Akutes Nierenversagen : Prävention und Recovery

Akutes Nierenversagen :
Prävention und Recovery
FlüssigkeitsManagement
bei ANV
Wilfred Druml
Abteilung für Nephrologie
Medizinische Universitätsklinik III,
AKH-Wien
[email protected]
20. Kongress der DIVI
Hamburg, 03. – 05. Dezember 2014
ANV: Prävention / Recovery
Flüssigkeitsmanagement
I. Quantität
Was ist der optimale Flüssigkeitsstatus zur
Unterstützung der Nierenfunktion?
„milde Hypervolämie“???
II. Qualität
Welche Infusionslösungen sollten zur Erhaltung/
Wiederherstellung der Nierenfunktion eingesetzt
werden bzw. welche sind eher „nephrotoxisch“?
Katecholamine ohne adäquate
Volumengabe
75-jährige Patienten mit Hypovolämie/ hypovol. Schock nach
viraler Gastroenteritis, Noradrenalin-Therapie und inadäquater
Volumengabe
Renale Hypoperfusion und ANV nach
Kreislauftherapie
bei Sepsis ohne
ausreichende
Volumengabe
Vasokonstriktor erst nach Volumenoptimierung !
von Afschin Soleiman, Wien
Early Use of Vasopressors after
Injury: Caution before Constriction
Sperry JL et al.
J Trauma 2008; 64: 9-14
Independent hazard
ratio (HR) for early
vasopressor (EV) use
and aggressive early
cristalloid
resuscitation at 12 and
24 hours post injury.-
Volumen und Niere
Beachte…

.. ein Volumenmangel, eine Hypovolämie erhöht die
Gefahr der Ausbildung einer renalen Dysfunktion…

.. erste Maßnahme in der Prävention des ANV muss
Kreislauftherapie muss die Volumenoptimierung
darstellen, dann erst darf mit der
Vasokonstriktorgabe begonnen werden !
Volumen und Niere
Frage…
…Normovolämie akzeptiert…
aber führt eine Hypervolämie, wie immer
behauptet wird, zu einer Steigerung der
renalen Perfusion und Funktion?
Fluid accumulation, survival and recovery
of kidney function in critically ill patients
with acute kidney injury
Bouchard J et al.
Kidney int 2009;
46:422-27
Cumulative probability
of survival by fluid
overload status.
(a) Survival estimates by
fluid overload status at
dialysis initiation.
(P=0.005).
(b) Survival estimates by
fluid overload status at
AKI diagnosis in nondialyzed patients.
(P=0.04).
Fluid resuscitation in septic shock:
A positive fluid balance and elevated
central venous pressure are associated
with increased mortality
Boyd JH et al.
Crit Care Med 2011; 39: 259-65
A, Survival curves, adjusted for age, APACHE II score, severity of shock
(dose of norepinephrine), for fluid balance quartiles at 12 hrs.
Quartiles 3 and 4 have significant increases in mortality vs. both Q1, Q2.
B, Survival curves, adjusted for age, APACHE II score, dose of
norepinephrine for cumulative fluid balance quartiles at day 4.
Fluid balance and urine volume are
independent predictors of
mortality in acute kidney injury
Teixeira C. et al.
Crit Care 2013: 17: R 19
Cumulative fluid balance in survivors and non-survivors in the
first seven days of ICU stay
A rational approach to
perioperative fluid management
Chappell D. et al.
Anesthesiology 2008; 109: 723-40
Electron microscopic
view of the endothelial
glycocalyx.
Eine inadäquate
Volumentherapie
(Qualität/ Quantität)
(zer-)stört die
endotheliale
Barriere!!
Infusionstherapie
Schädigung der endothelialen Barriere
Eine quantitativ oder qualitativ inadäquate
Infusionstherapie schädigt die endotheliale
(Barriere-) Funktion
….wir brauchen Endothelstreichler!
Raised Venous Pressure: A Direct
Cause of Renal Sodium Retention
and Edema
Firth JD et al.
Lancet 1988, i: 1121
Effects of increasing
venous pressure on GFR,
sodium excretion, and
fractional sodium excretion
in kidneys perfused with a
constatn arterial pressure
Increased Central Venous Pressure Is
Associated With Impaired Renal Function
and Mortality in a Broad Spectrum of
Patients With Cardiovascular Disease
Damman K. et al.
