Nefrotoxiciteit van GBCA
Uitgangsvraag
Hoe kan post-contrast acute nierschade (PC-AKI) worden voorkomen bij toediening van Gadolinium-Based Contrast Agents (GBCA)?
Subvragen
1. Is toediening van GBCA geassocieerd met een toegenomen risico op PC-AKI vergeleken met placebo/niet-versterkte beeldvorming?
2. Is er een verschil in het risico op PC-AKI tussen hoge en lage dosering GBCA?
3. Is er een verschil in het risico op PC-AKI tussen verschillende GBCA?
Aanbeveling
Maak een individuele risico-batenanalyse met de aanvragende arts en nefroloog van de patiënt om te zorgen voor een strikte indicatie voor gadolinium-versterkte MRI met lineaire GBCA bij patiënten met eGFR < 30 ml/min/1,73m2.
Gebruik de optimale GBCA dosis gebaseerd op gewicht van de patiënt die nodig is om een diagnostische MRI te verrichten in lokale doseringsprotocollen.
Pas geen profylactische maatregelen toe om PC-AKI te voorkomen bij hoog-risico patiënten (eGFR<30ml/min/1.73m2) die GBCA IV krijgen in een standaarddosis.
Vervang geen ICM door GBCA om PC-AKI te voorkomen bij CT en/of DSA.
Overwegingen
Compared to the large amount of literature of the incidence and prevention of PC-AKI after administration of Iodine-based contrast media (ICM), little is known on this subject after administration of GBCA. In general, it is said that GBCA are less nephrotoxic than ICM, and the above-described literature seems to acknowledge that.
It is generally recommendable to use the lowest GBCA dose needed to achieve a diagnostic examination, and usually the standard dose of 0.1 mmol/kg suffices for most clinical indications (ESUR 2017).
Looking more deeply into the chemistry of CM and the results of experimental studies, another picture emerges (Nyman, 2002). First of all, ICM concentrations are expressed in mgI/ml and GBCA concentrations in mmol/ml, a fundamental difference. One mol of Iodine atoms corresponds to 126.9g of I, whereas 1 mol of Gd atoms corresponds to 157.3g of Gd. As most of the commercially available GBCA are 0.5mmol/ml, they thus contain 78.65 mg/ml of Gd. When it comes to Iodine, 0.5mmol/ml I, corresponds to 63mgI/ml. But ICM are usually used in concentrations ranging from 300mg/ml - 400mg/ml, i.e. 2.36mmol/ml - 3.15 mmol/ml. The commercially available iodine doses are thus much higher than the commercially available gadolinium doses (Nyman, 2002).
Furthermore, GBCA contain one attenuating Gd atom per molecule, whereas ICM monomers contain 3 attenuating I atoms per molecule and ICM dimers contain 6 attenuating I atoms per molecule. The combination of more attenuating atoms per molecule and the difference in attenuation of Gd and I at different photon energies, results in the fact that at 120 kVp CT, approximately 110mgI/ml monomer equally attenuates with 0.5mmol/ml Gd. At 80kVp CT, approximately 95mgI/ml monomer equally attenuates with 0.5mmol/ml Gd (Nyman 2002). For DSA a concentration of 60 to 80mg/ml I monomer, produces the same attenuation as 0.5mmol/l GBCA at commonly used 70-90 kVp range (Nyman, 2002).
Thus, in order to achieve the same amount of attenuation in CT with an ICM monomer 300mg/ml, a triple Gd 0.5mmol/ml dose has to be administered. This also means that DSA attenuation produced by an ICM monomer 300mg/ml is achieved with a 4 - 5 times higher Gd 0.5mmol/ml dose. The above results show that changing from ICM to GBCA in CT and DSA is not a safe option due the 3 to 5 times higher GBCA doses necessary to achieve the same amount of attenuation.
Therefore, the working group concludes that, especially in interventional radiology, using GBCA would potentially lead to more harmful effects compared to ICM, and would not recommend substituting ICM with GBCA. This is in line with a systematic review in which the authors concluded that GBCA does not appear to be safer than iodinated contrast in patients at risk of PC-AKI (Boyden, 2008).
