Antibiotic- and Fluid-Focused Bundles Potentially Improve Sepsis Management, but High-Quality Evidence Is Lacking for the Specificity Required in the Centers for Medicare and Medicaid Service’s Sepsis Bundle (SEP-1)*

Abstract

Objective: To address three controversial components in the Centers for Medicare and Medicaid Service’s sepsis bundle for performance measure (SEP-1): antibiotics within 3 hours, a 30 mL/kg fluid infusion for all hypotensive patients, and repeat lactate measurements within 6 hours if initially elevated. We hypothesized that antibiotic- and fluid-focused bundles like SEP-1 would probably show benefit, but evidence supporting specific antibiotic timing, fluid dosing, or serial lactate requirements would not be concordant. Therefore, we performed a meta-analysis of studies of sepsis bundles like SEP-1. Data Sources: PubMed, Embase, ClinicalTrials.gov through March 15, 2018. Study Selection: Studies comparing survival in septic adults receiving versus not receiving antibiotic- and fluid-focused bundles. Data Extraction: Two investigators (D.J.P., P.Q.E.). Data Synthesis: Seventeen observational studies (11,303 controls and 4,977 bundle subjects) met inclusion criteria. Bundles were associated with increased odds ratios of survival (odds ratio [95% CI]) in 15 studies with substantial heterogeneity (I 2 = 61%; p < 0.01). Survival benefits were consistent in the five largest (1,697–12,486 patients per study) (1.20 [1.11–1.30]; I 2 = 0%) and six medium-sized studies (167–1,029) (2.03 [1.52–2.71]; I 2 = 8%) but not the six smallest (64–137) (1.25 [0.42–3.66]; I 2 = 57%). Bundles were associated with similarly increased survival benefits whether requiring antibiotics within 1 hour (n = 7 studies) versus 3 hours (n = 8) versus no specified time (n = 2); or 30 mL/kg fluid (n = 7) versus another volume (≥ 2 L, n = 1; ≥ 20 mL/kg, n = 2; 1.5–2 L or 500 mL, n = 1 each; none specified, n = 4) (p = 0.19 for each comparison). In the only study employing serial lactate measurements, survival was not increased versus others. No study had a low risk of bias or assessed potential adverse bundle effects. Conclusions: Available studies support the notion that antibiotic- and fluid-focused sepsis bundles like SEP-1 improve survival but do not demonstrate the superiority of any specific antibiotic time or fluid volume or of serial lactate measurements. Until strong reproducible evidence demonstrates the safety and benefit of any fixed requirement for these interventions, the present findings support the revision of SEP-1 to allow flexibility in treatment according to physician judgment.

Hospital nurse staffing and sepsis protocol compliance and outcomes among patients with sepsis in the USA: a multistate cross-sectional analysis

“…Several investigators have questioned the use of the SEP-1 bundle and its association with patient outcomes, noting the need for additional evidence 18 19. Yet, all have failed to estimate the value of nurses—the clinicians who most often implement components of the SEP-1 bundle and actively monitor the status of these critically ill patients.…”

What Is the Utility of Measuring Lactate Levels in Patients with Sepsis and Septic Shock?

“…Rigid care bundles such as SEP-1 that emphasize timeliness over accuracy may contribute to the Lactate monitoring is increasingly emphasized in current sepsis guidelines and quality measures despite a paucity of evidence that checking lactate levels improves outcomes. 1 Han and colleagues retrospectively observed that for patients with an initial elevated lactate, delays in subsequent lactate draws were associated with increased mortality and increased time to antibiotics. 2 However, this and other retrospective studies suffer from ascertainment bias whereby lactate measurements increase detection of cases with less clinical severity.…”

What's new in critical illness and injury science? Antibiotics in critical care: Therapeutic toolbox

“…In patients with suspicion for infection, but without clinical evidence of cardiovascular or biochemical insufficiency, a goal of 3 h may be more realistic and acceptable. [24] Unknown variables still exist, such as variations in biologic phenotypes, where the host-response pattern to intervention is not as predicted. [25]…”