Professional Documents
Culture Documents
IJP Volume 7 Issue 4 Pages 9215-9224
IJP Volume 7 Issue 4 Pages 9215-9224
ir
Original Article (Pages: 9215-9224)
Abstract
Background:
Fluid resuscitation is the mainstay of treatment to counteract massive plasma leakage in dengue shock
syndrome. We aimed to determine the differences in clinical outcomes and hemodynamic parameters
of children with dengue shock syndrome post restrictive and liberal fluid resuscitation.
Materials and Methods: A retrospective observational study of pediatric patients who were between
one month to 18 years old, presented with clinical criteria for dengue hemorrhagic fever (DHF) grade
III and IV based on WHO classification of dengue fever in 2011, and admitted to the Saiful Anwar
General Hospital, Malang- Indonesia, from January 2016 to December 2016. Patients were divided in
two groups: resuscitated with either <40 ml/kg body weight [BW] (restrictive group) or > 40ml/kg
BW (liberal group) solutions; then we analyzed the clinical outcomes and hemodynamic parameters
between two groups.
Results
Among 100 patients, 92 patients were classified as DHF grade III and 8 patients were DHF grade IV.
74 patients were in the restrictive group and 24 patients were in the liberal group. Median age at
diagnosis was 6 years old, and 56% of patients were female. No significant differences were observed
between length of stay in pediatric intensive care unit (P=0.09), and duration of ventilator use
(P=0.68). The restrictive group had 53% lower mortality compared to the liberal group (P=0.18). This
study also showed that there were no significant differences in hemodynamic parameters between two
groups based on measurement with USCOM which were preload component (SVV) (P=0.89),
inotropy components (SMII) (P=0.07), SVRI (P=0.85) as well as the cardiac index (P=0.66).
Conclusion
This study showed that there is no difference in clinical outcomes (length of mechanical ventilation
and length of PICU stay), and hemodynamic parameters (preload, inotropy, afterload, and cardiac
index) in Dengue Shock Syndrome patients who receive restrictive or liberal fluid resuscitation.
Key Words: Children, Dengue Shock Syndrome, Liberal, Fluid resuscitation, Restrictive.
*Please cite this article as: Yuliarto S, Kadafi KT, Anitasari D. Restrictive versus Liberal Fluid Resuscitation in
Children with Dengue Shock Syndrome: the differences in Clinical Outcomes and Hemodynamic Parameters.
Int J Pediatr 2019; 7(4): 9215-24. DOI: 10.22038/ijp.2018.36587.3186
*Corresponding Author:
Saptadi Yuliarto, Pediatric Intensivist, Address: Saiful Anwar General Hospital, JA Suprapto street 2, Malang,
East Java, Indonesia. Postal code 65111; Fax: +62-341-564-755
Email: : dr.saptadiyuliarto@gmail.com
Received date: Nov.14, 2018; Accepted date: Dec. 22, 2018
(USCOM 1A, USCOM PVT Ltd, Coffs discontinued if therapeutic goals are
Harbor, NSW, Australia). The measured achieved or total fluid amount is 40 ml/kg,
parameters included stroke volume or patient reveals sign of fluid overload
variation (SVV), Smith-Madigan Inotropy (liver enlargement or rales). In case of
Index (SMII), potential for kinetic ratio persistent shock following 40 ml/kg of
(PKR), stroke volume index (SVI), cardiac fluid bolus or fluid overload, diuretics and
index (CI), and systemic vascular vasoactive agents are administered based
resistance index (SVRI). We measured on CI and SVRI level. Inotropes
aortic valve (AV) diameter by using (dopamine 5-10 mcg/kg/min, dobutamine
patient’s age, weight, and height. We also 5-20 mcg/kg/min, or epinephrine 0.05-0.3
used Doppler to measured velocity time mcg/kg/min) are given in low CI – high
integral (VTI). We obtained stroke volume SVRI case, and can be combined with
(SV) using available AV diameter and vasodilator (milrinone 0.5-0.75
VTI. In context of preload; SVV is mcg/kg/min) if blood pressure is normal.
defined as stroke volume which is Vasopressor (norepinephrine 0.05
variation by respiratory cycle. We can mcg/kg/min-1 mcg/kg/min or epinephrine
measure CI by incorporating heart rate >0.3 mcg/kg/min) is given in high CI –
with SV. Afterload in the form of SVR and low SVRI case. Combination of inotropes
SVRI can be computed with the input of and vasopressor are given in low CI- low
blood pressure. Inotropy in the form of SVRI case.
