Therapeutic Toxic Class

A)

Specific Substances

A)

1.2.1) MOLECULAR FORMULA
1) Al-P

Available Forms Sources

A)

1) It is used as a phosphine source, in semiconductor research, as an insecticide, and as a fumigant.

Life Support

A)

Clinical Effects

0.2.1)

A) USES: Aluminum phosphide (AIP, aluminum monophosphide, aluminum (III) phosphide, phostoxin, fumitoxin) is an inorganic dark grey or yellow crystalline compound used as a fumigant, pesticide, and in semiconductor research.
B) TOXICOLOGY: Its toxicity is secondary to the release of phosphine gas on contact with moisture or moist air. Phosphine blocks cytochrome C oxidase. This document covers effects from ingestion of aluminum phosphide. Information on the effects of inhalation of phosphine gas are covered in a separate management.
C) EPIDEMIOLOGY: Reported exposures are relatively rare in North America, but can be fatal. Worldwide, in certain countries such as in the Indian subcontinent, toxic exposures to humans are more common.
D) WITH POISONING/EXPOSURE

1) MILD TO MODERATE TOXICITY: Nausea, vomiting, diarrhea, and abdominal pain are common. Mucous membrane irritation is common. Tachycardia, fatigue, headache, anxiety, restlessness, and electrolyte abnormalities (hypomagnesemia, hypermagnesemia) may develop.
2) SEVERE TOXICITY: CNS excitation or depression, hypotension, dysrhythmias, left ventricular dysfunction, metabolic and respiratory acidosis, esophageal strictures, elevated liver enzymes, and acute lung injury may develop. Pancreatitis and acute renal failure are rare complications.

0.2.3)

A) WITH POISONING/EXPOSURE

1) Hypotension, shock, and either tachycardia or bradycardia occur commonly.

0.2.20)

A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
C) At the time of this review no information about possible male reproductive effects was found in available references.

0.2.21)

A) Rats fed diets containing levels of 0.337 to 0.996 mg/kg of phosphine derived from aluminum phosphide had no toxicity and no increased incidence of neoplasms.

Laboratory Monitoring

A)

B)

C)

D)

E)

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) For mild to moderate exposures, the mainstay of treatment is good supportive care. Do not induce emesis in cases of aluminum phosphide ingestion as this could cause off-gassing of phosphine and secondary contamination in enclosed areas. Monitoring of cardiac, hepatic, and renal functions should occur. Fluid and electrolytes should also be measured, and circulatory and respiratory support given as needed for symptoms.

B) MANAGEMENT OF SEVERE TOXICITY

1) For severe overdoses, supportive care is again the most important initial measure. Severe metabolic acidosis can be treated with sodium bicarbonate, and standard treatment for dysrhythmias may be needed. Treat seizures with benzodiazepines; add barbiturates and propofol as needed. Respiratory distress with pulmonary edema and/or acute lung injury may be treated with supplementary oxygen and mechanical ventilation. Hypotension can be treated initially with fluids and then pressors, such as dopamine or norepinephrine. If circulatory collapse is resistant to treatment, mechanical support (eg, intra-aortic balloon pump, cardiopulmonary bypass, or extracorporeal membrane oxygenation) should be considered. Patients who survive should have endoscopy performed to evaluate for esophageal injury or strictures.
2) PROTECTION OF STAFF: Caregivers have developed symptoms believed to be related to phosphine exposure produced from patients who have ingested aluminum phosphide. Good ventilation should be assured and caregiver exposure should be minimized.

C) DECONTAMINATION

1) PREHOSPITAL: Prehospital gastrointestinal (GI) decontamination is not recommended because of the potential for formation of phosphine gas and the potential for abrupt deterioration.
2) HOSPITAL: The role of GI decontamination is not clear, as contact with water has the potential to form phosphine gas. Activated charcoal could be considered for patients with recent aluminum phosphide ingestion (less than one hour) who are awake, alert, and cooperative. Endoscopic removal of aluminum phosphide tablets can be considered if it can be performed rapidly.

D) AIRWAY MANAGEMENT

1) Airway management is one of the primary issues with phosphine toxicity; patients may get critically ill quickly, and early intubation may be needed. Patients should be moved to fresh air as soon as possible, and treated with supplemental oxygen and assisted ventilation as needed. Bronchospasm can be treated with B2 agonists and oral or parenteral corticosteroids.

E) ANTIDOTE

1) None

F) ENHANCED ELIMINATION

1) There is no evidence for the use of dialysis, hemoperfusion, urinary alkalinization, or multiple dose charcoal. Dialysis or hemoperfusion are unlikely to be helpful for phosphine exposures.

G) PATIENT DISPOSITION

1) HOME CRITERIA: There is no role for home management of aluminum phosphide exposures.
2) OBSERVATION CRITERIA: All patients with exposures should be sent to a healthcare facility for observation for at least a period of 6 to 8 hours of observation. Patients may be discharged home if they are asymptomatic or clearly improving and stable for discharge with careful instructions to return if any respiratory symptoms develop.
3) ADMISSION CRITERIA: Patients with worsening or severe symptoms should be admitted to the hospital, and depending on the severity of their symptoms (eg, respiratory distress requiring intubation, hypotension, dysrhythmias, CNS depression), may require an ICU bed. Patients can be discharged once they are hemodynamically stable with clear improvement or asymptomatic from their exposure.
4) CONSULT CRITERIA: Consult a medical toxicologist and/or poison centers for any patient with significant aluminum phosphide poisoning. Other helpful consultants may include critical care physicians and pulmonologists to help management of the patient's symptoms.

H) PITFALLS

1) One concern from off-gassing of phosphine from aluminum phosphide exposure is that the characteristic odor might be masked by olfactory fatigue at higher concentrations. The minimal detectable concentration via phosphine's decaying fish odor is 1 to 3 parts per million (ppm) in air. Patients should be removed from the exposure as the first line of treatment. Severe symptoms, such as pulmonary edema, may be delayed up to 72 hours after exposure.

I) TOXICOKINETICS

1) Aluminum phosphide reacts rapidly with water or acids to form phosphine. Phosphine is absorbed rapidly in the human body as reflected by the abrupt onset of symptoms, of which can range from immediate to within a few hours. Some toxic manifestations, such as abnormalities in liver function tests or pulmonary edema, may be delayed for up to 1 to 3 days.

J) PREDISPOSING CONDITIONS

1) Patients at extremes of age or underlying morbidities, such as chronic lung disease, may be more susceptible to phosphine exposure.

K) DIFFERENTIAL DIAGNOSIS

1) Includes other irritant or toxic gases, such as chlorine or cyanide gases.

0.4.3)

A) Move patient to fresh air and monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as needed. Bronchospasm can be treated with B2 agonists and oral or parenteral corticosteroids.

0.4.4)

A) Irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes.

0.4.5)

A) OVERVIEW

1) Remove contaminated clothing and wash exposed area thoroughly with soap and water.

Range Of Toxicity

A)

Clinical Effects

Summary Of Exposure

A)

B)

C)

D)

1) MILD TO MODERATE TOXICITY: Nausea, vomiting, diarrhea, and abdominal pain are common. Mucous membrane irritation is common. Tachycardia, fatigue, headache, anxiety, restlessness, and electrolyte abnormalities (hypomagnesemia, hypermagnesemia) may develop.
2) SEVERE TOXICITY: CNS excitation or depression, hypotension, dysrhythmias, left ventricular dysfunction, metabolic and respiratory acidosis, esophageal strictures, elevated liver enzymes, and acute lung injury may develop. Pancreatitis and acute renal failure are rare complications.

Vital Signs

3.3.1)

A) WITH POISONING/EXPOSURE

1) Hypotension, shock, and either tachycardia or bradycardia occur commonly.

3.3.4)

A) WITH POISONING/EXPOSURE

1) Hypotension, cardiac dysrhythmias, and shock are common in acute poisoning (Jamshed et al, 2014; Jadhav et al, 2012; Nayyar & Nair, 2009; Shah et al, 2009; Chacko & Shivaprasad, 2008; Akkaoui et al, 2007; Verma et al, 2007; Chugh et al, 1989; Chugh et al, 1989a; Singh et al, 1989; Banjaj & Wasir, 1988; Khosla et al, 1988; Misra et al, 1988; Chopra et al, 1986).

3.3.5)

A) WITH POISONING/EXPOSURE

1) Tachycardia was a common finding following acute aluminum phosphide ingestion (Sulaj et al, 2015; Jadhav et al, 2012; Chacko & Shivaprasad, 2008; Akkaoui et al, 2007; Verma et al, 2007; Chugh et al, 1989b; Khosla et al, 1988).
2) Bradycardia was observed in 9 of 30 acute aluminum phosphide poisoning cases (Chugh et al, 1989b).

Heent

3.4.3)

A) WITH POISONING/EXPOSURE

1) MYDRIASIS: Medical records of patients with aluminum phosphide poisoning, admitted to a hospital in Tehran, Iran from 2000 to 2007, were analyzed retrospectively. Of the 471 patients admitted with aluminum phosphide poisoning, approximately 41% developed neurologic signs and symptoms with mydriasis occurring in approximately 23% of the patients (Shadnia et al, 2009).
2) EYE IRRITATION: Five adults in one family (ages 22 to 60) presented to the emergency department (ED) with nausea, vomiting, dizziness, coughing, and eye burning sensation approximately 15 hours following exposure to a pesticide containing aluminum phosphide that was applied without warning to the apartment where they were living. The patients symptoms improved following presentation to the ED (Alhelail & Aldawwas, 2015).

