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Re: Adrenaline syringes: community perspective

Dear Editor,

We read with interest the paper by Unsworth [1] regarding the over prescribing of adrenaline syringes. We are sure we are not the only community paediatric team who have similar concerns, although perhaps from a different perspective. Dr Unsworth writes of the safety issues. We have more experience of the practical problems.

Thanks to the availability of prompt training for school staff by community personnel, it is now rare for a child actually to be excluded from school because they have an adrenaline injection device, however, they may very well be excluded from other activities such as guide camp or trips abroad.

There is also the increasing problem of young people with adrenaline injection devices moving on to college or work places. Who should train staff there?

Other problems with adrenaline injection devices in our local community include two being lost on the bus, and one being accidentally fired into the interphalangeal joint of a child’s thumb with the needle becoming bent like a fish hook.

There is also the issue of keeping them in date. Parents often forget to renew them, particularly those kept in school. Whilst it does not need to be kept in a refrigerator, adrenaline does deteriorate in warm conditions, and injection devices should be checked to make sure the adrenaline inside remains clear and colourless.

Often an adrenaline injection device has been prescribed with no demonstration to the child or family on how to give it, nor when to give it. Surely antihistamine should also be prescribed in every case? In most children, it is the only medication, which is going to be needed. Families also need clear instructions on when to call an ambulance. They could easily make the mistake of trying to take a deteriorating child to hospital in their own car, instead of calling a paramedic ambulance, or even assume that they do not need to go to hospital at all if they have given adrenaline. As Dr Unsworth points out the adrenaline injection does not always save the child's life.

We would suggest that when an adrenaline injection device is prescribed it must be demonstrated to the parent and child, if old enough. A dummy pen is helpful for this. Demonstration should be repeated with each repeat prescription of the device. The child and family should always have a written management protocol, including instructions on expected symptoms, when to give antihistamine, when to call an ambulance and when to give adrenaline. Such a protocol can then be passed rapidly to the community paediatric team to support the prompt training of school staff.

It is worth remembering that clinical responsibility for the safe administration of a drug rests with the prescriber.

Dr Toni Wolff
Consultant Community Paediatrician

Mrs Chris Rumney
School Health Liaison Nurse
Birmingham Specialist Community Trust

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Re: Controversies in paediatrics?

I was very disappointed to see that the first contribution to the series 'Controversy' was not written by a paediatrician. There are plenty of controversial topics in paediatrics, including the one cited. There are also plenty of paediatricians perfectly qualified to take part in informed debate about them, again including the topic cited. The absence of a contrasting viewpoint in the same issue suggested to me the feature should be called 'Opinion' rather than 'Controversy' because the article is not a balanced review of the current state of allergy practice.

The BPA and latterly RCPCH have championed for decades the holistic approach to the care of children. Paediatricians are best placed to assess the integrated needs of a child with medical problems. This principle is very relevant to developing areas of specialisation in which there is an under supply of expert advice, such as in allergy. Paediatric allergists assess the impact of the diagnosis on many non-medical facets of a child's life, including family lifestyle, integration into schools and peer groups and the facilitation of appropriate independence from parental supervision.

It is tiring to have to rehearse the arguments for the adequate protection of subjects at risk of anaphylaxis. Epinephrine (as all doctors should now be calling adrenaline) is not the only help given in clinic to families with an allergic child. It is part of the integrated management plan, which appears to be effective [1] though difficult to measure [2].

It is very hard to prove that epinephrine saves lives and I agree that the notional 'number needed to treat' with epinephrine to prevent a death from anaphylaxis is very high. Unsworth's title suggests that this 'very high number' (my phrase) is too high. How has he measured that? What is too many? He quotes a prevalence of about 1% of Americans having peanut allergy. That is approximately 3 million subjects. We do not restrict insulin syringes to just a few insulin dependent diabetics because diabetes is so common that we cannot adequately care for all of them. Every allergic child has the right to best available care, which is not restricted to the first 100 through the clinic door (if they can find an allergy clinic).

