Symposium

Dengue shock
Senaka Rajapakse
Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Sri Lanka

ABSTRACT
Shock syndrome is a dangerous complication of dengue infection and is associated with high mortality. Severe dengue
occurs as a result of secondary infection with a different virus serotype. Increased vascular permeability, together with
myocardial dysfunction and dehydration, contribute to the development of shock, with resultant multiorgan failure.
The onset of shock in dengue can be dramatic, and its progression relentless. The pathogenesis of shock in dengue is
complex. It is known that endothelial dysfunction induced by cytokines and chemical mediators occurs. Diagnosis is largely
clinical and is supported by serology and identification of viral material in blood. No specific methods are available to
predict outcome and progression. Careful fluid management and supportive therapy is the mainstay of management.
Corticosteroids and intravenous immunoglobulins are of no proven benefit. No specific therapy has been shown to be
effective in improving survival.

Key Words: Dengue, shock, DHF, DSS, myocarditis, corticosteroids, fluids

main symptoms were body aches, headache, loss of appetite,

INTRODUCTION
Infection with dengue virus imperils about 20 million people
every year in tropical and subtropical countries.[1] The mortality
rate is around 1−2%. The spectrum of disease manifestations
is wide, ranging from asymptomatic or mild infection, through
varying degrees of thrombocytopenia and vascular leakage
that is typical of dengue hemorrhagic fever (DHF), to a severe
shock syndrome and multiorgan failure.[2] Multiple organs can be
affected: liver damage, rhabdomyolysis, myocardial depression,
and various neurologic and ophthalmologic manifestations have
been reported.[2] The case fatality of severe dengue in Asian
countries is around 0.5–3.5%.[3]
CASE REPORT
A 49-year-old woman was admitted to hospital with fever for
5 days. She had no significant previous medical history. Her
Address for correspondence:
Dr Senaka Rajapakse, E-mail: senaka.ucfm@gmail.com
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120
vomiting, and high fever. On day 5 of the illness, a full blood
count showed a platelet count of 45,000 mm3. She was admitted
to the ICU. On admission, she was conscious and alert, but was
restless and looked ill. She had a diffuse cutaneous blanching
erythema. Her pulse rate was 120 beats per minute and blood
pressure 130/80mmHg, with a postural drop of 20 mmHg. The
heart sounds were normal. Her respiratory rate was 28/min, and
her lungs were clear. Her abdomen was soft, with no free fluid;
epigastric and right hypochondrial tenderness was present. She
was neurologically normal. Her electrocardiogram (ECG) was
normal, apart from sinus tachycardia. DHF was the likely clinical
diagnosis. Intravenous (IV) Hartmann solution 2 ml/kg/h was
commenced in view of the postural drop in blood pressure. She
became hypotensive 4 h after admission, with blood pressure
falling to 70/40 mmHg, and her heart rate increased to 140/
min. A repeat ECG showed diffuse T wave inversions. An urgent
echocardiogram showed global hypokinesia, with an ejection
fraction of 40%. Based on a clinical diagnosis of dengue shock
syndrome (DSS) plus myocarditis, dobutamine and noradrenaline
infusions were started. Repeat platelet count was 22,000mm3 and
the hematocrit 48%. Fluids were given with caution, and fresh
frozen plasma (FFP) and platelet transfusion was commenced.
She then had coffee grounds aspirate through the nasogastric
tube and was therefore started on omeprazole 80 mg bolus
followed by 8 mg/h infusion. She remained in intractable shock,
with no response to inotropes or intravenous hydrocortisone,
and required ventilation due to worsening pulmonary edema.
Her ECG now showed widespread T wave inversions with first-
degree heart block. She progressively deteriorated, became anuric,
Journal of Emergencies, Trauma, and Shock I 4:1 I Jan - Mar 2011

and developed adult respiratory distress syndrome (ARDS). She
also developed complete heart block, for which a temporary
pacemaker was inserted. Although rate control was achieved,
her blood pressure remained low on maximum inotropes. She
was started on IV immunoglobulins 0.4 mg/kg by infusion. Her
condition continued to deteriorate, and blood pressure became
unrecordable. External cardiac massage alone seemed to raise
the blood pressure to recordable levels. Repeat echocardiogram
showed a dilated, globally hypokinetic heart, and it appeared
that the myocardium was not responding to inotropes at all.
