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Arsenic Poisoning, Emergency Medicine

Basics

Description

- Arsenic exists in several forms-gas (arsine, or lewisite), organic, elemental, and inorganic - Inorganic forms (pentavalent and trivalent arsenic) are most frequently involved in toxic exposures: - Pentavalent arsenic uncouples oxidative phosphorylation - Most pentavalent arsenic is converted to the more toxic trivalent arsenic in the body - Trivalent arsenic binds sulfhydryl groups and interferes in hemoglobin production - Some trivalent arsenic may be methylated into species of varying toxicity - The more reactive species are DNA damaging and genotoxic

- Peripheral dysesthesias - Headache - Seizures

- Cardiovascular: - Prolonged QTc interval - Hypotension (acute) or hypertension (chronic) - Dysrhythmias, primarily ventricular - Nonspecific ST segment changes - Noncardiogenic pulmonary edema

- Pulmonary: - Inhalational exposure increases lung cancer risk and respiratory mortality - Large acute ingestion (8 mg/kg) may lead to severe respiratory distress - Pulmonary edema, hemorrhagic bronchitis, and bronchopneumonia

- GI: - Nausea, vomiting after ingestion and possibly inhalation - Protracted and may be refractory to antiemetics at usual doses - Can have hemorrhagic gastroenteritis; corrosive to GI tract

- Rice water diarrhea - Abdominal pain - Garlic odor to breath, vomit, stools - Causes acute hepatitis; chronically, can cause portal HTN - A possible association with diabetes mellitus in chronic exposure

- Miscellaneous (usually associated with chronic exposure) - Acute rhabdomyolysis - Blackfoot disease in Taiwan: Gangrene from loss of circulation to extremities - Dermatitis, such as toxic erythroderma and hyperkeratotic, hyperpigmented lesions - Hemolytic anemia (more pronounced with arsine gas exposure) - Hypothyroidism (antagonizes thyroid hormone) - Increased risk of carcinoma (liver/basal cell/squamous cell of skin/bronchogenic) - Leukopenia (after several days) - Mees lines (white bands across the nails owing to growth arrest caused by arsenic) - Patchy alopecia - Raynaud phenomenon and vasospasticity

- Chronic toxicity: - Addison disease - Guillain-Barr пїЅ syndrome or other neuropathy - Raynaud phenomenon - Thromboangiitis obliterans, or other vasculitides - Vitamin deficiency (B3, B6, or B12) - Wernicke-Korsakoff syndrome

- ABCs: - Cardiac monitor - Isotonic crystalloids as needed for hypotension

- Naloxone, thiamine, and dextrose (D50W) as indicated for altered mental status - Cardiovascular: - Vasopressors if refractory hypotension is present - Central venous pressure monitoring to prevent pulmonary/cerebral edema - Avoid type IA, IC and III antidysrhythmic agents, which worsen QTc prolongation - Continuous cardiac monitoring for QTc prolongation

- Neurologic: - Treat seizures with benzodiazepines - Assist ventilation for respiratory failure from neuromuscular weakness

- Decontamination: - Orogastric lavage or aspiration may be helpful within the 1st hr of ingestion - Activated charcoal does not bind arsenic - If opacities are seen on abdominal film, administer whole bowel irrigation (polyethylene glycol) at 1-2 L/hr until repeat radiographs are clear - If dermal exposure, decontaminate skin as 1st step in management

- Elimination: - Hemodialysis not routinely effective - Consider for patient with renal failure or other hemodialysis indications - Continue chelation throughout hemodialysis sessions

- Naloxone: 0.4-2.0 mg (peds: 0.1 mg/kg) IV, may repeat up to 10 mg for suspected opioid intoxication - Thiamine: 100 mg IM or IV (peds: 1 mg/kg) - Vasopressors after sufficient fluids - Dopamine 5 Ојg/kg/min, increase by 5-10 Ојg/kg/min (q10-30min) Max.: 20 Ојg/kg/min - Norepinephrine 0.01-3 Ојg/kg/min, start at 2 Ојg/min, titrate to MAP 65-90 mm Hg

  • Acute toxicity:Caused by intentional ingestion, malicious poisoning, or medication error
  • Minimal lethal ingested dose ~2 mg/kg
  • Chronic toxicity:Resulting from occupational exposures, water or food contamination, or use of folk remedies containing arsenic
  • Ingestion is the primary route of exposure
  • Inhalational toxicity is possible from arsine gas exposure

Etiology

  • Most cases seen in the ED result from intentional ingestion or malicious poisoning
  • Sodium arsenate, found in ant killer, is the most common acute exposure in the US
  • Contaminated food and water supplies are the most common cause worldwide
  • Inorganic arsenic trioxide has been recently approved as a chemotherapeutic agent for acute myelogenous leukemia (AML)
  • Melarsoprol, an organic arsenical, has been used to treat trypanosomiasis since 1949
  • Found in pesticides, certain folk remedies (herbal balls), industrial wood preservatives
  • May be released as arsine gas from combustion of zinc- and arsenic-containing compounds

