Veilig gebruik van contrastmiddelen

Initiatief: NVvR Aantal modules: 48

Veilig gebruik van contrastmiddelen bij patiënten met Myasthenia Gravis

Uitgangsvraag

Wat is de rol van contrastmiddelen (CM) bij patiënten met exacerbaties van myasthenia gravis na CM-toediening?

Aanbeveling

Onthoud patiënten met myasthenia gravis niet van beeldvorming met CM omdat het risico op exacerbatie door CM erg laag is.

Overwegingen

Mehrizi, et al. (2014) found that in 81 CTs with contrast and in 23 MRIs with contrast no presence or absence of ADRs was reported. The study was not included in the systematic literature analysis because of severe methodological limitations. There were no cases of increasing myasthenic weakness. No immediate increased risk was noted about gadolinium- based contrast agents with regards to worsening myasthenic symptoms. There is no immediately increased risk for exacerbation of myasthenic weakness with the use of modern low-osmolar ICM. No weakness was reported in patients who received IV GBCA. The authors concluded that there is no immediately increased risk for exacerbation of myasthenic weakness with the use of modern low-osmolar radiologic contrast agents.

 

All three studies had significant methodological limitations. There seems to be only a very minimal risk of a myasthenic crisis following the administration of iodine-based contrast media. This does not justify withholding ICM for diagnostic studies.

 

There is no data on any risk after administration of other contrast media, such as gadolinium-based or ultrasound contrast agents.

 

Recommendations

Do not withhold contrast media to patients with myasthenia gravis, as the risk of a contrast media-induced myasthenic exacerbation is very low.

Onderbouwing

It is unclear whether contrast media can cause exacerbation of myasthenia gravis (MG) symptomatology for which MG patients should be warned or premedicated.

 

 

Very low GRADE

The evidence is very uncertain about the effect of contrast media on exacerbations in patients with myasthenia gravis.

 

Sources: Rath, 2017, Somashekar, 2013

 

 

 

No GRADE

No literature was found regarding the risk of neurological exacerbations of myasthenia in MG patients with using contrast medium in comparison to MG patients with different contrast medium administration or contrast medium

administration without preventive strategy.

Description of studies

 

Rath, et al. (2017) performed a retrospective cohort study, where the rate of acute adverse events as well as delayed clinical worsening up to 30 days was analysed. In 73 patients with confirmed MG who underwent contrast-enhanced CT studies with the administration of low osmolality iodinated contrast agents (ICAs) and compared to 52 patients who underwent unenhanced CT studies. Limitations of this study were (1) selection bias for the enhanced and unenhanced CT scans (2) the relatively low patient numbers (3) the retrospective nature of the investigation which entails the possibility that some adverse events might have been missed in some patients as they had to rely on electronic medical records. To minimize this effect, investigators only included patients with a sufficient clinical information available. Finally, the exact characteristics of the used contrast agents could not be extracted retrospectively from the available data in all patients; therefore, they could not compare the potential side effects of different ICAs with each other.

 

In a retrospective cohort study by Somashekar, et al. (2013), a computed tomography (CT) was performed in 267 paediatric and adult patients with clinically confirmed MG between January 1, 1995, and December 31, 2011. CT was performed without intravenous administration of contrast material in 155 patients and with intravenous administration of low-osmolality contrast material in 112 patients. Electronic medical records were searched to identify myasthenia gravis–related symptoms (i.e., bulbar, ocular, respiratory, or

extremity weakness) before (≤14 days) and after (≤45 days) each CT examination. All contrast-enhanced CT examinations were performed with one of a variety of low-osmolality contrast media. A variety of baseline characteristics and risk factors were collected for each patient, with attention to (a) the disease status of the patient’s myasthenia gravis immediately before CT (i.e. stable, worsening, or improving), (b) history of thymectomy, and (c) acute or chronic cardiac and/ or pulmonary and/or neuromuscular disease not related to myasthenia gravis. Limitations of this study were (1) retrospective nature of the study (2) selection bias between the control group and the experimental group, (3) some adverse events may not have been captured and (4) unable to determine the volume or type of contrast material administered in a large fraction of patients owing to incomplete documentation.

 

Results

 

Rath, et al. (2017) found that 9 of 73 patients (12.3%) experienced a delayed worsening of myasthenic symptoms, i.e., they reached the primary endpoint of progressing by at least one grade in the MGFA classification within 30 days. The medical files of all 9 patients were reviewed and it was concluded that in none of these 9 patients the exacerbation was causally related to the contrast medium. The rate was higher in comparison with the control group of patients receiving CT scans without ICM (3.8%), but the difference did not reach statistical significance. In a subgroup analysis, six of these nine patients (8.2% of all patients) developed a severe deterioration, i.e., a myasthenic crisis, or died in comparison with none in the control group. The mean time to worsening within 30 days did not differ significantly between the two study groups and was 11.1 days for patients with contrast-enhanced CT studies and 13 days in the control group.

