Crystalloid vs Colloid in Initial Management of Dengue Shock Syndrome – A Meta-Analysis of Randomized Controlled Trials

Abstract

Background:
Dengue shock syndrome is a serious complication of dengue fever characterized by vascular leakage and disorder of hemostasis. The mainstay of therapy is by intravenous fluid replacement in such cases. However, there has long been a debate about whether crystalloid or colloid solutions should be used during initial management of
dengue shock syndrome.

Methods:
We searched the PubMed and Cochrane database for randomized controlled trials regarding fluid management in dengue shock syndrome. The search results were independently screened by both authors, first by title, then abstract and lastly by full text. Three studies were included based on the inclusion criteria. Data was extracted and
calculations were done using RevMan 5.3 software. We selected two outcomes, the first being recurrent shock after initial fluid therapy and the second being decrease of hematocrit value. Random effect model was used for calculations.

Results:
We grouped the intravenous fluids into colloid and crystalloid groups. Comparison was done based on recurrent shock and decrease of hematocrit after initial fluid therapy. The odds ratio of recurrent shock with crystalloid vs colloid was 1.17 (0.83, 1.65). Heterogeneity was I2 =0%. Overall effect was Z=0.90 (P=0.37). The mean difference of hematocrit decrease with crystalloid vs colloid was -4.41 (-5.69, -3.14). Heterogeneity was I2 =15%. Overall effect was Z=6.79 (P<0.00001).

Conclusion:
The meta-analysis shows slight advantage of colloid in decreasing hematocrit if used during initial therapy. However, there was no significant difference between crystalloids and colloids in terms of preventing recurrent shock. In the light of this finding the current WHO guideline seems appropriate in managing dengue shock syndrome. However, this study was limited by small number of included studies and the P value of the comparison of recurrent shock was non-significant. Further studies may be warranted to explore the role of colloids in the initial management of dengue shock syndrome.

Full text

CRYSTALLOID VS COLLOID IN THE
INITIAL MANAGEMENT OF DENGUE
SHOCK SYNDROME:
A META-ANALYSIS OF RANDOMIZED
CONTROLLED TRIALS
Agnibho Mondal1, Bishal Gupta2
1. Department of Tropical Medicine
2. Department of Microbiology
School of Tropical Medicine, Kolkata
Presented at the 9th CME of STMIDI on August 18, 2019

BACKGROUND
•Dengue shock syndrome is a serious complication of dengue fever
•Characterized by
•Vascular leakage
•Disorder of hemostasis
•The mainstay of therapy is by intravenous fluid replacement.
•However, there has long been a debate about whether crystalloid or
colloid solutions should be used during initial management of
dengue shock syndrome.

THE QUESTION
•Crystalloid or colloid
•Which one is better during initial management of dengue shock syndrome
•In respect to clinical outcome and blood parameters

LITERATURE SEARCH
•We searched PubMed and Cochrane database
•Search term – “dengue AND shock AND syndrome AND randomized controlled
trial [Publication Type]”
•Search results were manually filtered by
•Studies comparing colloid vs crystalloid solutions in early management of dengue shock syndrome

OUTCOME
•Primary outcome
•Recurrent shock after initial therapy
•Secondary outcome
•Drop in hematocrit after initial therapy

INCLUSION OF STUDIES
•Inclusion criteria
•Compare crystalloid vs colloid therapy for initial management of DSS
•Available outcome –recurrent shock and drop of hematocrit
•All literature search results were reviewed independently by both authors
•First by Title, then Abstract and then Full Text
•Any contradiction was resolved by discussion between the authors
•Three studies qualified for inclusion in this meta-analysis

INCLUSION FLOWCHART
56 results found by
the search term
6 studies manually
selected by title
4 studies remain after
removing duplicates
3 studies match the
inclusion criteria

