Avoid triggering agents - This is the primary consideration. Patients are rarely identified prior to surgery as having porphyria, and the triggering potential of several drugs is still unknown. Barbiturates and Etomidate - the most prominent drugs that trigger porphyria Other drugs known to trigger porphyria - midazolam, ropivacaine, sulfonamides, amphetamines, chlordiazepoxide, diazepam, lorazepam, glutethimide, pentazocine, antipyrine, aminopyridine, phenytoin, methsuximide, chloramphenicol, tolbutamide, chlorpropamide, lead, ethanol, ergot preparations, methyldopa Other triggers - Fasting, stress, hypothermia, activation of the hepatic P-450 system, and certain chemicals or porphyrinogenic drugs Treatment - includes removal of precipitating factors, liberal hydration, hematin, heme arginate, and glucose. Hematin and heme arginate - both inhibit ALA synthase and will shorten an attack.
Autosomal dominent inherited. There are 8 types, but of particular interest to anesthesia providers is: Acute intermittent porphyria (AIP), variegate porphyria, and coproporphyria. ALA synthetase is an enzyme which is controlled by the amount of circulating heme and hepcidin. If the patient has a chronically low heme production, ALA synthetase activity will go unchecked and symptoms of porphyria appear. Signs and symptoms include fever, muscle weakness, GI disturbances, nausea and vomiting, dark urine, neurological disturbances (ie siezures, cranial nerve defects, psychosis, and peripheral neuropathy), and SIADH (dilutional hyponatremia and fluid overload). Fasting, stress, hypothermia, activation of the hepatic P-450 system, and certain chemicals or porphyrinogenic drugs can all trigger porphyria. Unfortunately, of these are common components of surgery and would typically INDUCE heme synthesis. However, because porphyria is caused by one or more deficiencies in enzymes needed to produce heme, these result in an accumulation of the heme precursors rather than the heme. Symptoms of the disease most likely result because of increased ALA synthetase activity, accumulation of porphyrin in the tissues, or decreased heme production.
