Nutrition support for critically ill patients
Hasan M. Al-Dorzi MD
College of Medicine, King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
Search for more papers by this authorCorresponding Author
Yaseen M. Arabi MD
Intensive Care Department, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
Correspondence
Yaseen M. Arabi, MD, Intensive Care Dep, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
Email: [email protected]
Search for more papers by this authorHasan M. Al-Dorzi MD
College of Medicine, King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
Search for more papers by this authorCorresponding Author
Yaseen M. Arabi MD
Intensive Care Department, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
Correspondence
Yaseen M. Arabi, MD, Intensive Care Dep, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
Email: [email protected]
Search for more papers by this authorThis and other JPEN podcasts are available at https://nutritioncare.org/podcasts
Abstract
Nutrition support is an important aspect of the management of critically ill patients. This review highlights the emerging evidence on critical care nutrition and focuses on the pathophysiologic interplay between critical illness, the gastrointestinal tract, and nutrition support and the evidence on the best route, dose, and timing of nutrition. Although indirect calorimetry is recommended to measure energy expenditure, predictive equations are commonly used but are limited by their inaccuracy in individual patients. The current evidence supports early enteral nutrition (EN) in most patients, with a gradual increase in the daily dose over the first week. Delayed EN is warranted in patients with severe shock. According to recent trials, parenteral nutrition seems to be as effective as EN and may be started if adequate EN is not achieved by the first week of critical illness. A high protein dose has been recommended, but the best timing is unclear. Immuno-nutrition should not be routinely provided to critically ill patients. Patients receiving artificial nutrition should be monitored for metabolic derangements. Additional adequately powered studies are still needed to resolve many unanswered questions.
CONFLICT OF INTEREST
Yaseen M. Arabi is the principal investigator (PI) and Hasan M. Al-Dorzi is the co-investigator in the PI-initiated ongoing clinical trial “Replacing Protein via EN in a Stepwise Approach in Critically Ill Patients Randomized Controlled Trial-REPLENISH Trial” (ClinicalTrials.gov identifier: NCT04475666) sponsored by King Abdullah International Medical Research Center (KAIMRC).
REFERENCES
- 1Nicolo M, Heyland DK, Chittams J, Sammarco T, Compher C. Clinical outcomes related to protein delivery in a critically ill population: a multicenter, multinational observation study. JPEN J Parenter Enter Nutr. 2016; 40(1): 45-51.
- 2Otani S, Coopersmith CM. Gut integrity in critical illness. J Intensive Care. 2019; 7(1): 1-7.
- 3MacDonald TT, Monteleone I, Fantini MC, Monteleone G. Regulation of homeostasis and inflammation in the intestine. Gastroenterology. 2011; 140(6): 1768-1775.
- 4Wischmeyer PE, McDonald D, Knight R. Role of the microbiome, probiotics, and ‘dysbiosis therapy'in critical illness. Curr Opin Crit Care. 2016; 22(4): 347.
- 5Clark JA, Coopersmith CM. Intestinal crosstalk–a new paradigm for understanding the gut as the “motor” of critical illness. Shock. 2007; 28(4): 384.
- 6Fock Ricardo Ambrósio, Blatt Solange Lúcia, Beutler Beatriz, Pereira Juliana, Tsujita Maristela, de Barros Francisco Erivaldo Vidal, Borelli Primavera. Study of lymphocyte subpopulations in bone marrow in a model of protein–energy malnutrition. Nutrition. 2010; 26(10): 1021–1028. https://doi.org/10.1016/j.nut.2009.08.026.
- 7Rai J, Gill S, Kumar BS. The influence of preoperative nutritional status in wound healing after replacement arthroplasty. Orthopedics. 2002; 25(4): 417-421.
- 8Hernandez G, Velasco N, Wainstein C, et al. Gut mucosal atrophy after a short enteral fasting period in critically ill patients. J Crit Care. 1999; 14(2): 73.
- 9Wan X, Bi J, Gao X, et al. Partial enteral nutrition preserves elements of gut barrier function, including innate immunity, intestinal alkaline phosphatase (IAP) level, and intestinal microbiota in mice. Nutrients. 2015; 7(8): 6294-6312.
- 10Kang W, Kudsk K. Is there evidence that the gut contributes to mucosal immunity in humans?. JPEN J Parenter Enteral Nutr. 2007; 31(3): 246.
