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INTRODUCTION
Adequate nutrition is important in critically ill patients because it is significantly associated with improved clinical outcomes [1]. Critically ill patients with acute respiratory failure have distinct nutritional requirements. Malnutrition can affect lung function by causing impaired respiratory muscle function, depressed ventilator drive, and an impaired immune system [2]. In addition, patients with pre-existing chronic lung disease are often malnourished at the time of admission [3].
Providing optimal nutrition to critically ill patients with acute respiratory failure is challenging. Nutritional support in critically ill patients is often interrupted by clinical events, and airway manipulation is a major event that causes the longest duration of interruption [4]. Owing to their complexity, critically ill patients with acute respiratory failure may benefit from consultation with a nutritional support team (NST). In a study of 13,103 patients in coronavirus disease 2019 (COVID-19) intensive care unit (ICU), implementation of the NST system was significantly associated with a lower in-hospital mortality rate; this result was consistent with a subgroup analysis of patients with ARDS and mechanical ventilator support [5].
Nutritional support for nonintubated patients with acute respiratory failure is even more challenging. If clinical conditions are aggravated, patients may become intolerant to an oral diet and require reassessment of the nutritional plan [6]. Patients requiring non-invasive ventilation or a high-flow nasal cannula are frequently kept nil per os in clinical practice during initial management [7,8]. In patients receiving oral nutrition, prolonged NIV administration results in energy and protein underfeeding [9]. In contrast to the intubated patients, enteral nutrition (EN) via a nasogastric tube may not only provide nutrition but also increase the risk of airway complications, such as mucus plugging, desaturation after vomiting, and aspiration pneumonia [10].
Early intervention by a multidisciplinary nutrition team may facilitate individualized nutritional management by assessing patient conditions, including overall respiratory status, cognitive status, nutritional risk, and diet tolerability [6]. In 2021, the National Medical Center revised the preexisting NST protocol, which previously provided recommendations only upon physician discretion, and initiated mandatory NST monitoring by a multidisciplinary team at the time of admission for all patients who were hospitalized in the ICU. The NST team regularly follows up and adjusts nutritional support after admission.
To the best of the authors' knowledge, no previous research has studied the relationship between NST activity and clinical outcomes in patients with acute respiratory failure. Thus, this study aimed to evaluate the effects of routine NST monitoring and active intervention protocols on the clinical outcomes of critically ill patients with acute respiratory failure.
MATERIALS AND METHODS
This study was conducted in accordance with the principles of the Declaration of Helsinki. The study design was approved by the Institutional Review Board of the National Medical Center (No. NMC-2022-11-111). The requirement for informed consent was waived by the Institutional Review Board.
Study Design and Subjects
This was a single-center retrospective cohort study. This study included patients aged >18 years with acute respiratory failure at the time of admission to the ICU of the National Medical Center, Seoul, Korea, from October 2018 to September 2022. Acute respiratory failure was defined as a respiratory failure requiring a high-flow nasal cannula, noninvasive ventilation, or mechanical ventilation. Patients admitted to the COVID-19 isolation unit were excluded. Additionally, patients who stayed in the ICU for less than 7 days were excluded to evaluate the effect of nutritional support during ICU care.
The patients were divided into two groups based on the time of initiation of regular screening for nutritional support in July 2021. Patients admitted to the ICU before the routine screening protocol were included in the pre-monitoring group, and patients who were admitted after protocol initiation were included in the post-monitoring group. The primary outcome was 28-day mortality after ICU admission. Secondary outcomes included the supplied/target calorie ratio, supplied/target protein ratio on day 7, and complications.
Target amount of calorie and protein was defined based on the European Society for Clinical Nutrition and Metabolism (ESPEN) guideline, 25–30 kcal/kg/day for calorie and 1.2–1.5 g/day for protein requirement [11]. If the patient had acute or chronic kidney or chronic liver disease, such as liver cirrhosis, the nutritional target was modified according to the ESPEN guidelines [12,13]. Early initiation of EN within 48 hours was encouraged unless contraindications from the guidelines were present. The nutritional plan was designed to progressively increase the daily amount and reach 70%–100% of the caloric and protein requirements within 3–7 days.
Nutrition Support Team
The ICU Nutrition Support Team at the National Medical Center is a multidisciplinary team consisting of intensivists, residents, specialized nurses, nutritionists, and pharmacists. Before the novel protocol, the NST consulted with the selected patients only if the attending physician requested advice. In July 2021, the NST initiated a routine screening protocol to assess the nutritional status of all ICU patients.
