Version July 2025
INTRODUCTION —
Acute high-dose exposure to arsenic, a metalloid element, can cause severe systemic toxicity and death. Acute inorganic arsenic exposure should be on the differential diagnosis of a patient with abdominal pain, nausea, vomiting, and profuse diarrhea, particularly with concomitant cardiovascular dysfunction and encephalopathy [1]. Arsenic has been used as a homicidal and suicidal poison for centuries and is referred to as the "king of poisons" and the "poison of kings" [2-4]. Arsenic has been involved in mass poisonings, including bread in Hong Kong (1857), beer in Staffordshire, England (1900), curry in Wakayama, Japan (1998), and church coffee in New Sweden, Maine, United States (2003) [1,2]. Arsine gas is a rare, highly toxic form of occupational arsenic exposure that can cause massive hemolysis and multiorgan failure.
This topic discusses evaluation and management of patients with acute arsenic and arsine gas exposure and poisoning.
●Chronic arsenic exposure can result in chronic toxicity that can include skin changes, skin and other cancers, peripheral sensorimotor neuropathy, diabetes mellitus, cardiovascular effects, peripheral vascular disease, and hepatotoxicity; the evaluation and management is discussed elsewhere. (See "Arsenic exposure and chronic poisoning".)
●The general evaluation and management of the poisoned patient is discussed elsewhere. (See "General approach to drug poisoning in adults" and "Approach to the child with occult toxic exposure" and "Initial management of the critically ill adult with an unknown overdose".)
TOXICOLOGY AND SOURCES OF EXPOSURE OF ARSENIC AND ARSINE —
The toxicity of an arsenical compound depends on arsenic's valence and complexed chemical structures. Trivalent arsenicals avidly bind to sulfhydryl groups on proteins, glutathione, and cysteine and interfere with enzyme systems involved in cellular respiration (inhibiting pyruvate dehydrogenase), gluconeogenesis and glucose uptake, and glutathione metabolism [1]. Pentavalent arsenicals interfere with adenosine triphosphate production during glycolysis and oxidative phosphorylation. Approximately 50 to 70 percent of pentavalent arsenic will be reduced to trivalent [1]. Primary target organs for organic and inorganic arsenic are the gastrointestinal tract, skin, bone marrow, kidneys, and the central and peripheral nervous systems. The pharmacology of arsenic exposure is discussed in detail separately. (See "Arsenic exposure and chronic poisoning", section on 'Pathophysiology of arsenic toxicity'.)
Acute high-dose exposure to inorganic and toxic forms of organic (eg, melarsoprol) arsenic tends to be intentional and occurs much less often compared with chronic exposures, which are typically environmental or occupational. Acute exposure has been reported with intentional or accidental poisoning (often with homicidal intent) with arsenic trioxide-containing pesticides or rodenticide bait [1]. Fatalities from contamination of herbal and folk remedies have been reported [5]. Acute toxicity can also occur occupationally from acute inhalation of dust or fumes with high levels of arsenic. Acute oral exposure to inorganic arsenic at doses of 600 mcg per kg body weight per day or higher has resulted in death [6]. The LD50 of arsenic trioxide has been reported as 14 mg/kg [4]. Sources of arsenic exposure are discussed further separately. (See "Arsenic exposure and chronic poisoning", section on 'Sources of exposure and regulatory limits'.)
Chronic arsenic exposure is more common and typically occurs from drinking water, dietary ingestion (eg, rice products, herbal remedies, folk medicines), and occupational exposures (eg, smelting and refining). Sources of arsenic exposure and regulatory limits are discussed in detail separately. (See "Arsenic exposure and chronic poisoning", section on 'Sources of exposure and regulatory limits'.)
Arsenic trioxide (ATO) is used to treat acute promyelocytic leukemia at doses ≤0.3 mg/kg/day. In therapeutic dosing, plasma total arsenic concentrations are typically 10 to 55 ng/mL [7]. (See "Initial treatment of acute promyelocytic leukemia in adults", section on 'ATO plus ATRA'.)
Arsine (AsH3) gas is colorless, nonirritating, water-soluble, and can have a garlic or fishy odor [8,9]. Arsine gas preferentially binds to hemoglobin and is oxidized to hemolytic agents (arsenic dihydride and elemental arsenic). Arsine depletes glutathione stores. Renal tubular destruction occurs from hemoglobin and haptoglobin complexed with arsine deposits. Compared with other forms of arsenic exposure, acute intravascular hemolysis is a unique toxicity of arsine gas. Exposure is typically from inhalation following unexpected industrial reactions that produce arsine gas, such as acid application to arsenic-containing ores or metals. Examples of occupational settings include ore refining and semiconductor, computer chip, and fiberoptic manufacturing. Multiple patients could seek care if all were exposed in an enclosed space.
