1. Kontrastvielu nozīme invazīvajā radioloģijā
P.Stradiņa Klīniskā Universitātes slimnīca
Latvijas Kardioloģijas centrs
Dace Sondore

2. Aktualitātes “Ideālas’’ kontrastvielas īpašības
Kontrastvielu ietekme uz kardiorenālo sistēmu
Kontrastvielu inducēts -akūts nieru bojājums(CI-AKI)
-Kas ir CI-AKI?
-Kuri ir riska pacienti?
Kā samazināt CI-AKI risku?
-Nefrotoksisko medikamentu pārtraukšana
-Šķidruma palielināšanas stratēģija
-Farmakoloģiskās profilakses stratēģija
-Kontrastvielas daudzuma ierobežošana
-Kontrastvielu izvēle 2

3. Kontrastvielu attīstības virzieni
Reducēt osmolaritāti līdz fizioloģiskam līmenim
Ne-jonu struktūras
Lielāks molekulu izmērs
Lielāks joda saturs
Sabalansēts Na+, Ca2+ daudzums

4. Hiperosmolaritāte un pacienta komforts
Šķidruma izvilkšana no:
Eritrocītiem
Endoteliālām šūnām
Intesticiālām spraugām
Hipervolēmija
Asinsvadu dilatācija
Diskomforts, Drudzis, Sāpes

5. Osmolaritāte un Viskozitāte
Viscosity, 37o
mPa.s
Osmolality
mOsm/kg H2O
Ionic
Non-ionic
High- osmolar
Iso-osmolar
Low-
osmolar a
BJU International (2000), 86 Suppl. 1, 1±10
H.S. THOMSEN and S.K. MORCOS*
Radiographic contrast media
Fig. 2. The a, osmolality (mOsm/kg water)
and b, viscosity at 370C of currently
available iodinated contrast media. The
values in the bars show the iodine content
(mg/mL). The ionic HO media are shown
in green, the ionic LO medium in red, the
non-ionic LO media in light green and nonionic
iso-osmolar media in light red.
Thomson HS & Morcos SK. BJU International 2000; 86 (Suppl. 1):1-10

6. Iodixanol vs Iopromide femorālā angiogrāfijā
Pacienti, %
P<0.001
P<0.001
Justesen P et al. Cardiovasc Intervent Radiol. 1997;20:

7. Iodixanol vs Ioxaglate ventrikulogrāfijā
Pacienti ar diskomfortu (karstuma sajūtu) injekcijas laikā, %
P = 0.02
Iodixanol vs Ioxaglate in Cardioangiography
In the double-blind, randomized trial by Tviet et al, 102 patients with normal renal function and suspected coronary disease referred for cardioangiography were given either iodixanol 320 mg I/mL (n=53) or ioxaglate 320 mg I/mL (n=49) (Tviet, p614). The only discomfort reported by patients was warmth during injection of CM into the left ventricle, reported by all but 1 patient in each group (Tviet, p615, 616). The intensity of discomfort, rated as mild, moderate or severe, was significantly lower in the iodixanol group compared with the ioxaglate group (P=0.02) (Tviet, p615).
Reference:
Tveit K, Bolz KD, Bolstad B, et al. Iodixanol in cardioangiography. A double-blind parallel comparison between iodixanol 320 mg I/ml and ioxaglate 320 mg I/ml. Acta Radiol. 1994;35(6):
Tveit K et al. Acta Radiol. 1994;35:

8. Kontrastvielas elektrolītu ietekme uz sirds funkciju dzīvnieku modelī
Sabalansētu elektrolītu () nozīme
Elektrolīti
Efekts
Nātrijs
Kontraktilitātes spēks
Kalcijs
Ventrikuļu fibrilācija
 Nātrijs
 Kalcijs
Kontraktilitātes uzlabošanās
Chai C-M et al. Acad Radiol 2004;11:

9. Elektrolītu saturs kontrastvielās (CM)
Iodine [C]
mg I/mL
Viscosity
mPas 37°
Osmolality
mOsm/kg H20
Na+
mmol/L
*Ca++
Iodixanol
(Visipaque)
320
11.8
290 (iso) 19
0.3
Iotrolan
300
8.1
320 (iso) 6
Iopromide
(Ultravist)
5.4
610 (low)
Ioxaglate
7.5
580 (low)
155
Diatrizoat
290
5.0
1530 (high)
126
*Free ion concentration, Ca++ bound to EDTA not included.
Dunkel et al. Acta Radiol. 1995(Suppl) 399: ; VisipaqueTM Prescribing Information 2006

10. Kontrastvielu ietekme uz kardiorenālo sistēmu
KSS pacientiem pēc PCI vispārīgie kardiovaskulārie riska faktori palielina hospitālās mirstības risku
Samazināta nieru funkcija KSS pacientiem pēc PCI palielina komplikāciju risku un hospitālās mirstības risku
Nozīmīgai pacientu daļai pēc PCI iespējami gan kardiovaskulārie riska faktori, gan nieru bojājums 10

