Severe Dengue From ED to

ICU
Dr Yasmin Gani
Disclaimer

• This slide was prepared for the Webinar Series on Dengue infection on
3rd February 2022, by Dr Yasmin Mohamed Gani, Infectious Disease
Physician at Hospital Sungai Buloh, Malaysia.
• This is intended to share within healthcare professionals, not for public.
• This webinar is organised by Malaysian Society of Infection Control and
Infectious Diseases (MyICID) & Institute for Clinical Research, NIH in
conjunction of World NTD Day 2022.
 What do we know about dengue

1. Basic facts
2. Spectrum of dengue infection
3. Dynamic nature of disease
4. Complications of each phases
5. ‘Newer’ complications
1. Bleeding /Leaking and bleeding
2. Organ ‘ failures’
1. Myocarditis
2. CNS: ICB/Cerebral Edema/
Vasculitis/Epidural hematoma
3. Liver failures

3. HLH
Warning signs

CPG Management of Dengue Infection in Adults (3rd Edition) 4

4 cornerstones of dengue
Is it DENGUE?

1. PHASE OF ILLNESS

4.BLOOD RESULTS DECISION 2. CLINICAL EXAMINATION

3. VITAL SIGNS
 Bleeding Organ dysfunction
Dehydration Leaking Bleeding
Encephalitis Leaking and Bleeding HLH
Organ Failures

SEPSIS

WHAT CAN I EXPECT IN EVERY STAGE

 Volume deficit
Causes of
Bleeding
shock in
dengue Organ dysfunction
Sepsis
JD @ EMERGENCY DEPT
Case 1-
• 32 year old male • pH 7.37/ pCO 42/ HCO3 23/ Lactate 3.0 wbc
• Obese 100kg ( ABW: 80) 6.6 hb16.7 hct 49 plt 105
• Presented with fever x day 3
arthalgia/ myalgia • Impression : IMP : Dengue fever day 5 of illness
vomiting > 5 times/day
loose stool 3x today in febrile phase with warning signs persistent
vomitting , diarrhea , with hemaconcentration
• no bleeding tendency and low platelet , not in shock no leaking NS 1
no h/o jungle trekking +ve
no h/o recent travel
• Clinically
• alert, GCS 15/15, warm peripheries, CRT 2 secs, • Plan
good pulse volume • encourage orally
Lungs clear • strict i/o chart
cvs drnm PA soft, non tender, no
hepatosplenomegaly • cont 3cc/kg/hr repeat
• Bp 130/90 • fbc , vbg , lactate at 330am trace all bloods
pending
• Pr 100
Time 0030 0330 0500 0700

HCt 49 45 45.4 44

PLT 127 123 103 103

Lactate 3.0 1.7 1.8 ND

IVD 5cc/kg 5cc/kg 3cc/kg 3cc/kg

120/80
Warm/
Bp /pr 130/90 No 130/90 good vol
observat Urine
100 96
ion output
400cc
Impression

• Dehydration
• Leaking
• Bleeding
• Leaking and bleeding
Frequent pitfalls

Not realizing
that the initial
presentation Not reducing
No timed/
could be the drips after
frequent
dehydration outcome
reviews
and leading to achieved
high fluid
boluses
Concept of next review time

Count the amt of IVD bottles to get an

accurate
measurement of what went in
Specify the next review time
What’s new the current CPG?
CPG 2015
Emphasis on oral fluid intake
IV fluid therapy only indicated in
certain group
Easier calculation of maintenance fluid
requirement (NICE)
Stress on adjusted body weight in
obese patient
JD @ Ward
 Day 4 of admission
Day 4 @ Day 4 @ Day 4 @ 6pm Day 4 @ 11 Day 5 @

GIVING TOO Hb
7am

13
2pm

14
pm

14.3
6am

15.7

MUCH DURING HCT 45 42 44 49 55

Platelet 103 90 50 30 20
FEBRILE PHASE ALT/AST 79/110 200/550
Vbg/lactate Hco3 ND Hco3 20/1.8 18/ 2.5 18/4.7
22/1.8

