Extracorporeal support in critically ill Extracorporeal support in - - PowerPoint PPT Presentation

Extracorporeal support in critically ill Extracorporeal support in critically ill patients : patients : When, How and How Much? When, How and How Much?

Claudio Ronco, MD Claudio Ronco, MD

Department of Nephrology, Department of Nephrology,

• St. Bortolo Hospital,
• St. Bortolo Hospital,

International Renal Research Institute International Renal Research Institute Vicenza Vicenza -

• Italy

Italy

1.

• 1. Indications

Indications

2.

• 2. Timing of initiation (+/

Timing of initiation (+/-

• discontinuation)

discontinuation)

3.

• 3. Modality

Modality

4.

• 4. Dose/prescription

Dose/prescription

• Non

Non-

• obstructive oliguria (
• bstructive oliguria (>

>200mL/12 hr) or anuria 200mL/12 hr) or anuria

• Azotemia (urea

Azotemia (urea>30 mmol/L) or uremic organ involvement >30 mmol/L) or uremic organ involvement

• Hyperkalemia (K+ >6.5 mmol/L) or rapidly rising

Hyperkalemia (K+ >6.5 mmol/L) or rapidly rising

• Severe acidemia (pH <7.1) from metabolic acidosis

Severe acidemia (pH <7.1) from metabolic acidosis

• Progressive and/or uncontrolled dysnatremia

Progressive and/or uncontrolled dysnatremia

• Uncontrolled hyperthermia and/or hypothermia (>39.5 C)

Uncontrolled hyperthermia and/or hypothermia (>39.5 C)

• Clinically significant, diuretic

Clinically significant, diuretic-

• unresponsive organ edema

unresponsive organ edema

• Drug overdose with dialyzable toxin

Drug overdose with dialyzable toxin

• Coagulopathy requiring large amount of blood products

Coagulopathy requiring large amount of blood products

Any Critical Care or Nephrology Textbook

Renal Replacement Therapy Renal Support Therapy

Life Threatening Indications Absolute Nutrition support Volume removal in refractory CHF Immuno-modulation in sepsis Cancer chemotherapy Attenuate ARDS-induced respiratory acidosis Volume homeostasis in multi-organ dysfunction/failure Solute control Fluid balance Acid-base regulation

Mehta CRRT 2008 Conference

Apache Apache -

• SOFA

SOFA M O S T Score M O S T Score

RRT RRT

1 1 2 2 3 3 4 4 5 5

RRT RRT SCUF SCUF RRT RRT SCUF SCUF ECLS ECLS RRT RRT SCUF SCUF ECLS ECLS LiverS LiverS RRT RRT SCUF SCUF ECLS ECLS LiverS LiverS HVHF HVHF-

• CPFA

CPFA

% % Mortality Mortality

100 100 80 80 60 60 40 40 20 20

Kidney Kidney K + 1 K + 1 K + 2 K + 2 K + 3 K + 3 K + 3 K + 3 + Sepsis + Sepsis

CRRT ECLS SCUF

LiverSupport - HVHF CPFA - CAST

• Onset of symptoms?

Onset of symptoms?

• Biochemical/biomarker thresholds?

Biochemical/biomarker thresholds?

• Relative to onset of AKI?

Relative to onset of AKI?

• Relative to ICU admission?

Relative to ICU admission?

• RIFLE Class?

RIFLE Class?

Numerous factors/complex process Numerous factors/complex process No broad consensus to guide No broad consensus to guide

• Considerable variation in RRT practice

Considerable variation in RRT practice

• Surveys of Practice (Europe, US)

Surveys of Practice (Europe, US)

• Limited quality data on

Limited quality data on when when to initiate to initiate

Mehta et al Am J Nephrol 1999; Wright et al Anaesthesia 2003; Ronco et al NDT 2001; Ricci et al NDT 2006; Hyman et al Am J Nephrol 2002; Adhikari, personal communication

• Biologic rationale

Biologic rationale

• Consistency of findings across studies

Consistency of findings across studies

• Early RRT (however defined) contributes to:

