Glufosinate Ammonium (GLA) Herbicide Ingestion

Mechanism of Toxicity

1. Inhibiting glutamine synthetase (GS) — the enzyme that converts glutamate + NH₃ → glutamine. In plants this is lethal (nitrogen metabolism arrest). In humans, GS inhibition leads to:
   • Hyperammonemia — ammonia accumulates in blood (NH₃ > 90 µg/dL is a threshold associated with severe neurotoxicity)
   • Disruption of glutamate/GABA balance — GLA also inhibits glutamate decarboxylase (GAD), reducing GABA synthesis → net CNS excitation
   • Direct NMDA receptor agonism (structural similarity to glutamate)
2. Surfactant toxicity — commercial formulations contain polyoxyethylene alkyl ether surfactants, contributing to multi-organ injury
3. No antidote exists

Clinical Course — Characteristically BIPHASIC with a LATENT PERIOD

The latent period is a critical pitfall — patients may appear stable and be sent home, only to decompensate later.

Clinical Features

Neurological (most prominent, delayed onset)

• Seizures — GLA is the most seizurogenic pesticide class; incidence ~31.5% of ingestions (Park et al., 2018, PMID 28421825)
  • Onset: 12–24 h post-ingestion
  • Type: generalized tonic-clonic (85.7%)
  • Duration: typically resolve by 72 h with treatment
• Delirium, confusion, stupor, coma
• Anterograde amnesia (often persistent, even after recovery)
• 6th cranial nerve palsy (reported)
• Respiratory depression / respiratory arrest (mechanical ventilation often required)

Metabolic

• Hyperammonemia — hallmark finding; correlates with severity
  • NH₃ > 90 µg/dL predicts late neurological complications
  • Elevated NLR (neutrophil-to-lymphocyte ratio) at ED presentation also predicts neurotoxicity (Kim et al., 2022, PMID 35164661)

Multi-organ

• Acute kidney injury
• Hepatotoxicity
• Cardiovascular: bradycardia, hypotension
• Respiratory: aspiration pneumonitis, ARDS

Investigations

Management

1. Decontamination

• Gastric lavage — if within 1–2 h of ingestion and airway protected
• Activated charcoal — adsorption; give if airway intact and no contraindication
• Skin/eye decontamination if dermal exposure

2. Supportive Care (cornerstone — no antidote)

• Airway management: early intubation for impaired consciousness or respiratory depression; patients can deteriorate rapidly at 12–24 h
• IV fluids for hydration
• Seizure control: benzodiazepines (first line), phenobarbital or levetiracetam for refractory seizures; seizures are self-limited by 72 h
• Ammonia reduction: lactulose, dietary protein restriction, rifaximin (limited data)
• Vasopressors for hemodynamic instability

3. Extracorporeal Elimination

• Hemodialysis (IHD) / CRRT — may reduce plasma GLA concentration in early/severe poisoning
  • Renal clearance of GLA is 1.6–1.8× greater than extracorporeal clearance → IHD best suited for patients with AKI or very high plasma levels
  • Charcoal hemoperfusion — emerging evidence; case reports show reduction in ICU stay (2026 case report)
  • Benefit in preventing seizures/respiratory arrest remains uncertain; limit to patients with severe or deteriorating course

4. Monitoring

• ICU admission for all moderate-to-severe ingestions
• Observe minimum 24–48 h even if initially asymptomatic (latent period risk)
• Serial ammonia levels, neuro checks, respiratory monitoring

Prognosis

• Most patients survive with supportive care
• Persistent anterograde amnesia is the most common sequela (mechanism: hippocampal excitotoxicity via glutamate excess)
• Mortality is higher with: large ingestion volume, delayed presentation, early respiratory failure
• Seizure activity itself does not independently predict mortality (Park et al., 2018)
• Predictors of severe outcome (Nguyen et al., 2025, PMID 41437860): high GLA ingested volume, early neurological signs, elevated ammonia

Key Pearls

1. Do not discharge early — the latent period (6–12 h) gives false reassurance
2. Ammonia is your friend — serial NH₃ levels guide prognosis better than clinical appearance
3. Seizures are common and expected — anticipate and treat, but seizure presence alone doesn't worsen prognosis
4. Amnesia may be permanent — counsel patients and families
5. No antidote — all management is supportive