Standards for Intravascular Contrast Administration to Adult Patients
www.rcr.ac.uk
Standards for intravascular contrast administration to adult patients
Third edition
Faculty of Clinical Radiology Standards for intravascular contrast 2 www.rcr.ac.uk administration to adult patients
Contents Renal function monitoring 10 Renal impairment 10 Foreword 3 Perioperative liver transplantation period 11 Recommended standards 4 Breastfeeding 11 Pregnancy 11 1. Introduction 5 Haemodialysis 11 2. General safety issues 5 Recording of the agent used 11 3. Practical safety issues 5 10. The treatment of reactions 11 4. Prescribing contrast 6 Nausea/vomiting 11 Ur ticaria 11 5. Patient information and consent 6 Bronchospasm 11 6. Identifying patients at increased risk Laryngeal oedema 12 from contrast administration 7 Hypotension 12 7. Recommendations for contrast use in patients at Generalised anaphylactic reaction 12 increased risk 7 Recording and investigation of significant History of previous contrast reaction 7 suspected contrast reactions 12 Asthma 7 Contrast medium extravasation 12 Multiple allergies or a documented severe allergy Delayed skin reactions 13 requiring therapy 8 11. Conclusion 13 Renal disease, diabetes mellitus and conditions associated with renal impairment 8 References 14 Risk factors for acute kidney injury in adults Appendix 1. Contrast-induced acute receiving iodinated contrast media 8 kidney injury 16 Metformin 9 Appendix 2. Chronic kidney disease stages 17 8. Other special cases 9 Appendix 3. Clinical features and clinicopathological Pregnancy 9 definition of NSF 18 Lactation 9 Thyroid 9 Appendix 4. European Medicines Agency classification Interleukin-2 treatment 9 of gadolinium-based contrast agents 20 9. Gadolinium contrast agents 10 Appendix 5. Definitions of confounded and Advice 10 unconfounded cases of contrast reaction 21
RCR Standards The standards are not regulations governing practice but attempt to define the aspects of radiological The Royal College of Radiologists (RCR), a registered services and care which promote the provision of a charity, exists to advance the science and practice of high-quality service to patients. radiology and oncology. All of the standards produced by the RCR can be found It undertakes to produce standards documents to on the College website www.rcr.ac.uk/standards provide guidance to radiologists and others involved in the delivery of radiological services with the aim of Francis classification of RCR Standards improving the service for the benefit of patients by defining best practice, and promoting advances in • Fundamental standards of minimum safety and quality practice. in respect of which non-compliance should not be tolerated. Failures leading to death or serious harm The standards documents cover a wide range of topics. should remain offences for which prosecution can be All have undergone an extensive consultation process to brought against organisations. There should be a ensure a broad consensus, underpinned by published defined set of duties to maintain and operate an evidence where applicable. Each is subject to review effective system to ensure compliance. four years after publication or earlier if appropriate. • Enhanced quality standards: such standards could set The RCR has committed to reviewing all relevant requirements higher than the fundamental standards, publications in line with the recommendations of the but would be discretionary matters for commissioning Francis report and, where appropriate, applying the and subject to availability of resources. category of standard defined by Francis (fundamental, enhanced or developmental).1 This document contains • Developmental standards which set longer term goals standards that fall within the enhanced category. for providers: these would focus on improvements in effectiveness and are more likely to be the focus of commissioners.1 Standards for intravascular contrast Standards for intravascular contrast administration to adult patients administration to adult patients www.rcr.ac.uk 3
Foreword These revised guidelines are necessary because of the ever-changing literature about both iodinated contrast media and gadolinium-based contrast agents (GBCAs). The RCR would like to thank the original authors, Professors Sameh Morcos and Peter Dawson, along with Dr Mark Downes, Dr Giles Roditi, Dr Andrew Lewington (Renal Association) and Dr Grant Baxter, who were largely responsible for this revision. The RCR would also like to thank the members of the Professional Support and Standards Board (PSSB) who made significant contributions. This document replaces Standards for intravascular contrast administration to adult patients, second edition (BFCR[10]4) and Gadolinium-based contrast media and nephrogenic systemic fibrosis (BFCR[07]14) which have been withdrawn. These standards fall within the enhanced category as defined by the Francis report, see RCR Standards (page 2).1
Richard FitzGerald Vice-President, Clinical Radiology The Royal College of Radiologists
Current standards documents Standards for the provision of an significant radiological findings, Standards for the recording of second ultrasound service Second edition opinions or reviews in radiology departments Standards of practice of computed Standards for patient consent particular tomography coronary angiography to radiology, Second edition Standards for a results (CTCA) in adult patients acknowledgement system Standards of practice and guidance for Cancer multidisciplinary team meetings trauma radiology in severely injured Standards for providing a 24-hour – standards for clinical radiologists, patients diagnostic radiology service Second edition Standards and recommendations for the Standards for providing a 24-hour Standards for Learning from reporting and interpretation of imaging interventional radiology service Discrepancies meetings investigations by non-radiologist Standards for Self-assessment of medically qualified practitioners and Standards for radiofrequency ablation Performance teleradiologists (RFA), Second edition Standards for the Reporting and Standards for the NPSA and RCR safety Standards for patient confidentiality and Interpretation of Imaging investigations checklist for radiological interventions PACS and RIS Standards for Ultrasound Equipment Standards for the provision of Standards for the communication of teleradiology within the United critical, urgent and unexpected Kingdom Standards for intravascular contrast 4 www.rcr.ac.uk administration to adult patients
Recommended Standard 4 Standard 7 standards In cases where there is a previously GBCAs deemed to be high-risk in reported moderately severe or regard to their association with the Standard 1 severe reaction to intravascular development of nephrogenic An individual trained in recognising contrast, caution should be systemic fibrosis (NSF) are and treating severe contrast exercised and the need for the use contraindicated in patients with reactions, including anaphylaxis, of contrast should be re-examined severe chronic or acute renal should be immediately available in with respect to an unenhanced impairment, patients in the peri- the department where contrast is study or other potential methods of operative liver transplantation administered. investigation. period and in neonates.
