Preventie van jodium-geïnduceerde hyperthyroïdie (IIHT) na het gebruik van jodiumhoudend contrastmiddel
Uitgangsvraag
Wat zijn strategieën voor de preventie van jodium-geïnduceerde schildklierdysfunctie (IIHT) na het gebruik van jodiumhoudend contrastmiddel (CM) bij:
- Patiënten met een geschiedenis van hart- en vaatziekten
- Patiënten van meer dan 65 jaar oud
- Patiënten met een geschiedenis van schildklier problemen (struma, hyperthyroïdie, hypothyroïdie)
Aanbeveling
Meet de schildklierfunctie niet routinematig voor toediening van jodiumhoudend CM.
Overweeg meting van de schildklierfunctie bij patiënten met een verhoogd risico op het ontwikkelen van jodium-geïnduceerde hyperthyreoïdie, vooral bij personen ouder dan 65 jaar en patiënten met ernstige cardiovasculaire morbiditeit.
Overweeg een profylactische behandeling in geselecteerde patiënten met subklinische hyperthyreoïdie, die jodiumhoudend CM ontvangen, bijvoorbeeld patiënten ouder dan 65 jaar oud of met ernstige cardiovasculaire morbiditeit.
Start profylactische therapie één dag voor CM-toediening en continueer 14 dagen met thiamazol (30 mg eenmaal per dag) en voeg indien nodig kaliumperchloraat toe (500mg tweemaal per dag).
Vermijd isotopen-beeldvorming van de schildklier en/of behandeling met radioactief jodium tot 4-8 weken na injectie van jodiumhoudend CM. Of geef geen jodiumhoudend CM 4-8 weken voor een geplande isotopen-scintigrafie van de schildklier of voor een behandeling met radioactief jodium.
Overwegingen
Iodine-based contrast medium (ICM) is administered during a CT-scan in volumes of 60-150 ml with iodine concentrations of 270-400 mg iodine (mgI) per ml. The total iodine dose of the ICM with organically bound iodine that is administered is between 16,000 and 60,000 mgI. Since ICM are excreted unchanged in the urine and are not metabolized, this iodine load will not be available to the thyroid. More important is that bottles of ICM contain small amounts of inorganic free iodide, depending on shelf-life and exposure to light, which might be directly available for thyroid uptake. Concentrations are in the range of 0,002-0,03 mgI/ml and as a result, an amount of approximately 0.1-4.5 mgI free iodide will be injected (0,001-0,007% of the amount of injected organically bound iodine) (Rendl, 2001; van der Molen, 2004). This amount is about 1-30 times the recommended daily allowance for iodine of 150 mg. A recent study, however, showed no increased levels of free iodide in the thyroid glands of ICM-treated animals (Hichri, 2020).
In a nested case-control study it was found that ICM exposure was associated with a risk of hyperthyroidism (defined as TSH < 0.1 mU/l; OR 2.50, 95%CI 1.06-5.93) and a risk of hypothyroidism (defined as TSH>10 mU/l; OR 3.05, 95%CI 1.07-8.72) (Rhee, 2012). In a recent meta-analysis, however, it was shown that the absolute risk of IIHT was very low with an estimated prevalence of 0.1% (95%CI 0.0-0.6%) (Bervini, 2021). IIHT develops when the normal response to excess iodine with acute inhibition of the organification of iodine (i.e., acute Wolff-Chaikoff effect), is impaired. Risk factors include nontoxic diffuse or nodular goiter, latent Graves’ disease, and long-standing iodine deficiency.
The reported prevalence of overt iodine induced hypothyroidism ranges from 0-8.1% (Bednarczuk, 2021). It develops when the thyroid fails to escape from the acute Wolff-Chaikoff effect, which may occur in euthyroid patients with a wide variety of thyroid disorders such as previous Hashimoto’s thyroiditis, Graves’ disease, thyroiditis, or previous thyroid surgery (Lee, 2015). It should be noted that published studies on prevalence are highly heterogeneous with respect to background iodine intake, selection of patients with or without previous history of thyroid disease, sample size, type of radiological examination, definition of thyroid disease and follow-up period. There are several case reports of iodine- induced thyrotoxicosis describing complications such as atrial fibrillation, heart failure or even thyroid storm (See Bednarczuk 2021, Table 2).
