Case 3.3


Prepared by Dr Maria Pak

Case Presentation

A 19-year-old man presented to the ED.  The patient is an employee in a nutritional supplement store.  He states that he took an herbal supplement intended for energy and weight loss.  He states that he only ingested a single pill.  Shortly after ingestion, he began experiencing palpitations and chest pain.  His chest pain is pleuritic in nature, severity of 5/10, diffusely located over his chest with no radiation, and exacerbated by movement and breathing.

Hospital course: The patient was admitted to the ICU service.  He was started on an esmolol drip, which was later switched to propanolol.  It was found that the ingested supplements contained clenbuterol and tamoxifen. His CPK was elevated to the level of rhabdomyolysis.  Rhabdomyolysis was treated with IVF hydration. CPK and creatinine gradually trended down.  Lactic acidosis also resolved.  Cardiology was consulted for the elevated troponin, and 2D-echo showed mild LVH and impaired relaxation.  He was continued on beta-blocker therapy and troponin gradually trended down.  His hypotension and tachycardia resolved by hospital day 6.  He was discharged on hospital day 8.


Anabolic steroids have been used by strength athletes for almost five decades in order to improve performance by increasing muscle mass and strength.  Among the numerous documented toxic and hormonal effects of AAS, attention has been focused especially on the cardiovascular effects during recent years. Increases in blood pressure and peripheral arterial resistance are known from experimental studies, but there are also effects on the heart muscle, primarily left ventricular hypertrophy with restricted diastolic function.  Severe cardiac complications such as cardiac insufficiency, ventricular fibrillation, ventricular thromboses, myocardial infarction, or sudden cardiac death in individual strength athletes with acute steroid abuse have also been reported.

More recently, beta-agonists have been used as anabolic agents to increase body weight and build muscle strength. Clenbuterol [4-amino-(t-butylamino)methyl-3,5-dichlorobenzyl alcohol] is a β2-adrenergic receptor agonist that has been shown to have a significant effect on muscle metabolism in a variety of muscle atrophy models, including hind-limb suspension atrophy, starvation induced atrophy, and denervation induced atrophy. Additionally, clenbuterol is known to induce a significant repartitioning effect by increasing the growth of skeletal muscle at the expense of fat tissues in most livestock species.  It is licensed as a bronchodilator for use in human medicine in Spain and other countries in the European Community. It is also used as bronchodilator and tocolytic for the treatment of respiratory disease in horses and cattle and to relax the uterus in cows at parturition. Clenbuterol  causes regression in body lipids, muscle growth, and weight gain and has been illegally used in the past as a growth promoter in young cattle.

β1-adrenoceptors are found in many areas of the body including the heart, kidney, white adipose tissue and the brain, where, in particular, high concentrations are found in the pineal gland. Receptors in the heart mediate positive chronotropic and inotropic responses; those in the kidney control renin release from the  juxtaglomerular apparatus, whereas those in adipose tissue control lipolysis. In the brain, β1-adrenoceptors control the secretion of melatonin from the pineal gland and also appear to have a role in mood alterations. In blood vessels, β2-adrenoceptors have classically been considered to be dominant but in a number of arteries, including the coronary, mesenteric and saphenous, β1-adrenoceptors also mediate vasodilatation

Prolonged activation of β1-adrenoceptors has deleterious effects on the heart.  For example, the use of xamoterol as an inotropic agent is associated with increased mortality, and transgenic mice with relatively mild cardiac over expression of β1- adrenoceptors rapidly develop cardiac failure.  Chronic activation of cardiac β1- adrenoceptors is associated with apoptosis of cardiomyocytes. This may be a significant factor in the greatly increased risk of heart failure in people taking cocaine or amphetamines and in the success associated with the use of β-adrenoceptors antagonists for the treatment of cardiac failure.

β2-adrenoceptors have a wider distribution than β1-adrenoceptors and control a wide variety of functions in the body. They also mediate positive inotropic and chronotropic effects in the heart. The human heart has a significant (up to 40% of total β- adrenoceptors) population of β2-adrenoceptors. In the lung, the activation of β2- adrenoceptors causes not only a bronchodilator effect but also reduces the release of bronchoconstrictor mediators and increases the release of surfactants and mucus. β2- adrenoceptors mediate a powerful vasodilator effect in small coronary blood vessels and skeletal muscle blood vessels. Other effects seen in skeletal muscle include increased growth and speed of contraction, glycogenolysis and tremor. In the pancreas, there is an increase in both insulin and glucagon secretion, and glycogenolysis in the liver is increased.

