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Dr. A. Arunkumar, M.D.(Pediatrics),
Consultant Pediatrician,
KMCH, Erode.
Dengue as an emerging disease
 DEN was a minor, geographically
restricted disease until mid-20th
century
 World War II/global cargo
transport of Aedes mosquitoes
likely responsible for
dissemination
 DEN/DHF present in the WHO
regions of the Americas, South-
East Asia, Eastern Mediterranean
and Western Pacific; Africa
reports DEN but only sporadic
DHF 1
 DHF first documented in 1950s in
the Philippines and Thailand.
Dengue virus (DENV)
 Single-stranded RNA virus
 Member of Flavivirus family
Selected
Flaviruses
Tick-borne encephalitis virus
West Nile virus
Murray Valley encephalitis virus
Japanese encephalitis virus
St. Louis encephalitis virus
DENV 1
DENV 3
DENV 2
DENV 4
Yellow Fever virus
Dengue virus (cont.)
 Four serotypes (really species): DENV-1, -2, -3, -4
 All cause full spectrum of disease
 Infection confers lifelong serotype-specific immunity and
short-term (2-3 months) cross-immunity
 Humans can have four infections in a lifetime
 Genetic variation within serotypes
 Some genetic variants thought to be more virulent
 Dengue virus causes an acute febrile illness (called dengue)
Transmission of dengue virus
Febrile, viraemic
boy with dengue
virus infection
Time
Mosquito bites boy
and gets dengue
virus in the blood
meal
Time
Transmission of dengue virus
8 to 12 days later
Dengue-infected
mosquito bites girl
and …
Extrinsic Incubation Period
within the mosquito
Time
Affected by temperature
Transmission of dengue virus
… transmits the dengue
virus to her
Time
Transmission of dengue virus
3 to 14 days later
Girl can pass dengue
virus to another
mosquito if bitten
while she is
viraemic
Intrinsic Incubation Period
within the girl
Time
Transmission of dengue virus
Breeding areas and transmission
 Ae aegypti immature stages are typically found in water-filled
habitats associated with human habitation;
 Lays eggs in artificial, water-holding containers, and
occasionally bromeliads and tree holes
 Primarily feeds from dawn to dusk, rests in dark areas and
bites indoors
 Most female Ae. aegypti mosquitoes spend their lifetime in
or around the houses where they emerge as adults, meaning
people rather than mosquitoes rapidly move the virus within
and between communities
Breeding sites: plants, pools, water-filled buckets, used tires, empty oil drums, water storage containers etc.
Credit:WHO
Other routes of transmission
 Evidence of transmission of dengue through receipt
of donor organs or tissue1
−Bone marrow transplant and renal transplant
 Evidence of transmission of dengue through receipt
of blood products (RBC transfusion)2,3
 Seven reports of transmission after occupational
exposure in a health-care setting
 DENV can be transmitted from the mother to the
fetus in utero or to the neonate at parturition
(vertical transmission)
Platelets
12
Clinical course of dengue
Dengue is a systemic and dynamic disease.
Dengue is NOT a platelet count disease
13
Clinical course of dengue
Incubation period
After the incubation period, the illness begins abruptly.
It is characterized by 3 phases:
Febrile phase – commences at symptom onset
Critical
Phase
0 1 2 3 4 6 8 10
Days
Febrile Phase
Critical phase – commences around time of defervescence*
* Defined as when body temperature drops to less than 38°C and remains below this level.
Recovery phase – commences when plasma leakage resolves
Recovery Phase
Viraemia:
headache, nausea, myalgia,
body ache and rash
Virology and Serology
0 1 2 3 4 5 6 7 8 9 10
Phases of dengue: Febrile Critical Recovery
Adapted from WCL Yip, 1980 by Hung NT, Lum LCS, Tan LH 14
Days of illness:
Virology and Serology
0 1 2 3 4 5 6 7 8 9 10
Viraemia
Phases of dengue: Febrile Critical Recovery
IgM/IgG
Adapted from WCL Yip, 1980 by Hung NT, Lum LCS, Tan LH 15
Days of illness:
40
38
6 Key features:
1. Temperature
Defervescence Bi-phasic/
Saddle back picture
Subnormal
temperature
Virology and Serology
0 1 2 3 4 5 6 7 8 9 10
Viraemia
Phases of dengue: Febrile Critical Recovery
4. WBC
5. Platelet
6. HCT
Platelet
Haematocrit
IgM/IgG
Adapted from WCL Yip, 1980 by Hung NT, Lum LCS, Tan LH 16
Days of illness:
40
38
6 Key features:
1. Temperature
Laboratory
changes
WBC
Virology and Serology
0 1 2 3 4 5 6 7 8 9 10
Viraemia
Phases of dengue: Febrile Critical Recovery
Bleeding
Reabsorption
Fluid overload
Dehydration
Organ Impairment
4. WBC
5. Platelet
6. HCT
Platelet
Haematocrit
IgM/IgG
Adapted from WCL Yip, 1980 by Hung NT, Lum LCS, Tan LH 17
Days of illness:
40
38
6 Key features:
1. Temperature
2. Oral intake
3. Urine output
Potential
clinical issues
Laboratory
changes
WBC
Capillary permeability
Shock
18
Vignette of febrile phase
• Usually lasts 2 to 7 days
• High temperature; may be modified by antipyretics
• Common symptoms: myalgia, headache, retro-orbital pain, aches, rash
• Difficult to differentiate dengue from viral febrile illness
• Normal CBC in first 1 to 2 days of fever
Children
Nausea and vomiting may be prominent
1 Lum et al. Quality of Life of Dengue Patients. Am J Trop Med Hyg, 2008.
19
Transition from febrile phase to critical phase
• Usually day 4 to day 7 of illness
• Could be as early as day 3 or as late as day 7 or 8
• Coincides with defervescence
Clinical Warning Signs
1. Severe abdominal pain
2. Persistent vomiting
3. Mucosal bleed
4. Lethargy; restlessness
5. Liver enlargement >2cm
6. Clinical fluid accumulation
Laboratory Warning Signs
1. Leukopenia
2. Rapid decrease platelet count
3. Rising haematocrit
Development of warning signs:
Identify dengue patients already in shock or at risk of developing shock
20
What happens during the critical phase?
Increased vascular permeability
Significant plasma leakage
Development of warning signs
Deterioration in patient’s condition
How long does plasma leakage last?
24 – 48 hours
What could happen without treatment?
Death
Shock occurs when critical volume of plasma is lost through leakage.
Shock is often preceded by warning signs.
Body temperature may be sub-normal when shock occurs.
The total white cell count may increase (instead of leukopenia) in patients
with severe bleeding at this stage.
21
Do all dengue patients enter critical phase?
NOT all patients will experience the critical phase
Clinical course of patient without significantly increased vascular permeability:
• Fever subsides  general condition improves and appetite recovers
• May have leukopenia
• Mild to moderate thrombocytopenia
22
Vignette of recovery phase
What happens in recovery phase?
1. Improvement in general well-being and stable haemodynamic status
2. Diuresis
3. Biphasic fever
4. May have bradycardia, itching
5. Isles of white in the a sea of red
Vascular permeability reverts to normal
 Gradual reabsorption of extravascular fluid in next 48 to 72 hours
Clues to progression from critical phase to recovery phase
Clinical clues:
Laboratory clues:
1. HCT stabilizes.
HCT may lower due to dilutional effect of reabsorbed fluid (haemodilution).
2. WBC usually starts to rise soon after defervescence.
3. Thrombocytopenia persists longer than leucopenia.
23
When to consider severe dengue?
