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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.

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Thursday, November 1, 2018

A 32-year-old woman and her 36-year-old husband with no past medical history presented to the ED with palpitations, headache, a feeling of warmth all over, and a rash extending from their upper chests to their faces.

The blood pressures of the wife and husband were 91/56 mm Hg and 93/61 mm Hg, respectively. Both were mildly tachycardic with heart rates of 112 bpm and 108 bpm. The patients described intense pruritus, and they had patchy blanching and erythema over their chests and faces with mild eyelid edema. They reported that their symptoms started five to 10 minutes after sharing an ahi tuna poke bowl.

What Is the Differential Diagnosis?

Allergic reaction, MSG reaction, disulfiram reaction, tyramine reaction, and carcinoid syndrome.

What Is the Diagnosis?

The patients were diagnosed with scombroid fish poisoning. Onset is usually within minutes to hours. Patients present with findings similar to those of an allergic reaction, including flushing (face, neck, torso), urticaria, bronchospasm, angioedema, dizziness, palpitations, and hypotension. Other symptoms include abdominal cramping and diarrhea. They may last 12-24 hours if untreated.

What Is the Pathophysiology of Scombroid?

The poisoning is due to inadequate cooling and poor fish preservation. This occurs most commonly in mackerel, tuna, and yellowfin tuna. The reaction is due to histamine, which is formed from histidine from the histidine decarboxylase from bacteria found in dark-meat fish.

What Is the Management/Treatment?

Treatment is mainly supportive:

  • Use an antihistamine such as diphenhydramine.
  • Use IV fluids for hypotension.
  • Give albuterol for signs of bronchospasm.

Other Illnesses Caused by Marine Toxins





Toxin and Mechanism





Amnestic shellfish poisoningShellfish like mussels (Eastern Canada, northeastern and western United States)Domoic acid; stimulates glutamate receptorsGI symptoms onset <24 hours and neurologic onset <48 hours; may last yearsAmnesia, weakness, mental status changes, pain, visual disturbances; may have GI symptoms
CiguateraLarge reef fish like barracuda, snapper, grouper, and sea bass (tropical areas)Ciguatoxin (odorless, tasteless, heat-stable); opens sodium channelsThree to 30 hours, may recur later; can lasts for monthsFacial and perioral paresthesias, temperature reversal sensation, GI symptoms, dental pain
Diarrheic shellfish poisoningShellfishOkadaic acid; inhibits protein phosphatases30 minutes to 12 hoursDiarrhea, nausea, vomiting, abdominal cramps
Neurotoxic shellfish poisoningShellfish (Western Florida and the Caribbean)Brevetoxins; opens sodium channelsThree to six hours; may last up to 72 hoursSimultaneous GI and neurologic symptoms: paresthesias, hot/cold reversal, myalgia, vertigo
Paralytic shellfish poisoningShellfish (Northwest and northeast United States, southern Chile, North Sea, Japan)Saxitoxin; blocks sodium channels30 minutes, daysFacial and perioral paresthesias, headache, dizziness, muscular weakness, ataxia, dysmetria, respiratory depression
Tetrodotoxin Puffer fish (fugu), blue-ringed octopus, horseshoe crabs/legsBlocks sodium channelsMinutes to hoursGI symptoms, progressive paresthesias and weakness (bulbar), ataxia, ascending paralysis, respiratory depression

Select characteristics of syndromes caused by marine toxins. Adapted from Clin Infect Dis 2005;41(9):1290.

The patients were treated with intravenous normal saline and diphenhydramine 50 mg. Their symptoms dramatically improved, and they were discharged home after brief observation.

Suggested Readings:

Lavon O, Lurie Y, Bentur Y. Scombroid fish poisoning in Israel, 2005-2007. Isr Med Assoc J 2008;10(11):789;

Sobel J, Painter J. Illnesses caused by marine toxins. Clin Infect Dis 2005;41(9):1290;

Saturday, September 29, 2018

A 27-year-old man presented by EMS was agitated, confused, and combative. EMS said they had received a call for a patient who was minimally responsive lying on the sidewalk. They noted the patient with pinpoint pupils and decreased respirations. The concern was that he had been using heroin, so he was given 2 mg intranasal naloxone. This caused the patient to become acutely confused and combative. He was awake and alert but oriented x 0. His vital signs included a temperature of 99.1°F, a heart rate of 122 bpm, a respiratory rate of 26 bpm, and pulse oximetry of 97% on room air.