11. Dažādu kontrastvielu ventrikuļu fibrilācijas risks un laiks līdz VF sākumam
P<0.001
P<0.01
P<0.05
P<0.05
P<0.05
P<0.05
Laiks līdz VF, sec
VF incidence, %
Chai C-M, Karlsson JOG, Almen T. Incidence of Ventricular Fibrillation during Left Coronary Arteriography in Pigs: Comparison of a solution of the nonionic dimer iodixanol with solutions of 5 different nonionic monomers. Acta Radiol 2008; 49:
This slide illustrates the frequency of VF following injection of 6 different CM (20 ml; 0.5ml/s)) - each into the LCA of a group of 14 pigs. A high frequency of VF (100%) and short period from injection to start of VF (22-29 sec) was seen for all CM tested except iodixanol - where the incidence of FV was only 21%, occurring 39s post injection
Data not shown: From Chai 2007
Prolongation of QRS time and QTc time were the only vector-electrographic signs that showed significant differences (P<0.05) between solutions and correctly ranked the risk of VF
QRS time is related to the depolarization process; QTc time to depolarization and repolarization
Study Conclusions:
Higher viscosity combined with a more physiologic electrolyte composition of a solution may delay changes in the electrolyte composition of the myocardial interstitial fluid, and thereby delay start of VF
The optimal electrolyte composition of a CM may vary with its viscosity
Chai C-M et al. Acta Radiol 2008; 49:

12. Kardiovaskulārie riska faktori, kas palielina hospitālo mirstību
Odds Ratio (95% CI)
Vecums >55 g
1.07 ( )
Sievietes
1.49 ( )
Nestabila hemodinamika
7.82 ( )
Šoks
19.92 ( )
LVEF <20%
3.02 ( )
LVEF 20%-29%
1.92 ( )
MI 1-14 d pre PCI
3.25 ( )
MI >14 d pre PCI
1.62 ( )
Perifēro asinsvadu slimība
1.72 ( )
HSM, patreiz
3.59 ( )
HSM, agrāk
2.36 ( )
KSS ar LM stenozi
2.33 ( )
Wu C et al. J Am Coll Cardiol. 2006; 47: 12

13. Hroniskas nieru slimības izplatība pacientiem ar KSS
Reddan DN et al. J Am Soc Nephrol. 2003;14: 13

14. Kontrastvielu inducēts – akūts nieru bojājums (CI-AKI)
CI-AKI ir izplatīta and potenciāli bīstama komplikācija pacientiem, kas saņēmuši kontrastvielu
McCullough PA et al. Am J Cardiol. 2006;98(suppl):5K-13K. 14

15. Situāciju pasliktina…
CI-AKI risks palielinās un klīniski ir nozīmīgāks pacientiem ar hronisku nieru slimību (CKD) (it īpaši kombinācijā ar cukura diabētu),
ja (eGFĀ) <60 mL/min/1.73m2
McCullough PA et al. Am J Cardiol. 2006;98 (Suppl S1):2-4. 15

16. CI-AKI definīcija un izpausme
Nieru funkcijas pasliktināšanās 3 dienās pēc kontrastvielas saņemšanas, ja nav citu etioloģisko faktoru
Vispārēji definēts kā  SCr par ≥25% no izejas līmeņa vai ≥ 0.5 mg/dL (44 μmol/L)
Laika periods
 SCr 1–2 dienās,  GFĀ dēļ
Pīķis 3–4 dienās pēc kontrastvielas saņemšanas
Morcos SK. In: Textbook of Contrast Media. 1999: 16

17. CI-AKI vai CIN?
Definīcijai: Kontrastvielu inducēts- akūts nieru bojājums ir dodama priekšroka, lai gan atšķirības definīcijās kontrastvielu inducēta nefropātija (CIN) vs CI-AKI joprojām paliek diskutējamas

18. CI-AKI joprojām paliek 3
CI-AKI joprojām paliek 3. nozīmīgākais riska faktors hospitālās nieru mazspējas attīstībā
Incidence, %
129 epizodes pacientiem
380 epizodes 4622 pacientiem
Hospital-acquired renal insufficiency: increase in SCr of 0.5 mg/dL for patients with baseline SCr of 1.9 mg/dL or less, 1.0 mg/dL for patients with a baseline SCr of 2.0 – 4.9 mg/dL, and 1.5 mg/dL for patients with baseline SCr >5.0 mg/dL
Hou SH et al. Am J Med. 1983;74: ; Nash K et al. Am J Kidney Dis. 2002;39: 18