Standard 2 Standard 5 Standard 8 A formal record of the decision to For elective examinations in When using GBCAs, renal function inject intravascular contrast should patients who have a history of must be known for all patients be made before administration. previous contrast reaction, receiving agents deemed as high consideration should be given to risk. Knowledge of renal functional Standard 3 referral to a specialist drug allergy status is also generally advisable for service for assessment and testing patients receiving agents classed as The individual administering the against a panel of contrast medium risk. contrast must check that there are compounds to determine the safety no contraindications to its use and of administration. Standard 9 ensure that the patient understands Significant suspected contrast that it is to be given and agrees to Standard 6 the procedure. reactions should be formally The dose of non-ionic iodine-based documented with full details, contrast medium should be investigated appropriately with minimised, taking into advice given to the patient and consideration the indication and referral made to a specialist drug the patient’s body weight. allergy service to help guide future management. Standards for intravascular contrast Standards for intravascular contrast administration to adult patients administration to adult patients www.rcr.ac.uk 5
1. Introduction 2. General safety issues 3. Practical safety issues The use of intravascular contrast in Non-ionic, low or iso-osmolar An individual trained in recognising radiology continues to increase. iodinated media are five to ten and treating severe contrast The potential risks of intravascular times safer than the older, high reactions, including anaphylaxis, administration of contrast must be osmolar ionic contrasts.2 should be immediately available in weighed against the potential the department. This could be a Both low osmolar iodinated media benefits. Withholding contrast may registered nurse or radiographer or and GBCAs are associated with a deprive patients of the benefits of other appropriately trained very low rate of adverse events valuable diagnostic information or healthcare professional. (0.15% for low osmolar iodine necessary therapy. This document contrast and 0.04% for gadolinium There should be systems in place to aims to provide guidance on how contrast).3 call an appropriately trained doctor intravascular contrast may be used who can deal immediately with a as safely as possible. Most adverse events are mild and severe contrast reaction. If required, can be managed in the radiology this may include a crash team. This document deals with department.3 administration of intravascular In the presence of risk factors, the A major life-threatening contrast contrast to adult patients. For decision about contrast reaction is rare. The incidence of children and neonates, a paediatric administration should only be taken radiologist should be consulted. severe reactions with non-ionic by the radiologist responsible for contrast media is 0.04% and very the procedure. This decision serious reactions is 0.004%.2,3 For process should include the location GBCAs, the severe adverse reaction of the proposed examination with rate is even lower, estimated to be reference to resuscitation capability. 0.0025%.4 In view of the risk of contrast To minimise risk, it is important to nephrotoxicity, dehydration of identify individuals at an increased patients before contrast risk of an adverse event. administration is undesirable and Appropriate steps to reduce the should be avoided. risk of contrast reactions should Facilities for the treatment of acute always be taken. adverse reactions should be readily available and regularly checked within the department. A patient should not be left alone or unsupervised in the first five minutes after an injection of any intravascular contrast. Standards for intravascular contrast 6 www.rcr.ac.uk administration to adult patients
It is advisable that the patient 4. Prescribing contrast 5. Patient information remains on the premises for at least A formal record of the decision to and consent 15 minutes following the injection. inject intravascular contrast should Most severe reactions occur during The patient should always be fully be made before administration. this time. In patients at increased informed about any procedure and How this is achieved will depend on risk of a reaction, this should be understand what it will involve. local circumstances, but may increased to 30 minutes. Appropriate patient information include: leaflets should be available in the All contrast reactions, with details • Setting up a patient group department. The individual of their nature, severity and the directive to cover specific scan administering the contrast must specific compound used, should be protocols check that there are no included in the radiological report, contraindications to its updated in the patient’s hospital • A formal written record by the administration and ensure that the notes and on the radiology radiologist, signed and dated on patient understands that it is to be information system (RIS). the request and either filed in the given and agrees to proceed. radiology department or scanned into the RIS • Recording the decision Standard 1 electronically, directly into the RIS Standard 3 An individual trained in as part of the vetting and The individual administering recognising and treating protocol assignation process the contrast must check that severe contrast reactions, • A formal prescription on the there are no contraindications including anaphylaxis, should patient’s drug chart. to its use and ensure that the be immediately available in patient understands that it is the department where to be given and agrees to the contrast is administered. procedure. Standard 2 A formal record of the decision to inject intravenous contrast should be made before administration. Standards for intravascular contrast Standards for intravascular contrast administration to adult patients administration to adult patients www.rcr.ac.uk 7
