FLUID TREATMENT CHOICE

IN DENGUE INFECTION

Djatnika Setiabudi

Child Health Department

Medical Faculty Padjadjaran University
 Outline

 Introduction
 Dengue Classification (WHO 2011)
 Patophysiology
 Fluid Treatment
 Resume
 Dengue Infection

Burden of disease
 Endemic in > 100 tropical and subtropical countries
 50–100 million dengue fever infections per year globally
 500,000 cases of severe dengue  DHF and DSS
 Average case fatality 2–5%

 Indonesia (Profil Kesehatan tahun 2010):

- DHF the second most hospitalized patients
- 156,086 cases; insidence rate 65.7/100,000 /year
- Case Fatality Rate (CFR): 0.87%
 New Guidelines
WHO /SEARO,
2011

Important notes:

1. Clinical spectrum added:

expanded dengue
syndrome

2. If fever and significant

plasma leakage: DHF clinical
diagnosis is most likely even
if there is
no bleeding manifestation
or thrombocytopenia
Manifestations of dengue virus infection
(WHO, 2011)
WHO classification of dengue infections
and grading of severity of DHF (2011)
 DENGUE VIRUS INFECTION

FEVER BLEEDING HEPATOMEGALY INCREASE TROMBOCYTOPENIA

ANOREXIA MANIFESTATION VASCULAR
VOMITING PERMEABILITY

Plasma leakage :
Hemoconcentration
Hipoproteinemia
Dehydration
Pleural effusion
Ascites
Hypovolemia

DIC Shock

G.I. Anoxia Acidosis

bleeding

Suchitra (1993) Death

The course of Dengue illness
Perjalanan penyakit Demam Dengue

Suhu reda, klinis membaik,

nafsu makan membaik

Time of fever defervescence

(Saat suhu reda)
emp

Hari sakit
 Perjalanan penyakit DBD

Klinis memburuk, lemah, gelisah,

tangan kaki dingin, nafas cepat,
diuresis berkurang,
tidak ada nafsu makan

Time of fever defervescence

emp

Fase demam Fase syok Fase konvalesens

Hari sakit
 Principle of dengue management

1. Fluid replacement
Vascular permeability increase Plasma leakage
 hemoconcentration  hypo-volemic shock
2. Early detection and managememnet of
circulatory disturbance:
Clinically and serial Blood laboratory exam
3. Detection and management of bleeding
manifestation:
Clinically and laboratory exam
4. Supportive and symptomatic treatment
Fluid treatment: Principle of “4-J”

 Jalan/jalur pemberian : per oral – intravena ?

 Jenis cairan :
oralit- jus buah - kristaloid – koloid ?

 Jumlah cairan :
rumatan – dehidrasi atau hemokonsentrasi?
Syok atau tidak syok

 Jadwal pemberian :
bolus - per jam – per hari ?
Indication for intravenous fluid

- (Persistent) vomiting
- Nausea and anorexia (small drinking)
- Abdominal pain and tenderness
- Impaired concioussness
- Increasing Haematocrit value
- Circulatory disturbance
 Choice of fluids
 Suspected dengue and Dengue Fever:
- isotonic crystalloid : normal saline, Ringer’s
lactate, Ringer’s acetate, Ringer’s dextrose

 Dengue hemorrhagic Fever (DHF I and II):

- isotonic crystalloid : glucose contained solution?

 DSS: crystalloid versus colloid ?

 TANDA VITAL TIDAK STABIL
Penurunan jumlah urine output
Tanda-tanda syok
DBD derajat III*

Oksigen melalui face mask atau kanula hidung

Penggantian volume secara cepat: inisiasi terapi IV
10 ml/kg/jam larutan isotonik kristaloid selama 1-2 jam

Perbaikan Tidak ada perbaikan

Periksa ABCS
Pengurangan dari 10 ml/kg/jam (Acidosis, Bleeding, Calcium,
menjadi 7, 5, 3, 1.5 ml/kg/jam Sugar), dan koreksi
sesuai keadaan klinis dan hasil
pemeriksaan hematokrit

Peningkatan hematokrit Penurunan hematokrit

Koloid IV Transfusi darah :

Perbaikan lebih lanjut
(Dextran 40 atau HES) FWB10 ml/kg
atau PRC 5 ml/kg

Menghentikan terapi IV
selama 24-48 jam
Perbaikan

Pengurangan dari 10 ml/kg/jam

menjadi 7, 5, 3, 1.5 ml/kg/jam
tergantung keadaan klinis dan
hematokrit . Hentikan terapi IV
selama 24-48 jam

* Dalam kasus dengan syok yang lebih berat (DBD derajat IV) laju IV adalah 10 ml/kg selama 10-
15 menit atau 20 mL/kg dalam 30 menit, selanjutnya dikurangi menjadi 10 ml/kg/jam

Tatalaksana DSS (DBD III dan IV)

Randomised Controlled Trials
of Fluid Management in DSS
 Dung NM, Day NP, Tam DT, Loan HT, Chau HT, Minh LN, et al.
Fluid replacement in dengue shock syndrome: a randomized, double-blind
comparison of four intravenous-fluid regimens.