3.4.5)

A) WITH POISONING/EXPOSURE

1) Phosphine is irritating to the mucous membranes of the nose, mouth, throat, and respiratory tract.

3.4.6)

A) WITH POISONING/EXPOSURE

1) Phosphine is irritating to the mucous membranes of the nose, mouth, throat, and respiratory tract.
2) POLYDIPSIA/CASE SERIES: A review of records of hospital admissions in Tirana, Albania from 2009 to 2013 identified 140 fatalities from aluminum phosphide poisoning. The primary route of exposure in 96% of the cases was ingestion, and the mean period of time from exposure to hospital admission was 3.91 hours (+/- 5.11 hours). The aluminum phosphide dose ranged from 0.5 tablet to 5 tablets (0.5 to 5 g of active component [ie, phosphine]). At hospital arrival, profound thirst was reported in 74 of the 140 patients (53%) (Sulaj et al, 2015)

Cardiovascular

3.5.2)

A) CONDUCTION DISORDER OF THE HEART

1) WITH POISONING/EXPOSURE

a) Cardiac dysrhythmias and changes secondary to electrolyte imbalance have been described in sublethal acute exposure. Transient atrial fibrillation and subendocardial infarction have been reported (Chopra et al, 1986).
b) Cardiac dysrhythmias were observed in 16 of 25 adult patients with acute aluminum phosphide poisoning (Khosla et al, 1988).
c) ECG abnormalities in acute aluminum phosphide poisoning may include sinus tachycardia, sinus dysrhythmia with ST-segment depression in lead II, III, and AVF, ST elevation, atrial fibrillation, T wave inversion in V5-6, sinus arrest, chaotic atrial pacemaker, complete heart block, bundle branch block, and ventricular premature complexes followed by ventricular tachycardia (Jamshed et al, 2014; Singh et al, 1989; Khosla et al, 1988; Misra et al, 1988) .

B) TACHYARRHYTHMIA

1) WITH POISONING/EXPOSURE

a) Tachycardia was a common finding following acute aluminum phosphide ingestion (Chacko & Shivaprasad, 2008; Akkaoui et al, 2007; Verma et al, 2007; Chugh et al, 1989b; Khosla et al, 1988) .
b) CASE SERIES: Medical records of patients with aluminum phosphide poisoning, admitted to a hospital in Tehran, Iran from 2000 to 2007, were analyzed retrospectively. Of the 471 patients admitted with aluminum phosphide poisoning, 78% developed cardiovascular signs and symptoms, with tachycardia occurring in 40% of the patients (Shadnia et al, 2009).
c) CASE REPORT: A 39-year-old man ingested 3 pellets (9 g) of aluminum phosphide and developed somnolence, dyspnea, hypotension, recurrent ventricular tachycardia, and metabolic acidosis. He died about 5 hours after ingestion (Alter et al, 2001).
d) CASE REPORT: A 19-year-old man presented with abdominal pain, nausea, and vomiting approximately 60 minutes after intentionally ingesting 10 500-mg tablets containing 56% aluminum phosphide. He was hypotensive (92/65 mmHg) and tachycardic (120 bpm). An echocardiogram was normal, indicating a left ventricular ejection fraction of 60%. Approximately 5 hours after presentation and after activated charcoal administration, the patient's clinical status deteriorated with a decrease in his blood pressure (85/45 mmHg), increased pulse rate (160 bpm), metabolic acidosis, and development of pulmonary edema. A repeat echocardiogram revealed a left ventricular ejection fraction of 30% with global hypokinesis. Laboratory data revealed an elevated serum troponin concentration (12.7 mg/mL). Three hours later, the patient developed monomorphic sustained ventricular tachycardia (180 bpm). Despite intensive supportive therapy, including 6 electrocardioversion attempts, the patient continued to deteriorate with refractory ventricular tachycardia, progressive hypotension, acidosis, and respiratory failure, resulting in death (Jadhav et al, 2012).
e) CASE SERIES: A review of records of hospital admissions in Tirana, Albania from 2009 to 2013 identified 140 fatalities from aluminum phosphide poisoning. The primary route of exposure in 96% of the cases was ingestion, and the mean period of time from exposure to hospital admission was 3.91 hours (+/- 5.11 hours). The aluminum phosphide dose ranged from 0.5 tablet to 5 tablets (0.5 to 5 g of active component [ie, phosphine]). At hospital arrival, sinus tachycardia was reported in 61 of the 140 patients (44%) (Sulaj et al, 2015).

C) BRADYCARDIA

1) WITH POISONING/EXPOSURE

a) Bradycardia was observed in 9 of 30 acute aluminum phosphide poisoning cases studied (Chugh et al, 1989b).
b) CASE SERIES: Medical records of patients with aluminum phosphide poisoning, admitted to a hospital in Tehran, Iran from 2000 to 2007, were analyzed retrospectively. Of the 471 patients admitted with aluminum phosphide poisoning, 78% developed cardiovascular signs and symptoms with bradycardia occurring in 8% of the patients (Shadnia et al, 2009).
c) CASE REPORT: A 16-year-old girl developed nausea, vomiting, and diarrhea and collapsed after ingesting an aluminum phosphide insecticide tablet. She presented to hospital with refractory hypotension, bradycardia, shallow respirations and trismus. She died approximately 1 hour after presentation (Ragone et al, 2002).

D) HYPOTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) All 9 patients who ingested new aluminum phosphide tablets developed shock (6 died) in a prospective study of 16 patients with acute aluminum phosphide poisoning (Chopra et al, 1986).
b) In a study of 25 adult patients with acute aluminum phosphide poisoning, 23 developed circulatory failure (Khosla et al, 1988).
c) Severe hypotension on presentation is more common in patients who do not survive. In a series of 26 patients with significant aluminum phosphide poisoning (defined as developing hypotension at some time after ingestion), blood pressure was unrecordable on presentation in 8 of 10 who died compared with 1 of 16 who survived (Singh et al, 2006).
d) Hypotension was reported in 2 patients who intentionally ingested 1 to 3 tablets of a fumigant containing aluminum phosphide. Each 3 gram tablet of the fumigant contained 56% aluminum phosphide (Akkaoui et al, 2007).
e) CASE REPORT: Hypotension (70 mmHg systolic) was reported in a 34-year-old man who ingested 2 tablets, each containing 3 grams aluminum phosphide, in a suicide attempt. The patient recovered with supportive care (Verma et al, 2007).
f) CASE REPORT: A 25-year-old woman presented with severe nausea and vomiting approximately 30 minutes after ingesting 10 tablets containing 50% aluminum phosphide. The patient developed tachycardia (up to 160 bpm), hypotension (systolic pressure less than 90 mmHg and MAP less than 60 mmHg), and metabolic acidosis. Despite supportive measures, including continuous venovenous hemodiafiltration and administration of fluids and vasopressors, her condition continued to deteriorate and she subsequently died approximately 48 hours postingestion (Chacko & Shivaprasad, 2008).
g) CASE SERIES: Medical records of patients with aluminum phosphide poisoning, admitted to a hospital in Tehran, Iran from 2000 to 2007, were analyzed retrospectively. Of the 471 patients admitted with aluminum phosphide poisoning, 78% developed cardiovascular signs and symptoms, with hypotension being the most frequently reported, occurring in 96% of the patients (Shadnia et al, 2009).
h) CASE REPORT: A 39-year-old man ingested 3 pellets (9 g) of aluminum phosphide and developed somnolence, dyspnea, hypotension, recurrent ventricular tachycardia, and metabolic acidosis. He died about 5 hours after ingestion (Alter et al, 2001).
i) CASE REPORT: A 16-year-old girl developed nausea, vomiting, and diarrhea and collapsed after ingesting an aluminum phosphide insecticide tablet. She presented to hospital with refractory hypotension, bradycardia, shallow respirations and trismus. She died approximately 1 hour after presentation (Ragone et al, 2002).
j) CASE REPORT: Progressive hypotension, refractory ventricular tachycardia, acidosis, and respiratory failure, resulting in death, occurred in a 19-year-old man who intentionally ingested 10 500-mg tablets containing 56% aluminum phosphide (Jadhav et al, 2012).
k) CASE SERIES: A review of records of hospital admissions in Tirana, Albania from 2009 to 2013 identified 140 fatalities from aluminum phosphide poisoning. The primary route of exposure in 96% of the cases was ingestion, and the mean period of time from exposure to hospital admission was 3.91 hours (+/- 5.11 hours). The aluminum phosphide dose ranged from 0.5 tablet to 5 tablets (0.5 to 5 g of active component [ie, phosphine]). Cardiovascular collapse was the most common presenting symptom, occurring in 128 of the 140 patients (92%) (Sulaj et al, 2015).

