Emergency treatment of anaphylaxis
Authors: F Estelle R Simons
Journal: BMJ (2008)

The Resuscitation Council of the United Kingdom recently updated its guidelines on the emergency treatment of anaphylactic reactions.1 The guidelines stress the importance of an early call for help from a resuscitation team or an ambulance. They introduce the ABCDE approach (airway, breathing, circulation, disability (level of consciousness), and exposure (of the skin)). They emphasise that prompt intramuscular injection of adrenaline (epinephrine) is the initial treatment of choice, along with other measures as indicated. These may include placing the patient in a comfortable position, providing airway management, giving high flow oxygen, and rapidly administering a large volume of intravenous fluid. They also advise subsequent referral to an allergy specialist for risk assessment and institution of long term measures to reduce risk.

No new drugs are available for the acute treatment of anaphylaxis. Currently used agents such as adrenaline, glucocorticoids, H1 antihistamines, and H2 antihistamines were introduced before the era of randomised controlled trials and evidence based medicine. Systematic reviews of these drugs are being conducted to document the existing evidence base.2 3 4 This consists of clinical experience and expert opinion, observational studies, epidemiological studies, fatality studies, in vitro studies, and randomised, placebo controlled investigations in animal models and in people who have had anaphylaxis previously but are not experiencing it at the time of the study.5 6 7

Few published national guidelines are available on the treatment of anaphylaxis, but they all agree that adrenaline is fundamental to acute management.1 8 Interestingly, no agreement exists on the initial dose of intramuscular adrenaline, which—for patients age 12 years or more—is 0.5 mg in the UK guidelines and 0.3-0.5 mg in most others.1 8

Adrenaline prevents and relieves laryngeal oedema and circulatory collapse through its α1 adrenergic effects. It provides bronchodilation and reduces the release of histamine and other mediators through its β2 adrenergic effects. A brief window of opportunity seems to exist, during which even a relatively low intramuscular dose—such as 0.3 mg—is efficacious. Failure to inject adrenaline promptly increases the risk of a biphasic anaphylactic reaction, and death. Although adrenaline is sometimes blamed for causing myocardial ischaemia and cardiac dysrhythmias, anaphylaxis itself can cause these problems before adrenaline is given.6 7 Transient palpitations, tremor, and pallor after injection of adrenaline reflect the anticipated pharmacological effects of the drug.

In healthcare settings, the risk of harmful effects is lower with intramuscular adrenaline than with intravenous adrenaline. As pointed out in the revised UK guidelines, continuous monitoring and dose titration by an appropriately trained specialist are mandatory if adrenaline is given intravenously.1 Error and delay in adrenaline dosing have been attributed to the common practice of using ratios—such as 1:1000—to express drug concentrations, so mass concentrations such as milligrams per millilitre are preferred.9

In community settings, although adrenaline autoinjectors might be overprescribed in some countries, they are either not available or not affordable in many others,10 and even when they are readily available and affordable they are underused during anaphylactic reactions. Limitations of currently available adrenaline autoinjectors include a restricted range of premeasured doses and needle lengths.6 7

In contrast to universal recommendations for injecting adrenaline in anaphylaxis, national guidelines do not agree on the role of other commonly used drugs such as glucocorticoids, H1 antihistamines, and H2 antihistamines; indeed, H2 antihistamines are not even mentioned in the UK guidelines.1 8 It might therefore be possible to study these other drugs prospectively in rigorously designed, randomised, placebo controlled multicentre trials in which they are tested individually, with appropriate precautions, in addition to standard of care treatment which includes adrenaline, positioning the patient comfortably, airway management, supplemental oxygen, and intravenous fluid, as indicated.

Placebo controlled trials of adrenaline would clearly be unethical1 4 5 6 7—indeed, the underuse of adrenaline for treating anaphylaxis in healthcare settings is also a concern.11 However, it might be possible to conduct randomised trials comparing two different doses of adrenaline—for example, the two commonly recommended initial intramuscular doses of 0.3 mg and 0.5 mg.

Randomised controlled trials of any intervention would be difficult to conduct in people who present to accident and emergency departments with anaphylaxis, because no baseline measurements are available, and symptoms and signs of anaphylaxis might be resolving as a result of first aid treatment or endogenous production of adrenaline, angiotensin II, endothelin, and other substances. 

Such studies might be possible, however, in well equipped healthcare settings in which anaphylaxis sometimes occurs—for example, in selected patients undergoing a physician supervised controlled challenge with a food or an insect sting as part of their anaphylaxis risk assessment, or in those receiving allergen specific immunotherapy. In these settings, staffed by professionals with appropriate training and experience in the prevention, recognition, and management of anaphylaxis, it would be possible to obtain informed consent and baseline measurements would be available. Moreover, if anaphylaxis inadvertently occurs, standard of care treatment with adrenaline, positioning the patient comfortably, airway management, supplemental oxygen, and intravenous fluid would be instituted promptly, as indicated. Continuous cardiac and blood pressure monitoring and pulse oximetry could be performed. Improved ability to confirm the clinical diagnosis of anaphylaxis with a laboratory test, and validation of anaphylaxis severity scores and other clinical outcome measures, would help to facilitate such studies.12

In summary, the revised UK Guidelines on Emergency Treatment of Anaphylactic Reactions are an important resource and a model for other national and international anaphylaxis guidelines being developed. The possibility of conducting randomised controlled trials in anaphylaxis should be considered.