Beyond NSF: Acute GBCA adverse reactions

Transcription

1 Source images Beyond NSF: Acute GBCA adverse reactions Martin R. Prince, MD, PhD, FACR

2 Disclosures Patent Agreements: GE, Siemens, Philips, Hitachi, Toshiba, Bayer, Bracco, Mallinckrodt, Medrad, Nemoto, Topspins, Epix, Lantheus Nephrogenic Systemic Fibrosis (NSF) Papular morphology Dimpling

3 NSF Associations Renal Failure: 80% on dialysis Pro-inflammatory Conditions Acidosis Hyperphosphatemia Epoetin Gadolinium Contrast Agents High dose Nonionic JMRI 2009;30:

4 RSNA 2010: Ayako Taketomi- Takahashi et. al. 13,252 GBCA enhanced exams Agent: Incidence of Reaction type Gadodiamide 0.14% nonionic linear Gd:DTPA 0.55% ionic linear Gd:DOTA 0.34% macrocyclic ion Gadoteridol 2.32% macrocyclic non History of Gd rxn 21% pooled

5 Adverse Reactions MRI centers Murphy et al. Academic Radiology 1999;6: Contrast agent n AE rate Gadoteridol % nonallergic 0.35 total AE (Macrocyclic) 0.14% allergic 0.3 severe AE 0.02% severe Gd:DTPA 0.15 (linear ionic) (These AE rates are specific to the experience at the institutions studied in this publication.) % total 0.001% severe Gadodiamide % total (linear Macro- nonionic) Linear 0.00% severe cyclic Linear ionic nonionic

6 Adverse events in 158,796 GBCA administrations Contrast agents # of Exams Mild AE Moderate AE Severe AE All events Events per 1000 injections Arrest, death Gadobenate (Multihance) Gd: DTPA (Magnevist) 33, * 3 66, Gadodiamide (Omniscan) Gadoteriodol (Prohance) 55, Total 158, * *statistically significantly higher than Gd:DTPA and gadodiamide with p < AJR 2011;196: AJR 2011:196:w

7 Comparison of adverse event patients with age/exam matched controls AE Patients (n = 94) Controls (n = 94) p-value Gender (f/m) 72/22 = /45 = 1.1 < (w/yates) Weight (lbs) Creatinine (mg/dl) Mean Gd Dose(mL) Asthma Prior Gd exposure Prior Gd reaction (Fisher s exact) Prior allergic event < Inpatient Steroid pretreatment

8 Rate of GBCA adverse events by type* of MRI examination Type of GBCAenhanced exam # of Exams # of Reactions Reactions/10,000 Exams Brain 72, Orbit/Face/Neck Spine 23, Cardiac Breast Abdomen 20, ** Pelvis Extremity MR Angiography 14, Total 158, * When > one type of study was performed with a single injection, the study was only counted once based upon the primary reason. * *statistically significantly higher rate compared to brain (p < 0.001)

9 US FDA Medwatch Database 2004 to n/surveilance/adversedrugeffects/ucm htm All spontaneous reports of adverse events to the FDA are entered into an Adverse Event Reporting System (AERS) AE occurred outside US and NSF excluded

10 Market Share Data available from IMS Health Incorporated ( provided directly by companies in the form of liters of GBCA sold each year. Converted into doses administered by dividing the total volume sold for each agent by 17 ml Each manufacturer contacted for doses administered each year to verify IMS data

11 Adverse events in USA reported to Food and Drug Administration from (excluding NSF) Gadobenate dimeglumine Gadoteridol Gd:DTPA Gadodiamide Optimark Death Doses (millions) Deaths per million doses AJR 2011:196:w

12 Comparison between local reports and FDA Local: adverse events/1000 injections FDA: deaths/million Gadobenate Gd: DTPA Gadodiamide

13 Gadobenate dimeglumine (Multihance) more severe AEs (1 death) FDA data more deaths with Gadobenate dimeglumine Gadobenate contraindicated if prior Gd rxn Incidence of death (Gd) < 1/million (comparable to the risk of death from a car accident if driving 78 miles) Gadolinium based contrast agents are extraordinarily safe

14 One in 1 million chance of death Driving 78 miles (~100 kilometers) One chest X-ray Smoking 1.4 cigarettes Drinking 1.5 bottles of wine National Tranportation Safety Board 2008 ACR manual on Radiation Safety

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18 Pooled Data from 7 Studies Murphy, et al. Acad Radiol. 1999;6: Li, et al. Br J Radiol. 2006;79: Dillman. et al. AJR. 2007;189: Bleicher, et al. AJR. 2008;191:W Abujudeh, et al. AJR. 2010;194: Forsting, et al. Eur J Radiol :e Morgan, et al. Radiology. 2011; 259:

19 Pooled Data from 7 Studies (numbers in green are our data) GBCA Injections Non-severe % Severe % Total 999, (0.06) (0.003) Gadopentetate 715, (0.05) (0) Gadodiamide 74, (0.02) 0 (0) Gadoteridol 94, (0.3) 0.02 (0.03) Gadobenate 28, (0.1) 0.04 (0.009) Gadobutrol Unspecified 87, Courtesy of HL Zhang, MD

20 Leiner & Kucharczyk JMRI special issue on NSF 2009:30: Risk is relative, not absolute. Not only is the risk of NSF small compared with the risk of CIN but also with risk of severe allergic reactions

21 ionic vs. nonionic in 337,647 patients Ionic Nonionic odds ratio Total 12.66% 3.13% 0.22 Severe 0.22% 0.04% 0.19 Very severe 0.04% 0.004% 0.10 Death* n = 1 n = 1 * Death rate ~ 6/1 million Katayama et al Radiology 1990;175:616-8 (These AE rates are specific to the experience at the institutions studied in this publication.)

22 nonionic contrast media significantly reduce the frequency of severe and potentially life-threatening ADRs to contrast media at all levels of risk and use of these media represents the most effective means of increasing the safety of contrast media examinations Katayama et al Radiology 1990;175:616-8 (These AE rates are specific to the experience at the institutions studied in this publication.)

23 Adverse reactions: Iodinated contrast vs. GBCA Hunt, AJR 2009; 193: Nonionic GBCA Iodine Total dose 298, ,439 # Reactions 458 (0.15%) 64 (0.04%) - Need treatment 79 (0.03%) 15 (0.01%) - Severe 15 (0.005%) 4 (0.0025%) Death 1 ( %)

24 Risk factors Previous reaction to GBCA H/O asthma and other allergies Previous allergic reactions to iodinated contrast agents

25 Suggestions on how to prevent adverse events Outpatient center: NSF is rare, code = 911 ACLS trained radiologists Crash cart Run Mock codes Consider nonionic Gadolinium prefer hand injection; avoid remote power injection Hospital based MRI: code team readily available Consider ionic and macrocyclic agents Only one GBCA consider nonionic Macrocyclic

26 Summary Gadolinium is extraordinarily safe but Allergic Reactions can be lethal: Most acute reactions are mild Severe reactions can be life threatening Crash Cart, ACLS training, mock codes Consider nonionic Gd when GFR >30 especially in outpatient imaging centers where code team is 911 Consider nonionic macrocyclic if GFR< 30