Acute hypersensitivity reactions often create stress and confusion and appropriate training and clear protocols are advisable. In addition, depending on the location where a patient suffers an acute hypersensitivity reaction to contrast media, the available expertise of the personnel that cares for such a patient may differ. Similarly, the availability of equipment and drugs to treat a (possible serious) hypersensitivity (or anaphylactic) reaction will be different. In a radiology or cardiology department the possibilities are different (and usually more limited) than in a department of emergency medicine or on a hospital ward. In addition, different treatments will have variable modes of action. What is the most appropriate management of a patient with an acute hypersensitivity reaction to contrast media?

To answer the clinical question a systematic literature analysis was performed.

P (Patient): patients with acute hypersensitivity reaction after contrast media administration;

I (Intervention): treatment, antihistamines, corticosteroids, epinephrine, adrenalin, dopamine, norepinephrine, noradrenalin, histamine H1 antagonists, histamine H2 antagonists, H1 antihistamines, H2 antihistamines, adrenergic beta-2 receptor agonists, glucocorticoids, management/treatment of hypersensitivity reactions/allergic reactions after contrast media, antihistamines, volume resuscitation, bronchodilators;

C (Comparison): conservative treatment or comparison of interventions mentioned above;

O (Outcomes): duration of acute reaction, severity of complaints, morbidity, mortality, costs, hospitalization in an IC-unit, length of stay.

Relevant outcome measures

The working group considered morbidity, mortality, and hospitalization in an IC-unit, critical outcome measures for the decision-making process, and duration of acute reaction, length of stay and costs important outcomes for the decision-making process.

Methods

The databases Medline (OVID) and Embase were searched from 1^s of January 1985 to 28^th of December 2017 using relevant search terms for systematic reviews (SRs), randomized controlled trials (RCTs) and observational studies (OBS).

Search terms are shown under the Tab “Literature Search”. The literature search procured 328 hits: 20 SR, 64 RCTs and 224 OBS. Based on title and abstract a total of 47 studies were selected. After examination of full text all studies were excluded, and no studies definitely included in the literature summary.

4 studies describing treatment effects of acute adverse reactions were found. Although these studies did not fulfil the search criteria, a short description is included in the literature summary, due to lack of other evidence. Since no control groups were available, no evidence tables or risk of bias tables or conclusions of these studies are included.

The guideline development was assisted by the Knowledge Institute of the Federation Medical Specialists and was financed by the Quality Funds for Medical Specialists (Stichting Kwaliteitsgelden Medisch Specialisten: SKMS).

Goal

The aim of the Part 2 of Safe Use of Contrast Media guidelines is to critically review the present recent evidence with the above trend in mind and tries to formulate new practical guidelines for all hospital physicians to provide the safe use of contrast media in diagnostic and interventional studies. The ultimate goal of this guideline is to increase the quality of care, by providing efficient and expedient healthcare to the specific patient populations that may benefit from this healthcare and simultaneously guard patients from ineffective care. Furthermore, such a guideline should ideally be able to save money and reduce day-hospital waiting lists.

Users

This guideline is intended for all hospital physicians that request or perform diagnostic or interventional radiologic or cardiologic studies for their patients in which CM are involved.

It was challenging to find representation for the patient’s perspective, since the guideline does not discuss a specific group of patients with a disease. The Dutch Kidney Patients Association was invited to participate in an advisory board to the working group, but declined since this subject was not specific enough for them to give adequate input; The Dutch Kidney Patients Association did provide written feedback for specific modules during the commentary phase. The Dutch Kidney Patients Association and the Patient Federation of the Netherlands was invited to participate in the invitational conference in which the framework of the guideline was discussed. Furthermore, the concept guideline has been submitted for feedback during the comment process to the Patient Federation of the Netherlands and the Dutch Kidney Patient Association.

In the different phases of guideline development, the implementation of the guideline, and the practical enforceability of the guideline were taken into account. The factors that could facilitate or hinder the introduction of the guideline in clinical practice have been explicitly considered. The implementation plan can be found with the Related Products. Furthermore, quality indicators were developed to enhance the implementation of the guideline. The indicators can also be found with the Related Products.

AGREE

This guideline has been developed conforming to the requirements of the report of Guidelines for Medical Specialists 2.0 by the advisory committee of the Quality Counsel. This report is based on the AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II) (www.agreetrust.org), a broadly accepted instrument in the international community and on the national quality standards for guidelines: “Guidelines for guidelines” (www.zorginstituutnederland.nl).

