3 RRT Improve metabolic milieu for Support pt and effects of complications from MOFImprove metabolic milieu forIncreasing survivalRecovery of multiple organ systemsVolume overload without oligoanuria or azotemiaCHFPostoperativeWithhold RRTIf return of renal function is likelyConservative management likely to succeed
6 MOST: Cardiac Support Uncontrolled studies improve myocardial elastance with HF and adequate fluid balanceUNLOAD Trial (Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure)RCT, multicenter, (N=200) excluded sCR > 3 mg/dLImproved 48-hours weight loss↓ re-hospitalization rates and ED visits at 90 days↑ diuretic responsivenessNo change in mortality, CHF class and QOLCostanzo et al. J Am Coll Cardiol 49:675–683, 2007
8 Liver extracorporeal support therapies Non-cell basedRRT (IRRT, CRRT, SLED)Hemoperfusion, hemoabsorptionPlasma exchangePlasmaphoresis, Plasma filtration absorption, Selective plasma filtration technology (SEPET)Albumin basedMolecular adsorbent recirculating system (MARS)Single pass albumin dialysis (SPAD)Cell-based synthetic functionHuman hepatocytesPorcine hepatocytesCerda et al. Seminars in Dialysis—Vol 24, No –202
9 Cell-based Liver Purposes Detoxification Provide synthetic Provide regulatory functionsCell sourcesPrimary porcine hepatocytesImmunologic reactionsImmortalized human cellsRare sourceLoose their liver function by timeCells derived from hepatic tumorsFear of tumorgenicitySmall single-center phase I and II trialsProof of principleCerda et al. Seminars in Dialysis—Vol 24, No –202
11 Systemic Inflammatory Response Syndrome (SIRS) Vs Systemic Inflammatory Response Syndrome (SIRS) Vs. Compensatory Anti-inflammatory Response Syndrome (CARS)
12 Sepsis management - MOST HVHFHigh cut-off hemofiltersHemoadsorptionNon-specificCharcoalResinPlasma filtration coupled with adsorption (CPFA)Improved MAPDecrease the need for norepinephrineGrootendorst et al.J Crit Care 1992;7:67–75.Bellomo et al: Intensive CareMed 29:1222–1228, 2003
13 HICOSS trial (High Cut-Off Sepsis study) N = 120Septic shock with AKIConventional membrane vs. HCO membrane (cut-off of 60 kD)5 days on CVVHDStopped prematurely after 81 patientsNo difference in 28-day mortality (31% vs. 33%)No difference in vasopressor need, MV, or LOSNo difference in albumin levelsHonore et al. Proc 10th WFSCICCM,Florence, Italy, 2009.
14 Sepsis management - MOST SpecificPolymyxin BEUPHAS trial (single center_Italy)Improve MAP/vasopressor use↑PaO2 ⁄FIO2↓Mortality and SOFAEUPHRATES trial (multicenter_US)Cruz et al. JAMA. 2009;301(23):Ding et al. ASAIO Journal 2011; 57:426 – 432.
19 RRT modality and mortality Bagshaw et al. Crit Care Med 2008 Vol. 36, No. 2
20 Renal recovery Evidence for CRRT benefit on renal recovery Strong physiologic rationaleObservational studiesEpidemiologic studies (n=3000)No benefit found in RCTsAll RCTs have significant limitations
21 Cost Mayo Clinic study N= 161, retrospective observational study Mean adjusted total costs through hospital discharge$ for IHD$140,733 for CRRT (P< .001).Rauf et al. J Intensive Care Med May-Jun;23(3):
23 Case 65 yo ♀ with PMH of ESLD, DM, HTN Presented with sepsis, DIC, AKI Started on CVVH for AKI stage IIIQb 200 ml/minRF 4500 ml/hCitrate 300 ml/h22 mEq/L Bicarbonate Prismasate® bathHer dialyzer clots every four hoursWhat to do?
