CASE REPORT
Intisari Sains Medis 2022, Volume 13, Number 3: 625-631
Variations of dengue shock syndrome cases and
their management: report of three cases
Gede Bagus Mahendra Wirajaya1*, Ayu Agung Pradnya Paramitha Dwi Sutanegara1,
Published by Intisari Sains Medis
1
General Practitioner, Rumkit Tk II Udayana,
Denpasar, Bali, Indonesia;
2
Department of Internal Medicine, Rumkit Tk II
Udayana, Denpasar, Bali, Indonesia;
*Corresponding author:
Gede Bagus Mahendra Wirajaya;
General Practitioner, Rumkit Tk II Udayana,
Denpasar, Bali, Indonesia;
drmahendrawirajaya@gmail.com
Received: 2022-09-22
Accepted: 2022-10-15
Published: 2022-11-02
INTRODUCTION
Dengue fever (DF) is an infectious
disease transmitted by the Aedes aegypti
mosquito virus.1 It is one of the main
causes of arthropod-borne viral diseases
transmitted to humans by mosquito
bites. Dengue fever is found in tropical
and subtropical areas, mostly urban and
semi-urban areas.2 Aedes mosquitoes are
generally found in tropical and subtropical
areas. This disease has several serotypes,
namely DENV-1, -2, -3 and -4. Infection
with one DENV serotype provides lifelong
immunity but does not confer long-term
immunity to other serotypes. Thus, a
person can be infected up to four times
with each serotype.1
Dengue fever is generally divided
into manifestations such as DF, Dengue
Haemorrhagic Fever (DHF) and Dengue
Published
Open access:
by Intisari Sains Medis | Intisari Sains Medis 2022; 13(3): 625-631 | doi: 10.15562/ism.v13i3.1507
http://isainsmedis.id/
Desak Nyoman Desy Lestari2
ABSTRACT
Background: Dengue hemorrhagic fever (DHF)
occurs due to plasma leakage due to increased
vascular permeability, which is also supported by an
active complement system, which makes DHF fall into
complications such as shock or dengue shock syndrome
(DSS). The comprehensive management of DSS could
prevent morbidity and mortality in patients. We aimed
to report three variations of dengue shock syndrome
cases and their management.
Case presentation: Three cases of DSS from our
hospital. Two case reports with clinical dengue fever
patients with shock and one case report with clinical
dengue patients with shock and complications of acute
liver failure. The first case was a 24 years olds male patient
with classic signs of dengue fever plus spontaneous
bleeding in the form of nosebleeds accompanied by
hemodynamic disturbances. Laboratory examination
Keywords: Acute liver failure, dengue shock syndrome, management, transaminitis.
Cite This Article: Wirajaya, G.B.M., Sutanegara, A.A.P.P.D., Lestari, D.N.D. 2022. Variations of dengue shock
syndrome cases and their management: report of three cases. Intisari Sains Medis 13(3): 625-631. DOI: 10.15562/
ism.v13i3.1507
Shock Syndrome (DSS). In Indonesia
itself, in 2014, based on data from the
Directorate General of Disease Control
and Environmental Health, Ministry
of Health, RI that the incidence rate of
dengue hemorrhagic fever was <51 per
100,000 population, but there are still some
provinces that are above 51 per 100,000
population, such as the province of Bali,
East Kalimantan, North Kalimantan, West
Kalimantan, Riau Islands, DKI Jakarta,
DI Yogyakarta and North Sulawesi.
Symptoms of dengue fever vary from
asymptomatic to the presence of fever,
rash, bleeding manifestations and others.
A physical examination generally done
is a tourniquet test or Rumpel leed test
to provoke bleeding, laboratory tests that
can be done simply are by performing a
complete peripheral blood examination.3,4
To differentiate the diagnosis of DF and
P-ISSN: 2503-3638, E-ISSN: 2089-9084
revealed severe thrombocytopenia. In the second
case, a male patient with dengue shock syndrome
accompanied acute liver failure. The patient complains
of heartburn and nausea accompanied by tea-like
urine. Dengue patients with abdominal pain typical
of liver disorders, nausea, vomiting and anorexia, and
hepatomegaly with or without jaundice are typical
of liver disorders. The third case, a male patient with
dengue shock syndrome, accompanied the suspicion
of ascites. The main treatment is the administration
of isotonic crystalloid fluids according to body weight.
While in cases of acute liver failure, NAC can be given.
Conclusion: We found three cases of DSS with some
complications. It is important to know the right
treatment immediately so that complications do not
occur.
