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Association between blood caspase-9 concentrations and septic patient prognosis
Leonardo Lorente1, María M Martín2, Raquel Ortiz-López3
1Intensive Care Unit, Hospital Universitario de Canarias, Ofra, s/n. La Laguna, 38320, Tenerife, Spain. lorentemartin@msn.com.
Insights
Blood caspase-9 levels are associated with sepsis patient prognosis. Higher concentrations indicate a poorer outcome, suggesting caspase-9 as a potential prognostic marker in sepsis management.
Area of Science:
- Biochemistry
- Critical Care Medicine
- Molecular Biology
Background:
- Limited data exists on the role of caspase-9, a key initiator of the intrinsic apoptosis pathway, in septic patients.
- Previous findings indicate higher serum caspase-9 levels in sepsis patients compared to healthy individuals.
- The prognostic value of blood caspase-9 concentrations in sepsis remains uninvestigated.
Purpose of the Study:
- To investigate the association between blood caspase-9 concentrations and prognosis in patients with sepsis.
- To determine if caspase-9 levels can serve as a predictive biomarker for sepsis outcomes.
Main Methods:
- An observational, prospective study conducted across three Spanish hospitals.
- Inclusion of patients admitted to intensive care units with sepsis.
- Serum caspase-9 concentrations measured at sepsis diagnosis; 30-day mortality as the primary outcome.
Main Results:
- Non-surviving patients exhibited significantly higher APACHE-II, SOFA scores, lactic acid, serum caspase-9 levels, age, INR, septic shock rates, aPTT, and history of diabetes mellitus, along with lower platelet counts.
- Multiple logistic regression revealed a significant association between serum caspase-9 concentrations and mortality (OR=1.985, p<0.001), independent of age, SOFA, lactic acid, septic shock, and diabetes history.
- No significant difference was observed in the area under ROC curves when comparing serum caspase-9 with SOFA or lactic acid.
Conclusions:
- The study's primary novel finding is the association between blood caspase-9 concentrations and prognosis in septic patients.
- Caspase-9 may serve as a potential prognostic biomarker for sepsis.
- Further research is warranted to confirm these preliminary findings, considering study limitations such as the absence of data on Surviving Sepsis Campaign bundle adherence.
Background:
There are few data on caspase‑9 (intrinsic apoptosis pathway initiating caspase) in septic patients. Higher serum caspase‑9 levels in septic patients than in healthy subjects have been found. However, there are no data on the prognosis of septic patients and blood caspase‑9 concentrations. Therefore, the objective of this study was to analyze the potential association between blood caspase‑9 concentrations and prognosis in septic patients.
Methods:
Three Spanish hospitals participated in the recruitment of septic patients admitted to intensive care units in this observational and prospective study. Serum caspase‑9 concentrations were determined at the time of sepsis diagnosis. The 30-day mortality was the outcome variable.
Results:
Higher Acute Phisiology and Chronic Health Evaluation(APACHE)-II (p < 0.001), Sepsis-related Organ Failure Assessment score (SOFA) (p < 0.001), serum lactic acid levels (p = 0.001), serum caspase‑9 levels (p < 0.001), age (p < 0.001), International normalized ratio (INR) (p = 0.001), rate of septic shock (p = 0.001), Activated partial thromboplastin time (aPTT) (p = 0.03), rate of diabetes mellitus (p = 0.04), and lower platelet counts (p = 0.01) were found in non-surviving (n = 80) than in surviving patients (n = 134). Multiple logistic regression analysis showed an association between serum caspase‑9 concentrations and mortality (Odds Ratio (OR) = 1.985; 95% Confidence Interval (CI) = 1.359-2.900; p < 0.001) regardless of age, SOFA, lactic acid and septic shock and history of diabetes mellitus. No significant differences were found when we compared area under ROC curves of serum caspase‑9 with SOFA (p = 0.92) and with lactic acid (p = 0.59).
Conclusions:
The main novel finding of our study was the association between blood caspase‑9 concentrations and septic patient prognosis. However, our study showed some limitations (for example, the absence of data in respect to execution of Surviving Sepsis Campaign bundles); thus, more research could be interesting to confirm our preliminary findings.
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