Emergency Medical Treatment of Anaphylactic Reactions

7Accid Emerg Med 1999;16:243-247 243

CONSENSUS GUIDELINES J Accid Emerg Med: first published as 10.1136/emj.16.4.243 on 1 July 1999. Downloaded from

Emergency medical treatment of anaphylactic reactions

Project Team of the Resuscitation Council (UK)

1. Objective of document tary document offers guidance to general prac- Anaphylaxis seems to be increasingly common, titioners and A&E staffwho are usually the first almost certainly associated with appreciable physicians to become involved. Anaphylactic increase in prevalence of allergic disease over reactions may occur within hospital as a result the last two or three decades. Although the of attempted hyposensitisation, the administra- drug treatment and management of anaphy- tion of drugs including anaesthetic agents, or laxis is described elsewhere,' anaphylaxis con- contrast materials. Some specialist groups have tinues to be poorly managed. There are two issued recommendations for the management main problems. First, epinephrine (adrenaline) of emergencies that occur under these specific is greatly under-used: chlorpheniramine and circumstances.'-' The present guidance is not hydrocortisone injections are more often given. intended to replace existing advice for defined Second, there has been a vogue for inappropri- groups in hospital nor to influence the essential ate use of intravenous epinephrine (adrena- individual advice and management provided in line), both by paramedics and in accident and specialist clinics. emergency (A&E) departments, when epinephrine (adrenaline) should have been given 2. Recognition of anaphylactic and intramuscularly. Published recommendations anaphylactoid reactions for the management of anaphylaxis also vary. 2.1. There are no universally accepted This document provides a broad consensus on definitions of anaphylactic and anaphylactoid the appropriate emergency management of reactions. Disparate mechanisms can lead to acute anaphylactic reactions by first medical serious symptoms and signs due to sudden responders who are unlikely to have specialised activation of mast cells and basophils. The knowledge. term anaphylaxis is usually used for hypersen- No definitive clinical trials have been per- sitivity reactions typically mediated by immu- http://emj.bmj.com/ formed to provide an unequivocal evidence noglobulin E (IgE). Anaphylactoid reactions base: moreover such evidence is unlikely to be are similar, but do not depend upon hypersen- forthcoming. A wealth of experience does, sitivity. For simplicity the term anaphylaxis will however, exist. This has been integrated be used here for both types of reactions unless through the wide membership of the Project there is an important distinction to be made. Team which was convened under the aegis of Their manifestations and management are the Resuscitation Council of the United King- similar so that the distinction becomes impor- on September 26, 2021 by guest. Protected copyright. dom with representation from four royal tant only when considering the follow up man- colleges and three specialist associations: other agement. Both may present clinically with members were coopted because of their angio-oedema, urticaria, dyspnoea, and hypo- individual expertise. Consensus was achieved tension. But some patients may die from acute after two meetings and multiple circulation of irreversible asthma or laryngeal oedema with working papers. An earlier document from few more generalised manifestations. Other broadly the same group (but at that time symptoms include rhinitis, conjunctivitis, ab- representing the Joint Royal Colleges and dominal pain, vomiting, diarrhoea, and a sense Ambulance Liaison Committee) has dealt with of impending doom. There is also usually a the management of anaphylaxis by colour change: the patient may appear either paramedics-who are often the first to attend flushed or pale. Cardiovascular collapse is a out ofhospital emergencies.2 This complemen- common manifestation6 especially in response to intravenous drugs or stings, and is caused by Members of Project Team: Professor Douglas Chamberlain (Chairman), Dr Judith Fisher (also for the Royal College of vasodilatation and loss of plasma from the General Practitioners), Dr Michael Ward (also for the blood compartment. Cardiac dysfunction or Association of Anaesthetists). Coopted: Dr Andrew Cant (for the Royal College of Paediatrics & Child Health), Dr Peter arrhythmias are due principally to hypoten- Dawson (for Royal College of Radiologists), Dr Pamela Ewan, sion, or rarely to underlying disease,7 8 or to Mrs Angela Fritz (for the Anaphylaxis Campaign), Dr Gideon Lack, Professor Tak Lee (for the British Society for Allergy & epinephrine (adrenaline) that has been admin- Correspondence to: Clinical Immunology), Dr John Martin (for the British National istered intravenously.9 Anaphylactic reactions Professor D Chamberlain, Formulary), Dr Barbara Phillips (for the Royal College of Paedi- atrics & Child Health), Dr Richard Pumphrey (for the Royal vary in severity and progress may be rapid, 25 Woodland Drive, Hove, College ofPathologists), Dr George Rylance (for the Royal Col- slow, or (unusually) biphasic.'0 Rarely manifes- East Sussex BN3 6DH lege of Paediatrics & Child Health), Mr Howard Sherriff (for (e-mail: British Association of Emergency Medicine), and Professor tations may be delayed by a few hours (adding [email protected]). David Warrell (for the Royal College of Physicians). to diagnostic difficulty), or persist for more 244 24Project Team ofthe Resuscitation Council (UK)