 

Somashekar, et al. (2013) demonstrated that intravenous administration of a low osmolality iodine-based contrast medium (ICM) is associated with a significant increase in the frequency of disease-related symptoms within 1 day of administration (P=0.01) compared to no intravenous administration of contrast media. The exacerbation frequency is 5.7% above the baseline rate observed in unenhanced CT control group (6.3%- 0.6%). This implies that intravenous low-osmolality ICM is associated with a 5%–6% frequency of acute symptom exacerbation in patients with myasthenia gravis. No difference in symptom frequency at 2–7 days or 8–45 days after CT were detected, indicating that the association between intravenous low-osmolality ICM and symptom progression is a relatively acute association. The contrast-enhanced CT group was associated with a significant reduction in time to disease-related symptom progression following CT (median time to onset of symptom progression, 2.5 days with contrast-enhanced CT vs 14.0 days with unenhanced CT; P=0.05). Acute exacerbations were primarily respiratory (five patients with new-onset dyspnoea: four in contrast-enhanced CT group and one in unenhanced CT group, two patients with progressive dyspnoea: both in the contrast-enhanced CT group), and one patient with progressive weakness: in contrast-enhanced CT group.

 

Summary of study’s conclusions

 

Rath, et al. (2017) concluded that ICM administration for CT studies in MG patients should not be withheld if indicated, but patients particularly those with concomitant acute diseases should be carefully monitored for exacerbation of symptoms.

 

Somashekar, et al. (2013) concluded that intravenous administration of low-osmolality contrast media is significantly associated with exacerbation of myasthenia gravis–related symptoms. Exacerbations most commonly manifest as new or progressive acute respiratory compromise. Yet, review of the medical files showed no causative effect of the contrast medium.

 

Level of evidence of the literature

The level of evidence regarding the outcome measure neurological exacerbations of myasthenia started on a low GRADE due to the observational nature of the included studies and was downgraded by one level to a very low GRADE because of number of included patients.

A systematic review of the literature was performed to answer the following question:

 

P (Patients): Patients with myasthenia gravis and an indication for examination with contrast media.

I (Intervention): Contrast medium administration with or without preventive strategy (prednisolone, acetylcholine-reuptake inhibitors).

C (Comparison): No contrast medium administration, different contrast medium administration; contrast medium administration without preventive strategy.

O (Outcomes): Neurological exacerbations of myasthenia.

 

Relevant outcome measures

 

The guideline development group considered neurological exacerbations of myasthenia as a critical outcome measure for decision making.

 

A priori, the working group did not define the outcome measures listed above but used the definitions used in the studies.

 

Search and select (Methods)

The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms from January 1st, 2000, until March 4th, 2021. The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 84 hits. Studies were selected based on the following criteria: (1) patients with myasthenia gravis (2) indication for examination with contrast media (3) comparison to patients with no contrast medium administration, different contrast medium administration or contrast medium administration without preventive strategy and (4) the previously described outcome. Eleven studies were initially selected based on title and abstract screening. After reading the full text, nine studies were excluded (see Table of excluded studies in ‘Appendices to modules’), and two studies were included. One study, mentioned in the justifications, was not included in our literature analysis (Mehrizi,2014). It did not meet our PICO criteria and was excluded because of the wrong population, including children, and the absence of a comparison group.

 

Results

Two studies (Rath, 2017; Somashekar, 2013) 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.

  1. Mehrizi M, Pascuzzi RM. Complications of radiologic contrast in patients with myasthenia gravis. Muscle Nerve 2014; 50(3): 443-444.
  2. Rath J, Mauritz M, Zulehner G, Hilger E, Cetin H, Kasprian G, et al. Iodinated contrast agents in patients with myasthenia gravis: a retrospective cohort study. Journal of Neurology 2017; 264(6): 1209-1217.
  3. Somashekar DK, Davenport MS, Cohan RH Dillman JR, Ellis JH. Effect of intravenous low- osmolality iodinated contrast media on patients with myasthenia gravis. Radiology 2013; 267(3): 727-734.

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.

 

Initiative

  • Radiological Society of the Netherlands (NVvR)

In association with

  • Netherlands Association of Internal Medicine (NIV)
  • The Dutch Association of Neurosurgery (NVvN)
  • The Dutch Society of Allergology and Clinical Immunology (NVvAKI)
  • The Dutch Society of Cardiology (NVVC)
  • The Dutch Society of Clinical Chemistry and Laboratory Medicine (NVKC)
  • The Dutch Society of Endocrinology (NVE)
  • The Dutch Society of Neurology (NVN)
  • The Dutch Society of Obstetrics and Gynaecology (NVOG)
  • The Dutch Society of Surgery (NVvH) / The Dutch Society of Vascular Surgery (NVvV)

Initiatief en autorisatie

Initiatief:
  • Nederlandse Vereniging voor Radiologie
Geautoriseerd door:
  • Nederlandse Internisten Vereniging
  • Nederlandse Vereniging voor Cardiologie
  • Nederlandse Vereniging voor Heelkunde
  • Nederlandse Vereniging voor Neurochirurgie
  • Nederlandse Vereniging voor Neurologie
  • Nederlandse Vereniging voor Obstetrie en Gynaecologie
  • Nederlandse Vereniging voor Radiologie
  • Nederlandse Vereniging voor Klinische Chemie en Laboratoriumgeneeskunde
  • Nederlandse Vereniging voor Allergologie en Klinische Immunologie
  • Nederlandse Vereniging voor Endocrinologie
  • Nederlandse Vereniging voor Vaatchirurgie

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.

Volgende:
Jodiumhoudend CM en Diabetes Mellitus (DM)