Early RRT (however defined) contributes to:

• Improved survival

Improved survival

• Improved renal recovery (to dialysis independence)

Improved renal recovery (to dialysis independence)

• Shorter duration of RRT support

Shorter duration of RRT support

• Reduced lengths of stay in ICU

Reduced lengths of stay in ICU

• Pre

Pre-

• morbid kidney function (i.e. Kidney reserve)

morbid kidney function (i.e. Kidney reserve)

• Current kidney function

Current kidney function

• Expected demand on kidney capacity

Expected demand on kidney capacity

• Goals for clinical management

Goals for clinical management

• Prevention

Prevention of organ dysfunction

• f organ dysfunction
• Uremic toxicity

Uremic toxicity

• Other organ toxicity (i.e. ARDS)

Other organ toxicity (i.e. ARDS)

• Modulate organ

Modulate organ cross cross-

• talk

talk

• i.e. Lung

i.e. Lung-

• Kidney, Heart

Kidney, Heart-

• kidney

kidney

• Logistics/organization

Logistics/organization

• Country

Country

• Type of institution

Type of institution

• Type of ICU

Type of ICU

• Service providing RRT

Service providing RRT

• Individual practice/local culture

Individual practice/local culture

• Resources/costs

Resources/costs

• Theoretical Advantages:

Theoretical Advantages:

• Uremic/metabolic control

Uremic/metabolic control

• Volume control

Volume control

• Acid

Acid-

• base homeostasis

base homeostasis

• Non

Non-

• renal organ function

renal organ function

• Mitigate inflammation/oxidative stress

Mitigate inflammation/oxidative stress

• Improved clinical outcomes (i.e. survival)

Improved clinical outcomes (i.e. survival)

10 15 20 25 30 35 15 30 45 40 20 25 Days

Urea (mmol/L)

40 Early start Late start

Theoretical Better Uremic Control

• Theoretical drawbacks:

Theoretical drawbacks:

• Need for catheter insertion

Need for catheter insertion

• Potential for catheter

Potential for catheter-

• related infection

related infection

• Exposure to extracorporeal circuit

Exposure to extracorporeal circuit

• Potential unnecessary exposure to RRT

Potential unnecessary exposure to RRT

Study Year Patients Serum Urea (mmol/L) Mortality (%) Early Late Early Late Parsons 1964 33 48 71 25 88 Fischer 1966 162 54 82 51 77 Kleinknecht 1972 320 33 59 29 42 Conger 1975 18 18 43 20 64 Lange 1987 36 <29 >29 43 67 Gettings 1999 100 15 34 61 80 Tsai 2005 98 <80 >80 63 97

5 10 15 20 25 40 20 10 30 Days of CRRT Urea (mmol/L)

Early ~ Mortality 61% Late ~ Mortality 80%

Gettings et al ICM 1999

Critically Ill Trauma: Biochemistry

• 2 small single centre

2 small single centre retrospective studies retrospective studies

• Early: for oliguria

Early: for oliguria (<100ml/8hrs) (<100ml/8hrs)

• Late: conventional

Late: conventional indications indications

• RRT started earlier after

RRT started earlier after surgery in surgery in early early

• Shorter stay in ICU

Shorter stay in ICU

• Survival benefit

Survival benefit

Demirkilic et al J Card Surg 2004; Elahi et al Eur J Cardiothora Demirkilic et al J Card Surg 2004; Elahi et al Eur J Cardiothorac Surg 2004 c Surg 2004

Liu et al CJASN 2006

n-=243

Urea <27 mmol/L Urea 27 mmol/L

p

Urea (mmol/L) 17 41

<0.001

Creatinine (umol/L) 301 415

<0.001

• No. Organ Failures

4 3

0.008

Sepsis (%) 37 46

0.14

Initial RRT (CRRT) (%) 69 43

0.001

Mortality (%) Day 14 Day 28 20 35 25 41

0.09

Adjusted RR 1.85 (95% CI 1.16-2.96)