than 24 hours.7 Reactions may follow exposure may cause short lived sensitivity. Second to a variety of agents with insect stings, drugs attacks are by no means invariable in response

or contrast media, and some foods being the to penicillin20 or contrast agents, and approxi- J Accid Emerg Med: first published as 10.1136/emj.16.4.243 on 1 July 1999. Downloaded from most common. Peanut and tree nut allergy has mately half remain vulnerable after insect recently been recognised as particularly stings.2' Peanuts on the other hand, may leave dangerous.'1 Muscle relaxants may cause ana- patients with a persistent predisposition to phylaxis while anaesthetic agents are important anaphylaxis after a first attack, but eventual causes of anaphylactoid reactions.3 12 1 Block- resolution occurs in some. ers may increase the severity of an anaphylactic reaction and antagonise the response to epinephrine (adrenaline). " They may also increase the incidence of anaphylaxis, but the data are 3. Considerations in relation to treatment limited and inconsistent." '4 The complex 3.1. Epinephrine (adrenaline) is generally nature of anaphylaxis has been described in agreed to be the most important drug for any reviews. 517 severe anaphylactic reaction,. although there 2.2. The lack of any consistent clinical mani- has been no standard recommendation for festation and a wide range of possible presenta- tions may cause diagnostic difficulty. Clinical dose or route. As an a receptor agonist, it experience has shown that many patients with reverses peripheral vasodilation and reduces genuine anaphylaxis do not always receive oedema. Its P receptor activity dilates the appropriate medication. Rarely, patients have airways, increases the force of myocardial con- been given injections of epinephrine (adrena- traction, and suppresses histamine and leukot- line) inappropriately for vasovagal reactions or riene release. Epinephrine (adrenaline) works panic attacks. Diagnostic problems have arisen best when given early after the onset of the particularly in children. Guidelines for the man- reaction" but it is not without risk, particularly agement of shock from anaphylaxis must there- when given intravenously.9 Epinephrine fore take into account the inevitability of some (adrenaline) when given intramuscularly is diagnostic errors, with an emphasis on the need very safe. Adverse effects are extremely rare, for safety of any recommended measures. and the only case of myocardial infarction 2.3. In each case, a full history and examina- reported after its intramuscular administration tion should be undertaken as soon as circum- had numerous risk factors for coronary stances permit. The history ofprevious allergic disease.23 Sometimes there has been uncer- reactions is important as well as that of the tainty as to whether complications (for exam- recent incident. Special attention should be ple myocardial ischaemia) have been due to the paid to the condition ofthe skin, the pulse rate, effects of the allergen itself or to epinephrine the blood pressure, the upper airways, and