© 2008 Universitair Ziekenhuis Gent
RENAL REPLACEMENT THERAPY IN PATIENTS WITH SEPSIS AND ACUTE KIDNEY INJURY
Prof. Dr. Raymond Vanholder
University Hospital Ghent
Belgium
22© 2008 Universitair Ziekenhuis Gent
TIMING START RRT
TYPE OF STUDY N PARAMETER EFFECT ES
Gettings et al, 1999 Retrospective 243 BUN 76 +
Guerin et al, 2000 Prospective
Observational post hoc
510 Time after admission 0
Bouman et al, 2002 RCT*, 4 arms 106 Fixed time point (12 hrs) vs. classical parameters
0
Elahi et al, 2004 Retrospective 64 UO vs. other** +
Demirkiliç et al, 2004 Retrospective 61 UO vs. other** +
Liu et al, 2006 Observational 243 BUN 76 0 unadj
+ adj
Piccinni et al, 2006 Retrospective 80 Septic shock +
ES: Early Start; BUN: Blood Urea Nitrogen; UO: urine output; + favors ES; 0 neutral*: early vs. late low vol (<36 L/d) HF – early high vol(>72L/d) no late comparator; **: UO <100 mL/d to start vs. other parameters (K, crea) irrespective of UOGettings et al, Intens Care Med, 1999; Guerin et al, Am J Resp CCM, 2000; Bouman et al, CCM, 2002; Elahi et al, Eur J Cardio-thor Surg, 2004; Demirkiliç et al, J Card Surg, 2004; Liu et al, Clin JASN 2006 ; Piccinni et al, Intens Care Med 2006
33© 2008 Universitair Ziekenhuis Gent
C. Bouman, Crit Care Med, 30: 2205-2211; 2002
Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: A prospective, randomized trial
Bouman, Catherine S. C. MD; Oudemans-van Straaten, Heleen M. MD, PhD; Tijssen, Jan G. P. MD, PhD; Zandstra, Durk F. MD, PhD; Kesecioglu, Jozef MD, PhD
From the Departments of Intensive Care (CSCB) and Clinical Epidemiology (JGPT), Academic Medical Center, Amsterdam, The Netherlands; the Department of Anesthesiology, Cardiothoracic and Neurosurgical Intensive Care Unit, University Medical Center, Utrecht, The Netherlands (JK); and the Department of Intensive Care, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands (HMOvS, DFZ).Address requests for reprints to: Catherine S. C. Bouman, MD, Academic Medical Center, Department of Intensive Care, Meibergdreef 9, Amsterdam NL-1105 AZ, The Netherlands. E-mail: [email protected]
44© 2008 Universitair Ziekenhuis Gent
V. Seabra et al, AJKD, 52: 272-284; 2008
55© 2008 Universitair Ziekenhuis Gent
IMPACT ON MORTALITY
V. Seabra et al, AJKD, 52: 272-284; 2008
66© 2008 Universitair Ziekenhuis Gent
V. Seabra et al, AJKD, 52: 272-284; 2008
IMPACT ON RECOVERY RENAL FUNCTION
77© 2008 Universitair Ziekenhuis Gent
V. Seabra et al, AJKD, 52: 272-284; 2008
ABSTRACTBackground Some studies have suggested that early institution of renal replacement therapy (RRT) might be associated with improved outcomes in patients with acute renal failure (ARF).Study Design A systematic review and meta-analysis of randomized controlled trials and cohort comparative studies to assess the effect of early RRT on mortality in patients with ARF.Setting & Population Hospitalized adult patients with ARF.Selection Criteria for Studies We searched several databases for studies that compared the effect of “early” and “late” RRT initiation on mortality in patients with ARF. We included studies of various designs.Intervention Early RRT as defined in the individual studies.Outcomes The primary outcome measure was the effect of early RRT on mortality stratified by study design. The pooled risk ratio (RR) for mortality was compiled using a random-effects model. Heterogeneity was evaluated by means of subgroup analysis and meta-regression.Results 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% confidence interval, 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% confidence interval, 0.64 to 0.82; P < 0.001). The overall test for heterogeneity among cohort studies was significant (P = 0.005). Meta-regression yielded no significant associations; however, early dialysis therapy was associated more strongly with lower mortality in smaller studies (n < 100) by means of subgroup analysis.Limitations Paucity of randomized controlled trials, use of variable definitions of early RRT, and publication bias preclude definitive conclusions.Conclusion This hypothesis-generating meta-analysis suggests that early initiation of RRT in patients with ARF might be associated with improved survival, calling for an adequately powered randomized controlled trial to address this question.
