Kassa Darge, MD, PhD. Sunrise Workshop UPDATE ON CONTRAST MEDIA: New agents, new concerns & strategies for safe use

Transcription

1 Sunrise Workshop UPDATE ON CONTRAST MEDIA: New agents, new concerns & strategies for safe use Kassa Darge, MD, PhD Professor of Radiology and Surgery Perelman School of Medicine University of Pennsylvania Radiologist-in-Chief & William L. Van Alen Endowed Chair Department of Radiology Children s Hospital of Philadelphia (CHOP) Philadelphia

2 CENTER FOR PEDIATRIC CONTRAST ULTRASOUND [CPCU] Department of Radiology Children s Hospital of Philadelphia partly supported by Bracco Diagnostics Inc., Monroe Township, NJ

3 Objectives Safety of US contrast agents in CHILDREN intravenous intravesical

4 US contrast agents

5 US contrast agents SonoVue -Lumason [Bracco] Optison [GE Healthcare] Definity [Lantheus Medical Imaging] Levovist [Schering AG]

6 US contrast agents SonoVue -Lumason [Bracco] Optison [GE Healthcare] Shell: Phospholipid; Gas: Sulphurhexafluoride Shell: Albumin; Gas: Octafluoropropane Definity [Lantheus Medical Imaging] Levovist Shell: Phospholipid; Gas: Octafluoropropane [WITHDRAWN]

7 Objectives Safety of US contrast agents in CHILDREN intravenous intravesical

8 Indications Currently in pediatrics: 1. Tumor 2. Trauma 3. Vascular

9 intravenous US contrast agents Lumason [SonoVue ] Optison Review studies Most retrospective Only studies with >20 patients

10 Lumason SonoVue intravenous US contrast agents 305 patients [ yr] Indications; Focal liver lesions [47%] Blunt abdominal trauma [37%] Minor transient AEs = 2 - tachycardia = 1 - hypertension = 1 44 patients 44 IV injections Focal liver lesions No AEs AE=Adverse Events

11 Lumason SonoVue intravenous US contrast agents 183 patients [ yr] 287 IV injections Indications; Native liver [45%] Transplant liver [31%] Spleen [10%] Kidney [7%] AEs = None AE=Adverse Events

12 Lumason SonoVue intravenous US contrast agents 137 patients 167 IV injections Tumor Severe AE = 1 - anaphylactic reaction Code cart in the vicinity of the US unit AE=Adverse Events

13 Lumason SonoVue intravenous US contrast agents 40 patients [0-26 yr] 79 IV injections Indications; Liver [42] Spleen [9] Kidney [3] Minor transient AEs = 2 - nausea = 1 - single wheal = 1 AE=Adverse Events

14 Lumason SonoVue intravenous US contrast agents 37 patients [1-17 yr] 39 IV injections Indications; Liver [16] Kidney [10] Spleen [4] Minor transient AEs = 1 - nausea = 1 AE=Adverse Events

15 Lumason SonoVue Lumason SonoVue intravenous US contrast agents 30 patients [ yr] 39 IV injections Indications; Liver transplant AEs = none 27 patients [4-13 yr] Indications; Blunt abdominal trauma AEs = none AE=Adverse Events

16 Lumason SonoVue intravenous US contrast agents 2012 Dec;42(12): survey 148 questionnaires returned 2012 publication 30 centers 948 IV injections Indications: - trauma/tumor/infection Minor AEs = 5 [0.5%] - taste alteration = 3 - urticaria = 2 - hyperventilation = 1 AE=Adverse Events

17 Optison Definity Optison Comprehensive safety evaluation: intravenous US contrast agents 34 patients [ yr] 134 IV injections Optison - 8 Definity Tumors Minor transient AEs = 3 [Optison ] - taste alteration = 2 - lightheadedness+tinitus = 1 20 patients 20 IV injections Cardiac Minor AEs = 4 - transient headache = 3 - taste alteration = 1 AE=Adverse Events

18 intravenous US contrast agents SUMMARY Lumason [SonoVue ] Number of PATIENTS 1707 Number of INJECTIONS 1891 Number of ADVERSE EVENTS 11 Percentage of adverse events/injections 0.58% TYPES OF ADVERSE EVENTS Serious: 1 - anaphylactic reaction 1 Minor: 10 - taste alteration 3 - urticaria 2 - nausea 2 - tachycardia 1 - hyperventilation 1 - hypertension 1 - single wheal 1

19 Lumason SonoVue intravenous US contrast agents ADULTS Adverse events in children: 0.58%

20 Lumason SonoVue intravenous US contrast agents ADULTS Experience from post-marketing surveillance of the estimated 1,651,451 patients exposed to SonoVue from April 1, 2001 through December 31, 2010 during the market use of this product (including events from observational studies, investigator-initiated studies and publications) shows a total of 217 cases of serious AEs (reporting rate: 0.013%), of which, 213 patients were considered to have AEs with some kind of relationship to the administration of SonoVue (probable, possible or unlikely) and 4 patients were considered to have AEs clearly unrelated to SonoVue administration.

21 intravenous US contrast agents Contraindication? History of hypersensitivity reactions of sulphur hexafluoride lipid microspheres Cardiac shunt [right-to-left or bidirectional] FDA REMOVED contraindication 10-35% of children/adults intracardiac shunts Agitated normal saline used over many decades Earlier approvals of US contrast agents no such contraindication Incorrect comparison with macroaggregated albumin (nuclear medicine) Large safety studies not support contraindication

22 intravenous US contrast agents CONCLUSION High safety profile with <1% of adverse events, predominantly minor ones

23 Objectives Safety of US contrast agents in CHILDREN intravenous intravesical

24 Indication Intravesical US contrast agent administration for diagnosis of vesicoureteral reflux: Contrast enhanced voiding urosonography

25 intravesical US contrast agents Dysuria Transient macrohematuria Abdominal discomfort/pain Anxiety/crying Urinary retention Frequency Blood/mucous discharge Perineal irritation Urethral pain Urinary tract infection Vomiting

26 Lumason SonoVue intravesical US contrast agents Prospective study Primary objective safety evaluation ONLY cevus with SonoVue Comprehensive evaluation Follow-up after a week NO serious adverse events 37 (3.7%) patients minor events Self-limited adverse events Catheterization likely cause High safety profile!

27 intravesical US contrast agents Iodinated CA Radionuclide No CA Dysuria Transient macrohematuria Abdominal discomfort/pain Anxiety/crying Urinary retention Frequency Blood/mucous discharge Perineal irritation Urethral pain Urinary tract infection Vomiting

28 intravesical US contrast agents Adverse events are more likely due to bladder catheterization rather than the US contrast agent

29 CEUS in children intravenous & intravesical high safety profile

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