Research Article

Targeted Interventions in Critically Ill Children with

Severe Dengue
Suchitra Ranjit, Gokul Ramanathan, Balasubramaniam Ramakrishnan1, Niranjan Kissoon2
Pediatric Intensive Care Unit, Apollo Children’s Hospital, 1Department of Medical Education, Apollo Hospitals, Chennai, Tamil Nadu, India, 2Department of Pediatrics
and Emergency Medicine, BC Children’s Hospital and Sunny Hill Health Centre for Children, UBC, Vancouver, BC V6H 3V4, Canada

Abstract
Background: The World Health Organization guidelines provide suggestions on early recognition and treatment of severe dengue (SD);
however, mortality in this group can be high and is related both to disease severity and the treatment complications. Subjects and Methods: In
this prospective observational study, we report our results where standard therapy (ST) was enhanced by Intensive Care Unit (ICU) supportive
measures that have proven beneficial in other conditions that share similar pathophysiology of capillary leak and fluid overload. These include
early albumin for crystalloid‑refractory shock, proactive monitoring for symptomatic abdominal compartment syndrome (ACS), application
of a high‑risk intubation management protocol, and other therapies. We compared outcomes in a matched retrospective cohort who received
ST. Results: We found improved outcomes using these interventions in patients with the most devastating forms of dengue (ST+ group). We
could demonstrate decreased positive fluid balance on days 1–3 and less symptomatic ACS that necessitated invasive percutaneous drainage
(7.7% in ST+ group vs. 30% in ST group, P = 0.025). Other benefits in ST+ group included lower intubation and positive pressure ventilation
requirements (18.4% in ST+ vs. 53.3% in ST, P = 0.003), lower incidence of major hemorrhage and acute kidney injury, and reduced pediatric
ICU stays and mortality (2.6% in ST+ group vs. 26% in ST group, P = 0.004). Conclusion: Children with SD with refractory shock are at
extremely high mortality risk. We describe the proactive application of several targeted ICU supportive interventions in addition to ST and
could show that these interventions resulted in decreased resuscitation morbidity and improved outcomes in SD.

Keywords: Albumin, colloids, fluid overload, intra‑abdominal hypertension, plasma leak, resuscitation morbidity, severe dengue, shock

IntRoductIon Pediatric ICU (PICU) days, and mortality as compared to a

matched retrospective cohort with SD who received standard
Outcomes of dengue infections are usually excellent;[1‑3]
therapy (ST) as per the WHO guidelines.
however, mortality in severe dengue (SD) shock can be as high
as 44%–72%,[4‑7] with fluid overload (FO) and malignant edema
due to capillary leak being major contributors.[1‑7] subjects and Methods
While FO has been alluded to both in the World Health Setting and patient selection
Organization (WHO) guideline and our dengue publications,[3,6,7] Consecutive patients aged 2 months to 16 years with SD
therapeutic interventions to manage malignant edema and admitted to a 10‑bed PICU between September 2009 and
prevent treatment morbidity have not been fully described. November 2015 were included. All patients received ST as
Cognizant of this shortcoming, we focused on several per the WHO guidelines.[1] However, patients admitted from
pathophysiology‑based Intensive Care Unit (ICU) and October 2011 to November 2015 also received one or more
emergency department (ED) interventions which may be useful targeted interventions in addition to standard therapy (ST+) in
in severe and refractory dengue shock.
Address for correspondence: Dr. Suchitra Ranjit,
In this prospective observational study, we aimed to determine Pediatric Intensive Care and Emergency Services, Apollo Children’s
Hospital, Greams Road, Chennai - 600 006, Tamil Nadu, India.
the effect of these proactively applied interventions on
E-mail: [email protected]
mortality, positive fluid balance (PFB), ventilator requirements,

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DOI: How to cite this article: Ranjit S, Ramanathan G, Ramakrishnan B,

10.4103/ijccm.IJCCM_413_17 Kissoon N. Targeted interventions in critically ill children with severe
dengue. Indian J Crit Care Med 2018;22:154‑61.