She died in asystole shortly afterwards, 15 h after admission.
Investigation results received after the patient’s death showed
positive IgM and IgG antibodies to dengue. Dengue PCR was
also positive. All bacterial cultures were negative. Serum cortisol
levels were normal.
PATHOGENESIS OF SHOCK IN DSS
Dengue viruses are transmitted to humans by infected
mosquitoes, mainly Aedes aegypti and Aedes albopictus.[2] There are
four serotypes of the dengue virus: types 1, 2, 3, and 4. Although
referred to as serotypes, these have actually been identified as
four different species belonging to the family Flaviviridae and
genus Flavivirus. Infection with the dengue virus has a wide
range of manifestations. Many infections are asymptomatic.
Symptomatic dengue results in two defined syndromes: dengue
fever (DF) and DHF/DSS. While DF is a simple, self-limiting
febrile illness, DHF is a severe and potentially life-threatening
condition. DHF/DSS is characterized by thrombocytopenia, with
the resultant hemorrhagic manifestations; in addition, there is
increased vascular permeability, resulting in depleted intravascular
volume and shock. Severe, profound shock is known to occur in
extreme cases and is associated with high mortality.
Two theories have been proposed to explain the pathophysiology
of DHF/DSS.[4] According to one theory, DHF/DSS is caused
by more virulent strains of the dengue virus. The other theory
suggests that DHF/DSS results from abnormal and exaggerated
host immune responses – in particular, the production of dengue
virus cross-reactive antibodies – which augments the infection. In
primary infection with the dengue virus, cross-reactive antibodies
that lack neutralizing activity are produced. During secondary
infection by a different serotype, the dengue virus and non-
neutralizing antibodies form virus−antibody complexes. The Fc
portion of these antibodies bind to FcγRI- and FcγRII-bearing
cells, resulting in an increased number of cells being infected
by the dengue virus.[5] This phenomenon is known as antibody-
dependent enhancement and is believed to play an important
part in the pathogenesis of shock.[5−8]
Patients with severe dengue die of progressively worsening
shock and multiorgan failure. The exact mechanism of this
phenomenon is not fully understood although it is thought that
increased vascular permeability occurs largely due to malfunction
of vascular endothelial cells induced by cytokines or chemical
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Rajapakse: Dengue shock
mediators,[9] as also occurs in severe sepsis. It appears that a Th1
response occurs in the first few days of dengue infection; this
later switches over to a Th2 response, which correlates with the
development of shock.[10] TNF-α, interleukin (IL)-2, IL-6, and
IFN-γ levels are highest in the first 3 days of illness, whereas
IL-10, IL-5, and IL-4 tend to appear later.[10] IL-2 and IFN-γ are
Th1-type cytokines, while IL-5 and IL-4 are Th2-type cytokines.
Dengue virus−infected monocytes and endothelial cells have
been shown to produce multiple cytokines, including TNF-α. [11,12]
In the presence of enhancing antibodies, monocytes infected
with dengue virus produce TNF-α. TNF-α has been shown to
induce plasma leakage in vitro.[13] Basophils and mast cells infected
with dengue virus produce IL-1 and IL-6, while IFN-γ, IL-2,
and TNF-α are also produced by virus-specific T lymphocytes
upon activation.[12,14] Lymphocytes infected with the dengue virus
produce IFN-α and IFN-γ,[15] IFN-α levels are higher in patients
with DHF, though there is no difference in its levels in different
grades of DHF.[16] IFN-γ levels are no different in patients
with DF and DHF.[15] The precise role played by interferon in
the pathogenesis of dengue shock is unclear. The cytokines
TNF-α,[17] IL-6,[10,18,19] IL-8,[19] IL-13,[10,20] IL-18,[10,20] and cytotoxic
factor[10] are significantly elevated in DHF as compared with DF.
