Early sepsis bundle compliance for non-hypotensive patients with intermediate versus severe hyperlactemia

ObjectiveTo compare the association of 3-h sepsis bundle compliance with hospital mortality in non-hypotensive sepsis patients with intermediate versus severe hyperlactemia.MethodsThis 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:1.Blood cultures before antibiotics.2.Parenteral antibiotics administered ≤ 180 min from ≥ 2 SIRS and lactate ordered, or ≤ 60 min from “time-zero”, whichever occurred first.3.Lactate result available ≤ 90 min post-order.4.30 mL/kg crystalloid bolus initiated ≤ 30 min from “time-zero”.The primary outcome was 60-day in-hospital mortality.Results2417 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.ConclusionWe 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.