this presentation contains epidemiology of propane poisoning, kinetics in overdose and clinical effects. in the management mainly focused on methhemoglobinemia.

1. PROPANIL POISONING
Dr KTD Priyadarshani
Registrar in Emergency Medicine
Teaching Hospital- Peradeniya
2023/04/18

2. SCOPE
 Overview
 Mechanism of toxic effects
 Kinetics in overdose
 Clinical effects
 Investigations
 Management

3. OVERVIEW
 Selective herbicide
 Used in paddy cultivation
 Commercial product 36-48% propanil
 Self poisoning with large doses , methemoglobinemia
is caused ,the case fatality can be as high as 10%

4. MECHANISM OF TOXIC EFFECTS
 Propanil (3,4-dichloropropioanilide) is hydrolyzed in vivo to 3,4-dichloroaniline
 Metabolized to other compounds, including 3,4-dichlorophenylhydroxylamine
 Toxicity is induced primarily by the 3,4-dichlorophenylhydroxylamine metabolite
 induces cellular dysfunction through formation of free radicals and depletion of intracellular glutathione
stores
 The major apparent biochemical
 production of metHb by oxidation of the ferrous haem (Fe2+ ) in erythrocytes to the ferric state (Fe3+ )
 MetHb is unable to bind and transport oxygen in the vascular system

6. KINETICS IN OVERDOSE
 Absorption
 No human data are available
 But sufficient propanil is absorbed with oral exposures to produce severe toxicity and death
 Distribution
 No human data are available.
 Propanil or its metabolites appear to have a long plasma half-life
 the clinical effects of metHb are prolonged for a number of days

7. CLINICAL EFFECTS
 Noted within six hours of ingestion of propanil
 Principle effect being metHb
 When poisoning is severe there may be an altered level of consciousness, lactic acidosis,
hypotension and hypoventilation secondary to tissue hypoxia
 Mortality rate is 12% in some series,

8. Gastrointestinal
effects
Pulmonary effects Cardiac effects Central nervous
system effects
Metabolic effects
Nausea,
vomiting and
diarrhea
Dyspnea
Hyperventilatio
n
Followed by
hypoventilation
and hypoxemia
with severe
poisoning
Tachycardia,
hypotension
and ischemic
changes on
ECG may occur
with severe
poisoning
Headache,
dizziness,
syncope,
confusion,
sedation, coma
and seizures
metabolic
acidosis with an
elevated lactate
(severe
poisoning)

9. DIFFERENTIAL DIAGNOSIS

10. DETERMINATION OF SEVERITY
 The assessment of severity of toxicity is determined by clinical grading of toxicity
 Clinical evidence of cyanosis, with ‘chocolate brown’ colored blood on white filter paper is
suggestive of severe propanil poisoning
 This can be quantified at the bedside using a simple bedside color chart

13. INVESTIGATIONS
 ABG
 Arterial blood gases (including metHb and lactate measurements) are the most important investigations for
diagnosis and monitoring
 Elevations in metHb are noted within a few hours of poisoning and may continue to rise beyond 6h
 In the absence of resources to directly measure metHb concentrations, the diagnosis is suspected
when;
 low saturations on pulse oximetry
 despite a normal or elevated pO2 on arterial blood gas

14. INVESTIGATIONS
 Once metHb is diagnosed, serial venous lactate measurements may be useful to monitor the
course of poisoning (including response to antidotes)
 Serum electrolytes, creatinine, urea, liver function tests, cardiac enzymes and glucose should
also be measured
 ECG
 All patients with significant metHb or acidemia should have a baseline ECG to detect silent ischemia
 CXR
 Pulmonary involvement
 TRALI

15. MANAGEMENT
 Gastric lavage if <2h (given the airway is protected )
 Adequate hydration
 Strict bed rest
 If cyanosis and/or impaired respiration is observed , give 100% oxygen
 Assisted ventilation may be necessary
 Normoglycemia
 since adequate glucose concentrations are required by the reducing enzymes present in erythrocytes and
the antidote methylene blue

16. ANTIDOTE
 Methylene blue is commonly used first line
 No clinical studies
 N-acetylcysteine (NAC) or ascorbic acid (Vitamin C) may also reverse metHb
 although very high doses were required
 considered in patients with severe propanil poisoning unresponsive to methylene blue, or where methylene
blue is unavailable

17. METHYLENE BLUE
 Methyl-thionium chloride
 The standard antidote for reversal of metHb
 First line antidote in acute symptomatic propanil
poisoning
 Propanil appears to produce prolonged and recurrent
MetHb
 methylene blue may be more effective if administered as an
infusion following the initial bolus

19. Moderate
poisoning
• 1mg/kg methylene blue as a bolus injection over 1
minute
• Reassess MetHb after one hour
• Repeat Methylene blue if toxicity persists
Severe
poisoning
• 2mg/kg methylene blue as a bolus injection over 1
minute
• followed by an infusion of 10 mg/hour for 10 hours
• Reassess metHb concentration within one hour of
commencement of the infusion
• If metHb > 20%,
• a further bolus injection of 2 mg/kg
• the infusion rate increased by 50%.
• If metHb < 20% then the infusion is maintained at the
the current rate

20. The maximum recommended daily dose of methylene blue is
7mg/kg, but toxicity has also been reported following doses of
4mg/kg
Adverse effects from methylene blue;
nausea, vomiting, diaphoresis, burning sensation of the mouth and
fingers and abdominal pain
Severe toxicity is also reported, including hypotension,
exacerbation of MetHb and hemolysis
 Methylene blue should not be administered to patients with G6PD
deficiency because;
 it is minimally effective
 may exacerbate the degree of MetHb
 induce hemolysis

21. N-acetylcysteine
 antioxidant
 donates sulfhydryl groups
 replacing depleted intracellular glutathione stores
 Empirically used in patients with moderate to severe propanil poisoning that is refractory to
methylene blue, or where methylene blue is unavailable
 Given the potential for hypotension and respiratory distress with severe propanil poisoning
 150mg/kg NAC over 4h, then
 50mg/kg NAC over 4h, then
 100mg/kg NAC over 16h. This infusion should be repeated until the patient has recovered.

22. Ascorbic acid (Vitamin C)
 an antioxidant that scavenges free radicals ,minimizing the formation of
metHb
 Oral ascorbic acid has been administered when methylene blue was
unavailable
 This may relate to the decrease in bioavailability with increasing doses of
oral ascorbic acid.
 Empirically used in patients with moderate to severe propanil poisoning
that is refractory to methylene blue
 intravenous ascorbic acid 2g infused over 24h is associated with limited
toxicity

23. OTHER METHODS
 Toluidine Blue-
 Only data available for Meth HB induced by 4-dimethylaminophenol-induced Meth
Hb
 Bolus 2mg/kg was 80% more effective than methylene blue and without side effects
 Exchange transfusion is life saving in severe poisoning not responding to
above drugs

24. REFERENCES
 Wiki Tox.org
 Life in the fast lane