Fluid Therapy and

Hemodynamic Monitoring

Cindy E. Boom
National Cardiovascular Center Harapan Kita
Jakarta - Indonesia

Curriculum Vitae
Name:
Dr. Cindy E.Boom.dr.,SpAn.,KAKV.,KAP
DOB : Duri, Riau April 22
Status : Married , 3 children
Education :
MD : Padjadjaran Univ. 1991
Anestesiologist : Padjadjaran Univ.1999
Cardiac Anesthesiologist : National Heart
Center 2001
Pediatric Cardiac Anesthesiologist :
Children Hospital Boston-MA-USA,2005
PhD : Padjadjaran Univ. 2008
Position : SMF National CV Center
Harapan Kita.

Water Function

Universal solvent
Transport nutrients
Removes waste
Lubricates
Shock absorber
Regulates body temperature

Fluid Compartment Physiology

Models for volumes of distribution of fluids
colloid
saline
glucose

Plasma
3L
4 - 5%

Interstitial
Compartment
10 L

Intracellular
Compartment 30 L
40%

Blood
cells
2L

20%

Composition of extracellular and intracellular

fluids

100
50

Mg++

50
100
150

HCO3Protein

K+

ClPO4- & organic anions

Ca++

Na+

INTRACELLULAR

150

EXTRACELLULAR

Anions

Cations

Six qualitative alterations

1

Hypotonic expansion

Ex. Excess water intake

Hypotonic contraction

Ex. Sodium loss from adrenal insufficiency

Isotonic expansion

Ex. IV drip of 0,9% NaCl

Isotonic contraction

Ex. Hemorrhage, burns

Hypertonic expansion

Ex. Sea water drowning

Hypertonic
contraction

Ex. Severe sweating, fever

Fluid Therapy

RESUSCITATION

Crystalloid

MAINTANANCE

Coloid

Electrolite

Nutrition

Repair
Replacement of an acute
loss (hemoragic, GI loss, 3rd
space)

1. Normal Requirement
2. Nutrition support

CO = SV x HR
Preload

Contractility
Vasoconstriction

Tissue Perfusion

Afterload

ADEQUATE OXYGEN TRANSPORT

Rumus Nuun-Freeman untuk Oxygen Delivery - Available O2

CO ( HR x SV) x O2 content ( Hb x SaO2 x 1,34) + ( pO2 x

0,003 )
Bila disederhanakan : CO x Hb x SaO2 x 1,34
Berarti : Bila CO dinaikkan hingga 2 x, maka Hb bisa turun
hingga nya dan tidak mengurangi Oxygen Delivery.
Av. O2 = 15 x 15 x 100% x 1,34 = 301,5
Av. O2 = 30 x 7,5 x 100% x 1,34 = 301,5

Hypovolemic Shock
Blood Pressure

Cardiac Output /
CO

Stroke Volume
/ SV

Contractility
Preload

Systemic Vascular
Resistance (SVR)

Heart Rate

Afterload

Cardiogenic ShocK
Blood Pressure

Cardiac Output /
CO

Stroke Volume
/ SV

Preload

Systemic Vascular
Resistance (SVR)

Heart Rate

Afterload

Contractility

Circulatory Shock
Blood Pressure

Cardiac Output /
CO

Systemic Vascular Resistance / SVR

Stroke Volume
/ SV

Contractility

Heart Rate

Preload

Afterload

Treatment Concept of Shock

Enhancing perfusion / Oxygen Delivery
DO2 = CO x CaO2
Cardiac
Output

Arterial O2 content

O2 delivery/ DO2 = HR x SV x Hb x SaO2 x 1.34 + Hb x PaO2

Inotropik

Fluids

Contractility

Preload
Vasoactive

Afterload

Transfuse

Partially dependent
on FIO2 & pulmonary
status

Optimize Oxygenation

O2 extraction

O2 utilisation

O2 transport

O2 uptake

Oxygen Delivery

Oxygen Comsumption

ScvO2
Cardiac Output
Stroke
Volume
Preload
- GEDI
- SW
- PPV

Arterial Oxygen
Content

Heart
Rate

Hemoglobin
Hb

Oxgenation
SaO2
Contractiliy
- GEF
- CFI
- dPmx

After Load
- SVRI

Pulmonary edema
- ELVI
- PVPI

Volume

+ -Vasopressors

- Inotropes +

Red Blood Cells

Oxygen Delivery Optimalisation

in Shock

DO2 = CO x Hb x SaO2x1,36

31

Oxygen Delivery Optimalisation

In Shock

DO2 = CO x Hb x SaO2 x 1,36

HR x SV
Preload

Oxygenation/
Ventilation

Afterload

Contractility

DO2 = CO x Hb x SaO2x1,36

HR x SV

Oxygenation/
Ventilation

Mech.
Vent.
Preload

Afterload

Contractility

DO2 = CO x Hb x SaO2x1,36

HR x SV

Oxygenation/
Ventilation

2
Preload

Afterload

Contractility
1

Terapi
Cairan

Mech.
Vent.

