Effect of Timely Lactate Measurement on In-hospital Mortality among Adults with Hypotension and Hyperlactatemia: An Observational Study on Two Cohorts

Abstract Background: Whether patients presented with hypotension and hyperlactatemia can benefit from timely lactate measurement and further lactate-guide resuscitation were not fully understood.Methods: This was a retrospective observational study based on the data from the Medical Information Mart for Intensive Care (MIMIC)-III Database and the eICU Collaborative Research Database (eICU). Patients with hypotension (defined as a minimal systolic blood pressure ≤90 mm Hg or minimal mean arterial pressure ≤65 mm Hg or requiring any vasopressors support during the first 24 h after ICU admission) and hyperlactatemia (defined as an initial lactate level > 2.0 mmol/L after ICU admission) were eligible.The primary exposure was the timely lactate measurement, which was defined as an initial lactate level measured within 1 h after ICU admission. The primary outcome was in-hospital mortality. The statistical approaches included multivariate regression, propensity score matching (PSM) and an inverse probability of treatment weighing (IPTW) and causal mediation analysis (CMA) were utilized to elucidate the relationship between timely lactate measurement and in-hospital mortality. Results: A total of 9978 patients were identified, of which 4257 in MIMIC-III and 5721 in eICU. Timely lactate measurement was associated with lower risk-adjusted in-hospital mortality both in MIMIC (OR 0.70 (95%CI 0.58-0.85; p<0.001)) and eICU (OR 0.75 (95%CI 0.64-0.88; p<0.001)). Time to initial intravenous fluid (IVF) in MIMIC mediated 6.7% (95%CI 1.4%-38%; p<0.001) of the beneficial effect of timely lactate measurement (p<0.001 for average causal mediation effect (ACME)) in terms of in-hospital mortality. Finally, delayed initial lactate measurements are also associated an increased in-hospital mortality in MIMIC and eICU.Conclusions: Timely lactate measurement is associated with a lower risk-adjusted in-hospital mortality among patients with hypotension and hyperlactatemia, which was proportional mediated through shortening the time to IVF. Delay in initial lactate measurement showed a positive association with in-hospital mortality.