The efficacy of prophylactic treatment for development of iodine-induced hyperthyroidism has not been convincingly demonstrated. The randomised study by Nolte (Nolte, 1996) did not show a reduction of IIHT in the prophylactic treatment group, but that study was clearly underpowered. The study by Fricke (Fricke, 2004) was not randomised and compared two different subpopulations which were selected to receive prophylactic treatment or not based on TSH level and 99mTechnetium thyroid uptake. Despite prophylactic treatment, two patients developed iodine induced hyperthyroidism. It should be noted, however, that the study by Fricke (2004) did not contain a comparable control group without prophylactic treatment.
The European Thyroid Association (ETA) has recently issued a guideline for the management of iodine-based contrast media-induced thyroid dysfunction (Bednarczuk, 2021). In view of the lack of well-designed studies in this field and to prevent conflicting statements as much as possible, we decided to adopt several of the ETA guideline recommendations.
In view of the low incidence of iodine-induced thyroid dysfunction, the usually mild symptoms and the self-limiting clinical course, routine testing of the thyroid function is not indicated before ICM administration. Baseline testing of thyroid function might be considered in patients at risk for development of iodine induced hyperthyroidism with a complicated clinical course, i.e., patients older than 65 years with clinically severe cardiovascular morbidity (Bednarczuk, 2021). Overt hyperthyroidism is generally considered an absolute contraindication to ICM administration, and alternative imaging, like MRI or ultrasound, is then recommended. In emergency cases, prophylactic treatment should be initiated. Subclinical hyperthyroidism is not a contra-indication for ICM administration. In patients older than 65 years with severe cardiovascular morbidity and subclinical hyperthyroidism, prophylactic treatment might be considered. A more conservative approach would be to measure thyroid function (TSH, FT4) 3-4 weeks after ICM administration. A commonly used prophylactic treatment protocol is thiamazole 30 mg once daily, started the day before ICM administration and continued for 14 days. It has been suggested that combination with potassium perchlorate (500mg twice a day) would be more effective. Treatment with thiamazole is usually well tolerated. Adverse effects are predominantly skin allergy (maculopapular rash, urticaria) and arthralgias. The most important adverse effect of potassium/sodium perchlorate is agranulocytosis, but this is a rare event (about 1 in 275 patients) and occurs predominantly at daily dosages above 1000mg given for several months.
Baseline subclinical hypothyroidism and overt hypothyroidism are not a contraindication to ICM administration.
Yet another relevant question in clinical practice is the minimal interval required between ICM injection and isotope imaging of the thyroid or radioactive iodine (RAI) treatment. The administration of ICM is known to suppress thyroidal RAI uptake, lasting for several weeks (Nygaard, 1998). Some studies on urinary iodine secretion after ICM administration for outpatient CT scans indicate that 75% of patients’ values returned to baseline within 5–6 weeks and 90% within 11 weeks (Lee 2015, Nimmons, 2013). A study performed in post- thyroidectomy patients requiring RAI treatment demonstrated that 1 month is sufficient for urinary iodine to return to its baseline value after the use of ICM (Padovani, 2012). These results may be used to guide the timing of RAI treatment as well as diagnostic scintigraphy with radioactive iodine or Tc-99m-pertechnetate following contrast exposure. The American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer (2015) state that concerns about iodine burden from IV contrast agents causing a clinically significant delay in subsequent whole-body scans or RAI treatment post-thyroidectomy is generally unfounded, as iodine is generally cleared within 4-8 weeks in most patients (Haugen, 2016). In doubtful situations, a spot or 24-h urinary iodine level may be checked before isotope studies. In line with the ETA guideline (Bednarczuk, 2021), we recommend postponing isotope imaging of the thyroid and RAI treatment for 4 to 8 weeks after ICM injection, or to withhold ICM administration 4 to 8 weeks before a planned RAI treatment.
Recommendations
In view of the low incidence of iodine induced thyroid dysfunction, the usually mild symptoms, and the self-limiting clinical course, routine testing of the thyroid function is not indicated before ICM administration. These recommendations are in line with the ETA guideline (Bednarczuk, 2021).
|
Do not routinely measure the thyroid function before administration of iodine-based contrast media.
