CPG 2010- Management of Dengue Infection in Adults (Revised 2nd Ed 2010) (1)

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    MINISTRY OF HEALTH MALAYSIA ACADEMY OF MEDICINE MALAYSIA

    CLINICAL PRACTICE GUIDELINESMOH/P/PAK/174.08 (GU)

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    Review of the Guidelines

    These guidelines were issued in 2010 and will be reviewed in

    2014 or sooner if new evidence becomes available.

    CPG Secretariat

    Health Technology Assessment Section

    Medical Development Division

    Ministry of Health Malaysia

    4th Floor, Block E1, Parcel E

    62590 Putrajaya.

    Electronic version available on the following websites :

    http://www.moh.gov.my

    http://www.acadmed.org.my

    These are Clinical Practice Guidelines on Management of Dengue

    Infection in Adults (Revised 2nd Edition) 2010. The CPG supersede the

    previous CPG on Management of Dengue Infection in Adults (2nd Edition) 2008.

    These guidelines are meant to be guides for clinical practice,

    based on the best available evidence at the time of develoment.

    Adherence to these guidelines may not necessary guarantee

    the best outcome in every case. Every healthcare provider is

    responsible for the management of his/her unique patient

    based on the clinical picture presented by the patient and

    the management options available locally.

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    GUIDELINES DEVELOPMENT AND OBJECTIVE

    GUIDELINES DEVELOPMENT

    The development group or these guidelines consisted o a amily medicine

    specialist, an emergency medicine specialist, a general physician, inectious

    disease physicians, intensivists, haematologists, public health physicians,

    a virologist and a nursing sister rom the Ministry o Health and Ministry o

    Higher Education, Malaysia. During the process o development o these

    guidelines, there was active involvement o a review committee.

    The previous edition o CPG (2003) was used as the basis or the

    development o these present guidelines.

    These guidelines provide:

    a. A detailed description o the clinical course o dengue illness which

    reects the dynamism and systemic nature o dengue that have crucial

    bearing on the patients management.

    b. A detailed description o the basic pathophysiological changes o

    severe dengue (i.e. plasma leakage and hypovolemia/shock) and

    provide guidance on the recognition o these changes and appropriate

    action o management.

    c. A brie discussion on WHO Classifcation (1997) and its limitations.

    d. Some useul guides on the dierential diagnoses that can be conused

    with dengue or vice versa; they were described according to the stage

    o disease.

    e. A more ocused guide on the disease monitoring in accordance with

    the dynamic changes as the disease progresses.

    . Emphasis on the importance o monitoring the plasma leakage (clinical

    signs o plasma leakage and haematocrit (HCT) and haemodynamic

    status o the patients.

    g. Clearer algorithm on uid management in severe dengue.

    h. Emphasis on the importance o recognising or suspecting signifcant

    occult bleed with some useul guides.

    i. A more systematic approach on the recognition o signs o recovery.

    Literature search was carried out at the ollowing electronic databases:

    International Health Technology Assessment Website, PUBMED, Cochrane

    Database o Systemic Reviews (CDSR), Journal ull text via OVID search

    engine, Comprehensive; Database o Abstracts o Reviews o Eectiveness,

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    Cochrane Controlled Trials Registered, CINAHL via EBSCO search

    engine. In addition, the reerence lists o all relevant articles retrieved were

    searched to identiy urther studies. Reerence was also made to other

    guidelines WHO Dengue Haemorrhagic Fever: Diagnosis, Treatment,

    Prevention and Control, WHO Geneva, 1997; Guidelines, Guidelines or

    DHF Case Management, Bangkok, Thailand 2002; Guidelines on Clinical

    Management O Dengue Fever / Dengue Haemorrhagic Fever 2005 SriLanka; WHO Regional Publication SEARO, 1999; Guidelines or Treatment

    o Dengue Fever/Dengue Hemorrhagic Fever in Small Hospitals, WHO

    Regional Ofce or SE Asia, New Delhi, 1999. There were very ew studies

    carried out on dengue patients in the adult population. Many o the studies

    included in these guidelines are based upon the management o dengue

    in children. The fndings o these studies were then extrapolated on to the

    adult population, taking into consideration our local practices.

    The clinical questions were divided into major subgroups and memberso the development group were assigned individual topics within these

    subgroups. The group members met a total o 15 times throughout the

    development o the guidelines. All literature retrieved were appraised by

    at least two members and presented in the orm o evidence tables and

    discussed during group meetings. All statements and recommendations

    ormulated were agreed by both the development group and review

    committee. Where the evidence was insufcient the recommendations were

    derived by consensus o the development group and review committee.

    The articles were graded using the modifed version o the criteria used

    by the Catalonia Agency or Health Technology Assessment and Research

    (CAHTAR) Spain, while the grading o recommendation in this guideline

    was modifed rom the Scottish Intercollegiate Guidelines Network (SIGN).

    The drat guidelines was posted on both the Ministry o Health Malaysia

    and Academy o Medicine, Malaysia websites or comment and eedback.

    These guidelines had also been presented to the Technical AdvisoryCommittee or Clinical Practice Guidelines, and the Health Technology

    Assessment and Clinical Practice Guidelines Council, Ministry o Health

    Malaysia or review and approval.

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    OBJECTIVES

    GENERAL OBJECTIVES

    To provide evidence-based guidance in the management o dengue

    inection in adult patients

    SPECIFIC OBJECTIVES

    To improve recognition and diagnosis o dengue cases and provide

    appropriate care to the patients

    To identiy severe dengue and carry out more ocused close monitoring

    and prompt appropriate management

    To provide guidance on appropriate and timely uid management andthe use o blood and blood products

    To improve on early and accurate notifcation o dengue cases or

    prompt public health intervention

    CLINICAL QUESTIONS

    Please reer to Appendix 6

    TARGET POPULATION

    Adult patients with dengue ever, dengue haemorrhagic ever or dengue

    shock syndrome and other orms o severe dengue.

    TARGET GROUP/USER

    These guidelines are applicable to primary care doctors, public health

    personnel, nurses, assistant medical ofcers, physicians and critical care

    providers involved in treating adult patients with dengue ever, dengue

    haemorrhagic ever or dengue shock syndromeand other orms o severedengue.

    HEALTHCARE SETTINGS

    Both outpatient and inpatient settings

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    CLINICAL INDICATORS FOR QUALITy MANAGEMENT

    PRIMARy INDICATORS

    i. Case atality rate (DF & DHF)

    Numerator: No o DF & DHF/DSS death

    Denominator: No o DF & DHF cases (clinically diagnosed)

    National target (9th Malaysian Plan):< 0.2%

    ii. DHF atality rate

    Numerator: No o DHF/ DSS death

    Denominator: No o DHF/ DSS cases (clinically diagnosed)

    National target (9th Malaysian Plan):

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    GUIDELINES DEVELOPMENT GROUP

    CHAIRPERSON

    Dr. Mahiran Mustaa

    Senior Consultant Inectious Disease Physician

    Hospital Raja Perempuan Zainab II

    Kota Bharu Kelantan

    MEMBERS(alphabetical order)

    Dr. Abdul Hamid Jaaar

    Assistant Director

    Communicable Disease Control Division

    Ministry o Health

    Dr. Norita Ahmad

    Consultant Inectious Disease Physician

    Hospital Raja Perempuan Zainab II

    Kelantan

    Dr. Ainul Nadziha Mohd. Hanafah

    Assistant DirectorHealth Technology Assessment Section

    Medical Development Division, MOH

    Dr. Salmah Idris

    Consultant PathologistHospital Sungai Buloh

    Selangor

    Dr. Chow Ting Soo

    Consultant Inectious Disease Physician

    Hospital Pulau Pinang

    Pulau Pinang

    Dr. Sheamini Sivasampu

    Principal Assistant Director

    Health Technology Assessment Section

    Medical Development Division MOH

    Dr. Faisal Salikin

    Emergency Medicine Specialist

    Hospital Kuala Lumpur

    Kuala Lumpur

    Ms Sin Lian The

    Nursing Sister

    Health Technology Assessment Section

    Medical Development Division MOH

    Dato Dr. Faraizah Abdul Karim

    Deputy Director

    National Blood Centre Kuala Lumpur

    Dato Dr. K. Sree Raman

    Senior Consultant Physician

    Hospital Tuanku Jaaar

    Negeri Sembilan

    Dr. Ho Bee Kiau

    Family Medicine Specialist

    Bukit Kuda Health ClinicSelangor

    Dr. Suresh Kumar

    Consultant Inectious Disease Physician

    Hospital Sungai BulohSelangor

    Dr Mohamad Ikhsan Selamat

    Principal Assistant Director

    Communicable Disease Control Division

    Ministry o Health

    Dr. Tan Cheng Cheng

    Senior Consultant Intensivist and

    Anaesthesiologist

    Hospital Sultanah Aminah Johor

    Dr. Jameela Sathar

    Senior Consultant Haematologist

    Hospital Ampang Selangor

    Dr. Tan Lian Huat

    Lecturer and Inectious Disease Physician

    University Malaya Medical Centre

    Selangor

    Dr. Lim Chew Har

    Consultant Intensivist & Anaesthesiologist

    Hospital Pulau Pinang

    Pulau Pinang

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    REVIEW COMMITTEE(alphabetical order)

    The drat guidelines was reviewed by a panel o independent expert reerees

    rom both public and private sectors, who were asked to comment primarily

    on the comprehensiveness and accuracy o interpretation o the evidence

    supporting the recommendations in the guideline.