J Am Coll Cardiol 2009; 53: 597
Event-Free Survival According to Tertiles of CVP HR: 1.22,
p = 0.047 for CVP 4 to 6 mm Hg; HR: 1.65, p < 0.0001 for
CVP >6 mm Hg, both compared with CVP 0 to 3.
Flüssigketisbilanz und
Akutes Nierenversagen
Prowle JR et al.
Nat Rev Nephrol 2010; 6: 107-15
Abnormalities that lead to a loss of ultrafiltration pressure in
patients with acute kidney injury. Only relatively small
pressure changes are required to abolish ultrafiltration
Elevated intra-abdominal pressure in acute
decompensated heart failure: a potential
contributor to worsening renal function?
Mullens W et al.
JACC 2008; 51: 300-6
Box and whisker plot for creatinine for patients with intraabdominal pressure (IAP) <8 mm Hg and ≥8 mm Hg at baseline
and Relationship between changes in renal function and changes in
intra-abdominal pressure (IAP)
Renal Decapsulation in the
Prevention of Post-ischemic Oliguria
Stone HH. et al.
Ann Surg 1977; 186: 343-52
Comparative renal clearances of creatinine, urea and free water following
suprarenal aortic occlusion and unilateral kidney decapsulation
Fluid management for the prevention and
attenuation of acute kidney injury
Prowle JR. et al.
Nat Rev Nephrol
2014; 10: 37-44
“Renales Kompartment-Syndrom”
Fluid overload and interstitial oedema contribute to
maintenance of AKI. In established AKI, renal dysfunction persists
despite resuscitation of syst. blood pressure and cardiac output.
Hypervolämie & Inflammation
Endotoxemia in chronic heart disease
Sharma R. et al. Am J Cardiol 2003; 92: 188-193
Positive Fluid Balance in the Immediate
Postoperative Period is an Indicator of
Acute Kidney Injury in Cardiovascular
Surgery Patients
Dass B et al.
Clin Nephrol 2012; 77: 438-44
Odds Ratio for AKI by unadjusted and multivariate logistic model
„Volumen-Überladungs- Syndrom“
Konsequenzen
 Herzinsuffizienz
 Lungenödem
 generalisierte Ödeme/ gestörte Gewebsoxygenierung
 Störung der Wundheilung
 Störung der Darmfunktionen
Störung der Motorik/Ileus und Resorption
Erhöhung der Permeabilität / Translokation/
Inflammation
 Erhöhung des intraabdominellen Druckes
 NIERENFUNKTIONSSTÖRUNG
Infusionstherapie
„Volumen ist gut für die Niere“
Ein Dogma fällt !
Association between systemic hemodynamics
and septic acute kidney injury in critically ill
patients: a retrospective observational study
Legrand M. et al.
Crit Care 2013; 17: R278
Statistical model of a
nonparametric logistic
regression showing the
relationship between
mean CVP during first 24
hours from
admission and the
probability of new or
persistent acute kidney
injury. incidence.
Fluid balance and acute
kidney injury
Prowle JR et al.
Nat Rev Nephrol 2010; 6: 107-15
Cumulative fluid
balances achieved in
the FACTT trial of
liberal
(more-conventional)
versus conservative
(more-restrictive)
fluid management
strategies in critically
ill patients with acute
lung injury
Paradigmenwechsel:
Von feucht zu trocken!
Glassford NJ & Bellomo R
Nature Rev Nephrol 2011;7:305
Comparison of mean daily furosemide dose and fluid balance between
survivors and nonsurvivors in Grams et al.’s study. a | Difference in
mean daily furosemide dose between survivors and nonsurvivors.
b | Difference in daily fluid balance between survivors and nonsurvivors
Comparison of Two FluidManagement Strategies in Acute
Lung Injury
Wiedemann HP et al.
N Engl J Med 2006;
354: 2564-75
Fluid Balance, Diuretic Use, and
Mortality in Acute Kidney Injury
Grams ME et al.
