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The Tox Cave by Gregory S. LaSala, MD; 
Rita G. McKeever, MD; & Jolene Yehl, MD




​The Tox Cave dissects 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 the authors' 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.

Please share your thoughts about the Tox Cave's posts.


Friday, November 1, 2019

A 15-year-old girl was brought to the emergency department by EMS after a seizure witnessed by her mother. She admitted that she had ingested "a handful of pills" in a suicide attempt five hours earlier. The mother said her daughter had a history of cutting but no prior suicide attempts.

Her past medical history was significant for depression, for which she took bupropion XL, and she reported past alcohol and marijuana use. Her initial vital signs were a temperature of 97.9°F, a pulse of 162 bpm, a blood pressure of 127/65 mm Hg, a respiratory rate of 14 bpm, and a pulse ox of 100% on room air. Her exam was significant for altered mental status, and she appeared post-ictal.

The patient had no focal neurologic deficits. Her heart rate was tachycardic, and she had no muscle rigidity, hyperreflexia, or myoclonus. Her ECG demonstrated a sinus tachycardia with a normal QRS but a QTc of 509 ms. She had another seizure while in the ED, and was given 1 mg lorazepam IV. The seizure then stopped.

She continued to have seizures despite frequent administration of lorazepam, and after her third episode, she was sedated with propofol and intubated. The patient was given multiple amps of bicarb, which had minimal effect on the QTc. The patient was transferred to the PICU.

The Mechanism of Bupropion

Bupropion is a monocyclic antidepressant structurally similar to amphetamines. It is a selective inhibitor of dopamine, serotonin, and norepinephrine reuptake. Bupropion also exerts anticholinergic effects. Peak serum levels are reached by three hours, but bupropion has a half-life of 21 hours. The main metabolite is hydroxybupropion, which has a potency similar to that of the parent drug and can explain the delayed presentation of bupropion overdose in some cases.

Bupropion Overdose Symptoms

Bupropion overdose can cause agitation or delirium. Seizures are seen in up to 21 percent to 37 percent of cases. (Am J Emerg Med. 1994;12[1]:43; Med J Aust. 2003;178[2]:61; Onset may be delayed by up to 14 hours after ingestion in the extended-release formulation. It may lead to status epilepticus, which can persist for days. There have been reports of bupropion toxicity mimicking brain death.

Bupropion overdose can result in hypertension, sinus tachycardia, widening of the QRS complex and QT prolongation, and ventricular arrhythmias. Cardiac arrest has been reported in massive overdoses. It can also cause vomiting.

Treatment for Bupropion Overdose

  • GI decontamination
  • Activated charcoal if given within one hour of ingestion
  • 50 g for normal adult
  • Whole bowel irrigation
  • 1-2 L/hr until the effluent is clear
  • Supportive care
  • Seizures
  • Benzodiazepines
  • Give levetiracetam followed by intubation and propofol infusion if the patient is in status epilepticus
  • QRS widening and QT prolongation
  • Electrolyte replacement
  • Boluses of NaHCO3 and continuous monitoring
  • Maintain a pH higher than 7.4
  • Cardiogenic shock
  • Intralipid emulsion has been reported to be successful.
  • ECMO has been reported to be successful.

Disposition After Bupropion Ingestion

All intentional ingestions should be admitted because of the potential for delayed onset of symptoms. Similarly, all possible pediatric ingestions should be admitted for observation.

Our patient's QTc increased to 519 ms when she arrived at the PICU. Her electrolytes were maximized and the QTc eventually decreased to below 500 ms with intermittent boluses of bicarb.

She developed mild hypotension on the first night, which resolved after a norepinephrine infusion was started. While performing sedation vacation over the next few days, the patient was found to be in status epilepticus, which was confirmed by EEG. She was administered levetiracetam and propofol. On hospital day four, the patient was awake, alert, and following commands. She was neurologically intact, and was transferred to psychiatry on hospital day five.

Tuesday, September 3, 2019

A 25-year-old woman presented with a rash, and reported that she was in South Carolina when she felt a stinging sensation. That was followed by blisters on her foot.