154 © 2018 Indian Journal of Critical Care Medicine | Published by Wolters Kluwer ‑ Medknow

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 Ranjit, et al.: Targeted Critical Care Interventions in Severe Dengue

an anticipatory manner. Thus, patients fell into two groups: the Standard therapy group
prospective cohort (ST+ group: October 2011–November 2015) Management included fluid resuscitation, blood components
and the matched retrospective cohort (ST group: September for major hemorrhage, intubation and ventilation for refractory
2009–September 2011). shock or respiratory failure, and peritoneal dialysis (PD) or
continuous renal replacement therapy (CRRT) for established
Inclusions and exclusions
acute kidney injury (AKI) or FO.[1,3]
Of all PICU admissions with dengue, only patients with
severe forms of dengue in the critical phase whose diagnosis Targeted intervention group
was laboratory confirmed were included. Non‑SD, those in In addition to ST, one or more targeted ICU interventions [Table 1]
the recovery phase of dengue, bacterial co‑infections, and were also implemented in a proactive manner.
moribund patients who died within 3 h of admission were
excluded from the study. Ethics
No new interventions were used in the ST+ group, rather
Demographic data the choice of preferred colloid differed in both groups, and
At baseline, demographic and clinical data, hemodynamic standard WHO recommendations were complemented by
status, number with hypotensive shock, complete blood well‑described ICU supportive therapies in a proactive
count, and Pediatric Risk of Mortality scores were entered anticipatory manner. The ST group also received ICU
in a standard datasheet and samples were drawn to confirm supportive interventions in addition to the standard WHO
dengue diagnosis and perform blood gas and lactate recommendations; however, these were applied in a reactive
measurements. manner in most cases. Since no new interventions were used,
and both colloids have been recommended in dengue,[1‑3,8] the
Protocol for management of severe dengue (for all
Institutional Ethics Committee approved the study and waived
patients) the need for informed consent.
Management of SD began in the ED, where there was
extensive training focusing on early recognition of shock and Statistical analysis
hemorrhage, serial cardiorespiratory monitoring, and carefully The results are expressed as mean ± standard deviation or
titrated fluids to correct hypovolemia while minimizing FO.[1,3] median and interquartile range, as appropriate. Comparisons

Table 1: Targeted interventions for patients with severe dengue and high mortality risk
Intervention Explanation/rationale Method
1. Restrictive resuscitation Colloids can reduce large volume requirements Indication: Unresolved shock* after 30 ml/kg crystalloid in
and colloid rescue in the first 3 h
severe shock using Albumin 1 g/kg over 4‑6 h included in hourly fluid rates,
albumin[8] repeat if shock not reversed*
2. FO and IAH Monitoring IAP through Foley catheter Monitor IAP Q2H through indwelling Foley catheter, zeroed
Institute medical measures if IAP >10 mmHg/cmH2O to the mid‑axillary line[9] in all patients with unresolved
Monitor for progression to ACS: Worsening circulatory shock who have received >30 ml/kg fluid in the initial 3 h
parameters, hypoxemia, oliguria, and worsening acidosis[9] Medical measures to reduce IAP: Fluid restriction (colloids
In established ACS, slow controlled drainage is preferred), consideration of diuretic (furosemide), sedation,
important as rapid decompression temporarily improves gastrointestinal decompression, minimize PEEP as tolerated[9]
hemodynamics, but has a high risk of hemodynamic For established ACS: Atraumatic catheter (pig tail) insertion
instability and hemorrhage with ultrasound guidance, with prior administration of
appropriate blood products if at bleeding risk
3. Respiratory support Preserve spontaneous respiratory efforts in order to Preference for noninvasive ventilation: NPPV, CPAP[10]
promote tenuous venous return
High‑risk intubation management protocol[11,12] Peri‑intubation PPV and apneic oxygenation
Prevent hemodynamic decompensation Peri‑intubation vasoactive infusion
Prevent severe hypoxemia Preference for ketamine, avoid benzodiazepines[11,12]
4. Prevention and Restricted indications for invasive lines Ultrasound‑guided placement of invasive lines by
management of major Blood products: Whole blood versus products[13] experienced personnel
hemorrhage TXA infusions[14] Preference for compressible sites
Salvage of patients with Minimizing the “lethal triad” of coagulopathy, hypothermia,
major hemorrhagic and acidosis[14,15]
complications
5. Fluid removal methods Diuretics In diuretic‑resistant FO and established AKI
and dialysis Peritoneal dialysis
CRRT versus SLED[16]
*And no bleeding. NIPPV: Noninvasive positive pressure ventilation; CPAP: Continuous positive airway pressure; FO: Fluid overload; IAP: Intra‑abdominal
pressure; IAH: Intra‑abdominal hypertension; ACS: Abdominal compartment syndrome; PCD: Percutaneous drainage; PEEP: Positive end‑expiratory
pressure; CRRT: Continuous renal replacement therapy; SLED: Sustained low‑efficiency dialysis; PPV: Positive pressure ventilation; AKI: Acute kidney
injury; TXA: Tranexamic acid

