title: Early sepsis bundle compliance for non-hypotensive patients with intermediate versus severe hyperlactemia.
abstract: OBJECTIVE
  To compare the association of 3-h sepsis bundle compliance with hospital mortality in non-hypotensive sepsis patients with intermediate versus severe hyperlactemia.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Emergency Medicine, Hofstra-Northwell School of Medicine, Hempstead, NY, United States; Icahn School of Medicine at Mount Sinai, New York, NY, United States. Electronic address: dleisman@northwell.edu.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Leisman
authors.affiliation: Department of Emergency Medicine, Hofstra-Northwell School of Medicine, Hempstead, NY, United States.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Zemmel D'Amore
authors.affiliation: Department of Emergency Medicine, Hofstra-Northwell School of Medicine, Hempstead, NY, United States.
authors.forename: Jeanie L
authors.initials: JL
authors.lastname: Gribben
authors.affiliation: Department of Neurosurgery, Hofstra-Northwell School of Medicine, Hempstead, NY, United States; Feinstein Institute for Medical Research, Manhasset, NY, United States.
authors.forename: Mary Frances
authors.initials: MF
authors.lastname: Ward
authors.affiliation: Krasnoff Quality Management Institute, Northwell Health System, New Hyde Park, NY, United States.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Masick
authors.affiliation: Department of Emergency Medicine, Hofstra-Northwell School of Medicine, Hempstead, NY, United States.
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Bianculli
authors.affiliation: Department of Emergency Medicine, Hofstra-Northwell School of Medicine, Hempstead, NY, United States.
authors.forename: Kathryn H
authors.initials: KH
authors.lastname: Bradburn
authors.affiliation: Department of Emergency Medicine, Hofstra-Northwell School of Medicine, Hempstead, NY, United States.
authors.forename: John K
authors.initials: JK
authors.lastname: D'Angelo
authors.affiliation: Department of Medicine, Hofstra-Northwell School of Medicine, Hempstead, NY, United States; Department of Science Education, Hofstra-Northwell School of Medicine, Hempstead, NY, United States.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Doerfler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016208:Databases, Factual; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D065906:Hyperlactatemia / Q000453:epidemiology*; D019344:Lactic Acid / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D058996:Quality Improvement; D018805:Sepsis / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D012720:Severity of Illness Index; D018746:Systemic Inflammatory Response Syndrome / Q000453:epidemiology*; D062606:Tertiary Care Centers; D013997:Time Factors; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents; D019344:Lactic Acid