DO2 = CO x Hb x SaO2x1,36

HR x SV

Oxygenation/
Ventilation

1
Mech.
Vent.

2
Preload

Afterload

Contractility
1

Terapi
Cairan

Vasoaktif

Transfusi
4

DO2 = CO x Hb x SaO2x1,36

HR x SV

Oxygenation/
Ventilation

1
Mech.
Vent.

2
Preload

Afterload

Contractility
1

Terapi
Cairan

Vasoaktif

Characteristics of Different
Volume Substitutes
IVVolume
Coag

Cryst<Gel<Dex<HSS
Cryst<Alb<Gel=HES<Dex

Anaphylactic

Cryst<HES=Alb<Dex<Gel

Cost

Cryst=Gel<HES<Dex<Alb

Volume Replacement Therapy

Crystalloids

Colloids

Lactated Ringers
Normal Saline
Hypertonic Sodium
Lactate

Albumin

Gelatin

Dextran

HES

Dextrose (free water)

water added to intravascular space

Vascular
space

ECF

Expansions of total body water no volume effect

Isotonic crystalloids
Crystalloids added to intravascular space

Vascular
space

Kt

ECF

Kt = 250 ml.min-1
Svensen et.al, Br.J.Anaesth,
1998

ECF

Proportional expansion of intra- and extravascular spaces

Crystalloids
True solutions
Freely distributed across semipermeable
membrane

Plasma expansion < infused volume

Rapidly excreted

Expansion ECF : Plasma Volume 3:1

Crystalloids
Extracellular space expanders
Limited plasma volume expansion

Maintain urine output

Reduce plasma oncotic pressure

Range of electrolyte content

CHEAP!

Is Normal Saline Normal?

Is 0,9% saline isotonic?
Normal plasma osmolality 280-290 mOsm/L
0,9% saline ~ 308 mOsm/L
Is it physiological?
pH = 6,35
Chloride load can cause acidosis
Abnormal saline?

Who was Ringer?

19th century physician
Worked with frogs heart
Developed his solution to replace frog plasma (Na+
= 130 mmol/l)
Original contained 130 mmol NaCl, plus 5 mmol KCl
+ 2,5 mmol CaCl2 (140 mmol Cl-)
Hartmann introduced 28 mmol NaLactate
Still hypotonic based on frog plasma

Ringers Lactate
Contains 131 mmol Na+, 5.4 mmol K+, 3.5
mmol Ca++, Lactate 28 mmol.
Calcium content may clot blood
Osmolarity = 273 mOsm/l
Lactate metabolised to CO2 and H2O and
converted to HCO3- in kidney

Acetated Ringer
Acetate Bicarbonate
Metabolized by muscular, renal and
cardiac tissues
Acetate is metabolized quickly even in
hemorrhagic shock
Does not increase the risk of lactate
acidosis

Hypertonic Solutions
Hypertonic fluid added to intravascular space

Vascular
space

ECF
ECF
Expansion of intravascular space
Contraction of ECF

Hypertonic Saline (7.5%)

High osmolality (2400 mOsm/L)
Small volume resuscitation
Reduces cerebral no-reflow in CPR
Fischer M Resuscitation 1996

Decreases brain water in head injury

Shelkh AA Crit.Care Med. 1996

Effective for a limited period only

Favre Schwelz.Med.Wochenschr.1996

Reversed trauma-induced immunosuppresion

Colmbra R J.Surg>Res. 1996

Hypertonic Saline Solutions

Benefits
Immediate improvement in hemodynamics
Increase in survival up to 100%
Low cost
Ready availability
No allergic risk or transmission of infectious agents
Risks
Uncontrolled internal hemorrhage
Hypernatremia
Hronic heart failure
Decreased platelet aggregation
Prolonged prothrombin/ partial thromboplastin times
Hypokalemia
Renal failure

Hypertonic Na-Lactate
1020 mosm/L, contains 504 mEq Sodium Lactate
Hypertonic solutions of sodium lactate in limited dose (max: 10
ml/kg in 12 hrs) could be used safely for fluid resuscitation
It will not cause hyperchloremic acidosis
It will increase cardiac output, limited effect on heart rate, a
slight decreased in MAP, a slight increased in PCWP, and a
decreased in SVR.
Lactate would be a good subtrate for energy metabolism of the
heart in the future.

Crystalloids solutions are distributed over the

entire Extracellular space.
And therefore crystalloids are indicated and
most effective when this space is depleted.

COLLOIDS

Colloids
Advantages:
Good Intra Vascular Volume
Prolonged plasma volume support
Moderate volume needed
Minimal risk of tissue edema
Enhances micovascular flow

Colloids
Disadvantages:
Risk of volume overload
Adverse effect on hemostasis
Adverse effect on renal function
Anaphylactic reaction
Expensive

Gelatins

Derived from hydrolyzed bovine collagen

Metabolized by serum collagenase
Histamine release (H1 blockers recommended)
Decreases Von Willebrand factor (VWF)
Bovine Spongiform Encephalopathy:
1:1,000.000

Albumins

Heat treated preparation of human serum

5% (50g/l), 25% (250g/l)
Half of infused volume will stay intravascular
COP = 20mmHg = plasma
25%, COP= 70mmHg, it will expand the vascular
space by 4-5 times the volume infused.
should not be used for volume resuscitation

Cochrane studies support mortality following

albumin infusion

Cardiac decompensation after rapid infusion of 20-25% albumin

Ionized Ca++
Aggravate leak syndrome MOF Enhance bleeding
Imparied Na+ & water excretion renal dysfunction

MW

DS

Max. dose

Plasmasteril
(HETstarch)

240.000

0.7

1.500/day

Pentastarch
(HESsteril)

200.000

0.5

2.500/day

Tetrastarch
(Voluven)

130.000

0.4

3.500/day

Characteristics of Colloids
Product

Name

Albumin

Conc.%

Oncotic
Pressure

Initial
Expansion
%

Stays
(days)

Max.
dose

4,5

20

80-100

200-400

Hemost.

