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Keywords:

  • allergy;
  • anaphylaxis;
  • disease management;
  • systematic review

Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. Sources of funding
  8. References
  9. Supporting Information

To cite this article: Kastner M, Harada L, Waserman S. Gaps in anaphylaxis management at the level of physicians, patients, and the community: a systematic review of the literature. Allergy 2010; 65: 435–444.

Abstract

Diagnosis and management of anaphylaxis can be a challenge because reactions are often unexpected and progress quickly. The focus of anaphylaxis management has mostly been on the acute episode, with little attention given to the long-term management of patients at risk. This is compounded by conflicting information in current guidelines and a general lack of agreement among clinicians about which management strategies are the most appropriate. We systematically reviewed the literature to identify and summarize studies that investigated gaps in anaphylaxis management. Our search included MEDLINE, EMBASE, CINAHL, and Evidence-Based Medicine Reviews. Studies were included if they addressed an outcome describing gaps in anaphylaxis knowledge, education, anaphylaxis management, and quality of life (QOL). Populations of interest were health care professionals involved in the care of patients at risk for anaphylaxis, and patients of any age, their parents, caregivers, and teachers in primary care, hospital or community settings. Of 5014 citations that were identified, the final 59 studies (selected from 75 full-text articles) met the inclusion criteria. Two hundred and two gaps were identified and classified according to major themes: gaps in knowledge and anaphylaxis management (physicians and patients); gaps in follow-up care (physicians); and QOL of patients and caregivers. Findings from this systematic review revealed gaps in anaphylaxis management at the level of physicians, patients, and the community. Findings will be used to provide a basis for developing interventional strategies to help address these deficiencies.

Management of anaphylaxis can be a challenge for several reasons. Allergic reactions can be severe, are often unexpected, and can progress quickly (1). Although definitions of anaphylaxis exist: ‘a serious allergic reaction that is rapid in onset and may cause death’ (United States) (2), and ‘a severe, life-threatening, generalized or systemic hypersensitivity reaction’ (Europe) (3), they may not be universally accepted or have poor uptake by practitioners because anaphylaxis symptoms are nonspecific and its presentation can be variable (3). Additionally, the lack of a clear definition of anaphylaxis can also hamper studies investigating the epidemiology and pathophysiology of this disorder (2). Another challenge is that there is no single diagnostic test that can be used routinely to identify anaphylaxis in clinical practice (4, 5). The focus of management has mostly been on the acute episode, with little attention given by physicians to the long-term management of patients at risk for anaphylaxis (4, 5). However, evidence shows that both immediate and long-term anaphylaxis management are inadequate in all settings (1, 6). Factors contributing to this care gap are poor training of primary care physicians (7), lack of access to epinephrine auto-injectors and specialist advice (7, 8), problems in school-based management (9), and a lack of anaphylaxis preventative strategies for patients and caregivers (10). This is compounded by conflicting information in guidelines about management, which are often anecdotal and nonevidence-based (1). There is also a general lack of agreement among clinicians on the appropriate dose and route of epinephrine administration, and which anaphylaxis management strategies are the most appropriate (11).

The first step toward closing these gaps is to investigate the current state of anaphylaxis management across different populations and settings. The objective of this study was to systematically review the literature to identify and summarize relevant studies that examined gaps in anaphylaxis management.

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. Sources of funding
  8. References
  9. Supporting Information

Search strategy

Studies were identified by searching MEDLINE (1966–August 2008), EMBASE (1980–2008), CINAHL (1982–August 2008), and Ovid Evidence-Based Medicine Reviews (Cochrane Database of Systematic Reviews and Clinical Trials Register, ACP Journal Club, Database of Abstracts of Reviews of Effects). We also searched the gray literature: websites of Anaphylaxis Canada, the Canadian Society of Allergy and Clinical Immunology (CSACI), American Academy of Allergy, Asthma, and Immunology (AAAAI), the Food Allergy and Anaphylaxis Network (FAAN), and digital dissertations. We hand searched relevant journals (e.g., Allergy, Journal of Allergy and Clinical Immunology, Annals of Allergy Asthma and Immunology), reviewed the reference lists of relevant articles, and contacted experts in the field. Search terms were generated using known terms and synonyms suggested by librarians and allergy specialists to capture all text words and Medical Subject Heading (MeSH) terms that describe gaps in anaphylaxis management. MeSH terms and text words were then combined with the Boolean ‘OR’ and then ‘AND-ed’ with ‘anaphylaxis’ in each database using Ovid interface.

