Dbd Blok 26 2014

Update on Management of Pediatric Dengue

Yulia Iriani

Disease Burden

2.5 billion people 2/5 of the world's popula@on are at risk.

50 million dengue infec@ons occur worldwide annually. 500 000 require hospitaliza@on each year. 90% are children < 5 years 2.5% die.

Endemic in >100 countries

Disease burden

Indonesia:

Major public health problem.

Leading cause of hospitaliza@on and death among children.

Hyperendemicity with all 4 serotypes circula@ng in urban areas.

Spreading to rural areas.

Causes of DHF Death

Delayed diagnosis: OPD prolonged shock IPD uid overload by hypotonic solu@ons (5% D/N/2 at M rate)

Not proper IV uid management

Prolonged shock grade IV

Without proper treatment > 4 hours

oHepa@c failure prognosis 50% survival o+ Renal failure prognosis 10% survival o+ 3 organ failure prognosis Miracle

> 10 hours Death !!!

Goals of dengue management

Recognize dengue infec@on at an early stage; Detect the early onset of plasma leakage in these pa@ents; and

Appropriately manage dehydra@on and hypovolemia. Reduce mortality and morbidity

Virus, Vector and Transmission

Ethiological agent

Aedes aegyp*

Dengue transmission

Disease Pathogenesis

Current Hypothesis DENV tropism

Cells of the immune system Organ pathology Endothelial cells

Virus virulence An@body-Dependent Enhancement Complement system ac@va@on Autoimmunity Host gene@c factors Cross-Reac@ve T-Cell response

Virus virulence

Certain DENV strain responsible for more severe disease

Primary infec@on with DENV-1 followed by infec@on with DENV-2 or DENV-3

Dierent serotype may vary in their abillity to infect dierent cell type

Proposed model of heterologous immunity in secondary dengue virus infec@ons and its implica@ons for the pathogenesis of dengue hemorrhagic fever. Primary DENV-2 infec@on and sequen@al DENV-1 and DENV-2 infec@ons are compared for illustra@on purposes. The naive T cell repertoire (pale colors) likely contains some cells with higher avidity for DENV-1 than DENV-2 (red; DENV-1 > DENV-2) and other cells with higher avidity for DENV-2 than DENV-1 (blue; DENV-2 > DENV-1). During primary infec@on, T cell popula@ons with higher avidity for the infec@ng serotype are preferen@ally expanded and enter the memory pool (shown as darker colors). When DENV-2 infec@on follows DENV-1 infec@on, the memory T cell popula@ons with higher avidity for the earlier infec@on expand more rapidly than do naive T cell popula@ons. Because these DENV-1specic memory T cells have lower avidity for DENV-2, viral clearance mechanisms are subop@mal, whereas proinammatory responses contribute to disease.

Secondary Infec@on or Immune Enhancement Hypothesis

Model of an.body-dependent enhancement of dengue infec.on An@body (Ab)-dependent enhancement of infec@on occurs when preexis@ng an@bodies present in the body from a primary (rst) dengue virus (DENV) infec@on bind to an infec@ng DENV par@cle during a subsequent infec@on with a dierent dengue serotype. The an@bodies from the primary infec@on cannot neutralize the virus. Instead, the Abvirus complex akaches to receptors called Fc receptors (FcR) on circula@ng monocytes. The an@bodies help the virus infect monocytes more eciently. The outcome is an increase in the overall replica@on of the virus and a higher risk of severe dengue. 2007 Nature Publishing Group Whitehead, S. S. et al. Prospects for a dengue virus vaccine. Nature Reviews Microbiology5, 518528 (2007). doi:10.1038/nrmicro1690 All rights reserved

Transient autoimmunity

Cross-react with some self-an@gens An@-NS1 Ab cross-reac@ve with endothelial cells could trigger these cells to express NO and undergo apoptosis (141), enhance expression IL-6, IL-8, ICAM-1, human thrombocyte cause thrombocytopenia

Clinical Manifesta@on

GUIDELINES

WHO 1997 WHO/TDR 2009 WHO SEARO 2011

Manifesta@on of Dengue Virus Infec@on

20

Table. Expanded dengue syndrome (Unusual or atypical manifesta@ons of dengue)

Course of Dengue Illness

Course of Dengue Illness

Plasma leakage 24 48 hours, 3rd 7th day of illness (usually: 4th 5th daya)

Time of fever defervesence Fever diminished Febrile shock/cri@cal phase

Dengue Fever

Day of illness

emp

Time of fever defervescence (Saat suhu reda)