6. Identifying patients at 7. Recommendations for • Leave the cannula in place and increased risk from contrast use in patients keep the patient under observation for 30 minutes after contrast administration at increased risk the procedure The ultimate responsibility for History of previous contrast • Be ready to treat any adverse intravascular contrast administration reaction reaction promptly and ensure rests with the person who prescribes that emergency drugs and it, although delivery of the injection Caution should be exercised when equipment are available. is frequently delegated to others there is a previously reported under local rules and protocols. moderately severe (such as Asthma bronchospasm or urticaria requiring Essential information which should treatment) or severe reaction (for Asthmatics are at an increased risk be sought from the patient before example, laryngeal or angioneurotic of severe contrast reactions by a a contrast injection includes oedema, severe bronchospasm or factor of six with low or iso-osmolar history of: collapse) to intravascular contrast.5,6 non-ionic contrast and by a factor of • Previous contrast reaction ten with high osmolar contrast.2 Advice • Asthma Advice Determine: • Renal problems Determine: • The exact nature of the previous • Diabetes mellitus reaction • Whether the patient has true • Metformin therapy. asthma or chronic obstructive • The specific compound used on pulmonary disease (COPD) Ideally, this information will be that occasion. available when the examination is • Whether the asthma is currently Re-examine the need for the use of requested but should always be well controlled. contrast, with respect to an checked in the department before unenhanced study or other If the patient is wheezy or reports injection. potential methods of investigation. that their asthma is currently not well controlled, and the Assess the risk–benefit ratio of the examination is not urgent, it should procedure, bearing in mind that a be deferred and the patient non-diagnostic examination may be referred back for appropriate as or more detrimental to the medical therapy. patient than the perceived risk from contrast exposure. If the asthma is well controlled, reassess the need for intravascular For elective examinations, consider contrast with respect to an referral to a specialist drug allergy unenhanced study or other service for assessment and testing potential methods of investigation. of the patient against a panel of contrast compounds to determine If the injection is deemed the safety of administration. necessary: If the injection is deemed • For iodine contrast, use a necessary: non-ionic low or iso-osmolar compound • Use a different contrast compound to that previously • Maintain close medical used (preferably one that has supervision been tested and shown to • Leave the cannula in place and be safe) observe the patient for 30 • Maintain close medical minutes after the procedure supervision • Be ready to treat any adverse reaction promptly and ensure that emergency drugs and equipment are available. Standards for intravascular contrast 8 www.rcr.ac.uk administration to adult patients
Multiple allergies or a documented Renal disease, diabetes mellitus In practice, many units ask patients severe allergy requiring therapy and conditions associated with under the age of 70 the question renal impairment ‘Do you have diabetes, high blood Individuals with multiple well- pressure, heart failure or any kidney documented allergies or a single In the presence of renal impairment, problems, kidney failure or have you very severe allergy are at increased all contrast – including non-ionic ever been on dialysis?’ If the risk.2,5,6 low osmolar, iso-osmolar media and patient’s answer is anything other high-volumes of GBCAs – are than an unequivocal ‘no’, and for all Advice nephrotoxic. patients due to receive intra-arterial Determine the nature of the Previous terminology such as contrast, an eGFR is mandated. allergies and their sensitivity. (NB: contrast nephrotoxicity, contrast- However, asking such a question there is no specific cross reactivity induced nephropathy (CIN) or allows a busy unit to proceed with with shellfish or topical iodine in radiocontrast nephropathy (RCN) contrast without recourse to blood acute contrast reactions.) have been replaced by contrast- results if the patient replies ‘no’ to induced acute kidney injury In those with multiple or severe all these points. (CI-AKI), in line with other causes of allergies, re-examine the need for Patients who have an acute illness acute kidney injury.8,9 (See contrast administration with respect or who are known to have renal Appendix 1 for a definition of to an unenhanced study or other disease should have an eGFR or, CI-AKI). potential methods of investigation. preferably, serum creatinine For elective examinations, consult estimations obtained from the Risk factors for acute kidney injury with a specialist drug allergy service previous seven days, which can be in adults receiving iodinated for testing the patient against a assessed against a baseline. contrast media panel of contrast compounds to Particular care should be taken in determine safety of administration.7 Increased risk is associated with: patients who are acutely or severely The potential risks of intravascular • Chronic kidney disease (adults unwell, such as with hypotension or administration of contrast must be with an estimated glomerular hypovolaemia. In these cases, scans weighed against the potential filtration rate [eGFR] of less than are likely to be carried out on an benefits. 