SEARCH

SEARCH BY CITATION

Keywords:

  • Anaphylaxis [*drug therapy];
  • Glucocorticoids [therapeutic use];
  • Humans

Abstract

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Implications for practice
  10. Implications for research
  11. Acknowledgements
  12. Data and analyses
  13. Appendices
  14. What's new
  15. History
  16. Contributions of authors
  17. Declarations of interest
  18. Sources of support
  19. Differences between protocol and review
  20. References

Background

Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may result in death. Anaphylaxis guidelines recommend glucocorticoids for the treatment of people experiencing anaphylaxis. 

Objectives

We sought to assess the benefits and harms of glucocorticoid treatment during episodes of anaphylaxis.

Search methods

In our previous version we searched the literature until September 2009. In this version we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE (Ovid) (1956 to September 2011), EMBASE (Ovid) (1982 to September 2011), CINAHL (EBSCOhost) (to September 2011). We also searched the UK National Research Register and websites listing ongoing trials, and contacted international experts in anaphylaxis in an attempt to locate unpublished material.

Selection criteria

We planned to include randomized and quasi-randomized controlled trials comparing glucocorticoids with any control (either placebo, adrenaline (epinephrine), an antihistamine, or any combination of these).

Data collection and analysis

Two authors independently assessed articles for inclusion.

Main results

We found no studies that satisfied the inclusion criteria.

Authors' conclusions

We are, based on this review, unable to make any recommendations for the use of glucocorticoids in the treatment of anaphylaxis.

Glucocorticoids for the treatment of anaphylaxis  

Anaphylaxis is a serious allergic reaction that is rapid in onset and may result in death. It is commonly triggered by a food, insect sting, medication, or natural rubber latex. The reaction typically occurs without warning and can be a frightening experience both for those at risk and their families and friends. Steroids (glucocorticoids) are often recommended for use in the management of people experiencing anaphylaxis. However, the evidence base in support of the use of steroids is unclear. We therefore conducted a systematic review of the literature, searching key databases for high quality published and unpublished material on the use of steroids for the emergency treatment of anaphylaxis. In addition, we contacted experts in this health area and the relevant pharmaceutical companies. We were unable to find any randomized controlled trials on this subject through our searches. We conclude that there is no evidence from high quality studies for the use of steroids in the emergency management of anaphylaxis. Therefore, we can neither support nor refute the use of these drugs for this purpose.


Background

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Implications for practice
  10. Implications for research
  11. Acknowledgements
  12. Data and analyses
  13. Appendices
  14. What's new
  15. History
  16. Contributions of authors
  17. Declarations of interest
  18. Sources of support
  19. Differences between protocol and review
  20. References

Description of the condition

Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death (Sampson 2006). There is some evidence that the incidence of anaphylaxis is increasing (Decker 2008; Gupta 2003; Gupta 2007; Lin 2008; Poulos 2007; Sheikh 2001; Sheikh 2008). The lifetime risk may be as high as one in 100 individuals in the general population (Lieberman 2006; Neugut 2001; Simons 2002). There are many possible triggers, including food, insect venoms, medication and biologics, anaesthetics, diagnostic agents, natural rubber latex, vaccinations for prevention of infectious diseases, and exercise (Brown 2001; Brown 2004; Kemp 2002Peng 2004; Sampson 2005; Simons 2006; Simons 2009). In some individuals anaphylaxis is idiopathic (Webb 2006). During an episode of anaphylaxis, some 80% to 90% of individuals experience flushing, itching, hives, angioedema, or other skin or mucosal symptoms; up to 70% have stridor, dysphonia, cough, chest tightness, shortness of breath, wheezing, or other respiratory symptoms; and up to 45% have vomiting, diarrhoea, or cramp-like abdominal pain. Of note only 10% to 45% have cardiovascular symptoms, including chest pain, hypotension, or shock (Brown 2001; Brown 2004; Sampson 2006). Signs and symptoms usually occur within five to 30 minutes of exposure to the trigger, although occasionally they may not develop for hours, yet anaphylaxis may be fatal within minutes (Bock 2001; Bock 2007; Greenberger 2007; Pumphrey 2000; Pumphrey 2003; Pumphrey 2007; Sampson 1992). The signs, symptoms, and treatment of anaphylaxis are similar regardless of the trigger or the pathogenesis (Simons 2008).

Biphasic (late-phase) and protracted reactions occur in from < 1% to 20% of people with anaphylaxis. Most of these reactions are mild or moderate (Confino-Cohen 2010; Scranton 2009; Smit 2005). Fatalities appear to be rare. Risk factors for biphasic reactions include a severe initial reaction, presence of laryngeal oedema or hypotension, delay in the administration of adrenaline (epinephrine), too small a dose of adrenaline, and a history of a previous biphasic reaction (Douglas 1994; Ellis 2007; Lieberman 2005; Stark 1986).

Description of the intervention

Although adrenaline remains the main treatment for people experiencing anaphylaxis, glucocorticoids are given after the initial resuscitation period (Badger 2004; Chin 2004; Joint Task Force 2005; Korenblat 1999; Orbach 2005; Sampson 2006; Walters 2005). Indeed, in recent retrospective multi-centre studies in emergency departments glucocorticoids were reported to be more frequently administered than adrenaline, traditionally the initial treatment of choice in anaphylaxis (Clark 2004; Clark 2005; Gaeta 2007; McLean-Tooke 2003; Simons 2004a; Simons 2004b). This is in agreement with reports that glucocorticoid use for anaphylaxis is increasing (Gaeta 2007). H1-antihistamines are also commonly administered in anaphylaxis, despite the lack of published evidence for this intervention (Sheikh 2007; Simons 2004c).