At least 160 people were admitted to Philadelphia hospitals over one weekend in July for overdose caused by an adulterated heroin named Santa Muerte. This drug was being sold as some of the last remaining "pure heroin" in the city. Naloxone reversed patients' somnolence but then made them agitated and confused. A sample of the seized drug was analyzed by GC/MS and was found to contain heroin, fentanyl, and 5F-ADB. 5F-ADB is a synthetic cannabinoid, which explains the severe agitation and confusion that ensued. ("Information Regarding 'Santa Muerte' Stamped Drug Seizures Causing Hospitalizations in the Greater Philadelphia Area." The Center for Forensic Science Research and Education. July 25, 2018.

This recent epidemic of overdoses from adulterated heroin is similar to another epidemic in 1995 when heroin adulterated with scopolamine led to 370 reported overdoses in New York City. Hamilton, et al., reported extreme agitation with anticholinergic symptoms when these patients were given naloxone for reversal of respiratory depression. (J Toxicol Clin Toxicol 2000;38[6]:597.)

tox cave-Santa Muerte.jpg

Initial reports about Santa Muerte said the heroin was adulterated with an anticholinergic agent. Other adulterants considered were K2, PCP, Thorazine, atropine, and Benadryl. Patients were described as being agitated, combative, and delirious and as having flushed skin and dilated pupils.

5F-ADB is a synthetic cannabinoid that binds to the cannabinoid receptors to produce sympathomimetic effects. Symptoms include agitation, psychosis, hallucinations, anxiety, and tachycardia.

Many drugs have been adulterated with other substances over the years. It is important that physicians are aware of this and that they manage patients according to their presentation.

Like other heroin overdoses, naloxone should be administered to maintain adequate respiration. It is difficult to tell if giving naloxone will unmask another drug. The physician should be prepared to manage agitation when the somnolence is reversed by naloxone. Benzodiazepines can be used as an adjunct to treat the agitation. The patient's airway must be closely monitored, especially in circumstances where several doses of benzodiazepines were administered.

Our patient's symptoms improved after he was given 2 mg intravenous Ativan; he also received IV fluids and was monitored closely in the ED. The patient became progressively more awake, alert, and was oriented x 3. He asked for food and tolerated eating, and he walked around the ED with a steady gait prior to discharge.

Friday, August 31, 2018

A 30-year-old woman was brought in by EMS tearful and reluctant to answer questions initially. Her mother was with her and stated that the patient had been depressed and may have taken some pills in a suicide attempt. Her initial vitals on presentation were a temperature of 99.1°F, heart rate of 128 bpm, blood pressure of132/92 mm Hg, and a respiratory rate of 26 bpm. She had clear lungs and sinus tachycardia on cardiac monitoring. She admitted to having taken "a lot" of aspirin.

Initial Labs

CBC: WBC of 14, hemoglobin of 14 g/dL, hematocrit of 42%, platelet count of 250,000

BMP: Sodium of 132 mEq/L, potassium of 4 mEq/L, Cl of 99 mEq/L, bicarbonate of 16 mEq/L, BUN of 30 mg/dL, creatinine of 1.2 mg/dL, glucose of 105 mg/dL

Lactate: 2.6 mmol/L

Salicylate level: 62.2 mg/dL

Common Presentation of Salicylate Toxicity

  • Nausea, vomiting, gastric irritation
  • Tinnitus or hearing loss
  • Altered mental status: confusion, agitation, somnolence, coma
  • Seizures
  • Hypoglycemia
  • Tachypnea
  • Tachycardia
  • Acid-base disturbances: Central stimulation of the respiratory center results in hyperventilation, which leads to a respiratory alkalosis and a compensatory metabolic acidosis.
  • Hyperthermia because of the effects intracellularly of uncoupling oxidative phosphorylation
  • Cerebral and pulmonary edema

