What is the best course of action for a patient with primary respiratory alkalosis, hyperammonemia, lethargy, and a Glasgow Coma Scale (GCS) score of 6?

Management of Primary Respiratory Alkalosis with Hyperammonemia, Lethargy, and GCS 6

This patient requires immediate endotracheal intubation, ICU admission, aggressive ammonia-lowering therapy with nitrogen scavengers, and urgent hemodialysis given the severe hyperammonemia with coma (GCS 6). 1, 2

Immediate Airway Management

Intubate without delay. A GCS ≤8 is an absolute indication for endotracheal intubation to secure the airway and prevent aspiration. 1 The combination of altered consciousness (GCS 6) and respiratory alkalosis from hyperventilation mandates immediate airway control. 1

• Use rapid sequence induction for intubation 1
• For sedation, use short-acting agents only: propofol or dexmedetomidine (preferred in liver disease as it preserves cognitive function and reduces delirium) 1
• Avoid benzodiazepines and minimize opioids due to synergistic CNS depression 1
• Target normoventilation after intubation—avoid hyperventilation unless signs of cerebral herniation develop 1

Critical Initial Stabilization

Stop all protein intake immediately to halt nitrogen load and prevent further ammonia production. 1, 3, 2

Initiate aggressive caloric support to prevent catabolism, which worsens hyperammonemia:

• Provide ≥100 kcal/kg/day through IV dextrose at 8-10 mg/kg/min 1, 3, 2
• Add IV lipids starting at 0.5 g/kg/day, titrating up to 3 g/kg/day 1, 3, 2
• Reintroduce protein within 48 hours once ammonia decreases to 80-100 μmol/L, starting at 0.25 g/kg/day and increasing to 1.5 g/kg/day 1, 3, 2

Pharmacological Ammonia-Lowering Therapy

Initiate nitrogen scavengers immediately if ammonia levels exceed 150 μmol/L:

• Sodium benzoate and sodium phenylacetate (intravenous formulations preferred for rapid action) 1, 3, 2
• These agents work by providing alternative pathways for nitrogen excretion 1
• Continue nitrogen scavengers even during dialysis—they remain effective despite being dialyzed 1, 2

Administer L-carnitine: 50 mg/kg loading dose over 90 minutes, then 100-300 mg/kg/day, particularly if organic acidemia is suspected 2

Consider lactulose (orally or rectally) if hepatic encephalopathy is the suspected etiology, as it reduces blood ammonia by 25-50% 1, 4

Urgent Hemodialysis Indication

Initiate hemodialysis immediately given the severe presentation (GCS 6 with coma). 1, 3, 2

Specific indications present in this patient:

• Severe encephalopathy with coma (GCS 6) 1, 2
• Likely ammonia >300-400 μmol/L based on clinical severity 1, 3, 2
• Rapidly deteriorating neurological status 1, 3, 2

Hemodialysis is the most effective modality with 95-96% ammonia filtration fraction and provides the fastest ammonia reduction. 2 If the patient is hemodynamically unstable, continuous kidney replacement therapy (CKRT) is preferred and can be combined with ECMO support if needed. 2

Diagnostic Workup During Resuscitation

Obtain immediate laboratory testing to identify the underlying cause:

• Complete metabolic panel including liver function tests to assess for cirrhosis/acute liver failure 1, 5
• Plasma amino acid profile to identify urea cycle disorders 5
• Urine organic acids to identify organic acidemias 5
• Plasma acylcarnitine profile to identify fatty acid oxidation disorders 5
• Lactate and pyruvate levels to assess for mitochondrial disorders 5
• Blood and urine cultures to rule out infection as precipitant 1

Investigate common precipitants: infections, GI bleeding, electrolyte disorders (especially alkalosis), acute kidney injury, dehydration, constipation, and medications 1, 5

Brain imaging (CT or MRI) should be performed given the first episode of severe altered mental status to assess for cerebral edema, intracranial bleeding, or structural lesions. 1, 5

Monitoring Protocol

Check plasma ammonia levels every 3-4 hours until normalized, using proper collection technique (free-flowing venous/arterial blood, transported on ice, processed within 15 minutes). 1, 3, 2

Monitor continuously:

• Neurological status using GCS 1, 3
• Electrolytes, especially sodium and potassium 5, 2
• Blood glucose to prevent hypoglycemia 5, 2
• Acid-base status 5

Critical Pitfalls to Avoid

Duration of hyperammonemic coma directly correlates with irreversible neurological damage. Coma lasting >3 days or ammonia >1,000 μmol/L predicts poor neurological outcomes. 1, 3 Early aggressive intervention is essential.

Do not delay dialysis while waiting for medical therapy to work in a comatose patient—neurological function can deteriorate rapidly. 1, 6

Avoid prolonged protein restriction beyond 48 hours, as this causes catabolism and paradoxically worsens hyperammonemia. 1, 3, 2

The respiratory alkalosis is a compensatory response to hyperammonemia (tachypnea attempting to blow off CO2), not the primary problem—focus on lowering ammonia, not correcting the alkalosis. 6, 7, 8, 9