"New Paradigm of Safe Fluid Therapy- Total Balanced Concept”

(Crystalloid & Colloid)

Indication of Fluid Therapy- Dehidration- Fluid losses during surgery- Acute hypovolemia e.g because of massive blood loss- Acidosis or alkalosis, electrolyte imbalances- Application of drugs

Crystalloid

Colloid

Type of Fluid

Dextran

Albumin

Gelatin

HES(Hydroxyethyl

starch)

NaCl 0.9%/ 0,45%

Other

Ringerfundin®

Mannitol

Glucose 5%

RA

etc.

Electrolyte concentrates

consist of :

electrolytes

& macro molecule

consist of :

electrolytes

consist of : high

concentration of electrolytes

Natural

Syntetis

RL

“ Does the electrolyte composition is a MATTER ?? ”

Sebagian besar cairan kristalloid & koloid yang ada mengandung campuran elektrolit yang tidak fisiologis – un-balanced

Pada awal 1990, mulai dikenal dan didefinisikan “ hyperchloremic acidosis” , pasca infusi cairan NaCl .

Penggunaan dalam jumlah besar dari cairan un-balanced ini dapat berakibat gangguan keseimbangan asam-basa

Respirasi• Hiperventilasi• Penurunan kekuatan otot nafas

dan menyebabkan kelelahan otot• Sesak

Metabolik• Peningkatan kebutuhan

metabolisme• Resistensi insulin• Menghambat glikolisis anaerob• Penurunan sintesis ATP• Hiperkalemia• Peningkatan degradasi protein

Otak• Penghambatan metabolisme dan

regulasi volume sel otak• Koma

Kardiovaskular• Gangguan kontraksi otot jantung• Dilatasi arteri,konstriksi vena, dan

sentralisasi volume darah• Peningkatan tahanan vaskular paru• Penurunan curah jantung, tekanan

darah arteri, dan aliran darah hati dan ginjal

• Sensitif thd reentrant arrhythmia dan penurunan ambang fibrilasi ventrikel

• Menghambat respon kardiovaskular terhadap katekolamin

AKIBAT DARI ASIDOSIS BERATAKIBAT DARI ASIDOSIS BERAT

7Adrogue HJ, Nicolaos EM: Management of life-threatening Acid-Base Disorders,

Review Article; NEJM 1998

Note :Hespan (HES 600/0.75 in NS)

Hextend (HES 670/0.75 in Balance)

Hypercloremic acidosis and the adverse event are minimal in fluid with SID = 28 compare SID = 0

wilkes, Anest Analgesia 2001

Quantitative approach of acid-base equilibrium

COCO22 STRONG ION DIFFERENCESTRONG ION DIFFERENCE WEAK ACIDWEAK ACID

pCOpCO22 SIDSID AAtottot

Control by Control by respiratory respiratory

systemsystem

Electrolyte Electrolyte composition in composition in

plasma plasma ((control by renalcontrol by renal))

CCononccentraentration oftion of protein (protein (control by control by liver and liver and metabolimetabolic c

statusstatus))

VARIABEL INDEPENDENVARIABEL INDEPENDEN

Pharmaceutical contribution

Plasma

NaNa++

142142

KK+ + 44CaCa++++

MgMg++++

ClCl--

103103

HCOHCO33--

2424

KATION ANION

SIDSID

Weak acidWeak acid(Alb-,P-)(Alb-,P-)

SID Plasma = (Kation–Anion) = 40 ± 2

Na+ = 142 mEq/L Cl- = 103 mEq/L

SID= 39 mEq/L 1 L 1 L

WATER EXCESS - HEMODILUTIONWATER EXCESS - HEMODILUTION

Plasma Water

Na+ = 142 /2 = 71 Cl- = 103/2 = 51

SID= 20 mEq/L

SID : 20 SID : 20 a acidosiscidosis dilusi dilusi

2 L

Na+ = 142 mEq/L Cl- = 103 mEq/L

SID= 39 mEq/L

Na + = 154 mEq/L Cl- = 154 mEq/L

SID = 0 mEq/L

1 L 1 L

PLASMA + PLASMA + NaCl NaCl 0.9% 0.9%

Plasma NaCl

Na+ = (142 + 154)/2 = 147 Cl- = (103+154)/2 = 128

SID= 19 mEq/L

1919 = a = acidosiscidosis

2 L

SID Plasma : SID Plasma : 3939

“Balanced Crystalloid & Colloid”

To avoid acid-base imbalances & edema cellular

Fully plasma adapted SID-eff plasma > SID-eff Kristaloid/koloid > 0

Isotonic to plasma

19/04/23 21

“How designing of Balanced Fluid“

Ringerfundin ® Balanced Crystalloid

Ringerfundin ® (Indonesia) = Sterofundin ISO

140 212.5 1

227

Ringerfundin – Plasma - adapted

- Electrolyte balance like in human plasma- Conventional infusion corrective effects

both unwanted and unknown.