SMII was calculated using a purpose-
2-5. Ethical consideration
written computer program based on Smith-
Madigan formula given with the input of This study was approved by Ethical
SV. SVV ≤30% was defined as fluid- Commission of Medical/Health
refractory shock, and >30% as fluid- Researches, Faculty of Medicine,
responsive shock. Each of the parameters University of Brawijaya, Saiful Anwar
SMII, PKR, and SVI was divided into 3 Hospital (letter no. 400/28/K.3/302/2018).
levels; that is: low, normal, and high, All participants’ parent or guardian
based on the respective normal value for provided informed written consent.
age (7). In addition, normal CI and SVRI 2-6. Inclusion and exclusion criteria
were 3.3-6.0 L/min/m2 and 800-1600
dyne.sec.cm-5 m-2, respectively; a below- In this study, DSS children with age from
normal value was categorized as a low, 1 month to 18 years old who were
while an above normal as high (8). A admitted to pediatric intensive care unit
pediatric emergency and intensive care (PICU), pediatric wards, and emergency
consultant or trained-senior resident room at a Saiful Anwar General Hospital
performed all measurements. from January 2016 to December 2016
were included. The exclusion criteria were
2-4. Hospital protocol children with congenital heart diseases,
The hospital protocol recommends fluid immunodeficiency disorders, autoimmune
bolus 20 ml/kg for 5-15 minutes in case of diseases, pulmonary diseases, hematology
DSS, and can be repeated until 40 ml/kg to diseases, and renal diseases.
achieve the therapeutic goals (normal 2-7. Data Analyses
heart/pulse rate and blood pressure
according to age, normal perfusion [CRT, Data were analyzed using SPSS for
urine output, mental status], cardiac index Windows 20.0 (IBM Corp., Chicago, IL).
[CI] 3.3-6.0 L/min/m2, and systemic Continuous variables were expressed as
vascular resistance [SVRI] 800-1600 mean and standard deviation (SD).
d.s/cm5/m2). Fluid bolus must be Variables with non-normal distributions
were summarized with medians and were similar between the restrictive and
interquartile ranges (IQR), as appropriate. liberal groups. Median age at restrictive
The two independent groups were group was 6.0 years old whereas median
compared using Mann-Whitney test. age at liberal group was 5.5 years old.
Categorical variables were expressed as Among the 100 cases, 92 (92%) patients
frequencies and percentages and analyzed were classified as DHF grade III and 8
with Chi-square tests or Fisher’s exact (8%) patients were DHF grade IV. In the
tests, as appropriate. Level of statistical restrictive group, the majority of DSS
significance was declared at p- value < patients 42 (56.8%) had a normal
0.05 levels. nutritional status, while 16 patients
(21.6%) had an underweight nutritional
3- RESULTS status and 16 patients (21.6%) had an
3-1. Baseline characteristics overweight nutritional status. In the liberal
group, among 26 patients, 15 (57.7%)
As shown in Table.1, one hundred patients had a normal nutritional status,
patients enrolled and were analyzed (74 while 7 (26.9%) patients had an
and 26 subjects in the restrictive and overweight nutritional status and 4
liberal groups, respectively). Of the 100 (15.4%) patients had an underweight
patients, 56 (56%) patients were female. nutritional status.
The median age and gender distribution
3-3. Hemodynamic parameters group, while median SVRI for 5-18 years
Regarding the hemodynamic parameters of old was 1959 d.s/cm5. In comparison, the
mean SVRI in liberal group was 1526.7 ±
the study patients (Table.3), no significant
244.0 d.s/cm5 for 0-2 years age group,
difference was observed among two
groups (P>0.05). The mean SVV was 2097.1 ± 715.1 d.s/cm5 for 3-4 years old,
while median SVRI for 5-18 years old was
similar in two groups: 29.0 ± 10.7% in
1970 d.s/cm5. There were no significant
restrictive group and 29,5 ± 12,2% in
liberal groups (P=0.89). Patients in differences in SVRI between two groups
(P>0.05), yet the level was higher than
restrictive groups had similar SMII
normal value, especially in >3 years old
compared with liberal groups (1 W/m2
versus 1.2 W/m2 ) (P=0.07); however, group. Cardiac index was similar in both
groups (P>0.05). Mean cardiac index for
SMII level in both groups was lower than
3-4 years old group in restrictive group
normal value according to age. Mean
SVRI in restrictive group was 1490.7 ± and liberal group was 3.48 ± 0.73
L/min/m2 and 3.00 ± 0.88 L/min/m2 ,
355.6 d.s/cm5 for 0-2 years age group,
respectively (P=0.66).