E) MYOCARDIAL DYSFUNCTION

1) WITH POISONING/EXPOSURE

a) Massive focal myocardial injury with elevated serum levels of cardiac enzymes may occur (Chugh et al, 1989; Chugh et al, 1989a; Singh et al, 1989; Banjaj & Wasir, 1988; Khosla et al, 1988; Misra et al, 1988; Chopra et al, 1986).
b) CASE REPORT: A 25-year-old man ingested 6 grams of aluminum phosphide and developed vomiting, abdominal pain, drowsiness, hemolysis, mild hypotension and anuria. An echocardiogram on the day of admission showed global hypokinesia with a left ventricular ejection fraction of 28%. Repeat echocardiogram several days later showed fair LV function with an ejection fraction of 55% (Lakshmi, 2002).
c) Reversible myocardial injury was reported in 2 patients who ingested an aluminum phosphide-containing fumigant. Each 3 gram tablet of the fumigant contained 56% aluminum phosphide (Akkaoui et al, 2007).

1) The first patient, a 19-year-old woman, ingested 3 tablets of the fumigant and subsequently developed abdominal pain, vomiting, sinus tachycardia (110 bpm), and hypotension (70/40 mmHg). An ECG, performed 2 hours postingestion, revealed ST-segment elevations in leads V1 and V2, and echocardiography showed hypokinesia in both ventricles and a left ventricle ejection fraction (LVEF) of 20% or less. Laboratory data revealed an elevated creatine kinase concentration of 1200 International Units/L (normal 100 International Units/L). With supportive care, the patient's condition gradually improved, and a repeat echocardiography, performed 8 days postadmission, revealed a LVEF of 30%.
2) The second patient, a 28-year-old man, ingested 1 tablet of the fumigant, and presented to the emergency department 2 hours later with vomiting, epigastric pain, and dizziness. Two hours postadmission, the patient also developed hypotension (90/50 mmHg). An ECG demonstrated ST-segment elevation in leads V2, V3, and V4, and laboratory data revealed elevated troponin (37.5 ng/mL) and creatine kinase (1110 International Units/L) concentrations. Echocardiography, performed 2 days postadmission, indicated global hypokinesia of the left ventricle with an LVEF of 30%. With supportive care, the patient gradually recovered, with a decrease in troponin concentration to 3.5 ng/mL on day 7 postingestion and an increase in the LVEF to 50% on day 8.

d) CASE REPORT (ADULT): A 25-year-old woman presented with severe nausea and vomiting approximately 30 minutes after ingesting 10 tablets containing 50% aluminum phosphide. The patient developed tachycardia (up to 160 bpm), hypotension (systolic pressure less than 90 mmHg and MAP less than 60 mmHg), and metabolic acidosis. An echocardiogram demonstrated severe impairment of left ventricular function with an ejection fraction of less than 30%, despite inotropic support with dobutamine and adrenaline, and her troponin-I level was elevated at 12.7 ng/mL (normal 0 to 0.4 ng/mL). Although an intraaortic balloon pump was inserted to support left ventricular function, the patient's condition continued to deteriorate and she subsequently died approximately 48 hours postingestion (Chacko & Shivaprasad, 2008).
e) CASE REPORT (ADULT): A 22-year-old woman ingested one 0.6 gram tablet containing 56% aluminum phosphide and presented to the emergency department 6 hours later with cardiogenic shock (hypotension (80/60 mmHg) and tachycardia (128 bpm)). An ECG revealed sinus tachycardia with ST depression and an echocardiogram indicated dilatation of all chambers, global hypokinesia, and a left ventricular ejection fraction (LVEF) of 35%. Despite intensive inotropic support with dobutamine and norepinephrine, the patient's tachycardia and hypotension persisted. An intraaortic balloon pump (IABP) was then inserted, resulting in improvement in the patient's hemodynamic status. On day 5 of IABP, the patient's blood pressure stabilized and a repeat echocardiogram revealed mild left ventricular global hypokinesia with an increase in LVEF to 45%. Following discontinuation of the IABP, the patient continued to improve clinically with an echocardiogram on day 16 that showed normal chambers and an LVEF of 65%, and an ECG demonstrating sinus tachycardia with no significant ST-segment or T wave changes (Siddaiah et al, 2009).
f) CASE REPORT (ADULT): A 40-year-old man presented with abdominal pain, tachycardia (110 bpm), and hypotension (70/30 mmHg) approximately 3 hours after intentionally ingesting one 3 gram aluminum phosphide tablet. An initial ECG revealed ST elevation with a broad QRS complex mimicking an inferior wall myocardial infarction. Despite intensive vasopressor support, his hypotension continued to persist. Repeat ECGs, obtained 6 hours postadmission and on hospital day 2, indicated severe myocardial injury. Although aggressive supportive therapy and resuscitative measures were given, the patient's condition continued to deteriorate and he died approximately 2 days postadmission. Postmortem examination of his heart showed severe myocyte vacuolation, and necrosis and myocytolysis of the myocardial fibers (Shah et al, 2009).
g) CASE REPORT (PEDIATRIC): Three children (ages 8, 5, and 3 years) presented to the emergency department with drowsiness, vomiting, diarrhea, and respiratory insufficiency following exposure of 25 tablets of an insecticide used to kill bed bugs in their room. The 8-year-old child died on route to the hospital. Suspecting organophosphorus poisoning, the other 2 children were treated accordingly. After 2 days of treatment, the 3-year-old showed clinical improvement and was subsequently discharged from the hospital. Approximately 10 hours after discharge, the patient died. The 5-year-old showed signs of hemodynamic instability, with delayed capillary refill of 4 seconds, and an echocardiography indicating an ejection fraction of less than 50%. Analysis of samples of the pesticide revealed that it contained aluminum phosphide. With supportive treatment for the next 48 hours, a repeat echocardiography indicated an improvement in his ejection fraction to 60%. Following 2 more days of observation, the patient was discharged without sequelae (Hirani & Rahman, 2010).

F) BRUGADA SYNDROME

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 56-year-old woman, with a suspected history of aluminum phosphide poisoning, presented to the emergency department with vomiting, severe dyspnea, and shock. An initial ECG demonstrated a type 1 Brugada pattern with ST-segment elevation in the right precordial leads (V1, V2, and V3) and QT prolongation. A 12-lead ECG also indicated recurrent ventricular tachycardia and a left bundle branch block pattern with a type 2 Brugada pattern. Despite intensive hemodynamic supportive therapy, the patient remained in shock, developed acute renal failure, and subsequently died (Nayyar & Nair, 2009).

G) CHEST PAIN

1) WITH POISONING/EXPOSURE

a) CASE SERIES: A review of records of hospital admissions in Tirana, Albania from 2009 to 2013 identified 140 fatalities from aluminum phosphide poisoning. The primary route of exposure in 96% of the cases was ingestion, and the mean period of time from exposure to hospital admission was 3.91 hours (+/- 5.11 hours). The aluminum phosphide dose ranged from 0.5 tablet to 5 tablets (0.5 to 5 g of active component [ie, phosphine]). At hospital arrival, chest pain was reported in 55 of the 140 patients (39%) (Sulaj et al, 2015).

Respiratory

3.6.2)

A) DYSPNEA

1) WITH POISONING/EXPOSURE

a) Cough, sputum production, and dyspnea have been noted.
b) CASE SERIES: Medical records of patients with aluminum phosphide poisoning, admitted to a hospital in Tehran, Iran from 2000 to 2007, were analyzed retrospectively. Of the 471 patients admitted with aluminum phosphide poisoning, approximately 19% developed respiratory signs and symptoms with dyspnea, tachypnea, and cyanosis occurring in approximately 33%, 33%, and 17% of the patients (Shadnia et al, 2009).
c) CASE REPORT: A 39-year-old man ingested 3 pellets (9 g) of aluminum phosphide and developed somnolence, dyspnea, hypotension, recurrent ventricular tachycardia, and metabolic acidosis. He died about 5 hours after ingestion (Alter et al, 2001).

B) ACUTE LUNG INJURY

1) WITH POISONING/EXPOSURE

a) Pulmonary edema, adult respiratory distress syndrome (ARDS), dyspnea, and cyanosis may develop after acute exposure (Jadhav et al, 2012; Chugh et al, 1989; Chugh et al, 1989a; Singh et al, 1989; Banjaj & Wasir, 1988; Khosla et al, 1988; Misra et al, 1988; Chopra et al, 1986) Singh, 1985.
b) Pulmonary edema was observed in 2 of 25 adult patients with acute aluminum phosphide poisoning (Khosla et al, 1988).
c) In a series of 26 patients with significant aluminum phosphide poisoning (defined as developing hypotension at some point after ingestion), pulmonary edema developed in 5 out of 10 patients who did not survive and 2 out of 16 patients who did survive (Singh et al, 2006).
d) CASE SERIES: A review of records of hospital admissions in Tirana, Albania from 2009 to 2013 identified 140 fatalities from aluminum phosphide poisoning. The primary route of exposure in 96% of the cases was ingestion, and the mean period of time from exposure to hospital admission was 3.91 hours (+/- 5.11 hours). The aluminum phosphide dose ranged from 0.5 tablet to 5 tablets (0.5 to 5 g of active component [ie, phosphine]). At hospital arrival, cyanosis and pulmonary edema were reported in 30% and 14%, respectively, of the 140 patients (Sulaj et al, 2015).