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 Ranjit, et al.: Targeted Critical Care Interventions in Severe Dengue

between the ST and ST+ groups were carried out using Intervention #4: Prevention and management of major
Student’s t‑test or Chi‑square or Fisher’s exact test, or the hemorrhage
Wilcoxon test, as appropriate. P = 0.05 was considered Approach in both groups
statistically significant. Central lines and arterial catheters were considered only in fluid
Intervention #1: Restrictive resuscitation and “albumin refractory shock, and both groups had invasive lines inserted
rescue” under ultrasound guidance with a preference for compressible
In both groups, and as suggested by the WHO guidelines, sites. Nasal tubes (tracheal/enteral) were avoided, thereby
controlled fluid replenishment aiming for the lower limit minimizing hemorrhagic complications.
of euvolemia was implemented. Further, in patients Approach in standard therapy group
who remained in shock despite 30 ml/kg crystalloid In the event of major hemorrhage, circulatory support and
over 3 h (crystalloid refractory shock), colloid was used for targeted blood components (platelets, fresh frozen plasma,
volume replacement, provided hemorrhage had been ruled cryoprecipitate, and packed red blood cells) were infused
out. repeatedly aiming to normalize deranged coagulation.
In the ST group, the majority received 4% gelatin (gelofusine)
Approach in the targeted intervention group
at volumes not >30 m/kg/day.
Hemorrhage and bleeding were controlled by a multipronged
In the ST+ group, albumin was the preferred colloid approach, including hemostatic measures in the first instance
(“Albumin Rescue”), this was administered at a dose of wherever possible. Other interventions included proactive
1 g/kg as an infusion over 6 h in addition to crystalloids, the efforts directed at minimizing components of the lethal triad and
total volumes of which were titrated to maintain perfusion preference for fresh whole blood (FWB) rather than individual
targets. blood components and tranexamic acid (TXA) infusion.
Intervention #2: Large volume ascites and intra-abdominal Intervention #5: Fluid removal and renal replacement
hypertension therapy
Approach in standard therapy group Fluid removal using diuretics was instituted in patients who
In this group, intra‑abdominal pressure (IAP) monitoring developed features of FO after shock/plasma leak was under
through bladder pressure measurement was performed in control. RRT was considered in diuretic‑resistant patients who
patients who developed tense ascitic collections. If the IAP developed FO and/or AKI.
was elevated, medical treatment followed by percutaneous
drainage was initiated [Table 1]. Approach in standard therapy group
In the ST group, PD and CRRT were used for diuretic‑resistant
Approach in targeted intervention group FO/AKI.
In this group, rather than waiting for clinically obvious
abdominal distension, the IAP was proactively monitored Approach in targeted intervention group
2 hourly in all patients who received >30 ml/kg fluid in 3–4 h, Sustained low‑efficiency dialysis (SLED) was preferentially
and elevated values were treated similarly. used for patients with diuretic‑resistant FO/AKI.

