FLUID BALANCE

AS A NEW BIOMARKER IN CRITICALLY ILL

▪ Fluid accumulation is associated with adverse
outcomes
▪ Pathophysiology of Fluid shifts in critical illness
▪ Relationship of fluid accumulation to multi
organ dysfunction
FLUID ACCUMULATION IS ASSOCIATED
WITH ADVERSE OUTCOMES
 SUMMARY OF CLINICAL STUDIES SHOWING AN
ASSOCCIATION BETWEEN FLUID BALANCE AND CLINICAL
OUTCOME
 NEGATIVE FLUID BALANCE PREDICTS
SURVIVAL IN PATIENTS WITH SEPTIC SHOCK
Alsous et al: CHEST 2000; 117:1749-1754
 Independent risk factors for 60-day mortality in the patients with
ARF were age, Simplified Acute Physiology Score II (SAPS II), heart
failure, liver cirrhosis, medical admission, mean fluid balance, and
need for mechanical ventilation
• Early RRT:
• RRT started within 2 days of ICU
admission
• Late RRT:
Outcome among patients treated with RRT
• RRT started more than 2 days after ICU
admission

was better when RRT was started early in the

course of the ICU stay.
39.4% 61.5%

44.8% 64.6%
ACUTE RENAL FAILURE, STRATIFIED BY TIME OF
INITIATION OF RENAL REPLACEMENT THERAPY (RRT)

Payen et al. Crtical Care 2008. 12:R74

Percentage of FO/body weight (%FO):
%FO = (daily (total input (L) – total output (L) x 100
body weight (kg)

METHODS
PICARD Data J Bouchard et al Kidney Int, 2009
Hypothesis: ▪ 618 critically ill patients with AKI
Fluid overload in ▪ 396 patients required dialysis
adult AKI
patients treated ▪ PICARD study
with dialysis
▪ Prospective cohort
would
independently ▪ 5 teaching U.S. hospital
contribute to ▪ Between 1999 and 2001
adverse
outcomes

EFFECT OF FLUID OVERLOAD IN CRITICALLY ILL

PATIENTS WITH AKI
PICARD Data J Bouchard et al Kidney Int, 2009
 Survival Non-survival P
Mean %FO at 8.8% 14.2% 0.01
dialysis initiation

RESULTS

PICARD Data J Bouchard et al Kidney Int, 2009

INFLUENCE OF FLUID ACCUMULATION ON
MORTALITY
PICARD Data J Bouchard et al Kidney Int, 2009
KAPLAN-MEIER SURVIVAL ESTIMATES BY FLUID
OVERLOAD STATUS AT DIALYSIS INITIATION
PICARD Data J Bouchard et al Kidney Int, 2009
INFLUENCE OF MODALITY ON FLUID
OVERLOAD
PICARD Data J Bouchard et al Kidney Int, 2009
WHAT IS THE FLUID OVERLOAD?
 •Usually implies a degree of pulmonary edema or
Fluid Overload: peripheral edema

Fluid •Specifies conditions when there is a positive fluid

accumulation: balance, with or without associated fluid overload

•Refers to the daily difference in all intake and outputs,

Daily fluid balance: which generally doesn’t include Insensible losses

Cumulative fluid •Is the sum of daily fluid balance over a set periode of
balance: time

The precentage of fluid • Is the cumulative fluid balance expressed as a percent of

body weight at baseline, usually at the admission in ICU.
overload (%FO) adjusted • A cut off of 10% has been associated with increased
for body weight: mortality

DEFINITIONS OF FLUID TERMS

Pathophysiology Of Fluid Shifts In
Critically Ill Patients:
Beyond The Volume Resuscitation and
‘Third Space’
The distribution of total body
water divided into the
intracellular (ICV) and
extracellular (ECV) spaces. For
60
an adult man 70 kg, the body plasma
Extracellular
water is equivalent to 60% of Inters

% of total body weight

50 Volume (ECV)
titial
total body weight. 14L
This amounts to approximately 40
42L, distributed as 40%
30 42L
intracellular volume (28L) and
20% extracellular volume (14L), Intra Intracellular
20
of which 10.5L is interstitial and cellular Volume (ICV)
28L
3.5L is plasma volume (red cell 10
volume is a component of
intracellular volume). 0

COMPOSITION OF BODY COMPARTEMENTS

WATER DISTRIBUTION AFTER
HEMORRHAGIC SHOCK

“THE THIRD SPACE”

The third space in its
traditional interpretation is a
functionally separated part
of the extra-cellular
compartment which cannot
be localised, but primarily
consumes fluid in the
perioperative context.

It is currently no more than a trapped

myth to explain the
otherwise apparently
unexplainable perioperative
fluid shifting

THE THIRD SPACE – THE OLD PARADIGM

1. The third-space fluid losses have never been measured directly,
and the actual location of the lost fluid remains unclear
2. Most of the data do not support the existence of a third space
3. The third space is a fiction

THIRD SPACE: FACT OR FICTION?