aus- (adrenaline) given as treatment for it. cultation of the chest. Peak flow should be 3.2. Epinephrine (adrenaline) may rarely fail measured where possible, and recorded. to reverse the clinical manifestations of ana- 2.4. No investigations can prove anaphylac- phylaxis, especially in late reactions or in tic sensitivity to an allergen other than giving a patients treated with P blockers. Other meas- http://emj.bmj.com/ challenge with the suspect agent. But an ures then assume greater importance, particu- attempt should always be made retrospectively larly volume replacement. to assess the likelihood that a severe reaction 3.3. Antihistamines (H1 blockers) should be was genuinely of an anaphylactic nature. While used routinely in the management of all this is a matter for a specialist clinic rather than anaphylactic reactions to help counter hista- part of emergency management, a possible mine mediated vasodilatation. They may be anaphylactic emergency provides an oppor- unhelpful for at least some anaphylactoid reac- on September 26, 2021 by guest. Protected copyright. tunity for specific blood tests. Some rely on tions that depend in part on other mediators measurements of specific IgE antibody: these but have the virtue of safety. Their use alone is, are useful but must be interpreted carefully. however, unlikely to be lifesaving. Measurement of mast cell tryptase can also 3.4. Corticosteroids are considered as slow assist with retrospective diagnosis.'8 Both of and take to 4-6 hours to these tests can be performed on 1O ml of clot- acting drugs may up ted blood which hospitals can send to a have an effect even if given intravenously. They reference laboratory. Ideally blood should be may, however, help in the emergency treatment taken 45 to 60 minutes after the reaction, but of an acute attack, and they also have a role in in any case not later than six hours after the preventing or shortening protracted reactions. event. The use of blood tests is to be They form an essential part of management in encouraged because future management can recurrent idiopathic anaphylaxis24 25 and are be helped by increased diagnostic certainty. also of special importance to asthmatics 2.5. No reliable epidemiological data are especially those who have been treated recently available on the incidence of anaphylaxis partly with corticosteroids. Although some authors because of the difficulty defining anaphylactic have expressed cautions about steroids,25 and reactions, but one study found an incidence of the contribution of individual drugs when sev- 1:2300 attendees at an A&E department eral are given is difficult to prove, clinical (equivalent to one episode per 15 000 of the experience shows that parenteral hydrocorti- population per annum) and fourfold more sone is ofvalue in anaphylaxis. The safest prac- (approximately one in 3500 per annum) in the tice is to use corticosteroids for all victims second part of the study the following year.'9 likely to be suffering from a severe anaphylactic Even the mortality is unknown. Some allergens reaction. Anaphylactic reactions 245

