"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 BERAT
7
Adrogue 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

CO
2
STRONG ION DIFFERENCE WEAK ACID
pCO
2
SID A
tot
Control by
respiratory
system
Electrolyte
composition in
plasma
(control by renal)
Concentration of
protein (control by
liver and metabolic
status)
VARIABEL INDEPENDEN
Pharmaceutical contribution
Plasma
Na
+
142
K
+
4
Ca
++
Mg
++
Cl
-
103
HCO
3
-
24
KATION ANION
SID
Weak acid
(Alb-,P-)
SID Plasma = (KationAnion) = 40 2

Na
+
= 142 mEq/L
Cl
-
= 103 mEq/L
SID= 39 mEq/L
1 L
1 L
WATER EXCESS - HEMODILUTION
Plasma
Water
Na
+
= 142 /2 = 71
Cl
-
= 103/2 = 51
SID= 20 mEq/L
SID : 20 acidosis 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 + NaCl 0.9%
Plasma
NaCl
Na
+
= (142 + 154)/2 = 147
Cl
-
= (103+154)/2 = 128
SID= 19 mEq/L
19 = acidosis
2 L
SID Plasma : 39
Balanced Crystalloid & Colloid
To avoid acid-base imbalances & edema cellular

Fully plasma adapted
SID-eff plasma > SID-eff Kristaloid/koloid > 0
Isotonic to plasma
03/09/2014 21
How designing of Balanced Fluid
Ringerfundin

Balanced Crystalloid

Ringerfundin (Indonesia) =Sterofundin ISO
140 21 2.5 1
2
27
Ringerfundin Plasma - adapted
- Electrolyte balance like in human plasma
- Conventional infusion corrective effects
both unwanted and unknown.


Ringerfundin - BE
pot
= 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)

Acetate Lactate
ANION ORGAN HCO
3
-
O
2
0
2
/HCO
3
-

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 O
2

consumption (mol O
2
/ mol substrat)
Acetate :
CH
3
COONa + 2 O
2
CO
2
+ H
2
O
+
NaHCO
3

Lactate :
CH
3
CHOH-COONa + 3O
2
2CO
2
+ 2H
2
O
+

NaHCO
3

Malate:
COONa-CH
2
-CHOH-COONa + 3 O
2
= 2
CO
2
+ H
2
O + 2 NaHCO
3

Comparison of O
2
consumption among
anions
Ringerfundin - Isotonic Solution
USA:
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-
4
Hennes H-J: Schdel-Hirn-Trauma. In: Neuroansthesie
(J-P Jantzen, W Lffler, Hrsg.), Thieme, Stuttgart 2000
misperception
Osmolarity & Osmolality

Osmolarity & Osmolality
- Real osmolality ~ Sum: osmotically active species
Plasma 288 mOsm /kg H
2
O

- 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/kgH
2
O)
- Osmotical coefficient := 0.93
Real Osmolality = 308 x 0.997 x 0.93
= 286 mosm/ kg H
2
O
Isotonicity ~
Real Osmolality 286 mosm/ kg H
2
O (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)
Ringerfundi
n (mmol/l)
Electrolyt
e (mmol/l)
Osmotically
active species
(mosmol/l)
Na
+
142 142 130 130 154 140
K
+
4.5 4.5 4 4 4
Ca
2+
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
HCO
3
+
24 24
Phospate
2-
1 1
Sulfate
2-
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 H
2
O)
287 254 254 286 283
Measured osmolality
**(mosmol/kg H
2
O
288 5
253 253
286 286
Osmolarity
vs
Osmolality
Hall JE. Medical Physiology. Saunders, 2011
Effects of Osmolarity on Cell Volume

