New

Paradigm
in Fluid Resuscitation
Bambang Pujo Semedi
Dept. Anethesiology and Intensive Therapy
Faculty of Medicine Airlangga University Dr Soetomo Hospital
SURABAYA
Fluid administration is one of the most widely
used therapies in hospitals and clinics...
Although the placement of this IV line is generally
recognized as a reasonable first step for the therapeutic
approach, but there is little agreement on what should be
done regarding fluid administration itself

Inappropriate understanding of the hemodynamic

accompanied by inadequate hemodynamic
monitoring often cause problems in the critical care
and perioperative patient
1999 UK Confidential Enquiry into Perioperative Death

Errors in fluid management (usually fluid excess) :

most common cause of perioperative morbidity, mortality
Some reasons why clinician give so much fluid
Preoperative fasting
Surgical blood loss
Evaporation
Urinary excretion
Many liters of
Vasodilation caused by anesthesia positive fluid balance
(epidural) during STANDARD
Transfer to third space
operation
Operation
Trans-capillary leak of albumin
caused by inflammatory mediators
 Dangerous Understanding
in Perioperative Setting
Insensible perspiration increased Inevitable & impressive
Intravascular deficit
exponentially with damage to fluid shift into a primarily
after fasting
skin barrier consuming 3rd space

Aggressive perioperative fluid approach

Accumulation of fluid in tissue

It is interpreted as unavoidable collateral damage

6
Four pathophysiologic "fundamentals" underlying
clinicians thinking of choosing aggressive fluids
in the perioperative period
1. The preoperatively fasted patient is hypovolemic, due to..
ongoing insensible perspiration
urinary output
2. The insensible perspiration increases dramatically when the
surgeon starts cutting the skin barrier
3. An unpredictable fluid shift toward 3rd space
Requires generous substitution
4. Hypervolemia is less harm than hypovolemic,
Kidneys will regulate the overload
Chappell D, Jacob M, Hofmann-Kiefer K, Conzen P, Rehm M. A Rational Approach
to Perioperative Fluid Management. Anesthesiology 2008; 109:723 40
7
 Perioperative
FLUID BALANCE

Unmeasurable output
Measurable input Measurable output Insensible loss
infusions blood loss
3rd space loss
transfusions urine production
Preoperative deficit

FACT:
Traditional fluid handling during major surgery an excess
of several litres in the perioperative fluid balance
8
 Perioperative Fluid Optimization
Under normal circumstances, the individual patients hydration
and volume state before surgery is unknown.
The exact target remains unclear, and many theoretically
possible targets cannot be measured in clinical routine
Double-label blood volume measurement, the current standard to
assess total body blood volume, is invasive, complex, and personnel
intensive

The principal goal is to optimize cardiac preload

But remember
OPTIMIZING does not necessarily mean MAXIMIZING
9
In 1977 Lamke and co-workers performed direct
perspiration measurement..
Insensible perspiration is generally highly overestimated
Basal evaporation : 0,5 - 1 mL/kg/hour
0,5 mL/kg/hour : through skin and airway in awake adult
1 mL/kg/hour : during abdominal surgery including losses
through surgical wound due to maximum bowel exposure

Traditional daily practice have been using 5-10

mL/kg/hour fluid maintenance for laparatomy !!!
10
Remember that in acute illness and
perioperative setting...
INTRAVENOUS FLUID is considered as a DRUG
Should be given if there are indications :
to correct hypovolemia
to maintain hydration
to improve tissue oxygenation by augmenting cardiac output
through increased SV

Avoid adverse effect !!

11
There are three different kinds of losses which are
UNMEASURABLE in clinical routine :
Preoperative deficit
Insensible perspiration
Inevitable third-space shift caused by surgery and
trauma

Replacement those of losses was

traditionally interpreted as appropriate
perioperative treatment
12
Impact of fasting on i.v volume is limited
Even after 10 hours of fasting (in patients not receiving bowel
preparation) iv blood volume is within normal range
Jacob M, Chappell D, Conzen P et.al. Blood volume is normal after
preoperative overnight fasting. Acta Anaesthesiologica Scandinavica
2008; 52: 522529.

The fact that blood volume is normally at

preoperative levels after the surgical procedure

Fluid excess largely represents perioperative

fluid shifting
13
Traditionalist says that :
Their strategy of generously replacing losses,
presumably towards a third space, SHOULD BE RIGHT

but...
Was this a correct conclusion?

14
 Surgical
manipulation
Crystalloids of 5-
Increases 5 10 % in 10 mL/kg/hour
interstitial waterload

Chan ST, Kapadia CR, Johnson AW et.al.

