Allergy Care Pathways Project
Anaphylaxis Pathway – final draft v16

Table of Contents

National Care Pathway 1

Anaphylaxis 1

Methodology 3

Recommendations 7

Research Priorities 8

Care Pathway for Children with Anaphylaxis 9

Conflict of interest 15

References 16

Appendix 1: Glossary 20

Appendix 2: Evidence Table: systematic reviews and primary research 21

Appendix 3: Evidence Table: Guidelines 27

National Care Pathway

Allergic conditions constitute the commonest cause of chronic disease in childhood and affect upwards of 20% of the population. They seriously impair quality of life and health of children and occasionally can lead to death. Children and young people who experience allergic conditions often received different levels of care which can affect health outcomes and interfere with schooling. The 2006 Department of Health review of allergy services recommended that there was a specific need to define care pathways for children with allergic conditions.

The terminology and format for care pathways is wide and varied. Critical pathways, care paths, clinical pathways are all patient focussed tools that provide the sequence and timing of actions to achieve patient outcomes with the greatest efficiency [20]. Integrated care pathways are important because they help to reduce unnecessary variations in patient care and outcomes [21].

The RCPCH has been commissioned by the Department of Health to develop 6 national care pathways for children with allergies. It is the intention of the Project Board to develop ideal evidence based national care pathways that are adopted for local use. These pathways will focus on standardising the level of care received by children with allergic conditions and defining the competences required to provide a high quality service.

The Allergy Care Pathways Project Board recommends that all locally adopted care pathways should be implemented by a multidisciplinary care team with a focus on improving services for children with allergic conditions. One important factor in implementing the care pathway is the use of audit tools to analyse unnecessary variations in care.

Anaphylaxis

Anaphylaxis is a severe, life-threatening, generalised or systemic hypersensitivity reaction which is characterised by rapidly developing life-threatening respiratory and/or circulation problems; it is usually associated with skin and mucosal changes [22;23].

Understanding the epidemiology and disease burden posed by anaphylaxis is important in order to develop insights into risk factors for its aetiology, and inform service provision and resource allocation decisions. Accurately characterising the epidemiology of anaphylaxis is however complicated by inconsistencies in disease definition [23] and the challenges in undertaking prospective cohort studies for a disorder that is relatively infrequent, and in which disease episodes are typically short-lived and are in the majority of cases self-limiting [24]. There is as a consequence concern about under-reporting, under-recognition and under-diagnosis of anaphylaxis, this further complicating any reliable assessment of its frequency or impact. This is important because despite the overall good prognosis, fatalities do occur, most commonly in young people; these fatalities are believed to be largely avoidable with appropriate emergency and preventative management [24-29].

A variety of data sources have been used in an attempt to estimate the incidence, lifetime prevalence, morbidity and case fatality ratio associated with anaphylaxis. These have included population surveys, case records from primary and secondary care, hospital episode statistics, adrenaline prescribing data and mortality statistics. Whilst all these available sources have some utility, population-based studies are likely to yield the most accurate data on the epidemiology and disease burden posed by anaphylaxis.

From the population-based data currently available, the incidence rate, where this is defined as the number of episodes of anaphylaxis that occur in a defined population over a given period of time, is estimated at between 80-210 episodes per million person-years [24]. Incidence varies by age, gender, geography and socio-economic position; the usual socioeconomic gradient between adverse health outcomes and deprivation seems to be reversed [30]. The limited data available on time trends suggests that the incidence of anaphylaxis has increased over recent decades and this appears in particular to be due to increases in allergies to foods in children and young people and adverse drug reactions in older people; greater awareness, recognition, reporting and recording are other possible explanations [30-36].

Anaphylaxis may be triggered by a wide range of factors, but may also occur spontaneously (idiopathic anaphylaxis). The most common trigger in childhood is food, followed by drug allergy. Anaphylaxis due to other triggers such as insect venom or exercise is rare [33;37]. The most frequent food triggers in childhood are peanut and nuts, cows milk, hen egg, fish and shellfish [38;39].