Fluid 3cc/kg-> 1.5 1.5cc/hr 1.5cc/hr→ 3cc/kg

1.5cc/kg cc/kg 3cc/kg

IO 3L/1.2 3L positive Urine

(1.8l) balance output x1

Bp/PR 120/76 120/65 110/60 110/79 110/80

Pr100 pr90 Pr 89 Pr 110 Pr 100

lungs clear clear Not Reduced Reduced

documented right base right base
 Non Shock dengue patient :
• In patients without co-morbidities who can tolerate
orally, adequate oral fluid intake of 2-3 litres daily
should be encouraged.
• This group of patients may not require intravenous fluid
therapy.
• Inappropriate intravenous fluid therapy had been
shown to prolong hospitalisation with a tendency to
develop more fluid accumulation
2. NOT
RECOGNIZING
COMPENSATED
SHOCK AND THUS
NOT GIVING
ENOUGH FLUIDs
JD @ D5
Day 5 @ 6am Day 5 @ 9am
• Clinically
Hb 15.7 14.8 peripheries cool/
HCT 55 49 CRT prolonged
Platelet 20 22
• CBD inserted :
ALT/AST 200/550
300cc
Vbg/lactate Hco3 Lactate 3.0
18/Lactate 4.7 Hco3 19 • Pt was moved to
Fluid 3cc/kg→ Medical acute
10cc/kg
ward
IO +4L balance
Uo: 80cc • Given 10cc/kg.
Bp/PR 110/90 120/80
Pr 100 Pr 96 Post bolus : bloods hct 49/ lactate 3 , bp 120/80 pr 100/
warmer peripheries
lungs Reduced right Reduced ae
base Warmer Drips reduced to 3 cc per kg and then to 2 cc per kg as she
peripheries was already 4L plus pos balance
 Day 5 @ 6am Day 5 @ Day 5 @12pm
9am

Hb 15.7 14.8

HCT 55 49 50

Platelet 20 22 19 3 • After review by

ALT/AST 200/550
specialist given 7cc per
kg x1 hr and 5cc/kg
Vbg/lactate 18/4.7 Lactate 3.0 Lactate
Hco3 19 3.5 x1hr of colloids : as
Hco3 18
Fluid 3cc/kg→ 3cc/kg 7cc/kg of colloids
persistent high hct/
10cc/kg
increasing lactate
IO +4L balance
Uo: 80cc/hr
Urine output
50cc/hr x2hrs • Repeated HCT
Bp/PR 110/90 120/80 Warm/crt 2sec
40/hb14/plt 15
Pr 100 Pr 96 Pr 106 Gv
110/80 • Lactate 3.0/ hco3 18
lungs Reduced right Reduced Reduced Ae right
base ae/RA
Warmer
base
RR-24
• Bp 120/80, Pr 107
peripheries
Frequent pitfalls

Did not
recognize that
Fluids were cut pt was still Use of colloid at
down too fast leaking and the right time
requires more
fluids
How to use a coloid
CPG Management of Dengue Infection in Adults (3rd 24
Edition)
Improvement clinically

CPG Management of Dengue Infection in Adults (3rd 25

Edition)
After first 5-10 ml/kg resuscitation – YES improving

• 1-
5 2H
• 1-
3 2H
• 1-
2 2H

CPG Management of Dengue Infection in Adults (3rd 26

Edition)
 So in Mr JD case he was bleeding as
• HCT dropped and he was still unstable
with tachycardia /lower limit of normal in
urine output and lactate was high

CPG Management of Dengue Infection in Adults (3rd 27

Edition)
High risk Bleeders

• LOW PLATELETS PLUS:

The not so silent bleeder: Coming so late….

