The compensatory reserve index predicts recurrent shock in patients with severe dengue

Abstract

Background: Dengue shock syndrome (DSS) is one of the major clinical phenotypes of severe dengue. It is defined by significant plasma leak, leading to intravascular volume depletion and eventually cardiovascular collapse. The compensatory reserve Index (CRI) is a new physiological parameter, derived from feature analysis of the pulse arterial waveform that tracks real-time changes in central volume. We investigated the utility of CRI to predict recurrent shock in severe dengue patients admitted to the ICU.

Methods: We performed a prospective observational study in the pediatric and adult intensive care units at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. Patients were monitored with hourly clinical parameters and vital signs, in addition to continuous recording of the arterial waveform using pulse oximetry. The waveform data was wirelessly transmitted to a laptop where it was synchronized with the patient's clinical data.

Results: One hundred three patients with suspected severe dengue were recruited to this study. Sixty-three patients had the minimum required dataset for analysis. Median age was 11 years (IQR 8-14 years). CRI had a negative correlation with heart rate and moderate negative association with blood pressure. CRI was found to predict recurrent shock within 12 h of being measured (OR 2.24, 95% CI 1.54-3.26), P < 0.001). The median duration from CRI measurement to the first recurrent shock was 5.4 h (IQR 2.9-6.8). A CRI cutoff of 0.4 provided the best combination of sensitivity and specificity for predicting recurrent shock (0.66 [95% CI 0.47-0.85] and 0.86 [95% CI 0.80-0.92] respectively).

Conclusion: CRI is a useful non-invasive method for monitoring intravascular volume status in patients with severe dengue.

Keywords: Compensatory reserve index (CRI); Dengue; Machine learning; Non-invasive monitoring; Pulse waveform; Re-shock; Shock.

Conflict of interest statement

BW reports receipt of honoraria from Takeda Pharmaceutical Company for membership of the Data Safety Monitoring Committee for their dengue vaccine trials and from Roche for contributions to their Severe Dengue Advisory Board.

Drs. Moulton and Mulligan are co-inventors of the CRI algorithm. The underlying intellectual property is assigned to the University of Colorado, which licensed the technology to Flashback Technologies, Inc. Drs. Moulton and Mulligan have equity interests in Flashback Technologies, where Dr. Moulton is the Chief Medical Officer and serves on the Board of Directors. Drs. Moulton and Mulligan receive royalty payments from the University of Colorado. The other authors have declared no conflicts of interest.

Development of the CRI algorithm has been supported in part by funding from the US Army Medical Research and Material Command (USAMRMC) under Grant Nos. DM09027, W81XWH-15-2-0007, W81XWH-09-1-0750, W81XWH-09-C-0160, W81XWH-11-2-0091, W81XWH-11-2-0085, W81XWH-12-2-0112, W81XWH-13-C-0121, and W81XWH-15-9-0001. The views, opinions, and/or findings contained in this report are those of the authors and should not be construed as an official Department of the Army position, policy, or decision unless so designated by other documentation.

© 2022. The Author(s).

Figures

Fig. 1

Dynamic changes in the compensatory reserve index (CRI), systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) during the first 48 h of fluid management. A The trajectories of CRI, SBP, DBP, and PP in a 9-year-old boy with DSS. B The trajectories of CRI, SBP, DBP, and PP in an 11-year-old boy with DSS and two re-shock episodes. Red line is CRI, dark grey line is SBP, light grey line is DBP, intermittent grey line is PP, and the vertical green line indicates episodes of clinical shock/re-shock

Fig. 2

Pearson’s correlation coefficient between compensatory reserve index (CRI) and heart rate (HR), systolic blood pressure (SBP) or diastolic blood pressure (DBP). The three panels describe partial Pearson’s correlation coefficients between CRI and heart rate (HR) (A), systolic blood pressure (SBP) (B) and diastolic blood pressure (DBP) (C) for all 63 cases included in the analysis. Solid black lines represent the estimated partial Pearson’s correlation coefficients between CRI values and the corresponding hemodynamic parameter at intervals from onset of the first shock episode, after adjusting for age, gender, and body weight. To perform these calculations, data within the first 8 h since the first shock were grouped every 30 min (for HR) or 1 h (for SBP and DBP). Vertical lines are corresponding 95% confidence intervals of the estimated partial Pearson’s correlation coefficient; repeated data was accounted for using bootstrap sampling. Number below each vertical line represents number of hemodynamic parameter measurements in each group (HR in A, SBP in B, and DBP in C). Correlations based on small numbers of observations (< 30) are unreliable and therefore they were excluded in these figures (> 9.25 h for HR, > 6.5 h for SBP and DBP)