Study selection

Studies were included if they were prospective or retrospective quantitative studies (including epidemiologic and intervention studies) or qualitative studies as long as they investigated gaps in anaphylaxis management, and could be addressed in the context of quality of life (QOL) of patients at risk for anaphylaxis or their caregivers. We excluded basic science or animal studies, case reports, and narrative reviews. Gaps in anaphylaxis management were defined according to different settings, populations, and outcomes. Outcomes of interest were gaps in knowledge and education, anaphylaxis management behaviors (e.g., prescribing by physicians, allergy avoidance by patients), QOL, and morbidity and mortality. Studies investigating these outcomes in different settings (primary care, hospital, and community) were categorized according to two broad populations: (1) physicians and other health care professionals involved in the care of patients at risk for anaphylaxis and (2) patients of any age, and their parents, caregivers, and teachers. From the physician/health care professional perspective, we defined knowledge or education gaps as an insufficient or conflicting understanding related to any aspect of anaphylaxis diagnosis, treatment, or management (e.g., symptoms, treatment options, dose, or route of epinephrine administration). Gaps in anaphylaxis management were defined as incorrect practice behaviors resulting from these knowledge gaps (e.g., diagnosis, prescribing, acute treatment administration, and management). For patients, we defined gaps in knowledge or education as a lack of understanding or insufficient knowledge about self-management (e.g., recognition and awareness of signs and symptoms, consequences of allergic reactions), and anaphylaxis behaviors as incorrect or insufficient actions on allergen avoidance, compliance with therapy, or preparedness for potential reactions.

Three authors were initially calibrated for applying the inclusion/exclusion criteria on a random sample of ten abstracts. Once agreement was at least 80% between the three authors, the titles and abstracts of potentially relevant citations were independently reviewed in duplicate by dividing the yield among the three reviewers. The final list of included studies was selected independently by two authors (MK, SW), who screened full-text articles by applying the inclusion/exclusion criteria. Agreement between reviewers for full-text review was over 90% beyond chance (k = 0.92, confidence interval 0.86–0.97). Any disagreements were resolved through consensus.

Study quality assessment

It was decided not to use a study quality assessment scale because there is evidence that they lack empirically supported components (12), and authors of scales can be influenced by their own perception of study quality (13). Studies were assessed according to each type of study design that was considered for inclusion in the systematic review. Study quality for randomized controlled trials (RCTs) was assessed according to specific methodological criteria that are the most relevant to the control of bias (randomization, allocation concealment, blinding, and follow-up) (14). Epidemiological studies (cohort, case–control, and cross-sectional) were assessed using critical appraisal factors according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement (15), because there is no current reliable tool available to assess the quality of observational studies (16). Qualitative studies were assessed using a guide developed by the Evidenced-Based Medicine Working Group consisting of appropriateness of study design, sampling, data collection methods, and analysis (17).

Data extraction and synthesis

Using a standardized form, two authors extracted data on the setting, study design and elements of study quality or critical appraisal factors, population characteristics, interventions (if applicable), outcomes, results, analysis, and follow-up. We anticipated that a meta-analysis would not be possible because studies were too heterogeneous to pool. However, potential sources of heterogeneity were explored according to differences in study design, participants, interventions (if applicable), settings, and outcomes. Findings were qualitatively assessed using grounded theory methodology to identify themes from the content analysis of data (18).

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. Sources of funding
  8. References
  9. Supporting Information

Of 5014 potentially relevant articles identified by our search, 4605 did not meet the inclusion/exclusion criteria or were duplicates and thus were excluded from the systematic review. Of 409 citations that were screened for relevance, 76 articles were selected for full-text review. We identified a further eight articles from the reference lists of relevant articles (n = 5) and hand searches of allergy journals (n = 3), but none were found from searching the gray literature. Of the total of 84 articles that were considered for review in full text, 59 met the inclusion/exclusion criteria and were included in the systematic review (1, 4, 9, 11, 19–73) (see Fig. 1).

image

Figure 1.  Study identification flowchart.