Severe dengue is defined by one or more of the following:
1. Severe plasma leakage
2. Severe bleeding
3. Severe organ impairment
Severe manifestations of dengue are related to severe plasma leakage
 Reduced organ perfusion and tissue hypoxia
 Organ impairment
24
When to consider severe dengue?
1. Severe plasma leakage
2. Severe bleeding
Patient has hypovolaemic shock
Patient has respiratory distress due to fluid accumulation: either pleural effusion
or ascites
Patient remains in shock despite IV isotonic crystalloid solution and the
hematocrit is decreasing
Bleeding can be occult and not recognized in a timely manner; important to do
frequent vital signs and monitor hematocrit
Severe bleeding exacerbates shock
Severe bleeding has been observed in adults who had no or only mild plasma
leakage
Bleeding usually occurs in the gastrointestinal tract, and only rarely in the brain
25
When to consider severe dengue?
3. Severe organ impairment
Consequences of hypovolaemic shock
Severe impairment of organs such as liver, kidneys and brain has been
observed in patients with only mild or no plasma leakage or after the critical
phase of dengue.*
It is defined as one of the following:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1000
IU/L
• Impaired consciousness
• Impaired cardiac function – raised cardiac enzymes with reduced left ventricular
function
Liver enzymes are frequently elevated during the critical and recovery phases.
* Trung et al. Liver involvement associated with dengue infection in adults in Vietnam. Am J Trop Med Hyg,
2010.
Conditions that mimic the febrile phase of dengue
Viral infections
Influenza, measles, rubella
Chikungunya, West Nile virus
Enterovirus
Other viral haemorrhagic fever
Infectious mononucleosis
Acute HIV seroconversion illness
Leptospirosis
Typhoid
Rickettsia infections (typhus, scrub typhus, etc.)
Malaria
Measles, rubella
Infectious mononucleosis, enterovirus
Chikungunya, West Nile virus,
Scarlet fever, meningococcal infection
Leptospirosis, typhoid
Rickettsia infections (typhus, scrub typhus, etc.)
Syphilis, acute HIV seroconversion illness
Autoimmune diseases (e.g. SLE)
Adverse drug reaction
Rotavirus
Salmonellosis
Other enteric infections
Bacterial infections
Febrile illness with
a rash
Parasitic infections
Diarrhoeal diseases
Conditions that mimic the critical phase of dengue
Acidotic breathing/
respiratory distress
Acute appendicitis
Acute cholecystitis
Perforated viscus
Diabetic ketoacidosis
Diabetic ketoacidosis
Lactic acidosis
Renal failure
Acute respiratory distress syndrome (ARDS)
Sepsis, septic shock
Acute gastroenteritis
Leptospirosis, typhoid, typhus, malaria
Viral hepatitis
Acute HIV seroconversion illness
Systemic lupus erythematosus
Idiopathic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Systemic vascultis
Acute leukaemia
Lymphoma
Other malignancies
Liver cirrhosis with portal hypertension
Adverse drug reaction
Acute abdomen
Infections
Autoimmune diseases
Malignancies
Others
Step 2: Clinical examination
General assessment:
Mental state
Hydration state
Haemodynamic state
Clinical evidence of warning signs:
Bleeding manifestations: mucosal bleeding
Abdominal tenderness
Liver enlargement
Fluid accumulation: pleural effusion, ascites
Other important signs:
Rash
Tachypnoea/acidotic breathing: indicates shock
Tourniquet test: repeat if negative or if there is no bleeding manifestation
Hemodynamic Assessment - Clinical Parameters
Parameters
Conscious
level
Capillary refill
time
Extremities
(color, temp)
Peripheral
pulse volume
Heart rate
(HR)
Pulse pressure
(PP)
Blood
pressure (BP)
Respiratory
rate (RR)
Urine output
1. Peripheral perfusion
3a. Organ perfusion (brain)
3b. Organ perfusion (kidney)
4. Respiratory compensation for tissue hypoxia
2. Cardiac output
Pallor in shock
Delayed capillary refill time.
The blood pressure was normal at this time.
The “5-in-1 maneuver” magic touch
CCTV-R
(1) colour,
(2) capillary refill time
(3) temperature of
extremities
(4) pulse volume
(5) pulse rate.
Hemodynamic Assessment - Stable Circulation
Parameters Stable Circulation
Conscious level Clear and lucid
Capillary refill time
Brisk (<2 seconds)
Extremities (color, temp) Warm and pink
Peripheral pulse volume
Good volume
Heart rate (HR) Normal HR for age
Pulse pressure (PP) Normal PP for age
Blood pressure (BP) Normal BP for age
Respiratory rate (RR) Normal RR for age
Urine output Normal
1. Normal Peripheral perfusion
2. Normal Cardiac output
3a. Normal Brain Perfusion
4. No Respiratory compensation
3b. Normal kidney perfusion
120
110
100
90
80
70
60
Time
LCS Lum
LUCID conscious level
Decreased urine output
Hemodynamic Changes in Compensated Shock
Normal or elevated systolic pressure
Rising diastolic pressure
Narrow pulse pressure – weak pulse
Tachycardia
Blood pressure
Reduced peripheral perfusion
Cool/cold and pale extremities
Prolonged capillary refill time
“Quiet” tachypnea
Heart rate
Hemodynamic Assessment – Compensated Shock
Parameters Stable Circulation Compensated shock
Conscious level Clear and lucid Clear and lucid
Capillary refill time
Brisk (<2 seconds)
Prolonged (>2 sec)
Extremities Warm and pink Cool peripheries
Peripheral pulse
volume
Good volume
Weak & thready
Heart rate (HR) Normal HR for age Tachycardia for age
Pulse pressure (PP) Normal PP for age
Normal systolic pressure
rising diastolic pressure
Blood pressure (BP) Normal BP for age
Narrowing PP
Postural hypotension
Respiratory rate (RR) Normal RR for age “Quiet” tachypnea
Urine output Normal Reducing trend
Reduced
peripheral
perfusion
Reduced cardiac
output
3a. Normal brain perfusion
Tissue acidosis
Reduced kidney perfusion
Parameters Stable Circulation Compensated shock
Conscious
level
Clear and lucid Clear and lucid
Capillary
refill time
Brisk (<2 sec)
Prolonged (>2 sec)
Extremities Warm and pink Cool peripheries
Peripheral
pulse volume
Good volume
Weak & thready
Heart rate
(HR)
Normal HR for age Tachycardia for age
Blood
pressure
(BP)
Normal BP for age
Normal systolic pressure,
rising diastolic pressure
Pulse
pressure
(PP)
Normal PP for age
Narrowing PP
Postural hypotension
Respiratory
rate (RR)
Normal RR for age “Quiet” tachypnea
Urine output Normal Reducing trend
Note that changes
are seen in all
parameters except
conscious level and
systolic blood
pressure
Hemodynamic Assessment - Compensated Shock (cont.)
120
110
100
90
80
70
60
Time
LCS Lum
Hemodynamic Changes in Hypotensive Shock
Decreased level of conscious
Oliguria or anuria
Increasing tachycardia
Systolic and diastolic pressures disappear
suddenly
Reduced peripheral perfusion
Very cold, clammy extremities
Mottled, peripheral cyanosis
Very prolonged capillary refill time
Kussmaul breathing
Blood pressure Heart rate
Feeble or absent peripheral pulse
Key clinical signs of deterioration: Changes in Mental State
• Restless, confused, extremely lethargic
• Seizures
• Agitation alternating with drowsiness
Hemodynamic Assessment – Hypotensive Shock
Infants and young children:
• Failure to recognize parents, focus or make eye contact
• Listen to parents: “Something is wrong with my child.”