DHF, DHF can be found in homeostatic
abnormalities and plasma leakage,
which can be assessed by an increase in
hematocrits of more than 20%, pleural
effusion and ascites. Pathophysiological,
DHF occurs due to plasma leakage due to
increased vascular permeability, which is
also supported by an active complement
system; this is what makes DHF can fall
into complications such as shock or known
as DSS. The shock condition in DSS can
be found in the presence of a fast and
weak pulse, narrowing of blood pressure
(<20 mmHg), hypotension, capillary
refill time >2 seconds, and cold acral
to impaired consciousness. Therefore,
in the management of cases of dengue
fever, patients must receive adequate fluid
therapy.1,4,5 We aimed to report three
variations of dengue shock syndrome
cases and their management.
625
 CASE REPORT

CASE PRESENTATION Nosebleeds appear on their own without moderately ill with compos mentis
any trauma. The feces and urinary are said consciousness (GCS E4V5M6). Blood
Case 1 to be normal. A history of allergies and pressure 80/60 mmHg, pulse 120x/minute
A 24-year-old man weighing 55 kg chronic disease was denied. The patient felt weak, respiratory rate 20x/minute
complained of fever five days before his had no previous history of dengue fever. with a temperature of 36oC and 99%
admission to the hospital. Fever is said to The patient’s family did not have a history oxygen saturation of room air. On general
occur during the day. Initially, the fever of similar complaints; a history of dengue examination of the nose, epistaxis was
occurred all over the body, came and went, fever, malaria, hypertension, and drug found, and examination of the lungs, heart
and was felt continuously with a measured or food allergies was denied. The patient and abdomen were within normal limits.
temperature of 39oC. Complaints had had no history of traveling to endemic The acral felt cold. A complete blood count
improved with fever-reducing drugs but areas. The patient denied a history of revealed severe thrombocytopenia with
did not have much effect. Until the day smoking and alcohol consumption. The an elevated hematocrit. The patient was
before entering the hospital, the fever was environment where the patient lives is a diagnosed with Dengue Shock Syndrome
gone. However, the patient still complains densely populated area. The patient does on the fifth day of fever and then treated
of weakness and no appetite, which not know whether his co-workers or with 1100 cc Ringer Lactate crystalloid
interferes with activities. In addition to neighbors have ever had DF. solution (fluid therapy according to
fever, the patient complained of headache, On physical examination, he was DSS management 10-2ml/kgBW),
nosebleeds, nausea and vomiting. He
felt a headache accompanied by a fever.
Headaches are said to be continuous and Table 1. Serial blood laboratory findings on the first case.
do not improve with rest. The patient also Parameter Fever day 5 Fever day 6 Fever day 7 Fever day 8
complained of nausea and vomiting five WBC (10^3/µL) 2.38 (L) 2.41 (L) 3.33 (L) 3.48 (L)
days before admission to the hospital. Neu % 40.0 (L) 27.5 (L) 28.6 (L) 31.3 (L)
He vomited three times containing the Lym % 40.3 (H) 53.9 (H) 44.1 (H) 50.6 (H)
food consumed by the patient. There was Mo % 18.9 (H) 17.8 (H) 24.9 (H) 14.4 (H)
a nosebleed five hours before admission Eo % 0.4 (L) 0.4 (L) 2.1 3.4
to the hospital. When in the emergency Ba % 0.4 0.4 0.3 0.3
HGB (g/dL) 18.3 (H) 16.5 15.5 15.1
room, the patient still had nosebleeds.
HCT % 53.9 (H) 48.9 45.5 44.8
The nosebleed on a patient was three PLT (10^3/µL) 16 (L) 19 (L) 20 (L) 39 (L)
times with a volume of approximately 1 cc.
Note. H: High; L: Low

Table 2. Serial blood test and urinalysis findings on the second case.
