Association of energy delivery with short-term survival in mechanically ventilated critically ill adult patients: a secondary analysis of the NEED trial.
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- Japanese Clinical Practice Guidelines for Rehabilitation in Critically Ill Patients 2023 [J-ReCIP 2023]. Unoki T, Hayashida K, Kawai Y, Taito S, Ando M, Iida Y, Kasai F, Kawasaki T, Kozu R, Kondo Y, Saitoh M, Sakuramoto H, Sasaki N, Saura R, Nakamura K, Ouchi A, Okamoto S, Okamura M, Kuribara T, Kuriyama A, Matsuishi Y, Yamamoto N, Yoshihiro S, Yasaka T, Abe R, Iitsuka T, Inoue H, Uchiyama Y, Endo S, Okura K, Ota K, Otsuka T, Okada D, Obata K, Katayama Y, Kaneda N, Kitayama M, Kina S, Kusaba R, Kuwabara M, Sasanuma N, Takahashi M, Takayama C, Tashiro N, Tatsuno J, Tamura T, Tamoto M, Tsuchiya A, Tsutsumi Y, Nagato T, Narita C, Nawa T, Nonoyama T, Hanada M, Hirakawa K, Makino A, Masaki H, Matsuki R, Matsushima S, Matsuda W, Miyagishima S, Moromizato M, Yanagi N, Yamauchi K, Yamashita Y, Yamamoto N, Liu K, Wakabayashi Y, Watanabe S, Yonekura H, Nakanishi N, Takahashi T, Nishida O; Committee for the Clinical Practice Guidelines of Early Mobilization and Rehabilitation in Intensive Care of the Japanese Society of Intensive Care Medicine. Unoki T, et al. J Intensive Care. 2023 Nov 7;11[1]:47. doi: 10.1186/s40560-023-00697-w. J Intensive Care. 2023. PMID: 37932849 Free PMC article. Review.
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- Relationship between Mini Nutritional Assessment Score and Infection in Critical Care Patients.
Chen-Yu Wang,1,2,3 Pin-Kuei Fu,1,4,5 Wen-Cheng Chao,1 Wei-Ning Wang,6 Chao-Hsiu Chen,6 and Yi-Chia Huang7,8,*
Abstract
Although energy intake might be associated with clinical outcomes in critically ill patients, it remains unclear whether full or trophic feeding is suitable for critically ill patients with high or low nutrition risk. We conducted a prospective study to determine which feeding energy intakes were associated with clinical outcomes in critically ill patients with high or low nutrition risk. This was an investigator-initiated, single center, single blind, randomized controlled trial. Critically ill patients were allocated to either high or low nutrition risk based on their Nutrition Risk in the Critically Ill score, and then randomized to receive either the full or the trophic feeding. The feeding procedure was administered for six days. No significant differences were observed in hospital, 14-day and 28-day mortalities, the length of ventilator dependency, or ICU and hospital stay among the four groups. There were no associations between energy and protein intakes and hospital, 14-day and 28-day mortalities in any of the four groups. However, protein intake was positively associated with the length of hospital stay and ventilator dependency in patients with low nutrition risk receiving trophic feeding. Full or trophic feeding in critically ill patients showed no associations with clinical outcomes, regardless of nutrition risk. Keywords: critically ill patients, full feeding, trophic feeding, nutritional risk scores, clinical outcomes
1. Introduction
Optimal energy delivery for patients in the intensive care unit [ICU] remains a challenge. Studies have shown that insufficient energy delivery is associated with increased nosocomial infection, prolonged hospital stay, and prolonged ventilator dependency [,,,]. If energy delivery could reach at least 80% of predicted calories, clinical outcomes might be improved [,,].However, in a large database study, it was revealed that 30–70% of predicted energy intake generated the lowest 30-day mortality []. The European Society for Clinical Nutrition and Metabolism [ESPEN] guideline recommends less than 70% of predicted energy intake for critically ill patients in the acute phase []. Several clinical investigations have shown that