Trend use isotonic solutions perioperatively
Smpelmann et al, Ansth Intensivmed 48 (2007): S73
Choong, K et al. Arch Dis Child 2006;91:828-835
Meta- analysis iv fluids in children:
-hypotonic vs. isotonic-
Isotonic solutions Hyponatremia
Crystalloids- Balanced Solution (BEL)
Total 37
Sodium 140
Chloride 127
Potassium 4
Magnesium 1
Calcium 2.5
Buffer 34
Osmolarity 309
0 25 50 75 100
deviation from normal (mmol/l)
Sterofundin- iso
Composition
1. Sodium 140 mmol/l
2. Potassium 4 mmol/l
3. Calcium 2,5 mmol/l
4. Magnesium 1 mmol/l
5. Chloride 127 mmol/l
6. Acetate 24 mmol/l
7. Malate 5 mmol/l
Osmolarity 309 mosmol/l
Is BEL physiological?
Osmolarity: yes
Cations: yes
Anions: compromise
Buffer: yes
BEL is almost physiological!

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
Ca
2+
-- 2.25 2.7 2.7 2.5 2.5 Ca is essential cofactor in coagulation cascade if Ca drop
leads prolonged blood coagulation
Mg
2+
-- 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
Malate
2-
-- -- -- -- 5.0
BEpot -24 -24 3.0 2.5 0 No change patients 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 O
2
-Consumption
Several Metabolisation Pathways
BE
pot
= 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
complete & 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 + Colloid Un-Balanced (NaCl)
Plasma
Colloid/NaCl
Na
+
= (142 + 154)/2 = 147
Cl
-
= (103+154)/2 = 128
SID= 19 mEq/L
SID : 39 19 : acidosis
2 L
Na
+
= 142 mEq/L
Cl
-
= 103 mEq/L
SID= 39 mEq/L
1 L
1 L
PLASMA + Colloid Balanced
Plasma
Tetraspan

(Balanced HES)
Na
+
= (142 + 140)/2 = 141
Cl
-
= (103+118)/2 = 110
SID= 31 mEq/L
SID : 39 31 : No acidosis
2 L
Cation
+
= 147 mEq/L
Cl
-
= 118 mEq/L
Malate = 5 mEq/L
Acetat
-
= 24 mEq/L
SID = 29 mEq/L

Acetat &
malate cepat
dimetabolisme
[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 correction
K
+
4 3 4 4.5
Ca
2+
3 5 2.5 2.5 Ca
2+
is essential cofactor in coagulation
cascade if Ca drop leads prolonged
blood coagulation
Mg
2+
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
Malate
2-
5
Mw (kdl) Polygeline
30
MFG
30
HES
130
HES
200
HES
670
HES
130
Albumin
30 -52
DS
0.4 0.5 0.75 0.42
C
2
:C
2
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 Gelatin
6% HES 200/0.5
6% Dextran 70
6% HES 200/0.62 and HES 450/0.7
10% HES 200/0.45 and 0.5
10% Dextran 40
~70%
~ 100 %
1oo%
145 %
~ 190 %
~2-3h
~3-4h
~ 4h
~ 3-4h
(?)
(?)
Same effect
and duration!
~ 7-9h
~ 4h
0
50 100 150 200
(%)
3.5 % Polygeline
4% Modified Fluid Gelatin
6%/10% HES 200/0.5 &
HES 130 / 0.4-0.42


6% Dextran 70
6% 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 acidosis
2. Volume efek sebanding dg HES
Not all Gelatin are the same
Gelofusine Minimal Hypercloremic acidosis
compare other Gelatin
Reff : SID = 26
Na
+
= 142 mEq/L
Cl
-
= 103 mEq/L
SID= 39 mEq/L

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

1 L
1 L
PLASMA + Gelofusine
Plasma
Gelofusine
Na
+
= (142 + 154)/2 = 148
Cl
-
= (103+120)/2 = 111
SID= 37 mEq/L
SID : 39 37 = No acidosis
2 L
Efektifitas berdasarkan bentuk
molekul & muatan negatif
-
-
-
-
-
-
-
-
-
-
-
Ukuran pori
Membrane
pemb darah
-
-
-
-
Eksresi
via urin
stretched 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 patients life
Thank You for Your Attention