Levels of IL-13,[10] IL-18,[10] and IL-8[21] correlate positively with
increasing grades of DHF. On the other hand, IL-12 levels are
high in uncomplicated DF, but low in dengue-induced shock.[20]
Levels of transforming growth factor-β (an inhibitor of Th1-
and enhancer of Th2-type cytokines) correlate with severity
of disease and show an inverse relationship with IL-12 levels.
Complement activation is a constant finding in DHF. Higher
complement levels correlate with increasing disease severity.
[4,22]
The dengue virus is also known to infect endothelial cells
and cause direct damage through apoptosis;[23] nonetheless, it is
believed that endothelial activation occurs predominantly through
an indirect mechanism.[13] Increased endothelial cell expression of
VCAM-1 and ICAM-1 occurs, and TNF-α is a key intermediary
in this process.[13] Dengue infections are associated with reduced
numbers of CD4+ T-cells, CD8+ T-cells, and natural killer
cells.[24] Levels of these cells are lowest at the point when the
fever settles and the onset of shock takes place, and increase
subsequently. B-cell numbers are not affected.
CLINICAL FEATURES OF DENGUE ILLNESS
PROGRESSING TO SHOCK
Dengue infection should be considered when patients who
live in areas where dengue is prevalent present with a febrile
illness together with hemorrhagic manifestations or features
of shock. The WHO case definitions for dengue shock are
shown in Box 1. Dengue infection begins as a febrile illness;
the fever is accompanied by constitutional symptoms and a
characteristic flushing of the skin. Intermittent high-grade
fever accompanied by chills and rigors is a feature. Vomiting,
headache, myalgia, epigastric discomfort, and abdominal pain
are common, and patients often feel quite ill.[25] The fever lasts
2−7 days and is followed by a fall in temperature; complications
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Rajapakse: Dengue shock
Box 1: WHO case definitions for dengue shock[1]
Features of dengue hemorrhagic fever
• Fever, or history of acute fever, lasting 2−7 days,
occasionally biphasic
• Hemorrhagic tendencies, evidenced by at least one of
the following
○ A positive tourniquet test
○ Petechiae, ecchymoses, or purpura
○ Bleeding from the mucosa, gastrointestinal tract,
injection sites, or other locations
○ Hematemesis or melena
• Thrombocytopenia (100000/mm3 or less)
• Evidence of plasma leakage due to increased vascular
permeability, manifested by at least one of the following;
○ A rise in hematocrit ≥20% above the average for age,
sex and population
○ A drop in hematocrit following volume replacement
equal to or greater than 20% of the baseline
○ Signs of plasma leakage such as pleural effusion, ascites
or hypoproteinemia
All four of the above PLUS evidence of circulatory
failure, manifested by
• Rapid weak pulse, and
• Narrow pulse pressure (<20mmHg)
OR
• Hypotension for age, and
• Cold, clammy skin, and restlessness
of dengue often take place at this point. Patients who remain ill,
despite their temperature returning to normal, are more likely
to develop shock. Shock generally occurs on day 3−4 of the
illness.[26] Thrombocytopenia is a characteristic finding. Platelet
counts below 100,000/mm3 together with a rise in the hematocrit
define DHF. In the classical shock syndrome, increased vascular
permeability results in third space fluid loss, leading to pleural
effusions, pericardial effusions, ascites, non-cardiogenic
pulmonary edema and, subsequently, hypotension. Right
hypochondrial pain occurs similar to that seen in cholecystitis;
acalculous cholecystitis is a characteristic feature of DHF.[27]
Myocarditis is a well-known complication[28] and although often
mild it can result in heart block and can be severe enough to
result in progressive and intractable acute heart failure with global
hypokinesia and acute cardiac dilatation.[28−30] Lactic acidosis,
which occurs[31] as a result of the sluggish circulation, possibly
contributes to myocardial depression in severe cases. Acute
hepatic derangement can occur though fulminant liver failure
is rare.[4] Acute renal failure is usually secondary to hypotension
in shock syndrome and is associated with increased mortality.[32]
Death is usually due to severe hemorrhage or intractable shock
with multiorgan failure.
