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The Tox Cave
The Tox Cave will dissect interesting ED cases from the perspective of a toxicologist, focusing on applying up-to-date management of the poisoned patient. The name Tox Cave was coined by a former toxicology fellow to describe our small office space, likening it to the Bat Cave. The Tox Cave is where Drexel toxicology fellows and attendings have gathered to discuss the nuances of toxicology over the years.
Monday, November 03, 2014

An 88-year-old man with a history of congestive heart failure, hypertension, and diabetes mellitus presented to the ED from a nursing home with altered mental status. EMS reported that the patient has had a decreased appetite, diarrhea, and weakness for three days. His initial vital signs were temperature 97.9°F, heart rate 79 bpm, blood pressure 116/64 mm Hg, respiratory rate 16 bpm, and pulse oximetry 98% on room air. His physical exam was remarkable for a depressed level of consciousness. Lab findings showed a creatinine of 2.6 mg/dl, a BUN of 60 mg/dl, and normal potassium and magnesium. His ECG is shown below.



The nursing home transfer sheet said the patient had reported yellow-tinted vision several days earlier. The patient’s medications include Lasix, digoxin, lisinopril, and insulin. Digoxin was last administered as prescribed six hours previously. A digoxin level was ordered and came back at 5.1 ng/ml.


Given the patient’s medication history, serum digoxin level, and altered mental status, digoxin-specific antibody fragments were administered for digoxin toxicity. The medical toxicologist and the emergency physician discussed the appropriate dose for this patient for full vs. partial reversal. Based on the serum digoxin concentration and his weight (80 kg), the calculated dosage for full reversal was four vials and for partial reversal was two vials of digoxin-specific antibody fragments. The dosage for full reversal was administered. One hour later, the patient became acutely short of breath.



The ECG in this case is consistent with digoxin toxicity, which may include T wave flattening, QT interval shortening, scooped ST segments with ST depression in the lateral leads (Salvador Dali sign [red arrow]), and increased amplitude of the U waves.



Other ECG findings include:

n Premature ventricular contractions are the most common rhythm disturbances caused by digitalis toxicity.

n Bradycardia, atrial tachyarrhythmias with AV block, various degrees of AV nodal blockade, ventricular tachycardia, ventricular fibrillation, and junctional rhythms.

n Bidirectional ventricular tachycardia, which is pathognomonic, is a rare finding. (See below.)



Image obtained from Edward Burns, MD.


The indications for digoxin-specific antibody fragments are:

n Life-threatening or unstable arrhythmias.

n Hyperkalemia in the acute setting (serum K >5 to 5.5 meq/L).

   • In a classic study, no patient with K >5.5 meq/L survived without antidotal therapy and no patient with K<5 meq/L died.

n Chronic elevation of serum digoxin concentration (SDC) with dysrhythmias, significant GI symptoms, or altered mental status.

n SDC ≥ to 15 ng/ml at any time ≥ 10 ng/ml six hours post ingestion regardless of symptoms.

n Acute ingestion of 10 mg of digoxin in an adult.

n Acute ingestion of 4 mg of digoxin in a child.

n End-organ dysfunction from hypoperfusion.


How are digoxin-specific antibody fragments dosed?

n Digoxin level

   • Acute digoxin level should be checked six hours post-ingestion.

   • Chronic digoxin concentration can be checked on presentation keeping in mind the time of last dose.



Note: Partial reversal should be considered in patients on chronic digoxin for CHF because they require the inotropic effects of digoxin for cardiac output.


Potential adverse effects of digoxin-specific antibody fragments administration and reversal of digoxin intoxication:

n Hypersensitivity reactions.

n Reversal of digoxin’s therapeutic effects resulting in cardiac deterioration manifesting as CHF exacerbation or tachydysrhythmias.

n Hypokalemia may result from intracellular shifting of potassium.

n Possible recurrence of digoxin toxicity in patients with renal failure resulting from failure to eliminate the digoxin-immune fragment complexes and release of unbound digoxin.

n Interference of digoxin-immune fragment complexes with routine total digoxin immunoassay measurements may result in falsely elevated levels.