Parameter Fever Day 3 Fever Day 4 Fever Day 5 Fever Day 6 Fever Day 7 Fever Day 8
Blood tests
WBC (10^3/µL) 3.2 (L) 3.2 (L) 4.49 9.02 8.58 9.35
Neu % 73.1 (H) 79.4 (H) 58.3 40.1 (L) 45.9 (L) 53.6
Lym % 15.6 (L) 15.0 (L) 32.3 31.0 43.0 (H) 34.5
Mo % 9.6 (H) 4.7 7.6 27.5 10.4 (H) 11.3 (H)
Eo % 0.7 (L) 0.6 (L) 1.1 (L) 0.7 (L) 0.2 (L) 0.1 (L)
Ba % 1.4 0.3 0.7 0.7 0.5 0.5
HGB (g/dL) 15.4 15.7 18.0 (H) 15.8 14.6 14.7
HCT (%) 48.3 49.0 54.3 (H) 47.8 45.3 44.6
PLT (10^3/µL) 87 (L) 44 (L) 14 (L) 23 (L) 46 (L) 86 (L)
SGPT (U/L) - - - 1764 (H) - 137 (H)
SGOT (U/L) - - - 211 (H) - -
Urinalysis
Color - - - Yellow - -
Clarity - - - cloudy - -
Protein - - - Positive(+3) - -
Urobilinogen - - - Normal - -
Bilirubin - - - Negative - -
faint blood - - - Positive(+3) - -
Erythrocytes - - - 15-20/lb - -
Leukocytes - - - 2-4 lb - -
Bacteria - - - Positive - -
HbsAg - - - Negatif - -
AntiHCV - - - Negatif - -
Note. H: High; L: Low

626 Published by Intisari Sains Medis | Intisari Sains Medis 2022; 13(3): 625-631 | doi: 10.15562/ism.v13i3.1507
 CASE REPORT

Table 3. Serial blood laboratory findings on day 1 until 4 of the third case. In addition to fever, the patient also
Fever day 4 complained of loose stools, nausea and
Fever Day Fever day Fever day vomiting—liquid defecation since 1 day
Parameter I II
1 2 3 before admission to hospital with dregs,
(07:30) (18:30)
WBC (10^3/µL) 7.78 3.20 (L) 4.03 8.79 8.19
no mucus and blood. The frequency of
Neu % 92.2 (H) 71.3 (H) 64.3 47.3 (L) 51.5 diarrhea at that time was more than 5 times
Lym % 2.8 (L) 13.1 (L) 25.8 31.5 28.9 a day. Nausea accompanied by vomiting
Mo % 4.6 15.0 (H) 9.4 (H) 20.8 (H) 19.0 (H) since 5 days before admission to the
Eo % 0.0 (L) 0.3 (L) 0.0 (L) 0.1 0.2 (L) hospital 10 times contain food consumed
Ba % 0.4 0.3 0.5 0.3 0.4 by the patient. The patient’s appetite begins
HGB (g/dL) 14.5 13.6 19.5 (H) 20.1 (H) 16.2 to decrease. There are no other complaints,
HCT (%) 43.1 40.3 57.1 (H) 57.3 (H) 46.4 such as cough and runny nose. A history of
PLT (10^3/µL) 183 117 (L) 7 (L) 4 (L) 5 (L)
allergies and chronic disease was denied.
Note. H: High; L: Low The patient’s family did not have a history
of similar complaints; a history of dengue
Table 4. Serial blood laboratory findings on day 5 until 8 of the third case.
fever, malaria, hypertension, and drug
Parameter Fever day 5 Fever day 6 Fever day 7 Fever day 8 or food allergies was denied. The patient
WBC (10^3/µL) 7.15 5.23 5.68 6.84 had no history of traveling to endemic
Neu % 46.6 (L) 58.5 65.7 65.5 areas. The patient denied a history of
Lym % 40.4 (H) 30.4 23.2 20.9 smoking and alcohol consumption. The
Mo % 12.2 (H) 9.8 (H) 8.6 9.5
environment where the patient lives is a
Eo % 0.4 (L) 1.1 (L) 2.1 3.7
Ba % 0.4 0.4 0.4 0.4 densely populated area. The patient is a
HGB (g/dL) 15.5 13.7 13.3 14.1 student.
HCT (%) 44.9 39.6 38.1 41.1 On physical examination, the general
PLT (10^3/µL) 7 (L) 16 (L) 55 (L) 142 (L) condition was weak with compos mentis
Note. H: High; L: Low consciousness (GCS E4V5M6). Blood
pressure 110/80 mmHg, pulse 100x/
paracetamol 3x500mg, antacid syrup patient had no complaints with a general minute, respiratory rate 20x/minute with
3x1 spoon, tranexamic acid 3x500mg for condition of weakness, compos mentis a measured temperature of 38oC and 99%
nosebleeds. The patient was evaluated for consciousness. Blood pressure 100/60 oxygen saturation of room air. The patient’s
15-30 minutes, blood pressure was 90/60 mmHg, pulse 80x/minute, lifting strength, weight was 84 kg. On examination, the
mmHg, pulse was weak 100x/minute, respiration 20x/minute, temperature 36oC lungs and heart were within normal limits.
acral started to warm, the fluid was with 99% oxygen saturation of room air— Meanwhile, on abdominal examination,
reduced to 385 cc/hour (7ml/kgBW/hour) physical examination within normal limits. bowel sounds increased with epigastric
and then monitored for 60 minutes. After The patient has been treated with Ringer tenderness. Extremities get a warm
60 minutes, the patient’s general condition Lactate 2200/24 ​​hours, paracetamol 3x500 impression with CRT <2 seconds.
