FRCA Notes

Porphyria

The curriculum asks rather succinctly for 'knowledge of porphyria'.

This ultimately rather rare disease has featured as a Primary FRCA Viva question in the past.

Resources

  • The porphyrias are a group of predominantly inherited disorders characterised by an abnormality in enzymatic haem synthesis
  • This leads to an accumulation of porphyrins and their precursors:
    • Amino-laevulinic acid (ALA)
    • Porphobilinogen (PBG)

  • It may be hereditary or acquired
    • Incidence 1 in 20,000
    • Most patients present between 15-40yrs and there is a female preponderance
  • These typically present with an acute attack ± skin photosensitivity
  • They are all autosomal dominant
  • Include:
    • Acute intermittent porphyria
    • Variegate copro-porphyria
    • Hereditary copro-porphyria
    • ALA dehydratase porphyria

Acute attack

  • Acute attacks occur when hepatic haem requirements are increased e.g.:

    • Triggers for acute attacks
    Alcohol
    Fasting or dehydration
    Stress
    Infection
    Menstruation or pregnancy
    Enzyme-inducing drugs

  • These events tend to reduce haem levels thus increasing ALA-synthetase activity and hence production of porphyrins
  • The excess porphyrins (ALA and PBG) leak into the circulation
  • Mortality of an acute attack is 10%, often due to concurrent infection, respiratory failure or dysrhythmias

  • Diagnosis is with elevated urinary ALA and PBG levels

Abdominal pain (95%)

  • Often severe and accompanied by vomiting, but without peritonitis
  • May be back or leg pain too

Autonomic instability (dysautonomia)

  • Leads to tachycardia (80%) and hypertension (40%)
  • Postural hypotension (21%)
  • Cardiac arrhythmia
  • In the long-term may cause renal dysfunction

Neurological presentations

  • Peripheral neuropathy(60%)
    • Typically a distal motor neuropathy
    • Mild paraesthesia

  • CNS palsies
    • Bulbar involvement (30%) ± subsequent aspiration, neuromuscular weakness and ventilatory failure
    • Seizures (10%)

  • Psychiatric disturbance (55%)

Supportive

  • Hydration
  • Correction of electrolyte imbalance (typically have hypo-Na+|K+|Mg2+)
  • Maintain carbohydrate intake
  • Either β- or ɑ-blockade to manage autonomic instability
  • Analgesia
  • FVC monitoring if bulbar weakness

Specific

  • Haematin infusion (haem arginate is used in the UK)
    • Halts the haem biosynthetic pathway in a temporary fashion by inducing negative feedback on ALA-synthetase
    • This reduces porphyrin build-up
    • Can, however, cause renal failure and coagulopathy

  • Cimetidine may also inhibit haem oxidase activity, reducing haem consumption and providing negative feedback to ALA-synthetase

Perioperative management of the patient with porphyria


History and examination

  • Patients with quiescent porphyria may be asymptomatic
  • Patients with a family history may be screened via genetic testing, but in urgent cases manage patient as if they have porphyria
  • Should carefully examine for:
    • Cardiovascular stability
    • Presence of bulbar symptoms
    • Ventilatory function
    • Presence of peripheral neuropathy (especially if regional anaesthesia considered)

Optimisation

  • Minimise fassting duration
    • Maintain carbohydrate levels with dextrose/saline infusion
    • However, pre-operative fluid restriction does not impact incidence of acute attacks

  • Pre-medicate to reduce risk of stress-induced acute attack; midazolam is probably not porphyrinogenic

  • Consider antacid pre-medication
    • Standard PPIs are safe with the exception of esomeprazole
    • Metoclopramide is ok but erythromycin should be avoided

Monitoring and access

  • AAGBI
  • Consider arterial line if dysautonomia

Anaesthetic technique

  • No known superiority of either general or regional anaesthesia

Induction

  • Propofol is not porphyinogenic
    • Ketamine, thiopentone and etomidate should all be avoided

  • Opioids
    • Fentanyl and other synthetic piperidines e.g. alfentanil, remifentanil are probably not porphyrinogenic
    • Morphine and oxycodone are safe

  • All common NMBA are safe (both aminosteroids and benzylisoquinoliniums)
  • Both neostigmine and sugammadex are safe

Maintenance

  • Volatile agents are safe
  • Nitrous oxide is safe
  • Some suggestion propofol infusion appears to be confer porphyrinogenic potential due repeated/prolonged exposure to the drug

Cardiovascular


Safe Unsafe
ɑ-blockers Amiodarone
β-blockers Hydralazine
Glycopyrrolate Non-DHP calcium channel blockers
Atropine Metaraminol (not classified)
Phenylephrine Dexmedetomidine
Clonidine

Obstetrics

  • Oxytocin is safe although carbetocin is not classified
  • Carboprost is safe
  • Tranexamic acid is safe
  • Ergometrine is not safe

Antibiotics

  • Most common perioperative antibiotics are safe
  • Exceptions include: flucloxacillin, clarithromycin

Anti-emetics

  • Avoid:
    • Cyclizine
    • Dexamethasone
    • Aprepitant

  • The vast majority of commonly-used analgesics are safe, including gabapentinoids
  • If unsafe drugs are inadvertently given, it is good practice to monitor urinary porphyrins for five days