Contrast Media IRTB 2013

1. Contrast MediaIRTB 2013 Dr Lyn Jones North Bristol NHS Trust

2. Dependent on inner diameter and length 3F 6-8 mls/s 4Fr 16-18 ml/s 5F 20-25 ml/s. Hand injection maximum 5-6mls/sec Flow rates

3. Slow the rate and increase the volume in slow flow arteries and for rotational programmes Slow the rate rise to prevent catheter recoil Max PSI should be documented on the catheter hub Dilute if i.a. injection for CT Examples Bilateral iliac: 20mls at 10mls/sec Arch aortogram: 35mls at 15mls/sec Single leg run off: 10mls at 5mls/sec SMA/Coeliac: 35mls at 6mls/sec Rotational renal transplant: 20mls at 7 mls/sec Post EVAR CT: 100mls diluted 50/70 mix with saline at 8 mls/sec Pump injectors

4. Contrast reactions • Warmth and/or pain, particularly uncomfortable for direct arterial injection • ICM less painful for intra-arterial injection • Dilute contrast when direct injection into smaller vessels • Flushing, metallic taste, headache • Can be reduced by slower injection • Dose dependent • N&V • Doesn’t matter how fast you give it • Anaphylactic reactions • Potentially life threatening • Constitutes 4:10,000 severe or life-threatening reactions

5. Anaphylaxis • Know the protocols • Know where your crash trolleys are • High risk patients: • Investigation justified? • Use alternative investigation or alternative contrast? • Omit contrast medium? • Steroid prophylaxis? • PO/IV? • Must be started 24 hours prior to administration.

6. HOCM Tri–iodinated benzoic acid (Ionic contrast, therefore charged particle) High Osmolality 1500-2300 mOsm/kg water (monomers) 690 mOsm/kg water (dimers) c/w Plasma Osmolality 280-303 mOsm/kg water LOCM Tri-iodinated substituted ring compound Side chains make molecule highly hydrophilic to increase solubility without dissociation Low Osmolality 580 mOsm/kg water (monomers)(Ultravist/Niopam/Optiray/Omnipaque) 272 mOsm/kg (dimers)(Visipaque)(Saline added to increase osmolality) also called isosmolar or ICM Contrast Terminology

7. HOCM 1:40,000 Mortality Higher incidence of adverse reactions 5% Allergy Higher incidence of contrast induced nephropathy (CIN) Not for use intravascularly LOCM 1:170,000 mortality 4:10,000 severe or life-threatening reactions Intravascular use: 80-90% intravenous, 10-20% intra-arterial HOCM v. LOCM

8. Contrast media adverse effects CIN • Contrast media induced nephropathy (CIN) is the sudden rapid deterioration of renal function resulting from contrast media administration and with no alternative clinical explanation • ↑ SCr ≥ 0.5mg/dl or ↑ SCr ≥ 25% • First described 1954 but became a concern only since the development of nonionic low osmolar contrast media (LOCM) in the 1980s; significantly reduced systemic and CNS toxicities Bartels ED et al. Acta Med Scand 1954 150: 297-302

9. Mechanism of CIN • Direct renal tubule toxicity • Vasoconstriction in vasa recta leading to medullary ischemia which exacerbates toxicity • Transient fall in GFR due to osmotic effects

10. Incidence of CIN • Controversial – concept of Hospital Induced Nephropathy (No control arm in published trials) • Negligible in patients with normal renal function, but if renal insufficiency then: • Intra-arterial ICM administration 8%-57% • Increases as GFR falls below 60ml/min/1.73sqm • Mehran R et al,J Am Coll Cardiol 2004 44 1393-9 • Intravenous ICM administration ~ 5% • Increases as GFR falls below 45ml/min/1.73sqm • Romano G et al, Eur Heart J 2008 29 2569 -76

11. Significance of CIN • Controversial • Development of CIN is associated with increased length of hospitalization, need for dialysis (<1%) and long term mortality • But no causal relationship yet proven; CIN may simply be an indicator of patients likely to fare poorly under any circumstances Contrast-induced nephropathy: what are the true clinical consequences? Rudnick M and Feldman H Clin J Am Soc Nephrol 2008; 3 (1): 263-272

12. Renal Function - Chronic * All GFR values are normalized to an average surface area (size) of 1.73m2

13. Which Iodinated Contrast Medium? • LOCM has reduced rate of CIN over HOCM • Pharmacokinetics of all currently used iodinated contrast media are similar • Low lipid solubility • Extremely low chemical activity with bodily fluids • Relatively low molecular weights • Half time in patients with normal renal function of 1-2 hours • “extracellular tracers” = class of compound