Consider measurement of thyroid function in high-risk patients for iodine-induced hyperthyroidism, especially in subjects older than 65 years and those with severe cardiovascular morbidity. |
In patients older than 65 years with severe cardiovascular morbidity and subclinical hyperthyroidism, prophylactic treatment might be considered. These recommendations are in line with the ETA guideline (Bednarczuk, 2021).
|
Consider prophylactic treatment prescribed by an internal medicine specialist in selected patients with subclinical hyperthyroidism receiving iodine-based contrast media (e.g., patients older than 65 years or severe cardiovascular morbidity), starting one day before contrast administration and continuing for 14 days with thiamazole 30 mg once daily and possible addition of potassium perchlorate 500 mg twice daily. |
After ICM injection, the iodine uptake by the thyroid gland is temporarily suppressed. Therefore, isotope imaging of the thyroid or RAI should be postponed after ICM injection. These recommendations are in line with the ETA guideline (Bednarczuk, 2021).
|
Avoid isotope imaging of the thyroid and/or radioactive iodine treatment for 4-8 weeks after iodine-based contrast media injection or withhold iodine-based contrast media administration for 4-8 weeks before planned isotope imaging of the thyroid or radioactive iodine treatment. |
Onderbouwing
Achtergrond
Iodine-based contrast media (ICM) contain substantial amounts of iodine which might result in iodine-induced hyperthyroidism (IIHT) or iodine-induced hypothyroidism. Depending on the magnitude of this risk and the clinical implications, prophylactic medication could be considered.
Conclusies
|
Very low GRADE |
The evidence is very uncertain about the effect of prophylactic drugs on the prevention of IIHT in patients with indication for iodinated contrast media administration and
Fricke, 2004; Nolte, 1996 |
Samenvatting literatuur
Description of studies
Randomized controlled study
Nolte et al. (1996) performed a prospective randomized study aiming to investigate the efficacy of prophylactic application of thyrostatic drugs in patients with subclinical hyperthyroidism undergoing elective coronary angiography. The authors screened patients for TSH who were admitted to the hospital for coronary angiography. Patients lived in an area of moderate iodine deficiency. Inclusion criteria were age between 40-75 years, TSH levels < 0.4 mU/L, normal FT3-index, normal FT4-index, and a normal 99mTechnetium-uptake. Those with manifest hyperthyroidism, large autonomous thyroid adenoma, immune related thyroid disease, urine iodine excretion > 200 mmol/mol creatinine, unstable angina pectoris or a Karnofsky Index < 50% were excluded. In addition, patients were also excluded if they were using thyroid hormones, thyrostatic drugs or amiodarone or had received contrast media during the previous 6 months. In total 51 patients fulfilled the criteria and were randomly assigned to one of three groups (17 patients in each group): group 1 received 20 mg of thiamazole once a day, group 2 was treated with 900 mg of sodium perchlorate (300mg 3 times a day) and group 3 received no special therapy. The treatment started 1 day before coronary angiography and lasted for 14 days. During angiography, patients were exposed to a mean contrast volume of 149ml, ranging from 50 to 410 ml. The three groups were comparable in age, sex, mean volume of contrast and goitre size. There were no side effects reported from the thyrostatic drugs. Follow up assessment was done 30 days after coronary angiography. Nolte (1996) defined IIHT as suppressed TSH (<0.4 mU/l) and increased FT4-index and/or FT3-index. Nolte (1996) defined iodine-induced hypothyroidism as increased TSH and reduced FT4-index 30 days after coronary angiography.