Acute v. Chronic Salicylate Ingestion

  • Acute ingestion:
    • Levels correlate with symptoms:
      • 30-45 mg/dL: Tinnitus and tachypnea
      • 45-60 mg/dL: Nausea and vomiting
      • 70-90 mg/dL: Tachycardia, altered mental status, and agitation
      • Toxic levels greater than 90-100 mg/dL are usually associated with severe toxicity.
  • Chronic ingestion:
    • The levels do not correlate with symptoms, and toxicity can occur at much lower levels.
    • Symptoms are generally more insidious and can appear similar to those of a septic patient.
    • The provider must have a greater index of suspicion because an unexplained anion gap acidosis may be the only indicator.

Risk Factors of Acute Respiratory Distress Syndrome (ARDS)

  • Cigarette smoking
  • Chronic salicylate toxicity
  • Presence of altered mental status

Management of Salicylate Overdoses?

  • Activated charcoal:
    • Be mindful of the time of ingestion.
    • Do not administer if a patient has a change in mental status because he may aspirate.
  • Alkalinize urine with sodium bicarbonate infusion (3 amps of sodium bicarbonate in D5W at 200 mL/hr) with the goal urinary pH between 7.5 and 8. It is important to keep potassium levels normal to promote urinary alkalinization. If the potassium is low, the patient will excrete hydrogen ions into the urine, acidifying it so that it can keep the potassium in the hydrogen potassium ATPase pump in the nephron.​
tox cave salicylate.jpg

  • Administer IV fluids to achieve euvolemia and ensure adequate urinary output.
  • Hemodialysis (HD):
    • Intermittent HD is the preferred modality of extracorporeal treatment (ECTR).
    • Indications:
      • If salicylate >7.2 mmol/L (100 mg/dL)
      • If salicylate >6.5 mmol/L (90 mg/dL) in the presence of impaired kidney function
      • In the presence of altered mental status
      • In the presence of new hypoxemia requiring supplemental oxygen
    • It is recommended to continue IV bicarbonate between ECTR sessions.
  • Check salicylate level and repeat every one to two hours until two sequential downward trending levels have been obtained.
  • Frequent blood gas monitoring.

Pearls and Pitfalls

If intubation becomes necessary, consider administering an intravenous bolus of sodium bicarbonate prior to RSI. Maintaining hyperventilation is important to avoiding respiratory acidosis, which can lead to rapid clinical deterioration. These patients will precipitously decline after intubation because patients on mechanical ventilation have difficulty maintaining a respiratory rate similar to native breathing. Exhaust all possibilities prior to intubating these patients.

  • Pharmacobezoars, aspirin-induced pylorospasm, and enteric-coated tablets can delay absorption.
  • Ensure correct interpretation of salicylate concentrations—labs report different units, including mg/dL, mg/L, and mmol/L.

The patient was immediately started on a bicarbonate infusion. She became more altered while in the ED, and had a repeat salicylate level of 92 mg/dL. Nephrology was consulted for immediate hemodialysis. She was diaphoretic and somewhat agitated at this point. A dialysis catheter was placed, and the patient was transferred to the ICU for hemodialysis. A repeat salicylate level was 54 mg/dL, and the patient's mental status began to improve. She required another session of dialysis, and a repeat level was 20 mg/dL. Repeat consecutive levels were checked and decreasing appropriately. She improved and was sent to a step-down unit, and psychiatry was consulted.


1. J Med Toxicol. 2015;11(1):149.

2. Ann Emerg Med. 2003 Apr 1;41(4):583.

3. Ann Emerg Med. 2015 Aug 1;66(2):165.

Monday, July 2, 2018

A 24-year-old man presented with uncontrollable epistaxis. He said he had been bleeding "a ton" from his nose continuously for four hours. He denied recent trauma, and explained that this epistaxis was sudden onset. He had no past medical history, and denied previous episodes of excessive bleeding. An examination demonstrated no signs of trauma and was unremarkable aside from the epistaxis. His nostrils revealed no obvious bleeding vessels for cauterization. His social history was remarkable for occasional drinking, marijuana use, and recent use of synthetic marijuana.

