Abstract

Recent advances in emergency medicine and the co-ordinated delivery of trauma care mean more critically-injured patients now reach the hospital alive and survive life-saving operations. Indeed, between 2008 and 2017, the odds of surviving a major traumatic injury in the UK increased by nineteen percent. However, the improved survival rates of severely-injured patients have placed an increased burden on the healthcare system, with major trauma a common cause of intensive care unit (ICU) admissions that last ≥10 days. Improved understanding of the factors influencing patient outcomes is now urgently needed. We investigated the serum metabolomic profile of fifty-five major trauma patients across three post-injury phases: acute (days 0–4), intermediate (days 5–14) and late (days 15–112). Using ICU length of stay (LOS) as a clinical outcome, we aimed to determine whether the serum metabolome measured at days 0–4 post-injury for patients with an extended (≥10 days) ICU LOS differed from that of patients with a short (<10 days) ICU LOS. In addition, we investigated whether combining metabolomic profiles with clinical scoring systems would generate a variable that would identify patients with an extended ICU LOS with a greater degree of accuracy than models built on either variable alone. The number of metabolites unique to and shared across each time segment varied across acute, intermediate and late segments. A one-way ANOVA revealed the most variation in metabolite levels across the different time-points was for the metabolites lactate, glucose, anserine and 3-hydroxybutyrate. A total of eleven features were selected to differentiate between <10 days ICU LOS vs. >10 days ICU LOS. New Injury Severity Score (NISS), testosterone, and the metabolites cadaverine, urea, isoleucine, acetoacetate, dimethyl sulfone, syringate, creatinine, xylitol, and acetone form the integrated biomarker set. Using metabolic enrichment analysis, we found valine, leucine and isoleucine biosynthesis, glutathione metabolism, and glycine, serine and threonine metabolism were the top three pathways differentiating ICU LOS with a p < 0.05. A combined model of NISS and testosterone and all nine selected metabolites achieved an AUROC of 0.824. Differences exist in the serum metabolome of major trauma patients who subsequently experience a short or prolonged ICU LOS in the acute post-injury setting. Combining metabolomic data with anatomical scoring systems allowed us to discriminate between these two groups with a greater degree of accuracy than that of either variable alone.

Highlights

  • Using intensive care unit (ICU) length of stay (LOS) as a clinical outcome, we aimed to determine whether the serum metabolome measured at days 0–4 post-injury for patients with an extended (≥10 days) ICU LOS differed from that of patients with a short (

  • In paediatric and adult trauma settings, several groups have investigated whether an assessment of injury severity at hospital presentation can aid in the identification of patients at risk of a prolonged ICU LOS [17–19,42]

  • Whilst some studies have reported either no or weak positive associations between injury severity scores and ICU LOS [42], others have shown that statistical models built on the anatomical scoring systems of ISS or New Injury Severity Score (NISS) can distinguish between patients who experience a short or long ICU LOS [17–19]

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Summary

Introduction

Recent advancements in emergency medicine and the co-ordinated delivery of trauma care mean more critically-injured patients reach the hospital alive and survive lifesaving operations. The improved survival rates of severely-injured patients have placed an increased burden on the healthcare system, with major trauma a common cause of intensive care unit (ICU) admissions that last ≥14 days [2–4]. Despite representing a small proportion of all hospital admissions, critically-ill patients with a prolonged ICU stay consume the greatest amount of resources on ICU wards [5–7]. Patients who experience an extended ICU length of stay (LOS) develop more secondary complications [6,8], are at a higher risk of in-hospital mortality [9] and are frequently discharged to rehabilitation centres or skilled nursing facilities [6]. To allocate resources and improve clinical outcomes, there is an urgent need to develop strategies to identify trauma patients at risk of a prolonged ICU LOS at the earliest opportunity

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