RISK OF BIAS ANALYSIS
Studies
Randomization
Process
Deviation from
intended intervention
Missing
outcome
data
Measurement
of outcome
Selection of
reported
result
Overall
Part 1
Part 2
Dung 1999
Low risk
Low risk
Low risk
Low risk
Low risk
Some concerns
Some concerns
Nhan
2001
Some concerns
Low risk
Low risk
Low risk
Low risk
Some concerns
High risk
Wills 2005
Low risk
Low risk
Low risk
Low risk
Low risk
Some concerns
Some concerns
Risk of bias analyzed by RoB tool version 2 by Cochrane Collaboration

DATA EXTRACTION AND CALCULATION
•Data was extracted after reading the full text of the
included studies
•A table was made from the extracted data regarding
•Occurrence of recurrent shock after initial fluid management
•Drop in hematocrit after initial fluid management
•For calculation RevMan 5.3 software was used
•We decided to use a fixed effect model for the purpose of
the calculations

ANALYIS RESULTS: RECURRENT SHOCK
•The odds ratio of crystalloid vs colloid was 1.17
•Confidence interval was 0.83 to 1.65
•Heterogeneity
•I2 = 0%
•Overall effect
•Z = 0.89 (P = 0.37)

ANALYIS RESULTS: HEMATOCRIT DECREASE
•The mean difference of crystalloid vs colloid was -4.46
•Confidence interval was -5.23 to -3.69
•Heterogeneity
•I2 = 15%
•Overall effect
•Z = 11.34 (P < 0.00001)

RECURRENT SHOCK HEMATOCRIT DROP
FUNNEL PLOTS

SUMMARY
•The meta-analysis shows slight advantage of
colloid in decreasing hematocrit
•No significant difference between crystalloids and
colloids in terms of preventing recurrent shock.

LIMITATIONS
•Small number of included studies
•Only 3 studies met the inclusion criteria
•Large P value (0.37) for the comparison of
recurrent shock

CONCLUSION
•In the light of the finding of this meta-analysis, the current guideline seems
appropriate in managing dengue shock syndrome.
•Which uses crystalloid first and then uses colloid for management of recurrent shock
•However colloid was significantly better at reducing hematocrit early
•So further studies may be warranted to explore the role of colloids in the initial
management of dengue shock syndrome

REFERENCES TO STUDIES
•N. M. Dung, N. P. J. Day, D. T. H. Tam, H. T. Loan,H. T. T. Chau, L. N. Minh, T. V. Diet, D. B. Bethell,R. Kneen, T. T. Hien,
N. J. White, and J. J. Farrar. Fluid Replacement in Dengue Shock Syndrome: A Randomized, Double-
BlindComparison of Four Intravenous-Fluid Regimens. Clinical Infectious Diseases 26 February
1999;29:787-94
•Ngo Thi Nhan, Cao Xuan Thanh Phuong, Rachel Kneen, Bridget Wills, Nguyen Van My,Nguyen Thi Que Phuong,
Chu Van Thien, Nguyen Thi Thuy Nga, Julie A. Simpson, Tom Solomon,Nicholas J. White and Jeremy Farrar. Acute
Management of Dengue Shock Syndrome:A Randomized Double-Blind Comparisonof 4 Intravenous Fluid
Regimensin the First Hour. Clinical Infectious Diseases Q 2 June 2000;32:204-13
•Bridget A. Wills, M.R.C.P., Nguyen M. Dung, M.D., Ha T. Loan, M.D., Dong T.H. Tam, M.D., Tran T.N. Thuy, M.D.,Le
T.T. Minh, M.D., Tran V. Diet, M.D., Nguyen T. Hao, M.D., Nguyen V. Chau, M.D., Kasia Stepniewska, Ph.D.,Nicholas
J. White, F.R.C.P., and Jeremy J. Farrar, F.R.C.P.. Comparison of Three Fluid Solutions for Resuscitationin Dengue
Shock Syndrome. The New England Journal of Medicine september 1, 2005;353:877-89.

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