A Dengue Hemorrhagic Fever ‘s Patient with Bilateral Pleural

EffusionFaried Irawanto

M. Vitanata Arfijanto

Department of Internal Medicine Medical Faculty of Airlangga Univ. - Dr Soetomo

Teaching Hospital Surabaya

2010

CASE REPORT

INTRODUCTION• Dengue is mosquito-borne infection that

causes severe flu like illness self limited dissease

• Dengue Aedes aegypty DF & DHF• Sometimes a potentially lethal complication

dengue haemorhagic fever (DHF) bleeding, syok syndrome

• Cases : 1997 15% 1999 33% 2002 36%

Map produced by the Agricultural Research Service of the US Department of Agriculture.Source: Slide #8 of a presentation by Gary G. Clark, PhD, entitled "Dengue: An emerging arboviral disease“.

Incidence Rate DHF (per 100.000 people)

2003-2008

01020304050607080

2003 2004 2005 2006 2007 2008

Incid

ence

rate

(IR

)

Source: Center For Data And Information Ministry Of Health Of Republic of Indonesia . 2009

• DHF with PE 25% small PE,(Wang, 2007) 4,5% moderate PE

1,9% massive PE• Plasma leakage

– Pleural effusion right side (serous fluid)– ascites

• Severe plasma leakage bilateral pleural effusion

• Pleural effusion resorption• Plasma leakage usually resolves after 48 hours

followed by convalescence periode

Patient’s Identity

Mrs. W/ 24 yoMoslem

A HousewifeFrom Trowulan-Jombang,

East Java, Indonesia

CASE REPORT

Admitted at Dr. SoetomoTeaching Hospital at April, 5

2010Referred from Jombang

HospitalWith DSS + ARDS

ANAMNESIS

Chief Complaint : Shortness of breath

Shortness of breath since 1 days before admission, continous, no cough.

Fever since 5 days before admissionThere are headache, muscle and bone pains, nausea,

anoreksia, no loss of body weightHistory of Past Illness :

No history of lung dissease, HT, liver dissease

April, 5 2010

PHYSICAL EXAMINATION

General Condition : Body weaknessGCS 456

April, 5 2010

BP 110/80 HR 80 bpm RR 32 x/mnt T 37.5˚C

Chest : Symmetric, Chest Percussion dullness, decreased breath sounds, friction-rub, Breathing Sound Vesicular Rales on Lower Chest (Bilateral) Heart Sound : Normal

Abdominal : Flat, Liver & spleen unpalpable, Shifting dulness (no ascites)

Extremities : Warm, Dry, Red

Head and Neck : Normal

Tourniquet test (+)

LABORATORY & RADIOLOGY RESULTApril, 5 2010

Blood Gas Analysis (Oxygen 2 lpm)

• PH : 7,48• PCO2 : 30 mmHg• PO2 : 70

mmHg• HCO3 : 22,3

mmol/L• BE : -1,2

mmol/L• O2 Sat : 95%

AP position

HBsAg (-)Widal (-)

Hb 11,9 g/dLLeuco 11,3 x 103/ul

Thrombo 82 x 103/ulPCV 35,0%BUN 11 mg/dLSC 0,8 mg/dLAST 396 IU/LALT 353 IU/LAlb 2,3 g/dLSodium 137,5 mmol/LPotassium 3,5 mmol/L

Urinalisis : normal limit

April, 5 2010

Consultation to Lung Departemen

A patient with bilateral pleural effusion that it can be caused by underlying

disease (DHF)

Evacuation 200 cc (Hemithorax D) Haemorrhagic fluid

Pleural fluid analysis :Cel = 200 sel/uL, mono nuclear cel = 15%, poli nuclear cel

= 85%, glucosa = 99mg/dL, protein = 3.3 g/dL, LDH = 3627 U/L,

rivalta positip

INITIAL ASSESSMENT

DHF gr II (5th day) + Bilateral Pleural Effusion

April , 5 2010

INITIAL PLANNING

Diagnostic

April, 5 2010

IgM & IgG anti dengueSerial CBC

Therapy

Nasal O2 3 lpm IVFD 1000 mL/24h

High Calorie High Protein 2100 kcalParacetamol 500 mg, tid, po

Monitoring

Vital signs, serial CBC

Fever Day

Platelet

Leucocyte

Haemoglobin

5 76 8 9

Haematocrit

3,94,0 3,5

4,1

6147

82

106

11

11,714

13,337%

34,5%

Respiration Rate

Evacuation 800 cc (D) + 200 cc (S) Haemorrhagic fluid

32

34

38

38

40

20

13

DISCHARGE

PROGRESS

April, 6 2010 (Fever d’6) BP=120/80 , HR=72x/m , t= 37,50C, rr=34x/m, IgM dan IgG positipPPT= 18,3 s (15,1), APPT= 35,2 s (32,6)O2 nasal 3 lpm, HCHP 2100 cal, RA 21 tts/mnt, Albumin 20% (100 cc), paracetamol 3x500 mg

