Terapi Cairan, HD Monitoring, Totilac Plbg

8/10/2019 Terapi Cairan, HD Monitoring, Totilac Plbg

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Fluid Therapy and

Hemodynamic Monitoring

Cindy E. BoomNational Cardiovascular Center Harapan Kita

Jakarta - Indonesia


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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.


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Water Function

Universal solvent

Transport nutrients

Removes waste

Lubricates

Shock absorber

Regulates body temperature


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Fluid Compartment Physiology

Models for volumes of distribution of fluids

Plasma

3 L

4 - 5%

Blood

cells

2 L

Interstitial

Compartment

10 L

Intracellular

Compartment 30 L

40%

colloid

saline

glucose

20%


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Composition of extracellular and intracellularfluids

INTRACELLULAR

EXTRACELLULAR

Na+

K+

Ca++

Mg++

Cl-

PO4-&

organicanions

HCO3-

Protein

Cations Anions150

100

50

0

50

100

150


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Six qualitative alterations

1 Hypotonic expansion Ex. Excess water intake

2 Hypotonic contraction Ex. Sodium loss from adrenal insufficiency

3 Isotonic expansion Ex. IV drip of 0,9% NaCl

4 Isotonic contraction Ex. Hemorrhage, burns

5 Hypertonic expansion Ex. Sea water drowning

6 Hypertonic

contraction

Ex. Severe sweating, fever


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Fluid Therapy

RESUSCITATION MAINTANANCE

ElectroliteColoidCrystalloid Nutrition

Replacement of an acute

loss (hemoragic, GI loss, 3rd

space)

1. Normal Requirement

2. Nutrition support

Repair


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Preload Contractility Afterload

Vasoconstriction

Tissue Perfusion

CO = SV x HR


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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


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Hypovolemic Shock

Blood Pressure

Cardiac Output /

CO

Stroke Volume/ SV

Contractility Afterload

Heart Rate

Systemic Vascular

Resistance (SVR)

Preload


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Cardiogenic ShocK

Blood Pressure

Cardiac Output /

CO

Stroke Volume/ SV

Afterload

Heart Rate

Systemic Vascular

Resistance (SVR)

Preload

Contractility


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Circulatory Shock

Blood Pressure

Cardiac Output /CO

Stroke Volume/ SV

Contractility Preload Afterload

Heart Rate

Systemic Vascular Resistance / SVR


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Treatment Concept of Shock

Enhancing perfusion / Oxygen Delivery

DO2 = CO x CaO2

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

Cardiac

Output Arterial O2content

Inotropik

Contractility

Vasoactive

Fluids

Preload

Afterload

Transfuse Partially dependent

on FIO2& pulmonary

status


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O2uptake O2transportO2extraction O2utilisation

Optimize Oxygenation

-

Oxygen Delivery Oxygen Comsumption

ScvO2Cardiac Output Arterial Oxygen

Content

Stroke

VolumeHeart

RateOxgenation

SaO2

Hemoglobin

Hb

Preload-GEDI

- SW

- PPV

After Load- SVRI

Contractiliy- GEF

- CFI

- dPmx

Pulmonary edema

- ELVI

- PVPI

VolumeVasopressors Inotropes

Red Blood Cells+- +

-+ - +


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Oxygen Delivery Optimalisation

in Shock

DO2 = CO x Hb x SaO2x1,36

31


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Oxygen Delivery Optimalisation

In Shock

DO2 = CO x Hb x SaO2 x 1,36

Oxygenation/

VentilationHR x SV

Preload Afterload

Contractility


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Oxygenation/VentilationHR x SV

Preload Afterload

Contractility

1Mech.Vent.


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Preload Afterload

Contractility

1Mech.

Vent.

1

TerapiCairan

2


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Preload Afterload

Contractility

1Mech.Vent.

1TerapiCairan

2

3Vasoaktif


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Preload Afterload

Contractility

1Mech.Vent.