Extracellular fluid volume expansion and third
space sequestration at the site of small bowel
anastomoses. British Journal of Surgery 1983;
70: 3639.
Bowel edema
15
 Volume effect is part of an infused bolus that does not
shift outwards, but remains inside the vasculature
What happens during volume loading?
Infusion of colloids to a primarily normovolemic
circulation without simultaneous blood withdrawal
60% of the infused amount directly loads the interstitial
space
It is more reasonable to infuse fluid not before but
when hypovolemia occurs

16
Fluid loading using coloid before performing a
neuraxial anesthesia is severely questionable

Volume effects of iso-oncotic colloids are about

100 % if it is used to substitute acute blood losses
Fluid administration in normovolemic will induce
hypervolemia tremendous shift of fluid and
colloids towards the interstitial space

17
Standard operation resulted in the use of
excessive fluid
Maintenance : 4-2-1 rules
Burn : Parkland formula
Dehidration
Deficit : Maintenance x hrs fasting
3rd space losses: 10-15 ml/kg/hrs
during major abdominal surgery
ACLS : 3:1 ratio replacement with
crystalloid in hemorrhage
Aggressive fluid strategies
adversely affect every body
system and organ
Prowle JR et al. Nat Rev Nephrol 2010; 6:107
Postoperative fluid overload : not benign problem
Lowell JA. Critical Care Med 1990; 18 : 728-33

Shires & Shoemaker Effect :

Liberal fluid administration became
standard practice in 80s & early
90s
7-10 weight gain is not uncommon
Proportionately increased risk of
morbidity and mortality
Effect Fluid Administration
Body water components
Capillary Cell Beverly Morningstar. Goal Directed Fluid Therapy : A Modern
membrane membrane Approach to Perioperative Fluid Management

ECF ICF Minerals, protein,

glycogen, fat
20% 40% 40%

Plasma Interstitial
volume(4.3%) fluid (15.7%)
Colloids
Crystalloid:
75-80% leaves vasculature after 20 minutes
5% Dextrose
 Crystalloids vs. Colloids distribution
Crystalloid vs Colloid Distribution
plasma ISF ICF Colloids
H2O H2O H2O more effective for ECBV
distribution volume

?
Na+ Na+ Na+
= plasma
Cl Cl
K+ K+ K+ + ~ISF
Proteins Proteins Proteins
plasma ISF ICF

H2O H2O H2O

Crystalloids
Na+ Na+ Na+
less effective for ECBV
Cl Cl
distribution volume K+ K+ K+
= plasma + ISF Proteins Proteins Proteins
Fluid Shifting: trigger or
effect of traditional
infusion behavior?

23
 FLUID SHIFTING is an often recognized
phenomenon during & after surgical procedures

An overwhelming
infusion therapy causes
severe perioperative
surgery & trauma problems which should
be avoidable
Impressive primary
fluid shift outwards

Aggressive fluid
resuscitation 24
Fluid shifting : a reinterpretation
according to current concepts

25
 Fluid shifting

Type 1 : PHYSIOLOGICAL Type 2 : PATHOLOGICAL

1. Protein-rich
1. Almost colloid & electrolytes free 2. Related to a morphological
2. Happen to a small extent all the time alteration of the vascular barrier
3. Can rise to pathological amounts due to :
Dilution of plasma proteins
outward-directed hydrostatic pressure

26
Fluid shifting
Fluid shifting is not only an intraoperative problem but a
postoperative problem.
Peak of fluid shifting at 5 (five) hours after trauma and
persists up to 72 hours depending on location and
duration of surgery.
Robarts WM: Nature of the disturbance in the body fluid compartments during and
after surgical operations. Br J Surg 1979; 66:691-5
How can it be?

28
The Endothelial Glycocalyx
Revised Starling Model in Volume Kinetics

29
Every healthy vascular endothelium is coated on the
luminal side by endothelial glycocalyx
Bound plasma the physiologically active
GLYCOCALYX constituents endothelial surface layer

Major part in vascular barrier function:

to prevent leucocyte adhesion
to prevent platelet aggregation
mitigation inflammation and tissue edema