As the dose to achieve significant enhancement for GBCA in MRI is much lower as in CT and DSA, it is not a surprise that the small amount of available literature shows no indication of PC-AKI after the administration of GBCA at the recommend standard dose of 0,1 mmol/kg.
Therefore, the working group sees no additive value in using any prophylactic measures (such as hydration, as described in part 1 of the guideline), and recommends not to use any. A recent Canadian guideline on GBCA in chronic kidney disease states that a standard dose of GBCA in patients with eGFR 30 to 60 is safe and no additional measures are necessary. In patients with eGFR <30 ml/min/1.73m2 and patients on dialysis, administration of GBCA should be considered individually (Schieda, 2019). Thus an individual risk-benefit analysis with the patient’s requesting physician and nephrologist should be made to ensure a strict indication for gadolinium-enhanced MRI with linear agents in patients with eGFR < 30 ml/min/1.73m2.
Onderbouwing
Achtergrond
From laboratory testing on cell lines and animals, it is known that Gd chelates are nephrotoxic. In daily practice, this nephrotoxicity is not an issue, as the required dose of these chelates is usually too low to lead to nephrotoxicity in patients.
Conclusies
|
Very low GRADE |
Administration of macrocyclic gadolinium-based contrast agents does not seem to be associated with an increased risk of PC-AKI.
Sources: (Deray, 2013; Kroencke 2001; Tombach 2001; Tombach 2002) |
|
Very low GRADE |
Administration of linear gadolinium-based contrast agents does not seem to be associated with an increased risk of PC-AKI.
Sources: (Broome 2007; Deray, 2013; Gok Oguz, 2013; Kittner 2007; Naito 2017; Townsend, 2000; Trivedi, 2009) |
|
Very low GRADE |
It is unknown whether administration of macrocyclic gadolinium-based contrast agents is associated with an increased requirement of dialysis.
Source: (Deray, 2013) |
|
Very low GRADE |
It is unknown whether administration of linear gadolinium-based contrast agents is associated with an increased requirement of dialysis.
Source: (Townsend, 2000) |
|
Very low GRADE |
There seems to be no dose-response association between macrocyclic gadolinium-based contrast agents and PC-AKI.
Sources: (Kroencke, 2001; Tombach, 2001; Tombach, 2000) |
|
Very low GRADE |
There seems to be no dose-response association between gadolinium-based contrast agents and PC-AKI.
Sources: (Broome 2007; Kittner 2007) |
|
Very low GRADE |
It is unknown whether there is a difference in the risk of PC-AKI between different gadolinium based contrast agents
Source: (Naito, 2017) |
Samenvatting literatuur
1. Gadolinium- Based Contrast Agents versus placebo/unenhanced imaging
Macrocyclic GBCA
Deray (2013) describe a prospective multicentre non-randomized study, comparing the renal safety of Gd-DOTA (macrocyclic GBCA) enhanced MRI with non-enhanced MRI in 114 patients with eGFR 15 - 60 ml/min/1.73 m2(Deray, 2013).Gd-DOTA was injected intravenously by a power injector at a dose of 0.1 mmol/kg. PC-AKI was defined as an increase in SC of at least 25% or 44.2mmol/kg above the baseline value. Serum creatinine levels were measured 72±24 hours after the MRI.
Linear GBCA
In a randomized controlled trial by Townsend (2000) 32 patients were included. They were divided into 2 categories, eGFR 30-60 (group 1) and eGFR 10 to 29 ml/min/1.73m2 (group 2) (Townsend, 2000). Patients in both groups were randomized to be infused with either Gd-BOPTA (linear GBCA) or saline, both at a dose of 0.2 mmol/kg. Both groups maintained saline infusion after the initial bolus and received a total of 250-300 ml saline. No MRI took place after the injection. PC-AKI was defined as an increase in serum creatinine (SC) > 44,2 µmol/l above the baseline value. SC was measured before the injection and for 7 consecutive days after the injection. In group 1, 9 patients received Gd and 6 saline, in group 2, 11 patients received Gd and 6 saline.