His vital signs were a heart rate of 85 bpm, blood pressure of 135/80 mmHg, temperature of 98°F, and pulse oximetry of 100% on room air. Blood work revealed a hemoglobin of 13, hematocrit of 39, platelet of 250, PT of 35, INR of 8, and a PTT of 140.

Reports have recently been recounted of synthetic cannabinoids adulterated with brodifacoum, a long-acting vitamin K antagonist normally used in rat poison. More than 160 people presented to a U.S. health care facility between March and April 2018 with unexplained bleeding. Four fatalities were reported, all in Illinois. Lab testing confirmed the presence of brodifacoum in 18 people. Users described bleeding from their eyes and ears as well as heavy menstrual periods, frequent and severe nose bleeds, and gum bleeding.​

This outbreak appears to be from an unintentional adulteration of synthetic marijuana, but some reports have users intentionally smoking marijuana with brodifacoum for a greater high and to potentiate the effects of the illicit drug. The first report in the literature was a 17-year-old boy who presented to the ED with mucosal and skin bleeding, and was found to have a prolonged PT. (Arch Pathol Lab Med 1997;121[1]:67.) Another case reported a 37-year-old-man who smoked crack cocaine mixed with brodifacoum and presented with a severe coagulopathy. (N Engl J Med 2001;345[9]:700.)


Brodifacoum is a vitamin K antagonist similar to Coumadin but much longer acting. It is categorized as a superwarfarin, first introduced in 1975 for warfarin-resistant rodents.

                   Coumadin   Brodifacoum

Half-life        20-60 hrs      20-130 days

LD50                 3 mg/kg        0.27 mg/kg

Brodifacoum causes anticoagulation by inhibiting the action of vitamin K 2,3-epoxide reductase in the vitamin K cycle. The deficiency in active vitamin K leads to functionally inactive vitamin K-dependent coagulation factors II, VII, IX, IX, X, and proteins C and S. Acute symptoms are all associated with bleeding, and include hemoptysis, hematuria, GI bleeding, retroperitoneal hemorrhage, intracranial hemorrhage, and epistaxis.

Treating brodifacoum toxicity is similar to Coumadin reversal; vitamin K and PCC administration are the mainstays of treatment. Brodifacoum is more complicated because of the prolonged half-life and prolonged period of anticoagulation. Brodifacoum poisoning patients must first be divided into two groups to decide which treatment to give.

Unintentional Ingestions

These are generally children who present to the ED after accidentally eating a pellet of rat poisoning. These patients are generally just curious and exploring their environment; they tend to put a pellet in their mouth. They should be examined for active bleeding, and can be discharged home if there is none. Performing coagulation studies is unnecessary because the effects on the PT/INR from superwarfarins are delayed. These children should follow up with their doctors, but do not need laboratory testing unless they develop bleeding. Those patients who have active bleeding on presentation should have lab studies consisting of CBC, BMP, PT/INR, PTT, and type and screen.

Anticoagulation is reversed using PCC or oral vitamin K. Patients can be discharged if bleeding is controlled, but they need close follow-up for INR checks and repeat dosing of vitamin K until PT/INR levels normalize for several days without treatment.

Intentional Ingestions

These patients should be admitted and serial PT/INRs obtained because brodifacoum can cause delayed coagulopathy. PCC along with IV vitamin K should be administered for life-threatening bleeding. These patients should be given oral vitamin K starting at 50 mg three to four times a day for the first two days after bleeding is controlled. Oral vitamin K is continued for weeks, even months, until the INR normalizes even when bleeding has resolved.

The patient in our case was given PCC and vitamin K 10 mg IV. Nasal packing was placed, and his bleeding eventually stopped. He was admitted for observation, and given vitamin K 50 mg orally every six hours. His bleeding stopped on day two, but his INR remained elevated at 6. Brodifacoum levels were obtained and found to be 42 ng/ml. He was discharged home on hospital day three, and prescribed vitamin K 50 mg oral twice a day. He was also given strong bleeding precautions and advised to avoid any physical injury. He continued this treatment for several weeks until his INR levels normalized.