Note: It is important to consider discussing the plan for reversal with the patient’s cardiology in anticipation for adverse effects associated with reversal.


The patient developed flash pulmonary edema, was started on BIPAP, and received dobutamine and epinephrine infusions for hypotension. The patient was admitted to the ICU and received treatment for decompensated heart failure secondary to digoxin reversal. The patient clinically improved within 48 hours. Repeat EKG is shown below.





1. Bismuth C, Gaultier M, et al. Hyperkalemia in Acute Digitalis Poisoning: Prognostic Significance and Therapeutic Implications. Clini Toxicol 1973;6(2):153.

2. Nelson L, Lewin N, et al, eds. Goldfrank's Toxicologic Emergencies. 9th Edition. New York: McGraw Hill; 2011.

3. Chan BS, Buckley NA. Digoxin-specific Antibody Fragments in the Treatment of Digoxin Toxicity. Clin Toxicol 2014;52(8):824.

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Thursday, October 02, 2014

A 33-year-old-male bodybuilder with a history of polysubstance abuse presents with agitation and combativeness. He was wearing sunglasses and shadow boxing in the air.


His initial vital signs were temperature 98°F, heart rate 120 bpm, blood pressure 140/90 mm Hg, respiratory rate 16, pulse oximetry 100% on room air. His physical exam is remarkable for tachycardia, agitation, and delirium, and his ECG is remarkable for sinus tachycardia with normal intervals. CBC and BMP are within normal limits; CPK is mildly elevated at 402 IU/L.


What is the differential diagnosis for this patient?

n Sympathomimetics (amphetamine, cocaine, PCP, synthetic cathinones [bath salts], synthetic cannabinoids)

n Anticholinergics

n CNS infection

n Hypoglycemia

n Head injury

n Thyroid storm

n Alcohol withdrawal syndrome

n Sedative-hypnotic withdrawal (baclofen, barbiturates, benzodiazepines, ethanol, gamma-hydroxybutyric acid [GHB] or GHB precursors gamma butyrolactone [GBL] and 1,4 butanediol [BD], volatile solvents)


The patient’s mental status and agitation improved with diazepam 10 mg IV x 2. He admits to using “2 to 3 mL of GHB every few hours around the clock to self-treat withdrawals.” The patient reports GHB use for bodybuilding, but he recently ran out and was unable to obtain more.


What are the GHB use or abuse scenarios?

n Medical uses (sodium oxybate for narcolepsy, cataplexy, and excessive daytime sleepiness symptoms)

n Recreational use

n Club or rave scenes

n Sports and athletics (bodybuilding)

n Date rape

n Use of GHB analogs/precursors (gamma butyrolactone or 1,4 butanediol)


How does GHB withdrawal present?

GHB withdrawal typically manifests within one to six hours, and may progress rapidly to refractory agitation, hallucinations, delirium, and death within 24 hours after last use. Clinical manifestations are similar to alcohol withdrawal syndrome with the exception of the autonomic instability being mild or absent and the agitation and delirium having a prolonged course.


Symptoms generally last four to 15 days with a mean of nine days. Clinical findings of GHB withdrawal include:


Central Nervous System

n Agitated delirium with confusion, anxiety, agitation, diaphoresis, insomnia, and tremors in early withdrawal

n Hallucinations, paranoid delusions, and profound delirium

n Increased muscle tone, myoclonic jerks, rigidity, and seizures

n Rotary or horizontal nystagmus



n Mild or absent autonomic instability

n Hypertension and tachycardia due to sympathetic stimulation


Gastrointestinal Symptoms

n Nausea and vomiting

n Abdominal cramps

n Diarrhea or constipation

n Urinary retention


Other Considerations

n Psychomotor agitation predisposes the patient to hyperthermia and rhabdomyolysis

n Clinical course may be unpredictable with improvement followed by rapid deterioration


How is GHB withdrawal managed?