Imminent total cardiorespiratory collapse
What is considered adequate urine output?
A patient with dengue shock should pass at least 0.5 ml/kg
urine per hour.
An indwelling catheter will give an accurate measurement. If
the urine volume exceeds this amount, consider reducing
the IV fluid therapy.
Hemodynamic Assessment – Monitoring urine output
Parameters
Stable
Circulation
Compensated
shock Hypotensive shock
Conscious
level
Clear and lucid Clear and lucid Restless, combative
Capillary
refill time
Brisk (<2 sec) Prolonged (>2
sec) Very prolonged, mottled skin
Extremities Warm and pink Cool peripheries Cold, clammy
Peripheral
pulse volume
Good volume
Weak & thready Feeble or absent
Heart rate
(HR)
Normal HR for
age
Tachycardia for
age
Severe tachycardia or
bradycardia in late shock
Blood
pressure
(BP)
Normal BP for
age
Normal systolic
pressure, rising
diastolic pressure
Hypotension
Unrecordable BP
Pulse
pressure
(PP)
Normal PP for
age
Narrowing PP
Postural
hypotension
Narrowed pulse pressure
(<20 mmHg)
Respiratory
rate (RR)
Normal RR for
age
“Quiet” tachypnea Kussmaul breathing
Urine output Normal Reducing trend Oliguria or anuria
Hemodynamic Assessment – Hypotensive Shock (cont.)
Reduced
peripheral
perfusion
Reduced
cardiac
output
Reduced brain perfusion
Severe tissue acidosis
No kidney perfusion
40
Pearls and pitfalls: dengue shock
Dengue shock presents as a physiologic-time continuum
Compensated shock in the early stage
(normal or elevated blood pressure)
Decompensated shock in the late stages
(hypotension & unrecordable blood pressure)
Stable
Warning
signs
Compensated
shock
Hypotensive
shock
Cardiac
arrest
Hours Hours Hours Min
Pitfall: Why is it easy to miss dengue shock?
Severe bleeding will exacerbate the shock state and if unrecognized will cause
refractory and irreversible shock with a very poor outcome.
Identification and treatment of early shock will improve clinical outcome.
Delayed treatment leads to a clinical course complicated by severe bleeding and
organ impairment.
Even in the severe shock state, the patient appears deceptively normal or “stable”
with a lucid conscious level.
A careful physical examination is critical to recognizing a patient in shock before the
stage of cardiovascular collapse.
Dengue investigation basics
Step 3: Investigations
• Complete blood count (CBC) with haematocrit (HCT) are usually
all that are necessary for monitoring
• Of special importance are:
• HCT;
• white blood cell count (WBC) and;
• platelet count
Dengue-specific diagnostic tests *
Other tests? *
Step 3: Investigations
• Blood chemistry tests (liver function, glucose, serum electrolytes, urea,
creatinine
• Should be considered in patients with risk factors and severe disease
• For confirmation, e.g. NS1/IgM rapid tests or nucleic acid detection
(depending on resources of health facility)
• Not necessary for the acute management of patients but valuable in
unusual manifestations, suspected dengue deaths in the area, or for
patients who progress rapidly from mild to severe dengue or death
* If available
43
Pearls: laboratory warning signs
Leucopenia
• Occurs 24 hours before rapid decrease in platelet count
• Not predictive of plasma leakage
• Good indicator that patient could have dengue
Rapid decrease in platelet count + rising trend in haematocrit
• Occur shortly before or at defervescence
• May precede changes in blood pressure and pulse pressure
• Indicate an increase in vascular permeability
NOTE: Changes in haematocrit may be masked by IV fluid therapy
Group A – Sent home
(all of following)
Group B
(any of following)
Group C
(any of following)
Getting adequate volume of
oral fluids
Passing urine at least once
every 4 to 6 hours
No warning signs
Has stable hematocrit and is
hemodynamically stable
Does not have co-existing
conditions
Has warning signs
Has co-existing condition:
Diabetes mellitus, renal
failure, pregnant, infant or
elderly
Has social circumstances:
Living alone or living far away
without a reliable means of
transport
Severe plasma leakage with
shock and/or fluid
accumulation with
respiratory distress
Severe bleeding
Severe organ impairment:
AST or ALT ≥1000 and/or
impaired consciousness
1. Give anticipatory
guidance before sending
home (see patient
handout)
2. Follow up daily
3. Do serial CBCs
4. Identify warning signs
early
1. Admit for inpatient care
2. Monitor haemodynamic
status frequently
3. Use HCT to guide
interventions
4. Use isotonic IV fluids
judiciously
5. Correct metabolic
acidosis, electrolytes as
needed
Requires emergency
treatment and urgent referral
Summary of management of dengue
Outpatient management: Group A
Group A – Send home if
patient meets all of the
following
Intake: Getting adequate
volume of oral fluids
Output: Passing urine at least
once every 4 to 6 hours
Does not have any warning
signs
Has stable haematocrit and
hemodynamic status
Does not have co-existing
conditions
Patients who are able to
“drink enough to pee enough”
1. Give anticipatory guidance
before sending home
(see patient handout)
1. Follow up daily
2. Do serial CBCs
3. Identify warning signs
early
Improved *REASSESS
Obtain reference HCT before starting IVF therapy
Start with isotonic
crystalloids
5–7 ml/kg/hr for 1–2
hours
* Reassess haemodynamic state
1. Vital signs
2. “5-in-1 magic touch”: CCTV-R
Colour
Capillary refill time
Temperature
Volume of pulse
Rate
3. Urine volume
IV isotonic crystalloids^
3–5 ml/kg/hr for 2–4 hours
IV isotonic crystalloids^
2–3 mL/kg/hr for 2–4 hours
Clinical improvement or
improved oral intake,
reduce IVF accordingly
Stop IVF therapy within
24–48 hours
If improvement in oral intake,
HCT remains same or minimal high:
1. Step-wise reduction in IVF
2. Consider glucose-electrolyte for
children
Continue to monitor patient until out
of critical period
Stop IVF within 24–48 hours
Group B: Dengue with warning signs (not in shock)
– Inpatient fluid management
Yes No
Urgent
blood
transfusion
• Colloid (10–20
ml/kg/hr)
• Evaluate to
consider blood
transfusion if
no clinical
improvement
Start isotonic crystalloid or colloid therapy
10–20 ml/kg (adult) or
20 ml/kg (child) over 15–30 minutes
Check haematocrit
Not improved
If improved
•Reduce IV
crystalloids
7–10 ml/kg/hr
for 1–2 hours
•Continue step-
wise reduction
with
crystalloids
Severe overt bleed
Increasing
Or high HCT
Group C: Emergency treatment – Summary
Colloid**
10 ml/kg/hr
for 30–60 minutes
If not improved,
recheck haematocrit
Decreasing HCT
IV crystalloid or colloid
10 ml/kg/hr for 1 hour
*REASSESS Improved
Step-wise reduction of
IV crystalloids
5–7 ml/kg/hr for 1–2 hours
3–5 ml/kg/hr for 2–4 hours
2–3 ml/kg/hr for 2–4 hours
Further boluses may be
required
Clinical improvement or
improved oral intake,
reduce fluids step-wise
Stop IV fluids at 24–48
hours
Try to obtain CBC, HCT,
GXM and other blood
readings before fluid
resuscitation
* Reassess the patient’s clinical condition: vital signs, peripheral perfusion (CCTV-R) & urine output and decide on the situation.