is stable, blood pressure is 100/60 mmHg, mg if necessary, and antacid syrup 3x1 A complete blood count revealed
a pulse is weak 100x/minute, and the fluid spoon. The next day the patient had no moderate thrombocytopenia. The patient
is warm, so the fluid is reduced to 270 cc/ complaints; general condition was stable has been diagnosed with DHF grade
hour (5ml/kgBW/hour). Then the patient and improving with blood pressure 100/60 1 day 3 and GEA dehydration, being
was monitored for 60 minutes, and the mmHg, pulse 88-90 beats per minute given crystalloid fluid therapy Ringer
general condition was stable; then, the palpable strong. From the complete blood Lactate 2780 ml/24 hours (according to
fluid was reduced to 165 cc/hour (3ml/ count results, platelets increased daily with the management of DHF in the ward),
kgBW/hour). a decrease in hematocrit. ranitidine 2x50 mg IV, ondansetron 2x4
On the sixth day of fever, the patient mg IV, paracetamol 4x500 mg, attapulgite
had no complaints, but the patient still felt Case 2 3x1 tablets and antacid syrup 3x1 spoon.
weak with compos mentis consciousness. A 19-year-old man weighing 84 kg came On the fourth day of fever, the
Obtained blood pressure 100/60 mmHg, with a chief complaint of fever 3 days patient had no diarrhea. The measured
pulse 120x/minute felt weak, respiration before his admission to the hospital. Fever temperature is 37.5oC. The general
20x/minute, temperature 36oC with 99% is said to start at night. Initially, the fever condition is stable. The complete blood
oxygen saturation of room air. Physical occurred all over the body, came and went, count showed a decrease in platelets from
examination found within normal limits, and was felt continuously with a measured the previous one. On the fifth day of fever,
warm acral. The patient was given fluid temperature of 39oC. Complaints had the patient complained of pain in the pit of
therapy RL 2200 ml/24 hours, paracetamol improved with fever-reducing drugs but the stomach accompanied by nausea and
3x500 mg if necessary, and antacid syrup did not have much effect. Complaints vomiting 2 times. The patient’s appetite
3x1 spoon. On the seventh day of fever, the interfere with the patient’s activities. begins to decrease. Obtained blood pressure

Published by Intisari Sains Medis | Intisari Sains Medis 2022; 13(3): 625-631 | doi: 10.15562/ism.v13i3.1507 627
 CASE REPORT
80/60 mmHg, pulse 120x/minute weak,
temperature 36oC, cold acral. Abdominal
examination revealed epigastric pain
in the right hypochondria—complete
blood count results in the presence of
severe thrombocytopenia with increased
hematocrit (22% hemoconcentration). The
patient was diagnosed with Dengue Shock
Syndrome/DHF grade III. Treatment with
1500cc crystalloid solution (10-20cc/
kgBW) was performed, and vital signs
were evaluated for 30 minutes. The general
condition was stable, so the fluid was
reduced to 588cc/hour (7cc/kgBW/hour)
and then evaluated for 60 minutes. Stable
condition, fluid reduced to 420cc/hour
(5cc/kgBW/hour) and then monitored for
60 minutes. Stable state, fluid reduced to
252cc/hour (3cc/kgBW/hour).
On the sixth day of fever, the patient
still complained of heartburn with nausea
without vomiting. The patient’s urine is
colored like tea. Blood pressure 100/70
mmHg, pulse 60x/minute felt weak,
respiration 20x/minute, temperature
36oC with 97% room air saturation, warm
acral. A general abdomen examination
revealed tenderness in the epigastrium to
the right hypochondria. A complete blood
count showed an increase in platelets
but still below 50,000 and a decrease in
hematocrit. Complete urine examination
showed cloudy yellow color, proteinuria,
erythrocytes in urine, protein +3, negative
bilirubin and normal urobilinogen.
Examination increased to SGPT 1764
U/L and SGOT 211 U/L. The patient
was checked for HBsAg, and Anti-HCV
was found non-reactive. The patient was
diagnosed with Dengue Haemorrhagic
Fever with expanded dengue, transaminitis
and acute liver failure. The patient was
given loading fluid of 0.9% NaCl 500 cc
followed by 40 TPM, hepatin 3x1 caplet,
and acetylcysteine 3x200 mg.
On day 7 of fever, the patient had no
complaints; general condition was stable,
and complete blood count results were
an increase in platelets from the previous
one and a decrease in hematocrit. On the
eighth day of fever, the patient had no
complaints with blood pressure 120/70
mmHg, pulse 84x/minute, respiration 20x/
minute, temperature 36oC, and oxygen
saturation of 99% of room air. A complete
blood count found that platelets increased
628
> 50,000 and SGPT decreased to 137 U/L.
The patient was treated as an outpatient
with lansoprazole 2x30 mg, hepatin 2x1
caplet, and acetylcysteine 3x200 mg.
The patient had no complaints during
outpatient control at the internal medicine
polyclinic on day 8. Blood pressure 120/80
mmHg, pulse 74x/minute, respiration
20x/minute, temperature 36oC, oxygen
saturation 99% of room air. The patient
continued to take hepatin 2x1 caplets.