Dext70

Macrod

60-70

120

30-40

1.5g/kg

+++

Dext40

Rheom

10

170-190

200

1.5g/kg

+++

Gelatin

Gelfusin

3-4

42

70-90

HES450/0.7

Plasmas6

24-30

100

120-182

20ml/kg

+++

HES200/0.5

Hesteril

30-37

100

3-4

33ml/kg

HES130/0.4

Voluven

36

100-110

50ml/kg

0-+

0-+

Disadvantages of Colloids
Anafilactic reaction

Coagulopathy
Renal toxic

Gelatin

Starch

Dekstran

Not common

Not common

Common &
severe

No

Yes ( dose
dependent)
Yes

Yes
Not common
(High dose)
No

No

Hepatotoxic

No

Possibly

Tissue depletion

No

Yes
No

Restricted use in renal

failure

No

Yes
No

Advantages of Colloids
Refiling IVF faster than crystalloids
Shock time become shorter
Remains in IVF longer than crystalloids
No interstitial edema
Preserves oncotic pressure effect
No interstitial edema

The goal of volume therapy

To temporarily increase plasma volume until bodys

own mechanisms can correct the hypovolemia.
All regulatory mechanisms are effective within 6
hours
Restore and maintain the normal balance of delivery
and oxygen supply

Best strategy to achieve these goals?

Crystalloids or Colloids?

The crystalloid versus colloid controversy

a never ending story?
Is the optimal approach
crystalloid + colloid??

Which Fluids?

Debate is unresolved
Dextrose solutions replace lost water only
Crystalloids resuscitate ECF
Colloids remain in the vascular compartment
Choose spesific fluids for spesific purposes!

Crystalloids vs. Colloids

Follow the physiologic principle

Not depends on the resuscitator
Depends on the patient
Maintain Hb and coagulation
factor value.

Changes in volume of body compartments

during fluid infusion
Compartment

Glucose 5%

NaCl 0.9%

Colloids

Intravascular

Interstitial

Intracellular

/-

Defek primer

Pilihan cairan

Dehidrasi

IFV

RL/RA

Perdarahan baru

IV

Koloid

Perdarahan lama

IV + IFV

Koloid + RL

IFV : Interstitial Fluid Volume

IV : Intra Vascular

Immunomodulatory effect of
fluid resuscitation

RL/NS in > 100mL/KgBW : proinflammatory

HS : antiinflammatory
HES/colloid : antiinflammatory

Menilai kecukupan volume intra-vaskular suatu

penilaian klinis yang sulit

Tanda2 Klinis ?

Menentukan parameter yang tepat

sebagai indikator kecukupan volume
intravaskuler
Fluid Challenge
menilai respons pasien terhadap
intervensi/ pemberian cairan

Intravascular volume evaluation

Static evaluation

Dynamic evaluation
Technique proposed to evaluate
hypovolemic

Signs of dehydration
Diminished skin turgor
Thirst
Dry mouth
Dry axillae
Hypernatremia, hyperproteinemia,
elevated hemoglobin/hematocrit

Circulatory signs of
hypovolemia

Overt hypovolemic

Masking
hypovolemic

Tachycardia
Arterial hypotension (severe cases)
Increased serum lactate (severe
cases)
Decreased toe temperature

Decreased renal perfusion

Concentrated urine (low urine
sodium concentration, high urine
osmolarity)
Increased blood urea nitrogen
relative to creatinine concentration
Persistent metabolic alkalosis

Fluid Challenge
A method assessing
responsiveness to fluid infusion

Passive Leg Rising

Transient hemodynamic effect of passive leg raising (PLR) on left
ventricular stroke volume or its surrogates could be an alternative
method to detect preload responsiveness in all categories of patients
receiving mechanical ventilation because the effect persists over
several breaths
PLR induces a translocation of venous blood from the legs to the
intra thoracic compartment resulting in a transient increase in right
ventricular and left ventricular preload
PLR as a reversible volume challenge is attractive because it is
easy to perform at the bedside
PLR induces a reversible volume challenge that is proportional to
body size, and does not result in volume overload in non preloadresponsive subjects

Passive Leg Rising

The effects of PLR on cardiac output presumably
depending on the existence of cardiac preload reserve

 Pressures and flow is measured during four sequential steps

A first set of measurements was obtained in the semirecumbent
position (45) (designated base 1)
Using an automatic bed elevation technique, the lower limbs were
then raised to a 45 angle while the patients trunk was lowered in
supine position
A second set of measurements (designated PLR) were obtained
during leg elevation, at the moment when aortic blood flow reached
its highest value
The body posture was then returned to the base 1 position and a
third set of measurements was recorded (base 2)
Finally, measurements were obtained after a 10-min infusion of 500
mL of saline (designated post- VE)

