Basic Fluid and

Volume Therapy

Patophysiology of Fluid
Shifts in Critically
Illness

The distribution of total body water

Distribution of body water
is 60% of body weight

The body water is

equivalent to 60% of total
body weight.

This amounts are

distributed as 40%
intracellular volume and
20% extracellular volume
of which is 15% is
interstitial and 5 % is
plasma volume (red cell
volume is a component of
intracellular volume)
C.H. Svensen et al. / Best Practice & Research Clinical Anaesthesiology 23 (2009) 213224

The Third Space :

the theory behind the story
1. Decrease blood volume

Intracellular Space
ICF

Interstitium Space

Intra
vascular

blood loss
urine output
GIT production

Third Space ??

2. Negative Net Water Flux

3. Third Space Development (?)
4. Intracellular Hyperosmolarity

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

M.Jacob et al. Best Practice & Research Clinical Anaesthesiology 23 (2009): 145-157

Fluids shifts within the

functional extra-cellular
compartment, from the
intravascular towards the
interstitial space,
Whereas the classical third
space is the location of the
lost fluid remains unclear and
most of studies do not
support the existence of a
third space
M.Jacob et al. Best Practice & Research Clinical Anaesthesiology 23 (2009): 145-157

Distribution of fluids for

increasing the blood volume
Intravascular
Extravascular

20%

40%

12

30

Capillary
membrane

36

16

6
6

Colloid is ideal for

volume therapy
75 kg
BW

Cell membrane
14.4

Intertitial

34

5 L of 0.9
NaCl
9.4 L of
D5W

12

30

1 L of 6% HES

11.6

30

0.6 L of 10%
HES

Body fluid volume

C.H. Svensen et al. / Best Practice & Research Clinical Anaesthesiology 23 (2009) 213224

Fluid Dynamics Across Capillary Beds :

The Classical Starling principles

The classical Starling principles of vascular barrier

functioning and capillaries on inward-directed colloid
osmotic pressure gradient is opposed to an outwarddirected hydrostatic pressure of fluid and colloids.
Jv, net filtration; Kf, filtration coefficient; Pc, capillary hydrostatic pressure;
Pi, oncotic pressure in the interstitial space; Pi, hydrostatic pressure in the
interstitial space; Pc, oncotic pressure in the vascular lumen; Pc, hydrostatic
pressure in the vascular lumen; s, reflection coefficient

M. Jacob et al. Best Practice & Research Clinical Anaesthesiology 23 (2009) 145157

Mechanisms of hypoalbuminemia in
critically illness and trauma

J.-L.Vincent, Best Practice & Research Clinical Anaesthesiology 23 (2009) 183191

Volume Kinetic during Infusion of Fluid

in Healthy and Diseases

Albumin
synthesis

Fluid Infusion

Plasma

leakage

Normal
endothelial gap

Interstitial

Plasma

Albumin
synthesis

Fluid Infusion

Critical Illness/ High Risk Surgery

lymph

lymph

Catabolism
Metabolism
Urinary/ GIT loss

leakage

Urinary/ GIT loss

Abnormal
endothelial gap

Interstitial Edema

Normal condition

Leakage >> lymph flow

tissue edema
Hemorrhage

Volume Kinetics for Infusion

of Crystalloids in Disease

to interstitium

Immediately reaches
equilibrium with interstitial
space during infusion

to urine

Computer simulation of how rapidly acetated Ringers solution leaves the plasma to
enter the interstital fluid space (Vt, light line) or is excreted as urine (dark line).

Hahn GR, Anesthesiology 2010

Intravascular Volume Effect of

Colloids
98

6% HES 130/0.4 Jacob 2003

Normovolemia/
hemodilution

85

5% Albumin Rehm 2000

90

6% HES 200/0.5 Jacob 2000

5% Albumin Rehm 2001

40

Interstitial

45

6% HES 200/0.5 Rehm 2001

25

Volume loading/
hypervolemia

Interstitial
50

75

Volume Effect (%)

100

Endogenous albumin augments plasma volume

expansion (after hemorrhage) despite adequate fluid
replacement
Hgb-albumin
difference dilution in Vc

Positive values indicate

translocation of albumin from
the interstitial fluid to the
plasma

Negative values show that

albumin leaves the plasma.

Computer simulation based on kinetic data : in which volunteers received infusions of 25 ml/kg acetated Ringers solution on
three separate occasions. Before two of these infusions, 450 and 900 ml blood was withdrawn.,
Hahn GR, Anesthesiology 2010

Distribution of colloid
Volume loading of 6% HES or albumin 5% in the
normovolemic hemodilution (acute blood loss)

Volume loading 6% HES and albumin 5%

in the hypervolemic

The volume remaining in the

intravascular space almost 90%

68% of the infused volume extravasating

into the interstitium within minutes

Jacob et al (2007, Lancet 369: 19841986)

Fluid Dynamics Across Capillary Beds :

The Classical Starling principles

The Starling Principle revisited :

The Endothelial Glycocalyx

Levick JR. J Physiol 2004; 557:704

Factors affecting the endothelial

glycocalyx :
The injurious mechanisms

Doherty M, Buggy DJ. Intraoperative fluids: how much is too much? British Journal of Anaesthesia 2012