Neurologic

3.7.2)

A) CENTRAL NERVOUS SYSTEM DEFICIT

1) WITH POISONING/EXPOSURE

a) High-level acute exposure produces fatigue, headache, drowsiness, dizziness, paresthesias, CNS depression, and coma (Alhelail & Aldawwas, 2015; Shadnia & Soltaninejad, 2011; Hirani & Rahman, 2010; Akkaoui et al, 2007; HSDB , 1996; Chugh et al, 1989; Chugh et al, 1989a; Singh et al, 1989; Banjaj & Wasir, 1988; Misra et al, 1988; Khosla et al, 1988; Chopra et al, 1986).
b) In a series of 26 patients with significant aluminum phosphide poisoning (defined as developing hypotension at some point after ingestion), altered sensorium developed in 8 of 10 patients who did not survive, and 6 of 16 patients who did survive (Singh et al, 2006).
c) CASE SERIES: Medical records of patients with aluminum phosphide poisoning, admitted to a hospital in Tehran, Iran from 2000 to 2007, were analyzed retrospectively. Of the 471 patients admitted with aluminum phosphide poisoning, approximately 41% developed neurologic signs and symptoms with dizziness, deep tendon reflex decrease, and headache occurring in approximately 31%, 31%, and 15% of the patients, respectively (Shadnia et al, 2009).
d) CASE REPORT: A 39-year-old man ingested 3 pellets (9 g) of aluminum phosphide and developed somnolence, dyspnea, hypotension, recurrent ventricular tachycardia, and metabolic acidosis. He died about 5 hours after ingestion (Alter et al, 2001).

B) SEIZURE

1) WITH POISONING/EXPOSURE

a) Seizures may occur following acute exposure (HSDB , 1996).

C) ANXIETY

1) WITH POISONING/EXPOSURE

a) Restlessness and anxiety were common symptoms reported following acute aluminum phosphide ingestion (Khosla et al, 1988).
b) CASE SERIES: Medical records of patients with aluminum phosphide poisoning, admitted to a hospital in Tehran, Iran from 2000 to 2007, were analyzed retrospectively. Of the 471 patients admitted with aluminum phosphide poisoning, approximately 41% developed neurologic signs and symptoms with agitation occurring in approximately 15% of the patients (Shadnia et al, 2009).
c) CASE SERIES: A review of records of hospital admissions in Tirana, Albania from 2009 to 2013 identified 140 fatalities from aluminum phosphide poisoning. The primary route of exposure in 96% of the cases was ingestion, and the mean period of time from exposure to hospital admission was 3.91 hours (+/- 5.11 hours). The aluminum phosphide dose ranged from 0.5 tablet to 5 tablets (0.5 to 5 g of active component [ie, phosphine]). At hospital arrival, restlessness was reported in 40 of the 140 patients (29%) (Sulaj et al, 2015).

D) COMA

1) WITH POISONING/EXPOSURE

a) CASE SERIES: Medical records of patients with aluminum phosphide poisoning, admitted to a hospital in Tehran, Iran from 2000 to 2007, were analyzed retrospectively. Of the 471 patients admitted with aluminum phosphide poisoning, approximately 28% became comatose, ranging in severity from grade I (67%) to grade IV (11%)(Shadnia et al, 2009).
b) CASE REPORT: A 19-year-old man presented to the emergency department comatose and in shock approximately 7.5 hours after ingesting 1 aluminum phosphide tablet (3 g). Laboratory data revealed severe metabolic acidosis (pH of 6.86), serum lactate level of 13 mmol/L, and a blood glucose concentration of 15 mg/dL. His oxygen saturation was 70%. An ECG demonstrated T-wave inversion and ST elevation with sinus tachycardia, and a troponin level was 0.36 mcg/L. Following administration of 2 50-mL IV boluses of 50% dextrose followed by a continuous infusion of 10% dextrose, his blood glucose concentration increased to 110 mg/dL; however, his neurological status remained unchanged. Despite gastric lavage and aggressive symptomatic and supportive therapy, including administration of IV fluids, magnesium sulfate, sodium bicarbonate, and N-acetylcysteine, the patient died 30 hours after presentation (Jamshed et al, 2014).
c) CASE SERIES: A review of records of hospital admissions in Tirana, Albania from 2009 to 2013 identified 140 fatalities from aluminum phosphide poisoning. The primary route of exposure in 96% of the cases was ingestion, and the mean period of time from exposure to hospital admission was 3.91 hours (+/- 5.11 hours). The aluminum phosphide dose ranged from 0.5 tablet to 5 tablets (0.5 to 5 g of active component [ie, phosphine]). At hospital arrival, coma with a Glasgow Coma Scale score less than 7 was reported in 52 of the 140 patients (37%) (Sulaj et al, 2015).

E) ISCHEMIC STROKE

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 30-year-old man, who, 11 days earlier, had been admitted to the hospital after intentionally ingesting 3 rice tablets (each tablet containing 56% aluminum phosphide and 44% ammonium carbonate) and was discharged 10 days later without evidence of neurologic toxicity, presented to the emergency department 4 hours after a sudden onset of left side hemiplegia and dysarthria. At presentation, the patient was lethargic and febrile (38.4 degrees C oral temperature), the neurologic examination revealed left hemifacial paresis and left hemiplegia and a brain MRI and brain MR angiography demonstrated ischemic lesions in the area of the right middle cerebral artery (MCA) and stenosis of the right MCA stem, respectively. There was no evidence of abnormalities of the cervical carotid and vertebral arteries, and the cardiac examination was normal. Laboratory analysis for hematologic disorders showed no abnormalities and tests for infectious and immunological disorders (eg, viral markers, collagen vascular diseases, hypercoagulable state inducing factors), as suspected causes of stroke, were negative. With supportive therapy, including antibiotic therapy, aspirin, atorvastatin, and enoxaparin, the patient was alert with no dysarthria, although his motor deficit persisted. He was discharged on hospital day 11 and at follow-up, 1 month later, demonstrated gradual improvement in his left side hemiparesis (Abedini et al, 2014).

Gastrointestinal

3.8.2)

A) VOMITING

1) WITH POISONING/EXPOSURE

a) Nausea and vomiting may occur (Jadhav et al, 2012; Hirani & Rahman, 2010; Nayyar & Nair, 2009; Shadnia et al, 2008; Chacko & Shivaprasad, 2008; Akkaoui et al, 2007; Abder-Rahman et al, 2000; Chopra et al, 1986). In 25 adult patients with acute aluminum phosphide poisoning, all developed profuse vomiting within minutes after ingestion (Khosla et al, 1988).
b) CASE SERIES: Medical records of patients with aluminum phosphide poisoning, admitted to a hospital in Tehran, Iran from 2000 to 2007, were analyzed retrospectively. Of the 471 patients admitted with aluminum phosphide poisoning, approximately 47% developed gastrointestinal signs and symptoms with vomiting occurring in 40% of the patients (Shadnia et al, 2009).
c) CASE REPORT: A 16-year-old girl developed nausea, vomiting, and diarrhea and collapsed after ingesting an aluminum phosphide insecticide tablet. She presented to hospital with refractory hypotension, bradycardia, shallow respirations and trismus. She died approximately 1 hour after presentation (Ragone et al, 2002).
d) CASE REPORTS: Five adults in one family (ages 22 to 60) presented to the emergency department (ED) with nausea, vomiting, dizziness, coughing, and eye burning sensation approximately 15 hours following exposure to a pesticide containing aluminum phosphide that was applied without warning to the apartment where they were living. The patients symptoms improved following presentation to the ED (Alhelail & Aldawwas, 2015).
e) CASE SERIES: A review of records of hospital admissions in Tirana, Albania from 2009 to 2013 identified 140 fatalities from aluminum phosphide poisoning. The primary route of exposure in 96% of the cases was ingestion, and the mean period of time from exposure to hospital admission was 3.91 hours (+/- 5.11 hours). The aluminum phosphide dose ranged from 0.5 tablet to 5 tablets (0.5 to 5 g of active component [ie, phosphine]). At hospital arrival, nausea and vomiting were reported in 48% and 46%, respectively, of the 140 patients (Sulaj et al, 2015).

B) ABDOMINAL PAIN

1) WITH POISONING/EXPOSURE

a) Abdominal pain has been reported after ingestion (Jadhav et al, 2012; Shah et al, 2009; Akkaoui et al, 2007; Singh et al, 2006; Lakshmi, 2002; Aggarwal et al, 1999; Chopra et al, 1986). Epigastric and abdominal pain were noted in 60% of adult patients following acute aluminum phosphide ingestion (Khosla et al, 1988).
b) CASE SERIES: Medical records of patients with aluminum phosphide poisoning, admitted to a hospital in Tehran, Iran from 2000 to 2007, were analyzed retrospectively. Of the 471 patients admitted with aluminum phosphide poisoning, approximately 47% developed gastrointestinal signs and symptoms with epigastric pain occurring in approximately 73% of the patients (Shadnia et al, 2009).
c) CASE SERIES: A review of records of hospital admissions in Tirana, Albania from 2009 to 2013 identified 140 fatalities from aluminum phosphide poisoning. The primary route of exposure in 96% of the cases was ingestion, and the mean period of time from exposure to hospital admission was 3.91 hours (+/- 5.11 hours). The aluminum phosphide dose ranged from 0.5 tablet to 5 tablets (0.5 to 5 g of active component [ie, phosphine]). At hospital arrival, abdominal pain was reported in 60 of the 140 patients (43%) (Sulaj et al, 2015).