    Dr. Christopher Lee

    Senior Consultant Inectious Disease Physician

    Hospital Sungai Buloh

    Selangor

    Proessor Luc Lum Chai See

    Proessor o Paediatrics

    University Malaya Medical Centre

    Selangor

    Datin Paduka Dr. Santha Kumari

    Senior Consultant Physician

    Hospital Tengku Ampuan Rahimah

    Selangor

    Dr. Radhakrishnan Sothiratnam

    Consultant Physician

    Columbia Asia Medical CentreNegeri Sembilan

    Dr. Rud yeoh Seok Ching

    Consultant Haematologist

    S. C. Yeoh Haemotology Consultancy Sdn Bhd

    Kuala Lumpur

    Datin Dr. Rugaah Bakri

    Deputy DirectorHealth Technology Assessment Section

    Medical Development Division

    Ministry o Health

    Dr. Tai Li Ling

    Senior Consultant Intensivist & Anaesthesiologist

    Hospital Kuala Lumpur

    Kuala Lumpur

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    EXTERNAL REVIEWERS(alphabetical order)

    The ollowing external reviewers provided eedback on the drat

    Dr. Alan Teh

    Consultant Physician & Haematologist

    Subang Jaya Medical Centre

    Selangor

    Dr. Maimunah Mahmud

    Family Medicine Specialist

    Klinik Kesihatan Jinjang

    Kuala Lumpur

    Dr. Chua Kaw Beng

    Consultant Virologist

    National Public Health Laboratory

    Ministry o Health

    Sungai Buloh, Selangor

    Dato Dr. Ravindran Jegasoth

    Head o Department and Senior

    Consultant O&G

    Hospital Kuala Lumpur

    Kuala Lumpur

    Dr. Jearam Menon

    Senior Consultant Gastroenterologist

    & Head o Department

    Hospital Queen Elizabeth

    Sabah

    Dr. Rashidi Ahmad

    Emergency Physician/Lecturer

    Hospital Universiti Sains Malaysia

    Kelantan

    Dato Dr. ST Kew

    Senior Consultant Physician

    International Medical University

    Kuala Lumpur

    Assoc. Pro. Dr. Shaiul Bahari Ismail

    Lecturer and Family Medicine Specialist

    Hospital Universiti Sains Malaysia

    Kelantan

    Dr. G. R. Letchuman Ramanathan

    Senior Consultant Physician

    Hospital Taiping

    Perak

    Dr. Tan It

    Consultant Anaesthetist

    Sunway Medical Centre

    Selangor

    Dato Dr. Lim yu Hoe

    Senior Consultant Physician

    Hospital Pulau Pinang

    Pulau Pinang

    Dr. S Visalach Purushothaman

    Senior Consultant Haematologist

    Hospital Ampang

    Selangor

    Dr. Mahathar Abdul Wahab

    Emergency Medicine Specialist

    Hospital Kuala Lumpur

    Kuala Lumpur

    Dr. yoong Kar yaw

    Consultant Physician

    Hospital Sultan Ismail

    Johor

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    TABLE OF CONTENTS

    GUIDELINES DEVELOPMENT AND OBJECTIVE i

    GUIDELINES DEVELOPMENT COMMITTEE v

    REVIEW COMMITTEE vi

    EXTERNAL REVIEWERS vii

    TABLE OF CONTENT viii

    1. EPIDEMIOLOGY 1

    2. VIROLOGY 3

    3. CLINICAL MANIFESTATIONS AND PATHOPHYSIOLOGY 3

    3.1 SPECTRUM OF DENGUE INFECTION 3

    3.2 CLINICAL COURSE OF DENGUE INFECTIONi.Febrile Phase

    ii.Critical Phase

    iii.Recovery Phase

    44

    4

    5

    3.3 PATHOPHYSIOLOGY OF PLASMA LEAKAGE IN DENGUE

    HAEMORRHAGIC FEVER (DHF) / DENGUE SHOCK SYNDROME (DSS)

    6

    3.4 TOURNIQUET TEST 8

    3.5 WHO DENGUE CLASSIFICATION

    3.5.1 Limitations o WHO classifcation3.5.2 Suggested WHO Classifcation 2009

    8

    89

    3.6 OTHER IMPORTANT MANIFESTATIONS 9

    3.7 DIAGNOSTIC CHALLENGES 10

    4. DISEASE NOTIFICATION 11

    5. LABORATORY INVESTIGATIONS 12

    5.1 DISEASE MONITORING LABORATORY TESTS 12

    5.2 DIAGNOSTIC TESTS

    5.2.1 Dengue Serology Tests

    5.2.2 Virus Isolation

    5.2.3 Polymerase Chain Reaction (PCR)

    5.2.4 Non-structural Protein-1 (NS1 Antigen)

    13

    13

    15

    15

    15

    6. INVESTIGATION OF POST MORTEM CASE 16

    7. MANAGEMENT OF DENGUE INFECTION 16

    7.1 OUTPATIENT MANAGEMENT 16

    7.2 PATIENT TRIAGING AT EMERGENCY AND

    OUTPATIENT DEPARTMENTS

    18

    7.3 CRITERIA FOR HOSPITAL REFERRAL / ADMISSION

    7.3.1 Reerral rom Primary Care Providers to Hospital

    7.3.2 Reerral rom Hospitals Without Specialist to Hospital with

    Specialists

    19

    19

    19

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    7.4 DISEASE MONITORING

    7.4.1 Principles o Disease Monitoring

    7.4.2 Outpatient Disease Monitoring

    7.4.3 Inpatient Disease Monitoring

    20

    20

    20

    20

    7.5 FLUID MANAGEMENT

    7.5.1 Dengue with Warning Signs7.5.2 Non-shock Patients (DHF Grade I & II)

    7.5.3 Dengue Shock Syndrome (DSS) (DHF Grade III &IV)

    23

    2324

    ALGORITHM A - FLUID MANAGEMENT IN COMPENSATED SHOCK

    ALGORITHM B - FLUID MANAGEMENT IN DECOMPENSATED SHOCK

    27

    28

    7.6 MANAGEMENT OF BLEEDING/HAEMOSTASIS

    7.6.1 Haemostatic Abnormalities in Dengue Inection

    7.6.2 How to Recognize Signifcant Bleeding?

    7.6.3 Management o Bleeding in Dengue7.6.4 Management o Upper Gastrointestinal Bleeding (UGIT)

    7.6.5 The Role o Prophylactic Transusions in Dengue

    7.6.6 The Role o Adjunctive Therapy in Dengue

    29

    29

    29

    2930

    30

    30

    7.7 INTENSIVE CARE MANAGEMENT

    7.7.1 Indications or Respiratory Support (Non-invasive and

    Invasive Ventilation)

    7.7.2 Indications or Haemodynamic Support

    7.7.3 Guide on Saety and Risk o Invasive Procedures

    31

    31

    31

    32

    8. DISCHARGE CRITERIA 33

    9. PREVENTION OF DENGUE TRANSMISSION IN HOSPITALS 33

    10. VACCINATION 34

    11. DENGUE IN PREGNANCY 34

    REFERENCES 36

    APPENDIX 1 -WORLD HEALTH ORGANIZATION CLASSIFICATION

    OF DF AND DHF (1997)

    46

    APPENDIX 2 -Methods o Sample Collection 48

    APPENDIX 3 - Home Care Advice Leaet 49

    APPENDIX 4 -Disease Monitoring Card 50

    APPENDIX 5 - Dengue Monitoring Chart 51

    APPENDIX 6 - Clinical Questions 52

    APPENDIX 7 - Search Strategy 54

    LIST OF ABBREVIATIONS 55

    ACKNOWLEDGEMENT 56

    DISCLOSURE STATEMENT 56

    SOURCES OF FUNDING 56

    LEVELS OF EVIDENCE & GRADES OF RECOMMENDATION

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    1. EPIDEMIOLOGyDengue is one o the most important arthropod-borne viral diseases in

    terms o human morbidity and mortality. Dengue has become an important

    public health problem. It aects tropical and subtropical regions around the

    world, predominantly in urban and semi urban areas.

    The number o reported dengue ever (DF) and dengue haemorrhagic

    ever (DHF) cases in Malaysia shows an increasing trend (Figure 1). The

    incidence rate also shows an upward trend rom 44.3 cases/100,000

    population in 1999 to 181 cases/100,000 population in 2007 (Figure 2).

    This exceeds the national target or the incidence rate o DF and DHF

    which is less than 50 cases/100,000 population. Dengue ever accounts

    or almost 95% o all reported cases. The serologically confrmed cases

    are approximately 40-50% o these cases at the time o notifcation. This

    relatively low percentage o seropositivity is due to lack o convalescent

    samples (second blood specimen) being sent or confrmation.

    The incidence rate is higher in the age group o 15 years and above (Figure

    2). The highest incidence rate is among the working and school-going age

    groups. An increase o dengue deaths in the adult population has been

    observed since 2002 (Figure 3). The case atality rates or both DF and DHF

    however remain well below 0.3% since 2002 (Figure 4).

    Most o the dengue cases reported were rom urban areas (70 80%)

    where there is a high density o its population and rapid development

    activities actors which avour dengue transmission.