Case 3
A 30-year-old man weighing 72 kg came
to the emergency room with complaints
of nausea and vomiting 3 days before
his admission to the hospital. Vomiting
is preceded by nausea after the patient
is late for lunch. He vomited about 6
times containing food; the last vomit was
greenish. The patient’s appetite began
to decrease until he arrived at the ER.
There was no previous history of fever,
cough and cold. The patient had a history
of gastritis and had no previous history
of dengue fever, malaria and typhoid
fever. The patient said he had not had a
bowel movement on admission to the
ER on the first day. The patient’s BAK
is said to be normal. The patient had no
history of traveling to endemic areas and
had no history of smoking and alcohol
consumption. The environment where
the patient lives is densely populated. The
patient is a nurse who is often on duty at a
clinic. It is said that patients are often late
to eat while on duty. The patient did not
know whether his friends or neighbors
had the same disease.
On physical examination, the general
condition was weak with compos mentis
consciousness (GCS E4V5M6). Blood
pressure 110/70 mmHg, pulse 103x/
minute, respiratory rate 20x/minute
with a measured temperature of 37oC
and 99% oxygen saturation of room
air. The Rumple Leed test was negative.
On general physical examination, it
found hollow eyes and dry oral mucosa.
Abdominal examination revealed normal
bowel sounds with epigastric tenderness.
Extremities obtained warm acral and CRT
<2 seconds.
On complete blood count, the results
were normal. The patient was diagnosed
early with dyspepsia with severe
Published by Intisari Sains Medis | Intisari Sains Medis 2022; 13(3): 625-631 | doi: 10.15562/ism.v13i3.1507
dehydration. Initial management was
given as loading therapy with crystalloid
NaCl 0.9% 1.000cc followed by 32 TPM,
omeprazole 2x40 mg IV, ondansetron
2x4 mg IV, antacid syrup 3x1 spoons and
sucralfate syrup 3x1 spoons.
The third patient complained of
starting to feel hot with abdominal pain.
The measured temperature is 38.0oC;
blood pressure is 130/60 mmHg, and
pulse is 103x/minute. This is the first day
of fever. On the second day of fever, the
patient complained of fever and nausea
with a measured temperature of 38.2oC,
blood pressure 120/80 mmHg, and pulse
of 81x/minute. On physical examination,
there was tenderness in the epigastrium—
Rumple Leed positive result. A complete
blood count was performed, and
thrombocytopenia (platelets > 100,000)
was found with no hematocrit increase.
The patient was given the same therapy as
before but added paracetamol 3x500 mg.
On the fourth day of fever, the
patient complained of bleeding gums
and dizziness. Blood pressure 110/80
mmHg, temperature 36.7oC, pulse 120x/
minute, weak. Abdominal examination
revealed distension and tenderness in the
epigastrium to the right hypochondria.
The complete blood count showed
severe thrombocytopenia with a
hemoconcentration of 29%. The patient
was given initial therapy with Ringer
Lactate crystalloid 500 cc/hour (7cc/
kgBW/hour) and then evaluated for 4
hours. After 4 hours, the fluid is reduced
to 360cc/hour (5cc/kgBW/hour), then
reduced after 4 hours to 216cc/hour
(3cc/kgBW/hour). The patient was given
tranexamic acid 3x500 mg IV. Patients
are scheduled for complete blood counts
every 12 hours.
On the fifth day of fever, the patient
complained of feeling bloated in the
stomach, sometimes with nausea
accompanied by weakness and bleeding
gums. The patient’s urine is colored like
tea. Abdominal examination revealed
positive distension and shifting dullness.
The measured temperature is 36.5oC, and
blood pressure is 90/70 mmHg with a
weak pulse of 120x/minute and cold feet. A
complete blood count revealed a decrease
in platelets from the previous one and a
30% hemoconcentration. The patient was

diagnosed with Dengue Shock Syndrome.
The patient was treated with 1440cc (10-
20cc/kgBW) fluids and evaluated for the
general condition for 30 minutes. The
general condition began to decrease after 30
minutes with blood pressure 90/70 mmHg
and pulse 120x/minute weak; the patient
was given HES colloid fluid 1440 cc (10-
20cc/kgBW) rapid drops for 15 minutes
and monitored for 30 minutes. After 30
minutes of pouring fluids, the spleen
begins to warm, blood pressure is 100/70
mmHg, the pulse is 100x/minute, fluid is
reduced to 504cc/hour (7cc/kgBW/hour)
and then evaluated for 60 minutes. After
that, the fluid was reduced to 360cc/hour
(5cc/kgBW/hour) and evaluated for 60
minutes. The patient was evaluated for 60
minutes with fluid reduced to 216cc/hour
(3cc/kgBW/hour). After that, the patient’s
vital signs stabilized. The patient was taken
blood every 12 hours; on the second hour,
there was severe thrombocytopenia with a
decrease in hematocrit.