Absence of fever, clinical improvement, return of

appetite

Time of fever defervescence DHF

Hari sakit

emp

Clinical worsening, malaise, agitated, cold and calmy

extremities, fast breathing, reduced OUP, no appetite

Critical phase Fever phase Recovery phase

Time of fever defervescence

Clinical Course of DHF

Clinical Case Deni@on


WHO/TDR 2009

WHO/TDR 2009

Dengue is one disease en@ty with dierent clinical presenta@ons and osen with

unpredictable clinical evolu@on and outcome

CRITERIA FOR DENGUE WARNING SIGNS

Probable Dengue live in /travel to dengue endemic area. Fever and 2 of the following criteria: Nausea, vomi@ng Rash Aches and pains Tourniquet test posi@ve Leukopenia Any warning sign Laboratory-conrmed dengue (important when no sign of plasma leakage)

Warning Signs* Abdominal pain or tenderness Persistent vomi@ng Clinical uid accumula@on Mucosal bleed Lethargy, restlessness Liver enlargment >2 cm Laboratory: increase in HCT concurrent with rapid decrease in platelet count

*(requiring strict observa@on and medical interven@on)

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

CRITERIA FOR SEVERE DENGUE

Severe plasma leakageleading to:

Shock (DSS) Fluid accumula@on with respiratorydistress

Severe bleeding

as evaluated by clinician

Severe organ involvement

Liver: AST or ALT >=1000

CNS: Impaired consciousness

Heart and other organs


WHO 1997

WHO SEARO 2011


Probable Dengue Fever

Fever of 2 to 7 days dura@on, with two or more of the following: Headache, retroorbital pain, myalgia, arthralgia, rash, hemorrhagic manifesta@ons, leukopenia, and suppor@ve serology or occurrence at the same loca@on and @me as other conrmed cases of dengue.

Conrmed Dengue Fever

Conrmed by laboratory criteria (isola@on of the dengue virus, demonstra@on of the dengue virus an@gen, serology, or genomic sequence).


Probable Dengue Fever

Acute febrile illness with >= 2 of the followingl: Headache. Retro-orbital pain. Myalgia. Arthralgia/bone pain. Rash. Haemorrhagic manifesta@ons. Leucopenia (wbc 5000 cells/mm3). Thrombocytopenia (platelet count

WHO Grading of DHF

Clinical Management of DHF

Principle of DHF Management

Primary abnormali@es in DHF Vasculopathy Thrombocytopenia Thrombopathy Coagulopathy

Severe DIC

Strategy of DHF Management

Suppor@ve therapy Drug: as indicated Plasma leakage volume replacement

How to choose uid solu@on 25% need colloid

Clinical course of DHF: unpredictable monitoring: Early detec@on and prompt treatment of

circulatory disturbance clinically & PCV bleeding manifesta@on clinically and lab

Outpa@ent management of pa@ents with dengue

Early dengue 80% of pa@ents make the rst visit to a medical doctor within the rst 2 days of fever

follow-up card diagnosis of suspected dengue, serial full-blood-count results (to include, at least, haematocrit [erythrocyte volume frac@on]) and indicators for admission, at the rst medical contact.

Oral uid

Steps for OPD screening during dengue outbreak

Outpa@ent management of pa@ents with dengue

Recommenda.ons for CBC: All febrile pa@ents at the rst visit to get the baseline HCT, WBC and PLT.

with warning signs. fever >3 days. circulatory disturbance/shock (+ glucose check). If leucopenia and/or thrombocytopenia (+), warning signs (+) immediate medical consulta@on.

Indica@on for admission

Excessive family concern or cant be followed up Very weak, cant eat or drink, not drinking/feeding poorly

Spontaneous bleeding Platelete counts 100.00/mm3 and/or rising Hct 10 20%

Clinical deteriora@on in defervescence Severe abdominal pain/vomi@ng Signicant dehydra@on requiring iv uids

Admit immediately

Signs of shock: Rapid pulse with no fever Prolonged capillary rell @me Cold clammy skin, mokling Narrowing of pulse pressure 20 mmHg Hypotension Oliguria, no urine for 4 6 hours Change of consciousness

Management of Febrile Phase

Res@ng, oral uids Reduc@on of fever Nutri@onal support Other suppor@ve and symptoma@c treatment

AB not necessary; may lead to complica@on Steroid ineec@ve; may cause harm

Management of Febrile Phase

IV uids: in case of doubt, provide iv uids Guided by: serial Hct, vital signs, urine output Volume: ~ mild to moderate isotonic dehydra@on (5 8% decit)

Just correct dehydra@on, discon@nue ASAP

Management of Cri@cal Phase

Treatment of severe dengue (DHF and DSS): prompt assessment replacement of uid needs live-saving, modify the severity of disease and prevent shock.