Intervention #3: Peri-intubation decompensation and the Results

high-risk intubation management protocol
During the ST‑only period, thirty of forty PICU admissions with
Noninvasive positive pressure ventilation (NIPPV) was
SD satisfied inclusion criteria, while during the ST+ period, of
the initial choice in both groups among patients requiring
respiratory support. Intubation and PPV were initiated for 43 patients with SD who required PICU admission, 38 qualified
failed NIPPV and for patients who presented in extremis. for inclusion and constituted the ST+ group [Figure 1a].
Table 2 describes the baseline demography. There were no
Approach in standard therapy group
differences in age, weight, and severity grades, including the
Peri‑intubation strategies for intubation included lower doses
number admitted with hypotensive shock between the groups.
of benzodiazepines and opioids, and in patients who developed
However, the admission hematocrit was lower in the ST group
peri‑intubation hypotension, fluid resuscitation and inopressors
compared to the ST+ group.
were initiated.
Table 3 describes the ICU supportive therapies and
Approach in targeted intervention group
complications of SD patients in both groups.
A high‑risk intubation management protocol comprising
of preemptive strategies to prevent peri‑intubation With respect to the choice of colloid in patients who remained
cardiorespiratory decompensation was used, including in shock despite 30 ml/kg crystalloid, 4% gelatin was the
preference for low‑dose ketamine, preintubation continuous preferred colloid in the ST group and one patient also received
positive airway pressure (CPAP), and inopressor infusions in albumin. In the ST+ group, albumin was used as the preferred
all cases prior to induction [Table 1]. colloid in 42% of patients (albumin rescue).

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 Ranjit, et al.: Targeted Critical Care Interventions in Severe Dengue

The ST+ group had a significant reduction in FO and less peri‑intubation cardiorespiratory decompensation [Table 1],
PFB on days 1–3 [Table 3 and Figures 1, 2]. A significantly and these were successful in maintaining peri‑intubation
fewer number required intubation and IPPV compared to cardiopulmonary stability in all the seven patients.
the ST group (18.4% ST+ vs. 53.3% in ST, P = 0.003).
With respect to hemorrhage, better control of shock led to
Furthermore, fewer patients in the ST+ group developed
a lower incidence of major hemorrhage in the ST+ group
symptomatic abdominal compartment syndrome (ACS) that
necessitated invasive percutaneous drainage compared to the (23.6% in ST+ vs. 53% in ST group) [Table 3], and among
ST group (7.7% vs. 30%, P = 0.025) [Table 3]. those with major hemorrhage, the total volume of infused
blood products was lower compared in the ST group
With regard to peri‑intubation events, hypotension occurred (44.4 ± 18.7 ml/kg vs. 79.9 ± 66.4 ml/kg, P = 0.228).
soon after induction in 3 of 16 intubated patients in the ST Hemostatic measures were successful in controlling local
group, all of whom were stabilized with fluid and inopressors hemorrhage in 5 patients, thereby avoiding the requirement
[Table 3]. for blood products: two patients had torrential nasopharyngeal
Among the ST+ group, all the seven patients who needed hemorrhage which was successfully controlled by cuff
emergent intubation received preemptive strategies to prevent tamponade of a Foley catheter inserted nasally, and in three
patients, local hemostatic sutures successfully controlled
large‑volume femoral arterial line hemorrhage.
The incidence of AKI was lower in the ST+ group (5.3% vs.
a 33%, P = 0.04). Among patients requiring RRT, two patients in
the ST group received PD and three underwent CRRT; all the
three who underwent CRRT developed hypothermia despite the
use of an in‑line CRRT fluid‑warming device and insulation of
b tubing. During the ST+ period, two patients developed AKI and
Figure 1: (a)Flow of patients in standard therapy group. (b) Flow pattern were dialyzed using SLED, the latter modality was tolerated
of patients in ST+ group well in terms of circulatory and temperature stability.

Table 2: Demography and patient details

Characteristics ST group (n=30) TI (ST+) group (n=38) P
Age (months), mean (95% CI) 57.03 (38.94‑75.13) 69.05 (54.46‑83.65) 0.157
Male sex, n (%) 14 (46.7) 19 (50) 0.785
Weight (kg), mean (95% CI) 19.10 (14.0‑24.2) 22.42 (17.9‑26.9) 0.125
Platelet, median (IQR) 19,500 (12,000‑23,000) 21,000 (15,000‑31,000) 0.086
Hematocrit, median (IQR) 36 (26‑44) 45 (39‑48) 0.001
Hypotensive shock at presentation (Grade IV DHF)*, n (%) 13 (43.3) 12 (31.6) 0.318
PRISM III, median (IQR) 4 (3‑17) 5 (3‑16) 0.253
*DHF grade as per the WHO classification 1997. DHF: Dengue hemorrhagic fever; WHO: World Health Organization; CI: Confidence interval;
IQR: Interquartile range; TI: Targeted intervention