- 11Krezalek MA, Yeh A, Alverdy JC, Morowitz M. Influence of nutrition therapy on the intestinal microbiome. Curr Opinion Clin Nutr Metab Care. 2017; 20(2): 131-137.
- 12Van LD, Casaer M, Gunst J. Autophagy and its implications against early full nutrition support in critical illness. Nutr Clin Pract. 2018; 33(3): 339-347.
- 13Lew CCH, Yandell R, Fraser RJ, Chua AP, Chong MFF, Miller M. Association between malnutrition and clinical outcomes in the intensive care unit: a systematic review. JPEN J Parenter Enteral Nutr. 2017; 41(5): 744-758.
- 14Maciel L, Franzosi O, Nunes D, Loss S, Rubin B, et al. Nutritional risk screening 2002 cut-off to identify high-risk is a good predictor of ICU mortality in critically ill Patients. Nutr Clin Pract. 2019; 34(1): 137.
- 15Kondrup J. Nutrition risk screening in the ICU. Curr Opin Clin Nutr Metab Care. 2019; 22(2): 159-161.
- 16Canales C, Elsayes A, Yeh DD, et al. Nutrition risk in critically ill versus the nutritional risk screening 2002: are they comparable for assessing risk of malnutrition in critically ill patients?. JPEN J Parenter Enteral Nutr. 2019; 43(1): 81-87.
- 17Compher C, Chittams J, Sammarco T, Nicolo M, Heyland DK. Greater protein and energy intake may be associated with improved mortality in higher risk critically ill patients: a multicenter, multinational observational study. Crit Care Med. 2017; 45(2): 156-163.
- 18Arabi YM, Aldawood AS, Al-Dorzi HM, et al. Permissive underfeeding or standard enteral feeding in high- and low-nutritional-risk critically ill adults. Post hoc analysis of the PermiT trial. Am J Respir Crit Care Med. 2017; 195(5): 652-662.
- 19Singer P, Blaser AR, Berger MM, et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr. 2019; 38(1): 48-79.
- 20Allingstrup MJ, Kondrup J, Wiis J, et al. Early goal-directed nutrition versus standard of care in adult intensive care patients: the single-centre, randomised, outcome assessor-blinded EAT-ICU trial. Intensive Care Med. 2017; 43(11): 1637-1647.
- 21Oshima T, Berger MM, De Waele E, et al. Indirect calorimetry in nutritional therapy. A position paper by the ICALIC study group. Clin Nutr. 2017; 36(3): 651-662.
- 22Tatucu-Babet O, Ridley E, Tierney A. Prevalence of underprescription or overprescription of energy needs in critically ill mechanically ventilated adults as determined by indirect calorimetry: a systematic literature review. JPEN J Parenter Enter Nutr. 2016; 40(2): 212.
- 23Frankenfield DC, Ashcraft CM, Galvan DA. Prediction of resting metabolic rate in critically ill patients at the extremes of body mass index. JPEN J Parenter Enter Nutr. 2013; 37(3): 361-367.
- 24Stapel SN, de Grooth HJ, Alimohamad H, et al. Ventilator-derived carbon dioxide production to assess energy expenditure in critically ill patients: proof of concept. Crit Care. 2015; 19: 370.
- 25McClave SA, Taylor BE, Martindale RG, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: society of critical care medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN). JPEN J Parenter Enter Nutr. 2016; 40(2): 159-211.
- 26Villet S, Chiolero RL, Bollmann MD, et al. Negative impact of hypocaloric feeding and energy balance on clinical outcome in ICU patients. Clin Nutr. 2005; 24(4): 502-509.
- 27Arabi YM, Aldawood AS, Haddad SH, et al. Permissive underfeeding or standard enteral feeding in critically ill adults. N Engl J Med. 2015; 372(25): 2398-2408.
- 28Rice TW, Wheeler AP, Thompson BT, et al. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA. 2012; 307(8): 795-803.
- 29Rugeles S, Villarraga-Angulo LG, Ariza-Gutierrez A, Chaverra-Kornerup S, Lasalvia P, Rosselli D. High-protein hypocaloric vs normocaloric enteral nutrition in critically ill patients: a randomized clinical trial. J Crit Care. 2016; 35: 110-114.
- 30Chapman M, Peake SL, Bellomo R, et al. Energy-dense versus routine enteral nutrition in the critically ill. N Engl J Med. 2018; 379(19): 1823-1834.
