Manifestation of Dengue Virus Infection
Dengue virus infection
Dengue Shock Syndrome:
Update Management
Asymptomatic
Symptomatic
Dengue hemorrhagic fever
Ampaiwan Chuansumrit, M.D.
Undifferentiated fever
Dengue fever
(plasma leakage)
(viral syndrome)
Department of Pediatrics
Faculty of Medicine Ramathibodi Hospital,
Without
With unusual
hemorrhage
hemorrhage
No shock
Dengue shock
syndrome
Mahidol University, Bangkok, Thailand
Dengue
Dengue fever
Hemorrhagic fever
Toxic
Stage
Restless,
Shock,
Hemorrhage
Acute onset of fever
Headache
Nausea
Vomiting
40oC
Plasma Volume in Dengue Hemorrhagic Fever
Convalescent Stage
ml/kg
80
70
60
50
39
Normal range
Febrile Stage
40
38
30
37
20
Flush face
Enlarged liver
Tourniquet test positive
Skin rash, petechiae, ecchymosis
10
0
-5
-4
-3
-2
-1
0
1
2
3
4
5
TOXIC
FEBRILE STAGE
1
2
4
Days of illness
5
6
7
8
9
Date of Disease
10
11
12
13
-30+
Romsai Suwanik, Prasong Tuchinda, et al. J Med Assoc Thai 1967; 50:48-66.
WHO Criteria 2009
Severity of DHF
Grade I:
CONVALESCENT STAGE
STAGE
3
No bleeding except positive
Dengue
Severe dengue
tourniquet test
Grade II: Spontaneous bleeding
with warning
signs
Grade III: Threaten shock
1. Severe plasma leakage
2. Severe hemorrhage
without
3. Severe organ impairment
Grade IV: Profound shock
1
Admission Criteria
• Warning signs and symptoms:
- severe abdominal pain
- severe nausea & vomiting
- irritability, restlessness
- lethargy, behavioral change
- cold clammy skin, clinical deterioration
- poor appetite, oliguria
- bleeding manifestations except petechiae &
ecchymosis
Admission Criteria
• Warning signs and symptoms:
Abnormal laboratory findings
- Hematocrit >42%
- Hematocrit rise >10-15%
- Platelet counts <100,000/mcL
Ramathibodi Clinical Practice Guideline, 2004
Comparison between WHO 1997 and 2009
WHO 1997
WHO 2009
Ramathibodi Clinical Practice Guideline, 2004
Prominent Features of DHF
• Shock is caused by plasma leakage,
Dengue without warning sign of plasma leakage
which results from increased vascular
DHF grade I
Dengue with warning sign of plasma leakage but no bleeding
permeability
DHF grade II
Dengue with warning sign of plasma leakage and bleeding
DHF grade III
Severe dengue with threatened shock
DHF grade IV
Severe dengue with profound shock
Dengue fever
• Bleeding is caused by vasculopathy,
thrombocytopenia, platelet dysfunction
and coagulopathy
Chuansumrit A, et al. Pediatrics and International Child Health 2013; 33(2):97-101.
Dengue Shock Syndrome (DSS)
• Mortality rate 13.9% in 1958 decreased to 0.12%
in the past five decades
Laboratory Finding of Dengue
Hemorrhagic Fever
• Rising Hct
• Of all fatal cases in 2007 were found in patients
with DHF (38%) and DSS (62%)
• Low WBC
• None of patients with DF died
• ↑ lymphocyte, ↑ atypical lymphocyte
• DHF grades III & IV (DSS) are high risk patients
• ↓ platelet counts
• Almost all patients with DSS with uncontrolled
massive bleeding died
• Positive tourniquet test
2
Dengue NS1 Antigen and Ig M in Patients with
Dengue Infection
NS1
120
Febrile
Ig M
100
Positive rate (%)
Dengue NS1 Antigen by Strip Method
NS1 & Ig M
80
60
40
C
C
C
T
T
T
20
0
Day-4
Day-3
Day-2
Day-1
Day 0
Day 1
Day 2
Day 3
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day of illness
Chuansumrit A, et al. Pediatr Infect Dis J 2008;27:43-8.
