CCCF Academy

Haines W, Ryan^1,2 ; Zolfaghari, Parjam^1,2 ; Wan, Yize^1,2 ; Pearse M, Pearse^1,2 ; Puthucheary, Zudin ^1,2 ; Prowle R, Prowle<sup>1,2,3

1</sup>Adult Critical Care Unit, The Royal London Hospital, Barts Health NHS Trust, Whitechapel Road, London, E1 1BB, UK
²William Harvey Research Institute, Queen Mary University of London, London, UK
³Department of Renal Medicine and Transplantation, The Royal London Hospital, Barts Health NHS Trust, Whitechapel Road, London, E1 1BB, UK
 

Introduction: Patients with prolonged ICU stay consume the majority of bed-days, have increased risk of late death, and a lower chance of returning directly home at hospital discharge. A definition and timeline of “persistent critical illness” has recently been developed [1, 2], however, the phenotype and potential biochemical signatures of this group are unknown. Muscle wasting is common amongst patients with persistent critical illness and associated with increased urea- 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 our pre-specified hypothesis we analysed two existing datasets of adults surviving ≥10 days following admission to ICU after major trauma.  Our primary analysis was based on a set of trauma-ICU admissions to the major trauma centre serving the North East London and Essex Trauma Network with a verification cohort of major 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 ICU stay of ≥10 days and those discharged from ICU before day 10. In a sub-group undergoing sequential 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: From the London cohort we included 1173 patients between February 1st, 2012 and May 1st, 2016. In patients in ICU for ≥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. In 2876 trauma-ICU admissions from MIMIC-III, urea:creatinine ratio similarly separated patients with ICU stay of <10 days and ≥10 days. In 107 patients undergoing serial CTs, muscle area fell consistently over time. For patients with second CTs from ≥10 days (n=48), L4-psoas area decreased by 27% [15-36], 32cm² [26-39] to 23cm² [15-28], p<0.001 and L3 muscle area by 19% [12-28], 174cm² [157-198] to 138cm² [112-161], p<0.001. Concurrently, urea:creatinine ratio rose by 111% [48-221], 47 [41-68] to 112 [50-222], p<0.001.
 
Conclusion: In patients admitted to ICU after major trauma, elevated urea:creatinine ratio accompanies skeletal muscle wasting and represents a biochemical signature of persistent critical illness. If prospectively confirmed, urea:creatinine ratio is a potential surrogate of catabolism to examine in epidemiological and interventional studies. 

1. Iwashyna TJ, Hodgson CL, Pilcher D, Bailey M, van Lint A, Chavan S, Bellomo R, (2016) Timing of onset and burden of persistent critical illness in Australia and New Zealand: a retrospective, population-based, observational study. Lancet Respir Med 4: 566-573

2. Bagshaw SM, Stelfox HT, Iwashyna TJ, Bellomo R, Zuege D, Wang X, (2018) Timing of onset of persistent critical illness: a multi-centre retrospective cohort study. Intensive Care Med 44: 2134-2144