Laparotomy will not save every patient with a leaking aortic aneurysm and epinephrine will not save every person who has anaphylaxis. Anaphylaxis is a critical situation in which prompt administration of epinephrine may (but occasionally may not) save a life. I think it unarguable that it is better to self- treat and probably survive than not self-treat and possibly die. Unsworth quotes one early paper about anaphylaxis from the US [3] and more recent British data [4,5]. These papers all say to me more that epinephrine is underused due to unavailability or inappropriate training and patient confusion than that epinephrine is useless or dangerous. Most subjects did not have epinephrine available. Several of the deaths reported by Pumphrey [5] were due to incorrect use of available epinephrine. In addition epinephrine appears to be more dangerous in the hands of doctors who give it IV than in the hands of allergic subjects who self- treat IM. I recommend your readers look at the report on the latest series of food related deaths [6].

In the absence of any perfect predictive test allergists are confined to basing risk of future severe reactions on just a few variables. The first is a history of previous severe reactions [3]. The majority of peanut allergics have had a severe reaction in the past [7,8] and more than 60% have asthma, the second known association with severe reactions [3,7]. According to current opinion, then, even after just one reaction to peanut most subjects are considered at risk of severe future reactions. Many minor reactors to peanut progress to more severe reactions [7] and new data confirm this convincingly [9]. I do not think there are adequate data to change my practice from needing a very good reason not to prescribe epinephrine to most (but not all) subjects who have reacted to peanut, a food known to be associated with a risk of a severe allergic reaction.

Doctors must remember epinephrine is prescribed to be available for response to infrequent exposure at an uncertain future date, not to be taken four times a day. I have referred to this in the past [10] as analogous to wearing a seatbelt on every car trip, every day, even though a serious car accident is unlikely on any individual day.

Unsworth is not up to date in his comments about the diagnosis of IgE mediated allergy. There are strong data from huge series of challenges, about the positive and negative predictive values of the tests used in allergy clinics [11,12,13]. Unsworth does not even mention formal challenges, the cornerstone of modern food allergy practice. No allergist would prescribe an epinephrine kit on the basis of a positive SPT in the absence of a significant history or formal challenge [14].

Children and adults at risk of food-related anaphylaxis have enough of life's pleasures denied to them. The provision of epinephrine kits allows normal life to go on, involving school, overnight stays at friends, camping and other normal activities of childhood. Anecdotally, parents seem to me less stressed when they leave clinic with information (however awful the scenarios described) and response strategies than when they arrive. I have never met a parent who reported being more scared of the epinephrine kits than of the prospect of allergen exposure (with or without epinephrine available).

Families must be taught when to use epinephrine and how to use autoinjectors. Until doctors can tell families that anaphylaxis will never happen we should continue to empower families, ensuring they are ready to respond as best they can to the disaster that allergen exposure represents. When anyone develops a real treatment for food-related anaphylaxis I can stop prescribing epinephrine kits to people who currently need them.

References

(1) Ewan, P. W. and Clark, A. T. Long term prospective observational study of patients with peanut and nut allergy after participation in a management plan. Lancet 357, 111-115. 2001.

(2) Hill, D. J., Heine, R. G., and Hosking, C. S. Management of peanut and tree nut allergies. Lancet 357, 87-88. 2001.

(3) Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents . N.Engl.J.Med. 1992;327:380-4.

(4) Pumphrey RS,.Stanworth SJ. The clinical spectrum of anaphylaxis in north-west England. Clin.Exp.Allergy 1996;26:1364-70.

(5) Pumphrey RS. Lessons for management of anaphylaxis from a study of fatal reactions. Clin.Exp.Allergy 2000;30:1144-50.

(6) Bock, S. A., Muqoz-Furlong, A., and Sampson, H. A. Fatalities due to anaphylactic reactions to foods. J.Allergy Clin.Immunol. 107, 191-193. 2001.