Association of -308 A of TNF-α and Bleeding
Positive
Negative
Predictor of Severe Dengue during
the Febrile Stage
• Rising hematocrit >25%
Case
Frequency
With
38
9/76 = 11.8%*
• Platelet count <40,000/μL
Without
63
5/126 = 4.0%*
• Prolonged coagulogram
*P = 0.04
Doubtful
• Soluble thrombomodulin >10 ng/ml
Butthep P, et al. Pediatr Infect Dis J 2006;25:894-7.
Chuansumrit A, et al. Southeast Asian J Trop Med Public Health 2010;41:326-32.
Management of Patients with DHF
• No specific treatment
Dengue shock syndrome
Severe dengue
• Massive leakage into the 3th space
• Hemorrhage
• Intensive supportive care
• Adequate & appropriate fluid
replacement
• Effective control of bleeding
Massive bleeding comes from multiple factors
- Capillary fragility
- Thrombocytopenia
- Coagulopathy
3
DHF Grade III
Appropriate Type and Rate of IV Fluid
Depend on stage of disease
• Febrile stage : dehydration due to poor appetite,
vomiting, high fever
– 5%D in NSS/2 rate = 50%-100% of maintenance
• Leakage stage/ toxic stage: Plasma leakage to the third
space, hemorrhage
– NSS or Ringer lactate, 5%D in NSS
– Colloid if massive leakage occur
– PRC if significant bleeding occur
• Convalescence stage: Leakage fluid return to vascular
circulation
– Decrease IV fluid to rate of KVO
Dengue shock: Impending shock (pulse pressure< 20 mmHg)
Isotonic fluid resuscitation 10 mL/kg in 1 hour
(NSS or RL or 5% D in NSS) x 1-2 doses
Check BS, serum electrolytes, BUN, Cr, LFT
cross match for Blood components
Correct hypoglycemia
If vital signs improve: Pulse pressure>20 mmHg
Urine output >1 mL/h or Sp gr 1.010-1.020
Monitor Hct; decreased
Decrease rate of IV fluid (5% D in NSS): 7 mL/kg/h x 1-2 h
5 mL/kg/h x 1-2 h
3 to 2 mL/kg/h thereafter
Gradually decrease rate of IV fluid according to monitoring
DHF Grade III
DHF Grade III
Dengue shock: Impending shock (pulse pressure< 20 mmHg)
Isotonic fluid resuscitation 10 mL/kg in 1 hour
(NSS or RL or 5% D in NSS) x 2-3 doses
If vital signs NOT improve:
If vital signs NOT improve :
Monitor Hct; Increased....... Massive Leakage
Colloid 10-20 mL/kg/h for 1-2 h
Dengue shock: Impending shock (pulse pressure< 20 mmHg)
Isotonic fluid resuscitation 10 mL/kg in 1 hour
(NSS or RL or 5% D in NSS) x 2-3 doses
IMPROVED
Decrease rate of IV fluid (5% D in NSS): 7 mL/kg/h x 1-2 h
5 mL/kg/h x 1-2 h
3 to 2 mL/kg/h thereafter
Gradually decrease rate of IV fluid according to monitoring
Monitor Hct; Decreased……BLEEDING
Colloid 10-20 mL/kg/h for 1-2 h waiting for
PRC 10-20 mL/kg in 1-2 h + FFP, + platelet concentrate
IMPROVED
Decrease rate of IV fluid (5% D in NSS): 7 mL/kg/h x 1-2 h
5 mL/kg/h x 1-2 h
3 to 2 mL/kg/h thereafter
Gradually decrease rate of IV fluid according to monitoring
DHF Grade IV (Severe Shock)
DHF Grade IV (Severe Shock)
Dengue shock: Profound shock
Isotonic fluid resuscitation 10 mL/kg in 10-15min
(NSS or RL) x 2-4 doses
Dengue shock: Profound shock
Isotonic fluid resuscitation 10 mL/kg in 10-15min
(NSS or RL) x 2-4doses
Check: BS, Ca, electrolytes, BUN, Cr, LFT, Coagulogram
ABG and cross match for blood components
Check: BS, Ca, electrolytes, BUN, Cr, LFT, Coagulogram
ABG and cross match for blood components
Correct hypoglycemia and hypocalcemia
IMPROVED
Correct hypoglycemia and hypocalcemia
If vital signs NOT improve: Monitoring in ICU
Monitor Hct; Increased
Change to colloid 10-20 mL/kg for 1-2 h
IMPROVED Change to 5% D in NSS
Gradually decrease rate of IV fluid according to monitoring