The β3- adrenoceptor is widely distributed in the gut, brain, genitourinary tract, uterus and white and brown adipose tissue.  The presence of the receptor in fat stimulated activity in the pharmaceutical industry to develop anti-obesity and anti-diabetic β3- adrenoceptor agonists that has so far been a success in rodents but not in humans.

A major  target for many illicitly used drugs in sport is the β2-adrenoceptor that is found in the heart, lungs and skeletal muscle where it controls rate and force, relaxes tone and stimulates growth. β2-adrenoceptor agonists are powerful bronchodilators, anabolic agents and, in combination with corticosteroids, powerfully enhance their anti-inflammatory actions.

A survey of 113 cases of clenbuterol poisoning cases in Spain in 1992 showed that more than half of those afflicted presented symptoms of tachycardia, muscle tremors, nervousness, myalgia, and headache.  Exposure and onset ranged from 15 minutes to 6 hours . The duration of symptoms varied between 90 minutes and 6 days.

Clenbuterol influences cell metabolism by combining with β2-adrenergic receptors and by increasing the cAMP concentration in cells. In adipocytes, stimulation of β-adrenergic receptors increases cyclic AMP levels and activates protein kinase A (PKA), which stimulates lipolysis by phosphorylating hormone-sensitive lipase and perilipin.

Adipose accumulation decreases dramatically by clenbuterol administration.  In this study pigs treated with clenbuterol had a lean meat percentage increase by 2%, the back fat thickness was reduced by ~0.2 cm, and the loin muscle area was reduced by 4.7 cm2.  This effect increased with the age of the pigs. Clenbuterol produces specific protein anabolic effects in skeletal muscle in addition to lipolysis in adipose tissue. The clenbuterol thickened the pig muscle fibers and reduced the sizes of the pig adipocyte cells. Histological sections and global evaluation of gene expression after administration of clenbuterol in pigs identified profound changes in adipose cells. With clenbuterol stimulation, adipose cell volumes decreased and their gene expression profile changed, which indicate some metabolism processes have been also altered.  These findings indicate that some metabolic processes, such as DNA transcription, protein translation and protein translocation, were enhanced in the adipose cells by clenbuterol stimulation.

However, data has revealed that clenbuterol is also capable of inducing significant myocyte apoptosis  and necrosis in the heart and slow-twitch soleus muscle of rats. Furthermore, the onset of myocyte death occurs at doses lower than those commonly used to demonstrate the hypertrophic effects of this agent

The skeletal myocyte death induced by administration of clenbuterol to whole animals in vivo is mediated by overstimulation of the myocyte β2-AR4.  When administered in vivo, clenbuterol also stimulates the β2-AR of the sympathetic nerve terminals, which augments their release of norepinephrine, and the β2-AR of the peripheral vasculature, which results in a reflex tachycardia. These neuromodulatory effects may act synergistically, increasing the release of norepinephrine from the sympathetic varicosities, which induces cardiomyocyte death through the β1-AR pathway

Administration of clenbuterol induced significant and clearly discernible myocyte death in the heart and slow-twitch soleus muscle. Bolus injection of doses as low as 10 μ of clenbuterol induces significant myocyte death in the heart and soleus muscle of rats. In response to sustained exposure to an agonist, β-AR desensitization and downregulation occur resulting in tachyphylaxis. However, because of clenbuterol’s long plasma half-life and the fact that it accumulates in specific tissue compartments, particularly the heart, it is difficult to predict whether chronic administration would be more or less myotoxic than a bolus injection.

The patient above was treated with beta-blocker therapy. Mcclennan et al performed a study on the effects of clenbuterol and propanolol n muscle mass.  They found that in animals treated with clenbuterol and propranolol, the changes in body weight and body composition observed in animals treated with clenbuterol alone were abolished. The Beta-blocking agent also abolished the effects of clenbuterol on both muscle growth and protein synthesis rate. However, the study showed that the effects of clenbuterol on muscle cyclic AMP, lactate and glycogen concentrations were still detectable after twice-daily injection of the drug for 7 days. The dose of propranolol employed in the study was able to inhibit the effects of clenbuterol on cardiac, fat and liver mass and on energy expenditure.


