1. Aluminum Phosphide poisoning
DR. Saiyed Zama Hussain

2. LEARNING OUTCOME Source Characteristics Mode of poisoning & fatal dose
Signs and symptoms
Diagnosis
Management

3. Acute Aluminum Phosphide poisoning
aluminum phosphide has emerged as the commonest suicidal agent in Northern India.
extremely lethal
usually suicidal, Adult male preponderance, in lower socio-economic strata, rural population
uncommonly accidental (Farmers, Children) and rarely homicidal

4. Availability
Celphos, Alphos, Quickphos, Phostoxin, Phosphotex, Fumigran, chemfume
3 gm tablets or 0.6 gm pellets

8. Characteristics of AlP
Greyish green tablet, metallic taste, garlicky odour.
Solid fumigant pesticide, insecticide and rodenticide.
commonly used as grain fumigant because of its near ideal properties;
Cheap
Toxic to all stages of insects,
highly potent,
does not affect seed viability,
free from toxic residues
leaves little residue on food grains (phosphite & hypophosphite of aluminium are non-toxic residues left in the grains).

9. Characteristics
Each 3 gm tablet releases 1 gm and each 0.6 gm pellet releases 0.2 gm of Phosphine gas on exposure to moisture.
HCl in stomach accelerate the convertion.
AlP + 3H2O → Al (OH)3 + PH3
AlP + 3HCl → AlCl3 + PH3
Phosphine gas is colourless and odorless. However on exposure to air it gives a foul odour (garlicky or decaying fish).

10. Pharmacokinetics Ingest AlP is absorbed by simple diffusion.
metabolised in liver & phosphine is slowly released.
Phosphine is oxidised slowly to oxyacids.
Excreted in urine as hypophosphine.
Inhale
Rapidly absorbed from the lungs.
Excreted unchanged form through lungs.

11. Mode of poisoning & fatal dose
Ingestion
Fatal dose: 0.5 g (1-3 tablets)
Fatal period: 1-4 hours. Majority die within 24 hours
Inhalation
Fatal dose: phosphine ppm
3. absorption through the skin (rare)

12. Mechanism of toxicity
react with gastric acid to form phosphine, a potent pulmonary and GI toxicant.
Inhibits respiratory chain enzymes, electron transport, cyt oxidase.
Formation of highly reactive hydroxyl radicals
leads to cell necrosis and death.

16. There is a decrease in the level of catalase and increase in the activity of superoxide dismutase.
Indicators of oxidative stress (reduced glutathione, malonyl dialdehyed) reach peak levels within 48 h of exposure, and normalize by day 5.

17. Signs & Symptoms INHALATION
MILD: irritation of mucous membrane, dizziness, easy fatigue, nausea, vomiting, diarrhoea, headache, tightness in the chest, acute respiratory distress
MODERATE: ataxia, numbness, paraesthesia, tremors, diplopia, jaundice, muscular weakness, incoordination and paralysis
SEVERE (PH3> 0.3 ppm): adult respiratory distress syndrome, cariac arrhythmias, congestive cardiac failure, pulmonary edema, convulsions, coma

18. INGESTION MILD: nausea, vomiting, headache, abdominal pain (usually recover) MODERATE & SEVERE: systemic manifestations are early and progressive and mostly fatal GIT: nausea, vomiting, diarrhoea, retrosternal pain, excessive thirst CVS: hypotension, shock, arrhythmias, myocarditis, dry pericarditis, acute congestive heart failure initial 3–6 h, sinus tachycardia, 6–12 h period ST-T changes and conduction disturbances, the later period, arrhythmias RS: cough, dyspnoea, Chest tightness, cyanosis, pulmonary edema, respiratory failure, Effusion, ARDS HEPATIC: jaundice, hepatitis, hepatomegaly RENAL: acute tubular necrosis, renal failure CNS: headache, dizziness, tremors, paresthesias, altered mental state, restlessness, convulsions, acute hypoxic encephalopathy, coma Other: acute adrenocortical insufficiency, severe metabolic acidosis, DIC, Hypomagnesemia, pancreatitis, hypo- or hyperglycemia, methhemoglobinemia, microangiopathic hemolytic anemia RARE: muscle wasting, tenderness and bleeding diathesis

19. Complications Cardiogenic shock (most common cause of death)
Pericarditis
Acute congestive cardiac failure
Acute massive GI bleeding
ARDS (high mortality)

20. Diagnosis A positive history of ingestion or clinical suspicion.
typical clinical features-
garlicky odour from the mouth
highly variable arrhythmias in a young patient with shock and no history of cardiac disease .
Silver Nitrate Test - Detection of phosphine in the exhaled air/stomach aspirate Using a silver nitrate impregnated strip or a specific phosphine detector tube.
gas chromatography with a nitrogen–phosphorous detector is the most specific and sensitive (mainly research purpose)
Cytochrome-c oxidase activity in platelets