Lifetime prevalence can be defined as the proportion of a defined population known to have experienced anaphylaxis during their lifetime. A review by a Working Group of the American College of Allergy, Asthma and Immunology summarised the findings from a number of seminal studies and concluded that anaphylaxis affects anywhere between 0.05-2.0% of the general population at some point in their lives, these large variations possibly reflect regional differences in the diagnostic criteria that tend to be used [40]. More recent work from the UK however suggests that the prevalence in the UK may be lower than this estimate; interrogation of a large database of GP records suggests that there are an estimated 40,000 people with a clinician-recorded diagnosis of anaphylaxis diagnosis in the UK [35].

The majority of episodes of anaphylaxis are self-managed by patients/carers – often sub-optimally using antihistamines and/or bronchodilators, but not adrenaline – and many people experiencing episodes of anaphylaxis will therefore not receive medical attention [41]. A proportion of episodes will result in the seeking of medical attention, of whom some (estimated at 28-100 hospital admissions per million people per year) will be admitted to hospital [24;42].

As a potentially fatal condition, anaphylaxis can have a profound impact on quality of life, this impact extending way beyond the acute phase of the illness. Although still often thought of mainly as an acute disorder, anaphylaxis should really be considered as a long-term condition [26]. The impact on the quality of life of carers should not be under-estimated.

There are at present no reliable ways of assessing of who will and will not experience severe episodes, but in general terms factors such as the speed of onset of the reaction, the dose of allergen required to trigger a reaction and severe previous reactions are markers of potentially severe future reactions [27]. Those with underlying asthma – especially if poorly controlled – and cardiovascular disease are particularly at risk of fatal outcomes [24-27;43]. Delay in receiving medical attention and in particular adrenaline treatment is another key factor that has repeatedly been implicated in fatal episodes [44;45]. The overall case fatality ratio, where this is defined as the proportion of cases of anaphylaxis that prove fatal of anaphylaxis, is estimated at less than 1% in the majority of case series, or in population terms as between 1-5.5 fatal episodes of anaphylaxis per million population per year [24]. Mortality statistics obtained for the Department of Health review showed that from 1993 to 2002 there were approximately 10 deaths per year in England and Wales in which anaphylaxis was a contributing cause [46]. Reported anaphylaxis fatality rates will inevitably underestimate the true incidence due to difficulties in diagnosis post-mortem. A case review of death certificates for adults and children in the UK recorded up to 20 probable anaphylactic deaths in the UK annually [47].

Methodology

Objectives

The aim of the project was to develop an evidence-based national care pathway for children with anaphylaxis. The underpinning principle was that the eventual pathway would:

§  describe the ideal pathway of care for children from the first presentation with suspected anaphylaxis in any healthcare setting to the desired patient endpoint

§  be informed by the best available research evidence and, in areas where research evidence is lacking, by the consensus of a multidisciplinary team of experts

§  define the steps in pathway on the basis of the competencies of health care professionals rather than the setting in which the care should be provided

§  provide a national template to facilitate local review of services for children with anaphylaxis to ensure consistent high quality care.

Stages of Pathway Development

The pathway was developed by a multi-disciplinary Anaphylaxis Working Group (AWG) chaired by Dr Andrew Clark and which reported to a Project Board chaired by Professor John Warner.

The AWG included health professionals with expertise in paediatric allergy, allergy nursing, pharmacy, primary care, secondary care, immunology, dietetics and emergency care and a parent/carer representative (Table 3). The AWG was supported by a full-time project manager.

There were two face-to-face meetings of the AWG, in September and October 2009 and one telephone conference in November 2009.

1.  Initial mapping

At its initial meeting the AWG mapped out the ideal care pathway for the five key stages: self care, ambulance care, emergency department (ED) care, inpatient/further care and outpatient management, including follow up.

2.  Evidence Review

A comprehensive evidence review was undertaken to identify the evidence base for a care pathway for children with anaphylaxis. A PICOS (Patient/Population, Intervention, Comparators, Outcomes and Studies) approach was used when formulating the search strategy.

Scoping search

An initial scoping search conducted between 3 August and 25 August 2009 focussed on clinical questions did not provide a comprehensive list of evidence. The full list of clinical questions used in the clinical questions used in the scoping search can be obtained from the RCPCH Science & Research Department. This strategy was not pursued and a general systematic search for the overall care of children with allergies was undertaken.