 A pilot study involving 50 children with DSS

 Children were randomised to receive:
crystalloid : normal saline (n=12), Ringer’s lactate (n=13)
colloid : dextran 70 (n=12) or 3% gelatin (n=13)
 Result:
- colloid group had significantly greater increases in mean
haematocrit (P=0·01), blood pressure (P=0·005), pulse
pressure (P=0·02)
 Overall : showed minor differences in the immediate
clinical responses to different fluids

Clin Infect Dis. 1999;29:787–94

 Ngo NT, Cao XT, Kneen R, Wills B, Nguyen VM, Nguyen TQ, et al.
Acute management of dengue shock syndrome: a randomized double-blind
comparison of 4 intravenous fluid regimens in the first hour.

 A larger study: 230 DSS children , compared the same four fluids
 Result:
- comparisons between all other solutions were not significant (However,
pulse pressure at presentation was identified as a potential confounder)
- in severe patients (pulse pressure < 10 mmHg) differences were found
 Conclusion:
- mild-to-moderate DSS patients have respond well to crystalloid treatment
- more severe: may require more aggressive management with colloids
- However, this study was statistically underpowered
- Recommendation:
further large-scale studies, stratified for admission pulse pressure,

Clin Infect Dis. 2001;32:204–13.

 Wills BA, Nguyen MD, Ha TL, Dong TH, Tran TN, Le TT, et al.
Comparison of three fluid solutions for resuscitation in dengue shock
syndrome.

 largest randomised study ,stratified for presenting pulse pressure.

 Group 1: Moderately shock (pulse pressure >10 to 20 mmHg, n=383)
were randomised to receive Ringer’s lactate (n=128), 6% dextran 70
(n=126) or 6% HES 200/0·5 (n=129).
 Group 2: severe shock (pulse pressure 10 mmHg) were randomised to
receive one of the colloids – dextran 70 (n=67) or HES (n=62)
 Result:
- Group 1: RL was found to be as effective as colloid therapy
- Group 2: - both colloid preparations performed equally result.
- dextran more adverse events than HES (allergic-reactions)
- no differences in severe adverse events
(significant bleeding or clinical fluid overload)

N Engl J Med. 2005;353:877–89.

 Characteristics of three Vietnam Studies
Author, Year Population Intervention: Study fluids

Dung et al., 50 Vietnamese child with Lactated Ringer’s solution, isotonic

1999 clinical DSS; saline, dextran, gelatin
5-15 years old Fluid rate :20mL/kg for 1 hr, then
10mL/kg for the 2nd hour
Nhan et al., 230 Vietnamese children Lactated Ringer’s solution, isotonic
2001 clinically diagnosed DHF saline, dextran, gelatin
DHF grade III = 222 Fluid rate :
DHF grade IV = 8 DHF grade III: 20mL/kg for 1 hr
1-15 years old DHF grade IV: 20ml/kg for 15min,
then 20mL/kg over the following hour

Willis et al., 512 Vietnamese children Lactated Ringer’s solution, starch,

2005 with clinical DSS dextran
Moderate shock = 383 Fluid rate:
Severe shock = 129 15mL/kg for 1 hr, then 10mL/kg for
2-15 years old the 2nd hr
 Kalayanarooj S.
Choice of colloidal solutions in dengue hemorrhagic fever patients.

 A study of 104 DHF patients with severe plasma leakage who

had failed to respond to crystalloids and required fluid
resuscitation
 compared bolus doses of two colloids, 10% dextran 40 (n=57)
and 10% HAES-steril (n=47)
 Objective: compare their effectiveness, impact on renal function
and haemostasis and any complications.
 Result:
- HAES-steril was found to be as effective as dextran 40.
- Both colloidal solutions were safe in these patients (no allergic
reactions, interference with renal function or haemostasis)

J Med Assoc Thai. 2008;91(suppl. 3):S97–103.

 SYSTEMATIC REVIEW

The Use of Colloids and Crystalloids in Pediatric

Dengue Shock Syndrome:
a Systematic Review and Meta-analysis*
Jalac SLR, de Vera M and Alejandria MM.

