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

50100 million dengue fever infections per year globally
500,000 cases of severe dengue DHF and DSS
Average case fatality 25%

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

ANOREXIA

MANIFESTATION

VOMITING

HEPATOMEGALY

INCREASE

TROMBOCYTOPENIA

VASCULAR
PERMEABILITY

Plasma leakage :
Hemoconcentration

Hipoproteinemia

Dehydration

Pleural effusion

Hypovolemia

DIC
G.I.
bleeding

Suchitra (1993)

Ascites

Shock
Anoxia
Death

Acidosis

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

emp

Time of fever defervescence

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, Ringers
lactate, Ringers acetate, Ringers 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

Pengurangan dari 10 ml/kg/jam

menjadi 7, 5, 3, 1.5 ml/kg/jam
sesuai keadaan klinis dan hasil
pemeriksaan hematokrit

Periksa ABCS
(Acidosis, Bleeding, Calcium,
Sugar), dan koreksi

Peningkatan hematokrit

Perbaikan lebih lanjut

Koloid IV
(Dextran 40 atau HES)

Penurunan hematokrit

Transfusi darah :
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 1015 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), Ringers lactate (n=13)
colloid
: dextran 70 (n=12) or 3% gelatin (n=13)
Result:
- colloid group had significantly greater increases in mean
haematocrit (P=001), blood pressure (P=0005), pulse
pressure (P=002)
Overall : showed minor differences in the immediate
clinical responses to different fluids
Clin Infect Dis. 1999;29:78794

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;32:20413.

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 Ringers lactate (n=128), 6% dextran 70
(n=126) or 6% HES 200/05 (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;353:87789.

Characteristics of three Vietnam Studies

Author, Year

Population

Intervention: Study fluids

Dung et al.,
1999

50 Vietnamese child with

clinical DSS;
5-15 years old

Lactated Ringers solution, isotonic

saline, dextran, gelatin
Fluid rate :20mL/kg for 1 hr, then
10mL/kg for the 2nd hour

Nhan et al.,
2001

230 Vietnamese children

clinically diagnosed DHF
DHF grade III = 222
DHF grade IV = 8
1-15 years old

Lactated Ringers solution, isotonic

saline, dextran, gelatin
Fluid rate :
DHF grade III: 20mL/kg for 1 hr
DHF grade IV: 20ml/kg for 15min,
then 20mL/kg over the following hour

Willis et al.,
2005

512 Vietnamese children

with clinical DSS
Moderate shock = 383
Severe shock = 129
2-15 years old

Lactated Ringers solution, starch,

dextran
Fluid rate:
15mL/kg for 1 hr, then 10mL/kg for
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):S97103.

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:

1.
2.

3.
4.
5.

6.

to compare the therapeutic effects of colloids

versus crystalloids of children with DSS in
reducing:
the recurrence of shock
the requirement for rescue fluids
the need for diuretics
the total volume of intravenous fluids given
the haematocrit level and pulse rates
mortality rates

Results:

1.

2.
3.
4.
5.

Colloids and crystalloids did not differ significantly in

decreasing:
t:he risk for recurrence of shock (RR 0.92, 95% CI 0.62 - 1.38)
the need for rescue fluids (RR 0.90, 95% CI 0.70 - 1.16)
mortality rates
total volume of intravenous fluids given
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
Adverse effect
expansion volume effect
on coagulation
(%)*
(hrs)
3% Gelatine
(MW = 35,000)

6080

34

+/

Allergic
potential

Other
significant
side-effects

++

10% Dextran 40
(MW = 40,000)

170180

46

++

6% Dextran 70
(MW = 70,000)

100140

68

++

6% Hydroxy-ethyl
starch = HES
(MW = 200,000/05)

100140

68

+/

6% HES
(MW = 400,000)

80100

1224

++

Renal failure in
hypovolaemic
patients

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

Undifferentiated
febrile illness

Symptomatic

Dengue Fever
syndrome

Dengue hemorrhagic fever

(plasma leakage)

(viral syndrome)

Without
haemorrhage

With unusual
haemorrhage

No shock

Dengue shock
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
Nadi kuat
Tek drh stabil
Ht turun
Diuresis 2ml/kgBB/jam

Tetesan dikurangi
5ml/kgBB/jam

Gelisah
Distres nafas
Frek nadi naik
Ht tinggi
Tek nadi <20mmHg
Diuresis kurang

Tetesan dinaikkan
10 ml/kgBB/jam
Evaluasi 12-24jam

3ml/kgBB/jam
1,5 mL/kg/jam
Tatalaksana DSS

Stop dalam 24-48jam

Tanda vital tidak stabil

DBD derajat I dan II

Jumlah Cairan :
Rumatan

: Halliday & Segar

BB (Kg)

Jumlah cairan / 24 jam

< 10
10 20
>20

100cc/kg BB
1000 + 50cc/kg BB untuk tiap kelebihan > 10 kg
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 =

Jumlah :

900 cc
2300 cc/24 jam

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

selanjutnya cairan disesuaikan bergantung pada
hasil monitoring Hematokrit dan klinis