Death of an apprentice bodybuilder following 2,4-dinitrophenol and clenbuterol intake.

We present the case of a 17-year-old man, who died after 2,4-dinitrophenol (DNP) and clenbuterol consumption, which he likely took for physical enhancement. Forensic post-mortem examination revealed a yellowish skin colour and nonspecific signs of asphyxia. Analytical confirmation of the intoxication was obtained in blood and urine, with high levels of DNP and clenbuterol. Both of these substances are used by bodybuilders as DNP enhance lipolysis and clenbuterol has anabolic properties, but their toxicity is underestimated. DNP uncouples oxidative phosphorylation, leading to thermogenesis and even relatively small doses can cause fatal hyperthermia. Clenbuterol is a ß2 agonist that causes electrolyte disturbances (hypokalemia and hyperglycemia mostly) and death have been described through coronary vasospasm. Given the circumstances in which the body was found and toxicological results, we believe the cause of death to be fatal hyperthermia from DNP intake. These substances are illegal in many countries, but easily bought online. Through this availability, the last decades have seen an increase of fatal intoxications. Websites selling them are regularly closed by French public authorities and Interpol, but unfortunately it seems insufficient.

A Case Series of Clenbuterol Toxicity Caused by Adulterated Heroin.

BACKGROUND: Adulteration of drugs of abuse may be done to increase profits. Some adulterants are relatively innocuous and others result in significant toxicity. Clenbuterol is a ß2-adrenergic agonist with veterinary uses that has not been approved by the U.S. Food and Drug Administration for human use. It is an infrequently reported heroin adulterant. We describe a cluster of hospitalized patients with laboratory-confirmed clenbuterol exposure resulting in serious clinical effects. CASE SERIES: Ten patients presented with unexpected symptoms shortly after heroin use. Seven evaluated by our medical toxicology service are summarized. Presenting symptoms included chest pain, dyspnea, palpitations, and nausea/vomiting. All patients were male, with a median age of 40 years (interquartile range [IQR] 38-46 years). Initial vital signs included a heart rate of 120 beats/min (IQR 91-137 beats/min), a respiratory rate of 20 breaths/min (IQR 18-22 breaths/min), a temperature of 36.8°C (IQR 36.7-37.0°C), a systolic blood pressure of 107 mm Hg (IQR 91-131 mm Hg), and a diastolic blood pressure of 49 mm Hg (IQR 40-70 mm Hg). Serum potassium nadir was 2.5 mEq/L (IQR 2.2-2.6 mEq/L), initial glucose was 179 mg/dL (IQR 125-231 mg/dL), initial lactate was 9.4 mmol/L (IQR 4.7-10.5 mmol/L), and peak creatine phosphokinase was 953 units/L (IQR 367-10,363 units/L). The median peak troponin level in six patients was 0.7 ng/mL (IQR 0.3-2.4 ng/mL). Three patients underwent cardiac catheterization and none had significant coronary artery disease. Clenbuterol was detected in all patients after comprehensive testing. All patients survived with supportive care. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Atypical presentations of illicit drug intoxication may raise concern for drug adulteration. In the case of heroin use, the presence of adrenergic symptoms or chest pain with hypokalemia, lactic acidosis, and hyperglycemia suggests adulteration with a ß-agonist, such as clenbuterol, and patients presenting with these symptoms often require hospitalization.

Case of low dose clenbuterol toxicity.

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.

Acute clenbuterol overdose manifestations in a suicide attempt--a case report.

A 30-year-old man was admitted to the intensive care unit after a suicide attempt with respiratory difficulties, tremor, sinus tachycardia and significant hypokalemia. On examination, the patient was lucid, fully conscious and did not exhibit positive symptoms. Sings were not typical for overdosing olanzapine, alprazolam and alcohol as declared by the patient. Additional anamnesis revealed high doses of ingested clenbuterol, a selective ß2-adrenergic agonist. Due to its anabolic and lipolytic properties, clenbuterol has become a commonly abused drug in bodybuilding industry and is not routinely detected by toxicology screens. This is the first known report of suicide attempt by clenbuterol overdosing.

Clenbuterol toxicity: a NSW poisons information centre experience.

