Lymphopenia and elevated NLR identify patients with septic shock who may benefit from corticosteroids: a target trial emulation study

Abstract Background Septic shock is the most severe form of sepsis and has high mortality. Despite the widespread use of corticosteroids, evidence of their benefit remains unclear; precision critical care medicine has sought to identify which patients will benefit. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are widely available markers of inflammation and immune function. This study aimed to determine whether these parameters can identify septic shock patients likely to benefit from corticosteroid treatment. Methods A target trial was emulated using data from the Medical Information Mart for Intensive Care IV database. Adult patients in the ICU for at least 24 h who met the Sepsis-3 definition for septic shock were included. The cohort was divided into those who received corticosteroids and those who did not. Covariates extracted included NLR and PLR. An Augmented Inverse Probability Weighting (AIPW) double-robust estimator was applied to evaluate the effect of corticosteroids on ICU mortality (primary outcome), in-hospital mortality, the need for renal replacement therapy, the duration of vasopressor therapy, and the length of ICU and hospital stay (secondary outcomes). Univariate AUROC was used to compare the predictive performance of the evaluated parameters. Results 5,533 septic shock stays were identified; 1,009 (18.23%) received corticosteroids. The corticosteroid group was much sicker than the control group, with higher Sequential Organ Failure Assessment (SOFA) scores and greater vasopressor requirements. After adjusting for confounding via an AIPW doubly robust estimator, the analysis revealed that lower baseline lymphocyte count (AUROC 0.65), higher NLR (AUROC 0.62), and higher PLR (AUROC 0.63) had modest but consistent ability to identify cases that benefited from corticosteroid therapy, as reflected by reduced ICU mortality. These compared favourably to the use of the maximum SOFA score (AUROC 0.65) and had similar predictive power for all secondary outcomes. Conclusion Lower lymphocyte count, higher NLR and PLR were associated with an increased likelihood of model-estimated benefit from corticosteroids. Although the predictive power of these markers was modest, their low cost and wide availability could make them appealing in low-resource settings. Further research into these simple parameters to guide the treatment of septic shock is warranted.