Glyophosate Poisoning Management

• Glyphosate is a non-selective herbicide, widely used in agriculture, forestry, industrial weed control and aquatic environments. 

• Proposed mechanisms of glyphosate surfactant herbicide (GlySH) toxicity to mammals include uncoupling of oxidative phosphorylation and glyphosate-or polyethoxethyleneamine (POEA)-mediated direct cardiotoxicity. 

• It can cause a wide range of clinical manifestations in human beings from skin and throat irritation to hypotension and death

The sign and symptom of Glyphosate toxicity

• Gastrointestinal symptoms are the most common manifestations after oral ingestion. It causes erosion of the gastrointestinal tract, difficulty in swallowing and gastrointestinal hemorrhage. Eye and skin irritation have occasionally been reported from dermal exposure. Inhalation of spray mist may cause oral/nasal discomfort, tingling and throat irritation.

• Cardiovascular, respiratory and renal systems may be affected; and signs and symptoms include tachypnea, dysrhythmias, hypotension, non-cardiogenic pulmonary edema, hypovolemic shock, oliguria and respiratory failure

• Seizures and depressed level of consciousness may also occur. 

• Death was often caused by severe hypotension and respiratory failure.

• Hyperkalemia may occur as a complication of renal failure.

Confirmation of Poisoning

• Glyphosate can be measured in the plasma, with levels above 734 µg/mL being measured in fatal cases

Severity

• The assessment of severity of toxicity is determined by dose ingested and clinical grading of toxicity.
• ingested dose- The ingestions of 5-50 mL may result in no symptoms or minor gastrointestinal symptoms only. 
• Moderate symptoms occur with 50-100 mL of the concentrate and severe symptoms are likely when 100 mL or more of the concentrate are ingested.

Clinical Grading of Toxicity

Asymptomatic

No abnormalities on physical or laboratory examination

Mild	Predominantly gastrointestinal symptoms with stable vital signs and no other organ involvement

Moderate

Gastrointestinal symptoms lasting longer than 24 hours Hypotension, responsive to intravenous fluids Pulmonary dysfunction not requiring intubation Acid base disturbance Evidence of transient hepatic renal damage or temporary oliguria

Severe

Pulmonary dysfunction requiring intubation Renal failure requiring dialysis Hypotension requiring pressor amines Cardiac arrest Coma Repeated seizures Death

Management of Glyphosate Toxicity

• There is no antidote for Glyphosate toicity and treatment is supportive.

• The mainstay of treatment for systemic toxicity is decontamination and aggressive supportive therapy. 

• <1 h after ingestion and who have no evidence of buccal irritation or burns - Gastric lavage or activated charcoal can be administered .

• If the ingestion occurs more than 1 hour, the monitoring should be done as follow:

Supportive 

• Hypotension may develop several hours after ingestion. 
• Cardiac monitoring should be available. 
• Hypotension should be treated initially with intravenous fluids and if unresponsive with pressor amines. 
• There is a risk of pulmonary oedema so aggressive fluid resuscitation is inadvisable. 
• Hyperkalaemia should be corrected.

Respiratory dysfunction

• Respiratory function should be monitored closely, oxygenation assured and intubation with assisted ventilation may be required. 
• If pulmonary oedema occurs positive respiratory pressure may be of value. 
• Urine output should be monitored and prevention of hypovolaemia and hypotension should be a priority. 
• Acidosis usually responds to bicarbonate therapy but may on occasion be resistant.
  

Elimination enhancement 

• Haemodialysis may be of value for renal failure or acidosis which does not respond to bicarbonate.

Severe systemic toxicity 

• The mechanism of action of intravenous fat emulsion (IFE) may be due to the lowering of serum concentration of the free surfactant glyphosate-or polyethoxethyleneamine (POEA)-mediated component of Glyphosate (which are more lipophilic) by dragging into the lipid sink formed by the IFE, thereby blunting its cardiovascular toxicity.