Acute Hemodialysis & CRRT in AKI

Acute Hemodialysis & CRRT in AKI

Paweena Susantitaphong,MD,MS1-3

1Physician Staff , Division of Nephrology, Department of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok

2 International Society of Nephrology (ISN) fellowship3Adjunct Instructor of Tufts University School of Medicine, Boston, USA.

DEFINITION

Acute Renal Failure Acute Kidney Injury

An abrupt (within 48h) reduction in kidney functionCurrently defined as an absolute increase in sCr of either ≥ 0.3 mg/dl or a percentage increase of ≥

50%or a reduction in Urine Output (documented oliguria

of < 0.5 cc/kg per h for > 6 h)

Crit Care 2007;11:R31

BackgroundBackground

Stage Serum creatinine Urine output

1 1.5–1.9 times baseline OR ≥ 0.3 mg/dl

(≥ 26.5 mmol/l) increase

< 0.5 ml/kg/h for

6–12 hours

2 2.0–2.9 times baseline < 0.5 ml/kg/h for

≥12 hours

3 3.0 times baseline OR Increase in

serum creatinine to ≥ 4.0 mg/dl

(≥353.6 μmol/l)

OR Initiation of renal replacement

therapy OR, In patients < 18 years,

decrease in eGFR to < 35 ml/min per

1.73 m2

< 0.3 ml/kg/h for

≥ 24

hours

OR Anuria for ≥12

hours

World Incidence of Acute Kidney Injury: A Meta-Analysis

Susantitaphong P, et al. CJASN 2013, June 6


No. studies 154 112 108 108 189No. subjects 3,585,911 3,303,992 3,281,715 3,281,715 29,400,495


No. studies 110 26 25 25 31No. subjects with AKI 429,535 8,226 42,354 42,354 6,534


No. studies 92 21 20 20 20 No. subjects with AKI 405,616 90,048 40,631 38,914 4,427 No. subjects without AKI 1,765,574 1,127,070 1,120,523 1,120,523 127,969


Acute Kidney Injury Increases Risk of Acute Kidney Injury Increases Risk of ESRD among ElderlyESRD among Elderly

Ishani A ,et al. J Am Soc Nephrol 2009; 20: 223–228

Coca SG, et al. AJKD 2010

Acute Kidney Injury Associates Acute Kidney Injury Associates with Increased Long-Term with Increased Long-Term

MortalityMortality

Lafrance JP ,et al. J Am Soc Nephrol 2010;21 :345-52

Renal Replacement Therapy

Timing of initiation ◦early VS late

Indications in Renal Fai Indications in Renal Failurelure

1. Uremiaiiiiiiii iiiiiiiii

N/V poor appetite gastritis with UGIB, ileus, colitis

Altered mental statusPericarditis (urgent indication)

Bleeding from platelet dysfunction (urgent indication)

IndicationsIndications 2. Refractory or progiiiiiii fl ui doverload 3. Uncontrollable iiiiiiiiiiii 4. Severe metabolic acidosis esp. olig

ur i a 5. Steady worsening of renal function - BUN > 70 100 mg/dl

Authors Year Design N Pre-RRT BUN Survival benefit Mode of

RRTEarly Late Early Late

Parsons et al 1961 Retro 33 120-150 >200 + HD

Fischer et al 1966 Retro 162 ~150 >200 + HD

Kleinknecht 1972 Retro 500 <93 >163 + HD

Conger 1975 Pro 18 70 150 + HD

Gillum et al 1986 Pro 34 60 100 ± ± HD

Gettings et al 1999 Retro 100 <60 >60 + CRRT

Bouman et al 2002 Pro 106 47 105 ± ± CVVH

Demirkilic et al 2004 Retro 61 + CVVHD

Elahi et al 2004 Retro 64 + CVVH

Liu et al 2006 Retro 243 <76 >76 + HD and

CRRT

Outcome of Early vs. Late RRT in AKI

Timing of renal replacement therapy initiation in acute renal failure: a meta-analysis