April, 8 2010 (Fever d’8)BP=110/70 , HR=88x/m, t= 36,80C, rr=38x/mO2 masker rebreathing 10 lpm, HCHP 2100 cal, Asering 1000 cc/ 24 hr, paracetamol 3x500 mg

April, 7 2010 (Fever d’7)BP=100/60 , HR=88x/m, t= 36,70C, rr=38x/mBUN= 11 mg/dL, Sc= 0,8 mg/dLAST= 189 IU/L, ALT= 246 IU/L, Alb= 3,1 g/dLO2 masker rebreathing 10 lpm, HCHP 2100 cal, Asering 1000 cc/ 24 hr, paracetamol 3x500 mg

PROGRESS

April, 13 2010BP=110/60 , HR=80x/m , t= 36,80C, rr=20x/mDISCHARGE

April, 12 2010BP=100/60 , HR=88x/m ,t= 36,30C, rr=24x/mHCHP 2100 cal

April, 9 2010 (Fever d’9)BP=110/60 , HR=80x/m , t= 37,20C, rr= 40x/mO2 masker rebreathing 10 lpm, HCHP 2100 cal, Asering 1000 cc/ 24 hr

DISCUSSION

Dengue infection

Vascular permeability

Trombocytopenia

Death

Syok

Anoksia

Bleeding manifestation

FeverAnoreksiavomiting

Plasma leakage

Hepatomegali

HypovolemiaDehydration

DIC

GI Bleeding

Suchitra, 1993

HemoconsentrationHypoproteinemiaPleural effusion

Ascites

Acidosis

• Tachychardia• Increased capillary refill time (>2 s)• Cool, mottled or pale skin• Diminished peripheral pulses• Changes in mental status• Oliguria• Sudden rise in haematocrit or continuously elevated

haematocrit despite administration of fluid• Narrowing of pulse pressure ( < 20 mmHg (2,7 kPa)• Hypotension ( a late finding representing uncorrected

shock )

Indications for hospitalization

Dengue haemorrhagic fever (DHF) Patient

Fever or history of fever, lasting 2-7 days, occasionally biphasic

+

Haemorrhagic tendencies +Thrombocytopenia (100,000 cells per mm3 or less) +Evidence of plasma leakage manifested by at least one of the following :• a rise in the haematocrit equal or greater than 20%

above average for age, sex and population• a drop in the haematocrit following volume

replacement treatment equal to or greater than 20% of baseline

• signs of plasma leakage such as pleural effusion, ascites and hipoproteinemia. Definition of dengue shock syndrome (DSS) : DHF cases with documented narrow pulse pressure (< 20 mmHg), hypotension or other signs of shock

+

The World Health Organization (WHO) case definitions of dengue haemorrhagic fever

• Accumulation of fluid between the layers of the membrane that lines the lungs and the chest cavity

• Normal: 1 mL of pleural fluid– Balance between

hydrostatic/oncotic forces and lymphatic drainage

• Abnormal: Pleural effusion– Disruption of balance

PLEURAL EFFUSION

Pathogenesis of pleural effusion

• Elevated capillary hydrostatic pressure (cardiac failure)

• Reduced capillary oncotic pressure (hypoalbuminemia)

• Enhanced capillary permeability (inflammation)

• Obstructed lymphatics (tumor)

• Movement of fluid from extrathoracic site (pancreatitis)

Light , 2002

• 363 (DHF) Chest photo thorax 25% with pleural effusion, mostly on the right side (Wang, 2007)

• Pleural effusion is mostly on the right side, as a constant finding, but in shock bilateral pleural effusion is a common finding (Srikiatkhachorn, 2009)

Pleural Effusion must be evacuated

Shortness of breathMassive pleural effusionNo coagulation dissorder

Guideline Management DHF1: Management (Probable ) DHF ( Adult

Without Shock)