Suggested Readings:

1. Outbreak Alert: Potential Life-Threatening Vitamin K-Dependent Antagonist Coagulopathy Associated with Synthetic Cannabinoids Use. Centers for Disease Control and Prevention, April 5, 2018;

2. La Rosa FG, Clarke SH, Lefkowitz JB. Brodifacoum intoxication with marijuana smoking. Arch Path Lab Med 1997;121(1):67.

3. Waien SA, Hayes D Jr, Leonardo JM. Severe coagulopathy as a consequence of smoking crack cocaine laced with rodenticide. New Engl J Med 2001;345(9):700.

4. Spahr JE, Maul JS, Rodgers GM. Superwarfarin poisoning: A report of two cases and review of the literature. Am J Hematol 2007;82(7):656.

5. Outbreak Alert Update: Potential Life-Threatening Vitamin K-Dependent Antagonist Coagulopathy Associated with Synthetic Cannabinoids Use. Centers for Disease Control and Prevention, April 23, 2018;​

Friday, June 1, 2018

Social media influences nearly every part of our lives—how we communicate, teach, and protest. It is powerful because it allows people around the world to connect instantaneously. One of those ways is the social media phenomenon popular since the early 2000s: internet challenges. These challenges range from funny, like the mannequin challenge, to charitable, such as the ice-water bucket challenge, to dangerous, like the blue whale challenge. Several of these can cause injury by ingestion or topical application.​

The Tide Pod Challenge

Concerns of safety arose shortly after laundry pods were introduced in 2012 when unintentional pediatric exposures were reported. Young children developed significant toxicity, including caustic injuries, respiratory distress, altered mental status, and even death. Those prompted efforts to make this household item safer. Some of the changes included making the packaging opaque, making the containers child-safe, and adding a bittering agent to the outer film. More recently, the Tide Pod Challenge has promoted the ingestion of laundry pods. Teenagers would record themselves chewing and gagging on these pods and then daring others to do it.

tox tide pods.jpg

Austin Kirk​

The Cinnamon Challenge

The challenge here was to eat a spoonful of cinnamon in 60 seconds without drinking anything to wash it down. Cinnamon is a caustic irritant composed of cellulose fibers that may cause a hypersensitivity reaction and pulmonary inflammation. Symptoms include coughing, gagging, vomiting, throat and nasal irritation, and chest tightness. Cinnamon may cause irritation and lead to aspiration. A Michigan teenager was hospitalized for four days in 2013 from a collapsed lung and pneumonia caused by the cinnamon challenge, and a 4-year-old died in 2015 after ingesting cinnamon. He accidently inhaled the cinnamon and asphyxiated. Treatment is supportive, and may include bronchodilators in those with asthma. (Pediatrics 2013;131[5]:833; Medical Daily, June 9, 2015;

tox cinnamon.jpg

Wikimedia Commons​

The Nutmeg Challenge

The nutmeg challenge and nutmeg abuse involve ingesting or snorting nutmeg. It has been reported to produce a high. Nutmeg contains myristicin, an oil that acts as a deliriant. The mechanism of toxicity is not known, but may involve monoamine oxidase inhibition and conversion to amphetamine analogues. Symptoms include tachycardia, dry mouth, nausea, hallucinations, and delirium. Symptoms may last for 24 hours after a full dose of nutmeg, and are mostly described as unpleasant. Treatment is supportive with antiemetics, IV fluids, and benzodiazepines as needed.

tox nutmeg.jpg

Wikipedia Commons​

The Salt and Ice Challenge

The salt and ice challenge has users placing salt on the skin with ice placed over it for as long as possible. This causes a burning sensation, and the challenge is the length of time the pain is endured. This may lead to second- and third-degree burns. A 12-year-old boy was hospitalized in 2012 for severe second-degree burns on his back. (Photo of patient with burns on her hand from doing this challenge.) Treatment includes supportive care and topical antibiotics. Transfer to a burn center may be necessary if the burns are severe enough. (CBS News, June 7, 2012;

tox salt ice.jpg


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