M. Joannidis

Internistische Intensiv- und Notfallmedizin

Universitätsklinik für Innere Medizin I

Volumen, auch schlecht für die Niere?

Fallbeispiel # 1

• 83 jährige Patientin, Hypertonie, Z.n. Apoplex mit Gangunsicherheit als Residuum, Globalherzinsuffizienz

• vor 3 Tagen gestürzt, RQW am re US mit großem Hämatom, seitdem wenig gegessen und getrunken

• Prämedikation: – Lasix 40 mg

– Aldactone 50 mg

– Renitec 10 mg

Fallbeispiel # 1

• 83 jährige Patientin, Hypertonie, Z.n. Apoplex mit Gangunsicherheit als Residuum, Globalherzinsuffizienz

• vor 3 Tagen gestürzt, RQW am re US mit großem Hämatom, seitdem wenig gegessen und getrunken

• Prämedikation:

• Lasix 40 mg, Aldactone 50 mg, Renitec 10 mg

• Aufnahmestatus:

• P 75, RR 106/50, reduzierter AZ, verwirrt,

• Zunge trocken, Lunge frei, HT o.B.

• US -Ödeme bds

• Bei Anlage eines Harnkatheters 100 ml Harn entleert, nach einer Stunde 20 ml

• US Niere: unauffällig, keine Hydronephrose

Labor (Patientin #1)

Astrup (venös):

– pH 7.36

– pCO2 38.9 mm Hg

– pO2 42.7 mm Hg

– HCO3- 22.2 mmol/l

• Serum: – K+ 7.4 mmol/l

– Na+ 126 mmol/l

– Cl- 91 mmol/l

– Ca 2.3 mmol/l

– P 1.2 mmol/l

– Glucose 116 mg/dl

– Kreatinin 2.47 mmol/l

– Harnstoff 112.6 mmol/l

– Hb 9.5 g/dl

– Protein 6.7 mg/dl

EKG

Labor (Patientin #1)

Astrup (venös):

– pH 7.36

– pCO2 38.9 mm Hg

– pO2 42.7 mm Hg

– HCO3- 22.2 mmol/l

• Serum: – K+ 7.4 mmol/l

– Na+ 126 mmol/l

– Cl- 91 mmol/l

– Ca 2.3 mmol/l

– P 1.2 mmol/l

– Glucose 116 mg/dl

– Kreatinin 2.47 mmol/l

– Harnstoff 112.6 mmol/l

– Hb 9.5 g/dl

– Protein 6.7 mg/dl

Serum Kreatinin vor 7 Monaten = 1,05 mg/dl

-> AKI Stadium 2 (2-fach< Anstieg < 3-fach)

UO= 20 ml/h seit 1 h

Was braucht die Patientin?

• Kristalloide?

• Kolloide?

• Dialyse?

• Diuretika?

• Keine Ahnung..

Was braucht die Patientin?

• Kristalloide?

• Kolloide?

• Dialyse?

• Diuretika?

• Keine Ahnung..

Cecconi, M. et al. Intensive Care Med (2015) 41:1529–1537

Fluid challenges in intensive care:

the FENICE study A global inception cohort study

Evolution der ANV Definition…

RIFLE

ARF

AKIN

KDIGO

2004 2007 2012 1949

Diagnose der

Akuten Nierenschädigung (AKI)

AKI Serum Kreatinin Harnausscheidung

Stadium 1 ≥1,5 bis <2,0-facher Anstieg innerhalb von 7d*

oder

Anstieg um >0,3 mg/dl innerhalb von 48 h

<0,5 ml/kg/h für 6-12 h

Stadium 2 ≥2,0 bis <3,0-facher Anstieg innerhalb von 7d* <0,5 ml/kg/h für ≥12 h

Stadium 3

≥3,0-facher Anstieg innerhalb von 7d*

oder

Anstieg* um >0,5 mg/dl (bei SCr >4 mg/dl)

oder

Beginn einer Nierenersatztherapie

<0,3 ml/kg/h für ≥24 h

oder

Anurie für ≥12 h

*Anstiege werden auf bekannten (Vorbefunde

innerhalb von 3 -12 Monaten)

oder

auf errechneten Referenzwert bezogen (MDRD-

Formel, falls keine Vorgeschichte von chronischer

Niereninsuffizienz besteht)

Kidney Int 2012, Suppl. 2012, 2: 1-138 www.KDIGO.org

Surgical Insult, Pain, Trauma,

Haemodynamic Instability

ADH RAAS SNS

OLIGURIA

Pathological

Reversible Irreversible

AKI

Mechanisms of Oliguria

Physiological

Lehner G et al, Nephron 2016

Die häufigsten Ursachen für AKI

• Hypovolämie

• Herzinsuffizienz

• Sepsis

• Medikamentenassoziierte AKI

(Nephrotoxine, NSAR, ACE Hemmer…)

Merkregel -> 4 H´s:

Hypovolämie, Herzinsuffizienz, Hyperinflammation, Hypermedikation

Volumengabe !

