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 ANOREXIA VOMITING

BLEEDING
MANIFESTATION

HEPATOMEGALY

INCREASE VASCULAR PERMEABILITY

TROMBOCYTOPENIA

Plasma leakage :
Hemoconcentration

Dehydration

Hipoproteinemia
Pleural effusion

Hypovolemia

Ascites

DIC
G.I. bleeding

Shock
Anoxia Death Acidosis

Suchitra (1993)

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 Early detection and managememnet of circulatory disturbance: Clinically and serial Blood laboratory exam Detection and management of bleeding manifestation: Clinically and laboratory exam

2.

3.

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

Penurunan hematokrit

Perbaikan lebih lanjut

Koloid IV (Dextran 40 atau HES)

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
Dung et al., 1999

Population
50 Vietnamese child with clinical DSS; 5-15 years old 230 Vietnamese children clinically diagnosed DHF DHF grade III = 222 DHF grade IV = 8 1-15 years old 512 Vietnamese children with clinical DSS Moderate shock = 383 Severe shock = 129 2-15 years old

Intervention: Study fluids

Lactated Ringers solution, isotonic saline, dextran, gelatin Fluid rate :20mL/kg for 1 hr, then 10mL/kg for the 2nd hour 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 Lactated Ringers solution, starch, dextran Fluid rate: 15mL/kg for 1 hr, then 10mL/kg for the 2nd hr

Nhan et al., 2001

Willis et al., 2005

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 ++ Renal failure in hypovolaemic patients Other significant side-effects

10% Dextran 40 (MW = 40,000)

6% Dextran 70 (MW = 70,000)

170180

46

++

100140

68

++

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

6% HES (MW = 400,000)

100140

68

+/

80100

1224

++

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 febrile illness

(viral syndrome)

Dengue Fever syndrome

Dengue hemorrhagic fever (plasma leakage)

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

Tidak ada perbaikan

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

Tetesan dikurangi 5ml/kgBB/jam

Tetesan dinaikkan 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)
< 10 10 20 >20

Jumlah cairan / 24 jam

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