Mechanism

  • Arsenic exists in several forms-gas (arsine, or lewisite), organic, elemental, and inorganic
  • Inorganic forms (pentavalent and trivalent arsenic) are most frequently involved in toxic exposures:Pentavalent arsenic uncouples oxidative phosphorylationMost pentavalent arsenic is converted to the more toxic trivalent arsenic in the bodyTrivalent arsenic binds sulfhydryl groups and interferes in hemoglobin productionSome trivalent arsenic may be methylated into species of varying toxicityThe more reactive species are DNA damaging and genotoxic

Diagnosis

Signs and Symptoms

  • CNS:Altered mental status/encephalopathyNeurodevelopmental deficits in childrenPeripheral neuropathyAcute: Sensory neuropathySubacute: Sensorimotor neuropathyPeripheral dysesthesiasHeadacheSeizures
  • Cardiovascular:Prolonged QTc intervalHypotension (acute) or hypertension (chronic)Dysrhythmias, primarily ventricularNonspecific ST segment changesNoncardiogenic pulmonary edema
  • Pulmonary:Inhalational exposure increases lung cancer risk and respiratory mortalityLarge acute ingestion (8 mg/kg) may lead to severe respiratory distressPulmonary edema, hemorrhagic bronchitis, and bronchopneumonia
  • GI:Nausea, vomiting after ingestion and possibly inhalationProtracted and may be refractory to antiemetics at usual dosesCan have hemorrhagic gastroenteritis; corrosive to GI tractRice water diarrheaAbdominal painGarlic odor to breath, vomit, stoolsCauses acute hepatitis; chronically, can cause portal HTNA possible association with diabetes mellitus in chronic exposure
  • Miscellaneous (usually associated with chronic exposure)Acute rhabdomyolysisBlackfoot disease in Taiwan: Gangrene from loss of circulation to extremitiesDermatitis, such as toxic erythroderma and hyperkeratotic, hyperpigmented lesionsHemolytic anemia (more pronounced with arsine gas exposure)Hypothyroidism (antagonizes thyroid hormone)Increased risk of carcinoma (liver/basal cell/squamous cell of skin/bronchogenic)Leukopenia (after several days)Mees lines (white bands across the nails owing to growth arrest caused by arsenic)Patchy alopeciaRaynaud phenomenon and vasospasticity

Essential Workup

  • Spot urine arsenic level
  • CBC

Diagnosis Tests & Interpretation

Lab

  • Spot urine arsenic level >1,000 Ојg/L may confirm diagnostic suspicion:Peaks 10-50 hr postingestion
  • Definitive test is 24 hr urine collection with speciation into organic and inorganic types of arsenic.
  • Blood levels not routinely helpful owing to short half-life in serum (~2 hr)
  • CBC to evaluate for anemia, leukopenia, basophilic stippling
  • Electrolytes, BUN/creatinine, and glucose
  • Urinalysis to look for evidence of hemolysis/rhabdomyolysis
  • Liver function tests
  • Total creatine phosphokinase (CPK) for rhabdomyolysis
  • Hair and nail arsenic levels:Do not help in acute settingMay help determine chronicity of exposure in select populations

Imaging

  • Plain abdominal radiographs to look for radiopaque foreign body
  • Cranial CT/other studies as indicated by patients condition

Differential Diagnosis

  • Acute toxicity:Acute appendicitis/colitis/gastroenteritisCeliac diseaseCholeraDistributive shockEncephalopathyToxic ingestionsAmanita mushroom poisoningCyclic antidepressants or other seizure-inducing toxinsOrganophosphates
  • Chronic toxicity:Addison diseaseGuillain-Barr пїЅ syndrome or other neuropathyRaynaud phenomenonThromboangiitis obliterans, or other vasculitidesVitamin deficiency (B3, B6, or B12)Wernicke-Korsakoff syndrome

Treatment

Pre-Hospital

  • If possible to do so safely, bring containers in suspected overdose/poisoning.
  • Decontaminate skin.
  • Support airway/breathing/circulation.
  • Cardiac monitoring

Initial Stabilization/Therapy

  • ABCs:Cardiac monitorIsotonic crystalloids as needed for hypotension
  • Naloxone, thiamine, and dextrose (D50W) as indicated for altered mental status
  • Cardiovascular:Vasopressors if refractory hypotension is presentCentral venous pressure monitoring to prevent pulmonary/cerebral edemaAvoid type IA, IC and III antidysrhythmic agents, which worsen QTc prolongationContinuous cardiac monitoring for QTc prolongation
  • Neurologic:Treat seizures with benzodiazepinesAssist ventilation for respiratory failure from neuromuscular weakness
  • Renal:Hemodialysis for renal failure
  • Alimentary:Dextrose, enteral or parenteral feeding may be beneficial