Bagshaw et al J Crit Care 2008

Hospital Mortality Stratified by Timing of implementation of RRT Hospital Mortality Stratified by Timing of implementation of RRT

• Late

Late by Urea: by Urea:

• Longer duration RRT

Longer duration RRT

• Higher rate of non

Higher rate of non-

• recovery

recovery

• Longer stay in hospital

Longer stay in hospital

• Late

Late by Creatinine by Creatinine

• Longer duration RRT

Longer duration RRT

• Higher rate of non

Higher rate of non-

• recovery

recovery

Seabra et al AJKD 2008

RCT: RR 0.64 (95% CI, 0.40-1.05) Cohort: RR 0.72 (95% CI, 0.64-0.82)

The process of decision making is linked to

indications leading to therapy initiation

Classic

Blood Purification

Alternative

• Fluid overload

Ultrafiltration

• Sepsis

HVHF - CPFA

What Modality of therapy?

Study Year N Population

Mortality (%) Fluid Overload (%FO) Survivors Non-Survivors

Goldstein 2001 21 Pediatric CVVH 57 16.4% 34% Foland 2004 113 Pediatric CVVH 39 7.8% 15.1% Gillespie 2004 77 Pediatric CVVH 50 %FO >10 (median) HR 3.02, 95% CI 1.5-6.1, p=0.002 Goldstein 2005 116 Pediatric CVVH 48 14.2 25.4 Payen 2008 1,120 Adult AKI 36 (+) Fluid Balance (per 1L/24hr) HR 1.21, 95% CI 1.1-1.3, p<0.001

Gillespie et al Pediatric Nephrol 2004

NEFROINT PREVIEW

IRA SECTION

• RIFLE CRITERIA
• AKIN CRITERIA

IRA SECTION

• RIFLE CRITERIA
• AKIN CRITERIA

RIFLE ALERT

RIFLE Alert

You reached RIFLE class You reached RIFLE class

• RISK

RISK

• Baseline Creatinine = 0.9

Actual creatinine = 1.55 x Baseline

Confirm

Algorithm for Initiation of Renal Replacement Therapy in Critically Ill Patients

(Sean Bagshaw, Dinna Cruz, Claudio Ronco, Under Review)

Patient admitted to ICU

Absolute indications?

Initiate renal replacement therapy

YES NO YES Assess: AKI severity & trend Illness severity & trajectory Acute Kidney Injury (AKI) present? Severe AKI ?

RIFLE-F AKIN III

NO Mild/ Moderate AKI?

RIFLE-R or I AKIN I or II

Any of the following? Rapidly worsening AKI Rapidly worsening illness severity Hypercatabolic state Fluid overload/ steady fluid accumulation Reduced renal reserve Low probability of immediate renal recovery YES NO Potential non-renal indications? Refractory septic shock/ sepsis Acute liver failure Severe tumor lysis syndrome Toxins* Refractory fluid overload Electrolyte disturbances Dysthermia NO

Consider initiating renal replacement therapy

YES YES NO YES

Reassess clinical status

• No consensus on

No consensus on When When to initiate RRT to initiate RRT

• Early initiation probably improves outcomes

Early initiation probably improves outcomes

• This can be suggested by RIFLE Class as a surrogate of

This can be suggested by RIFLE Class as a surrogate of timing timing

• AKI staging can also be useful to indicate modality, dose of

AKI staging can also be useful to indicate modality, dose of therapy and it can be used to implement an objective therapy and it can be used to implement an objective algorithm for RRT initiation algorithm for RRT initiation We need additional clinical studies! We need additional clinical studies!

Current Issues in Renal Replacement Therapy for AKI

• What are the indications?
• When should therapy be initiated? (and when should it be stopped?)
• How should prescription be made?
• Type of technique (Convection vs diffusion)
• Vascular Access and Equipment selection
• Membrane and Anticoagulation
• Frequency of the technique (Intermittent vs continuous)
• Dose of RRT (ml/h/Kg)
• Who is going to manage day by day routine?
• Should we use adjunctive therapies?