    6,543

    14,255

    19,429

    27,381

    10,146

    7,103

    16,368

    32,76731,545

    33,895

    39,65438,556

    46,542

    79.6

    43.040.9

    50.2

    46.5

    52.5 52.9

    47.348.9

    39.642.5

    47.3

    29.5

    0

    1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

    0.0

    10.0

    20.0

    30.0

    40.0

    50.0

    60.0

    70.0

    80.0

    90.0

    SerologyPositve(%)

    Total DF DHF Serology Positive (%)

    6,543

    14,255

    19,429

    27,381

    10,146

    7,103

    16,368

    32,76731,545

    33,895

    39,65438,556

    49,173

    79.7

    42.540.9

    50.2

    46.2

    52.4 53.0

    47.349.0

    39.6

    42.7

    47.348.7

    0

    10

    20

    30

    40

    50

    60

    70

    80

    90

    100

    0

    10,000

    20,000

    30,000

    40,000

    50,000

    60,000

    SerologyConfirmed(%)

    Noofcases

    Year

    Total (Clinical) DF DHF Serologically Confirm ed (%)

    Figure 1 : Number o Dengue Cases, Malasia 1995-2007

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    2

    0

    10

    20

    30

    40

    50

    60

    70

    80

    90

    1999 2000 2001 2002 2003 2004 2005 2006 2007Year

    NoO

    fDeath

    0 - 14 Years (IR) > 15 Years (IR)

    0.36

    0.63

    0.31 0.300.23

    0.30 0.280.23

    0.20

    0.00

    0.20

    0.40

    0.60

    0.80

    1.00

    1.20

    1.40

    1999 2000 2001 2002 2003 2004 2005 2006 2007

    Incide

    nce(per100,0

    00)

    Year

    Population (CFR) 0 - 14 Years (CFR) > 15 Years (CFR)

    44.330.2

    68.2

    133.6 125.9 132.5

    151.9144.7

    181

    0

    50

    100

    150

    200

    250

    1999 2000 2001 2002 2003 2004 2005 2006 2007Year

    Incidence

    (per

    100,

    000)

    Population 0 - 14 Years > 15 Years

    Figure 3 : Dengue Deaths b Age Group in Malasia, 1999-2007

    Figure 2 : Dengue Incidence Rate b Age Group in Malasia, 1999-2007

    Figure 4 : Dengue Case Fatalit Rate (CFR) b Age in Malasia, 1999-2007

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    3

    2. VIROLOGyDengue inection is caused by dengue virus which is a mosquito-borne

    avivirus. It is transmitted by Aedes aegypti and Aedes albopictus. There

    are our distinct serotypes, DEN-1, 2, 3 and 4. Each episode o inection

    induces a lie-long protective immunity to the homologous serotype but

    coners only partial and transient protection against subsequent inection

    by the other three serotypes. Secondary inection is a major risk actoror DHF due to antibody-dependent enhancement. Other important

    contributing actors or DHF are viral virulence, host genetic background,

    T-cell activation, viral load and auto-antibodies.

    All our serotypes can be isolated at any one time but the predominant

    circulating dengue virus will show a sinusoidal pattern (Figure 5). For

    example, DEN-3 was the predominant serotype in the early 90s with a peak

    in 1993, and then subsequently declined. It then re-emerged, reaching the

    peak in 2001. Other serotypes had been observed to be co-circulating at

    the same time

    3. CLINICAL MANIFESTATIONS AND PATHOPHySIOLOGy

    3.1 SPECTRUM OF DENGUE INFECTION

    The incubation period or dengue inection is 4-7 days (range 3-14).2 It

    may be asymptomatic or may result in a spectrum o illness ranging rom

    undierentiated mild ebrile illness to severe disease, with or withoutplasma leakage and organ impairment. Symptomatic dengue inection is a

    systemic and dynamic disease with clinical, haematological and serological

    profles changing rom day to day. These changes accelerate by the hour

    or even minutes during the critical phase, particularly in those with plasma

    leakage (reer to section 3.3).

    0

    10

    20

    30

    40

    50

    60

    70

    80

    90

    100

    %o

    fSerotype

    Den 1 (%) Den 2 (%) Den 3 (%) Den 4 (%)

    Figure 5 : Percentage o Dengue Serotpe in Malasia, 1991-2007

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    4

    Understanding the systemic and dynamic nature o dengue disease as well

    as its pathophysiological changes during each phase o the disease will

    produce a rational approach in the management o dengue

    3.2 CLINICAL COURSE OF DENGUE INFECTION

    Dengue inection is a dynamic disease. Its clinical course changes as the

    disease progresses. Ater the incubation period, the illness begins abruptly

    and will be ollowed by 3 phases: ebrile, critical and recovery phase (reer

    Figure 6). 3, 4

    i. Febrile Phase

    Typically, patients develop high grade ever suddenly. This acute ebrile

    phase usually lasts 2-7 days and oten accompanied by acial ushing,

    skin erythema, generalised body ache, myalgia, arthralgia and headache.3,4

    Some patients may have sore throat, injected pharynx and conjunctivalinjection. Anorexia, nausea and vomiting are common. These clinical

    eatures are indistinguishable between DF and DHF.5

    Mild haemorrhagic maniestations like positive tourniquet test or petechiae

    and mucosal membrane bleeding may be seen in DF and DHF.5,6 Per

    vaginal bleeding is common among young adult emales. Massive vaginal

    bleeding and gastrointestinal bleeding may occur during this phase but

    are not common.7, 6 The fndings o an enlarged and tender liver are more

    suggestive o DHF.5

    The earliest abnormality in the ull blood count is a progressive decrease

    in total white cell count. This should alert the physician to a high index

    o suspicion o dengue especially when there is positive history o

    neighborhood dengue. This disease should be notifed as early as possible

    to prevent disease rom assuming epidemic proportion.

    ii. Critical Phase

    The critical phase occurs towards the late ebrile phase (oten ater 3rd day

    o ever) or around deervescence (usually between 3rd to 5th day o illness

    but may go up to 7th day) when a rapid drop in temperature may coincide

    with an increase in capillary permeability in some patients. In other viral

    inections, the patients condition improves as the temperature subsides,

    but the contrary happens in DHF. At this point the patient will either become

    better i no or minimal plasma leak occurs, or worse i a critical volume o

    plasma is lost.3, 4,8, 9

    The critical phase lasts about 24-48 hours. (reer Figure 6) Varying

    circulatory disturbances (reer to Table 1) can develop. In less severe cases,

    these changes are minimal and transient. Many o these patients recover

    spontaneously, or ater a short period o uid or electrolyte therapy. In

    more severe orms o plasma leakage, the patients may sweat, become

    restless, have cool extremities and prolonged capillary refll time. The

    pulse rate increases, diastolic blood pressure increases and the pulse

    pressure narrows. Abdominal pain, persistent vomiting, restlessness,

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    altered conscious level, clinical uid accumulation, mucosal bleed or

    tender enlarged liver are the clinical warning signs o severe dengue or high

    possibility o rapid progression to shock.9, 10, 11 The patient can progress

    rapidly to proound shock and death i prompt uid resuscitation is not

    instituted.

    It is important to note that thrombocytopaenia and haemoconcentration(evidenced by a raised haemotocrit (HCT) rom baseline or a drop in HCT

    ater rehydration) are usually detectable beore the subsidence o ever

    and the onset o shock. Reer to 3.5.1 or urther details. The HCT level

    correlates well with plasma volume loss and disease severity. However, the

    levels o HCT may be equivocal when there is rank haemorrhage, early and

    excessive uid replacement or untimely HCT determinations.

    Leucopaenia with relative lymphocytosis, clotting abnormalities, elevation

    o transminases [typically the level o aspartate aminotransaminase(AST) is about 2-3 times the level o alanine aminotransaminase (ALT)],

    hypoproteinaemia and hypoalbuminaemia are usually observed.3, 4, 5

    iii. Recover Phase

    Ater 24-48 hours o deervescence, plasma leakage stops and is ollowed

    by reabsorption o extravascular uid. Patients general well being improves,

    appetite returns, gastrointestinal symptoms abate, haemodynamic status

    stabilises and diuresis ensues. Some patients may have a classical rasho isles o white in the sea o red.3 Some may experience generalised

    pruritus. Bradycardia and electrocardiographic changes are not uncommon

    during this stage. It is important to note that during this phase, HCT level

    stabilises or drops urther due to haemodilution ollowing reabsorption o

    extravascular uid. The recovery o platelet count is typically preceded by

    recovery o white cell count (WCC).

    Figure 6 : CLINICAL COURSE OF DHF12

    Note : Onset o deervescence usually occurs between day 3 to day 5 o illness

    40

    Viraemia

    Course ofdengue illness FEBRILE CRITICAL RECOVERY

    Shock / Bleeding Reabsorption / Fluid overloadDehydration

    Days of illness

    Temperature

    Potential

    clinical issues

    Laboratory

    changes

    Serology

    and virology

    Platelet

    Hematocrit

    IgM/IgG

    Organ Impairment

    1 2 3 4 5 6 7 8 9 1 0

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    Clinical deterioration oten occurs during the critical phase

    (plasma leakage) and it is thereore crucial to recognise the

    onset o this phase.

    The onset o critical phase is marked by plasma leakage and

    usually occurs around the onset o deervescence.

    Evidence o plasma leakage includes raised HCT (early marker),

    haemodynamic instability, uid accumulation in extravascular

    space (rather late marker) or hypoproteinemia.

    Abdominal pain, persistent vomiting, restlessness, altered

    conscious level, clinical uid accumulation, tender enlarged

    liver or mucosal bleed are the clinical warning signs o severe

    dengue or high possibility o rapid progression to shock.