Gok Oguz (2013) describes 144 patients with 1 or more risk factors for AKI (advanced age (> 75 years), diabetes mellitus, chronic kidney disease, congestive heart failure, using other nephrotoxins, and hypotension) in a prospective case-control study (Gok Oguz, 2013). Patients were divided into 2 groups, but the article does not state clearly what the criteria are to be included in either one of the groups. All 72 patients (mean eGFR 36 ml/min/1.73m2) in group 1 received intravenous injection with Gd-DTPA (linear GBCA), whereas all 72 patients (mean eGFR 39 ml/min/1.73m2) in group 2 received no Gd contrast. PC-AKI was defined as an increase of SC of at least 26.4 µmol/l or ≥ 50% from baseline. Before the MRI and at 6 h, 24 h, 72 h, and 168 h after the MRI, SC was measured.
Trivedi (2009) describe a retrospective study that included 162 patients who underwent MRI with gadodiamide (linear GBCA) and 125 controls that underwent unenhanced MRI (Trivedi, 2009). Patients were included when SC measurements were available during 7 days preceding MRI and 48 to 72 hours after MRI. Baseline eGFR was 103.1 +/- 49.5 ml/min/1.73m2 in the group receiving Gd and 103.4 +/- 48.4 ml/min/1.73m2 in the control group. PC-AKI was defined as SC >44.2 micromol/l compared to baseline.
Results
Outcome Post-Contrast Acute Kidney Injury (PC-AKI)
Four studies (Townsend, 2000, Deray, 2013, Gok Oguz, 2013 and Trivedi, 2009) reported on the incidence of PC-AKI after administration of GBCA. Due to the heterogeneity in study designs the results were not pooled.
Macrocyclic GBCA
Deray (2013) reported PC-AKI in one patient after injection with macrocyclic Gd-DOTA (1.4%).
Linear GBCA
There were no cases of PC-AKI in the studies Gok Oguz (2013), Townsend (2000) and Trivedi (2015) using a variety of linear GBCA.
Quality of evidence
The quality of certainty of evidence was graded as very low due to high risk of bias (see Table Risk of Bias assessment, downgraded by one point) and low number of patients (imprecision downgraded by two points).
Outcome Dialysis
Two studies reported on the requirement of dialysis after administration of GBCA. Both studies (Townsend, 2003 (linear GBCA) and Deray, 2013 (Macrocyclic GBCA)) reported that no subjects required dialysis.
Quality of evidence
The quality of certainty of evidence was graded as very low due to the low number of patients (imprecision downgraded by two points).
No studies reported on the outcome mortality.
2. High versus low dose of Gadolinium-Based Contrast Agents
Macrocyclic GBCA
Kroencke (2001) randomized 94 patients with suspected abnormality of the abdominal aorta or renal arteries to MR angiography after the IV injection of one of four doses of gadobenate dimeglumine (0.025, 0.05, 0.1, and 0.2 mmol/kg of body weight), a macrocyclic GBCA (Kroencke, 2001). SC was obtained pre-dose and at the 24-hr follow-up examination.
Tombach (2001) describe 21 patients in a randomized controlled, open-label trial. Patients were classified into two subgroups according to their creatinine clearance: group 1 (n=12), eGFR 30 to 80 ml/min/1.73m2 and group 2 (n =9), eGFR<30 ml/min/1.73m2(Tombach, 2001). Then, patients were randomly assigned to receive the higher dose of 0.3 mmol/kg of the macrocyclic GBCA gadobutrol (group 1, n=6/12; group 2, n=4/9) or the lower dose of gadobutrol of 0.1 mmol/kg (group 1, n=6/12; group 2,n=5/9). Changes in vital signs, clinical chemistry, and urinalysis results, including creatinine clearance, were monitored before, at 6 hours, and then every 24 hours until 72 hours (group 1) or 120 hours (group 2) after intravenous injection of gadobutrol.