Dose of treatment

• The concept of dose has not been clearly defined
• What does it mean ?

During CRRT During IHD During SLED

• Dose of what?

Marker molecules Utrafiltration Biomarkers of blood purification

• Adequacy and Inadequacy of treatment

THE ROLE OF INTENSIVE DIALYSIS IN ACUTE RENAL FAILURE THE ROLE OF INTENSIVE DIALYSIS IN ACUTE RENAL FAILURE Gillum et Al, Clin Nephrol 1986; 25:249 Gillum et Al, Clin Nephrol 1986; 25:249-

• 255

255 Prospective non randomized study on 34 patients allocated either Prospective non randomized study on 34 patients allocated either to an to an intensive HD regime (sufficient to maintain BUN < 60 mg/dl) or t intensive HD regime (sufficient to maintain BUN < 60 mg/dl) or to a

• a

non non-

• intensive HD (BUN>100mg/dl). Mortality 58.8 and 47.1 %

intensive HD (BUN>100mg/dl). Mortality 58.8 and 47.1 %

• respect. Conclusion
• respect. Conclusion
• .

. there is no advantage to intensive dialysis in the management of there is no advantage to intensive dialysis in the management of ARF ARF

• No effective control of prescription and delivery

No random allocation No control of UGR and PCR and hydration status Results only based on blood levels In 1986 intensive meant aggressive, complicated and less tolerated

CRRT: Impact on Outcomes CRRT: Impact on Outcomes

Severity of Disease Severity of Disease Survival % Survival %

High Dose High Dose Low Dose Low Dose

The Cleveland Clinic Observation The Cleveland Clinic Observation

100 100 90 90 80 80 70 70 60 60 50 50 40 40 30 30 20 20 10 10

Survival Time (Days) Survival Time (Days)

CUMULATIVE PROPORTION SURVIVAL CUMULATIVE PROPORTION SURVIVAL

50 50 40 40 30 30 20 20 10 10 1.0 1.0 .9 .9 .8 .8 .7 .7 .6 .6 .5 .5 .4 .4 .3 .3 .2 .2 .1 .1 .0 .0

Group 1 Group 1 Group 3 Group 3 Group 2 Group 2 (p = 0.0007) (p = 0.0007) (p = 0.0013) (p = 0.0013)

Ronco C, Bellomo R, Brendolan A, Dan M, Piccinni P, La Greca G. Ronco C, Bellomo R, Brendolan A, Dan M, Piccinni P, La Greca G. Effect of different Effect of different doses in continuous veno venous hemofiltration on outcomes of ac doses in continuous veno venous hemofiltration on outcomes of acute renal failure. ute renal failure. The Lancet 2000 The Lancet 2000

Survival Rates Stratified by Trial Group and by Presence of Sepsis

Trial Group No Sepsis (%) Sepsis (%) p-value Group1 55/126 (44%) 5/20 (25 %) 0.90 Group 2 76/122 (62 %) 3/17 (18 %) 0.001 Group 3 74/125 (59 %) 7/15 (47 %) 0.256

100 100 90 90 80 80 70 70 60 60 50 50 40 40 30 30 20 20 10 10 Group 1 Group 1 Group 2 Group 2 Group 3 Group 3

Overall Overall Septic patients Septic patients

DAILY HEMODIALYSIS AND THE OUTCOME OF DAILY HEMODIALYSIS AND THE OUTCOME OF ACUTE RENAL FAILURE ACUTE RENAL FAILURE Schiffl H, et Al. NEJM 2002; 346:305 Schiffl H, et Al. NEJM 2002; 346:305-