hypocaloric feeding or permissive underfeeding could shorten duration of ventilator dependency and lead to decreased hospital mortality in critically ill patients [,,,,]. Higher energy intake not only failed to show better clinical outcomes but generated poor consequences in some studies [,,]. In addition, no mortality differences were observed among patients receiving permissive underfeeding, trophic feeding, full caloric feeding, and energy-dense feeding [,,]. Findings related to the optimal energy delivery for critically ill patients remain inconsistent. Because of the high heterogeneity in critically ill patients, the American Society for Parenteral and Enteral Nutrition/ Society of Critical Care Medicine [ASPEN/SCCM] guideline suggests assessing nutritional status using the Nutritional Risk Screening Score [NRS 2002] [] or the Nutrition Risk in the Critically Ill [NUTRIC] score [], which are useful in designing suitable nutritional strategies for critically ill patients. Supplemental parenteral nutrition is recommended when enteral nutrition is insufficient, especially when a patient’s NRS 2002 score is ≥3 or NUTRIC score is ≥5 []. The items that are used to evaluate NUTRIC score include age, acute physiology and chronic health evaluation II [APACHE II] score, sequential organ failure assessment score, comorbidity, days from hospital to ICU admission, and interleukin-6 [IL-6] levels. Because IL-6 is not routinely measured in most ICUs, a modified NUTRIC score [mNUTRIC] without IL-6 level was applied for practical purposes []. Critically ill patients with high nutrition risk [mNUTRIC score ≥5] could benefit from higher energy delivery in order to decrease hospital mortality, as shown in our previous study and in various other investigations [,,,], although the opposite finding was reported in one study []. A post-hoc analysis in the PermiT trial by Arabi et al. [] found no significant difference in 90-day mortality between the permissive underfeeding and standard feeding group regardless of nutritional risk [high vs. low]. It is still unclear whether the status of nutritional risk should be considered when executing a nutrition intervention in critically ill patients. There is no doubt that the provision of energy intake is essential to improving the clinical outcomes of critically ill patients; however, it remains unclear whether the feeding type [full feeding vs. trophic feeding] and nutrition status [high nutrition risk vs. low nutrition risk] should be simultaneously considered in the ICU. We thus conducted a prospective, randomized clinical trial to determine which feeding strategy [full vs. trophic energy intakes] was associated with better clinical outcomes in patients with either high or low nutrition risk in the ICU. We hypothesized that either full or trophic feeding would be significantly associated with clinical outcomes in critically ill patients with high or low nutrition risk.
2. Subjects and Methods
2.1. Study Design and Sample Size Calculation
This was an investigator-initiated, single center, single blind [patients were blinded], randomized controlled trial [clinical trial no. NCT03365258, ClinicalTrials.gov Protocol and Results Registration System] at two medical ICUs of a tertiary medical center in central Taiwan. The study was conducted from December 2017 through March 2020. This study was approved by the Institutional Review Board of Taichung Veterans General Hospital [IRB No. CF17249A]. Informed consent was obtained from each patient or the patient’s legal representative prior to the intervention. The study sample size was calculated based on the detection of a significant correlation coefficient of 0.35 between energy intakes and hospital mortality with 80% statistical power, and a two-sided test with an α of 0.05. The required sample size was therefore a minimum of 62 subjects for each group.