C) DIARRHEA

1) WITH POISONING/EXPOSURE

a) Diarrhea may occur with aluminum phosphide poisoning (Hirani & Rahman, 2010).
b) In 25 adult patients, 60% developed diarrhea following acute aluminum phosphide ingestion (Khosla et al, 1988).
c) CASE SERIES: Medical records of patients with aluminum phosphide poisoning, admitted to a hospital in Tehran, Iran from 2000 to 2007, were analyzed retrospectively. Of the 471 patients admitted with aluminum phosphide poisoning, approximately 47% developed gastrointestinal signs and symptoms with both diarrhea and melena occurring in approximately 7% of the patients (Shadnia et al, 2009).

D) PANCREATITIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 34-year-old man presented with abdominal pain approximately 3 hours after ingesting 2 tablets (each tablet containing 3 grams of aluminum phosphide) in a suicide attempt. At presentation, the patient was tachycardic (90 bpm) and hypotensive (70 mmHg systolic). Arterial blood gas analysis indicated metabolic acidosis (pH 7.095, pCO2 16.1 mmHg, pO2 99 mmHg, HCO3 5 mmol/L). Following supportive treatment with fluids and vasopressors, the patient's condition stabilized; however, his abdominal pain continued to persist and was associated with nausea. Laboratory data revealed elevated amylase and lipase concentrations and an MRI of the abdomen confirmed the presence of pancreatitis. The patient gradually recovered with supportive care and was discharged 14 days post-ingestion (Verma et al, 2007).

E) STRICTURE OF ESOPHAGUS

1) WITH POISONING/EXPOSURE

a) CASE SERIES: Intentional ingestion of aluminum phosphide tablets in 11 patients resulted in esophageal strictures in all patients, as well as a tracheoesophageal fistula in one patient. Onset of symptoms ranged from immediately to 26 hours postingestion. All 11 patients recovered, requiring either endoscopic dilatation or surgical repair via gastric tube or feeding jejunostomy (Darbari et al, 2008).
b) CASE SERIES: Esophageal strictures were reported in 12 patients following intentional ingestion of 1 to 3 aluminum phosphide tablets. Onset of symptoms occurred 4 to 8 weeks postingestion. Two patients had 2 strictures each, and the other 10 patients each had 1 stricture. Seven strictures were in the upper third of the esophagus, 2 were in the middle third, and 5 were in the lower third, with the mean length as 1.96 +/- 0.75 centimeters (range 1 to 3 centimeters). Of the 12 patients, 5 responded to dilation, 4 were treated with steroids and dilation, and 3 required surgical intervention (Kochhar et al, 2010).
c) CASE SERIES: In a series of 104 patients with confirmed poisoning due to ingestion of aluminum phosphide tablets, 31 patients survived to discharge and were instructed to return if difficulty swallowing developed. Of the 31, 12 developed dysphagia an average of 39 days after the overdose. All 12 underwent endoscopy. Esophageal strictures were found in 10 patients, and tracheo-esophageal fistulas in the other 2 patients. The strictures were located 28 +/- 4 cm from the incisors, with an ulcerated margin in one patient, and pseudo- diverticula in one patient. The tracheo-esophageal fistulas were 20 and 22 cm from the incisors (Jain et al, 2010).

Hepatic

3.9.2)

A) LIVER DAMAGE

1) WITH POISONING/EXPOSURE

a) In 25 adult patients with acute aluminum phosphide poisoning, 5 had mild to moderate elevations of serum transaminases (Khosla et al, 1988).
b) Elevated serum transaminase levels were reported in 2 patients who intentionally ingested 1 to 3 tablets of a fumigant containing aluminum phosphide. Each 3 gram tablet contained 56% aluminum phosphide (Akkaoui et al, 2007).
c) CASE REPORT: Elevated liver enzyme levels (AST 556 units/L, ALT 356 units/L, and alkaline phosphatase 110 units/L) occurred in a 22-year-old woman following ingestion of one 0.6 gram tablet containing 56% aluminum phosphide (Siddaiah et al, 2009).

2) High-level acute exposure or chronic exposure may produce jaundice or hepatic damage. Increased serum transaminase levels may be noted (Chopra et al, 1986).

B) HYPERBILIRUBINEMIA

1) WITH POISONING/EXPOSURE

a) In 25 adult patients with acute aluminum phosphide poisoning, of 5 patients with elevated serum transaminases, 2 also had hyperbilirubinemia (Khosla et al, 1988).
b) In a series of 26 patients with significant aluminum phosphide poisoning (defined as developing hypotension at some point after ingestion), 4 developed jaundice (Singh et al, 2006).

Genitourinary

3.10.2)

A) ABNORMAL RENAL FUNCTION

1) WITH POISONING/EXPOSURE

a) In 25 adult patients with acute aluminum phosphide poisoning, one developed acute renal failure and another had mild proteinuria (Khosla et al, 1988).
b) In another series of 26 patients with severe aluminum phosphide poisoning (defined as developing hypotension at some point after ingestion), one patient developed acute renal failure (Singh et al, 2006).
c) CASE REPORT: Acute renal failure occurred in a 56-year-old woman with a suspected history of aluminum phosphide poisoning (Nayyar & Nair, 2009).

2) Renal damage has been reported following both acute and chronic exposure. Proteinuria and renal failure have been reported (Chopra et al, 1986).

Acid-Base

3.11.2)

A) METABOLIC ACIDOSIS

1) WITH POISONING/EXPOSURE

a) Metabolic acidosis is common with significant poisoning, and more severe acidosis is associated with decreased survival (Jadhav et al, 2012; Jaiswal et al, 2009).
b) CASE SERIES: Medical records of patients with aluminum phosphide poisoning, admitted to a hospital in Tehran, Iran from 2000 to 2007, were analyzed retrospectively. Arterial blood gas analyses performed at hospital admission showed a significant difference between survival and nonsurvival groups according to blood pH and HCO3 concentration. The mean blood pH and HCO3 concentration of the nonsurvival group (n=146) was 7.07 +/-0.18 and 9.95 +/- 2.71 mEq/L, respectively. In comparison, the blood pH and HCO3 concentration of the survival group was 7.32 +/-0.08 and 14.36 +/-3.30 mEq/L, respectively. All patients with an arterial pH less than 7.2 died, while all patients with an arterial pH of 7.35 or greater survived (Shadnia et al, 2009).
c) In 25 adult patients with acute aluminum phosphide poisoning, 8 had metabolic acidosis (Khosla et al, 1988).

1) Acidosis is more likely to be severe (pH < 7.1) in patients who do not survive (Singh et al, 2006).

d) CASE REPORT: Mixed metabolic and respiratory acidosis (pH 7.02, pO2 68 mmHg, pCO2 42 mmHg, HCO3 12 mmol/L) was reported in a 28-year-old man with severe poisoning after ingesting aluminum phosphide (Aggarwal et al, 1999).
e) CASE REPORT: Metabolic acidosis (pH 7.095, pCO2 16.1 mmHg, pO2 99 mmHg, HCO3 5 mmol/L) was reported in a 34-year-old man who ingested 2 tablets, each tablet containing 3 grams aluminum phosphide, in a suicide attempt. The patient recovered with supportive care (Verma et al, 2007).
f) CASE REPORT: A 25-year-old woman presented with severe nausea and vomiting approximately 30 minutes after ingesting 10 tablets containing 50% aluminum phosphide. The patient developed tachycardia (up to 160 bpm), hypotension (systolic pressure less than 90 mmHg and MAP less than 60 mmHg), and metabolic acidosis (pH 7.33, PaCO2 23.3, HCO3 12.1, base excess -13.8). Despite supportive measures, including continuous venovenous hemodiafiltration and administration of fluids and vasopressors, her condition continued to deteriorate and she subsequently died approximately 48 hours postingestion (Chacko & Shivaprasad, 2008).
g) CASE REPORT: A 39-year-old man ingested 3 pellets (9 g) of aluminum phosphide and developed somnolence, dyspnea, hypotension, recurrent ventricular tachycardia, and metabolic acidosis. He died about 5 hours after ingestion (Alter et al, 2001).
h) CASE REPORT: A 19-year-old man presented to the emergency department comatose and in shock approximately 7.5 hours after ingesting 1 aluminum phosphide tablet (3 g). Laboratory data revealed severe metabolic acidosis (pH of 6.86), serum lactate level of 13 mmol/L, and a blood glucose concentration of 15 mg/dL. His oxygen saturation was 70%. An ECG demonstrated T-wave inversion and ST elevation with sinus tachycardia, and a troponin level was 0.36 mcg/L. Following administration of 2 50-mL IV boluses of 50% dextrose followed by a continuous infusion of 10% dextrose, his blood glucose concentration increased to 110 mg/dL; however, his neurological status remained unchanged. Despite gastric lavage and aggressive symptomatic and supportive therapy, including administration of IV fluids, magnesium sulfate, sodium bicarbonate, and N-acetylcysteine, the patient died 30 hours after presentation (Jamshed et al, 2014).
i) CASE SERIES: A review of records of hospital admissions in Tirana, Albania from 2009 to 2013 identified 140 fatalities from aluminum phosphide poisoning. The primary route of exposure in 96% of the cases was ingestion, and the mean period of time from exposure to hospital admission was 3.91 hours (+/- 5.11 hours). The aluminum phosphide dose ranged from 0.5 tablet to 5 tablets (0.5 to 5 g of active component [ie, phosphine]). At hospital arrival, metabolic acidosis was reported in 123 of the 140 patients (88%) (Sulaj et al, 2015).