Several hemodynamic factors probably contribute to the
intractable shock seen in severe dengue. Clearly, the syndrome
122
of increased vascular permeability, the pathophysiology of which
is described above, is the prime reason for shock. Classically, an
increase in systemic vascular resistance as a result of extravasation
of plasma occurs, with a resultant reduction in preload. In
addition, associated myocardial depression is likely to contribute
to the shock.[28,30] Dehydration due to the associated vomiting
and poor intake may also play a role.
RISK FACTORS FOR THE DEVELOPMENT OF
DENGUE SHOCK
The factors which place patients at higher risk of developing
dengue shock are not clearly identified yet. DHF/DSS is
more likely to occur in infants[33] and the elderly.[33−35] Dengue
infection also appears to be more severe in females.[36] Severe
dengue is more likely to occur in patients with chronic illness
such as diabetes mellitus or asthma.[37,38] Although malnutrition
predisposes to many infectious diseases it does not appear to
increase the likelihood of severe dengue.[39] The serotype of the
infecting virus may influence the severity of dengue; DEN-1
infection, followed by DEN-2 infection, has been reported to
be associated with worse outcome.[40] There is some evidence
that genetic susceptibility (ethnic variation,[41] HLA typing,[42]
etc.) may play a role in the development of dengue shock, but
this has not been studied thoroughly.
DIAGNOSIS
The WHO guidelines on dengue have clearly defined criteria
for the diagnosis of dengue shock [Box 1].[1] Confirmation of
dengue infection is by serology or detection of dengue viral
material in blood by RT-PCR. Dengue-specific IgG and IgM
ELISA is widely used.[43] The test is relatively inexpensive, and
becomes positive for IgM antibodies on or after day 5 of the
fever. IgM ELISA has a sensitivity of 83.9–98.4% and a specificity
of 100%.[44] The presence of IgG antibodies indicates previous
infection; hence, the presence of both IgG and IgM antibodies
suggest the possibility of a secondary infection, although this
has not been validated in clinical studies. Cordeiro et al.[45]
proposed a two-dimensional classifier to differentiate primary
and secondary dengue infection based on dengue IgM ELISA
and the number of days since the onset of symptoms; the
method showed over 90% specificity and sensitivity. Serotyping
can also be done using ELISA.[46] RT-PCR for dengue viral
material can help to diagnose the illness early, before antibodies
become positive; the method, although relatively expensive, is
very sensitive and allows for serotyping.[47] While these tests are
used for diagnosis of dengue infection, they do not accurately
predict which patients are likely to develop dengue shock. The
association between high antibody titers or high viral load and
the clinical manifestations of dengue has not been studied. No
other biochemical investigations are available to predict which
patients will develop shock, which is largely a clinical diagnosis.
Hemoconcentration and dropping platelet counts herald the
onset of shock. Extravasation of fluid due to vascular leakage can
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 Rajapakse: Dengue shock

Table 1: Evidence base for key interventions in dengue shock

Therapy Recommendation
Ideal dose of fluids Not studied in trials. Intravenous bolus of 10−20 ml/kg recommended by WHO guidelines[1]
Type of fluid No difference between colloids and crystalloids.[49−51] No evidence from adult studies.
Platelet transfusion No clear evidence from trials. Required in the presence of hemorrhage. Effect of platelet transfusion short-lived in shock.[52]
Corticosteroids No clear evidence of benefit.[56−63] Most trials underpowered, poor methodological quality; not studied in adults.
IV immunoglobulins No evidence of benefit in published literature.
Inotropes and vasopressors No evidence from clinical trials. Empiric use of vasopressors (dopamine, noradrenaline) in shock, with addition of
inotropic agents (dobutamine, adrenaline) if myocardial depression present.