Current Resuscitation Council (UK) Guidelines for the Treatment of Anaphylaxis (Anaphylaxis UK Guidelines) recommend giving hydrocortisone 200 mg by intramuscular or slow intravenous injection after the initial resuscitation, for the treatment of adults or children more than 10 years of age. Other guidelines recommend methylprednisolone, triamcinolone, or prednisone by intravenous, intramuscular, or oral routes using different doses and dose regimens (Brown 2006; Joint Task Force 2005; Kemp 2002; Muraro 2007; Sampson 2005; Sampson 2006; Soar 2008). Glucocorticoid administration in anaphylaxis usually consists of either a single dose or a dose on the day of the event followed by a dose on each of the next few days.

How the intervention might work

The primary action of glucocorticoids is down-regulation of the late-phase eosinophilic inflammatory response, as opposed to the early-phase response. Short-term glucocorticoid treatment is seldom associated with adverse effects (Schleimer 2008).

Why it is important to do this review

There are uncertainties as to whether glucocorticoids administered for the treatment of anaphylaxis can prevent or ameliorate biphasic or protracted reactions. There is published evidence that they might be ineffective in this regard (Douglas 1994; Ellis 2007; Lieberman 2005; Stark 1986). The existing evidence for the use of glucocorticoids appears to consist mainly of retrospective studies, case reports, and other descriptive literature. A more comprehensive and structured search for literature on the benefits and risks of short-term glucocorticoid treatment in anaphylaxis is required in order to ascertain if, indeed, there is reasonable evidence for continuing to recommend glucocorticoid use in the treatment of this potentially life-threatening disease.

Objectives

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Implications for practice
  10. Implications for research
  11. Acknowledgements
  12. Data and analyses
  13. Appendices
  14. What's new
  15. History
  16. Contributions of authors
  17. Declarations of interest
  18. Sources of support
  19. Differences between protocol and review
  20. References

We sought to assess the benefits and harms of glucocorticoid treatment during episodes of anaphylaxis. We defined anaphylaxis as any serious systemic allergic reaction that is rapid in onset with potentially fatal manifestations. Such reactions usually involve more than one body system (for example skin, respiratory, gastrointestinal, or cardiovascular). We sought to include all anaphylactic events regardless of mechanism or trigger.

Methods

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Implications for practice
  10. Implications for research
  11. Acknowledgements
  12. Data and analyses
  13. Appendices
  14. What's new
  15. History
  16. Contributions of authors
  17. Declarations of interest
  18. Sources of support
  19. Differences between protocol and review
  20. References

Criteria for considering studies for this review

Types of studies

We did not distinguish between anaphylactic and anaphylactoid (also sometimes termed pseudoallergic) reactions in this review. We looked for randomized controlled trials (RCTs) comparing glucocorticoids with any control treatment (either placebo, adrenaline (epinephrine), antihistamine, or any combination of these).

Because we anticipated identifying very few, if any, RCTs investigating the treatment of anaphylaxis, we were also interested in quasi-randomized trials where the method of allocation was not truly random (for example consecutive allocation to each treatment group). We planned to apply the Cochrane approach using the methods detailed in Section 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) to assess the quality of both randomized and quasi-randomized studies.

Types of participants

We were interested in including all patients (infants, children, and adults; in hospital or other healthcare facility) experiencing an anaphylactic reaction caused by food, insect venoms, medication and biologics, anaesthetics, diagnostic agents, vaccinations for infectious disease, natural rubber latex, exercise, or any other trigger, as well as idiopathic disease.

Types of interventions

We were interested in any intervention with any glucocorticoid administered through any route (intravenous, intramuscular, or oral) in any dose or dose regimen. We excluded studies focusing on the use of glucocorticoids for the prevention of anaphylaxis.

Types of outcome measures

Our outcome measures of interest were as follows.

Primary outcomes

1. Mortality rate

Secondary outcomes

2. Prevention of biphasic or prolonged anaphylaxis (symptoms persisting or recurring in from one to 72 hours without any ongoing or additional exposure to the trigger) (Lieberman 2005; Sampson 2006)

3. Incidence of cardiovascular manifestations, e.g. chest pain, palpitations, shock

4. Incidence of respiratory manifestations, e.g. shortness of breath, cough, wheeze or stridor

5. Incidence of gastrointestinal manifestations, e.g. abdominal pain, diarrhoea, nausea, vomiting

6. Incidence of other clinical manifestations as included in the studies, e.g. neurological manifestation such as loss of consciousness or headaches, or skin manifestations such as urticaria, erythema, or oedema

Health service use

7. Hospitalization rate

8. Length of emergency department visit*

9. Length of hospital stay*

10. Rate of re-presentation to hospital

11. Incidence of any adverse events reported for any treatment delivered

*We acknowledged that the lengths of stay outcomes may be difficult to interpret given that worse clinical outcomes may be associated with shorter hospital stays. In the event of finding such data, we planned to interpret the outcomes with care and in the context of clinical outcomes.

Search methods for identification of studies

Electronic searches

In our previous version we searched the literature until September 2009. In this version we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3) using the following key words: anaphylaxis and glucocorticoids (see Appendix 1).

We searched MEDLINE (Ovid) (1956 to September 2011), see Appendix 2; EMBASE (Ovid) (1982 to September 2011), see Appendix 3; and CINAHL (EBSCOhost) (1982 to September 2011), see Appendix 4 using the Cochrane RCT filter (Higgins 2011).

We did not apply any language restriction.

Searching other resources

In an attempt to uncover additional relevant published data, grey literature, unpublished data, and research in progress, we also:

  • developed a database of first and last authors of potentially eligible studies and searched the Science Citation Index Expanded (SCI-EXPANDED) (1945 to 2009) using these names;

  • searched the bibliographies of identified studies;

  • compiled a database of international experts in anaphylaxis;

  • contacted relevant pharmaceutical companies;

  • searched the UK National Research Register;

  • searched websites listing ongoing trials, such as http://clinicaltrials.gov/, http://www.controlledtrials.com/, and http://www.actr.org.au/.