On day 5 of fever, the patient had no
complaints, with a temperature of 36oC,
blood pressure 120/80 mmHg, and pulse
80x/minute, and the patient was treated
with crystalloid fluid 20 drops per minute.
On day 6 of fever, the patient had no
complaints, had an increase in platelets
and a decrease in hematocrit. Therapy
is continued. On the seventh day of
fever, the patient began complaining of
itching and red spots on the legs, and the
general condition was stable. The results
of a complete blood count have shown
an increase in platelets. The patient was
given additional therapy with cetirizine
2x10 mg. On day 8 of fever, platelets
begin to rise above 50,000 with a decrease
in hematocrit. The patient is planned,
outpatient.
DISCUSSION
Dengue is an acute febrile disease
caused by infection with the dengue
virus (DENV), where DENV is a single
positive strand RNA flavivirus belonging
to the family Flaviviridae. Four main
virus serotypes exist (DENV-1, DENV-
2, DENV-3, and DENV-4).3 Humans are
infected with dengue through the bite
of female Aedes mosquitoes carrying
DENV, including Aedes albopictus and
Aedes aegypti.2 The incubation period for
Published by Intisari Sains Medis | Intisari Sains Medis 2022; 13(3): 625-631 | doi: 10.15562/ism.v13i3.1507
dengue virus infection is 4-7 days. Clinical
manifestations of DENV infection consist
of classic dengue fever (dengue fever),
dengue hemorrhagic fever (DHF), and
dengue shock syndrome (DSS). Dengue
fever is an acute high fever with signs
and symptoms similar to dengue fever.
Still, there are hemorrhagic signs such
as a positive tourniquet test, petechiae,
easy bruising or spontaneous bleeding. In
the late phase of fever, some individuals
develop hypovolemic shock (dengue
shock syndrome) due to plasma leakage.
The presence of warning signs such as
persistent vomiting, abdominal pain,
lethargy or restlessness and oliguria is
important for intervention. Abnormal
hemostasis and plasma leakage are the
main pathophysiological signs of DHF.
Thrombocytopenia (100,000 cells/mm3
or lower) and increased hematocrits/
haemoconcentration (≥20%) are findings
that occur before a decrease in fever or the
onset of shock. DSS is usually characterized
by a rapid, weak pulse with narrowing of
the pulse pressure (<20 mmHg (2.7 kPa))
or hypotension with cold, clammy and
restless acral.5
The pathogenesis of dengue is
associated with various viral and host
factors such as viral nonstructural protein
1 (NS1) antigen, DENV genomic variation,
subgenomic RNA, antibody-dependent
enhancement (ADE), cross-reactive T cell
memory, anti-DENV NS1 antibody and
autoimmunity. The severe manifestations
of dengue fever are ascribed to the
synergistic effect of all the factors.6
In this case series, we report 3 cases
of dengue shock syndrome (DSS) with
different clinical manifestations. In the
first case, a male patient with classic signs
of dengue fever plus spontaneous bleeding
in the form of nosebleeds accompanied by
hemodynamic disturbances. Laboratory
examination revealed thrombocytopenia.
This is suspected to be due to the
activation of the DENV NS1 antigen,
which disrupts the integrity of the
endothelial cell monolayer because this
protein reacts directly on the vascular
endothelium. The binding of DENV
NS1 to toll-like receptor 4 (TLR4) on
platelets triggers platelet activation,
causes aggregation and adherence to
endothelium and is phagocytosed by
CASE REPORT
macrophages causing thrombocytopenia
and bleeding.4 NS1-mediated release of
inflammatory cytokines from immune
cells also contributes to endothelial
hyperpermeability and vascular
leak. DENV NS1 can directly trigger
complement activity via an alternative
pathway, targeting liver cells and leading to
the stimulation of inflammatory cytokines.
This case leads to plasma leakage and fluid
accumulation in the third space, ultimately
leading to dengue shock syndrome. So
that in the third case, a male patient with
dengue shock syndrome accompanied
the suspicion of ascites from the physical
examination. Ascites are a sign of plasma
leakage. From host factors such as the
DENV antibody, NS1 releases cytokines in
a disorderly manner.
Several cytokines and chemokines
secreted by host endothelial cells are
anti-DENV NS1 antibody responses. In
addition to demonstrating the presence of
cell apoptosis, stimulation of anti-DENV
NS1 results in immune activation in
endothelial cells, releasing inflammatory
mediators such as MCP-1, IL-6 and IL-8.
