Exploring the impact of arginine-supplemented immunonutrition on length of stay in the intensive care unit: A retrospective cross-sectional analysis.

BACKGROUND: Arginine-supplemented enteral immunonutrition has been designed to optimize outcomes in critical care patients. Existing formulas may be isocaloric and isoproteic, yet differ in L-arginine content, energy distribution, and in source and amount of many other specialized ingredients. The individual contributions of each may be difficult to pinpoint; however, all cumulate in the body's response to illness and injury. The study objective was to compare health outcomes between different immunonutrition formulas. METHODS: Real-world data from October 2015 -February 2019 in the PINC AI™ Healthcare Database (formerly the Premier Healthcare Database) was reviewed for patients with an intensive care unit (ICU) stay and ≥3 days exclusive use of either higher L-arginine formula (HAF), or lower L-arginine formula (LAF). Multivariable generalized linear model regression was used to check associations between formulas and ICU length of stay. RESULTS: 3,284 patients (74.5% surgical) were included from 21 hospitals, with 2,525 receiving HAF and 759 LAF. Inpatient mortality (19.4%) and surgical site infections (6.2%) were similar across groups. Median hospital stay of 17 days (IQR: 16) did not differ by immunonutrition formula. Median ICU stay was shorter for patients receiving HAF compared to LAF (10 vs 12 days; P<0.001). After adjusting for demographics, visit, severity of illness, and other clinical characteristics, associated regression-adjusted ICU length of stay for patients in the HAF group was 11% shorter [0.89 (95% CI: 0.84, 0.94; P<0.001)] compared to patients in the LAF group. Estimated adjusted mean ICU length of stay was 9.4 days (95% CI: 8.9, 10.0 days) for the HAF group compared to 10.6 days (95% CI: 9.9, 11.3 days) for the LAF group (P<0.001). CONCLUSIONS: Despite formulas being isocaloric and isoproteic, HAF use was associated with significantly reduced ICU length of stay, compared to LAF. Higher arginine immunonutrition formula may play a role in improving health outcomes in primarily surgical critically ill patients.

Characteristics and feeding intolerance in critically ill adult patients receiving peptide-based enteral nutrition: A retrospective cross-sectional study.

BACKGROUND & AIMS: Patients who experience gastrointestinal (GI) intolerance and hyperglycemia (or glucose intolerance) may not achieve appropriate caloric requirements and experience poor outcomes. The aim was to examine patient characteristics, disease severity, and enteral nutrition (EN) formula use in relation to feeding intolerance and healthcare resource utilization. METHODS: A retrospective, cross-sectional design using real-world data from PINC AI™ Healthcare Database, 2015-2019 was used. Critically ill hospitalized adults who required ≥3 days of 100% whey peptide-based EN, other peptide-based diets, or intact-protein standard and diabetic EN formulas were included. Primary outcomes were enteral feeding intolerance, including GI intolerance and hyperglycemia. Pairwise comparisons of other peptide-based and standard intact-protein groups with 100% whey-peptide were completed. Associations between EN group with GI intolerance and hyperglycemia, respectively, were evaluated via multivariable logistic regressions. RESULTS: Across 67 US hospitals, 19,679 inpatients (3242,100% whey-peptide, 3121 other peptide-based, and 13,316 standard intact-protein) were included. The 100% whey-peptide group had higher severity of illness and frequencies of comorbidities compared with other peptide-based and standard intact-protein groups. Hospital length of stay, intensive care unit stay, and 30-day readmission were similar across peptide-based cohorts. After controlling for demographic, visit, and severity characteristics, odds of GI intolerance were 18% higher for the other peptide-based group and 15% higher for the standard intact-protein group compared with the 100% whey-peptide group (each P < 0.03). In secondary analysis, odds of hyperglycemia were 81% higher for the other peptide-based group compared with the subgroup of very high-protein/low carbohydrate 100% whey-peptide (P < 0.001). CONCLUSIONS: Lower GI intolerance and greater glycemic control were associated with the use of 100% whey-peptide formulas relative to other formulas. Appropriate and optimal delivery of EN using specialized peptide-based formulas is a strategy to minimize feeding intolerance and benefit critically ill patients.

The importance of providing dietary fiber in medical and surgical critical care.

