Acute toxic ingestions are a common reason for presentation to the emergency department (ED) and clinical scenarios range from benign accidental ingestions to large overdoses resulting in hemodynamic instability. A wide variety of toxins cause hemodynamic instability, from cardiotoxic medication to plant-based toxins, and even inhaled substances.¹ In the ED, the most important consideration in management of these toxicities involves decontamination, evaluating for airway protection, and managing any hemodynamic instability.¹

Medications such as beta blockers, calcium channel blockers, and digoxin can cause cardiogenic shock secondary to decreased inotropic and chronotropic effects. If the ingestion was within the first hour, activated charcoal should be considered for gastrointestinal decontamination and may prevent progression of toxidrome. The dose is 25 mg- 100 mg for adults and 0.5 mg/kg-1 mg/kg with maximum dose of 50 mg in children.¹ Whole-bowel irrigation can be considered; however, it is not recommended in unstable patients or those at risk for aspiration.

Fluid resuscitation is the initial management of hypotension. However, it should be used with caution in patients with cardiogenic shock. One to two liters of crystalloid is a reasonable starting amount.^1,2 Reversal agents should be used for specific toxins such as digoxin immune fab for digoxin toxicity high-dose insulin for beta blocker toxicity, or calcium for calcium channel blocker toxicity.^2,3 Vasopressors, ideally norepinephrine or epinephrine, are the next step if fluid resuscitation and antidotes are not successful.^2,3

Atropine or temporary pacing can be used for treatment of bradycardia. Lipid emulsion can be used as an adjunct to therapy and can act to bind lipophilic substrates of toxins and expedite their excretion. In addition, it is proposed to improve fatty acid phosphorylation, adenosine triphosphate production, and decrease nitric oxide production, which reduces vasodilation.^4,5 Amlodipine and verapamil toxicity have been shown to be responsive to this treatment.⁶

Methylene blue is an additional adjunct that can inhibit formation of nitric oxide, thus increasing vascular tone and blood pressure.⁵ Finally, extracorporeal membrane oxygenation (ECMO) can be used temporarily if all other measures fail.¹ Some evidence suggests improved mortality in patients who received veno-arterial (VA) ECMO for refractory toxin-induced shock.⁷ During this time, consultation with a cardiologist, intensivist, and medical toxicologist is required.

Dysrhythmias from Toxin Ingestion

Dysrhythmias can also be associated with toxin ingestion leading to cardiogenic shock. For example, tricyclic antidepressant overdose can lead to sodium channel blockade, which can cause QRS widening. In addition to supportive measures, sodium bicarbonate should be given as an initial bolus of 50 milliequivalents (mEq) to 100 mEq (or one mEq/kg-two mEq/ kg ).⁷ A continuous sodium bicarbonate infusion can also be started at 150 mEq in 1 L D5W at 250 mL per hour over four hours after the initial bolus.⁷ Toxicity from selective serotonin reuptake inhibitors and antipsychotic medications can lead to corrected QT interval (QTc) prolongation, which can lead to torsades de pointes. Ideally, these patients should be treated with magnesium sulfate until QTc normalizes.¹

In addition, there is a growing abuse of tianeptine (street name “ZaZa”), which is an atypical tricyclic antidepressant. It also has opioid receptor agonism.⁸ Thus, patients will present with hypotension and respiratory depression with QRS widening. Treatment should include a combination of sodium bicarbonate and naloxone.⁸

Alpha-2 agonists such as xylazine and clonidine also have the potential for abuse. The primary mechanism for hypotension from these agents is direct vasodilation from the adrenergic alpha receptor blockade. Initial management of hypotension should include resuscitation with crystalloid fluid but these individuals may require vasopressor support to improve adrenergic activity at the alpha receptors.⁹ Vasopressor of choice should include norepinephrine or epinephrine. Finally, although xylazine is lipophilic, evidence of success in treating overdose with intralipid has not yet been shown.⁸

Hypotension from toxin ingestion could also be from hypovolemia from loss of fluids through vomiting or diarrhea. For instance, amanita mushroom toxicity specifically can cause large amounts of watery diarrhea, which can lead to hypovolemic shock.¹ Cholinergic toxicity can also lead to insensible fluid loss. Acetaminophen toxicity can also have a similar effect during stage two of disease. A combination of prolonged emesis and hepatic injury can lead to hypovolemia.¹⁰ Specific antidotes for each toxicity should also be given in addition to the management of hypotension. For example, Digibind should be given for digoxin toxicity.

Inhaled Toxins

Inhaled toxins such as cyanide, carbon monoxide, and arsenic can also cause hypotension. They present the unique challenge in decontamination. If there is concern for gastrointestinal ingestion, as in the case of cyanide and arsenic, activated charcoal should be utilized.⁵ Otherwise the individual should be physically washed and decontaminated in case there are remnants of the poison on clothes and skin.

Like the other toxins, treatment for hypotension includes supportive management and specific treatment with antidotes, if possible. In the case of cyanide, there is a halt in aerobic metabolism.¹¹ This can lead to build up of lactic acid and eventually cause tissue necrosis, and end-organ damage, including cardiogenic shock.

Treatment includes hydroxocobalamin or sodium thiosulfate with amyl nitrate (Cyanokit ®), which can help restore aerobic respiration. Hydroxocobalamin can also remove nitric oxide and improve vasoconstriction.⁵ Excessive carbon monoxide exposure can lead to cardiac ischemia from poor aerobic respiration. Management should include high oxygen therapy to improve oxygen saturation and consequently aerobic respiration.¹² If necessary, hyperbaric oxygen can be utilized. Finally, arsenic poisoning can lead to severe gastroenteritis that causes vomiting and diarrhea. This can precipitate hypovolemic shock. Consequently, as no specific antidote is available, aggressive fluid resuscitation is the mainstay of treatment.¹³

The treatment of toxic exposures causing hemodynamic instability can represent a unique clinical challenge in the ED. In general, the mainstay of treatment includes decontamination followed by reversal agents if available. While these are being prepared, or in cases where they do not exist, supportive care is paramount.

For hypotension, fluid resuscitation followed by the initiation of vasopressors is the mainstay. Consider and manage sodium blockade and QT prolongation in the case of cardiac dysrhythmias, such as those that develop in tricyclic antidepressant overdose. Finally, consider adjunctive therapy such as high-dose insulin therapy or lipid emulsion for beta blocker or calcium channel blocker toxicity. In the most severe of cases, VA ECMO may be considered. All these treatments are best utilized in conjunction with a medical toxicologist, when available, or by calling the national poison control network at 1-800-222-1222.

Dr. Shah is a PGY-3 resident at Penn State Milton S. Hershey Medical Center.

Dr. Johnson is an assistant professor of emergency medicine at the Penn State Milton S. Hershey Medical Center and College of Medicine.

References

   
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