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Atracurium in a patient with acute intermittent porphyria.

The porphyrias are a group of inherited diseases characterized by disordered heme biosynthesis with the overproduction of heme precursors. Acute intermittent porphyria (AIP) along with variegate porphyria and hereditary coproporphyria are the most serious forms of the inducible hepatic porphyrias (1,2). Precipitating factors include increased steroid hormones (e.g., progesterone), impaired nutrition (e.g., starvation), and drugs. Clinical manifestations include abdominal pain, vomiting, constipation, photophobia, autonomic neuropathy, ascending polyneuropathy, and respiratory failure. The major concerns for anesthesiologists are that clinical crises can be induced by anesthetic drugs (3), and that neurologic lesions produced by demyelination are manifested as variable muscle weakness, unpredictable motor neuropathy, and autonomic neuropathy. Depolarizing and nondepolarizing muscle relaxants have been reported to be safe for these patients. We successfully used atracurium in a patient diagnosed as having AIP. A 32-yr-old Indian woman, ASA physical status 11, height 148 cm, weight 50 kg, was admitted with the diagnosis of primary infertility and scheduled for myomectomy and lysis of adhesions. She had been hospitalized several times over the past 5 yr for abdominal pain, headache, nausea, and vomiting. The diagnosis of AIP had been made approximately 1 yr before admission. Since then she had been treated with propranolol, 60 mg each morning, and had remained asymptomatic. A 24-h urine collection ordered by the hematology consultant 2 wk before admission revealed an elevated level of porphobilinogen (PBG) consistent with AIP as well as elevated levels of uroporphyrins and coproporphyrins. She denied any other medical problems. Physical examination and preoperative laboratory values were within normal limits. After a face mask induction of anesthesia with O,/N,O/ halothane, atracurium (30 mg IV) was administered and the trachea was intubated without difficulty. Anesthesia was maintained on O,/N,O/isoflurane, fentanyl, and atracurium. The total dose of atracurium was 55 mg IV. At the completion of surgery, residual muscle paralysis was reversed with neostigmine and glycopyrrolate. The recovery period and the postoperative period were uneventful, and the patient did not develop signs or symptoms of AIP. Exogenous lipid-soluble compounds induce the hepatic cytochrome P450 system, a group of hemoprotein isoenzymes that convert lipid-soluble, nonpolar drugs into water-soluble, polar compounds that are then renally excreted. The induction of the cytochome P450 system then triggers a need for heme. The first step of heme biosynthesis requires the enzyme hepatic Gaminolevulinic acid (ALA) synthetase. When activity or production of this rate-limiting enzyme is induced, whether by direct stimulation or de-repression of enzyme synthesis, increased heme precursor production then overwhelms the defective step in the pathway. For AIP, the defective step is diminished PBG deaminase activity, which results in intermediates in the pathway to this enzyme accumulating and spilling out of the liver into the circulation. Definitive diagnosis made by PEG deaminase assay is 95% sensitive when combined with an assay that shows increased activity of leukocyte ALA synthetase. During the latent period, the PBG deaminase assay is diagnostically accurate even when urinary biochemical abnormalities may be absent, although in acutely ill patients a quantitative test for urinary PBG is markedly elevated. Increases in ALA and PBG often precede an attack, and after an attack it is unusual for excretion of these precursors to decrease to normal levels except after prolonged periods of latency. The goal in the anesthetic management of a patient with AIP is to avoid precipitating clinical crises in the perioperative period. In a retrospective study of anesthetic use, Mustajoki and Heinonen (4) suggested that the inducing drugs seldom exacerbate latent AIP but may worsen symptoms during an acute episode. After measuring the effect of certain anesthetic agents on the activity of rat hepatic ALA synthase, Parikh and Moore (5) suggested that anesthesiologists avoid drugs that induce porphyria synthesis because alternative anesthetic combinations are available. Although many drugs have been incriminated (especially barbiturates) or are considered controversial (e.g., ketamine), the neuromuscular blocking drugs succinylcholine, decamethonium, d-tubocurarine, and gallamine are considered safe (6,7). Pancuronium and vecuronium have also been reported as safe but are considered controversial because of their steroid configuration. Atracurium, an intermediate-acting muscle relaxant, would now also ap-