Tombach (2002) enrolled 11 patients with end-stage renal failure who required haemodialysis treatment (Tombach, 2002). Purpose of the study was to assess the safety and dialysability of gadobutrol. Gadobutrol (1 mol/L) was injected intravenously at randomly assigned doses of either 0.3 or 0.1 mmol of gadolinium per kilogram of body weight for contrast-enhanced MR imaging.
Linear GBCA
Kittner(2007) randomized patients with suspected renal artery stenosis to 0.01, 0.05, 0.1, or 0.2 mmol/kg of the linear GBCA gadodiamide (n=69, 67, 69 and 61, respectively) (Kittner, 2007).Safety of gadodiamide was monitored by comparing the data of 12-lead ECGs, vital signs (blood pressure, body temperature, heart and respiratory rate), serum biochemistry (including renal parameters), and physical examinations collected immediately before and 24 h after gadodiamide administration.
Broome (2007) retrospectively studied the dialysis and MRI records (Broome, 2007). One hundred eighty six dialysis patients underwent 559 MRI exams; including 301 Gd enhanced MRI between 2000 and 2006. The linear GBCA gadodiamide was the sole Gd chelate used in either 0.1 mmol/kg or 0.2 mmol/kg.
Results
Outcome Post-Contrast Acute Kidney Injury (PC-AKI)
Five studies reported on the incidence of PC-AKI (Kroencke, 2001; Tombach, 2001, Tombach, 2002, Kittner, 2007 and Broome 2007). All five studies reported no cases of PC-AKI, using either linear or macrocyclic GBCA.
Quality of evidence
The quality of certainty of evidence was graded as very low due to high risk of bias (see Table Risk of Bias assessment, downgraded by one point) and the low number of patients (imprecision downgraded by two points).
No studies reported on the outcomes dialysis and mortality.
3. Nephrotoxicity of different gadolinium-based contrast agents
One study investigated the difference in nephrotoxicity between different gadolinium-based contrast agents.
Naito (2017) describes a prospective randomized study including 102 patients that were randomized to either receive 0.1 mmol/kg gadodiamide (linear GBCA) or 0.1 mmol/kg Gd-DTPA (linear GBCA) (Naito, 2017). eGFR in the gadodiamide group was 90.5 +/- 19.5 ml/min/1.73m2 and 94.1 +/- 26.4 ml/min/1.73m2 in the Gd-DTPA group. SC was measured 16-80 hour after the procedure. PC-AKI was defined as SC ≥ 44.2 micromol/l or ≥ 30% above baseline.
Results
Outcome Post-Contrast Acute Kidney Injury (PC-AKI)
In both groups, no PC-AKI occurred.
Quality of evidence
The quality of certainty of evidence was graded as very low due to high risk of bias (see Table Risk of Bias assessment, downgraded by one point) and the low number of patients (imprecision downgraded by two points).
No studies reported on the outcomes: dialysis and mortality.
Zoeken en selecteren
To answer our clinical question a systematic literature analysis was performed.
P (Patient) Patients who received Gadolinium-Based Contrast Agents (GBCA).
I (Intervention) Gadolinium based contrast agents, gadoterate meglumine, gadodiamide, gadobenate dimeglumine, gadopentetate dimeglumine, gadoteridol, gadoversetamide, gadobutrol.
C (Comparison) No GBCA or another type of GBCA, gadoterate meglumine, gadodiamide, gadobenate dimeglumine, gadopentetate dimeglumine, gadoteridol, gadoversetamide, gadobutrol.
O (Outcomes) Nephrotoxicity (acute and permanent), dialysis, mortality.
Relevance of outcome measures
The working group considered the outcomes nephrotoxicity, mortality and dialysis critical measures and outcome for the decision-making process.
The working group did not define the criteria for the outcomes a priori, but used the outcomes as defined in the studies. The working group considered a clinically relevant difference according to the standards of GRADE: a difference in relative risk of 25% for dichotomous outcomes and a difference of 10% for continuous outcomes (GRADE handbook, web-link in references).