1TerapiCairan

2

3

Vasoaktif

Transfusi

4


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Characteristics of DifferentVolume Substitutes

IVVolume Cryst


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Volume Replacement Therapy

Crystalloids Colloids

Lactated Ringers

Normal Saline

Hypertonic Sodium

Lactate

Albumin Gelatin Dextran HES


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Dextrose (free water)

Vascularspace

water added to intravascular space

Expansions of total body water no volume effect

ECF


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Isotonic crystalloids

ECF

Kt= 250 ml.min-1

Svensen et.al, Br.J.Anaesth,

1998

ECF

Vascular

space Kt

Proportional expansion of intra- and extravascular spaces

Crystalloids added to intravascular space


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Crystalloids

True solutions

Freely distributed across semipermeablemembrane

Plasma expansion < infused volume

Rapidly excreted

Expansion ECF : Plasma Volume 3:1


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Crystalloids

Extracellular space expanders

Limited plasma volume expansion

Maintain urine output

Reduce plasma oncotic pressure

Range of electrolyte content

CHEAP!


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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?


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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 hypotonicbased on frog plasma


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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 CO2and H2O and

converted to HCO3

- in kidney


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Acetated Ringer

AcetateBicarbonate

Metabolized by muscular, renal and

cardiac tissues Acetate is metabolized quickly even in

hemorrhagic shock

Does not increase the risk of lactateacidosis


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Hypertonic Solutions

ECF

ECF

Vascular

space

Expansion of intravascular space

Contraction of ECF

Hypertonic fluid added to intravascular space


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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


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Hypertonic Saline Solutions

Immediate improvement in hemodynamics

Increase in survival up to 100%

Low cost

Ready availability

No allergic risk or transmission of infectious agents

Benefits

Uncontrolled internal hemorrhage

Hypernatremia

Hronic heart failure

Decreased platelet aggregation

Prolonged prothrombin/ partial thromboplastin times Hypokalemia

Renal failure

Risks


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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 theheart in the future.


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Crystalloids solutions are distributed over theentire

Extracellular space.

And therefore crystalloids are indicated and

most effective when this space is depleted.


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COLLOIDS

ll d


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Colloids

Advantages:

Good Intra Vascular Volume

Prolonged plasma volume support Moderate volume needed

Minimal risk of tissue edema

Enhances micovascular flow


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Colloids

Disadvantages:

Risk of volume overload

Adverse effect on hemostasis

Adverse effect on renal function

Anaphylactic reaction

Expensive


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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


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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 vascularspace by 4-5 times the volume infused.

should not be used for volume resuscitation


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Cochrane studies support mortality following

albumin infusion

Cardiac decompensation after rapid infusion of 20-25% albumin

Ionized Ca++ Aggravate leak syndrome MOFEnhance bleeding

Imparied Na+ & water excretion renal dysfunction


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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


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Characteristics of Colloids

Product Name Conc.% Oncotic

Pressure

Initial

Expansion

%

Stays

(days)

Max.

dose

Hemost.

Albumin 4,5 20 80-100 200-400 0

Dext70 Macrod 6 60-70 120 30-40 1.5g/kg +++

Dext40 Rheom 10 170-190 200 6 1.5g/kg +++

Gelatin Gelfusin 3-4 42 70-90 7 0-+

HES450/0.7 Plasmas6 6 24-30 100 120-182 20ml/kg +++

HES200/0.5 Hesteril 6 30-37 100 3-4 33ml/kg +

HES130/0.4 Voluven 6 36 100-110 50ml/kg 0-+

i d f ll id


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Disadvantages of Colloids

Gelatin Starch Dekstran

Anafilactic reaction

Coagulopathy

Renal toxic

Hepatotoxic

Tissue depletion

Restricted use in renal

failure

Not common

No

No

No

No

No

Not common

Yes ( dose

dependent)

Yes

Possibly

Yes

Yes

Common &

severe

Yes

Not common(High dose)

No

No

No


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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


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Best strategy to achieve these goals?

Crystalloids or Colloids?

The crystalloid versus colloid controversy

a never ending story?

Is the optimal approach

crystalloid + colloid??


