Comment on “Predictive Effects of the Lactate/Albumin Ratio on Neurological Outcomes in Patients After Out-of-Hospital Cardiac Arrest”

Abstract

We read with great interest Nakada et al.'s large, nationwide analysis of the lactate/albumin ratio (LAR) measured on hospital arrival and its association with neurological outcomes after out-of-hospital cardiac arrest (OHCA) [1]. The authors should be commended for leveraging the Japanese Association for Acute Medicine (JAAM-OHCA) registry to test a biologically plausible composite biomarker across a broad population (n = 28,098) and for performing subgroup analyses addressing admission status and receipt of active post-resuscitation therapies. Their finding that LAR improved discrimination over lactate or albumin alone and modestly enhanced a reference model is relevant to early risk stratification in a condition where timely prognostic information is valuable. Nevertheless, several issues temper the translational value of the results.

First, the timing and selection for blood sampling were not standardized and depended on clinicians' discretion. This introduces selection bias, as patients undergoing longer evaluation or surviving slightly longer were more likely to have albumin measured, while albumin assays typically require more processing time than lactate [2]. Such variability may exaggerate LAR's prognostic value and likely contributed to the diminished incremental effect observed in admitted patients. Standardized, early sampling protocols would strengthen future validation.

Second, although discrimination metrics such as area under the curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were reported, the clinical impact remains unclear. An AUC of 0.83 is encouraging, yet the absolute gain over the reference model and its effect on decision thresholds were not quantified. Reporting predictive values, calibration, and net clinical benefit would clarify whether LAR provides practical guidance rather than only statistical improvement [3].

Third, residual confounding is possible. Albumin levels are influenced by chronic liver disease, nutritional status, and fluid balance [4], while lactate is affected by sepsis, epinephrine dosing, and prehospital variables [5]. These were not accounted for in the models, which may bias associations. Adjustment for comorbidity burden or sensitivity analyses excluding patients with advanced chronic disease would improve robustness.

Finally, operational considerations limit generalizability. Japan's emergency medical service (EMS) system, where field termination is rare, shapes the case mix and may not reflect other settings. External prospective validation with standardized sampling and serial biomarker kinetics will be essential to confirm clinical applicability.

In conclusion, Nakada et al. provide important large-scale evidence that LAR is associated with neurological outcomes after OHCA and improves prognostic discrimination beyond single biomarkers. Future studies should focus on standardized measurement, broader adjustment for confounders, and clinical utility analyses to establish whether LAR can serve as a practical adjunct in early post-resuscitation care.

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The authors have nothing to report.

The authors declare no conflicts of interest.

This article is linked to Nakada et al. paper “Predictive effects of the lactate/albumin ratio on neurological outcomes in patients after out-of-hospital cardiac arrest”. To view this article, visit https://doi.org/10.1002/ams2.70082.