88© 2008 Universitair Ziekenhuis Gent
Vinsonneau et al, Lancet, 368, 379-385, 2006
99© 2008 Universitair Ziekenhuis Gent
MOST RECENT STUDIES
IHD CVVHD P
Survival
Day 28 41.8% 38.9% 0.65
Day 60 (1ary EP) 32.5% 32.6% 0.98
Day 90 27.2% 28.5% 0.95
RRT duration (d) 11 11 0.84
Length ICU stay (d) 20 19 0.73
Length hosp stay (d) 30 32 0.66
Vinsonneau et al, Lancet, 368, 379-385, 2006
1010© 2008 Universitair Ziekenhuis Gent
R. L. Lins et al, NDT, advance access published October 14, 2008
1111© 2008 Universitair Ziekenhuis Gent
R. L. Lins et al, NDT, advance access published October 14, 2008
THE SHARF STUDY
1212© 2008 Universitair Ziekenhuis Gent Bagshaw et al, Crit Care Med, 36: 610-617; 2008
Continuous versus intermittent renal replacement therapy for critically ill patients with acute kidney injury: A meta-analysis
Bagshaw, Sean M. MD, MSc; Berthiaume, Luc R. MD; Delaney, Anthony MBBS, MSc; Bellomo, Rinaldo MD
From the Division of Critical Care Medicine, University of Alberta Hospital, University of Alberta, Edmonton, Alberta, Canada (SMB); Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia (SMB, RB); Departments of Critical Care Medicine and Community Health Sciences, Calgary Health Region and University of Calgary, Calgary, Alberta, Canada (LRB); and Intensive Care Unit, Royal North Shore Hospital, and Northern Clinical School, University of Sydney, Sydney, NSW, Australia (AD).
1313© 2008 Universitair Ziekenhuis Gent
W. Van Biesen et al, Crit Care Med, 36: 649-650; 2008
A tantalizing question: Ferrari or Rolls Royce? A meta-analysis on the ideal renal replacement modality for acute kidney injury at the intensive care unit
Van Biesen, Wim MD, PhD; Lameire, Norbert MD, PhD; Vanholder, Raymond MD, PhD
Renal Division; Department of Internal Medicine; University Hospital Ghent; Ghent, Belgium
1414© 2008 Universitair Ziekenhuis Gent
FACTORS AFFECTING CHOICE
Labor intensity
Cost
Availability of machines
Availability of SLEDD as alternative
1515© 2008 Universitair Ziekenhuis Gent
Extended Daily Dialysis: what?
Offering the choice between the advantages of a IHDF-monitor (high efficiency, low cost, high precision of UF control) in combination with the advantages of CRRT (extended treatment, smooth metabolic control) in a modular fashion, using one single type of dialysis machine
Dialysis monitor with:Water treatment moduleReverse osmosis unitHemofiltration capacityDialysate flow adjustment
1616© 2008 Universitair Ziekenhuis Gent
TOTAL NUMBER, DURATION, AND MEDIAN NUMBER OF TREATMENTS PERFORMED
EDD CVVH
Total no of treatment days
367 113
Median duration daily treatment(h)
7.5 (6-8) 19.5 (13.4-24)
Median no of treatments/patient
9 (3-39) 6 (3-15)
Kumar et al. Am J Kidney Dis 36:294-300,2000
1717© 2008 Universitair Ziekenhuis Gent
COMPARISON OF MAP DURING EDD VS. CVVH.
0102030405060708090
100
preMAP midMAP endMAP
CVVH
EDD
Kumar et al, AJKD, 36, 294-300, 2000
P=NS P=NS P=NS
1818© 2008 Universitair Ziekenhuis Gent
PERCENTAGE OF TREATMENT DAYS REQUIRING INOTROPIC SUPPORT
0
10
20
30
40
50
60
70
80
90
100
1 Inotrope 2 Inotropes 3+ Inotropes
CVVH
EDD
% o
f tr
ea
tme
nt
da
ys
Kumar et al, AJKD, 36, 294-300, 2000
1919© 2008 Universitair Ziekenhuis Gent
SINGLE PASS BATCH HEMODIALYSIS SYSTEM (GENIUS): PREPARATION OF DIALYSIS WATER AND DIALYSATE
2020© 2008 Universitair Ziekenhuis Gent
CUMULATIVE ULTRAFILTRATION VOLUME AND MEAN ARTERIAL PRESSURE DURING 18H OF EXTENDED HIGH-FLUX HD USING THE GENIUS SYSTEM
Lonnemann et al, NDT, 15, 1189-1193, 2000
2121© 2008 Universitair Ziekenhuis Gent
R. Busund et al, Int Care Med, 28: 1434-1439; 2002
PF: signif younger &less mechanicalventilation
2222© 2008 Universitair Ziekenhuis Gent
J. Tumlin et al, JASN, 19: 1034-1040; 2008
2323© 2008 Universitair Ziekenhuis Gent
Schiffl et al, NEJM, 346: 305-310; 2002
2424© 2008 Universitair Ziekenhuis Gent
P. Honore et al, Crit Care Med, 28: 3581-3587; 2000
Prospective evaluation of short-term, high-volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shock
Honore, Patrick, Jamez, Jean, Wauthier, Michel, Lee, Patrice, Dugernier, Thierry, Pirenne, Bruno, Hanique, Genevieve, Matson, James
