Association of Microvascular Function and Endothelial Biomarkers With Clinical Outcome in Dengue: An Observational Study.

BACKGROUND: The hallmark of severe dengue is increased microvascular permeability, but alterations in the microcirculation and their evolution over the course of dengue are unknown. METHODS: We conducted a prospective observational study to evaluate the sublingual microcirculation using side-stream dark-field imaging in patients presenting early (<72 hours after fever onset) and patients hospitalized with warning signs or severe dengue in Vietnam. Clinical findings, microvascular function, global hemodynamics assessed with echocardiography, and serological markers of endothelial activation were determined at 4 time points. RESULTS: A total of 165 patients were enrolled. No difference was found between the microcirculatory parameters comparing dengue with other febrile illnesses. The proportion of perfused vessels (PPV) and the mean flow index (MFI) were lower in patients with dengue with plasma than those without leakage (PPV, 88.1% vs 90.6% [P = .01]; MFI, 2.1 vs 2.4 [P = .007]), most markedly during the critical phase. PPV and MFI were correlated with the endothelial activation markers vascular cell adhesion molecule 1 (P < .001 for both) and angiopoietin 2 (P < .001 for both), negatively correlated. CONCLUSIONS: Modest microcirculatory alterations occur in dengue, are associated with plasma leakage, and are correlate with molecules of endothelial activation, angiopoietin 2 and vascular cell adhesion molecule 1.

Cardio-haemodynamic assessment and venous lactate in severe dengue: Relationship with recurrent shock and respiratory distress.

BACKGROUND: Dengue can cause plasma leakage that may lead to dengue shock syndrome (DSS). In approximately 30% of DSS cases, recurrent episodes of shock occur. These patients have a higher risk of fluid overload, respiratory distress and poor outcomes. We investigated the association of echocardiographically-derived cardiac function and intravascular volume parameters plus lactate levels, with the outcomes of recurrent shock and respiratory distress in severe dengue. METHODS/PRINCIPLE FINDINGS: We performed a prospective observational study in Paediatric and adult ICU, at the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam. Patients with dengue were enrolled within 12 hours of admission to paediatric or adult ICU. A haemodynamic assessment and portable echocardiograms were carried out daily for 5 days from enrolment and all interventions recorded. 102 patients were enrolled; 22 patients did not develop DSS, 48 had a single episode of shock and 32 had recurrent shock. Patients with recurrent shock had a higher enrolment pulse than those with 1 episode or no shock (median: 114 vs. 100 vs. 100 b/min, P = 0.002), significantly lower Stroke Volume Index (SVI), (median: 21.6 vs. 22.8 vs. 26.8mls/m2, P<0.001) and higher lactate levels (4.2 vs. 2.9 vs. 2.2 mmol/l, P = 0.001). Higher SVI and worse left ventricular function (higher Left Myocardial Performance Index) on study days 3-5 was associated with the secondary endpoint of respiratory distress. There was an association between the total IV fluid administered during the ICU admission and respiratory distress (OR: 1.03, 95% CI 1.01-1.06, P = 0.001). Admission lactate levels predicted patients who subsequently developed recurrent shock (P = 0.004), and correlated positively with the total IV fluid volume received (rho: 0.323, P = 0.001) and also with admission ALT (rho: 0.764, P<0.001) and AST (rho: 0.773, P<0.001). CONCLUSIONS/SIGNIFICANCE: Echo-derived intravascular volume assessment and venous lactate levels can help identify dengue patients at high risk of recurrent shock and respiratory distress in ICU. These findings may serve to, not only assist in the management of DSS patients, but also these haemodynamic endpoints could be used in future dengue fluid intervention trials.