Data collection and analysis

Three authors (AS, KC, and ES) undertook this review; KC co-ordinated the review.

Selection of studies

Two authors (KC and AS) ran the searches as detailed in the search strategy. Both authors independently reviewed titles and abstracts from the literature searches to identify relevant trials for full review. We planned to retrieve the full text copies of all potentially eligible studies and subject each to independent review using the inclusion criteria detailed above. KC wrote to authors of papers for additional information and screened responses for relevance as per the inclusion criteria.

We planned to resolve any disagreements by discussion between authors. In the case of consensus not being reached, we planned to involve the third author (ES) both to participate and, if necessary, arbitrate in the final decision.

Data extraction and management

Two authors (KC and AS) planned to independently extract data using a suitably adapted version of the data extraction form developed by the Cochrane Anaesthesia Review Group. We planned to resolve any disagreements by discussion between the authors; in the case of consensus not being reached, we planned to involve the third author (ES) both to participate and, if necessary, arbitrate in the final decision.

Assessment of risk of bias in included studies

In our previous version we planned to grade each parameter of trial quality as: A, low risk of bias; B, moderate risk of bias; C, high risk of bias. We planned to make an overall assessment for each randomized controlled trial using the same rating scale.

In this updated version of the review we planned to assess the quality of included RCTs following the Cochrane approach using the methods detailed in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We planned to concentrate on using the following five parameters to assess quality:

  • random sequence generation;

  • allocation concealment;

  • blinding of participants, personnel, and outcome assessors;

  • incomplete outcome data;

  • selective reporting;

  • other bias.

We planned to judge each parameter of trial quality as either: low risk of bias; high risk of bias; or unclear; and make an overall assessment for each RCT using the same grading system.

We planned to document the methodological quality of these trials (both randomized and quasi-randomized) following the Cochrane approach, using the methods detailed in Section 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Two authors (KC and AS) planned to independently assess study quality; we did not plan to mask review authors to study details. We planned to assess the agreement of authors on methodological quality assessment and to resolve disagreements by discussion and, if necessary, with the involvement of a third author (ES).

Measures of treatment effect

We intended to provide a risk ratio (RR) or mean difference for the primary outcome of each trial included, on the basis of an intention-to-treat analysis.

Unit of analysis issues

We anticipated that included studies would most likely follow a parallel group design, with individuals randomized to one of two arms of the trial. We did not anticipate identifying any cluster-randomised trials in this review.

Dealing with missing data

In any studies with missing data, in line with recommendations in the Cochrane Handbook, Section 16.1.2 (Higgins 2011), we intended to contact the authors for further information. In the event of being unable to obtain such information we would have reported this and discussed its potential impact. We did not intend to impute the missing data.

Assessment of heterogeneity

We planned to test for heterogeneity using the I2 statistic and significant heterogeneity would have been assumed if I2 was greater than 40% (that is more than 40% of the variability in outcome between trials could not be explained by sampling variation) (Higgins 2011).

Assessment of reporting biases

We planned to assess for selective reporting of outcomes by, where possible, comparing outcome measures listed in trial protocols and the published reports. Furthermore, we planned to assess for evidence of publication bias graphically using funnel plots and statistically using the Begg and Egger tests (Begg 1994; Egger 1997).

Data synthesis

We proposed to use Review Manager (RevMan 5.1) for data analysis and quantitative data synthesis. For dichotomous data, we planned to calculate individual and pooled statistics as relative risks (RR) with 95% confidence intervals (CI). For continuous data, we planned to calculate individual and pooled statistics as mean differences (MD) or standardized means differences with 95% CI. We planned to give consideration to the appropriateness of meta-analysis in the presence of significant clinical or statistical heterogeneity. We planned to undertake meta-analysis using fixed-effect or random-effects modelling, depending on whether or not data were found to be homogenous. In the absence of any statistically significant between study heterogeneity, we planned to report a pooled effect derived from the fixed-effect model. If we uncovered statistical heterogeneity, however, we planned to investigate this (see subgroup analysis and investigation of heterogeneity section). In the event of such a scenario, and if still considered clinically appropriate to pool data, we will report a pooled effect derived from the random-effects model in future updates. We planned to undertake quantitative analyses of outcomes, wherever possible, on an intention-to-treat basis.

Subgroup analysis and investigation of heterogeneity

We were interested in analysing data for the following subgroups.

1. Mild versus moderate versus severe anaphylaxis (Brown 2004).

  • Mild reactions (involving the skin and mucosa only): generalized erythema, urticaria, or angioedema including periorbital oedema.

  • Moderate reactions (features suggesting gastrointestinal, cardiovascular, or respiratory involvement): dyspnoea, stridor, wheeze, nausea, vomiting, dizziness (presyncope), diaphoresis, chest or throat tightness, or abdominal pain.

  • Severe reactions (hypoxia, hypotension, or neurological compromise): cyanosis or saturation of peripheral oxygen (SpO2) < 92% at any stage, hypotension (systolic blood pressure < 90 mm Hg in adults, confusion, collapse, loss of consciousness, or incontinence).

2. Mode of administration of treatment (e.g. intravenous versus intramuscular versus oral).

3. Time from onset of first anaphylaxis symptoms to receiving treatment.

4. Age (infants, children, adolescents, adults, and the elderly).

5. Different glucocorticoids according to the agent(s) used in each study.

Sensitivity analysis

We planned to undertake sensitivity analysis for the allocation of missing data by best and worst case analysis and also sensitivity analysis on the basis of only including randomized studies. This would have allowed an assessment of the impact on the review conclusions of excluding studies judged to be at high risk of bias.