2.2. Subjects and Feeding Procedure
The criteria for enrolled subjects were as follows: medical ICU patients, age older than 20 years, respiratory failure requiring mechanical ventilation support, and a predicted ICU stay longer than 72 h. Patients were excluded if they had any medical conditions requiring nil per os, total parenteral nutrition use only, feeding with gastrostomy or jejunostomy, history of metoclopramide-related extrapyramidal syndrome or torsades de pointes, or gastrointestinal bleeding. For each patient, nutrition risk was evaluated using an mNUTRIC score []. Patients with an mNUTRIC score equal to or higher than 5 [5–9 score] were allocated to the high nutrition risk group, while patients with a score equal to or lower than 4 [0–4 score] were placed in the low nutrition risk group. Patients in the same nutrition risk group were then randomly assigned to receive either full feeding or trophic feeding. Therefore, there were four study groups as follows: full feeding with high nutrition risk, trophic feeding with high nutrition risk, full feeding with low nutrition risk, and trophic feeding with low nutrition risk. Figure 1 shows the design and flow diagram of the study. The daily total [enteral plus parenteral] energy intake was calculated based on 25 kcal/kg/day in the full feeding group, and approximately 600 kcal/day in the trophic feeding group. The use of propofol, glucose infusion, and glucosaline were calculated as parenteral nutrition energy intakes. All patients received continuous feeding, and gastric residual volume was checked every 4 h. The feeding procedure was administered for six days. Patients who still required mechanical ventilator support were transferred to full energy feeding after day six. ![An external file that holds a picture, illustration, etc. Object name is nutrients-12-03518-g001.jpg][////i0.wp.com/www.ncbi.nlm.nih.gov/pmc/articles/PMC7696610/bin/nutrients-12-03518-g001.jpg] Patient recruitment and flow of the study.
2.3. Data Collection and Outcome Measurement
The patients’ data were collected or calculated and included age, gender, body mass index [kg/m2, BMI], mean energy and protein intakes for six days, serum albumin, C-reactive protein [CRP], APACHE II score, comorbidities, days in hospital to ICU admission, length of ventilator dependence, hospital and ICU stays, and survival days. The primary outcomes of the study were hospital, 14-day and 28-day mortalities. The secondary outcomes were the length of ventilator dependency, as well as hospital and ICU stays.
2.4. Statistical Analysis
All data were analyzed using the SAS statistical software package [version 9.4; Statistical Analysis System Institute Inc., Cary, NC, USA]. Intention-to-treat analysis was applied in the study. Continuous variables were compared using the Student’s t-test or Mann–Whitney Rank Sum test within the nutrition risk group. Categorical variables were compared using the Chi-square test or Fisher’s exact test. Multivariate logistic regression was used to estimate the odds ratios and 95% confidence intervals for hospital, 14-day and 28-day mortalities. Multiple linear regression was used to assess the associations of energy and protein intakes with the length of ventilator dependency, hospital stay, and ICU stay.
3. Results
We screened 3055 ICU patients, and a total of 150 patients were included in this study, with 50 high nutrition risk patients who received full feeding, 56 high nutrition risk patients who received trophic feeding, 24 low nutrition risk patients who received full feeding, and 20 low nutrition risk patients who received trophic feeding. Table 1 lists the patients’ demographic and biochemical characteristics, and actual energy and protein intakes in the four groups. The most common comorbidities were diabetes mellitus, congestive heart failure, liver cirrhosis, chronic obstructive pulmonary disease, immunocompromised disorders, end-stage renal diseases, and neurological disorders. High nutrition risk patients were older, had a higher APACHE II score, but had lower serum albumin level. There were no significant differences in hospital, 14-day and 28-day mortalities, length of ventilator dependency, or ICU and hospital stays among the four groups. Although we intended to deliver 25 kcal/kg/day to patients in the full feeding groups, their actual mean energy intake was only 21.21 kcal/kg/day for high nutrition risk patients and 22.84 kcal/kg/day for low nutrition risk patients, due to the disturbance of medical interventions.
