Continuous Renal-Replacement Therapy CRRT Kianoush Kashani 5th Anesthesia and Critical Care Conference Kuwait 2013 ©2011 MFMER | slide-1 RRT indications (traditional) Gibney et al. cJASN 3: 876-880, 2008. ©2011 MFMER | slide-2 RRT • Support pt and effects of complications from MOF • Improve metabolic milieu for • Increasing survival • Recovery of multiple organ systems • Volume overload without oligoanuria or azotemia • CHF • Postoperative • Withhold RRT • If return of renal function is likely • Conservative management likely to succeed ©2011 MFMER | slide-3 MultiOrgan Support Therapy (MOST) ©2011 MFMER | slide-4 Heart ©2011 MFMER | slide-5 MOST: Cardiac Support • Uncontrolled studies •  improve myocardial elastance with HF and adequate fluid balance • UNLOAD Trial (Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure) • • • • • RCT, multicenter, (N=200) excluded sCR > 3 mg/dL Improved 48-hours weight loss ↓ re-hospitalization rates and ED visits at 90 days ↑ diuretic responsiveness No change in mortality, CHF class and QOL Costanzo et al. J Am Coll Cardiol 49:675–683, 2007 ©2011 MFMER | slide-6 Liver ©2011 MFMER | slide-7 Liver extracorporeal support therapies • Non-cell based • RRT (IRRT, CRRT, SLED) • Hemoperfusion, hemoabsorption • Plasma exchange • Plasmaphoresis, Plasma filtration absorption, Selective plasma filtration technology (SEPET) • Albumin based • Molecular adsorbent recirculating system (MARS) • Single pass albumin dialysis (SPAD) • Cell-based  synthetic function • Human hepatocytes • Porcine hepatocytes Cerda et al. Seminars in Dialysis—Vol 24, No 2 2011. 197–202 ©2011 MFMER | slide-8 Cell-based Liver • Purposes • Detoxification • Provide synthetic • Provide regulatory functions • Cell sources • Primary porcine hepatocytes • Immunologic reactions • Immortalized human cells • Rare source • Loose their liver function by time • Cells derived from hepatic tumors • Fear of tumorgenicity • Small single-center phase I and II trials • Proof of principle Cerda et al. Seminars in Dialysis—Vol 24, No 2 2011. 197–202 ©2011 MFMER | slide-9 Sepsis ©2011 MFMER | slide-10 Systemic Inflammatory Response Syndrome (SIRS) Vs. Compensatory Anti-inflammatory Response Syndrome (CARS) ©2011 MFMER | slide-11 Sepsis management - MOST • HVHF • High cut-off hemofilters • Hemoadsorption • Non-specific • Charcoal • Resin • Plasma filtration coupled with adsorption (CPFA) • Improved MAP • Decrease the need for norepinephrine Grootendorst et al.J Crit Care 1992;7:67–75. Bellomo et al: Intensive CareMed 29:1222–1228, 2003 ©2011 MFMER | slide-12 HICOSS trial (High Cut-Off Sepsis study) • N = 120 • Septic shock with AKI • Conventional membrane vs. HCO membrane (cut-off of 60 kD) • 5 days on CVVHD • Stopped prematurely after 81 patients • No difference in 28-day mortality (31% vs. 33%) • No difference in vasopressor need, MV, or LOS • No difference in albumin levels Honore et al. Proc 10th WFSCICCM,Florence, Italy, 2009. ©2011 MFMER | slide-13 Sepsis management - MOST • Specific • Polymyxin B • EUPHAS trial (single center_Italy) • Improve MAP/vasopressor use • ↑PaO2 ⁄FIO2 • ↓Mortality and SOFA • EUPHRATES trial (multicenter_US) Cruz et al. JAMA. 2009;301(23):2445-2452 Ding et al. ASAIO Journal 2011; 57:426 – 432. ©2011 MFMER | slide-14 Lung ©2011 MFMER | slide-15 Respiratory support • Refractory ARDS • TV decreased from 6ml/kg to 4 ml/kg Terragni et al. Anesthesiology 2009; 111:826–35 ©2011 MFMER | slide-16 RRT modalities ©2011 MFMER | slide-17 Modalities of RRT • Hemodyalisis • IRRT • CRRT • Peritoneal dialysis • Transplant ©2011 MFMER | slide-18 RRT modality and mortality Bagshaw et al. Crit Care Med 2008 Vol. 36, No. 2 ©2011 MFMER | slide-19 Renal recovery • Evidence for CRRT benefit on renal recovery • Strong physiologic rationale • Observational studies • Epidemiologic studies (n=3000) • No benefit found in RCTs • All RCTs have significant limitations ©2011 MFMER | slide-20 Cost • Mayo Clinic study • N= 161, retrospective observational study • Mean adjusted total costs through hospital discharge • $93 611 for IHD • $140,733 for CRRT (P< .001). Rauf et al. J Intensive Care Med. 2008 May-Jun;23(3):195-203. ©2011 MFMER | slide-21 Anticoagulation ©2011 MFMER | slide-22 Case • 65 yo ♀ with PMH of ESLD, DM, HTN • Presented with sepsis, DIC, AKI • Started on CVVH for AKI stage III • • • • Qb 200 ml/min RF 4500 ml/h Citrate 300 ml/h 22 mEq/L Bicarbonate Prismasate® bath • Her dialyzer clots every four hours What to do? ©2011 MFMER | slide-23 CVVH -predilution • Partial loss of delivered RF by HF • ↓ need for anticoagulation Replacement fluid Access Flow Return UF ©2011 MFMER | slide-24 CVVH -postdilution • Higher clearance • ↑ chance of clotting Replacement fluid Access Flow Return UF ©2011 MFMER | slide-25 Effect of filtration on CVVH Hematocrit 60% Hematocrit 30% Maintain filtration fraction at 25% ©2011 MFMER | slide-26 Case Filtration fraction = [Quf (ml/min) / Qb (ml/min)] X 100 • • • Quf = 4500 ml/hour = 4500/60 = 75 ml/min Qb = 200 ml/min Current FF = (75/200) X 100 = 37.5% 1. 2. • • 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% ©2011 MFMER | slide-27 Anticoagulation: Options • No Heparin protocols • Heparin • Unfractionated • LMWH • Citrate • Others • Prostacyclin • Danaparoid • Hirudin/argatroban • Nafamostate mesylate ©2011 MFMER | slide-28 No Heparin Systemically Heparinized Citrate Gail Annich, University of Michigan ©2011 MFMER | slide-29 Citrate Vs. Heparin Filter life span Risk of bleeding Zhang et al. Intensive Care Med (2012) 38:20–28 ©2011 MFMER | slide-30 CRRT dosing ©2011 MFMER | slide-31 Meta-analysis Mortality Jun et al. Clin J Am Soc Nephrol 5: 956–963, 2010. ©2011 MFMER | slide-32 Meta-analysis Renal recovery Jun et al. Clin J Am Soc Nephrol 5: 956–963, 2010. ©2011 MFMER | slide-33 CRRT Timing ©2011 MFMER | slide-34 Early versus late RRT (Mortality) Karvellas et al. Critical Care 2011, 15:R72 ©2011 MFMER | slide-35 Early versus late RRT (Mortality) Karvellas et al. Critical Care 2011, 15:R72 ©2011 MFMER | slide-36 Early versus late RRT (RRT independence) Karvellas et al. Critical Care 2011, 15:R72 ©2011 MFMER | slide-37 ‫شكرا‬ “The best interest of the patient is the only interest to be considered” ©2011 MFMER | slide-38 Questions & Discussion ©2011 MFMER | slide-39