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Analysis of the differences between studies confirmed our hypothesis that a meta-analysis was not possible. We found considerable differences between studies for objectives, populations, study design, settings, outcomes, and study quality or appraisal (see study characteristics of included studies in the Appendix). The majority of studies were epidemiological consisting of cross-sectional surveys, case-based surveys, and prospective cohort studies (n = 36). Other studies were chart reviews (n = 11), qualitative studies (n = 7), systematic reviews (n = 4), and one RCT (n = 1). Eighty percent of the studies were spread across hospital or clinic (n = 24) and community (n = 23) settings, and populations varied across studies for age, and whether the objective of the study was to investigate patients with anaphylaxis or caregivers involved in the care of these patients.

We identified 202 gaps in anaphylaxis management across the 59 studies (1, 4, 9, 11, 19–73). Using grounded theory methodology (17), two authors independently categorized these gaps according to major themes and classified the frequency of these themes from the perspective of two broad populations: physicians (primary care, pediatricians, and allergy specialists) and patients or the community (schools, childcare centers, and allergy organizations). Major themes that included at least three gaps in anaphylaxis management are summarized in Table 1 (physician level) and in Table 2 (patient or community level).

Table 1.   Summary of anaphylaxis management gaps at the level of physicians
ThemeGap (number of gaps)Setting
  1. US, United States; UK, United Kingdom; AAAAI, American Academy of Allergy, Asthma and Immunology; ED, emergency department; FAAN, Food Allergy and Anaphylaxis Network; AAP, American Association of Pediatrics.

Lack of knowledgeAnaphylaxis
 The signs and symptoms or to  correctly diagnose (3)Army hospital database, US (43); Pediatric allergy hospital, UK (49); AAP organization, US (51)
Auto-injectors
 How to use (8)Community hospitals, UK (11); Pediatric medical convention, Canada (41); Tertiary pediatric hospital, Australia (59); Pediatric hospital allergy clinic, US (68); Hospital, New Zealand (72)
 Correct dose (6)Schools, UK (28); ED, UK (40); Pediatric convention, Canada (41); General hospitals, UK (47); Hospital, New Zealand (72)
 Appropriate route of administration (6)AAAAI members, US (27); ED, UK (40); Army hospital database, US (43); General hospitals, UK (47); Pediatric and general practice, Germany (58); Hospital, New Zealand (72)
 Inadequate or no training provided to patients on how to use (12)Communities, UK (1); Community hospitals, UK (11); Specialist pediatric allergy clinic, UK (21); FAAN organization, US (25); Schools, UK (32); Army hospital database, US (43); Pediatric allergy clinic, UK (49); Support group and pediatric allergy clinic, US (50); Tertiary pediatric hospital, Australia (59); Children’s hospital, France (63)
Anaphylaxis managementTreatment with epinephrine
 Infrequent (8)Independent childcare centers, US (24); EDs, US (31, 37); ED, UK (40); Army hospital database, US (43); Support group and pediatric allergy clinic, US (50); AAP members, US (51); Allergy clinic, France (60)
 Delayed administration (5)Communities, UK (1); AAAAI members, US (27); Data from communities of a national registry, US (29); ED, Australia (33); Children’s hospital, US (52)
Diagnostic coding of anaphylaxis
 Infrequent or not determined (3)Systematic review (4); EDs, US (37); Military medical center, US (46)
Follow-up carePrescribing auto-injectors or epinephrine
 Infrequent (6)EDs, US (31); Army hospital database, US (43); Multidisciplinary pediatric allergy clinic, UK (49); Tertiary pediatric hospital, Australia (59); Pediatric and general practices, Germany (58); Communities, US (67)
 Not the most commonly prescribed treatment for anaphylaxis (5)EDs, US (31, 37); Army hospital database, US (43); AAP members, US (51); Pediatric and general practices, Germany (58)
Referral to an allergy specialist
 Infrequently or not done after  acute reaction (6)University hospital ED, France (26); Schools, UK (28); EDs, US (31); Community pediatric service, UK (35); Army hospital database, US (43); The quintile of the most deprived local authority area, UK (71)
Table 2.   Summary anaphylaxis management gaps at the level of patients or the community
ThemeGap (number of gaps)Setting
  1. UK, United Kingdom; PAC, pediatric allergy clinic; US, United States; CO, consumer organization; GP, general practitioner; ED, emergency department; HMO, health maintenance organization; FAAN, Food Allergy and Anaphylaxis Network.