Methods
The databases Medline (OVID), Embase and the Cochrane Library were searched from 1st of January 1996 to March 2018 using relevant search terms for systematic reviews (SRs), randomized controlled trials (RCTs) and observational studies (OBS). The literature search produced 245 hits: 22 SR, 51 RCTs and 172 OBS. Based on title and abstract a total of 15 studies were selected. After examination of full text 7 articles were selected: 4 for subquestion 1, 2 for subquestion 2 and 1 for subquestion 3. Reasons for exclusion are reported in exclusion table (under the Tab “exclusion table”). The most relevant study characteristics of the included studies can be found in the evidence tables.
Referenties
- Boyden TF, Gurm HS. Does gadolinium-based angiography protect against contrast-induced nephropathy?: A systematic review of the literature. Catheter Cardiovasc Interv 2008; 71: 687 – 693.
- Broome DR, Girguis MS, Baron PW, Cottrell AC, Kjellin I, et al. Gadodiamide-associated nephrogenic systemic fibrosis: why radiologists should be concerned. AJR Am J Roentgenol 2007; 188: 586–592.
- Deray G, Rouviere O, Bacigalupo L, Maes B, Hannedouche T, et al. Safety of meglumine gadoterate (Gd-DOTA)-enhanced MRI compared to unenhanced MRI in patients with chronic kidney disease (RESCUE study). Eur Radiol 2013; 23: 1250–1259.
- Gok Oguz E, Kiykim A, Turgutalp K, Olmaz R, Ozhan O, Muslu N, Horoz M, Bardak S, Sungur MA. Lack of nephrotoxicity of gadopentetate dimeglumine-enhanced non-vascular MRI and MRI without contrast agent in patients at high-risk for acute kidney injury. Med Sci Monit 2013; 19: 942-8.
- GRADE handbook: https://gdt.gradepro.org/app/handbook/handbook.html
- Kittner T, Rudolf J, Fages JF, Legmann P, Aschauer M, Repa I, et al. Efficacy and safety of gadodiamide (Gd-DTPA-BMA) in renal 3D-magnetic resonance angiography (MRA): a phase II study. Eur J Radiol. 2007; 64: 456-64.
- Kroencke TJ, Wasser MN, Pattynama PM, Barentsz JO, Grabbe E, Marchal G, et al. Gadobenate dimeglumine-enhanced MR angiography of the abdominal aorta and renal arteries. AJR Am J Roentgenol. 2002; 179: 1573-1582.
- Naito S, Tazaki H, Okamoto T, Takeuchi K, Kan S, Takeuchi Y, Kamata K. Comparison of nephrotoxicity between two gadolinium-contrasts, gadodiamide and gadopentetate in patients with mildy diminished renal failure. J Toxicol Sci 2017; 42: 379 – 384.
- Nyman U, Elmståhl B, Leander P, Nilsson M, Golman K, Almén T. Are Gadolinium-based contrast media really safer than iodinated media for digital subtraction angiography in patients with azotemia? Radiology 2002; 223: 311- 318.
- Schieda N, Maralani PJ, Hurrell C, Tsampalieros AK, Hiremath S. Updated clinical practice guideline on use of Gadolinium-Based Contrast Agents in kidney disease issued by the Canadian Association of Radiologists. Can Assoc Radiol J 2019; in press. doi: 10.1016/j.carj.2019.04.001Tombach B, Bremer C, Reimer P, Kisters K, Schaefer RM, Geens V, Heindel W.Renal tolerance of a neutral gadolinium chelate (gadobutrol) in patients with chronic renal failure: results of a randomized study. Radiology 2001; 218(3): 651-7.
- Tombach B, Bremer C, Reimer P, Matzkies F, Schaefer RM, Ebert W, Geens V, Eisele J, Heindel W. Using highly concentrated gadobutrol as an MR contrast agent in patients also requiring hemodialysis: safety and dialysability. AJR Am J Roentgenol. 2002; 178: 105-9.
- Townsend RR, Cohen DL, Katholi R, Swan SK, Davies BE, Bensel K, Lambrecht L, Parker J. Safety of intravenous gadolinium (Gd-BOPTA) infusion in patients with renal insufficiency. Am J Kidney Dis. 2000; 36:1207-12.
