Door to lactate clearance: insights from a randomized trial in out of hospital cardiac arrest

Blood lactate is a key marker of tissue hypoperfusion and prognosis in critically ill patients, including those with cardiogenic shock (CS) and out-of-hospital cardiac arrest (OHCA). Recently, the concept of door-to-lactate clearance (DLC)—time from admission to normalization of lactate (<2 mmol/L) within 24 hours—has been proposed as a simple, bedside quality metric, analogous to door-to-balloon times in ST-elevation myocardial infarction care. Importantly, many major CS registries and trials have included patients with OHCA. Post-arrest physiology may transiently mimic shock, and high lactate may reflect mechanisms other than ongoing impaired perfusion. We therefore investigated the association of the DLC metric with cardiac function and outcome in OHCA patients across varying arrest durations.

This was a post-hoc exploratory sub-study of the BOX trial, which enrolled comatose resuscitated OHCA patients. Lactate and cardiac output were measured at predefined time points using arterial blood gas analysis and pulmonary artery catheterization. The association between mean cardiac index (0–24 h) and DLC ≤24 h was examined with logistic regression, adjusted for time-to-return of spontaneous circulation (ROSC) tertiles, initial left ventricular ejection fraction (LVEF), and the mean arterial pressure target intervention. The association between DLC ≤24 h and 1-year mortality was assessed with Cox regression using a 24-h landmark among patients alive at 24 h, adjusted for time to ROSC.

Of 789 patients, 692 (88%) had initial lactate ≥2 mmol/L and were analyzed. Median age was 64 yrs (IQR 54–72), 20% were female, median ROSC 20 min (13–27), LVEF 35% (25–45), cardiac index 1.67 L/min/m² (1.33–2.05), and lactate 5.8 mmol/L (3.6–8.4). Median DLC time was 6 h (6–24); 547 patients (79%) achieved DLC ≤24 h.

Among 24-h survivors (n=672), DLC ≤24 h was associated with lower 1-year mortality (34% vs. 59%) (HR 0.52; 95% CI 0.39–0.68). This effect was most evident with ROSC ≤15 min (HR 0.46; 0.22–0.98), and not statistically significant in longer ROSC strata (ROSC 16-23 min: HR: 0.80, 95%CI 0.43 - 1.49 and ROSC ≥24 min: HR: 0.75, 95%CI 0.52 - 1.09, respectively), P-interaction=0.47.

Median average cardiac index (0–24 h) was 1.82 L/min/m² (1.52–2.19). Higher cardiac index was associated with DLC ≤24 h only in patients with ROSC ≤15 min (OR per 10% increase 1.22; 95% CI 1.05–1.42), but not in those with ROSC 16–23 min (OR 1.06; 0.90–1.24) or ≥24 min (OR 0.96; 0.87–1.06; P-interaction=0.030).

In this OHCA cohort with initially reduced LVEF and cardiac index, the 24-h DLC quality metric was associated with survival and cardiac output primarily in patients with shorter arrest durations, with no statistically significant associations after prolonged arrests. Given that many CS patients present after OHCA, these findings suggest that the utility of DLC as a universal quality metric may depend on arrest duration.