Results

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Implications for practice
  10. Implications for research
  11. Acknowledgements
  12. Data and analyses
  13. Appendices
  14. What's new
  15. History
  16. Contributions of authors
  17. Declarations of interest
  18. Sources of support
  19. Differences between protocol and review
  20. References

Description of studies

There were no eligible studies (see table 'Characteristics of included studies').

Results of the search

We searched the databases up to September 2011. Our search revealed 1764 hits (see Figure 1). We screened 1587 records after we removed duplicates. After scrutiny of the remaining 18 abstracts, we did not find any studies that fulfilled the inclusion criteria. We searched websites listing ongoing trials, using anaphylaxis as a keyword, but failed to identify any potential studies. We contacted experts in the field of anaphylaxis but this also failed to contribute any relevant studies, published or unpublished.

thumbnail image

Figure Figure 1. Study flowchart (PRISMA template)

Download figure to PowerPoint

Included studies

There were no eligible studies (see table 'Characteristics of included studies').

Excluded studies

There were no eligible studies (see table 'Characteristics of excluded studies').

Risk of bias in included studies

There were no eligible studies.

Allocation

There were no eligible studies.

Blinding

There were no eligible studies.

Incomplete outcome data

There were no eligible studies.

Selective reporting

There were no eligible studies.

Other potential sources of bias

There were no eligible studies.

Effects of interventions

There were no eligible studies.

Discussion

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Implications for practice
  10. Implications for research
  11. Acknowledgements
  12. Data and analyses
  13. Appendices
  14. What's new
  15. History
  16. Contributions of authors
  17. Declarations of interest
  18. Sources of support
  19. Differences between protocol and review
  20. References

Summary of main results

This comprehensive review failed to identify any relevant randomized or quasi-randomized controlled trial evidence for the effectiveness of glucocorticoids in the management of people experiencing anaphylaxis. This contrasts with the important role of glucocorticoids in the prevention and treatment of asthma and other allergic disorders. In view of the difficulties of conducting research in an emergency context, this is not a particularly surprising finding (Simons 2007; Simons 2008). Clinicians should nonetheless be aware of the lack of a strong evidence base for the use of a glucocorticoid for the treatment of anaphylaxis. A clear statement should be made to this effect in anaphylaxis guidelines (Alrasbi 2007). Although there is little direct evidence of harm associated with use of glucocorticoids, there is, as noted above, persistent evidence that glucocorticoids are often inappropriately used as the first-line agent in place of adrenaline, which is more likely to prove life-saving (Sheikh 2008b ; Soar 2008). Consideration, therefore, needs to be given to conducting a randomized controlled trial (Simons 2008).

Overall completeness and applicability of evidence

We found no relevant evidence.

Quality of the evidence

We found no relevant evidence.

Potential biases in the review process

There is always the possibility that our searches failed to identify all relevant studies; we feel that this is, however, unlikely in the context of this review.

Agreements and disagreements with other studies or reviews

We are not aware of any other systematic reviews on this subject.

Implications for practice

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Implications for practice
  10. Implications for research
  11. Acknowledgements
  12. Data and analyses
  13. Appendices
  14. What's new
  15. History
  16. Contributions of authors
  17. Declarations of interest
  18. Sources of support
  19. Differences between protocol and review
  20. References

We found no relevant evidence for the use of glucocorticoids in the treatment of an acute episode of anaphylaxis. We are, therefore, unable to make any new recommendations based on the findings of this review. While we do not necessarily suggest that anaphylaxis guidelines no longer recommend glucocorticoids, these guidelines need to be more explicit about the basis of their recommendations regarding the use of these agents (Alrasbi 2007).

Implications for research

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Implications for practice
  10. Implications for research
  11. Acknowledgements
  12. Data and analyses
  13. Appendices
  14. What's new
  15. History
  16. Contributions of authors
  17. Declarations of interest
  18. Sources of support
  19. Differences between protocol and review
  20. References

There is a need for a more robust evidence base for the use of glucocorticoids in the treatment of anaphylaxis. Conducting trials in the context of a potentially life-threatening emergency is fraught with difficulties but, considering that glucocorticoids are not recommended as a first-line agent in anaphylaxis guidelines, it may be feasible to conduct experimental studies. Any future trials would need to consider in particular:

  • appropriate sample size with power to detect expected difference;

  • careful definition and selection of target patients;

  • appropriate comparator therapy;

  • appropriate outcome measures;

  • careful elucidation of any adverse effects;

  • the cost-effectiveness of the therapy;

  • appropriate safety measures, i.e. treatment with adrenaline injection(s), supplemental high-flow oxygen, and intravenous fluid resuscitation;

  • placement in the recumbent position or position of comfort with elevation of lower extremities;

  • appropriate continuous non-invasive monitoring of heart rate, blood pressure, and oxygenation; and

  • appropriately equipped healthcare facility with professionals who are trained and experienced with diagnosing and treating anaphylaxis.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Implications for practice
  10. Implications for research
  11. Acknowledgements
  12. Data and analyses
  13. Appendices
  14. What's new
  15. History
  16. Contributions of authors
  17. Declarations of interest
  18. Sources of support
  19. Differences between protocol and review
  20. References

We would like to thank Mike Bennett (content editor), Malcolm Fisher and Phil Lieberman (peer reviewers) for their help and editorial advice during the preparation of this systematic review. We would like to thank Munib Haroon, Dianne Lowe, and the Cochrane Child Health Field for their help and editorial advice during the preparation of the protocol for this systematic review. We would also like to thank Jane Cracknell from the Cochrane Anaesthesia Review Group. We wish to express our gratitude to the panel of experts for kindly responding to our enquiries for unpublished work and research in progress.