Ringerfundin - BEpot= 0

Ringerfundin can be applied to polytrauma patients

Acid Base Balance - BE

Ringerfundin - Low Oxygen consumption

Total consumption of oxygen is reduced for About 30% in the acute phase!

Ringerfundin :

- Low Oxygen consumption

Compare to RL & RA

- Gentle on the liver

Acetate and Malate – metabolized

in all organs and muscle –

(unlike Lactate - only Liver)

AcetateLactate

ANION ORGAN HCO

3-

O

2

02 /HCO3

-

Lactate Liver 1 3 3,0

Actetate

Muscle 1 2 2,0

Malate Muscle 2 3 1,5

Glukon. nn 1 5,5

5,5

Metabolic cost in term of O2 consumption (mol O2 / mol substrat)

Acetate :CH3COONa + 2 O2 CO2 + H2O + NaHCO3

Lactate :CH3– CHOH-COONa + 3O2 2CO2 + 2H2O + NaHCO3

Malate:COONa-CH2-CHOH-COONa + 3 O2  =  2 CO2 + H2O + 2 NaHCO3

Comparison of O2 consumption among anions

Ringerfundin - Isotonic SolutionUSA:Estimated 15,000 pediatric deaths a year attributed to postoperative hyponatremia secondary to infusion of hypotonic solutions

Neurotraumatology:Use of hypotonic solutions (RL & RA) contra-indicated: risk of brain edema

Isotonic

Source:Arieff AI: Editorial: Postoperative hyponatraemic encephalopathy following elective surgery in children. Pediatric Anaesthesia 1998; 8: 1-4Hennes H-J: Schädel-Hirn-Trauma. In: Neuroanästhesie (J-P Jantzen, W Löffler, Hrsg.), Thieme, Stuttgart 2000

misperceptionOsmolarity & Osmolality

Osmolarity & Osmolality- Real osmolality ~ Sum: osmotically active species Plasma 288 mOsm /kg H2O

- Theoretical Osmolarity = Sum: Cation + Anion NaCl 0.9% = Na :154 + Cl :154 = 304 mosm/l

-Osmotical coefficient : ~ 0.93 (protein binding)

- NaCl 0.9% (Na :154 mosm/l + Cl :154 mosm/l)

Theo Osmolarity : 304 mosm/l - Water content 99.7% (mosm/l mosm/kgH2O) - Osmotical coefficient := 0.93 Real Osmolality = 308 x 0.997 x 0.93 = 286 mosm/ kg H2O

Isotonicity ~ Real Osmolality 286 mosm/ kg H2O (Plasma)

R. Zander, Fluid Management, 2009

R. Zander, Fluid Management, 2009

NaCL 0.9% and Ringerfundin (RF)

more Isotonis compare to RL and RA

Plasma Ringer Lactate

(mmol/l)

Ringer Acetate

(mmol/l)

0.9% NaCl (mmol/l)

Ringerfundin (mmol/l)

Electrolyte (mmol/l)

Osmotically active species (mosmol/l)

Na+ 142 142 130 130 154 140

K+ 4.5 4.5 4 4 4

Ca2+ 2.5 1.3* 2.7 2.7 2.5

Mg+ 1.25 0.7 0 0 1

Cl- 103 103 108.7 108.7 154 127

HCO3+ 24 24

Phospate2- 1 1

Sulfate2- 0.5 0.5

Organic acid 1.5 1.5 28 28 29

Proteinate- 20 1

Glucose 5

Urea 5

∑ ∑ = 291 ∑ = 273 ∑ = 273 ∑ = 308 ∑ = 304

Theoritical osmolarity (mosm/l)

291 273 273 308 304

Water content (%) 94 99.7 99.7 99.7 99.7

Theoritical osmolarity (mosm/l)

310 273 273 308 304

Osmotic coefficient 0.93 0.93 0.93 0.93 0.93

Actual osmolality (mosmol/kg H2O)

287 254 254 286 283

Measured osmolality **(mosmol/kg H2O

288 ± 5 253 253 286 286

Osmolarity vs

Osmolality

• NaCl Hypercloremic acidosis• R Lactate Hypotonicity , Lactate metabolism• R Acetate Hypotonicity