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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!

ll d ll d


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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


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Changes in volume of body compartmentsduring fluid infusion

Compartment Glucose 5% NaCl 0.9% Colloids

Intravascular

Interstitial -

Intracellular / - -


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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


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Immunomodulatory effect offluid resuscitation

RL/NS in > 100mL/KgBW : proinflammatory

HS : antiinflammatory

HES/colloid : antiinflammatory

Menilai kecukupan volume intra-vaskularsuatu


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p

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


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Intravascular volume evaluation

Static evaluation Dynamic evaluation

Technique proposed to evaluate

hypovolemic

Overt hypovolemic Masking

hypovolemic

Fluid Challenge

A method assessing

responsiveness to fluid infusion

Signs of dehydrationDiminished skin turgor

Thirst

Dry mouth

Dry axillae

Hypernatremia, hyperproteinemia,

elevated hemoglobin/hematocrit

Circulatory signs ofhypovolemiaTachycardia

Arterial hypotension (severe cases)

Increased serum lactate (severe

cases)

Decreased toe temperature

Decreased renal perfusionConcentrated urine (low urine

sodium concentration, high urineosmolarity)

Increased blood urea nitrogen

relative to creatinine concentration

Persistent metabolic alkalosis

P i L Ri i


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Passive Leg Rising

Transient hemodynamic effect of passive leg raising (PLR) on leftventricular stroke volume or its surrogates could be an alternativemethod to detect preload responsiveness in all categories of patientsreceiving mechanical ventilation because the effect persists overseveral breaths

PLR induces a translocation of venous blood from the legs to theintra thoracic compartmentresulting in a transient increase in rightventricular 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 preload-responsive subjects

P i L Ri i


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Passive Leg Rising

The effects of PLR on cardiac output presumably

depending on the existence of cardiac preload reserve


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Pressures and flow is measured during four sequential steps

A first set of measurements was obtained in the semirecumbentposition (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 insupine position

A second set of measurements (designated PLR) were obtainedduring leg elevation, at the moment when aortic blood flow reachedits highest value

The body posture was then returned to the base 1 position and athird set of measurements was recorded (base 2)

Finally, measurements were obtained after a 10-min infusion of 500mL of saline (designated post- VE)

P i L Ri i


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Passive Leg Rising

PLR allows for a rapid and reversible preload challenge without

needing to infuse fluid

Parameterpressure 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


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Ultimately, whichever colloid is chosen, they should fulfill therequired principles for hypovolemia

Normalize blood volume

Regulate blood pressure

Stabilize cardiac function

Improve tissue perfusion

Raise oxygen delivery


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Significance of Fluid Therapy in Surgery

Fluid therapy

an integral and essential part of major surgery procedure especially in cardiacsurgery.

Physiological andbiochemical

changes

Physiological and biochemical changes in reversibly injured organ /miokardiumoccures

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

Cardiacpreload

Cardiac preload should be maintained for optimal heart function by providingadequate fluid infusion (crystalloidsor colloids)

S l ti C t i i H lf l


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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


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Profiling Lactate

a dead-end waste product of glycolysisdue to hypoxia

primary cause of O2 debt

key factor in acidosis-induced tissue

damage

Traditional View


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Profiling Lactate

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 compartmentsboth within and between cells.

a central player in cellular, regional and whole bodymetabolism.

At Present ( Lactate Revolution since 1970s )


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Lactic Acids and Lactate

HC

HO

CH3

CO2H

HC

HO

CH3

CO2-

Lactic Acid Lactate

glucose glycogen


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glucose 6-phosphate

pyruvate

NAD

NADH

ADP

ATP

lactate lactate

H+ H+

ATP

ADP

Acidosis

Alcalosis

alanine

1

34

+

-

-

plasmamembrane

mitochondrialmembrane

ADP

ATP

NADH + O2

NAD + H2O

CO2

2

Compartmentation of lactate metabolism(Chatham C J Rosiers C D Forder R J : American Journal of Physiology Endocrinology and Metabolism


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

Vol. 281, 2001)

Glucose GT G 6 P Glycogen

lactate

lactate

lactate lactate lactate

MCT

MCT

MCT

MCT

MCT

Pyruvate

Pyruvate

Acetyl CoA

Alanine

Alanine

Extracellular Intracellular

Mitochondri

a

S k l i d (SVI) (A) d di l ffi i (B) d


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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.