Passive Leg Rising

PLR allows for a rapid and reversible preload challenge without
needing to infuse fluid
Parameter pressure and flow
An increase in aortic blood flow 10% by PLR predicted a volume
expansion induced increase in aortic blood flow 15% with a
sensitivity of 97% and specificity of 94%
The effects of PLR on hemodynamics occurred rapidly after starting
the maneuver since in all responders, the highest value of aortic
blood flow and pulse pressure were observed within the first 30 secs

Conclusions
Fluid derangements are common
Proper monitoring and assesment essential
Fluid therapy should be based on the spesific needs of each
individual patient
Crystalloids are needed for basal fluid requirements and
compensation for internal fluid fluxes
Infusion of large volume of crystalloids for correction of major
intravascular volume deficit includes a considerable risk of tissue
oedema formation and organ dysfunction
Include colloids in the treatment of hypovolemia

 Ultimately, whichever colloid is chosen, they should fulfill the

required principles for hypovolemia
Normalize blood volume
Regulate blood pressure
Stabilize cardiac function
Improve tissue perfusion
Raise oxygen delivery

Significance of Fluid Therapy in Surgery

Fluid therapy

Physiological and
biochemical
changes

Cardiac
preload

an integral and essential part of major surgery procedure especially in cardiac

surgery.

Physiological and biochemical changes in reversibly injured organ /miokardium

occures
Metabolic shifts, fall in glucose levels, reduction tissue ATP levels, decrease in
intracellular pH, onset of oedema and fall in cardiac index and oxigen delivery

Cardiac preload should be maintained for optimal heart function by providing

adequate fluid infusion (crystalloids or colloids)

Solution Containing Halfmolar

Hypertonic Sodium Lactate
Superior due to
Hemodynamic efficacy and body fluid balance
Efficient energy substrate
Fuel for the myocardium to give an optimum cardiac index
Increase cardiac index
Low vascular resistance
Enhance oxygen delivery

Profiling Lactate
Traditional View
a dead-end waste product of glycolysis
due to hypoxia
primary cause of O2 debt
key factor in acidosis-induced tissue
damage

Profiling Lactate
At Present ( Lactate Revolution since 1970s )

were on the midst of a lactate shuttle era

an efficient energy substrate
an important intermediary in metabolic processes
mobile fuel for aerobic metabolism
a mediator of redox state among various compartments
both within and between cells.
a central player in cellular, regional and whole body
metabolism.

Lactic Acids and Lactate

CO2-

CO2H

HO

HO
CH3

CH3

Lactic Acid

Lactate

glucose

glycogen
plasma
membrane

Acidosis

glucose 6-phosphate

ADP
Alcalosis

ATP
ADP

NAD

ATP

NADH

alanine

pyruvate

4
ADP

mitochondrial
membrane ATP

3
NADH + O2

2
NAD + H2O

CO2

lactate

lactate

Compartmentation of lactate metabolism

(Chatham, C.J., Rosiers, C.D., Forder, R.J.: American Journal of Physiology Endocrinology and Metabolism
Vol. 281, 2001)

Glucose

GT

lactate

MCT

G-6-P
lactate

Glycogen
Alanine

Pyruvate

MCT

Extracellular

Intracellular

MCT

Acetyl-CoA
Pyruvate

lactate

MCT

lactate

MCT

lactate

Alanine

Mitochondri
a

Stroke volume index (SVI) (A) and myocardial efficiency (B) treated
with dichloroacetate (DCA) or saline (CON) at the onset of resuscitation

Barbee et al SHOCK 2000;14:208-214.

HSL: Clinical Evidence

I) Completed/ Published studies

15
Healthy
Preop
Postop

Lactate, mM

MID-CAB

10

Mustafa I et al Intensive Care

Med 2003;29:1279-85.

0
-20

20

40

60

time, min

80

100

120

140

Effect of hypertonic sodium-lactate versus sodium-chloride on

cardiac index in post cardiac surgery
CBP-NaLactate

OPCAB-NaLactate

CBP-NaCl

p<0.0001

p<0.0001

p<0.0001

Cardiac Index, L.min-1.m-2

5
4.00.2

4.20.2

3.80.2
3.30.1
3.40.2
2.90.1

1
Before
lactate
infusion

After
lactate
infusion

Before
lactate
infusion

After
lactate
infusion

Before
lactate
infusion

After
lactate
infusion

Mustafa & Leverve, Shock, 2001

Effect of hypertonic sodium-lactate versus sodium-chloride on oxygen

delivery in post cardiac surgery
CBP-NaLactate
p<0.0001

800
Oxygen Delivery, ml.min-1.m-2

OPCAB-NaLactate

CBP-NaCl

p<0.0001

p<0.001

700
600
500

58624

56123

55127

45423

48425
44320

400
300
200
Before
lactate
infusion

After
lactate
infusion

Before
lactate
infusion

After
lactate
infusion

Before
lactate
infusion

After
lactate
infusion

Mustafa & Leverve, Shock, 2001

Effect of hypertonic infusion (lactate versus NaCl)

on acide base status

Mustafa & Leverve, Shock 2002

P=0.0242

P<0.0001

Hemodynamic Effects

p = 0.002

p = 0.214

HSL

HSL

SVRI and PVRI were lower in HSL group as compared to RL group

HSL has a lowering effect on vascular resistance which is responsible

for decreasing the cardiac work, and consequently resulting in higher
cardiac index