(7) Hourihane JO, Kilburn SA, Dean P, Warner JO. Clinical characteristics of peanut allergy. Clin.Exp.Allergy 1997;27:634-9.

(8) Sicherer SH, Burks AW, Sampson HA. Clinical features of acute allergic reactions to peanut and tree nuts in children. Pediatrics 1998;102:e6.

(9) Vander Leek, T. K., Liu, A. H., Stefanski, K., Blacker, B, and Bock, S. A. The natural history of peanut allergy in young children and its association with serum peanut-specific IgE. J.Pediatr 2000;137:749-755.

(10) Hourihane JO'B Peanut Allergy. CPD Bulletin, Immunology and Allergy 1999;1(2):54-57.

(11) Sampson HA,.Ho DG. Relationship between food- specific IgE concentrations and the risk of positive food challenges in children and adolescents. J.Allergy Clin.Immunol. 1997;100:444-51.

(12) Eigenmann PA,.Sampson HA. Interpreting skin prick tests in the evaluation of food allergy in children. Pediatr Allergy Immunol. 1998;9:186-91.

(13) Sporik R., Hill, D. J., and Hosking, C. S. Specificity of allergen skin testing in predicting positive open food challenges to milk, egg and peanut in children. Clin.Exp.Allergy 30 (11), 1495-1498. 2000.

(14) Sicherer SH. Food allergy: when and how to perform oral food challenges. Pediatr Allergy Immunol. 1999;10:226-34.

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Re: Appropriate prescription of epinephrine remains the best available treatment.

Epinephrine kits enable a food allergic child at risk of anaphylaxis to lead a normal life and participate in childhood activities that could easily be denied by a parent terrified of another allergen exposure.

Avoidance of allergens rather than rescue epinephrine therapy is the basis of current management of food allergy. However, unexpected exposures are inevitable. 58% of children followed for five years experienced adverse reactions from accidental peanut exposure [1]. Peanut is the most common food allergen causing anaphylaxis and pervades, still often uncited, in food processing. Anaphylaxis related to foods most commonly occurs in patients who have had previous severe reactions. However, minor initial reaction does not exclude a subsequent severe reaction to peanut [2].

Any person at risk of anaphylaxis deserves the best available protection. It is reasonable to always have two Epipens available both at home and at school. A second Epipen provides back up if a faulty technique is used or one syringe is damaged. Anaphylaxis may be biphasic, recurring in 3% of children admitted with anaphylaxis [3].

As advocates of children, paediatricians are unlikely to hand out epinephrine syringes without due consideration of the impact on the child and their family. A comprehensive plan with written information is essential for any child seen with a food allergy whether or not epinephrine is prescribed. Scott et al showed 20% of children did not carry epinephrine outside the home and only 55% had unexpired epinephrine on them. However, successful demonstration was associated with repeat prescriptions, membership of a lay organisation for food allergy and being reviewed by an allergist [4]. Training packages for schools such as that devised by Vickers in Cambridge [5] are valuable.

Unsworth states that "Community use should be much more restricted with increased involvement and reliance on trained medical staff". Food allergy is the most common cause of anaphylaxis in children outside hospital. Early recognition and use of epinephrine is vital for successful outcome. The median time to respiratory or cardiac arrest was thirty minutes for food induced anaphylaxis in one series [6]. Surely this implies that the community is the setting where epinephrine should be given by appropriately trained parents and carers to a food allergic child with signs of anaphylaxis. Parents should be empowered as limited resources prevent medical staff being present immediately. Indeed, epinephrine iv by trained medical staff also appears to be more hazardous than the use of epinephrine im by allergic patients [7].

In the absence of any other treatments for food related anaphylaxis, the considered use of epinephrine kits as part of an integrated management plan is the best choice.

References

(1) Vander Leek, T.K., Liu, A.H., Stefanski, K., Blacker, B.,, and Bock, S.A. The natural history of peanut allergy in young children and its association with serum peanut-specific IgE. J. Pediatr 2000;137:749–755.