• 310

310

100 100 90 90 80 80 70 70 60 60 50 50 40 40 30 30 20 20 10 10

• Alt. Day
• Alt. Day

HD HD Daily Daily HD HD

p < 0.0 p < 0.01 1

Mortality % Mortality %

46 46 28 28

• Alt. Day
• Alt. Day

HD HD Daily Daily HD HD

N. N. 72 72 74 74

• Pr. Kt/V
• Pr. Kt/V

1.21 1.21 1.19 1.19

• Del. Kt/V
• Del. Kt/V

0.94 0.94 0.92 0.92 wD Kt/V wD Kt/V 3.0 3.0 5.8* 5.8*

O.R. for death O.R. for death

3.9* 3.9* 1.0 1.0

Survival Comparison: CVVH vs CVVHDF

Saudan et al, Kidney Int 2006 42 mL/kg/hr 25 mL/kg/hr

More RRT is Better

Odds Ratio: 1.95 (95% CI 1.48 - 2.58, p < 0.001)

Ronco 425 CVVH 20/h vs. 35-45 ml/kg/h* Bouman 106 CVVH 20ml/kg/h* vs. 48 ml/kg/h Schiffl 160 Alternate day vs. daily hemodialysis Saudan 206 CVVH 25 ml/kg/h vs. CVVHDF 42 ml/kg/h Total (fixed effects) Total (random effects)

1

10

Odds ratio

Study n treatment groups Favors increased dose

Kellum, Nat Clin Pract Nephrol 2007

Forest plot pooling trials of RRT dose

Standard versus high Standard versus high-

• dose CVVHDF for ICU

dose CVVHDF for ICU-

• related Acute

related Acute Renal Failure Renal Failure

Tolwani A et Al, JASN 2008

200 critically ill patients with ARF randomized to receive (pre-filter replacement) an effluent rate of 20 and 35 ml/Kg/h. Survival (ICU discharge or 30d) was 56% versus 49% (p=n.s.) Among hospital survivors renal reco very was 69% versus 80% (p=n.s.) The study was designed to detect an absolute survival difference of 20%

VA/NIH Acute Renal Failure Trial Network (ATN) Study

1124 patients 27 sites 3 years Intensive Management Strategy (561 patients) Randomization Stable hemodynamics (SOFA 0-2)

• IHD 6x/week @ Kt/V of

~1.2/session

• IHD 3x/week @ Kt/V of

~1.2/session Unstable hemodynamics (SOFA 3-4)

• CVVHDF @

35 mL/kg/hr, or

• SLED/EDD 6x/week
• CVVHDF @

20 mL/kg/hr, or

• SLED/EDD 3x/week

Less Intensive Management Strategy (563 patients)

ATN Study: Primary Outcome

VA/NIH Trial Group, NEJM 2008

ATN Practical Implications (positive) ATN Practical Implications (positive)

• A significant attention will be placed on prescription of RRT

dose and its real delivery

• Independent of dose, unstable and critically ill patients will

definitely be treated in larger proportion with CRRT, given the demonstrated hemodynamic intolerance to IHD

• Physicians will not expect RRT (even at high doses) to be

the panacea for critically ill patients, and they will be forced to try further therapeutic strategies

ATN Practical Implications (negative) ATN Practical Implications (negative)

• Very likely the paper will be misquoted and results will be

generalized to all patients

• Skeptical physicians will use this trial to justify therapeutic

nihilism

• Administrators will use this trial to spare money on fluids and

treatments and to limit application of high efficiency treatments

• Thousands of AKI patients may become at risk for under-

dialysis

RENAL Trial

1500 patients 35 sites 3 years Intensive CRRT (post-dilution CVVHDF at 40 ml/kg/hr

• f effluent)

(750 patients) Randomization Conventional CRRT (post-dilution CVVHDF at 25 ml/kg/hr

• f effluent)

(750 patients)

Mortality Outcomes in RENAL

Low dose High dose p Number of patients 743 722 Total number of study days 4190 4179 Mean Days of Study treatment/patient 5.9 (7.7) 6.3 ( 8.7) 0.35 Daily effluent (mls/hr)/patient 1772 (1257) 2698 (1154) <0.001 Dose delivered mls/kg/hr 22.0 (17.8) 33.4 (12.8) <0.001 % of prescribed 88 84 <0.001 Filters/day/patient 0.84 (0.81) 0.93 (0.86) <0.001 Patients treated with IHD in ICU 52 (7.0%) 55 (7.6%) 0.64