2071.2 ± 712.4 d.s/cm5 for 3-4 years
Values are presented as mean± standard deviation (SD) or median and interquartile ranges (IQR); SVRI:
SMII: P-value was considered significant if P-value < 0.05.
value in normal children (Smith BE). The due to sinus bradycardia (32). In critically
lower value of SMII in both groups ill children, adequate fluid resuscitation is
demonstrated the presence of myocardial a particular challenge for the physician
depression in some children with DSS since fluid hemostasis is maintained in a
even though the cause of cardiac narrow range and physiological
dysfunction in DSS is still unknown (29). compensation of both hypervolemia and
Although fluid administration was aimed hypovolemia is limited (33). SVV is a
at increasing intravascular volume to a reliable predictor in the assessment of fluid
certain extent, and could increase responsiveness in adult patients (34), and it
myocardial muscle fiber resulting in is important to monitor the need for fluid
increased strength of myocardial resuscitation and optimize the number of
contraction (29), another study mentioned preloads in critical children (32). We
that excessive fluid resuscitation could found that SVV in both groups has similar
also cause cardiac dysfunction in patients results (P=0.89), despite difference of fluid
with increased vascular permeability by resuscitation volumes. SVV less than 30%
causing myocardial edema (30). Moreover, was found in both groups which
one study stated that almost 58% of demonstrated patients with DSS had a
children with shock are refractory shock refractory shock condition. These results
that required vasoactive drugs which were consistent with previous study which
indicated a disruption of myocardial showed that most of refractory fluid
function (5). Therefore, our result showed conditions in children were reached after
that inotropy index correlated negatively fluid administration 40 ml/kg BW (5).
with the amount of intravenous fluid
Important changes in blood pressure also
resuscitation (Table.3).
take place during DSS, including enhanced
Because a causal relationship between peripheral vascular resistance with
cardiac dysfunction and the occurrence of diminished cardiac output and normal or
shock cannot be determined from this low central venous pressure (35). Thus we
study, we assumed cardiac dysfunction can measured SVRI which represented the
also be the result of coronary resistance to blood flow offered by all the
hypoperfusion from low cardiac output. systemic vasculature. Our study showed
Thus, we measured cardiac output there was an increased SVRI and similar
component in both groups. The Cardiac results (P=0.94) in both groups compared
Index (CI) is one of the hemodynamic to SVRI value in normal children (31). The
parameters on USCOM examination that elevated SVRI in DSS is likely to be
represents the cardiac output component. affected by contracted intravascular
Despite receiving different amounts of volume. We evaluated the clinical
fluid resuscitation, we found that CI values outcomes after fluid resuscitation in both
were similar (P=0.66), and still within groups and found that the median length of
normal limits in both groups (31). stay in PICU, duration of mechanical
Probably this result was due to ventilation, and fluid excess in both groups
compensation of increased heart rates for had no significant difference (P=0.09,
the poor blood circulation and tend to P=0.68, P=0.83, respectively). These
maintain mean arterial pressure (MAP) in results are likely to be affected by our
DSS patients. CI was also low during the critical care management in DSS children
toxic stage due to decreased preload (low which is based on our hospital protocol. In
end-diastolic volume) and depressed left this study, the use of noninvasive
ventricular ejection fraction. CI also hemodynamic monitoring, the restrictive
remained subnormal during convalescence fluid management, timely use of
fever revised and expanded edition. New City, Vietnam. Am J Trop Med Hyg.
Delhi: World Health Organization South East 2011;84:127-134.
Asia Regional Office; 2011.