[mmol/l] NS Ringer RL RA RFundin Plasma Benefit

Na+ 154 147 130 130 140 142 Na+ responsable for tonicity of fluid

Plasma equivalent of most important electrolytes (i.e Na & K) Less unintended correction

K+ -- 4.0 4 4 4.0 4.5

Ca2+ -- 2.25 2.7 2.7 2.5 2.5 Ca is essential cofactor in coagulation cascade if Ca drop leads prolonged blood coagulation

Mg2+ -- 1.0 -- -- 1.0 0.85 Less unintended correction

Cl- 154 156 108.7 108.7 127 103 Cl- at RF slightly higher in order to achive physiological osmolarity

HCO3 24 Infusion should have physiologi buffer base HCO3- to

maintain base-acidity but due to unstable of HCO3- , pharmaceutical using precursor : Lactate, Acetate, Malat.

RFundin: combine Acetate & Malat instead of Lactate:

1.Acetate/malat metabolize in most tissue cells of body compare to Lactate-clearing organ in liver & kidney

2.Lactate should not be used in hepatic insufficiency Lactate metabolize in liver lactate in solutin lead metabolic acidosis

3.Lactate should not be used in shock with hyperlactademia / lactic acidosis.

Lactate- -- -- 28.0 -- -- 1.5

Acetate- -- -- -- 28.0 24.0

Malate2- -- -- -- -- 5.0

BEpot -24 -24 3.0 2.5 0 No change patient‘s acid-base status

Tonicity [mOsm/l]

[mOsm/lkg)308

286

309

287

273

253

273

253

304

286

310

288

RF more Isotonic than RL & RA, RF will avoid risk hypotonicity concequences i.e at neurotrauma & cerebral edeme that can easily develop in preterm & newborn

Comparison among Crystalloid solution : Designing “Balanced Crystalloid”

Clinical Demands :

Optimization of few criteria leads to one solution for 95% of all patients

Plasma-adapted / Balance / Physiologis

Isotonic

Low O2-Consumption

Several Metabolisation Pathways

BEpot= 0 mmol/l Prof. Dr. Dr. M. Leuwer, Liverpool Univ

Gelatin HES (Hydroxy Etyl Starch) Dextran

Bahan Gelatin sapi Starch / Kanji / Amylum Gula bit

BM 30 – 35 kdl 200 kdl 130 kdl 40 – 70 kdl

MFG Polygeline NaCl RL NaCl RFundin NaCl

Gelofusine (BB)

Haemaccel

-Haes steril-Hemohes (Bb)-Widahes-Hestar

Fimahes

-Voluven-Venofundin (BB)

Tetraspan (Colloid HES Balance)

(BB)

Otsu-tran (OI)

BBraun develop both Gelatin & HES BBraun develop both Gelatin & HES complete & objective information of the profilecomplete & objective information of the profile

49

World of Colloid

50

Different solutions in comparison with plasma

Note especially the differences in sodium and chloride content!

HES 130 in 0.9% saline: i.e : Venofundin-BBraun & Voluven

wilkes, Anest Analgesia 2001

Na+ = 142 mEq/L Cl- = 103 mEq/L

SID= 39 mEq/L

Na + = 154 mEq/L Cl- = 154 mEq/L

SID = 0 mEq/L

1 L 1 L

PLASMA + PLASMA + Colloid Un-Balanced (Colloid Un-Balanced (NaCl) NaCl)

Plasma Colloid/NaCl

Na+ = (142 + 154)/2 = 147 Cl- = (103+154)/2 = 128

SID= 19 mEq/L

SID : 39 SID : 39 1919 : a : acidosiscidosis

2 L

Na+ = 142 mEq/L Cl- = 103 mEq/L

SID= 39 mEq/L 1 L 1 L

PLASMA + PLASMA + Colloid Balanced Colloid Balanced

Plasma Tetraspan ® (Balanced HES)

Na+ = (142 + 140)/2 = 141 Cl- = (103+118)/2 = 110

SID= 31 mEq/L

SID : 39 SID : 39 31 : No acidosis 31 : No acidosis

2 LCation+ = 147 mEq/L Cl- = 118 mEq/L

Malate = 5 mEq/LAcetat- = 24 mEq/L SID = 29 mEq/L

Acetat & malate cepat dimetabolis

me

[mmol/l] Haemaccel Gelofusine Voluven Fimahes Hextend Tetraspan Plasma Benefit

Na+ 145 154 154 138 143 140 142 Na+ responsable for tonicity of fluid

K+ Less unintended correctionK+ 4 3 4 4.5

Ca2+ 3 5 2.5 2.5 Ca2+ is essential cofactor in coagulation cascade if Ca drop leads prolonged blood coagulation

Mg2+ 0.9 1.0 0.85 Less unintended correction

Cl- 145 120 154 125 123 118 103 Cl- influence the SID

HCO3 24 Infusion should have physiologi buffer base HCO3- to maintain base-acidity but due to unstable of HCO3- , pharmaceutical using precursor : Lactate, Acetate, Malat.