30
Lira and Pinsky Annals of Intensive Care 2014, 4:38 Page 6 of 13
http://www.annalsofintensivecare.com/content/4/1/38

Figure 1 Schematic diagram of the primary forces defining transcapillary fluid movement. The opposing forces defining the steady-state
net flow of fluid from the capillary into the interstitial space are defined by the hydrostatic pressure differences between the capillary lumen (Pc)
and interstitial pressure (Pi) as opposed by the filtration coefficient (Kf) which itself is a function of the vascular endothelial cell integrity and the
intraluminal glycocalyx. This net efflux of fluid out of the capillary into the interstitium is blunted by an opposing oncotic pressure gradient moving
fluid in the opposite direction because capillary oncotic pressure (c) is greater than interstitial oncotic pressure (i). And like hydrostatic
 Glycocalyx & Ernest Starling :

Starlings principle: water Recent experiment and

retention within the update: transcapillary fluid
vascular compartment is loss seems to be limited by
due to a significant inward- an oncotic pressure gradient
directed colloid osmotic across the endothelial
pressure gradient between glycocalyx, a structure that
the intravascular and was unknown to Ernest
interstitial space Starling

An intact endothelial glycocalyx is a prerequisite

of a functional vascular barrier
32
What triggers the shedding of the
endothelial glycocalyx?
Iatrogenic
acute
hypervolemia

Oxidised
Proteases LDL Atrial
Ischemia/re natriuretic
TNF
perfusion peptide
(ANP)

Degradation of the
endothelial glycocalyx
33
Avoiding perioperative fluid shifting

34
Crystalloid vs Colloid: a misleading discussion
promotes type-1 shifting
Isolated Colloid
Acute
intravascular osmotic
Bleeding
deficit force is lost

Rational
substitution should
be performed with
iso-oncotic colloid

35
How to avoid perioperative uid shifting ?
Preserve endothelial glycocalyx to inhibit
type 2 shift
Release inflammatory mediators, stress, and
ischemia-reperfusion injury can hardly be avoided
Maintaining vascular normovolemia
Protect endothelial glycocalyx sheeding
Prevent interstitial edema
Avoid Hypervolemia is the way to limit type-II shifting
Avoid hypervolemia to prevent ANP release
Intentional prophylactic volume-loading to extend i.v blood volume
prior to induction of anesthesia or to anticipate acute bleeding
might compromise the vascular barrier
Colloids should be infused when intravascular fluid losses occur,
NOT BEFORE
Causal therapy of vasodilation in normovolemic patient caused by
general and/or neuraxial anesthesia is NOT INFUSION OF COLLOIDS.
re-establishing vasotonous with a vasopressor is more
reasonable
37
 The clinical decision to administer i.v fluids in acute
illness is followed by decisions on the amount and
type of fluid to be infused
In fact.patterns of fluid selection are dependent on
local practice patterns and marketing and not
necessarily based on evidence.
Like any other drug, i.v fluids have quantitative &
qualitative adverse effects, with the therapeutic
index depending on the type of fluid and the clinical
setting
Three criteria should be present when start to
administer iv fluid in acute illness :
evidence of fluid responsiveness such as pulse
pressure variation;
presence of signs of tissue hypoperfusion; and
absence of fluid overload
Let see these cases
First case
Woman, 25 years old, 55 kg with a diagnosis of postpartum
hemorrhage. Blood pressure of 80/40 mmHg, HR 130 / min, CRT 4
second.

Second case
Woman, 25 years old, 60 kg with a diagnosis septic shock e.c
peritonitis. She has been resuscitated with 3000 ml RL. Currently
blood pressure 70/40, HR 160 / min.
First Case
Clinical assessment and basic hemodynamic
monitoring
NIBP
ECG
CRT, skin perfusion
SpO2
No doubt
Hypovolemic Shock

FLUID RESUSCITATION
 Do you still need IBP, CVP, lactate,
echocardiography to decide to give
fluid for first case ??

However..
the second is very complicated case,
You have to think twice to give volume for
this patient
Fluid management goals vary depending on the
phase of acute illness and the focus is..

to achieve and maintain adequate effective circulating

volume during the Rescue and Optimization phases
to minimize complications during the Stabilization
phase and..
to restore a more normal fluid balance during De-
escalation phase.
Why is it necessary to detect hypoperfusion
as soon as possible?

Point of NO RETURN

Trauma Anesthesia
Siegel JH, Trauma : Emergency Surgery and Critical Care, 1987
In hypotensive patients the first thought by an
clinician certainly is fluid responsive or not
Curr Opin Crit Care 11:235239. a 2005 Lippincott Williams & Wilkins.

Hemodynamic monitoring is a central aspect of cardiovascular

diagnosis and titration of care.

Circulatory shock results primarily in inadequate tissue blood flow.