Philippine Journal of Microbiology and Infectious Diseases

2010;39(1):14-27
 Objectives:
 to compare the therapeutic effects of colloids
versus crystalloids of children with DSS in
reducing:
1. the recurrence of shock
2. the requirement for rescue fluids
3. the need for diuretics
4. the total volume of intravenous fluids given
5. the haematocrit level and pulse rates
6. mortality rates
 Results:
 Colloids and crystalloids did not differ significantly in
decreasing:
1. t:he risk for recurrence of shock (RR 0.92, 95% CI 0.62 - 1.38)
2. the need for rescue fluids (RR 0.90, 95% CI 0.70 - 1.16)
3. mortality rates
4. total volume of intravenous fluids given
5. the need for diuretics (RR=1.17, 95% CI 0.84 to 1.64)

 significant improvements from baseline in the haematocrit

levels and pulse rates of patients who were given colloids

 Allergic type reactions were seen in patients given colloids

 Conclusion:

 no significant advantage was found colloid over

crystalloids in reducing the recurrence of shock,
the need for rescue colloids, the total amount of
fluids, the need for diuretics, and in reducing
mortality

 Colloids decreased the haematocrit and pulse rates

of children with DSS after the first two hours of
fluid resuscitation
 Resume
 These studies show that the majority of DSS children can
be treated successfully with isotonic crystalloid solutions

 If a colloid is considered necessary:

- rely on personal experience
- familiarity with particular products
- local availability and cost

 A medium-molecular-weight preparation : optimal choice

- good initial plasma volume support
- good intravascular persistence and
- acceptable tolerability profile
 Characteristics of colloids
used for plasma volume support

Initial volume Duration of Other

Adverse effect Allergic
expansion volume effect significant
on coagulation potential
(%)* (hrs) side-effects
3% Gelatine
60–80 3–4 +/− ++
(MW = 35,000)
Renal failure in
10% Dextran 40
170–180 4–6 ++ + hypovolaemic
(MW = 40,000)
patients
6% Dextran 70
100–140 6–8 ++ +
(MW = 70,000)
6% Hydroxy-ethyl
starch = HES 100–140 6–8 + +/−
(MW = 200,000/0·5)
6% HES
80–100 12–24 ++ +
(MW = 400,000)

Management of dengue; Wills B. Halstead SB (Ed.) : 2008 Imperial College Press.

Note: *Infused volume; MW, molecular weight
Countries and areas at risk of dengue transmission, 2008
Dengue Classification........
 Dengue virus infection

Asymptomatic Symptomatic

Undifferentiated Dengue Fever Dengue hemorrhagic fever

febrile illness syndrome (plasma leakage)
(viral syndrome)

Without With unusual No shock Dengue shock

haemorrhage haemorrhage syndrome

Clinical Spectrum of Dengue Viral Infection, WHO 1997

WHO, 1997
 Ditjen Yanmed

Ditjen P2PL
 WHO/TDR
Guidelines 2009

These guidelines
are not intended toreplace
national guidelines but to
assist in the development of
national or regional
guidelines
Suggested dengue classification and level of severity
WHO, 2009
Tata laksana DBD derajat I & II
Cairan awal : Rumatan + 5%
(7ml/kgBB/jam)
Monitor tanda vital
Hb,Ht,trombo tiap 6-12jam

Perbaikan Tidak ada perbaikan

Tidak gelisah Gelisah

Nadi kuat Distres nafas
Tek drh stabil Frek nadi naik
Ht turun Ht tinggi
Diuresis 2ml/kgBB/jam Tek nadi <20mmHg
Diuresis kurang

Tetesan dikurangi Tetesan dinaikkan

5ml/kgBB/jam 10 ml/kgBB/jam

Evaluasi 12-24jam
3ml/kgBB/jam
1,5 mL/kg/jam
Tatalaksana DSS Tanda vital tidak stabil
Stop dalam 24-48jam
 DBD derajat I dan II

Jumlah Cairan :
Rumatan : Halliday & Segar

BB (Kg) Jumlah cairan / 24 jam

< 10 100cc/kg BB
10 – 20 1000 + 50cc/kg BB untuk tiap kelebihan > 10 kg
>20 1500 + 20cc/kg BB untuk tiap kelebihan > 20 kg

Kehilangan cairan : DHF dianggap dehidrasi sedang = 5-8%,

setiap 1% = 10cc/kg BB
 DBD derajat I dan II

Contoh : berat badan 18 kg

 Rumatan = (10 x 100) + (8x50) = 1400 cc

 Kehilangan cairan = 18 x 5 x 10 cc = 900 cc

 Jumlah : 2300 cc/24 jam

 Order untuk kebutuhan tiap jam ( + 100cc /jam) 

selanjutnya cairan disesuaikan bergantung pada
hasil monitoring Hematokrit dan klinis