Early resuscitation of dengue shock syndrome in children with hyperosmolar sodium-lactate: a randomized single-blind clinical trial of efficacy and safety

Abstract

Introduction: Dengue shock syndrome (DSS) fluid resuscitation by following the World Health Organization (WHO) guideline usually required large volumes of Ringer lactate (RL) that might induce secondary fluid overload. Our objective was to compare the effectiveness of the recommended volume of RL versus a smaller volume of a hypertonic sodium lactate solution (HSL) in children with DSS. The primary end point was to evaluate the effect of HSL on endothelial cell inflammation, assessed by soluble vascular cell adhesion molecule-1 (sVCAM-1) measurements. Secondarily, we considered the effectiveness of HSL in restoring hemodynamic fluid balance, acid-base status, and sodium and chloride balances, as well as in-hospital survival.

Methods: A prospective randomized single-blind clinical trial including 50 DSS children was conducted in the Pediatrics Department of Hasan Sadikin Hospital, Bandung, Indonesia. Only pediatric patients (2 to 14 years old) fulfilling the WHO criteria for DSS and new to resuscitation treatments were eligible. Patients were resuscitated with either HSL (5 ml/kg/BW in 15 minutes followed by 1 ml/kg/BW/h for 12 hours), or RL (20 ml/kg/BW in 15 minutes followed by decreasing doses of 10, 7, 5, and 3 ml/kg BW/h for 12 hours).

Results: In total, 50 patients were randomized and included in outcome and adverse-event analysis; 46 patients (8.2 ± 0.5 years; 24.9 ± 1.9 kg; mean ± SEM) completed the protocol and were fully analyzed (24 and 22 subjects in the HSL and RL groups, respectively). Baseline (prebolus) data were similar in both groups. Hemodynamic recovery, plasma expansion, clinical outcome, and survival rate were not significantly different in the two groups, whereas fluid accumulation was one third lower in the HSL than in the RL group. Moreover, HSL was responsible for a partial recovery from endothelial dysfunction, as indicated by the significant decrease in sVCAM-1.

Conclusion: Similar hemodynamic shock recovery and plasma expansion were achieved in both groups despite much lower fluid intake and fluid accumulation in the HSL group.

Trial registration: ClinicalTrials.gov NCT00966628. Registered 26 August 2009.

Figures

Figure 1

Profile of the randomized controlled trial.

Figure 2

Study flow chart.

Figure 3

Effect of treatments on systolic blood pressure and hematocrit. Open circles, RL; solid circles, HSL.

Figure 4

Effect of treatments on fluid balance. Open circles, RL; solid circles, HSL.

Figure 5

Effect of treatments on homeostasis (D-dimer) and endothelial cell dysfunction (sVCAM-1). Open bars, RL; solid bars, HSL. Comparisons were performed by using Wilcoxon tests for paired data (effect of time) and Mann–Whitney tests for unpaired data (difference between the two groups).

Figure 6

Effect of treatments on sodium and chloride balance. Open bars, RL; solid bars, HSL. Comparisons were performed by using Mann–Whitney tests.