CLINICAL FEATURES OF ACUTE TOXICITY
Immediate onset manifestations — Gastrointestinal symptoms following acute ingestion of inorganic arsenic may develop within minutes or hours. With severe toxicity, after hours to several days, multiorgan dysfunction gradually develops and can peak one to two weeks after ingestion [10]. With less severe illness, the gastrointestinal symptoms (possibly associated with mild hypotension or a dry, hacking cough) can persist for several days without development of the multisystem illness.
Gastrointestinal — Acute arsenic toxicity starts with gastrointestinal symptoms, including nausea, vomiting, abdominal pain, and profuse watery diarrhea [1]. Intravascular volume depletion and hypotension are common. In severely poisoned patients, there may be a garlic odor of the breath and stool [11]. In a case report, severe rice-watery diarrhea followed by abdominal pain, nausea, and pancreatitis was likely related to acute arsenic toxicity from an excessive dose of arsenic trioxide during induction therapy for acute promyelocytic leukemia [12].
Less severely acutely poisoned patients may experience a metallic taste and irritated mucous membranes that can mimic pharyngitis.
Multiorgan dysfunction — Multiorgan illness can include vasodilatory shock, myocardial dysfunction, central nervous system (CNS) toxicity, acute respiratory distress syndrome, acute kidney injury, hepatitis, pancreatitis, and rhabdomyolysis [10]. Proteinuria, hematuria, acute tubular necrosis, and anuria can accompany the acute kidney injury [6,11]. In some cases, acute encephalopathy can develop and progress over several days, with delirium, coma, and seizures [1,13].
Dysrhythmias — Acute arsenic poisoning can cause QTc interval prolongation and ventricular dysrhythmias (ie, torsades de pointes) [14]. In severe cases, patients may experience bradycardia, asystole, or cardiovascular collapse [1,11,15,16].
Rashes — Rashes can occur during the acute stage (ie, days) of the exposure and weeks to months afterwards. In the acute stage, pruritic maculopapular eruptions (sometimes in intertriginous areas), transient flushing erythema, facial edema, and miliaria have been described [17,18].
Subacute-onset skin and nail changes are discussed below. (See 'Rashes and nail changes' below.)
Hemolysis, hematuria (arsine gas) — A triad of abdominal pain, hematuria, and jaundice has been described as characteristic of arsine poisoning. Following a significant arsine gas exposure, hemolysis and other symptoms typically develop after a delay of 2 to 20 hours [9,19]. Symptom severity is typically related to the degree of exposure, although differences in individual susceptibility have been reported. Patients initially develop headache, abdominal pain, flank/back pain, nausea, vomiting, malaise, generalized weakness, dizziness, and dyspnea. Hematuria is typically noticed four to six hours after exposure. Subsequent findings can include oliguria/anuria, jaundice, anasarca, dyspnea, cyanosis, hypotension, or altered mental status. Urine can have brown, red, or black discoloration (described as "tea-colored") and the skin can develop a reddish bronze tint [8,20].
Hemolysis can last three to four days; acute kidney injury is commonly reported in patients who develop massive hemolysis. Severe toxicity can include multiorgan failure, acute respiratory distress syndrome, liver injury, shock, and cardiovascular collapse [21].
Individuals who survive the acute hemolysis and multiorgan failure have been reported to subsequently develop arsenic-induced peripheral neuropathy and cutaneous manifestations (eg, desquamation and Mees' lines) [20,22,23].
A patient may be unaware of the exposure, especially if at a lower dose, since symptoms may not develop for up to 24 hours and are initially nonspecific (eg, headache, malaise, nausea, abdominal or flank pain) [8,24]. Some experts define mild arsine gas toxicity as the presence of nonspecific symptoms and/or mild hemolysis without oliguria [19].
Subacute onset manifestations — If a patient severely poisoned with inorganic arsenic survives the initial illness, they can develop subacute-onset signs and symptoms, including peripheral neuropathy, headaches, confusion, irritability, memory problems, sixth cranial nerve palsy, sensorineural hearing loss, cough, hemoptysis, pulmonary infiltrates, pancytopenia, and skin and nail changes [1].