- Trivedi H, Raman L, Benjamin H, Batwara R. Lack of nephrotoxicity of gadiodiamide in unselected hospitalized patients. Postgrad Med 2009; 121: 166 – 170.
Evidence tabellen
Table of Exclusions after reading full text
|
Author and Year |
Reason of exclusion |
|
Belling 2002 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Cochran 2002 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Cohan 1997 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Conner 2017 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Conner 2017 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Davenport 2012 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Ding 2018 |
Does not discuss treatment of extravasation |
|
Ding 2018 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Earhart 2011 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Fallscheer 2007 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Kim 2017 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Kim 2017 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Nicola 2016 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Rose 2015 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Sbitany 2010 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Schaverien 2008 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Schummer 2010 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Sonis 2017 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Sonis 2017 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Sum 2006 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Tonolini 2012 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Tonolini 2016 |
No comparison therapies. Letter tot the editor on the occasion of Nicola 2016 |
|
Tsai 2007 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Vandeweyer 2000 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Wang 2007 |
Does not fulfil selection criteria. No control group. Descriptive. |
|
Wilson 2011 |
Does not fulfil selection criteria. No control group. Descriptive. |
Verantwoording
Autorisatiedatum en geldigheid
Laatst beoordeeld : 24-06-2020
Laatst geautoriseerd : 24-06-2020
Geplande herbeoordeling : 01-01-2025
Validity
The board of the Radiological Society of the Netherlands will determine at the latest in 2024 if this guideline (per module) is still valid and applicable. If necessary, a new working group will be formed to revise the guideline. The validity of a guideline can be shorter than 5 years, if new scientific or healthcare structure developments arise, that could be seen as a reason to commence revisions. The Radiological Society of the Netherlands is considered the keeper of this guideline and thus primarily responsible for the actuality of the guideline. The other scientific societies that have participated in the guideline development share the responsibility to inform the primarily responsible scientific society about relevant developments in their field.
Initiative
Radiological Society of the Netherlands
Authorization
The guideline is submitted for authorization to:
- Association of Surgeons of the Netherlands
- Dutch Association of Hospital Pharmacists
- Dutch Federation of Nephrology
- Dutch Society for Allergology and Clinical Immunology
- Dutch Society for Dermatology and Venereology
- Dutch Society of Intensive Care
- Netherlands Association of Internal Medicine
- Netherlands Society of Cardiology
- Netherlands Society of Emergency Physicians
- Netherlands Society of Intensive Care
- Radiological Society of the Netherlands
Algemene gegevens
General Information
The guideline development was assisted by the Knowledge Institute of the Federation Medical Specialists (www.kennisinstituut.nl) and was financed by the Quality Funds for Medical Specialists (Stichting Kwaliteitsgelden Medisch Specialisten: SKMS).
Doel en doelgroep
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.
Samenstelling werkgroep
Working group members
A multidisciplinary working group was formed for the development of the guideline in 2016. The working group consisted of representatives from all relevant medical specialization fields that are involved with intravascular contrast administration.
All working group members have been officially delegated for participation in the working group by their scientific societies. The working group has developed a guideline in the period from May 2016 until July 2019.
The working group is responsible for the complete text of this guideline.