Process of Care in RENAL

Comparison of RENAL with ATN

Variable RENAL VA/NIH

Enrolled 1508 1124 Mean age (yrs) 64.5 59.7 CRRT as initial therapy (%) 100 ~50 Weight (kg) 80.6 84.1 Sepsis (%) 49.5 63 % Pts receiving Tx before random 64.3 ICU Days before random 2.1 6.7 Urea at baseline (mmol/L) 23.3 24.2 Total SOFA score (resp, CVS, liver, coag) 7.55 7.40 Ventilation 73.9% 80.6%

Comparison of RENAL with ATN

Variable RENAL VA/NIH Mortality day 90 44.7% Mortality day 60 52.5% RRT days (at 28 days) 7.4 13.1 Hospital LOS (days) 25.2 48 Dialysis dependence @day 28 13.3% 45.2% Dialysis dependence @day 60 24.6% Dialysis dependence @day 90 5.6%

CRRT-Associated Mortality in Major RCTs

Clinical Trial Comparison APACHE II Endpoint Mortality

Ronco et al (2000) CRRT Dose 22 15-day

2

59%

3

Mehta et al (2001) IHD vs CRRT 25.5 Hospital 66% Augustine et al (2004) IHD vs CRRT

• Hospital

68% Saudan et al (2006) CRRT Dose 25 90-day 66%

3

Vinsonneau et al (2006) IHD vs CRRT 25 60-day 68% Lins et al (2008) IHD vs CRRT 27 Hospital 58% Tolwani et al (2008) CRRT Dose 26 Hospital 60%

3

ATN Trial (2008) Dialysis Dose 26.3 60-day 52.5%

4

RENAL Trial (2009) CRRT Dose ~26

1

90-day 45%

1: APACHE III score 102-103 2: After CRRT cessation 3: Mortality in low-dose group 4: Overall (CRRT + IHD) mortality

RENAL Trial: Major Points

• Initial response to RENAL will be focused largely on the

negative primary outcome result

• HOWEVER, survival and renal recovery outcomes were

substantially better in this trial compared to previous AKI studies involving similar patient populations

• The excellent outcomes in RENAL were likely associated

with:

• The nearly exclusive use of CRRT while patients were in the ICU
• Early initiation of therapy

Delivery of Prescribed CRRT Dose

• Ronco (heparin)

% delivery ≈ 95% (compensatory UF increases) Filter changed every 24 hrs

• Saudan (heparin)

Delivered dose during first 24 hrs = 83% Filter changed every 24 hrs for first two days

• Tolwani (citrate RCA in 91% of patients)

Patients achieving >80% of prescribed dose = 79%

• ATN (no anticoagulation in 60% of patients)

Average daily CRRT duration = 21 hrs (88%)

• RENAL (heparin): 85% delivery of prescribed dose

CRRT Prescription vs Delivery

Venkataraman et al, J Crit Care, 2002

Prescribed Dose (ml/kg/hr) Delivered Dose (ml/kg/hr) Time/Day (hours)

24.5±6.7 16.6±5.4 16.1±3.5

68% of prescribed dose 67% of total hours in day

A prospective multicentre observational study in 30 intensive care units (ICUs) in eight

countries from June 2005 to December 2007.

The observational DOse REsponse Multicentre International collaborative initiative (DO-

RE-MI) analyzes how different modalities of RRT are truly chosen and executed in the field:

Main Results:

CVVHDF remains the most commonly used technique (49%) Clotting and clinical problems represent the most common causes of treatment interruption During RRT, a large variability of administered doses was observed among patients and also within the same patient in different days. In a large proportion of cases, while prescription is around 35ml/kg/h, effective delivery of dose is approximately 20% less

10 20 30 40 50 60

<5 5-10 10-15 15-20 20-25 25-30 30-35 35-40 40-45 45-50 50-55 55-60 60-65 65-70 70-75 >=75

Dose of CRRT (mL/Kg/hr) Patients (%) Delivered dose Prescribed dose

DoReMi Database (N=865)