She noticed swelling of her foot, and had continued pain. She took pictures of the bite on days two and six. (Below.) She reported that she had a similar sting the previous summer. She said she had no fever, shortness of breath, or dizziness. Her vital signs were a temperature of 98.6°F, a heart rate of 80 bpm, a blood pressure of 100/60 mm Hg, a respiratory rate of 16 bpm, and an SPO2 of 100% on room air.

She was alert and in no distress. Her oropharynx was clear without lesions or edema, and her lungs clear. Her left foot was swollen, with erythema and multiple pustular lesions. She reported no calf tenderness.

 tox cave-fire ant bite-rash-day 2.jpg

Day Two.

tox cave-fire ant bite-rash-day 6.jpg

Day Six.

The suspected culprit was the fire ant (Solenopsis invicta). These aggressive ants are found primarily in the southeastern United States. Fire ants lock their mandible on their victims and inject venom multiple times from a stinger.

Local reactions are often painful and appear as a wheal, followed by sterile pustules, and then pustules with an umbilicated appearance on an erythematous base after 24 hours. Local edema occurs in large local reactions. Reported systemic reactions include anaphylaxis, DIC, rhabdomyolysis, renal failure, seizure, and bronchoconstriction.

Fire ant venom are hypercoagulable, and contain multiple components that can inhibit Na+/K+/ATPase and uncouple oxidative phosphorylation. The venom contains an alkaloid component that produces the pustule, pain, and an aqueous portion with allergenic activity. Deaths associated with fire ant stings are caused by anaphylaxis or massive envenomation.

Fire ants are within the order Hymenoptera, which includes honeybees, yellow jackets, hornets, and wasps. Their stings are common and associated with toxicity and potentially fatal allergic reactions.

Toxin and mechanism





HoneybeeMelittin disrupts cell membranes, and releases histamine. Pain, allergic reaction, DIC, rhabdomyolysisIce pack for discomfort, remove stinger, therapy for allergic reaction, and anaphylaxis
Wasps, hornets, yellow jacketsAllergic reaction
Black widow spiderAlpha-latrotoxin triggers a massive neurotransmitter release and neurotoxicity.Pain, hypertensionLocal wound care, pain control, muscle relaxant, antivenin
Brown recluse spiderSphingomyelinase D causes vascular injury, skin necrosis, and hemolysis.Necrotic wounds are usually painless initially, but two to eight hours later ulcerate and become hemorrhagic and painful; systemic reaction occurs 24-72 hours later.Wound care, pain control
Bark scorpionNeurotoxicity due to sodium channel opening.Pain, paresthesias, hypersalivation, cranial nerve dysfunction (opsoclonus), neuromuscular toxicity, autonomic findingsSupportive treatment, high-grade envenomation; antivenin, benzodiazepines

The patient was diagnosed with a large local reaction to a fire ant sting. She was treated with prednisone, and pain was controlled with ibuprofen. Secondary infection was considered, and she was also prescribed an antibiotic. Supportive treatment with cold compresses and foot elevation was also recommended. She reported improvement of symptoms by day 10.

Monday, July 1, 2019

A 45-year-old woman presented to the emergency department with nausea and vomiting. Her symptoms had started seven days earlier and steadily worsened. She reported generalized abdominal pain and distention and that her eyes appeared yellow.

The patient had no past medical history, took no medications, and said she did not drink or use drugs. Her history showed that she had been drinking an herbal preparation every day for the past five months to ameliorate her heavy menstrual periods.

The patient had mild right upper quadrant tenderness but no distention, rebound, or guarding. Her lungs were clear, and her heart rate and rhythm were normal. She had scleral icterus, and her skin was without erythema or jaundice.

Her lab results were remarkable for a WBC of 10, creatinine of 1.2 mg/dL, AST of 1020 U/L, ALT of 970 U/L, total bilirubin of 3.5 mg/dL, and INR of 1.2.