Working group
Brummer I., emergency physician, Treant Healthcare Group, Emmen
de Geus H.R.H., internist-intensivist, Erasmus Medical Centre, Rotterdam
de Monchy J.G.R., allergologist, DC-Klinieken, Amsterdam
Dekker H.M., radiologist, Radboud University Medical Centre, Nijmegen
Dekkers I.A., clinical epidemiologist and radiologist in training, Leiden University Medical Centre, Leiden
Geenen R.W.F., radiologist, Noordwest Ziekenhuisgroep (NWZ), Alkmaar
Gotte M., cardiologist, Free University Medical Centre, Amsterdam (from July 2018)
Kardaun S.H., dermatologist, University Medical Centre Groningen, Groningen (until March, 2018)
Leiner T., radiologist, University Medical Centre Utrecht, Utrecht (until November 2018)
van der Molen A.J., radiologist, Leiden University Medical Centre, Leiden (chairman)
van der Putten K., nephrologist, Tergooi, Hilversum
van der Vlugt M., cardiologist, Radboud University Medical Centre, Nijmegen (until April 2018)
Wikkeling O.R.M., vascular surgeon, Heelkunde Friesland Groep, location: Nij Smellinghe Hospital, Drachten
Zielhuis S.W., hospital pharmacist, Medical Centre Leeuwarden, Leeuwarden
Methodological support
Buddeke J., advisor, Knowledge Institute of the Federation Medical Specialists (from April 2018)
Harmsen W., advisor, Knowledge Institute of the Federation Medical Specialists (from April 2018)
Mostovaya I.M., senior advisor, Knowledge Institute of the Federation Medical Specialists
Belangenverklaringen
Conflicts of interest
The working group members have provided written statements about (financially supported) relations with commercial companies, organisations or institutions that are related to the subject matter of the guideline. Furthermore, inquiries have been made regarding personal financial interests, interests due to personal relationships, interests related to reputation management, interest related to externally financed research and interests related to knowledge valorisation. The statements on conflict of interest can be requested at the administrative office of the Knowledge Institute of Medical Specialists and are summarised below.
|
Last name |
Function |
Other positions |
Personal financial interests |
Personal relations |
Reputation management |
Externally financed research |
Knowledge valorisation |
Other interests |
Signed |
|
Brummer |
Emergency physician |
None |
None |
None |
None |
None |
None |
None |
February 23rd, 2018 |
|
De Geus |
Internist-Intensivist Erasmus MC Rotterdam |
None |
None |
None |
None |
None |
None |
None |
March 31st, 2016 |
|
Dekker |
Radiologist |
None |
Not applicable |
Not applicable |
Not applicable |
Not applicable |
Not applicable |
Not applicable |
July 10th, 2016 |
|
Dekkers |
Radiologist in training and PhD-candidate |
None |
None |
Not applicable |
Not applicable |
Not applicable |
Not applicable |
Not applicable |
July 8th, 2016 |
|
Geenen |
Radiologist |
Member of commission prevention of PC-AKI |
None |
None |
None |
None |
None |
Has held several presentation about contrast media on invitation (GE, BAYER) |
March 25th, 2016 |
|
Kardaun |
Dermatologist – researcher Universitair Medisch Centrum Groningen: unpaid |
Replacing dermatologist in clinical practice - unpaid |
None |
None |
None |
None |
None |
None |
February 24th, 2016 |
|
Roodheuvel |
Emergency physician |
Instructor OSG/VvAA for courses on echography – paid position Member of department for burn treatment – unpaid. |
None |
None |
None |
None |
None |
None |
December 21st, 2015 |
|
Van der Molen |
Chairman |
None |
None |
None |
None |
None |
Not applicable |
One-off royalties Springer Verlag (2014) Incidental payments for presentations or being day chairman at contrast safety congress (2016 Netherlands + Europe |
September 6th, 2016 |
|
Van der Putten |
Internist nephrologist |
None |
None |
None |
None |
None |
None |
None |
October 14th, 2015 |
|
Van der Vlugt |
Cardiologist |
None |
None |
None |
Chairman of the working group Cardiac MRI & CT and Nuclear imaging of the Netherlands Society of Cardiology |
None |
None |
None |
March 1st, 2016 |
|
Wikkeling |
Vascular surgeon |
None |
None |
None |
None |
None |
None |
Not applicable |
July 19th, 2016 |
|
Zielhuis |
Hospital pharmacist |
None |
In the past (2013-2015) has participated in an advisory panel on expensive medication for the companies AbbVie and Novartis. Has received an expense allowance for this. Both forms do not produce contrast media that this guideline is about. Currently not active in an advisory panel. |
None |
None |
None |
None |
None |
January 8th, 2016 |
Inbreng patiëntenperspectief
Input of patient’s perspective
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.
Methode ontwikkeling
Evidence based
Implementatie
Implementation
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.
Werkwijze
Methodology
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 (www.kwaliteitskoepel.nl). 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: http://richtlijnendatabase.nl/over_deze_site/over_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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Bijlagen
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