Chapter 58 Anaphylaxis
Anaphylaxis is a symptom complex accompanying the acute reaction to a chemical recognised as hostile. In the classical reaction the patient has been previously sensitised (immediate hypersensitivity or type 1 hypersensitivity), although the sensitising agent may be unknown. The term ‘anaphylactoid reaction’ is used to describe reactions clinically indistinguishable from anaphylaxis, in which the mechanism is non-immunological, or has not been determined. Recent consensus meetings have suggested the use of the term ‘anaphylactoid’ be discontinued and ‘anaphylaxis’ used to describe the symptom complex which may be either ‘non-immune’ or ‘immune’.1 Non-immune anaphylaxis may be produced by direct drug effects, physical factors or exercise, and a causative agent cannot always be determined. The mediators involved are the same as those in other acute inflammatory responses such as sepsis, but the rate of release is more rapid and of shorter duration.
AETIOLOGY
Neugut et al.2 estimated 1400–1500 deaths per year in the USA and between 3.3 and 40.9 million patients at risk. They estimated radiocontrast media and penicillin to be the greatest cause of death, with food and stings the next groups. In contrast a postmortem study of 56 deaths in the UK3 attributed 19 deaths to venoms, 16 to foods and 19 to drugs and radiocontrast media.
The direct histamine-releasing effects of some drugs may produce reactions due to the effect of histamine alone, and such reactions are related to volume, rate and amount of infusion. Recent work suggests that the site of release of histamine may be important in its clinical effects. Drugs such as morphine and Haemaccel release histamine from skin alone,4 and are unlikely to produce symptoms such as bronchospasm, whereas drugs which produce release from lung mast cells (e.g. atracurium, vecuronium and propofol) may be more likely to produce bronchospasm.5 Direct histamine release is usually a transient phenomenon, but in some patients severe manifestations may occur, particularly with Haemaccel and vancomycin.
Anaphylactic reactions are usually seen in fit and well patients. It is likely that the adrenal response to stress ‘pretreats’ sick patients, and blocks the release and effects of anaphylactic mediators. The exception to this appears to be patients with asthma, in whom reactions to the additives in steroid and aminophylline preparations may occur, and this may be related to the reduced catecholamine response in asthma.6 Patients on β-blockers and with epidural blockade may be more likely to develop adverse responses due to histamine release, and this may also be related to reduced catecholamine responsiveness. Reactions occurring in these groups are more difficult to treat.
CLINICAL PRESENTATION
The latent period between exposure and development of symptoms is variable, but usually occurs within 5 minutes if the provoking agent is given parenterally. Reactions may be transient or protracted (lasting days), and may vary in severity from mild to fatal. Recurrent anaphylaxis is described. Cutaneous, cardiovascular, respiratory or gastrointestinal manifestations may occur singly or in combination.
Cutaneous features include piloerection, erythematous flush, generalised or localised urticaria, angioneurotic oedema, conjunctival injection, pallor and cyanosis. Awake patients may experience an aura, warning of an impending reaction. Cardiovascular system involvement occurs most commonly and may occur as a sole clinical manifestation.7 It is characterised by initial bradycardia then sinus tachycardia, hypotension and the development of shock.
In patients reacting due to venom desensitization, bradycardia may be severe and require treatment.8