Epidemiology and Outcomes of Cancer-Related Versus Non-Cancer-Related Sepsis Hospitalizations

Abstract

Objective: Cancer and its treatment are known to be important risk factors for sepsis, contributing to an estimated 12% of U.S. sepsis admissions in the 1990s. However, cancer treatment has evolved markedly over the past 2 decades. We sought to examine how cancer-related sepsis differs from non-cancer-related sepsis.

Design: Observational cohort.

Setting: National Readmissions Database (2013-2014), containing all-payer claims for 49% of U.S.

Patients: A total of 1,104,363 sepsis hospitalizations.

Interventions: We identified sepsis hospitalizations in the U.S. National Readmissions Database using explicit codes for severe sepsis, septic shock, or Dombrovskiy criteria (concomitant codes for infection and organ dysfunction). We classified hospitalizations as cancer-related versus non-cancer-related sepsis based on the presence of secondary diagnosis codes for malignancy. We compared characteristics (site of infection and organ dysfunction) and outcomes (in-hospital mortality and 30-d readmissions) of cancer-related versus non-cancer-related sepsis hospitalizations. We also completed subgroup analyses by age, cancer types, and specific cancer diagnoses.

Measurements and main results: There were 27,481,517 hospitalizations in National Readmissions Database 2013-2014, of which 1,104,363 (4.0%) were for sepsis and 4,150,998 (15.1%) were cancer related. In-hospital mortality in cancer-related sepsis was 27.9% versus 19.5% in non-cancer-related sepsis. The median count of organ dysfunctions was indistinguishable, but the rate of specific organ dysfunctions differed by small amounts (e.g., hematologic dysfunction 20.1% in cancer-related sepsis vs 16.6% in non-cancer-related sepsis; p < 0.001). Cancer-related sepsis was associated with an adjusted absolute increase in in-hospital mortality ranging from 2.2% to 15.2% compared with non-cancer-related sepsis. The mortality difference was greatest in younger adults and waned with age. Patients (23.2%) discharged from cancer-related sepsis were rehospitalized within 30 days, compared with 20.1% in non-cancer-related sepsis (p < 0.001).

Conclusions: In this cohort of over 1 million U.S. sepsis hospitalizations, more than one in five were cancer related. The difference in mortality varies substantially across age spectrum and is greatest in younger adults. Readmissions were more common after cancer-related sepsis.

Figure 1:. Study Flow

Identification methods for sepsis and cancer are presented in Supplemental Table 1

Figure 2:. Cancer-Related versus Non-Cancer-Related Sepsis Relative Risk of Mortality

Solid black line indicates relative risk of mortality. Dashed lines indicate 95% confidence limits. Grey bars indicate the distribution of sepsis hospitalizations by age. Adjusted for: gender, payer type, income quartile, site of infection, comorbidities (CHF, MI, complicated diabetes, severe liver disease, cerebrovascular disease, hemiplegia, chronic kidney disease, and chronic respiratory disease)

Figure 3:. Cancer-Related versus Non-Cancer-Related Sepsis Mortality Risk Difference

Solid black line indicates risk difference in mortality. Dashed lines indicate 95% confidence limits. Grey bars indicate the distribution of sepsis hospitalizations by age. Adjusted for: gender, payer type, income quartile, site of infection, comorbidities (CHF, MI, complicated diabetes, severe liver disease, cerebrovascular disease, hemiplegia, chronic kidney disease, and chronic respiratory disease)