The Canadian Association of Radiologists Guidelines for the Prevention of Contrast-induced Nephropathy: A Critical Appraisal

Canadian Association of Radiologists Journal 62 (2011) 238e242 www.carjonline.org

Critically Appraised Topic / E´valuation critique

The Canadian Association of Radiologists Guidelines for the Prevention of Contrast-induced Nephropathy: A Critical Appraisal Luigi Lepanto, MD*, An Tang, MD, Jessica Murphy-Lavallee, MD, Jean-Sebastien Billiard, MD Department of Radiology, Centre Hospitalier de l’Universit e de Montr eal, Montr eal, Qu ebec, Canada

Abstract Objective: The purpose of this study is to critically appraise the Canadian Association of Radiologists (CAR) guidelines on the prevention of contrast-induced nephropathy (CIN). Methods: The Appraisal of Guidelines Research and Evaluation (AGREE) tool is a questionnaire that consists of 23 key items organized in 6 domains (scope and purpose, stakeholder involvement, rigor of development, clarity and presentation, applicability, editorial independence). Four radiologists read the guidelines and completed the questionnaire independently. To assess the quality of the evidence, the articles listed in the bibliography were reviewed, and the following data were collected and tabulated: the type of contrast, the administration route, and the level of evidence (Centre for Evidence Based Medicine, University of Oxford). Results: The highest score was for scope and purpose (92%), whereas the lowest scores were for rigor of development (50%) and applicability (40%). The score for the remaining domains were the following: stakeholder involvement (59%), clarity and presentation (69%), and editorial independence (63%). Although the bibliography of the CAR guidelines list 46 articles, only 33 were deemed pertinent to support the recommendations related to risk stratification or risk reduction of CIN. Only 3 articles dealt specifically with intravenous injection of iodinated contrast. Four articles dealt with ionic contrast, and, in 17 references, the contrast type was not specified. The best evidence (level 1) was in support of risk-reduction recommendations, but, in 8 of the 9 articles cited, the route of administration studied was exclusively intra-arterial. Conclusion: It would be appropriate to revisit the topic of CIN and formulate new guidelines. A formal systematic review of the literature should be undertaken and the data extraction should specifically address contrast type and route of administration, as well as the applicability of any recommendations. Resume Objectif: L’etude visait a` evaluer de fac¸on critique les lignes directrices de l’Association canadienne des radiologistes (CAR) pour la prevention de la nephropathie aux produits de contraste (NPC). Methodes: La grille AGREE (Appraisal of Guidelines Research and Evaluation) consiste en un questionnaire comprenant 23 crite`res organises en six domaines (champ et objectifs, participation des groupes concernes, rigueur d’elaboration, clarte et presentation, applicabilite et independance editoriale). Quatre radiologistes ont lu les lignes directrices et rempli le questionnaire de fac¸on independante. Pour evaluer la qualite des preuves utilisees, les articles de la bibliographie ont fait l’objet d’un examen et les donnees suivantes ont ete recueillies et totalisees: le type de produit de contraste, la voie d’administration et le niveau de preuve (Centre for Evidence Based Medicine, Universite d’Oxford). Resultats: Le score le plus eleve a ete obtenu pour la dimension champ et objectifs (92%), tandis que les scores les plus bas ont ete enregistres pour la rigueur d’elaboration (50%) et l’applicabilite (40%). Les scores obtenus dans les autres domaines sont les suivants: participation des groupes concernes, 59%; clarte et presentation, 69%; independance editoriale, 63%. Bien que la bibliographie des lignes directrices de la CAR compte 46 articles, seuls 33 d’entre eux ont ete juges pertinents pour appuyer les recommandations relatives a` la stratification ou a` la reduction du risque de NPC. Seulement trois articles traitaient specifiquement de l’injection intraveineuse de produits de contraste iodes. Quatre articles traitaient des produits de contraste ioniques, tandis que 17 des articles cites ne precisaient pas le type de produit de contraste utilise. Le niveau de preuve le plus eleve (niveau 1) provient des references liees aux recommandations visant la reduction du risque, mais huit des neuf articles cites ne portaient que sur l’administration par voie intra-arterielle. Conclusion: Il serait opportun de revenir sur la NPC et de formuler de nouvelles lignes directrices. Un examen systematique formel de la documentation devrait eˆtre entrepris. Le processus d’extraction des donnees devrait s’attarder specifiquement au type de produit de contraste * Address for correspondence: Luigi Lepanto, MD, Department of Radiology, Centre Hospitalier de l’Universite de Montreal, 1058, St-Denis Street, Montreal, Quebec H2X 3J4, Canada. E-mail address: [email protected] (L. Lepanto). 0846-5371/$ - see front matter Ó 2011 Canadian Association of Radiologists. All rights reserved. doi:10.1016/j.carj.2010.07.008