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HSL: Clinical Evidence

I) Completed/ Published studies


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0

5

10

15

-20 0 20 40 60 80 100 120 140

Healthy

Preop

PostopMID-CAB

Lacta

te,mM

time, min

Mustafa I et al Intensive Care

Med 2003;29:1279-85.


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Effect of hypertonic sodium lactate versus sodium chloride on


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1

2

3

4

5

6

CardiacIndex,

L.m

in-1.m

-2

Afterlactateinfusion

Beforelactateinfusion





2.90.1

3.80.2

3.40.2

4.00.24.20.2

3.30.1

p


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200

300

400

500

600

700

800

OxygenDelivery,ml.min-1.m

-2

44320

58624

48425

5512756123

45423







p


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P=0.0242

P


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

Hemodynamic Effects

HSL HSL

p = 0.214p = 0.002

HSL has a lowering effect on vascular resistance which is responsible

for decreasing the cardiac work, and consequently resulting in higher

cardiac index


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P l d P t


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55

60

65

70

75

80

85

B L-1 R L-2

DenyutJantung,

denyut/menit

68

70

72

74

76

78

80

82

84

86

B L-1 R L-2

TekananArteriRerata,mmHg

6

7

8

9

10

11

12

B L-1 R L-2

TekananVenaSentral,mmHg

21

21.5

22

22.5

23

MPAPTekananArteriP

ulmonalRerata,mmHg

RL

HSL

13

13.5

14

14.5

PCWP

TekananBaji

KapilerParu,mmHg

RL

HSL

= RL

= HSL

*

Preload Parameters

Cardiac Index


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Cardiac Index

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

Note: (a) : RL : NLH (b) : 26%-40% : 25%

* : significant; **: very significant; ***: sangat sangat bermakna

0

0.5

1

1.5

2

2.5

3

3.5

4

B L-1 R L-2

CI,L/menit.m

2

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

B L-1 R L-2

CI,L/menit.m

2

(a) (b)

*** * * * *** ***


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Tissue Oxygenation (DO )


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Tissue Oxygenation (DO2)

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

Note: (a) : RL : HSL (b) : 26%-40% : 25%

0

100

200

300

400

500

600

700

800

900

B L-1 R L-2

DO2,mL/menit

0

200

400

600

800

1000

1200

B L-1 R L-2

DO2,mL/menit

(a) (b)

** ** *

Tissue Oxygenation (DO )

Ti O ti (DO )


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Delta of Oxygen Delivery inVarious Ejection Fraction

-0.5

-0.3

-0.1

0.1

0.3

0.5

0.7

0.9

1.1

1.3

1.5

21 21 2 5 27 28 2 9 3 2 3 2 32 33 33 33 3 4 3 4 34 3 4 3 4 3 5 3 5 36 36 37 37 37 37 37 38 39 39 39 40 40 40

Ejection Fraction

DeltaofOxygenDelive

ry

1

2

3

4

Tissue Oxygenation (DO2)Tissue Oxygenation (DO2)

4 0m-2

500

RL

HSL


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2.0

2.5

3.0

3.5

4.0

cardiacind

ex,

L.m

in-1.m

300

350

400

450

500

Baseline Load-1 Mt Load-2 Baseline Load-1 Mt Load-2

DO2,m

L.m

in-1

A B

C D

1000

1500

2000

2500

3000

SVRI,dyn.s.cm-5

100

150

200

250

300

350

P

VRI,dyn.s.cm-5

Baseline Load-1 Mt Load-2 Baseline Load-1 Mt Load-2

p = 0.0017

p = 0.019 p = 0.0356

p = 0.0130

Boom CE PhD Dissertation

Hyperosmolar sodium-lactate infusion during cardiac surgery


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Figure 2.Intra-operative changes inbody fluids, sodiumand potassiumexcretion in patients treated withRLorHL. White columns: patients treated with RL; black columns: patients treated with HL. Panel A: urinary output(L); Panel B: cumulativefluid intakes(L); Panel C: body fluid balance (L); Panel D: sodiumexcretion output(mmol); Panel E: chloride excretion (mmol); E: sodium/chloride ratio. Results are expressed as meanssem,statistical comparisonsbetween RL and HL by unpaired studentst test for: urineoutput (p


