Temporal Transitions of the Hyperinflammatory and Hypoinflammatory Phenotypes in Critical Illness
Authors' conclusion
The prevalence of the Hyperinflammatory phenotype, as assigned using a parsimonious biomarker classifier model, decreases over the first several days of critical illness, irrespective of acute respiratory distress syndrome diagnosis. The transition from Hyperinflammatory to Hypoinflammatory mediates a trajectory toward recovery beyond the resolution of organ failure.
Study context
- Population
- Critically ill patients with biomarkers available at multiple time points (Days 0–4): MARS cohort, ALVEOLI (ARDS) and CLOVERS (sepsis) RCTsMARS 2,407
- Comparison
- Hyperinflammatory to Hypoinflammatory vs Persistently Hyperinflammatory
Methodological detailslongitudinal phenotype assignment (Days 0-4), validated parsimonious classifier model (plasma IL-8, protein C, serum bicarbonate), mediation analysis
- Longitudinal phenotype assignment (Days 0-4)
- Validated parsimonious classifier model (plasma IL-8, protein C, serum bicarbonate)
- Mediation analysis
Primary result
As reported in the abstract
- In all three cohorts, switching from Hyperinflammatory (Day 0) to Hypoinflammatory associated with significantly improved mortality vs persistently Hyperinflammatory
Further findings
Prevalence of Hyperinflammatory phenotype over time, MARS · Days 0, 2, 4
- Hyperinflammatory at Day 0
- 36.0%
- Hyperinflammatory at Day 2
- 15.6%
- Hyperinflammatory at Day 4
- 6.3%
Prevalence of Hyperinflammatory phenotype over time, ALVEOLI · Days 0, 3
- Hyperinflammatory at Day 0
- 26.4%
- Hyperinflammatory at Day 3
- 13.4%
Prevalence of Hyperinflammatory phenotype over time, CLOVERS · Days 0, 3
- Hyperinflammatory at Day 0
- 24.8%
- Hyperinflammatory at Day 3
- 5.7%
Mediation by organ failure
- Only a minor proportion of the mortality improvement attributable to ameliorating organ failure
Parts of this Brief are withheld: the automatic checks could not confirm them against the abstract.
Original publication
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