In a twice-weekly meeting, the NST assessed the baseline nutritional status and identified the nutritional target. After reviewing the patient’s clinical course, the NST decides the time to start nutrition supply, suggests a nutrition regimen, and reviews all other components related to nutrition, including the infusion rate and micronutrient supply. In addition, pharmacists consulted about the dose, adverse effects, and cross-reactivity of the prescribed medications.
The novel nutrition protocol integrates the Korean Society for Parenteral and Enteral Nutrition (KSPEN), ESPEN, and American Society for Parenteral and Enteral Nutrition (ASPEN) guidelines. Target calorie and protein intakes were adopted from the ESPEN guidelines and were individualized for each patient. The feeding formula, daily schedule, and monitoring protocol were based on the KSPEN guidelines. Daily monitoring of feeding tolerance, body weight, daily intake, and output glucose levels was recommended for all patients. Laboratory parameters such as albumin, electrolytes, blood urea nitrogen to creatinine ratio, liver function tests, and nitrogen balance were checked according to the schedule suggested by the KSPEN guidelines.
Data Collection
Age, sex, BMI, cause of ICU admission, and underlying diseases were recorded as patient characteristics. Data related to disease severity, such as the Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, arterial partial pressure of oxygen (PaO2)/ inspiratory fraction of oxygen (FiO2) ratio, and vasopressor use were collected.
Nutrition-related variables were collected, including the modified Nutrition Risk in Critically Ill (NUTRIC) score, nutrition route, total amount of calories supplied on day 7, and total amount of protein supplied on day 7. Initial nutritional status was assessed using the criteria proposed by Funk and Ayton [14]. NST monitoring was defined as the regular evaluation of patients’ nutritional status by the NST team during bedside rounds after ICU admission. NST intervention was defined as a formal report for nutrition adjustment that was written after NST monitoring or in response to consultation by physicians.
Data on interruption of enteral feeding, its causes, and nutrition-related complications were collected. Nutrition-related complications include gastrointestinal intolerance, diarrhea, catheter-related infections, hyperglycemia, acute kidney injury, and volume overload. The 28-day mortality and ICU length of data were collected to assess the clinical outcomes.
Statistical Analysis
Fisher’s exact and Pearson’s chi-square tests were performed for categorical variables, and Student t-test was used for continuous variables. Univariate and multivariate Cox regression analyses were used to assess the relationship between the prognostic factors and 28-day mortality. After including variables with P-values of <0.10 in the univariate model, as well as age, sex, and BMI, adjusted hazard ratio (aHR) and 95% CIs were calculated in the multivariable analysis by enter methods after excluding selected variables showing collinearity in the model. Statistical significance was accepted for two-sided P-values <0.05. All statistical analyses were performed using SPSS version 29.0 (IBM Inc.).
RESULTS
After screening 1,617 patients admitted to the medical ICU, 990 with acute respiratory failure were identified. From these, 488 patients diagnosed with COVID-19 and 350 patients who stayed in the ICU for less than seven days were excluded from the study. A total of 152 patients (n=96 in the pre-monitoring group and n=56 in the post-monitoring group) were included in the final analysis (Figure 1).
Baseline Characteristics
The baseline characteristics of the study population are summarized in Table 1. The mean age of patients was 67.4±14.2 years and 106 patients (69.7%) were male. There was no difference in age, sex, BMI. Comorbidities were similar in both groups, except for chronic kidney disease. More patients in the pre-monitoring group had chronic kidney disease; however, the number of patients requiring renal replacement therapy did not differ between the two groups.
In terms of disease severity, APACHE II score was significantly higher in post-monitoring group (P<0.001). The SOFA scores and PaO2/FiO2 ratios were not significantly different. The percentage of vasopressor use was similar between the two groups. There was no significant difference in the primary causes of ICU admission; nonetheless, the percentage of patients admitted for pulmonary-related reasons tended to be higher in the pre-monitoring group.
The initial nutritional status did not differ significantly between the pre- and post-monitoring groups. Most patients had some form of malnutrition, and over 40% of patients in both groups had protein malnutrition. The nutritional risk did not differ significantly between the two groups. A total of 36 patients (38.3%) in the pre-monitoring group and 28 patients (50.0%) in the post-monitoring group were more likely to benefit from increased caloric intake [15], with a modified NUTRIC score ≥5 (Table 2).
Nutritional Outcomes
The details of the nutritional support are summarized in Table 3. In the post-monitoring group, 43 patients (76.8%) received NST intervention, which was significantly higher than in the pre-monitoring group. The time from ICU admission to initiation of feeding was significantly shorter in the post-monitoring group. Patients in the post-monitoring group initiated enteral feeding a median of one day after ICU admission, whereas those in the pre-monitoring group had a median delay of 3 days before enteral feeding initiation (P<0.001).