The early provision of soluble/insoluble fiber to the patient who is critically ill has been controversial in the past. Especially in the setting of hemodynamic instability, dysmotility, or impaired gastrointestinal transit, fear of inspissation of formula with precipitation of nonocclusive mesenteric ischemia (NOMI)/nonocclusive bowel necrosis (NOBN) limited its utilization by medical and surgical intensivists. The incidence of NOMI/NOBN has been estimated at 0.2%-0.3% for all intensive care unit (ICU) patients receiving enteral nutrition (EN), and the occurrence of inspissated formula is even less. The science supporting a benefit from providing fiber has recently increased exponentially. The fermentation of soluble fibers leading to the production of short chain fatty acids supports gut barrier function, modulates immune responses, and promotes refaunation of commensal organisms. The "butyrate effect" refers to local (gastrointestinal tract) and systemic anti-inflammatory responses mediated by the M2 polarization of macrophages, inhibition of histone deacetylase, and stimulation of ubiquitous G protein receptors. Both soluble and insoluble fiber have been shown to promote intestinal motility, reduce feeding intolerance, and shorten hospital length of stay. The benefit of providing dietary fiber early upon admission to the ICU outweighs its minimal associated risk. The point at which the intensivist determines that is safe to initiate EN, both soluble and insoluble fiber should be included in the enteral formulation.

Healthcare Resource Utilization and Cost Comparisons of High-Protein Enteral Nutrition Formulas Used in Critically Ill Patients.

Background: High-protein enteral nutrition is advised for patients who are critically ill. Options include immunonutrition formulas of various compositions and standard high-protein formulas (StdHP). Additional research is needed on the health economic value of immunonutrition in a broad cohort of severely ill hospitalized patients. Objective: The study goal was to compare healthcare resource utilization (HCRU) and cost between immunonutrition and StdHP using real-world evidence from a large US administrative database. Methods: A retrospective cohort study was designed using the PINC AI™ Healthcare Database from 2015 to 2019. IMPACT® Peptide 1.5 (IP) was compared with Pivot® 1.5 (PC), and StdHP formulas. Inclusion criteria comprised patients age 18+ with at least 1 day's stay in the intensive care unit (ICU) and at least 3 out of 5 consecutive days of enteral nutrition. Pairwise comparisons of demographics, clinical characteristics, HCRU, and costs were conducted between groups. Multivariable regression was used to assess total hospital cost per day associated with enteral nutrition cohort. Results: A total of 5752 patients were identified across 27 hospitals. Overall, a median 7 days of enteral nutrition was received over a 16-day hospital and 10-day ICU stay. Median total and daily hospital costs were lower for IP vs PC ($71 196 vs $80 696, P<.001) and ($4208 vs $4373, P=.019), with each higher than StdHP. However, after controlling for covariates such as mortality risk, surgery, and discharge disposition, average total hospital cost per day associated with IP use was 24% lower than PC, and 12% lower than StdHP (P<.001). Readmissions within 30 days were less frequent for patients receiving IP compared with PC (P<.02) and StdHP (P<.001). Discussion: Choice of high-protein enteral nutrition for patients in the ICU has implications for HCRU and daily hospital costs. Considering these correlations is important when comparing formula ingredients and per unit costs. Among the enteral nutrition products studied, IP emerged as the most cost-saving option, with lower adjusted hospital cost per day than PC or StdHP. Conclusions: Using a select immunonutrition formula for critically ill patients may provide overall cost savings for the healthcare system.

The 2016 ESPEN Arvid Wretlind lecture: The gut in stress.

The gut has a major influence on the course of the human stress response in critical illness for several reasons; the quantity of its immune tissue, the extent of interface with the external environment, the expanse of the microbiome, and its access to the systemic circulation. In critical illness, it is not uncommon to lose mucosal barrier function, which exposes the host to the downside effects of luminal contents and epithelial cell regulation. In that setting, the microbiome is converted to a pathobiome, upregulation of metabolic and immune responses occurs, and homeostatic defense systems are compromised. Awareness of this process mandates that greater attention be given to the interplay between the gut and systemic responses, and that modulation of the gastrointestinal tract be considered in every therapeutic intervention in the critical care setting.

Targeted Physician Education Positively Affects Delivery of Nutrition Therapy and Patient Outcomes: Results of a Prospective Clinical Trial.