21. Silver Nitrate Test
5 ml of gastric aspirate + 15 ml of water are put in a flask and the mouth is covered with a filter paper impregnated with 0.1 N silver nitrate. Flask is heated at 50C for minutes. Filter paper turns black if phosphine present.
A piece of filter paper impregnated with 0.1 N silver nitrate solution is used in the form of mask through which the patient breathes for 5-10 minutes. Filter paper turns black if phosphine present. (POSITIVE only when >6 g is ingested)

22. Laboratory investigations
mainly done to assess the prognosis.
Leucopenia indicates severe toxicity.
Increased SGOT or SGPT and metabolic acidosis indicate moderate to severe poisoning.
low magnesium,
potassium may be increased or decreased.
Raised urea/creatinine
plasma renin level - direct relationship with mortality and to the dose of pesticide.
The serum level of cortisol is low in severe poisoning.

23. Chest X-ray - ARDS / pleural effusion
ECG - shows various manifestations of cardiac injury
(ST depression or elevation, bundle branch block,
ventricular tachycardia, ventricular fibrillation).
Echocardiography - Wall motion abnormalities, generalized LV hypokinesia , decreased EF and pericardial effusion

24. POISONING MANAGEMENT: GENERAL PRINCIPLES
Initial resuscitation and stabilization
Removal of toxin from the body
Prevention of further poison absorption
Enhancement of poison elimination
Administration of antidote
Prevention of re – exposure
Supportive treatment

25. Treatment should not be delayed for confirmatory diagnosis.
Early arrival, resuscitation, intensive monitoring and supportive therapy may result in good outcome.
No specific antidote.
the key to treatment lies in rapid decontamination and resuscitative measures.
correcting electrolyte abnormalities & Shock.
Monitoring of vitals and Initial investigations
Repeated ECG and echocardiography can reveal cardiac dysfunction early.

26. INITIAL EVALUATION AND RESUSCITATION
Immediate primary survey and ABC.
The health care provider must take personal protection measures, including full face mask and rubber gloves during decontamination.

27. DECREASE THE EXPOSURE OF POISON
The victim should be removed to fresh air immediately.
As phosphine is absorbed through the cutaneous route, decontamination of skin and eyes must be done with plain water.
After ingestion, gut decontamination is useful within 1–2 h.

28. To reduce the absorption
Gut decontamination should not be performed without airway protection.
Potassium permanganate (1:10,000) is used as it oxidises phosphine to nontoxic phosphate. followed by a slurry of activated charcoal approximately 100 gm.
0.1 – 0.2% copper sulphate can be used. It precipitates as copper sulphide and coats over phosphurus particles and is also an emetic.
Sorbitol solution 1–2 ml/kg may be used as cathartic.
In vitro experimental findings suggest that vegetable oils and liquid paraffin, inhibit phosphine release from the ingested AlP.
The possible role of coconut oil is concluded in a case report even 6 h post ingestion
Ca gluconate & NaHCO3can neutralize stomach acidity.

32. HEMODYNAMIC SUPPORT
2-3 litres of NS within the first 8-12 hr guided by CVP and PCWP.
The aim is to keep the CVP cm H2O.
Some workers recommend 3-6 litres in 3 hr.
norepinephrine or phenylephrine for low BP.
IABP in toxic myocarditis with refractory shock.

33. EARLY IDENTIFICATION AND MANAGING OTHER ORGAN FAILURES
Patients who develop cyanosis and are not responding to oxygen therapy, then methemoglobinemia should be ruled out.
Symptomatic methemoglobinemia is treated with methylene blue (1% solution) 2 mg/kg of body weight over 5 mins, which and can be repeated if the cyanosis is not resolved.

34. Hydrocortisone 200-400 mg 4-6 hrly is given to
combat shock,
reduce the dose of dopamine,
check capillary leakage in lungs (ARDS) and
to potentiate the responsiveness of the body to endogenous and exogenous catecholamines.
All types of ventricular arrhythmias are seen and management is the same as in other situations.
Patients may require up to ml of sodium bicarbonate to correct acidosis.
Dialysis may be required for severe acidosis and acute renal failure.

35. Phosphine excretion increased by
Maintaining adequate hydration and renal perfusion with fluids and low dose (4-6 μg/kg/min) dopamine.
Diuretics like frusemide can be given if SBP>90 mm Hg.

36. OTHER SUPPORTIVE THERAPY
magnesium sulfate has been shown to improve outcome.
The dosages were different in different studies:
(a) 3 g over 3 h, f/b 6 g/day for 3–5 days,
(b) 1g stat, f/b 1 g/h for 2h, f/b 1–1.5 g/6h for 5–7 day
(c) 4 g stat, 2 g after 1h and then 1g every 3 hourly
Hyperglycemia at admission is significant poor prognostic factor. treatment of hyperglycemia may improve the outcome.

