What is the cause of metabolic alkalosis and hyperammonemia (elevated ammonia levels)?

From the Guidelines

Metabolic alkalosis and hyperammonemia should be managed by treating the underlying cause, correcting electrolyte imbalances, and using ammonia-scavenging agents as recommended in the consensus guidelines for management of hyperammonaemia in pediatric patients receiving continuous kidney replacement therapy 1.

Management of Metabolic Alkalosis

For metabolic alkalosis, treatment includes:

• Volume repletion with normal saline (0.9% NaCl) at 100-200 mL/hour
• Potassium replacement (typically KCl 10-20 mEq/hour) if hypokalemic
• Possibly acetazolamide 250-500 mg orally or IV every 6-8 hours to enhance bicarbonate excretion

Management of Hyperammonemia

For hyperammonemia, treatment includes:

• Discontinuing all oral feeds and providing adequate calories (≥100 kcal/kg daily) as intravenous glucose and lipids 1
• Maintaining a glucose infusion rate of 8–10 mg/kg/min and providing lipids (0.5 g/kg daily, up to 3 g/kg daily) 1
• Using nitrogen-scavenging agents such as sodium benzoate and sodium phenylacetate at the recommended dosage 1
• Considering hemodialysis (HD) or continuous kidney replacement therapy (CKRT) in severe cases or when ammonia levels are high 1

Key Recommendations

• CKRT is recommended as the first-line treatment for hyperammonaemia when possible, with a blood flow rate (Qb) of 30–50 ml/min and a dialysate flow rate (Qd)/Qb >1.5 1
• HD may be used as an initial therapy in patients with blood ammonia levels >1,000 μmol/l (1,703 μg/dl) or in cases of rapidly deteriorating neurological status 1
• Hybrid therapy, combining HD and CKRT, may be used to gradually reduce ammonia levels while controlling the rebound effect 1

Important Considerations

• Prompt recognition and treatment of metabolic alkalosis and hyperammonemia are essential to prevent neurological complications like hepatic encephalopathy
• The choice of dialysis modality should be made jointly by pediatric, internal medicine, nephrology, metabolism, and critical care teams, taking into account the availability of dialysis equipment and/or staff, the diagnosis and overall condition of the patient, and the trend in serum ammonia levels 1

From the Research

Metabolic Alkalosis

• Metabolic alkalosis is a widespread acid-base disturbance, especially in hospitalized patients, characterized by the primary elevation of serum bicarbonate and arterial pH, along with a compensatory increase in Pco2 consequent to adaptive hypoventilation 2, 3.
• The pathogenesis of metabolic alkalosis involves either a loss of fixed acid or a net accumulation of bicarbonate within the extracellular fluid, which can be caused by various factors such as vomiting, aldosterone or cortisol excess, licorice ingestion, chloruretic diuretics, excess calcium alkali ingestion, and genetic diseases 2.
• Severe metabolic alkalosis in critically ill patients, with an arterial blood pH of 7.55 or higher, is associated with significantly increased mortality rate 2, 3.

Hyperammonemia

• Hyperammonemia is a medical emergency that can progress to cerebral edema, seizures, coma, and death, and can be caused by various factors including hepatic encephalopathy secondary to cirrhotic disease or portosystemic shunting, as well as non-cirrhotic aetiologies 4.
• Measurement of plasma ammonia is recommended for patients with acute, unexplained, altered mental status, as early identification allows early effective management which may prevent irreversible brain damage 4.

Relationship between Metabolic Alkalosis and Hyperammonemia

• There is no direct relationship between metabolic alkalosis and hyperammonemia mentioned in the provided studies, as they appear to be two separate medical conditions with different pathophysiologies and causes 2, 3, 5, 4.