Peripheral neuropathy — Patients usually develop a painful sensorimotor peripheral neuropathy one to three weeks after acute poisoning. This has been described as beginning with distal paresthesias, followed rapidly by an ascending sensory loss and weakness, which can sometimes mimic Guillain-Barré syndrome [1,25-29]. This is similar to the neuropathy that develops with chronic low-level exposure. (See "Arsenic exposure and chronic poisoning", section on 'Neurologic'.)
Partial recovery from peripheral neuropathy can occur in some cases, especially in the more mild cases of poisoning [27,30].
Hepatitis, pancytopenia — Patients usually develop hepatitis and pancytopenia within a week. The hematologic changes are usually reversible once exposure ceases.
Rashes and nail changes — The following skin and nail changes can develop weeks to months following an acute exposure [1,17,18,28,31,32]:
●Patchy alopecia
●Mees lines (also called transverse leukonychia) – horizontal 1 to 2 mm white lines on the nails that occur from a disturbance in the nail matrix keratinization and typically become visible 30 days after the poisoning (picture 1)
●Beau's lines (horizontal nail ridges) and nail dystrophy
●Periungual pigmentation or total leukonychia
●Acral hyperkeratosis and lamellar desquamation
●Herpetic-like mouth ulcers
Latent manifestations — Severely poisoned patients are also at risk for developing the latent effects associated with chronic arsenic toxicity (eg, cancer), which are discussed separately. (See "Arsenic exposure and chronic poisoning", section on 'Clinical features and latent effects of chronic exposure'.)
DIAGNOSTIC EVALUATION
History — A history or suspicion of exposure or ingestion of an arsenic-containing product is critical to the evaluation since blood or urine arsenic concentrations do not result rapidly, and the immediate onset clinical manifestations are similar to other conditions. A history may need to be obtained from close contacts, co-workers, or emergency medical personnel if the patient is critically ill. The following questions may be helpful:
●Do other individuals in close proximity or at the same workplace have similar symptoms?
●If workplace exposure occurred, were there any odors (eg, garlic, fishy)? If there was an accident with a chemical reaction, were the substrates or products known? However, the lack of a reported odor does not exclude a potentially significant arsine gas exposure.
●In a patient with an intentional ingestion, what was the arsenic species and concentration in the product? Was there an empty bottle found at the scene?
The diagnosis may be straightforward by the time a patient develops acute or subacute-onset manifestations. However, if the patient's first presentation for medical attention is for the subacute-onset manifestations, it is important to ask if there was a preceding gastrointestinal illness. The gastrointestinal illness may not be present if the arsenic poisoning was only low-dose. (See "Arsenic exposure and chronic poisoning", section on 'Clinical features and latent effects of chronic exposure'.)
Arsenic concentrations — In a patient with concern for acute arsenic or arsine gas toxicity, a urine or blood concentration should be obtained, but if the clinical presentation and history are highly suspicious, treatment should be started urgently prior to the return of the test results. Arsenic concentration testing is discussed in detail separately. (See "Arsenic exposure and chronic poisoning", section on 'Arsenic concentrations'.)
In an acutely-ill patient, we obtain a spot urine arsenic concentration. The laboratory should be instructed to speciate the sample in order to measure the toxic (inorganic) species. A spot urine creatinine (Cr) should also be obtained to correct for urine concentration. If the exposure was suspected to have just occurred (ie, within hours), a blood arsenic concentration may be useful but can be artefactually elevated from recent ingestion of dietary nontoxic forms (eg, fish, shellfish). In general, measurement of inorganic arsenic concentration in urine is preferable to blood because blood arsenic is cleared rapidly into the tissues.
In an acutely symptomatic patient, the urine inorganic arsenic concentration is usually >1000 mcg/L. Since some small exposure to arsenic from daily life is expected, comparing the patient's result with the population background mean concentrations can help determine if a concentration is elevated. For example, in the United States, the 95th percentile of urine inorganic arsenic species, which includes both inorganic arsenic as well as the inorganic metabolites (creatinine corrected) is 15.1 mcg/gram creatinine [33]. Population levels are discussed in greater detail separately. (See "Arsenic exposure and chronic poisoning", section on 'Urine'.)