** Colloid is preferable if the patient has already received several boluses of crystalloid
IV: intravenous, HCT: hematocrit, IVF: intravenous fluids
Hypotensive shock
Mental status remains good, even in compensated shock
Hypotensive shock can cause seizures or alternating states of drowsiness
with agitation.
Confusion may be caused by electrolyte imbalances – hyponatremia,
hypocalcemia, hypokalemia, severe liver dysfunction or in unusual cases
encephalopathy.
In very rare cases, intracerebral bleeding, usually associated with trauma
Which organ is most frequently affected in severe dengue?
Liver enzymes are frequently elevated during the critical and recovery phases
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1000 IU/L
Supportive therapy – maintain euglycemia and adequate tissue perfusion
What about the brain?
Monitoring organ function
48
Paracetamol should be discontinued during the critical phase
Minor mucosal bleeding:
epistaxis,
gum bleeding,
not uncommon
Risks for bleeding
49
1. Gastrointestinal tract (most common site)
2. Any form of trauma:
Venepuncture sites
Chest tube insertion sites
Nasogastric tube insertion may cause severe epistaxis
Where are the sites of major bleeding?
Pathophysiology of thrombocytopenia
1. Early bone marrow suppression1
2. Peripheral immune-mediated platelet destruction via DENV
binding to platelets in the presence of DENV antibody2
3. Platelets aggregate on DENV-infected endothelium, resulting in
platelet destruction or clearance by macrophages3
4. Haemophagocytosis4
Even when actively bleeding, platelet transfusion not helpful
1 Schexneider KO, Reedy EA. Curr Hematol Rep, 2005, 4:145-148.
2 Hathirat P et al. SE Asian J Trop Med Public Health, 1993, 24 Suppl 1:80-85. Oishi K et al. J Med Virol, 2003, 71:25-64.
3 Saito M et al. Clin Exp Immunol, 2004, 138:299-303.
4 Honda S et al. Am J Trop Med Hyg, 2009, 80(5):841-845.
Why might giving platelets not help?
50
When should you consider repeating blood transfusion?
Give: 5–10 ml/kg of fresh packed red blood cells or
10–20 ml/kg of fresh whole blood at appropriate rate
Reduce colloid/crystalloid infusions, except to maintain euglycemia
What is a good clinical response?
• Improving haemodynamic state – vital signs, peripheral
perfusion and urine output
• Improving acid-base balance
1. Further blood loss
2. Unstable haemodynamic state
3. No appropriate rise in HCT after blood transfusion (i.e.
3% to 4% increase in HCT for every 10 cc/kg of packed
red blood cells given)
Group C: Emergency treatment
of haemorrhagic complications
51
Other complications
Fluid overload (excessive accumulation) is a major complication in
dengue shock
+
Causes:
Increased capillary permeability (plasma leakage)
One or more of the following:
1. Excessive and/or too rapid IV fluids
2. Use of hypotonic rather than isotonic crystalloid solutions
3. Transfusion of FFP, platelet concentrates and cryoprecipitate
4. Continuation of IV fluids after plasma leakage has resolved
5. Co-morbid conditions, e.g. congenital or ischaemic heart
disease, chronic lung disease, renal disease
52
Clinical features of fluid overload
Respiratory distress – rapid, shallow breathing, chest wall
in-drawing, abdominal distension
Late features: more severe respiratory distress – raised
JVP, wheezing, hypertension, bounding pulse,
abdominal pain
Very late features: very severe respiratory distress
Pulmonary oedema – Hypoxaemia
Heart failure – Haemodynamic instability
Cardio-respiratory failure
53
AS FLUID ACCUMULATION INCREASES
Management of fluid overload – stopping IV
fluids
Is an important milestone during the course of dengue management.
Why?
Plasma leakage stops. Allows fluid in pleural and peritoneal cavities
to return to intravascular compartments.
Diuresis and resolution of pleural effusion and ascites
When should IVF be stopped?
Signs of cessation of plasma leakage:
• Stable vital signs, peripheral perfusion and oral intake and
urine output improve
• HCT decreases in the presence of good pulse volume
• Resolving bowel/abdominal symptoms
54
Other issues to be managed
Hypoglycaemia – Correct with 1–2 ml/kg of Dextrose 10%,
followed by glucose-electrolyte infusion to maintain euglycaemia.
Hypokalaemia – Usually occurs during recovery phase and use of
diuretics. Correct by adding potassium chloride into infusion or
encourage patients to drink coconut or fruit juice.
Hyperglycaemia
Hyperkalaemia – associated with metabolic acidosis and acute
kidney injury
May resolve with correction of shock.
55
Other issues to be managed (cont.)
Metabolic acidosis –
• Tissue hypoxia in shock
Action: Treat shock, metabolic acidosis corrects itself
Hypocalcaemia – usually in association with multiple blood
transfusions. Correct with 10% calcium gluconate infusion.
Co-infections and nosocomial infections
Action: Be vigilant and treat promptly.
Check for thrombophlebitis and remove suspicious lines.
Regular change of peripheral intravenous lines.
56
Supportive care and adjunct therapy
Cardiac conduction defect – usually asymptomatic
Inotropes should be used only in severe hypotension while giving
fluid resuscitation to restore circulation.
Use small doses of inotropes unless proven myocarditis.
Large doses of inotropes may give a false impression of a “good”
blood pressure.
Liver impairment – Avoid hepatotoxic drugs such as paracetamol
and acetaminophen. Supportive care usually leads to spontaneous
recovery.
57
Supportive care and adjunct therapy
Management of acute kidney injury
Most common organ to suffer from shock.
Oliguria and Anuria are consequences of hypoperfusion.
Are not indications for diuretics, especially during the critical phase
The priority is to give fluid resuscitation to achieve haemodynamic stability.
Urine may start to flow once stability is achieved.
58
Rash – characteristic of dengue
Stable haematocrit with oral intake and off IV fluids
No fever for 24 – 48 hours
Improvement in clinical status
Increasing trend of platelet count (usually preceded by rising WBC)
Who needs to be followed up?
Discharge criteria
General well-being, good appetite, stable haemodynamic status, adequate
urine output, no respiratory distress and no organ dysfunction
Follow up patients with organ impairment
Case 1
• 11 months infant
• Admitted for fever
• Dengue positive
• Did not develop any signs of plasma leak /
bleeding
• Moderate thrombocytopenia
• Managed in ward with oral fluids alone, and
monitoring
• Improved well and discharged.
Case 2
• 9 yr male child
• admitted on day 5 fever
• Increasing hematocrit, early shock
• Platelets went down upto 15000
• Managed with iv fluids alone as per protocols
• Improved well and discharged
Case 3
• 15 yr old male
• Admitted on day 4 of fever
• Shifted to ICU on day 3 in view of early
compensated shock
• Developed ARDS / pulmonary edema / altered
sensorium
• Mechanically Ventilated and managed as per
protocols
• Improved well.
Case 4
• 8 yr male child
• Admitted for high grade fever
• Dengue positive
• Grossly Elevated liver enzymes / no shock
• Prolonged sleepiness ?encephalopathy
• Managed conservatively / symptomatically
• Improved well
Caricaya papaya and Nilavembu -
myth or boon?