 Case 1 Day 4 of illness, in decompensated shock, serum lactate 5

 HCT 43, Plt count 5000
 liver impaired

Thought Process Consider bleeding as inappropriately low HCT and pt is unstable

Get blood on standby while trying fluid boluses

comorbidities make it more confusing
CPG Management of Dengue Infection in Adults (3rd Edition) 30
NO IMPROVEMENT
AFTER FIRST 10-20
ML/KG RESUS

CPG Management of Dengue Infection in Adults (3rd Edition) 31

AFTER 2ND
10-20
ML/KG

• 1-
5 2H CONSIDER
BLEEDING
• 1-
3 2H
• 1-
2 2H

CPG Management of Dengue Infection in Adults (3rd Edition) 32

4. WHEN ITS NOT
ABOUT FLUIDS
• THINK NORMAL ANION GAP
ACIDOSIS DUE TO TOO
MUCH SALINE
• THINK STARVATION
ACIDOSIS IN NORMAL
LACTATE/ NORMAL SUGAR
ACIDOSIS
• THINK NORMAL ANION GAP
ACIDOSIS IN PREGNANCY
Case 2
• 23 yr old/ Malay / Lady
• Admitted to a private hospital day 4 of illness
• Fever never settled → PCM 1g prn up to tds
• Transferred to HSB on day 8 of illness → worsening transaminitis

▪ Alert, GCS 15/15

▪ Tachycardic
▪ Good pulse volume, CRT < 2s Warm peripheries
▪ Urine output 100cc/hr
▪ “White islands in sea of red”
▪ Lungs : right lower zone reduced air entry, crepitations bilateral lower to mid zones
▪ Abdo : Tender hepatomegaly 2-3FB
Initial labs results
Dengue NS1 +ve (day 4)
Dengue IgM +ve (day 6 )
D5 D6 D7 D8
Hb 12 12.3 12.1 12 RP : 2.6/133/3.5/76
CRP 44
Hct 37 38 37 37 Ferritin >20000

WCC 1.8 2.1 2.9 2.2

Plt 107 103 90 64
AST 129 889 1541 2051
ALT 49 317 492 553
TSB 9 34 56 63
INR 1.48 1.6
Lactate 6 5
 Q - Besides Dengue HLH any other differential
diagnosis
D5 D6 D7 D8
• 1. Community acquired
sepsis with DIVC Hb 12 12.3 12.1 12
• 2. Nosocomial sepsis Hct 37 38 37 37
• 3. Dengue shock with WCC 1.8 2.1 2.9 2.2
bleeding and leaking Plt 107 103 90 64
AST 129 889 1541 2051
ALT 49 317 492 553
TSB 9 34 56 63
INR 1.48 1.6
Lactat 6 5
e
CXR day 8
Q. What will you do?
• Blood and IV fluids
• Dexamethasone, Antibiotics
• Methylprenisolone , Antibiotics
• Methylprednisolone/Dexamethasone alone

• Imp: Dengue Fever with HLH and acute liver injury,

clinically pt not in shock
• Iv fluid bolus 7cc/kg over 1hr and gradually reduce
• Iv dexamethasone 8mg tds
• IV NAC and Admit ICU for close dynamic monitoring
 By day 10 of illness
• Required on and off CPAP → VM 40%
• Lactates were improving to 2.7 -3
• But LFTs were worsening + coagulopathy

D8 D10
Hb 12 11.2
Hct 37 38 D8 D10
WCC 2.2 15 INR 1.48 Failed
Plt 58 98 Lactate 4-5
AST 2051 2638 LDH 10,937
ALT 553 570 CK 1035
TSB 63 91 Ferritin >1650 40,000
How did we manage this?

• Upgraded antibiotics rocphine → tazocin

• KIV for antifungal IF BP drops
mPS
• Off dexa → methypred 500 mg
 By day 13
• Battling with infection
• Spike of temp, 38.5, new lung finding suggestive of pneumonia
• CXR : bilateral pleural effusion
• BP stable, never requiring inotropes
• Oxygenation : VM 40%
• GCS full
 Treatment

• IV methylpred for 3 days ( day 10-day 13 )