- 31Marik PE, Hooper MH. Normocaloric versus hypocaloric feeding on the outcomes of ICU patients: a systematic review and meta-analysis. Intensive Care Med. 2016; 42(3): 316-323.
- 32Al-Dorzi HM, Albarrak A, Ferwana M, Murad MH, Arabi YM. Lower versus higher dose of enteral caloric intake in adult critically ill patients: a systematic review and meta-analysis. Crit Care. 2016; 20(1): 358.
- 33Silva C, de Vasconcelos S, da Silva T, Silva F. Permissive or trophic enteral nutrition and full enteral nutrition had similar effects on clinical outcomes in intensive care: a systematic review of randomized clinical trials. Nutr Clin Pract. 2018; 33(3): 388.
- 34Parikh HG, Miller A, Chapman M, Moran JL, Peake SL. Calorie delivery and clinical outcomes in the critically ill: a systematic review and meta-analysis. Crit Care Resusc. 2016; 18(1): 17–24.
- 35Bufarah M, Costa N, Losilla M, et al. Low caloric and protein intake is associated with mortality in patients with acute kidney injury. Clin Nutr ESPEN. 2018; 24: 66-70.
- 36Jeong DH, Hong S-B, Lim C-M, et al. Relationship between nutrition intake and 28-Day mortality using modified NUTRIC score in patients with sepsis. Nutrients. 2019; 11(8): 1906.
- 37Vanhorebeek I, Verbruggen S, Casaer MP, et al. Effect of early supplemental parenteral nutrition in the paediatric ICU: a preplanned observational study of post-randomisation treatments in the PEPaNIC trial. Lancet Respir Med. 2017; 5(6): 475-483.
- 38Thiessen SE, Derde S, Derese I, et al. Role of glucagon in catabolism and muscle wasting of critical illness and modulation by nutrition. Am J Respir Crit Care Med. 2017; 196(9): 1131-1143.
- 39Van Dyck L, Casaer MP, Gunst J. Autophagy and its implications against early full nutrition support in critical illness. Nutr Clin Pract. 2018; 33(3): 339-347.
- 40Casaer MP, Wilmer A, Hermans G, Wouters PJ, Mesotten D, Van den Berghe G. Role of disease and macronutrient dose in the randomized controlled EPaNIC trial: a post hoc analysis. Am J Respir Crit Care Med. 2013; 187(3): 247-255.
- 41Koekkoek WACK, van Setten CHC, Olthof LE, Kars JCNH, van Zanten ARH. Timing of PROTein INtake and clinical outcomes of adult critically ill patients on prolonged mechanical VENTilation: the PROTINVENT retrospective study. Clin Nutr. 2019; 38(2) 883-890.
- 42Lee Z-Y, Airini IN, Barakatun-Nisak M-Y. Relationship of energy and protein adequacy with 60-day mortality in mechanically ventilated critically ill patients: a prospective observational study. Clin Nutr. 2018; 37(4): 1264-1270.
- 43Arabi YM, Al-Dorzi HM, Mehta S, et al. Association of protein intake with the outcomes of critically ill patients: a post hoc analysis of the PermiT trial. Am J Clin Nutr. 2018; 108(5): 988-996.
- 44Doig GS, Simpson F, Bellomo R, et al. Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial. Intensive Care Med. 2015; 41(7): 1197-1208.
- 45Rugeles S-J, Rueda J-D, Díaz C-E, Rosselli D. Hyperproteic hypocaloric enteral nutrition in the critically ill patient: a randomized controlled clinical trial. Indian J Crit Care Med. 2013; 17(6): 343.
- 46Rugeles S, Villarraga-Angulo LG, Ariza-Gutiérrez A, Chaverra-Kornerup S, Lasalvia P, Rosselli D. High-protein hypocaloric vs normocaloric enteral nutrition in critically ill patients: a randomized clinical trial. J Crit Care. 2016; 35: 110-114.
- 47Azevedo JRA, Lima HCM, Montenegro WS, et al. Optimized calorie and high protein intake versus recommended caloric-protein intake in critically ill patients: a prospective, randomized, controlled phase II clinical trial. Rev Bras Ter Intensiva. 2019; 31(2): 171-179.
- 48Davies ML, Chapple L-AS, Chapman MJ, Moran JL, Peake SL. Protein delivery and clinical outcomes in the critically ill: a systematic review and meta-analysis. Crit Care Resusc. 2017; 19(2): 117.
