Serum Procalcitonin and Peripheral Venous Lactate for Predicting Dengue Shock and/or Organ Failure: A Prospective Observational Study

Abstract

Background: Currently, there are no biomarkers that can predict the incidence of dengue shock and/or organ failure, although the early identification of risk factors is important in determining appropriate management to reduce mortality. Therefore, we sought to determine the factors associated with dengue shock and/or organ failure and to evaluate the prognostic value of serum procalcitonin (PCT) and peripheral venous lactate (PVL) levels as biomarkers of dengue shock and/or organ failure.

Methodology/principal findings: A prospective observational study was conducted among adults hospitalized for confirmed viral dengue infection at the Hospital for Tropical Diseases in Bangkok, Thailand between October 2013 and July 2015. Data, including baseline characteristics, clinical parameters, laboratory findings, serum PCT and PVL levels, management, and outcomes, were recorded on pre-defined case report forms. Of 160 patients with dengue, 128 (80.0%) patients had dengue without shock or organ failure, whereas 32 (20.0%) patients developed dengue with shock and/or organ failure. Using a stepwise multivariate logistic regression analysis, PCT ≥0.7 ng/mL (odds ratio [OR]: 4.80; 95% confidence interval [CI]: 1.60-14.45; p = 0.005) and PVL ≥2.5 mmol/L (OR: 27.99, 95% CI: 8.47-92.53; p <0.001) were independently associated with dengue shock and/or organ failure. A combination of PCT ≥0.7 ng/mL and PVL ≥2.5 mmol/L provided good prognostic value for predicting dengue shock and/or organ failure, with an area under the receiver operating characteristics curve of 0.83 (95% CI: 0.74-0.92), a sensitivity of 81.2% (95% CI: 63.6-92.8%), and a specificity of 84.4% (95% CI: 76.9-90.2%). Dengue shock patients with non-clearance of PCT and PVL expired during hospitalization.

Conclusions/significance: PCT ≥0.7 ng/mL and PVL ≥2.5 mmol/L were independently associated with dengue shock and/or organ failure. The combination of PCT and PVL levels could be used as prognostic biomarkers for the prediction of dengue shock and/or organ failure.

Conflict of interest statement

All authors have declared that no competing interests exist in this study. Roche Diagnostics (Thailand) Ltd. provided Elecsys BRAHMS PCT as a gift for this study. All authors have declared that the Roche Diagnostics (Thailand) Ltd. had no role in study design, data collection and/or analysis, the decision to publish, or preparation of the manuscript.

Figures

Fig 1. Flow diagram showing the recruitment of study patients.

ELISA, enzyme-linked immunosorbent assay; RT-PCR, reverse-transcriptase polymerase chain reaction.

Fig 2. Serum procalcitonin and peripheral venous lactate at admission in dengue patients.

(A) Serum procalcitonin levels among patients with and without dengue shock and/or organ failure. (B) Peripheral venous lactate levels among patients with and without dengue shock and/or organ failure. Data are presented as box and whisker plots with median (horizontal line), interquartile range (box), maximum value within 1.5 of interquartile range (whiskers), outliers (circles), and extreme outliers (asterisks).

Fig 3. Receiver operating characteristic curves for serum procalcitonin and peripheral venous lactate in the prediction of dengue shock and/or organ failure at admission.

(A) The area under the receiver operating characteristic curve (AUROC) for serum procalcitonin at admission was 0.69 (95% confidence interval [95% CI]: 0.59–0.80). (B) The AUROC for peripheral venous lactate at admission was 0.78 (95% CI: 0.68–0.88). (C) The AUROC for a combined bioscore at admission was 0.83 (95% CI: 0.74–0.92). (D) The AUROC for the number of warning signs at admission was 0.77 (95% CI: 0.68–0.87).

Fig 4. Daily changes in serum procalcitonin and peripheral venous lactate during hospitalization.

(A) Changes in average serum procalcitonin (ng/mL) levels among patients with and without dengue shock and/or organ failure by survival status. (B) Changes in peripheral venous lactate (mmol/L) levels among patients with and without dengue shock and/or organ failure by survival status. Data are presented as box and whisker plots with median (horizontal line), interquartile range (box), and maximum value within 1.5 of interquartile range (whiskers).