• Proposed mechanisms:
– active components such as papain, chymopapain,
cystatin, L-tocopherol, ascorbic acid, flavonoids,
cyanogenic glucosides and glucosinolates
– membrane-stabilizing properties
– ALOX 12 and PTAFR genes upregulation
– A. paniculata showed the highest antiviral
inhibitory effect on DENV-1 by antiviral assay
based on cytopathic effects
Real life scenario
Conclusion of study
• More large scale and randomised controlled
studies are needed to really assess whether
these herbal products have any benefit in
dengue patients.
Summary
• Dengue is not a disease of platelets.
• Proper monitoring and early detection of
complications will result in
better survival rates.
Decreased complications.
Decreased icu stay.
Decreased morbidity.
THANK YOU

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Pediatric dengue management - Dr. Arunkumar, MD(Paed)

  • 1. Dr. A. Arunkumar, M.D.(Pediatrics), Consultant Pediatrician, KMCH, Erode.
  • 2. Dengue as an emerging disease  DEN was a minor, geographically restricted disease until mid-20th century  World War II/global cargo transport of Aedes mosquitoes likely responsible for dissemination  DEN/DHF present in the WHO regions of the Americas, South- East Asia, Eastern Mediterranean and Western Pacific; Africa reports DEN but only sporadic DHF 1  DHF first documented in 1950s in the Philippines and Thailand.
  • 3. Dengue virus (DENV)  Single-stranded RNA virus  Member of Flavivirus family Selected Flaviruses Tick-borne encephalitis virus West Nile virus Murray Valley encephalitis virus Japanese encephalitis virus St. Louis encephalitis virus DENV 1 DENV 3 DENV 2 DENV 4 Yellow Fever virus
  • 4. Dengue virus (cont.)  Four serotypes (really species): DENV-1, -2, -3, -4  All cause full spectrum of disease  Infection confers lifelong serotype-specific immunity and short-term (2-3 months) cross-immunity  Humans can have four infections in a lifetime  Genetic variation within serotypes  Some genetic variants thought to be more virulent  Dengue virus causes an acute febrile illness (called dengue)
  • 5. Transmission of dengue virus Febrile, viraemic boy with dengue virus infection Time
  • 6. Mosquito bites boy and gets dengue virus in the blood meal Time Transmission of dengue virus
  • 7. 8 to 12 days later Dengue-infected mosquito bites girl and … Extrinsic Incubation Period within the mosquito Time Affected by temperature Transmission of dengue virus
  • 8. … transmits the dengue virus to her Time Transmission of dengue virus
  • 9. 3 to 14 days later Girl can pass dengue virus to another mosquito if bitten while she is viraemic Intrinsic Incubation Period within the girl Time Transmission of dengue virus
  • 10. Breeding areas and transmission  Ae aegypti immature stages are typically found in water-filled habitats associated with human habitation;  Lays eggs in artificial, water-holding containers, and occasionally bromeliads and tree holes  Primarily feeds from dawn to dusk, rests in dark areas and bites indoors  Most female Ae. aegypti mosquitoes spend their lifetime in or around the houses where they emerge as adults, meaning people rather than mosquitoes rapidly move the virus within and between communities Breeding sites: plants, pools, water-filled buckets, used tires, empty oil drums, water storage containers etc. Credit:WHO
  • 11. Other routes of transmission  Evidence of transmission of dengue through receipt of donor organs or tissue1 −Bone marrow transplant and renal transplant  Evidence of transmission of dengue through receipt of blood products (RBC transfusion)2,3  Seven reports of transmission after occupational exposure in a health-care setting  DENV can be transmitted from the mother to the fetus in utero or to the neonate at parturition (vertical transmission)
  • 12. Platelets 12 Clinical course of dengue Dengue is a systemic and dynamic disease. Dengue is NOT a platelet count disease
  • 13. 13 Clinical course of dengue Incubation period After the incubation period, the illness begins abruptly. It is characterized by 3 phases: Febrile phase – commences at symptom onset Critical Phase 0 1 2 3 4 6 8 10 Days Febrile Phase Critical phase – commences around time of defervescence* * Defined as when body temperature drops to less than 38°C and remains below this level. Recovery phase – commences when plasma leakage resolves Recovery Phase Viraemia: headache, nausea, myalgia, body ache and rash
  • 14. Virology and Serology 0 1 2 3 4 5 6 7 8 9 10 Phases of dengue: Febrile Critical Recovery Adapted from WCL Yip, 1980 by Hung NT, Lum LCS, Tan LH 14 Days of illness:
  • 15. Virology and Serology 0 1 2 3 4 5 6 7 8 9 10 Viraemia Phases of dengue: Febrile Critical Recovery IgM/IgG Adapted from WCL Yip, 1980 by Hung NT, Lum LCS, Tan LH 15 Days of illness: 40 38 6 Key features: 1. Temperature Defervescence Bi-phasic/ Saddle back picture Subnormal temperature
  • 16. Virology and Serology 0 1 2 3 4 5 6 7 8 9 10 Viraemia Phases of dengue: Febrile Critical Recovery 4. WBC 5. Platelet 6. HCT Platelet Haematocrit IgM/IgG Adapted from WCL Yip, 1980 by Hung NT, Lum LCS, Tan LH 16 Days of illness: 40 38 6 Key features: 1. Temperature Laboratory changes WBC
  • 17. Virology and Serology 0 1 2 3 4 5 6 7 8 9 10 Viraemia Phases of dengue: Febrile Critical Recovery Bleeding Reabsorption Fluid overload Dehydration Organ Impairment 4. WBC 5. Platelet 6. HCT Platelet Haematocrit IgM/IgG Adapted from WCL Yip, 1980 by Hung NT, Lum LCS, Tan LH 17 Days of illness: 40 38 6 Key features: 1. Temperature 2. Oral intake 3. Urine output Potential clinical issues Laboratory changes WBC Capillary permeability Shock
  • 18. 18 Vignette of febrile phase • Usually lasts 2 to 7 days • High temperature; may be modified by antipyretics • Common symptoms: myalgia, headache, retro-orbital pain, aches, rash • Difficult to differentiate dengue from viral febrile illness • Normal CBC in first 1 to 2 days of fever Children Nausea and vomiting may be prominent 1 Lum et al. Quality of Life of Dengue Patients. Am J Trop Med Hyg, 2008.
  • 19. 19 Transition from febrile phase to critical phase • Usually day 4 to day 7 of illness • Could be as early as day 3 or as late as day 7 or 8 • Coincides with defervescence Clinical Warning Signs 1. Severe abdominal pain 2. Persistent vomiting 3. Mucosal bleed 4. Lethargy; restlessness 5. Liver enlargement >2cm 6. Clinical fluid accumulation Laboratory Warning Signs 1. Leukopenia 2. Rapid decrease platelet count 3. Rising haematocrit Development of warning signs: Identify dengue patients already in shock or at risk of developing shock
  • 20. 20 What happens during the critical phase? Increased vascular permeability Significant plasma leakage Development of warning signs Deterioration in patient’s condition How long does plasma leakage last? 24 – 48 hours What could happen without treatment? Death Shock occurs when critical volume of plasma is lost through leakage. Shock is often preceded by warning signs. Body temperature may be sub-normal when shock occurs. The total white cell count may increase (instead of leukopenia) in patients with severe bleeding at this stage.
