This webinar is organized by MyICID and Institute for Clinical Research (ICR), NIH, Ministry of Health in conjunction with Neglected Tropical Disease Day 2022. The purpose of this webinar is to refresh and update our knowledge on Dengue fever, which has been overshadowed by COVID-19 since the beginning of the pandemic. Presenter: Dr Yasmin Mohamed Gani, Infectious Disease Physician at Hospital Sungai Buloh, Malaysia. #dengue #WorldNTDDay #BeatNTDs #BestScienceforAll

1. Severe Dengue From ED to
ICU
Dr Yasmin Gani

2. 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.

3. 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

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

5. 4 cornerstones of dengue
1. PHASE OF ILLNESS
3. VITAL SIGNS
2. CLINICAL EXAMINATION
4.BLOOD RESULTS DECISION
Is it DENGUE?

6. WHAT CAN I EXPECT IN EVERY STAGE
Dehydration
Encephalitis
Bleeding
Leaking
Leaking and Bleeding
Organ Failures
Organ dysfunction
Bleeding
HLH
SEPSIS

7. Causes of
shock in
dengue
Volume deficit
Bleeding
Organ dysfunction
Sepsis

8. JD @ EMERGENCY DEPT

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

10. 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
Bp /pr
5cc/kg
130/90
100
5cc/kg
No
observat
ion
3cc/kg
130/90
96
3cc/kg
120/80
Warm/
good vol
Urine
output
400cc

11. Impression
• Dehydration
• Leaking
• Bleeding
• Leaking and bleeding

12. Frequent pitfalls
No timed/
frequent
reviews
Not realizing
that the initial
presentation
could be
dehydration
and leading to
high fluid
boluses
Not reducing
the drips after
outcome
achieved

13. Concept of next review time
Specify the next review time
Count the amt of IVD bottles to get an
accurate
measurement of what went in

14. 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
What’s new the current CPG?

15. JD @ Ward

16. Day 4 of admission
GIVING TOO
MUCH DURING
FEBRILE PHASE
Day 4 @
7am
Day 4 @
2pm
Day 4 @ 6pm Day 4 @ 11
pm
Day 5 @
6am
Hb 13 14 14.3 15.7
HCT 45 42 44 49 55
Platelet 103 90 50 30 20
ALT/AST 79/110 200/550
Vbg/lactate Hco3
22/1.8
ND Hco3 20/1.8 18/ 2.5 18/4.7
Fluid 3cc/kg->
1.5cc/kg
1.5
cc/kg
1.5cc/hr 1.5cc/hr→
3cc/kg
3cc/kg
IO 3L/1.2
(1.8l)
3L positive
balance
Urine
output x1
Bp/PR 120/76
Pr100
120/65
pr90
110/60
Pr 89
110/79
Pr 110
110/80
Pr 100
lungs clear clear Not
documented
Reduced
right base
Reduced
right base

18. 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

19. 2. NOT
RECOGNIZING
COMPENSATED
SHOCK AND THUS
NOT GIVING
ENOUGH FLUIDs

20. JD @ D5
• Clinically
peripheries cool/
CRT prolonged
• CBD inserted :
300cc
• Pt was moved to
Medical acute
ward
• Given 10cc/kg.
Day 5 @ 6am Day 5 @ 9am
Hb 15.7 14.8
HCT 55 49
Platelet 20 22
ALT/AST 200/550
Vbg/lactate Hco3
18/Lactate 4.7
Lactate 3.0
Hco3 19
Fluid 3cc/kg→
10cc/kg
IO +4L balance
Uo: 80cc
Bp/PR 110/90
Pr 100
120/80
Pr 96
lungs Reduced right
base
Reduced ae
Warmer
peripheries
Post bolus : bloods hct 49/ lactate 3 , bp 120/80 pr 100/
warmer peripheries
Drips reduced to 3 cc per kg and then to 2 cc per kg as she
was already 4L plus pos balance