BACKGROUND: Malnutrition is a continuing epidemic among hospitalized patients. We hypothesize that targeted physician education should help reduce caloric deficits and improve patient outcomes. MATERIALS AND METHODS: We performed a prospective trial of patients (n = 121) assigned to 1 of 2 trauma groups. The experimental group (EG) received targeted education consisting of strategies to increase delivery of early enteral nutrition. Strategies included early enteral access, avoidance of nil per os (NPO) and clear liquid diets (CLD), volume-based feeding, early resumption of feeds postprocedure, and charting caloric deficits. The control group (CG) did not receive targeted education but was allowed to practice in a standard ad hoc fashion. Both groups were provided with dietitian recommendations on a multidisciplinary nutrition team per standard practice. RESULTS: The EG received a higher percentage of measured goal calories (30.1 ± 18.5%, 22.1 ± 23.7%, P = .024) compared with the CG. Mean caloric deficit was not significantly different between groups (-6796 ± 4164 kcal vs -8817 ± 7087 kcal, P = .305). CLD days per patient (0.1 ± 0.5 vs 0.6 ± 0.9), length of stay in the intensive care unit (3.5 ± 5.5 vs 5.2 ± 6.8 days), and duration of mechanical ventilation (1.6 ± 3.7 vs 2.8 ± 5.0 days) were all reduced in the EG compared with the CG (P < .05). EG patients had fewer nosocomial infections (10.6% vs 23.6%) and less organ failure (10.6% vs 18.2%) than did the CG, but these differences did not reach statistical significance. CONCLUSION: Implementation of specific educational strategies succeeded in greater delivery of nutrition therapy, which favorably affected patient care and outcomes.

"CAN WE FEED?" A mnemonic to merge nutrition and intensive care assessment of the critically ill patient.

As care of the critically ill patient grows more complex, so does the breadth of knowledge required of the intensivist to deliver quality service. Nutrition is one area of many where the complexity of care has grown and the opportunity for improving patient outcomes has become evident. The use of mnemonics has proven successful in compartmentalizing information that must be considered in complex decision-making processes. The authors propose one such mnemonic, "CAN WE FEED?" to assist in the development and initiation of early enteral nutrition therapy in the intensive care unit (ICU). Critical illness severity (C), age (A), and nutrition risk screening (N) are considered when performing a baseline evaluation of the critically ill patient upon presentation to the ICU. Wait for resuscitation (W) is a key component in the care of most critically ill patients and is an important consideration prior to the initiation of feeding. Energy requirements (E) are determined using conventional weight-based equations, indirect calorimetry, or combinations of both techniques. The more practical aspects of support that follow include formula selection (F), enteral access (E), efficacy (E), and the determination of tolerance (D). With careful consideration of these components through the use of the mnemonic "CAN WE FEED?" the intensivist can successfully implement a nutrition plan, and the clinical nutritionist can appreciate where nutrition therapy appropriately intervenes in the initial resuscitation and management of the critically ill patient.

Physician-delivered malnutrition: why do patients receive nothing by mouth or a clear liquid diet in a university hospital setting?

BACKGROUND: Traditional practices of placing patients nil per os (NPO) or on clear liquid diet (CLD) deter delivery of optimal nutrition care and are not always supported by sound physiologic principles. OBJECTIVE: This perspective survey evaluated the incidence of this practice, the reasons for such orders, and the response to intervention by the Multidisciplinary Nutrition Team (MNT). METHODS: All patients admitted to University of Louisville Hospital were monitored by MNT dietitians and were candidates for the study if they were placed NPO upon CLD for ≥ 3 days. The MNT determined appropriateness of diet orders. RESULTS: Out of 1192 admissions, 22.6% of the patients (n = 262, 61% male, mean age 46.1 years) were found to be NPO or on CLD for ≥ 3 days (mean 5.2 days NPO, 1.04 days CLD), and were entered in the study. Uncertainty regarding the reason for the specific diet order occurred more often when patients were placed on CLD than when made NPO (32.1% vs. 15.0% of cases, respectively, P < 0.05). NPO diet orders were more often deemed appropriate by the MNT than were orders for CLD (58.6% vs. 25.6%, respectively, P < 0.05). Compliance with MNT recommendations was low at 40.0%. CONCLUSIONS: Despite an active MNT, 22% of patients were made NPO or placed on CLD for a prolonged period of time. More than a third of diet orders for NPO and two thirds of orders for CLD were inappropriate and poorly justified. Improving the adequacy of nutrition therapy is hampered by noncompliance with MNT recommendations.

Poor validity of residual volumes as a marker for risk of aspiration in critically ill patients.