  • 21. 21 Do all dengue patients enter critical phase? NOT all patients will experience the critical phase Clinical course of patient without significantly increased vascular permeability: • Fever subsides  general condition improves and appetite recovers • May have leukopenia • Mild to moderate thrombocytopenia
  • 22. 22 Vignette of recovery phase What happens in recovery phase? 1. Improvement in general well-being and stable haemodynamic status 2. Diuresis 3. Biphasic fever 4. May have bradycardia, itching 5. Isles of white in the a sea of red Vascular permeability reverts to normal  Gradual reabsorption of extravascular fluid in next 48 to 72 hours Clues to progression from critical phase to recovery phase Clinical clues: Laboratory clues: 1. HCT stabilizes. HCT may lower due to dilutional effect of reabsorbed fluid (haemodilution). 2. WBC usually starts to rise soon after defervescence. 3. Thrombocytopenia persists longer than leucopenia.
  • 23. 23 When to consider severe dengue? Severe dengue is defined by one or more of the following: 1. Severe plasma leakage 2. Severe bleeding 3. Severe organ impairment Severe manifestations of dengue are related to severe plasma leakage  Reduced organ perfusion and tissue hypoxia  Organ impairment
  • 24. 24 When to consider severe dengue? 1. Severe plasma leakage 2. Severe bleeding Patient has hypovolaemic shock Patient has respiratory distress due to fluid accumulation: either pleural effusion or ascites Patient remains in shock despite IV isotonic crystalloid solution and the hematocrit is decreasing Bleeding can be occult and not recognized in a timely manner; important to do frequent vital signs and monitor hematocrit Severe bleeding exacerbates shock Severe bleeding has been observed in adults who had no or only mild plasma leakage Bleeding usually occurs in the gastrointestinal tract, and only rarely in the brain
  • 25. 25 When to consider severe dengue? 3. Severe organ impairment Consequences of hypovolaemic shock Severe impairment of organs such as liver, kidneys and brain has been observed in patients with only mild or no plasma leakage or after the critical phase of dengue.* It is defined as one of the following: • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1000 IU/L • Impaired consciousness • Impaired cardiac function – raised cardiac enzymes with reduced left ventricular function Liver enzymes are frequently elevated during the critical and recovery phases. * Trung et al. Liver involvement associated with dengue infection in adults in Vietnam. Am J Trop Med Hyg, 2010.
  • 26. Conditions that mimic the febrile phase of dengue Viral infections Influenza, measles, rubella Chikungunya, West Nile virus Enterovirus Other viral haemorrhagic fever Infectious mononucleosis Acute HIV seroconversion illness Leptospirosis Typhoid Rickettsia infections (typhus, scrub typhus, etc.) Malaria Measles, rubella Infectious mononucleosis, enterovirus Chikungunya, West Nile virus, Scarlet fever, meningococcal infection Leptospirosis, typhoid Rickettsia infections (typhus, scrub typhus, etc.) Syphilis, acute HIV seroconversion illness Autoimmune diseases (e.g. SLE) Adverse drug reaction Rotavirus Salmonellosis Other enteric infections Bacterial infections Febrile illness with a rash Parasitic infections Diarrhoeal diseases
  • 27. Conditions that mimic the critical phase of dengue Acidotic breathing/ respiratory distress Acute appendicitis Acute cholecystitis Perforated viscus Diabetic ketoacidosis Diabetic ketoacidosis Lactic acidosis Renal failure Acute respiratory distress syndrome (ARDS) Sepsis, septic shock Acute gastroenteritis Leptospirosis, typhoid, typhus, malaria Viral hepatitis Acute HIV seroconversion illness Systemic lupus erythematosus Idiopathic thrombocytopenic purpura Thrombotic thrombocytopenic purpura Systemic vascultis Acute leukaemia Lymphoma Other malignancies Liver cirrhosis with portal hypertension Adverse drug reaction Acute abdomen Infections Autoimmune diseases Malignancies Others
  • 28. Step 2: Clinical examination General assessment: Mental state Hydration state Haemodynamic state Clinical evidence of warning signs: Bleeding manifestations: mucosal bleeding Abdominal tenderness Liver enlargement Fluid accumulation: pleural effusion, ascites Other important signs: Rash Tachypnoea/acidotic breathing: indicates shock Tourniquet test: repeat if negative or if there is no bleeding manifestation
  • 29. Hemodynamic Assessment - Clinical Parameters Parameters Conscious level Capillary refill time Extremities (color, temp) Peripheral pulse volume Heart rate (HR) Pulse pressure (PP) Blood pressure (BP) Respiratory rate (RR) Urine output 1. Peripheral perfusion 3a. Organ perfusion (brain) 3b. Organ perfusion (kidney) 4. Respiratory compensation for tissue hypoxia 2. Cardiac output
  • 31. Delayed capillary refill time. The blood pressure was normal at this time. The “5-in-1 maneuver” magic touch CCTV-R (1) colour, (2) capillary refill time (3) temperature of extremities (4) pulse volume (5) pulse rate.
  • 32. Hemodynamic Assessment - Stable Circulation Parameters Stable Circulation Conscious level Clear and lucid Capillary refill time Brisk (<2 seconds) Extremities (color, temp) Warm and pink Peripheral pulse volume Good volume Heart rate (HR) Normal HR for age Pulse pressure (PP) Normal PP for age Blood pressure (BP) Normal BP for age Respiratory rate (RR) Normal RR for age Urine output Normal 1. Normal Peripheral perfusion 2. Normal Cardiac output 3a. Normal Brain Perfusion 4. No Respiratory compensation 3b. Normal kidney perfusion
  • 33. 120 110 100 90 80 70 60 Time LCS Lum LUCID conscious level Decreased urine output Hemodynamic Changes in Compensated Shock Normal or elevated systolic pressure Rising diastolic pressure Narrow pulse pressure – weak pulse Tachycardia Blood pressure Reduced peripheral perfusion Cool/cold and pale extremities Prolonged capillary refill time “Quiet” tachypnea Heart rate
  • 34. Hemodynamic Assessment – Compensated Shock Parameters Stable Circulation Compensated shock Conscious level Clear and lucid Clear and lucid Capillary refill time Brisk (<2 seconds) Prolonged (>2 sec) Extremities Warm and pink Cool peripheries Peripheral pulse volume Good volume Weak & thready Heart rate (HR) Normal HR for age Tachycardia for age Pulse pressure (PP) Normal PP for age Normal systolic pressure rising diastolic pressure Blood pressure (BP) Normal BP for age Narrowing PP Postural hypotension Respiratory rate (RR) Normal RR for age “Quiet” tachypnea Urine output Normal Reducing trend Reduced peripheral perfusion Reduced cardiac output 3a. Normal brain perfusion Tissue acidosis Reduced kidney perfusion
  • 35. Parameters Stable Circulation Compensated shock Conscious level Clear and lucid Clear and lucid Capillary refill time Brisk (<2 sec) Prolonged (>2 sec) Extremities Warm and pink Cool peripheries Peripheral pulse volume Good volume Weak & thready Heart rate (HR) Normal HR for age Tachycardia for age Blood pressure (BP) Normal BP for age Normal systolic pressure, rising diastolic pressure Pulse pressure (PP) Normal PP for age Narrowing PP Postural hypotension Respiratory rate (RR) Normal RR for age “Quiet” tachypnea Urine output Normal Reducing trend Note that changes are seen in all parameters except conscious level and systolic blood pressure Hemodynamic Assessment - Compensated Shock (cont.)