The percentage of patients who achieved 70% of the required calories on day 7 was higher in the post-monitoring group (69.6%) than in the pre-monitoring group (56.3%), although the difference was not significant. Protein supplied per weight on day 7 was significantly higher in the post-monitoring group. While the total supplied/required calorie on day 7 tended to increase without a significant difference, data on day 5 showed significant improvement. The number of patients receiving less than 50% of the required calories on day 7 decreased from 25 (26.0%) to 9 (16.1%), but the difference was not significant.
A higher percentage of patients in the pre-monitoring group received total parenteral nutrition, which was administered using a premixed formula. No significant differences were observed between the pre- and post-monitoring groups in terms of complications related to nutritional therapy. In post-monitoring group, 23 patients (41.1%) experienced gastrointestinal intolerance and 38 (67.9%) had diarrhea after the initiation of enteral feeding, whereas in the pre-monitoring group, 57 patients (59.4%) experienced diarrhea, with data on gastrointestinal intolerance not collected during pre-monitoring period. Additionally, the interruption of enteral feeding tended to be more frequent in the post-monitoring group; however, the difference was not significant. Among the 35 patients in the post-monitoring group, 19 interruptions occurred before the procedures; 12 were due to hemodynamic instability compared to 21 interruptions before the procedures, and 18 were due to hemodynamic instability among the 48 patients in the pre-monitoring group.
Clinical Outcomes
The 28-day mortality rate was significantly lower in the post-monitoring group than that in the pre-monitoring group (28.3% vs. 55.1%, P=0.002) (Table 4). The length of ICU stay was longer in the post-monitoring group than in the pre-monitoring group (23.5 days vs. 17.7 days, P=0.022) (Table 4). The need for mechanical ventilation and ventilator-free days were not significantly different between the two groups (Table 4). In the univariate analysis, SOFA score, NST intervention, and total supplied/required protein on day 7 were significant risk factors for predicting 28-day mortality (Table 5). Even after adjusting age, sex, BMI, SOFA score, and total supplied/required protein on day 7, regular NST monitoring was significantly associated with a reduced risk of 28-day mortality (adjusted HR, 0.42; 95% CI, 0.24–0.74; P=0.002) (Table 5).
DISCUSSION
In our study, the NST protocol involving comprehensive and regular nutritional monitoring in the ICU had significant association with improved 28-day mortality in patients with acute respiratory failure. Additionally, the total supplied-to-required calorie and protein ratios on day 7 were higher in the post-monitoring group, although the results were not statistically significant.
In patients with acute respiratory failure, delayed enteral feeding is recommended during uncontrolled life-threatening hypoxemia, hypercapnia, or acidosis [11]. However, guidelines also suggest that low-dose EN should be initiated as soon as the patient’s condition stabilizes, and it is challenging to decide when and to what extent to initiate nutrition. Aggressive NST intervention may help clinicians plan feeding and achieve the target amount of energy, especially protein, which is important in the recovery phase of a critical illness. Consistent with a study in a tertiary hospital in Korea [16], protocolized nutritional support significantly reduced the time to feeding initiation from ICU admission, from 4.6 days to 2.1 days.
In addition, the number of patients supplied with less than 50% of the required amount of calories or proteins tended to decrease in the post-monitoring group. Before the novel protocol, adjustment of the nutritional regimen by the NST was provided only upon request, resulting in only 29.2% of the pre-monitoring group receiving NST intervention, with a median time interval from ICU admission to NST intervention of 7 days. The NST screened patients at the time of ICU admission, allowing 76.8% of post-monitoring patients to receive NST intervention in a timely manner, with a median of 5 days, leading to higher target achievement on both day 5 and 7.
Numerous studies have been conducted to determine the appropriate amount and timing of protein delivery to reduce mortality in critically ill patients [17-19]. Recent research suggests that adequate nutrition in the ICU is significantly associated with improved 28-day mortality [20,21]. Our study aimed to assess the impact of NST on short-term outcomes by minimizing unnecessary delays in nutritional support during the ICU stay. We found that achieving more than 70% of the required protein level by day 7 was a significant prognostic factor for decreased 28-day mortality.
Although the total supplied/required protein ratio on day 7 did not significantly differ between the pre- and post-monitoring groups, the ratio was significantly higher in post-monitoring group on day 5. Additionally, the percentage of patients who were undersupplied protein (<50%) on day 7 tended to be lower in the post-monitoring group. Achieving adequate protein supply in critically ill patients may have contributed to the improved mortality in the post-monitoring group.