Appendices

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Implications for practice
  10. Implications for research
  11. Acknowledgements
  12. Data and analyses
  13. Appendices
  14. What's new
  15. History
  16. Contributions of authors
  17. Declarations of interest
  18. Sources of support
  19. Differences between protocol and review
  20. References

Appendix 1. Search strategy for CENTRAL and The Cochrane Library

#1 MeSH descriptor Anaphylaxis explode all trees

#2 anaph?l* or (acute near allerg*)

#3 (#1 OR #2)

#4 MeSH descriptor Hydrocortisone explode all trees

#5 MeSH descriptor Prednisolone explode all trees

#6 MeSH descriptor Betamethasone explode all trees

#7 MeSH descriptor Clobetasol explode all trees

#8 MeSH descriptor Cortisone explode all trees

#9 MeSH descriptor Anti-Inflammatory Agents explode all trees

#10 MeSH descriptor Immunosuppressive Agents explode all trees

#11 MeSH descriptor Pregnenediones explode all trees

#12 MeSH descriptor Glucocorticoids explode all trees

#13 MeSH descriptor Triamcinolone Acetonide explode all trees

#14 MeSH descriptor Triamcinolone explode all trees

#15 MeSH descriptor Drug Hypersensitivity explode all trees

#16 prednisolone or betamethasone or cortison* or deflazacort or calcort or dexamethasone or hydrocortisone or efcortesol or hydrocortone or solu-cortef or methylprednisolone or solu-medrone or depo-medrone or triamcinolone or kenalog

#17 (#4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16)

#18 (#3 AND #17)

Appendix 2. Search Strategy for MEDLINE (OvidSP)

#1. exp Anaphylaxis/

#2. (anaph?l* or (acute adj3 allerg*)).mp.

#3. #1 or #2

#4. exp Hydrocortisone/ or exp Prednisolone/ or exp Betamethasone 17-Valerate/ or exp Betamethasone/ or exp Clobetasol/ or exp Cortisone/ or exp Anti-Inflammatory Agents/ or exp Immunosuppressive Agents/ or exp Pregnenediones/ or exp Glucocorticoids/ or exp Prednisone/ or exp Dexamethasone Isonicotinate/ or exp Dexamethasone/ or exp Steroids/ or exp Methylprednisolone/ or exp Triamcinolone Acetonide/ or exp Triamcinolone/ or exp Drug Hypersensitivity/

#5. (prednisolone or betamethasone or cortison* or deflazacort or calcort or dexamethasone or hydrocortisone or efcortesol or hydrocortone or solu-cortef or methylprednisolone or solu-medrone or depo-medrone or triamcinolone or kenalog).mp.

#6. #4 or #5

#7. #3 and #6

#8. ((randomized controlled trial or controlled clinical trial).pt. or randomized.ab. or placebo.ab. or clinical trials as topic.sh. or randomly.ab. or trial.ti.) not (animals not (humans and animals)).sh.

#9. #7 and #8

Appendix 3. Search strategy for EMBASE (OvidSP)

#1. exp anaphylaxis/

#2. (anaph?l* or (acute adj3 allerg*)).mp.

#3. #1 or #2

#4. hydrocortisone/ or prednisolone/ or betamethasone valerate/ or betamethasone/ or clobetasol/ or cortisone/ or antiinflammatory agent/ or pregnane derivative/ or glucocorticoid/ or prednisone/ or dexamethasone isonicotinate/ or dexamethasone/ or steroid/ or methylprednisolone/ or triamcinolone acetonide/ or triamcinolone/ or drug hypersensitivity/

#5. (prednisolone or betamethasone or cortison* or deflazacort or calcort or dexamethasone or hydrocortisone or efcortesol or hydrocortone or solu-cortef or methylprednisolone or solu-medrone or depo-medrone or triamcinolone or kenalog).ti,ab.

#6. #4 or #5

#7. #3 and #6

#8. (placebo.sh. or controlled study.ab. or random*.ti,ab. or trial*.ti,ab.) not (animals not (humans and animals)).sh.

#9. #7 and #8

Appendix 4. Search strategy for CINAHL (EBSCOhost)

S1 (MM "Anaphylaxis")

S2 TX anaphyl* or (acute allerg*)

S3 S1 or S2

S4 TX (prednisolone or betamethasone or cortison* or deflazacort or calcort or dexamethasone or hydrocortisone or efcortesol or hydrocortone or solu-cortef or methylprednisolone or solu-medrone or depo-medrone or triamcinolone or kenalog)

S5 (MM "Hydrocortisone") or (MM "Prednisolone") or (MM "Betamethasone") or (MM "Cortisone") or (MM "Antiinflammatory Agents") or (MH "Immunosuppressive Agents+") or (MH "Glucocorticoids") or (MM "Dexamethasone") or (MM "Steroids") or (MM "Methylprednisolone") or (MM "Triamcinolone") or (MH "Drug Hypersensitivity+")

S6 S4 or S5

S7 S3 and S6

S8 TX random* or trial* or multicenter* or ((double or single or triple) and (mask* or blind*)) or placebo*

S9 S7 and S8

History

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Implications for practice
  10. Implications for research
  11. Acknowledgements
  12. Data and analyses
  13. Appendices
  14. What's new
  15. History
  16. Contributions of authors
  17. Declarations of interest
  18. Sources of support
  19. Differences between protocol and review
  20. References

Protocol first published: Issue 1, 2009

Review first published: Issue 3, 2010

DateEventDescription
31 May 2012AmendedContact details updated.
17 April 2012AmendedContact details updated.
6 February 2012New search has been performedWe updated the methods section.
6 February 2012New citation required but conclusions have not changedIn the previous version of our review (Choo 2010) we ran the database searches until September 2009. In this version we re-ran the database searches until September 2011. We found no new studies that fitted our inclusion criteria.
31 August 2010AmendedContact details updated.
17 March 2010AmendedAziz Sheikh's affiliation updated. Acknowledgement section corrected.
8 January 2009Amended

1. Minor edits made to text: correcting typos and inserting three new references in background section: Gupta 2003; Gupta 2007; Sheikh 2008.