Literature search strategy

A systematic search was conducted between 26 and 27 August 2009; this covered searches in the Cochrane Library, Medline, the National Guidelines Clearing House, the Scottish Intercollegiate Network (SIGN) and the National Institute for Clinical Excellence (NICE). An updated final search will be conducted upon completion of all of the pathways in July 2010.

Search terms were compiled by pearling expert identified papers for keywords. The terms identified and used included: hypersensitivity, adolescen$, child$, infant and anaphylaxis. A copy of the full search strategy can be obtained from the RCPCH Science & Research Department. The search was not restricted by language. In order to collate the most contemporary evidence base the search was restricted to the period 1 January 1990 – 26 August 2009. The results of the search were compiled in a Reference Manager library to allow for easy identification of duplicates. There was no systematic attempt to identify grey literature. Additional papers for inclusion were identified by snowballing the references of the appraised papers. Handsearching was conducted by working group members.

Inclusion/exclusion criteria

Participants: Children and young people aged 0-18 with anaphylaxis and/or an allergic condition related to anaphylaxis. Mixed studies were included where it was possible to extract data on children and young people. Where there was no evidence directly relating to children adult studies were included on the recommendation of expert opinion, otherwise adult studies were excluded.

Interventions: Studies that included preventative and therapeutic interventions in any setting by any health professional, including self care.

Comparators: Any comparator, including no comparator.

Outcome measures: The outcomes examined in the review of evidence included symptoms (mild/moderate/severe), quality of life and mortality.

Studies: Systematic reviews of key interventions and clinical guidelines/guidance based on reviews of evidence were included. Primary research was considered, including RCTs, non-controlled trials, case-control studies and cohort studies. Case reviews with more than 3 reports were also considered where there was no other evidence.

Evidence Appraisal Methods

The evidence was appraised in 3 stages: an initial title review, an abstract and title review and finally an appraisal.

Stage 1

The project manager initially reviewed 831 titles; this resulted in 199 systematic reviews, primary papers and guidelines.

Abstracts and titles were then reviewed by the AWG Chair; this resulted in 37 systematic reviews and/or primary papers and 6 guidelines for appraisal by the AWG members.

Stage 2

Stage 1 was conducted by the AWG Chair who reviewed the 199 titles and abstracts of the clinical guidelines and papers using 3 measures: meets study criteria (e.g. anaphylaxis), concerned with/applicable to children and young people and guideline, systematic review or primary research with original data.

This process resulted in 37 systematic reviews and/or primary papers and 6 guidelines for appraisal by the AWG members

Stage 3 – systematic reviews and primary research

Thirty seven systematic reviews and primary research passing stage 1 and 2 were critically appraised by two reviewers from the AWG using modified Critical Appraisal Skills Program (CASP) tools [48]. The CASP tools can be obtained from the RCPCH Science & Research Department. Data extraction was performed concurrently with the critical appraisal. Conflicts were resolved using de-identified appraisals and the consensus of the AWG members. All included papers were synthesised into an evidence table and assigned an evidence level by the AWG according to the SIGN methodology (Table 1) [49].

This process resulted in the inclusion of 12 papers and an additional 17 papers for review through snowballing the reference lists. After the completion of the stage 3 appraisal of the systematic reviews and primary research 19 papers were marked for inclusion.

Stage 3 – guidelines

All documents setting clinical standards and passing stage 1 and 2 were reviewed by the RCPCH Clinical Standards Team to ensure College standards for endorsement were met as part of the RCPCH appraisal and endorsement process. One component of this was to appraise the guideline using a modified version of the AGREE tool [50]. Any methodological weaknesses were highlighted in the evidence tables and all included guidelines were assigned an appropriate grade accordingly. Due to time and resource constraints within the project design recommendations from the clinical guidelines have been accepted verbatim. Methodological weaknesses of each clinical guideline were highlighted in the evidence table (Table 5).

This process resulted in the inclusion of 4 clinical guidelines. All but one clinical guideline appraised used the SIGN methodology (Table 2) to grade their recommendations. The Resuscitation Council UK Guideline [51] used the RCP Concise Guidance to Good Practice [52]; this is highlighted in the evidence table.