Prospective interventional study
Fricke et al. (2004) performed a prospective study that had the objective to identify which patients with subclinical hyperthyroidism should receive prophylactic medication before coronary angiography to prevent IIHT. The authors screened all patients admitted for coronary angiography and included all patients with a basal TSH level of less than 0.3 mU/l and normal levels of T3 and FT4. Patients with thyroid antibodies or using medication for thyroid disease were excluded. Additional exclusion criteria were use of amiodarone, renal insufficiency (serum creatinine >133 mmol/l) or administration of contrast agents during the previous 3 months. Indication for prophylactic drug treatment was determined by the TSH level and the results of 99mTechnetium scintigraphy. No prophylactic medication was given to patients with 1) homogenous tracer distribution in the thyroid, 99mTechnetium thyroid uptake (TCTU) less than 1.5%, and TSH ranging from 0.05 to less than 0.3 mU/l; 2) homogenous tracer distribution in the thyroid, TCTU less than 1.0%, and TSH less than 0.05 mU/l; and 3) focal uptake and TCTU less than 1.0%. All other patients received 900 mg perchlorate (divided in 3 doses per day) for 2 weeks, starting at least 3 hours before coronary angiography. Thiamazole was added depending on the volume of the autonomous thyroid volume: 20 mg for 7 days in case of a volume of 5- 10 ml, and 60 mg thiamazole in the first week followed by 20 mg in the second week in case of a volume > 10 ml. Age was no selection criterion, mean age was 65±8.7 years. Coronary angiography was performed with an average of 157(±85 ml) iopromide containing 370 mg iodine per ml. In total 56 patients underwent coronary angiography without and 19 patients with prophylactic medication, i.e., 6 patients perchlorate only and 13 patients perchlorate combined with thiamazole. Follow up assessment was done at 1, 14, and 28 days after coronary angiography. This paper did not specifically define IIHT.
Results
Results will be described separately for the previously described subgroups.
- Iodine-induced hyperthyroidism (IIHT)
The prospective randomized controlled study by Nolte (1996) reported one case of IIHT in the thiamazole group (1/17), one case in the perchlorate group (1/17), and two cases in the control group (2/17). Thyroid hormone levels were only slightly elevated in all cases. Only two persons developed mild clinical symptoms of hyperthyroidism, one in the thiamazole group and one in the perchlorate group, but none of these needed treatment with thyrostatic drugs.
The prospective interventional study by Fricke (2004) reported two cases of IIHT in the group receiving prophylactic drug treatment (2/19). In one case prophylactic drug treatment had to be stopped because of side effects, which was followed by development of hyperthyroidism. In the other case, the patient demonstrated mild hyperthyroidism the day after coronary angiography despite prophylactic treatment with perchlorate, which was stabilized within a few days with the administration of thiamazole (Fricke, 2004). There we no cases of IIHT in the group of 56 patients who did not receive prophylactic drug treatment.
TSH, thyroid hormones and 99mTechnetium-uptake
The prospective randomized controlled study by Nolte (1996) measured TSH, delta TSH (response 30 min after 200μg of TRH i.v.), mean FT4-index, mean FT3-index and 99mTechnetium-uptake at baseline and after follow-up of 30 days. The authors reported a significant decrease in TSH and increase in FT4- and FT3-index in the control group, whereas these values remained unchanged in the intervention groups or showed a slight increase (TSH in the thiamazole group). Alterations of 99mTechnetium-uptake were minimal in both intervention groups but was significantly reduced in the control group after 30 days.
TSH and free thyroxine
The prospective interventional study by Fricke (2004) reported TSH, FT4 and T3 at baseline and at 1, 14 and 28 days after coronary angiography. Within the group receiving prophylactic treatment (n=19), two cases of hyperthyroidism occurred. One patient developed IIHT after interruption of the prophylactic treatment because of side effects. The other patient demonstrated mild IIHT the day after ICM administration despite prophylactic treatment with perchlorate, which was quickly resolved after addition of thiamazole. The remaining 17 patients in the prophylactic treatment group showed stable TSH and T3 levels, except for a slight TSH increase and T3 decrease at day 28. In this group, FT4 was slightly elevated at day 14 and slightly decreased at day 28. The group without prophylactic treatment (n=56) showed an increase of TSH at day 1 and day 14, with an increase of FT4 day 14 and day 28 and a transient decrease in T3 at day 1 All changes in TSH, FT4 and T3 were within the reference range.
- Iodine induced hypothyroidism
The prospective randomized study by Nolte (1996) found no cases of iodine-induced hypothyroidism 30 days after coronary angiography. Fricke (2004) did not report this outcome measure.
Level of evidence of the literature
Observational studies start at a low GRADE. Note: interventional studies.
The level of evidence regarding the outcome measure IIHT started on a low GRADE and was further downgraded to a very low GRADE levels because of study limitations (risk of bias) and the number of included patients (imprecision).