Although most forms of shock may show some increase in CO

initially in response to fluid loading, fully one-half of all
hemodynamically unstable ICU patients are not preload responsive
Assessment hemodynamic response to
volume challenge is paramount
To optimize preload (then improve hemodynamic) but
avoid complication
to determine responders (patients who will benefit
from if they are given volume) from non-responders
(patients for whom volume expansion may be
deleterious).
In most studies, > 15 % increase in CO is considered as
a positive response to volume challenge.
Determine who fluid responder is
Flat segment
Preload unresponsiveness
Give fluid..

Be careful
to give fluid
in this area

No more fluid..
Inappropriate fluid management acute
hypervolemia secretion of ANP
degradation of glycocalyx fluid shift
interstitial edema impair tissue oxygenation
END ORGAN DYSFUNCTION
The trouble with volume status assessment
Limited direct bedside CO measurement
Clinical surrogates used:
VS (BP, HR), CRT
examination (chest)
U/O
lab: Hg, serum and urinary Na
ongoing losses (EBL, NG, etc.)
fluid balance charts
CXR (pulmonary congestion)
 The trouble with volume status assessment

Surrogate measures : accurate prediction of volume

status is less than 50% of the time, even by
experienced clinicians
HR, BP, U/O, CVP, labs values lack specificity in identifying volume
deficit do not correlate with CO
lead to over- or under-transfusion of fluids
Goal directed therapy and obtain flow parameters
from CO monitoring will facilitate to manage DO2
Stphan F et al. Br J Anaesth 2001; 86:754
McGee S et al. JAMA 1999;281:1022
 Accumulative clinical studies pointed out that positive
fluid balance and weight gains are associated with a
worse prognosis.
Fluid accumulation within the tissue could alter the
diffusion of oxygen promoting hypoxic cellular
injury.
Fluid resuscitation is recommended as a first-line
treatment, particularly during the first hour, but the
volume and type of fluid that should be used remain
controversial.
The Endothelial Surface Layer (ESL)
Healthy vascular endothelium coated by endothelial
glycocalyx a layer of membrane-bound proteoglycans and
glycoproteins.
 The Endothelial Glycocalyx
Glycocalyx affect endothelial permeability
lPrevent leukocyte and platelet adhesion.
lDecreases inflammation.
lBounds plasma proteins and fluids.
700 ~ 1000 mL of non-circulatory plasma fixed within.
Maintains oncotic gradient despite intravascular and
extravascular equilibration.

Jacob M. et al: The endothelial glycocalyx affords compatibility of starlings principle

and high cardiac interstitial albumin level. Cardiovasc Res 2007; 73:575-86
 Mechanical stress
Endotoxin exposure
Mediator SIRS
Intact glycocalyx ANP(Atrial Natriuretic Peptide) Loss glycocalyx

Hyperglycemia
Reperfusion injury
Oxidized-LDL
 HES 6%, 200
Intact glicocalix
without ANP

HES 6%, 200

with ANP
Loss glicocalix
 Q2. What is known about fluid choice in acute illness? on the luminal side of healthy vasculature7 plays a v
Is there evidence of harm or benefit associated with maintaining vascular integrity.12 13 Concordant wi
specific types? observations, this revised model accounts for th

Revised Starling
Physiological filtration across a
healthy endothelial surface layer
Transendothelial pressure drives

Model flow into the interstitium

Healthy Person
Transcapillary escape
Subglycocalyx space is protein-free of albumin occurs
and the plasma-subglycocalyx across large pores
oncotic pressure difference
opposes filtration There is no reabsorption
across capillary walls

Intravascular space Lymphatic flow is the only

pathway for return of
protein-rich fluid into the
A revised Starling model has been circulation

recognized that the endothelial Interstitial fluid space protein concentration does not
influence filtration
glycocalyx located on the luminal
side of healthy vasculature plays a Albumin is in constant flux across the vascular barrier

vital role in maintaining vascular

integrity. Interstitial space

Fig 1 The revised Starling model in health. Key updates to the original model: overall filtration is much less than predicted by the original
the important forces are the transendothelial pressure difference and the plasma subglycocalyx oncotic pressure difference. Interstiti
pressure is not a determinant of transvascular filtration. There is no reabsorption of fluid into the intravascular space from the interstit
 centred outcomes. Accordingly, the goal is to minimize toxicity. been considered preferable with faster plasma clearance

nloaded from http://bja.oxfordjournals.org/ by guest on January 7, 2016

Clinical context should determine choice in specific situations. (even with repeated administration).26 However as seen in
Albumin is either not widely available or is expensive in most large investigator-initiated RCTs, risks of impaired kidney func-
countries and the Saline versus Albumin Fluid Evaluation (SAFE) tion with HES appear to be persistent, generic, and dose-
study specifically examined safety among nearly 7000 adults dependent.27 It is unclear if these results are generalizable
in the intensive care unit (ICU).20 With respect to1.mortality
Levick or to other semisynthetic colloids, like gelatin or polygeline
JR, Michel CC. Microvascular fluid exchange and the revised Starling principle.
Systemic inflammatory states 2.
Cardiovasc Res2010;87: 198 210
Lee WL, Slutsky AS. Sepsis and endothelial permeability. N Engl J Med 2010; 363: 68191