Himmelfarb, J. et al. Clin J Am Soc Nephrol 2008;3:962-967

Conceptual model for development and

clinical course of acute kidney injury

The major goal

is to keep this kidney perfused

(….and hopefully filtrating)

Himmelfarb, J. et al. Clin J Am Soc Nephrol 2008;3:962-967

Conceptual model for development and

clinical course of acute kidney injury

Kann „Volumen“ der Niere

schaden?

Der Menge

an Flüssigkeit

Art der

Flüssigkeit

…abhängig von

Fluid Accumulation has

consequences: HAGIE

Hospital acquired generalised interstitial edema

Lyons W. Crit Care Med 2000

Lyons W. J Trauma 2002

Minimised by –

Fluid “restriction” and colloid

resuscitation to appropriate

haemodynamic targets

Surviving Sepsis Campaign 2012

MANAGEMENT OF SEVERE SEPSIS

Initial Resuscitation (grade 1A):

a) CVP 8–12 mm Hg

b) MAP ≥ 65 mm Hg

c) Urine output ≥ 0.5 mL/kg/hr

d) Superior vena cava oxygenation saturation (Scvo2) 70%

or mixed venous oxygen saturation (Svo2) 65%

SCC 2012, Dellinger R etal , Crit Care Med 2013

Fluid resuscitation in septic shock: A positive fluid

balance and elevated central venous pressure are

associated with increased mortality

Boyd, John H et al Critical Care Medicine. 39(2):259-265, February 2011.

Fluid Balance CVP

12 hours:

Fluid balance +4,9 L

Fluid balance +8,2 L

4 days:

Fluid balance +13,0 L

Fluid balance +20,1 L

Fluid resuscitation in septic shock: A positive fluid

balance and elevated central venous pressure are

associated with increased mortality

Boyd, John H et al Critical Care Medicine. 39(2):259-265, February 2011.

12-hr fluid balance: Survivors vs. nonsurvivors within CVP groups

Einflußfaktoren auf die GFR

Prowle JR et al., Nat Rev Nephrol 2010; 6: 107-15

Massive

Tubulusschwellung

Interstitielles Ödem,

erhöhter ZVD

Erhöhter intrabdomineller

Druck

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 constant arterial pressure

Raised Venous Pressure : A Direct Cause of

Renal Sodium Retention and Edema

Association between systemic hemodynamics and septic acute

kidney injury in critically ill patients:

a retrospective observational study

Legrand et al. Critical Care 2013, 17:R278

Statistical model of nonparametric logistic

regression showing the relationship

between mean central venous pressure

during the first 24 hours after admission

and the probability of new or persistent

acute kidney injury.

Note the plateau for the incidence of acute

kidney injury (AKI) when the lower limit of

central venous pressure (CVP) was between 8

and 12 mmHg. Over this limit, the rise in CVP

was associated with a sharp increase in new

or persistent AKI incidence.

Intraabdominal Hypertension/

Abdominal Compartment Syndrome (ACS)

Maerz and Kaplan, Critical Care Medicine 2008

Intra Abdominal Hypertension and

Abdominal Compartment Syndrome

Pre-disposing Factors Common Etiological Factors

Dalfino K et al, Intensive Care Medicine 2008

Oliguria

azotemia

Pathophysiology of CRS Type 1

Renal hypoperfusion

Reduced oxygen delivery

Necrosis / apoptosis

Decreased GFR

Resistance to ANP/BNP

BIOMARKERS

KIM-1

Cystatin-C

N-GAL

Creatinine

Hemodynamically mediated damage

Immune mediated damage

Humorally mediated damage

Humoral

signalling Cytokine

secretion

Exogenous factors

Contrast media

ACE inhibitors

Diuretics

Acute

Kidney

Injury

Caspase

activation

Apoptosis

Caspase

activation

Apoptosis

Decreased

perfusion

Acute decompensation

Ischemic insult

Coronary angiography

Cardiac surgery

Decreased CO Increased

venous

pressure

Toxicity

Vascocostriction.