Seabra VF, Balk EM, Liangos O, Sosa MA, Cendoroglo M, Jaber BL

• We identified 23 studies (5 randomized or quasi-randomized controlled trials, 1 prospective and 16 retrospective comparative cohort studies, and 1 single-arm study with a historic control group).• By using meta-analysis of randomized trials, early RRT was associated with a nonsignificant 36% mortality risk reduction (RR, 0.64; 95% CI, 0.40 to 1.05; P = 0.08). • Conversely, in cohort studies, early RRT was associated with a statistically significant 28% mortality risk reduction (RR, 0.72; 95% CI, 0.64 to 0.82; P < 0.001). • The overall test for heterogeneity among cohort studies was significant (P = 0.005). • However, early dialysis therapy was associated more strongly with lower mortality in smaller studies (n < 100) by means of subgroup analysis.

Am J Kidney Dis. 2008 Aug;52(2):272-84.

Effect of early renal replacement therapy (RRT) initiation on non-recovery of renal function in AKI

Am J Kidney Dis. 2008 Aug;52(2):272-84.

Clinical symptoms

Solute level (Blood urea nitrogen, serum creatinine)

Interval between ICU/hospital admission and renal replacement therapy initiation

Days between biochemical diagnosis of AKI and renal replacement therapy initiation

Severity of AKI (AKIN/RIFLE) classification

Prognostic scores

Number of organ failure

Parameters that were used in studies for classify

early and late renal replacement therapy initiation in AKI

Parameters that were used in studies for classify

early and late renal replacement therapy initiation in AKI



Modality of RRT◦Intermittent VS Continuous

Dialysis : ModalityDialysis : Modality

Intracorporeal Vs Extracorporeal (PD vs. HD - CRRT?)


Intracorporeal Vs Extracorporeal (PD vs. HD - CRRT?)

Intermittent Vs Continuous (IHD,SLED vs. CRRT?)

Note IHD Intermittent Hemodialysis

SLED Sustained Low-Efficiency Dialysis

CRRT Continuous Renal Replacement Therapy

RRT Modalities

INTERMITTENT CONTINUOUS

IHD SLED/EDD CRRT

SCUF

CAVH

CVVH

CAVHD

CVVHD

CAVHDF

CVVHDF

Mechanism of Mechanism of clearanceclearance

Hemodialysis = DiffusionHemofiltration = ConvectionHemodiafiltration = Diffusion + Convection

Diffusiont = 0 t = equilibrium

Concentration gradientMolecular weight: speed & sizeMembrane resistance: membrane & unstir fluid layer

T =0

Ultrafiltratio n (Convectio

n)

T = later

Dialysis : ModalityDialysis : ModalityIntermittent Hemodialysis


6-12 hrs

Sustained Low-Efficiency Dialysis (SLED)

Hemodialysis in ARF patient-Long duration 6-12 hrs-Dialysate flow 70-300 ml/min-Critically-ill patient

Dialysis : ModalityDialysis : ModalityContinuous Renal Replacemet Therapy

(CRRT)

Separated system Automated system

Renal Replacement Therapy : Renal Replacement Therapy : ModalityModality

Continuous Renal Replacemet Therapy (CRRT)

Separated CVVH systemSeparated CVVH system

: A one-year prospective observational study , 192 critically ill patients with AKI.

: Separated system CVVH with the pre-dilution. Mean CVVH dose of

34.9±2.7mL/kg/h.

: The APACHEII score was 23.2±8.4 and the SOFA was 12.0±4.3.

: No complications. The survival rate was 32.3%.

Conclusion: Separated system CVVH is simple, safe, and efficient and could

provide cheaper treatments than the integrated system. It could thus be an

effective, alternative treatment for critical acute kidney injury patients when the

integrated mode is unavailable

Automated CVVH systemAutomated CVVH system

PD(24 hrs)

IHD (4 hrs)

SLED( 6-12 hrs)

CRRT(24 hrs)

Solute removal per day

+ +++ +++ +++

Hemodynamic stability

best poor Fair-good good

Cost person and time

++ + +++ +++

Complication -Infection-high sugar-visceral trauma

BP drop BP drop - Air embolism- BP drop

Renal Replacement Therapy : Renal Replacement Therapy : ModalityModality

Slow continuous ultrafiltration (SCUF)