Table 3: Intensive care supportive therapies and complications in severe dengue

Outcome ST group (n=30) TI (ST+) (n=38) P
Albumin use, n (%) 1 (3.3) 16 (42.1) 0.0001
Day 1 PFB 7.5 (6.3‑12.8) 6.2 (4.7‑7.2) 0.004*
Day 2 PFB 7.1 (4‑9.6) 4.2 (2.5‑6.5) 0.045*
Day 3 PFB 1 (−0.4‑1.0) −0.5 (−3.0‑3.0) 0.079
Grand PFB* 17.8 (10.8‑25.2) 10.02 (5.7‑18.2) 0.009*
Requirement for PPV#, n (%) 20 (66.6 ) 10 (26.3 ) 0.001
Requirement of invasive ventilation, n (%) 16 (53.3) 7 (18.4) 0.001
Peri‑intubation complications 3/16 0/7 0.52
Percutaneous drainage of ACS, n (%) 9 (30) 3 (7.9) 0.01
Number of patients with major hemorrhage^, n (%) 16 (53.3) 9 (23.6) 0.01
Volume of blood products transfused (ml/kg), mean±SD 79.9±66.4 44.4±18.7 0.228
Incidence of AKI, n (%) 10 (33.3) 2 (5.3) 0.002
*Grand PFB: PFB for 1st 72 h, #Invasive + NIPPV, ^Major hemorrhage was considered to be present in patients with clinical evidence of bleeding,
persistent or recurrent shock, and fall in hematocrit >10%. Mean PFB calculation=(Total fluid intake [L]−total fluid output [L])/ICU admission body
weight (kg) × 100 (%). SD: Standard deviation; CI: Confidence interval; PFB: Positive fluid balance; AKI: Acute kidney injury; NIPPV: Noninvasive
positive pressure ventilation; ACS: Abdominal compartment syndrome; PPV: Positive pressure ventilation; TI: Targeted intervention; ST: Standard therapy

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 Ranjit, et al.: Targeted Critical Care Interventions in Severe Dengue

b
Figure 2: (a) Box plots showing positive fluid balance on days 1, 2, and 3, with P value 0.004 ( Day-1), 0.045 ( Day 2), 0.079 ( Day 3). (b) Box plots
showing grand positive fluid balance on the first 72 h of pediatric Intensive Care Unit. ST: Standard therapy group; ST+: Targeted intervention group

Table 4: Outcomes of patients with severe dengue requiring intensive care

Outcome ST (n=30) TI (ST+) (n=38) P
PICU days, mean (95th CI) 3.95 (2.93‑4.96) 3.64 (2.72‑4.56) 0.79
Hospitalization days, mean (95th CI) 6.9 (4.95‑8.84) 6.0 (4.41‑7.60) 0.69
Mortality among DHF Grade IV* patients (%) 8/13 (61) 1/12 (8.3) 0.01
Mortality among all patients (%) 8 (26) 1 (2.6) 0.008
*DHF Grade IV (WHO classification 1997). CI: Confidence interval; WHO: World Health Organization; DHF: Dengue hemorrhagic fever; PICU: Pediatric
Intensive Care Unit; TI: Targeted intervention; ST: Standard therapy

Overall, the PICU days and mortality were significantly major hemorrhage management
reduced in ST+ group versus ST group [mortality 2.6% vs. • One required albumin and major hemorrhage
26%, P = 0.004, Table 4]. management.
• Of The 5 interventions were utilized in the ST+ group • Five patients required three interventions each as follows:
as follows [Figure 3 and Table 3], the following findings • Two required albumin, intubation, and major
were noted [Figure 3]: hemorrhage management
• “Albumin rescue” was used most frequently in • One required intubation, peritoneal drains, and major
16 (42%) patients with unresolved shock despite hemorrhage management
30 ml/kg crystalloid and was the sole intervention in • One patient required albumin, major hemorrhage
11 patients management, and peritoneal drain for ACS
• Only one patient required tracheal intubation. • One required intubation, major hemorrhage
• Three patients required two interventions as follows: management, and SLED.
• Two required high‑risk intubation management and • Two patients required four interventions each: Albumin,