Carbazochrome sodium sulfonate (AC-17) No evidence of benefit. Single trial, underpowered.[78]
Nasal continuous positive airway pressure (NCPAP) Effective in acute respiratory failure in DSS.[79]

be detected radiologically (chest radiography for pleural effusions,
echocardiography for pericardial effusions, ultrasonography
for ascites). The presence of fluid around the gall bladder,
together with thickening of the gallbladder wall, has been
shown to be associated with shock. [27,48] None of these features,
however, predict the development of severe shock syndrome
or mortality. Patients with shock do, however, show a variety
of metabolic derangements, including lactic acidosis, elevated
transaminases, and rising serum creatinine and blood urea. Pulse
oximetry and arterial blood gas analysis showing hypoxia may
indicate the development of pulmonary edema, which may be
cardiogenic or non-cardiogenic. Electrocardiography is useful in
identifying early myocarditis (T wave and ST segment changes
are seen).[28] Echocardiography is the main investigation used to
diagnose myocardial dysfunction and should be done early when
impending shock is suspected. The place of cardiac troponins
in diagnosing myocarditis has not been evaluated.
MANAGEMENT
The WHO has issued guidelines for the management of DSS.
[1]
Much of the evidence on therapeutic measures in dengue are
from children, and evidence from adults is lacking [Table  1].
Close monitoring is required as shock can develop rapidly, and
transfer to an ICU is indicated. The patient should be kept under
close observation. Pulse, blood pressure, and respiration should
be monitored–continuously if possible or at least every 15 min.
Oxygen saturation should be monitored using a pulse oximeter,
and oxygen should be given by face mask. Two wide-bore cannulae
should be inserted for venous access. Blood should be drawn for
grouping and cross-matching, blood urea, serum electrolytes, liver
function tests, full blood count, prothrombin time, and c-reactive
protein. Paracetamol may be used to control the fever.
The only known effective treatment in DSS is timely and
aggressive fluid resuscitation. No trials have been conducted
comparing the use of intravenous fluids vs placebo due to
obvious ethical considerations. Fluids used for volume expansion
include normal saline, Ringer lactate, 5% glucose diluted 1:2 or
1:1 in normal saline, plasma, plasma substitutes, or 5% albumin.
There is no evidence that colloids are superior to crystalloids
for resuscitation. Three studies conducted in Vietnam have
compared the use of crystalloids and colloids. Dung et al.[49]
compared four IV fluid regimens (Ringer lactate, normal saline,
Journal of Emergencies, Trauma, and Shock I 4:1 I Jan - Mar 2011
3% gelatin, and dextran 70) in 50 children aged 5−15 years
with dengue shock; no difference was seen in the occurrence
or duration of shock between the groups. No difference was
seen between the fluid requirements of crystalloids or colloids.
All patients recovered. However, this study was thought to be
underpowered to detect a difference between the two groups.
Ngo et al.[50] conducted a larger study comparing the same fluid
regimens in 230 children aged 1−15 years. The study included a
larger proportion of patients with more severe grades of DHF.
Although a trend towards benefit with colloids over crystalloids
was shown, a clear difference between the four regimens was not
demonstrated. Subgroup analysis showed that more severely ill
patients may benefit from early administration of colloids. Wills
et al.[51] compared three fluid regimens (Ringer lactate, dextran
70, and 6% hydroxyethyl starch) in 512 children aged 2−15 years
with dengue shock. The authors stratified the study population
into two groups; moderate shock (pulse pressure >10 and <20
mmHg) and severe shock (pulse pressure <10 mmHg). Patients
with moderate shock (n = 383) were randomized to receive
Ringer lactate, dextran, or starch and those in severe shock
(n = 129) were randomized to receive dextran or starch. No
statistically significant differences were seen in either severity
group in the requirement for colloid subsequent to the initial
episode of shock, in the volumes of rescue colloid, in total
parenteral fluid administered, or in the number of days in the
hospital. The authors concluded that treatment with colloids
did not provide any benefit over treatment with Ringer lactate
in patients with moderate shock. In patients with severe shock,
no clear benefit with either starch or dextran was demonstrated.
Despite the fact that there is no evidence to support the use of
colloids in patients with severe shock, the authors felt that it
would be unethical to compare colloids to crystalloids in such
patients since it is generally accepted that colloids are needed in
cases of severe shock.
