Elevated urea-to-creatinine ratio provides a biochemical signature of muscle catabolism and persistent critical illness after major trauma

Purpose: Muscle wasting is common amongst patients with persistent critical illness and associated with increased urea production, but reduced creatinine production. We hypothesised that elevated urea:creatinine ratio would provide a biochemical signature of muscle catabolism and characterise prolonged intensive care (ICU) admissions after major trauma. Methods: Using pre-specified hypotheses, we analysed two existing data sets of adults surviving >= 10 days following admission to ICU after major trauma. We analysed trauma-ICU admissions to the major trauma centre serving the North East London and Essex Trauma Network, with a verification cohort of trauma-ICU cases from the MIMIC-III database. We compared serum urea, creatinine, and urea:creatinine ratio (ratio of concentrations in mmol/L) between patients with persistent critical illness (defined as ICU stay of >= 10 days) and those discharged from ICU before day 10. In a sub-group undergoing sequential abdominal computerised tomography (CT), we measured change in cross-sectional muscle area (psoas muscle at L4 vertebral level and total muscle at L3 level) and assessed for relationships with urea:creatinine ratio and ICU stay. Results are provided as median [interquartile range]. Results: We included 1173 patients between February 1st, 2012 and May 1st, 2016. In patients with ICU stay >= 10 days, day 10 urea:creatinine ratio had increased by 133% [72-215], from 62 [46-78] to 141 [114-178], p < 0.001; this rise was larger (p < 0.001) than in patients discharged from ICU before day 10, 59% [11-122%], 61 [45-75] to 97 [67-128], p < 0.001. A similar separation in trajectory of urea:creatinine ratio was observed in 2876 trauma-ICU admissions from MIMIC-III. In 107 patients undergoing serial CTs, decrease in L4 psoas and L3 muscle cross-sectional areas between CTs significantly correlated with time elapsed (R-2 = 0.64 and R-2 = 0.59, respectively). Rate of muscle decrease was significantly greater (p < 0.001 for interaction terms) in 53/107 patients with the second CT during evolving, current or recent persistent critical illness. In this group, at the second CT urea:creatinine ratio negatively correlated with L4 psoas and L3 muscle cross-sectional areas (R-2 0.39, p < 0.001 and 0.44, p < 0.001). Conclusion: Elevated urea:creatinine ratio accompanies skeletal muscle wasting representing a biochemical signature of persistent critical illness after major trauma. If prospectively confirmed, urea:creatinine ratio is a potential surrogate of catabolism to examine in epidemiological and interventional studies.