Warning Signs for Dengue Shock

When Patients Develop DSS: 3 to 6 days after onset of symptoms

Initial Warning Signals Disappearance of fever Drop in platelets Increase in hematocrite

Alarm Signals Severe abdominal pain Prolonged vomiting Abrupt change from fever to hypothermia Change in level of consciousness (irritability or somnolence)

Four Criteria for DHF Fever Hemorrhagic manifestations Excessive capillary permeability 100,000/mm3 platelets

Management of Cri*cal Phase


Indica@ons for IV uid: Pa@ent cannot have adequate oral uid intake or is vomi@ng.

HCT con@nues to rise 10%20% despite oral rehydra@on.

Impending shock/shock.


General principles of uid therapy in DHF Cri@cal period: Isotonic crystalloid solu@ons Used hyper-onco@c colloid solu@ons (osm. >300 mOsm/l) such as dextran 40 or starch solu@ons in:

massive plasma leakage, not responding to the minimum volume of crystalloid

Obese: ideal body weight used as a guide to calculate the uid volume


General principles of uid therapy in DHF Volume: maintenance +5% dehydra@on, to maintain a just adequate intravascular volume and circula@on.

Dura@on iv uid therapy With shock: should not exceed 24 to 48 hours for Without shock: may have to be longer but not more than 60 to 72 hours.

Requirement of uid based on ideal body weight

Rate of IV uid in adults and children

DHF Gr I and II

uid allowance (oral + IV): maintenance (for one day) + 5% decit (oral and IV uid together), administered over 48 hours

Adjusted according to the rate of plasma loss, guided by : clinical condi@on, vital signs, urine output and haematocrit levels.


DHF Gr I and II Management of Cri*cal Phase

Monitoring during Cri@cal Phase

General condi@on, appe@te, vomi@ng, bleeding and other signs and symptoms Monitoring

As frequently as indicated Peripheral perfusion

every 24 hours in non-shock pa@ents 12 hours in shock pa@ents Vital signs

every 4-6 hours in stable cases, more frequent in unstable pa@ents or suspected bleeding

Serial hematocrit

every 8 to 12 hours in uncomplicated cases hourly in profound/prolonged shock or uid overload

Urine output


Dengue Shock Syndrome

DSS: hypovolemic shock caused by plasma leakage Fluid resuscita@on is dierent from other types of shock.

DHF Grade III >> respond to 10 ml/kg over 1 hour or bolus Fluid adjustment ~ clinical condi@on, vital signs, urine output and haematocrit levels


Rate of Infusion in DSS Management of Cri*cal Phase

Prolonged/profound shock: DHF Grade IV

Fluid resuscita@on more vigorous 10 20 ml/kg of bolus uid as fast as possible, ideally within 10 to 15 minutes failed:

2nd bolus failed: Correc@on ABCS

Inves@ga@on of ABCS


Laboratory Inves@ga@ons

Profound shock Complica@ons No clinical improvement in spite of adequate volume replacement ABCS

A-Acidosis Blood gas

LFT, BUN, Cr

B-Bleeding Haematocrit

C-Calcium Electrolyte,

Ca++

S-Blood sugar BS

(dextros@ck)


Treatment of Complica@on

Electrolyte imbalance Hyponatremia Hypocalcemia 10% Ca gluconate 1 mL/kg/dose, IV push slowly every 6 hours


Fluid overload: avoid the common causes of uid overload, which are

Early IV uid therapy- in the febrile phase Excessive use of hypotonic solu@ons Non-reduc@on in the rate of IV uid aser ini@al resuscita@on Blood loss replaced with uids in cases with occult bleeding Judicious uid removal using colloids with controlled diuresis (furosemide 1 mg/kg infusion over 4 hours) or dialysis


Large pleural eusions, ascites Careful @tra@on of intravenous uids Large pleural eusions during the recovery phase aser 48 hours - small doses of furosemide (0.25-0.5 mg/kg at 6 hours interval for 1 to 2 doses).

Avoid inser@on of intercostal drains and tracheal intuba@on


Disseminated intravascular coagula@on Seriously sick pa@ents + bleeding and DIC

heparin therapy and cryoprecipitate (1 unit per 5 kg body weight) followed by platelets (4 units/m2 or 10-20 mL/kg) within 1 hour and fresh frozen plasma (FFP 10-20 mL/kg).

Frequent clinical assessment and regular coagula@on prole (PT, aPTT, brinogen, platelet and FDP) are mandatory, as indicated

Criteria for discharging

Fever (-), at least 24 hours without an@pyre@c Return of appe@te. Visible clinical improvement. Sa@sfactory urine output. A minimum of 23 days have elapsed aser recovery from shock.

No respiratory distress from pleural eusion and no ascites.

Platelet count >50 000/mm3.

Dbd Blok 26 2014

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