40 millilitres [ml]/minute [min]/ urgent or emergency basis and the 1.73 m2 are at particular risk) If the injection is deemed potential risks of contrast use must necessary: • Heart failure be weighed against the potential benefits. • For iodine contrast, use a • Renal transplant non-ionic low or iso-osmolar Further preventative strategies • Age 75 years or older compound should include offering intravenous • Hypovolaemia volume expansion to patients at risk • Maintain close medical of CI-AKI. supervision • Increasing dose of contrast or repeated administration of In the presence of acute illness, • Leave the cannula in place and contrast volume expansion regimes can observe the patient for 30 include the use of isotonic sodium minutes after the procedure • Intra-arterial administration of bicarbonate or 0.9% sodium contrast.8,9 • Be ready to treat any adverse chloride. reaction promptly and ensure To minimise the risk of CI-AKI, joint Consideration should be given to that emergency drugs and guidance from the Renal temporarily stopping angiotensin- equipment are available. Association, British Cardiovascular converting enzyme (ACE) inhibitors Intervention Society (BCIS) and the There is no conclusive evidence of and angiotensin II receptor blockers RCR recommends that eGFR should benefit for the prophylactic use of (ARBs) in the presence of chronic be available for all non-emergency kidney disease with an eGFR less steroids in the prevention of severe 10 patients. For patients who are in a 2 reactions to contrast.5,6 than 40 ml/min/1.73 m (see stable clinical condition, an eGFR Appendix 2 for chronic kidney within the previous three months is disease stages).11 satisfactory. Early involvement by a nephrology team has been shown to be Standards for intravascular contrast Standards for intravascular contrast administration to adult patients administration to adult patients www.rcr.ac.uk 9
beneficial in patients at significant Advice 8. Other special cases risk of CI-AKI. There is no need to stop metformin Pregnancy There is insufficient evidence at this after contrast in patients with serum stage to advocate any creatinine within the normal Where iodinated contrast is pharmacological treatment reference range and/or eGFR administered during pregnancy, attempting to reduce the incidence >60 ml/min/1.73 m2. If serum due to the small theoretical risk of of CI-AKI prophylactically. creatinine is above the normal thyroid suppression in the fetus, reference range or eGFR is below thyroid function should be The dose of non-ionic iodine-based 60, any decision to stop metformin measured in the first week after contrast medium should be for 48 hours following contrast birth.13 minimised, taking into medium administration should be consideration the indication and made in consultation with the Lactation the patient’s body weight. referring clinic. A very small percentage of the For computed tomography (CT) injected dose enters the breast milk angiographic studies, the efficiency and virtually none is absorbed of the iodine-based contrast Standard 4 across the normal gut, hence no medium should be maximised by In cases where there is a special precaution or cessation of using a saline flush (this aids peak previously reported breastfeeding is required.13 enhancement and also helps moderately severe or severe volume expansion/hydration) and reaction to intravascular Thyroid minimising applied tube kilovoltage contrast, caution should be (this also minimises radiation Intravascular contrast should not be exercised and the need for dose).12 administered if the patient is the use of contrast should be hyperthyroid. In patients with A hydration regime should be re-examined with respect to thyroid cancer, the use of iodinated maintained post contrast an unenhanced study or other contrast media will preclude administration. potential methods of therapeutic radio-iodine treatment investigation. for two months.14 Magnetic Metformin resonance imaging (MRI) is the Standard 5 Metformin is not recommended for preferred staging method in these use in diabetics with renal For elective examinations in patients. impairment because it is excreted patients who have a history of Isotope thyroid imaging should also exclusively via the kidneys. previous contrast reaction, be avoided for two months after Accumulation of metformin may consideration should be given intravascular administration of result in the development of lactic to referral to a specialist drug iodinated contrast.15 acidosis – a serious complication. allergy service for assessment There is a lack of any valid evidence and testing against a panel of Interleukin-2 treatment that lactic acidosis is really an issue contrast compounds to after administration of iodinated determine the safety of A specific risk of delayed skin rash is contrast media in patients taking administration. associated with interleukin-2 metformin. The problems caused to therapy. Oncologists should be patients and clinicians by stopping Standard 6 informed that they should always the drug and its increasing use in indicate if the patient is on this drug The dose of non-ionic poorly controlled diabetic patients when referring them for a contrast iodine-based contrast regardless of renal function have injection.16 medium should be minimised, been considered when formulating taking into consideration the this advice. It does, however, remain indication and the patient’s the case that renal function should body weight. be known in patients taking metformin who require intravenous or intra-arterial iodinated contrast medium administration. Standards for intravascular contrast 10 www.rcr.ac.uk administration to adult patients
9. Gadolinium-based three months later, it is now Advice recognised that clinical contrast agents The following risk minimisation manifestations may present years measures should be used for GBCAs are remarkably safe, with a later, the reasons for and GBCAs. This advice is adapted from lower adverse event rate for both mechanisms underlying this are not the current Medicines and allergic type reactions and understood currently.19 nephrotoxicity. However, their Healthcare products Regulatory 24 administration in patients with Some GBCAs have been much Agency (MHRA) advice. severe renal failure has been more associated with the associated with the development of development of NSF than others. Renal function monitoring The Committee for Medicinal the very rare condition nephrogenic Renal function should be tested in Products for Human Use (CHMP) of systemic fibrosis (NSF). See advice all patients receiving high-risk the European Medicines Agency below to minimise this risk from agents and is generally advisable (EMEA) has classified these as low, GBCAs in the following vulnerable for patients receiving medium-risk medium and high risk (see groups: agents. It is particularly important Appendix 4 for details).20,21 • Patients with renal impairment to screen patients aged 65 years or The EMEA’s Scientific Advisory older and patients with chronic • Patients in the perioperative liver Group on Diagnostics concluded diseases, such as diabetes, which transplantation period that