The ideal dose of fluids has not been studied in clinical trials,
and recommendations are based on practices in centers that have
treated large numbers of cases. In the case of shock, fluids should
be administered as a rapid (over less than 20 min) intravenous
bolus of 10−20 ml/kg body weight. If shock persists, and the
hematocrit is rising, plasma, plasma substitutes, or albumin
should be given as a rapid bolus and repeated if necessary to
a total dose or 20−30 ml/kg of colloid. If shock persists, and
particularly if the hematocrit decreases, fresh whole-blood
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Rajapakse: Dengue shock
transfusion may be required (10 ml/kg). With appropriate use of
fluid resuscitation in DSS, mortality rates have been shown to be
<0.2%. It is important to reduce the IV fluids once the patient
is recovering, as overhydration can result in intravascular fluid
overload once the vascular permeability reverses with recovery.
Platelet transfusions are usually given to patients who develop
serious hemorrhagic manifestations or have very low platelet
counts, although the exact platelet count at which platelets should
be given has not been defined. Transfused platelets survive only
for a very short period in patients with shock syndrome.[52] The
degree of elevation of circulating platelets after transfusion varies
directly with the amount of platelets transfused and inversely with
the degree of shock. Blood transfusion is required in patients
with severe hemorrhage. There is some evidence of benefit
with fresh frozen plasma transfusion in increasing the platelet
counts,[53] although the effect of plasma transfusion in dengue
shock has not been studied in a controlled clinical trial.
The WHO guidelines for the management of dengue do not
discuss the role of corticosteroids. While corticosteroids have
various immunosuppressant effects, evidence of beneficial
effects of corticosteroids on the deranged immunological
mechanisms in dengue is very limited. In patients with ARDS,
high-dose corticosteroids have been shown to reduce the levels
of the cytokines TNF-α, interleukin (IL)-1β, IL-6, and IL-8.[55]
However, Medin et al.[54] demonstrated that no reduction was
seen in IL-8 after treatment with dexamethasone in patients
with dengue. No other studies have examined the effects
of corticosteroids on the cytokine cascade. Clinical trials of
corticosteroids have been inconclusive so far and for the most
part have been underpowered and lacking in methodological
quality.[56−63] Some of the early studies demonstrated possible
beneficial effects of corticosteroids in dengue shock. Min et al.,[56]
in a randomized controlled study of children with DSS treated
with hydrocortisone, demonstrated a statistically significant
mortality benefit with corticosteroids in children aged 8 years
and over, although this benefit was not seen in younger children.
Futrakul et al.[57] reported a series of 22 children with shock
syndrome who were treated with pulsed methylprednisolone
therapy vs saline and plasma replacement. Nine out of 11 children
in the corticosteroid-treated group survived, while in the group
treated with saline and plasma replacement, all died. Significant
hemodynamic improvement was seen in the nine survivors
after administration of methylprednisolone. This study was
non-blinded and non-randomized. However, subsequent studies
of corticosteroids in dengue have all failed to show any benefit
either in terms of survival or hemodynamic improvement,[58−62]
and a Cochrane review on the subject concluded that there
was no evidence of benefit in using corticosteroids in DSS.
[64]
It must be noted that the previous studies have been small:
the total number of patients in all the randomized controlled
studies was 284. Of three other non-randomized studies, one
study showed no benefit, one study showed a survival benefit,
and one very small study showed hemodynamic improvement,
including apparent improvement in plasma leakage. All these
124
studies were underpowered, were conducted a long time ago, and
have only studied children. There is no evidence from clinical
trials regarding the effect of corticosteroids in adults.
Replacement doses of corticosteroids are thought to improve
mortality and duration of shock in patients with septic shock
who showed a blunted adrenocortical response to the ACTH
stimulation test.[65] Cortisol levels are low in a subgroup of
patients with septic shock, and a blunted cortisol response
to ACTH stimulation is associated with poor prognosis.[66] In
contrast, cortisol levels are high in DHF during both the acute
and convalescent phases.[67] A correlation between cortisol levels
and prognosis in dengue has not been studied. Although some
clinicians use steroids in treatment,[68] there is currently no clear
evidence to justify the use of corticosteroids in the treatment of
DSS. There is a clear need for adequately powered, randomized,
double-blind, placebo-controlled clinical trials in both children
and adults to fully evaluate the possible benefit or lack of benefit
of corticosteroids in dengue infection.