    3.3 PATHOPHySIOLOGy OF PLASMA LEAKAGE IN DENGUEHAEMORRHAGIC FEVER (DHF)/DENGUE SHOCK SyNDROME (DSS)

    The primary pathophysiological abnormality seen in DHF and DSS is an

    acute increase in vascular permeability that leads to leakage o plasma

    into the extravascular compartment, resulting in haemoconcentration and

    hypovolaemia or shock.13,3,4 Hypovolaemia leads to reex tachycardia and

    generalised vasoconstriction due to increased sympathetic output.14,15

    Clinical maniestations o vasoconstriction in various systems are as

    ollows :

    a. Skin - coolness, pallor and delayed capillary refll time

    b. Cardiovascular system - raised diastolic blood pressure and a narrowing

    o pulse pressure

    c. Renal system - reducing urine output

    d. Gastrointestinal system - vomiting and abdominal pain

    e. Central nervous system lethargy, restlessness, apprehension, reduced

    level o consciousness

    . Respiratory system tachypnoea(respiratory rate >20/min)

    In patients whose consciousness is not obtunded, intense thirst is another

    prominent symptom. At the same time, the inadequate perusion o the

    tissue leads to increased anaerobic glycolysis and lactic acidosis. I the

    hypovolaemia is not corrected promptly, the patient will progress to a

    reractory shock state. By then, the tissue perusion would not respond to

    vasopressor drugs, even i the blood pressure and intravascular volume

    were to be restored and cardiac output would remain depressed. The

    resultant lactic acidosis urther depresses the myocardium and worsensthe hypotension.15 The common late complications o prolonged shock

    are massive bleeding, disseminated intravascular coagulopathy (DIC) andmulti-organ ailure which are oten atal.

    The ollowing table is the summary o the continuum o various

    pathophysiological changes in a patient who progresses rom normal

    circulatory state to hypovolaemic shock.

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    Table 1 : A continuum o pathophsiological changes rom normal circulation to

    compensated and decompensated/ hpotensive shock(Adapted rom15)

    Normal Circulation Compensated shockDecompensated /

    Hpotensive shock

    Clear consciousnessClear consciousness shock can be

    missed i you do not touch the patient

    Change o mental state restless,

    combative or lethargy

    Brisk capillary refll time (2 sec)Mottled skin, very prolonged

    capillary reil l time

    Warm and pink extremities Cool extremities Cold, clammy extremities

    Good volume peripheral pulses Weak & thready peripheral pulses Feeble or absent peripheral pulses

    Normal heart rate or age TachycardiaSevere tachycard ia wi th

    bradycardia in late shock

    Normal blood pressure or age

    Normal systolic pressure with

    raised diastolic pressure

    Postural hypotension

    Hypotension/unrecordable BP

    Normal pulse pressure or age Narrowing pulse pressureNarrowed pulse pressure

    (

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    3.4 TOURNIQUET TEST

    In DHF grade 1, a positive tourniquet test serves as the only indicator ohaemorrhagic tendency. The sensitivity o the test varies widely rom as lowas 0% to 57%, depending on the phase o illness the test was done andhow oten the test was repeated, i negative. In addition 5-21% o patientswith dengue like illness had positive tourniquet test but subsequently have

    negative dengue serology.22, Level 1

    A recent study demonstrated that there was 95.3% positive preditivevalue i ever, positive tourniquet test, leucopenia/ thrombocytopaenia/haemoconcentration were used as screening criteria.23, Level 8

    The tourniquet test may be useul as an additional tool when the diagnosis

    is in doubt, especially when the platelet count is still relatively normal.

    How to perorm tourniquet testInate the blood pressure cu on the upper arm to a point midway

    between the systolic and diastolic pressures or 5 minutes.

    A positive test is when 20 or more petechiae per 2.5 cm (1 inch)

    square are observed.

    Recommendation

    The tourniquet test may be helpul in the earl ebrile phase (less

    than three days) in dierentiating dengue rom other ebrile illnesses.(Grade C)

    3.5 WHO DENGUE CLASSIFICATION

    Based on current WHO dengue classifcation scheme (reer Appendix 1), thekey dierentiating eature between DF and DHF is the presence o plasmaleakage in DHF. However, in the early ebrile phase o dengue inection,the symptoms can overlap and one cannot dierentiate DF and DHF.

    DHF is urther classifed as mild (grades I and II) or severe (grades III andIV), the presence o shock being the main dierence. Grades III and IV areclassifed as Dengue Shock Syndrome (reer Appendix 1).

    (Note : The existing WHO dengue classifcation is being reviewed and revised)

    3.5.1 Limitations o WHO classifcation22, Level 1

    It has been observed that the existing WHO classifcation scheme hasseveral limitations as the disease has spread to new regions and inected

    older age groups. For example:1. Dengue with shock without ulflling all the 4 criteria or DHF

    There have been many case reports o patients with severe dengue with shockwho do not ulfl all the 4 criteria or DHF. These patients would have beenclassifed as dengue ever i the WHO criteria are to be strictly applied.

    2. Severe organ impairmentPatients with severe organ impairment such as liver, respiratory,cardiac and brain dysunction are not captured as having severe

    disease based on the existing classifcation.

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    3. Plasma leakage in DHF

    The requirement o 20% increase in HCT as one o the evidence oplasma leakage is difcult to ulfll due to several issues:

    a. Baseline HCT is not available in most patients and thereore, theinterpretation o plasma leak can only be made retrospectively

    b. Early uid administration may aect the level o HCTc. Bleeding will aect the HCT level

    4. The existing classifcation scheme is oten not useul or diseasemanagement because the correct disease classifcation can only bemade towards the end o the illness.

    Patients can present with severe dengue without ulfllingALL the4 criteria (reer Appendix 1) or DHF/DSS.

    3.5.2 Suggested WHO Classifcation 2009The classifcation into levels o severity has a high potential or being opractical use in the clinicians decision as to where and how intensivelythe patient should be observed and treated (i.e. triage, which is particularlyuseul in outbreaks).

    Figure 7: Suggested Dengue Classifcation and Level o Severit

    Source: World Health Organization. Dengue Guidelines or Diagnosis, Treatment,Prevention and Control - New Edition 2009. WHO: Geneva; 2009

    3.6 OTHER IMPORTANT MANIFESTATIONS

    Severe bleeding or organ impairment might occur without plasma leakage.The Following maniestations are important in dengue inection but areoten under- recognised or misdiagnosed:

    Figure 1.4 Suggested dengue case classification and levels of serverity

    DENGUE + WARNING SIGNS SEVERE DENGUE

    Probable denguelive in/ travel to dengue endemic area.

    Fever and 2 of the following criteria:

    l Nausea, vomitingl Rash

    l Aches and pains

    l Torniquet test positive

    l Leukopenia

    l Any warning sign

    Laboratory-confirmed dengue(important when no sign of plasma leakage)

    Warning signs*

    l Abdominal pain or tenderness

    l Persistent vomiting

    l Clinical fluid accumulation

    l Mucosal bleed

    l Lethargy, restlessness

    l Liver enlargment > 2cm

    l Laboratory: increase in HCT concurrentwith rapid decrease in platelet count

    * (requiring strict observation and medical intervention)

    CRITERIA FOR SEVERE DENGUE

    Severe plasma leakage leading to :

    l Shock (DSS)

    l Fluid accumulation with respiratory distress

    Severe bleedingas evaluated by clinician

    Severe organ involvement

    Liver : AST or ALT > = 1000

    CNS : Impaired consciousness

    Heart and other organs

    1. Severe plasma leakage

    2. Severe haemorrhage

    3. Severe organ impairment

    with warning signs

    without

    CRITERIA FOR DENGUE + WARNING SIGNS

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    1 0

    1. Acute abdomen :

    Acute abdominal pain is a common symptom in dengue inection. It can

    be due to hepatitis, acalculous cholecystitis and shock, and occasionally

    misdiagnosed as acute appendicitis.24, Level 8; 25, Level 8 The history o

    onset o ever beore the abdominal pain, and laboratory fndings o

    leucopenia, thrombocytopenia, or prolonged APTT with normal PT

    help to dierentiate acute abdominal pain due to dengue inection romother surgical causes.24, Level 8 Furthermore, in patients with shock, the

    abdominal pain is relieved by intravenous uid therapy.

    2. Hepatitis and liver ailure :

    Hepatitis is common in patients with DF/DHF and may be mild or

    severe regardless o the degree o plasma leakage. In some cases,

    liver ailure may occur.22,Level 1 The patients with liver ailure have a high

    propensity to bleed, especially gastrointestinal bleeding. 26, Level 8; 11, Level 8

    3. Neurological maniestation :

    Patients with dengue inection may have neurological maniestations,

    (

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    1 1

    FEBRILE PHASE

    Table 2 : Dierential diagnoses or dengue illness during ebrile phase

    Clinical sndrome Dierential diagnoses

    Flu-like sndrome

    Inuenza

    Measles

    Chikungunya

    AdenovirusInectious mononucleosis

    Acute HIV seroconversion illness

    Rash

    Rubella

    Measles

    Scarlet ever

    Meningococcal inection

    Chikungunya

    Drug

    DiarrheaRotavirus

    Food poisoning

    Neurological maniestationMeningoencephalitis

    Febrile seizures

    CRITICAL PHASETable 3:Dierential diagnoses or dengue illness during critical phase

    Clinical sndrome Dierential diagnoses

    Acute abdomen

    Acute appendicitis

    Acute cholecystitisPerorated viscus

    Viral hepatitis

    Diabetic ketoacidosis

    Shock Septic shock

    Respirator distress

    (Kussmauls breathing)

    Diabetic ketoacidosis

    Renal ailure

    Lactic acidosis

    Leucopaenia &

    thromboctopenia bleeding

    Acute leukaemiaImmune thrombocytopaenia purpura

    Thrombotic Thrombocytopenic purpura

    Malaria / Leptospirosis / Typhoid / Typhus

    Bacterial sepsis

    SLE

    Acute HIV seroconversion illness

    4. DISEASE NOTIFICATION

    All suspected dengue cases must be notifed by telephone to the nearesthealth ofce within 24 hours o diagnosis, ollowed by written notifcationwithin a week using the standard notifcation ormat.29 Any delay in notifcationwill increase the risk o dengue transmission in the locality o the residence.In 2007, 98.4% o dengue cases were notifed by public and private hospitalswith only 1.6% rom the government and private clinics. The average day oillness at the time o notifcation was about 4-5 days ater the onset o illnesseven though patients might have presented themselves to the healthcare

    acilities at day 1-3 day o ever.