the cyclic products (the three are associated with renal failure. • Infants, neonates and the elderly products with the lowest risk) can be used for patients with severely Renal impairment • Women who are pregnant or reduced renal function when a breastfeeding. For patients with severe chronic contrast enhanced MRI scan is renal impairment (eGFR <30 ml/ NSF is an extremely rare but serious clearly the best method of min/1.73 m2) or acute renal and potentially life-threatening examination. They did not impairment, use of a high-risk agent condition characterised by the recommend contraindicating the is contraindicated. If, after clinical deposition of collagen in the skin use of these GBCAs in patients with review, use of a low-risk agent is which becomes thickened, coarse renal impairment because, in some appropriate or if it is necessary to and hard, sometimes leading to cases, there are no alternatives, use a medium-risk agent, a single contractures and joint immobility. although dose should be limited to lowest dose possible can be used (a Patients with NSF can have systemic the minimum consistent with the dose not exceeding 0.1 millimoles involvement of other organs, investigation being carried out. This [mmol]/kilogram [kg] body weight) including the lungs, liver, muscles classification has not been revised and should not be repeated for at and heart. The cause of NSF is not since initial publication but remains least seven days. fully understood but the consensus appropriate as research continues is that it is associated with the to reinforce the association of cases Avoid administering GBCAs in administration of gadolinium of NSF, both unconfounded and acute kidney injury while creatinine 25 contrast agents (particularly linear confounded in nature, with the use is rising. chelates) in patients with severe of the high-risk classified linear For patients with moderate chronic renal impairment. A diagnosis of chelates (see Appendix 5 for renal impairment (eGFR 30–59 ml/ NSF is based on a combination of definitions of confounded and min/1.73 m2), if, after clinical review, 11,22,23 clinical and pathological criteria unconfounded cases). it is necessary to use a high-risk 17 (see Appendix 3). The RCR High-risk GBCAs are agent, a single lowest dose possible published guidance on GBCAs and contraindicated in patients with should be used and should not be NSF soon after this association was severe chronic or acute renal repeated for at least seven days. 18 first identified in 2007. While in impairment, patients in the most instances of NSF, the onset of perioperative liver transplantation symptoms can be identified to be period and in neonates. from the day of exposure to two or Standards for intravascular contrast Standards for intravascular contrast administration to adult patients administration to adult patients www.rcr.ac.uk 11
Perioperative liver transplantation Recording of the agent used 10. The treatment of period When they are available, ‘peel-off reactions Use of a high-risk agent is tracking labels found on the vials, Simple guidelines for the treatment contraindicated for patients in the syringes or bottles should be stuck of reactions are presented perioperative liver transplantation onto or scanned into the patient below.28,29 period. If the use of a low-risk agent record to maintain an accurate note is required, or if it is necessary to of the name and batch of the Nausea/vomiting use a medium-risk agent, a single gadolinium contrast agent used. lowest dose possible can be used The dose used should also be • Transient: supportive treatment and should not be repeated for at documented. • Severe, protracted: appropriate least seven days. Suspected adverse reactions anti-emetic drugs should be should be reported on a Yellow considered. Breastfeeding Card to the MHRA.27 Breastfeeding should be Urticaria discontinued for at least 24 hours • Scattered, transient: supportive after use of a high-risk agent. The treatment, including observation decision as to whether to continue Standard 7 or suspend breastfeeding for 24 • Scattered, protracted: GBCAs deemed to be hours after use of a medium-risk or appropriate H1-antihistamine high-risk in regard to their low-risk agent should be at the orally or intramuscularly should association with the clinician’s discretion in consultation be considered. Drowsiness and/ development of NSF are with the mother. or hypotension may occur contraindicated in patients • Profound: consider adrenaline with severe chronic or acute Pregnancy 1:1000, 0.1–0.3 ml (0.1–0.3 renal impairment, patients in milligrams [mg]) intramuscularly. Use of any GBCA is not the perioperative liver Repeat, as needed. recommended during pregnancy transplantation period and unless absolutely necessary. in neonates. Bronchospasm Haemodialysis Standard 8 • Oxygen by mask (6–10 litre [l]/ min) There is no evidence to support the When using GBCAs, renal initiation of haemodialysis for function must be known for all • β-2-agonist metered dose inhaler prevention or treatment of NSF in patients receiving agents (2–3 deep inhalations) patients not already undergoing deemed as high risk. • Adrenaline: haemodialysis, as emergency Knowledge of renal functional initiation of dialysis entails status is also generally – Elevate patient’s legs significant risks. However, those advisable for patients – Normal blood pressure: patients already established on receiving agents classed as adrenaline 1:1000, 0.1–0.3 ml dialysis should be dialysed promptly medium risk. (0.1–0.3 mg) intramuscularly. after contrast administration Use smaller dose in a patient (certainly within 24 hours).26 with coronary artery disease or elderly patient Standards for intravascular contrast 12 www.rcr.ac.uk administration to adult patients
