What is the ideal glucose range for a patient with sepsis in the ICU? A retrospective analysis of MIMIC-IV

IMPORTANCE: Clinical trials have produced inconclusive results regarding the optimal glucose range for a patient with sepsis in the intensive care unit (ICU) receiving insulin treatment. OBJECTIVE: To investigate the optimal glucose range in patients with sepsis in the ICU independent of confounding covariates. DESIGN: Targeted trial emulation of glucose ranges using causal inference targeted maximum likelihood estimation and longitudinal mixed-effects models combined with survival models. SETTING: Single-centre, academic referral hospital in Boston, Massachusetts, USA. PARTICIPANTS: Adults fulfilling sepsis 3 criteria with at least three glucose readings and insulin treatment from the Medical Information Mart for Intensive Care (MIMIC)-IV database (2008-2019). EXPOSURE: Five predefined glucose distributions with means at 100, 130, 160 (baseline), 190 and 220 mg/dL mimicking current guidelines' recommendations (140-180 mg/dL). MAIN OUTCOME AND MEASURE: The primary outcome was in-hospital mortality. Modified counterfactual treatment-policy risks across distinct time-weighted glucose ranges were estimated. RESULTS: Of 73 181 eligible patients, 8002 patients with a median age of 66 years (41% women, 67% white ethnicity, 57% diabetes) were included. There was a U-shaped curve between glucose range and mortality in patients without diabetes, but overall, this association was not significant (mean glucose at 100 mg/dL with 21% mortality and mean glucose at 220 mg/dL with 26% mortality, p-for-trend 0.26). Mortality was lowest at 17%, with mean glucose between 130 and 160 mg/dL. Hypoglycaemic events (