©2011 MFMER | slide-1

Continuous Renal-Replacement TherapyCRRT

Kianoush Kashani

5th Anesthesia and Critical Care ConferenceKuwait 2013

©2011 MFMER | slide-2

RRT indications (traditional)

Gibney et al. cJASN 3: 876-880, 2008.

©2011 MFMER | slide-3

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-4

MultiOrgan Support Therapy (MOST)

©2011 MFMER | slide-5

Heart

©2011 MFMER | slide-6

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-7

Liver

©2011 MFMER | slide-8

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-9

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-10

Sepsis

©2011 MFMER | slide-11

Systemic Inflammatory Response Syndrome (SIRS) Vs. Compensatory Anti-inflammatory Response Syndrome (CARS)

©2011 MFMER | slide-12

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-13

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-14

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-15

Lung

©2011 MFMER | slide-16

Respiratory support

• Refractory ARDS

• TV decreased from 6ml/kg to 4 ml/kg

Terragni et al. Anesthesiology 2009; 111:826–35

©2011 MFMER | slide-17

RRT modalities

©2011 MFMER | slide-18

Modalities of RRT

• Hemodyalisis• IRRT • CRRT

• Peritoneal dialysis• Transplant

©2011 MFMER | slide-19

RRT modality and mortality

Bagshaw et al. Crit Care Med 2008 Vol. 36, No. 2

©2011 MFMER | slide-20

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-21

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-22

Anticoagulation

©2011 MFMER | slide-23

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-24

CVVH -predilution

• Partial loss of delivered RF by HF

• ↓ need for anticoagulation Access Return

UFFlow

Replacement fluid

©2011 MFMER | slide-25

CVVH -postdilution

• Higher clearance

• ↑ chance of clotting Access Return

UFFlow

Replacement fluid

©2011 MFMER | slide-26

Effect of filtration on CVVH

Hematocrit30%

Hematocrit60%

Maintain filtration fraction at 25%

©2011 MFMER | slide-27

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. Decrease Quf to 3000 ml/hour (50 ml/min)2. Increase Qb to 300 ml/min• FF = 50/200 X 100 = 25%• FF = 75/300 X 100 = 25%

©2011 MFMER | slide-28

Anticoagulation: Options

• No Heparin protocols

• Heparin• Unfractionated • LMWH

• Citrate

• Others• Prostacyclin • Danaparoid • Hirudin/argatroban• Nafamostate mesylate

©2011 MFMER | slide-29

No Heparin Systemically Heparinized

Gail Annich, University of Michigan

Citrate

©2011 MFMER | slide-30

Citrate Vs. Heparin

Zhang et al. Intensive Care Med (2012) 38:20–28

Filter life span Risk of bleeding

©2011 MFMER | slide-31

CRRT dosing

©2011 MFMER | slide-32

Meta-analysisMortality

Jun et al. Clin J Am Soc Nephrol 5: 956–963, 2010.

©2011 MFMER | slide-33

Meta-analysisRenal recovery

Jun et al. Clin J Am Soc Nephrol 5: 956–963, 2010.

©2011 MFMER | slide-34

CRRT Timing

©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 (Mortality)

Karvellas et al. Critical Care 2011, 15:R72

©2011 MFMER | slide-37

Early versus late RRT (RRT independence)

Karvellas et al. Critical Care 2011, 15:R72

©2011 MFMER | slide-38

شكر ا

“The best interest of the patient is the only interest to be considered”

©2011 MFMER | slide-39

Questions & Discussion