OBJECTIVE: To describe the epidemiology and toxicity of clenbuterol in exposures reported to the NSW Poisons Information Centre (NSWPIC). DESIGN AND SETTING: Retrospective observational study analysing data from all calls about clenbuterol exposure recorded in the NSWPIC database from 1 January 2004 to 31 December 2012. The NSWPIC coversthe Australian jurisdictions New South Wales, Tasmania and the Australian Capital Territory 24 hours a day and provides after-hours cover for the rest of Australia for 7 nights each fortnight. MAIN OUTCOME MEASURES: Total number of exposures, source of call (hospital, health care worker, member of the public), time from exposure to call, reasons for drug use, clinical features and advice given. RESULTS: Callers reported 63 exposures to clenbuterol, with a dramatic increase from three in 2008 to 27 in 2012. Of the 63 calls, 35 were from hospital, two from paramedics, one from general practice and 21 direct from the public. At least 53 patients (84%) required hospitalisation. The commonest reasons for use were bodybuilding and slimming. The most common features were tachycardia (24 patients), gastrointestinal disturbance (16) and tremor (11). Exposure was also associated with cardiotoxicity including one cardiac arrest in a 21-year-old man. CONCLUSION: Although a well recognised doping issue among elite athletes, clenbuterol use has spread out into the general public, especially during 2012, and should be considered in patients using bodybuilding or slimming products who present with protracted sympathomimetic features. The potential for misuse of this substance requires reconsideration of its current poison schedule registration and its availability.

[Clinical features and treatment of acute clenbuterol poisoning in children].

OBJECTIVE: To study clinical features, treatment and curative effects in children with acute clenbuterol poisoning, in order to provide a basis for early diagnosis and treatment. METHODS: Clinical data of 28 hospitalized children with acute clenbuterol poisoning in April 2011 were retrospectively studied. RESULTS: Of the 28 patients, there were 15 males and 13 females, aged 1 to 13 years (mean age 6.5±4.8 years). Vomiting, palpitations and limb shaking were found as main clinical manifestations in the patients. Main changes of blood biochemical included hypokalemia, lactic acidosis, hyperglycemia, hypsocreatinkinase. Snus tachycardia and S-T segment depression were observed on ECG. Patients' symptoms were gradually alleviated after 12-78 hours by use of beta blockers, potassium supplement, protecting the heart and other symptomatic and supportive treatment. Blood biochemical indexes were improved after 48 hours of admission. All of the patients were cured after 5 days. The symptoms of the patients do not longer occur during a follow up of half a month. CONCLUSIONS: Acute clenbuterol poisoning is characterized by vomiting, palpitations, limb shaking, hypokalemia, lactic acidosis and tachycardia in children. An early effective treatment of this disease can improve prognosis in children.

Late diagnosis of an outbreak of leanness-enhancing agent-related food poisoning.

INTRODUCTION: Ractopamine is a leanness-enhancing agent approved in the United States and 26 other countries to reduce body fat content, increase muscle mass, and improve growth rate of certain food-producing animals. Other ß-agonists with stronger pharmacologic effects, especially clenbuterol, had been illegally used as leanness-enhancing agents in the United States, China, and the European Union, and foodborne poisonings related to clenbuterol residue in meat or liver were rarely reported in the European Union and China. We describe an unusual outbreak of leanness-enhancing agent-related food poisoning in Taiwan and its associated diagnostic challenge. REPORT OF THE OUTBREAK: Twelve patients presented to the emergency department of a regional hospital after having dinner together. Their clinical manifestations included nausea, vomiting, palpitation, facial flush, trunk or limb numbness, tremor, headache, weakness, chill, and dyspnea. Laboratory workup revealed the presence of hypokalemia, leukocytosis, and hyperglycemia. Poisoning attributable to ß-agonists was suspected; however, the diagnosis of leanness-enhancing agent poisoning was delayed because there was no leftover meat for analysis and because the veterinary medicine was illegal in Taiwan. Clenbuterol and salbutamol were eventually detected in 10 patients' urine sample by using liquid chromatography-tandem mass spectrometry, and the concentrations ranged from 54 to 806 µg/L and from 0 to 4052 µg/L, respectively. CONCLUSION: ß-Agonist leanness-enhancing agent-related food poisonings are rarely encountered, especially in those countries where relevant veterinary medicines are banned, and may thus pose diagnostic challenge to both emergency physicians and clinical toxicologists.

A descriptive study of adverse events from clenbuterol misuse and abuse for weight loss and bodybuilding.