Zoeken en selecteren
A systematic review of the literature was performed to answer the following question: What are strategies for the prevention of IIHT, with a special interest in patients described above.
P (Patient): Patients with an indication of ICM administration with a special interest for the subgroups described above.
I (Intervention): Prevention strategy for IIHT: methimazole (synonym: thiamazole), propylthiouracil, perchlorate.
C (Comparison): No prevention strategy for IIHT or different prevention strategy.
O (Outcomes): Iodine-induced hyperthyroidism, iodine-induced hypothyroidism.
Relevant outcome measures
The guideline development group considered iodine-induced hyperthyroidism (IIHT) as a critical outcome measure for decision making, and iodine-induced hypothyroidism as important outcome measures for decision making.
The working group defined the outcome measures as follows: iodine-induced hyperthyroidism is the clinical condition of hyperthyroidism (e.g., palpitations, tremulousness, heat intolerance) caused by iodinated contrast media, which usually occurs weeks or months after its administration (Bednarczuk, 2021; Bervini, 2021). Iodine-induced hypothyroidism is the clinical condition of hypothyroidism (e.g., fatigue, weight gain, cold intolerance) caused by iodinated contrast media, which usually occurs weeks or months after its administration. Both iodinated contrast media induced hyperthyroidism and hypothyroidism are usually self-limiting conditions and resolve within weeks to months.
The working group did not define a minimal clinical important difference beforehand, because it is unclear what the prevalence of IIHT is in the no-prevention-strategy group (control group) with risk factors for IIHT (the previously described groups at risk for IIHT). Because literature about the subject is scarce, it was decided to provide only a descriptive analysis.
Search and select (Methods)
The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms until July 7th, 2021. The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 188 hits. Studies were selected based on the following criteria: studies with comparative design, comparing different prevention strategies for IIHT in the previously described subgroups. Forty-two studies were initially selected based on title and abstract screening. After reading the full text, forty studies were excluded (see Table of excluded studies in ‘Appendices to modules’), and two studies were included.
Results
Two studies were included in the analysis of the literature. Important study characteristics and results are summarized in the evidence tables. The assessment of the risk of bias is summarized in the risk of bias tables.
Referenties
- Bednarczuk T, Brix TH, Schima W, Zettinig G, Kahaly GJ. 2021 European Thyroid Association guidelines for the management of iodine-based contrast media-induced thyroid dysfunction. Eur Thyroid J. 2021; 10(4): 269-284.
- Bervini S, Trelle S, Kopp P, Stettler C, Trepp R. Prevalence of iodine-induced hyperthyroidism after administration of iodinated contrast during radiographic procedures: A systematic review and meta-analysis of the literature. Thyroid 2021; 31: 1020-1029.
- Fricke E, Fricke H, Esdorn E, Kammeier A, Lindner O, Kleesiek K, Horstkotte D, Burchert W. Scintigraphy for risk stratification of iodine-induced thyrotoxicosis in patients receiving contrast agent for coronary angiography: a prospective study of patients with low thyrotropin. J Clin Endocrinol Metab 2004; 89(12): 6092-6096.
- Hichri M, Vassaux G, Guigonis JM, Juhel T, Graslin F, Guglielmi J, et al. Proteomic analysis of iodinated contrast agent-induced perturbation of thyroid iodide uptake. J Clin Med. 2020; 9(2): 329.
- Lee SY, Rhee CM, Leung AM, Braverman LE, Brent GA, Pearce EN. A review: Radiographic iodinated contrast media-induced thyroid dysfunction. J Clin Endocrinol Metab. 2015; 100(2): 376-383.
- Nimmons GL, Funk GF, Graham MM, Pagedar NA. Urinary iodine excretion after contrast computed tomography scan: implications for radioactive iodine use. JAMA Otolaryngol Head Neck Surg. 2013; 139(5): 479–482.
- Nolte W, Müller R, Siggelkow H, Emrich D, Hüfner M. Prophylactic application of thyrostatic drugs during excessive iodine exposure in euthyroid patients with thyroid autonomy: a randomized study. Eur J Endocrinol 1996; 134(3): 337-341.
