1. CRRT(Continuous Renal Replacement Therapy)with Case Reports(Timing,treatment modalities,general settings)Assist. Prof. Dr.Yusuf SavranDokuz Eylul University Internal Medicine ICU 2. Case- 158 years-old male with diagnosed Type 2 Diabetesmellitus, hypertension and COPDSepsis secondary to pneumoniaMultiorgan failure including oliguric acute renalinsufficiencyMechanically ventilated0.15g/kg/dk norepinephrine infusion needed toresume systolic blood pressure > 60 mmHg 3. Case - 235 years-old maleCrash injury in earthquakeSplenic rupture, splenectomy performed.Perop. 10 units erythrocyte suspensionBilateral fasciothomy applied to both lower extremity due tocompartment syndromeSevere rabdomyolisis , ARF (CK: 10000,Creatinin:12 mg/dl)Severe metabolic acidosisTA:85/50 mmHg despite inotropic support (Dopamin10 mcg/kg/dk) 4. Case-350 years-old female with no comorbidityMultilobar pneumoniaARDS,Septic shock and MOF development 24 hoursafter initiation of antibiotherapyMetabolic acidosisMechanical ventilationNE: 0.5 mcg/kg/dk infusion needed to resumeMAP >60 mmHg 5. Case - 470 years-old male operated for left femur neck fractureDischarged - Acute respiratory distress 1 weeks laterTA:70/40 mmHg, ABG:ph:7.25 pO2:60 pCO2:20HCO3:12 Sa02:88%Thorax BT Angiography:Massive PTEOliguricCreatinine:3.5 mg/dl (creat:1.0 mg/dl 1 week ago) 6. Case - 540 years-old femaleBipolar disorder on Lithium treatmentCommits suicide by 50 tablets Lithium ingestionUnconscious TA:70/40 mmHg Glasgow score :6Severe arrythmias (+)Aspiration pneumonia (+)MOF (anuric ,elevated liver enzymes and coagulationparameters) 7. Case - 672 years-old female with past history of CHD (3 vessel CABG) and CRF (lowclearance) admitted to Emergency service unconsciousTA:80/40 mmHg, N:160/dk arrythmic,ventilation superficial,intubatedABG Ph:7.25 PO2:58 mmHg Pco2:70 mmHg HCO3:26 SaO2:%86Chest X-ray: Acute pulmonary edemaEKG:AF with high ventricular responseCranial CT: schemic strokeMechanically ventilatedEcho: EF:35%,PAP:35 mmHg,LV Global hypokineticARF on CRF(creat:1.6 mg/dl 3.2 mg/dl) 8. Acute renal injury in ICUUnstabileContinuous drug replacementMechanically ventilatedUnconsciousAccompanying findings : Sepsis or MOFWhich RRT ? 9. Renal Replacement Therapy AlternativesIntermittent Hemodialysis(iHD)CRRT Modalities SCUF CAVH - CVVH CAVHD - CVVHD CAVHDF - CVVHDF SLED-EDD 10. Disadvantages of iHDSudden declines in plasma osmolarityUF in limited timencrease in body temperatureInability to remove cytokinesSo how shall we treat ??? 11. Why CRRT ?Similar to normal physiology: rate slow, period enhancedBetter tolerance especially in hemodynamic instabilityAllows removal of great amounts of fluidEfficient clearanceMedium and large sized solutes can be cleared more efficientlyInflammatory mediators cleared more effectivelyAllows supplementary replacement fluid delivery 12. Fluid andanticoagulationDOSETiming ofinitiationMembrane 13. The technique and timing as well as the typeof renal replacement therapy used may affect patientssurvival and recovery of renal function.Palevsky PM et al., Curr Opin Crit Care. 2005;11:548-554.Demirkilic U, J Card Surg. 2004;19:17-20.Swartz RD et al., Am J Kidney Dis. 1999; 34:424-432. 14. INITIATION of TREATMENTWHEN? 15. RIFLE CriteriaCurr Opin Crit Care 8: 509-514 (2002)Level ofinjuryOutcomemeasures 16. RIFLE Stratification in Patients Treated with CRRTBell et al, Nephrol Dial Transplant 2005Bell et al, Nephrol Dial Transplant2005 17. From RIFLE to AKINSerum CreatinineIncrease SCr 24.6mmol/L2-3 foldsStage 1Stage 2Stage 3 18. The Acute Kidney Injury NetworkClassification ( AKIN)Crti Care 11:R31 (2007) 19. CRRT Modalities SCUF- Slow Continuous Ultrafiltration Ultrafiltration CVVH- Continuous Veno-Venous Hemofiltration Convection CVVHD- Continuous Veno-Venous Hemodialysis Diffusion CVVHDF- Continuous Veno-Venous Hemodiafiltration Diffusion and Convection 20. ConvectionHydrostatic pressure causes water movement through the membrane.During this movementPressure1. 2. 3.timeConcurrent water and solute movementDriving force: pressure gradientFMC Pazarlama Departman 2011Medium and large sized moleculesremovedwater also drags the molecules that can not be diffused . 