BACKGROUND AND AIMS: Elevated residual volumes (RV), considered a marker for the risk of aspiration, are used to regulate the delivery of enteral tube feeding. We designed this prospective study to validate such use. METHODS: Critically ill patients undergoing mechanical ventilation in the medical, coronary, or surgical intensive care units in a university-based tertiary care hospital, placed on intragastric enteral tube feeding through nasogastric or percutaneous endoscopic gastrostomy tubes, were included in this study. Patients were fed Probalance (Nestle USA) to provide 25 kcal/kg per day (to which 10 yellow microscopic beads and 4.5 mL of blue food coloring per 1,500 mL was added). Patients were randomized to one of two groups based on management of RV: cessation of enteral tube feeding for RV >400 mL in study patients or for RV >200 mL in controls. Acute Physiology and Chronic Health Evaluation (APACHE) III, bowel function score, and aspiration risk score were determined. Bedside evaluations were done every 4 hrs for 3 days to measure RV, to detect blue food coloring, to check patient position, and to collect secretions from the trachea and oropharynx. Aspiration/regurgitation events were defined by the detection of yellow color in tracheal/oropharyngeal samples by fluorometry. Analysis was done by analysis of variance, Spearman's correlation, Student's t-test, Tukey's method, and Cochran-Armitage test. RESULTS: Forty patients (mean age, 44.6 yrs; range, 18-88 yrs; 70% male; mean APACHE III score, 40.9 [range, 12-85]) were evaluated (21 on nasogastric, 19 on percutaneous endoscopic gastrostomy feeds) and entered into the study. Based on 1,118 samples (531 oral, 587 tracheal), the mean frequency of regurgitation per patient was 31.3% (range, 0% to 94%), with a mean RV for all regurgitation events of 35.1 mL (range, 0-700 mL). The mean frequency of aspiration per patient was 22.1% (range, 0% to 94%), with a mean RV for all aspiration events of 30.6 mL (range, 0-700 mL). The median RV for both regurgitation and aspiration events was 5 mL. Over a wide range of RV, increasing from 0 mL to >400 mL, the frequency of regurgitation and aspiration did not change appreciably. Aspiration risk and bowel function scores did not correlate with the incidence of aspiration or regurgitation. Blue food coloring was detected on only three of the 1,118 (0.27%) samples. RV was < or =50 mL on 84.1% and >400 mL on 1.4% of bedside evaluations. Sensitivities for detecting aspiration per designated RV were as follows: 400 mL = 1.5%; 300 mL = 2.3%; 200 mL = 3.0%; and 150 mL = 4.5%. Low RV did not assure the absence of events, because the frequency of aspiration was 23.0% when RV was <150 mL. Raising the designated RV for cessation of enteral tube feeding from 200 mL to 400 mL did not increase the risk, because the frequency of aspiration was no different between controls (21.6%) and study patients (22.6%). The frequency of regurgitation was significantly less for patients with percutaneous endoscopic gastrostomy tubes compared with those with nasogastric tubes (20.3% vs. 40.7%, respectively; p = .046). There was no correlation between the incidence of pneumonia and the frequency of regurgitation or aspiration. CONCLUSIONS: Blue food coloring should not be used as a clinical monitor. Converting nasogastric tubes to percutaneous endoscopic gastrostomy tubes may be a successful strategy to reduce the risk of aspiration. No appropriate designated RV level to identify aspiration could be derived as a result of poor sensitivity over a wide range of RV. Study results do not support the conventional use of RV as a marker for the risk of aspiration.

Clinical use of the respiratory quotient obtained from indirect calorimetry.

