Varying association of laboratory values with reference ranges and outcomes in critically ill patients: An analysis of data from five databases in four countries across Asia, Europe and North America

Background Despite wide usage across all areas of medicine, it is uncertain how useful standard reference ranges of laboratory values are for critically ill patients. Objectives The aim of this study is to assess the distributions of standard laboratory measurements in more than 330 selected intensive care units (ICUs) across the USA, Amsterdam, Beijing and Tarragona; compare differences and similarities across different geographical locations and evaluate how they may be associated with differences in length of stay (LOS) and mortality in the ICU. Methods A multi-centre, retrospective, cross-sectional study of data from five databases for adult patients first admitted to an ICU between 2001 and 2019 was conducted. The included databases contained patient-level data regarding demographics, interventions, clinical outcomes and laboratory results. Kernel density estimation functions were applied to the distributions of laboratory tests, and the overlapping coefficient and Cohen standardised mean difference were used to quantify differences in these distributions. Results The 259 382 patients studied across five databases in four countries showed a high degree of heterogeneity with regard to demographics, case mix, interventions and outcomes. A high level of divergence in the studied laboratory results (creatinine, haemoglobin, lactate, sodium) from the locally used reference ranges was observed, even when stratified by outcome. Conclusion Standardised reference ranges have limited relevance to ICU patients across a range of geographies. The development of context-specific reference ranges, especially as it relates to clinical outcomes like LOS and mortality, may be more useful to clinicians.