Clin JASN 2011;6:966-973
Relative odds of death by FACTT study day 60 associated
with average daily fluid balance and furosemide dose
following AKI
Conclusions …a positive fluid balance after in-hospital AKI carried a
strong and consistent association with mortality, independent of liberal or
conservative fluid management. Higher diuretic dose after AKI onset had
a protective effect on survival; this relationship appeared to be mediated
by post-AKI fluid balance…in the appropriate patient, diuretics may not
be contraindicated.
Impact of restrictive fluid balance focused
to increase lung procurement on renal
function after kidney transplantation
Ninmabres E. et al
NDT 2010; 25: 2352-56
Differences in donor management with regard to the CVP value
CVP < 6 mm
Hg
(n = 88)
CVP ≥ 6 mm
Hg
(n = 154)
Pvalue
Use of vasopressor drugs
91%
89.6%
0.84
Hypotension in ICU
38.6%
34.4%
0.45
Fluid balance from BD to
OR (ml)
482 ± 1223
840 ± 1575
0.05
Urine output from BD to
OR (ml)
308 ± 154
288 ± 154
0.32
BD to OR, brain death to organ retrieval. Values are % or mean ± SD.
Conclusion: ….without impacting either kidney graft
survival or DGF development….
Avoiding common problems
associated with intravenous
fluid therapy
Hilton AK et al.
Med J Austral 2008; 189: 509-13
• Nierenversagen
Hypothetical curve of the risk of fluid therapy-related
complications versus volume of fluid infused
The Importance of Fluid
Management in Acute Lung Injury
Secondary to Septic Shock
Murphy CV et al.
Chest 2009; 136: 102-09
Hospital mortality according to whether or not patients achieved
AIFR (adequate initial fluid resuscitation), CLFM (conservative late
fluid management), both, or neither.
Effects of norepinephrine on renal
perfusion, filtration and oxygenation
in vasodilatory shock and acute
kidney injury
Redfors B al
Intensive Care Med 2010; 37: 60-67
Individual data on the
relationship between target
mean arterial pressure
(MAP) and glomerular
filtration rate (GFR)
In all patients but one, GFR
was higher at target MAP of
75 vs. at 60 mmHg.
In two patients with
diabetes type II (dashed
lines), GFR was considerably
lower (35–60%) at 90 vs. at
75 mmHg
Lower mean arterial blood pressure and
systemic oxygen delivery on day of early
AKI are associated with increased risk of
progressive AKI and mortality
Raimundo M & Ostermann M. et al. 2012; Abstract
Risk of progression to AKI III in correlation to oxygen delivery
and to mean arterial pressure
High versus Low Blood-Pressure
Target in Patients with Septic Shock
Asfar P. et al.
N Engl J Med 2014: e-pub
Mean Arterial Pressure during the 5-Day Study Period
Sodium administration in
critically ill patients
Bihari S. et al.
Crit Care Resusc 2013; 15: 296-300
Daily administered sodium according to diagnostic category
Diagnostic
category
N (%)
Sodium
administered
(mmol/d)
109 (30.6)
301.5 (283.3)
61 (17.0)
373.8 (349.6)
Burns
3 (0.8)
440.0 (259.8)
Sepsis
127 (35.6)
294.5 (215.9)
38 (10.6)
262.4 (182.4)
Post-operative
Trauma
ALI/ARDS
0.9 % NaCl = 52.2 % of sodium administered
Erbsünden der
Infusionstherapie
Faktum:
..die heutige Infusiontherapie induziert oft eine
Hypervolämie…
Hypernaträmie auf der
Intensivstation
Hauptursachen
40
35
30
25
20
15
10
5
0
Positive
sodium
balance
Furosemide
Renal
insufficiency
Osmotic
diuresis due
to urea
Fever
Water loss via
tubes
Diabetes
insipidus
Osmotic
diuresis due
to glucose
Diarrhea
80% der Fälle an der ICU aufgetreten, nur bei 20% bei der
Aufnahme bestehend !
nach Lindner/ Funk, AJKD 2009
Infusionslösungen
„Physiologisches Kochsalz“
154 mmol/l Natrium,
154 mmol/l Chlorid,
308 mosmol/kg
= weder
isoton
noch
„normal“
oder
physiologisch
Warum
die weltweit am häufigsten verwendete Infusionslösung?
Hyperchloremia After Noncardiac Surgery
Is Independently Associated with
Increased Morbidity and Mortality:
A Propensity-Matched Cohort Study
McCluskey SA. et al.