jig) should be administered intramuscularly, Consider when compatible history of severe allergic-type and repeated after about five minutes in the reaction with respiratory difficulty and/or hypotension absence ofclinical improvement or ifdeteriora- J Accid Emerg Med: first published as 10.1136/emj.16.4.243 on 1 July 1999. Downloaded from especially if skin changes present tion occurs after the initial treatment especially if consciousness becomes-or remains- impaired as a result of hypotension. In some Oxygen treatment cases several doses may be needed, particularly when available if improvement is transient. The doses of epinephrine (adrenaline) recommended for children are as follows: >11 Stridor, wheeze, years, up to 500 ,ug intramuscularly (0.5 ml respiratory distress, or 1: 1000 solution); 6-11 years, 250 jg intramus- clinical signs of shock * cularly (0.25 ml 1:1000 solution); 2-5 years, 125 jig intramuscularly (0.125 ml 1: 1000 solution); and <2 years: 62.5 gg intramuscularly (by additional dilution 1: 1000 solution). Epinephrine (adrenaline) t As for adults, doses may be repeated after 1:1000 solution five minutes if necessary. 0.5 ml (500 jg) IM Devices for home use currently known as the EpiPen or Anapen and the EpiPen Jr or Anapen Junior that can inject 300 jg or 150 jig Repeat in 5 minutes if no clinical respectively are available. The drug may there- improvement fore have been administered by parents before medical help is available. The doses can be regarded as equivalent to the 250 jg and 125 Antihistamine (chlorpheniramine) jig more generally recommended. Other self 10-20 mg IM/or slow IV administration devices include Min-I-Jet Adrenaline which contains 1 mg (1000 jg) of epinephrine (adrenaline). This allows incre- IN ADDITION mental dose selection, but it should not be used in children because of the risk of overdose. 4.4. Intravenous epinephrine (adrenaline) in a dilution of at least 1:10 000 (never 1: 1000) is For all severe or recurrent If clinical manifestations reactions and patients of shock do not respond hazardous and must be reserved for patients with asthma give to drug treatment with profound shock that is immediately life hydrocortisone give 1-2 litres IV fluid.t threatening and for special indications, for 100-500 mg IM/or slow IV Rapid infusion or one repeat example during anaesthesia. The injection dose may be necessary should be given as slowly as seems reasonable while heart rate and the http://emj.bmj.com/ Figure 1 Anaphylactic reactions for adults: treatment byfirst medical responder. *An monitoring electrocar- inhaled fl,2 agonist such as salbutamol may be used as an adjunctive measure if diogram. Electrocardiographic monitoring is bronchospasm is severe and does not respond rapidly to other treatment. tIfprofound shock mandatory if epinephrine (adrenaline) is given isjudged immediately life threatening give cardiopulmonary resuscitationladvanced life intravenously. Note also that a further 10-fold support if necessary. Consider slow intravenous (IV) epinephrine (adrenaline) 1:10 000 solution. This is hazardous and is recommended onlyfor an experienced practitioner who dilution to 1: 100 000 epinephrine (adrenaline) can also obtain IV access without delay. Note the different strength ofepinephrine allows finer titration ofthe dose and increases its (adrenaline) that is requiredfor IV use. fA crystalloid may be safer than a colloid.26 IM = safety by reducing the risk of unwanted adverse intramuscular. effects and dangerous complications.9 25 on September 26, 2021 by guest. Protected copyright. 4. Recommendation for management 4.5. An antihistamine (chlorpheniramine) 4.1. The recommendations are summarised should be administered. Caution is needed to in algorithms shown in fig 1 (for adults) and fig avoid drug induced hypotension: administer 2 (for children). either by slow intravenous injection or by 4.2. All victims should recline in a position intramuscular injection. Its use may be helpful of comfort. Lying flat with or without leg and is unlikely to be harmful. The dose for elevation may be helpful for hypotension but children and adults is determined by age as unhelpful for breathing difficulties. If available, follows: >11 years, 10-20 mg intramuscularly; should be administered 6-11 years, 5-10 mg intramuscularly; and 1-5 oxygen at high flow years: 2.5-5 mg intramuscularly. rates (10-15 litres/min). Cardiopulmonary 4.6. Hydrocortisone (as sodium succinate) resuscitation must be performed if the need should be administered after severe attacks to arises. help avert late sequelae. This is of particular 4.3. Epinephrine (adrenaline) should be importance for asthmatics (who are at in- administered intramuscularly to all patients creased risk of severe or fatal anaphylaxis) if with clinical signs of shock, airway swelling, or they have been treated with corticosteroids definite breathing difficulty,6 and will be previously. The dose of hydrocortisone should rapidly absorbed. Manifestations such as in- be given by slow intravenous or intramuscular spiratory stridor, wheeze, cyanosis, pro- injection-care being taken to avoid inducing nounced tachycardia, and decreased capillary further hypotension. The dose for adults and filling alerts the physician to the likelihood of a children is determined by age as follows4: >11 severe reaction. For adults, a dose of 0.5 ml years, 100-500 mg; 6-11 years, 100 mg; and epinephrine (adrenaline) 1:1000 solution (500 1-5 years, 50 mg. 246 26Project Team ofthe Resuscitation Council (UK)