Tekanan Arteri Pulmonal Rerata, mmHg

80

75

70

65

60
Tekanan Arteri Rerata, mmHg

55
B
L-1
R

21.5

21
MPAP
L-2

22.5

RL

22

HSL

84

82

80

78

76

74

72

70

Tekanan Vena Sentral, mmHg

85

Tekanan Baji Kapiler Paru, mmHg

Denyut Jantung, denyut/menit

Preload Parameters
86
12

68
B
L-1

23
R
11

L-2

13.5

13
PCWP

10
9

6
B

14.5

RL

14

HSL

L-1
R
L-2

= RL

= HSL

Cardiac Index
Cardiac index graphs in (a) both groups and (b) HSL group:
(a)
***

(b)
*

***

***

4.5

3.5

CI, L/menit.m2

CI, L/menit.m2

2.5
2
1.5
1

3.5
3
2.5
2
1.5
1

0.5

0.5

0
B

L-1

L-2

L-1

Note: (a) : RL
: NLH (b) : 26%-40%
: 25%
* : significant; ** : very significant; *** : sangat sangat bermakna

L-2

Delta Cardiac Index

Delta of Cardiac Index in
Various Ejection Fraction

Delta of Cardiac Index

2
1.5
1
2
3
4

1
0.5
0
21 21 25 27 28 29 32 32 32 33 33 33 34 34 34 34 34 35 35 36 36 37 37 37 37 37 38 39 39 39 40 40 40

-0.5
Ejection Fraction

Tissue Oxygenation (DO2)

Oxygen delivery graphs in (a) both groups and (b) HSL group:
(a)

**

900

(b)

**

800

1000

DO2, mL/menit

700

DO2, mL/menit

1200

600
500
400
300

800
600
400

200
200

100
0

0
B

Note: (a)

L-1

: RL

: HSL (b)

L-2

: 26%-40%

: 25%

L-1

L-2

Tissue
TissueOxygenation
Oxygenation(DO
(DO2)2)

Delta of Oxygen Delivery

Delta of Oxygen Delivery in

Various Ejection Fraction
1.5
1.3
1.1
0.9
0.7
0.5
0.3
0.1
-0.1
-0.3
-0.5

1
2
3
4
21 21 25 27 28 29 32 32 32 33 33 33 34 34 34 34 34 35 35 36 36 37 37 37 37 37 38 39 39 39 40 40 40

Ejection Fraction

3.5
p = 0.0017
3.0

2.0

300

3000

Load-2

Baseline Load-1
350

2500

2000
p = 0.019
1500

p = 0.0130

400

350

Mt

450

2.5

Baseline Load-1
SVRI, dyn.s.cm-5

500

DO2, mL.min-1

4.0

PVRI, dyn.s.cm-5

cardiac index, L.min-1.m-2

RL
HSL

Mt

Load-2

300
250

p = 0.0356

200
150
100

1000

Baseline Load-1

Mt

Load-2

Baseline Load-1

Mt

Load-2

Boom CE PhD Dissertation

Hyperosmolar sodium-lactate infusion during cardiac surgery

Figure 2. Intra-operative changes in body fluids, sodium and potassium excretion in patients treated with RL or
HL. White columns: patients treated with RL; black columns: patients treated with HL. Panel A: urinary output
(L); Panel B: cum ulative fluid intakes (L); Panel C: body fluid balance (L); Panel D: sodium excretion output
(mmol); Panel E: chloride excretion (mmol); E: sodium/chloride ratio. Results are expressed as meanssem,
statistical comparisons between RL and HL by unpaired studentst test for: urine output (p<0.0001); cumulative
fluid intakes (p<0.0001); body fluid balance (p<0.0001), sodium excretion (p<0.0001) and chloride excretion
(p<0.0001). Sodium /chloride ratio was expressed as median, comparisons between HL and RL by the nonparametric test of Man & Withney (p=0.0037).

Boom CE PhD Dissertation

Afterload Parameters
350

2500

PVRI, dynes.detik/cm5.m2

SVRI, dynes.detik/cm5.m2

3000

**

2000
1500
1000
500
0

250
200
150
100
50
0

Note:

300

L-1

: RL

: HSL

L-2

L-1

L-2

Conclusion
Lactate is a major physiological substrate
It can be oxidized, recyled, or used as precursor for other energy metabolism

It is of major interest in acute conditions

Energetic substrate for brain, heart, kidney
Prevention of ischemia-reperfusion injury

Hypertonic Sodium-Lactate possesses several cardiac

and hemodynamic properties

Increase cardiac output

Decrease pulmonary and systemic vascular resistance
Increase oxygen delivery
Increase total urine output
Decrease total fluid balance

Osmolarity
mOsm/L

LactateNa+

HSL

Cl-

K+

Ca++

Total

Tonicity
mOsm/L

504.15

504.15

504.15

6.74

6.74

4.02

4.02

1.36

1.36

1020.42

516.25

Increases
Intravascular
volume

Improves
Hemodynamic
Inotropic effect +
vascular resistance

Tissue perfusion
=

HSL

Prevents/Corrects
Metabolic Acidosis

Prevents/Corrects
Cellular edema

Improves
Capillary leakage

Urine output
MAP
Mix Ven O2 sat

HSL (Totilac) Acute Toxicology Study

by Prof. Elin Yulinah, ITB (2004)

Objective:
To determine the LD50 (Lethal Dose) of Totilac (up to 5000mg/kg bw)
Methods:
6 groups of mice (male & female) were given different doses of Totilac (from
0mg/kgBW to 5000mg/kgBW)
Results:
Clinical Symptoms due to intoxication: none found
Death occurrence: administration of 5000mg/KWBW did not cause any death
Body weight: no significance differences between control and test treatment
group
Macroscopic observation of pathological organ: none
Defecation: increase of defecation in female (but not abnormal)
Conclusion:
The intravenous LD50 of the test substance in mice is above 5000 mg/kg BW,
therefore it is safe and the study can be continued to toxicity sub-chronic
study.