  • 36. 120 110 100 90 80 70 60 Time LCS Lum Hemodynamic Changes in Hypotensive Shock Decreased level of conscious Oliguria or anuria Increasing tachycardia Systolic and diastolic pressures disappear suddenly Reduced peripheral perfusion Very cold, clammy extremities Mottled, peripheral cyanosis Very prolonged capillary refill time Kussmaul breathing Blood pressure Heart rate Feeble or absent peripheral pulse
  • 37. Key clinical signs of deterioration: Changes in Mental State • Restless, confused, extremely lethargic • Seizures • Agitation alternating with drowsiness Hemodynamic Assessment – Hypotensive Shock Infants and young children: • Failure to recognize parents, focus or make eye contact • Listen to parents: “Something is wrong with my child.” Imminent total cardiorespiratory collapse
  • 38. What is considered adequate urine output? A patient with dengue shock should pass at least 0.5 ml/kg urine per hour. An indwelling catheter will give an accurate measurement. If the urine volume exceeds this amount, consider reducing the IV fluid therapy. Hemodynamic Assessment – Monitoring urine output
  • 39. Parameters Stable Circulation Compensated shock Hypotensive shock Conscious level Clear and lucid Clear and lucid Restless, combative Capillary refill time Brisk (<2 sec) Prolonged (>2 sec) Very prolonged, mottled skin Extremities Warm and pink Cool peripheries Cold, clammy Peripheral pulse volume Good volume Weak & thready Feeble or absent Heart rate (HR) Normal HR for age Tachycardia for age Severe tachycardia or bradycardia in late shock Blood pressure (BP) Normal BP for age Normal systolic pressure, rising diastolic pressure Hypotension Unrecordable BP Pulse pressure (PP) Normal PP for age Narrowing PP Postural hypotension Narrowed pulse pressure (<20 mmHg) Respiratory rate (RR) Normal RR for age “Quiet” tachypnea Kussmaul breathing Urine output Normal Reducing trend Oliguria or anuria Hemodynamic Assessment – Hypotensive Shock (cont.) Reduced peripheral perfusion Reduced cardiac output Reduced brain perfusion Severe tissue acidosis No kidney perfusion
  • 40. 40 Pearls and pitfalls: dengue shock Dengue shock presents as a physiologic-time continuum Compensated shock in the early stage (normal or elevated blood pressure) Decompensated shock in the late stages (hypotension & unrecordable blood pressure) Stable Warning signs Compensated shock Hypotensive shock Cardiac arrest Hours Hours Hours Min Pitfall: Why is it easy to miss dengue shock? Severe bleeding will exacerbate the shock state and if unrecognized will cause refractory and irreversible shock with a very poor outcome. Identification and treatment of early shock will improve clinical outcome. Delayed treatment leads to a clinical course complicated by severe bleeding and organ impairment. Even in the severe shock state, the patient appears deceptively normal or “stable” with a lucid conscious level. A careful physical examination is critical to recognizing a patient in shock before the stage of cardiovascular collapse.
  • 41. Dengue investigation basics Step 3: Investigations • Complete blood count (CBC) with haematocrit (HCT) are usually all that are necessary for monitoring • Of special importance are: • HCT; • white blood cell count (WBC) and; • platelet count
  • 42. Dengue-specific diagnostic tests * Other tests? * Step 3: Investigations • Blood chemistry tests (liver function, glucose, serum electrolytes, urea, creatinine • Should be considered in patients with risk factors and severe disease • For confirmation, e.g. NS1/IgM rapid tests or nucleic acid detection (depending on resources of health facility) • Not necessary for the acute management of patients but valuable in unusual manifestations, suspected dengue deaths in the area, or for patients who progress rapidly from mild to severe dengue or death * If available
  • 43. 43 Pearls: laboratory warning signs Leucopenia • Occurs 24 hours before rapid decrease in platelet count • Not predictive of plasma leakage • Good indicator that patient could have dengue Rapid decrease in platelet count + rising trend in haematocrit • Occur shortly before or at defervescence • May precede changes in blood pressure and pulse pressure • Indicate an increase in vascular permeability NOTE: Changes in haematocrit may be masked by IV fluid therapy
  • 44. Group A – Sent home (all of following) Group B (any of following) Group C (any of following) Getting adequate volume of oral fluids Passing urine at least once every 4 to 6 hours No warning signs Has stable hematocrit and is hemodynamically stable Does not have co-existing conditions Has warning signs Has co-existing condition: Diabetes mellitus, renal failure, pregnant, infant or elderly Has social circumstances: Living alone or living far away without a reliable means of transport Severe plasma leakage with shock and/or fluid accumulation with respiratory distress Severe bleeding Severe organ impairment: AST or ALT ≥1000 and/or impaired consciousness 1. Give anticipatory guidance before sending home (see patient handout) 2. Follow up daily 3. Do serial CBCs 4. Identify warning signs early 1. Admit for inpatient care 2. Monitor haemodynamic status frequently 3. Use HCT to guide interventions 4. Use isotonic IV fluids judiciously 5. Correct metabolic acidosis, electrolytes as needed Requires emergency treatment and urgent referral Summary of management of dengue
  • 45. Outpatient management: Group A Group A – Send home if patient meets all of the following Intake: Getting adequate volume of oral fluids Output: Passing urine at least once every 4 to 6 hours Does not have any warning signs Has stable haematocrit and hemodynamic status Does not have co-existing conditions Patients who are able to “drink enough to pee enough” 1. Give anticipatory guidance before sending home (see patient handout) 1. Follow up daily 2. Do serial CBCs 3. Identify warning signs early
  • 46. Improved *REASSESS Obtain reference HCT before starting IVF therapy Start with isotonic crystalloids 5–7 ml/kg/hr for 1–2 hours * Reassess haemodynamic state 1. Vital signs 2. “5-in-1 magic touch”: CCTV-R Colour Capillary refill time Temperature Volume of pulse Rate 3. Urine volume IV isotonic crystalloids^ 3–5 ml/kg/hr for 2–4 hours IV isotonic crystalloids^ 2–3 mL/kg/hr for 2–4 hours Clinical improvement or improved oral intake, reduce IVF accordingly Stop IVF therapy within 24–48 hours If improvement in oral intake, HCT remains same or minimal high: 1. Step-wise reduction in IVF 2. Consider glucose-electrolyte for children Continue to monitor patient until out of critical period Stop IVF within 24–48 hours Group B: Dengue with warning signs (not in shock) – Inpatient fluid management
  • 47. Yes No Urgent blood transfusion • Colloid (10–20 ml/kg/hr) • Evaluate to consider blood transfusion if no clinical improvement Start isotonic crystalloid or colloid therapy 10–20 ml/kg (adult) or 20 ml/kg (child) over 15–30 minutes Check haematocrit Not improved If improved •Reduce IV crystalloids 7–10 ml/kg/hr for 1–2 hours •Continue step- wise reduction with crystalloids Severe overt bleed Increasing Or high HCT Group C: Emergency treatment – Summary Colloid** 10 ml/kg/hr for 30–60 minutes If not improved, recheck haematocrit Decreasing HCT IV crystalloid or colloid 10 ml/kg/hr for 1 hour *REASSESS Improved Step-wise reduction of IV crystalloids 5–7 ml/kg/hr for 1–2 hours 3–5 ml/kg/hr for 2–4 hours 2–3 ml/kg/hr for 2–4 hours Further boluses may be required Clinical improvement or improved oral intake, reduce fluids step-wise Stop IV fluids at 24–48 hours Try to obtain CBC, HCT, GXM and other blood readings before fluid resuscitation * Reassess the patient’s clinical condition: vital signs, peripheral perfusion (CCTV-R) & urine output and decide on the situation. ** Colloid is preferable if the patient has already received several boluses of crystalloid IV: intravenous, HCT: hematocrit, IVF: intravenous fluids Hypotensive shock
  • 48. Mental status remains good, even in compensated shock Hypotensive shock can cause seizures or alternating states of drowsiness with agitation. Confusion may be caused by electrolyte imbalances – hyponatremia, hypocalcemia, hypokalemia, severe liver dysfunction or in unusual cases encephalopathy. In very rare cases, intracerebral bleeding, usually associated with trauma Which organ is most frequently affected in severe dengue? Liver enzymes are frequently elevated during the critical and recovery phases Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1000 IU/L Supportive therapy – maintain euglycemia and adequate tissue perfusion What about the brain? Monitoring organ function 48 Paracetamol should be discontinued during the critical phase
  • 49. Minor mucosal bleeding: epistaxis, gum bleeding, not uncommon Risks for bleeding 49 1. Gastrointestinal tract (most common site) 2. Any form of trauma: Venepuncture sites Chest tube insertion sites Nasogastric tube insertion may cause severe epistaxis Where are the sites of major bleeding?