24 CVVH -predilution Partial loss of delivered RF by HF ↓ need for anticoagulationReplacement fluidAccessReturnUFFlow
26 Effect of filtration on CVVH Hematocrit60%Hematocrit30%Maintain filtration fraction at 25%
27 Filtration fraction = [Quf (ml/min) / Qb (ml/min)] X 100 CaseFiltration fraction = [Quf (ml/min) / Qb (ml/min)] X 100Quf = 4500 ml/hour = 4500/60 = 75 ml/minQb = 200 ml/minCurrent FF = (75/200) X 100 = 37.5%Decrease Quf to 3000 ml/hour (50 ml/min)Increase Qb to 300 ml/min FF = 50/200 X 100 = 25% FF = 75/300 X 100 = 25%
28 Anticoagulation: Options No Heparin protocolsHeparinUnfractionatedLMWHCitrateOthersProstacyclinDanaparoidHirudin/argatrobanNafamostate mesylateOur options for anticoagulation during CRRT are quite limited. There is NO gold standard. Every technique is associated with risks / benefits and complications.It is essential to correct any technical imperfections in the circuit prior to commencing any treatment. Particularly important is the positioning of the cannulae, and ensuring that there is good free flow from both lumen of the DLC. These cannulae are a frequent source of problems in babies as they tend to kink at the skin entrance.The main advantage that I see with pre-dilution is not prolonging the life of a filter and circuit but enhancing clearance. The other options of NOT anticoagulating are really temporizing in individual cases and can only be recommended for short term use. They do NOT address the more common problems of preventing clot in the greater majority of patients.That leaves us with either systemic or regional anticoagulation. I am only going to deal with the more common techniques used. NEXT SLIDE
29 Citrate No Heparin Systemically Heparinized In addition, heparin damages platelets, as can be demonstrated in this slide.Thanks to Dr. Gail Annich in Ann Arbor at University of Michigan for allowing me to use this slide.The slide represents scanning electron microscopy of the surface of extracorporeal circuits from an animal study. The right side of each image is a x 5 magnification of the area selected.Figure A = a circuit that was not heparinized. Note the clumping of platelets and fibrin strands.Figure B = represents a heparinized circuit - note the shape of the plateletsFigure C = a circuit where the clotting was prevented by a special circuit material that Dr. Annich and her colleagues have been working on, and heparin was NOT used - note the shape of the platelets now.CitrateGail Annich, University of Michigan
30 Citrate Vs. Heparin Filter life span Risk of bleeding Zhang et al. Intensive Care Med (2012) 38:20–28
35 Early versus late RRT (Mortality) AbstractIntroduction: Our aim was to investigate the impact of early versus late initiation of renal replacement therapy(RRT) on clinical outcomes in critically ill patients with acute kidney injury (AKI).Methods: Systematic review and meta-analysis were used in this study. PUBMED, EMBASE, SCOPUS, Web of Scienceand Cochrane Central Registry of Controlled Clinical Trials, and other sources were searched in July Eligible studiesselected were cohort and randomised trials that assessed timing of initiation of RRT in critically ill adults with AKI.Results: We identified 15 unique studies (2 randomised, 4 prospective cohort, 9 retrospective cohort) out of 1,494citations. The overall methodological quality was low. Early, compared with late therapy, was associated with asignificant improvement in 28-day mortality (odds ratio (OR) 0.45; 95% confidence interval (CI), 0.28 to 0.72). Therewas significant heterogeneity among the 15 pooled studies (I2 = 78%). In subgroup analyses, stratifying by patientpopulation (surgical, n = 8 vs. mixed, n = 7) or study design (prospective, n = 10 vs. retrospective, n = 5), there wasno impact on the overall summary estimate for mortality. Meta-regression controlling for illness severity (AcutePhysiology And Chronic Health Evaluation II (APACHE II)), baseline creatinine and urea did not impact the overallsummary estimate for mortality. Of studies reporting secondary outcomes, five studies (out of seven) reportedgreater renal recovery, seven (out of eight) studies showed decreased duration of RRT and five (out of six) studiesshowed decreased ICU length of stay in the early, compared with late, RRT group. Early RRT did not; however,significantly affect the odds of dialysis dependence beyond hospitalization (OR to 1.13, I2 = 69.6%).Conclusions: Earlier institution of RRT in critically ill patients with AKI may have a beneficial impact on survival. However,this conclusion is based on heterogeneous studies of variable quality and only two randomised trials. In the absence ofnew evidence from suitably-designed randomised trials, a definitive treatment recommendation cannot be made.Karvellas et al. Critical Care 2011, 15:R72
36 Early versus late RRT (Mortality) Karvellas et al. Critical Care 2011, 15:R72
37 Early versus late RRT (RRT independence) Karvellas et al. Critical Care 2011, 15:R72
38 شكراً“The best interest of the patient is the only interest to be considered”