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Dengue in PICU

DR.SAGAR S.LAD
PAEDIATRIC INTENSIVIST AND NEONATOLOGIST
DNB,DCH(AUS),FELLOWSHIP NEONATOLOGY (AUSTRALIA)
PED CRITICAL CARE(AUSTRALIA)
JEHANGIR APOLLO HOSPITAL AND SAHYADRI SUPERSPECIALITY
HOSPITAL,PUNE
Scope of presentation
•Pathogenesis
•Clinical feature-DF,DHF,DSS,3 phases of dengue
•Fluid management- compensated shock and hypotensive shock.
•Role of HCT
•Complication-1.Respiratory
•2.Bleeding
•3.Cardiac,Encephaloapthy
•4.HLH
•5.AKI
•6.ACS.
Dengue virus
Dengue is caused by single stranded RNA virus belonging to genus Flavivirus and
family Flaviviridae
Four serotypes (DEN-1, 2, 3, 4) of dengue virus have been identified. It is
transmitted by the bite of two common vectors Aedes aegypti and Aedes
albopictus.
.
Pathogenesis
•Primary infection -undifferentiated fever
•Secondary infection results in an
-antibody dependent enhancement of viral replication
-overwhelming host immune response, cytokine storm
-endothelial dysfunction leads to increased vascular permeability and capillary leak,
-hemo-concentration and shock
-The endothelial dysfunction is lasts for 24-48 hours.
Pathogenesis
•Thrombocytopenia
-due to alteration in megakaryocytopoieses
- increased peripheral destruction due formation of auto Ab to Ns1 ag and platelets
-increased consumption and impaired aggregation of platelet
•Bleeding tendencies
- abnormalities in clotting factor
-secondary to abnormalities in hemostasis resulting from hypoxia, acidosis, shock
-low platelet count, endothelial dysfunction, and DIC.
Clinical presentation:
1.Febrile phase 2.Critical phase 3. Recovery phase
1.Febrile phase: 2-7 days
- Fever, flushing, skin erythema, generalized body ache, myalgia, arthralgia, retro-orbital
pain, headache, congestion of throat, eyes, flushing of palms and soles, nausea, vomiting
and anorexia.
- Tender hepatomegaly.
- Hemorrhagic manifestations like petechiae or mucosal bleeding
- Tourniquet test done during this stage maybe positive indicating increased capillary
fragility
- Total white cell count may show a progressive decline.
- Watch for warning signs of severe dengue.
Critical phase
- Leaky phase, From 3 to 7 days of illness, starting with defervescence and appearance of
warning signs
- Clinically - warning signs like abdominal pain, persistent vomiting, mucosal bleeds, lethargy,
restlessness, hepatomegaly, clinical fluid accumulation like ascites or pleural effusion
- Often accompanied by rapid decline in platelet counts
- This phase lasts for 24-48 hours, and may extend up to 72 hours
Dengue case classification (WHO 2009)
Dengue c/f Dengue ± warning signs Severe Dengue
Probable dengue: Fever and 2 of the Any warning sign Severe plasma leakage
following criteria:
• Nausea, vomiting • Abdominal pain or tenderness • -Shock
• Rash • Persistent vomiting -Fluid accumulation with respiratory
distres
• Aches and pains • Clinical fluid accumulation Severe bleeding
• Tourniquet test positive o Leukopenia • Mucosal bleed • Lethargy, restlessness Severe organ impairment
• Liver enlargement >2 cm • Liver: AST or ALT ≥ 1000
• CNS: impaired consciousness
• Heart and other organ involvement
• Any warning sign • Bleeding (coffee ground vomitus
,black colour stool)
Laboratory-confirmed dengue Increase in HCT concurrent with rapid
(important when there is no sign of decrease in platelet count
plasma leakage
- Children with compensated shock with normal systolic blood pressure
- Typical presentation - cold clammy extremities, tachycardia, silent tachypnea, weak pulses and
a narrow pulse pressure (≤ 20 mmHg) without hypotension
- Hypotensive shock. -Hypotension being a late sign of shock in children, can progress to
multiorgan dysfunction and severe metabolic acidosis
- Many patients improve spontaneously
- Some may progress to severe dengue with multiorgan dysfunction despite adequate
intravenous fluids
Recovery phase
-Plasma leakage stops and reabsorption start
- Diffuse maculo-papular rash with significant pruritus is common during this phase
- Also, the general wellbeing and appetite improves. Leucopenia and thrombocytopenia
gradually improve over time.
