Improvements in Sepsis-associated Mortality in Hospitalized Patients with Cancer versus Those without Cancer. A 12-Year Analysis Using Clinical Data

Abstract

Rationale: There have been advances in both cancer and sepsis treatment over the past several decades, yet little is known about trends in sepsis-associated mortality in patients with versus without cancer.Objectives: To assess trends in sepsis-associated mortality in hospitalized patients with and without cancer using objective clinical criteria to identify sepsis and detailed clinical data to adjust for severity of illness.Methods: This was a retrospective cohort study at a tertiary referral hospital and cancer center. Adult in-patients with clinical indicators of sepsis (U.S. Centers for Disease Control and Prevention Adult Sepsis Event criteria) were identified between 2003 and 2014. Patients with cancer were identified using diagnosis codes from their hospitalization or the preceding 90 days. Sepsis-associated in-hospital mortality rates were assessed in 3-year intervals. Multivariable logistic regression models were used to adjust for case mix and severity of illness and to test for subgroup interactions in trends.Results: The cohort included 20,975 patients with sepsis, of whom 7,489 (35.7%) had cancer (61.7% solid and 38.3% hematologic). Sepsis-associated mortality rates in patients with cancer decreased from 31.3% in 2003-2005 to 26.0% in 2012-2014 (absolute decrease, 5.2% [95% confidence interval (CI), 2.3-8.2%]). This mortality reduction persisted after risk adjustment (adjusted odds ratio, 0.53 [95% CI, 0.45-0.63] in 2012-2014 relative to 2003-2005). In contrast, sepsis-associated mortality rates increased in patients without cancer from 20.9% in 2003-2005 to 23.9% in 2012-2014 (absolute increase, 2.1% [95% CI, 0.1-4.1%]), but were stable after risk-adjustment (adjusted odds ratio, 0.90 [95% CI, 0.79-1.03]) (P < 0.001 for comparison of trends between patients with vs. without cancer on both crude and adjusted analysis). Among patients with cancer, declines in risk-adjusted sepsis-associated mortality were observed in both solid and hematologic cancer subgroups, with both community-onset and hospital-onset sepsis, in patients receiving active cancer treatments, and in patients requiring mechanical ventilation at sepsis onset.Conclusions: Sepsis-associated mortality rates declined significantly over a 12-year period in patients with cancer, but not in patients without cancer. Potential explanations include advances in the management of cancer and/or better sepsis treatments specifically in patients with cancer. Further research is needed to elucidate the reasons for our findings and to assess their generalizability to other hospitals.

Keywords: Adult Sepsis Event; cancer; sepsis; trends.

Figure 1.

Flow diagram for study cohort derivation. *The U.S. Centers for Disease Control and Prevention (CDC) Adult Sepsis Event definition was modified to exclude patients who otherwise would meet organ dysfunction criteria solely based on elevated lactate, decreased platelets, or phenylephrine use.

Figure 2.

Sepsis-associated in-hospital mortality rates by specific solid and hematologic cancer diagnosis categories. (A) Sepsis-associated mortality rates for patients with solid cancer, stratified by the presence of metastases. Sample size: breast (n = 213 with mets vs. 150 with no mets), genitourinary (n = 298 vs. 298), gastrointestinal (n = 822 vs. 529), lung (n = 848 vs. 143), other (n = 591 vs. 902), and overall (n = 2,979 vs. 1,644). (B) Sepsis-associated mortality rates for patients with hematologic cancer, stratified by presence of stem cell transplant. Sample size: leukemia (230 with stem cell transplant vs. 383 with no transplant), lymphoma (171 vs. 915), multiple myeloma (51 vs. 251), and overall (413 vs. 2,453). mets = metastases.

Figure 3.

Trends in sepsis-associated in-hospital mortality rates in patients with and without cancer. (A) Unadjusted annual trends in in-hospital mortality (all patients with sepsis). (B) 3-year interval mortality rates adjusted for case mix and severity of illness (all patients with sepsis). The numbers of sepsis deaths per 3-year interval in patients with cancer were 571/1,826 (31.3%) in 2003–2005, 580/1,975 (29.4%) in 2006–2008, 517/1,914 (27.0%) in 2009–2011, and 462/1,774 (26.0%) in 2012–2014. The number of sepsis deaths in patients without cancer were 655/3,134 (20.9%) in 2003–2005, 697/3,352 (20.8%) in 2006–2008, 779/3,404 (22.9%) in 2009–2011, and 828/3,596 (23.0%) in 2012–2014. Values presented in B represent the adjusted odds ratios for mortality in each 3-year period (with 95% confidence intervals).