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Note: : RL : HSL

0

500

1000

1500

2000

2500

3000

B L-1 R L-2

SVRI,dyn

es.detik/cm5.m

2

0

50

100

150

200

250

300

350

B L-1 R L-2

PVRI,dyn

es.detik/cm5.m

2

**

Afterload Parameters

Conclusion


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Conclusion

It can be oxidized, recyled, or used as precursor for other energy metabolism

Lactate is a major physiological substrate

Energetic substrate for brain, heart, kidney

Prevention of ischemia-reperfusion injury

It is of major interest in acute conditions

Increase cardiac output

Decrease pulmonary and systemic vascular resistance

Increase oxygen delivery

Increase total urine output

Decrease total fluid balance

Hypertonic Sodium-Lactate possesses several cardiacand hemodynamic properties

Osmolarity

mOsm/LTonicity

mOsm/L


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HSL

Lactate-

Na+

K+

Ca++

Cl-

mOsm/L mOsm/L

504.15

6.74

4.02

1.36

1020.42 516.25

0

504.15 504.15

6.74

4.02

1.36

Total

Increases


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HSL

Intravascular

volume

Improves

Hemodynamic

Inotropic effect +

vascular resistance

Prevents/Corrects

Cellular edema

Improves

Capillary leakage

Prevents/Corrects

Metabolic Acidosis

Tissue perfusion=

Urine output MAP

Mix Ven O2sat

HSL (Totilac) Acute Toxicology Study


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HSL (Totilac ) Acute Toxicology Studyby 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 (from0mg/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 treatmentgroup

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-chronicstudy.

Experimental/Clinical Proofs


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Experimental/Clinical Proofs

Increases


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Totilac

Intravascular

volume

Improves

Hemodynamic

Inotropic effect +

vascular resistance

Prevents/Corrects

Cellular edema

Improves

Capillary leakage

Prevents/Corrects

Metabolic Acidosis

Tissue perfusion=

Urine output MAP

Mix Ven O2sat

Effect of acute infusion of sodium lactate or sodium chloride


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-0.6

-0.5

-0.4

-0.3

-0.2

-0.1

0.0

Deltahemoglobin,g

1 2

in patients after cardiac surgery

Na-lactate, n = 40Na-chloride, n = 401 = 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)

* **

*

Mustafa,PhD dissertation

Increases

I t l


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Totilac

Intravascular

volume

Improves

Hemodynamic

Inotropic effect +

vascular

resistance

Prevents/Corrects

Cellular edema

Improves

Capillary leakage

Prevents/Corrects

Metabolic Acidosis

Tissue perfusion=

Urine output MAP

Mix Ven O2sat

Effect of hypertonic infusion (lactate versusNaCl)


96/123

Mustafa & Leverve, Shock, 2002

on hemodynamic


97/123


on vascular resistance indexes (SVRI & PVRI)


98/123

on vascular resistance indexes (SVRI & PVRI)

in patients after cardiac surgery






-50

-40

-30

-20

-10

0

10

*

* *

$

Delta,PV

RI,dynes/cm2m2

1 2

-800

-600

-400

-200

0

200

*

*

*

DeltaSVR

I,dynes/cm2m

2

$$


Increases

Intravascular


99/123

Totilac

Intravascular

volume

Improves

Hemodynamic

Inotropic effect +

vascular resistance

Prevents/Corrects

Cellular edema

Improves

Capillary leakage

Prevents/Corrects

Metabolic Acidosis

Tissue perfusion=

Urine output MAP

Mix Ven O2sat

Effect of hypertonic infusion (lactate versusNaCl)

