Porphyria

Learning objectives

Porphyrias are a heterogeneous group of inherited genetic disorders of heme biosynthesis
The heme biosynthetic pathway is most active in the liver and bone marrow
Porphyrins are organic cyclical compounds found in heme, the iron-containing ring structure found in hemoglobin, myoglobin, and all of the cytochromes

Acute porphyrias: Potential to develop acute neurovisceral crises
- Acute intermittent porphyria (AIP)
- Variegate porphyria (VP)
- Hereditary coproporphyria (HCP)
- 5-aminolaevulinic acid (ALA) dehydrase deficiency
- Triggers for an acute crisis
  - Fasting
  - Dehydration
  - Infection
  - Drugs
  - Endogenous hormones
  - Stress
  - Smoking
  - Alcohol
Non-acute: Do not deteriorate into acute crises, less relevant for anesthesiologists
- Porphyria cutanea tarda
- Congenital erythropoietic porphyria
- Erythropoietic protoporphyria

Presentation of an acute crisis

Almost all patients have severe abdominal pain, usually associated with tachycardia
Symptoms and signs of acute crises vary greatly and can mimic other conditions

Symptoms and signs	Features	May be misdiagnosed as
Abdominal pain	Recurrent, severe, poorly localized Associated nausea and vomiting Absence of fever or leucocytosis	Another cause of acute abdomen Endometriosis/pelvic inflammatory disease Irritable bowel syndrome Opiate addiction
Cardiovascular signs	Tachycardia Tachyarrhythmia Hypertension
Weakness	Proximal > distal Upper limbs > lower Up to 20% develop respiratory failure May progress to bulbar paresis in severe cases	Guillain-Barré syndrome Poliomyelitis Acute lead poisoning Vasculitis
Psychiatric features	Mood disturbance Confusion Psychosis	Anxiety disorder Somatization disorder Acute psychosis Acute confusional state
Pain and sensory disturbance	Back, thigh, or extremity pain Sensory neuropathy over the trunk	Chronic fatigue syndrome Fibromyalgia Chronic pain syndromes
Seizures	CNS manifestation of porphyria Secondary to hyponatremia	Epilepsy
Other autonomic features	Constipation Gastoparesis Postural hypotension
Cutaneous lesions	Only in VP and HCP Vesicular rash Photosensitivity	Porphyria cutanea tarda Bullous skin disease
Hyponatremia and other electrolyte disturbance	Low serum sodium Low serum magnesium	Other disorders of sodium and water balance

Once an acute crisis has been diagnosed, management consists of the following:

Commonly used drugs and their safety profile

Drug	Safe	Unsafe	Undetermined
I.v. anesthetic agents	Propofol	Thiopentone, ketamine	Etomidate
Inhalational anesthetic agents	Isoflurane, desflurane, nitrous oxide	Sevoflurane
Local anesthetics	Bupivacaine, prilocaine, lidocaine		Levobupivacaine, ropivacaine
Neuromuscular blocking agents and removal	Succinylcholine, all non-depolarizing muscle relaxants, neostigmine
Analgesics	Fentanyl, alfentanil, remifentanil, morphine, hydromorphone, meperidine, tramadol, ibuprofen, aspirin	Oxycodone, diclofenac	Pentazocine, mefenamic acid
Sedative premedication	Lorazepam, phenothiazines (chlorpromazine), temazepam
Antibiotics	Gentamicin, co-amoxiclav, penicillins, vancomycin, tazocin, meropenem	Rifampicin, erythromycin
Cardiovascular drugs	Adrenaline, noradrenaline, milrinone, atropine, glycopyrrolate, β-blockers, phenylephrine, magnesium, angiotensin 2 inhibitors, fibrinolytic drugs	Ephedrine	Vasopressin, metaraminol
Miscellaneous	Syntocin, carboprost, tranexamic acid, aprotinin		Dexamethasone, hydrocortisone

Anesthesiologists should be aware of the perioperative factors that may trigger or worsen an acute crisis in porphyria