CAR guidelines for CIN prevention / Canadian Association of Radiologists Journal 62 (2011) 238e242

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et a` la voie d’administration utilises, ainsi qu’a` l’applicabilite des recommandations formulees. Ó 2011 Canadian Association of Radiologists. All rights reserved. Key Words: Contrast media; Kidney failure; Practice guidelines; Contrast-induced nephropathy; Appraisal of Guidelines Research and Evaluation (AGREE); Radiology

Introduction Clinical guidelines play an important role in the practice of medicine. Formalized practice guidelines attempt to elevate the quality of medical care by identifying those practices, supported by evidence, that are in the best interests of the patients. An important aspect of this process is the appraisal of guidelines on a regular basis to guarantee that the recommended practices are in keeping with the evolution of knowledge and to modify the guidelines accordingly when necessary. Contrast-induced nephropathy (CIN) has become a topic of intense interest, in large part because of an ever-increasing number of patients who receive intravenous injection of iodinated contrast for computed tomography studies. Because of the risk posed by an evergrowing number of patients subjected to intravenous contrast agents, the Canadian Association of Radiologists (CAR) decided to form a committee charged with developing guidelines for practicing radiologists [1]. Appraisal of Guidelines Research and Evaluation (AGREE) is an international collaboration whose goal is to improve the quality and effectiveness of clinical practice guidelines by establishing a framework for their development, reporting, and assessment. A product of this collaboration is the development of an appraisal instrument for assessing the methodological quality of clinical practice guidelines (The AGREE Collaboration, AGREE Instrument, www.agreecollaboration.org). Although this tool is a very useful guide, it does not assess the quality of the evidence used to elaborate the guidelines. The purpose of this study was to

critically appraise the CAR guidelines on the prevention of CIN. This will be done in 2 steps: first, the AGREE appraisal tool will be applied to assess the guidelines, and second, the bibliography submitted as evidence within the guidelines will be appraised. Methods The AGREE tool is a questionnaire that consists of 23 key items organized into 6 domains (Table 1). Each domain is intended to capture a separate dimension of guideline quality. The 6 domains are the following: scope and purpose, stakeholder involvement, rigor of development, clarity and presentation, applicability, and editorial independence. It is recommended that the appraisal be carried out by at least 2 appraisers and preferably 4. In this case, 4 appraisers participated in the evaluation (ie, the authors). The appraisers are radiologists specialized in abdominal imaging, with 5-20 years of experience. Each item is rated on a 4-point scale that ranges from 4 (‘‘strongly agree’’) to 1 (‘‘strongly disagree’’), with 2 mid points (3 [‘‘agree’’] and 2 [‘‘disagree’’]). The scale measures the extent to which a criterion (item) has been fulfilled. For each item, there is the opportunity for an appraiser to include comments. Domain scores can be calculated by summing up all the scores of the individual items in a domain and by standardizing the total as a percentage of the maximum possible score for that domain. The 4 appraisers were instructed to read the guidelines thoroughly. They were then instructed to complete the AGREE

Table 1 The Appraisal of Guidelines Research and Evaluation (AGREE) tool for the appraisal of clinical practice guidelines Scope and purpose

Stakeholder involvement

Rigor of development

Clarity and presentation

Applicability

Editorial independence

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23.

The overall objective(s) of the guideline is (are) specifically described. The clinical question(s) covered by the guideline is (are) specifically described. The patients to whom the guideline is meant to apply are specifically described. The guideline development group includes individuals from all the relevant professional groups. The patients’ views and preferences have been sought. The target users of the guideline are clearly defined. The guideline has been piloted among end users. Systematic methods were used to search for evidence. The criteria for selecting the evidence are clearly described. The methods used for formulating the recommendations are clearly described. The health benefits, adverse effects, and risks have been considered in formulating the recommendations. There is an explicit link between the recommendations and the supporting evidence. The guideline has been externally reviewed by experts before its publication. A procedure for updating the guideline is provided. The recommendations are specific and unambiguous. The different options for management of the condition are clearly presented. Key recommendations are easily identifiable. The guideline is supported with tools for application. The potential organizational barriers in applying the recommendations have been discussed. The potential cost implications of applying the recommendations have been considered. The guideline presents key review criteria for monitoring and/or audit purposes. The guideline is editorially independent from the funding body. Conflicts of interest of guideline development members have been recorded.