id b t t


100/123

Mustafa & Leverve, Shock2002

on acide base status

Increases

Intravascular


101/123

HSL

Intravascular

volume

Improves

Hemodynamic

Inotropic effect +

vascular resistance

Prevents/Corrects

Cellular edema

Improves

Capillary leakage

Prevents/Corrects

Metabolic Acidosis

Tissue perfusion=

Urine output MAP

Mix Ven O2sat


on pH and bicarbonate in patients after cardiac surgery


102/123

on pH and bicarbonate in patients after cardiac surgery






-0.025

0

0.025

0.05

0.075

De

eltapH,units

1 2

*

$

*

*

$

-4

-2

0

2

4

6

8

Bicarbon

ate,mmol/L

1 2

* *

*

$ $

Increases

Intravascular


103/123

HSL

Intravascular

volume

Improves

Hemodynamic

Inotropic effect +

vascular resistance

Prevents/Corrects

Cellular edema

Improves

Capillary leakage

Prevents/Corrects

Metabolic Acidosis

Tissue perfusion=

Urine output MAP

Mix Ven O2sat


104/123


on plasma sodium and chloride in patients after cardiac surgery


105/123

on plasma sodium and chloride in patients after cardiac surgery






0

2

4

6

8

DeltaplasmaSodium,mmol/L

1 2

**

* *

0

2.5

5

7.5

10

Deltaplasm

aChloride,mmol/L

1 2

*

$

$*

*

*


Totilac: Clinical Evidence


106/123

Totilac: Clinical Evidence

**

Lactate and brain recovery from ischemia-reperfusion injury


107/123

*

****

*

*

20

40

60

80

100

3.0 mM

Glucose

3.0 mMGlucose

+0.2mM

IAA

6.0 mM

Lactate

6.0 mMLactate

+0.2 mM

IAA

1.5 mMGlucose

+3.0 mMLactate

Neuron

allyfunctionalsuccess(%)after

5-minh

ypoxiaand30-minreo

xygenation

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

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 periodand reoxygenation

Slices in which anaerobic lactate production was blocked during the initial stage of hypoxic didnot recover


108/123


109/123

Ichai et al, Intensive Care Medicine, 2008

The Use of Hypertonic Sodium Lactate Solutionin Intracranial Tumor Removal Surgery.Is it safe?

An observational studyDoddy Tavianto, Marsudi Rasman, Deddy Koesmayadi


110/123

ResultThe benefit of hypertonic sodium lactate in Coronary ArteryBypass 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

To observe the safety of hypertonic sodium lactate in

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.

EtCO2keep 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

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

Great thanks to Prof. Kahdar Wiriadisastra, PhD, Benny Atmadja Wiryomartani MD,

Setyowidhi, MD, MZ Arifin MD and all staffs of Department of Neurosurgery, HasanSadikin General Hospital and St. Borromeus Hospital, Bandung, Indonesia.

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

y , , y yDepartment of Anesthesiology and Reanimation, Faculty of Medicine Padjadjaran University

Hasan Sadikin General Hospital, Bandung, Indonesia

Background

Conclusion

Methods

Objective

Acknowledgment

Result

Pre-Operative and 6 Hours Post-OperativeLaboratory Examination

T til N Cl 0 9% P L di S i l A th i i TURP


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111

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% afterspinal anesthesia)

TOTILAC vs NaCl 0.9% for TURP


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112

Sodium hypetronic lactate (Totilac)

4mL/kgBW in 20 minutesSodium chloride 0.9% (NaCl) 4

mL/kgBW in 20 minutes

Check sodium, osmolarity, pH

Spinal anesthetic : Bupivacaine 2-2.5 mL

TURP operation30 minutes of operation check sodium, osmolality & pH

Sodium Level Osmolality


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113

137

138

139

140

141

142

143

Awal Cairan Awal Durante Op Pasca Op

KonsentrasiNatrium(

mEq/L

)

NLH

NaCl 0.9%

Sodium Level

287

288

289

290

291

292

293

294

295

A wal Cairan A wal Durante Op Pas caOp

Osmolalita

s(mOsm/kg)