Decrease rate of IV fluid to 10 mL/kg/h 1-2 h
Decrease rate of IV fluid (5% D in NSS): 7 mL/kg/h x 1-2 h
5 mL/kg/h x 1-2 h
3 mL/kg/h thereafter
Gradually decrease rate of IV fluid according to monitoring
4
ไขเลือดออกเดงกีที่มีอาการรุนแรงมาก
DHF Grade IV (Severe Shock)
Dengue shock: Profound shock
Isotonic fluid resuscitation 10 mL/Kg in 10-15min
(NSS or RL) x 2-4 doses
Check: BS, Ca, electrolytes, BUN, Cr, LFT, Coagulogram
ABG and cross match for blood components
Correct hypoglycemia and hypocalcemia
If vital signs NOT improve: Monitoring in ICU
Monitor Hct; Decreased……BLEEDING
Colloid 10 mL/kg for 1-2 h waiting for
PRC 10-20 mL/Kg/1-4 h and FFP + plt concentrate
IMPROVED
Change to 5%D in NSS
Refractory DSS / Recurrent shock
ไดรับ isotonic crystalloid
และ colloid >50-70 มล./กก. ในระยะเวลา 4-6 ชม.
•
แกไขภาวะน้ําตาลต่ําในเลือด
acidosis และภาวะแคลเซียมต่ํา
•
ตรวจ: CBC, BS, electrolyle, BUN, Cr,
•
จองเลือดและสวนประกอบของเลือด
LFT, Ca, Coagulogram, Blood gas
หอผูปวยเวชบําบัดวิกฤต
ระบบหายใจ
หยุดเลือดออก
ระบบการไหลเวียนเลือด
Volume depletion
การรักษาดวยสารน้ํา
Gradually decrease rate of IV fluid according to monitoring
Volume overload
รักษาภาวะน้ําเกิน และรักษา
ประคับประคองการทํางานของ
อวัยวะตางๆ ที่ลมเหลว
Invasive Procedure
• Avoid as possible
• Performed by experienced personnel
• Restore hemostasis
– Platelet concentrate to reach platelet
count of >60,000/μL
Cardiovascular System
• Inotropes:
dobutamine, dopamine, adrenaline
• Vasoactive agent:
arterial vasodilator, vasopressor
– In cases of urgency, 90-100 μg/kg of
recombinant activated factor VII
Respiratory System
Chest AP
• Risk: massive pleural effusion, pulmonary
hemorrhage, ARDS
• Management:
– No thoracocentesis
– No intercostal chest drainage
– Non-invasive ventilation: BIPAP
– Invasive mechanical ventilation:
rapid sequence intubation
July 29, 2007
5
Chest Decubitus
Volume Overload
• Furosemide 0.05 mg/kg/hr
(max 0.4 mg/kg/hr)
• Renal replacement therapy
July 29, 2007
Abdominal Compartment Syndrome
• Transduction of bladder pressure
measured by Foley’s catheter
– normal value <12 cm H2O
– >20 cm H2O
• Abdominal paracentesis by using
Tenchkoff catheter
Predictor of Serious Bleeding
• GI bleeding: hematemesis, melena,
hematochezia
• Aspirin, NSAIDS e.g. ibuprofen
• Prolonged shock
• Vaginal bleeding unresponsive to premarin
• Underlying bleeding disorder: hemophilia,
von Willebrand disease
Blood Component Therapy
• RBC: replacement of massive blood loss
• Platelet concentrate: massive bleeding in
patients with thrombocytopenia
• FFP: bleeding in patients with coagulopathy
• Cryoprecipitate: fibrinogen replacement in
patients with massive bleeding
Concealed Bleeding
After the adequate volume replacement, internal
bleeding is suspected in the following conditions
- Patient with refractory shock who has a
hematocrit < 40%
- Systolic and diastolic BP is elevated or
normalized, but the pulse rate is rapid (> 130/min in
children, > 150/min in infants less than 1 year old)
- A drop in hematocrit of > 10% within 10 h of
fluid replacement
6
Transfusion Requirement in Patients with Dengue
Infection at Ramathibodi Hospital, Bangkok
Early Diagnosis of Massive Bleeding
1997
2000-2003
(n = 160)
(n = 413)
17 (10.6%)
27 (6.5%)
19 (7.4%)
• Rate and volume of blood loss
• Bleeding of 1.5 ml/kg/min in > 20
min or 150 ml/min
• Replacement with 50% blood
volume in < 3 h
• Transfusion rate
2004-2007
(n = 258)
• Required blood component
- Platelet conc.
