Etomidate: an ‘immunologically safe’ anaesthetic agent?

In their article on allergy, plasma IgE levels and anaphylactoid response (Anaesthesia 1985; 40:362-5) Dr Watkins and his colleagues state that etomidate is devoid of plasma histamine releasing properties. They also state that this drug ‘has not been directly implicated in an immediate anaphylactoid reaction so far’. Unfortunately, both views have to be corrected and I wish to draw your readers’ attention to two recent case reports where etomidate was shown to have caused an immediate anaphylactoid reaction.’.’ (Both papers were in German, one appearing simultaneously with Dr Watkins’ paper.) Anaesthesia was induced with alcuronium 2 mg, thiopentone 500 mg, suxamethonium 100 mg and fentany10.2 mg in a 54-year-old patient who weighed 94 kg and with known allergy towards acetylsalicylic acid and phenacetin. He received, during maintenance, 24 mg alcuronium and a further 0.2 mg of fentanyl, together with nitrous oxide and oxygen; after 2 hours 0.254.5 vol% halothane was added to the inspired mixture. Towards the end of the procedure, etomidate 4 mg was given. Two to three minutes after the injection, the authors’ observed generalised erythema, severe urticaria and hypotension, and the systolic blood pressure decreased from 120 to 85 mm Hg. The symptoms completely disappeared within 45 minutes following treatment with an antihistaminic and a corticosteroid. The last increment of alcuronium had been given 30 minutes before. so etomidate was alleged to have caused this anaphylactoid reaction grade 11, according to the classification proposed by Lorenz and D ~ e n i c k e . ~ However, skin tests were not carried out, nor were IgE levels measured in this patient.’ The second case2 was a 63-year-old patient with known penicillin allergy, scheduled for coronary artery bypass grafting. Central venous and arterial lines were inserted under anaesthetic with mepivacaine. Anaesthesia was induced with pancuronium 2 mg, fentany10.2 mg, flunitrazepam 0.7 mg and etomidate 4 mg, and the trachea intubated with the aid of suxamethonium 100 mg. Marked tachycardia developed, the heart rate exceeded 170 beats/minute and hypotension developed, the systolic blood pressure decreased, from 105 to 50 mm Hg and erythema appeared on the neck. Dexamethasone 100 mg, norepinephrine 0.5 mg and verapamil 5 mg were immediately injected from readyfor-use syringes; successful resuscitation required infusion of lo00 ml crystalloid and 1000 ml plasma protein solution and a further dose of noradrenaline 0.5 mg, adrenaline I mg, verapamil 10 mg, methylprednisolone I g and 9.2 mmol calcium. Surgery was postponed because of the severity of the reaction. When skin tests (both epicutaneous and scratch) were carried out 5 weeks after the event, a positive reaction was demonstrated solely for etomidate; propylene glycol and all other drugs were negative. There was also a response to carticaine and penicilloyl-polylysine. Hence, for definitive surgery exactly the same induction manoeuvre was chosen, but the etomidate was omitted. Anaesthesia and surgery proceeded uneventfully; catecholamines were not required. There can be no doubt that this anaphylactoid (or anaphylactic?) reaction grade 111 was caused by etomidate. Publication of the case prompted an editorial by Lorenz who advocated the use of dimetinden maleate 0. I mg/kg plus cimetidine 5 mg/kg as a short-term infusion in patients at risk, 3&10 minutes before the induction of anae~thesia .~ We want to refer to an earlier article by Watkins, about the histamine releasing properties of etomidate, in which he admits that there is some suggestion of synergistic histamine release.’ Indeed, whereas Doenicke and coworkers, in an experimental study on human volunteers, found no evidence for direct histamine liberation,6 they were able to demonstrate an effect when etomidate was used in conjunction with suxamethonium, alcuronium, pancuronium or lorme ta~epam. ’*~*~ According to the authors, even nonpharmacological manipulations, such as tracheal intubation, may modulate histamine release caused by drugs.” Consequently, in the individual patient there is no absolute safety, even when using an ‘immunologically safe’ drug such as etomidate. It is a pity that we were not able to measure IgE serum level in our patient, nor could we examine his family. It is therefore not possible for us to contribute to Dr Watkins’ interesting hypothesis.