Medical nutrition therapy and clinical outcomes in critically ill adults: a European multinational, prospective observational cohort study (EuroPN)

Abstract

Background: Medical nutrition therapy may be associated with clinical outcomes in critically ill patients with prolonged intensive care unit (ICU) stay. We wanted to assess nutrition practices in European intensive care units (ICU) and their importance for clinical outcomes.

Methods: Prospective multinational cohort study in patients staying in ICU ≥ 5 days with outcome recorded until day 90. Macronutrient intake from enteral and parenteral nutrition and non-nutritional sources during the first 15 days after ICU admission was compared with targets recommended by ESPEN guidelines. We modeled associations between three categories of daily calorie and protein intake (low: < 10 kcal/kg, < 0.8 g/kg; moderate: 10-20 kcal/kg, 0.8-1.2 g/kg, high: > 20 kcal/kg; > 1.2 g/kg) and the time-varying hazard rates of 90-day mortality or successful weaning from invasive mechanical ventilation (IMV).

Results: A total of 1172 patients with median [Q1;Q3] APACHE II score of 18.5 [13.0;26.0] were included, and 24% died within 90 days. Median length of ICU stay was 10.0 [7.0;16.0] days, and 74% of patients could be weaned from invasive mechanical ventilation. Patients reached on average 83% [59;107] and 65% [41;91] of ESPEN calorie and protein recommended targets, respectively. Whereas specific reasons for ICU admission (especially respiratory diseases requiring IMV) were associated with higher intakes (estimate 2.43 [95% CI: 1.60;3.25] for calorie intake, 0.14 [0.09;0.20] for protein intake), a lack of nutrition on the preceding day was associated with lower calorie and protein intakes (- 2.74 [- 3.28; - 2.21] and - 0.12 [- 0.15; - 0.09], respectively). Compared to a lower intake, a daily moderate intake was associated with higher probability of successful weaning (for calories: maximum HR 4.59 [95% CI: 1.5;14.09] on day 12; for protein: maximum HR 2.60 [1.09;6.23] on day 12), and with a lower hazard of death (for calories only: minimum HR 0.15, [0.05;0.39] on day 19). There was no evidence that a high calorie or protein intake was associated with further outcome improvements.

Conclusions: Calorie intake was mainly provided according to the targets recommended by the active ESPEN guideline, but protein intake was lower. In patients staying in ICU ≥ 5 days, early moderate daily calorie and protein intakes were associated with improved clinical outcomes. Trial registration NCT04143503 , registered on October 25, 2019.

Keywords: Calorie; Critical illness; Mechanical ventilation; Nutrition; Protein; Survival; Weaning.

Fig. 1

Flowchart. *No values on calorie and protein intake were provided for 20 and 41 patients who received oral nutrition only. ICF Informed consent form, LAR legal representative

Fig. 2

Daily calorie and protein intake, and distribution of nutrition resources. Intake is presented as median, interquartile range, minimum, and maximum values with outliers versus pre-defined targets (blue horizontal bars) based on the 2019 ESPEN Guideline on Clinical Nutrition in Critical Care, and with proportion of nutrition resources used on a respective day. ESPEN-defined daily calorie intake targets were 10 kcal/kg on D1, 15 kcal/kg on D2–D3, 20 kcal/kg on D4–D6, 25 kcal/kg on D7–D15. ESPEN-defined daily protein intake targets were 0.6 g/kg on D1, 0.9 g/kg on D2–D3, 1.3 g/kg on D4–D15. Non-nutritional calories included the use of glucose solutions, propofol, clevidipine, and citrate from renal replacement therapy. Patients without any nutrition on a respective day were counted with 0 kcal or 0 g protein. The EN and/or PN categories also included patients who had received small amounts of calories/protein from oral nutrition/ONS. EN enteral nutrition, ON oral nutrition, ONS oral nutritional supplements, PN parenteral nutrition

Fig. 3

Confounder-adjusted, time-varying association of a medical nutrition therapy providing fewer vs more calories, with outcomes. Columns 1 and 4: Hypothetical medical nutrition therapy comparisons analyzing different levels of daily calorie intakes: low: < 10 kcal/kg; moderate: 10–20 kcal/kg; high: > 20 kcal/kg (Table 1). Columns 2 and 3, and 5 and 6: Corresponding time-varying associations of different hypothetical medical nutrition therapies with the hazard of successful weaning from invasive mechanical ventilation (IMV), or 90-day mortality. Gray areas indicate days with an identical calorie intake. Due to specifications of the model, this intake could have been at any intake level. Solid lines indicate hazard ratios (HR), and hatched lines indicate corresponding 95% confidence intervals (CI). Reference medical nutrition therapy is the one which provides fewer calories [e.g., a HR (and 95% CI) < 1 would indicate a longer survival time but also a longer time until extubation associated with the medical nutrition therapy providing more calories]. Please note that HRs (and corresponding 95% CIs) must be 1 for the first 2 days for IMV and 4 days for survival due to the specification of the lag time, and also for time intervals, in which calorie intake was identical within the relevant time window that affects the hazard. From the 90-day survival analysis, the HRs for the first 30 days are displayed due to estimation stability as the majority of deaths occurred until this day

Fig. 4

Confounder-adjusted, time-varying association of a medical nutrition therapy providing fewer vs more protein, with outcomes. Columns 1 and 4: Hypothetical medical nutrition therapy comparisons analyzing different levels of daily protein intake: low: < 0.8 g/kg; moderate: 0.8–1.2 g/kg; high: > 1.2 g/kg (Table 1). Columns 2 and 3, and 5 and 6: Corresponding time-varying associations of different hypothetical medical nutrition therapies with the hazard of successful weaning from invasive mechanical ventilation (IMV), or 90-day mortality. Gray areas indicate days with an identical protein intake. Due to specifications of the model, this intake could have been at any intake level. Solid lines indicate hazard ratios (HR), and hatched lines indicate corresponding 95% confidence intervals (CI). Reference medical nutrition therapy is the one which provides fewer protein [e.g., a HR (and 95% CI) < 1 would indicate a longer survival time but also a longer time until extubation associated with the medical nutrition therapy providing more protein]. Please note that HRs (and corresponding 95% CIs) must be 1 for the first 2 days for IMV and 4 days for survival due to the specification of the lag time, and also for time intervals, in which protein intake was identical within the relevant time window that affects the hazard. From the 90-day survival analysis, the HRs for the first 30 days are displayed due to estimation stability as the majority of deaths occurred until this day