Association of nitrogen-balance trajectories with clinical outcomes in critically ill COVID-19 patients : A retrospective cohort study

INTRODUCTION ET BUT DE L’ÉTUDE: The intensity and duration of the catabolic phase in COVID-19 patients might differ between survivors and non-survivors. The purpose of the study was to assess the association between nitrogen-balance trajectories and outcome in critically ill COVID-19 patients. MATÉRIEL ET MÉTHODES: It is a retrospective monocentric observational study, achieved into the intensive care unit of the University Hospital of Clermont-Ferrand, France. Patients admitted to intensive care from January 2020 to May 2021 for COVID-19 pneumonia were included. Patients were excluded if referred from another ICU, if their ICU length of stay was < 72 h, or if they were treated with renal replacement therapy during the first seven days after ICU admission. Data were collected prospectively at admission and during ICU stay. Death was recorded at the end of ICU stay. Comparisons of nitrogen-balance time course according to outcome were made using two-way ANOVA. At days 3, 5, 7, 10 and 14, uni and multivariate logistic regression analyses were achieved to assess the impact of a non-negative nitrogen-balance on ICU death. At Days 3, 5 and 7, to represent the relationship between nitrogen-balance and protein intakes, linear and non-nonlinear models were run and the protein intakes necessary to reach a zero nitrogen-balance were determined. Subgroup analyses were carried out by BMI, age, and sex. RÉSULTATS ET ANALYSES STATISTIQUES: Ninety-nine patients were included. At Day 3, similar negative nitrogen-balances were observed in survivors and non-survivors: −16.4 g/d [−26.5, −3.3] and −17.3 g/d [−22.2, −3.8] (P = 0.54). The trajectories of nitrogen-balance over time thus differed between survivors and non-survivors (P = 0.01). In survivors, nitrogen-balance increased over time, whereas in non-survivors, nitrogen-balance decreased from Day 2 to Day 6, and thereafter increased slowly up to Day 14. At Day 5 and 7, a non-negative nitrogen-balance was protective from death. Administering higher protein amounts was associated with higher nitrogen-balances. CONCLUSION: We report a prolonged catabolic state in COVID patients that seemed more pronounced in non-survivors than in survivors. Our study underlines the need for monitoring urinary nitrogen excretion to guide protein intakes in COVID-19 patients.