Physiological filtration across a

damaged endothelial surface layer
Transendothelial pressure still
determines flow into the interstitium e
r spac
ula
c
t ravas
In
albumin flux via
a greater number
of large pores
Conformational changes
in the interstitial matrix
Shedding of the glycocalyx with promote fluid retention
intravascular volume depletion

In systemic inflammatory
states such as surgery and
Lymphatic clearance is overwhelmed resulting in
sepsis, interstitial pressures interstitial oedema

decrease, and porosity Interstitial fluid space protein concentration does not

increases as the integrity of

influence filtration and there is expansion of the
interstitial space

the glycocalyx barrier is lost. Interstital space

Fig 2 The revised Starling model during critical illness. During critical illness, loss of the glycocalyx, reduction in the effective circulating intravascular
volume, and expansion of the interstitial space occur. Expansion of the interstitial space is shown as a relative increase in the proportion of extravas-
cular fluid. Infusion of colloid solution increases the plasma volume, while infusion of crystalloid increases intravascular volumefiltration remains
low in both cases when capillary pressures are low. Conversely, oedema occurs regardless of fluid type when capillary pressures are supranormal.
Beware.
All resuscitation fluids can contribute to the formation of
interstitial oedema and FLUID BALANCE MAY BE MORE
IMPORTANT THAN FLUID TYPE.
Selection of specific fluids should be based on the
understanding that
differences in efficacy are modest, while differences in
safety are significant
Raghunathan K, Murray PT, Beattie WS, Lobo DN, Myburgh J, Sladen R, Kellum JA, Mythen MG, Shaw AD, ADQI XII
Investigators Group: Choice of fluid in acute illness: what should be given? An international consensus. Br J Anaest 2014,
5:772783.
Making an optimal preload in critically ill patients
is very challenging

Under resuscitation Over resuscitation

Ideal
Area
Restriction

Lets go to
Liberal

Goal Directed
Therapy
Goal-Directed Therapy (GDT)
Intensive monitoring and aggressive management of
perioperative hemodynamics in high risk patients to optimize
oxygen delivery
It can be extrapolated in critically illness (i.e sepsis)
Early reports in the literature first appeared around 2000
Standard of care:
most major centres in US
NICE* guidelines in UK for surgical patients
almost all current periop fluid literature

*NICE: National Institute for Health and Clinical Excellence

 Target Resuscitation is
BP = SVR ADEQUATE DO2
X
DO2 = CI x 13.4 x Hb x SaO2
Airway &
Breathing
Support
Preload Contractility Afterload

Volume Inotropes Vasopressor

Vasodilator
SEDATION O2 demand
Vasopressor SVR BP

Inotropik
 Response to Volume Expansion
Volume expansion
Intake of salty food and fluids
Excessive IV fluids / hypervolemia

Right atrial distension

increase venous capacitance

Secretion of ANP

inhibit renin secretion

vasodilation inhibit aldosterone secretion
increased renal NaCl
and H2O excretion
Conclusion
The protection or restoration of glycocalyx might be
considered an important goal
A respectful strategy for the glycocalyx may decrease the
capillary leak and improve tissue oxygenation
giving the right amount of fluids
choosing fluids with no impact on glycocalyx degradation.
Correct hypovolemia and avoiding hypervolemia will
protect the vascular barrier and minimize perioperative and
critically ill fluid shifting

70
 Conclusion

Perioperative fluid shifting to interstitial space is caused by :

wrong infusion solutions associate with a false indication
A decided differential indication of balanced isotonic
crystalloids and iso-oncotic colloids is key to prevent
perioperative fluid shifting :
Crystalloids: to replace extra-cellular losses through insensible
perspiration & urine output
Colloids: therapy of choice to replace acute blood losses below the
transfusion border
Fluid resuscitation should be applied in a goal-directed
manner and targeted to physiologic needs of individual
patients
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Be a longlife
learner...
Thank you