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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.
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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