• Abx hx
• IV Rocephin 2g OD (4/5/18 - 6/5/18) D8 -3/7
• IV Tazocin 4.5g QID (6/5/18 - 9/5/18) D10 – 4/7
• IV Vancomycin (6/5/18 - 13/5/18) D10 – 8/7 ( C&S)
• IV Imipenem 500mg QID (9/5/18) D13 – 5/7 (T: 38 )
• IV unasyn 3g 3H (10/5/18) D14 (T : 38)
• IV Fluconazole 400mg BD (10/5/18) D14 (T:38)
By day 14

• She was afebrile

• Platelets have gone up
• Ventilation NPO2 3l/min
• Subsequently transferred to ward on day 16 of illness – after 8 days in
ICU
Why Liver failure?

• Prolonged shock, ischemic hepatitis

• Direct viral effect
• Dysregulated host response
• Drugs induced liver injury
• Pre –existing liver damage
• Co –infections – leptospirosis, sepsis, acalculous cholecystitis, viral
hepatitis
Suspect true HLH - Dengue

• presence of persistent fever beyond D7,

• shock and MOD beyond plasma leakage phase
• worsening cytopenias,
• hyperferritinemia more than 10,000 U/L,
• hypertriglyceridemia and raised LDH.
The 3 players

• Macrophages/ Histiocytes
• present foreign antigens to lymphocytes.
• Natural killer cells
• NK cells eliminate damaged, stressed, or infected host cells such as macrophages → response to viral infection or malignancy

• Cytotoxic lymphocytes (CTLs)

• activated T lymphocytes that lyse autologous cells such as macrophages bearing foreign antigen associated with
Class I histocompatibility

• In HLH - NK cells and/or CTLs fail to eliminate activated macrophages -→ excessive macrophage activity →
highly elevated levels of interferon gamma plus other cytokines→ primary mediator of tissue damage
“HS may still be under recognized if any of the diagnostic criteria or
HS scoring system are used solely without taking into consideration
the clinical picture as a whole”
“H Score is the most user friendly among the HS diagnostic criteria….”
“…not validated for infection associated HS…”
“…. the clinician’s judgment is still the most important tool.”

Med J Malaysia Vol 72 No 1 February 2017

 5-year retrospective single-center study in all adult patients
with SD admitted to a tertiary intensive care unit in
Malaysia

• Thirty-nine of 180 (22%) patients with SD died.

• 12% had HLH defined as an HLH probability ≥70% according to histo score
(HScore); 43% died.
• High risk of mortality
• Peak ALT/AST/FERRITIN/nadir Platelets/increasing age associated
with death

MAJOR ARTICLE
HLH in Severe Dengue • cid 2020:70 (1 June) • 2247
CNS symptoms in the presence of liver
failure strongly suggests HLH

• CNS sx : seizures, meningitis, encephalopathy, ataxia,

hemiplegia, cranial nerve palsies, mental status
changes, irritability. (31%)
Pearls of care

• True HLH vs Hypotensive / inadequate resuscitation driving the hyperinflammatory

syndrome
• Steroids/ Ivig/ immunosuppressants
• The “need to normalize” parameters often adds to volume → Regular dynamic
monitoring is necessary
• Supportive therapy: CVVH/ LASIX/ NAC/ intubation
• High risk bleeding
• Watch out for vasculitic bleeds
• Antibiotics for bacterial translocation/ think of empirical antifungals if necessary
• Targeted transfusion in case of ongoing bleeds
• ACUTE LIVER FAILURE PROTOCOLS
ACUTE LIVER FAILURE PROTOCOL

AASLD 2018
A SUBSET OF PATIENTS IMPROVE
SPONTANEOUSLY

• PLT STARTS
INCREASING
• APETITE IMPROVES
• AST MAY PEAK BUT
INR STARTS
SPONTANEOUSLY
IMPROVING/ STATIC
• THESE PATIENTS
MAY NOT NEED
AGGRESSIVE
TREATMENT
 Summary

No One is an expert!

Dont forget the basics
Improve the recognition of Compensated shocks
Dont act on one parameter alone
Everything is a therapeutic trial
READ THE GUIDELINES
Thank you