The herbal and dietary supplement market is worth $180 billion with more than 20 percent of the U.S. population reporting use. The Dietary Supplement Health and Education Act defined dietary supplements in 1994 as a category of food, which placed them under different regulations from those for drugs. Manufacturers of these supplements are not required to test them in clinical trials, and they are considered safe until proven otherwise.

Drugs, however, are considered unsafe until proven otherwise, and must have clinical trials supporting their safety. The incidence of severe adverse effects associated with dietary supplements has increased, and hepatotoxicity has been associated with many of these herbal remedies and is a significant cause of morbidity and mortality.

Herbal Preparations Associated with Hepatotoxicity

Herbal preparationClinical useMechanism of toxicity
Pennyroyal (Mentha pulegium)Used as a stimulant to combat weakness and by women to start or regulate menstrual periods.Contains the toxin pulegone, which depletes glutathione stores.
Kava-kava (Piper methysticum)Used for anxiety and stress.The alkaloid piper methysticum is hepatotoxic.
Chaparral (Larrea tridentata)Used to treat pain, bronchitis, and skin conditions.Potent inhibitor of lipoxygenase and COX pathways.
Germander (Teucrium chamaedrys)Used as an antipyretic, for weight loss, and as a cholesterol-lowering agent.Contains furan diterpenoids, which are cytotoxic-forming oxygen radicals leading to hepatocellular apoptosis.
Comfrey (Symphytum officinale)Used for upset stomachs, ulcers, and heavy menstruation.Contains pyrrolizidine alkaloids, which cause direct hepatic-veno occlusive disease.

Hepatic veno-occlusive disease (or sinusoidal obstruction syndrome) is characterized by sinusoidal hypertrophy and venous occlusion. Patients present with hepatomegaly and cirrhosis. Veno-occlusive disease of the liver may occur as a result of ingestion of pyrrolizidine alkaloid-containing herbal remedies. Plants containing this hepatotoxin include Heliotropium spp, Crotalaria spp (found in teas made from certain bushes), Senecio spp (ragwort), and Symphytum spp (comfrey).

This is a diagnosis of exclusion. A thorough history should be taken to rule out other sources of hepatotoxicity. An acetaminophen level and hepatitis panel should be sent, and ultrasound and CT of the abdomen should be done. The initial treatment for these patients is discontinuing the offending agent; this will suffice for a majority of cases. Patients who are sicker or present later in their course should receive supportive care with IV fluids and close monitoring of their liver enzymes.

Initiating N-acetylcysteine (NAC) may be considered because a majority of these herbal preparations cause glutathione depletion or produce oxygen radicals. Both of these mechanisms appeared to be reversed by NAC. Severe cases may develop liver damage and go on to need a liver transplant, so early consultation with gastroenterology is necessary.

We determined that our patient had been drinking pennyroyal tea. She was admitted for further workup, and toxicology and GI were consulted. Her acetaminophen level was 0, and her hepatitis panel was nonreactive. Her abdominal CT was unremarkable, and a liver ultrasound showed some mild hepatic congestion and biliary dilation.

Her presentation was thought to be related to the herbal tea, and she was advised to discontinue it. She was given IV fluids and administered NAC as a 21-hour protocol similar to that used in acetaminophen toxicity. Her AST/ALT decreased by more than half, and her bilirubin had decreased to 2 mg/dL after two days. She was discharged with no further sequelae.


1. Whiting PW, Clouston A, Kerlin P. "Black cohosh and other herbal remedies associated with acute hepatitis." Med J Aust. 2002;177(8):432.

2. Bunchorntavakul C, Reddy KR. Herbal and dietary supplement hepatotoxicity. Aliment Pharmacol Ther. 2013;37(1):3.

3. Haller CA, Kearney T, et al. Dietary supplement adverse events: report of a one-year poison center surveillance project. J Med Toxicol. 2008 Jun;4(2):84;

Saturday, June 1, 2019

An 11-year-old boy with cerebral palsy presented to the emergency department unresponsive. His mother said the child was in his normal state earlier that morning, but was blue and unresponsive when she tried to wake him from his morning nap. A home pulse oximeter reported an oxygen level of 55%.

