Metabolic septic shock sub-phenotypes, stability over time and association with clinical outcome
An erratum to this article was published (Intensive Care Med, Aug 2026 ↗)
Authors' conclusion
Three metabolic subgroups exist in septic shock which evolve over time. Persistence of low lysophospholipid sub-phenotypes is associated with mortality.
Study context
- Population
- Patients with septic shock included soon after shock onset in the LeoPARDS and VANISH trialsLeoPARDS 470, VANISH 173 patients
- Comparison
- Low lysophospholipid metabolic sub-phenotypes (clusters 2 and 3) vs high lysophospholipid sub-phenotype (cluster 1)
Methodological detailstwo double-blind randomized trials, k-means clustering, elastic net classifier, serial sampling (up to four time points), 474 metabolites; clusters identified in LeoPARDS (1402 samples) and predicted in VANISH (493 samples)
- Two double-blind randomized trials
- K-means clustering
- Elastic net classifier
- Serial sampling (up to four time points)
- 474 metabolites; clusters identified in LeoPARDS (1402 samples) and predicted in VANISH (493 samples)
Primary result
As reported in the abstract
Mortality with persistence of low lysophospholipid sub-phenotypes
Each group vs cluster 1Odds ratio (95% CI)P value
Cluster 2LeoPARDS
3.66(1.88–7.20)
P = 0.0001Cluster 3LeoPARDS
2.49(1.29–4.81)
P = 0.006Cluster 2VANISH
4.13(1.17–15.61)
P = 0.03Cluster 3VANISH
3.22(1.09–9.92)
P = 0.04- Three metabolic sub-phenotypes found; main determinants lipid species, especially lysophospholipids
- 3
Further findings
Circulating cytokine levels
- Low lysophospholipid sub-phenotypes associated with higher circulating cytokine levels
Heterogeneity of treatment effect by baseline metabolic sub-phenotype
- No heterogeneity of treatment effect for any trial intervention
Original publication
Metabolic septic shock sub-phenotypes, stability over time and association with clinical outcome. Intensive Care Med. Published 31 March 2025. doi:10.
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