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1. EPURAREA EXTRACORPOREALA RENALA

2. La Conferita Acute Kidney Injury Network (Amsterdam-2005 ) s-a recomandat utilizarea termenului de leziune renala acuta (acute kidney injury – AKI), în DETRIMENTU IRA, REZERVATA CAZURILOR cele mai grave ale AKI B.Filipoiu, Smart Medical Solutions ↓ filtrarii glomerulare ↑ rapida a nivelului seric al compuşilor azotaţi neproteici ( azotemie / retenţie azotata acuta ) ± oligurie IRA Scaderea brusca şi potenţial reversibila a funcţiei renale perturbarea metabolismului hidroelectrolitic şi acido -basic ± oligurie ( diminuarea diurezei sub 0,5 ml/kg/ ora timp de mai mult de 6 ore) ↑ creatininei serice cu 0,3 mg/dl <48 de ore ( valorile absolute) ↑ creatininei serice cu 50% ( valorile relative ) AKI

3. B.Filipoiu, Smart Medical Solutions

4. De ce crrt ? B.Filipoiu, Smart Medical Solutions Mimeaza indeaproape functia renale fiziologica Foloseste fluxuri mici - previne episoadele hipotensive Este bine tolerata de pacientii instabili hemodinamic Restabileste si mentine echilibrul electrolitic si acido-bazic Indeparteaza cantitati importante de apa si produsi de excretie , in timp Favorizeaza recuperarea functiei renale

5. C ontinuous R enal R eplacement T herapy B.Filipoiu , Smart Medical Solutions Tehnica de purificare extracorporeala care are intentia de a substitui functia renala pentru o perioada de timp indelungata , fiind aplicata timp de 24h/ zi INCET & CONTINUU REGLEAZA ECHILIBRUL ACIDO-BAZIC SI ELECTROLITIC - mimeaza functia renala fiziologica - previne degradarea renala - incurajeaza recuperarea functiei renale INDEPARTEAZA MARI CANTITATI DE FLUIDE SI PRODUSI DE EXCRETIE IN PERIOADA DE TIMP IMPORTANTA

6. Terapii crrt SCUF - Ultrafiltrare Lenta Continua CVVH - Hemofltrare Veno-Venoasa Continua CVVDH - Hemodializa Veno-Venoasa Continua CVVHDF - Hemodiafiltrare Veno-Venoasa Continua B.Filipoiu, Smart Medical Solutions

7. B.Filipoiu , Smart Medical Solutions

8. ULTRAFILTRAREA B.Filipoiu, Smart Medical Solutions Trecerea unui lichid prinr -o membrana semipermeabila pe baza gradientului de presiune ( diferenta intre presiunea pozitiva si cea negativa din circuit ) Obiectivul principal este reducerea bilantului pozitiv

9. ULTRAFILTRAREA Pompa de sange realizeaza o presiune poziti va impingand sangele prin membrana hemofiltrului B.Filipoiu , Smart Medical Solutions Blood In Blood Out to waste (from patient) (to patient) HIGH PRESS LOW PRESS Fluid Volume Reduction P ompa de efluent creeaza o presiune negativa tragand ultrafiltratul prin filtru

10. I ndicata in: ● bilant pozitiv ● edem pulmonar ● rezistenta la diuretice ( fara uremie sau dezechilibre acido-bazice importante ) S C U F B.Filipoiu , Smart Medical Solutions

11. DIFUZIA B.Filipoiu, Smart Medical Solutions Presupune migrarea unei solutii de la concentratie mare la concentratie mai mica pe baza diferentei de concentratie intre sange si dializat si va dura pana la stabilirea echilibrului de concentratie dintre cele doua solutii Dializatul si sangele circula in contracurent la nivelul filtrului

12. DIFUZIA Este dependenta de: - dimensiunile moleculelor - permeabilitatea membranei pentru particule specifice - fluxurile de sange si dializat B.Filipoiu , Smart Medical Solutions Dialysate Out Dialysate In Blood In Blood Out to waste (from patient) (to patient) HIGH CONC LOW CONC

13. B.Filipoiu , Smart Medical Solutions Indicata in: ● eliminarea toxinelor cu greutate moleculara (GM) mica ( uree , creatinina , fosfati ) C V V H D

14. CONVECTIA B.Filipoiu, Smart Medical Solutions Mobilizarea unei solutii prin membrana dializorului , cu ajutorul unui solvent Proces fizic dependent de: - marimea porilor membranei filtrului - greutatea moleculara a substantelor ( GM medie si mare)

15. B.Filipoiu , Smart Medical Solutions Blood In Blood Out to waste (from patient) (to patient) HIGH PRESS LOW PRESS Repl. Solution CONVECTIA

16. ADSORBTIA Unele particule implicate in raspunsul inflamator adera la membrana filtrului : beta 2-microglobulin (GM 11.8 kD ), TNF (GM 52 kD ),etc B.Filipoiu , Smart Medical Solutions Presupune aderarea moleculelor la suprafata interna a membranei semipermeabile

17. B.Filipoiu, Smart Medical Solutions Indicata in : ● dezechilibrul acido-bazic ● dezechilibrul electrolitic (cu sau fara exces de lichid ) C V V H

