What is the recommended management for glufosinate ammonium poisoning?

Management of Glufosinate Ammonium Poisoning

Glufosinate ammonium poisoning should be managed as a hyperammonemia emergency with aggressive supportive care, serial ammonia monitoring, and early consideration of hemodialysis for severe cases, as the primary toxicity mechanism is glutamine synthetase inhibition leading to ammonia accumulation and neurological complications.

Immediate Stabilization and Monitoring

• Secure airway, breathing, and circulation immediately — intubate prophylactically if neurological deterioration is anticipated, as respiratory failure commonly occurs after a latency period of up to 48 hours 1, 2, 3.
• Monitor serial serum ammonia levels every 3-4 hours until normalized, as peak ammonia >90 μg/dL (53 μmol/L) predicts neurological complications with high sensitivity 2, 1.
• Assess neurological status continuously for encephalopathy, seizures, memory disturbances, speech ataxia, tremor, and altered consciousness 2, 3.
• The latency period for neurological complications typically occurs within 48 hours post-ingestion, even after an initial asymptomatic interval 2, 3.

Metabolic Management

• Stop all protein intake immediately to halt nitrogen load and prevent further ammonia production 1, 4.
• Provide aggressive caloric support with ≥100 kcal/kg/day through IV dextrose (glucose infusion rate 8-10 mg/kg/min) and lipids (0.5-3 g/kg/day) to prevent catabolism, which worsens hyperammonemia 1, 4.
• Reintroduce protein within 48 hours once ammonia decreases to 80-100 μmol/L, starting at 0.25 g/kg/day and advancing to 1.5 g/kg/day to prevent catabolic protein breakdown 1, 5.

Pharmacological Therapy

• Administer L-carnitine 50 mg/kg loading dose over 90 minutes, then 100-300 mg/kg/day, as glufosinate inhibits glutamine synthetase similar to organic acidemias 1, 6, 7.
• Consider nitrogen-scavenging agents (sodium benzoate, sodium phenylacetate) if ammonia levels rise above 150 μmol/L (255 μg/dL) 1, 5.

Kidney Replacement Therapy Indications

Initiate hemodialysis or continuous kidney replacement therapy (CKRT) when:

• Ammonia levels exceed 300-400 μmol/L (513-681 μg/dL) despite medical therapy 1, 4.
• Rapidly deteriorating neurological status, coma, or cerebral edema develops 8.
• Moderate to severe encephalopathy is present (lethargy, hypotonia, absent reflexes, seizures, or coma) 8, 1.
• Ammonia rapidly rises to >300 μmol/L within hours despite supportive measures 8, 1.

Dialysis Modality Selection

• Hemodialysis is the most effective modality with 95-96% ammonia filtration fraction and provides the fastest ammonia reduction 1.
• CKRT (specifically high-dose continuous venovenous haemodialysis) is preferred for hemodynamically unstable patients 8, 1.
• For ammonia >1,000 μmol/L (1,703 μg/dL), initiate either HD or high-dose CKRT immediately 8, 1.
• Hybrid therapy (HD followed by CKRT) can be used when ammonia >1,500 μmol/L (2,555 μg/dL) to achieve rapid reduction while preventing rebound hyperammonemia 8.
• Continue nitrogen scavengers during dialysis as they remain effective despite being dialyzed 1.

Toxicokinetic Considerations

• Glufosinate exhibits a two-compartment model with T½α of 1.84 hours and T½β of 9.59 hours 9.
• Renal clearance is approximately 77.9 ml/min, with primarily urinary excretion 9.
• The apparent distribution volume is 1.44 L/kg, suggesting moderate tissue distribution 9.

Critical Pitfalls to Avoid

• Do not delay treatment waiting for ammonia results — clinical deterioration correlates with coma duration, not just peak ammonia level 1, 5.
• Ensure ammonia samples are collected from free-flowing venous or arterial blood, transported on ice, and processed within 15 minutes to avoid falsely elevated results 4.
• Do not prolong protein restriction beyond 48 hours, as this causes catabolism and paradoxically worsens hyperammonemia 1, 5.
• Recognize that neurological complications can develop after an asymptomatic interval, requiring prophylactic intubation in moderate to severe ingestions 2, 9, 3.

Prognosis

• Duration of hyperammonemic coma (not absolute ammonia level) is the most important prognostic factor for permanent neurological damage 5.
• Adverse outcomes including memory loss, seizures, and cognitive impairment are associated with coma lasting >3 days or peak ammonia >1,000 μmol/L 5, 3.
• Early aggressive treatment with ammonia control significantly improves neurological outcomes 2, 9.