Regular NST meetings at the National Medical Center include bedside rounding involving residents and nursing staff, enabling the NST team to suggest individualized nutritional regimens after considering other patient factors, such as dietary compliance, comorbidities, and pressure sores. Additionally, in our practice, multidisciplinary NST provide consultations on patient management, such as electrolyte management, glycemic control, and micronutrient support. Medication dosages and drug–drug interventions were also adjusted. Management by the NST could have contributed to reduced 28-day mortality by influencing not only the achievement of nutrition targets but also the improvement of other clinical factors.
The rate of EN interruption was higher in the post-monitoring group; however, the difference was not significant. Interruption of enteral feeding was observed when the patient was hemodynamically unstable, to focus on effective resuscitation, or for the concern that gastrointestinal tolerability may decrease with vasopressor demand [22,23]. The higher frequency of interruptions in the post-monitoring group might be attributed to increased severity and more frequent requirement of vasopressors. Despite the more frequent interruptions, NST monitoring helped avoid unnecessary cessation of enteral feeding and provided appropriate Parenteral Nutrition regimens to complement the nutrition supply, thereby improving clinical outcomes. Mo et al. [24] also suggested that NST services significantly decrease the fasting period in the ICU.
No significant differences were observed between the pre- and post-monitoring groups in complications related to nutrition therapy. A higher proportion of patients in the post-monitoring group experienced diarrhea, and more patients received EN. In addition, more patients in the post-monitoring group tended to experience volume overload, despite a higher percentage of oral or EN-only regimens. Further, 32 of the 37 (86.5%) patients with volume overload required vasopressors: 16 of 20 patients (80.0%) in the pre-monitoring group and 16 of 17 patients (94.1%) in the post-monitoring group. The greater number of patients in the post-monitoring group who required resuscitation may have resulted in a higher prevalence of volume overload.
In another Korean retrospective study of 148 patients, multidisciplinary NST resulted in a significantly decreased duration of mechanical ventilation and a decreasing trend in ICU and hospital length of stay (LOS) [25]. In contrast, in our study, ventilator-free days did not show significant differences and ICU LOS was significantly longer in the post-monitoring group. However, our study population was different from those of other studies in that we included selected patients who were hospitalized in the medical ICU and diagnosed with acute respiratory failure. Considering that mechanical ventilation and a higher PaO2/FiO2 ratio significantly increase ICU LOS [26], and that ventilator weaning is likely to be prolonged in patients with chronic respiratory disorders [27], the effect of aggressive NST intervention on other clinical outcomes might have been diluted in our study population in the medical ICU.
This study had several limitations. First, this was a single-center study that included only patients hospitalized in a medical ICU with respiratory failure. It may be difficult to generalize this finding to other patients, such as those in the trauma unit. Nevertheless, this study showed that, along with the effectiveness of aggressive NST intervention, adequate protein supply, notably reaching 70% of the target amount within 1 week, had a positive impact on survival outcomes in patients with acute respiratory failure. Second, this study did not assess nutritional supply between days 7 and 28. However, our primary objective was to evaluate improvements in nutritional delivery under the direct supervision of the new NST protocol during the acute and early recovery phases of critical illness. Further studies are needed to capture the overall nutritional improvement in patients. Third, this study was unable to conduct a valid analysis of intermediate outcomes, such as 90-day mortality, due to a significant amount of missing data. Nonetheless, a trend indicating improvement in 90-day mortality was observed, suggesting that further research with a prospective design is warranted. Fourth, we included a small number of patients because our hospital primarily treated patients with COVID-19 during the COVID-19 pandemic. COVID-19 patients were excluded from this study because the NST made nutritional plans without on-site intervention during the early phase of severe COVID-19 infection. In addition, the retrospective study design did not control for confounding variables.
In conclusion, regular monitoring by a multidisciplinary NST could have been a contributing factor to the reduced risk of 28-day mortality in critically ill patients with acute respiratory failure. Comprehensive NST activity helped patients achieve their nutritional targets and improved overall patient management. Therefore, active nutritional intervention involving a multidisciplinary nutrition support team is recommended for managing critically ill patients with acute respiratory failure.
KEY MESSAGES
▪ Routine monitoring and active intervention by a nutritional support team could have contributed to the improved 28-day mortality in critically ill patients with acute respiratory failure.
▪ A higher percentage of patients achieved the target calorie and protein intakes in the post-monitoring group than in the pre-monitoring group although this difference was not significant.
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