Experimental/Clinical Proofs

Increases
Intravascular
volume
Improves
Hemodynamic
Inotropic effect +
vascular resistance

Tissue perfusion
=

Totilac

Prevents/Corrects
Metabolic Acidosis

Prevents/Corrects
Cellular edema

Improves
Capillary leakage

Urine output
MAP
Mix Ven O2 sat

Effect of acute infusion of sodium lactate or sodium chloride

in patients after cardiac surgery

Delta hemoglobin, g

0.0
-0.1
-0.2
-0.3
-0.4

-0.5

-0.6

1 = change between 0 and 15 minutes (end of infusion)

2 = change between 0 and 120 minutes
NaCl or Na-lactate was infused during 15 minutes
*p < 0.05 versus 0 (univariate t test)
$ p < 0.05 lactate versus chloride (unpaired student t test)

Na-lactate, n = 40
Na-chloride, n = 40

Mustafa,PhD dissertation

Increases
Intravascular
volume

Totilac

Improves
Hemodynamic
Inotropic effect +
vascular
resistance
Prevents/Corrects
Metabolic Acidosis

Prevents/Corrects
Cellular edema

Improves
Capillary leakage

Tissue perfusion
=

Urine output
MAP
Mix Ven O2 sat

Effect of hypertonic infusion (lactate versus NaCl)

on hemodynamic

Mustafa & Leverve, Shock, 2002

Effect of acute infusion of sodium lactate or sodium chloride

on CI and SV in patients after cardiac surgery
15

*
0.6

*
*

0.4

0.2

Stroke volume

Delta Cardiac index

0.8

*
10

0
1

1 = change between 0 and 15 minutes (end of infusion)

2 = change between 0 and 120 minutes
NaCl or Na-lactate was infused during 15 minutes
*p < 0.05 versus 0 (univariate t test)
$ p < 0.05 lactate versus chloride (unpaired student t test)

Na-lactate, n = 40
Na-chloride, n = 40

Mustafa,PhD dissertation

Effect of acute infusion of sodium lactate or sodium chloride

on vascular resistance indexes (SVRI & PVRI)
in patients after cardiac surgery

Delta SVRI, dyne s/cm2 m2

0
-200

-400

-600
-800

10
Delta, PVRI, dyne s/cm2 m2

200

1 = change between 0 and 15 minutes (end of infusion)

2 = change between 0 and 120 minutes
NaCl or Na-lactate was infused during 15 minutes
*p < 0.05 versus 0 (univariate t test)
$ p < 0.05 lactate versus chloride (unpaired student t test)

0
-10

-20
-30
-40
-50

*
1

Na-lactate, n = 40
Na-chloride, n = 40

Mustafa,PhD dissertation

Increases
Intravascular
volume

Improves
Hemodynamic
Inotropic effect +
vascular resistance

Tissue perfusion
=

Totilac

Prevents/Corrects
Metabolic Acidosis
Prevents/Corrects
Cellular edema

Improves
Capillary leakage

Urine output
MAP
Mix Ven O2 sat

Effect of hypertonic infusion (lactate versus NaCl)

on acide base status

Mustafa & Leverve, Shock 2002

Increases
Intravascular
volume

Improves
Hemodynamic
Inotropic effect +
vascular resistance

Tissue perfusion
=

HSL

Prevents/Corrects
Metabolic Acidosis

Prevents/Corrects
Cellular edema
Improves
Capillary leakage

Urine output
MAP
Mix Ven O2 sat

Effect of acute infusion of sodium lactate or sodium chloride

on pH and bicarbonate in patients after cardiac surgery
$
*

0.05
0.025
0
-0.025

*
1

8
Bicarbonate, mmol/L

Deelta pH, units

0.075

4
2

-2
-4

1 = change between 0 and 15 minutes (end of infusion)

2 = change between 0 and 120 minutes
NaCl or Na-lactate was infused during 15 minutes
*p < 0.05 versus 0 (univariate t test)
$ p < 0.05 lactate versus chloride (unpaired student t test)

Na-lactate, n = 40
Na-chloride, n = 40

Increases
Intravascular
volume

Improves
Hemodynamic
Inotropic effect +
vascular resistance

Tissue perfusion
=

HSL

Prevents/Corrects
Metabolic Acidosis

Prevents/Corrects
Cellular edema
Improves
Capillary leakage

Urine output
MAP
Mix Ven O2 sat

Cell volume regulation according electroneutrality and tonicity

principles:
the case of hyperosmolar sodium-lactate (II)

Electroneutrality

+
Na
~
Na+

Cl-

K+

Na+out > Cl-out

Cl- in is released out
together with water

ClWater

Tonicity Equilibrium
[Na++Cl- ]out
>>
[K++Cl- ]in
= further flux of water in->out
= further cell shrinkage