Continuous arteriovenous hemofiltration (CAVH)

Continuous venovenous hemofiltration (CVVH)

Continuous arteriovenous hemodialysis (CAVHD)

Continuous venovenous hemodialysis (CVVHD)

Continuous arteriovenous hemodiafiltration (CAVHDF)

Continuous venovenous hemodiafiltration (CVVHDF)

Vascular access

Slow continuous ultrafiltration (SCUF)

Continuous venovenous hemofiltration (CVVH)

Continuous venovenous hemodialysis (CVVHD)

Continuous venovenous hemodiafiltration (CVVHDF)

Vascular access

Mechanism of Clearance

Measuring device

Filtrate

SCUF

Slow Continuous Ultra-Filtration

Arteriovenous or venovenous QUF 100 – 300 mL/day

Perform to maintain fluid balance, no significant convective clearance

No replacement fluid

Replace-ment fluid

Measuring device

Filtrate

CVVH

Continuous Veno-Venous HemoFiltration

Veno-venous circuit High permeable membrane Typical UF rate 1 – 2 L/h Requires at least a blood pump

(Flow > 50 ml/min) required Replacement fluid

(pre-dilution VS post-dilution)

CVVHD Continuous Veno-

Venous HemoDialysis High permeable membrane At least a Blood pump and a pump

for Dialysate (10-30 ml/min or 1-2.5 L/h) required

No replacement fluid UF for volume control, some

convective clearance at high rate

Dialysate

Measuring device

Filtrate

Continuous VenoVenous HemoDiaFiltration

High permeable membrane Ultrafiltration flow > 6 ml/min

(9-12 L/day) 1 pump for dialysate

(10-30 ml/min or 1-2.5 L/h)) Replacement fluid

Dialysate

Replace-ment fluid

Measuring device

Filtrate

CVVHDF

Continuous Renal Replacement TherapyContinuous Renal Replacement Therapy

Volume Control

Diffusive Clearance

Convective Clearance

Volume Replacement

SCUF Yes - + No

CVVH Yes - +++ Yes

CVVHD Yes +++ + No

CVVHDF Yes ++ ++ Yes

IHD CRRT

Study N Mode of RRT

ICU hospital mortality

P-value

Hospital mortality

P-value

Comments

RCTMehta, 200132

166 CRRT/IHD

59.5% vs 41.5%

<0.02

65.5% vs 47.6%

< 0.02

Unexplained randomization problems

Augustine 200433

80 CVVHD/IHD

NA NA 67.5% vs 70%

NS Underpowered Inadequate delivered dose of dialysis

Uelinger 200534

125 CVVHDF/IHD

34% vs 38%

0.71 47% vs 51%

0.72

Enrollment problems Underpowered

Vinsonneau 200635

360 CVVHDF/IHD

NA NA NA NA 60 day mortality 32.6% vs 31.5% ,p =0.98

Changes in dialysis dose Underpowered

Lins 200936 316 CRRT/IHD

NA NA 58.1% vs 62.5%

NS

Meta-analysis (Relative risk)Tonelli ,200237

>600 CRRT/IHD

NA NA 0.96 NS Used different types of mortality

Kellum , 200238

1,400 CRRT/IHD

NA NA 0.93 NS After adjustment for study quality and severity of illness, mortality was lower in CRRT patients

Rabindranath, 200739

1,550 CRRT/IHD

1.06 NS 1.01 NS Cochrane meta-analysis

Pannu ,200840

6,058 CRRT/IHD

NA NA 1.1 NS Systematic review

Mortality Mortality

Study N Mode of RRT Definition of renal outcome

Outcome P-value Comments

CohortJacka , 200541 93 IHD/CRRT Dialysis

dependence at discharge

64.3% vs 12.5%

0.0003 Higher severity score in CRRT group

,200742 2,202 IHD/CRRT Requirement of chronic dialysis after 90 days

16.5% vs 8.3%

NA Higher long-term mortality in IHD vs CRRT ; after 10 yrs total risk of ESRD almost the same in both groups