* Severe reactions with slow onset due to Consider when compatible history of severe allergic-type idiopathic anaphylaxis.

reaction with respiratory difficulty and/or hypotension * Reactions in severe asthmatics or with a J Accid Emerg Med: first published as 10.1136/emj.16.4.243 on 1 July 1999. Downloaded from especially if skin changes present severe asthmatic component. * Reactions with the possibility of continu- ing absorption of allergen. Oxygen treatment * Patients with a previous history ofbiphasic when available reactions. 4.9. An inhaled 12 agonist such as salbutamol is useful27 as an adjunctive measure if is a major feature that does not Stridor, wheeze, bronchospasm respiratory distress, or respond rapidly to other treatment. clinical signs of shock * 4.10. All sufferers from anaphylaxis should be advised of the benefits of wearing some device such as a bracelet that will inform bystanders at the time of any future attack. Epinephrine (adrenaline) 1:1000 solution:t Precautions should be taken, where practica- >11 years, 500 jg IM (0.5 ml) ble, to avoid exposure to the suspected 250 jig if child is small or prepubertal allergen. 6-11 years, 250 ,ug IM (0.25 ml) 4.1 1. Investigation and assessment at a 2-5 years, 125 jig IM (0.125 ml) <2 years, 62.5 gg IM (using twofold dilution) specialist allergy clinic is recommended for all i patients who have suffered a severe reaction. 5. Cautions Repeat in 5 minutes if no clinical 5.1. In patients who are taking tricyclic improvement antidepressants or monoamine oxidase inhibi- tors the dose of epinephrine (adrenaline) should be much reduced because of an interaction Antihistamine (chlorpheniramine): which is potentially dangerous. Some fluorohy- >1 1 years, 10-20 mg IM drocarbons used as refrigerants as well as 6-11 years, 5-10 mg IM cocaine sensitise" the heart to epinephrine 1-5 years, 2.5-5 mg IM (adrenaline) and are contraindications to its use. 5.2. The use of epinephrine (adrenaline) by the intravenous route in the special circum- IN ADDITION stances given in paragraph 4.4 should usually be reserved for medically qualified personnel who have experience of it, who know that it must be administered with extreme care, and For all severe or recurrent If clinical manifestations who are aware of the hazards associated with reactions and patients of shock do not respond its use. http://emj.bmj.com/ with asthma give to drug treatment 5.3. The subcutaneous route for epinephrine hydrocortisone: give 20 ml/kg body weight * (adrenaline), sometimes recommended for >11 years, 100-500 mg IM IV fluid. children on anecdotal evidence only, has no or slow IV Rapid infusion or one repeat 6-11 years, 100mg IM dose may be necessary role in anaphylaxis because its absorption is or slow IV J appreciably slower.29 Unnecessary delay in 1-5 years, 50 mg IM achieving adequate plasma concentrations is or slow IV inappropriate when dealing with this emer- on September 26, 2021 by guest. Protected copyright. gency. Figure 2 Anaphylactic reactions for children: treatment byfirst medical responder. *An 5.3. Warnings must be given, when appro- inhaled I2 agonist such as salbutamol may be used as an adjunctive measure if priate, in relation to the two strengths of epine- bronchospasm is severe and does not respond rapidly to other treatment. tIfprofound shock isjudged immediately life threatening give cardiopulmonary resuscitation/advanced life phrine (adrenaline) that are available for injec- support if necessary. Consider slow intravenous (IV) epinephrine (adrenaline) 1:10 000 tion. For anaphylaxis, epinephrine (adrenaline) solution. This is hazardous and is recommended onlyfor an experienced practitioner who is used in a dilution of 1:1000 intramuscularly can also obtain IV access without delay. Note the different strength ofepinephrine (adrenaline) that is requiredfor IV use. tA crystalloid may be safer than a colloid.26 whereas a dilution of 1:10 000 is used intrave- IM = intramuscular. nously principally for cardiac arrest (with the rare additional indications outlined in para- graphs 4.4 and 5.2). 4.7. If severe hypotension does not respond 5.4. All who treat anaphylaxis should be rapidly to drug treatment, fluid should be aware of the potential for confusion between infused. A crystalloid may be safer than a anaphylaxis and a panic attack. Victims of pre- colloid.26 A rapid infusion of 1-2 litres may be vious anaphylaxis may be particularly prone to needed. Children should receive 20 ml/kg rap- panic attacks if they think they have been idly, followed by another similar dose if there is re-exposed to the allergen that caused a previ- no clinical response. ous problem. The sense of anxiety and breath- 4.8. Patients with even moderately severe lessness leading to hyperventilation are symp- attacks should be warned of the possibility of toms that resemble anaphylaxis in some ways. an early recurrence of symptoms and in some While there is no hypotension, pallor, wheeze, circumstances should be kept under observa- or urticarial rash/swelling, there may some- tion for 8-24 hours. This caution is particularly times be an erythematous rash associated with applicable to: anxiety which adds to the diagnostic difficulty. Anaphylactic reactions 247