37. Many therapeutic agents with antioxidant properties have been tried in experimental animal studies, like n-acetylcysteine, glutathione, melatonin, vitamin C and beta carotene, but there is a need for human trials.
The possible role of trimetazidine for cardiovascular manifestation has been demonstrated, which is an anti-ischemic drug that acts by reducing oxygen consumption.

38. RATIONALE OF USING ECMO IN POISONING
Most death occur due to severe but reversible cardiovascular dysfunction, and inability to maintain tissue perfusion
ECMO Supports the failing organs ( Heart & Lung) till the toxins are
metabolized or eliminated
Drug is distributed from central blood compartment
Allows time for Hemodialysis /Hemoperfusion

39. INDICATIONS OF ECMO IN POISONING
VA- ECMO
life threatening haemodynamic instability
Severe Myocardial dysfunction
Cardiac arrest
VV- ECMO
severe ARDS
Inhalation leading to respiratory failure
Aspiration

40. CONTRAINDICATIONS Absolute Relative Uncontrolled coagulopathy
Severe intracranial bleeding
Relative
Advanced age
irreversible brain injury
Irreversible organ failure
the role of ECMO in many of the conditions that were formerly regarded as contraindications, such as sepsis, trauma, malignancy
and pulmonary haemorrhage, has been reappraised by new insights.

41. A comparison of survival with and without extracorporeal life support treatment for severe poisoning due to drug intoxication.
Resuscitation Nov;83(11):
A retrospective cohort analysis
2350 patients affected by poisoning were seen in these hospitals and 253 patients needed vasopressor support.
Patients with persistent cardiac arrest or refractory shock due to poisoning
Total no of patients: 62 (14 underwent ECLS & 48 treated conventionally)
Thirty-five (56%) patients survived: 12/14 (86%) ECLS patients and 23/48 (48%) non-ECLS patients
Author concluded that, in case of refractory cardiac arrest & severe shock unresponsive to conventional therapies, poisoned patients
may benefit from ECPB

42. Our experience at DMCH
November 2015V olume 49, Issue 5, Pages 651–656

43. ECMO was continued for 10 days & patient recovered
Accidental inhalation of aluminium phosphide fumes lead to severe myocardial dysfunction
Inspite of very high inotropic support & IABP haemoynamics did not improve
ECMO was continued for 10 days & patient recovered

44. OUR EXPERIENCE IN ALUMINIUM PHOSPHIDE POISONING…
August 2013 – till date
Aluminium Phosphide Poisoning cases: 37
Procedure performed: VA ECMO
ECMO Weaned off successfully: 28
Survival (Discharged for hospital & on follow up): 24(65%)
All these patients were managed medically as per the guidelines and were shifted to us when haemodynamic stabilization & shock was resistant to medical management.

45. PATIENT CHARECTERSTICS PRE ECMO: HAEMODYNAMICS
PARAMETER
MEAN + SD
HEART RATE (BPM)
MEAN BLOOD PRESSURE (mm of Hg)
ECHOCARDIOGRAPHY (EF%)

46. PATIENT CHARECTERSTICS PRE ECMO: ECG RHYTHM
SINUS TACHYCARDIA 15
SINUS BRADYCARDIA 5
IDIOVENTRICULAR RHYTHM 2
ATRIAL FIBRILLATION 3
JUNCTIONAL RHYTHM 1
WIDE COMPLEX TACHYCARDIA/ VT 9
Two Patients required defibrillation
VENTRICULAR FIBRILLATION
Required CPR & Defibrillation

47. PATIENT CHARECTERSTICS PRE ECMO: LAB VALUES
PARAMETER
MEAN + SD pH
HCO3 BE
LACTATE LEVELS

48. ECMO is underutilized modality in poisoning cases with severe shock/respi failure.
There are fair chances of reversibility of toxin induced refractory shock.
The early results are encouraging, though the data is not sufficient.

49. Poor Prognostic markers
lack of vomiting after ingestion,
hyperglycemia and
time lapsed after exposure.
refractory shock,
ARDS, mechanical ventilation
metabolic acidosis,
hyperleucocytosis,
altered mental status, Coma
severe hypoxia,
GI bleeding,
Pericarditis ,arrythmias
high APACHE II score,
acute kidney injury,

50. Mortality The mortality rate is variable, from 37-100%
survival is unlikely if more than 1.5 g is ingested.
serum phosphine level of more than 1.6 mg/dl correlates with mortality.
Can reach more than 60% even in experienced and well equipped centre.
95% die within 24 hours and the commonest cause is arrhythmia.
Death after 24 hours is due to shock, acidosis, ARDS and arrhythmia.

51. Take Home Message To treat or not to treat?
Initial aggressive management can sometimes alter the outcome.
Rapid resuscitation, Decontamination, steroids, sodabicarb, MgSO4, Diuretics, Dopamine, Dialysis are mainstay of treatment.
Antioxidants, Trimetazidime, ECMO may be tried

52. Thank You