12. Biswas HH, Ortega O, Gordon A,
3. Hadinegoro SR, Moedjianto I, Standish K, Balmaseda A, Kuan G,et al. Early
Chairulfatah A, Alam A, Setiabudi D, Hapsari clinical features of dengue virus infection in
MM, et al. Handbook for diagnosis and nicaraguan children: a longitudinal analysis.
management of dengue virus infection in PloS Negl Trop Dis. 2012;6:e1562.
children. Jakarta: Coordination work unit of
13. Guzman MG, Kouri G. Dengue: an
infection and tropical diseases IDAI; 2014:1-
update. Lancet Infect Dis.2002;2:33-42.
26.
14. Reitsma S, Slaaf DW, Vink H, van
4. Yacoub S, Griffiths A, Chau TT,
Zandvoort MA, oude Egbrink MG. The
Simmons CP, Wills B et al. Cardiac function
endothelial glycocalyx: composition,
in Vietnamese patients with different dengue
functions, and visualization. Pflugers Arch.
severity grades. Crit Care Med. 2012; 2007;454(3):345-59.
40(2):477-83.
15. Puerta-Guardo, Glasner DR, Harris E.
5. Yuliarto S. Hemodynamic parameter
Dengue virus NS1 disrupts the endothelial
changes in pediatric shock after fluid
glycocalyx leading to hyperpermeability. PloS
resuscitation and vasoactive drugs therapy.
Pathog. 2016;12(7):e1005738.
Jakarta: University of Indonesia (thesis); 2014.
16. Chappell D, Westphal M, Jacob M.
6. Ranjit S, Kissoon N, Jayakumar I.
The impact of the glycocalyx on
Aggressive management of dengue shock
microcirculatory oxygen distribution in critical
syndrome may decrease mortality rate: a
illness. Curr Opin Anaesthesiol.
suggested protocol. Pediatr Crit Care Med.
2009;22(2):155-62.
2005;6(4):412-9.
17. Becker BF, Chappell D, Bruegger D,
7. Giraldo D, Sant’Anna C, Perisse AR,
Annecke T, Jacob M. Therapeutic strategies
March Mde F, Souza AP, Mendes A, et al.
targeting the endothelial glycocalyx: acute
Characteristics of children hospitalized with
deficits, but great potential. Cardiovasc Res.
dengue fever in an outbreak in Rio de Janeiro, 2010;87(2):300-10.
Brazil. Trans R Soc Trop Med Hyg.
2011;105:601-3. 18. Dellinger RP, Levy MM, Carlet JM,
Bion J, Margaret M, et al. Surviving Sepsis
8. Pinsky MR, Payen D. Functional
Campaign: International guidelines for
hemodynamic monitoring. Crit Care.
management of severe sepsis and septic shock.
2005;9(6):566-72.
Crit Care Med. 2008;36:296–327.
9. Bunnag T, Kalayanarooj S. Dengue
19. Santhanam I, Sangareddi S,
shock syndrome at the emergency room of
Venkataraman S, Kissoon N,
Queen Sirikit National Institute of Child
Thiruvengadamudayan V, Kasthuri RK. A
Health, Bangkok, Thailand. J Med Assoc Thai
prospective randomized controlled study of
2011;94:S57-S63.
two fluid regimens in the initial management
10. Wills B, Nguyen MD, Ha TL, Dong of septic shock in the emergency department.
THT, Tran TNT, Le TTM, et al. Comparison Pediatr Emerg Care. 2008;24:647-55.
of three fluid solutions for resuscitation in
20. Jozwiak M, Monnet X, Teboul JL.
dengue shock syndrome. N Engl J Med.
Prediction of fluid responsiveness in ventilated
2005;353:877-.89.
patients. Ann Transl Med. 2018;6(18):352.
11. Anders KL, Nguyet NM, Chau NVV,
21. Somasetia DH, Setiati TE, Sjahrodji
Hung NT, Thuy TT, Lien LB,et al.
AM, Idjradinata PS, Setiabudi D, Roth H.
Epidemiological factors associated with
Early resuscitation of dengue shock syndrome
dengue shock syndrome and mortality in
in children with hyperosmolar sodium-lactate:
hospitalized dengue patients in Ho Chi Minh
a randomized single-blind clinical trial of