Echocardiographic Parameters and Mortality in Pediatric Sepsis: A Systematic Review and Meta-Analysis*
Authors: Sanfilippo Filippo , La Rosa Valeria , Grasso Chiara , Santonocito Cristina , Minardi Carmelo , Oliveri Francesco , Iacobelli Roberta , Astuto Marinella 
Published: December 2020

Objective:
We conducted a systematic review and meta-analysis to investigate the prognostic value of echocardiographic parameters in pediatric septic patients.

Data Sources:
MEDLINE, PubMed, and EMBASE (last update April 5, 2020).

Study Selection:
Observational studies of pediatric sepsis providing echocardiographic parameters in relation to mortality.

Data Extraction:
Echocardiography data were categorized as those describing left ventricular systolic or diastolic function, right ventricular function, and strain echocardiography parameters. Data from neonates and children were considered separately. Analysis is reported as standardized mean difference and 95% CI.

Data Synthesis:
We included data from 14 articles (n = 5 neonates, n = 9 children). The fractional shortening was the most commonly reported variable (11 studies, n = 555 patients) and we did not identify an association with mortality (standardized mean difference 0.22, 95% CI [–0.02 to 0.47]; p = 0.07, I
2 = 28%). In addition, we did not find any association with mortality also for left ventricular ejection fraction (nine studies, n = 417; standardized mean difference 0.06, 95% CI [–0.27 to 0.40]; p = 0.72, I
2 = 51%), peak velocity of systolic mitral annular motion determined by tissue Doppler imaging wave (four studies, n = 178; standardized mean difference –0.01, 95% CI [–0.34 to 0.33]; p = 0.97, I
2 = 0%), and myocardial performance index (five studies, n = 219; standardized mean difference –0.51, 95% CI [–1.10 to 0.08]; p = 0.09, I
2 = 63%). However, in regard to left ventricular diastolic function, there was an association with mortality for higher early wave of transmitral flow/peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging ratio (four studies, n = 189, standardized mean difference –0.45, 95% CI [–0.80 to –0.10]; p = 0.01, I
2 = 0%) or lower peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging wave (three studies, n = 159; standardized mean difference 0.49, 95% CI [0.13–0.85]; p = 0.008, I
2 = 0%). We did not find any association with mortality for early wave of transmitral flow/late (atrial) wave of trans-mitral flow ratio (six studies, n = 273; standardized mean difference 0.28, 95% CI [–0.42 to 0.99]; p = 0.43, I
2 = 81%) and peak velocity of systolic mitral annular motion determined by tissue Doppler imaging wave measured at the tricuspid annulus (three studies, n = 148; standardized mean difference –0.18, 95% CI [–0.53 to 0.17]; p = 0.32, I
2 = 0%). Only a few studies were conducted with strain echocardiography.

Conclusions:
This meta-analysis of echocardiography parameters in pediatric sepsis failed to find any association between the measures of left ventricular systolic or right ventricular function and mortality. However, mortality was associated with higher early wave of transmitral flow/peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging or lower peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging, indicating possible importance of left ventricular diastolic dysfunction. These are preliminary findings because of high clinical heterogeneity in the studies to date.