  • 50. Pathophysiology of thrombocytopenia 1. Early bone marrow suppression1 2. Peripheral immune-mediated platelet destruction via DENV binding to platelets in the presence of DENV antibody2 3. Platelets aggregate on DENV-infected endothelium, resulting in platelet destruction or clearance by macrophages3 4. Haemophagocytosis4 Even when actively bleeding, platelet transfusion not helpful 1 Schexneider KO, Reedy EA. Curr Hematol Rep, 2005, 4:145-148. 2 Hathirat P et al. SE Asian J Trop Med Public Health, 1993, 24 Suppl 1:80-85. Oishi K et al. J Med Virol, 2003, 71:25-64. 3 Saito M et al. Clin Exp Immunol, 2004, 138:299-303. 4 Honda S et al. Am J Trop Med Hyg, 2009, 80(5):841-845. Why might giving platelets not help? 50
  • 51. When should you consider repeating blood transfusion? Give: 5–10 ml/kg of fresh packed red blood cells or 10–20 ml/kg of fresh whole blood at appropriate rate Reduce colloid/crystalloid infusions, except to maintain euglycemia What is a good clinical response? • Improving haemodynamic state – vital signs, peripheral perfusion and urine output • Improving acid-base balance 1. Further blood loss 2. Unstable haemodynamic state 3. No appropriate rise in HCT after blood transfusion (i.e. 3% to 4% increase in HCT for every 10 cc/kg of packed red blood cells given) Group C: Emergency treatment of haemorrhagic complications 51
  • 52. Other complications Fluid overload (excessive accumulation) is a major complication in dengue shock + Causes: Increased capillary permeability (plasma leakage) One or more of the following: 1. Excessive and/or too rapid IV fluids 2. Use of hypotonic rather than isotonic crystalloid solutions 3. Transfusion of FFP, platelet concentrates and cryoprecipitate 4. Continuation of IV fluids after plasma leakage has resolved 5. Co-morbid conditions, e.g. congenital or ischaemic heart disease, chronic lung disease, renal disease 52
  • 53. Clinical features of fluid overload Respiratory distress – rapid, shallow breathing, chest wall in-drawing, abdominal distension Late features: more severe respiratory distress – raised JVP, wheezing, hypertension, bounding pulse, abdominal pain Very late features: very severe respiratory distress Pulmonary oedema – Hypoxaemia Heart failure – Haemodynamic instability Cardio-respiratory failure 53 AS FLUID ACCUMULATION INCREASES
  • 54. Management of fluid overload – stopping IV fluids Is an important milestone during the course of dengue management. Why? Plasma leakage stops. Allows fluid in pleural and peritoneal cavities to return to intravascular compartments. Diuresis and resolution of pleural effusion and ascites When should IVF be stopped? Signs of cessation of plasma leakage: • Stable vital signs, peripheral perfusion and oral intake and urine output improve • HCT decreases in the presence of good pulse volume • Resolving bowel/abdominal symptoms 54
  • 55. Other issues to be managed Hypoglycaemia – Correct with 1–2 ml/kg of Dextrose 10%, followed by glucose-electrolyte infusion to maintain euglycaemia. Hypokalaemia – Usually occurs during recovery phase and use of diuretics. Correct by adding potassium chloride into infusion or encourage patients to drink coconut or fruit juice. Hyperglycaemia Hyperkalaemia – associated with metabolic acidosis and acute kidney injury May resolve with correction of shock. 55
  • 56. Other issues to be managed (cont.) Metabolic acidosis – • Tissue hypoxia in shock Action: Treat shock, metabolic acidosis corrects itself Hypocalcaemia – usually in association with multiple blood transfusions. Correct with 10% calcium gluconate infusion. Co-infections and nosocomial infections Action: Be vigilant and treat promptly. Check for thrombophlebitis and remove suspicious lines. Regular change of peripheral intravenous lines. 56
  • 57. Supportive care and adjunct therapy Cardiac conduction defect – usually asymptomatic Inotropes should be used only in severe hypotension while giving fluid resuscitation to restore circulation. Use small doses of inotropes unless proven myocarditis. Large doses of inotropes may give a false impression of a “good” blood pressure. Liver impairment – Avoid hepatotoxic drugs such as paracetamol and acetaminophen. Supportive care usually leads to spontaneous recovery. 57
  • 58. Supportive care and adjunct therapy Management of acute kidney injury Most common organ to suffer from shock. Oliguria and Anuria are consequences of hypoperfusion. Are not indications for diuretics, especially during the critical phase The priority is to give fluid resuscitation to achieve haemodynamic stability. Urine may start to flow once stability is achieved. 58
  • 59. Rash – characteristic of dengue Stable haematocrit with oral intake and off IV fluids No fever for 24 – 48 hours Improvement in clinical status Increasing trend of platelet count (usually preceded by rising WBC) Who needs to be followed up? Discharge criteria General well-being, good appetite, stable haemodynamic status, adequate urine output, no respiratory distress and no organ dysfunction Follow up patients with organ impairment
  • 60. Case 1 • 11 months infant • Admitted for fever • Dengue positive • Did not develop any signs of plasma leak / bleeding • Moderate thrombocytopenia • Managed in ward with oral fluids alone, and monitoring • Improved well and discharged.
  • 61. Case 2 • 9 yr male child • admitted on day 5 fever • Increasing hematocrit, early shock • Platelets went down upto 15000 • Managed with iv fluids alone as per protocols • Improved well and discharged
  • 62. Case 3 • 15 yr old male • Admitted on day 4 of fever • Shifted to ICU on day 3 in view of early compensated shock • Developed ARDS / pulmonary edema / altered sensorium • Mechanically Ventilated and managed as per protocols • Improved well.
  • 63. Case 4 • 8 yr male child • Admitted for high grade fever • Dengue positive • Grossly Elevated liver enzymes / no shock • Prolonged sleepiness ?encephalopathy • Managed conservatively / symptomatically • Improved well
  • 64. Caricaya papaya and Nilavembu - myth or boon? • Proposed mechanisms: – active components such as papain, chymopapain, cystatin, L-tocopherol, ascorbic acid, flavonoids, cyanogenic glucosides and glucosinolates – membrane-stabilizing properties – ALOX 12 and PTAFR genes upregulation – A. paniculata showed the highest antiviral inhibitory effect on DENV-1 by antiviral assay based on cytopathic effects
  • 66. Conclusion of study • More large scale and randomised controlled studies are needed to really assess whether these herbal products have any benefit in dengue patients.
  • 67. Summary • Dengue is not a disease of platelets. • Proper monitoring and early detection of complications will result in better survival rates. Decreased complications. Decreased icu stay. Decreased morbidity.