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

Introduction et but de l'etude: 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. Materiel et methodes: 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. Resultats 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(s): 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.Copyright © 2023

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

BACKGROUND & AIMS: The intensity and duration of the catabolic phase in COVID-19 patients can differ between survivors and non-survivors. The purpose of the study was to assess the determinants of, and association between, nitrogen balance trajectories and outcome in critically ill COVID-19 patients. METHODS: This retrospective monocentric observational study involved patients admitted to the intensive care unit (ICU) of the University Hospital of Clermont Ferrand, France, from January 2020 to May 2021 for COVID-19 pneumonia. 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 the time course of nitrogen balance according to outcome were analyzed using two-way ANOVA. At days 3, 5, 7, 10 and 14, uni- and multivariate logistic regression analyses were performed to assess the impact of a non-negative nitrogen-balance on ICU death. To investigate the relationships between nitrogen balance, inflammatory markers and protein intake, linear and non-nonlinear models were run at days 3, 5 and 7, and the amount of protein intake necessary to reach a neutral nitrogen balance was calculated. Subgroup analyses were carried out according to BMI, age, and sex. RESULTS: 99 patients were included. At day 3, a similar negative nitrogen balance was 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, but decreased from day 2 to day 6 in non-survivors, and thereafter increased slowly up to day 14. At days 5 and 7, a non-negative nitrogen-balance was protective from death. Administering higher protein amounts was associated with higher nitrogen balance. 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 the amount of protein intake required by COVID-19 patients.

Prognostic value of serum albumin and urea nitrogen excretion in COVID-19 ICU patients: a single-center, prospective, cohort study

Introduction. Catabolic syndrome is typical for most critical illness situations. A long progressive course of hypercatabolism is considered by a number of authors as a prognostic criterion for negative clinical outcome of the disease. Objective. Evaluation of the prognostic value of some indicators of the severity of catabolic syndrome in ICU patients with COVID-19. Materials and methods. A prospective cohort study was conducted in 55 patients of the intensive care unit in the period from May 2020 to March 2021. The severity of hypercatabolism was determined by the dynamics of serum albumin and daily urinary nitrogen excretion within 14 days from admission to the ICU. Comparative analysis of nonparametric quantitative data was carried out using the Mann–Whitney test. To determine the predictive value of the diagnostic test, we plotted using the curves of operating characteristics (ROC, Receiver Operating Characteristics) with the subsequent determination of the sensitivity and specificity at the separation point. Results. ROC analysis revealed moderate sensitivity (75.9 %) and low specificity (58.1 %) of the daily urinary nitrogen excretion during the first 14 days of treatment in the ICU in patients with severe SARS-CoV-2. It was also shown that the dynamics of serum albumin has a low predictive value for negative clinical outcome. It should be noted that in the group of survived patients a significant increase in daily urinary nitrogen excretion was observed on days 4–7 (p = 0.022) and 8–14 (p = 0.01) of intensive therapy. Conclusion. Nitrogen urinary excretion is a more accurate prognostic marker of poor clinical outcome than serum albumin in ICU patients with severe COVID-19. The main feature of the catabolic syndrome in patients with positive clinical outcome is a progressive increase in the rate of urinary nitrogen excretion from 4 to 14 days after admission to ICU. © 2021, Practical Medicine Publishing House LLC. All rights reserved.

Qualitative and quantitative muscle ultrasound changes in patients with COVID-19-related ARDS.

OBJECTIVES: Severe forms of the novel coronavirus-19 (COVID-19) are associated with systemic inflammation and hypercatabolism. The aims of this study were to compare the time course of the size and quality of both rectus femoris and diaphragm muscles between critically ill, COVID-19 survivors and non-survivors and to explore the correlation between the change in muscles size and quality with the amount of nutritional support delivered and the cumulative fluid balance. METHODS: This was a prospective observational study in the general intensive care unit (ICU) of a tertiary care hospital for COVID-19. The right rectus femoris cross-sectional area and the right diaphragm thickness, as well as their echo densities were assessed within 24 h from ICU admission and on day 7. We recorded anthropometric and biochemical data, respiratory mechanics and gas exchange, daily fluid balance, and the number of calories and proteins administered. RESULTS: Twenty-eight patients were analyzed (65 ± 10 y of age; 80% men, body mass index 30 ± 7.8 kg/m2). Rectus femoris and diaphragm sizes were significantly reduced at day 7 (median = -26.1 [interquartile ratio [IQR], = -37.8 to -15.2] and -29.2% [-37.8% to -19.6%], respectively) and this reduction was significantly higher in non-survivors. Both rectus femoris and diaphragm echo density were significantly increased at day 7, with a significantly higher increase in non-survivors. The change in both rectus femoris and diaphragm size at day 7 was related to the cumulative protein deficit (R = 0.664, P < 0.001 and R = 0.640, P < 0.001, respectively), whereas the change in rectus femoris and diaphragm echo density was related to the cumulative fluid balance (R = 0.734, P < 0.001 and R = 0.646, P < 0.001, respectively). CONCLUSIONS: Early changes in muscle size and quality seem related to the outcome of critically ill COVID-19 patients, and to be influenced by nutritional and fluid management strategies.

Protein requirements for critically ill ventilator-dependent patients with COVID-19.

BACKGROUND: Recent studies indicate critically ill patients with coronavirus disease 2019 (COVID-19) are hypermetabolic; however, protein requirements in critically ill COVID-19 patients are unknown. Our intent was to evaluate the nitrogen accretion response to varying protein intakes for critically ill ventilator-dependent patients with COVID-19. METHODS: Adult patients (age ≥ 18 years) with COVID-19, admitted to the intensive care unit (ICU) and who required mechanical ventilation were retrospectively evaluated. Patients received continuous enteral nutrition (EN), including supplemental protein boluses, and had a 24-h urine collection for determination of nitrogen balance (NBAL). Data are expressed as mean ± SD with a P-value < .05 as significant. RESULTS: Twenty-two patients provided 29 NBAL determinations. Protein intake from EN and protein supplements was 0.9 ± 0.7 g/kg/day at the time of the NBAL with an NBAL of -12.1 ± 10.9 g/day at 7 ± 4 days in the ICU. Combined caloric intake from EN and propofol at the time of the NBAL was 12 ± 8 kcal/kg/day. Nitrogen equilibrium (NBAL of -4 g/day or better) occurred in five patients. Patients achieving nitrogen equilibrium received more protein than those with a negative NBAL (1.2 ± 0.4 g/kg/day vs 0.8 ± 0.8 g/kg/day, P = .046). The linear regression for NBAL in response to graded increases in protein intake was as follows: NBAL = 8.5 × protein intake (g/kg/day) - 18.8 (r = 0.450, P < .001). CONCLUSION: Critically ill ventilator-dependent patients with COVID-19 exhibit significant variability in nitrogen accretion response to increases in protein intake and often have a markedly negative NBAL.