19. Kādi izmeklējumi ar kontrastvielu lietošanu ir cēlonis nieru mazspējai?
Aptuveni 50% gadījumu novēro invazīvajā kardioloģijā
Hospital-acquired renal insufficiency: increase in SCr of 0.5 mg/dL for patients with baseline SCr of 1.9 mg/dL or less, 1.0 mg/dL for patients with a baseline SCr of 2.0 – 4.9 mg/dL, and 1.5 mg/dL for patients with baseline SCr >5.0 mg/dL
Nash K et al. Am J Kidney Dis. 2002;39: 19

20. CI-AKI incidenci palielina pieaugošs riska faktoru skaits
Riska faktori
Nieru bojājums
Cukura diabēts
Nestabila hemodinamika
Malnutrīcija (hipoalbuminēmija, hipoholesterinēmija)
Anēmija
Liels kontrastvielas daudzums (>200 mL)
Hiponātriēmija
Nefrotoksiska efekta
incidence (%)
n=84
n=80
n=28
n=5
n=2
Rich MW et al. Arch Intern Med. 1990;150: 20

21. CI-AKI sekas
Pieaug ne-renālo slimību incidence (sepsis, elpošanas mazspēja, asiņošanas)
Pieaug kardiovakulāro komplikāciju skaits
Pieaug gultu dienu skaits
Palielinās mirstība
Levy EM et al. JAMA. 1996;275:
McCullough PA et al. Am J Med. 1997;103:
National Kidney Foundation. Am J Kidney Dis. 2004;43(Suppl 1):S16-S41. 21

22. Sistēmiskās komplikācijas pacientiem ar CI-AKI pēc PCI
Mayo Klīnikas reģistrs iekļauti 7586 pacienti
P<0.001
P<0.001
Pacienti, %
P=0.05
P<0.001
CI-AKI defined as increase SCr >0.5 mg/dL
ARDS, adult respiratory distress syndrome
Rihal CS et al. Circulation. 2002;105: 22

23. Hospitālā mirstība pēc kontrastvielas saņemšanas
Mayo Klīnikas reģistrs: N=7586
CI-AKI: SCr  >0.5 mg/dL
P<0.001
Rihal CS et al. Circulation. 2002;105: 23

24. Ilgtermiņa rezultāti: CI-AKI sekas pēc KV saņemšanas
6-mēnešu MACE
Dažādu iemeslu mirstība
P=0.0001
P=0.003
P=0.0008
P=0.0001
MACE, major adverse cardiac events
Harjai KJ et al. Am J Cardiol. 2008;101: 24

25. CI-AKI: Ilgtermiņa prognoze pacientiem ar nieru mazspēju
100 80 60 40 20
P<0.001
No notikumiem brīva dzīvildze (%)
Saglabāta nieru funkcija (nepaaugstināts SCr)
Nieru funkcijas pasliktināšanās (CI-AKI) 1 2 3 4 5 6 7 8 9 10 11 12
Mēneši
Gruberg L et al. J Am Coll Cardiol. 2000;36:
Reference:
Gruberg L, Mintz GS, Mehran R, et al. The prognostic implications of further renal function deterioration within 48 h of interventional coronary procedures in patients with pre-existent chronic renal insufficiency. J Am Coll Cardiol. 2000;36: 25

26. CADILLAC pētījums: 1-gada mirstība pēc KV saņemšanas, atkarībā no CrCl
CrCl, mL/min
100
>60
50-60 90
40-50
30-40 80
Dzīvildze (%) 70
20-30 60
<20 50
P< (visām grupām) 40 50
100
150
200
250
300
350
400
450
500
Laiks (dienās)
Sadeghi HM et al. Circulation. 2003;108:2769–2775. 26

27. CADILLAC pētījums: mirstība, atkarībā no CI-AKI attīstības
CI-AKI (n=86)
No CI-AKI (n=1798)
Relatīvais risks (95% CI)
P-value
30-dienu mirstība (%)
16.2
1.2
13.8
(7.3, 26.2)
<0.0001
1-gada mirstība (%)
23.3
3.2
7.4
(4.7, 11.7)
Sadeghi HM. et al. Circulation. 2003; 108:2769–2775. 27

28. CI-AKI riska aprēķināšana
Riska faktori
Punktu skaits
Hipotenzija 5
IABP
HSM
Vecums >75 g 4
Anēmija 3
Cukura diabēts
Kontrastvielas daudzums
1 uz 100 ml
SCr >1.5mg/dL vai
GFĀ<60mL/min/1.73m2
2, ja 40-60
4, ja 20-39
6, ja <20
Summa
Mehran R et al. J Am Coll Cardiol. 2004;44: 28