2: Fluid Treatment DHF patient in the Emergency Ward

3: Management DHF with increased Ht > 20 %

4: Management Spontan Bleeding for Adult

5: Management DSS

Management DHF (Adult) Suspect DHF

Spontan Bleeding dan Masif (-)Syok (-)

-Hb, Ht (n)-Platelet < 100.000-Kristaloid Fluid-Hb, Ht, Platelet / 24 hr

-Hb, Ht 10-20%-Platelet < 100.000-Kristaloid Fluid-Hb, Ht, Tromb /12 hr

-Hb, Ht > 20%-Platelet < 100.000

- management fluid treatment DHF with

Ht ↑ > 20%

( 2 )

Criteria for discharging inpatients

• Absence of fever for at least 24 h without the use of antifever

• Return of appetite• Visible clinical improvement• Good urine output• Stable haematocrit• Passing of at least 2 days after recovery from shock• No respiratory distress from pleural effusion or ascites• Platelet count of more than 50.000 per mm3

SUMMARY• Report a woman 24 yo with dengue

haemorrhagic fever grd II and bilateral pleural effusion

• Dengue hemorrhagic fever (DHF) is acute febrile disseases which occur in the tropics, can be life-threatening, and are caused by four closely related virus serotypes of the genus Flavivirus, family Flaviviridae self limited disease

• Around the time of defervescence, DHF patients localised plasma leakage manifested as accumulation of fluid in pleural and abdominal cavities and haemoconcentration.

...Cont’d• The extent of plasma leakage varies between

individual patients and can lead to intravascular volume depletion requiring fluid resuscitation.

• Pleural effusion is mostly on the right side, as a constant finding, but in shock bilateral pleural effusion is a common finding.

THANK YOU

Suramadu Bridge

Srikiatkhachorn, 2009

Clinical aspects

Dengue VirusDEN-1, 2, 3, 4

Undifferentiatedfever

Dengue Fever(DF)

Dengue Hemorrhagic Fever(DHF/DSS)

WithoutHemorrhage

With unusualhemorrhage

No shock(DHF)

Shock(DSS)

World Health Organization. Dengue Haemorrhagic Fever: Diagnosis, treatment, prevention and control. 2 ed. 1997

Light, R. W. N Engl J Med 2002;346:1971-1977

April, 5-2010 April, 6-2010 April, 7-2010 April, 8-2010 April, 9-2010

Hb 11,9 g/dL 11,7 g/dL 13,1 g/dL 14,0 g/dL 13,3 g/dL

Leuco 11,3 x 103/ul 3,9 x 103/ul 4,0 x 103/ul 3,5 x 103/ul 4,1 x 103/ul

Thrombo 82 x 103/ul 61x 103/ul 47 x 103/ul 82 x 103/ul 106 x 103/ul

PCV 35,0% 37,0% 34,5% - -

BUN 11 mg/dL - 11 mg/dL - -

SC 0,8 mg/dL - 0,8 mg/dL - -

AST 396 IU/L - 189 IU/L - -

ALT 353 IU/L - 246 IU/L - -

Alb 2,3 g/dL - 3,1 g/dL - -

Sodium 137,5 mmol/L - - - -

Potassium 3,5 mmol/L - - - -

PROGRESSION

Map showing the distribution of dengue fever in the world, as of 2006. Map produced by the Agricultural Research Service of the US Department of Agriculture.Source: Slide #8 of a presentation by Gary G. Clark, PhD, entitled "Dengue: An emerging arboviral disease". Cyan: Areas infested with Aedes aegypti. Red: Areas with Aedes aegypti and recent epidemic dengue fever

PROGRESSION

April, 5 2010 April, 12 2010

2-9

2-93-65-8

9-352-6

3-12

7-145-162-142-21Incubation

Kyasanur Forest disease

Omsk HFYellow feverDF, DHF, DSS

HF renal syndrome/ Hantavirus pulmonary syndrome

Rift Valley Fever

Crimean-Congo HF

New World HF (Argentinean HF, Bolivian HF, etc.)