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appraisal form, consulting the guidelines when necessary to assess the different items. The appraisals were conducted independently, and the final results were collated by 1 of the authors. To assess the quality of the evidence, the articles listed in the bibliography were reviewed, and the following data were collected and tabulated: (1) the type of contrast used; (2) the administration route of the contrast; and (3) the level of evidence (Centre for Evidence Based Medicine, University of Oxford). The articles were subdivided into 2 groups by 1 of the authors. The articles in the first group were referenced in the guidelines to support recommendations on risk identification and stratification [2e18]. The second group of articles supported recommendations on risk reduction (ie, fluid administration, choice of contrast, and pharmacologic prevention) [19e34]. Each article was assessed by 1 of 3 authors, and the results were tabulated by the remaining author.

Table 2 Appraisal of Guidelines Research and Evaluation (AGREE) tool applied to the Canadian Association of Radiologists (CAR) guidelines for the prevention of contrast-induced nephropathy Item Scope and purpose

1 2 3

4 4 4

3 3 2

4 4 4

4 4 4

92

4 5 6 7

3 1 4 1

4 1 3 3

4 1 4 1

3 1 3 1

59

8 9 10 11 12 13 14

2 1 1 2 3 1 1

2 2 2 3 4 1 1

3 1 2 4 4 1 1

2 1 2 4 3 1 1

50

15 16 17 18

3 4 4 4

2 4 3 1

3 4 4 3

3 4 4 1

69

19 20 21

1 1 1

2 1 2

4 1 3

1 1 1

40

Editorial 22 independence 23

4 1

4 1

3 2

4 1

63

Stakeholder involvement

Rigor of development

Results The scores from each appraiser for each of the 23 items evaluated are summarized in Table 2. The overall score for each domain is also shown, expressed as a percentage of the maximum possible score. The highest score was given for the description of scope and purpose (score, 92%). The clinical question and the objectives of the guidelines were clearly stated. With regard to stakeholder involvement (score, 59%), the weakest aspects related to the absence of any evaluation of patients’ views and preferences, as well as the absence of a pilot program to evaluate the guidelines before general dissemination. The score for rigor of development was 50%. As stated in the methodology of the guidelines document, 2 of the authors used the existing guidelines in a number of radiology departments from 5 Canadian cities as a starting point, and, after an in-depth literature search with critical review, a consensus document was drawn up. This working document then was discussed by a panel, and a final consensus document was produced. Although the terms in-depth search and critical review are used, there is no explicit description of the literature review process. No formal methodology is described, and no external review process was described in validating the guidelines. No procedure is proposed in the document for updating the guidelines. Where explicit references are used, an explicit link was made between recommendation and supporting evidence. The score for clarity and presentation was 69%. The AGREE document suggests the distribution of tools (eg, forms) to aid in the application of the guidelines; although clear tables and algorithms are provided in the guidelines document, no addition material is available. The lowest score was assigned for applicability (score, 40%). The logistics of dealing with patients in the context of outpatient examinations for computed tomography with intravenous infusion, in the view of the appraisers, was not adequately assessed. Also, a clear distinction was not made between intravenous and intraarterial injection of iodinated contrast, both in terms of the pertinence of the supporting evidence and the application of the guidelines. Editorial independence received a score of 63% only because no specific mention is made of the possibility or

Appraiser Appraiser Appraiser Appraiser Domain 1 2 3 4 score, %

Clarity and presentation

Applicability

absence of potential conflicts of interest. There is no reason to believe, however, that conflicts of interest were present. The results of the appraisal of the pertinent articles cited in the text of the guidelines are summarized in Tables 3e5. Although the bibliography of the CAR guidelines lists 46 articles, only 33 were deemed pertinent to support the recommendations related to risk stratification or risk reduction of CIN. With regard to the route of contrast administration (Table 3), only 3 articles deal specifically with intravenous injection of iodinated contrast, whereas 17 articles report findings after intra-arterial injection. In 9 articles, the route of administration is not specified. Some of these articles, as well as those that reported on patients having received either intravenous or intra-arterial injections, are review articles or expert opinions. With regard to contrast type (Table 4), 4 articles deal with ionic contrast, and, in 17 Table 3 Route of contrast administration: articles referenced in the Canadian Association of Radiologists (CAR) guidelines on contrast-induced nephropathy Route of administration

Risk stratification references Risk reduction references

Intravenous

Intra-arterial

Either

Not specified

11,16

3,4,6e9,12e14

1,2,5

10,15,17

19

21,22,25,27, 28,30,31,33

23

18,20,24,26, 29,32

CAR guidelines for CIN prevention / Canadian Association of Radiologists Journal 62 (2011) 238e242 Table 4 Contrast type: articles referenced in the Canadian Association of Radiologists (CAR) guidelines on contrast-induced nephropathy Contrast type Ionic