Diagnosis — The diagnosis of acute arsenic toxicity is suspected in a patient with characteristic signs and symptoms of toxicity (eg, vomiting, diarrhea, vasodilatory shock, dysrhythmias, multiorgan dysfunction, and/or encephalopathy) and a history of inorganic arsenic-containing product exposure or overdose. The key to the diagnosis of arsenic poisoning rests in the history of ingestion or clues that suggest exposure to arsenic. Without the history of exposure, the diagnosis is often not suspected since it can mimic more common conditions (eg, gastroenteritis, sepsis). The diagnosis is confirmed by an elevated urine inorganic arsenic concentration.
The diagnosis of arsine gas poisoning is suspected in a patient with abdominal pain, hematuria, hemolysis, and/or jaundice following an industrial accident or other incident. The diagnosis is confirmed by an elevated urine inorganic arsenic concentration. Hematological testing consistent with intravascular hemolysis (ie, poikilocytosis, anisocytosis, fragmented erythrocytes, reticulocytosis) and urinalysis demonstrating hematuria supports the diagnosis. (See "Diagnosis of hemolytic anemia in adults".)
Ancillary studies — We obtain the following in a patient with suspected acute arsenic toxicity to determine the degree of poisoning:
●Laboratory tests – We obtain a complete blood count, tests of kidney and liver function, troponin, lactate, and a urinalysis. Serial testing is required since many become abnormal days to weeks following an acute exposure.
●Radiographs – Abdominal radiographs may demonstrate gastrointestinal radiopaque material soon after ingestion, although the absence of opaque material does not rule out exposure. A chest radiograph should be obtained in any patient with respiratory symptoms.
●Electrocardiogram (ECG) – This should be obtained to assess the QTc interval.
DIFFERENTIAL DIAGNOSIS —
The differential diagnosis of acute arsenic toxicity includes other conditions associated with vomiting and diarrhea, such as infectious (eg, cholera) or food-born gastrointestinal illness. A mass arsenic poisoning scenario can mimic a viral gastroenteritis outbreak. Compared with gastroenteritis, arsenic-induced vomiting does not typically improve with antiemetic medications, hypotension does not resolve with intravenous crystalloid, and QTc interval prolongation can occur. The gastrointestinal symptoms persist longer than with typical viral gastroenteritis. (See "Approach to the adult with acute diarrhea in resource-abundant settings" and "Diagnostic approach to diarrhea in children in resource-abundant settings".)
The differential diagnosis of acute arsenic toxicity can also include the following:
●Conditions that cause vasodilatory shock and inflammation-related myocardial dysfunction, such as sepsis or pancreatitis. (See "Definition, classification, etiology, and pathophysiology of shock in adults", section on 'Combined'.)
●Microtubular toxins (eg, colchicine, autumn crocus) or processes that inhibit turnover of highly proliferative cells (eg, acute radiation exposure), which can cause leukopenia in addition to vomiting, diarrhea, and multisystem organ failure. (See "Potentially toxic plant ingestions in children: Clinical manifestations and evaluation", section on 'Gastroenteritis with systemic toxicity' and "Clinical manifestations, evaluation, and diagnosis of acute radiation exposure", section on 'Clinical manifestations'.)
●Poisoning from thallium, found in a rodenticide banned in the United States but available in many other countries, as well as available in supplements and internet products, can present with abdominal pain, vomiting, diarrhea, and progress to painful neuropathy and multisystem organ failure. Widespread alopecia occurs (frequently with hair roots turning an orange-brown color) over two to three weeks but classically spares the inner third of the eyebrows. (See "Overview of rodenticide poisoning", section on 'Thallium'.)
The differential diagnosis of arsine gas poisoning includes conditions that cause massive intravascular hemolysis, such as clostridial sepsis (see "Diagnosis of hemolytic anemia in adults", section on 'Intravascular hemolysis'). Stibine (antimony trihydride) is a colorless gas with a rotten-egg odor that has similar toxicity to arsine [34,35]. Stibine can be produced when an acid reacts with an antimony-containing metal or when a highly electropositive metal (eg, aluminum) reacts with water [36]. Exposure is rare and may occur in workers in battery-forming areas of lead-storage battery plants [37].
MANAGEMENT
Immediate-onset symptoms with known or suspected exposure — Acute arsenic toxicity can be life-threatening, requiring urgent assessment of the exposure (eg, dose, timing), elimination of any further exposure, aggressive cardiopulmonary support, and possible administration of chelation therapy. Since arsenic concentration results are typically not immediately available, treatment decisions must be based on the history, physical examination, and the degree of clinical toxicity and suspicion for arsenic poisoning [1,38].