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Albumin use was associated with shock resolution with

lesser PFB in the ST+ group and the decreased FO may have
contributed to the lower incidence of malignant edema and
ACS [Table 3].
Plasma leak leading to tense ascitic fluid collections and
raised IAP resulting in ACS can develop rapidly during
large‑volume fluid therapy. ACS can further exacerbate shock
and oliguria leading to even more fluid infusion and further IAP
increase.[9] While extensively reported in trauma and burns,
dengue‑associated ACS has been infrequently reported and is
quite likely to be underrecognized.[3,7,23] Proactive monitoring
Figure 3: Pictogram depicting targeted interventions among 38 patients in of IAP in SD receiving > 30 ml/kg in the first 2–3 h can prompt
the ST+ group. P-drain: Peritoneal drain; ACS: Abdominal compartment earlier recognition and control of IAP.
syndrome; RRT-SLED: Renal replacement therapy with slow extended
daily dialysis; ST+: Targeted intervention group
With respect to respiratory issues, SD patients may develop
hypoxemic respiratory failure due to various reasons; however,
PPV can worsen shock by decreasing venous return to the
peritoneal drain, intubation, and major hemorrhage
heart.[1,3] Evidence supports efforts to preserve the patient’s
management
• One patient required all the five interventions. spontaneous respiratory drive by the use of either NIPPV or
CPAP in dengue,[2,3,10] and it was the initial choice of respiratory
support in both the ST and ST+ groups.
dIscussIon
Patients who fail NIV, or present in extremis, may need
In this report, we describe several ICU‑ and ED‑targeted
intubation, but this can be fraught with complications.
interventions that were applied in an anticipatory manner in
Intubation of the hypoxemic, shocked, acidotic dengue patient,
addition to the standard WHO recommendations in the sickest
patients with dengue. These were associated with decreased who may also be bleeding, may be associated with worsening
fluid accumulation and lower incidence of ACS, intubation, and hypoxemia, hypotension, aspiration, and cardiac arrest,[2,11] and
ventilator requirement, less AKI, PICU days, and lower mortality in these complications were seen more frequently in the ST group.
children with SD as compared to ST. These findings are important A high‑risk intubation management protocol which comprises
because dengue fever occurs mostly in low‑/middle‑income preemptive measures to avoid peri‑intubation deterioration
countries with limited resources and hence an approach that limits have been well described and include minimal sedatives,
treatment morbidity and mortality and conserves intensive care peri‑intubation PPV, and inopressors[11,12] and was successful
resources is important. While the gold standard for proving benefit in preventing peri‑intubation complications in the ST+ group.
is the randomized clinical trial, a pragmatic approach based on Moreover, sedatives used for induction and after
improving outcomes may be more practical.[17] intubation can worsen hypoperfusion by vasodilation and
The WHO guidelines emphasize the crucial importance of myocardial depression (benzodiazepines) and by blunting
restrictive fluid resuscitation in order to minimize FO;[1,2] however, adrenergic‑mediated stress response (opioids).[11,12] Ketamine
FO is common in hypotensive dengue patients who require large was used preferentially in the ST+ group since it can augment
volumes for shock reversal.[3] Colloid rescue is suggested by the blood pressure and is preferred for emergency induction of
WHO and Centers for Disease Control and Prevention (CDC) patients with acute circulatory instability.[12]
in refractory shock despite crystalloids where hemorrhage has The WHO guidelines stress that control of shock is the most
been excluded.[1,3,17] During the ST period, we used gelatin in important method to prevent hemorrhagic complications and
children with unresolved shock despite initial resuscitation with organ failure in dengue patients,[1] and this was borne out in
crystalloid, since dextran was one of the two colloids used in an the ST+ group, where better control of shock may have been
RCT in dengue shock that compared colloids versus crystalloids responsible for a lower incidence of major hemorrhage and
and reported improved shock resolution with colloids.[18] renal failure.
Albumin was preferred in the ST+ group and is suggested by Major hemorrhage can compound plasma leak and lead to much
the CDC in SD.[17] A strategy using “Albumin Rescue” has
worse shock in dengue, and management dictates a delicate balance
been shown to show decreased “fluid creep” and mortality
between correction of shock and coagulopathy and avoiding FO/
in severe burn shock, another condition which shares similar
massive transfusions; these patients have a high mortality risk.[1,3]
pathophysiology of extensive capillary leak and tendency
for compartment syndromes as SD.[19,20] In septic shock, In the ST group, a standard approach was followed in the event
reported benefits of albumin include support of the disrupted of major hemorrhage, and large volumes of blood components
glycocalyx,[21] better safety profile, and less complications were transfused in an attempt to correct deranged hemostasis
compared to the other synthetic colloids.[22] and reverse shock.

