To compare the association of 3-h sepsis bundle compliance with hospital mortality in non-hypotensive sepsis patients with intermediate versus severe hyperlactemia.

This was a cohort study of all non-hypotensive, hyperlactemic sepsis patients captured in a prospective quality-improvement database, treated October 2014 to September 2015 at five tertiary-care centers. We defined sepsis as 1) infection, 2) ≥2 SIRS criteria, and 3) ≥1 organ dysfunction criterion. “Time-zero” was the first time a patient met all sepsis criteria. Inclusion criteria: systolic blood pressure>90 mmHg, mean arterial pressure>65 mmHg, and serum lactate≥2.2 mmol/L. Primary exposures: 1) intermediate(2.2–3.9 mmol/L) versus severe(≥4.0 mmol/L) hyperlactemia and 2) full 3-h bundle compliance. Bundle elements:

The primary outcome was 60-day in-hospital mortality.

2417 patients met inclusion criteria. 704(29%) had lactate≥4.0 mmol/L versus 1775 patients with lactate 2.2–3.9 mmol/L. Compliance was 75% for antibiotics and 53% for fluids. Full-compliance was comparable between lactate groups (n=200(29%) and 488(28%), respectively). We observed 424(17.5%) mortalities: intermediate/non-compliant – 182(14.9%), intermediate/compliant – 41(8.4%), severe/non-compliant – 147(29.2%), severe/compliant – 54(27.0%) [difference-of-differences=4.3%, CI=2.6–5.9%]. In multivariable regression, mortality predictors included severe hyperlactemia (OR=1.99, CI=1.51–2.63) and bundle compliance (OR=0.62, CI=0.42–0.90), and their interaction was significant: p_{(interaction)}=0.022.

We observed a significant interaction between 3-h bundle compliance and initial hyperlactemia. Bundle compliance may be associated with greater mortality benefit for non-hypotensive sepsis patients with less severe hyperlactemia.