In a patient suspected of acute arsenic poisoning, consultation with a regional poison center, clinical toxicologist, or regional Pediatric Environmental Health Specialty Units (for pediatric poisoning in the United States) is recommended to guide management. (See 'Regional poison centers' below and 'Regional Pediatric Environmental Health Specialty Units' below.)
Supportive care — A patient with suspected acute arsenic toxicity requires aggressive supportive care, typically in an intensive care unit. Supportive management of critically-ill patients with suspected poisoning are discussed separately. (See "Initial management of the critically ill adult with an unknown overdose" and "Approach to the child with occult toxic exposure".)
Fluid balance and electrolytes require close monitoring since cerebral edema, pulmonary edema, and QTc interval prolongation with dysrhythmias are known complications. Serum potassium, magnesium, and ionized calcium concentrations should be monitored and repleted to minimize QTc prolongation. If signs of cerebral or pulmonary edema develop, further intravenous fluids should be withheld and vasopressors initiated for blood pressure support. Vasopressor infusion may be necessary for refractory hypotension or shock. There is a report of extracorporeal membrane oxygenation (ECMO) for cardiovascular support [6]. (See "Use of vasopressors and inotropes" and "Extracorporeal life support in adults in the intensive care unit: Overview".)
Medications that prolong the QTc interval (table 1) should be avoided when possible. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes", section on 'Drugs that prolong the QT interval'.)
Ventricular dysrhythmias may develop and should be treated with standard protocols. (See "Overview of the acute management of tachyarrhythmias", section on 'Wide QRS complex tachyarrhythmias'.)
Role of decontamination
●Dermal – Skin decontamination is particularly important in cases of poisoning from arsenical pesticides. Arsenic can be removed with soap, water, and scrubbing the skin. Remove contaminated clothing and wash the pesticide from the skin and hair taking care to avoid contaminating medical personnel [11]. A patient with known arsine gas exposure does not need decontamination.
●Gastrointestinal (GI) – Since arsenic is rapidly absorbed and causes vomiting and profuse diarrhea, there is typically no role for decontamination of the GI tract. In a patient who presents within 30 to 60 minutes after ingestion of concentrated arsenic-containing liquid compounds, nasogastric aspiration may be attempted to decrease the absorbed dose.
Some experts suggest a single dose of activated charcoal (in conjunction with airway protection in patients with a decreased level of alertness) when even a small amount of absorption of an arsenical compound might be beneficial [1]. However, evidence for benefit is limited, and charcoal administration is often precluded by the extent of GI symptoms.
In a patient with radiopaque material visualized in the GI tract on abdominal radiographs, some experts suggest administering whole-bowel irrigation (WBI) until the material is no longer seen on repeat radiographs, but this requires careful monitoring of serum electrolytes and fluid status [1]. WBI may not be necessary if the patient is already having profuse diarrhea. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Whole bowel irrigation'.)
Chelation for symptomatic patients
Critically-ill — In addition to the supportive care, in a patient who is critically ill from suspected or confirmed acute arsenic poisoning (eg, lethargy, coma, seizures, ventricular dysrhythmias, or shock), we recommend parenteral chelation [1,38-41]. Chelation is most effective when started as soon as possible after arsenic exposure; delaying chelation decreases its efficacy [38,42]. In a patient with signs and symptoms highly suspicious for acute arsenic poisoning, even in the absence of a known exposure, we start chelation before laboratory confirmation of arsenic concentrations is available [1,38].
Options for parenteral chelation include unithiol (sodium 2,3-dimercapto-1-propane sulfonate [DMPS]) or dimercaprol (British Anti-Lewisite [BAL]) (table 2). However, DMPS is not approved by the United States (US) Food and Drug Administration and BAL is not being manufactured. If DMPS is available, it is preferable to BAL because it causes fewer adverse effects and does not redistribute arsenic to the brain [38,39]. DMPS is available in some countries (eg, Germany) and has been used off-label in the US [6,43]. If no parenteral chelator is available, using an oral chelator such as DMSA (meso-2,3-dimercaptosuccinic acid [succimer]), possibly administered via nasogastric tube, can be attempted.