Roger’s text book of PICU 7 th edition
Roger’s text book of PICU 7 th edition
.Roger’s text book of PICU 7 th edition
CDC guideline,National dengue guideline and IAP guideline
CDC guideline,National dengue guideline and IAP guideline
Colloids indication
•Patients with prolonged shock or severe ongoing plasma leakage -high haematocrit despite fluid
resuscitation
•Patients with clinical signs of fluid overload. Among colloids Dextran – 40, 5% albumin are
preferred.
Indications of ionotrope
•Fluids management is main in dengue shock, vasoactive infusions are not preferred.
• If child is hypotensive and intravascular hypovolemia is ruled out after giving adequate volume
(40-60mL/kg over 1-2 hours)
• USG measured dynamic changes in vena cava diameter
• Mechanism of shock in such a patient is due to myocardial dysfunction,do ECHO.
• Start with Low dose inotropic agents like epinephrine or dopamine is hypotensive.
Milrinone if myocardial dysfunction and compensated shock present.
1. Respiratory distress/ failure
Respiratory distress during critical phase of dengue, may be due to following causes
◦ Massive pleural effusion or ascites causing lung collapse during the critical phase
◦ Acute pulmonary edema due to myocardial dysfunction or fluid overload
◦ Severe metabolic acidosis due to uncorrected shock
◦ Pulmonary hemorrhage
◦ ARDS
Treat by - initially NIV sos ventilation
Respiratory distress/ failure
•Drainage of the effusions is indicated only when high ventilator pressure settings for adequate
gas exchange.
•Pulmonary edema due to fluid overload -Fluid restriction, diuretic infusion, positive pressure
ventilation, early renal replacement therapy
•Serum potassium levels should be monitored and treated to prevent complications of severe
hypokalemia induced by diuresis.
ARDS
•Severe plasma leakage in to the alveoli and the cytokine storm related to endothelial
dysfunction seems the likely cause.
•High PEEP may be needed in the presence of chest wall edema, ascites, pleural effusion or
pulmonary edema.
•ARDS is atypical manifestation of severe dengue can occur without clinical signs of fluid
overload or a massive pleural effusion.
•Management remains ventilation strategy similar to other cases of ARDS, with more emphasis
on fluid titration according to hematocrit. ARDS ventilation ,ECMO.
2.Management of bleeding
•Major bleeds are gastrointestinal bleed or occult bleed (intra-abdominal) with associated shock.
Refractory shock is the major risk factor for severe bleeding.
• Other common risk factors are severe or persistent metabolic acidosis, renal or liver failure,
NSAID usage and anticoagulant therapy.
•Clinical features that help recognize a major bleed include the following clinical scenarios:
1. Obvious blood loss
2. Rapid fall in HCT in a shocked child
3. Refractory shock not responding to fluid bolus of 40-60 ml/kg
4. Hypotensive shock associated with low or normal HCT prior to fluid resuscitation
Use of FFP and platelet
• Transfusion of 10-20 mL/kg of fresh whole blood or fresh packed red cells if fluid overload , they
are rich in 2,3 DPG
• If shock plus low HCT a second fresh blood transfusion should be considered.
• FFP -no role in the treatment of uncomplicated DHF/DSS.
