林口長庚紀念醫院 加護腎臟科 / 陳永昌

Outline

Introduction

CRRT Nomenclature

Applications for CRRT

Fluid Management in CRRT

Clinical Aspects

Evidence Based Medicine

Conclusions

AKI in ICUs

In ICUs, acute kidney injury (AKI) frequently occurs in patients with medical or surgical complications and multiorgan failure

Worse prognosis

Standard intermittent renal replacement (IHD) treatments are often contraindicated

RIFLE Classification

GFR criteria Urine output criteria

Risk Increase SCr x 1.5 or GFR decrease >25%

UO < 0.5ml/kg/h x 6 hr

Injury Increase SCr x 2 or GFR decrease >50%

UO < 0.5ml/kg/h x 12 hr

Failure Increase SCr x 3 or GFR decrease >75% or

SCr > 4 mg/dl

UO < 0.3ml/kg/h x 24 hr or anuria x 12 hr

Loss Complete loss of kidney function > 4 weeksESRD End stage renal disease (> 3 months)

(Bellomo R et. al. Critcal Care 2004)

Contraindication to Hemodialysis

Hemodynamic instability (hypotension, presence of significant cardiovascular disease)

Lack of access to circulation

Lack of highly trained staff and/or equipment

Indication and Timing of Dialysis for AKI Renal Replacement vs. Renal Support

Renal replacement Renal support

Purpose

Timing of intervention

Indications for dialysis

Dialysis dose

Replace renal function

Based on level

biochemical markers

Narrow

Extrapolated from ESRD

Support other organs

Based on individual

need

Broad

Targeted for overall support

CRRT vs. IHD

CRRT IHD

Hemodynamic stabilityFluid removalDialysis efficiencyAnticoagulationPatient mobilizationSpecialty personnelDrug dosing/deliveryVolume restriction

StableSlow, gentle, completeLow efficiency, long timeFrequently necessaryPossible PerhapsEasierMinimal

UnstableRapid, harsh, incompleteHigh efficiecy, short timeZero heparin possiblePossibleDefinitelyDifficultSignificant

Continuous Renal Replacement Therapy (CRRT)

CAVH: Continuous arteriovenous hemofiltration

CAVHD: Continuous arteriovenous hemodialysis

CAVHDF: Continuous arteriovenous hemodiafiltration

CVVH: Continuous venovenous hemofiltration

CVVHD: Continuous venovenous hemodialysis

CVVHDF: Continuous venovenous hemodiafiltration

AVSCUF: Arteriovenous slow continuous ultralfiltration

VVSCUF: Venovenous slow continuous ultralfiltration

VX

X

CRRT: AV vs. VV

Arteriovenous therapies (AV) Technique simplicity Required large-bore arterial catheter Blood flow dependent on MAP

Venovenous therapies (VV) No arterial line Pump-assisted Blood flow independent of blood pressure

CGMH CRRT Order

1. Diagnosis2. CVVH Solution A 3000 cc + 15% KCl __ cc IVF (500~ cc/hr)3. CVVH Solution B 3000 cc + 7% NaHCO3 240 cc IVF(500~cc/hr)4. Record I/O Q1h and Keep I/O _____5. Check: BUN,Cr, Na, K, Cl, Ca, P QD; Mg QW1,46. Blood flow 120ml/min7. Check ACT Q6h and Keep ACT at 200~250 secP.S. 15% KCl 6 cc/3L

7.5 cc/3L9 cc/3L10.5 cc/3L12 cc/3L

2.012 meq/L K2.515 meq/L K3.018 meq/L K3.521 meq/L K4.024 meq/L K

Multi-mode continuous renal replacement machine

Applications for CRRT (1)

Renal application (renal replacement and renal support)Acute renal failure (specifically complicated ARF with multiple organ failure)

Oligouric ARF needs large amount of fluid or nutrition

Fluid overloading

An alternative to HD in the mass casualty situation

Electrolytes and acid base disturbance

Applications for CRRT (2)

Non-renal application Hepatic failure complicated with hepatic coma Congestive heart failure refractory to diuretics Overhydration during & after cardiac surgery (CPB & after) Sepsis Life-threatening hyperthermia Hemofiltration for poisoning (lactic acidosis, lithium poisoning) Cytokine removal: Acute respiratory distress syndrome Chemofiltration, chemoperfusion