RAA activation, Na + H2O

retention, vasoconstriction

BNP

Sympathetic Activation

Hormonal factors

Monocyte

Activation Endothelial

activation

Natriuresis

Acute

Heart

Disease

or

Procedures

ADQI Acute Dialysis Quality Initiative Consensus Group ADQI

More in AHF

Ähnliche Situation in der Sepsis unter

“Fluid Resuscitation”?

Was

nun....?

Restricting volumes of resuscitation fluid in adults with septic shock

after initial management:

the CLASSIC randomised, parallel-group, multicentre feasibility trial

P.B. Hjortrup et al , Intensive Care Med 2016

DOI 10.1007/s00134-016-4500-7

Fluid restriction group:

isotonic crystalloid (saline or Ringer’s

solutions) fluid boluses of 250–500 mL

in the case of severe hypoperfusion

defined as either

1. Plasma lactate of > 4 mmol/L,

2. MAP below 50 mmHg in spite of the

infusion of norepinephrine,

3. mottling beyond the edge of the

kneecap (mottling score greater

than 2)

4. oliguria, but only in the first 2 h after

randomisation (< 0.1 mL/kg IBW in

the last hour).

151 adult patients with septic shock

Standard group:

Fluids as long as circulation improves

Restricting volumes of resuscitation fluid in adults with septic shock

after initial management:

the CLASSIC randomised, parallel-group, multicentre feasibility trial

P.B. Hjortrup et al , Intensive Care Med 2016 DOI 10.1007/s00134-016-4500-7

Fluid Management in ALI Fluid and Catheter Treatment Trial(FACTT)

ARDS Clinical Network Trial, NEJM 2006

Fluid balance / week

Conserv. Strategy (n=503): Liberal Strategy (n=498):

-136 (+ 491) ml + 6992 (+502) ml

Pat. on RRT: conservative 10% liberal 14% (p=0.06)

Furosemide Doses and Changes in Serum

Creatinine During the FACTT Trial

ARDS Clinical Network Trial, NEJM 2006

Furosemide Dose

Grams M E et al. CJASN 2011;6:966-973

AKI ?

Biomarker?

Serum Creatinine

Diuretics for control of hypervolemia may improve

outcome.......?

Chawla LS et al, Crit Care 2013, 17:R207

Development and standardization of a furosemide

stress test to predict the

severity of acute kidney injury

Urinary Output response to 1.0-1.5 mg/kg furosemide in patients with AKI stage I or II

Sensitivity 84%

Sensitivity 87%

Welches

Flüssigkeitsmanagement?

Kristalloide? Kolloide?

theoretisch ~3-facher

Volumeneffekt ….

aber

fraglicher klinischer

Benefit

Are Colloids Better Than Crystalloids for Fluid

Resuscitation in Critically Ill Patients?

B. Hohertz et al, Annals of Emergency Medicine, Volume 65, no. 4 : April 2015

Perel P, Roberts I, Ker K., Colloids versus crystalloids for fluid resuscitation

in critically ill patients. Cochrane Database Syst Rev. 2013;(2):CD000567.

Osmotic Nephrosis: Acute Kidney Injury With Accumulation of Proximal

Tubular Lysosomes Due to Administration of Exogenous Solutes

Dickenmann M et al, Am J Kidney Dis 2008, 51:491-503

HES

Gelatine

Mannit

Dextrane

The Cochrane Library 2013, Jul 23;7

RESULTS: This review included 42 studies (11,399 patients)…..

…RIFLE-I (injury) outcome with a RR of AKI of 1.22 (95% CI 1.08 to 1.37; 8338

patients)….

…significant increase in the need for RRT in the HES treated individuals compared to

individuals treated with other fluid therapies (RR 1.31, 95% CI 1.16 to 1.49; 19 studies,

9857 patients). ..

….Overall, methodological quality of the studies was good 9857 patients)

AUTHORS' CONCLUSIONS: The current evidence suggests that all HES products

increase the risk in AKI and RRT in all patient populations and a safe volume of any HES

solution has yet to be determined. In most clinical situations it is likely that these risks

outweigh any benefits, and alternate volume replacement therapies should be used in

place of HES products.