Uchino,200743 1,218 IHD/CRRT Dialysis dependence at hospital discharge

33.8% vs 14.5%

<0.0001 Results remained significant in patients without prior CKD

RCTMehta ,200132 166 IHD/CRRT 1) Dialysis

dependence at hospital discharge2)CKD at hospital discharge and dealth

1) 7% vs 14%2) 17% vs 4%

1) NS2) 0.01

The percentage of CKD in baseline (≥2mg/dL) was higher in patients with IHD (NS)

Augustine,200433 80 IHD/CRRT Discontinuation of dialysis at discharge

4 pts vs 5 pts

NS Small number of patients

Uehlinger,200534 125 IHD/CVVHDF 1) Rate of dialysis dependence2) Absence of renal recovery

1) 1pt vs 1pt2) 58% vs 50%

1) NA2) 0.61

Similar proportions of patients with CKD at baseline

Vinsonneau,200635 360 IHD/CVVHDF 1) Rate of renal recovery at ICU discharge2) Rate of renal recovery at hospital discharge

1)90% vs 93%2) 100 vs all but 1patient

1) 0.52) NA

Not possible to determine difference in proportion of patients with CKD in the 2 groups

Meta-analysisRabindranath, 200739

1,550 IHD/CRRT number of surviving patients not requiring RRT

RR=0.99 NS Cochrane meta-analysis

Pannu ,200840 6,058 IHD/CRRT chronic dialysis RR=0.91 NS Systematic review

Renal recovery Renal recovery

Indication for CRRT

• Cardiovascular failure

• Hypercatabolism

• Cerebral edema

• Liver failure

• Sepsis

• Adult respiratory distress syndrome

• Cardiopulmonary bypass

• Crush syndrome



Modality of RRT◦Intermittent VS Continuous

Dose of RRT◦Daily vs AD

Dialysis Dose Dialysis Dose MeasurementsMeasurements

The treatment dose of RRT can be defined

by various aspects

◦Efficiency

◦Intensity

◦Frequency

◦Clinical efficacy

Ricci Z & Ronco C: Crit Care Clin 2005.

Efficiency of RRTEfficiency of RRT (Clearance, K) (Clearance, K)

Cle

aran

ce

(ml/m

in)

Pisitkun et al. Contr Nephrol 2004.

Intensity of RRT (Kt)D

aily

cle

ara

nc

e (

ml/d

ay

)

24h 8h 3h


Weekly Clearance of RRT

We

ekly

Cle

ara

nc

e

(ml/w

ee

k)

24h 8h 8h 3h 3h

Continuous Alt.days x7 days x3 days x7 days


“Effects of different doses in CVVH on outcomes of ARF”

Effect of Delivered RRT Dose : CRRT

1009080706050403020100

20 ml/kg/hr 35 ml/kg/hr 45 ml/kg/hr

Overall

Ronco C. , et al. The LANCET 2000

RCT, n=425


1009080706050403020100

20 ml/kg/hr 35 ml/kg/hr 45 ml/kg/hr

Overall Septic patients

“Effects of different doses in CVVH on outcomes of ARF”

Ronco C. , et al. The LANCET 2000RCT, n=425

Saudan P, et al. Kidney Int 2006; 70:1312-7

RCT, n=206

“Effects of different doses in CRRT on outcomes of ARF”

UF/Dialysis 24/18 ml/kg/hr

UF/Dialysis 25/0 ml/kg/hr



RCT, n=1124


RCT, n=1508 NEJM 2009

Effect of Dialysis Dose on Survival in Critically Ill Patients Requiring RRT

100-

90-

80-

70-

60-

50-

40-

30-

20-

10-

0-Severity of Disease

Su

rviv

al %

High RRT Dose

Low RRT Dose

Paganini et al: Blood Purif 2001.