2. Order of authors for citation amended. Previously: Sheikh, Simons, Choo; now reads: Choo, Simons, Sheikh

Contributions of authors

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Implications for practice
  10. Implications for research
  11. Acknowledgements
  12. Data and analyses
  13. Appendices
  14. What's new
  15. History
  16. Contributions of authors
  17. Declarations of interest
  18. Sources of support
  19. Differences between protocol and review
  20. References

Conceiving the review: Aziz Sheikh (AS) and Estelle Simons (ES)

Co-ordinating the review: Karen Choo (KC)

Undertaking manual searches: KC

Screening search results: KC and AS

Organizing retrieval of papers: KC

Screening retrieved papers against inclusion criteria: KC and AS

Appraising quality of papers: there were no eligible studies

Abstracting data from papers: there were no eligible studies

Writing to authors of papers for additional information: there were no eligible studies

Providing additional data about papers: there were no eligible studies

Obtaining and screening data on unpublished studies: KC and AS

Data management for the review: KC and AS

Entering data into Review Manager (RevMan 5.1): KC

RevMan statistical data: there were no eligible studies

Other statistical analysis not using RevMan: there were no eligible studies

Double entry of data: there were no eligible studies

Interpretation of data: there were no eligible studies

Statistical inferences: there were no eligible studies

Writing the review: KC, AS, and ES

Securing funding for the review: AS

Performing previous work that was the foundation of the present study: AS and ES

Guarantor for the review (one author): AS

Person responsible for reading and checking review before submission: KC, AS and ES

Sources of support

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Implications for practice
  10. Implications for research
  11. Acknowledgements
  12. Data and analyses
  13. Appendices
  14. What's new
  15. History
  16. Contributions of authors
  17. Declarations of interest
  18. Sources of support
  19. Differences between protocol and review
  20. References

Internal sources

  •          Allergy & Respiratory Research Group, Centre for Population Health Sciences, The University of Edinburgh, UK.

External sources

  • No sources of support supplied

Differences between protocol and review

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Implications for practice
  10. Implications for research
  11. Acknowledgements
  12. Data and analyses
  13. Appendices
  14. What's new
  15. History
  16. Contributions of authors
  17. Declarations of interest
  18. Sources of support
  19. Differences between protocol and review
  20. References

We amended the Types of participants section slightly by including the following additional inclusion criteria: biologics, anaesthetics, exercise, as well as idiopathic disease.

In November 2011 we updated the risk of bias tool.