Similar to corticosteroids, the place of IV immunoglobulins
(IVIG) is also not mentioned in the WHO guidelines on the
management of dengue. Theoretically, the immunomodulatory
effects of IVIG can be postulated to have effects on the dengue
virus−induced cytokine cascade.[69,70] IVIG selectively triggers
the production of IL-1 receptor antagonist (IL-1ra),[70] and also
prevents the generation of the complement membrane attack
complex (C5b-9) and subsequent complement-mediated tissue
damage.[69] There is limited evidence that IVIG is beneficial in
the treatment of septic shock in neonates,[71] and a meta-analysis
has demonstrated an overall reduction in mortality in adults with
severe sepsis/septic shock.[72]
Ostranoff et al.[73] reported a series of five patients in Brazil with
dengue and severe thrombocytopenia who were treated with
IVIG (500 mg/kg/ day infusions over 3 h for 5 days). Clinical
improvement, together with improvement in platelet count, was
seen in these patients. The only published randomized controlled
trial investigating the effect of IVIG on thrombocytopenia
showed no benefit;[74] IVIG seemed to have no effect on platelet
counts. Seriously ill patients with hemorrhage or shock were
excluded from that study and hence the possible effects of IVIG
on DSS were not studied. One important conclusion was that
IVIG was safe, no significant side effects being encountered
during the trial. Alejandria [75] discusses an unpublished
randomized controlled trial conducted in the Philippines that
compared treatment with IVIG vs placebo in children with
DSS. This study showed a significant mortality reduction with
IVIG treatment. Overall, however, there is currently insufficient
evidence to make any recommendation regarding the use of
IVIG in dengue shock.[76]
Carbazochrome sodium sulfonate (AC-17) is a hemostatic drug
with a capillary-stabilizing action. It has been shown to reduce
the vascular hyperpermeability induced by vasoactive substances
through an agonist-induced inhibition of phosphoinositide
Journal of Emergencies, Trauma, and Shock I 4:1 I Jan - Mar 2011

hydrolysis.[77] Its effect in DSS has been investigated in a
randomized clinical trial (RCT), conducted in 95 Thai children. [78]
The primary outcome measure was the prevention of capillary
leakage as evidenced by the presence of pleural effusion, and the
secondary outcome was the prevention of shock. No evidence
of benefit in either outcome measures was seen with treatment
of DSS with AC-17, although the study was underpowered to
detect a potential treatment benefit.
An RCT compared the use of nasal continuous positive airway
pressure (NCPAP) vs oxygen by mask in patients with DSS
and acute respiratory failure.[79] The study was conducted in 37
Vietnamese children. The primary outcome measure was a PaO2
>80 mmHg after 30 min. Although the study was small, NCPAP
effectively decreased hypoxemia and reduced the number of
children requiring intubation and ventilation. Thus, NCPAP
appears to be an effective treatment in acute respiratory failure
associated with DSS.
The role of different inotropic and vasopressor agents in dengue
shock has not been investigated in clinical trials. Vasopressor
drugs such as noradrenaline and dopamine are indicated in shock
that is unresponsive to fluids but no clinical trials are available
on their use in dengue. In the case of cardiac dysfunction, it is
appropriate to use cardiac inotropic drugs such as dobutamine
or adrenaline in combination with a vasopressor although, again,
no evidence is available.
CONCLUSION
DSS is a dangerous condition that can rapidly progress to death.
Diagnosis is based largely on clinical grounds. No specific
therapy has yet been proven to be of value, and the mainstay of
management continues to be careful fluid resuscitation. While
no definite benefit has been shown of colloids over crystalloids,
colloids will continue to have a place in the management of severe
shock, pending further research. The role of corticosteroids and
immunoglobulins in dengue shock is clearly an area for future
research. Much of the recommendations are based on research
done in children, and management protocols for adults are
based on extrapolation of these findings. Further research on
the management of dengue shock in adults is clearly needed.
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How to cite this article: Rajapakse S. Dengue shock. J Emerg
Trauma Shock 2011;4:120-7.
Received: 15.07.09. Accepted: 04.11.09.
Source of Support: Nil. Conflict of Interest: None declared.
127
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