Hematologic

3.13.2)

A) HEMOLYSIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 28-year-old man developed vomiting, abdominal pain, metabolic acidosis, and hypotension after ingesting a tablet of aluminum phosphide. Twenty-four hours after admission he had evidence of hemolysis (jaundice, increased unconjugated bilirubin, anemia, elevated plasma hemoglobin and hemosiderin in urine). G-6-PD level estimated 8 weeks later was normal (Aggarwal et al, 1999).

B) ANEMIA

1) WITH POISONING/EXPOSURE

a) Leukopenia, leukocytosis, anemia, polycythemia, or monocytosis may be noted.
b) CASE REPORT: Anemia and thrombocytopenia (hemoglobin 7.8 g/dl, leukocyte count 8600/mm(2), platelet count 41/mm(2)) was reported in a 22-year-old woman following ingestion of one 0.6 gram tablet containing 56% aluminum phosphide. The patient's hematological parameters normalized following platelet and packed cell transfusions (Siddaiah et al, 2009).

C) METHEMOGLOBINEMIA

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 25-year-old man ingested 6 grams of aluminum phosphide and developed vomiting, abdominal pain, hypotension, drowsiness, hemolysis, and myocardial depression. Twenty-four hours after admission, he developed methemoglobinemia (17%) that responded to methylene blue (Lakshmi, 2002).
b) CASE REPORTS: Two patients, 32-year-old and 46-year-old men, presented to the emergency department following intentional ingestion of 2 and 5 aluminum phosphide tablets, respectively. The first patient was asymptomatic on arrival; however, the second patient presented with abdominal pain and vomiting. Although the patients received decontamination with gastric lavage and activated charcoal, and supportive care, hemolysis and hematuria developed. Suspecting methemoglobinemia after observing a decrease in oxygen saturation despite high FIO2-promoted intubation and mechanical ventilation, cooximetry was performed, revealing methemoglobin concentrations of 40% and 30%, respectively. Both patients were unresponsive after administration of vitamin C in the first patient (methylene blue was not available) and methylene blue in the second patient. Both patients subsequently died (Shadnia et al, 2011).

Endocrine

3.16.2)

A) DISORDER OF ENDOCRINE SYSTEM

1) WITH POISONING/EXPOSURE

a) Adrenocortical injury with elevated serum cortisol levels has been reported (Chugh et al, 1989c).

B) HYPOGLYCEMIA

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 19-year-old man presented to the emergency department comatose and in shock approximately 7.5 hours after ingesting 1 aluminum phosphide tablet (3 g). Laboratory data revealed severe metabolic acidosis (pH of 6.86), serum lactate level of 13 mmol/L, and a blood glucose concentration of 15 mg/dL. His oxygen saturation was 70%. An ECG demonstrated T-wave inversion and ST elevation with sinus tachycardia, and a troponin level was 0.36 mcg/L. Following administration of 2 50-mL IV boluses of 50% dextrose followed by a continuous infusion of 10% dextrose, his blood glucose concentration increased to 110 mg/dL; however, his neurological status remained unchanged. Despite gastric lavage and aggressive symptomatic and supportive therapy, including administration of IV fluids, magnesium sulfate, sodium bicarbonate, and N-acetylcysteine, the patient died 30 hours after presentation (Jamshed et al, 2014).

C) HYPERGLYCEMIA

1) WITH POISONING/EXPOSURE

a) CASE SERIES: A review of records of hospital admissions in Tirana, Albania from 2009 to 2013 identified 140 fatalities from aluminum phosphide poisoning. The primary route of exposure in 96% of the cases was ingestion, and the mean period of time from exposure to hospital admission was 3.91 hours (+/- 5.11 hours). The aluminum phosphide dose ranged from 0.5 tablet to 5 tablets (0.5 to 5 g of active component [ie, phosphine]). At hospital arrival, hyperglycemia was reported in 22 of the 140 patients (16%) (Sulaj et al, 2015).

Reproductive

3.20.1)

A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
C) At the time of this review no information about possible male reproductive effects was found in available references.

3.20.2)

A) LACK OF INFORMATION

1) At the time of this review, no data were available to assess the teratogenic potential of this agent.

3.20.3)

A) LACK OF INFORMATION

1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

3.20.4)

A) LACK OF INFORMATION

1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS20859-73-8 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

3.21.2)

A) Rats fed diets containing levels of 0.337 to 0.996 mg/kg of phosphine derived from aluminum phosphide had no toxicity and no increased incidence of neoplasms.

3.21.3)

A) LACK OF EFFECT

1) Rats fed diets containing levels of 0.337 to 0.996 mg/kg of phosphine derived from aluminum phosphide had no toxicity and no increased incidence of neoplasms (Hackenberg, 1972).

Genotoxicity

A)

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor vital signs and mental status.
B) Monitor continuous pulse oximetry.
C) Institute continuous cardiac monitoring and obtain an ECG.
D) Monitor serum electrolytes, renal function, and liver enzymes.
E) Obtain a chest radiograph in patients with respiratory symptoms.

4.1.2)

A) Monitor serum electrolytes, renal function, and liver enzymes.

4.1.4)

A) OTHER

1) MONITORING

a) Monitor vital signs and mental status.
b) Monitor continuous pulse oximetry.

2) ECG

a) Institute continuous cardiac monitoring and obtain an ECG.

3) CHEST RADIOGRAPH

a) Obtain a chest radiograph in patients with respiratory symptoms.

4) OTHER

a) In India, where aluminum phosphide ingestion is a common method of suicide, the diagnosis is confirmed by having the patient breathe on a paper moistened with a fresh solution of silver nitrate. If the paper turns black, the test is considered positive for phosphine (Christophers et al, 2002).

Treatment

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients with worsening or severe symptoms should be admitted to the hospital, and depending on the severity of their symptoms (eg, respiratory distress requiring intubation, hypotension, dysrhythmias, CNS depression), may require an ICU bed. Patients can be discharged once they are hemodynamically stable with clear improvement or asymptomatic from their exposure.

6.3.1.2) HOME CRITERIA/ORAL

A) There is no role for home management of aluminum phosphide exposures.

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a medical toxicologist and/or poison centers for any patient with significant aluminum phosphide poisoning. Other helpful consultants may include critical care physicians and pulmonologists to help management of the patient's symptoms.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) All patients with exposures should be sent to a healthcare facility for observation for at least a period of 6 to 8 hours of observation. Patients may be discharged home if they are asymptomatic or clearly improving and stable for discharge with careful instructions to return if any respiratory symptoms develop.

Monitoring

A)

B)

C)

D)

E)

Oral Exposure

6.5.1)

A) Prehospital gastrointestinal decontamination is not recommended because of the potential for formation of phosphine gas and the potential for abrupt deterioration.

6.5.2)

A) SUMMARY

1) The role of GI decontamination is not clear, as contact with water has the potential to form phosphine gas. Activated charcoal could be considered for patients with recent aluminum phosphide ingestion (less than one hour) who are awake, alert, and cooperative. Endoscopic removal of aluminum phosphide tablets can be considered if it can be performed rapidly.

B) ACTIVATED CHARCOAL

1) CHARCOAL ADMINISTRATION

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

2) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

6.5.3)

A) SUPPORT

1) CIRCULATORY/RESPIRATORY SUPPORT: Anticipate need to provide circulatory support and possible development of pulmonary edema.

a) Standard antiarrhythmic therapy may be required; obtain an ECG and institute continuous cardiac monitoring as indicated.

1) MAGNESIUM SULFATE: Intravenous magnesium sulfate has been used in cases of shock and cardiac arrhythmias when hypomagnesemia is present (Banjaj & Wasir, 1988). Treatment with vasopressors and intravenous magnesium sulfate has been recommended (Gupta & Ahlawat, 1995).
2) INTRA-AORTIC BALLOON PUMP: An intra-aortic balloon pump was successfully used as a bridge to recovery in a young adult who presented with cardiogenic shock and severe left ventricular dysfunction, unresponsive to intensive inotropic support, following ingestion of one 0.6-gram tablet containing 56% aluminum phosphide (Siddaiah et al, 2009).

b) Replace fluids and electrolytes as indicated.

B) MONITORING OF PATIENT

1) Monitor vital signs and mental status.
2) Monitor continuous pulse oximetry.
3) Institute continuous cardiac monitoring and obtain an ECG.
4) Monitor serum electrolytes, renal function, and liver enzymes.
5) Obtain a chest radiograph in patients with respiratory symptoms.

C) METABOLIC ACIDOSIS

1) Aggressive correction of metabolic acidosis with sodium bicarbonate may improve outcome, although the data supporting this is from an uncontrolled study.
2) COHORT STUDY: A study, involving 40 patients with aluminum phosphide poisoning, was conducted to determine what effect full correction of severe metabolic acidosis had on patient outcome (Jaiswal et al, 2009).

a) All 40 patients developed metabolic acidosis, with a Base Excess of -15.7 +/- 3.34 (range -21 to -11) and an average pH of 7.201 +/- 0.143. All patients were treated with full correction of their metabolic acidosis. A immediate dose of intravenous NaHCO3 was administered (administered NaHCO3 (mEq) = 0.6 x body weight (kg) x base excess), with repeat arterial blood gases hourly and subsequent sodium bicarbonate administration determined by blood gas results. After two consecutive blood gases with arterial pH above 7.4, subsequent blood gases were done at 2, 4 or 6 hourly intervals.
b) Overall, 22 of the 40 patients (55%) survived, and the sodium bicarbonate requirement was lower for survivors (554 +/- 128.33 mL) compared with non-survivors (722.22 +/- 253.85 mL) . In comparison, overall survival was 30.36% in 112 historic controls treated by the same authors with half-correction of metabolic acidosis.
c) The use of historic controls makes is difficult to attribute the survival difference solely to bicarbonate administration.