- Nygaard B, Nygaard T, Jensen LI, Court-Payen M, Søe-Jensen P, Nielsen KG, Fugl M, Hansen JM. Iohexol: effects on uptake of radioactive iodine in the thyroid and
on thyroidfunction. Acad Radiol. 1998; 5(6): 409-414. - Padovani RP, Kasamatsu TS, Nakabashi CC, Camacho CP, Andreoni DM, Malouf EZ, et al. One month is sufficient for urinary iodine to return to its baseline value after the use of water-soluble iodinated contrast agents in post-thyroidectomy patients requiring radioiodine therapy. Thyroid. 2012; 22(9): 926–930.
- Rendl J, Saller B. Schilddrüse und Röntgenkontrastmittel: Pathophysiologie, Häufigkeit und Prophylaxe der jodinduzierten Hyperthyreose. Dt Ärztebl 2001; 98(7): A402–406.
- Rhee CM, Bhan I, Alexander EK, Brunelli SM. Association between iodinated contrast media exposure and incident hyperthyroidism and hypothyroidism. Arch Intern Med 2012; 172(2): 153-159.
- Van der Molen AJ, Thomsen HS, Morcos SK; Contrast Media Safety Committee, European Society of Urogenital Radiology (ESUR). Effect of iodinated contrast media on thyroid function in adults. Eur Radiol 2004; 14(5): 902-907.
Verantwoording
Autorisatiedatum en geldigheid
Laatst beoordeeld : 28-11-2022
Laatst geautoriseerd : 28-11-2022
Geplande herbeoordeling :
Validity
The Radiological Society of the Netherlands (NVvR) will determine around 2027 if this guideline (per module) is still valid and applicable. If necessary, the scientific societies will form a new guideline group 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 a reason to commence revisions. The Radiological Society of the Netherlands is the owner of this guideline and thus primarily responsible for the actuality of the guideline. 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.
Algemene gegevens
General Information
The Kennisinstituut van de Federatie Medisch Specialisten (www.kennisinstituut.nl) assisted the guideline development group. The guideline was financed by Stichting Kwaliteitsgelden Medisch Specialisten (SKMS) which is a quality fund for medical specialists in The Netherlands.
Samenstelling werkgroep
Guideline development group (GDG)
A multidisciplinary guideline development group (GDG) was formed for the development of the guideline in 2020. The GDG consisted of representatives from all relevant medical specialization fields which were using intravascular contrast administration in their field.
All GDG members have been officially delegated for participation in the GDG by their scientific societies. The GDG has developed a guideline in the period from June 2020 until November 2022. The GDG is responsible for the complete text of this guideline.
Guideline development group
- Dekkers I.A. (Ilona), clinical epidemiologist and radiologist, Leiden University Medical Center, Leiden
- Geenen R.W.F. (Remy), radiologist, Noordwest Ziekenhuisgroep, Alkmaar
- Kerstens M.N. (Michiel), internist-endocrinologist, University Medical Centre Groningen
- Krabbe J.G. (Hans), clinical chemist-endocrinologist, Medisch Spectrum Twente, Enschede
- Rossius M.J.P. (Mariska), radiologist, Erasmus Medical Centre, Rotterdam
- Uyttenboogaart M. (Maarten), neurologist and neuro-interventionalist, University Medical Centre Groningen
- van de Luijtgaarden K.M. (Koen), vascular surgeon, Maasstad Ziekenhuis, Rotterdam
- van der Molen A.J. (Aart), chair guideline development group, radiologist, Leiden University Medical Center, Leiden
- van der Wolk S.L. (Sabine), gynaecologist-obstetrician, Haga Ziekenhuis, Den Haag
- van de Ven A.A.J.M. (Annick), internist-allergologist-immunologist, University Medical Centre Groningen (until 1.7.2022)
- van der Houwen, T.B. (Tim), internist-allergologist-immunologist, Amsterdam University Medical Center (from 1.7.2022)
Invited experts
- van Maaren M.S. (Maurits), internist-allergologist-immunologist, Erasmus MC, Rotterdam
Belangenverklaringen
Conflicts of interest
The GDG members have provided written statements about (financially supported) relations with commercial companies, organisations or institutions that were 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 from the administrative office of Kennisinstituut van de Federatie Medisch Specialisten (secretariaat@kennisinstituut.nl) and were summarised below.
