The Role of Fluid Resuscitation in Dengue Shock Syndrome: A Comprehensive Systematic Review of Randomized Controlled Trials and Primary Studies

Abstract

Introduction: Dengue shock syndrome (DSS) represents the most severe manifestation of dengue virus infection, characterized by acute endothelial hyperpermeability leading to profound intravascular volume depletion. Despite the absence of specific antiviral therapy, parenteral fluid replacement remains the cornerstone of management. However, WHO recommendations regarding fluid type, volume, and de-escalation strategies rest upon limited and ageing evidence.

Methods: This systematic review, conducted in accordance with PRISMA 2020 guidelines, synthesized evidence from 24 primary studies (5 randomized controlled trials, 19 observational studies) encompassing >11,000 patients. Eligibility included RCTs, cohort, case-control, and cross-sectional studies evaluating intravenous or oral fluid therapy in children and adults with dengue hemorrhagic fever, DSS, or severe dengue. Fourteen prespecified outcome domains were extracted. Methodological quality was assessed using Cochrane RoB 2, Newcastle-Ottawa Scale, and ROBINS-I, with GRADE certainty rating per outcome.

Results: Isotonic crystalloid demonstrated non-inferiority to synthetic colloid for initial resuscitation in moderate paediatric DSS (RR 1.08, 95% CI 0.78-1.47). Cumulative fluid volume at 24 hours discriminated mechanical ventilation requirement with AUC 0.871 (threshold 181 mL/kg), and colloid-to-crystalloid ratio with AUC 0.781 (threshold 1.6). Liberal-colloid maintenance strategy increased respiratory compromise odds 8.84-fold (p<0.001) and respiratory support odds 8.16-fold (p<0.001) while reducing recurrent shock (RR 0.13, p=0.043). Ventilated children exhibited 22.4% mortality versus 0.1% in non-ventilated. Dengue-associated acute kidney injury occurred in 4.8-35.1%, with fatality 22.4% versus 5.7% without renal injury.

Discussion: The evidence supports reconceptualizing DSS fluid therapy from volume-maximizing to volume-titrating paradigm. Colloid physiological advantages in surrogate haemodynamic endpoints do not translate into survival benefit, and prolonged colloid exposure is positively harmful, particularly where respiratory support is unavailable.

Conclusion: Isotonic crystalloid constitutes first-line resuscitation for moderate DSS. Cumulative volume and colloid proportion are modifiable, dose-dependent determinants of respiratory failure, renal injury, and mortality. Adequately powered multicentre RCTs in paediatric and adult DSS with protocolised de-resuscitation represent the highest research priority.