A 28-year-old woman from rural Maharashtra presents to the emergency department with acute onset severe abdominal pain, tachycardia (HR 110/min), and confusion. She reports a 3-day history of constipation and dark urine. On examination, she has proximal muscle weakness and hyponatraemia (Na+ 128 mEq/L). Urine porphobilinogen (PBG) is markedly elevated at 50 mg/L (normal <4 mg/L). What is the most appropriate immediate management?

Explanation

## Acute Intermittent Porphyria (AIP) Management ### Clinical Recognition This patient presents with the classic triad of acute porphyria: 1. **Neurovisceral symptoms**: severe abdominal pain, tachycardia, confusion, proximal weakness 2. **Hyponatraemia**: due to SIADH (syndrome of inappropriate antidiuretic hormone secretion) 3. **Elevated urinary PBG**: diagnostic marker of acute attack **Key Point:** Acute intermittent porphyria is a life-threatening metabolic emergency requiring rapid enzyme inhibition and metabolic support. ### Pathophysiology of the Acute Attack During an acute attack, ALA synthase (ALAS) is maximally upregulated, leading to: - Excessive accumulation of neurotoxic precursors (ALA and PBG) - Neurological dysfunction (autonomic instability, encephalopathy, seizures, respiratory paralysis) - Abdominal symptoms (pain, ileus, constipation) - Hyponatraemia from SIADH ### Immediate Management Strategy | Step | Rationale | |------|----------| | **IV Heme (hemin) infusion** | Suppresses ALAS-1 via negative feedback; reduces PBG production within hours | | **High-dose dextrose (300–500 g/day)** | Provides non-protein calories; reduces amino acid catabolism and ALAS-1 activation | | **Fluid resuscitation** | Corrects hyponatraemia cautiously (avoid hypotonic fluids); maintains renal perfusion | | **Supportive care** | Analgesia (avoid barbiturates, sulfonamides, NSAIDs—all porphyrinogenic) | **High-Yield:** Heme infusion is the definitive acute treatment—it is the ONLY intervention that directly suppresses the enzymatic block. Response is typically seen within 24–48 hours. **Clinical Pearl:** Dextrose alone (without heme) is slower and less effective; heme infusion is the gold standard for severe or refractory attacks. ### Why Other Options Fail - **Plasmapheresis**: Not first-line; reserved for fulminant cases with severe neurological deterioration or respiratory compromise - **Phenobarbital**: Absolutely contraindicated—it is a potent porphyrinogenic agent and will worsen the attack - **Surgical exploration**: Abdominal pain in AIP is metabolic, not surgical; unnecessary laparotomy risks further stress and worsening **Warning:** Avoid all porphyrinogenic drugs: barbiturates, sulfonamides, NSAIDs, oral contraceptives, and many antibiotics. Use only safe analgesics (paracetamol, opioids) and safe antibiotics (penicillins, cephalosporins).