|
Last name |
Function |
Other positions |
Personal financial interests |
Personal relations |
Reputation management |
Externally financed research |
Knowledge valorisation |
Other interests |
Signed |
Actions |
|
Dekkers IA |
Radiologist, LUMC |
Clinical Epidemiologist
Member of contrast media safety committee, European Society of Urogenital Radiology (no payment)
Member, Gadolinium Research and Education Committee, European Society of Magnetic Resonance in Medicine, and Biology (no payment) |
No |
No |
No |
No |
No |
Received consultancy fees from Guerbet, 2019- 2022 |
July 24th, 2020, Reaffirmed October 12th, 2022 |
No restrictions: received in part 3 of the guideline speaker fees, but this guideline does not mention specific medication, not of working mechanism, nor of side effects. |
|
Geenen RWF |
Radiologist, Noordwest ziekenhuisgroep /Medisch specialisten Noordwest |
Member of contrast media safety committee, European Society of Urogenital Radiology (no payment) |
No |
No |
No |
No |
No |
No |
April 11th, 2020, Reaffirmed October 12th, 2022 |
No restrictions |
|
Houwen T, van der |
Internist - Immunologist - Allergologist, Amsterdam UMC, also seconded allergologist in Huid Medisch Centrum |
None |
None |
None |
None |
None |
None |
None |
July 11th, 2022 Reaffirmed October 12th, 2022 |
No restrictions |
|
Kerstens MN |
Internist- endocrinologist, UMCG |
Chairman Bijniernet (no payment) |
No |
No |
No |
No |
No |
No |
July 1st, 2020, reaffirmed October 25th, 2022 |
No restrictions |
|
Krabbe JG |
Clinical chemist, Medisch Spectrum Twente |
No |
No |
No |
No |
No |
No |
No |
September 1st, 2020, Reaffirmed October 13th, 2022 |
No restrictions |
|
Luijtgaarden KM, van de |
Vascular surgeon, Maasland Ziekenhuis |
No |
No |
No |
No |
No |
No |
No |
August 1st, 2020, reaffirmed October 26th, 2022 |
No restrictions |
|
Molen AJ, van der |
Radiologist LUMC |
Member of contrast media safety committee, European Society of Urogenital Radiology (no payment)
Member, Gadolinium Research and Education Committee, European Society of Magnetic Resonance in Medicine, and Biology (no payment) |
No |
No |
No |
No |
No |
Received consultancy fees from Guerbet, 2019- 2022 |
July, 24th, 2020 Reaffirmed October 12th, 2022 |
No restrictions: received in part 3 of the guideline speaker fees, but this guideline does not mention Specific medication, not of working mechanism, nor of side effects. |
|
Rossius MJP |
Radiologist Erasmus Medical Centre |
Medical coordinator (no payment) |
No |
No |
No |
No |
No |
No |
April 7th, 2020, Reaffirmed October 13th, 2022 |
No restrictions |
|
Uyttenboogaart M |
Neurologist and neuro- interventionalist UMCG |
Advisor International Federation of Orthopaedic Manipulative Physical Therapist / Nederlandse Vereniging Manuele Therapie |
No |
No |
Subsidy Hart Stichting for CONTRAST (Consortium of New Treatments in Acute Stroke): WP8 Stroke logistics and Epidemiology: financing of 2 PhD students by the Hart Stichting / PPS Allowance |
Work package leader CONTRAST (Consortium of New Treatments in Acute Stroke): WP8 Stroke logistics and Epidemiology |
No |
No |
June 30th, 2020, reaffirmed October 26th, 2022 |
No restrictions: the CONTRAST consortium wp8 is only about organisation and treatment of stroke. Stroke is not in this guideline. |
|
Ven AAJM, van de |
Internist- allergologist- immunologist, UMCG |
Education and research related to work as internist- allergist |
No |
No |
No |
No |
No |
No |
April 7th, 2020, Reaffirmed October 19th, 2022 |
No restrictions |
|
Wolk S, van der |
Gynaecologist- obstetrician, Haga Ziekenhuis |
No |
No |
No |
No |
No |
No |
No |
June 30th, 2021, reaffirmed October 25th, 2022 |
No restrictions |
Inbreng patiëntenperspectief
Input of patient’s perspective
The guideline does not address a specific adult patient group, but a diverse set of diagnoses. Therefore, it was decided to invite a broad spectrum of patient organisations for the stakeholder consultation. The stakeholder consultation was performed at the beginning of the process for feedbacking on the framework of subjects and clinical questions addressed in the guideline, and during the commentary phase to provide feedback on the concept guideline. The list of organisations which were invited for the stakeholder consultation can be requested from the Kennisinstituut van de Federatie Medisch Specialisten (secretariaat@kennisinstituut.nl). In addition, patient information on safe use of contrast media in pregnancy and lactation was developed for Thuisarts.nl, a platform to inform patients about health and disease.
