What are the inpatient orders for a patient with acute encephalopathy due to hyperammonemia?

Inpatient Orders for Acute Encephalopathy from Hyperammonemia

Immediately discontinue all oral feeds, initiate IV glucose at 8-10 mg/kg/min with IV lipids (0.5-3 g/kg daily) to achieve ≥100 kcal/kg daily, start nitrogen-scavenging agents (sodium benzoate and sodium phenylacetate), and prepare for urgent hemodialysis or continuous kidney replacement therapy (CKRT) if ammonia >150 μmol/L with deteriorating neurological status or >300-400 μmol/L despite medical therapy. 1, 2

Immediate Initial Orders

Nutritional Management

• NPO (nothing by mouth) - stop all protein intake immediately to halt nitrogen load 1, 2
• IV dextrose 10% at 8-10 mg/kg/min to prevent catabolism and protein breakdown 1, 2
• IV lipid emulsion starting at 0.5 g/kg daily, titrate up to 3 g/kg daily for adequate calories 1, 2
• Target total caloric intake ≥100 kcal/kg daily to prevent endogenous protein catabolism driving further ammonia production 1, 2

Pharmacological Orders

Nitrogen-Scavenging Agents (FDA-approved for acute hyperammonemia) 3:

• Sodium phenylacetate + sodium benzoate IV:
  • Loading dose: 250 mg/kg (if <20 kg) or 5.5 g/m² (if >20 kg) of each agent over 90-120 minutes 1, 3
  • Maintenance infusion: Same dose over 24 hours continuously 3

L-Arginine Hydrochloride IV (dose depends on suspected urea cycle disorder) 1, 2:

• For OTC/CPS deficiency: 200 mg/kg (if <20 kg) or 4 g/m² (if >20 kg) 1
• For ASS/ASL deficiency: 600 mg/kg (if <20 kg) or 12 g/m² (if >20 kg) 1

L-Carnitine IV (if organic acidemia suspected):

• Loading dose: 50 mg/kg over 90 minutes 2
• Maintenance: 100-300 mg/kg daily 2

Dialysis Orders (Critical Decision Point)

Indications for urgent CKRT/hemodialysis 4, 1:

• Ammonia >150 μmol/L with rapidly deteriorating neurological status, coma, or cerebral edema 4
• Ammonia persistently >400 μmol/L despite medical management 4
• Rapid rise to >300 μmol/L within hours uncontrolled by medications 4
• Moderate to severe encephalopathy at any ammonia level 4

Preferred modality: High-dose CVVHD 4, 1:

• Blood flow rate (Qb): 30-50 ml/min 4
• Dialysate flow rate (Qd)/Qb ratio >1.5 4
• Use warmed dialysate to maintain hemodynamic stability 4
• Continue until ammonia <200 μmol/L on two consecutive hourly measurements 4

Alternative: Intermittent hemodialysis for most rapid clearance - achieves 50% reduction in ammonia within 1-2 hours, then transition to CKRT to prevent rebound 4, 2

Monitoring Orders

Laboratory Monitoring

• Ammonia levels every 3-4 hours until normalized, then every 6-8 hours 1, 2
  • Critical: Draw from free-flowing venous/arterial blood, transport on ice, process within 15 minutes to avoid false elevations 1, 2
• Basic metabolic panel every 6 hours during CKRT to monitor electrolytes 1, 2
• Glucose monitoring every 2 hours initially with high-dose dextrose infusion 1

Neurological Monitoring

• Neurological assessments every 2 hours using Glasgow Coma Scale 2, 5
• Monitor for signs of cerebral edema: pupillary changes, posturing, bradycardia 4

Diagnostic Workup (While Initiating Treatment)

• Plasma amino acid profile to identify specific urea cycle defect 5
• Urine orotic acid (elevated in OTC deficiency) 5
• Urine organic acids to rule out organic acidemias 5
• Plasma acylcarnitine profile 5
• CT or MRI brain to assess for cerebral edema and exclude structural lesions 5
  • Look for symmetric involvement of insular cortex and cingulate gyrus with restricted diffusion - characteristic of hyperammonemic encephalopathy 6, 7

Protein Reintroduction (After 24-48 Hours)

Do not prolong protein restriction beyond 48 hours - this causes catabolism and paradoxically worsens ammonia 1, 2:

• Reintroduce protein gradually at 0.25 g/kg daily increments 1
• Target 1.5 g/kg daily as tolerated 1
• Begin when ammonia trending down toward 80-100 μmol/L 2

Critical Pitfalls to Avoid

Duration of hyperammonemic coma is the most important prognostic factor - not the rate of ammonia clearance - so speed of treatment initiation is paramount 4. Delayed recognition leads to irreversible neurological damage 1, 2.

Ammonia levels in cirrhotic patients do not correlate well with encephalopathy severity 8, but in acute hyperammonemia from urea cycle defects or other causes, levels >200 μmol/L are associated with cerebral herniation and poor outcomes 5.

Nitrogen scavengers are dialyzed during CKRT but remain effective when used concurrently - do not discontinue them 2.

In acute liver failure with ammonia >150 μmol/L, protein administration may be deferred for 24-48 hours only while monitoring arterial ammonia, as protein can worsen cerebral edema in this specific setting 4. However, this is the exception - in most hyperammonemic encephalopathy, prolonged protein restriction worsens outcomes 1, 2.