BACKGROUND: The respiratory quotient (RQ) obtained from indirect calorimetry (IC), defined by the ratio carbon dioxide production (VCO2)/oxygen consumption (VO2), is affected by extremes of substrate use by the body. Underfeeding, which promotes use of endogenous fat stores, should cause decreases in the RQ, whereas overfeeding, which results in lipogenesis, should cause increases in the RQ. Marked increases in VCO2 (with subsequent increases in RQ) in response to overfeeding may cause respiratory compromise in patients with limited pulmonary reserve. Thus, variation in the RQ in response to the feeding regimen may indicate inappropriate feeding and serve as a marker for patient intolerance. This prospective, multicenter study was designed to determine the clinical use of RQ for monitoring adequacy and tolerance of nutrition support. METHODS: Patients in any 1 of 30 long-term acute care Kindred hospitals made nil orally (NPO) and placed on total parenteral or enteral feeding were eligible for this study. Arterial blood gas, serum ketones, 24-hour collection of urine urea nitrogen, and IC measurements were obtained on all. Actual volume of enteral/parenteral feeding infused over the 24 hours before performance of IC was documented. RESULTS: A total of 263 patients (mean age, 70.2 years, 57.4% male) were entered in the study. Of the 263 study patients, 88.6% required mechanical ventilation, and 92.0% received enteral tube feeding only. Overall, 41.5% of patients were overfed, receiving >110% of required calories, whereas 34.2% were underfed, receiving <90% of required calories. The ratio of calories provided/required correlated significantly with overall measured RQ (p < .0001; R2 = .16). Correcting for the metabolism of protein by calculating a nonprotein RQ (NPRQ) from a 24-hour urine urea nitrogen did not improve this correlation (p < .0001, R2 = .32). Using a measured NPRQ >1.0 to identify overfeeding had an acceptable specificity of 85.1% but a low sensitivity of 38.5%. Similarly, use of a NPRQ <0.85 to determine underfeeding had a specificity of 72.2% and a sensitivity of 55.8%. Comparing the measured NPRQ with a predicted reference RQ (based on percent infusion of carbohydrate/fat and the Lusk table) did not improve the overall use of RQ. In the majority of patients (67.7%), comparison of the measured NPRQ to the predicted value failed to differentiate appropriate (meeting 100% +/- 10% of requirements) from inappropriate feeding. Deviation of the measured NPRQ from predicted failed to identify factors unrelated to substrate use purported to affect the RQ (such as acid/base disturbances or hyper/hypoventilation). Increasing measured RQ did correlate significantly with increasing respiratory rate (p = .002, R2 = .04) and decreasing tidal volume (p = .002, R2 = .04), suggesting reduced tolerance with development of shallow rapid respirations and ventilatory compromise. CONCLUSIONS: Although changes in the overall and nonprotein RQ correlate to percent calories provided/required, low sensitivity and specificity limit its efficacy as an indicator of over- or underfeeding. The RQ should not be used to finely adjust the nutrition support regimen. Elevation of overall measured RQ > or = 1.0 may be associated with reduced tolerance and mild respiratory compromise. The clinical use of RQ is limited to a marker of test validity (to confirm measured RQ values are in physiologic range) and a marker for respiratory tolerance of the nutrition support regimen.

Achievement of steady state optimizes results when performing indirect calorimetry.

BACKGROUND: The use of steady state as the endpoint for performance of indirect calorimetry (IC) is controversial. We designed this prospective study to evaluate the necessity and significance of achieving steady state. METHODS: Patients with respiratory failure placed on mechanical ventilation in a short- or long-term acute care unit at any 1 of 3 university-based urban hospitals were eligible for the study. The 24-hour total energy expenditure (TEE) was determined by a Nellcor Puritan Bennett 7250 continuous IC monitor. Measured gas exchange parameters were obtained and averaged every 1 minute for the initial hour and then every 15 minutes for the next 23 hours. Over the initial hour, resting energy expenditure (REE) was averaged for intervals over the first 20, 30, 40, and 60 minutes, and for various definitions of steady state where oxygen consumption (VO2) and carbon dioxide production (VCO2) changed by <10%, 15%, and 20%. Coefficient of variation (CV) was calculated for VO2 over the first 30 minutes of study. RESULTS: Twenty-two patients (mean age, 52.8 years, 59% male, mean Acute Physiology and Chronic Health Evaluation (APACHE III) score 42.0) were entered in the study. The best correlation between short-term "snapshot" REE and the 24-hour TEE was achieved by the steady-state period defined by the most stringent criteria (change in VO2 and VCO2 by <10%). The average REE for all steady-state and interval periods correlated significantly to TEE with no significant difference in the absolute values for REE and TEE. Adding 10% for an activity factor to the average REE for each steady-state and interval period again correlated to TEE in a similar fashion with the same R value, but the absolute values for REE + 10% for all steady-state and interval periods were significantly different than the corresponding TEE. In those patients with less variation (CV for VO2 < or = 9.0), the REE obtained for the steady-state period defined by the most stringent criteria still had the best correlation, but similar correlation could be obtained by interval testing of > or = 30-minute duration. In those patients with greater variation (CV for VO2 >9.0), interval testing of at least 60 minutes or more was required to attain levels of correlation similar to that achieved by the steady-state period defined by the most stringent criteria. CONCLUSIONS: These data support the use of steady state, best defined as an interval of 5 consecutive minutes whereby VO2 and VCO2 change by <10%. The mean REE from this period correlates best to the 24-hour TEE regardless of CV. IC testing can be completed after achievement of steady state. Activity factors of 10% to 15% should not be added to the steady-state REE, because this practice significantly decreases the accuracy. In patients who fail to achieve steady state, the CV helps to determine the appropriate duration of IC testing. In those patients with a low CV (< or = 9.0), 30-minute test duration is adequate. In patients with CV >9.0, test duration of at least 60 minutes may be required. These latter patients should be considered for 24-hour IC testing.