Median prescribed = 34 mL/kg/h Median delivered = 27 mL/kg/h

Ronco et al, 2009

Dose of CRRT (mL/kg/h) Patients (%)

DELIVERED AND PRESCRIBED CLEARANCE DELIVERED AND PRESCRIBED CLEARANCE Factors affecting discrepancy Factors affecting discrepancy

• Blood flow rate

Blood flow rate lower than that displayed by the dialysis machine lower than that displayed by the dialysis machine Inadequate vascular access Inadequate vascular access

• Dialysate/ Filtrate flow

Dialysate/ Filtrate flow lower than that displayed by the dialysis lower than that displayed by the dialysis

• machine. Excessive filtration fraction
• machine. Excessive filtration fraction
• Inadequate performance of the hemofilter

Inadequate performance of the hemofilter-

• hemodialyzer

hemodialyzer

• Incorrect priming procedures

Incorrect priming procedures

• Loss of surface area (clotting, air)

Loss of surface area (clotting, air)

• Loss of permeability (clogging of the membrane)

Loss of permeability (clogging of the membrane)

• High blood viscosity and hematocrit

High blood viscosity and hematocrit

• Excessive filtration fraction

Excessive filtration fraction

Assessment of Inadequate RRT Dose Delivery

Modified from Santoro et Al, Kidney Int 2000

• The National Cooperative Dialysis Study (NCDS) should give

pause to those who favor a systematic reduction in CRRT dose

• NCDS performed in American chronic HD patients during the late 1970

s

• Flawed analysis of data resulted in misinterpretation of the results and

downward trend in US dose prescription for 15 years

• Basic problem: under-prescription of dose combined with no assessment
• f dose delivery
• The results were disastrous, with residual effects still influencing clinical

practice in the US

• The NCDS debacle argues strongly against a

rush to judgment with regard to the dosing trial results

Interpretation of Dose Trial Results: A Cautionary Note for Physicians

Effect of Dialysis Dose on Patient Outcome

Ronco, Int J Artif Organs 2008

• Recent multicenter RCTs have failed to confirm earlier trials suggesting a

benefit of higher CRRT dose in critically ill patients

• Nevertheless, these RCTs have confirmed that CRRT is the standard of care for

AKI in the ICU

• Several differences (total effluent dose, convective contribution, timing of

treatment initiation) exist among the various CRRT dose/outcome trials, making it difficult to establish a standard dose

• For the time being, 30 to 35 mL/kg/hr is a reasonable target for prescription to

make sure no less than 25 mL/kg/hr is effectively delivered

• The excellent patient outcomes in RENAL mandate a careful analysis of

RRT application and other processes of care in the study

• Based on standard practice in chronic dialysis, routine assessment of

delivered CRRT dose should be an integral aspect of AKI patient management in the future

Summary

In Conclusion

• More is better until a certain point
• Increasing the dose of renal replacement cannot

provide immortality

• High dose RRT is not a remedy for bad clinical

practice

Start Early!

Shoot slow?

20 40 60 80 100 120 140 160 Time to RRT start ATN RENAL

Die quick!

40 42 44 46 48 50 52 54 Mortality RENAL ATN2

% mortality hours to start

Make it continuous!

Use of continuous or intermittent therapy 2000 4000 6000 8000 10000 ATN RENAL IHD sessions CRRT sessions Dialysis dependence for survivors at 28 days 10 20 30 40 50 ATN RENAL

24 times more IHD !! >300% increase in dialysis dependence!!

Do not stop until the fight is over!

In Conclusion

Indications for extracorporeal support may be different from the classic indications for RRT There is a certain trend towards an early start although solid evidence is still missing Higher doses provide benefit until a certain point (breaking points may be different in different subjects) Continuous modalities seem to offer benefits in critically ill patients both in terms of survival and in terms of renal recovery Patients should be treated adequately, early enough to avoid development of complications, with techniques providing good clinical tolerance, avoiding premature stopping of extracorporeal support.

Like I said shoot quick, shoot straight, shoot continuously and stop shooting late! And do not stop until the fight is

• ver