How to manage hyponatremia in patients with acute intermittent porphyria (AIP)?

Management of Hyponatremia in Acute Intermittent Porphyria

Hyponatremia in acute intermittent porphyria (AIP) should be corrected slowly due to the combined mechanisms of hypovolemia and syndrome of inappropriate antidiuretic hormone secretion (SIADH). 1

Pathophysiology of Hyponatremia in AIP

Hyponatremia is a common electrolyte abnormality during acute attacks of AIP, occurring in 25-60% of symptomatic cases 1. It typically develops through two main mechanisms:

1. Hypovolemia: Due to poor oral intake, vomiting, and fluid losses during acute attacks
2. SIADH: Inappropriate ADH secretion as part of the autonomic dysfunction in AIP

Assessment of Hyponatremia in AIP

When evaluating hyponatremia in a patient with AIP:

• Monitor electrolytes regularly during acute attacks 1
• Assess volume status to determine if hypovolemic, euvolemic, or hypervolemic
• Check serum sodium concentration to determine severity:
  • Mild: 130-134 mEq/L
  • Moderate: 125-129 mEq/L
  • Severe: <125 mEq/L 2
• Evaluate for neurological symptoms (confusion, seizures, altered mental status)

Management Algorithm

Step 1: Treat the Underlying Acute Attack

• Administer intravenous hemin (3-4 mg/kg body weight daily) 1
• Provide intravenous carbohydrate loading (approximately 300 g/day) 1
• Avoid porphyrinogenic medications that may worsen the attack 1

Step 2: Correct Hyponatremia Based on Severity and Symptoms

For Asymptomatic or Mildly Symptomatic Hyponatremia:

• Correct sodium slowly to prevent osmotic demyelination syndrome 1
• Target correction rate: No more than 8-10 mEq/L in 24 hours 3, 2
• If hypovolemic: Cautious isotonic (0.9%) saline infusion
• If euvolemic (SIADH): Fluid restriction (typically <1-1.5 L/day)

For Severely Symptomatic Hyponatremia (seizures, altered consciousness):

• Administer 3% hypertonic saline as bolus therapy 3
• Target initial increase: 4-6 mEq/L within 1-2 hours to reverse severe symptoms 3
• Do not exceed correction limit of 10 mEq/L in first 24 hours 3
• Once severe symptoms resolve, slow the correction rate

Step 3: Ongoing Monitoring

• Check serum sodium every 2-4 hours during active correction
• Monitor for signs of fluid overload
• Assess neurological status frequently
• Adjust correction rate if sodium rises too quickly

Special Considerations

• Avoid hypertonic saline unless severely symptomatic, as rapid correction risks osmotic demyelination syndrome
• Seizure management: Use magnesium sulfate, benzodiazepines, or levetiracetam for seizures associated with hyponatremia, as many anticonvulsants (barbiturates, hydantoins, carbamazepine, valproic acid) are contraindicated in AIP 1
• Avoid medications that may exacerbate AIP or hyponatremia (consult porphyria drug databases: https://www.porphyria.org/patient-resources/drug-safety-database-for-ahp/ and http://www.drugs-porphyria.org/) 1

Pitfalls to Avoid

1. Overly rapid correction: Can lead to osmotic demyelination syndrome, which may cause parkinsonism, quadriparesis, or death 3
2. Inadequate monitoring: Failure to check sodium levels frequently during correction
3. Inappropriate anticonvulsant use: Using porphyrinogenic anticonvulsants for seizure management
4. Delayed hemin administration: Failure to promptly treat the underlying acute attack
5. Overlooking precipitating factors: Not identifying and removing triggers of the acute attack

In cases where hemin is unavailable, hemodialysis has been reported as an alternative treatment option for severe acute attacks of AIP 4, which may also help manage associated electrolyte abnormalities including hyponatremia.