All lactate are not equal substudy of the BOX trial

Abstract

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The BOX trial was supported by a grant (NNF17OC0028706) from the Novo Nordisk Foundation. Dr. Hassager's work is funded by a grant (R186-2015-2132) from the Lundbeck Foundation. Background Lactate levels following out-of-hospital cardiac arrest (OHCA) are associated with arrest duration (time to ROSC) and mortality. However, given the complexity of lactate generation and clearance, lactate levels assessed at hospital arrival represent not only time to ROSC but also the quality of resuscitation, circulatory stability following ROSC, dose of epinephrine administered, kidney, liver, and mitochondrial function in the early post-cardiac arrest phase. Accordingly, we describe the lactate levels at hospital arrival according to time to ROSC and one-year mortality. Method In this sub-study of the randomized clinical BOX trial, blood lactate levels were measured immediately at hospital arrival. Time to ROSC was registered in the medical records. Patients were divided into two groups according to median time to ROSC (≤ 18 min or > 18 min). The primary outcome was one-year mortality. Results The study included 768 (97% of the randomized population) patients of which 386 (50%) patients had ≤ 18 min and 382 (50%) patients had > 18 min to ROSC. The median age (64 (54-73) years) and sex distribution (81% men) was similar in both groups. One-year mortality was 76 (20%) and 199 (52%) in the ≤ 18 min and > 18 min to ROSC groups respectively. Mean lactate levels were 3.8 mmol/L (95%CI: 3.5-4.1) and 5.9 mmol/L (95%CI: 5.4-6.2), respectively. Lactate levels differed significantly between one-year survivors and non-survivors in the patients with ≤ 18 min to ROSC (mean difference: 1.9 mmol/L, 95%CI: 1.0 - 2.8) but not for patients with > 18 min to ROSC (mean difference: 0.6 mmol/L, 95%CI: -0.1-1.3), Figure 1. Further, lactate’s ability to predict one-year mortality was fair in the ≤ 18 min group with an Area Under Receiver Operating Characteristic Curve (AUC) of 0.68 (95%CI: 0.62-0.75) but poor for the > 18 min groups with an AUC of 0.55 (95%CI: 0.50-0.61) (DeLong's test for two ROC curves, p = 0.004), Figure 2. Conclusion Lactate's predictive value for one-year mortality decreases with increasing time to ROSC in OHCA. This highlights the importance of individualized clinical approaches based on lactate dynamics in OHCA patients.Figure 1Figure 2