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    1 2

    Notifcation should be done as soon as a clinical diagnosis o dengue is

    suspected; serological confrmation is not necessary. Notifed cases will be

    ollowed up by the health authorities or the verifcation o case defnition

    and preventive measures. It is also important to note that re-notifcation

    has to be done i the diagnosis has been changed rom DF to DHF or DF

    to other diagnosis.

    Failure to notiy is liable to be compounded under the Prevention and

    Control o Inectious Diseases Act, 1988 (Act 342).30

    5. LABORATORy INVESTIGATIONS

    5.1 DISEASE MONITORING LABORATORy TESTS

    Full Blood Count (FBC)

    1. White cell count (WCC) :

    In the early ebrile phase WCC is usually normal but will decreaserapidly as the disease progresses.5, Level 8 This trend o leucopenia

    should raise the suspicion o possible dengue inection.

    2. Haematocrit (HCT) :

    A rising HCT is a marker o plasma leakage in dengue inection and

    helps to dierentiate between DF and DHF but it can be masked in

    patients with concurrent signifcant bleeding and in those who receive

    early uid replacement.22, Level 1 Setting the patients baseline HCT in the

    early ebrile phase o disease will be very useul in the recognition o

    a rising HCT level.

    3. Thrombocytopaenia :

    Thrombocytopaenia is commonly seen in dengue inection.22,Level 1 In

    the early ebrile phase, platelet count is usually within normal range

    but it will decrease rapidly as the disease progresses to the late ebrile

    phase or at deervescence and it may continue to remain low or the

    frst ew days o recovery.

    There is a signifcant negative correlation between disease severity

    and platelet count 3, Level 9;31Level 8 but it is not predictive o bleeding.32,

    Level 8; 33, Level 1; 34, Level 6;35, Level 8; 36, Level 8

    Liver Function Test

    Elevated liver enzymes is common and is characterised by greater elevation o

    the AST as compared to the ALT.37,Level 8 The requency and degree o elevation

    o the liver enzymes are higher with DHF compared to DF.

    38, Level 8;

    37, Level 8

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    1 3

    Leucopaenia ollowed by progressive thrombocytopaenia is

    suggestive o dengue inection.

    A rising HCT accompanying progressive thrombocytopaenia is

    suggestive o DHF.

    There is no local data available on the normal range o HCT in adults.

    In the absence o a baseline HCT level, a HCT value o >40% in

    emale adults and >46% in male adults should raise the suspicion

    o plasma leakage.

    Recommendation

    The baseline HCT and WCC should be established as early aspossible in all patients with suspected dengue. (Grade A)

    Serial FBC and HCT must be monitored as the disease progresses.

    (Grade A)

    5.2 DIAGNOSTIC TESTS

    Defnitive diagnosis o dengue inection can only be confrmed in the

    laboratory. However, the interpretation o laboratory diagnostic results

    should be done in the clinical context. Laboratory confrmatory tests includeantibody detection (serology), virus isolation, detection o virus genetic

    materials (polymerase chain reaction -PCR) and detection o dengue virus

    protein (NS1 antigen).

    5.2.1 DENGUE SEROLOGy TESTS

    Haemagglutination Inhibition Test

    The haemagglutination Inhibition (HI) test has been the gold standard or

    serological diagnosis. However, because it is labour intensive and requires

    paired samples or interpretation, this test is now being used mainly orresearch purposes to dierentiate between primary and secondary dengue

    inections.

    Dengue IgM test

    The IgM capture enzyme-linked immunosorbent assay (ELISA) is the most

    widely used serological test. This antibody titre is signifcantly higher in

    primary inections, compared to secondary inections. Once the IgM is

    detectable, it rises quickly and peaks at about 2 weeks ater the onset o

    symptoms, and it wanes to undetectable levels by 60 days. However insome patients, it may persist or more than 90 days. A positive result thus

    has to be intepreted and correlated cautiously with the clinical picture. I

    the dengue IgM test is the only available diagnostic test in the hospital,

    then establishing a negative IgM early in the illness, and demonstrating a

    positive serology later will be essential to exclude alse negative results.

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    In one study, IgM was detected in only 55% o patients with primary dengue

    inections between day 4-7 onset o ever, and it became positive in 100%

    o the patients ater day 7. However, in secondary dengue inections, IgM

    was detected in only 78% o patients ater day 7.39, Level 7. In another study,

    28% o secondary dengue inections were undiagnosed when IgM was the

    only test perormed.4, Level 9; 40,Level 8; 41, Level 8

    Indirect IgG ELISA test

    In primary and secondary dengue inection, dengue IgG was detected in

    100% o patients ater day 7 o onset o ever. Thereore dengue IgG is

    recommended i dengue IgM is still negative ater day 7 with the negative

    IgG in the initial test sample.39, level 7; 40, level 8; , level 8

    Please reer to Appendix 2 or methods o sample collection

    Dengue Rapid tests

    Simple rapid tests such as the strip assays (immunochromatography test)

    are available or qualitative detection o dengue IgM and IgG (e.g. Pan Bio

    Dengue IgM ELISA and Dengue IgM Dot Enzyme Immunoassay).

    The yield o rapid tests was shown to be higher when samples were

    collected later in the convalescent phase o inection, with good specifcity

    and could be used when ELISA test were not available 43, Level 1 But the

    result had to be interpreted in the clinical context because o alse positive

    and negative results.44,Level 8;45, Level 8; 41, Level 8; 46, Level 8 It isrecommended that

    the dengue IgM Capture ELISA test be done ater a rapid test, to confrm

    the status.44,Level 8

    Note : False positive dengue serolog

    Serological tests or dengue have been shown to cross-react with: other avivirus Japanese Encephalitis.47, Level 9; 41, Level 8

    non-avivirus malaria, leptospirosis, toxoplasmosis, syphilis48,Level ; 45, Level 8

    connective tissue diseases rheumatoid arthritis44, Level 8

    Recommendation

    In order to establish serological confrmation o dengue illness aseroconversion o dengue IgM needs to be demonstrated. Thereorea dengue IgM should be taken as soon as the disease is suspected.(Grade C)

    Dengue IgM is usually positive ater day 5-7 o illness. Thereore anegative IgM taken beore day 5-7 o illness does not exclude dengueinection. (Grade B)

    I dengue IgM is negative beore day 7, a repeat sample must be takenin recovery phase. (Grade B)

    I dengue IgM is still negative ater day 7 with negative IgG tested at lessthen 7 days, dengue IgG is recommended or diagnostic confrmation.(Grade C)

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    5.2.2 VIRUS ISOLATION

    Virus isolation is the most defnitive test or dengue inection. It can only be

    perormed in the lab equipped with tissue culture and other virus isolation

    acilities. It is useul only at the early phase o the illness. Generally, blood

    should be collected beore day 5 o illness; i.e. beore the ormation o

    neutralizing antibodies.

    During the ebrile illness, dengue virus can be isolated rom serum, plasma

    and leucocytes. It can also be isolated rom post mortem specimens. The

    monoclonal antibody immunouorescence test is the method o choice or

    identifcation o dengue virus. It may take up to two weeks to complete the

    test and it is expensive.

    Note: Virus isolation has a poor yield i compared with molecular tests. It is most probably due

    to the viability o the virus and the quality o the samples.49,Level 8

    5.2.3 POLyMERASE CHAIN REACTION (PCR)

    Molecular tests such as the reverse transcriptase ploymerase chain

    reaction (RT- PCR) are useul or the diagnosis o dengue inection in the

    early phase (< 5 days o illness). It was shown to have a sensitivity o 100%

    in the frst 5 days o disease, but reduced to about 70% by day 6, ollowing

    the disappearance o the viraemia.50, Level 8;42, Level 8; 51, Level 8

    An additional advantage o RT- PCR is the ability to determine dengueserotypes 52, Level 7; 42, Level 8; 53, Level 8; 49, Level 8; 54, Level 8

    Limitations o RT- PCR are:

    a) This test is only available in a ew centres with acilities and trained

    personnel (e.g. IMR, HKL, National Public Health Laboratory and University Malaya

    Medical Centre).

    b) The test is expensive

    c) The specimen requires special storage temperatures and short

    transportation, time between collection and extraction (reer Appendix 1)

    In view o these limitations, the use o RT- PCR should only be considered

    or in-patients who present with diagnostic challenges in the early phase

    o illness.