- 49Lambell KJ, King SJ, Forsyth AK, Tierney AC. Association of energy and protein delivery on skeletal muscle mass changes in critically ill adults: a systematic review. JPEN J Parenter Enter Nutr. 2018; 42(7): 1112-1122.
- 50Weijs PJ, Looijaard WG, Beishuizen A, Girbes AR, Oudemans-van Straaten HM. Early high protein intake is associated with low mortality and energy overfeeding with high mortality in non-septic mechanically ventilated critically ill patients. Crit Care. 2014; 18(6): 701.
- 51Bendavid I, Zusman O, Kagan I, Theilla M, Cohen J, Singer P. Early administration of protein in critically ill patients: a retrospective cohort study. Nutrients. 2019; 11(1).
- 52Koekkoek WK, van Setten CC, Olthof LE, Kars JH, van Zanten AR. Timing of PROTein INtake and clinical outcomes of adult critically ill patients on prolonged mechanical VENTilation: the PROTINVENT retrospective study. Clin Nutr. 2019; 38(2): 883-890.
- 53de Koning MSLY, Koekkoek WACK, Kars JCNH, van Zanten ARH. Association of PROtein and CAloric intake and clinical outcomes in adult SEPTic and non-septic ICU patients on prolonged mechanical ventilation: the PROCASEPT retrospective study. JPEN J Parenter Enter Nutr. 2020; 44(3): 434.
- 54Wischmeyer PE. Tailoring nutrition therapy to illness and recovery. Crit Care. 2017; 21(3): 316.
- 55Simpson F, Doig GS. Parenteral vs. enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle. Intensive Care Med. 2005; 31(1): 12-23.
- 56Elke G, van Zanten AR, Lemieux M, et al. Enteral versus parenteral nutrition in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials. Crit Care. 2016; 20(1): 1-14.
- 57Harvey SE, Parrott F, Harrison DA, et al. Trial of the route of early nutritional support in critically ill adults. N Engl J Med. 2014; 371(18): 1673-1684.
- 58Reignier J, Boisrame-Helms J, Brisard L, et al. Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2). Lancet. 2018; 391(10116): 133-143.
- 59Heidegger C, Berger M, Graf S, et al. Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial. Lancet. 2013; 381(9864): 385.
- 60Casaer MP, Mesotten D, Hermans G, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011; 365(6): 506-517.
- 61Fivez T, Kerklaan D, Mesotten D, et al. Early versus late parenteral nutrition in critically ill children. N Engl J Med. 2016; 374(12): 1111-1122.
- 62Shi J, Wei L, Huang R, Liao L. Effect of combined parenteral and enteral nutrition versus enteral nutrition alone for critically ill patients: a systematic review and meta-analysis. Medicine (Baltimore). 2018; 97(41):e11874.
- 63Alsharif DJ, Alsharif FJ, Aljuraiban GS, Abulmeaty M. Effect of supplemental parenteral nutrition versus enteral nutrition alone on clinical outcomes in critically ill adult patients: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2020; 12(10): 2968.
- 64Tian F, Heighes PT, Allingstrup MJ, Doig GS. Early enteral nutrition provided within 24 hours of ICU admission: a meta-analysis of randomized controlled trials. Crit Care Med. 2018; 46(7) 1049-1056.
- 65Lewis S, Andersen H, Thomas S. Early enteral nutrition within 24 h of intestinal surgery versus later commencement of feeding: a systematic review and meta-analysis. J Gastrointest Surg. 2009; 13(3): 569-575.
- 66Hsieh P-H, Su H-Y, Lin C-Y, Kang Y-N, Chang C-C. Infection rate among nutritional therapies for acute pancreatitis: a systematic review with network meta-analysis of randomized controlled trials. PLoS One. 2019; 14(7):e0219151.
- 67Reintam Blaser A, Starkopf J, Alhazzani W, et al. Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines. Intensive Care Med. 2017; 43(3): 380-398.
- 68Metheny N, Krieger M, Healey F, Meert K. A review of guidelines to distinguish between gastric and pulmonary placement of nasogastric tubes. Heart Lung. 2019; 48(3): 226.
- 69Zhang Z, Xu X, Ding J, Ni H. Comparison of postpyloric tube feeding and gastric tube feeding in intensive care unit patients: a meta-analysis. Nutr Clin Pract. 2013; 28(3): 371-380.
- 70Melis M, Fichera A, Ferguson MK. Bowel necrosis associated with early jejunal tube feeding: a complication of postoperative enteral nutrition. Arch Surge. 2006; 141(7): 701-704.