18. B.Filipoiu , Smart Medical Solutions Indicata in SIRS, MSOF, ARF, sepsis, rabdomioloza,etc C V V H D F

19. vs. DIFUZIE CONVECTIE B.Filipoiu , Smart Medical Solutions

20. Bellomo & Ronco . Critical Care. 2000 INDICATII CRRT • Litiu • Metanol • Etilen glicol • Salicilati • Barbiturice • Metformin • Aminoglicozide • Metronidazol • Carbapeneme • Cefalosporine • Peniciline Acidoza metabolica Azotemia Hiperpotasemie (K >6.5 mmol/L) Disnatremia severa progresiva (Na >180 or 115 mmol/L) Coagulopatii care necesita cantitati mari de solutii (risc edem pulmonar) Hipertermie (>39,5ºC) Oligurie ( <200 ml/12 h)/ Anurie(<180ml/24h Sepsis Supraincarcarea volemica Sindromul de liza tumorala Edemul cerebral Rabdomioliza ARDS

21. Indicatiile Kdigo¹ B.Filipoiu , Smart Medical Solutions 1-KDIGO-Kidney Disease Improving Global Outcomes UTILIZAREA DIURETICELOR 3.4.1: We recommend not using diuretics to prevent AKI. (1B) 3.4.2: We suggest not using diuretics to treat AKI, except in the management of volume overload. (2C) 5.2.2: We suggest not using diuretics to enhance kidney function recovery, or to reduce the duration or frequency of RRT. (2B) 2 . INITIEREA CRRT 5.1.1: Initiate RRT emergently when life-threatening changes in fluid, electrolyte, and acid-base balance exist. (Not Graded) 5.1.2: Consider the broader clinical context, the presence of conditions that can be modified with RRT, and trends of laboratory tests—rather than single BUN and creatinine thresholds alone—when making the decision to start RRT. (Not Graded) 3. SEVRAREA DE CRRT 5.2.1: Discontinue RRT when it is no longer required, either because intrinsic kidney function has recovered to the point that it is adequate to meet patient needs, or because RRT is no longer consistent with the goals of care. (Not Graded)

22. Indicatiile Kdigo¹ B.Filipoiu , Smart Medical Solutions 1-KDIGO-Kidney Disease Improving Global Outcomes 4. ANTICOAGULAREA 5.3.2: For patients without an increased bleeding risk or impaired coagulation and not already receiving effective systemic anticoagulation, we suggest the following: 5.3.2.2: For anticoagulation in CRRT, we suggest using regional citrate anticoagulation rather than heparin in patients who do not have contraindications for citrate. (2B) 5. DOZE IN CRRT 5.8.4: We recommend delivering an effluent volume of 20–25ml/kg/h for CRRT in AKI (1A). This will usually require a higher prescription of effluent volume. (Not Graded) In conclusion, there are now consistent data from two large multicenter trials (Hannover Dialysis Outcome Stud, ARFTN study, etc )showing no benefits of increasing CRRT doses in AKI patients above effluent flows of 20–25ml/kg/h. In clinical practice, in order to achieve a delivered dose of 20–25ml/kg/h, it is generally necessary to prescribe in the range of 25–30ml/kg/h, and to minimize interruptions in CRRT .

23. B.Filipoiu , Smart Medical Solutions Evidente clinice : Ronco et al, 2000 (using post-dilution hemofiltration) and Saudan et al, 2006 found that lower doses around 20 -25ml/kg/h were inferior to higher effluent flows of around 35 to 45 mL/kg/h in terms of survival (15 to 20% reduction in mortality) Two other studies by Bouman et al, 2002 (48 vs 20 mL/kg/h) and Tolwani et al, 2008 (20 vs 35 ml/kg/hr ) however found no difference in survival with higher effluent rates The VA/HIH Acute renal failure Trial Network or ATN study in NEJM 2008 I n-hospital mortality through day 60 was 51.2% among patients undergoing intensive therapy and 48.0% among those undergoing less-intensive therapy  In the more intensive arm IHD and or SLED were used six times per week and CVVHDF at an effluent flow rate of 35 mL/kg/h The RENAL study by the ANZICS CTG in  NEJM 2009 compared 25 v 40 mL/kg/). No difference in mortality between the two groups at 90 days, a higher incidence of hypophosphatemia in the higher dose group . DOZE IN CRRT

24. E FECTUL ST asupra membranei – A DSORBTIA H EPARINEI Heparin a este molecula incarcata negativ (SO 4 ) Ionii (+) ai PEI leaga ionii (-) ai Heparin ei Pre vine formarea trombinei si coagularea Garanteaza o durata de viata a filtrului de pana la 72 h Polyethyleneimine (PEI) AN69 membran a AN69 ST membran a AN69 ST membran a B.Filipoiu , Smart Medical Solutions