The mother placed the child on oxygen and called 911. He was still unresponsive on arrival, and his physical examination demonstrated flaccid paralysis and a GCS score of 3 with fixed dilated pupils. He was tachycardic with shallow respirations. His initial vital signs were a temperature of 36.9°C, a heart rate of 136 bpm, a respiratory rate of 16 bpm, and a blood pressure of 89/38 mm Hg.

The boy was G-tube dependent, and his mother stated that he also had chronic GI bleeding and was supposed to see the gastroenterologist the next day. His medication list included valproic acid, felbamate, topiramate, and baclofen. His initial VBG showed a pH of 7.01, a CO2 of 126.02, and an HCO3 of 31.1, with a lactic acid of 2.8. He was intubated because of his mental status and admitted to the PICU, where the mother reported that she had also given him 240 mL of magnesium citrate to prep him for a colonoscopy he was due to have the following day.

What Is the Differential?

  • Brain stem herniation
  • Sepsis
  • Baclofen, topiramate, or valproic acid overdose
  • Hyperammonemia secondary to valproic acid
  • Hypermagnesemia

 tox cave-magnesium hypermagnesemia.jpg

The Clinical Effects of Hypermagnesemia

Normal serum levels range from 1.3 to 2.2 mEq/L. Only one percent of total body magnesium is found in the extracellular space. Serum levels of magnesium are a poor indicator of total body stores, and symptoms only correlate loosely with serum levels.

  • 3-5 mEq/L: Cutaneous vasodilation, nausea, vomiting, hypotension, and bradycardia.
  • 5 mEq/L: Deep tendon reflexes decrease, the patient may be sedated, and there may be a direct effect on skeletal muscle activity and ECG changes.
  • >10 mEq/L: Muscle paralysis may occur with respiratory failure; hypotension and cardiac conduction abnormalities will occur with lengthening of the PR, QT, and QRS intervals.
  • > 20 mEq/L: Ventricular dysrhythmias and cardiac arrest.
  • Hypermagnesemia has also been reported to cause parasympathetic blockade, which results in fixed dilated pupils mimicking brain stem herniation.

Mechanism of Toxicity

  • Inhibits Na/K/ATPase pump, leads to decreased intracellular potassium, and prolongs repolarization, which leads to the ECG changes seen.
  • Is a competitive antagonist of calcium channels by inhibiting flow calcium into the cell, decreasing skeletal muscle and cardiac muscle contraction.
  • Inhibits the release of glutamate at the NMDA receptor, leading to CNS depression and respiratory depression.

Causes of Hypermagnesemia

Most reports of hypermagnesemia are iatrogenic in nature.

  • Magnesium sulfate infusion for patients with preeclampsia/eclampsia.
  • The use of magnesium sulfate with charcoal as a cathartic for overdose patients. This practice was stopped after numerous case reports in the 1970s and 1980s.
  • Magnesium citrate, Milk of Magnesia (magnesium hydroxide), and magnesium sulfate enemas for constipation.
  • A man died in 2001 from hypermagnesemia after gargling daily with Epsom salts (100% magnesium sulfate). 
tox cave-magenesemia epsom salt.jpg

Clinical Risk Factors for Hypermagnesemia

  • Underlying renal insufficiency
  • Hyperparathyroidism
  • Addison's disease
  • A retrospective review of hypermagnesemia cases due to oral ingestion found patients to have some form of GI compromise: bleeding, colitis, constipation, or ulcers.

What is the Treatment for Hypermagnesemia

  • Cardiac monitoring should be initiated to evaluate for dysrhythmias and hypotension.
  • Treatment should be initiated at levels >5 mEq/L with symptoms or >8 mEq/L regardless of symptoms.
  • Normal saline should be administered for hypotension and to enhance renal excretion. Furosemide also enhances renal excretion of magnesium.
  • Intravenous calcium gluconate should also be administered because calcium is thought to antagonize the effects of the magnesium ion. Use 1-2 g calcium gluconate over five to 10 minutes followed by an infusion.
  • Hemodialysis will also rapidly remove magnesium for patients with renal insufficiency or in severe cases not responding to the above treatment.