•FFP or platelet transfusions do not improve the coagulopathy or thrombocytopenia, hence
should be considered only if bleeding persists despite two fresh whole blood transfusions.
•Platelet transfusions in a non-shock patient may be considered only when significant
thrombocytopenia exists and an invasive procedure is being planned.
3.Myocardial dysfunction
Cardiac manifestations of dengue are
• Cardiogenic shock (diastolic and systolic dysfunction)
• Myocarditis
• Pericardial effusion
• Arrhythmias (like supraventricular tachycardia, ventricular arrhythmias)
• Conduction blocks –use of isoprenaline and sos pacing
Myocardial dysfunction
•ECHO-decreased left ventricular systolic function ,y ejection fraction (EF)
•Lab-Elevation of Troponin T and CK-MB levels,Pro BNP.
•Both diastolic and systolic dysfunction treat with lusiotropic(milrinone/dobutamine)
and inotropic agents.
4.Neurological complications
Dengue virus being non-neurotropic
During an outbreak or in endemic regions can be due to atypical dengue infection.
Common manifestations are seizures and encephalopathy.
• Low Na
• Intracranial bleeding
•Impaired cerebral perfusion and Raised intracranial pressure
• Acute liver failure resulting in toxic encephalopathy
• Rarely encephalitis, meningitis -AHNE
• Demyelination - Acute Disseminated Encephalomyelitis, Transverse myelitis
• Ischemic stroke (due to dengue vasculitis)
•Management - airway, breathing and circulation
•Anti-raised ICP measures in patients with significant cerebral edema -
3%Nacl 5ml/kg TDS or infusion of 0.1-1 ml/kg/hr-excellent result,
•Anticonvulsant – fosphenytoin,Leveracetam.
• High dose steroids pulse dose of methyl prednisolone 30mg/kg for 3-5 days for ADEM or
transverse myelitis,ANEC with good recovery
•Peripheral nervous system manifestations like Guillain-Barre syndrome (GBS), neuritis and
cranial nerve palsies.
8 yr with status epilepticus and shock,Acute Hemorrhagic Necrotising Encephalopathy
Acute Hemorrhagic Necrotising Encephalopathy
5.Hepatitis
Moderate elevation of transaminases occurs in majority of patients with severe dengue. The
mechanism of liver injury includes
• Direct viral invasion of hepatocytes
• Dysregulated immune response
• Secondary - ischemic injury due to shock, hypoxia and acidosis
• Co-infection with hepatitis A, E
• Hepatotoxic drugs – acetaminophen overdose
Fulminant FHF think of HLH
Hepatitis
•Present as acute liver failure,elevated transamines
•These patients develop multiorgan dysfunction requiring intensive monitoring, fluid
management, close monitoring for hypoglycemia, bleeding, encephalopathy,
hyperammonemia and electrolyte abnormalities.
•Use of supportive therapy and NAC infusion.
6.Hemophagocytic Lymphohisitiocytosis (HLH)
•HLH or MAS- cytokine strom unregulated T cell function .
•HLH should be strongly suspected in dengue patients persistent high grade fever, bicytopenia,
hyperferritinemia with worsening coagulopathy despite stabilization of shock.
•Ferritin levels are often elevated to the tune of 1,000 mcg/L.
•Bone marrow may show evidence of hemophagocytosis.
•However, a negative bone marrow should not preclude a diagnosis of HLH.
Proposed HLH diagnostic criteria Filipovich, 2009.
1. Any -3 of 4:
a. Fever
b.Splenomegaly
c.Cytopenias (minimum 2 cell lines reduced)
d.Hepatitis
2.And at least 1 of 4: a.Hemophagocytosis, b.Ferritin, c.IL2 ,d.Absent or very decreased NK
function
3.Other results supportive of HLH diagnosis: a. Hypertriglyceridemia,b. Hypofibrinogenemia
c. Hyponatremia
4.Molecular diagnosis of hemophagocytic lymphohistiocytosis (HLH) or X-linked
lymphoproliferative syndrome (XLP).