Anest Analg 2013; 117: 412-21
Spline function graph of the probability of dying within 30 days of
surgery and the postoperative maximum serum chloride concentration
on postoperative day 1 or day 2. A, Unadjusted figure. B, Adjusted by
propensity match.
A double-blind crossover RCT on the
effects of 2-L infusions of 0.9% saline and
plasma-lyte® 148 on renal blood flow
velocity and renal cortical tissue perfusion
in healthy volunteers
Chowdhury AH. et al.
Ann Surg 2012;
256; 18-24
Changes in renal
cortical tissue
perfusion after
infusion of 2 L of
0.9% saline and
Plasma-Lyte 148 over
1 hour.
Association Between a Chloride-Liberal
vs Chloride-Restrictive Intravenous Fluid
Administration Strategy and Kidney Injury
in Critically Ill Adults
Yunos NM et al.
JAMA 2012; 308: 1566-72
Development of Stage 2 or 3 AKI while in the Intensive Care Unit (ICU)
Hydrops lysosomalis generalisatus an underestimated side effect of
hydroxyethyl starch therapy?
Schmidt-Hieber M et al. Eur J Haematol. 2006;77:83-5
A. Liver biopsy diffuse hyperplasia of foamy portal macrophages and Kupffer cells;
B. in addition to vacuolization of PAS-positive hepatocytes;
C. immunohistochemical staining of macrophages anti-CD68;
D. and E. replacement of bone marrow by foamy macrophages with decentralized
nucleus and wide, vacuole-containing cytoplasm
F. enhanced iron deposition (blue) with ferritin granules within macrophages
HAES in der Sepsis:
ein Damoklesschwert?
Hagne Ch. et al.
Schweiz Med Forum 2009; 9: 304-06
Osmotische Nephrose in der Nierenbiopsie 6 Monate nach Akutereigniss.
A. Feinvesikuläre Vakuolisierung des Zytoplasmas der
Tubulusepithelzellen, unauffälliges Glomerulum.
B, C: Tubuli mit isometrisch vakuolisiertem Zytoplasma der Epithelzellen
(4500 ml Voluven in 5 Tagen, dann 2000 ml während CVVHF).
Intensive Insulin Therapy and
Pentastarch Resuscitation in
Severe Sepsis
Brunkhorst FM. et al.
N Engl J Med 2008;
358: 125-39
Cumulative Effect of Volume
Resuscitation on the Need
for Renal-Replacement
Therapy and the Rate of
Death at 90 Days
Pentastarch = 10%
264/0.45
Hydroxyethyl Starch or Saline for Fluid
Resuscitation in Intensive Care
Myburgh JA/ CHEST investigators
NEJM 2012; 376: 1901-11
Kaplan–Meier estimates of the probability of survival for patients
receiving either HES 6% [130/0.4] or saline.
Hydroxyethyl starch 130/0.42 versus
Ringer's acetate in severe sepsis
Perner A.– 6S-Trial Group
N Engl J Med 2012; 367: 124-34
Time to death survival curves
censored at day 90
for the two
intervention
groups in
intention-to treat
population. In
Kaplan–Meier
analysis survival
time did not differ
significantly
between the two
groups
(P = 0.07).
The impact of crystalloid and
colloid infusion on the kidney
in rodent sepsis
Schick MA et al.
Intensive Care Med 2010; 36: 541
Morphological alterations of the kidney (total injury score) and
serum NGAL after 24 h (sterolso = balanced solution).
Safety of gelatin for volume resuscitation
a systematic review and meta-analysis
Thomas-Reddel DO. et al.
Intensive Care Med 2012:38: 1134-42
Acute kidney injury: Forest plots of pooled estimates
Albumin Replacement in Patients
with Severe Sepsis or Septic Shock
Caironi P. et al.
N Engl J Med 2014: e-pub
Probability of Survival from Randomization through Day 90.
Akutes Nierenversagen :
Prävention und Recovery
FlüssigkeitsManagement
bei ANV
Wilfred Druml
Abteilung für Nephrologie
Medizinische Universitätsklinik III,
AKH-Wien
[email protected]
Vielen Dank für Ihre Aufmerksamkeit!