BACKGROUND: Clenbuterol is a ß2-agonist approved in the United States for veterinary use in nonfood animals. Clenbuterol use is emerging among bodybuilders and fitness enthusiasts attracted to the hypertrophic and lipolytic effects. CASES: This was a retrospective chart review of clenbuterol exposures reported to 2 poison control centers. Misuse of clenbuterol for weight loss and bodybuilding was reported in 11 of 13 clenbuterol users. Reported clinical effects included tachycardia, widened pulse pressure, tachypnea, hypokalemia, hyperglycemia, ST changes on electrocardiogram (ECG), elevated troponin, elevated creatine phosphokinase (CPK), palpitations, chest pain, and tremor. Measured serum clenbuterol concentration was 2983 pg/mL post 4.5 mg ingestion. Co-ingestants included T3 and anabolic steroids. Treatments included activated charcoal, benzodiazepines, ß-blockers, potassium replacement, and intravenous (IV) fluid. CONCLUSIONS: There is an increasing use of the Internet for illicit drug use for bodybuilding and weight loss purposes. These patients may not present as the stereotype of illicit drug abusers, but as healthy athletic low-risk patients. Clinical effects persisted greater than 24 hours with evidence of myocardial injury in 2 patients. Clenbuterol is increasingly being abused within the bodybuilding subculture. These cases illustrate the hidden dangers of clenbuterol abuse among bodybuilders and fitness enthusiasts.

A descriptive study of an outbreak of clenbuterol-containing heroin.

STUDY OBJECTIVE: Illicit drugs may be adulterated with substances other than the sought-after substance of abuse. Although the true incidence and clinical effects of this practice are unknown, geographically disparate outbreaks of clinically significant adulteration continue to occur. We report on a recent outbreak of clenbuterol-adulterated heroin occurring along the East Coast of the United States. METHODS: After identification of index cases, 5 US poison centers collaborated with state and territorial health departments to alert the public of clenbuterol-tainted heroin. A case definition of clenbuterol-tainted heroin toxicity was promulgated, and emergency departments (EDs) were asked to contact poison centers when cases were identified. RESULTS: We identified 34 probable or confirmed ED presentations in 5 states during a 6-month period. Thirteen of the 34 patients met the criteria for "confirmed" exposures. Clenbuterol was identified in the blood and or urine of 12 of these 13 patients. Clenbuterol concentrations ranged from 2.4 to 26 ng/mL in the blood and 9.4 to 12,526 ng/mL in the urine. Symptoms included nausea, chest pain, palpitations, dyspnea, and tremor. Physical findings included significant tachycardia, hypotension, and laboratory evidence of hyperglycemia, hypokalemia, and increased lactate levels. Six patients demonstrated biochemical evidence of myocardial injury. Ten patients received beta-adrenergic antagonists without adverse effect. CONCLUSION: The adulteration of heroin by clenbuterol was associated with sympathomimetic effects, metabolic acidosis, and myocardial injury. The report also highlights how collaborative efforts among poison centers using the Centers for Disease Control and Prevention's Epi-X system rapidly identified a disease outbreak.

Acute clenbuterol overdose resulting in supraventricular tachycardia and atrial fibrillation.

OBJECTIVE: We are presenting a case illustrating the complex metabolic and rhythm disturbances associated with acute clenbuterol intoxication. BACKGROUND: Clenbuterol is a long-acting beta2-adrenergic agonist primarily used in veterinary medicine in the United States. It has become a common drug of abuse by body builders because of its reported anabolic and lipolytic properties. In this case report, a body builder using veterinary clenbuterol developed significant electrolyte and cardiac manifestations. CASE REPORT: A 31-year-old man presented to the emergency department approximately 30 minutes after ingesting 1.5 ml (a tenfold dosing error) of Ventipulmin syrup (72.5 mcg/ml clenbuterol HCl). The product was brought to the emergency department (ED) by the patient. He reported no current use of anabolic steroids. He presented in an anxious state with complaints of palpitations and shortness of breath. Vital signs upon examination were as follows: BP, 122/77 mmHg (16.3/10.3 kPa); HR 254 bpm; RR, 22 bpm; Temperature, 97.1 degrees F (36 degrees C); and oxygen saturation, 100% on ambient air. His electrocardiogram (ECG) demonstrated supraventricular tachycardia with a ventricular rate of 254 bpm. Esmolol was recommended for rate control after the unsuccessful use of adenosine and diltiazem. Laboratory studies showed potassium, 2.1 mmol/L; magnesium, 1.3 mg/dL (0.54 mmol/L); phosphorus, 1.0 mg/dL (0.32 mmol/L); serum glucose, 209 mg/dL (11.6 mmol/L); creatinine, 0.8 mg/dL (70.7 micromol/L); AST, 20 U/L; ALT, 55 U/L; hemoglobin, 12.6 g/dL (126 g/L); CPK total, 87 U/L; and troponin I, 0.23 mug/L. The patient's urine was negative for any drugs of abuse. Clenbuterol levels were not obtained. A second ECG, 16 hours post ingestion, reflected atrial fibrillation with a ventricular rate of 125 to 147 bpm. On hospital day 3, he was electively cardioverted to sinus rhythm; heart rate and rhythm returned to normal, and he was discharged with oral metoprolol. DISCUSSION: Clenbuterol is approved for use in countries outside the U.S. as a bronchodilator for the treatment of acute asthma exacerbations in humans. Although clenbuterol is not a steroid hormone, it possesses anabolic properties that increase muscle mass. Its longer duration of action compared to other beta2-agonists (such as albuterol) make it a desired agent for body-building because of its high and prolonged serum level. The mechanism for the short and long-term cardiovascular complications of clenbuterol is complex. The anabolic effects of clenbuterol are associated with its beta2-adrenoreceptor agonist activity on striated skeletal muscles. In addition, clenbuterol promotes lipolysis through adipocyte beta3-adrenoreceptors. CONCLUSION: Considering the significant number of body-building enthusiasts, physicians will continue to encounter clenbuterol abuse in their clinical practices.