A magnesium level was obtained for our patient, and was >20 mEq/L. The patient was given IV normal saline, furosemide, and 1 g of calcium gluconate. A central line was placed, and he received an infusion of calcium chloride. The next day, the patient's magnesium level was 5 mEq/L. His hospital course was complicated by aspiration pneumonia, but he was discharged from the hospital two weeks later back at his baseline.


  • Nelson LS, Hoffman RS, Howland MA, Lewin NA, Goldfrank LR. Goldfrank's Toxicologic Emergencies, (ebook). McGraw Hill Professional; 2019.
  • Nordt SP, Williams SR, et al. Hypermagnesemia following an acute ingestion of Epsom salt in a patient with normal renal function. J Toxicol Clin Toxicol. 1996;34(6):735.
  • Smilkstein MJ, Steedle D, et al. Magnesium levels after magnesium-containing cathartics. J Toxicol Clin Toxicol. 1988;26(1-2):51.

Wednesday, May 1, 2019

A 37-year-old man presented to the ED with thigh pain. He said his e-cigarette battery exploded in his pants pocket after he placed his keys in the pocket. He said he took his pants off immediately and noted that the battery had melted.

His initial vital signs were a temperature of 98.7°F, heart rate of 112 bpm, blood pressure of 159/95 mm Hg, and pulse oximetry of 98% on room air. He had a large area of burns of different degrees on his right thigh. Total body surface area of nine percent with first-, second-, and third-degree burns was noted.

may tox cave vaping leg.jpg

may tox cave vaping leg 2.jpg

E-cigarette use, or vaping, has risen significantly in the past 10 years. The device heats up a nicotine-containing solution that is inhaled. They may also be used to deliver other drugs like marijuana. The vast majority of these devices are powered by lithium ion batteries. These batteries are more typically used because they are lightweight and store more energy than other batteries, but they are also susceptible to thermal runaway, a condition involving overheating and spontaneous explosion. Circumstances that can lead to explosions include improper storage and charging, modifications of the device, and defective or poor-quality devices.

Reported e-cigarette explosion injuries include flame burns, chemical burns (alkali), blast injuries, inhalation injuries, and fractures. Patients have presented with injuries to the face (20%), hands (33%), and thigh and groin (53%).

How Should These Burns be Managed?

  • Wounds should be carefully irrigated and debrided to remove residual material.
  • Pain control
  • Many of these require consultation with appropriate specialists, depending on the injury, and transfer to a burn center.

What Tests Should be Done?

Most of these batteries are made of lithium-cobalt or lithium-manganese oxides. These metals may leak onto the skin and have the potential to be absorbed systemically. Lithium, manganese, and cobalt levels could be considered, but results may not be readily available.

The patient's lithium, manganese, and cobalt levels were sent. His clothes were removed, and the area was decontaminated. Due to the extent and nature of his burns, the patient was transferred to a burn center for further management.


  • Brownson EG, Thompson CM, et al. Explosion injuries from e-cigarettes [letter]. New Engl J Med. 2016;375(14):1400;
  • Kumetz EA, Hurst ND, et al. Electronic cigarette explosion injuries. Am J Emerg Med. 2016;34(11):2252.
  • Nicoll KJ, Rose AM, et al. Thigh burns from exploding e-cigarette lithium ion batteries: First case series. Burns. 2016;42(4):e42.
  • Maraqa T, Mohamed M, et al. Too hot for your pocket! Burns from E-cigarette lithium battery explosions: A case series. J Burn Care Research. 2018;39(6):1043.
  • Jones CD, Ho W, et al. E-cigarette burn injuries: Comprehensive review and management guidelines proposal. Burns. 2018 Nov 12; pii: S0305-4179(18)30279.
  • Treitl D, Solomon R, et al. Full and partial thickness burns from spontaneous combustion of e-cigarette lithium-ion batteries with review of literature. J Emerg Med. 2017;53(1):121.