A mild anaphylactic reaction that triggers 12 Fisher M McD, Baldo BA. Anaphylactoid reactions during anaesthesia. Clinics in Anaesthesiology 1984;2:677-92. panic causes particular diagnostic difficulty. 13 Toogood JH. Risk of anaphylaxis in patients receiving beta- Problems can also arise with vasovagal attacks blocker drugs. _Allergy Clin Immunol 1988;81:1-5. J Accid Emerg Med: first published as 10.1136/emj.16.4.243 on 1 July 1999. Downloaded from 14 Hepner MJ, Ownby DR, Anderson JA, et al. Risk ofsystemic after immunisation procedures, but the ab- reactions in patients taking beta-blocker drugs receiving sence of rash, breathing difficulties, and allergen immunotherapy injections. J Allergy Clin Immunol swelling is a useful distinguishing feature as is 1990;86:407-1 1. 15 Bochner BS, Lichtenstein LM. Anaphylaxis. N Engl J Med the slow pulse of a vasovagal attack compared 1991;324: 1785-90. with the rapid pulse of a severe anaphylactic 16 Brown AFT. Anaphylactic shock: mechanisms and treatment. JAccid Emerg Med 1995;12:89-100. episode. 17 Ewan PW. Anaphylaxis. BMJ 1998; 316:1442-5. 18 Schwartz LB, Bradford TR, Rouse C, et al. Development of 1 Ewan PW. Treatment of anaphylactic reactions. Prescribers' a new, more sensitive immunoassay for human tryptase: use journal 1997;37: 125-32. in systemic anaphylaxis. J Clin Immunol 1994;14:190-204. 2 Statement from the Resuscitation Council (UK) and the Joint Royal Colleges Ambulance Service Liaison Com- 19 Stewart AG, Ewan PW. The incidence, aetiology and man- mittee. The use of adrenaline for anaphylactic shock (for agement of anaphylaxis presenting to an accident and ambulance paramedics). Ambulance UK 1997;12:16. emergency department. Q J Med 1996;89:859-64. 3 Association of Anaesthetists of Great Britain and Ireland 20 Weiss ME, Adkinson NF. Immediate hypersensitivity and British Society of Allergy and Clinical Immunology. reactions to penicillin and related antibiotics. Clin Allergy Suspected anaphylactic reactions associated with anaesthesia. 1988;18:515-40. Revised edition. London: 1995. 21 Hunt KJ, Valentine MD, Sobotka AK, et al. A controlled 4 Board of Faculty of Clinical Radiology, Royal College of trial of immunotherapy in insect hypersensitivity. N Engl Jt Radiologists. Advice on the management of reactions to intra- Med 1978;299:157-61. venous contrast media. London: Royal College of Radiolo- 22 Patel L, Radivan FS, David TJ. Management of anaphylac- gists, 1996. tic reactions to food. Arch Dis Child 1994;71:370-5. 5 Department of Health, Welsh Office, Scottish Office 23 Saff R, Nahhas A, Fink JN. Myocardial infarction induced Department of Health, DHSS (Northern Ireland). Immu- by coronary vasospasm after self-administration of epine- nisation against infectious disease. London: HMSO, 1996. phrine. Ann Allergy 1993;70:396-8. 6 Fisher M. Treatment of acute anaphylaxis. BMJ7 1995;311: 24 Wiggins CA, Dykewicz MS, Patterson R. Idiopathic 731-3. anaphylaxis: a review. Ann Allergy 1989;62: 1-5. 7 Fisher M McD. Clinical observations on the pathophysiol- 25 Brown AFT. Therapeutic controversies in the management ogy and treatment of anaphylactic cardiovascular collapse. Accid Med 1998;15:89-95. Anaesth Intensive Care 1986;14:17-21. of acute anaphylaxis._ Emerg 8 Jones E, Joy M. Acute myocardial infarction after a wasp 26 Schierhout G, Roberts I. Fluid resuscitation with colloid or sting. BrHeart3' 1988;59:506-8. crystalloid solutions in critically ill patients: a systematic 9 Barach EM, Nowak RM, Lee TG, et al. Epinephrine for review of randomised trials. BMJ 1998;316:961-4. treatment of anaphylactic shock. JAAMA 1984;251:2118- 27 Turpeinen M, Kuokkanen J, Backman A. Adrenaline and 22. nebulised salbutamol in acute asthma. Arch Dis Child 1984; 10 Douglas DM, Sukenick E, Andrade WP, et al. Biphasic sys- 59:666-8. temic anaphylaxis: an inpatient and outpatient study. Jf 28 Cregler LL. Cocaine: the newest risk factor for cardiovas- Allergy Clin Immunol 1994;93:977-85. cular disease. Clin Cardiol 1991;14:449-56. 11 Ewan PW. Clinical study of peanut and nut allergy in 62 29 Simons FE, Roberts JR, Gu X, et al. Epinephrine absorption consecutive patients; new features and associations. BMJ in children with a history of anaphylaxis. J Alergy Clin 1996;312: 1074-8. Immunol 1998;101:33-7. http://emj.bmj.com/ on September 26, 2021 by guest. Protected copyright.