    5.2.4 NON-STRUCTURAL PROTEIN-1 (NS1 Antigen)

    NS1 antigen is a highly conserved glycoprotein that seems to be essential

    or virus viability. Secretion o the NS1 protein is a hallmark o avivirus

    inecting mammalian cells and can be ound in dengue inection as well

    as in yellow ever and West Nile virus inection. This antigen is present inhigh concentrations in the sera o dengue inected patients during the early

    phase o the disease.55, Level 8; 56,Level 8

    The detection rate is much better in acute sera o primary inection (75%-

    97.3%) when compared to the acute sera o secondary inection (60% -

    70%).57, Level 8;58, Level 8;59, Level 8;60, Level 8 The sensitivity o NS1 antigen detection

    drops rom day 4-5 o illness onwards and usually becomes undetectable

    in the convalescence phase.61,Level 8;60, Level 8; 58,Level 8;59,Level 8

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    Table 4 : A Stepwise Approach On Outpatient Management o Dengue Inection

    It is important to evaluate every patient in a stepwise manner as in the ollowing :

    Step 1: Overall assessment1. History

    Date of onset of fever/ illness

    Oral intake Assess for alarm signs refer to Table 5

    Diarrhoea

    Bleeding

    Change in mental state/seizure/dizziness

    Urine output (frequency, volume and time of last voiding)

    Other important relevant histories:

    - Family or neighbourhood history o dengue

    - Jungle trekking and swimming in waterall (consider leptospirosis, typhus, malaria)

    - Recent travel

    - Recent unprotected sexual or drug use behaviour (consider acute HIV seroconversion illness)

    - Co-morbidities (consider sepsis particularly in patients with diabetes mellitus)

    2. Physical examination

    i. Assess mental state and Glasgow Coma Scale (GCS) score

    ii. Assess hydration status

    iii. Assess haemodynamic status

    - Skin colour

    - Cold/ warm extremities

    - Capillary flling time (normal

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    Table 5 : Warning signs 8, level 8, 9, level 8

    Abdominal pain or tenderness

    Persistent vomiting

    Clinical uid accumulation (pleural effusion, ascites)

    Mucosal bleed

    Restlessness or lethargy

    Tender enlarged liver

    Laboratory : Increase in HCT concurrent with rapid decrease in platelet

    Table 6 : Clinical and Laborator Criteria or Patients Who Can be Treated at Home

    1. Able to tolerate orally well, good urine output and no history o bleeding

    2. Absence o clinical alarm signals (reer Table 5)

    3. Physical examination:

    Haemodynamically stable-pink, warm extremities

    -normal capillary flling time (normal 20mmHg)

    -no disproportionate tachycardia

    No tachypnoea or acidotic breathing

    No hepatomegaly or abdominal tenderness

    No bleeding maniestation

    No sign o pleural eusion ascites No alterations in mental state and ull GCS score

    4. Investigation:

    Stable serial HCT

    In the absence o a baseline HCT level, a HCT value o >40% in emale adults

    and >46% in male adults should raise the suspicion o plasma leakage.

    Thereore admission may be required

    Adapted rom65, Level 9; 66, Level 9; 67,Level 9

    7.2 PATIENT TRIAGING AT EMERGENCy & TRAUMA / OUTPATIENT DEPARTMENTThe purpose o triaging patients is to determine whether they require urgent

    attention. This is to avoid critically ill patients being missed upon arrival.

    68, Level 9; 65 Level 9; 69,Level 9;70, Level 9

    Triage Checklist:

    1. History o ever

    2. Abdominal pain

    3. Vomiting

    4. Dizziness/ ainting

    5. Bleeding

    Vital parameters to be taken :

    Mental state,blood pressure, pulse, temperature, cold or warm peripheries

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    7.3 CRITERIA FOR HOSPITAL REFERRAL / ADMISSION

    7.3.1 Reerral rom primar care providers to hospital

    The decision or reerral and admission must not be based on a single clinical

    parameter but should depend on the Total Assessment o the patient.

    Reerral rom primar care providers to hospital1. Symptoms :

    Alarm signals (reer to Table 5)

    Bleeding maniestations

    Inability to tolerate oral uids

    Reduced urine output

    Seizure

    2. Signs :

    Dehydration

    Shock (reer to Table 1)

    Bleeding

    Any organ ailure

    3. Special Situations :

    Patients with co-morbidity e.g.Diabetes, Hypertension, Ischaemic

    Heart Disease, Coagulopathies, Morbid Obesity, Renal Failure,Chronic Liver disease, COPD,

    Elderly (more than 65 years old)

    Pregnancy

    Social actors that limit ollow-up e.g. living ar rom health

    acility, no transport, patient living alone, etc

    4. Laboratory Criteria: Rising HCT accompanied by reducing platelet count

    7.3.2 Reerral From hospitals without specialist to hospitals with specialists

    Early consultation with the nearest physician should be initiated orALL

    DHF or DF with organ dysunction/ bleeding.

    Prerequisites or transer

    1. All eorts must be taken to optimise the patients condition beore

    and during transer.

    2. The Emergency Departmentand/orMedical Department o the receiving

    hospital must be inormed prior to transer.

    3. Adequate and essential inormation must be sent together with the

    patients that includes uid chart, monitoring chart and investigation

    results.

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    7.4 DISEASE MONITORING

    7.4.1 Principles o Disease Monitoring

    1. Dengue is a systemic and dynamic disease. Thereore disease

    monitoring is governed by dierent phases o the disease.

    2.The critical phase (plasma leakage) may last or 24-48 hours. Monitoring

    needs to be intensifed and requent adjustments in the uid regimemay be required.

    3. Recognition o onset o reabsorption phase is also important

    because intravenous uid regime needs to be progressively reduced/

    discontinued at this stage.

    7.4.2 Outpatient Disease Monitoring

    Every patient suspected o dengue attending the outpatient/ emergency

    and trauma department should be assessed in stepwise manner asrecommended in Table 4.

    Daily or more requent ollow up is necessary especially rom day 3 o

    illness, until the patient becomes aebrile or at least 24- 48 hours without

    antipyretics. A disease monitoring record has been developed and it is

    recommended to be used or outpatient care (reer to Appendix 4.).

    7.4.3 Inpatient Disease Monitoring

    Immediately ater admission every patient with suspected dengue shouldbe reviewed thoroughly similar to the stepwise approach in outpatient (reer

    to Table 4).The plan o management and monitoring should be based on

    the phase o the disease and the haemodynamic status o the patient.

    Table 8 summarises the parameters and requency o monitoring according

    to the dierent phases o the illness.

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    Table 7: Issues o Monitoring According to Dierent Phases O Dengue Illness

    Phases o illness Issues :

    Febrile

    - Dierentiation o dengue illness rom other ebrile

    illnesses.

    - Not possible to dierentiate DF rom DHF.

    Critical

    - Plasma leakage occurs as patient progresses to

    late ebrile phase or as temperature begins to

    deervescence (T < 38.0 C).

    - Clinical deterioration occurs during this phase due to

    plasma leakage.

    - Plasma leakage results in haemoconcentration and

    hypovolemia/ shock.

    - Excessive plasma leakage due, in part, to intravenous

    uid therapy may cause respiratory distress.

    - Bleeding can be precipitated by prolonged shock and

    shock can be perpetuated by bleeding.

    - May mimic acute abdomen o other causes.

    - May be conused with septic shock or other orms

    o shock.

    Reabsorption

    - Cessation o plasma leakage.

    - Reabsorption o uid rom extravascular compartment.

    - Haemodilution occurs ollowing uid reabsorption.

    - Hypervolaemia and pulmonary oedema i intravenous

    uid therapy is continued.

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    Table 8 : Parameters and Frequenc o Monitoring According to Dierent

    Phases o Dengue Illness

    Parameters or monitoringFrequenc o monitoring

    Febrile phase Critical phase Recover phase

    Clinical Parameters

    General well being

    Appetite/ oral intake

    Warning signs

    Smptoms o bleeding

    Neurological/ mental state

    Daily or more

    requently towards

    late ebrile phase

    At least twice a

    day and more

    requently as

    indicated

    Daily or more

    requently as

    indicated

    Haemodnamic status

    Pink/cyanosis

    Extremities(cold/warm)

    Capillaryrelltime

    Pulsevolume PR

    BP

    Pulsepressure

    Respirator status

    RR

    SpO2

    4-6 hourly

    depending on

    clinical status

    2-4 hourly

    depending on

    clinical status

    In shock

    Every 15-30

    minutes till

    stable then 1-2

    hourly

    4-6 hourly

    Signs o bleeding, abdominal

    tenderness, ascites and

    pleural eusion

    Daily or more

    requently towards

    late ebrile phase

    At least twice a

    day and more

    requently asindicated

    Daily or more

    requently as

    indicated

    Urine output 4 hourly

    2-4 hourly

    In shock

    Hourly

    4-6 hourly

    Parameters or monitoringFrequenc o monitoring

    Febrile phase Critical phase Recover phase

    Clinical Parameters

    FBC + HCT

    Daily or more

    requently i

    indicated

    4-12 hourlydepending on

    clinical status

    In shock

    Repeated

    beore and

    ater each

    attempt o uid

    resuscitation

    and as

    indicated

    Daily

    BUSE/ Creatinine

    LFT

    RBS

    Coagulation profle

    HCO3/ TCO

    2/ Lactate

    As indicated

    At least daily or

    more requently

    as indicated

    In shock

    Crucial to

    monitor acid-

    base balance/

    ABG closely

    As indicated

    Adapted rom 2, Level 9; 65, Level 9

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    7.5 FLUID MANAGEMENT

    7.5.1 Dengue with Warning Signs (reer to Table 5)

    Recognising and monitoring or warning signs are crucial in identiyingpatients who may deteriorate into severe dengue.

    All patients with warning signs should be considered for monitoring

    in hospitals. Common pitfalls in uid therapy:

    * Treating patient with unnecessary uid bolus based on raised

    * HCT as the sole parameter without considering other clinicalparameters

    * Excessive and prolonged fxed uid regime in stable patients

    * Inrequent monitoring and adjustment o inusion rate

    * Continuation o intravenous uid during the recovery phase

    Cases o dengue with warning signs will probably recover with earlyintravenous rehydration. Some cases will deteriorate to severe dengue. Ithe patient has dengue with warning signs, the action plan should be as

    in Table 9a.Table 9a: Action Plan or Patient who has Dengue with Warning Signs

    Obtain a baseline HCT beore uid therapy.