Intact Glycocalyx
Mediator, inflammation
Acute hypervolemia Secretion of
ANP

Loss Glycocalyx leakage

tissue edema
Journal of Surgical Research 165, 136141 (2011)

What is the Atrial Natriuretic Peptide (ANP)

Volume expansion
Intake of salty food and fluids
excessive IV fluids / hypervolemia

Right atrial distension

increase venous capacitance
secretion of Atrial Natriuretic Peptide (ANP)

vasodilation

inhibit renin secretion

inhibit aldosterone secretion

increased renal NaCl and H2O excretion

Acute Hypervolemia will increase ANP secretion

2 1000 ml of crystalloid

500 ml of HES +
1000 ml of crystalloid

Acute hypervolemia

Acute hypervolemia

Responses in the concentrations of ANP in central () and peripheral () veins before and during spinal anaesthesia for Caesarean delivery after a
volume load of 2 1000 ml of crystalloid solution (a) and 500 ml of colloid + 1000 ml of crystalloid solution (b). **p < 0.01, ***p < 0.001 (ANOVA for
repeated measures).

Pouta AM: Effect of intravenous fluid preload on vasoactive peptide secretion during Caesarean section under spinal anaesthesia. Anaesthesia 1996: 51.128-132

ANP is similar with a

heparinase trigger
glycocalix
degradation

HES 6%, 200

with hypovolemia

Intact glicocalix

HES 6%, 200

with hypervolemia

Loss glicocalix
Leakage tissue
edema

Perioperative liberal fluid management

hypervolemia

secretion of ANP

degradation of glycocalix

fluid shift

interstitial edema

Fluid shifting :
the current concept
Fluid shifting from the vasculature towards the
interstitial space should is divided into two types:
Type 1 is a physiological

Crystaloids Shifts

almost colloid-free shift of fluid and

electrolytes out of the vasculature, in a small
extent all the time
Type 2, the pathological

Crystaloids and Colloids

Shift

plasma shift is protein-rich

related to a damage of the vascular barrier
Strunden MS et al. Annals of Intensive Care 2011

Fluid option
Blood and components
Crystalloid
Colloid
Hypertonic solution

Isotonic crystalloids
Advantages
Cheap

Easy to store and warm

Established safety
Predictable rise in cardiac output

Large volumes needed

Disadvantages14

Dilutional coagulopathyIncrease cytokine activation7

No oxygen carrying capacity
May Increase ICP

Composition of IV Crystalloids
Plasma

Na

Cl

Ca

Buffer

pH

141

103

4-5

Bicarb

7.4

Russel L, McLean AS. The Ideal Fluid. Curr Opin Crit Care 2014, 20:360365

Colloids
Proposed Benefits
Smaller volume
Less pulmonary edema
Stays in the intravascular space
return to normal
Quicker
hemodynamics
Smaller package
Antioxidant and antinflammatory effects

Colloids
Disadvantages
Transmission of diseases

Increased bleeding
Hypersensitivity reactions
Renal failure
Accumulation
Taken up by RES
Dose limit (20-33mL/kg)

Cost

Hypertonic Saline
Rapid plasma volume expansion

of fluid to vascular space secondary to increased

Pull
concentration gradient

Decreases ICP

Potential benefits in TBI patients

Military use
Weighs less

1 liter NS bag=2744 cm3 in volume and 1.1 kg

Storage space for helicopters and ground ambulances

Hypertonic Saline
Hypertonic saline

7.5% or 7.2%
Dextran 70 (RescueFlow) or HES (HyperHAES)
Osmolarity 2500 mOsm/liter
Na+: 1200 mmol/liter
Total volume 250ml

Natural Colloids :
Albumin
trial 2004 (N Engl J Med 2004)
SAFE
Double blind RCT, 7000 pts, 16 ICUs, 18 month period

4% albumin v 0.9% normal saline

First 4 days volume albumin to saline (1:1.4)
No difference in 2 groups in 28 all day cause mortality
group analysis: difference between trauma and sepsis
Sub
patients

RR of death pts with severe sepsis= 0.87

trauma mortality higher for albumin v saline (13.5%
Overall
v 10%)
TBI increase in mortality

Bio-physiology of Colloids

Crystalloid vs colloid
distribution
Fluids

Plasma

Interstitial

Intracellular

Alb5%

1000

Expafusin 6%

1000

Poligeline

700

300

Dextran 40

1600

-260

-340

Dextran 70

1300

-130

-170

NaCl 0.9%

200

800

NaCl 1.8%

320

1280

-600

NaCl 0.45%

141

567

292

RL

200

800

D5%

83

333

583

Summary

The integrity of the glycocalyx determines vascular

permeability and is adversely affected by many
conditions seen in the critically ill patient

Intravenous fluids, both colloids and crystalloids,

need to be considered as a drug with risk

The ideal fluid is one that achieves the desired

outcome, has a favourable pharmacokinetics with
sustained increase intravascular volume, no tissue
storage, no adverse electrolyte, acid-base,
haematological, infectious diseases