Lack of knowledgeAnaphylaxis
 Signs and symptoms, and which  foods to avoid (8)Community GP practice, UK (19); Independent childcare centers, US (24); PAC, CO, Australia (44); PAC, UK (49); University, UK (53); Childcare setting, US (62); Children’s hospital, France (63); Communities, US (67)
 General management (5)Schools, UK (32); Pediatric allergy service, Australia (39); Pediatric allergy clinics, CO, Australia (44); PAC, UK (49)
Provision of educational materials
 Lacking or inaccurate (6)Community-based GP practice, UK (19); North Amercian EDs (31); Pediatric allergy clinics, CO, Australia (44); Multidisciplinary PAC, UK (49); Military hospital, medical school or HMO, US (56); Hospital PAC, US (68)
Auto-injectors
 How to use or incorrectly use (7)Community hospitals, UK (11); Allergy and clinical immunology clinic, Canada (20); PAC, UK (22); Schools, UK (28); Pediatric allergy service, Australia (39); Childcare setting, US (62); Hospital PAC, US (68)
 Receive inadequate, infrequent or no instruction on its use (10)Community-based GP practice, UK (19); The FAAN organization, US (25); Schools, UK (28, 32); Schools, Canada (35); Pediatric allergy service, Australia (39); Multidisciplinary PAC, UK (49); Children’s hospital, France (63)
Anaphylaxis managementAuto-injectors
 Do not carry one, or unavailable  at the time of reaction (8)Community-based GP practice, UK (19); Data from a national registry, US (29); Children’s hospital, US (34); Food allergy support group, PAC, US (50); University, UK (53); School districts, US (57); Communities, US (67); Hospital PAC, US (68)
 Carry it but do not use it (4)Pediatric allergy service, Australia (39); Local support group and PAC, US (50); Pediatric and general practices, Germany (58); University-based allergy clinic, US (73)
Anaphylaxis management plans
 Do not have one (5), or missing  information (4)Schools, UK (28, 32); Pediatric allergy service, Australia (39); School districts, US (57); Children’s hospital, France (63); Schools, US (64)
Quality of lifeRestrictions and disruptions of social activities and interactions (7)Specialty clinic, University Allergy practice, US (30); Community pediatric service, UK (35); PACs, CO, Australia (44); Anaphylaxis educational seminar, children’s hospital, community support group, Canada (54); Schools, Sweden (55); The FAAN organization, US (69)
Fear and anxiety of severe reactions (4)Prairie city communities, Canada (38); Anaphylaxis educational seminar, a children’s hospital, and a community support group, Canada (54); Schools, Sweden (55)
Lack of understanding by others (3)Anaphylaxis educational seminar, children’s hospital, community support group, Canada (54); Schools, Sweden (55)
Feeling of being a bother or an outsider (3)Prairie city communities, Canada (38); Schools, Sweden (55)

Gaps in anaphylaxis management –physician level

Gap analysis revealed three main themes concerning the physician population: (1) lack of knowledge (anaphylaxis and auto-injectors); (2) anaphylaxis management (treatment with epinephrine and diagnostic coding of anaphylaxis); and (3) follow-up care (prescribing auto-injectors or epinephrine, and referral to an allergy specialist) (Table 1).

Theme 1: Lack of knowledge

Anaphylaxis knowledge

Three studies indicated that primary care physicians and pediatricians have insufficient knowledge to identify the signs and symptoms of anaphylaxis or to correctly diagnose anaphylaxis (43, 49, 51).

Auto-injectors

Gaps in epinephrine auto-injector use revealed that physicians not only lacked the knowledge on how to use auto-injectors (11, 41, 59, 68, 72), but they also did not provide adequate instructional training to patients (1, 11, 22, 25, 32, 43, 49, 50, 59, 63). One study found that patients who were prescribed auto-injectors by their primary care physicians either never carried the device or were less aware of how to activate it compared to those who received their prescription from allergists (22). Other gaps were lack of familiarity with the device (68), or the inability to correctly demonstrate all the steps in its use (62, 68, 72). Injecting the device into a thumb (59) or forgetting to hold the auto-injector at the site for >5 s (41, 59) were also major errors. Other gaps were related to physicians’ lack of knowledge of the correct dose of auto-injector administration. Few physicians knew the two available doses of epinephrine auto-injectors (40, 41, 47). Furthermore, one study indicated that some children were incorrectly prescribed a low-dose auto-injector even though they reached a weight of 30 kg, which would require a full dose (28). Lack of knowledge of the correct route of epinephrine administration was also an identified gap. First-line use by physicians of subcutaneous (s.c.) or intravenous epinephrine instead of the recommended intramuscular (i.m.) route (across all levels of severity) was demonstrated in a number of studies (27, 40, 43, 47, 58, 72).