Elevated levels of IL-6 and IL-8 correlated
with clinical manifestations of DHF. It has
been reported that IL-6 and IL-8 increased
in dengue cases compared to dengue cases.
IL-6, a pro-inflammatory cytokine, plays
a role in severe dengue fever and other
cytokines such as IL-1 and TNF-α; IL-8 is
increased in cases of DHF. IL-8 also plays
a role in intravascular coagulation in DHF
patients.6,7 Hemodynamic disturbances
found in suspected cases are due to plasma
leakage and spontaneous bleeding causing
shock. An increase in the hematocrit
value indicates plasma leakage into the
extravascular space, starting on the third
day of fever.
In the second case, a male patient with
dengue shock syndrome accompanied
acute liver failure. The patient complains
of heartburn and nausea accompanied
by tea-like urine. Dengue patients with
abdominal pain typical of liver disorders,
nausea, vomiting and anorexia, and
hepatomegaly with or without jaundice
are typical of liver disorders. The disorder
can be seen in this case, but there is no
jaundice. On laboratory examination, we
found transaminitis. Dengue patients had
an increase in AST and ALT at 63%-97%
629
 CASE REPORT
and 45%-96%; only 4% of cases had a 10-
fold increase in transaminitis.7 In this case,
the patient’s AST and ALT were 1764 and
211, several times within normal limits.
This patient is similar to the case report of
Lewis et al., 2020 where the results of AST
and ALT showed a several-fold increase.8
It is said that liver function involvement is
when the AST increases above 1000.
The patient has been tested for
hepatitis markers with negative results.
The pathogenesis of liver disorders in
dengue is still unknown. Still, there are
several hypotheses, such as the direct
effects of the virus causing hepatocyte
cell necrosis and apoptosis, the immune
response of cells to liver cells, circulatory
disorders, metabolic acidosis and hypoxia
caused by hypotension or localized plasma
leakage in the liver. Liver damage is a
manifestation of severe dengue fever and
is thought to occur due to the role of anti-
DENV NS1. An increase in IL-8 is also
associated with thrombocytopenia and an
increase in alanine transaminase (ALT). A
study conducted by Lin et al., 2008 showed
that the anti-DENV NS1 antibody binds
to the vascular endothelium of the portal
and central veins in rat liver. Pathological
changes include hepatic fibrosis, fatty
liver, cell infiltration, necrosis and vesicle
formation. High elevations of AST and
ALT were also found.9 Hepatocytes and
Kupffer cells may be the target cells for viral
replication, and apoptotic mechanisms
occur. Nitric Oxide (NO) regulation
induces anti-DENV NS1 antibody to
induce endothelial cell apoptosis. Liver
involvement associated with dengue fever
in the absence of shock and complications
is also increased.
Management of dengue fever in the
form of supportive management. Based on
WHO, 2011, in dengue shock syndrome,
fluid resuscitation and ABCs (airway,
breathing, circulation, blood sugar) are
carried out simultaneously and quickly to
secure hemodynamics. Give fluids 10-20
ml/kg quickly, for 10-15 minutes. When a
shock is resolved (systolic blood pressure
of 100 mmHg and pulse pressure of more
than 20 mmHg, pulse rate less than 100
beats per minute with sufficient volume,
warm and not pale skin), the amount of
fluid is reduced to 7 ml/kgBW/hour. Rapid
recovery from shock without sequelae and
630
the absence of inflammation of the pleura
and peritoneum suggest functional changes
in vascular integrity from structural
endothelial damage.5 An increase in
hematocrit or hemoconcentration results
from plasma leakage. With evidence of an
increase in hematocrit of more than 20%
of the initial hematocrit or 10-15% above
the baseline. Fluid therapy of 10 ml/kgBW
showed a faster decrease in hematocrit.
Hematocrit values stabilized
​​ again on
days 7 and 8.10 of fever. This patient is
consistent with our case, where there was
a decrease in hematocrit on days 7 and 8.
The liquid used is an isotonic crystalloid
in the critical phase. Hyper-oncotic colloid
solutions (osmolarity > 300 mOsm/l)
such as dextran 40 or HES (hydroxyethyl
starch) solutions can be used in patients
with massive plasma leakage and
inadequate patients with a minimum
crystalloid volume. Intravascular than
colloids. In addition, it can trigger
pulmonary edema if there is an increase
in capillary permeability, especially as a
result of extensive fluid resuscitation. The
presence of lactic acidosis, hemodynamic
instability and hemoconcentration
are some of the side effects of using
crystalloids. Administration of RL
solution (20ml/kgBW) as a bolus causes
a brief increase in vascular volume
before being distributed throughout the
interstitial (extravascular) compartment
so that a 20 ml bolus within 1 hour, only
5 ml remains in the intravascular space,
and 15 ml enters the intravascular space.