M. Jacob et al. Best Practice & Research Clinical Anaesthesiology 23 (2009) 145–157
 Critical Illness/
Normal High risk surgery
Normal Increased
Alb endothelial gap permeability/gap
synthesis infusion

leakage

Interstitial

Interstitial
leakage
Plasma

Plasma
Lymph Lymph

catabolism In critical illness →

catabolism Urinary/Gu leakage >> lymph
t loss
flow → tissue edema
Haemorrhage

VOLUME KINETIC DURING INFUSION OF

FLUID IN HEALTHY AND LEAKAGE;
ALBUMIN PHARMACOKINETIC
 SMALL PROPORTION

ORIGINAL STARLING PRINCIPLE: THE ROLE

OF LYMPH DEFENCES AGAINST EDEMA
FORMATION
 capillary cell
membrane membrane

Mineral, protein,
ECW ICW gycogen, fat
20% 40% 40%

Interstitial o Clearance of crystalloid during anesthesia and

Plasma surgery is 10-20% of that in awake volunteers
Volume 4.3% fluid 15.7%
o Crystalloid leaves the plasma space, equilibrates
colloids with interstitial space after 20-30 min

crystalloid:
75-80% leaves vasculature after 20 minutes
5% dextrose

VOLUME KINETICS FOR INFUSION FLUIDS

Hahn GR, Anesthesiology 2010
 “Pathologic “Pathologic
shift” shift”
Interstitial fluid

Delayed clearance
Immediately reaches
shifting equilibrium with
interstitial space during
plasma infusion

VOLUME KINETICS FOR INFUSION OF CRYSTALLOID

DURING SURGERY AND PRE-ECLAMPSIA
Hahn GR, Anesthesiology 2010
WHAT ABOUT COLLOID?
• According classical starling’s principle, infused iso-
oncotic colloids do not change the intravascular
colloid osmotic pressure and cannot cross the
barrier.
• Therefore, they should remain theoretically by 100%
within the circulatory space

INTRAVASCULAR VOLUME EFFECT OF COLLOID

 The context sensitivity of volume effects of iso-oncotic colloids

The context sensitivity of volume effects of iso-oncotic colloids: while 6%

hydroxethylstarch or 5% human albumin remain within the circulation to
almost 100% if infused as a substitute during acute blood loss (left-hand
column), the preparations vanish out of the vasculature to a large extent if
applied as a hypervolaemic bolus (right-hand column).Drawn
schematically according to Jacob et al (2007, Lancet 369: 1984–1986) with
permission.
 Fluid is filtered from the arterial end of
Jv is much less than predicted by starling’s
capillaries and absorbed from the venous
principle, and the major route for return to
end. Small proportion returns to the
the circulation is as a lymph
circulation as lymph
QUESTIONS RAISED
What is the underlying pathomechanism by which
hypervolemia has the power to impair the
functioning of a primarily intact vascular barrier?

For the answer, we have to extend our view on

vascular physiology towards a small structure
that was unknown to Ernest Starling.

The Endothelial Glycocalix

Healthy vascular endothelium coated by endothelial glycocalyx –
a layer of membrane-bound proteoglycans and glycoproteins.

THE ENDOTHELIAL GLYCOCALIX

 THE ENDOTHELIAL GLYCOCALIX

▪ Glycocalyx affect endothelial permeability.

• Prevent leukocyte and platelet adhesion.
• Decreases inflammation.
• Bounds plasma proteins and fluids.
→ Maintains “oncotic gradient” despite
intravascular and extravascular equilibration.

Jacob M. et al: The endothelial glycocalix affords compatibility of starling’s

principle and high cardiac interstitial albumin level. Cardiovasc Res 2007;
73:575-86
 FLUID SHIFTING

Fluid shift into the interstitial space can be

divided into two types:

Type 1 – physiologic shift :

•Colloid-free fluid and electrolytes (crystalloid)
•Vascular barrier intact

Type 2 – pathologic shift :

•Protein-rich fluids (colloid)
•Functionally altered vascular barrier
 FLUID SHIFTING

Fluid shifting is not only an intraoperative problem but

a postoperative problem.

Peak of fluid shifting at 5 hrs after trauma and persists

up to 72 hrs depending on location and duration of
surgery.

Robarts WM: Nature of the disturbance in the body fluid compartements

during and after surgical operations. Br J Surg 1979; 66:691-5
 MANAJEMEN PERIOPERATIF
Pada perioperative sudah terjadi kerusakan primer akibat stres
pembedahan.
Yang perlu dilakukan untuk membatasi pathologic shift tipe 2 :
1. hindari hipervolemik akibat koloid untuk mencegah pelepasan
ANP. Koloid hanya digunakan untuk mengganti perdarahan
2. Hindari volume loading profilaksis karena dapat merusak barrier
vaskuler
3. Memberi terapi vasopressor untuk pasien normovolemi yang
mengalami vasodilatasi akibat general anestesi atau neuraxial
blok
FLUID ACCUMULATION, FLUID
OVERLOAD AND MULTI ORGAN
DYSFUNCTION
 Aggressive Fluid
Strategies Adversely
Affect Every System And
Organ