29. CI-AKI riska aprēķins incidence (%) Riska punktu summa
Mehran R et al. J Am Coll Cardiol. 2004;44: 29

30. Nozīmīgas nieru disfunkcijas (SRD) riska aprēķināšana
Riska faktori
Punkti
Sievietes
1.5
Vecums ≥80
2.0
Cukura diabēts
3.0
Akūts
2.5
Neatliekams
3.5
HSM
4.5
SCr 1.3 – 1.9 mg/dL
5.0
SCr ≥2.0 mg/dL
10.0
Pre-PCI IAPB
13.0
Summa
SRD: new dialysis, ≥2.0 mg/dL absolute increase in SCr, or a ≥50% increase in SCr
Brown JR et al. Am Heart J. 2008;155: 30

31. Nozīmīgas nieru disfunkcijas (SRD) riska aprēķins
Riska faktori
Punkti
78 g.v. sieviete
1.5
AKS bez ST
3.0
SCr 1.5 mg/dL
2.5
CD, 2. tips
4.5
HSM
5.0
Punktu summa
16.5
SRD risks
9.3%
SRD: new dialysis, ≥2.0 mg/dL absolute increase in SCr, or a ≥50% increase in SCr
Brown JR et al. Am Heart J. 2008;155: 31

32. Relatīvā SRD riska faktoru izplatība pacientiem pirms PCI*  
*akūta/neatliekama
SRD: new dialysis, ≥2.0 mg/dL absolute increase in SCr, or a ≥50% increase in SCr
Brown JR et al. Am Heart J. 2008;155: 32

33. Nieru funkcijas klasifikācija Kidney Disease Outcome Quality Initiative (K/DOQI)
“Hroniska nieru slimība” (CKD)
Nieru funkcija
eGFĀ (mL/min/1.73 m2)  CrCl (mL/min)
I pakāpe
II pakāpe
III pakāpe
IV pakāpe
V pakāpe
CKD riska factori/bojājums ar samazinātu GFĀ
Viegli samazināta nieru funkcija
Vidēji samazināta nieru funkcija
Izteikti samazināta nieru funkcija
Nieru mazspēja Beigu stadijas nieru slimība
130
120
110
100 90 80 70 60 50 40 30 25 20 15 10 5
McCullough PA, Soman SS. Crit Care Clin. 2005;12:
References:
1. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Available at: Accessed October 15, 2007.
2. McCullough Pa, Soman SS. Contrast-induced nephropathy. Crit Care Clin. 2005;21: 33

34. Nieru mazspējas pacientu identifikācijas kļūdas
Vecums, g
Normāls SCr
Patienti ar samazinātu eGFĀ
40-59 Jā
1.2%
60-69
12.6%
≥70
47.3%
Duncan L et al. Nephrol Dial Transplant 2001; 16: 34

35. GFĀ priekšrocības, salīdzinot ar SCr, nieru funkcijas noteikšanā
Rādītājs ir sensitīvāks un plaši atspoguļo fizioloģiskos un pataloģiskos faktorus
Tā līmenis korelē ar glomerulārā un tubulo-intersticiālā bojājuma smaguma pakāpi
Tā līmenis samzinās pirms urēmijas pazīmēm un simptomiem
McCullough PA. Rev Cardiovasc Med. 2003;(4 Suppl 1):S2-6. 35

36. eGFĀ kalkulators Age Creatinine MDRD mL/min/1.73m2
MS PowerPoint slide © Stephen Z. Fadem, M.D. and Brian Rosenthal. All rights reserved 36

37. CI-AKI riska faktori Modificējamie Nemodificējamie Klasiskie
Zems efektīvais cirkulējošais tilpums
Nieru mazspēja anamnēzē
Nefrotoksisko medikamentu lietošana
CD ar iepriekšēju nieru mazspēju
Liels kontrastvielas daudzums
Lielāks vecums
Augstas osmolaritātes un jonētas KV
HSM III-IV un samazināta LVEF
Mazs laika posms starp invazīvām proc.
Iespējamie
Hipertenzija
Afroamerikāņi un citas ne-baltās rases
Hipoalbuminēmija
Anamnēzē nieru operācija
Hiperholesterinēmija
AIDS
Hipotenzija procedūras laikā
Nodozs poliarterīts
Toprak O. J Urol. 2007;178: 37

38. Nefrotoksisko medikamentu pārtraukšana
Nefrotoksiskie medikamenti būtu jāpārtrauc vismaz ≥24 stundas pirms kontrastvielas lietošanas pacientiem ar AKI risku (eGFĀ <60 mL/min)
Palielināts risks
NSAIDs (gan COX-1, gan COX-2 inhibitori)
Aminoglikozīdi
Ciklosporīni
Takrolimus (FK-506)
Amfoteriīins B
Neskaidrs risks
AKE-I and ARB
Pastāvīgie diurētiķi
Stacul F et al. Am J Cardiol. 2006;98(suppl):59K-77K; Alamartine E et al. Eur J Int Med. 2003;14: ; Evenepoel P. Best Pract Res Clin Anaesthesiol. 2004;18:37-52; Gleeson TG et al. AJR Am J Roentgenol. 2004;183: ; Heyman SN et al. Invest Radiol. 1999;34: 38

