According to a study published in JAMA Network Open, although sepsis was the most common immediate cause of death at 6 US academic and community hospitals, most patients had severe chronic comorbidities, making sepsis-associated deaths unpreventable through better hospital-based care.1

Per Sepsis-3 criteria, sepsis was defined as infection with a concurrent rise in Sequential Organ Failure Assessment Score by 2 or more points from the pre-infection baseline. Researchers also identified suboptimal aspects of sepsis care such as delay in initiating antibiotics, source control, or inappropriate initial antibiotic therapy. The preventability of each sepsis-associated death was rated on a 6-point Likert scale.

Data for 568 patients were included in this retrospective medical review; 395 of these patients died in the hospital, and 173 were discharged to hospice. The mean age was 70.5 years (standard deviation, 16.1 years), and 289 were men.

Sepsis was present in 300 terminal hospitalizations (52.8%; 95% CI, 48.6%-57.0%) and was the immediate cause of death in 198 patients (34.9%; 95% CI, 30.9%-38.9%). Moreover, 40.3% patients who died of sepsis had a hospice-qualifying condition on admission (95% CI, 34.7%-46.1%), illustrating the prominent role of chronic illness as a risk factor for sepsis.

After sepsis, the most common immediate causes of death were progressive cancer (16.2%) and heart failure (6.9%).

The most common underlying causes of death in patients with sepsis were solid cancer (21.0%), chronic heart disease (15.3%), hematologic cancer (10.3%), dementia (9.7%), and chronic lung disease (9.0%).

Of the 300 sepsis-associated deaths, there were 68 (22.7%) cases with suboptimal care. The most common problems were delay in antibiotics (48.5%), delay in source control (27.9%), and inappropriate initial antibiotic therapy (23.5%).

Based on the Likert scale rating, 264 of the 300 deaths from sepsis were considered unpreventable. Thirty deaths were rated as potentially preventable (11 were judged definitely or moderately likely preventable and 25 were considered possibly preventable).

Interrater reliability of the preventability of sepsis-associated deaths, however, was modest. The Krippendorff α values for classifying sepsis as a cause of death were 0.60 at site 1, 0.66 at site 2, and 0.53 at site 3.2 “In a book written by Krippendorff describing interpretation of Krippendorff α, he suggested that a minimum Krippendorff α of 0.67 was required for even tentative conclusions, a level none of the sites in this study achieved,” noted Laura Evans, MD, from the Division of Pulmonary, Critical Care and Sleep Medicine at New York University School of Medicine in New York City, in a commentary.2 Thus, the results reported about preventability should be interpreted with caution.

Further, Dr Evans said that the lower rate of suboptimal care (22.7%) in this study “suggests that sepsis care in hospitals included in this study may have been substantially better than that in many other hospitals, with correspondingly fewer opportunities for improvement and fewer sepsis-associated deaths deemed to be preventable through better hospital care.” In other words, more deaths from sepsis may be preventable in hospitals that have greater gaps in sepsis care.

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Nonetheless, Dr Evans noted that with the current available tools for identifying and managing sepsis, some sepsis-associated deaths are not preventable. “This study does not change the established priority for early identification and management of patients with sepsis,” stated Dr Evans. It points to the “need for improved rapid diagnostics that can be used to trigger time-sensitive interventions that can be applied across different resource settings…to reduce sepsis-associated deaths to their lowest possible levels.”

Disclosures: Chanu Rhee, MD, MPH, has received royalties and personal fees from UpToDate. David K. Warren, MD, MPH, has received funding from a vaccine study from Pfizer and personal fees from Centene Corp, Carefusion/BD, Pursuit Vascular Inc., and PDI Inc. Michael Klompas, MD, MPH, has received personal fees from UpToDate.

References

1. Rhee C, Jones TM, Hamad Y, et al; Centers for Disease Control and Prevention (CDC) Prevention Epicenters Program. Prevalence, underlying causes, and preventability of sepsis-associated mortality in US acute care hospitals. JAMA Netw Open. 2019;2(2):e187571.

2. Evans L. A closer look at sepsis-associated mortality. JAMA Netw Open. 2019;2(2):e187565.