How infection affects the relationship between leukocyte count and mortality risk in intensive care

Leukocyte count is widely available and included in Intensive Care Unit prognostic systems. We hypothesised that the relationship between leukocytosis and mortality risk might differ in critically ill patients admitted with infection, where leukocytosis may be an adaptive response. We performed a registry-based study using the Australian and New Zealand Intensive Care Society Adult Patient Database between 2010 and 2023, across 212 Intensive Care Units. Using descriptive statistics and mixed-effects multivariable logistic regression, we evaluated the association between early peak leukocyte count and mortality, according to whether infection was the primary diagnosis. We examined 2,016,578 patients, of whom 1,742,195 had non-infective illnesses (86.4%). In this group, there were 115,613 (6.6%) deaths, and a progressive increase in the adjusted odds of mortality as leukocyte counts increased above 8 × 109/L, peaking at 40 × 109/L (adjusted odds ratio 2.40 (99% CI 2.16–2.66)). This was equivalent to a rise in risk-adjusted mortality from 5.4% (99% CI 5.1–5.6) for leukocyte counts of 8–12 × 109/L, to 9.4% (99% CI 8.6–10.1) for leukocyte counts at 40 × 109/L. Amongst 274,383 patients with infection, there were 37,350 (13.6%) deaths. Leukocytosis had no effect on the odds of mortality. This group had a risk-adjusted mortality of 12.8% (99% CI 12.2–13.3) for leukocyte counts of 8–12 × 109/L and 13.0% (99% CI 11.8–14.1) for leukocyte counts at 40 × 109/L. Lower leukocyte counts, even within the normal range, were associated with mortality in both groups. The presence of infection determines the prognostic significance of leukocytosis in the critically ill.