The mainstay of treatment includes supportive care and aggressive use of benzodiazepines for agitation.

n Monitoring: Cardiac monitoring and trend CPK in patients with agitation at risk for rhabdomyolysis

n Symptom control: agitation, delirium, seizures, hyperthermia. Recommend diazepam 10 mg IV every five to 10 minutes and titrate to restfulness. Rapid onset of action and presence of active metabolites (temazepam and oxazepam) increase the duration of action. In benzodiazepine-refractory cases, consider the use of barbiturates or propofol, but avoid the use of antipsychotics for agitation because they are often ineffective and may lower seizure threshold. Physical restraints may be cautiously used but should be removed quickly because they may worsen hyperthermia and rhabdomyolysis.

n Hypertension management: Treat with benzodiazepines. Beta-blockers are contraindicated because they may worsen hypertension and coronary ischemia. Fluids, nutritional support, and electrolyte repletion (thiamine, folic acid, and magnesium) may be indicated, similar to alcohol-withdrawal patients.

n Disposition: Admission to a critical care setting may be indicated for patients manifesting severe or progressive symptoms.


Case Conclusion

The patient was admitted to a monitored setting with a diagnosis of GHB withdrawal. He had multiple episodes of agitation and combativeness during his admission. He was administered escalating doses of diazepam, a total of 480 mg of diazepam IV during his eight-day hospital stay. The patient recovered in eight days, and was referred to drug rehabilitation.



1. Dyer JE, Roth B, Hyma BA. Gamma-hydroxybutyrate withdrawal syndrome. Ann Emerg Med 2001;37(2):147.

2. Tarabar AF, Nelson LS. The gamma-hydroxybutyrate withdrawal syndrome. Toxicol Rev 2004;23(1):45.

3. Craig K, Gomez HF, et al. Severe gamma-hydroxybutyrate withdrawal: A case report and literature review. J Emerg Med 2000;18(1):65.

Tuesday, September 02, 2014

A 60-year-old man presents to the ED with shortness of breath and a productive cough with black sputum for one day. Initial ED vitals were blood pressure 141/85 mm Hg, heart rate 115 beats per minute, temperature 38.2°C, and respiratory rate 32 breaths per minute. His oxygen saturation of 83% on room air improved to 97% with 3L supplemental oxygen by nasal cannula.


His physical exam is remarkable for tachycardia and scattered rhonchi with expiratory wheezes. His right thumb and index finger are burned, and his lips are cracked with blistering.


The chest x-ray shows bilateral infiltrates. He is started on empiric antibiotics for suspected community-acquired pneumonia, and is admitted to the hospital.


What is the difference between crack and cocaine? Cocaine is a naturally occurring alkaloid with unique local anesthetic and sympathomimetic activity. It is has anesthetic and vasoconstrictive properties, and is a heat-labile white powder that can be injected or inhaled. Crack, on the other hand, is produced by mixing cocaine hydrochloride with a strong base, like sodium bicarbonate. It is then extracted with alcohol or ether to form a lipid-soluble, heat-stable, free-base form that vaporizes with heat and therefore can be smoked (freebasing). In contrast, cocaine will burn when lit. Crack derives its name from the characteristic crackling sound it makes when heated and smoked. It is rapidly absorbed through the pulmonary circulation and reaches the CNS within seconds.



What are possible clinical findings suggesting crack use?

·   Crack eye: Corneal defect because of corneal anesthesia and loss of corneal reflex when cocaine is volatilized.

·   Crack fingers: Thermal burns from handling the crack pipe.

·   Crack lips: Cracked and blistered lips resulting from contact with a very hot pipe.

·   Madarosis: Loss of facial hair from thermal injury.

·   Melanoptysis: Cough productive of black sputum from inhaling carbonaceous residues.


How is crack lung diagnosed?