– Decreased blood pressure: Recording and investigation of • Skin blistering, paraesthesiae, adrenaline 1:1000, 0.5 ml (0.5 significant suspected contrast altered tissue perfusion and mg) intramuscularly. reactions increasing or persistent pain for more than four hours suggest • For anaphylaxis (severe Laryngeal oedema severe injury. In this case, seek multisystem reaction) or for surgical advice (plastic • Oxygen by mask (6–10 l/min) severe urticaria or angioedema surgeon).31–33 without systemic features, record • Adrenaline 1:1000, 0.5 ml (0.5 mg) details of the incident with a intramuscularly. Repeat as Delayed skin reactions description in the report and needed. notes, including generic and • Skin reactions have been reported proprietary names of the contrast up to a week after the Hypotension used plus batch number administration of contrast • Isolated hypotension medium, more commonly with • For anaphylaxis, take blood dimeric iodine-based contrast – Oxygen by mask (6–10 l/min) samples for mast cell tryptase in media.15 Symptomatic treatment line with recommendations in – Intravenous fluid: rapidly, only is required. The reaction Anaphylaxis: assessment to normal saline or lactated should be noted in the patient’s confirm an anaphylactic episode Ringer’s solution record, but it is the case that the and the decision to refer after status and significance of these – If unresponsive: adrenaline emergency treatment for a reactions are uncertain. 1:1,000, 0.5 ml (0.5 mg) suspected anaphylactic intramuscularly. Repeat as episode30 needed. • Discuss the patient’s suspected • Vagal reaction (hypotension and contrast reaction with them and Standard 9 bradycardia) their carers, if appropriate, and Significant suspected contrast provide written information – Elevate patient’s legs reactions should be formally – Oxygen by mask (6–10 l/min) • Arrange referral to a specialist documented with full details, drug allergy service to help guide investigated appropriately – Atropine 0.6–1.0 mg future management with advice given to the intravenously, repeat if patient and referral made to a • Suspected adverse reactions necessary. After 3–5 min, to specialist drug allergy service should be reported on a Yellow 3 mg total (0.04 mg/kg) to help guide future Card to the MHRA.27 – Intravenous fluids: rapidly, management. normal saline or lactated Contrast medium extravasation Ringer’s solution. • Record details of the incident with Generalised anaphylactic reaction management advice in the report and notes • Call for resuscitation team • Elevate the affected limb • Suction airway if needed • Apply ice packs to the affected • Elevate patient’s legs if area hypotensive • If symptoms resolve such that an • Oxygen by mask (6–10 l/min) outpatient can be allowed home, • Adrenaline: 1:1000, 0.5 ml (0.5 mg) supply the patient with an intramuscularly appropriate advice leaflet • H1 blocker, for example, • If symptoms do not resolve diphenhydramine 25–50 mg quickly, admit and monitor intravenously. Standards for intravascular contrast Standards for intravascular contrast administration to adult patients administration to adult patients www.rcr.ac.uk 13
11. Conclusion The intention of this standards document is to clarify those factors The use of intravascular contrast that should be taken into account has become fundamental to for the prevention and treatment of modern radiology and the adverse events related to the use of compounds used in daily practice intravascular contrast. Compliance are extremely safe. However, as our with the proposed standards should knowledge expands regarding the translate directly into high-quality potential to prevent and risk care for the many patients referred manage adverse events associated to departments of radiology for with the use of intravascular diagnostic imaging and image contrast, so it is appropriate that guided intervention. guidance is revised and standards are set for safe administration. This Approved by the Clinical Radiology Faculty Board: 30 October 2014. most recent revision to the RCR guidance builds upon earlier work. The main areas of change are: • The nomenclature and definitions in relation to contrast-induced acute kidney injury (CI-AKI) • A focus on maintaining hydration of patients at risk of CI-AKI and minimising the dose of intravascular contrast used for any individual patient taking into account patient factors, the indication for the examination and technical scan parameters • Clearer identification of patients at risk and explicit documentation of adverse events when they occur (preferably with the use of electronic record systems such as RIS/picture archiving and communication systems [PACS]) such that patients are better prepared for future imaging investigations. Standards for intravascular contrast 14 www.rcr.ac.uk administration to adult patients
References 1. The Mid Staffordshire NHS 8. National Institute of Health and 14. van der Molen AJ, Thomsen HS, Foundation Trust Public Inquiry. Care Excellence. NICE Clinical Morcos SK; Contrast Media Chaired by Robert Francis QC. Guidelines (CG169): Acute Safety Committee, European Report of the Mid Staffordshire kidney injury: prevention, Society of Urogenital Radiology NHS Foundation Trust Public detection and management of (ESUR). Effects of contrast Inquiry. London: The Stationery acute kidney injury up to the media on thyroid function in Office, 2013. point of renal replacement adults. Eur Radiol 2004; 14: therapy. London: National 902–907. 2. Katayama H, Yamaguchi K, Institute of Health and Care Kozuka T, Takashima T, Seez P, 15. The Royal College of Excellence, 2013. Matsuura K. Adverse reactions Radiologists. Imaging for to ionic and non-ionic contrast 9. Khwaja A. KDIGO clinical oncology: Collaboration media. A report from the practice guidelines for acute between clinical radiologists Japanese Committee on the kidney injury. Nephron Clin and clinical oncologists in Safety of Contrast Media. Pract 2012; 120: c179–c184. diagnosis, staging and Radiology 1990; 175: 621–628. radiotherapy planning. London: 10. The Renal Association, British The Royal College of 3. Hunt CH, Hartman RP, Hesley Cardiovascular Interventional Radiologists, 2004. GK. Frequency and severity of Society and The Royal College adverse effects of iodinated and of Radiologists. Prevention of 16. Morcos SK, Thomsen HS, Webb gadolinium contrast materials: contrast induced acute kidney JA. Contrast-media-induced retrospective review of 456,930 injury (CI-AKI) in adult patients. nephrotoxicity: a consensus doses. AJR Am J Roentgenol London: The Royal College of report. Contrast Media Safety 2009; 193: 1124 –1127. Radiologists, 2013. Committee, European Society of Urogenital Radiology (ESUR). 