Tissue Edema

Diffusion Distance

Celullar damage

FLUID ACCUMULATION AND MULTI ORGAN

DYSFUNCTION
Prowle JR et al. Nat Rev Nephrol 2010;6:107
 THE CONSEQUENCES OF TISSUE EDEMA
❑ An increased intercapillary distance, as would occur with tissue
oedema,reducing DO2 by progressive falls in arterial oxygen tension results in
a change in the DO2/VO2 relationship with VO2 falling at much higher levels of
global DO2
❑ Acute Kidney Injury:
✓ Reduced GFR (Uremia)
✓ Water and salt retention
❑ Bacterial translocation
❑ gastrointestinal function
✓ Increased gut permeability
✓ Impaired wound healing
✓ Anastomostic dehiscence
SO WHAT IS THE BEST STRATEGY ?
Adequate Initial Fluid Resuscitation (AIFR):
was defined as the administration of an initial fluid bolus of > 20 mL/kg prior
to and achievement of a central venous pressure of > 8 mm Hg within 6 h
after the onset of therapy with vasopressors.

Conservative Late Fluid Management (CLFM):

was defined as even to negative fluid balance measured on at least 2
consecutie days during the first 7 days after septic shock onset.

THE IMPORTANCE OF FLUID MANAGEMENT IN ACUTE

LUNG INJURY SECONDARY TO SEPTIC SHOCK
Murphy ert al: CHEST 2009; 136-102-109
 AIFR
CLFM

THE IMPORTANCE OF FLUID MANAGEMENT IN ACUTE

LUNG INJURY SECONDARY TO SEPTIC SHOCK
Murphy ert al: CHEST 2009; 136-102-109
 No oligouria

Oligouria

FLUID BALANCE AND URINE VOLUME ARE INDEPENDENT

PREDICTORS OF MORTALITY IN ACUTE KIDNEY INJURY

Teixeira et al. Critical Care 2013, 17:R14

In summary, both fluid
balance and urine volume
were found to be
Diuretics
independent predictors of
mortality in adult critically
ill patients with AKI.
No-diuretics
Of interest, diuretic use
appeared to be
independently associated
with better survival in this
study

FLUID BALANCE AND URINE VOLUME ARE INDEPENDENT

PREDICTORS OF MORTALITY IN ACUTE KIDNEY INJURY

Teixeira et al. Critical Care 2013, 17:R14

APPROACH TO FLUID MANAGEMENT
 APPROACH TO FLUID MANAGEMENT
• Use crystalloids only when replacing urine production and
insensible perspiration.
Minimize type • Use colloids or blood products for substitution of acute blood
1 shifting loss

• Goal-directed method with available parameters

• Conservatively to avoid acute hypervolemia
Minimize type • Use colloids instead of crystalloids.
2 shifting

Chappel D. Matthias Jacob et al. A rational Approach to perioperative Fluid

Management. Anesthesiology 2008; 109:723-40
• The endocrine response to surgery consists of an increased secretion of
catabolically active hormones, most importantly cortisol, glucagon, and
catecholamine

• Anesthesiologists might contribute to a reduction of stress release of

inflammatory mediators by using neuraxial blocks.

• Single-dose neural blockade, applied as either intraoperative epidural or

spinal anesthesia, has only a transient stress-reducing effect, without
prolonged endocrine or metabolic effects.

• Continuous neuraxial analgesia over 48–72 h using local anesthetics

seems to be a possibility to reduce the metabolic stress response.

• Nevertheless, carefully maintaining intravascular volume without

hypervolemic peaks as far as possible currently seems to be the most
promising concept.

• Prophylactic fluid boluses to anticipate acute bleeding or to extend

intravascular blood volume in a primary normovolemic patient should
no longer be considered state-of-the-art
Morbidity Procedure
Comorbidities
Preop hydration
Bowel preparation
Anaesthesia/neuroaxial
Restrictive blockade Liberal

Bowel ischemia Goal- Bowel oedema

 risk of:
directed  risk of:
Organ hypoperfusion Oedema
SIRS Ileus
Sepsis PONV
MOF Pulm complication
 cardiac demands

Hypovolemia normovolemia Hypervolemia

STRATIFICATION OF PERIOPERATIVE
HEMODYNAMIC MONITORING
Bundgaard-Neilsen M et al. Acta Anaesthesiol Scan 2009;53:843
 Percentage of FO/body weight (%FO)
%FO = (daily (total input (L) – total output (L) x 100
Body weight (kg) at ICU admission

• If %FO<10%: → check for the sign of hypoperfusion

• Macrodynamic:
• Vitals sign: Heart Rate, RR, consciousness, capillary refill, turgor
• Pressure: MAP, CVP
• Flow/volume: Preload monitoring (GEDI, SV, SVV, ECHO)
• Microdynamic and anaerob met:
• ScvO2, CO2 gap, BE or lactate
• If %FO>10%:
• >>> intake: → conservative fluid management (restrict)
• Anuria/oligouria: → Fluid removal (Furosemide, IHD, CRRT)
• Capillary leakage: → Fluid Removal + Albumin hyperoncotic?

USE FLUID BALANCE AND FLUID OVERLOAD

PARAMETER TO START CONSERVATIVE
STRATEGY RATHER THAN CREATININE..?
TERIMA KASIH