Basics
Description
- 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 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
Diagnosis
Signs and Symptoms
- CNS:
- Altered mental status/encephalopathy
- Neurodevelopmental deficits in children
- Peripheral neuropathy
- Acute: Sensory neuropathy
- Subacute: Sensorimotor neuropathy
- 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
Essential Workup
- Spot urine arsenic level
- CBC
Diagnosis Tests & Interpretation
Lab
- Spot urine arsenic level >1,000 μg/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 setting
- May 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/gastroenteritis
- Celiac disease
- Cholera
- Distributive shock
- Encephalopathy
- Toxic ingestions
- Amanita mushroom poisoning
- Cyclic antidepressants or other seizure-inducing toxins
- Organophosphates
- Chronic toxicity:
- Addison disease
- Guillain-Barr � syndrome or other neuropathy
- Raynaud phenomenon
- Thromboangiitis obliterans, or other vasculitides
- Vitamin 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 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
- 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 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
- 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 center
- Agents
- Dimercaprol (British anti-Lewisite)
- DMSA (succimer)
- Elimination:
- Hemodialysis not routinely effective
- Consider for patient with renal failure or other hemodialysis indications
- Continue 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 PO
- Caution: 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/h
- Used to treat rhabdomyolysis
- Ensure 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 fluids
- Dopamine 5 μg/kg/min, increase by 5-10 μg/kg/min (q10-30min) Max.: 20 μg/kg/min
- Norepinephrine 0.01-3 μg/kg/min, start at 2 μg/min, titrate to MAP 65-90 mm Hg
- Max.: 20 μg/min
Follow-Up
Disposition
Admission Criteria
Symptomatic arsenic exposures should be admitted to an intensive care setting. �
Discharge Criteria
- Asymptomatic patients with a spot urinary arsenic level <50 μg/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 symptoms
- Suspect 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. �
Additional Reading
- Agency for Toxic Substances and Disease Registry. Toxicologic Profile for Arsenic. US Department of Health and Human Services. August 2007.
- Chen �Y, Parvez �F, Gamble �M, 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 �MF, Beck �BD, Chen �Y, et al. Arsenic exposure and toxicology: A historical perspective. Toxicol Sci. 2011;123(2):305-332.
- Munday �SW, Ford �M. Arsenic. In: Goldfranks Toxicologic Emergencies. 9th ed. New York, NY: McGraw-Hill; 2010.
- Tournel �G, Houssaye �C, Humbert �L, 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 �
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)