(2) Hourihane JO, Kilburn SA, Dean P, Warner JO. Clinical characteristics of peanut allergy. Clin. Exp. Allergy 1997; 27:634–9.

(3) Lee JM and Greenes DS. Biphasic anaphylactic reactions in pediatrics Pediatrics 2000 vol.106, No 4, 762–6

(4) Sicherer SH, Forman JA and Noone SA. Use assessment of self administered epinephrine among food allergic children and paediatricians Pediatrics 2000 vol.105, No 2, 359-362

(5) Vickers DW, Maynard L and Ewan PW. Management of children with potential anaphylactic reactions in the community: a training package and proposal for good practice. Clin. Exp. Allergy 1997; 27: 898–903.

(6) Pumphrey RS. Lessons for management of anaphylaxis from a study of fatal reactions. Clin. Exp. Allergy 2000; 30:1144–50.

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Re: The author responds

I was pleased to see that my article [1] provoked lively discussion [2,3,4] of this important issue. I am not surprised that others are also concerned about poor compliance. I agree with Wolffand Rumney [2] that adrenaline should never be the sole prescription. In addition to anti-histamines, prednisolone has a place. The idea of a written management plan also seems sensible.

Hourihane [3] contrasted prescription of adrenaline with provision of insulin syringes in diabetes mellitus. We do not restrict provision of insulin syringes in that context because to do so would inevitably promote hyperglycaemia and ill health in all cases, ranging from coma to retinopathy. The risk benefit ratio is clearly in favour of daily insulin use. By contrast, the "very high" number of adrenaline prescriptions required to (perhaps) prevent death in food allergic individuals, does by contrast raise concerns about the risk benefit ratio. In our clinics, where we see large numbers ofboth adults and children, reviewing the last few years, we have seen one fatal and two near fatal episodes related to adrenaline usage (submitted for publication). Admittedly, all three were in adults. Hourihane prescribes "epinephrine" to "most (but not all) subjects who have reacted to peanut" .He does not explain why some patients do not get the prescription. Those with a previous history of only mild reactions can go on to suffer severe/life threatening reactions [5], so all informed families will surely demand adrenaline. He would not prescribe adrenaline in the absence of a significant clinical history of true nut allergy, (and I applaud that) but others regrettably do, and I know from personal experience that once the mistake is made, it is hard to reverse. I like the seat belt analogy, but seat belts have few side effects. Regarding positive and negative predictive values oflgE based allergy blood tests, my point is that often these tests are misleading. Patients with eczema, (a common fmding in those presenting with possible nut or food allergy) typically have high background 19E levels and false positives are common.

Dr Abay reminds us that trained medical staff including doctors may administer adrenaline incorrectly. That fact does not justify delegation of responsibility instead to the lay public. They are surely more likely to make errors, despite training and or management plans. Expecting the lay public to confidently decide whether to use the adrenaline or not, is expecting a lot. Fatal episodes do indeed tend to occur within minutes of allergen exposure and can evolve to anaphylaxis rapidly, even in cases where previous reactions have been benign. Families may well misjudge and or err on the side of caution, giving adrenaline early for what was likely to turn out to be another benign reaction. Hence my keenness for restriction of community use and increased reliance on trained medical staff.

Let us remember that whilst many thousands of children and adults experience unpleasant but essentially benign reactions each year, very very few prove fatal [1]. In the community context, focusing on the higher risk groups including asthmatics would be my preference.

Dr D J Unsworth
Consultant Immunologist

References

(1) Unsworth Dl .Adrenaline syringes are vastly over prescribed. Arch Dis Child 2001;84:410-411
(2) WolffT & Rumney C Adrenaline syringes: community perspective. Arch Dis Child 2001;84:410-411 EL1
(3) Hourihane J .Controversies in paediatrics ? Arch Dis Child 2001;84:410-411 EL2
(4) Abay J. Appropriate prescription of epinephrine remains the best available treatment. Arch Dis Child 200;84:410-411 EL3
(5) Vander Lek T .K. Liu A.H. Stefanski K. Blacker. Bock S.A. the natural history of peanut allergy in young children and its association with serum specific IgE. J.Paediatr 2000;137: 749-755.