Hydroxyethyl starch (HES) versus other fluid therapies:

effects on kidney function.

Mutter TC, Ruth CA, Dart AB.

Albumin

• Albumin verbessert Diurese bzw. Flüssigkeitsbilanz

(Sepsis, Herzchirurgie – HLM)

• Keinerlei Signal für Nierenschädigung in der Sepsis

(ALBIOS)

• Albumin reduziert AKI bei

Leberzirrhose/Standardtherapie bei hepato-renalem

Syndrom

Dubois M-J et al, Critical Care Medicine. 34(10):2536-2540, October 2006

Caironi P et al, N Engl J Med 2014;370:1412-21

Lee EH et al, Anesthesiology 2016 Feb 18 epub.

Caironi P et al, N Engl J Med 2014;370:1412-21.

Wiedermann CJ et al, Gastroenterol Res Pract. 2015;2015:912839

Crystalloid fluid therapy:

is the balance tipping towards

balanced solutions?

Young P & Joannidis M, Intensive Care Med. 2014 Dec;40(12):1966

Normal saline can induce metabolic acidosis and renal hypoperfusion!

Effect of a Buffered Crystalloid Solution vs Saline on Acute

Kidney Injury Among Patients in the Intensive Care Unit

The SPLIT Randomized Clinical Trial

Young P et al, JAMA. 2015 Oct 27;314(16):1701-10

Only 77 patients with sepsis

~1,7 L fluids (median) in 48h administered

Volumentherapie…

Schädigung der Niere durch

Infusionslösungen?

“Chloridreiche”

Lösungen

(0.9% NaCl)?

potentiell

schädlich

Künstliche

Kolloide:

HES/Gelatine (?)

schädlich

“Balancierte”

Lösungen

Albumin

Kristalloide? Kolloide?

…also, für die Niere gesprochen:

• Volumengabe, gut bei Hypovolämie

– Kristalloide als Mittel der ersten Wahl

– Biologische Kolloide>synthetischen Kolloide

– Kein HES!

• Volumengabe, sinnlos bei Euvolämie

– Man kann die GFR nicht anschupfen….!

• Volumengabe, schädlich für die Niere bei

Hypervolämie

– Diuretika helfen!

– Frühzeitig an Vasopressoren, ggf. Inotropika denken!

Danke für Ihre Aufmerksamkeit! michael.joannidis@i-med.ac.at

49. Gemeinsame Jahrestagung der ÖGIAIN und DGIIN 7-10. Juni 2017 , Congress Innsbruck

Personalisierte Intensivmedizin im Zeitalter der Standardisierung

Beispiel #2

53 jährige Patientin,

Vorstellung in der Notaufnahme wegen zunehmender Atemnot , Fieber,

Schüttelfrost, Husten, verminderte Harnausscheidung seit 2 Tagen

Vorerkrankungen: DM II, schwere art. Hypertonie

Prämed: Metformin, Labetalol, Irbesartan

SP: RR 83/50, Puls 102, adipös, SO2 90% unter RL, AF 26

Beinödeme bds., Herz o.B.

Lunge: Deutliche Stauungs-RGs beidseits

• Serum:

– Kreatinin 3,02 mg/dl

– Harnstoff 75,2 mg/dl

– Glucose 277 mg/dl

– CRP 37,8 mg/dl

– Leuko 21,000/µl

– Hb 10.6 g/dl

Beispiel #2

53 jährige Patientin,

Vorstellung in der Notaufnahme wegen zunehmender Atemnot , Fieber, Schüttelfrost, Husten,

verminderte Harnausscheidung seit 2 Tagen

DM II, schwere art. Hypertonie

Prämed: Metformin, Labetalol, Irbesatan

SP: RR 83/50, Puls 102, adipös, SO2 90% unter RL, AF 26

Beinödeme bds., Herz o.B.

Lunge: Deutliche Stauungs-RGs beidseits

• Harn:

– Leuko 25

– Nitrit positiv

– pH 6

– Protein 750

– Ery 150

Labor

Blutgase (arteriell)

– pH 7,47

– pCO2 25,3 mm Hg

– pO2 58 mm Hg

– HCO3- 21,3 mmol/l

– BE -4,7

– Laktat 49 mg/dl (<19,8) ~5,5 mmol/l

Welche Therapie?

1. Diuretika (a real dose!!)

2. HES

3. Albumin

4. Albumin + Kristalloide

5. Vasopressoren + Kristalloide

6. Vasopressoren

Welche Therapie?