11 (64.7%)
11 (40.7%)
11 (57.9%)
- Packed red cells
8 (47.1%)
16 (59.2%)
16 (84.2%)
- FFP
5 (29.4%)
7 (25.9%)
9 (47.4%)
No data
No data
8 (42.1%)
- Cryoprecipitate
Suggested Dose of Recombinant Activated Factor VII in
Controlling Bleeding in Patients with DHF
Algorithm for Use of rFVIIa in Controlling Bleeding
Persistent massive
bleeding
• Failure to conventional blood component therapy
Attempt to correct
Hct >24%, plt >50,000-100,000/μl
Fibrinogen 100 mg/dl
FFP 10-20 ml/kg
First dose of rFVIIa 100 μg/kg
T 37oC, pH > 7.2
Platelet 0.2-0.4 unit/kg (10 units)
Cryoprecipitate 0.2 unit/kg
• rFVIIa 100 μg/kg at 15-30 min interval if the bleeding is not
Bleeding
Bleeding
Bleeding
stopped
markedly decreased
Slowed down
Second dose of
significant reduced (1-2 doses are usually used) followed
30 min interval
by 100 μg/kg at 1-4 h interval (1-2 doses are usually used)
Subsequent dose at
1-4 h interval
(1-3 doses are usually used)
Massive Bleeding in a Patient with
Dengue Shock Syndrome
• A 7-year-old boy exhibited hematemesis
Report of Massive Bleeding in a Patient
with Dengue Shock Syndrome
Time
Bleeding
Treatment
0
bleeding from NG tube,
rFVIIa 100 μg/kg i.v.
and hematochezia with shock
• During 10 hours of management
- Whole blood 200 ml
- Packed red blood cells 750 ml
hematochezia
15 min
blood in NG tube
disappeared
2h
hematochezia 400 ml
PRC 250 ml
2 h 45 min
hematochezia 300 ml
PRC 250 ml, FFP 200 ml
PRC 250 ml
- Fresh frozen plasma 600 ml
3 h 15 min
hematochezia 200 ml
- Platelet concentrate 7 units
4-24 h
no further bleeding
7
Superimposed Infection
• Multi-organ failure
• Invasive procedure in high risk patients
• Bacteria: S aureus, Salmonella,
S pneumoniae
• Fungus: Aspergillus spp
Prognosis
• Case-fatality rate
– 6 out of total 732 cases = 0.82%
– 6 out of 106 cases with DSS = 5.7%
• Utilization of rFVIIa
– 17 out of total 732 cases = 2.3%
– 6 out of 17 cases died = 35.3%
Faculty of Medicine Ramathibodi Hospital, Mahidol University,
Bangkok, Thailand
•
•
•
•
•
•
•
•
•
•
•
Wandee Varavithya, MD.
Somsak Lolekha, MD.
Subharee Suwanjutha, MD.
Teerachai Chantarojanasiri, MD.
Pongsak Khowsathit, MD.
Kanchana Tangnararatchakit, MD.
Anant Khositseth, MD.
Suthep Wanichakul, MD.
Pimpan Kitpoka, MD.
Wathanee Chaiyaratana, MSc.
Staff & nurses at ICU, Wards Pediatrics 2 & 5
8