Implementatie
Implementation
During different phases of guideline development, implementation and practical enforceability of the guideline were considered. 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 in the ‘Appendices to modules’. Furthermore, quality indicators were developed to enhance the implementation of the guideline. The indicators can also be found in the ‘Appendices to modules’.
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 based 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 GDG identified the relevant subject matter for the guideline. The framework is consisted of both new matters, which were not yet addressed in part 1 and 2 of the guideline, and an update of matters that were subject to modification (for example in case of new published literature). Furthermore, a stakeholder consultation was performed, where input on the framework was requested.
Clinical questions and outcomes
The outcome of the stakeholder consultation was discussed with the GDG, after which definitive clinical questions were formulated. Subsequently, the GDG formulated relevant outcome measures (both beneficial and harmful effects). The GDG rated the outcome measures as critical, important and of limited importance (GRADE method). Furthermore, where applicable, the GDG defined relevant clinical differences.
Search and select
For clinical questions, specific search strategies were formulated, and scientific articles published in several electronic databases were searched. First, the studies that potentially had the highest quality of research were reviewed. The GDG selected literature in pairs (independently of each other) based on the title and abstract. A second selection was performed by the methodological advisor based on full text. The databases used, selection criteria and number of included articles can be found in the modules, the search strategy in the appendix.
Quality assessment of individual studies
Individual studies were systematically assessed, based on methodological quality criteria that were determined prior to the search. For systematic reviews, a combination of the AMSTAR checklist and PRISMA checklist was used. For RCTs the Cochrane risk of bias tool and suggestions by the CLARITY Group at McMaster University were used, and for cohort studies/observational studies the risk of bias tool by the CLARITY Group at McMaster University was used. The risk of bias tables can be found in the separate document Appendices to modules.
Summary of literature
The relevant research findings of all selected articles were shown in evidence tables. The evidence tables can be found in the separate document Appendices to modules. The most important findings in literature were 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 included studies 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 levels for the quality of scientific evidence: high, moderate, low, or very low. These levels provide information about the certainty level of the literature conclusions (http://www.guidelinedevelopment.org/handbook).
The evidence was summarized in the literature analysis, followed by one or more conclusions, drawn from the body of evidence. The level of evidence for the conclusions can be found above the conclusions. Aspects such as expertise of GDG members, local expertise, patient preferences, costs, availability of facilities and organisation of healthcare aspects are important to consider when formulating a recommendation. These aspects are discussed in the paragraph justifications. The recommendations provide an answer to the clinical question or help to increase awareness and were based on the available scientific evidence and the most relevant justifications.
Appendices
Internal (meant for use by scientific society or its members) quality indicators were developed with the guideline and can be found in the separate document Appendices to modules. In most cases, indicators were not applicable. For most questions, additional scientific research on the subject is warranted. Therefore, the GDG formulated knowledge gaps to aid in future research, which can be found in the separate document Appendices to modules.
Commentary and authorisation phase
The concept guideline was subjected to commentaries by the involved scientific societies. The list of parties that participated in the commentary phase can be requested from the Kennisinstituut van de Federatie Medisch Specialisten (secretariaat@kennisinstituut.nl). The commentaries were collected and discussed with the GDG. The feedback was used to improve the guideline; afterwards the GDG made the guideline definitive. The final version of the guideline was offered to the involved scientific societies for authorization and was authorized.
Literature
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 Kwaliteit, 2012. Available at: [URL].
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: [URL].
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- 1110. Erratum published in: BMJ 2008;336(7654).
Ontwikkeling van Medisch Specialistische Richtlijnen: stappenplan. Kennisinstituut van Medisch Specialisten, 2020.