4. Prince MR, Zhang H, Zou Z, 11. Guerbet LLC. Advisory Eur Radiol 1999; 9: 1602–1613. Staron RB, Brill PW. Incidence of committee briefing document. immediate gadolinium contrast Dotarem® (gadoterate 17. Girardi M, Kay J, Elston DM, media reactions. AJR Am J meglumine) injection. Medical Leboit PE, Abu-Alfa A, Cowper Roentgenol 2011; 196(2): Imaging Drugs Advisory SE. Nephrogenic systemic 138–143. Committee (MIDAC). fibrosis: clinicopathological London: Medical Imaging definition and workup 5. Morcos SK, Thomsen HS, Webb Drugs Advisory Committee recommendations. J Am Acad JAW, Contrast Media Safety Meeting, 2014. Dermatol 2011; 65: 1095–1106. Committee of the European Society of Urogenital Radiology. 12. Wintersperger B, Jakobs T, 18. The Royal College of Prevention of generalized Herzog P et al. Aorto-iliac Radiologists. Gadolinium-based reactions to contrast media: a multidetector-row CT contrast media and nephrogenic consensus report and angiography with low KV systemic fibrosis. London: guidelines. Eur Radiol 2001; 11: settings: Improved vessel The Royal College of 1720–1728. enhancement and simultaneous Radiologists, 2007. reduction of radiation dose. Eur 6. Morcos SK, Thomsen HS. 19. Thomson LK, Thomson PC, Radiol 2005; 15: 334–341. Adverse reactions to iodinated Kingsmore DB et al. Diagnosing contrast media. Eur Radiol 2001; 13. Laskey W, Aspelin P, Davidson C nephrogenic systemic fibrosis in 11: 1267–1275. et al. Nephrotoxicity of the post-FDA restriction era. iodixanol versus iopamidol in J Magn Reson Imaging 2014; 7. National Institute of Health and patients with chronic kidney June 5 epub ahead of print. Care Excellence. NICE Clinical disease and diabetes mellitus Guidelines (CG183): Drug allergy 20. Elmholdt R, Olesen ABB, undergoing coronary – Diagnosis and management of Jørgensen B et al. Nephrogenic angiographic procedures. Am drug allergy in adults, children systemic fibrosis in Denmark – A Heart J 2009; 158: 822–828. and young people. London: nationwide investigation. PLoS National Institute of Health and One 2013; 8(12): e82037. Care Excellence, 2014. Standards for intravascular contrast Standards for intravascular contrast administration to adult patients administration to adult patients www.rcr.ac.uk 15
21. The PLOS ONE Staff. Correction: 29. Tomsen HS, Morcos SK, Nephrogenic systemic fibrosis in Members of Contrast Media Denmark – A nationwide Safety Committee of European investigation. PLoS One 2014; Society of Urogenital Radiology 9(6): e10 0 4 07. (ESUR). In which patients should serum creatinine be measured 22. www.renal.org/information- before iodinated contrast resources/the-uk-eckd-guide/ medium administration? Eur ckd-stages#sthash.0hKLLiNJ. Radiol 2005; 15: 749–754. dpbs (last accessed 11/11/2014) 30. National Institute for Health 23. Edwards BJ, Laumann AE, and Clinical Excellence. Nardone B et al. Advancing Anaphylaxis: assessment to pharmacovigilance through confirm an anaphylactic academic-legal collaboration: episode and the decision to the case of gadolinium-based refer after emergency treatment contrast agents and for a suspected anaphylactic nephrogenic systemic fibrosis episode. London: National – a research on adverse drug Institute for Health and Clinical events and reports (RADAR) Excellence, 2011. report. Br J Radiol 2014; 87: 2014 037. 31. Cohan RH, Ellis JH, Garner WL. Extravasation of radiographic 24. Medicines and Healthcare contrast material: recognition, products Regulatory Agency. prevention, and treatment. Drug safety update. London: Radiology 1996; 200: 593–604. Medicines and Healthcare products Regulatory Agency, 32. Cohan RH, Dunnick NR, Leder 2010. RA, Baker ME. Extravasation of nonionic radiologic contrast 25. Prince MR, Zhang H, Morris M media: efficacy of conservative et al. Incidence of nephrogenic treatment. Radiology 1990; 176: systemic fibrosis at two large 65 – 67. medical centers. Radiology 2008; 248: 807–816. 33. Bellin MF, Jakobsen JA, Tomassin I et al. Contrast 26. Zou Z, Zhang HL, Roditi GH, medium extravasation injury: Leiner T, Kucharczyk W, Prince guidelines for prevention and MR. Nephrogenic systemic management. Eur Radiol 2002; fibrosis: Review of 370 biopsy- 12: 2807–2812. confirmed cases. JACC Cardiovasc Imaging 2011; 4: 1206–1216. 27. www.yellowcard.gov.uk (last accessed 11/11/2014) 28. Webb JA, Stacul F, Thomsen HS, Morcos SK, Members of the Contrast Media Safety Committee of the European Society of Urogenital Radiology. Late adverse reactions to intravascular iodinated contrast media. Eur Radiol 2003; 13: 181–184. Standards for intravascular contrast 16 www.rcr.ac.uk administration to adult patients
Appendix 1. Contrast-induced acute kidney injury
CI-AKI is defined when one of the following criteria is met. • Serum creatinine rises by ≥26 micromoles (μmol)/l within 48 hours • Serum creatinine rises ≥1.5 fold from the baseline value, which is known or presumed to have occurred within one week • Urine output is <0.5 ml/kg/hour for more than six consecutive hours. If a baseline serum creatinine is not available within one week, the lowest serum creatinine value recorded within three months of the episode of AKI can be used. If a baseline serum creatinine value is not available within three months and AKI is suspected: • Repeat serum creatinine within 24 hours • A reference serum creatinine value can be estimated from the nadir serum creatinine value if the patient recovers from AKI.
Standards for intravascular contrast Standards for intravascular contrast administration to adult patients administration to adult patients www.rcr.ac.uk 17
Appendix 2. Chronic kidney disease stages11
Chronic kidney GFR ml/min/1.73 m2 Description disease (CKD) stage 1 90+ Normal kidney function but urine findings or structural abnormalities or genetic trait point to kidney disease 2 60–89 Mildly reduced kidney function, and other findings (as for stage 1) point to kidney disease 3A 45–59 Moderately reduced kidney function 3B 30–44 4 15–29 Severely reduced kidney function 5 <15 or on dialysis Very severe or end-stage kidney failure (sometimes called established renal failure) Standards for intravascular contrast 18 www.rcr.ac.uk administration to adult patients
Appendix 3. Clinical features and clinicopathological definition of NSF
Clinical features of NSF
Initial presentation • Pain • Pruritus • Swelling • Erythema • Usually starts in the legs.