25. TERAPIA SEPSISULUI- oXiris ® Este o membrana AN 69 – tratata cu polyetilenimina (PEI), un polimer cationic care grefeaza heparina Este preheparinizata , ceea ce reduce trombogenitatea si ofera un real ajutor in cazul pacientilor CU coagulopatiI Poate fi folosita in toate modalitatile de terapie CRRT Proprietatile adsorbante : Adsorbtia endotoxinelor : membrana PEI retine endotoxinele ( incarcate electric negativ ) Adsorbtia cytokinelor : membrana cu structura “de burete ” adsoarbe concentratii mari de citokine B. Filipoiu, Smart Medical Solutions Grefarea cu PEI este de 3 x mai mare decat in cazul ST

26. sa previna infundarea filtrului sa nu induca sangerari sa aiba antidot fara efecte sistemice usor de monitorizat sa aiba T ½ scurt actiune limitata la nivelul circuitului extracorporeal ANTICOAGULANTUL OPTIM

27. ANTICOAGULAREA CU HEPARINA Functioneaza prin activarea antitrombinei III→inhibarea fact. IX si fact. X Complicatii : sangerari , HIT ( trombocitopenia indusa de heparina ), hiperkaliemia Doza recomadata : bolus: 20-40UI/ kgc rata continua: 10-20UI/ kgc /h B.Filipoiu , Smart Medical Solutions aPTT = 1,5-2× val de referinta

28. ANTICOAGULAREA CU CITRAT Infuzia solutiei cu citrat pe linia arteriala a circuitului extraorporeal determina formarea unui complex calciiu-citrat care, prin saderea concentratiei de calciu ionizat (F IV) in sange , impiedica procesul de coagulare Citratul leaga toti cationii divalenti In functie de terapie si fluxurile utilizate , un procent de Ca- Citrat este filtrat si pierdut in efluent , prin urmare , doar o mica parte din citratul infuzat este livrata pacientului Complexele Ca- citrat sunt metabolizate , in principal, la nivel hepatic, dar si la nivelul rinichilor si muschilor scheletici 1 mmol Citrat 3 mmoli Bicarbonat F, R, Ms

29. Solutie citrat-Prismocitrate ® 18/0 Pungi PVC free de 5 l, cu valabilitatate 12 luni Posibilitate conectare spike si luer lock 18 moli Citrat 54 moli bicarbonat Se metabolizeaza PBP DIALIZAT Solutie fara calciu- Prism0cal® B22 Nivel fiziologic de HCO3¯ (22+3), glucoza , Na,K Nivel usor crescut de Mg – util pentru a compensa pierderile Punga Polyolefin de 5l cu valabilitate 12 luni Conectare luer lock si spike INLOCUITOR PRISMASOL 2 / PHOXILIUM

30. DOZE IN CRRT ( anticoagulant:heparina )

31. CVVHDF-35ml/kg/h Ex.: pac 70 kg B.Filipoiu , Smart Medical Solutions Flux sange = ≈2x G – in functie de FF Pompa presange (PBP)= max 10 ml/kg/h → 700ml/h Dializat = 875 ml/h Inlocuitor =875 ml/h

32. CVVHDF-protocol citrat

33. PRESIUNEA TRANSMEMBRANARA (TMP ) B.Filipoiu , Smart Medical Solutions TMP = - Effluent P Filter P + Return P ------------------------- 2 POZ POZ SAU NEG

34. FRACTIA DE FILTRARE (FF) FF%= Rata de ultrafiltrare = Fluxul de inlocuitor + Eliminare lichid pacient 15-20% maximum pentru a reduce riscul de coagulare >25% determina hemoconcetratie in F→ coagulare Cresterea fluxului de sange scade FF ( cand eSTE utilizata postdilutia ) B.Filipoiu , Smart Medical Solutions Rata de ultrafiltrare Fluxul de sange (1- Hct )

35. DOZA DE EFLUENT Doza EFL.= B.Filipoiu , Smart Medical Solutions Q PBP + Q Dializat + Q Inlocuitor ( pre+post ) Greutate Doza UFR= Q B(1-Htc) Q B(1-Htc)+ Qpre X Q UF BW

36. Prismaflex - o singura platforma pentru toate tipurile de terapii de epurare extracorporeala (CRRT, MARS, CO2 REMOVAL/PRISMLUNG, TPE) VERSATILITATE CRESCUTA- PUTEM SCHIMBA CU USURINTA TIPUL DE TERAPIE (CVVHDF, CVVHD, CVVHF, SCUF) IN TIMPUL TRATAMENTULUI, FARA A FI NECESARA OPRIREA APARATULUI SAU SCHIMBAREA SETULUI TRATAMENTE SIGURE PENTRU PACIENT SI USOR DE CONDUS (ACCESUL VASCULAR SI MONITORIZARAEA STRICTA A APTT-ULUI TERAPEUTIC-70-90S) MEMBRANE DEDICATE PENTRU FIECARE TIP DE TERAPIE- ST, OXIRIS-CE ASIGURA DURATA TRATAMENTELOR DE PANA LA 72 DE H POSIBILITATI VARIATE DE ANTICOAGULARE- HEPARINA/ CITRAT, PREDILUTIE O ECHIPA CARE VA STA INTODEAUNA LA DISPOZITIE B.Filipoiu, Smart Medical Solutions