BAL had been used historically if DMPS was unavailable [1]. BAL has not been manufactured for more than one year. If stock is available, evidence is lacking regarding the stability and efficacy of BAL after expiration. Although BAL increased the elimination of arsenic and may have helped to inhibit or reverse some of the toxic effects, it is unclear if it prevented the development of peripheral neuropathy or any residual CNS changes. BAL was associated with significant dose-related, adverse effects, had a narrow therapeutic index, caused febrile reactions and sterile abscesses, increased risk of hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, and had to be used cautiously in patients with known peanut allergy because it was formulated in peanut oil [1,38]. Animal evidence suggests that BAL shifted arsenic into the brain and could thus worsen encephalopathy or provoke seizures. BAL may have been minimally effective in the presence of arsenic-induced hepatotoxicity [39].
Once a patient receiving parenteral chelation is able to take an oral medication, we suggest transitioning to either DMSA or oral DMPS, if available [1,38,40,41,44].
Evidence supporting benefit for chelation is from several uncontrolled studies and animal studies that demonstrate survival from lethal inorganic arsenic exposure when BAL, DMPS, or DMSA are given promptly [39,42,45]. For example, a study of 55 patients with encephalopathy from arsenical syphilis treatment found that treatment with BAL was associated with an overall mortality rate of only 11 percent [42]. In 33 patients with severe encephalopathy (eg, coma, seizures), early treatment with BAL was associated with lower mortality; the mortality rate was 25 percent (6/24) when BAL was started within six hours of symptom onset compared with 55 percent (5/9) when BAL was started more than nine hours (mean 30 hours) after symptom onset. In addition, case series and case reports describe clearance of arsenic from the blood and urine, reversal of acute toxicity, and improved survival despite very high urine and blood arsenic concentrations [6,45-47]. Evidence for DMPS, which is a water-soluble analog of BAL (sulfonic acid group instead of a hydroxyl group), is based on structural similarity and animal studies [38,48].
Not critically ill and can take oral medications — In addition to the supportive care, in a patient who is symptomatic but not critically-ill and able to take oral medications, we suggest chelation orally [1,38-41]. Options include DMSA and oral DMPS (the latter not available in the US) (table 2). DMSA (an oral hydrophilic analogue of BAL) is the preferred chelator in patients who can tolerate oral intake.
During chelation treatment, we obtain 24-hour urine arsenic concentrations to follow arsenic excretion over time [1]. A reasonable endpoint for chelation is a 24-hour urinary inorganic arsenic concentration of <50 mcg/L.
Evidence is based on case series and reports, animal studies, and the structural similarities of DMSA with BAL [38,48]. As an example, a case series described six children (≤4 years old) with unintentional ingestion of large doses of ant bait containing arsenic trioxide [46]. All six children vomited shortly after exposure and had spot urine total arsenic concentrations >1800 mcg/L, which in other acute exposures has been associated with severe symptoms. They were all treated with DMSA and did not develop further clinical toxicity. However, the authors acknowledged that it is unclear whether chelation was necessary or helpful.
In adults, evidence does not exist for the use of oral DMPS for the treatment of acute arsenic poisoning. In one trial of 21 patients with chronic arsenic toxicity, oral DMPS was associated with subjective symptom improvement and increased urinary arsenic excretion, but there was no difference in hematological parameters and skin histology [49].
Additional considerations if hemolysis or arsine gas poisoning — The management of arsine gas toxicity is essentially the management of acute, potentially massive drug-induced hemolytic anemia combined with acute inorganic arsenic toxicity. (See "Drug-induced hemolytic anemia".)
All patients with known arsine gas exposure (eg, in an enclosed space with someone who develops toxicity) require at least 24 hours of monitoring since symptoms can develop progressively. If hemolysis does not develop, the patient can be discharged following this observation. Otherwise, they should be hospitalized until hemolysis has ceased.
In a patient with toxicity from arsine gas exposure, additional considerations for management include the following:
●IV fluids should be administered to maintain adequate urine output. Treatment of heme pigment-induced kidney injury is discussed separately. (See "Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)".)
Hemodialysis may be necessary if kidney injury becomes severe and may be required for months, but some patients may ultimately recover kidney function. Hemodialysis will not remove the hemoglobin/haptoglobin complexes that have been deposited in the kidney tubule. (See "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose".)
●Red blood cell transfusions may be necessary; the indication depends on the patient's condition. (See "Indications and hemoglobin thresholds for RBC transfusion in adults".)
●In a critically ill patient with signs of massive hemolysis, we suggest either blood exchange transfusion or therapeutic plasma exchange [19,50]. These therapies may increase the clearance of arsenic oxidation products, red cell debris, and plasma hemoglobin and terminate ongoing hemolysis. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology".)