Effect of acute infusion of sodium lactate or sodium chloride

on plasma sodium and chloride in patients after cardiac surgery

2
0

Delta plasma Chloride, mmol/L

Delta plasma Sodium, mmol/L

$
*

10

$
*

7.5
5

*
*

2.5
0

1 = change between 0 and 15 minutes (end of infusion)

2 = change between 0 and 120 minutes
NaCl or Na-lactate was infused during 15 minutes
*p < 0.05 versus 0 (univariate t test)
$ p < 0.05 lactate versus chloride (unpaired student t test)

Na-lactate, n = 40
Na-chloride, n = 40

Mustafa,PhD dissertation

Totilac: Clinical Evidence

Neuronally functional success (%) after

5-min hypoxia and 30-min reoxygenation

Lactate and brain recovery from ischemia-reperfusion injury

**

100

**

80
60

*
*

40
20
*
3.0 mM 3.0 mM 6.0 mM 6.0 mM
Glucose Glucose
Lactate Lactate
+
+
0.2mM
0.2 mM
IAA
IAA

1.5 mM
Glucose
+
3.0 mM
Lactate

Slices with lactate showed a significantly higher degree of recovery

Slices with anaerobic lactate production by pre-hypoxia glucose exhibited functional recovery

80% recovery even glucose utilization was blocked during the later part of the hypoxic period
and reoxygenation

Slices in which anaerobic lactate production was blocked during the initial stage of hypoxic did
not recover

Schurr et al, Brain Res., 1997, 744, 105 -11

Ichai et al, Intensive Care Medicine, 2008

The Use of Hypertonic Sodium Lactate Solution

in Intracranial Tumor Removal Surgery. Is it safe?
An observational study

Doddy Tavianto, Marsudi Rasman, Deddy Koesmayadi

Department of Anesthesiology and Reanimation, Faculty of Medicine Padjadjaran University
Hasan Sadikin General Hospital, Bandung, Indonesia

Background
The benefit of hypertonic sodium lactate in Coronary Artery
Bypass Grafting Surgery has been documented for its lactate
and hypertonicity properties leading to improvement of cardiac
performance and hemodynamic status. There are several
evidences from animal and human studies supporting the
clinical benefit of hypertonic solution in improving cerebral
blood flow and reducing intracranial pressure in neurotrauma.
Lactate, previously thought to be a waste product, recently gets
its new paradigm for its role as a fuel for cells containing
mitochondrion especially cardiac and brain cells. Based on
hypothesis that the hypertonicity and lactate properties have
the beneficial effects for the brain, we have conducted an
observational study on the use of hypertonic sodium lactate for
intracranial tumor removal surgery

Result
Result

Pre-Operative and 6 Hours Post-Operative

Laboratory Examination

Objective

To observe the safety of hypertonic sodium lactate in

Methods
intracranial tumor removal surgery
10 patients underwent intracranial tumor removal surgery,
ASA class 1 and 2, Glasgow Coma Scale = 15
Normal level of blood sodium and lactate
No history of renal and liver disease.
Anesthesia technique:
- Induction: propofol 2 mg/kgBW, vecuronium 0.2
mg/kgBW, fentanyl 3 g/kgBW,
O2 :N2O=50%:50%, isoflurane 2-3 volume%
- Maintenance: propofol 200 mg - 300 mg/hr,
isoflurane 0.4 volume%, fentanyl 1 g/kgBW,
vecuronium 0.1 mg/kgBW as needed.
EtCO2 keep between 25-30 mmHg
Hypertonic lactate solution (Totilac, Innogene Kalbiotech
Pte.Ltd, PT Kalbe Farma, Indonesia) continuously infused at
dose of 1.5 ml/kgBW/hr during the whole surgical periode.
Additional fluid: Ringer Lactate, Hydroxy Ethyl Starch solution
as needed to maintain MAP 65-75 mmHg

Good surgical field due to reduced brain tissue edema

No mannitol needed during surgery

All patients were extubated already in the operating theatre
No significant changes in arterial pH, blood sodium and lactate
level
No adverse events found during the treatment

Conclusion
Hypertonic sodium lactate solution is safe to be used in intracranial tumor
removal surgery. Good surgical field due to reduced brain tissue edema
were observed in all patient

Acknowledgment
Great thanks to Prof. Kahdar Wiriadisastra, PhD, Benny Atmadja Wiryomartani MD,
Setyowidhi, MD, MZ Arifin MD and all staffs of Department of Neurosurgery, Hasan
Sadikin General Hospital and St. Borromeus Hospital, Bandung, Indonesia.