Later results • Thickened skin and subcutaneous tissues – ‘woody’ texture and brawny plaques • Fibrosis of internal organs; for example, muscle, diaphragm, heart, liver, lungs • Contractures • Cachexia • Death, in a proportion of patients.
At-risk patients
Higher risk • Patients with chronic kidney disease (CKD) 4 and 5 (Appendix 2) (glomerular filtration rate [GFR] <30 ml/min/1.73 m2) • Acute renal failure • Patients on dialysis • Patients with reduced renal function who have had or are awaiting liver transplantation.
Lower risk • Patients with CKD 3 (GFR 30–59 ml/min/1.73 m2) • Children under one year (immature renal function).
Notes: 1. No cases of NSF have been reported in patients with GFR greater than 60 ml/min/1.73 m2 and it appears that those few cases reported with estimated GFR above 30 were actually in acute renal failure in which estimated GFR is inappropriate. 2. The role of various possible co-factors in the pathogenesis of NSF is not proven but there are suspicions that both hyperphosphataemia and the use of erythropoietin may have a bearing. 3. In the absence of specific information, it remains wise to manage pregnant patients, whatever their renal function, in the same way as children aged less than one year, to protect the fetus. Standards for intravascular contrast Standards for intravascular contrast administration to adult patients administration to adult patients www.rcr.ac.uk 19
Clinicopathological definition of NSF (Girardi criteria)17
The diagnosis of NSF is made with a combination of clinical and pathological scoring. For the clinical score there are major criteria (patterned plaques, joint contractures, cobblestoning and marked induration/peau d’orange) and minor criteria (skin puckering/banding, superficial NSF, dermal papules and scleral plaque in patients aged over 45). A clinical score is then summated with: >1 Major – Highly consistent = 4 1 Major – Consistent = 3 >1 Minor – Suggestive = 2 0–1 – Minor = 1 Another diagnosis = 0 The pathology score follows a similar system for which the interested reader can find details in the referred original article.27
Pathology/clinical 0 1 2 3 4
0 Alternative diagnosis (Dx)
1 Not NSF Inconsistent
2 Not NSF Suggestive Consistent
3
Consistent NSF
4 Inconsistent Standards for intravascular contrast 20 www.rcr.ac.uk administration to adult patients
Appendix 4. European Medicines Agency classification of gadolinium-based contrast agents20,21
NSF risk Generic name Trade name T1 specific Notes category relaxivity in blood at 1.5 T – mmol-1 s-1
High Gadodiamide Omniscan 4.6 Non-ionic linear chelate, contraindicated when GFR <30ml/min/1.73 m2. Incidence of NSF – triggering agent, estimated 3–7% in at-risk subjects (624 unconfounded cases – 2009 data). Gadopentate Magnevist 4.3 Ionic linear chelate, contraindicated when dimeglumine GFR <30 ml/min/1.73 m2. Incidence of NSF – triggering agent, estimated to be 0.1–1% in at risk subjects (221 unconfounded cases – 2014 data). Gadoversetamide Optimark 5.2 Non-ionic linear chelate, contraindicated when GFR <30 ml/min/1.73 m2. Incidence of NSF – triggering agent, no clear data but five reported cases, likely similar incidence to gadodiamide to which it is chemically related. Limited use in European Union (EU). Medium Gadobenate MultiHance 6.7 Ionic linear chelate, 2–3% protein binding, dimeglumine significant hepatic excretion. Incidence of NSF – no unconfounded cases with MultiHance criteria. Gadofosveset Ablavar 19.0 Ionic linear chelate, strong albumin binding trisodium (previously for blood-pool contrast, significant hepatic Vasovist) excretion, not currently commercially available in EU. Incidence of NSF – one unconfounded report unclear as to whether meets Girardi criteria. Gadoxetate Primovist 8.7 Ionic linear chelate, 10% protein binding and disodium 50% hepatic excretion. Incidence of NSF – no reports of NSF. Low Gadobutrol Gadovist 5.3 Non-ionic cyclic chelate. Incidence of NSF – four unconfounded reports unclear as to whether meet Girardi criteria. Gadoterate Dotarem 4.2 Ionic cyclic chelate. Incidence of NSF – no meglumine unconfounded reports. Gadoteridol Prohance 4.4 Non-ionic cyclic chelate. Incidence of NSF – single unconfounded report unclear as to whether meets Girardi criteria. Standards for intravascular contrast Standards for intravascular contrast administration to adult patients administration to adult patients www.rcr.ac.uk 21
Appendix 5. Definitions of confounded and unconfounded cases of contrast reaction
Unconfounded: In ‘unconfounded’ cases only one GBCA had been given before development of NSF. Confounded: If two different GBCAs had been injected within eight weeks of each other (maybe longer), it is impossible to determine with certainty which agent triggered the development of NSF and the situation is described as ‘confounded’. However, the agent that is most likely responsible is the one which has triggered NSF in other unconfounded situations. Triggering agent: To be described as an NSF triggering agent, there must be at least 5–10 NSF cases, validated by adequate documentation including deep skin biopsy, following exposure to a GBCA. Citation details
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