Table 1
Demographic and biochemical characteristics, clinical outcomes, and energy and protein intakes in high and low nutrition risk critically ill patients treated with full or trophic feeding. CharacteristicsHigh Nutrition RiskLow Nutrition RiskFull Feeding [n = 50]Trophic Feeding [n = 56]Full Feeding [n = 24]Trophic Feeding [n = 20]Age [year]72.32 ± 14.18 *70.18 ± 12.97 **57.13 ± 16.8558.80 ± 16.30Gender [women/men]27/23 *37/1916/87/13Body mass index [kg/m2]24.39 ± 5.8523.31 ± 3.8422.82 ± 4.5724.94 ± 7.60Mean 6-day energy intake kcal/day1260.20 ± 305.18 †614.60 ± 109.491350.49 ± 334.11 †645.20 ± 173.28kcal/kg/day21.21 ± 5.56 †10.48 ± 2.3722.84 ± 5.19 †11.31 ± 4.65Mean 6-day protein intake g/day50.36 ± 15.82 †27.89 ± 12.3954.28 ± 14.43 †30.18 ± 17.01g/kg/day0.84 ± 0.27 †0.48 ± 0.210.92 ± 0.20 †0.52 ± 0.35Albumin [g/dL]2.89 ± 0.58 *2.84 ± 0.583.22 ± 0.573.06 ± 0.50C-reactive protein [mg/dL]10.60 ± 10.58 *13.49 ± 11.295.97 ± 7.529.21 ± 8.03APACHE II score28.28 ± 4.19 *28.29 ± 5.29 **20.67 ± 4.1818.70 ± 4.87mNUTRIC score6.66 ± 1.08 *6.61 ± 1.19 **3.58 ± 0.883.25 ± 0.97Length of ventilator dependency [day]24.46 ± 25.1221.52 ± 19.4621.0 ± 18.8619.45 ± 19.23Length of ICU stay [day]16.88 ± 11.4415.54 ± 13.1711.81 ± 8.6814.35 ± 12.30Length of hospital stay [day]36.44 ± 26.8433.16 ± 20.7428.17 ± 18.2732.40 ± 28.38Mortality [n, %] Hospital mortality12, 24%11, 19.64%6, 25%4, 20%14-day mortality1, 2%2, 3.57%1, 4.17%028-day mortality8, 16%6, 10.71%3, 12.5%1, 5%Comorbidities [n, %] Diabetes mellitus25, 50%32, 57.14%9, 37.50%5, 25%Congestive heart failure16, 32%19, 33.93%3, 12.5%2, 10%Liver cirrhosis2, 4%4, 7.14%00COPD11, 22%22, 39.29%7, 29.17%7, 35%Immunocompromised disorders18, 36%19, 33.93%7, 29.17%6, 30%End-stage renal disease9, 18%†13, 23.21%2, 8.33%2, 10%Neurological disorders9,18%9, 16.07%4, 16.67%2, 10% A logistic regression analysis showed there were no associations of energy and protein intakes with hospital, 14-day and 28-day mortalities in any of the four groups [Table 2]. We further assessed the associations of energy and protein intakes with secondary outcomes [i.e., the length of ventilator dependency, and hospital and ICU stays] after adjusting for potential confounders [Table 3]. Energy intakes were not associated with any secondary outcomes in any group. However, protein intake was positively associated with the length of ventilator dependency and hospital stay in low nutrition risk patients receiving trophic feeding. Higher serum albumin was associated with shorter length of ventilator dependency [β = −10.97, standard error = 4.81, p = 0.03], hospital stay [β = −12.63, standard error = 5.06, p = 0.02], and ICU stay [β = −9.41, standard error = 3.08, p < 0.01] in high nutrition risk patients receiving trophic feeding after adjusting for age, gender, BMI, and total energy intake.
Table 2
Adjusted odds ratios of hospital mortality, 14-day mortality, and 28-day mortality in high and low nutrition risk critically ill patients treated with full or trophic feeding 1. Hospital Mortality14-Day Mortality28-Day MortalityOR95% CI p OR95% CI p OR95% CI p Total energy intakes [kcal/day] High nutrition risk with full feeding11.00–1.000.8410.91–1.10111.00–1.010.39High nutrition risk with trophic feeding11.00–1.010.390.990.98–1.010.5110.99–1.010.88Low nutrition risk with full feeding10.99–1.000.2311.00–1.000.9211.00–1.000.92Low nutrition risk with trophic feeding1.190.68–2.090.54-1.020.98–1.070.4Total protein intakes [g/day] High nutrition risk with full feeding1.010.96–1.060.771.41999.990.961.050.97–1.140.22High nutrition risk with trophic feeding0.960.89–1.030.220.940.75–1.180.570.980.91–1.050.57Low nutrition risk with full feeding0.880.75–1.040.130.960.85–1.080.520.220.01–4.030.52Low nutrition risk with trophic feeding1.10.91–1.320.32-0.44