How should I emergently manage a patient with acute urea poisoning and hyperammonemia?

Emergency Management of Acute Urea Poisoning with Hyperammonemia

Immediately stop all protein intake, secure the airway if neurological status is deteriorating, initiate aggressive caloric support with IV dextrose and lipids, and prepare for urgent hemodialysis or continuous kidney replacement therapy (CKRT) if ammonia levels exceed 300-400 μmol/L or if the patient shows rapidly declining mental status. 1, 2

Immediate Stabilization (First 30 Minutes)

Airway and Circulation

• Intubate immediately if the patient shows declining consciousness, respiratory distress, or visible signs of encephalopathy (lethargy, hypotonia, absent reflexes, seizures, or coma). 3, 2
• Establish large-bore IV access for aggressive fluid resuscitation and medication administration. 2
• Secure hemodynamic stability with isotonic crystalloid infusion. 3

Stop Nitrogen Load

• Cease all protein intake immediately to halt further ammonia production—this is the single most critical initial intervention. 1, 2, 4
• Do not delay this step; every minute of continued protein intake worsens the hyperammonemic crisis. 1

Contact Poison Control and Toxicology

• Call Poison Control (1-800-222-1222 in the US) immediately for guidance on urea-specific toxicity management. 3
• Request urgent consultation with a medical toxicologist or clinical toxicologist, as specialized antidotes and extracorporeal therapies may be lifesaving. 3

Aggressive Caloric Support (Within First Hour)

Prevent Catabolism

• Provide ≥100 kcal/kg/day through IV dextrose and lipids to prevent protein breakdown, which paradoxically worsens hyperammonemia. 1, 4
• Maintain glucose infusion rate at 8-10 mg/kg/min using 10% or 20% dextrose solutions. 1, 2
• Start IV lipid emulsion at 0.5 g/kg/day, titrating up to 3 g/kg/day for additional non-protein calories. 1, 2

Critical Pitfall to Avoid

• Do not prolong protein restriction beyond 48 hours—once ammonia levels decrease to 80-100 μmol/L, reintroduce protein starting at 0.25 g/kg/day and gradually increase to 1.5 g/kg/day to prevent catabolism-induced rebound hyperammonemia. 1, 4

Pharmacological Nitrogen Scavenging

Indications for Nitrogen Scavengers

• Initiate sodium benzoate and sodium phenylacetate if plasma ammonia exceeds 150 μmol/L. 1, 4, 5

Dosing Protocol (FDA-Approved)

• Sodium benzoate + sodium phenylacetate: 250 mg/kg (if weight <20 kg) or 5.5 g/m² (if weight >20 kg) given as a bolus over 90 minutes, followed by the same dose as a continuous infusion over 24 hours. 5
• L-carnitine: 50 mg/kg loading dose over 90 minutes, then 100-300 mg/kg/day as maintenance. 1, 2

Key Evidence

• In a large FDA study of 316 patients with 1,045 hyperammonemic episodes, sodium phenylacetate/benzoate reduced mean ammonia from 200.9 μmol/L to 101.6 μmol/L within 4 hours, with 80% patient survival and 97% recovery from coma. 5
• Continue nitrogen scavengers even during dialysis—they remain effective and are not contraindicated despite being partially removed by dialysis. 1

Kidney Replacement Therapy Decision Algorithm

Absolute Indications for Immediate Dialysis

• Ammonia >300-400 μmol/L despite medical therapy (nitrogen scavengers, caloric support). 3, 1, 4
• Rapidly deteriorating neurological status, coma, or cerebral edema with ammonia >150 μmol/L. 3, 1
• Moderate to severe encephalopathy (defined as lethargy, distal flexion, hypotonia, weak suck, absent Moro reflex, constricted pupils, bradycardia, stupor, coma, decerebrate posture, flaccid tone, pupils non-reactive to light). 3
• Rapid rise in ammonia to >300 μmol/L within a few hours that cannot be controlled with non-dialytic measures. 3

Choice of Dialysis Modality

• Hemodialysis (HD) is first-line when available—it achieves 95-96% ammonia filtration fraction and reduces ammonia by 50% within 1-3 hours. 1, 6
• High-dose continuous venovenous haemodialysis (CVVHD) is preferred for hemodynamically unstable patients, with blood flow rate (Qb) 30-50 ml/min and dialysate flow rate (Qd)/Qb >1.5. 3, 1
• For ammonia >1,000 μmol/L, initiate either intermittent HD or high-dose CKRT immediately without delay. 3, 1
• For ammonia >1,500 μmol/L, consider a hybrid strategy: initial intermittent HD followed by CKRT to achieve rapid clearance while minimizing rebound hyperammonemia. 1
• Warm the dialysate to maintain hemodynamic stability, especially in neonates and small children. 3

When to Step Down Dialysis

• Transition from HD or high-dose CKRT to standard CKRT when ammonia falls <200 μmol/L on two consecutive hourly measurements, keeping in mind that nitrogen-scavenging agents may be sufficient to prevent rebound. 3

Peritoneal Dialysis

• Peritoneal dialysis is significantly less effective than HD or CKRT and should only be used if no other modality is available. 1, 6

Laboratory Monitoring Protocol

Ammonia Monitoring

• Check plasma ammonia every 3-4 hours until normalized, using proper technique: free-flowing venous or arterial blood, transported on ice, processed within 15 minutes to avoid false elevations. 1, 4
• Improper sampling is a common pitfall leading to falsely elevated levels and inappropriate interventions. 4

Additional Labs

• Obtain baseline: CBC, comprehensive metabolic panel, liver function tests, arterial blood gas, serum lactate, blood alcohol level. 2
• Monitor for severe acidosis, elevated lactate, deranged liver function, leukocytosis, elevated CRP, renal failure, and thrombocytopenia—these predict poor outcomes. 2

Prognostic Factors and Critical Timing

Duration of Coma is the Most Important Prognostic Factor

• Coma lasting >3 days predicts poor neurological outcome—this is the single strongest predictor of irreversible brain damage. 3, 1
• Peak ammonia levels >1,000 μmol/L are associated with severe irreversible brain damage and death. 1, 7
• Delayed recognition and treatment leads to irreversible neurological damage, seizures, and death—every hour of delay worsens outcome. 1, 4, 8

Neonatal-Onset Considerations

• In neonates with ammonia ≥600 μg/dL (360 μmol/L), hemodialysis is indicated immediately to rapidly remove ammonia and mitigate brain damage. 7
• Even with combined hemodialysis and liver transplantation, neuroprotective effects remain limited once severe hyperammonemia (≥600 μg/dL) has occurred. 7

Common Pitfalls to Avoid

• Do not administer anything by mouth (including water or milk) unless advised by poison control—there is no evidence that dilution helps and it may cause emesis and aspiration. 3
• Do not delay dialysis waiting for ammonia levels to "trend"—if clinical criteria are met (coma, seizures, ammonia >300-400 μmol/L), initiate dialysis immediately. 3, 1
• Do not stop nitrogen scavengers during dialysis—they remain effective and should be continued concurrently. 1
• Do not use activated charcoal for urea ingestion—it is ineffective for inorganic compounds and metals. 3