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Global Case-Fatality Rates in Pediatric Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis
Bobby Tan1, Judith Ju-Ming Wong2, Rehena Sultana1
1Duke-NUS Medical School, Singapore.
Insights
Global pediatric sepsis mortality rates are higher in developing countries than developed ones, with younger children and septic shock posing greater risks. Despite a declining trend, disparities persist, highlighting the need for targeted interventions and international collaboration to reduce pediatric sepsis burden.
Area of Science:
- Pediatric critical care medicine
- Global health epidemiology
- Infectious disease research
Background:
- Global patterns of case-fatality rates (CFRs) in pediatric severe sepsis and septic shock are not well understood.
- Significant disparities in outcomes may exist between developing and developed countries.
Purpose of the Study:
- To systematically review and meta-analyze pediatric severe sepsis and septic shock CFRs globally.
- To identify temporal trends and factors associated with mortality in different regions.
Main Methods:
- Systematic search of multiple databases (PubMed, Web of Science, EMBASE, CINAHL, Cochrane Central) for relevant studies up to January 2017.
- Inclusion of prospective observational studies and randomized clinical trials reporting CFRs in children (excluding neonates).
- Meta-analysis and meta-regression to pool CFR estimates and assess associations with study period, design, severity, age, and geographic location.
Main Results:
- Ninety-four studies including 7,561 patients were analyzed.
- Pooled CFRs were significantly higher in developing countries (31.7%) compared to developed countries (19.3%).
- Higher CFRs were observed in Africa, Asia, and South America compared to North America, with septic shock and younger age as significant risk factors. Earlier study periods showed higher CFRs.
Conclusions:
- A persistent disparity in pediatric sepsis CFRs exists between developing and developed nations, despite an overall declining trend.
- Younger age and septic shock are associated with increased mortality.
- Further research into vulnerable populations and enhanced international collaboration are crucial to mitigate the global burden of pediatric sepsis.
Importance:
The global patterns and distribution of case-fatality rates (CFRs) in pediatric severe sepsis and septic shock remain poorly described.
Objective:
We performed a systematic review and meta-analysis of studies of children with severe sepsis and septic shock to elucidate the patterns of CFRs in developing and developed countries over time. We also described factors associated with CFRs.
Data Sources:
We searched PubMed, Web of Science, Excerpta Medica database, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Cochrane Central systematically for randomized clinical trials and prospective observational studies from earliest publication until January 2017, using the keywords "pediatric," "sepsis," "septic shock," and "mortality."
Study Selection:
Studies involving children with severe sepsis and septic shock that reported CFRs were included. Retrospective studies and studies including only neonates were excluded.
Data Extraction And Synthesis:
We conducted our systematic review and meta-analysis in close accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled case-fatality estimates were obtained using random-effects meta-analysis. The associations of study period, study design, sepsis severity, age, and continents in which studies occurred were assessed with meta-regression.
Main Outcomes And Measures:
Meta-analyses to provide pooled estimates of CFR of pediatric severe sepsis and septic shock over time.
Results:
Ninety-four studies that included 7561 patients were included. Pooled CFRs were higher in developing countries (31.7% [95% CI, 27.3%-36.4%]) than in developed countries (19.3% [95% CI, 16.4%-22.7%]; P < .001). Meta-analysis of CFRs also showed significant heterogeneity across studies. Continents that include mainly developing countries reported higher CFRs (adjusted odds ratios: Africa, 7.89 [95% CI, 6.02-10.32]; P < .001; Asia, 3.81 [95% CI, 3.60-4.03]; P < .001; South America, 2.91 [95% CI, 2.71-3.12]; P < .001) than North America. Septic shock was associated with higher CFRs than severe sepsis (adjusted odds ratios, 1.47 [95% CI, 1.41-1.54]). Younger age was also a risk factor (adjusted odds ratio, 0.95 [95% CI, 0.94-0.96] per year of increase in age). Earlier study eras were associated with higher CFRs (adjusted odds ratios for 1991-2000, 1.24 [95% CI, 1.13-1.37]; P < .001) compared with 2011 to 2016. Time-trend analysis showed higher CFRs over time in developing countries than developed countries.
Conclusions And Relevance:
Despite the declining trend of pediatric severe sepsis and septic shock CFRs, the disparity between developing and developed countries persists. Further characterizations of vulnerable populations and collaborations between developed and developing countries are warranted to reduce the burden of pediatric sepsis globally.
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