Fluid Management in Dengue Infection

Leonard Nainggolan
Div. Tropical and Infectious Disease
Dept. Internal Medicine
Faculty of Medicine Universitas Indonesia
Pathogenesis and Patophysiology of
Dengue Infection:

Virulence and viral load

Immune complex disease
T-cell-mediated
ADE
Complement CAPILLARY
Autoimmune disease ENDOTHELIUM
Apoptosis
Innate immunity
Cytokine Tsunami
Genetic
 Innate immune response upon virus
injection in the capillary vessel

Noisakran S, Guey CP. Alternate hypothesis on the pathogenesis of Dengue Hemorrhagic Fever (D
HF)/ Dengue Shock Syndrome (DSS) in Dengue Virus Infection. Exp Biol Med 2008;233:401-8.
Lei HY et al. Immunopathogenesis of Dengue infection. J Biomed 2001
Nature Reviews Nephrology 6, 361-370 (June 2010)
The movement of material is generally accomplished via routes situated either across (i.e., transcellular) or in between
(i.e., paracellular) the cells forming the barrier. While the paracellular transport occurs via the intercellular junctions, there
are at least three transcellular routes described so far:
(a) water and small molecules are moved via membrane transporters that have a different distribution/orientation on
opposite fronts of a barrier cell;
(b) transcytosis, defined as the transport of macromolecular cargo from one front of a polarized cell to the other within
membrane-bounded carrier(s), and
(c) pores or channels which are patent openings through the barrier cells with or without selective permeability for
different molecules. Together, these processes contribute to the success of multicellular organisms.
 Transport pathways across the endothelium.

Tarbell J M Cardiovasc Res 2010;87:320-330

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author
2010. For permissions please email: [email protected].
Hematokrit ↑
Dengue Case Management
 Dengue Case Management

Fluid Replacement Therapy

Bed rest
Anti-pyretics (avoid aspirin and
NSAIDs)
Monitor Blood Pressure, haematocrite,
platelets level, and level of
consciousness
 Fluid Replacement

Resuscitation Management

Crystalloid Coloid Electrolyte Nutrition

Repair

Replace acute loss 1. Normal requirements

(Hemorrhage, GI loss, Third (IWL + urine+ faeces)
compartment) 2. Nutritional Support
 Volume Replacement Therapy

Crystalloids Colloids
Ringer’s Lactated
Ringer Acetate
Normal Saline

Albumin Gelatin Dextran HES

PPL solutions solutions solutions
Sebagian besar cairan kristaloid & koloid yang ada
mengandung campuran elektrolit yang tidak
fisiologis – unbalanced

Pada awal 1990, mulai dikenal dan didefinisikan

“ hyperchloremic acidosis” pasca infus cairan NaCl

Penggunaan dalam jumlah besar dari cairan unbalanced ini

dapat berakibat gangguan keseimbangan asam-basa

19
STRONG I ON DI FFERENCE
Gamblegram Mg++
Ca++
K+ 4

HCO3- SID
Weak acid
(Alb-,P-)
As. Organik kuat

= {[Na+] + [K+] + [kation divalen]} - {[Cl-] + [As.organik kuat-]}

Na+ Cl-

KATION ANION
 Hubungan SID, H+ & OH-

Konsentrasi H+
[H+] ↑↑ [OH-] ↑↑

SID↓ SID
SID↑
Na Na Na
Cl Asidosis Cl Alkalosis
Cl

(–) SID (+)

Dalam cairan biologis (plasma) dgn suhu 370C, SID hampir selalu positif,
biasanya berkisar 30-40 mEq/Liter

28/03/2019 21
 ‘Balanced’ Solution
• Pemberian NaCl dalam jumlah yang besar dapat
menyebabkan asidosis metabolik.
• Berkembang cairan yang didesign lebih ‘physiologic’
or ‘balanced’

SID = Na+] + [K+] - [Cl-]

 Pengaruh dilusi akibat infus
kristaloid
• Terjadi bila pemberian dalam jumlah besar
• Kristaloid dengan SID-eff = 0 seperti NaCl 0.9%,
masih akan menyebabkan metabolik asidosis.
• Kristaloid dengan SID-eff (+), akan
menyebabkan keseimbangan asam-basa lebih
kearah metabolik alkalosis

23
 Kristaloid dengan
SID –eff : 24 mEq/L
adalah ‘seimbang’ untuk
pemberian intravena secara
cepat
Designing ‘Balanced’ Crystalloids , T. J. MORGAN, B. VENKATESH
Critical Care and Resuscitation 2003; 5: 284-291
28/03/2019 24
Size, Electricity charge
Dengue guidelines for diagnosis, treatment, prevention, and control.
World Health Organization, UNICEF, UNDP. New Edition 2009.
 SIFAT-SIFAT PENGGANTI PLASMA YG IDEAL