Lassa feverMarburg HFEbola HFDisease

Tick

TickMosquito

Mosquito

RodentMosquito

Tick

RodentRodentUnknown

Unknown

Vector

Lassa

Ebola

Rift Valley feverPhlebovirus

Crimean-Congo hemorrhagic fever

NairovirusBunyaviridae

Agents of HFRS and HPS

Hantavirus

VirusGenusFamily

Kyasanur Forest disease

Omsk HFYellow fever

Flaviviridae DengueFlavivirus

New World Arenaviridae

Arenavirus

Arenaviridae

MarburgFilovirusFiloviridae

Hemorrhagic fevers

Macrophage

Bone Marrow

Stem cell

Ag-Ab complex

Lymphocytes

Platelets

Thrombocytopenia

Successful treatment of DHF depends on early recognition and careful monitoring of the development of shock.

Hepatocellular injury manifested by hepatomegaly, elevation of ALT, and coagulopathy are common in DHF and even in DF, although hepatomegaly is absent.

Hepatic disfunctions in dengue

Co - infection can modify clinical presentations of dengue disease and result in missed or delayed diagnosis and treatment and possible misinterpretation as unusual manifestations.

Co-infection in dengue patients

J Med Assoc Thai 2002; 85: S298 J Med Assoc Thai 2002; 85: S298- 301. Pediatr Pediatr Infect Infect Dis Dis J 1998; 17: 81 J 1998; 17: 81- 2. Med J Med J Aust Aust 1994; 160: 22 1994; 160: 22-6. 6.

Management

DENGUE-MONOCYTES

PLA2 Lymphocytes activation Proinflammator

y cytokine

Protein Binding

Arachidonat metab

Eicosanoid

IL-1 IL -6

Malfunction endothel

dystructionendothel

INCREASED VASCULAR PERMEABILITY

CAPILLARY LEAKAGE

Prostacyclin Thromboxsan

e Leucotrienes

Dengue shock syndrome

TNF-

Nasronudin, 2005

Complement

C3a, C5a

Primary Infection Secondary Infection

Immune Response to Dengue infection

Virus Virus

Clinical Symptoms, Fever

Ant

ibod

y le

vel

Clinical Symptoms, Fever

IgG antibodies

IgM antibodies

NS1 Ag NS1 Ag

Primary infection:High level of IgM that appears 4-6 days after symptoms and may persist for up to 10 weeks.IgG appears 2 weeks after onset and persists for life.

Secondary infection:Low levels of IgM (may not be produced or at undetectable levels in 20% of patients).IgG rise rapidly 1-2 days after onset of symptoms at higher levels than primary infection.

SUMMARY

Sept, 25 Sept, 27 Oct, 5 Oct, 14Oct, 9

Points of Events

Tamiflu (Oseltamivir)

Antibiotics

Ventilatory Support

H5N1 positive

ICU Setting

H5N1 negative

Category 1

05

101520253035404550

Category 1

020406080

100120140160180200

trombo...

7.559 7.48

7.46

26.4

34 34109

5954

99

<60

<60

CO2 Saturati

on

pH

pO2

O2 Saturation

Sep, 25 2006 Sep, 26 2006 Sep, 27 2006

Intermediate Care Intensive Care

PROGRESSIONBLOOD GAS ANALYSIS

PROGRESS

April, 6 2010 (Fever d’6) BP=120/80 , HR=72x/m , t= 37,50C, rr=34x/mHb=11,7 g/dL, L= 3,9 x 103/ulT= 61x 103/ul, HCT= 37,0%IgM dan IgG positip

April, 8 2010 (Fever d’8)BP=110/70 , HR=88x/m, t= 36,80C, rr=38x/mHb= 14,0 g/dL, L= 3,5 x 103/ulT= 82 x 103/ul

April, 7 2010 (Fever d’7)BP=100/60 , HR=88x/m, t= 36,70C, rr=38x/mHb=13,1 g/dL,L=4,0 x 103/ul, T= 47 x 103/ulHCT= 34,5%, BUN= 11 mg/dL, Sc= 0,8 mg/dLAST= 189 IU/L, ALT= 246 IU/L, Alb= 3,1 g/dL

PROGRESS

April, 13 2010BP=110/60 , HR=80x/m , t= 36,80C, rr=20x/mDISCHARGE

April, 12 2010BP=100/60 , HR=88x/m ,t= 36,30C, rr=24x/m

April, 9 2010 (Fever d’9)BP=110/60 , HR=80x/m , t= 37,20C, rr= 40x/mHb=13,3 g/dL, L= 4,1 x 103/ul, T= 106 x 103/ulEvacuation of pleural effusion –> OK paru 800 cc (D) & 200 cc(S)

April, 12 2010