Identification of subject matter

During the initial phase of the guideline development, the chairman, working group and the advisor inventory the relevant subject matter for the guideline. Furthermore, an Invitational Conference was organized, where additional relevant subjects were discussed. A report of this meeting can be found in Related Products.

Clinical questions and outcomes

During the initial phase of guideline development, the chairman, working group and advisor identified relevant subject matter for the guideline. Furthermore, input was acquired for the outline of the guideline during an Invitational Conference. The working group then formulated definitive clinical questions and defined relevant outcome measures (both beneficial land harmful effects). The working group rated the outcome measures as critical, important and not important. Furthermore, where applicable, the working group defined relevant clinical differences.

Strategy for search and selection of literature

For the separate clinical questions, specific search terms were formulated and published scientific articles were sought after in (several) electronic databases. Furthermore, studies were scrutinized by cross-referencing for other included studies. The studies with potentially the highest quality of research were looked for first. The working group members selected literature in pairs (independently of each other) based on title and abstract. A second selection was performed based on full text. The databases, search terms and selection criteria are described in the modules containing the clinical questions.

Quality assessment of individual studies

Individual studies were systematically assessed, based on methodological quality criteria that were determined prior to the search, so that risk of bias could be estimated. This is described in the “risk of bias” tables.

Summary of literature

The relevant research findings of all selected articles are shown in evidence tables. The most important findings in literature are described in literature summaries. When there were enough similarities between studies, the study data were pooled.

Grading quality of evidence and strength of recommendations

The strength of the conclusions of the scientific publications was determined using the GRADE-method. GRADE stands for Grading Recommendations Assessment, Development and Evaluation (see http://www.gradeworkinggroup.org/) (Atkins, 2004).

GRADE defines four gradations for the quality of scientific evidence: high, moderate, low or very low. These gradations provide information about the amount of certainty about the literature conclusions. (http://www.guidelinedevelopment.org/handbook/).

Formulating conclusions

For diagnostic, etiological, prognostic or adverse effect questions, the evidence was summarized in one or more conclusions, and the level of the most relevant evidence was reported. For intervention questions, the conclusion was drawn based on the body of evidence (not one or several articles). The working groups weighed the beneficial and harmful effects of the intervention.

Considerations

Aspects such as expertise of working group members, patient preferences, costs, availability of facilities and organisation of healthcare aspects are important to consider when formulating a recommendation. These aspects were discussed in the paragraph Considerations.

Formulating recommendations

The recommendation answers the clinical question and was based on the available scientific evidence and the most relevant considerations.

Constraints (Organisation of healthcare)

During the development of the outline of the guideline and the rest of the guideline development process, the Organisation of healthcare was explicitly taken into account. Constraints that were relevant for certain clinical questions were discussed in the Consideration paragraphs of those clinical questions. The comprehensive and additional aspects of the Organisation of healthcare were discussed in a separate chapter.

Development of quality indicators

Internal (meant for use by scientific society or its members) quality indicators are developed simultaneously with the guideline. Furthermore, existing indicators on this subject were critically appraised; and the working group produces an advice about such indicators. Additional information on the development of quality indicators is available by contacting the Knowledge Institute for the Federation Medical Specialists. (secretariaat@kennisinstituut.nl).

Knowledge Gaps

During the development of the guideline, a systematic literature search was performed the results of which help to answer the clinical questions. For each clinical question the working group determined if additional scientific research on this subject was desirable. An overview of recommendations for further research is available in the appendix Knowledge Gaps.

Comment- and authorisation phase

The concept guideline was subjected to commentaries by the involved scientific societies. The commentaries were collected and discussed with the working group. The feedback was used to improve the guideline; afterwards the working group made the guideline definitive. The final version of the guideline was offered for authorization to the involved scientific societies and was authorized.

References

Brouwers MC, Kho ME, Browman GP, et al. AGREE Next Steps Consortium. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ. 2010;182(18):E839-E842.

Medisch Specialistische Richtlijnen 2.0. Adviescommissie Richtlijnen van de Raad Kwalitieit, 2012. Available at: https://richtlijnendatabase.nl/over_deze_site/richtlijnontwikkeling.html.

Schünemann H, Brożek J, Guyatt G, et al. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available at: http://gdt.guidelinedevelopment.org/central_prod/_design/client/handbook/handbook.html.

Schünemann HJ, Oxman AD, Brozek J, et al. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ. 2008;336(7653):1106-10. Erratum published in: BMJ 2008;336(7654).

Ontwikkeling van Medisch Specialistische Richtlijnen: stappenplan. Kennisinstituut van Medisch Specialisten.

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