1. Koloid bebas zat pirogen, antigen dan tidak toksik

2. Tekanan osmotik koloid (TOK) yang adekuat dicapai dengan waktu
paruh beberapa jam. TOK hendaknya dipertahankan diatas 2,7
kPa (20mmHg)
3. Larutan stabil dan mudah disimpan dalam waktu yang lama
4. Metabolisme dan ekskresi koloid tidak menimbulkan efek yang tidak
diinginkan pada resipien (Aman)
5. Infus tidak mengakibatkan koagulopati, hemolisis, aglutinasi
sel darah merah, atau gangguan cocok silang
6. Mengganti kehilangan darah secara cepat
7. Menormalkan aliran sirkulasi mikro
8. Memperbaiki hemoreologi
9. Memperbaiki penyediaan O2 dan fungsi organ
S. Sunatrio. Pemilihan koloid dalam praktek klinis. Resusitasi Cairan 2000; 59-75
 KOMPOSISI

1000 ml ~ 40 g gelatin (succinylated gelatin, presented

in 500 ml flexible packs) dan beberapa ion lainnya
Electrolyte composition: mmol/L
• Sodium 130
• Potassium 5.4 Pelarut
• Calcium 0.9
Ringer
• Magnesium 1.0
• Chloride 85 (low)
Acetate
• Acetate 27
 Gelafusal dengan pelarut Ringer Acetate, lebih balans dengan
minimal risiko asidosis hiperkloremik

Hyperchloremic acidosis symptoms :

- Postoperative confusion
- Headache RECOVERY
- Abdominal pain
- Nausea and vomiting

1. Wilkes N J et al.:The effects of balanced versus saline-based hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients Anesth Analg 93 (2001) 811-816
2. Williams E L et al.:The effect of intravenous Lactated Ringer‘s solution versus 0.9% sodium chloride solution on serum osmolarity in human volunteers Anesth Analg 88 (1999) 999-1003
 Gelatine Solutions

“Not All Gelatine are the same”

Characteristic Modified fluid Polygelin Oxypolygelatin
gelatin (MFG)
Process Succinylated Urea-linked gelatin
gelatin
Molecule Weight 30,000 Dalton 35,000 Dalton 30,000 Dalton
Molecule shape stretched Small and globular small and globular
polypeptides molecular polypeptide chains
polypeptide chains
Charge significant multiple Less negative charge Less negative charge
negative charge
 Molecular Shape of Semi-Synthetic Gelatins
Mw=30000 Dalton Mw=35000 Dalton
-

Urea-linked Polygeline
Succinylated, negatively
(Haemaccel)
charged
Modified Fluid Gelatin/
MFG
(-) (-) “Repelling Effect”:
(-) (-)
(-)
negative charges of
(-)
(-)
endothelial cells will repell with
(-) negative charges of
(-)
(-) MFG molecules

(-)
(-)
(-)
Result:
(-) Strong Volume effect, Longer
(-)
(-) Duration effect
(-) & minimalism chloride
(-) (-)
 Koloid yang bebas zat pirogen, antigen dan tidak toksik (1)
 TOK dicapai dengan adekuat, bertahan selama 3-4 jam dan TOK
dipertahankan 34 mmHg(1)
 Stabil dan mudah disimpan dalam waktu yang lama (3 Tahun) (1)
 Metabolisme dan ekskresi koloid tidak menimbulkan efek yang tidak
diinginkan pada resipien (Aman terhadap ginjal) (1,2)
 Tidak mengganggu koagulasi dan hemostasis, atau gangguan
cocok silang (1)
 Sebagai pengganti plasma Gelafusal dapat memperbaiki hemoreologi,
memperbaiki aliran sirkulasi mikro, penyediaan O2 dan fungsi organ
(1,3)

Ref :
1. Package Insert Gelafusal
2. Schortgen at al. Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a
multicentre randomized study. The Lancet 2001;357:911-16
3. Sunatrio. Pemilihan koloid dalam praktek klinis. Resusitasi Cairan 2000; 59-75
KOMPOSISI CAIRAN INFUS RL

KOMPOSISI:
Na+ 130 mEq/L
Cl- 109 mEq/L
K+ 4 mEq/L
Ca2+ 2.7 mEq/L
Laktat 28 mEq/L
 Komposisi Elektrolit Koloid
Molecule Plasma Gelatin HES
Brand Plasma Haemaccel Gelafusal Voluven Widahes Sanbe Hest Tetraspan
Sodium ( Na+ ) 140 145 130 154 154 154 140
Potassium ( K+ ) 5 2.6 5.4 4
-)
Chloride ( Cl 105 145 85 154 154 154 118
Calcium 2.2 3.1 0.9 2.5
Magnesium 1 1 1
Bicarbonate 24
Lactate 1
Acetate 27 24
Phosphat +
Malate 5
Sulphate +

SID = Na + K - Cl 40 2.6 50.4 0 0 0 26

 Gelatine with negative charges of molecule (anion)

-- - -
membrane
-
- -
- ---------------------- pore size
-

- ----------------------
- -
-
- - -
stretched molecule, excretion
strong negative charge via urine
negative charges repel from another
Polygeline
MFG