References

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Implications for practice
  10. Implications for research
  11. Acknowledgements
  12. Data and analyses
  13. Appendices
  14. What's new
  15. History
  16. Contributions of authors
  17. Declarations of interest
  18. Sources of support
  19. Differences between protocol and review
  20. References
  • Additional references
  • Alrasbi 2007
  • Alrasbi M, Sheikh A. Comparison of international guidelines for the emergency medical management of anaphylaxis. Allergy 2007;62:838-41. [MEDLINE: 17620061]
  • Anaphylaxis UK Guidelines
  • Working Group of the Resuscitation Council (UK). Emergency treatment of anaphylactic reactions. Guidelines for healthcare providers. http://www.resus.org.uk/pages/reaction.pdf. 2008.
  • Badger 2004
  • Badger NO, Butler K, Hallman LC. Excessive anticoagulation and anaphylactic after rechallenge with lepirudin in a patient with heparin induced thrombocytopenia. Pharmacotherapy 2004;24:1800-3. [MEDLINE: 15585446]
  • Begg 1994
  • Begg CB, Mazumdar M. Opening characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088-101. [MEDLINE: 7786990]
  • Bock 2001
  • Bock SA, Monoz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. Journal of Allergy and Clinical Immunology 2001;107:191-3. [MEDLINE: 11150011]
  • Bock 2007
  • Bock SA, Munoz-Furlong A, Sampson HA. Further fatalities caused by anaphylactic reactions to food, 2001-2006. Journal of Allergy and Clinical Immunology 2007;119:1016-8. [MEDLINE: 17306354]
  • Brown 2001
  • Brown AFT, McKinnon D, Chu K. Emergency department anaphylaxis: a review of 142 patients in a single year. Journal of Allergy and Clinical Immunology 2001;108:861-6. [MEDLINE: 11692116]
  • Brown 2004
  • Brown SG. Clinical features and grading of anaphylaxis. Journal of Allergy and Clinical Immunology 2004;114:371-6. [MEDLINE: 15316518]
  • Brown 2006
  • Brown SGA, Mullins RJ, Gold MS. Anaphylaxis: diagnosis and management. Medical Journal of Australia 2006;185:283-9. [MEDLINE: 16948628]
  • Chin 2004
  • Chin SM, Fergurson JW, Bajurnows T. Latex allergy in dentistry. Review and report of case presenting as a serious reaction to latex dental dam. Australian Dental Journal 2004;49:146-8. [MEDLINE: 15497359]
  • Clark 2004
  • Clark S, Bock SA, Gaeta TJ, Brennar BE, Cydulka RK, Camargo CA. Multicenter study of emergency department visits for food allergies. Journal of Allergy and Clinical Immunology 2004;113:347-52. [MEDLINE: 14767453]
  • Clark 2005
  • Clark S, Long AA, Gaeta TJ, Camargo CA Jr. Multicenter study of emergency department visits for insect sting allergies. Journal of Allergy and Clinical Immunology 2005;116:643-9. [MEDLINE: 16159637]
  • Confino-Cohen 2010
  • Confino-Cohen R, Goldberg A. Allergen immunotherapy-induced biphasic systemic reactions: incidence, characteristics, and outcome: a prospective study. Annals of Allergy and Asthma Immunology 2010;104:73-8. [MEDLINE: 20143649]
  • Decker 2008
  • Decker WW, Campbell RL, Luke A, St. Stauver JL, Weaver A, Bellolio MF, et al.The etiology and incidence of anaphylaxis in Rochester, Minnesota: A report from the Rochester Epidemiology Project. Journal of Allergy and Clinical Immunology 2008;112:1161-5. [MEDLINE: 18992928]
  • Douglas 1994
  • Douglas DM, Sukenick E, Andrade WP, Brown JS. Biphasic systemic anaphylaxis: an inpatient and outpatient study. Journal of Allergy and Clinical Immunology 1994;93:977-85. [MEDLINE: 8006319]
  • Egger 1997
  • Egger M, Davey-Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-34. [MEDLINE: 9310563]
  • Ellis 2007
  • Ellis AK, Day JH. Incidence and characteristics of biphasic anaphylaxis: a prospective evaluation of 103 patients. Annals of Allergy, Asthma and Immunology 2007;98:64-9. [MEDLINE: 17225722]
  • Gaeta 2007
  • Gaeta TJ, Clark S, Pelletier AJ, Camargo CA. National study of US emergency department visits for acute allergic reactions, 1993 to 2004. Annals of Allergy, Asthma and Immunology 2007;98:360-5. [MEDLINE: 17458433]
  • Greenberger 2007
  • Greenberger PA, Rotskoff BD, Lifschultz B. Fatal anaphylaxis: postmortem findings and associated comorbid diseases. Annals of Allergy, Asthma and Immunology 2007;98:252-7. [MEDLINE: 17378256]
  • Gupta 2003
  • Gupta R, Sheikh A, Strachan DP, Anderson HR. Increasing hospital admissions for systemic allergic disorders in England: analysis of national admissions data. BMJ 2003;327:1142-3. [MEDLINE: 14615340]
  • Gupta 2007
  • Gupta R, Sheikh A, Strachan DP, Anderson HR. Time trends in allergic disorders in the UK. Thorax 2007;62:91-6. [MEDLINE: 16950836]
  • Higgins 2011
  • Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available fromL www.cochrane-handbook.org.
  • Joint Task Force 2005
  • Joint Task Force on Practice Parameters. The diagnosis and management of anaphylaxis: an updated practice parameter. Journal of Allergy and Clinical Immunology 2005;115 Suppl:483-525. [MEDLINE: 15753926]
  • Kemp 2002
  • Kemp SF, Lockey RF. Anaphylaxis: a review of causes and mechanisms. Journal of Allergy and Clinical Immunology 2002;110:341-8. [MEDLINE: 12209078]
  • Korenblat 1999
  • Korenblat P, Lundie MJ, Dankner RE, Day JH. A retrospective study of epinephrine administration for anaphylaxis: how many doses are needed?. Allergy and Asthma Proceedings 1999;20:383-6. [MEDLINE: 10624495]
  • Lieberman 2005
  • Lieberman P. Biphasis anaphylactic reactions. Annals of Allergy, Asthma and Immunology 2005;95:217-26. [MEDLINE: 15753908]
  • Lieberman 2006
  • Lieberman P, Camargo CA, Bohike K, Jike H, Miller RL, Sheikh A, et al.Epidemiology of anaphylaxis: Findings of the ACCAI Epidemiology of Anaphylaxis Working Group. Annals of Allergy, Asthma and Immunology 2006;97:596-602. [MEDLINE: 17165265]
  • Lin 2008
  • Lin RY, Anderson AS, Shah SN, Nurruzzaman F. Increasing anaphylaxis hospitalizations in the first 2 decades of life: New York State, 1990-2006. Annals of Allergy, Asthma and Immunology 2008;101:387-93. [MEDLINE: 18939727]
  • McLean-Tooke 2003
  • McLean-Tooke AP, Bethune CA, Fay AC, Spickett GP. Adrenaline in the treatment of anaphylaxis: what is the evidence?. BMJ 2003;327:1332-5. [MEDLINE: 14656845]
  • Muraro 2007
  • Muraro A, Roberts G, ClarkA, Eigenmann PA, Halken S, Lack G, et al.The management of anaphylaxis in childhood: position paper of the European Academy of Allergology and Clinical Immunology. Allergy 2003;62:857-71. [MEDLINE: 17590200]