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Re: Prescribing epinephrine alone is not the complete answer to managing food allergy

Dear Editor

Unsworth believes epinephrine autoinjectors are vastly overprescribed [1] and addresses an important issue. Most of the reasons he gives and the papers he quotes consider provision of epinephrine autoinjector in isolation and fail to recognise that children with food allergy need a complete management package. For example, he uses evidence that patients fail to carry syringes, have out of date syringes or are unable to use them, as reasons for not prescribing epinephrine. However, these argue for improved training. This highlights the problem that most doctors dealing with children with food allergy, whether in primary or secondary care, lack appropriate expertise.

Unsworth argues for better asthma control rather than epinephrine prescription. Whilst we would support excellent asthma control, this should not be seen as a substitute for epinephrine.

There is much discussion on the risks of epinephrine, but careful review of the literature shows that these are mainly related to administration by the IV route or to overdose. Intramuscular epinephrine is very safe.[2] He exaggerates the risks e.g. in hypertension but fails to make a proper risk assessment. If a patient with hypertension developed anaphylaxis, one should not hesitate to use epinephrine. This comes back to the need for a complete strategy which includes clearly defining situations for self-use and provision of a written treatment plan.[3]

The most difficult issue is who requires epinephrine. We would not claim to know the answer as this will require longitudinal data on natural history, but we have devised and evaluated a management plan. We assess and grade the severity of the allergy (on a clinical basis) and provide emergency medication for self / parent-administration, tailored to the individual. Epinephrine autoinjectors are prescribed to patients who have had any airway involvement, even if this is minor e.g. slight laryngeal oedema. In general patients with cutaneous only reactions do not receive epinephrine autoinjector, but this will depend on the dose of allergen causing the reaction and on whether they have coincident asthma. The management plan also included detailed advice on avoidance, training (and annual re-training) in the use of all medications, training of school staff, and provision of a written treatment plan. In addition, other allergies, including asthma were treated.

We have evaluated this strategy in 567 nut allergic patients (70% of whom were children) over 13600 patient months.[3] Approximately 80% had epinephrine autoinjector available (some had been prescribed Epipen before referral, outside our criteria). The incidence of subsequent reactions fell from an expected 50% to 15%, but furthermore these were of greatly reduced severity. Most required no treatment or oral antihistamines (part of our emergency medication) but IM epinephrine was required by a small number of patients and was always effective. In only 1/567 patients Epipen was required but had not been prescribed (an adult).

Accurate diagnosis is essential as well as an assessment of the severity of the allergy. This means that diagnosis must be made from the clinical history supported by tests and not from the results of RAST (serum specific IgE) tests alone.[4]

Epinephrine autoinjectors may or may not be overprescribed but Unsworth’s arguments do not address the real issues and one cannot answer the question from his paper. The issues discussed reveal the confusion amongst non-allergists, for example, by focusing on epinephrine alone. The treatment of a child with food allergy requires a holistic approach and this underlines the need for paediatric allergists

References

(1) Unsworth DJ. Adrenaline syringes are vastly overprescribed. Arch Dis Child 2001;84:410-1.

(2) Project Team of the Resuscitation Council (UK). Emergency medical treatment of anaphylactic reactions. J Accid Emerg Med 1999;16(4):243-7.

(3) Ewan P, Clark A. Long-term prospective observational study of the outcome of a management plan in patients with peanut and nut allergy referred to a regional allergy centre. Lancet 2001; 357: 111-5.

(4) Clark AT, Ewan PW. Evaluation of tests for nut allergy in allergic and tolerant patients shows clinical data is essential for interpretation. J Allergy Clin Immunol 2001;107:s192.