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Older age, male sex, and acute illness severity were all independently associated with an increased long-term risk of death among close to 95,000 adult sepsis survivors in England, researchers found.

In addition to a patient's age and sex, data from a nationally representative sample of sepsis survivors treated at 192 critical care units in England also found an incremental association between scores on the Acute Physiology and Chronic Health Evaluation (APACHE) II assessment test and long-term death risk (adjusted HR 1.11 for every 5-point score increase), Manu Shankar-Hari, PhD, of St. Thomas' Hospital in London, England, and colleagues reported in .

Septic shock was associated with a lower long-term risk for death, as was organ dysfunction involving 4 or more organs, but the researchers noted that the fact that both of these are associated with increased death during index sepsis treatment could explain these associations.

Shankar-Hari said this could help inform the long-term management of sepsis survivors. He told MedPage Today that identifying sepsis survivors with increased long-term mortality risk could help researchers develop strategies for reducing this risk. His own research team is currently conducting designed to determine if pneumococcal vaccination can preventing infection-related rehospitalization in sepsis survivors.

The newly published study involved 94,748 adult sepsis survivors treated from 2009 to 2014, with survival status determined in March 2015.

Sepsis-specific characteristics included site of infection, number of organ dysfunctions, and septic shock, while generic characteristics included age, sex, ethnicity, severe comorbidities and acute illness severity (defined by APACHE II scores), dependency, and surgical status.

Cox regression analysis was used to estimate adjusted hazard ratios for both generic and sepsis-specific characteristics. Long-term mortality with maximum follow-up of 6 years was the main study outcome.

Just under half (46.5) of the sepsis survivors in the cohort were female and 9 out of 10 (90.8%) were non-Hispanic white. Their mean age was 61.3, and 46.3% of the cohort had respiratory site infections.

Among the main findings:

• One year after hospital discharge for sepsis, 15% of survivors had died and an additional 6% to 8% died annually over the subsequent 5 years of follow-up.
• Other independent generic predictors of long-term mortality included severe comorbidities, dependency, and nonsurgical status.
• Site of infection was a sepsis-specific independent risk factor for long-term morbidity, with respiratory and cardiovascular sepsis sites associated with slightly greater risk.
• 2-3 organ dysfunctions was associated with an increased risk for death versus single organ dysfunction (adjusted HR 1.18; 95% CI 1.03-1.14; adjusted HR 1.07; 95% CI 1.01-1.13, respectively).

"Our observations that acute illness severity and site of infection at index admission are associated with increased risk of long-term mortality in sepsis survivors has biological plausibility and informs future research," Shankar-Hari and colleagues wrote. "Acute illness severity and illness trajectory seen with critical care admissions for sepsis are associated with health before the illness causing hospitalization, immune responses in sepsis, and early appropriate clinical management. Immune abnormalities seen in patients with sepsis appear to persist in sepsis survivors."

The researchers noted that a new infection or infection relapse are among the most common reasons for rehospitalization in sepsis survivors, "which is potentially associated with the site of infection at index sepsis admission."

"Thus, observational studies identifying biological characteristics and value of parsimonious clinical prediction tools using generic and sepsis-specific risk factors to predict risk of long-term adverse health in sepsis survivors would be valuable," they wrote. " The future interventional trials may include clinical practice interventions such as extended follow-up care either by primary care physicians or with targeted follow-up clinics or immunological interventions informed by acute sepsis illness biology."