Interstitial, it uses a 1:3 ratio. In shock
patients, it is usually effective in restoring
circulating blood volume. However, this is
different from a colloid fluid; in the same
volume, a larger and longer-lasting plasma
volume expansion (intravascular) will be
obtained, so the tissue is expected to be
well-oxygenated and hemodynamically
more stable. This therapeutic option is
useful in preventing recurrent shock and
reducing the need for large amounts of
intravenous fluids to reduce fluid overload.
However, the side effects of colloids are the
risk of anaphylaxis and coagulopathy.11
In the third case, when the patient was
in shock, crystalloid fluid therapy in
the form of RL and colloid fluid in the
form of HES was intended to accelerate
the return of hemodynamics to normal.
Published by Intisari Sains Medis | Intisari Sains Medis 2022; 13(3): 625-631 | doi: 10.15562/ism.v13i3.1507
A study by Setiati, 2000 on pediatric
patients with DSS concluded that the
mortality of patients receiving HES colloid
was 6%, significantly lower than those
receiving RL. HES 6%, it was concluded
that there was no significant difference
in mortality between the two groups.14
In a study conducted at the Tangerang
General Hospital in 2018, crystalloid and
colloid combination therapy had the same
effectiveness. Patients who were given
crystalloid solutions and crystalloid-
colloid combinations did not significantly
differ in the hematocrit value. However, it
was found that there were differences in
platelet values i​​ n the group of patients who
were given crystalloids and crystalloid-
colloid combinations, although this was
not the main parameter to assess the
effectiveness of therapy because a decrease
in platelets in the DHF cycle could occur
between days 5-7.15
In the second case, DSS with acute
liver failure was treated with NAC
(N-acetylcysteine). NAC is known to
prevent liver disorders caused by free
radicals, improve hemodynamics and
optimize oxygen to liver tissue. Patients
treated with NAC early on will give good
results. Antioxidant enzymes such as
glutathione peroxidase and glutathione
reductase can be reduced during the acute
phase of dengue. The antioxidant activity
of NAC can increase plasma antioxidants
such as glutathione peroxidase and
glutathione reductase to reduce oxidative
stress. N-acetylcysteine ​​(NAC) is produced
after the acetylation reaction of the amino
acid L-cysteine. It acts as a source of
reduced glutathione and directly attacks
free radicals in the body. A study on mice
concluded that NAC could cure acute liver
failure without sequelae. NAC exhibits
antiviral activity by reducing infectivity in
DENV-infected HepG2 cells, suppressing
DENV replication, and reducing oxidative
damage. NAC can also reduce dengue virus
infectivity during admission, replication,
post-translation, RNA synthesis, and
exocytosis.6,16 In a retrospective analysis,
the dose of NAC given was intravenously
100 mg/kg/day for 5 days, followed by 12.5
mg/day. kgBW/hour for 4 hours followed
by 6.25 mg/kgBW/hour for 72 hours.17
In general, the clinical manifestations
of severe dengue hemorrhagic fever vary

from person to person. In these three
cases, all patients had no previous history
of DHF. This patient is in contrast to the
theory that people who are later infected
with a different type of dengue virus may
experience something called “antibody-
dependent enhancement,” in which the
body’s immune response makes clinical
symptoms of dengue fever worse and
increases a person’s risk of developing
a fever and severe bleeding. The ADE
(antibody-dependent enhancement)
theory states that at certain concentrations,
heterotypic antibodies bind but do not
neutralize virions of the next infecting
DENV type. This virus-immune complex
is recognized by the Fcγ receptor, which
facilitates viral entry and replication in
target immune cells. This patient initiates
an immune cascade that results in leakage
of blood vessels and causes severe dengue
fever. The level of pre-existing anti-DENV
antibodies is directly related to the severity
of secondary dengue disease in humans.18
CONCLUSION
Severe dengue, or DSS, has a variety
of clinical manifestations. The main
mechanism of DSS is plasma leakage,
marked by a decrease in blood pressure
until the pulse is felt weak. In the case of
DSS with acute liver failure, there was an
increase in SGOT and SGPT; this is one
of the complications of DSS. The main
treatment is the administration of isotonic
crystalloid fluids according to body weight.
While in cases of acute liver failure, NAC
can be given, currently, not many studies
discuss the relationship between NAC
therapy and DSS complications of acute
liver failure.
CONFLICT OF INTEREST
The authors declare that they have no
competing financial or personal interests.
Published by Intisari Sains Medis | Intisari Sains Medis 2022; 13(3): 625-631 | doi: 10.15562/ism.v13i3.1507
AUTHOR CONTRIBUTION
All authors contributed equally in
conducting the study and writing and
revising the manuscript.
FINANCIAL SUPPORT
This research received no specific grant
from public, commercial, or not-for-profit
funding agencies.
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