Theme 2: Anaphylaxis management

Treatment with epinephrine

Eight studies identified that epinephrine use in acute allergic reactions is infrequent (24, 31, 37, 40, 43, 50, 51, 60). Furthermore, significant delay in epinephrine administration (i.e., ≥ 5 min) was also found to be an important gap in clinical practice (1, 27, 29, 33, 52).

Diagnostic coding

Accurate diagnosis is also hindered by the lack of diagnostic coding – two studies indicated that anaphylaxis coding by physicians was not done in all cases of anaphylaxis in the emergency department (ED) (37, 46). There are also an insufficient number of codes available to document episodes of diagnosed anaphylaxis (4).

Theme 3: Follow-up care

Prescribing auto-injectors or epinephrine

Many studies indicated that the rate of auto-injector prescription is low across different settings: pediatric and military hospitals (43, 49, 59), general community practices (hospital or office-based) (58, 67), and ED (31). One study found that residents were significantly less likely to prescribe an auto-injector than more senior staff (59). Studies also indicated that antihistamines and steroids were prescribed more often than adrenaline (31, 37, 43, 51, 58).

Referral to an allergy specialist

Lack of referral for an allergy consultation was also identified. Five studies found that few patients were referred to an allergist after being seen for an acute reaction in community or hospital clinics (35, 43, 71) or the ED (26, 31). However, one study found that allergy testing and follow-up were more frequent in children attending hospital clinics (28).

Gaps in anaphylaxis management –patient and community level

Analysis of gaps in the patient and community population revealed three major themes: (1) lack of knowledge (anaphylaxis and auto-injectors); (2) anaphylaxis management [auto-injectors and anaphylaxis management plans (AMPs)]; and (3) QOL (see Table 2).

Theme 1: Lack of knowledge

Anaphylaxis

Patients and parents of children at risk for anaphylaxis lacked the knowledge to recognize the signs and symptoms of anaphylaxis (19, 24, 53, 62, 63) and were unaware of which foods to avoid (49, 67). Other barriers to care were the lack of knowledge in the general management of anaphylaxis (39, 49), the extent to which allergens should be excluded from a child’s diet and environment (32, 44), and how to react in an anaphylactic emergency (32). One study reported that teachers and staff had not received formal training on how to manage acute allergic reactions in a school setting (32).

Provision of information

Provision of anaphylaxis educational materials to patients was also lacking. Studies showed that most patients were not given accurate information by their primary care physicians on anaphylaxis management (19), were not given discharge instructions from the ED on avoidance of the offending allergen (31, 56), or written information on indications for auto-injectors (68). One study found that children who were referred by general pediatricians to allergy specialist care were given more advice and had better knowledge then those who were referred to allergy specialists from primary care (49).

Auto-injectors

Knowledge gaps in auto-injector use included lack of awareness and inadequate training on how to use auto-injectors. Patients in most community settings (schools, childcare centers), hospitals, or allergy clinics were either not able to recall all the steps for correct auto-injector use (11, 39, 62) or were unable to correctly activate the device (20, 22, 28, 68). Lack of instruction and training on how to use auto-injectors was a major gap identified in eight studies. These included patients or families who were not shown how to use the device (19, 25, 32, 49, 63) and school teachers who were not provided training on the device (28, 32, 36, 39).

Theme 2: Anaphylaxis management

Auto-injectors

Seven studies identified that many patients did not carry an auto-injector or did not have one available at the time of a reaction (29, 34, 50, 53, 57, 67, 68). One study suggested that hesitation in using or forgetting to carry the device may in part explain these behaviors (19). Furthermore, even when patients or parents of children with anaphylaxis carried auto-injectors, many did not use it (39, 50, 58, 73). The most common reasons for not using auto-injectors were: ‘I recognized the symptoms but gave Benadryl first’ and ‘I did not think the reaction was serious’ (50).

