Another study is raising questions about whether compliance with a federally mandated hospital protocol aimed at improving sepsis care and management is associated with better outcomes.
The study, published this week in JAMA Network Open, found that sepsis patients who received care that was noncompliant with the Centers for Medicare and Medicaid Services (CMS) Severe Sepsis and Septic Shock Management Bundle (SEP-1) tended to be older, have more comorbidities, and have more complex clinical presentation than those who received compliant care. When those factors were accounted for, SEP-1 compliance was no longer associated with improved mortality.
The study comes on the heels of a systematic review and meta-analysis, published last month in the Annals of Internal Medicine, that found no evidence that SEP-1 compliance was associated with improved mortality.
Sepsis occurs when the immune system overreacts to an infection, triggering a chain of events that can lead to tissue damage, organ failure, and death. More than 1.7 million American are treated for sepsis each year, and an estimated 250,000 die from it. Implemented in 2015 by CMS, SEP-1 is a bundle of measures that includes administration of broad-spectrum antibiotics to all patients with possible sepsis within 3 hours of recognition. Other elements of SEP-1 include rapid infusion of fluid, blood cultures, lactate measurement, vasopressors for fluid-refractory hypotension, and re-evaluation of volume status.
SEP-1 was adopted based on evidence that bundle compliance was associated with lower mortality rates. In 2023, CMS announced it was transitioning SEP-1 from a pay-for-reporting to a pay-for-performance measure. That means hospitals will be rewarded for SEP-1 compliance.
But the authors of the new study say the findings cast more doubt on the mortality benefit and raise the question of whether hospitals should be penalized for not complying with a one-size-fits-all approach that may not improve outcomes and doesn't account for the complexity of sepsis patients.
"The lack of an association between SEP-1 compliance and mortality after adjusting for these factors raise concerns that CMS's decision to transition SEP-1 to a pay-for-performance measure may not catalyze meaningful gains in sepsis survival," lead study author Chanu Rhee, MD, MPH, of the Harvard Pilgrim Health Care Institute, said in a press release from the institute.
'From protective to null'
For the retrospective study, a team of US researchers led by Rhee analyzed data on adult sepsis patients treated at four academic teaching hospitals in Massachusetts, Iowa, and California from January 2019 through December 2022. Their aim was to identify the clinical characteristics of patients who received SEP-1–compliant care versus those who received noncompliant care and to assess the association between SEP-1 compliance and hospital mortality.
"Most previous studies of bundle compliance have relied on administrative and/or electronic health record (EHR) data, limiting their ability to identify complex clinical factors that are not usually captured in structured fields (such as clinicians' initial level of suspicion for infection, difficult intravenous access, need for urgent bedside procedures, and competing noninfectious diagnoses)," the authors wrote. "Identifying these factors could help highlight important barriers to timely sepsis care and provide a better understanding of the association of bundle compliance with outcomes."
The study included 590 patients (median age, 65; 55.8% male), of whom 335 (56.8%) received SEP-1–compliant care and 255 (43.2%) received noncompliant care. In terms of baseline clinical characteristics, patients in the noncompliant group were more likely to be 65 years and older (55.7% vs 47.2%; odds ratio [OR], 1.41; 95% confidence interval [CI], 1.01 to 1.95), to have diabetes (31.8% vs 21.5%; OR, 1.70; 95% CI, 1.17 to 2.46), and to have multiple comorbidities (38.8% vs 29.6%; OR, 1.51; 95% CI, 1.07 to 2.13) than those in the compliant group.
The lack of an association between SEP-1 compliance and mortality after adjusting for these factors raise concerns that CMS's decision to transition SEP-1 to a pay-for-performance measure may not catalyze meaningful gains in sepsis survival.
On presentation, patients in the noncompliant group had a higher incidence of septic shock (42.0% vs 31.9%; OR, 1.54; 95% CI, 1.10 to 2.16), kidney dysfunction (34.1% vs 23.9%; OR, 1.65; 95% CI, 1.15 to 2.37), and thrombocytopenia (16.9% vs 11.0%; OR, 1.16; 95% CI, 1.02 to 2.62) compared with patients in the compliant group. They also had more nonfebrile presentations (53.3% vs 36.1%; OR, 2.02; 95% CI, 1.45 to 2.82), impaired mental status (36.1% vs 28.1%; OR, 1.45; 95% CI, 1.02 to 2.05), need for bedside procedures (22.4% vs 12.2%; OR, 2.06; 95% CI, 1.33 to 3.21), acute concurrent noninfectious illnesses (54.9% vs 45.1%; OR, 1.48; 95% CI, 1.07 to 2.06), and noninfectious illness as the primary factor associated with their presentation (32.9% vs 21.2%; OR, 1.82; 95% CI, 1.08 to 3.08).
In the unadjusted mortality analysis, SEP-1 compliance was associated with lower crude mortality rates compared with noncompliance (11.9% vs 16.1%; OR, 0.60; 95% CI, 0.37 to 0.98). But there was no statistically significant difference between groups after successively adjusting for demographics and comorbidities (adjusted OR [AOR], 0.71; 95% CI, 0.42 to 1.18), infection source (AOR, 0.71; 95% CI, 0.43 to 1.20), severity of illness (AOR, 0.86; 95% CI, 0.50 to 1.49), and clinical markers of complexity (AOR, 1.08; 95% CI, 0.61 to 1.91).
"Adjusting for these confounders, many obtainable only through detailed medical record review, shifted the effect estimate for the association between SEP-1 compliance and mortality from protective to null," the authors wrote.
Addressing the full spectrum of sepsis care
The authors say that while there is room to improve SEP-1 bundle compliance rates, the findings indicate that noncompliance doesn't mean patients are receiving poor care "but can reflect the complexity of some sepsis presentations and the frequent presence of other acute conditions that require simultaneous diagnosis and management."
They also note that the debate over the impact of SEP-1 is one of the reasons why groups such as the Infectious Diseases Society of America have called on CMS to retire SEP-1 and shift the focus to risk-adjusted outcome metrics that give hospitals more flexibility to customize sepsis care.
"If we truly want to improve sepsis outcomes, we must move beyond simple admission bundles and focus on strategies that address the full spectrum of sepsis care," said senior study author Michael Klompas, MD, MPH, of Harvard Medical School.