Potential Complications of CRRT

Technical Clinical

Vascular access malfunction

Circuit clotting

Circuit explosion

Catheter and circuit kinking

Insufficient blood flow

Line-catheter disconnection

Fluid balance errors

Loss of efficiency

Bleeding, Hematomas

Thrombosis

Infection and sepsis

Allergic reactions

Hypothermia

Nutrient losses

Insufficient blood purification

Hypotension, arrhythmia

Fluid Removal vs. Fluid Regulation

Fluid removal Fluid regulation Normal kidney

IHD

PD

CRRT

＋＋＋＋＋＋＋＋＋＋＋

＋＋＋＋－－＋＋＋

Hemofiltration

(CAVH, CVVH)

Hemodialysis

(CAVHD, CVVHD)

Hemodiafiltration

(CAVHDF, CVVHDF)

Fluid Convection Convection ConvectionSolute Convection Diffusion Convection ＋

DiffusionBack transport None Possible Possible

Fluid and Solute Removal in CRRT

Components of Fluid Regulation

Fluid Balance

Fluid composition

Electrolyte and Acid Base homeostasis

Nutritional balance

Temperature control

Volume Adjustment for Fluid Management

Level 1: Ultrafiltrate volume limited to match anticipated needs for fluid balance over 8-24 hours. Limited replacement fluid.

Level 2: Ultrafiltrate volume greater than hourly intake. Net fluid balance achieved by hourly replacement fluid administration.

Level 3: Ultrafiltrate volume adjusted greater than hourly intake. Net fluid balance targeted to achieve specific hemodynamic parameters eg. CVP, PAWA, MAP.

Sliding Scale for Volume Adjustment

Desired volume change (ml/hr)

PAWP < 6

PAWP 6-8

PAWP 9-11

PAWP 12-14

PAWP 15-17

PAWP 18-20

PAWP 21-22

PAWP >22

+ 175 ml and notify nephrologist

+ 125 ml

+ 75 ml

Zero balance

50 ml

75 ml

100 ml

125 ml and notify nephrologist

Electrolyte and Acid Base Derangements

Continuous therapies can be used to correct water and electrolyte imbalances

Hypo-hypernatremia can be corrected not only achieving a normal plasma sodium concentration, but also by restoring the normal body sodium content

Hyperkalemia can also be corrected: the efficiency of continuous arteriovenous and venovenous hemofiltration in removing potassium is low

AKI in Neonates

Continuous arteriovenous hemofiltration is especially useful in the treatment of acute renal failure in neonates and small babies (Ronco et al. 1984, 1986)

CRRT as a successful bridge to liver transplantation should be considered in children with unrelenting hyperammonemia not amenable to routine medical therapy (Chen CY et al. 2000)

Treatment of Multiple Organ Dysfunction and Sepsis with CRRT

Eicosanoids, cytokines (tumor necrosis factor and interleukins such as IL-1, IL-6, and IL-8), endothelin, and platelet-activating factor may all contribute to the reduction of renal blood flow and GFR during sepsis

ARF cannot be treated effectively unless the underlying problems are resolved

CVVH using the high-permeability membranes allows extraction of significant quantities of circulating macromolecules (MW 30 kDa)

CRRT of AKI in Burns Patients

CRRT may maintain a good uremic control for severely catabolic burns patients with multiorgan dysfunction Treatment is possible despite cardiovascular instability and total parenteral nutrition can be givenCAVHD appears to give somewhat better uremic control, but the difference in mortality is not significant Large burns, pulmonary burns and septicemia seems to be bad prognostic signs (Leblanc et al. 1999)

Advantage of CRRT for Nutritional Support

Fluid restrictions are removed Electrolyte overload is avoidedHyperosmolar nutrition solutions are safeCRRT result in a cumulative Kt/V or small solute removal rate equivalent or superior to conventional intermittent 4 hours HD IHD daily X 4 hr: Kt/V weekly 7.5 IHD X three sessions /week: Kt/V weekly 3.2 CAVHD: Kt/V weekly 6.2 CVVHD: Kt/V weekly 8.0 (Leblanc M. et al. Semin Dial 1995)CRRT provide adequate clearance of nitrogenous compounds with the avoidance of repeatedly high peak serum nitrogen values (Clark WR et al. JASN 1994)