- 71Ichimaru S. Methods of enteral nutrition administration in critically ill patients: continuous, cyclic, intermittent, and bolus feeding. Nutr Clin Pract. 2018; 33(6): 790-795.
- 72McNelly AS, Bear DE, Connolly BA, et al. Effect of intermittent or continuous feed on muscle wasting in critical illness: a phase 2 clinical trial. Chest. 2020; 158(1): 183-194.
- 73Doig GS, Simpson F, Heighes PT, et al. Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial. Lancet Respir Med. 2015; 3(12): 943-952.
- 74Ohbe H, Jo T, Matsui H, Fushimi K, Yasunaga H. Differences in effect of early enteral nutrition on mortality among ventilated adults with shock requiring low-, medium-, and high-dose noradrenaline: a propensity-matched analysis. Clin Nutr. 2020; 39(2): 460-467.
- 75Wollersheim T, Frank S, Müller M, et al. Measuring energy expenditure in extracorporeal lung support patients (MEEP)–Protocol, feasibility and pilot trial. Clin Nutr. 2018; 37(1): 301-307.
- 76Ohbe H, Jo T, Yamana H, Matsui H, Fushimi K, Yasunaga H. Early enteral nutrition for cardiogenic or obstructive shock requiring venoarterial extracorporeal membrane oxygenation: a nationwide inpatient database study. Intensive Care Med. 2018; 44(8): 1258-1265.
- 77Renaudier M, de Roux Q, Bougouin W, et al. Acute mesenteric ischaemia in refractory shock on veno-arterial extracorporeal membrane oxygenation. Eur Heart J Acute Cardiovasc Care. 2020; 10(1): 62-70.
- 78Al-Dorzi HM, Arabi YM. Enteral nutrition safety with advanced treatments: extracorporeal membrane oxygenation, prone positioning, and infusion of neuromuscular blockers. Nutr Clin Pract. 2021; 36(1): 88-97.
- 79Mesejo A, Montejo-González JC, Vaquerizo-Alonso C, et al. Diabetes-specific enteral nutrition formula in hyperglycemic, mechanically ventilated, critically ill patients: a prospective, open-label, blind-randomized, multicenter study. Criti Care. 2015; 19: 390.
- 80Liu M-Y, Tang H-C, Hu S-H, Chang S-J. Peptide-based enteral formula improves tolerance and clinical outcomes in abdominal surgery patients relative to a whole protein enteral formula. World J Gastrointest Surge. 2016; 8(10): 700–705.
- 81Jakob SM, Bütikofer L, Berger D, Coslovsky M, Takala J. A randomized controlled pilot study to evaluate the effect of an enteral formulation designed to improve gastrointestinal tolerance in the critically ill patient—the SPIRIT trial. Crit Care. 2017; 21(1): 140.
- 82Wischmeyer PE. Enteral nutrition can be given to patients on vasopressors. Crit Care Med. 2020; 48(1): 122-125.
- 83Ginguay A, De Bandt JP, Cynober L. Indications and contraindications for infusing specific amino acids (leucine, glutamine, arginine, citrulline, and taurine) in critical illness. Curr Opin Clin Nutr Metab Care. 2016; 19(2): 161-169.
- 84Bertolini G, Iapichino G, Radrizzani D, et al. Early enteral immunonutrition in patients with severe sepsis: results of an interim analysis of a randomized multicentre clinical trial. Intensive Care Med. 2003; 29(5): 834-840.
- 85Heyland D, Muscedere J, Wischmeyer P, et al. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med. 2013; 368(16): 1489.
- 86van Zanten AR, Dhaliwal R, Garrel D, Heyland DK. Enteral glutamine supplementation in critically ill patients: a systematic review and meta-analysis. Crit Care. 2015; 19(1): 294.
- 87Luiking YC, Poeze M, Deutz NE. A randomized-controlled trial of arginine infusion in severe sepsis on microcirculation and metabolism. Clin Nutr. 2020; 39(6): 1764-1773.
- 88Lin J-J, Chung X-J, Yang C-Y, Lau H-L. A meta-analysis of trials using the intention to treat principle for glutamine supplementation in critically ill patients with burn. Burns. 2013; 39(4): 565-570.
- 89Houdijk AP, Rijnsburger ER, Jansen J, et al. Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma. Lancet. 1998; 352(9130): 772-776.