●The role of chelation (eg, BAL, DMPS) is controversial and not recommended by all experts, especially if the patient is undergoing whole blood exchange transfusion or plasma exchange as that will also increase arsenic clearance [51]. Chelation will not prevent hemolysis or clear arsenic bound to proteins and is not a replacement for blood exchange transfusion or therapeutic plasma exchange, but can be offered if the patient cannot undergo these therapies. However, chelators may bind circulating arsine oxidation products that can cause delayed onset toxicity (eg, neuropathy). Given the very elevated arsenic concentrations reported in patients exposed to arsine gas, the benefits of chelation are likely similar to those of acute arsenic poisoning. (See 'Chelation for symptomatic patients' above.)
●Some experts will administer acetylcysteine to a patient with arsine gas toxicity [8]. There is a theoretical benefit since acetylcysteine regenerates glutathione stores, which are depleted by arsine, but evidence supporting benefit does not exist.
Evidence for treatment of arsine gas exposure is based on case series and case reports [8,16,19,20,52]. The historic fatality rate for arsine poisoning is reported to be 25 to 50 percent [9,19]. A study of 11 patients with massive hemolysis who were treated with plasma exchange reported no fatalities [19]. Hemolysis ended within 24 hours of the plasma exchange. There was 55 to 177 mg of arsenic recovered in the discarded plasma and the mean urine arsenic concentrations decreased from 1092 to 307 mcg/L following plasma exchange. In several case series, patients with severe hemolysis (nine patients total) survived following treatment with blood exchange transfusion [20,23,53].
Presentation for subacute onset manifestations — In a patient with subacute manifestations (eg, peripheral neuropathy, pancytopenia, dermatitis) and potentially ongoing arsenic exposure, we wait for laboratory confirmation of elevated urine inorganic arsenic concentration prior to starting chelation. If the urine inorganic arsenic concentration is elevated, we offer chelation with preferably DMPS (if available) or DMSA. Evidence is based on several studies that found chelation (albeit with BAL) was associated with a decreased duration of arsenical dermatitis [42,54] and on case reports of improved neuropathy and increased urine arsenic excretion with DMPS [55,56]. For example, a study of 63 patients with dermatitis from arsenical syphilis treatment found that treatment with BAL was associated with improvement in rash in 83 percent over a mean of 2 to 3 days, compared with a mean of 16 days prior to use of BAL [42].
FOLLOW-UP —
Patients surviving acute arsenic poisoning should be instructed to follow up with an environmental medicine specialist to assess for subacute and latent onset effects that may develop weeks to years after the exposure. (See 'Occupational/environmental medicine clinicians' below.)
SPECIAL POPULATIONS
Pediatrics — Children can become poisoned with arsenic through accidental ingestion, as in the case of two siblings who drank outdated arsenic-containing pesticide stored in a water bottle [6].
Pregnancy — Intrauterine fetal demise and preterm labor with neonatal death have been reported in patients who ultimately survived multiorgan failure from acute arsenic toxicity [10,57]. Inorganic arsenic crosses the placenta and can cause fetal toxicity [57]. (See "Occupational and environmental risks to reproduction in females: Specific exposures and impact", section on 'Arsenic'.)
ADDITIONAL RESOURCES
Regional poison centers — Regional poison centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison centers".)
Regional Pediatric Environmental Health Specialty Units — For pediatric arsenic exposures and poisonings in the United States, the (PEHSUs) are a national network of experts in the prevention, diagnosis, management, and treatment of health issues that arise from environmental exposures from preconception through adolescence.
Occupational/environmental medicine clinicians — Clinicians specializing in Occupational and Environmental Medicine can be located by contacting the Association of Occupational and Environmental Clinics (AOEC), a group of occupational medicine clinics (frequently academically affiliated) with board-certified occupational medicine physicians (phone: 202-347-4976; website), or the American College of Occupational and Environmental Medicine Physicians (https://www.acoem.org/).
Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Lead and other heavy metal poisoning".)
SUMMARY AND RECOMMENDATIONS
●Sources of exposure – Sources of acute arsenic exposure include arsenic trioxide-containing pesticides or rodenticide bait, contamination of herbal and folk remedies, occupation inhalation of dust or fumes, and arsenic trioxide used to treat acute promyelocytic leukemia. Exposure to arsine gas can occur from inhalation following unexpected industrial reactions in ore refining and semiconductor, computer chip, and fiberoptic manufacturing. (See 'Toxicology and sources of exposure of arsenic and arsine' above.)