Treatment of Dengue HLH
1. Corticosteroids
a. Dexamethasone at 10mg/m2/day for initial 5 days followed by tapering over 4-8
weeks
2. Intravenous immunoglobulin (IVIG) 2g/kg over 5 days or over 2 days
Few authors have used cyclosporine and or etoposide along with IVIG or steroids.
Some patients with dengue present in the early febrile phase or in the critical phase
with a significant isolated hyperferritinemia (>10,000 mg/L). In such cases, prior to
treatment, other criteria to suggest worsening organ dysfunction (mainly liver
dysfunction – transaminases, coagulopathy) should be looked for in addition to
criteria for HLH.
HLH leading to MODS
6.Renal failure
•Dengue fever can result in acute kidney injury (AKI) especially in severe cases.
•Microvascular injury due to hypoxia,shock,acidosis
• Fluid management, modification of drug doses for GFR, avoidance of nephrotoxic medications,
monitoring of electrolytes, early institution of renal replacement therapies are the principles
in management.
• PD,CRRT,HD.
Fluid overload -prevention
•Although, fluid overload occurs as a consequence of capillary leak, excessive intravenous
fluids (IVF) or giving hypotonic fluids.
• In addition, administration of hypotonic fluids such as 5% dextrose, half normal saline or
Isolyte P not to be used at all.
•Colloids can be used during resuscitation of hypotensive shock thereby reducing the need for
large volumes of crystalloids to maintain the intravascular volume.
Treatment of fluid overload
1. Fluid overload without shock or respiratory distress - Discontinuation of fluids.
Diuresis occurs spontaneously or can be augmented with furosemide infusion during the
recovery phase.
2. Fluid overload with respiratory distress without shock –use NIV. Low dsoe Diuretics-0.05 -
0.1 mg/kg/hour without compromising hemodynamic stability. Careful monitoring of urine
output and perfusion is mandatory.
3. Fluid overload with respiratory distress and shock - Requires intensive care monitoring with
invasive lines, ventilator support either invasive or noninvasive and initiation renal
replacement therapy for ultrafiltration.
Abdominal compartment syndrome
•ACS defined as abdominal distention with

•oliguria or anuria

•respiratory decompensation
•hypotension or shock
•metabolic acidosis

Abdominal compartment syndrome in children. Pediatr Crit Care Med. 2001


Jan;2(1):51
Abdominal compartment syndrome
•Aggressive fluid resuscitation and severe plasma leakage are the main risk factors
• Intra-abdominal pressure should be monitored using Foley’s catheter in-situ in patients
receiving fluids more than 30 mL/kg in first 3 hours.
•Treatment of ACS
i) Optimize sedation and analgesia
ii) Decompress gastrointestinal tract
iii) Decrease the ventilator pressures (PEEP) as feasible
iv) Prefer colloids for correcting ongoing shock
v) Drainage of ascites should be slow and controlled with close monitoring for bleeding and
worsening shock. Colloid infusion can be given along with drainage to treat worsening shock.
Conclusion
•Dengue should be considered in any child presenting with acute short febrile illness during an
outbreak.
•Children with warning signs should be meticulously monitored with HCT,no hypotonic fluid
•No diuretics in leaky phase
•Fluid therapy as guideline by WHO
•Shock, severe bleeding, severe organ dysfunctions are manifestations of severe dengue
•Atypical presentations are relatively common during an outbreak like ANE,raise ICP good response to
3%Nacl.
•HLH should be kept in mind and need aggressive treatment.
•Intensive care monitoring, organ support therapies, anticipation and treatment of complications are
the strongholds in managing patients with multiorgan involvement.
References
1.Roger’s text book of PICU 7 th edition
2.WHO guideline of management of dengue 2009
3.IAP concensus of management of Dengue 2014
4,National Dengue management guideline 2016.

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