39. Vai ir efektīvi farmakoloģiskie līdzekļi kontrastvielas inducēta- AKI profilaksei?

40. Farmakoloģiskās profilakses stratēģija
Potenciāli kaitīgās vielas
Furozemīds
Manitols
Endotelīna receptoru antagonisti
Vielas, kas nav pārliecinoši pierādījušas efektīvu CI-AKI riska samazināšanu
N-Acetilcisteīns
Fenoldopam/dopamīns
Ca-kanālu blokatori
Ātriju nātrijuētiskais peptīds
Potenciāli labvēlīgās vielas, kuras nepieciešams papildus pētīt
Teofilīns/aminofilīns
Statīni
Askorbīnskābe
Prostaglandīns E1
The CIN Consensus Working Panel reviewed all of the published literature on pharmacologic agents evaluated for their efficacy in reducing the risk of contrast-induced nephropathy (CIN). Some trials were negative, some positive, and some had conflicting results. The panel divided these agents into the 3 categories listed on this slide, but state that no drugs are approved by regulatory authorities anywhere in the world for the prevention of CIN.
Reference:
Stacul F, Adam A, Becker CR, et al. Strategies to reduce the risk of contrast-induced nephropathy. Am J Cardiol. 2006;98(suppl):59K-77K.
Stacul F et al. Am J Cardiol. 2006;98(suppl):59K-77K.

41. 44% ± 8% injicētā kontrasta tiek evakuēts,
salīdzināts pre- and 48 h post-angiogrāfijas SCr
pre: 262 ± 56 mg%; n=7
post: 254 ± 40 mg%; n=3
Danenberg HD, Lotan C, Varshitski B et al. Removal of contrast medium from the coronary sinus during coronary angiography: feasibility of a simple and available technique for the
prevention of nephropathy. Cardiovascular Revascularization Medicine 9 (2008) 9– 13
Abstract Background: Contrast-induced nephropathy (CIN) is a major complication of percutaneous coronary interventions with currently limited preventive measures.
Objectives: To prevent CIN, we assessed the safety and feasibility of contrast removal from the
coronary sinus (CS) during coronary angiography.
Methods: We attempted contrast removal on seven patients undergoing coronary angiography with preexisting renal insufficiency (mean serum creatinine=262F56 mg%).
Results: In four patients, a balloon catheter could not be successfully deployed in the CS. In three
patients, a balloon catheter with distal side holes was positioned in the CS orifice. The balloon was inflated to occlude the CS concurrent with coronary injections, and 12–16 ml of blood was aspirated after each injection. The procedure appeared to be safe, without adverse events and elevations of serum creatinine levels. Contrast media were effectively withdrawn (44%F8%) as assessed by fluoroscopy and dilution of blood. The increased venous pressure at the time of injection reduced coronary flow, allowing for small volumes of administered contrast.
Conclusions: Occlusion of the CS during coronary angiography with aspiration of contrast media is safe and effective in reducing contrast load during coronary interventions. This procedure may reduce the risk for CIN in prone patients.
Danenberg HD et al. Cardiovasc Revasc Med. 2008; 9: 9-13.

42. Profilakses secinājumi
Patreiz neviens medikaments vai mehāniska ārstēšana nav sevi pierādījusi kā efektīva terapija kontrastvielas inducētā- AKI riska mazināšanā
Profilaktiska hemodialīze vai hemofiltrācija nav lietderīga kā efektīva CI-AKI profilakses stratēģija

43. Kontrastvielu veidi un daudzums

44. Kontrastvielas daudzums un CI-AKI incidence
Lielāks kontrastvielas daudzums (>100 mL) asociējas ar biežāku CI-AKI provocēšanu riska pacientiem
Kaut gan, arī neliels (~30 mL) tās daudzums ļoti augsta riska pacientiem var provocēt CI-AKI un akūtu nieru mazspēju ar nepieciešamu dialīzi
McCullough PA, Wolyn R, Rocher LL, Levin RN, O'Neill WW. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med. 1997;103:
Morcos SK, Thomsen HS, Webb JAW, Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR). Contrast-media-induced nephrotoxicity: a consensus report. Eur Radiol. 1999;9:
Taliercio CP, Vlietstra RE, Fisher LD, Burnett JC. Risks for renal dysfunction with cardiac angiography. Ann Intern Med. 1986;104:
Gruberg L, Mintz GS, Mehran R, Gangas G, Lansky AJ, Kent KM, Pichard AD, Satler LF, Leon MB. The prognostic implications of further renal function deterioration within 48 h of interventional coronary procedures in patients with pre-existent chronic renal insufficiency. J Am Coll Cardiol. 2000;36(5):
Freeman RV, O'Donnell M, Share D, Meengs WL, Kline-Rogers E, Clark VL, DeFranco AC, Eagle KA, McGinnity JG, Patel K, Maxwell-Eward A, Bondie D, Moscucci M; Blue Cross-Blue Shield of Michigan Cardiovascular Consortium (BMC2). Nephropathy requiring dialysis after percutaneous coronary intervention and the critical role of an adjusted contrast dose. Am J Cardiol. 2002;90:
Briguori C, Manganelli F, Scarpato P, Elia PP, Golia B, Riviezzo G, Lepore S, Librera M, Villari B, Colombo A, Ricciardelli B. Acetylcysteine and contrast agent-associated nephrotoxicity. J Am Coll Cardiol. 2002;40:
Manske CL, Sprafka JM, Strony JT, Wang Y. Contrast nephropathy in azotemic diabetic patients undergoing coronary angiography. Am J Med. 1990;89:
Davidson C et al. Am J Cardiol. 2006;98(suppl):42K-58K; Manske CL et al. Am J Med. 1990;89: 44 44