Atypical reactions associated with heroin use--five states, January-April 2005.

Heroin use typically produces a well-recognized syndrome of euphoria, miosis, and respiratory and central nervous system depression; cardiovascular effects are not a common finding. In January 2005, a man aged 21 years in New Jersey was hospitalized with an atypical reaction (e.g., tachycardia and palpitations) after reported heroin use. During the next 3 months, 25 additional persons in five states were reported to poison control centers (PCCs) and local public health agencies with a similar reaction after reported heroin use; in all, 24 of 26 patients were hospitalized. Analysis of drug specimens or testing of urine was performed in certain cases; in eight patients, the veterinary pharmaceutical clenbuterol was detected. This report describes four representative cases and summarizes the investigation by state and local health and law enforcement authorities and CDC into the 26 cases of atypical reactions after heroin use reported in five states (Connecticut, New Jersey, New York, North Carolina, and South Carolina) during January 28-April 17, 2005. Unintentional or intentional adulteration of illicit drugs such as cocaine or heroin is an additional potential hazard associated with their use.

Food poisoning by clenbuterol in Portugal.

This paper describes the occurrence of four cases of acute food poisoning, involving a total of 50 people, due to the ingestion of lamb and bovine meat containing residues of clenbuterol. Symptoms shown by the intoxicated people may be generally described as gross tremors of the extremities, tachycardia, nausea, headaches and dizziness. Analytical methodology developed for the determination of clenbuterol in meat, liver and blood samples is described. Procedures are described which should be followed when the described symptoms are evident in a group of people who have ingested contaminated meat, and particularly liver of ruminants.

[Adrenergic beta-agonist intoxication]. / Intoxicação por agonista beta adrenérgico.

The authors describe two clinical cases (father and daughter), observed in the Hospital Urgency with distal tremors, anxiety, palpitations, nausea, headaches and dizziness, two hours after ingestión of cow liver. They also had leucocytosis (with neutrophylia), hypokalemia and hyperglycaemia. After treatment with potassium i.v. and propranolol, the symptoms disappeared. The symptoms recurred at home because the patients didn't take the prescribed medication and persisted for five days, with spontaneous disappearance. The serum of both patients revealed the presence of clenbuterol (65 hg/ml - father and 58 hg/ml - daughter). The animal's liver had a concentration of 1,42 mg/kg. Clenbuterol is a ß-adrenergic agonist with low specificity, with some veterinary indications. However, this substance has been illegally used as a growth's promotor. We intend to alert doctors for this problem, particularly those that work in the Urgency.

Myotoxic effects of clenbuterol in the rat heart and soleus muscle.

Myocyte-specific necrosis in the heart and soleus muscle of adult male Wistar rats was investigated in response to a single subcutaneous injection of the anabolic beta(2)-adrenergic receptor agonist clenbuterol. Necrosis was immunohistochemically detected by administration of a myosin antibody 1 h before the clenbuterol challenge and quantified by using image analysis. Clenbuterol-induced myocyte necrosis occurred against a background of zero damage in control muscles. In the heart, the clenbuterol-induced necrosis was not uniform, being more abundant in the left subendocardium and peaking 2.4 mm from the apex. After position (2.4 mm from the apex), dose (5 mg clenbuterol/kg), and sampling time (12 h) were optimized, maximum cardiomyocyte necrosis was found to be 1.0 +/- 0.2%. In response to the same parameters (i.e., 5 mg of clenbuterol and sampled at 12 h), skeletal myocyte necrosis was 4.4 +/- 0.8% in the soleus. These data show significant myocyte-specific necrosis in the heart and skeletal muscle of the rat. Such irreversible damage in the heart suggests that clenbuterol may be damaging to long-term health.