Nonionic

Table 5 Levels of evidence (Centre for Evidence Based Medicine, University of Oxford): articles referenced in the Canadian Association of Radiologists (CAR) guidelines on contrast-induced nephropathy Levels of evidence

Either Not specified

Risk 3,6 4,9,16 8,14 stratification Risk 21,25 22,23,27,28,30,31,33 reduction

1a,b,c

1,2,5,7,10e13,15,17 18e20,24,26,29,32

references, the contrast type is not specified. The best evidence (Table 5) is in support of risk-reduction recommendations, with 9 articles assessed as level 1. However, in 8 of these articles, the route of administration studied is exclusively intra-arterial. In the remaining article, patients with either intra-arterial or intravenous administration were studied, but most received contrast by the intra-arterial route. Discussion The time and effort put into establishing clinical practice guidelines is often done on a voluntary basis. The authors of the CAR practice guidelines on CIN are to be commended for their contribution. The importance of clinical guidelines has long been recognized and is behind the creation of the AGREE Collaboration. AGREE is an international collaboration of researchers and policy makers who seek to improve the quality and effectiveness of clinical practice guidelines by establishing a shared framework for their development, reporting, and assessment. The appraisal tool developed by this collaboration will aid in improving existing guidelines and guide the formulation of new ones. Assessing the validity of the tool is beyond the scope of this article, but there is ongoing work by the AGREE Next Steps Consortium to refine the tool and validate its use. In a recent publication, researchers evaluated the usefulness of the items in the appraisal instrument and found that quality ratings of the AGREE domains were significant predictors of outcome measures associated with guideline adoption [35,36]. Since the publication of the CAR guidelines on contrast nephropathy in 2007, several studies and reviews have been published on the topic. In the radiology literature, some investigators’ findings raise doubts about the true incidence of CIN [37,38]. This is based on the observation that creatinine elevation can be accounted for by the background fluctuation of kidney function, underlying disease, or treatment. Other investigators have found that long-term adverse effects are rare after intravenous administration of contrast agents for computed tomography studies [39]. Several prospective, randomized trials that compared the incidence of CIN with different contrast agents indicate that the incidence is lower when the route of contrast agent administration is intravenous rather than intra-arterial [40e44]. The CIN Consensus Working Panel stated the following: intra-arterial administration of contrast media may be associated with a greater risk for CIN above that observed with intravenous administration [45].

241

2a,b,c 3a,b,c 4

Risk 8 4e7,13 9 stratification Risk 21e23,25,27, reduction 28,30,31,33

5

1e3,11,12,14e17 10 18,19

20,24,26,29,32

With respect to the CAR guidelines on contrast nephropathy, rigor of development and applicability are the dimensions that scored the lowest on the appraisal tool. Evidence-based practice requires that appropriate literature search and bibliographic research methods be applied in the evaluation of a specific clinical question. Aside from reviewing specific randomized controlled trials, systematic reviews and existing practice guidelines can be consulted. Our analysis shows that the evidence level of the references cited in the guidelines document is variable. In the case of intravenously administered contrast, the supporting evidence is scarce and poor in quality. The failure to distinguish between intravenous and intra-arterial injection of contrast agent is a shortcoming. Although only a few articles in the bibliography of the guidelines deal with ionic contrast, the fact that this is rarely if ever used in today’s practice questions the validity of the evidence used. More importantly, in a significant number of the references cited, neither the type of contrast (ionic or nonionic) nor the route of administration is specified. It is clear that, in a revision of the guidelines, these must be specifically addressed. Applicability of any practice guidelines is an important issue. The logistics involved in screening patients for predisposing factors to renal disease referred for medical imaging can be quite onerous. The impact on health professionals and patients alike must be taken into account. Guidelines that are impractical to apply will, ultimately, be ignored. A pilot program to study appropriateness in the clinical context and feasibility are excellent strategies to avoid difficulties in application of recommended guidelines. In conclusion, it is important to emphasize that the purpose of our appraisal is to offer constructive criticism on a process that must be ongoing. New evidence will always be produced and must be incorporated within existing guidelines. In our view, it would be appropriate to revisit the topic of CIN and formulate new guidelines. A formal systematic review of the literature must be undertaken, and the data extraction should specifically address contrast type and route of administration, as well as the applicability of any recommendations. References [1] Benko A, Fraser-Hill M, Magner P, et al. Canadian Association of Radiologists: consensus guidelines for the prevention of contrastinduced nephropathy. Can Assoc Radiol J 2007;58:79e87.

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