D) SEIZURE

1) SUMMARY

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

2) DIAZEPAM

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

3) NO INTRAVENOUS ACCESS

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

4) LORAZEPAM

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

5) PHENOBARBITAL

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

6) OTHER AGENTS

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

E) ACUTE LUNG INJURY

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

F) HYPOTENSIVE EPISODE

1) SUMMARY

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

2) DOPAMINE

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

3) NOREPINEPHRINE

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

4) INTRA-AORTIC BALLOON PUMP

a) An intra-aortic balloon pump was successfully used in a 22-year-old woman who presented with cardiogenic shock, persistent hypotension, and severe left ventricular dysfunction, unresponsive to intensive inotropic support, following ingestion of one 0.6-gram tablet containing 56% aluminum phosphide (Siddaiah et al, 2009).
b) CASE REPORT: A 25-year-old woman presented with severe nausea and vomiting approximately 30 minutes after ingesting 10 tablets containing 50% aluminum phosphide. The patient developed tachycardia (up to 160 bpm), hypotension (systolic pressure less than 90 mmHg and MAP less than 60 mmHg), and metabolic acidosis. An echocardiogram demonstrated severe impairment of left ventricular function with an ejection fraction of less than 30%, despite inotropic support with dobutamine and adrenaline, and her troponin-I level was elevated at 12.7 ng/mL (normal 0 to 0.4 ng/mL). Although an intraaortic balloon pump was inserted to support left ventricular function, the patient's condition continued to deteriorate and she subsequently died approximately 48 hours post-ingestion (Chacko & Shivaprasad, 2008).

G) VENTRICULAR ARRHYTHMIA

1) VENTRICULAR DYSRHYTHMIAS SUMMARY

a) Obtain an ECG, institute continuous cardiac monitoring and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders (particularly hypokalemia, hypocalcemia, and hypomagnesemia). Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.

2) LIDOCAINE

a) LIDOCAINE/INDICATIONS

1) Ventricular tachycardia or ventricular fibrillation (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010; Vanden Hoek et al, 2010).

b) LIDOCAINE/DOSE

1) ADULT: 1 to 1.5 milligrams/kilogram via intravenous push. For refractory VT/VF an additional bolus of 0.5 to 0.75 milligram/kilogram can be given at 5 to 10 minute intervals to a maximum dose of 3 milligrams/kilogram (Neumar et al, 2010). Only bolus therapy is recommended during cardiac arrest.

a) Once circulation has been restored begin a maintenance infusion of 1 to 4 milligrams per minute. If dysrhythmias recur during infusion repeat 0.5 milligram/kilogram bolus and increase the infusion rate incrementally (maximal infusion rate is 4 milligrams/minute) (Neumar et al, 2010).

2) CHILD: 1 milligram/kilogram initial bolus IV/IO; followed by a continuous infusion of 20 to 50 micrograms/kilogram/minute (de Caen et al, 2015).

c) LIDOCAINE/MAJOR ADVERSE REACTIONS

1) Paresthesias; muscle twitching; confusion; slurred speech; seizures; respiratory depression or arrest; bradycardia; coma. May cause significant AV block or worsen pre-existing block. Prophylactic pacemaker may be required in the face of bifascicular, second degree, or third degree heart block (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010).

d) LIDOCAINE/MONITORING PARAMETERS

1) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).

3) AMIODARONE

a) AMIODARONE/INDICATIONS

1) Effective for the control of hemodynamically stable monomorphic ventricular tachycardia. Also recommended for pulseless ventricular tachycardia or ventricular fibrillation in cardiac arrest unresponsive to CPR, defibrillation and vasopressor therapy (Link et al, 2015; Neumar et al, 2010). It should be used with caution when the ingestion involves agents known to cause QTc prolongation, such as fluoroquinolones, macrolide antibiotics or azoles, and when ECG reveals QT prolongation suspected to be secondary to overdose (Prod Info Cordarone(R) oral tablets, 2015).

b) AMIODARONE/ADULT DOSE

1) For ventricular fibrillation or pulseless VT unresponsive to CPR, defibrillation, and a vasopressor therapy give an initial dose of 300 mg IV followed by 1 dose of 150 mg IV. For stable ventricular tachycardias: Infuse 150 milligrams over 10 minutes, and repeat if necessary. Follow by a 1 milligram/minute infusion for 6 hours, then a 0.5 milligram/minute. Maximum total dose over 24 hours is 2.2 grams (Neumar et al, 2010).

c) AMIODARONE/PEDIATRIC DOSE

1) Infuse 5 milligrams/kilogram as a bolus for pulseless ventricular tachycardia or ventricular fibrillation; may repeat twice up to 15 mg/kg. Infuse 5 milligrams/kilogram over 20 to 60 minutes for perfusing tachycardias. Maximum single dose is 300 mg. Routine use with other drugs that prolong the QT interval is NOT recommended (Kleinman et al, 2010).

d) ADVERSE EFFECTS

1) Hypotension and bradycardia are the most common adverse effects (Neumar et al, 2010).

H) CORTICOSTEROID

1) Corticosteroids have not been shown to be efficacious (Banjaj & Wasir, 1988).

I) EXPERIMENTAL THERAPY

1) Parenteral atropine (1 mg/kg intraperitoneal) and pralidoxime (5 mg/kg intraperitoneal) improved survival in a rat model when given 5 minutes after intragastric aluminium phosphide administration. Short-term survival increased 2.5 times (3.4 +/- 2.5 hours versus 1.4 +/- 0.3 hours) over untreated controls in 9 of 15 animals. The remaining 6 animals made a complete recovery and were observed up to 30 days. Plasma cholinesterase levels were inhibited by 47% in treated rats, as compared with controls (Mittra et al, 2001).

Inhalation Exposure

6.7.1)

A) Move patient to fresh air as soon as possible from inhalational exposures.

6.7.2)

A) SUPPORT

1) Move patient to fresh air and monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as needed. Bronchospasm can be treated with B2 agonists and oral or parenteral corticosteroids.

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

6.8.1)

A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

6.9.1)

A) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

6.9.2)

A) SKIN ABSORPTION

1) It is not known whether or not dermal exposure can result in systemic toxicity (EPA, 1985).

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

A)

1) There is no evidence for the use of dialysis, hemoperfusion, urinary alkalinization, or multiple dose charcoal. Dialysis or hemoperfusion are unlikely to be helpful for phosphine exposures.

Abstracts

Case Reports

A)

1) A 6-year-old boy was admitted with complaints of epigastric pain, vomiting, and altered sensorium 6 hours after intentional ingestion of an unknown quantity of aluminum phosphide (Celphos) tablets; signs and symptoms began 2 hours postingestion.

a) On admission, pulse was 128/minute and regular, respiratory rate 46/minute and blood pressure 80/60 mmHg; he was drowsy, restless, and showed slowly reactive pupils. Treatment included gastric lavage with potassium permanganate 1:5000, intravenous fluids, magnesium sulfate, and oxygen inhalation.
b) As his condition deteriorated, he was given intravenous dopamine infusion and hydrocortisone. That therapy also failed, and he expired after 3 hours of cardiorespiratory failure. The mother and 3 siblings (aged 3 to 10 years) who also ingested the tablets at the same time, succumbed 8 hours and 30 minutes postingestion, respectively (Ahmad et al, 1991).

Range Of Toxicity

Summary

A)

Minimum Lethal Exposure

A)

1) ADULT

a) A 25-year-old woman developed severe tachycardia, hypotension, metabolic acidosis, and left ventricular dysfunction with an ejection fraction of less than 30% after ingesting 10 tablets containing 50% aluminum phosphide. Despite supportive measures including continuous veno-venous hemodiafiltration and administration of fluids and vasopressors, her condition continued to deteriorate and she subsequently died approximately 48 hours postingestion (Chacko & Shivaprasad, 2008).
b) A 40-year-old man presented with abdominal pain, tachycardia (110 bpm), and hypotension (70/30 mmHg) approximately 3 hours after intentionally ingesting one 3-gram aluminum phosphide tablet. An initial ECG revealed ST elevation with a broad QRS complex mimicking an inferior wall myocardial infarction. Despite intensive vasopressor support, his hypotension continued to persist. Repeat ECGs, obtained six hours following admission and on hospital day 2, indicated severe myocardial injury. Although aggressive supportive therapy and resuscitative measures were given, the patient's condition continued to deteriorate and he died approximately 2 days after admission. Postmortem examination of his heart showed severe myocyte vacuolation, and necrosis and myocytolysis of the myocardial fibers (Shah et al, 2009).
c) Progressive hypotension, refractory ventricular tachycardia, acidosis, and respiratory failure, resulting in death, occurred in a 19-year-old man who intentionally ingested 10 500-mg tablets containing 56% aluminum phosphide (Jadhav et al, 2012).
d) A 19-year-old man presented to the emergency department comatose and in shock approximately 7.5 hours after ingesting 1 aluminum phosphide tablet (3 g). Laboratory data revealed severe metabolic acidosis (pH of 6.86), serum lactate level of 13 mmol/L, and a blood glucose concentration of 15 mg/dL. His oxygen saturation was 70%. An ECG demonstrated T-wave inversion and ST elevation with sinus tachycardia, and a troponin level was 0.36 mcg/L. Following administration of 2 50-mL IV boluses of 50% dextrose followed by a continuous infusion of 10% dextrose, his blood glucose concentration increased to 110 mg/dL; however, his neurological status remained unchanged. Despite gastric lavage and aggressive symptomatic and supportive therapy, including administration of IV fluids, magnesium sulfate, sodium bicarbonate, and N-acetylcysteine, the patient died 30 hours after presentation (Jamshed et al, 2014).