45. Kontrastvielas daudzums un CI-AKI risks pacientiem ar smagu CKD un DM
Pacienti ar CI-AKI
Pacienti , kuriem vajag dialīzi
Pacientu raksturojums
N=59
Azotēmiski insulīna-atkarīgi diabētiķi
Vid. vecums = 37 g
Vid. SCr = 5.9 mg/dL
CI-AKI incidence (%)
This slide illustrates the importance of CM volume in very high-risk patients (ie, those with diabetes and advanced CKD). Manske and coworkers studied 59 insulin-dependent diabetic patients with a mean SCr of 5.9 mg/dL (522 µmol/L) who underwent coronary angiography as part of their evaluation for renal transplant surgery (Manske pp616,617). Control patients included 24 azotemic diabetic patients undergoing inpatient evaluation but not angiography. SCr values obtained at baseline and 24 hours after angiography were compared, and a value that was more than 10% above baseline was considered significantly increased. Patients who developed CIN received significantly more CM than patients who did not develop CIN (P=0.004) (Manske p617). For each 5-mL increment in CM dose, there was a 65% increase in the risk of CIN in these very high-risk patients (Manske p619).
Reference:
Manske CL, Sprafica JM, Strony JT, Wang Y. Contrast nephropathy in azotemic diabetic patients undergoing coronary angiography. Am J Med. 1990;89:
Kontrastvielas daudzums, mL 45
Manske CL et al. Am J Med. 1990;89: 45

46. Izejas līmeņa CrCl x 3.7 = max kontrastvielas daudzums*
Maksimālā kontrastvielas daudzuma aprēķināšana CI-AKI riska mazināšanai
This recent study demonstrates a relationship between the ratio of baseline renal function (eGFR, calculated using the MDRD formula) to CM volume (eGFR/CM volume in mL) and the likelihood of a 0.5 mg/dL increase in baseline SCr within 1-2 days post-PCI. This predictive model was developed in a PCI study population comprised of unselected patients enrolled in the NHLBI Dynamic Registry. CIN incidence was 1.5%, suggesting a low-risk population.
Laskey WK, Jenkins, C, Selzer F, et al. Volume to Creatinine Clearance Ratio:A Pharmacokinetically Based Risk Factor for Prediction of Early Creatinine Increase After Percutaneous Coronary Intervention. JACC 2007; in press.
Izejas līmeņa CrCl x 3.7 = max kontrastvielas daudzums*
* Calculated using Cockcroft-Gault; based on an unselected PCI study population
Laskey WK. et al. J Am Coll Cardiol 2007;50(7): 46

47. Salīdzinošie pētījumi pēc PCI
Iodixanol
-Visipaque
Ioversol
Iopromide
-Ultravist
Ioxaglate
P=NS
P=0.011
P=0.03
Mehran (ICON)
(N=145)
Hernandez
(N=250)
Nie
(N=208)
Mehran R. Presented at TCT 2006; Hernandez et al. ESC 2007, abstract; Nie et al. ACC/SCAI 2008, abstract.