14. Controversy over choice of iodinated contrast medium • A meta-analysis of the renal safety of isosmolar iodixanol compared with low-osmolar contrast media McCullough PA, J Am Coll Cardiol 2006; 48 (4): 692-9 • GE unit ordered to pay $11.3 million over false advertising claims against competitor; judge denies request that GE subsidiary Amersham disgorge $1 billion in profits Toulant C Available at http://www.law.com/jsp/article.jsp?id=1202429880602 (last accessed 01/01/2010) • Nephrotoxicity of iso-osmolar contrast media meta-analysis of randomized controlled trials Heinrich MC et al. Radiology 2009 250 (1) 68-86 • Cardiac angiography in renally impaired patients (CARE) study: a randomised double-blind trialof contrast-induced nephropathy in patients with chronic kidney disease Solomon RJ et al. Circulation 2007 115: 3189-96

15. Choice of radiographic iodinated contrast medium (RICM) • Both LOCM and ICM are acceptable for intravenous administration. No evidence to distinguish CIN risk even in high risk patients • Limited evidence that ICM carries a smaller risk than LOCM for intra-arterial administration but both acceptable Ellis J and Cohan R, Radiol Clin N Am 2009 47 801 - 811

16. Reduction in risk of CIN • Identify patients at risk • Acute kidney injury/ARF • Chronic renal disease • eGFR < 40ml/min/1.73sqm for intra-venous ICM • eGFR < 60ml/min/1.73sqm for intra-arterial ICM • Dose Reduction or Elimination (consider alternative agents) • Hydration • Optimal regime not known, IV, earlier and longer probably better • Consider N acetyl cysteine • Evaluate risks/benefits of ICM for individual patient • No absolute renal contraindication to ICM administration • Most CIN resolves without untoward clinical effects

17. Alternative agents – CO2 CO2 is an endogenous, invisible, compressible, soluble, non-viscous and buoyant gas provides a relatively low contrast, negative contrast agent Advantages • Eliminated by one pass through the lungs • Lacks allergic potential and renal toxicity • Low viscosity (1/400 that of iodinated contrast) • Easy delivery through microcatheter or between catheter and wire • Flows readily into bleeding sites • Allows superior opacification of portal vein via wedge portal venography or parenchymal injection

18. Alternative agents - CO2 Disadvantages • Potential neurotoxicity and cardiac ischemia • Contraindicated in cerebral and coronary circulations, thoracic aorta, brachial artery or if the patient has a significant AV shunt • Invisible • Potential undetected air contamination; use sealed delivery system • Buoyant • Rises to non-dependent portion of a larger diameter vessel; potential to overestimate stenoses and may not fill dependent vessels • Prone position and head elevated position contraindicated • Compressible • Potential excessive volumes or explosive delivery (use of finite volume plastic bag delivery system is recommended) • Caution with intestinal ischemia, pulmonary compromise, AAA and N2O anaesthesia

19. Alternative agents - CO2 Advice • Disposable cylinder, individually tested with initial test venous injection and pulmonary artery imaging • Use closed system and never connect CO2 cylinder directly • Flush regularly with CO2, not saline • Wait 2-5 minutes between injections to minimise risk of ischemia • Change patient position and use vasodilators • Use high resolution DSA with high frame rate and scene summation soft ware to optimise image Hawkins I et al. Radiol Clin N Am 2009 47 813-825

20. Alternative imaging - Gadolinium

21. Alternative imaging - Gadolinium • For allergy to RICM, obtain MRA for diagnosis then use Duplex and low dose GdCM to guide plasty (painful intra-arterial injection and poor opacification) • Nephrotoxicity at equi-attenuating volumes worse than LOCM, so no use if renal function↓ • Risk of Nephrogenic Systemic Fibrosis (NSF) if patient has renal compromise

22. Nephrogenic Systemic Fibrosis (NSF)

23. Gadolinium chelates • High risk—Omniscan (gadodiamide), OptiMARK (gadoversetamide), Magnevist (gadopentetic acid) • Medium risk—MultiHance (gadobenic acid), Primovist (gadoxetic acid), Vasovist (gadofosveset) • Low risk—Gadovist (gadobutrol), ProHance (gadoteridol), Dotarem (gadoteric acid) MHRA Medicines and Healthcare products Regulatory Agency and CHM Commission on Human Medicines in Drug Safety Update January 2010 Volume 3, Issue 6 page 3-5

24. Contrast Media Summary • LOCM has excellent safety profile currently (0.04% life-threatening reactions) • Optimize administration protocols for individual radiographic equipment • Caution in patients with Renal Compromise • Justification, optimization, dose reduction • Hydration (+/- NAC) • Consider use of alternative agents (CO2)

26. Nephrogenic Systemic Fibrosis (NSF) • First cases diagnosed in 1997, but correlation with exposure to GdCM first reported in 2006 • Variable clinical picture • early erythema, pain, neuropathy inflammatory reaction, gastroenteritis, lungs, eyes • late skin thickening and hardening, contractures, disabilities • Gadolinium salts present in affected skin supports causality • Depends on stability of chelate; related to free Gd

27. Gadolinium chelates