Anaphylaxis management plans

Lack of AMPs in schools was also identified as a problem in five studies (28, 32, 39, 57, 63). Furthermore, many AMPs did not provide epinephrine auto-injector administration instructions and were missing essential components such as critical emergency contact and health history information (64).

Theme 3: Quality of life

Studies indicated that the main factors that negatively affected the QOL for patients at risk for anaphylaxis and their caregivers were restrictions and disruptions of social activities and interactions. Findings from six studies indicated that restrictions affected patients and their caregivers differently (30, 35, 44, 54, 55, 69). Patients expressed their restrictions in terms of limitations on social activities such as birthday parties, sleepovers, and field trips (30, 54), and the feeling of sadness from having to abstain from certain foods (55). Family members were affected by restrictions designed to ensure the allergic child’s safety, which often affected the entire family (35, 54). In one study, parents felt challenged by the need to keep their child safe from accidental allergen exposures yet not overly restrict their child’s life and social opportunities (44).

Fear and anxiety in parents were related to insufficient information about how to manage anaphylaxis (54), and living with the fear of their child’s new experiences in social situations (38). Key events such as a new accidental exposure, information about new potential risks, and child developmental changes (e.g., increased independence) were also triggers of anxiety (54, 55). Other studies showed that QOL may also be impaired by obstacles to coping, such as lack of understanding by others and the feeling of being a bother or an outsider. In one study, adolescents perceived that other people did not understand the seriousness of their condition, showed indifference to their requests for special meal orders, or felt subject to teasing and harassment (54). Lack of public understanding, unwillingness to accommodate, and hostility were also identified as major obstacles to coping (54). In one study, children in schools perceived themselves as being a bother, an outsider, and causing trouble for others because of special food requests which involved extra work for their friends (55). From the caregiver perspective, mothers saw the auto-injector as a visual reminder that their child was ‘different’ and the worry that they would be treated differently or excluded (38).

Discussion

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. Sources of funding
  8. References
  9. Supporting Information

Our systematic review identified over 200 gaps in anaphylaxis management. Themes that were common to physicians, patients, and caregivers in all settings were insufficient knowledge of anaphylaxis and its management, and how to use epinephrine auto-injectors. Consideration of these gaps is particularly important given the increasing prevalence of anaphylaxis, especially in young children (74). Although this apparent rise in the prevalence of anaphylaxis may be explained by the recently broadened definition of anaphylaxis (2, 75), the findings of our review highlight the current landscape of anaphylaxis management across different settings and populations. However, the extent of deficits reported in the included studies is surprising and troubling, as children at risk for anaphylaxis depend on others to help treat them (i.e., family, schools, and community), yet at every level, deficiencies have been identified.

Our findings indicated that lack of information is an important barrier to coping, and patients’ QOL is severely affected. Anaphylaxis is a lifelong medical condition for most, requiring strict avoidance of the offending allergen, as there is currently no other available therapy. There is clearly a need for improved patient education to better support those at risk and their caregivers. The provisions of appropriate educational materials about emergency self-care and avoidance and for specific immunotherapy (e.g., management of Hymenoptera venom allergy) have the potential to assist patients and caregivers of children at risk because it helps to develop successful coping strategies, which can positively impact QOL. For children at risk, coping strategies can be especially helpful as they mature and assume more responsibility for their condition.

