Abstract
Patients in the intensive care unit (ICU) are at high risk of mortality which is not well predicted. Previous studies noted that leucine has prognostic value in a variety of diseases. This study investigated whether leucine concentration was a useful biomarker of metabolic and nutritional status and 6-month mortality in ICU. We recruited 454 subjects admitted to ICU (348 and 106 in the initiation and validation cohorts, respectively) with an acute physiology and chronic health evaluation (APACHE II) score ≥ 15. We measured plasma leucine concentrations, traditional biomarkers, and calculated APACHE II and sequential organ failure assessment (SOFA) scores. Leucine levels were weakly correlated with albumin, prealbumin, and transferrin levels (r = 0.30, 0.12, and 0.15, p = 0.001, 0.029, and 0.007, respectively). During follow-up, 116 (33.3%) patients died. Compared to patients with leucine levels between 109 and 174 μM, patients with leucine > 174 μM or <109 μM had a lower cumulative survival rate. Death was also associated with age, higher APACHE II and SOFA scores, C-reactive protein, and longer stays in the ICU, but with lower albumin, prealbumin, and transferrin. Patients with leucine levels > 174 μM had higher alanine aminotransferase levels, but no significant differences in other variables; patients with leucine levels < 109 μM had higher APACHE II and SOFA scores, higher incidence of using inotropic agents, longer ICU and hospital stays, but lower albumin and transferrin levels. Multivariable analysis demonstrated that leucine > 174 μM was an independent predictor of mortality, especially early mortality. However, among patients who stayed in ICU longer than two weeks, leucine < 109 μM was an independent predictor of mortality. In addition, leucine < 109 μM was associated with worse ventilator weaning profiles. These findings were similar in the validation cohort. Our study demonstrated a U-shape relationship between leucine levels and mortality rate in ICU.
Highlights
Patients admitted to the intensive care unit (ICU) are at high risk of morbidity and mortality [1,2,3]
We demonstrated that blood leucine concentrations had a clear correlation with the total amount of essential amino acids, indicating that leucine can potentially represent the quantity of fundamental elements for protein synthesis [12]
From April 2017 to February 2020, for the initiation cohort, patients were consecutively enrolled at the contemporary medical and cardiac ICU based on these inclusion criteria: (1) they were at critical status with an APACHE II score ≥ 15, (2) they needed to stay in the ICU > 48 hours, and (3) they were older than 20 years old
Summary
Patients admitted to the intensive care unit (ICU) are at high risk of morbidity and mortality [1,2,3]. In 1950, Cuthbertson et al defined distinct catabolic pathophysiology and nutritional deficiency at different phases throughout the trajectory of critical illness [4]. Nutritional parameters, including albumin, prealbumin, and transferrin, provide prognostic value in critical patients [6,7,8,9] All these nutritional biomarkers are proteins with a complex process of synthesis that depends on the amount of amino acids present; a variety of factors may interfere with the level of these biomarkers, such as inflammation, caloric intake, and iron storage. Further investigation is merited to understand the value of measuring blood leucine levels in patients with critical illness
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