  • Neugut 2001
  • Neugut AI, Ghatak AT, Miller RL. Anaphylaxis in the United States. An investigation into its epidemiology. Archives of Internal Medicine 2001;161:15-21. [MEDLINE: 11146694]
  • Orbach 2005
  • Orbach H, Katz U, Sherer Y, Shoenfeld Y. Intravenous immunoglobulin: adverse effects and safe administration. Clinical Reviews in Allergy and Immunology 2005;29:173-84. [MEDLINE: 16391392]
  • Peng 2004
  • Peng MM, Jick H. A population-based study of the incidence, cause and severity of anaphylaxis in the United Kingdom. Archives of Internal Medicine 2004;164:317-9. [MEDLINE: 14769628]
  • Poulos 2007
  • Poulos LM, Waters AM, Correll PK, Loblay RH, Marks GB. Trends in hospitalizations for anaphylaxis, angioedema, and urticaria in Australia, 1993-1994 to 2004-2005. Journal of Allergy and Clinical Immunology 2007;120:878-84. [MEDLINE: 17931562]
  • Pumphrey 2000
  • Pumphrey RS. Lessons for management of anaphylaxis from a study of fatal reactions. Clinical and Experimental Allergy 2000;30:1144-50. [MEDLINE: 10931122]
  • Pumphrey 2003
  • Pumphrey RS. Fatal posture in anaphylactic shock. Journal of Allergy and Clinical Immunology 2003;112:451-2. [MEDLINE: 12897756]
  • Pumphrey 2007
  • Pumphrey RSH, Gowland MH. Further fatal allergic reactions to food in the United Kingdom, 1999-2006. Journal of Allergy and Clinical Immunology 2007;119:1018-9. [MEDLINE: 17349682]
  • RevMan 5.1
  • Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.1 for windows. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.
  • Sampson 1992
  • Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal food anaphylaxis in children. New England Journal of Medicine 1992;327:380-4. [MEDLINE: 1294076]
  • Sampson 2005
  • Sampson HA, Munoz-Furlong A, Bock SA, Schmitt C, Bass R, Chowdhury BA, et al.Symposium on the definition and management of anaphylaxis: summary report. Journal of Allergy and Clinical Immunology 2005;115:584-91. [MEDLINE: 15753908]
  • Sampson 2006
  • Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, et al.Second symposium on the definition and management of anaphylaxis: summary report - Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. Journal of Allergy and Clinical Immunology 2006;117:391-7. [MEDLINE: 16461139]
  • Schleimer 2008
  • Schleimer RP. Pharmacology of glucocorticoids in allergic disease. In: Adkinson NF Jr, Yunginger JW, Busse WW, Bochner BS, Holgate ST, Simons FER editor(s). Middleton's Allergy Principles and Practice. 7th Edition. St Louis: Mosby Inc, 2008:1549-74.
  • Scranton 2009
  • Scranton SE, Gonzalez EG, Waibel KH. Incidence and characteristics of biphasic reactions after allergen immunotherapy. Journal of Allergy and Clinical Immunology 2009;123:493-8. [MEDLINE: 19064282]
  • Sheikh 2001
  • Sheikh A, Alves B. Age, sex, geographical and socio-economic variations in admissions for anaphylaxis: analysis of four years of English hospital data. Clinical and Experimental Allergy 2001;31:1571-6. [MEDLINE: 11678857]
  • Sheikh 2007
  • Sheikh A, ten Broek VM, Brown SGA, Simons FER. H1-antihistamines for the treatment of anaphylaxis with and without shock. Cochrane Database of Systematic Reviews 2007, Issue 1. [DOI: 10.1002/14651858.CD006160.pub2; MEDLINE: 17253584]
  • Sheikh 2008
  • Sheikh A, Hippisley-Cox J, Newton J, Fenty J. Trends in national incidence, lifetime prevalence and adrenaline prescribing for anaphylaxis in England. Journal of the Royal Society of Medicine 2008;101:139-43. [MEDLINE: 18344471]
  • Sheikh 2008b
  • Sheikh A, Shehata YA, Brown SGA, Simons FER. Adrenaline (epinephrine) for the treatment of anaphylaxis with and without shock. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/14651858.CD006312.pub2]
  • Simons 2002
  • Simons FER, Peterson S, Black CD. Epinephrine dispensing patterns for an out-of-hospital population: a novel approach to studying epidemiology of anaphylaxis. Journal of Allergy and Clinical Immunology 2002;110:647-51. [MEDLINE: 12373275]
  • Simons 2004a
  • Simons FER. First aid treatment of anaphylaxis to food: Focus on epinephrine. Journal of Allergy and Clinical Immunology 2004;113:837-44. [MEDLINE: 15131564]
  • Simons 2004b
  • Simons FER. Epinephrine (adrenaline) in the first-aid, out-of-hospital treatment of anaphylaxis. Anaphylaxis. Chichester: Wiley, 2004:228-47.
  • Simons 2004c
  • Simons FER. Advances in H1-antihistamines. New England Journal of Medicine 2004;351:2203-17. [MEDLINE: 15548781]
  • Simons 2006
  • Simons FER. Anaphylaxis, killer allergy: long-term management in the community. Journal of Allergy and Clinical Immunology 2006;117:367-77. [MEDLINE: 16461138]
  • Simons 2007
  • Simons FE, Sheikh A. Evidence-based management of anaphylaxis. Allergy 2007;62:827-9. [MEDLINE: 17620059]
  • Simons 2008
  • Simons FER. Anaphylaxis. 2008 Mini-primer on allergic and immunologic diseases. Journal of  Allergy and Clinical Immunology 2008;121 Suppl:402-7. [MEDLINE: 18241691]
  • Simons 2009
  • Simons FER. Anaphylaxis: Recent advances in assessment and treatment. Journal of Allergy and Clinical Immunology 2009;124:625-36.
  • Smit 2005
  • Smit DV, Cameron PA, Rainer TH. Anaphylaxis presentations to an emergency department in Hong Kong: incidence and predictors of biphasic reactions. Journal of Emergency Medicine 2005;28:381-8. [PUBMED: 15837017]
  • Soar 2008
  • Soar J, Pumphrey R, Cant A, Clarke S, Corbett A, Dawson P, et al.Working Group of the Resuscitation Council (UK). Emergency treatment of anaphylactic reactions: guidelines for healthcare providers. Resuscitation 2008;77:157-69. [PUBMED: 18358585]
  • Stark 1986
  • Stark BJ, Sullivan TJ. Biphasic and protracted anaphylaxis. Journal of Allergy and Clinical Immunology 1986;78:76-83. [MEDLINE: 3722636]
  • Walters 2005
  • Walters BA, Van Wyck DB. Benchmarking iron dextran sensitivity: reactions requiring resuscitative medication in incident and prevalent patients. Nephrology, Dialysis, Transplantation 2005;20:1438-42. [MEDLINE: 15840683]
  • Webb 2006
  • Webb LM, Lieberman P. Anaphylaxis: a review of 601 cases. Annals of Allergy, Asthma and Immunology 2006;97:39-43. [MEDLINE: 16892779]
  • References to other published versions of this review
  • Choo 2010
  • Choo KJL, Simons FER, Sheikh A. Glucocorticoids for the treatment of anaphylaxis. Cochrane Database of Systematic Reviews 2010, Issue 3. [DOI: 10.1002/14651858.CD007596.pub2]