Regarding health care professionals, our review confirmed that there is still a lack of clarity among physicians and in existing guidelines on how to appropriately manage patients at risk for anaphylaxis, even though clinical practice guidelines for anaphylaxis management exist (2, 5, 76, 77). A lack of a universally accepted definition of anaphylaxis may also in part explain these identified knowledge gaps. For example, some practitioners still think that ‘shock’ needs to be present for an anaphylaxis diagnosis even though this has been eliminated from new definitions. The majority of studies that were included in the systematic review were published prior to 2006, for which the most recent definition of anaphylaxis published by Sampson et al. (2) do not apply. The new definition may also not be universally accepted because the need to consider several clinical criteria in its definition can be complicated or may not be relevant to all physicians (including allergists) or countries. More robust evidence is needed to guide practice at all levels. However, this is a challenge for several reasons. First, the first-line use of epinephrine for anaphylactic emergencies is largely based on expert opinion and suboptimal evidence (78). Second, there needs to be universal agreement on the optimal route and dose of epinephrine administration. Although studies advocate the i.m. over the s.c. route of epinephrine administration for treatment of anaphylaxis (2, 79, 80), this conclusion is largely based on studies investigating the differences in the plasma levels of epinephrine concentrations achieved through both routes (81). Third, the recommended dose of i.m. administration for adults for the emergency medical treatment of anaphylaxis varies from a maximum initial dose of 0.3–0.5 mg in Canada, the United States, Australia, and the United Kingdom (21, 80) to 0.5–1.0 mg in other European countries (76, 80). Another challenge is epinephrine dosing in children, which is problematic because there are only two fixed doses of epinephrine auto-injectors available: a 0.15 mg dose for children weighing between 10 and 25 kg (22–55 lb) and a 0.3 mg dose for children weighing ≥25 kg (≥55 lb) (82). However, as Sicherer et al. (79) point out, providing the appropriate dose for children who fall below the lowest weight parameter (15 kg) can be difficult and can lead to overdosing (with the 0.15 mg dose in infants who weigh <15 kg).

Strengths and limitations

To our knowledge, no systematic review has previously attempted to synthesize available evidence on the gaps in anaphylaxis management across different populations and settings. To reduce the effects of bias, we ensured that our literature search was comprehensive with well-defined terms and inclusion/exclusion criteria, screening articles independently at each level of article selection using standardized data extraction forms, and measuring inter-rater reliability using kappa statistics. A potential limitation to our study is that it was not possible to combine the results in a meta-analysis because the studies were too heterogeneous to pool. However, we addressed potential sources of variability between relevant studies (in addition to random error) by the rigorous study quality assessment and critical appraisal of studies, as well as the differences between studies for populations, settings, and outcomes.

Another possible limitation of our study is that we did not limit our search to study designs with the best quality of evidence such as RCTs. However, our objective was to identify gaps in anaphylaxis management, which can be addressed in prospective, retrospective, or qualitative studies, but most appropriately in epidemiologic evaluations that assess risk factors and long-term rare outcomes such as in cross-sectional and cohort studies. In fact, prospective, placebo-controlled trials in anaphylaxis research are largely lacking because they are difficult to conduct and unethical in most cases. This is evidenced by a recent systematic review that attempted to assess the benefits and harms of adrenaline in the emergency treatment of anaphylaxis, but failed to retrieve any randomized or quasi-randomized trials (78). Controlled studies are also difficult to conduct because anaphylactic reactions are relatively uncommon or under recognized, are unpredictable, and can occur in health care settings even if preventive efforts are established (82). Furthermore, there is great variability among patients for the clinical presentation of anaphylaxis. Patients vary in the onset of symptoms after exposure (from minutes to hours), the number and severity of symptoms (from mild to fatal within minutes) (83), and the exposure may be fatal even if optimal treatment is provided immediately (1).

Lastly, the included studies that were captured by our systematic review are most representative of anaphylaxis from food allergy in mostly pediatric patients. However, the authors recognize that adequate management of anaphylaxis should also include other important causes of anaphylaxis such as drug allergy, which can particularly affect elderly patients with comorbidities such as cardiovascular disease requiring treatment with β-blockers or angiotensin-converting enzyme (ACE)-inhibitors.

Conclusions

The classification of the specific domains of anaphylaxis management gaps that were identified in this systematic review will provide an enhanced understanding of the learning and practice needs of physicians, patients, and their caregivers in different settings. Our future work will target the development of interventional strategies and practice tools to address these knowledge and practice gaps, which are needed to improve anaphylaxis management at all levels.

Acknowledgment

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. Sources of funding
  8. References
  9. Supporting Information

We would like to acknowledge Silas Lamb, who provided research support in the collection and management of study data.

Sources of funding

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. Sources of funding
  8. References
  9. Supporting Information

This research was funded by an educational grant from King Pharmaceuticals Canada.

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. Sources of funding
  8. References
  9. Supporting Information

Supporting Information

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. Sources of funding
  8. References
  9. Supporting Information

Appendix S1. Characteristics of included studies.

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FilenameFormatSizeDescription
ALL_2294_sm_AppendixS1.pdf112KSupporting info item

Please note: Wiley Blackwell is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.