●Clinical manifestations – Following acute ingestion of inorganic arsenic, gastrointestinal symptoms (vomiting, profuse watery diarrhea) may develop within minutes or hours. Intravascular volume depletion and hypotension are common. With severe toxicity, after hours to several days, multiorgan dysfunction (vasodilatory shock, myocardial dysfunction, coma, seizures, acute respiratory distress syndrome, acute kidney injury, hepatitis, pancreatitis, rhabdomyolysis) gradually develops. QTc interval prolongation and ventricular dysrhythmias (ie, torsades de pointes) can occur. Patients may experience a metallic taste and there may be a garlic odor of the breath and stool. (See 'Clinical features of acute toxicity' above.)
Subacute-onset manifestations include peripheral neuropathy, confusion, irritability, sixth cranial nerve palsy, sensorineural hearing loss, pulmonary infiltrates, and pancytopenia. Skin and nail changes can include patchy alopecia, Mees' lines (picture 1), acral hyperkeratosis, and lamellar desquamation. (See 'Subacute onset manifestations' above.)
Arsine gas exposure can also cause severe hemolysis and acute kidney injury. A triad of abdominal pain, hematuria, and jaundice has been described as characteristic of arsine poisoning. The urine can have brown, red, or black discoloration (described as "tea-colored"), and the skin can develop a reddish bronze tint. (See 'Hemolysis, hematuria (arsine gas)' above.)
●Diagnostic evaluation – Clinical suspicion for exposure or ingestion is important since blood or urine arsenic concentrations do not result rapidly and the immediate-onset manifestation are similar to other conditions (eg, severe gastroenteritis). In an acutely ill patient, we obtain a spot urine arsenic concentration and instruct the laboratory to speciate the sample to measure the toxic (inorganic) species. Obtain an electrocardiogram (ECG) to assess the QTc interval. (See 'Diagnostic evaluation' above.)
●Management – Acute arsenic toxicity requires urgent assessment of the exposure, elimination of any further exposure, aggressive cardiopulmonary support, and possible chelation. Treatment decisions must be based on the degree of clinical toxicity and suspicion for arsenic poisoning since arsenic concentrations do not result rapidly. Consultation with a specialist (eg, regional poison center, clinical toxicologist) is recommended to guide management. (See 'Management' above and 'Additional resources' above.)
Perform skin decontamination with soap, water, and scrubbing in cases of poisoning from arsenical pesticides. (See 'Role of decontamination' above.)
●Chelation – In a patient who is critically ill from suspected or confirmed acute arsenic poisoning (eg, lethargy, coma, seizures, ventricular dysrhythmias, or shock), in addition to the supportive care, we recommend parenteral chelation, if available (Grade 1C). Early administration of chelation has been associated with lower mortality rates. Parenteral chelators include unithiol (sodium 2,3-dimercapto-1-propane sulfonate [DMPS]) (table 2), which is not approved by the United States (US) Food and Drug Administration. Dimercaprol (British Anti-Lewisite [BAL]) is no longer an option since it is not being manufactured. If no parenteral chelator is available, using an oral chelator (possibly administered via nasogastric tube) can be attempted. (See 'Immediate-onset symptoms with known or suspected exposure' above.)
In a patient who is symptomatic but not critically ill and able to take oral medications, we suggest chelation orally (Grade 2C). Options include DMPS and DMSA (meso-2,3-dimercaptosuccinic acid [succimer]) (table 2). Chelation increases urinary arsenic excretion and has been associated with decreased duration of arsenical dermatitis. Oral chelation is also an option in patients with subacute manifestations and an elevated urine arsenic concentration. (See 'Not critically ill and can take oral medications' above and 'Presentation for subacute onset manifestations' above.)
●Arsine gas exposure – In a critically ill patient with signs of massive hemolysis from arsine gas, we suggest either blood exchange transfusion or therapeutic plasma exchange rather than supportive care alone or chelation therapy (Grade 2C). These therapies may increase the clearance of arsenic oxidation products, terminate ongoing hemolysis and have been associated with decreased mortality. All patients with known arsine gas exposure require at least 24 hours of monitoring since symptoms can develop progressively. (See 'Additional considerations if hemolysis or arsine gas poisoning' above.)
●Follow up – Patients surviving acute arsenic poisoning should be instructed to follow up with an environmental medicine specialist to assess for subacute and latent onset effects that may develop weeks to years after the exposure. (See 'Occupational/environmental medicine clinicians' above.)