NLH

NaCl 0.9%

Osmolality

The level of Na serum & osmolality in TOTILAC is higherbus still within normal

boundaryprevents hyponatremia

pHaLactate


114/123

114

7.26

7.287.3

7.32

7.34

7.36

7.38

7.47.42

7.44

7.46

Prehidrasi Cai ran Awal Durante Pasca op

pH HSL

NaCl

0

1

2

3

4

5

6

7

8

Prehi dras i C ai ra n Aw al D uran te Pas ca o p

Laktat(mmol/L)

HSL

NaCl

The lactate level in TOTILAC is higherbut then itll decrease; thismeans that lactate is metabolized

In TOTILAC there was no acidosis, while in NaCl 0.9% there was acidosis.

Burn Wound


115/123

Burn Wound

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 willrepresent around 2 L of fluid.therefore 6 L ofother fluids is infused

Total real infusion will only be 7 Liters (smaller totalvolume) to fulfill the needs of 8 liters of fluid loss

Clinical practice by Dr. Poengky,

plastic surgeon in RSPP, Indonesia:

Totilac vs RL in Dengue Shock in pediatric patients


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g p p

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 SOPGroup II : treated as outlined on DSS SOP

Recurrent shock :

Group I : HSL 5 mL/kg 1xHES 130/0,4RL (DSS SOP)Group II : as outlined on DSS SOP

Blood Pressure


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Systole Blood Pressure

0.00

20.00

40.00

60.00

80.00

100.00

120.00

0 0.25 0.5 1 2 3 4 5 6 9 12 18 24

Hour of treatment (H)

Systole(mmHg)

Totilac

RL

Diastole Blood Pressure

0.00

10.00

20.00

30.00

40.00

50.00

60.00

70.00

80.00

0 0.25 0.5 1 2 3 4 5 6 9 12 18 24

Hour of treatment (H)

Diastole(mmHg)

Totilac

RL

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

Cumulative fluid balance in 24H


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Cumulative fluid balance in 24H

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)

Cumulatif fluid balance

-500.00

0.00

500.00

1000.00

1500.00

2000.00

2500.00

0 0.25 0.5 1 2 3 4 5 6 9 12 18 24

Hour of treatment

Cumulativefluidbalance

(m

l) Totilac RL

InjuryTrauma, Sepsis, Ischemia, Hypoxia, Cardiogenic


119/123

Trauma, Sepsis, Ischemia, Hypoxia, Cardiogenic

capillary leakage

cell volume (swelling effect)Interstitial edema

Intravascular volume

Tissue perfusion

Fluid administrationCrystalloids, Colloids,

Blood, Plasma or Albumin

Intravascular Volume-hemorrhage Hemodynamic failure

cardiac fail reVasomotricity


120/123

Low Tissue Perfusion

-vasodilation

-capillary leakage

-urinary losses (DKA)

-cardiac failure

-cardiogenic shockDysregulation

Metabolic acidosis

pH, Bicarbonate, BE

Interstitial Edema

Clinical signs

Hte, Hb, Albumin

Cellular Swelling

(edema)

Natremia

-CO/CI

-MAP

-Urine output

-MV ox sat-(lactate?)

Conclusion


121/123

It can be oxidized, recyled, or used as precursor for other energy metabolism

Lactate is a major physiological substrate

Energetic substrate for brain, heart, kidney

Prevention of ischemia-reperfusion injury

It is of major interest in acute conditions

Increase cardiac output

Decrease pulmonary and systemic vascular resistance

Increase oxygen delivery

Increase total urine output

Decrease total fluid balance

Hypertonic Sodium-Lactate possesses several cardiacand hemodynamic properties

Conclusion


122/123

Conclusion

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) byattracting intracellular chloride (maintenance of

electroneutrality)

Induces a powerful diuretic effect with a negative fluidbalance, without involving any hypovolemia

Sodium-lactate as new therapeutic conceptin clinical practice and critical care!


123/123

Thank You

Documents

Terapi Cairan, HD Monitoring, Totilac Plbg