RFundin: combine Acetate & Malat instead of Lactate:

1.Acetate/malat metabolize in most tissue cells of body compare to Lactate-clearing organ in liver & kidney

2.Lactate should not be used in hepatic insufficiency Lactate metabolize in liver lactate in solutin lead metabolic acidosis

3.Lactate should not be used in shock with hyperlactademia / lactate acidosis.

Lactate- 20 28 1.5

Acetate- 24

Malate2- 5

Mw (kdl) Polygeline

30MFG

30

HES

130

HES

200

HES

670

HES

130

Albumin

30 -52

DS 0.4 0.5 0.75 0.42

C2:C2 ratio 9 : 1 6 : 1

Duration 2-3 hours 3-4 hours 4 – 6 hours

Comparison among Colloid solution : Designing “Balanced Colloid”

Ringerfundin ® & Tetraspan ® “clinically proven” for Pediatric

Pediatric aged up to 12 years ASA I-III undergoing

perioperative.

Comparison between HES

60

Tetraspan, Colloid Balanced HES 130/0.42

Volume & Duration effect of colloid (in hypovolemic volunteers)

68

0 50 100

150

200

(%)

3.5 % Polygeline

4% Modified Fluid Gelatin6% HES 200/0.5

6% Dextran 706% HES 200/0.62 and HES 450/0.710% HES 200/0.45 and 0.5

10% Dextran 40

~70%

~ 100 %

1oo%

145 %

~ 190 %

~2-3h

~3-4h

~ 4h

~ 3-4h(?)

(?)Same effectand duration!

~ 7-9h~ 4h

0 50 100

150

200

(%)

3.5 % Polygeline

4% Modified Fluid Gelatin6%/10% HES 200/0.5 & HES 130 / 0.4-0.42

6% Dextran 706% HES 200/0.62 and 450/0.7

10% Dextran 40

~50-60%

~ 100/ 145%

1oo- 140 %

~ 190 %

~2-3h

~3-4h, 4-6 h

~3-4/4 -9h

~3-4h(?)

Gelofusine (MFG)

= HES

Karakteristik Gelofusine® , ,modified fluid gelatin (MFG):

Polygelin

Proses suksinilasi gelatin

Urea-linked gelatin

Berat molekul 30,000 Dalton 35,000 Dalton

Bentuk molekul stretched polypeptides

kecil dan globular molecular polypeptide chains

Muatan Bermuatan negatif kuat

sedikit muatan negatif

Benefit Muatan Negative pada molekul Gelofusine®: 1.Mengurangi kebutuhan Clorida pada solution nya Minimal Hypercloremic acidosis2.Volume efek sebanding dg HES

Not all Gelatin are the same

Gelofusine – Minimal Hypercloremic acidosisGelofusine – Minimal Hypercloremic acidosis

compare other Gelatincompare other Gelatin

Reff : SID = 26

Na+ = 142 mEq/L Cl- = 103 mEq/L

SID= 39 mEq/L

Na + = 154 mEq/L Cl- = 120 mEq/LSID = 34 mEq/L

1 L 1 L

PLASMA + PLASMA + Gelofusine Gelofusine

Plasma Gelofusine

Na+ = (142 + 154)/2 = 148 Cl- = (103+120)/2 = 111

SID= 37 mEq/L

SID : 39 SID : 39 3737 = No acidosis = No acidosis

2 L

Efektifitas berdasarkan bentuk molekul & muatan

negatif-

-

-

--

-

-

-

-

-

-

Ukuran pori

Membrane

pemb darah-

-

-

-

Eksresi via urinstretched molekul,

Muatan negatif kuat

MFG (Gelofusine)

BM 30 kdl

Polygeline/ Haemaccel

BM 35 kdl

Globular

Tetraspan ®

Balanced HES

130/0.42

Total “Balanced” solution

Ringerfundin®

Balanced Crystalloid

Gelofusine®

No Dose Limit

colloid gelatin without acidosis

Safety is about anticipation

B.Braun; we value your patient’s life…

Thank You for Your Attention