2) PEDIATRIC

a) Three children (ages 8, 5, and 3 years) presented to the emergency department with drowsiness, vomiting, diarrhea, and respiratory insufficiency following exposure of 25 tablets of an insecticide used to kill bed bugs in their room. The 8-year-old child died on route to the hospital. Suspecting organophosphorus poisoning, the other 2 children were treated accordingly. After 2 days of treatment, the 3-year-old showed clinical improvement and was subsequently discharged from the hospital. Approximately 10 hours after discharge, the patient died. The 5-year-old showed signs of hemodynamic instability, with delayed capillary refill of 4 seconds, and an echocardiography indicating an ejection fraction of less than 50%. Analysis of samples of the pesticide revealed that it contained aluminum phosphide. With supportive treatment for the next 48 hours, a repeat echocardiography indicated an improvement in his ejection fraction to 60%. Following 2 more days of observation, the patient was discharged without sequelae (Hirani & Rahman, 2010).

B)

1) Among 25 adults with acute aluminum phosphide poisoning, 10 died. All patients who died had consumed 3 or more aluminum phosphide tablets (Khosla et al, 1988b).

a) On admission, all were delirious and in severe shock. Death occurred within 1 to 6 hours of admission (Khosla et al, 1988b).

2) The median lethal dose of aluminum phosphide in humans is 20 milligrams/kilogram (EPA, 1985). In a 70 kg adult, less than 500 mg of aluminum phosphide may be fatal if ingested; pellets contain 3 grams (Banjaj & Wasir, 1988).
3) Eleven of 15 adult patients who ingested between 1.5 and 9 grams of aluminum phosphide died (Singh et al, 1985).
4) In a series of 83 fatalities from aluminum phosphide ingestion, the doses ingested ranged from 1 to 3 tablets (each tablet was 3 g of 56% aluminum phosphide and 44% ammonium carbonate; fatal doses were 1.68 to 5.04 g aluminum phosphide) (Sinha et al, 2005).
5) By 1988, 319 cases of fatality in India due to aluminum phosphide ingestion had been published (Kabra & Narayanan, 1988).
6) A review of hospital admission records in Tirana, Albania from 2009 to 2013 identified 140 fatalities from aluminum phosphide poisoning. The primary route of exposure in 96% of the cases was ingestion, and the mean period of time from exposure to hospital admission was 3.91 hours (+/- 5.11 hours). The aluminum phosphide dose ranged from 0.5 tablet to 5 tablets (0.5 to 5 g of active component [ie, phosphine]). Death occurred within 24 hours after presentation in 85% of the patients. Presenting signs and symptoms included nausea, vomiting, abdominal pain, chest pain, cyanosis, pulmonary edema, restlessness, metabolic acidosis, hypomagnesemia, hyperglycemia, coma, and cardiovascular collapse (Sulaj et al, 2015).

Maximum Tolerated Exposure

A)

1) INHALATION: Phosphine is a highly toxic gas, especially to organs with high oxygen flow and demand.
2) AIRBORNE CONCENTRATION: The minimal detectable (decaying fish odor) airborne concentration is 1 to 3 parts per million (ppm) in air. The gas dissipates rapidly; it is primarily toxic in closed spaces.
3) FUMIGATION: Aluminum phosphide residues of about 0.01 ppm in foodstuffs following fumigation have been considered to be within safety limits for human consumption (Dieterich et al, 1967).

B)

1) In a series of 40 patients with aluminum phosphide tablet ingestions, 33 patients ingested fresh tablets and 7 patients ingested exposed tablets (tablets that are exposed to the air and come into contact with moisture, releasing phosphine gas). The survival rate was 45.5% for patients who ingested fresh tablets as compared with 100% survival rate in patients who ingested exposed tablets (Jaiswal et al, 2009).

C)

1) In a series of 92 cases of aluminum phosphide poisoning, 58 patients ingested less than 1 gram of aluminum phosphide and 34 patients ingested more than 1 gram (Singh et al, 1991). Vomiting occurred in all patients. Survival was reported in 26 patients. No relationship was established between the amount ingested and mortality in this study.
2) Toxic mechanisms may include free radical generation and lipid peroxidation; following acute aluminum phosphide ingestion, mortality has been greater than 50 percent (Chugh et al, 1996).
3) Two patients developed vomiting, abdominal pain, hypotension, elevated liver enzyme concentrations, and reversible myocardial injury (ST segment elevation and left ventricular hypokinesia with a left ventricular ejection fraction of 30% or less) after ingesting 1 to 3 tablets of a fumigant containing aluminum phosphide. Each 3-gram tablet contained 56% aluminum phosphide. Both patients recovered with supportive care (Akkaoui et al, 2007).
4) A 34-year-old man developed tachycardia, hypotension, metabolic acidosis, and pancreatitis after ingesting 2 tablets, each containing 3 grams aluminum phosphide, in a suicide attempt. The patient recovered with supportive care (Verma et al, 2007).
5) A 22-year-old woman presented with cardiogenic shock and severe left ventricular dysfunction after ingesting one 0.6-gram tablet containing 56% aluminum phosphide. Following insertion of an intra-aortic balloon pump and intensive supportive care, toxic myocarditis resolved and the patient recovered (Siddaiah et al, 2009).
6) A 30-year-old man developed left side hemiplegia and left hemifacial paresis with dysarthria 11 days after intentionally ingesting 3 rice tablets (each tablet containing 56% aluminum phosphide and 44% ammonium carbonate). A brain MRI and a brain MR angiography revealed ischemic lesions in the area of the right middle cerebral artery (MCA) and stenosis of the right MCA stem, respectively. With supportive therapy, the patient's general condition gradually improved, although his motor deficit persisted, and he was discharged on hospital day 11. A follow-up examination, 1 month later, demonstrated improvement in his left side hemiparesis (Abedini et al, 2014).
7) CASE SERIES: According to the medical records of 471 patients with aluminum phosphide poisoning who were admitted to a hospital in Tehran, Iran from 2000 to 2007, an average of 1.6 aluminum phosphide tablets were ingested (range 0.25 to 7 tablets), with 73% of the patients ingesting 1 to 3 tablets, 17% ingesting more than 3 tablets, and 10% ingesting less than 1 tablet. Of those patients who survived (n=325), the mean number of tablets ingested was 1.49 +/-0.93 as compared to 1.92 +/- 0.86 tablets (p=0.19) ingested by the patients who did not survive (n=146) (Shadnia et al, 2009).

D)

1) Three children (ages 8, 5, and 3 years) presented to the emergency department with drowsiness, vomiting, diarrhea, and respiratory insufficiency following exposure of 25 tablets of an insecticide used to kill bed bugs in their room. The 8-year-old child died on route to the hospital. Suspecting organophosphorus poisoning, the other 2 children were treated accordingly. After 2 days of treatment, the 3-year-old showed clinical improvement and was subsequently discharged from the hospital. Approximately 10 hours post-discharge, the patient died. The 5-year-old showed signs of hemodynamic instability, with delayed capillary refill of 4 seconds, and an echocardiography indicating an ejection fraction of less than 50%. Analysis of samples of the pesticide revealed that it contained aluminum phosphide. With supportive treatment for the next 48 hours, a repeat echocardiography indicated an improvement in his ejection fraction to 60%. Following 2 more days of observation, the patient was discharged without sequelae (Hirani & Rahman, 2010).

E)

1) Rats fed diets containing 0.337 to 0.996 mg/kg of phosphine derived from aluminum phosphide had no toxicity and no evidence of an increased incidence of neoplasms (Hackenberg, 1972).

Workplace Standards

A)

1) Not Listed

B)

1) Not Listed

C)

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
2) EPA (U.S. Environmental Protection Agency, 2011): Not Assessed under the IRIS program. ; Listed as: Aluminum phosphide
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D)

1) Not Listed

Toxicity Information

7.7.1)

A) References: RTECS, 1996

Pharmacology Toxicology

Toxicologic Mechanism

A)

B)

Physicochemical

Physical Characteristics

A)

Molecular Weight

A)

Animal Toxicology

References

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FeedBack

ALUMINUM PHOSPHIDE

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Acid-Base

Hematologic

Endocrine

Reproductive

Carcinogenicity

Genotoxicity

Monitoring Parameters Levels

Life Support

Patient Disposition

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Enhanced Elimination

Case Reports

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Workplace Standards

Toxicity Information

Toxicologic Mechanism

Physical Characteristics

Molecular Weight

General Bibliography