21. The concentration gradient between the sides of the membrane causes the solutes to movefrom the dense concentration to less dense concentration.Different concentrations(effective for small molecular sizes) Solute concentration equals on both sides1. 2. 3.Driving force: concentration gradientFMC Pazarlama Departman 2011timeDiffusion 22. SCUF (Slow continuous ultrafiltration)In case of fluid overload6-7 L/day ultrafiltrateBlood flow rate 24 hoursPreDPostDUFRF 24. CVVHD (Hemodialysis)Solute clearance by diffusion UF rate 2-7 L/day Flow rate of dialysate fluid:15-45 ml/dk Blood flow rate:100-200 ml/dk No replacement fluid Clearance of urea: 24-30 L/dayDialUF 25. CVVHDF(Hemodiafiltration)Blood flow rate:100-200 ml/minFlow rate of dialysate fluid:15-45 ml/dkHigh removal rate of solutes (clearance of urea:30-60 ml/min.)Clearance of solutes:% 75 dialysis% 25 hemofiltrationDial UF rate 12-20 L/day Replacement fluid in need. UFRF 26. Principles of CRRT clearance CRRT clearance of solute is dependent on the following:The molecule size of the soluteThe pore size of the semi-permeable membrane 27. Principles of CRRT clearance Small molecules easily pass through a membranedriven by diffusion and convection. Middle and large size molecules are cleared primarilyby convection. Semi-permeable membrane remove solutes with amolecular weight of up to 50,000 Daltons. Plasma proteins or substances highly proteinboundwill not be cleared. 28. Membrane types and characteristics Hemofilter membrane are composed of:High flux materialSynthetic/biocompatible material Structural design is characterized by: High fluid removalMolecular cut-off weight of 30,000-50,000Daltons. 29. Semi-permeable Membrane The semi-permeable membrane provides: An interface between the blood and dialysatecompartment. Biocompatibility minimizes:Severe patient reactions Decreases the complement activation 30. The decision of the type of RRT is influencedby many factors: Availability Experience Catabolic state Hemodynsmic stability Primary goal ?Removal of excess fluid ?Removal of excess solutes ?Both? 31. Decision of modalityIf the primary goal is removal of excess fluid :SCUF, CVVHFIn catabolic state and excess low molecular size solutes :CVVHD If the primary goal is removal of excess inflammatory mediators:CVVHDF 32. We decided on the modality DOSE ? 33. The higher the ultrafiltration rate (UFR),the greater the solute clearance. 34. Prospective study on 425 patients - 3 groups: Study: survival after 15 days of HF stop recovery of renal function 35. 20mL/Kg/hr 35mL/Kg/hr 45mL/Kg/hr15-daysSurvival41% 57% 58% 36. Effect of BUN at CVVH Initiation on Survival80706050403020100Survivors Non Survivorsp < 0.01Group 1 Group 2 Group 3Blood Urea Nitrogen (mg/dl)p < 0.01 p < 0.01 37. Conclusions:An increased treatment dose from 20 ml/h/kg to 35 ml/h/kgsignificantly improved survival.A delivery of 45ml/kg/hr did not result in further benefit interms of survival, but in the septic patient an improvementwas observed.Our data suggest an early initiation of treatment and aminimum dose delivery of 35 ml/h/kg improve patientsurvival rate. 38. EIHF vs Conventional45mL/Kg/hr for 6 hours then 20mL/Kg/hr vs 20mL/Kg/hr28-day Survival: 55% vs 27.5% 39. J Am Soc Nephrol. 2008 Jun;19(6):1233-8. 40. CVVHDF: more may not be betterCVVHDF: 20mL/Kg/HrCVVHDF: 35mL/Kg/Hr 41. Intense ConventionalHemodynamic stable IHD /SLED 6x/week withKt/V of 1.2-1.4IHD /SLED 3x/week with Kt/V of1.2-1.4Hemodynamic unstable CVVHDF 35mL/Kg/Hr CVVHDF 20mL/Kg/Hr 42. 60 days mortalityIntensive: 53.6%Less Intensive: 51.5% 43. Randomized(Post-dilution CVVH)1508Low dose(25ml/Kg/hr)761High dose(40ml/Kg/hr)747Lost to follow up = 1Consent withdrawn = 2Consent not obtained = 23Analyzed722Lost to follow-up = 0Consent withdrawn = 2Consent not obtained = 16Analyzed743 44. RENAL StudyHighIntensityLowIntensity90-days mortality 44.7% 44.7%28-days mortality 38.5% 36.5% 45. What have we learned about doses ?Before the ATN trialCRRT: 35mL/kg/hrDaily iHDAfter the ATN trialSOFA 0-2: 3x/week iHD (Kt/V 1.2)SOFA 3-4: CRRT 20 mL/kg/hr or SLED 3x/week 46. In SummaryDecide on the treatment modalityaccording to the primary goalStart treatment as early as possibleDecide on the dose for every patientindividually 47. Thank you