48. Atšķirības dažādos pētījumos
Mehran (ICON)
N=145
Hernandez
N=250
Nie
N=208
Pacienti ar NM,%
Ioxaglate: 100
Iodixanol: 100
(Visipaque) NA
Iopromide: 100
(Ultravist)
Pacienti ar CD, %
Ioxaglate: 40.5
Iodixanol: 50.7
Ioversol: 100
Iopromide: 26.5
Iodixanol: 27.4
KV daudzums, mL
Ioxaglate: 204
Iodixanol: 217
Ioversol: 196
Iodixanol: 194
Iopromide: 205
Iodixanol: 212
Šķidruma nodrošināšana
0.45% IV saline
3.7 L
0.9% IV saline
1 L
≥1 L
N-Acetilcisteīna lietošana
72%
100% 0%
Pēc procedūras SCr
1 random
48-72 h
1 fixed
72 h
2 fixed
48 & 72±6 h
Differences Between Trials: Mehran, Ni, Hernandez, and Nie (Ni removed from slides)
The 4 trials described here were conducted with patients having different levels of risk and using different protocols. As presented earlier, the presence of DM and the volume of the CM used have a substantial effect on the incidence of CIN. These trials varied widely in the percentage of diabetics included and in the volume of CM used. In addition, the trials were different with regard to their hydration protocols and their use of preventive agents such as NAC. The difference in terms of post-CM SCr sampling is also notable.
RI: All of the patients in the ICON and Nie trials had RI; RI was much lower in Ni patients and unreported in Hernandez.
DM: 100% of patients in the Hernandez trial were diabetics compared with about half of those in the ICON trial and one-fourth of those in the Ni and Nie trials. In addition, within the ICON and Ni trials, more iodixanol patients had DM compared with patients receiving a LOCM. In association with RI, DM has been shown to greatly increase the risk for CIN.
Volume of CM: Approximately 200 mL of CM was used in the ICON, Hernandez, and Nie trials; half as much was used in the Ni trial.
Volume expansion: Different volumes and types of IV hydration fluids were used in these 4 trials.
NAC: All patients in the Hernandez trial received NAC, compared with 72% of ICON patients and none of the Ni or Nie patients. The protective effect of NAC is controversial, making it difficult to compare these trials.
Post-CM SCr measurement: The Hernandez trial used 1 fixed measurement at 72 hours and the Nie trial used 2 fixed measurements at 48 and 72±6 hours; the ICON trial used 1 random measurement between 48 and 72 hours, and the Ni trial did not report the timing post-CM SCr measurement. We have seen earlier that the use of one random measurement over an extended period of time to determine the incidence of a random event like CIN (which typically occurs between 0 and 72 hours) may be a less effective way of capturing the actual incidence of CIN compared to the use of multiple and/or specific measurement times (as in Hernandez and Nie).
Although all 4 of these new trials report a numerically lower incidence of CIN in the iodixanol group compared with the LOCM, the difference is significant only in the Hernandez and Nie trials, the 2 trials using fixed measurements of postprocedure SCr.
Caution should be used when reviewing preliminary data in abstract form.
References:
Mehran R. ICON: Ionic versus nonionic contrast to obviate worsening nephropathy after angioplasty in chronic renal failure patients. TCT 2006, abstract.
Ni JW, Zhang RY, Zhang JS, Zhang X, Shen WF. Safety of isosmolar nonionic dimer contrast medium during percutaneous coronary intervention. J Intervent Radiol. 2006;15:
Hernandez et al. Comparison of iodixanol versus ioversol for prevention of contrast induced nephropathy in diabetic patients undergoing coronary angiography or intervention. ESC 2007, abstract.
Nie B, Cheng WJ, Li YF, Cao Z, Yang Q, Zhao YX et al. Safety and diagnostic efficacy of iodixanol vs iopromide in patients with renal insufficiency undergoing coronary angiography: a randomized, controlled trial. ACC 2008, abstract.
Mehran R. Presented at TCT 2006; Hernandez et al. ESC 2007, abstract; Nie et al. ACC/SCAI 2008, abstract.

49. Izo-osmolārā jodixanola priekšrocības nieru aizsargāšanā, salīdzinot ar LOCM- META analīze
Apvienoti dati no 16 prospektīviem, randomizētiem, dubultakliem pētījumiem:
-Iodixanol(Visipaque) (n=1382) vs
-LOCM (n=1345: iohexol (Omnipaque) n=381, iopamidol n=69, iopromide(Ultravist) n=106, ioxaglate n=789)
Nieru mazspēja definēta kā:
-SCr ≥1.3 mg/dL (sievietēm) un ≥1.5 mg/dL (vīriešiem)
-Vai kalkulētais CrCl ≤60 mL/min
CI-AKI (SCr palielinās par ≥0.5 vai ≥1.0 mg/dL) , ko izvērtē 3. dienā pēc kontrastvielas saņemšanas
LOCM, low-osmolar CM
McCullough PA et al. J Am Coll Cardiol. 2006;48: 49

50. Jodixanola vs LOCMs META-analīze: demogrāfiskie dati
Iodixanol (Visipaque)
N = 1382
LOCM
N = 1345
Vecums, vidējais, g
61.2
61.8
Vīrieši
1011
988
Pacienti ar CKD
362
373
Pacienti ar cukura diabētu
293
275
Pacienti ar CKD + DM
115
117
The iodixanol and LOCM treatment groups were comparable in term of age and gender. The demographics of the subgroups stratified on the basis of renal impairment, diabetes, or both were also comparable (McCullough p694).
Reference:
McCullough PA, Bertrand ME, Brinker JA, Stacul F. A meta-analysis of the renal safety of isosmolar iodixanol compared to low-osmolar contrast media. J Am Coll Cardiol. 2006;48:
Demogrāfiskie dati abās grupās ir~ vienādi
McCullough PA et al. J Am Coll Cardiol. 2006;48:

51. Meta-analīze: kopsavilkums
Abās jodixanola un LOCM grupās maksimālais absolūtais SCr pieaugums bija pacientiem ar CKD+DM
Jodixanola lietošana samazināja CI-AKI biežumu, kas definēts kā SCr ≥0.5 mg/dL
Biežāk CI-AKI attīstījās pacientiem ar CKD un CKD+DM, nevis tikai ar DM
The IA use of the IOCM iodixanol was associated with small rises in SCr. The maximum increase seen within 3 days after iodixanol administration was 0.06 mg/dL for all patients, 0.07 mg/dL for the subgroups of patients with CKD, and 0.10 mg/dL in the subgroup of high-risk patients with CKD plus DM.
Iodixanol is associated with a low incidence of CIN in both the total population and in the higher risk subgroups with CKD with or without DM.
Independent predictors of CIN identified through logistic regression analysis included CKD (OR=3.1, 95% CI 1.7 to 5.6) and CKD plus DM (OR=2.7, 95% CI 1.4 to 5.1).
Key point: The IA use of the IOCM iodixanol is associated with small rises in SCr.
Reference:
McCullough PA, Bertrand ME, Brinker JA, Stacul F. A meta-analysis of the renal safety of isosmolar iodixanol compared to low-osmolar contrast media. J Am Coll Cardiol. 2006;48:
McCullough PA et al. J Am Coll Cardiol. 2006;48:

52. ACC/AHA klīniskās prakses vadlīnijas
2007

53. 2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for PCI and ACC/AHA 2007 Guidelines for Management of Patients With UA/NSTEMI
Class I recommendation*
In CKD patients undergoing angiography, iso-osmolar contrast agents are indicated and are preferred (Level of Evidence A†)
2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for PCI
In 2008, the American College of Cardiology/American Heart Association Task Force on Practice Guidelines released the 2007 focused update of the ACC/AHA/SCAI 2005 guideline update for PCI. Based on new data from the RECOVER trial and the McCullough meta-analysis, the new guidelines recommend that patients with CKD or CKD and DM be given IOCM as these are associated with lower rates of CIN compared to LOCM (King, p13).
This recommendation is of the highest level, Class I, where the benefit far outweighs the risk (benefit >>>risk) and the procedure/treatment SHOULD be performed/administered (King, p3). In addition, the level of evidence supporting this recommendation is the highest level, A, where multiple population risk strata were evaluated and there is general consistency of direction and magnitude of effect (King, p3).
Reference:
King SB, Smith SC, Hirshfeld JW, et al focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2008;117:1-35.
Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am coll Cardiol. 2007;50:e1-e157.
*Class I: Benefit >>>risk and the procedure/treatment SHOULD be performed/administered
†Level of Evidence A: Multiple (3-5) population risk strata evaluated; general consistency of direction and magnitude of effect
King SB et al. Circulation. 2008;117:1-35; Anderson JL et al. J Am Coll Cardiol. 2007;50:e1-e157.

54. Society Recommendations: Type of CM for High-risk Patients
Iso-osmolar
Low-osmolar
ACC/AHA/SCAI 2007 (PCI)  –
ACC/AHA 2007 (UA/NSTEMI)
Hungarian Society of Nephrology 2007
National Kidney Foundation (K/DOQI) 2005
Norwegian Society of Nephrology 2004
German Cardiac Society 2004
ESUR 2005
French Radiologic Society 2004 54 54

55. Kontrastvielu izvēle LKC 2007-2008
Izoosmolāro KV patēriņš:
Iodixanol (Visipaque) ~10~15%
Zemas osmolaritātes KV:
Iopromid (Ultravist) ~45%
Iohexol (Omnipaque) ~45%

56. Kontrasvielu izvēle LKC 2009-2010
Izoosmolāro KV patēriņš:
Iodixanol (Visipaque) ~70%
Zemas osmolaritātes KV:
Iopromid (Ultravist) ~10%
Iohexol (Omnipaque) ~20%

57. Secinājumi
CI-AKI ir potenciāli bīstama komplikācija pacientiem, kuriem nepieciešama koronarogrāfija un PCI
CI-AKI riska mazināšanas stratēģijas ietver:
Pietiekamu šķidruma nodrošināšanu
Kontrastvielas devu samazināšanu
Piemērotas kontrastvielas izvēli
Arvien lielāks skaits biedrību rekomendē izo-osmolāras kontrastvielas pacientiem ar augstu CI-AKI risku 57

58. Paldies par uzmanību!