Zhang J,  He Q, Liu QY, Guo W, Deng XM, Zhang W, Hu X and Li N. Differential gene expression profile in pig adipose tissue treated with/without clenbuterol.  BMC Genomics 2007, 8:433

Baker JS,  Graham M, Davies B. Gym users and abuse of prescription drugs. Journal of the Royal Society of Medicine (2006)  9 9:331-332.

Maclennan PA, Edwards RHT. Effects of clenbuterol and propranolol on muscle mass. Biochem. J. (1989) 264, 573-579.

Spurlock DM, McDaneld TG and McIntyre LM.  Changes in skeletal muscle gene expression following clenbuterol administration.  BMC Genomics 2006, 7:320

Burniston JG, Clark WA,, Tan LB, Phil D, andGoldspink DF. Dose-dependent separation of the hypertrophic and myotoxic effects of the β2-adrenergic receptor agonist clenbuterol in rat striated muscles. Muscle Nerve. 2006 May ; 33(5): 655–663.

Burniston JG, Clark WA,, Tan LB, and Goldspink DF.   Relative myotoxic and haemodynamic effects of the β-agonists fenoterol and clenbuterol measured in conscious unrestrained rats.  Exp Physiol. 2006; 91(6): 1041–1049.

Davis E, Loiacono R and Summers RJ.  The rush to adrenaline: drugs in sport acting on the b-adrenergic system.  British Journal of Pharmacology (2008) 154, 584–597.

Salleras L, Dominguez A, Mata E, Taberner JL, Moro I, Salva P. Epidemiologic Study of an outbreak of Clenbuterol Poisoning in Catalonia, Spain.  Public Health Reports 1995, 110(3):338-342.

Case 3.2


Prepared by Dr Kyle Perry

Case presentation:

A 64 year-old male presents to the emergency department pulseless with CPR in process.  EMS reports that the patient had a witnessed arrest in a nearby casino and bystander CPR was promptly initiated.  EMS arrived approximately 10 minutes after the collapse and placed a combitube before transporting the patient to the hospital.  In the ED, the patient was intubated and placed on a monitor which showed pulseless electrical activity (PEA.)  The patient received multiple doses of epinephrine and atropine and was then found to be in ventricular fibrillation.  He was then defibrillated and converted to sinus rhythm with return of pulses.  Hypothermic therapy was initiated, and the patient was admitted to the ICU.  The patient gradually became hypotensive, and vasopressors were started and an aortic balloon pump was placed for pressure support.  Initially, his Troponin I was 0.07, but gradually increased to 1.11 after 2 hours, 6.03 after 7 hours, and 19.93 after 14 hours.  Initial ECG showed a left bundle branch block.  He underwent a cardiac catheterization on hospital day #2 which showed a total occlusion of the right coronary artery.  Stent placement was attempted by was unsuccessful.  The patient expired on hospital day #3.

Pulseless Electrical Activity:

The term PEA can be used to describe any organized or disorganized rhythm that is unable to produce a palpable pulse.  For example, a patient can show normal sinus rhythm on the monitor, but if no pulse is present, the patient is still said to be in PEA.  The American Heart Association has divided the PEA algorithm into to basic pathways:  “Shockable” rhythms and “Not Shockable” rhythms.  “Shockable” rhythms include ventricular fibrillation and ventricular tachycardia.  The key component to either pathway is high quality CPR.  The central medications to the algorithms are Epinephrine 1 mg q 3-5 minutes and Atropine 1 mg q 3-5 minutes (up to 3 doses.)  Treatable causes of PEA should be sought after and reversed.  These are often referred to as the H’s and T’s.



Hydrogen ion (acidosis)







Tension pneumothorax

Thrombosis (coronary or pulmonary)


Even with current advancements in resuscitative technique, prognosis of cardiac arrest is very poor, with only 3-8% of patients being discharged neurologically intact.