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 Ranjit, et al.: Targeted Critical Care Interventions in Severe Dengue

Among the ST+ group, among the nine children with intractable improved over time accounting for the improved results.
hemorrhage, bleeding was controlled with significantly lower While we cannot attribute outcomes to any particular therapy,
volumes of blood products using a multipronged approach, the evidence seems possible that approaches targeted to the
including hemostatic measures where applicable, preferential underlying pathophysiology may be beneficial and justify their
use of FWB rather than individual blood components, inclusion in future large‑scale research endeavors in critically
minimizing components of the lethal triad, and TXA infusion. ill dengue patients.
Modern transfusion medicine advocates fractionation of whole
blood into its components to better accommodate specific blood conclusIon
deficiencies, logistics, and financial reasons.[24] The use of the proactive targeted interventions was
associated with improved outcomes [Tables 3 and 4]
However, the WHO and CDC advocate FWB as the product
in a sick cohort of SD patients at the highest risk of
of choice in SD with hemorrhagic shock, as FWB can correct
complications and death.
hemostatic deficiencies and improve circulation and oxygen
delivery with minimal FO[1,2,17] although this may be difficult While both groups received standard ICU supportive therapies
to procure from modern blood banks. in conjunction with standard WHO therapy, the ST+ group
received specific interventions that were proactively targeted
There is a resurgence of interest in FWB, and trauma and
to the underlying pathophysiology of capillary leak, FO, shock
cardiac‑surgical literatures report that FWB transfusions are
and bleeding, and these may have contributed to improved
associated with a decreased incidence of hypothermia, acidosis,
outcomes.
infections, FO, and organ failure.[13] FWB can reverse dilution
coagulopathy, and one single warm unit has hemostatic effect Financial support and sponsorship
similar to 10 units of platelet concentrates, thus conferring Nil.
major benefits in terms of avoiding FO.[13]
Conflicts of interest
In addition to coagulopathy, bleeding in SD patients may occur There are no conflicts of interest.
due to activated fibrinolysis.[25] TXA, an antifibrinolytic agent,
has been reported in the setting of dengue with bleeding[26] and
is also useful in trauma patients to overcome fibrinolysis and
RefeRences
1. World Health Organization, Special Programme for Research and
improve hemostasis.[14] Training in Tropical Diseases. Dengue Hemorrhagic Fever: Diagnosis,
Treatment, Prevention and Control. 3rd ed. Geneva: World Health
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Organization, Special Programme for Research and Training in Tropical
hypothermia, and acidosis is familiar in major trauma[15] which Diseases; 2009.
can also occur in bleeding dengue patients where preexisting 2. World Health Organization, Special Programme for Research and
coagulopathy is compounded by hypothermia and acidosis, Training in Tropical Diseases. Handbook for Clinical Management of
Dengue. Geneva: World Health Organization, Special Programme for
but may be underrecognized.[27]
Research and Training in Tropical Diseases; 2012. Available from:
Hypothermia is a potent anticoagulant and has been reported http://www.wpro.who.int/mvp/documents/handbook_for_clinical_
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FO and AKI.[2,3,6] While CRRT was long considered most Am J Trop Med Hyg 2011;84:127‑34.
5. Wang CC, Liu SF, Liao SC, Lee IK, Liu JW, Lin AS, et al. Acute
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shock syndrome may decrease mortality rate: A suggested protocol.
All the three patients in the ST group who received CRRT Pediatr Crit Care Med 2005;6:412‑9.
became hypothermic despite measures to circumvent 7. Kamath SR, Ranjit S. Clinical features, complications and atypical
temperature drop in the extracorporeal circuit. Of note, SLED manifestations of children with severe forms of dengue hemorrhagic
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