    Give crystalloids solution (such as 0.9% saline).

    Start with 5-7 ml/kg/hour or 1-2 hours, then reduce to 3-5 ml/kg/hr or 2-4 hrs

    and then reduce to 2-3 ml/kg/hr or less according to the clinica response. I the clinical parameters are worsening and HCT is rising, increase the rate o

    inusion.

    Reassess the clinical status, repeat the HCT and review uid inusion rates

    accordingly

    7.5.2 Non-Shock Patients (DHF Grade I & II)There are no studies that have looked at uid therapy in non shock denguepatients. Increased oral uid intake may be sufcient in some patients who are

    haemodynamically stable and not vomiting. However IV uid (0.9% saline isrecommended) is indicated in patients with increasing HCT (indicating on-goingplasma leakage) despite increased oral intake. IV uid therapy should also beconsidered in patients who are vomiting and not tolerating orally.71, level 9; 65, level 9

    The normal maintenance requirement or IV uid therapy in such patientscould be calculated based on the ormula in Table 9b. Frequent adjustmento maintenance uid regime is oten needed during the critical phase.Oten 1.2-1.5 times the normal maintenance will be required during thecritical phase. I the uid inusion rate exceeds more than the maintenance

    requirement, the inusion rate should be reviewed within 4 to 6 hours.

    A rising HCT AND/ OR haemodynamic instability indicates on-goingplasma leakage and will require an increase in the IV uid inusion rate. Ipatients deteriorate and progress to shock, uid resuscitation is indicated(reer to the section on 7.5.3).71, level 9; 65, level 9

    Reduce or consider discontinuation o IV uid therapy when patients beginto show signs o recovery (usually ater 24-48 hours o deervescence, orthe HCT drops in a stable patient).

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    Table 9b : Calculations for normal maintenance of intravenous uid infusion

    * Normal maintenance uid per hour can be calculated based on

    the ollowing ormula (Equivalent to Hallida-Segar ormula) :

    4 mL/kg/h or frst 10kg body weight

    + 2 mL/kg/h or next 10kg body weight

    + 1 mL/kg/h or subsequent kg body weight* For overweight/obese patients calculate normal maintenance uid

    based on ideal body weight(Adapted rom 2, Level 9)

    Ideal bodweight can be estimated based on the ollowing ormula: 72,Level9

    Female: 45.5 kg + 0.91(height -152.4) cm

    Male: 50.0 kg + 0.91(height -152.4) cm

    Recommendation

    Encourage adequate oral uid intake. (Grade C)

    IV uid is indicated in patients who are vomiting or unable to tolerate

    oral uids. (Grade C)

    IV uid is also indicated in patients with increasing HCT (indicating

    on-going plasma leakage) despite increased oral intake. (Grade C)

    Crystalloid is the uid o choice or non shock patients. (Grade C)

    7.5.3 Dengue Shock Sndrome (DSS) (DHF Grade III & IV)

    Dengue shock syndrome is a medical emergency. Recognition o shock in

    its early stage (compensated shock) and prompt uid resuscitation will give

    a good clinical outcome.73,Level 2 Reer Table 1 or details. However, ailure to

    recognise the compensated shock phase will ultimately lead to decompensated

    (hypotensive) shock and a more complicated disease course.

    Pulse pressure o < 20 mmHg and systolic pressure < 90 mmHg are late

    signs o shock in adults.

    All patients with dengue shock should be managed in high dependency

    intensive care units. Fluid resuscitation must be initiated promptly

    and should not be delayed while waiting or admission to ICU or high

    dependency unit.

    Following initial resuscitation there maybe recurrent episodes o shock

    because capillary leakage can continue or 24-48 hours.

    IV uid therapy is the mainstay o treatmentor dengue shock.2, Level 9; 73, Level

    2; 74,Level 2To date, only three randomised controlled trials studying dierent

    types o uid regime in DSS in children aged rom 5 to 15 years o age

    are available.73, Level 2; 74, Level 2;75, Level 2Our recommendations are extrapolated

    rom these studies. These studies showed no clear advantage o using any

    o the colloids over crystalloids in terms o the overall outcome.However,

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    colloids may be preerable as the uid o choice in patients with intractable

    shock in the initial resuscitation. Colloids seem to restore the cardiac

    index and reduce the level o HCT aster than crystalloids in patients with

    intractable shock. 74Level 2 The choice o colloids includes gelatin solution

    (e.g. Gelausine) and starch solution (e.g. Voluven).

    Principles for uid resuscitationThe volume o initial and subsequent uid resuscitation depends on the

    degree o shock and can vary rom 10-20 mL/kg ideal body weight. The

    volume and rate o uid replacement should be careully titrated to the

    clinical response to maintain an eective circulation while avoiding an over-

    replacement.

    Improvement in the ollowing parameters indicates adequate uid resuscitation:

    Clinical parametersImprovement o general well being/mental state

    Warm peripheries

    Capillary refll time

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    Reer to the Algorithm A and Algorithm B or details.

    Recommendation

    For initial resuscitation

    Crystalloids are the uid o choice in patients with DSS.(Grade A)

    Colloids may be preerred as the uid o choice in patients withsevere shock. (Grade B)

    When two cycles o initial resuscitation with crystalloids ail to restore

    haemodynamic stability, colloids should be considered.(Grade C)

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    HCT = haematocrit

    1GXM: require first stage cross match or emergency O

    2fresh blood: less than 5 days

    IV crystalloid 5 - 7ml/kg/hr for

    1 - 2 hours, then:

    oreduce to 3 - 5 ml/kg/hr for

    2 - 4 hours;

    o reduce to 2 - 3 ml/kg/hr for

    2 - 4 hours

    If patient continues to improve,fluid can be further reduced

    Monitor HCT 4 - 6 hourly

    If the patient is not stable,

    act according to HCT levels:

    o if HCT increases, consider

    bolus fluid administration or

    increase fluid administrationo if HCT decreases, consider

    transfusion with fresh whole

    blood

    Consider to stop IV fluid at

    48 hours of plasma leakage / defervescence

    COMPENSATED SHOCK

    (systolic pressure maintained but has signs of reduced perfusion) Fluid resuscitation with isotonic crystalloid 5 - 10 ml/kg/hr over 1 hour

    FBC, HCT, before and after fluid resuscitation, BUSEC, LFT, RBS, PT/APTT, Lactate/HCO3, GXM1

    Check HCT

    Administer 2nd bolusof fluid

    10-20 ml/kg/hr for 1 hr

    Consider significantoccult/overt bleed

    Initiate transfusion with

    fresh blood2(whole blood/packed cell)

    If patient improves,

    reduce to 7-10 ml/kg/hr

    for 1 - 2 hours

    Then reduce further

    IMPROVEMENT

    IMPROVEMENT

    YES

    YES NO

    NO

    or high

    ALGORITHM A - FLUID MANAGEMENT IN COMPENSATED SHOCK

    REVISEDJULY 2010

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    ALGORITHM B - FLUID MANAGEMENT IN DECOMPENSATED SHOCK

    Consider to stop IV fluid at48 hours of plasma leakage

    / defervescence

    HCT = haematocrit

    1GXM: require first stage cross match or emergency O

    2fresh blood: less than 5 days

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    7.6 MANAGEMENT OF BLEEDING/HAEMOSTASIS7.6.1 Haemostatic Abnormalities in Dengue InectionThe haemostatic changes that occur in dengue inection are a result oendothelial activation.76 level 9; 77, level 8; 78, level 5 This leads to thrombocytopaeniaand coagulation activation which are an intrinsic part o the disease.76, level9; 77, level 8; 78, level 5

    Thrombocytopaenia and coagulation abnormalities do not reliably predictbleeding in dengue inection.34, level 6; 33, level 1; 36, level 8

    Markers o endothelial activation such as elevated levels o thrombomodulin,tissue actor and Von Willebrand actor are more oten seen in severedengue.79, level 6; 80, level 6 Increased levels o these proteins may promotemicrovascular thrombosis and end-organ damage.81, level 9

    7.6.2 How to Recognise Signifcant Occult Bleeding?Bleeding is considered signifcant when it results in haemodynamicinstability. Bleeding rom the gums or per vagina, epistaxis and petechiaeare common but will usually cease spontaneously and are oten notsignifcant.2, level 9 Signifcant bleeding or disseminated intravascularcoagulation usually occurs ollowing prolonged shock and acidosis.32, level 8

    Suspect signifcant occult bleeding in the ollowing situations:

    Haematocrit not as high as expected or the degree o shock to be explained by

    plasma leakage alone. 32, level 8

    A drop in haematocrit without clinical improvement despite adequate uid

    replacement (40-60 ml/kg).32, level 8; 66, level 9

    Severe metabolic acidosis and end-organ dysunction despite adequate uid

    replacement.32, level 8

    7.6.3 Management o Bleeding in Dengue

    Mild bleeding such as rom the gums, per vagina, epistaxis or petechiae,

    usually cease spontaneously and do not require blood transusion.2, level 9

    Transusion o blood and blood components in dengue is indicated whenthere is evidence o signifcant bleeding.32, level 8

    Transusion o blood in patients with signifcant bleeding

    Transused 5-10ml/kg o resh-packed red cells or 10-20 ml/kg o resh

    whole blood at an appropriate rate and observe the clinical response.

    Consider repeating the blood transusion i there is urther blood loss or no

    appropriate rise in HCT ater blood transusion.

    Recommendation

    Patients with mild bleeding such as rom the gums or per vagina,

    epistaxis and petechiae do not require blood transusion. (Grade C)

    Blood transusion with whole blood or packed cell (preerably less than 1

    week) blood component is indicated in signifcant bleeding. (Grade C)

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    7.6.4 Management o Upper Gastrointestinal Bleeding

    No studies have looked at the use o proton pump inhibitor in upper GIT

    bleeding in dengue.

