1. Protective Effects Of
N-acetyl Cysteine On
Aluminum Phosphide-induced
Oxidative Stress In Acute
Human Poisoning
Clinical Toxicology (2013)-51
Dr. Sukumar. M
Junior Resident
Department Of Medicine
AIIMS
Dr. Sravan
Senior Resident
Department Of Medicine
AIIMS

2. ALUMINIUM PHOSPHIDE
• A solid fumigant which has been extensively
used since 1940s.
• One of the most common causes of suicidal
death in north India.
• Poisoning may be
Suicidal /accidental / homicidal
• About 300,000 deaths due to this poisoning
has occurred world wide.

3. ALUMINIUM PHOSPHIDE – LETHAL DOSE &
FORMULATIONS
• Lethal dose for a 70 Kg adult ranges from
150 mg to 500 mg..!
• In INDIA, it is marketed as 0.5 gm & 3 gm
pellets. (56%)
CELPHOS
QUICKPHOS
GRAINPHOS
MEPHOS
PHOSTOXIN
SANPHOS
PHOSIDAL

4. ALUMINIUM PHOSPHIDE –
MECHANISM OF ACTION
• AlP+3H2O Al (OH)3 + PH3
• AlP+3 HCL AlCl3 + PH3
• Phosphine gas liberated induces oxidative stress
in the body.
• It inhibits cytochrome oxidase and other
mitochondrial enzymes to produce free radicals.
• Free radicals  damage biological
macromolecules  cell death

5. ALUMINIUM PHOSPHIDE POISONING –
CLINICAL PRESENTATION

6. ALUMINIUM PHOSPHIDE
POISONING - DIAGNOSIS
• History
• Typical clinical features
• Detection of phosphine
– Silver nitrate test of the lavage fluid.

7. MANAGEMENT
• As there is no specific antidote, management
is still not satisfactory.
• Only supportive therapy is possible.
– Gastric lavage within 6 hours of ingestion
• Potassium permanganate (1:10000)
• Activated charcoal 50-100 gm.
• Medicated liquid paraffin has also been used to
increase the excretion of AlP and PH3.

8. MANAGEMENT
• Magnesium sulphate has been tried as a
reducing agent but did not improve survival
rate in controlled clinical trials.
• Oxygen is given for hypoxia
• Antacids and proton pump inhibitors are
added for symptomatic relief.
• Shock is managed with
crystalloids, vasopressors and steroids.

9. PROGNOSIS
• Verry baddd… !
• Mortality rate variable 37% - 100%
• Cause of death is due to shock
, ARDS, metabolic acidosis and arrythmias.

10. N-ACETYL CYSTEINE
• Cheap, Safe Anti oxidant.
• Has mucolytic, anti-inflammatory, antioxidant
and immunomodulatory effects and hence used
in:
1. Paracetamol toxicity
2. Renal protection
3. Interstitial lung disease
4. COPD
Antioxidant property is made use in the
treatment of AlP poisoning

12. OBJECTIVE
Evaluate the effects of NAC on Aluminum
Phosphide-induced oxidative stress in acute
human poisoning

13. METHODS
Study Design
– Prospective
– Randomized Controlled
– Open-label trial

14. Study period
• April 2010 to May 2011
Setting
• Loghman Hakim Poison Center,
Tehran, Iran
METHODS

15. Sample Size
• 22 patients (11 men and 11 women) in NAC
treatment group
• 15 patients (8 men and 7 women) in control
group.
Ethical Clearance
• By Ethical Committee of Shahid University of
Medical Sciences, Tehran-Iran (Grant number:
89-01-113-7348)
METHODS

16. • Patients suspicious of Alumunium
phosphide ingestion of all age groups
with evidence such as availability of a
poison bottle or a label found by the
relatives who brought the patient to the
casuality.
INCLUSION CRITERIA

17. EXCLUSION CRITERIA
• Diabetes mellitus
• Cardiovascular diseases
• Respiratory diseases
• Renal and hepatic failure
• Patients who have received the medical
management in any medical center before
admission.

18. DATA OBTAINED AT ADMISSION

19. • Plasma lipid peroxide levels measured as
malondialdehyde(MDA) levels/litre.
• Total Antioxidant capacity(TAC) measured by
Ferric Reducing Ability of plasma(FRAP) assay.
• Markers were studied twice, first one on
admission and the second one after 24 hours
in both groups.
OXIDATIVE STRESS MARKERS

20. Gastric lavage within first 6 hours of ingestion
Potassium permanganate(1:10,000)
Activated charcoal 1 g/kg orally
Sodium bi carbonate 44mEq orally
Magnesium sulfate 4 – 6 g as iv infusion
Calcium gluconate 4 – 6 g as iv infusion
Adequate hydration
& Supportive therapy.
COMMON TREATMENT

21. NAC TREATMENT GROUP
140 mg/kg/IV infusion as a loading dose
70 mg/kg/IV infusion every 4 hours
up to 17 doses
All the patients were followed up until discharge
from the hospital or death.

22. STATISTICAL ANALYSIS
• Data was analysed with computer software.
• Chi-square test was used for finding
statistically significant difference between
the groups.
• Non parametric variables compared by
Whitney U Test.
• Parametric variables compared by student t
test.
• p values < 0.05 considered statistically
significant

23. RESULTS
• Cause of poisoning was intentional in nature
in all patients.
• Most common clinical manifestations:
– During admission:
• Vomiting, abdominal pain
– During hospitalisation:
• Hypotension and metabolic acidosis

24. DATA ANALYSIS AT ADMISSION

25. RESULTS
• Laboratory datas like
hemogram, RFT, LFT, coagulation profile on &
24 hs after admission was normal in both
groups.
• Rate of mechanical ventilation(p 0.04)
• Duration of hospitalization (p 0.02)
• Mortality rate
–All decreased in NAC group

26. • There was a significant difference between two groups in
MDA and TAC levels at the time of admission.
• This might be due to nutritional differences between patients
BASELINE STRESS MARKERS

27. • NAC group showed a significant decrease in MDA levels after 24 hours.
• Control groups showed a significant increase in MDA levels after 24 hours
COMPARISON OF MDA LEVELS

28. COMPARISON OF TAC LEVELS
• NAC group showed no significant increase in TAC levels after 24 hours
• Control group showed a significant increase in TAC levels after 24 hours

29. LIMITATIONS OF STUDY
• Small number of cases.
• Lack of blinding
• Difference in total anti oxidant capacity
of the two groups on admission time

30. CONCLUSION
• Oxidative stress may have an important
role in acute aluminum phosphide
poisoning.
• NAC administration should be
considered in the management of this
poisoning

31. Was the assignment of the patients to treatment valid? Yes
Was the randomization list concealed ? No
Was the follow up of the patients sufficiently long and complete ? Yes
Were the patients ,clinicians and the study personnel kept “blind”
to treatment ?
No
Were the groups treated equally ,apart from experimental
treatment ?
Yes
Were the groups similar at the start of the trial apart from the
experimental therapy ?
Yes
Does these results apply to our patient ? Yes
Is our patient so different from those in the study that its results
cannot apply ?
No
Is the treatment feasible in our setting ? Yes
CRITICAL APPRAISAL

32. Thank You….