From the Departments of Intensive Care Medicine (Drs. Honore, Dugernier, and Pirenne) and Nephrology (Drs. Jamez and Wauthier), St-Pierre Hospital, Ottignies, Belgium; the Department of Clinical Research and Pediatric Critical Care (Drs. Lee and Matson), Dallas Hospital, Dallas, TX; and the Department of Internal Medicine and Biostatistics (Dr. Hanique), Nivelles Hospital, Nivelles, Belgium
2525© 2008 Universitair Ziekenhuis Gent
C. Ronco et al, The Lancet, 256: 26-30; 2000
2626© 2008 Universitair Ziekenhuis Gent
P. Saudan et al, KI, 70: 1312-1317; 70
2727© 2008 Universitair Ziekenhuis Gent
C. Bouman, Crit Care Med, 30: 2205-2211; 2002
Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: A prospective, randomized trial
Bouman, Catherine S. C. MD; Oudemans-van Straaten, Heleen M. MD, PhD; Tijssen, Jan G. P. MD, PhD; Zandstra, Durk F. MD, PhD; Kesecioglu, Jozef MD, PhD
From the Departments of Intensive Care (CSCB) and Clinical Epidemiology (JGPT), Academic Medical Center, Amsterdam, The Netherlands; the Department of Anesthesiology, Cardiothoracic and Neurosurgical Intensive Care Unit, University Medical Center, Utrecht, The Netherlands (JK); and the Department of Intensive Care, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands (HMOvS, DFZ).Address requests for reprints to: Catherine S. C. Bouman, MD, Academic Medical Center, Department of Intensive Care, Meibergdreef 9, Amsterdam NL-1105 AZ, The Netherlands. E-mail: [email protected]
2828© 2008 Universitair Ziekenhuis Gent
Palevsky et al, NEJM, 359, 1: 7-20; 2008
Intensive vs less intensive therapy
Intermittent hemodialysis (hemodynamically stable)
Intensive: daily except Sunday
Less intensive: alternate days except Sunday
Sustained low-efficiency dialysis (hemodynamically unstable)
Intensive: daily except Sunday
Less intensive: alternate days except Sunday
Continuous renal replacement therapy (hemodynamically unstable)
Intensive: 35 mL/h/kgBW substitution
Less intensive: 20 mL/h/kgBW substitution
2929© 2008 Universitair Ziekenhuis Gent
Palevsky et al, NEJM, 359, 1: 7-20; 2008
KAPLAN–MEIER PLOT OF CUMULATIVE PROBABILITIES OF DEATH CUMULATIVE PROBABILITY OF DEATH FROM ANY CAUSE IN THE ENTIRE STUDY COHORT
3030© 2008 Universitair Ziekenhuis Gent
COMMENTS
Standard IHD more efficient than in Schiffl et al
Hemodiafiltration
Shifts among therapies possible
Kt/V not a validated parameter of adequacy in AKI
More adequate treatment may also have negative impact
REAL-LIFE STUDIES
3131© 2008 Universitair Ziekenhuis Gent
SINGLE PASS BATCH HEMODIALYSIS SYSTEM (GENIUS): PREPARATION OF DIALYSIS WATER AND DIALYSATE
3232© 2008 Universitair Ziekenhuis Gent
GENIUSR
S. Eloot et al, NDT, 22: 2962-2969; 2007
3333© 2008 Universitair Ziekenhuis Gent Eloot et al, KI, 73: 765-770
RESULTS: TOTAL SOLUTE REMOVAL TSR
3434© 2008 Universitair Ziekenhuis Gent
PERCENTAGE CHANGE VS. 4 HRS
Eloot et al, KI, 73: 765-770
3535© 2008 Universitair Ziekenhuis Gent
COMMENTS
Standard IHD more efficient than in Schiffl et al
Hemodiafiltration
Shifts among therapies possible
Kt/V not a validated parameter of adequacy in AKI
More adequate treatment may also have negative impact
REAL-LIFE STUDIES
3636© 2008 Universitair Ziekenhuis Gent
ANTIBIOTIC CONCENTRATION AND SLEDD
Kielstein et al, NDT, in press
MIC 90
3737© 2008 Universitair Ziekenhuis Gent
PRACTICE PATTERNS IN THE MANAGEMENT OF ACUTE RENAL FAILURE IN THE CRITICALLY ILL PATIENT: AN INTERNATIONAL SURVEY
RICCI et al. Nephrol Dial Transpl, 21: 690–696, 2006
3838© 2008 Universitair Ziekenhuis Gent
COMMENTS
Standard IHD more efficient than in Schiffl et al
Hemodiafiltration
Shifts among therapies possible
Kt/V not a validated parameter of adequacy in AKI
More adequate treatment may also have negative impact
REAL-LIFE STUDIES
3939© 2008 Universitair Ziekenhuis Gent
CONCLUSIONS
At this moment, there are no definite data favoring an earlier start of RRT than the conventional criteria
There is no difference in outcome between intermittent an continuous dialysis strategies
Although under well controlled circumstances, intensified strategies seem to improve outcome, under real life circumstances this difference seems to disappear
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