Crack lung is a pulmonary syndrome of dyspnea, hypoxia, and fever associated with inhalational use of crack cocaine within 48 hours. Diffuse infiltrates are often seen on chest x-ray. (Below.) ABG analysis may show acute respiratory alkalosis, hypoxemia, and elevated A-a gradient. Additional diagnostic testing to help differentiate crack lung from other conditions include laboratory testing (cardiac markers), ECG, imaging studies (high-resolution computed tomography), cultures, bronchoalveolar lavage, and lung biopsy.



Photo courtesy of


How is crack lung managed?

·   The treatment of crack lung is largely supportive care.

·   Broad-spectrum antibiotics are usually initiated for possible CAP and aspiration pneumonia. No evidence supports using antibiotics to treat crack lung.

·   Glucocorticoids have been reported to improve clinical and radiographic findings when used in the treatment of alveolar hemorrhage because of crack lung, although their efficacy has not been evaluated in randomized controlled studies.

·   Patients should be encouraged to abstain from crack cocaine.


Case Conclusion

The patient received antibiotics, steroids, and nebulized albuterol during his hospital admission. His symptoms and chest x-ray findings improved within 24 hours. Blood cultures were negative, and antibiotics were discontinued. He was discharged home with instructions to discontinue use of crack cocaine and given a prescription for oral steroids and an albuterol inhaler.

Thursday, August 07, 2014

Case 1: A 26-year-old woman presented to the ED with fever and rash for one day. The patient reported a diffuse pruritic rash that started yesterday on her head and neck.


Initial ED vitals include temperature 38.3°C, blood pressure 120/79 mm Hg, heart rate 110 bpm, and respirations 18 bpm. Her physical exam was remarkable for a diffuse erythematous, blanching, morbilliform rash with areas of confluence over 90 percent of her body and cervical and submandibular adenopathy.



Pertinent labs include platelets of 86 and WBC count of 1.4 with a normal eosinophil count. The patient’s medication list includes dextroamphetamine and lamotrigine. Fifteen days before, her physician started her on lamotrigine 50 mg daily for ADHD, and two days earlier, increased the dose to 75 mg daily.


Case 2: A 19-year-old man with a history of seizure disorder presents to the ED with a rash and flu-like symptoms for two weeks. He describes the rash as itchy and diffuse. Initial vitals include a temperature of 36.7°C, blood pressure 135/71 mm Hg, heart rate 122 bpm, and respirations 18 bpm. Physical examination demonstrates a diffuse morbilliform rash with confluence over the torso and desquamation of the head and neck with sparing of mucous membranes. The WBC count is 15.8 with an eosinophil count of 1,738 cells/μL. The patient reported he was prescribed lamotrigine for seizures eight weeks earlier.


The patient is discharged with a diagnosis of exfoliative dermatitis, prescribed diphenhydramine and prednisone, and given instructions to follow up with dermatology. Two days later, the dermatologist performed a skin biopsy, and recommends continuation of diphenhydramine and prednisone.


What is the differential diagnosis of rash?

·         Infectious

·         Autoimmune

o   Still’s disease

o   Acute cutaneous lupus erythematosus

·         Neoplastic

o   Angioimmunoblastic T-cell lymphoma

o   Sezary syndrome

·         Drug-induced

o   Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)

o   Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome

o   Acute generalized exanthematous pustulosis (AGEP)


How is DRESS diagnosed?

DRESS, a drug-induced hypersensitivity reaction, is a clinical diagnosis. The onset is typically two to six weeks following exposure to an offending medication. Initial symptoms may include fever, malaise, lymphadenopathy, facial edema, and a morbilliform rash that progresses to a diffuse, confluent erythema.


At least one internal organ is involved in most cases. Manifestations include hepatitis, acute interstitial nephritis, interstitial pleuritis, eosinophilic myocarditis, pericarditis, diarrhea, pancreatitis, autoimmune thyroiditis, encephalitis, meningitis, myositis, polyneuritis, or uveitis.


A commonly used validated scoring system is the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR).


RegiSCAR Scoring System for Classifying DRESS Cases





Score < 2, no cases; 2-3 possible cases; 4-5 probably cases; >5 definite cares.