1. Diuretika (a real dose!!)

2. HES

3. Albumin

4. Albumin + Kristalloide

5. Vasopressoren + Kristalloide

6. Vasopressoren

Merke

Ohne Perfusion keine Diurese!

Verlauf

0

20

40

60

80

100

120

140

160

Aufnahme 8h 20h 32h

0

0,5

1

1,5

2

2,5

3

3,5

MAP

Stundenharn

S-Kreatinin

Arterenol

+Imipenem 3*1g

Danke für Ihre Aufmerksamkeit

michael.joannidis@i-med.ac.at

Preservation and optimization of renal function:

Strategies of maintaining renal perfusion in the ICU

• Volume Resuscitation/Challenge – depending on response ->

CI/MAP increase mandatory (!)

– CVP > 5-8 mm Hg (< 12 mm Hg)

– MAP > 65-75 mm Hg ( 85 mm Hg chronic hypertension, < 95 mm Hg)

– ScvO2 > 70% , lactate < 4mmol/l

• Early Resuscitation -> after stabilization, apply conservative fluid

regimen (even by giving high dose diuretics)

– Monitor IAP (in risk patients)

– Avoid artificial colloids, especially HES in sepsis

– Albumin may be an alternative in certain conditions (sepsis)

– Preferably use balanced solution (?)

• Vasopressors: NE , combined with vasopresssin (refractory shock)

• Inotropes:

– Levosimendan for acute heart failure/septic myocardial depression (?)

Optimierung der Nierenperfusion

• Volumenstatus (Flüssigkeit)

• Vasopressoren (Nordrenalin>Vasopressin)

• Inotropika

High versus Low Blood-Pressure Target in

Patients with Septic Shock

Asfar P et al., N Engl J Med 2014;370:1583-1593

Multicenter, open-label trial, patients with

septic shock were treated to maintain a mean

arterial pressure target of either 80 to 85 mm

Hg or 65 to 70 mm Hg.

Levosimendan for Prevention of Acute Kidney Injury After

Cardiac Surgery:

A Meta-analysis of Randomized Controlled Trials

Zhou C et al, AJKD, Volume 67, Issue 3, 2016, 408–416

Levosimendan (Levo) reduced the incidence of acute kidney injury

-> Levosimendan (Levo) reduced the need for renal replacement therapy

(odds ratio [OR], 0.43; P = 0.002).

Effects of levosimendan on systemic and regional

hemodynamics in septic myocardial depression

Morelli A et al, Intensive Care Med. 2005

-> Improvement of microcirculation (sublingual)!

Morelli A et al, Crit Care 2010

N=15/15, LEV < 55%, levosimendan 0.2 µg/kg/min, dobutamine 5 µg/kg/min

Therapie des AKI • Schock -> Schocktherapie

• Hypovolämie – Volumensubstitution: Kristalloide – bilanzierte Lösungen (z.B. Elomel, Ringer-

Laktat), isotones Kochsalz bei Hyponatriämie

• Sepsis – Volumen (>1000 ml Kristalloide, 30 ml/kg über 4-6h),

– Vasopressoren (z.B. Arterenol 5mg/50ml Perfusor starten mit 0.5-1,ml/h

– Dosierung nach MAP (> 65 mmHg) , bei vorbestehender chronischer Hypertonie höher (> 80 mm Hg)

– Rasche Antibiotikagabe

• Reduziertes effektiv zirkulierendes Volumen: – Herzinsuffizienz

• pos. inotrope Substanzen (Levosimendan 12 mg /24h>Dobutamin, )

– Leberzirrhose

• Vasopressinanaloga (z.B. Terlipressin max 6 x 2 mg)

• Albumin (200 ml/20%)

• Parazenthese beim abdominellem Kompartment-Syndrom (IAP > 20 mm Hg)

• Medikamentös induziertes AKI – Absetzen der Prämedikation

Zusätzliche iatrogene Nierenschädigung, soweit möglich, vermeiden:

Aminoglykoside, Vancomycin, Teicoplanin, Amphothericin B

NSAR, ACE Hemmer, Metformin absetzen

0,9% NaCl < 1000 ml -1500ml !

-> alternativ „balancierte“ Elektrolytlösungen geben

künstlichen Kolloide vor allem HES

(jodhaltige i. v. Röntgenkontrastmittel)

Achtung!