Unrecognised anaphylaxis to propofol or fentanyl

Abstract

We were interested to read the recent letter regarding a patient who died as the result of an anaphylactic reaction while undergoing anaesthesia (Konarzewski & De'Ath. Anaesthesia 2001; 56: 497–8). We would like to make the following comments. We agree with the authors' conclusion that the elevated serum tryptase and methylhistamine levels (185 µg.l−1 and 51.6 ng.µmol−1, respectively) in the post-mortem blood samples suggest an anaphylactic reaction as the aetiology to this patient's cardiac arrest. The patient had also suffered an adverse event whilst undergoing an anaesthetic 8 months previously. It is possible to hypothesise that this episode was also anaphylactic in origin but there is no laboratory evidence to substantiate this. We would, however, question their interpretation that propofol or fentanyl was the causative allergen. They point out that severe allergic reactions during anaesthesia have an incidence of 1 : 13 000 and this rises to 1 : 6500 if muscle relaxants are used. Studies have shown that muscle relaxants are responsible for 75–80% of anaphylactic reactions occurring during anaesthesia [1, 2]. Exploring the possibility of previous exposure to anaesthetic agents reveals that their patient had undergone several uneventful general anaesthetics between 1960 and 1974. During this period propofol was not available for clinical use and the administration of fentanyl was not commonplace. If the patient had received a muscle relaxant as part of these anaesthetics, the choice would have been one of succinylcholine, alcuronium, pancuronium, tubocurarine or gallamine. With this in mind, previous sensitisation would only be of issue with pancuronium and possibly fentanyl. During their patient's recent first anaesthetic, propofol, fentanyl and vecuronium were used and, during the second, propofol, fentanyl and pancuronium. Vecuronium and pancuronium are both aminosteroids. Studies have demonstrated that allergenic cross-reactivity exists between these two agents [3, 4]. The first published case report of proven anaphylaxis to vecuronium was in a patient who had previously suffered anaphylactic shock following exposure to pancuronium [5]. Additionally the authors do not state whether lidocaine was added to the propofol. A previous case of anaphylaxis to lidocaine administered in this way has been reported [6]. Although true allergy to amide local anaesthetics is rare, the inclusion of lidocaine in propofol is often overlooked when investigating anaphylactic reactions [7]. It is interesting to note that the patient was premedicated with ranitidine for her first anaesthetic. H2 antagonism has previously been reported to reduce the magnitude of anaphylactic reactions and may explain why the patient's first episode (if anaphylactic in origin) was less severe [8]. As the authors state, it is not possible to say with confidence which drug caused the anaphylactic reaction but in the absence of immunological testing we would conclude that the balance of probability favours the muscle relaxants.