Adapted from Am J Med 2011;124(7):588.


What is the cause of DRESS syndrome?

The exact pathophysiology of DRESS syndrome is unclear. Proposed mechanisms involve the accumulation of reactive arene oxide metabolites, a genetic predisposition, immunological response, or reactivation of herpes viruses. Anticonvulsants (phenytoin, carbamazepine, phenobarbital, lamotrigine) are among the most common causes of DRESS syndrome and share cross-reactivity. In addition to the anticonvulsants, case reports have identified other causative agents such as allopurinol, dapsone, minocycline, and sulfasalazine.


What is the treatment for DRESS syndrome?

There are no specific treatment guidelines, and some of the treatments are controversial.

·         Cessation of all potentially offending agents and avoidance of re-exposure to similar agents

·         Supportive care

·         Exfoliative dermatitis

o   IVF, replete electrolytes, nutritional support

·         Severe organ involvement

o   Systemic corticosteroids have been used successfully, but have not been evaluated in randomized trials

o   IV N-acetylcysteine for drug-induced hepatitis

o   IVIG has been used but remains controversial


Case 1 Continuation: The patient was admitted to the hospital with a diagnosis of suspected DRESS syndrome. The patient was started on methylprednisolone 80 mg IV q 8 hours and diphenhydramine 25 mg IV prn. The patient’s rash improved with residual patches on her feet and arms. A repeat CBC showed a WBC count of 0.6 and platelet count of 92, which improved by day three to 6.5 and 123, respectively. The patient was discharged on day four with a steroid taper and outpatient follow-up instructions.


Case 2 Continuation: Five days after the initial ED visit, the patient returned via EMS after being found unconscious. He was in asystole on presentation. Labs were remarkable for a platelet count of 38 and a WBC count of 12 with an eosinophil count of 720 cells/μL and 10% atypical lymphocytes. He was in acute renal failure (Cr 1.3) and acute liver failure (AST 1737, ALT 1619) with a coagulopathy (PT 70.4, PTT >230, fibrinogen < 60, and a D-dimer>20). Blood cultures were negative. He was placed on ECMO, and pronounced dead 24 hours later. The outpatient skin biopsy reported findings consistent with DRESS syndrome, and the autopsy revealed eosinophilic myocarditis.


Conclusion: DRESS syndrome is a rare but potentially life-threatening condition with an estimated mortality rate of 10 percent. Suspicion must be high because it may present as a spectrum of nonspecific clinical and laboratory findings.

Monday, June 23, 2014

A 58-year-old man presented unresponsive following a seizure at home. His brother stated that he became progressively confused over the course of a few hours and then started shaking. EMS reports tonic-clonic seizures that resolved following administration of 5 mg of midazolam IM.

The patient was unresponsive and hyperthermic on arrival. He was intubated for airway protection, covered with ice packs, and administered normal saline intravenously. His rectal temperature is 41.9˚C (107.4˚F), blood pressure is 94/45 mm Hg, heart rate is 160 beats/minute, and the respiratory rate is 16 breaths/minute with an oxygen saturation of 96% on 100% FiO2. The skin is diaphoretic with no signs of trauma. The pupils are 3 mm in diameter and reactive. He has no response to noxious stimuli, and his reflexes are 1+ bilaterally. The remainder of the exam is unremarkable.

The brother reveals that the patient has been prescribed olanzapine, tizanidine, diflunisal, and gabapentin, and he had recently used cocaine. Of note, the ambient temperature on this mid-July day is 89°F.

His initial ABG demonstrates a pH of 7.28, CO2 of 41.5, pO2 of 140.6, HCO3 of 19, and lactate of 6.1. His CPK is 2,038 with a troponin of 9. The patient is in acute renal failure with a creatinine 3.1. A urinary drug screen was positive for benzodiazepines and cocaine. Non-contrast head CT is unremarkable.

What is the differential for toxin-induced hyperthermia?

Managing Toxin-Induced Hyperthermia

  • Prehospital and hospital preparation
    • Undress patient and cover in ice and water-soaked sheets.
    • Hospitals must be adequately prepared with ice packs or tepid water and cooling fans.