    Endoscopy and endoscopic injection therapy in upper GIT haemorrhage

    increases the risk o bleeding and must be avoided.82, Level 7

    Generally, most o the GIT bleed will improve ater 48-72 hours o the

    deervescence. A persistent bleed beyond this time will require urther

    investigation.

    Recommendation

    Endoscopy and endoscopic injection therapy in upper GIT

    haemorrhage should be avoided. (Grade C)

    Blood transusion with whole blood or packed cell (as resh as is

    available, preerably less than one week old) blood components is

    indicated in signifcant bleeding. (Grade C)

    7.6.5 The Role o Prophlactic Transusions in Dengue

    Prophylactic transusion with platelets and resh rozen plasma do not

    produce sustained changes in the coagulation status and platelet count in

    patients with DHF/DSS.83,Level 8 ; 84, Level 8

    Prophylactic transusion with platelets and resh rozen plasma do not

    change or reduce the bleeding outcome in DHF. 83, Level8; 84, Level 8 ; 36, Level 8

    Inappropriate transusion o blood components increases the risk o

    pulmonary oedema and respiratory embarrassment.83,Level 8

    Recommendation

    There is no role or prophylactic transusion with platelets and reshrozen plasma in dengue patients. (Grade C)

    7.6.6 The Role o Adjunctive Therap in Dengue

    There is insufcient evidence to support the use o recombinant activated

    actor VII in dengue patients with signifcant bleeding.85, Level 3; 86, Level 9 The

    coagulation system is activated in dengue and inusion o activated actor

    concentrates may increase the risk o thrombosis.87, Level 9

    There is insufcient evidence to support the use o intravenousimmunoglobulin88, Level 3and steroids89, Level 1 in the management o dengue

    patients.

    However there are anedoctal reports,72, Level 9 that demonstrated a dramatic

    response when pulse methylprednisolone and high dose immunoglobulin

    G (lgG) was used in the early phase o haemophagocytic syndrome.

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    7.7 INTENSIVE CARE MANAGEMENT

    The management o DSS in the intensive care unit (ICU) ollows the general

    principles o management o any critically ill patient in the ICU. However,

    certain aspects which are o particular relevance to the management

    o DSS are discussed here. There are several papers reviewing dengue

    patients who were admitted to ICU. Several indications or ICU care were

    observed as listed in the box below. 10, Level 8, 90, Level 8; 91, Level 8

    Indications or reerral to Intensive Care:

    1. Recurrent or persistent shock

    2. Requirement or respiratory support (non-invasive and invasive ventilation)

    3. Signifcant bleeding

    4. Encephalopathy or encephalitis

    7.7.1 Indications or respirator support (non-invasive and invasive ventilation)

    The main objectives o respiratory support are to support pulmonary gas

    exchange and to reduce the metabolic cost o breathing.

    In general, respiratory support should be considered early in a patients

    course o illness and should not be delayed until the need arises. The

    decision to initiate respiratory support should be based on clinical

    judgement that considers the entire clinical situation.92,Level 9

    In patients with metabolic acidosis, respiratory support should be

    considered despite the preservation o relatively normal arterial blood pH.

    When PaCO2

    is higher than expected to compensate or the acidosis, the

    patient should be promptly intubated.

    Formula to calculate the expected PaCO2

    = 1.5 x [HCO3-] + 82 mmHg

    In patients with encephalopathy and GCS o

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    Formula : MAP ( Mean Arterial Pressure)

    = DBP + 1/3 (SBP - DBP)DBP = diastolic blood pressure

    SBP = systolic blood pressure

    7.7.3 Guide on saet and risk o invasive procedures

    a. Central venous catheter (CVC) insertion

    Volume resuscitation does not require a CVC i sufcient peripheral

    intravenous access can be obtained (e.g. 14- or 16-gauge intravenous

    catheters). In act, peripheral intravenous catheterisation may be preerable

    because a greater ow rate can be achieved through a shorter catheter,

    assuming the catheters are o equal diameter.96, Level 8 When a CVC o 8.5

    French or larger (i.e. an introducer) is used, the length o tubing becomes

    the rate limiting actor, not the CVC.

    There are no studies on dengue patients with regards to invasive

    procedures and bleeding risks. In general, thrombocytopaenia and other

    bleeding diathesis are relative contraindications to CVC placement as

    high emoral, low internal jugular, and subclavian venous punctures are

    difcult to compress and coner an increased risk o uncontrolled bleeding.

    However, studies have shown that the incidence o bleeding in patients

    with coagulopathy varies ( 0 - 15.5% ).97, Level 8; 98, Level 8; 99, Level 8; 100, Level 8; 101,Level 8

    When CVC is indicated in dengue patients (e.g. poor peripheral venousaccess, requirement o vasopressors) it should be inserted by an

    experienced operator and under ultrasound guidance i available.102, Level 8;

    103, Level 1

    There are multiple insertion sites to choose rom: emoral vein, external

    jugular vein, internal jugular vein, subclavian vein, brachial vein and cephalic

    vein. However, because the subclavian vein and artery are not accessible

    to direct compression, the subclavian site is least appropriate or a patient

    with a bleeding diathesis104, Level 9;105, Level 9

    Recommendation

    Volume resuscitation does not require a central venous catherisation

    (CVC) i sufcient peripheral intravenous access can be obtained.

    (Grade C)

    When CVC is indicated, it should be inserted by a skilled operator,

    preerably under ultrasound guidance i available. (Grade C)

    Subclavian vein cannulation should be avoided as ar as possible.(Grade C)

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    b. Arterial catheter insertion

    Intra-arterial cannulation is useul as it enables continuous arterial pressure

    monitoring and repeated arterial blood gas sampling. It has a very low

    incidence o bleeding (1.8 2.6%)106,Level 8

    Recommendation

    An arterial catheter should be inserted in DSS patients who require

    intensive monitoring and requent blood taking or investigations.

    (Grade C)

    c. Gastric tube

    I a gastric tube is required, the nasogastric route should be avoided.

    Consider orogastric tube as this is less traumatic.

    d. Pleural tap and chest drainIntercostal drainage o pleural eusions should be avoided as it can lead to

    severe haemorrhage and sudden circulatory collapse.107,Level 9

    Recommendation

    Intercostal drainage or pleural eusion is not indicated to relieve

    respiratory distress. Mechanical ventilation should be considered.

    (Grade C)

    8. DISCHARGE CRITERIA

    The ollowing should be taken into consideration beore discharging a patient.65,

    Level 9; 66,level 9

    Aebrile or 48 hours

    Improved general condition

    Improved appetite

    Stable haematocrit

    Rising platelet count

    No dyspnoea or respiratory distress rom pleural eusion or ascites

    Resolved bleeding episodes

    Resolution/recovery o organ dysunction

    9. PREVENTION OF DENGUE TRANSMISSION IN HOSPITALS

    Patients are viraemic and hence potentially inectious during the ebrile

    phase.108, Level 8; 109,Level 8 There are a ew small studies that demonstrate higherlevels and prolonged duration o viraemia in patients with DHF.110, Level 6; 111, Level 8

    There are no scientifc studies that address the efcacy o mosquito

    repellents or mosquito netting in reducing dengue transmission in

    hospitalised patients. However several community studies have shown

    that the use o mosquito netting/screening was efcacious in preventing

    transmission o dengue in the community.112, Level 3; 113, Level 8

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    Generally, repellent products with higher concentrations o DEET (N,N-

    diethyl-m-toluamide) were ound to have longer repellence times.114, Level 8

    A consensus dengue guideline advised the use o mosquito netting

    or repellent day and night or hospitalised dengue patients to reduce

    nosocomial inection.66, Level 9

    10. VACCINATION

    There is no eective vaccine available or dengue.115, Level 8; 116, Level 9

    11. DENGUE IN PREGNANCy

    There are very ew studies addressing the management o dengue in

    pregnancy. Generally the presentation and clinical course o dengue in

    pregnant women is similar to that in non-pregnant individuals. 118, Level 8

    117, Level 8; However, the signs and symptoms may be conused with othercomplications o pregnancy such as toxaemia, Haemolysis, Elevated Liver

    Enzymes, Low Platelets (HELLP) syndrome.119, Level 9

    There are some reports o an increased incidence o prematurity, in-utero

    death and abruptio placenta in these women.v 117, Level 8; 120, Level 8

    The ollowing physiological changes in pregnancy may make the diagnosis

    and assessment o plasma leakage challenging :

    Elevation o HCT in dengue is masked by haemodilution due to increasein plasma volume especially in the 2nd and 3rd trimester. Serial HCT

    measurement is crucial or disease monitoring in pregnancy.

    The detection o third space uid accumulation is difcult due to the

    presence o gravid uterus.

    Baseline blood pressure is oten lower and pulse pressure wider

    Baseline heart rate may be higher.

    Management o inected pregnant patients close to delivery :

    Risk o bleeding is at its highest during the period o plasma leakage

    (critical phase).

    I possible, avoid Lower Segment Caesarean Section (LSCS) or induction

    o labour during critical phase (plasma leakage).119, Level 9

    Procedures/manoeuvres that may provoke or augment labour should be

    avoided during this critical phase.

    Care or the mother should be provided in a multidisciplinary way in an area

    o the hospital where there are trained personnel available to handle labour

    and its complications.

    The baby should be observed or vertical transmission o dengue ater

    delivery.119, Level 9

    Recommendation

    All pregnant women with suspected dengue inection must be admitted.

    (Grade C)

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