic effects in livestock, but banned due to risk of toxicity from contaminated meat
  • toxicity may also occur from contamination of illicit drugs, such as heroin
  • more recently it has been used by the general public for body building and as a slimming agent (increases BMR and fat catabolism)

MECHANISM OF ACTION

  •  synthetic sympathomimetic amine
  • long acting beta-2-adrenergic agonist

TOXICOKINETICS

  • Absorption: well absorbed orally with high bioavailability, peak serum concentrations at 2-3 hours post-ingestion
  • Distribution: as an amphetamine-like lipid soluble weak base it has a large volume of distribution
  • Metabolism and elimination: long t1/2 25 – 40 hours

RISK ASSESSMENT

  • Estimated doses that produced typical beta-2-agonist features range from 30 to 300mcg
  • there have been multiple outbreaks from eating contaminated meat, with effects lasting 3-5 days
  • Doses used by bodybuilders usually range from 20 to 200mcg, up to three times daily

CLINICAL FEATURES

Effects include:

  • Sympathomimetic effects due to beta agonism: restlessness/ anxiety, headache, diaphoresis, tachycardia, tachypnoea, tachyarrhythmias, hypertension
  • Gastrointestinal disturbance: N&V, diarrhoea
  • Rhabdomyolysis
  • Metabolic effects: hypokalaemia, hyperglycaemia, less commonly hypoglycaemia, hypomagnesaemia, hypophosphataemia
  • Myocardial ischaemia in otherwise healthy people
  • Hypotension may also be seen due to beta 2 agonism
  • Respiratory distress after nasal insufflation

Complications

  • Intracranial hemorrhage (intracerebral hemorrhage, SAH)
  • Acute cardiogenic pulmonary edema
  • Hypertensive encephalopathy
  • Aortic or carotid artery dissection
  • Arrhythmia
  • Acute coronary syndromes

INVESTIGATIONS

(Guided by clinical assessment)

Laboratory tests

  • ECG (ACS, dysrhythmia)
  • Paracetamol level if deliberate self harm
  • FBC, UEC, glucose, LFTs, CK, troponin, CMP

MANAGEMENT

Resuscitation

  • attend to ABCs
  • treat agitation, seizures and hypertension and other sympathomimetic effects with benzodiazepines initially
  • for refractory hypertension consider metoprolol or esmolol infusion – may be a risk of unopposed alpha agonism worsening hypertension, in which case labetolol may be preferred

Supportive care and monitoring

Decontamination

  • consider 50g activated charcoal <1h after ingestion (uncertain benefit)

Disposition

  • Observe for a minimum of 4 hours after ingestion or 8 hours if slow release
  • most cases should be discussed with a toxicologist

References and Links

Journal articles

  • Brett J, Dawson AH, Brown JA. Clenbuterol toxicity: a NSW poisons information centre experience. Med J Aust. 2014 Mar 3;200(4):219-21. PubMed PMID: 24580525. [Free Full Text]

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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