Totilac vs NaCl 0.9% Pre-Loading Spinal Anesthesia in TURP

(Dandy M, Ike Sri Redjeki, Tatang Bisri)

Site: Hasan Sadikin Hospital, Indonesia

Subject Size and Inclusion Criteria :

22 TURP patients

Methodology (in both Totilac and NS groups):

4 cc/kgBW/20 min before spinal anesthesia

Results:

Plasma sodium level, osmolality, arterial pH was maintained better

in Totilac group
None of patients in Totilac group required ephedrine vs. 5
patients in NS (ephedrine is injected if decrease of BP is > 30% after
spinal anesthesia)

111

TOTILAC vs NaCl 0.9% for TURP

Sodium hypetronic lactate (Totilac)

4mL/kgBW in 20 minutes

Sodium chloride 0.9% (NaCl) 4

mL/kgBW in 20 minutes

Check sodium, osmolarity, pH

Spinal anesthetic : Bupivacaine 2-2.5 mL

TURP operation
30 minutes of operation check sodium, osmolality & pH
112

Osmolality

143

295

142
141
NLH

140

NaCl 0.9%

139
138
137

Osmolalitas (mOsm/kg)

Konsentrasi Natrium (mEq/L)

Sodium Level
294
293
292

NLH

291

NaCl 0.9%

290
289
288
287

Awal

Cairan Awal Durante Op Pasca Op

Awal

Cairan Awal Durante Op

PascaOp

The level of Na serum & osmolality in TOTILAC is higher bus still within normal
boundary prevents hyponatremia
113

Lactate

pHa

6
5
HSL

NaCl

3
2
1
0
Prehidrasi

Cairan Awal

Durante

Pasca op

pH

Laktat (mmol/L)

7.46
7.44
7.42
7.4
7.38
7.36
7.34
7.32
7.3
7.28
7.26

HSL
NaCl

Prehidrasi

Cairan Awal

Durante

Pasca op

The lactate level in TOTILAC is higher but then itll decrease; this
means that lactate is metabolized
In TOTILAC there was no acidosis, while in NaCl 0.9% there was acidosis.
114

Burn Wound
Clinical practice by Dr. Poengky,
plastic surgeon in RSPP, Indonesia:
Totilac represents 2x the volume required, with
maximum of 4 bags per day
For example: the volume required on the first day is
8 liters, when 1 liter of Totilac is used, then it will
represent around 2 L of fluid. therefore 6 L of
other fluids is infused
Total real infusion will only be 7 Liters (smaller total
volume) to fulfill the needs of 8 liters of fluid loss

Totilac vs RL in Dengue Shock in pediatric patients

Study Procedure
Group I : Hypertonic Sodium Lactate (HSL) 5 mL/kg (15 minute)
Group II: Ringer Laktat (RL) 20 mL/kg (15 minutes)
If shock persist: repeat once time (x1)
If shock reverse:
Group I: continued by HSL 1 mL/kg until 12 hours, then
followed by RL as outlined on DSS SOP
Group II : treated as outlined on DSS SOP
Recurrent shock :
Group I : HSL 5 mL/kg 1x HES 130/0,4 RL (DSS SOP)
Group II : as outlined on DSS SOP

Blood Pressure
Systole Blood Pressure

Systole (mmHg)

120.00
100.00
80.00

Totilac

60.00

RL

40.00
20.00
0.00
0

0.25

0.5

12

18

24

Hour of treatment (H)

p>0.05 (no significant difference) between Totilac and RL group in BP

Diastole (mmHg)

Diastole Blood Pressure

80.00
70.00
60.00
50.00

Totilac

40.00
30.00
20.00
10.00
0.00

RL

0.25

0.5

Hour of treatment (H)

12

18

24

Cumulative fluid balance in 24H

Cumulatif fluid balance

Cumulative fluid balance

(ml)

2500.00
2000.00
1500.00
Totilac

1000.00

RL

500.00
0.00
-500.00

0.25 0.5

12

18

24

Hour of treatment

Note: Fluid balance= fluid intake-urine output

Totilac group show very significant lower fluid balance compare to RL group, even
until 12 H after Totilac was stopped (p value:0.000)

Injury
Trauma, Sepsis, Ischemia, Hypoxia, Cardiogenic

capillary leakage
cell volume (swelling effect)
Interstitial edema
Fluid administration
Crystalloids, Colloids,
Blood, Plasma or Albumin

Intravascular volume
Tissue perfusion

Intravascular Volume
-hemorrhage
-vasodilation
-capillary leakage
-urinary losses (DKA)

Vasomotricity
Dysregulation

Hemodynamic failure

-cardiac failure
-cardiogenic shock

Low Tissue Perfusion

Metabolic acidosis
pH, Bicarbonate, BE

Interstitial Edema
Clinical signs
Hte, Hb, Albumin

-CO/CI
-MAP
-Urine output
-MV ox sat
-(lactate?)

Cellular Swelling
(edema)
Natremia

Conclusion
Lactate is a major physiological substrate
It can be oxidized, recyled, or used as precursor for other energy metabolism

It is of major interest in acute conditions

Energetic substrate for brain, heart, kidney
Prevention of ischemia-reperfusion injury

Hypertonic Sodium-Lactate possesses several cardiac

and hemodynamic properties

Increase cardiac output

Decrease pulmonary and systemic vascular resistance
Increase oxygen delivery
Increase total urine output
Decrease total fluid balance

Conclusion
Sodium-lactate as new therapeutic concept
in clinical practice and critical care!
It is metabolized and provides energy to almost every cells
(including the brain!)
It is a preferred source immediately after ischemia
Its infusion to the patient
improves hemodynamic after cardiac surgery
corrects metabolic acidosis
decreases cellular volume (correction of cellular edema) by
attracting intracellular chloride (maintenance of
electroneutrality)
Induces a powerful diuretic effect with a negative fluid
balance, without involving any hypovolemia

Thank You..