Ed Treatment/Procedures

  • Decontamination:Orogastric lavage or aspiration may be helpful within the 1st hr of ingestionActivated charcoal does not bind arsenicIf opacities are seen on abdominal film, administer whole bowel irrigation (polyethylene glycol) at 1-2 L/hr until repeat radiographs are clearIf dermal exposure, decontaminate skin as 1st step in management
  • Ensure that no one else is contaminated and environment is evaluated
  • Ensure that electrolytes such as calcium, magnesium, and potassium are replaced
  • Evaluate need for chelation therapy, based on levels, acuity of exposure, clinical symptoms:Consult with medical toxicologist/poison centerAgentsDimercaprol (British anti-Lewisite)DMSA (succimer)
  • Elimination:Hemodialysis not routinely effectiveConsider for patient with renal failure or other hemodialysis indicationsContinue chelation throughout hemodialysis sessions

Medication

  • Dimercaprol (British anti-Lewisite): 3 mg/kg deep IM q4h for 24 h, then q6h for the next 24 h, then q12h until able to tolerate POCaution: Contraindicated in patients with peanut allergies
  • Dextrose 50%: 25 g (50 mL) (peds: 0.5 g/kg D25W) IV for hypoglycemia
  • DMSA (succimer): 10 mg/kg PO q8h for 5 d, then q12h for 14 d
  • Sodium bicarbonate: 1 mEq/kg IV bolus, followed by infusion of 150 mEq in 1 L of D5W at 150 mL/hUsed to treat rhabdomyolysisEnsure that potassium and other electrolytes are monitored and replaced during infusion
  • Naloxone: 0.4-2.0 mg (peds: 0.1 mg/kg) IV, may repeat up to 10 mg for suspected opioid intoxication
  • Thiamine: 100 mg IM or IV (peds: 1 mg/kg)
  • Vasopressors after sufficient fluidsDopamine 5 Ојg/kg/min, increase by 5-10 Ојg/kg/min (q10-30min) Max.: 20 Ојg/kg/minNorepinephrine 0.01-3 Ојg/kg/min, start at 2 Ојg/min, titrate to MAP 65-90 mm Hg
  • Max.: 20 Ојg/min

Follow-Up

Disposition

Admission Criteria

Symptomatic arsenic exposures should be admitted to an intensive care setting. пїЅ

Discharge Criteria

  • Asymptomatic patients with a spot urinary arsenic level <50 Ојg/L may be discharged
  • Suspected chronic exposures who do not require admission should be referred for outpatient evaluation and 24 hr urine collection
  • Ensure that home environment is safe for patient prior to discharge

Follow-Up Recommendations

  • Psychiatric follow-up for intentional overdoses
  • Primary care follow-up for cancer screening and monitoring

Pearls and Pitfalls

  • Arsenic poisoning results in a myriad of signs and symptomsSuspect acute arsenic poisoning when patients present with gastrointestinal distress and neurologic findings.Suspect chronic arsenic poisoning in patients who present with neurologic deficits, nonspecific wasting, and hyperkeratotic skin lesions.
  • Consult a medical toxicologist/poison center regarding the need for chelation therapy.

A special thanks goes to Dr. Gerald Maloney Jr, who contributed to the previous edition. пїЅ

Additional Reading

  • Agency for Toxic Substances and Disease Registry. Toxicologic Profile for Arsenic. US Department of Health and Human Services. August 2007.
  • Chen пїЅY, Parvez пїЅF, Gamble пїЅM, et al. Arsenic exposure at low-to-moderate levels and skin lesions, arsenic metabolism, neurological functions, and biomarkers for respiratory and cardiovascular diseases: Review of recent findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh. Toxicol Appl Pharmacol. 2009;239:184-192.
  • Hughes пїЅMF, Beck пїЅBD, Chen пїЅY, et al. Arsenic exposure and toxicology: A historical perspective. Toxicol Sci. 2011;123(2):305-332.
  • Munday пїЅSW, Ford пїЅM. Arsenic. In: Goldfranks Toxicologic Emergencies. 9th ed. New York, NY: McGraw-Hill; 2010.
  • Tournel пїЅG, Houssaye пїЅC, Humbert пїЅL, et al. Acute arsenic poisoning: Clinical, toxicological, histopathological, and forensic features. J Forensic Sci. 2011;56(suppl 1):S275-S279.

Codes

ICD9

985.1 Toxic effect of arsenic and its compounds пїЅ

ICD10

  • T57.0X1A Toxic effect of arsenic and its compounds, accidental (unintentional), initial encounter
  • T57.0X2A Toxic effect of arsenic and its compounds, intentional self-harm, initial encounter
  • T57.0X3A Toxic effect of arsenic and its compounds, assault, initial encounter
  • T57.0X4A Toxic effect of arsenic and its compounds, undetermined, initial encounter

SNOMED

  • 81844008 Toxic effect of arsenic AND/OR its compounds (disorder)
  • 216792005 Accidental poisoning by arsenic and its compounds and fumes (event)
  • 219123000 Self poisoning by arsenic or its compounds (disorder)
  • 418685002 Poisoning by arsenic or its compounds of undetermined intent (disorder)