  1. 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care – Part 7.2: Management of Cardiac Arrest. Circulation 2005; 112: IV-58 – IV-66.
  2. Tintanelli, Judith. Emergency Medicine: A Comprehensive Study Guide. Sixth Edition. (Burgess, Bouzoukis 540-541) McGraw-Hill, 2004.

Case 3.1


Prepared by Dr Julie Nguyen

Case presentation:
An 18-year-old African-American woman with no significant past medical history, presented to the ED complaining of cough, fever, generalized weakness, and worsening dyspnea for a week.  The patient was tachycardic, tachypneic and hypothermic.  Her labs showed leukocytosis, thrombocytosis, and coagulopathy. She had an anion gap of 21 and lactic acid of 6.7.  Her d-dimer was elevated and troponin level was 5.86. CT scan of her chest showed a massive bilateral PE in the main pulmonary arteries.  Lower extremity duplex did not show presence of DVTs.  The patient was admitted to the MICU where she was intubated secondary to persistent hypoxia (pulse ox 70-80%) despite receiving supplemental oxygen therapy.  TEE was done and showed a thrombus in the right ventricle.  Patient was treated with a bolus dose of TPA, as well as heparin drip.  She also was transfused with FFP in order to correct her coagulopathy and hypofibrinogenemia.

The patient deteriorated while in the MICU.  She was transferred to Children’s hospital the following day as a possible candidate for ECMO therapy.  A cardiac catheterization was performed, but was unsuccessful in removing the thrombus.  Local TPA infusion was done instead and the patient was continued on a heparin drip.  ECMO was not started because it was felt that the patient would not benefit from it at this time due to prolong hypoxia and multi-organ system failure.  Patient subsequently expired on hospital day #4.

Fibrinolytic therapy in Pulmonary Embolism
Thrombolytic agents activate plasminogen to form plasmin, resulting in accelerated lysis of thrombi. Common thrombolytic regimens include tPA, streptokinase, and urokinase. Streptokinase is antigenic and can cause immunologic sensitization and allergic reaction; tPA was associated with more rapid clot lysis and fever bleeding complications. Thrombolytic agents have been used in STEMI, stroke, phlegmasia cerula dolens  and central venous catheter clearance.

•    Persistent hypotension (SBP<90mmHg or drop in SBP>40mmHg from baseline)
•    Severe hypoxemia
•    Substantial perfusion defect
•    Right ventricular dysfunction
•    Free floating right atrial or ventricular thrombus
•    Patent foramen ovale
Thrombolytic therapy accelerates clot lysis and is associated with short-term physiologic benefits, but has not been shown to improve mortality. Despite the lack of demonstrable mortality benefit, most clinicians accept massive PE as an indication for thrombolysis because successful therapy can be life saving. The risk versus benefits of thrombolysis should always be weighted on a case-by-case basis.

ECMO in the treatment of PE in adults
ECMO (extracorporeal membrane oxygenation) was first developed by Dr. Gibbon Jr. in 1953.  The idea is to remove deoxygenated blood from the body, oxygenate it, and return it back to the body.  This is similar to the idea of cardiopulmonary bypass but there are subtle differences.  The goal of ECMO is to allow the heart and lungs to rest from the high levels of oxygen and airway pressures that are required for ventilation and oxygenation.  It is a bridge to definitive therapy.

ECMO table
The use of ECMO has been mainly utilized in the pediatric population, especially in neonates.  Most of the studies and data on ECMO are within the pediatric population.  It has not been well studied in the adult population and the success rate varies.

Here are the indications and contraindications/exclusions for the use of ECMO in adults.


  • Cardiac or lung diseases that are acute, life threatening, unresponsive to standard conventional therapy, and are thought to be reversible.
  • It has been mainly used for ARDS in adults
  • No clear indications for PE


  • More than 10 days on mechanical ventilation
  • Age > 65 years old
  • Contraindications to anticoagulation
  • Necrotizing pneumonia
  • Multiple system organ failure
  • Terminal underlying disease
  • Major or irreversible CNS injury

Sherwin’s Critical Care is an education module that focuses on various aspects of critical care relevant to the practice of Emergency Medicine.   These are real cases as managed in the ED.  All postings are HIPAA compliant.