  • Initiate aggressive correction of body temperature.
    • Monitor core temperature with rectal, esophageal, or bladder probe.
    • Lower the body temperature within the first hour.
      • Higher morbidity and mortality occurs in patients where cooling is delayed and temperatures stay above 38.9˚C (102.2˚F) for more than 30 minutes.

    • Avoid interference with thermoregulation.
      • Anticholinergics and antipsychotics
      • Restraints

    • Stop active cooling when the patient has reached 38.3˚C (101˚F).
      • Avoid iatrogenic hypothermia and monitor for rebound hyperthermia.

  • Aggressive use of benzodiazepines for treating agitation and seizures and preventing shivering
    • Additional benefit of treating the other causes of hyperthermia-serotonin syndrome and ethanol and sedative-hypnotic withdrawal
    • Phenytoin is not effective for treating most drug-induced seizures.
    • If unable to control agitation, seizures, and shivering, the patient should be intubated and paralyzed with a nondepolarizing neuromuscular blocker.

  • Patients are at risk for multi-organ failure.
    • Acute kidney injury may result from volume depletion, hypotension, direct heat effect, and rhabdomyolysis.
      • The use of sodium bicarbonate for rhabdomyolysis is controversial and no longer recommended.

    • Bleeding associated with coagulation disturbances and thrombocytopenia in the setting of hyperthermia is associated with poor outcomes.

The Relationship between Cocaine and Hyperthermia

Potentially high mortality rates occur when hyperthermia develops in patients with cocaine intoxication. Hyperthermia in patients intoxicated with cocaine is related to the extent of their psychomotor agitation and the ambient temperature.

A study in New York found that on days with a maximum daily temperature of 31.1˚C (88˚F) or higher, the mean daily number of cocaine overdose deaths was 33 percent higher than on days with a lower maximum temperature. Heat produced by psychomotor agitation in cocaine-toxic patients is associated with an increase in excitatory amino acids in the central nervous system and the blockade of reuptake of biogenic amines leading to increased adrenergic activity. Peripherally, cocaine induces vasoconstriction preventing heat dissipation.

The patient underwent noninvasive cooling using a mechanical cooling blanket with continuous core temperature monitoring, and he was started on a midazolam infusion. The patient’s temperature was 38˚C (100.4˚F) on admission to the medical intensive care unit. He continued to deteriorate overnight with two asystolic events. He was aggressively treated for his acidosis with continuous veno-venous hemofiltration and bicarbonate infusion. The patient required norepinephrine, epinephrine, vasopressin, dopamine, and milrinone infusions for cardiovascular support. An intra-aortic balloon pump was placed by cardiothoracic surgery. Multi-organ failure progressed, the family withdrew care, and the patient died 20 hours after ED presentation. His final diagnosis was cocaine-induced hyperthermia.


1. Marzuk PM, Tardiff K, et al. Ambient Temperature and Mortality from Unintentional Cocaine Overdose. JAMA 1998;279(22):1795.

2. Vassallo SU, Delaney KA. Thermoregulatory principles. In: Nelson LS, Lewin NA, et al, eds. Goldfrank's Toxicologic Emergencies. 9th ed. New York, NY: McGraw Hill; 2011:228-248.


About the Author

Gregory S. LaSala, MD; Rita G. McKeever, MD; and Jolene Okaneku, MD

Drs. LaSala, McKeever, and Okaneku are medical toxicology fellows at Drexel University College of Medicine in Philadelphia. Dr. LaSala, top, did his emergency medicine residency at Pennsylvania State University Hospital/Hershey Medical Center, and is a board member of the American College of Medical Toxicology Fellows in Training. Dr. McKeever, center, completed her residency at Drexel University College of Medicine and is a board member of the American College of Medical Toxicology Fellows in Training. Dr. Okaneku, bottom, is a graduate of Jefferson Medical College and of the emergency medicine residency at Drexel.

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