Regional Chemotherapy plus Hemofiltration vs. Hemoperfusion

Regional intra-arterial chemotherapy: drug delivery 1.5~2 x systemic dose

Regional chemotherapy plus hemofiltration: drug delivery 3~4 x systemic dose

Regional chemotherapy plus hemoperfusion: drug delivery 5~8 x systemic dose

Ability to overcome drug delivery problems and resistance

Improves survival for HCC, pancreatic cancers, and hepatic metastasis colorectal cancer (Muchmore et al. 1999)

CRRT in Liver Support

Requirements for liver supportDetoxificationFluid regulationAcid-Base and electrolyte homeostasisIndications of CRRT support Combines renal and liver failure Liver transplant Mx of complications of decompensated liver disease

– Ascites– Encephalopathy

Post Cardiac Surgery AKI

Intra-operative support and post-operative problems Oxygenator membranes and cytokine generation Blood tubing and extraction of plasticizers (DEHP) Prolonged bypass time and hemodynamic consequences

Application of aggressive ultrafiltration in the cardiac support of children and outcome improvement

Dialysis variants added to extracorporeal cardiac support system VAD and support ECMO and support IABP and support

(Lin CY, Chen YC, Fang JT et al. JN 2008)

Evidence Based Medicine (1)

Optimal way to deliver CRRT does not existAcute Dialysis Quality Initiative (ADQI) aims at establishing an evidence-based appraisal and set of consensus recommendations to standardize care and direct further researchhttp://www.ADQI.net

Evidence Based Medicine (2)

Levels of EvidenceLevel I: Randomized trials with low false positive () and low false negative () error (i.e. high power)

Level II: Randomized trials with high error or low power

Level III: Non-randomized concurrent cohort studies

Level IV: Non-randomized historic cohort studies

Level V: Case series, case reports, expert opinion

Evidence Based Medicine (3)

Grades of RecommendationsGrade A: Supported by at least 2 level I studies

Grade B: Supported by only 1 level I study

Grade C: Supported level II studies

Grade D: Supported by at least 1 level III study

Grade E: Supported by only level IV or V studies

Evidence Based Medicine (4)

CRRT use in a variety of non-ARF conditions including intoxication with dialyzable/filterable drugs or toxins, cardiac failure, ARDS, and pediatric cardiac surgery or sepsis and systemic inflammationInsufficient evidence to recommend the use of CRRT for non-ARF indications outside clinical investigation (Grade E)CRRT use may be advantageous in the management of ICU patients with ARF (Grade E)CRRT is recommended over IHD for patients with AKI who have, or are at risk for, cerebral edema (Grade C)

CVVH Dose (1)

(Ronco C et al. Lancet 2000)

CVVH Dose (2)

CVVH Dose (3)

Intensive vs. Less-Intensive Strategy (1)

(Palevsky PM et al. NEJM 2008)

Intensive vs. Less-Intensive Strategy (2)

Intensive vs. Less-Intensive Strategy (3)

CVVHDF vs. CVVH (1)

(Saudan P et al. KI 2006)

CVVHDF vs. CVVH (2)

CVVHDF vs. CVVH (3)

p=0.0005

CRRT vs. IHD (1)

(Tonelli M et al. AJKD 2002)

CRRT vs. IHD (2)

(Vinsonneau C et al. Lancet 2006)

CRRT vs. IHD (3)

CRRT vs. IHD (4)

CRRT vs. IHD (5)

B.E.S.T. Kidney Investigators

(Uchino S et al. ICM 2007)

Less Chronic Kidney Disease in CRRT

(Bell M et al. ICM 2007)

Conclusions

CRRT are safe, simple, effective, and well tolerated in the management of patients with multiple organ failure and acute renal failure Maintenance of water, and electrolyte balance Removal of metabolic waste products Removal of inflammatory mediators of MOSF Facilitate full nutrition support The treatment of choice in critically ill patients with acute renal failure No particular form of CRRT has yet shown to be superior of survival

Scheme for Selection of a Renal Replacement Therapy in ICUs: Patient-

Center ApproachingRenal Failure requiring renal replacement therapy

Uni-organ failure Multi-organ failure

Intermittent Hemodynamically Hemodynamically hemodialysis stable unstable

Main problems: Main problems: CRRT

biochemical/uremia fluid overload or cytokines

Intermittent Hemodialysis CRRT (EDD, SLED)

IHDIntolerance