Elevated urea-to-creatinine ratio provides a biochemical signature of muscle catabolism and persistent critical illness after major trauma
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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.
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].
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 (R2 = 0.64 and R2 = 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 (R2 0.39, p < 0.001 and 0.44, p < 0.001).
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.
KeywordsMuscle wasting Major trauma Sarcopenia Creatinine Urea Intensive care unit acquired weakness Urea–creatinine ratio
Royal London ACCU office, Royal London Hospital Trauma audit team, Dr. Bhavi Trivedi (powerInsight access), Prof Karim Brohi, Mr. Nigel Tai and Mr. Wayne Sapsford (Collector Trauma database access).
All authors reviewed and approved the final manuscript. JP and PZ were responsible for the study concept and RH, PZ, ZP, and JP for study design. Data extraction was undertaken by RH, PZ, and JP. RH, PZ, ZP, and JP were responsible for data analysis and JP, PZ, ZP, YW, and RP provided comments and review of draft analyses.
Compliance with ethical standards
Conflicts of interest
ZP is on specialist advisor boards for GlaxoSmithkline, Fresunius Kabi and Faraday Pharmaceuticals and has given lectures and/or performed consultancy work for Lyric Pharmaceuticals, Faraday Pharmaceuticals, Orion Pharmaceuticals and Nestle. RP holds research grants, has given lectures and/or performed consultancy work for BBraun, GlaxoSmithkline, Medtronic, Intersurgical and Edwards Lifesciences. JP has given lectures and/or performed consultancy work for Fresenius Medical, Baxter, Nikkiso, Biomerieux, Abbott, Medibeacon and Quark Pharma.
As this study was carried out on the basis of analysis of routinely collected data by the usual care team, consent for sharing of anonymised patient level data is not available. The investigators will consider proposals for sub-analyses on a collaborative basis.
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