Clinical Scorecard: Identification of Clinical Subphenotypes in Sepsis Through Mixed Data Analysis and Treatment Response Variability: A Cluster Analysis from Multicenter Observational Research

At a Glance

Key Highlights

• Sepsis is a heterogeneous syndrome with diverse clinical subphenotypes affecting treatment response.
• Mixed data clustering methods incorporating categorical and continuous variables can classify sepsis subphenotypes.
• Treatment effectiveness varies among subphenotypes, highlighting the need for precision medicine approaches.

Guideline-Based Recommendations

Diagnosis

• Use clinical and biomarker data including demographics, vital signs, organ failure indicators, and coagulation markers for subphenotype classification.
• Apply mixed data clustering methods to incorporate both categorical and continuous clinical variables.

Management

• Initiate standard sepsis bundle treatments within one hour: fluid resuscitation, early appropriate antimicrobials, and vasopressors for septic shock.
• Consider adjunctive therapies such as corticosteroids, polymyxin B hemoperfusion, recombinant thrombomodulin, antithrombin III, immunoglobulin G, and vasopressin with clinical judgment due to weak guideline recommendations.

Monitoring & Follow-up

• Monitor clinical variables at ICU admission including SOFA score components, inflammatory markers, coagulation parameters, and organ function indicators.
• Assess treatment response variability across identified subphenotypes to guide ongoing management.

Risks

• Adjunctive therapies lack conclusive evidence and may carry risks; use should be individualized based on subphenotype and clinical judgment.
• Heterogeneity in sepsis patients may lead to variable outcomes if treatments are not tailored.

Patient & Prescribing Data

ICU patients with severe sepsis or septic shock enrolled in multicenter registries in Japan

Six adjunctive therapies commonly used but weakly recommended show variable effectiveness across subphenotypes; no single therapy conclusively improves outcomes in all patients.

Clinical Best Practices

• Incorporate mixed data clustering techniques to identify clinically relevant sepsis subphenotypes.
• Use comprehensive clinical variables at ICU admission for patient stratification.
• Apply precision medicine principles by tailoring adjunctive therapies to subphenotype-specific treatment responses.
• Continue standard sepsis bundle interventions promptly while considering adjunctive therapies on a case-by-case basis.
• Recognize the limitations of current evidence and rely on clinical judgment when using weakly recommended treatments.

References

• Guidelines for Management of Sepsis and Septic Shock
• Tohoku Sepsis Registry (UMIN000010297)
• FORECAST Sepsis Study (UMIN000019742)
• Sequential Organ Failure Assessment (SOFA) Score