21. 3
Day 5 @ 6am Day 5 @
9am
Day 5 @12pm
Hb 15.7 14.8
HCT 55 49 50
Platelet 20 22 19
ALT/AST 200/550
Vbg/lactate 18/4.7 Lactate 3.0
Hco3 19
Lactate
3.5
Hco3 18
Fluid 3cc/kg→
10cc/kg
3cc/kg 7cc/kg of colloids
IO +4L balance
Uo: 80cc/hr
Urine output
50cc/hr x2hrs
Bp/PR 110/90
Pr 100
120/80
Pr 96
Warm/crt 2sec
Pr 106 Gv
110/80
lungs Reduced right
base
Reduced
ae/RA
Warmer
peripheries
Reduced Ae right
base
RR-24
• After review by
specialist given 7cc per
kg x1 hr and 5cc/kg
x1hr of colloids : as
persistent high hct/
increasing lactate
• Repeated HCT
40/hb14/plt 15
• Lactate 3.0/ hco3 18
• Bp 120/80, Pr 107

22. Frequent pitfalls
Fluids were cut
down too fast
Did not
recognize that
pt was still
leaking and
requires more
fluids
Use of colloid at
the right time

23. How to use a coloid

24. CPG Management of Dengue Infection in Adults (3rd
Edition)
24

25. CPG Management of Dengue Infection in Adults (3rd
Edition)
25
Improvement clinically

26. CPG Management of Dengue Infection in Adults (3rd
Edition)
26
After first 5-10 ml/kg resuscitation – YES improving
5
• 1-
2H
3
• 1-
2H
2
• 1-
2H

27. CPG Management of Dengue Infection in Adults (3rd
Edition)
27
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

28. High risk Bleeders
• LOW PLATELETS PLUS:

29. 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 andpt is unstable
Get blood on standby while trying fluid boluses
comorbidities make it more confusing

30. CPG Management of Dengue Infection in Adults (3rd Edition) 30

31. CPG Management of Dengue Infection in Adults (3rd Edition) 31
NO IMPROVEMENT
AFTER FIRST 10-20
ML/KG RESUS

32. CPG Management of Dengue Infection in Adults (3rd Edition) 32
AFTER 2ND
10-20
ML/KG
5
• 1-
2H
3
• 1-
2H
2
• 1-
2H
CONSIDER
BLEEDING

33. 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

34. 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

35. Initial labs results
D5 D6 D7 D8
Hb 12 12.3 12.1 12
Hct 37 38 37 37
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
RP : 2.6/133/3.5/76
CRP 44
Ferritin >20000
Dengue NS1 +ve (day 4)
Dengue IgM +ve (day 6 )

36. Q - Besides Dengue HLH any other differential
diagnosis
• 1. Community acquired
sepsis with DIVC
• 2. Nosocomial sepsis
• 3. Dengue shock with
bleeding and leaking
D5 D6 D7 D8
Hb 12 12.3 12.1 12
Hct 37 38 37 37
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
Lactat
e
6 5

37. CXR day 8

38. 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

39. 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
WCC 2.2 15
Plt 58 98
AST 2051 2638
ALT 553 570
TSB 63 91
D8 D10
INR 1.48 Failed
Lactate 4-5
LDH 10,937
CK 1035
Ferritin >1650 40,000

40. How did we manage this?
• Upgraded antibiotics rocphine → tazocin
• KIV for antifungal IF BP drops
• Off dexa → methypred 500 mg
mPS

41. 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

42. 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)

43. 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

44. 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

45. 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.

46. 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

47. “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

48. • 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
M A J O R A R T I C L E
HLH in Severe Dengue • cid 2020:70 (1 June) • 2247
5-year retrospective single-center study in all adult patients
with SD admitted to a tertiary intensive care unit in
Malaysia

49. 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%)

50. 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

51. ACUTE LIVER FAILURE PROTOCOL
AASLD 2018

52. 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

53. 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

54. Thank you