Anticoagulation

Drugs Advantages Disadvantages

Heparin Good anticoagulation Thrombocytopenia , Bleeding

Regional heparin Reduced bleeding Complex management

LMWH Less thrombocytopenia

Bleeding

Citrate Lower risk for bleeding Metabolic alkalosis, Hypocalcemia, Special dialysate

Prostacycline Reduced bleeding risk HypotensionPoor efficacy

Saline flushes No bleeding risk Poor efficacy

aPTT (seconds)

Bolus dose Rate change Repeat aPTT

< 40 1,000 U +200 U/hr In 6 hrs40.1-45.0 Nothing +100 U/hr In 4 hrs45.1-55.0 Nothing No change In 6 hrs55.1-65.0 Nothing Stop 1/2 hr and

-100 U/hr

In 4 hrs

>65.0 Nothing Stop 1 hr and

-200 U/hr

In 4 hrs

Dose heparin for CRRTDose heparin for CRRT

: Heparin solution is made by mixing 1 ml of 10,000 U/ml of heparin in 19 ml of normal saline for a heparin concentration of 500U/ml. : Initial bolus is 25 U/kg followed by an infusion of 5U/kg/hr. : The goal of treatment is to maintain systemic prefilter aPTT (45 -55 seconds, 1.5 times control)

Derangement Cause and signs AdjustmentMetabolic acidosis

Insufficient removal of metabolic acidsAnion gap increases Loss of buffer substrate is higher than delivery

Citrate metabolism decreases ( decreases, total Ca/iCa increase [more than 2.1-2.5], and anion gap Increases)

Increase CRRT dose (filtrate or dialysate flow) to 35 ml/kg per hr

Increase bicarbonate replacement or Increase bicarbonate dialysate flow or give additional bicarbonate or increase citrate flow (cave accumulation)

Decrease citrate delivery or stop Increase dialysate or filtrate flow, Increase bicarbonate replacement or increase bicarbonate dialysate flow

Metabolic alkalosis

Delivery of buffer substrate is higher than loss

Decrease loss of buffer due to a decline in filtrate flow

Decrease bicarbonate replacement or decrease bicarbonate dialysate flow or stop additional bicarbonate iv or decrease citrate flow (cave accumulation)

Change filterIncrease filtrate flow

Hypocalcemia Loss of calcium is higher than delivery ( decreases and total Ca/iCa is normal)

Citrate metabolism decrease ( metabolism acidosis , total ca/iCa increase, and anion gap increases)

Increase iv calcium dose

Increase iv calcium dosedecrease or stop citrate deliveryincrease dialysate or filtrate flowincrease bicarbonate replacement or increase bicarbonate dialysate flow

Hypercalcemia Delivery of calcium is higher than loss Decrease iv calcium doseHypernatremia Delivery of sodium is higher than loss

Decreased loss of sodium due to a decline in filtrate flow

Recalculate default settingsProtocol violation-Decrease sodium replacement-Decrease dialysate sodium content-Decrease trisodium citrate flowChange filter

Hyponatremia Loss of sodium is higher than delivery Recalculate default settingsProtocol violation-Increase sodium replacement-Increase dialysate sodium content-Increase trisodium citrate flow

Common complications for citrate

EXAMPLE

Vascular access-Bleeding-Thrombosis -Hematoma-Aneurysm formation-Hemothorax-Pneumothorax-Pericardial tamponade-Arrthymias-Air embolism-Infection

Extracorporeal circuit-Air embolism-Reduced filter life-Reduced dialysis dose-Hypothermia-Bioincompatibility-Immunologic activation-Anaphylaxis

Hematologic complicationsNeed for anticoagulantion-Hypocalcemia-Metabolic alkalosis-Hypernatremia-Citrate intoxication-BleedingThrombocytopeniaBleedingHemolysisHeparin-induced thrombocytopenia

Electrolyte disturbances-Hypophosphatemia-Hypomagnesemia-Hypocalcemia-Hypokalemia-Hyponatremia-Hypernatremia

Hemodynamic instability

Volume management errors

Nutritional losses-Amino acids & proteins-Poor glycemic control-Vitamin deficiencies-Trace minerals

Acid-base disturbances-Metabolic acidosis-Metabolic alkalosis-Citrate-induced alkalosis & acidosis

Altered drug removal

Delayed renal recovery

Common complications in CRRT

Thank you

Documents

Acute Hemodialysis & CRRT in AKI