- 90Rice TW, Wheeler AP, Thompson BT, et al. Enteral omega-3 fatty acid, γ-linolenic acid, and antioxidant supplementation in acute lung injury. JAMA. 2011; 306(14): 1574.
- 91Koekkoek WK, Panteleon V, van Zanten AR. Current evidence on ω-3 fatty acids in enteral nutrition in the critically ill: a systematic review and meta-analysis. Nutrition. 2019; 59: 56-68.
- 92Lu C, Sharma S, McIntyre L, et al. Omega-3 supplementation in patients with sepsis: a systematic review and meta-analysis of randomized trials. Ann Intensive Care. 2017; 7(1): 58.
- 93Rice T, Wheeler A, Thompson B, DeBoisblanc B, Steingrub J, Rock P; NIH NHLBI Acute Respiratory Distress Syndrome Network of Investigators. Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury. JAMA. 2011; 306(14): 1574-1581.
- 94van Zanten A, Sztark F, Kaisers U, et al. High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition and nosocomial infections in the ICU: a randomized clinical trial. JAMA. 2014; 312(5): 514.
- 95Manzanares W, Lemieux M, Elke G, Langlois PL, Bloos F, Heyland DK. High-dose intravenous selenium does not improve clinical outcomes in the critically ill: a systematic review and meta-analysis. Crit Care. 2016; 20(1): 1-16.
- 96Scholz SS, Borgstedt R, Ebeling N, Menzel LC, Jansen G, Rehberg S. Mortality in septic patients treated with vitamin C: a systematic meta-analysis. Crit Care. 2021; 25(1): 1-10.
- 97The National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. Early high-dose Vitamin D3 for critically ill, Vitamin D–deficient patients. N Engl J Med. 2019; 381(26): 2529-2540.
- 98Amrein K, Oudemans-van Straaten HM, Berger MM. Vitamin therapy in critically ill patients: focus on thiamine, vitamin C, and vitamin D. Intensive Care Med. 2018; 44(11): 1940-1944.
- 99Vesterlund GK, Thomsen T, Møller MH, Perner A. Effects of magnesium, phosphate and zinc supplementation in ICU patients—Protocol for a systematic review. Acta Anaesthesiol Scand. 2020; 64(1): 131-136.
- 100Blaser AR, Starkopf J, Kirsimägi Ü, Deane A. Definition, prevalence, and outcome of feeding intolerance in intensive care: a systematic review and meta-analysis. Acta Anaesthesiol Scand. 2014; 58(8): 914-922.
- 101Reignier J, Mercier E, Le Gouge A, et al. Effect of not monitoring residual gastric volume on risk of ventilator-associated pneumonia in adults receiving mechanical ventilation and early enteral feeding: a randomized controlled trial. JAMA. 2013; 309(3): 249-256.
- 102Wang Z, Ding W, Fang Q, Zhang L, Liu X, Tang Z. Effects of not monitoring gastric residual volume in intensive care patients: A meta-analysis. Int J Nurs Stud. 2019; 91: 86-93.
- 103Lewis K, Alqahtani Z, Mcintyre L, et al. The efficacy and safety of prokinetic agents in critically ill patients receiving enteral nutrition: a systematic review and meta-analysis of randomized trials. Crit Care. 2016; 20(1): 259.
- 104Heyland DK, van Zanten AR, Grau-Carmona T, et al. A multicenter, randomized, double-blind study of ulimorelin and metoclopramide in the treatment of critically ill patients with enteral feeding intolerance: PROMOTE trial. Intensive Care Med. 2019; 45(5): 647-656.
- 105Heyland D, Dhaliwal R, Lemieux M, Wang M, Day A. Implementing the PEP uP protocol in critical care units in Canada: results of a multicenter, quality improvement study. JPEN J Parenter Enter Nutr. 2015; 39(6): 698.
- 106Doig GS, Simpson F, Finfer S, et al. Effect of evidence-based feeding guidelines on mortality of critically ill adults: a cluster randomized controlled trial. JAMA. 2008; 300(23): 2731-2741.
- 107Terzi N, Darmon M, Reignier J, et al. Initial nutritional management during noninvasive ventilation and outcomes: a retrospective cohort study. Crit Care. 2017; 21(1): 293.
- 108Martindale R, Patel JJ, Taylor B, Arabi YM, Warren M, McClave SA. Nutrition therapy in critically ill patients with coronavirus disease 2019. JPEN J Parenter Enteral Nutr. 2020; 44(7): 1174-1184.