Abstract
BACKGROUND: Serial leukocyte counts have been investigated as a prognostic marker in critical illness. Our aim was to explore which immune cell type (total leukocytes, neutrophils, lymphocytes or neutrophil: lymphocyte ration (NLR)) best predicted mortality in critically ill patients. To address this, we conducted a systematic review, meta-analysis, and meta-regression of studies published within the past 10 years, archived on PubMed and Embase. Only studies reporting immune cell counts in critically ill patients on admission and within the subsequent week were included. Meta-regression was conducted to assess the effect of illness severity (reflected by study mortality rate) and underlying diagnosis (with 'general ICU patients' as a reference group) on the difference between immune cell counts between survivors and non-survivors. Meta-analysis and meta-regression were performed using Stata (version 19.5, StataCorp) and data presented as mean difference with (95% confidence intervals). RESULTS: Thirty studies including 26,441 reporting patient mortality were included. Neutrophil: lymphocyte ratio (NLR) best predicted mortality and was lower among survivors at on days 0-1 (-0.29 (-0.45 to -0.12), p = 0.001), 2-4 (-1.02 (-1.57 to -0.48), p < 0.001), and 5-7 (-0.69 (-1.00 to -0.38), p < 0.001). Lymphocyte count was higher at equivalent time points. Meta-regression of NLR suggest that heterogeneity between studies was partly explained by underlying illness severity on days 0-1 (mean difference decreases by 0.13 (0.05, 0.20) for a 10% increase in mortality, p = 0.001), but not at other time points. Underlying diagnosis did not explain heterogeneity between studies. We were unable to perform a meta-analysis investigating the association between leukocyte counts and secondary infections as only three studies reported this data. CONCLUSION: A higher NLR count was associated with increased mortality throughout the first week of critical illness. Further work is required to define of cut- off values using an ordinal scale of lymphocyte count that accurately reflects immune dysfunction and risk of mortality. PROSPERO REGISTRATION NUMBER: : CRD42024514115.