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Nutrition for Critically Ill Patients: How Much Is Enough?

Nutrition for Critically Ill Patients: How Much Is Enough? Healthy adults have a closely interrelated nutritional, metabolic, and immune system that regulates food requirements and responds well to short-term nutritional deprivation but not to nutrient excess.1 However, when critically ill, patients no longer have control over their food intake, and clinicians may administer nutritional support with little understanding of individual patient needs in the light of inflammatory demands, injury responses, and the underlying influences of genotype and age.2 Because robust evidence about the nutritional requirements for critically ill patients at the various stages of their illness is lacking, particularly when they are acutely ill,3 clinicians often base nutritional support on “requirements” based on averages and guesswork. Nutritional support in excess of actual requirements may contribute to metabolic stress.4 In the intensive care unit (ICU), parenteral nutrition can facilitate excessive early provision of nutrients during a period of considerable uncertainty about requirements. This was illustrated in the study by Casaer et al,5 in which very early targeting of full feeding requirements with parenteral nutrition in the first few days was not beneficial. The authors of that study suggested the possibility that nutrition might suppress the normal activation of acute mechanisms necessary to remove cellular damage.6 In patients receiving mechanical ventilation, enteral feeding rarely delivers consistently more than 80% of the target full feeding, but it is still reasonable to question whether further restriction of enteral nutrition would be preferable during the early stages of an acute illness. In this issue of JAMA, Rice and colleagues, writing for the National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network,7 report findings examining whether there is any advantage to restricting the amount of initial enteral intake among mechanically ventilated patients with acute lung injury (ALI). The EDEN study was a large, unblinded trial from 44 sites that recruited 1000 patients soon after starting ventilation and developing ALI (about 80% of which was attributable to primary pneumonias or sepsis). The study hypothesis was that administration of considerably reduced, trophic feeding (about 25% of the target full feeding) during the first 6 days would increase ventilator-free days (VFDs) compared with a more actively advanced conventional full enteral nutrition regimen achieving a target intake of 80%. This hypothesis was not supported by the study findings: there was no difference between trophic feedings vs full enteral feedings in VFDs or any important secondary end points, including ICU stay, organ failure–free days, 28-day mortality, and 60-day mortality. Nonetheless, this study highlights several important practical points. The majority of these patients can be fed nasogastrically; the majority tolerate gastric residual volumes of 400 mL, measured at 6-hour intervals, without high rates of aspiration or increased ventilator-associated pneumonia; and using a protocolized approach for feeding allows clinicians to deliver a greater volume of the target feeding amounts than prior groups have reported. One potentially confounding factor was that the study was initially combined in a factorial design with another study, the OMEGA trial,8 which randomized patients to receive a supplement containing omega-3 fatty acids, γ-linolenic acid, and antioxidants until stopped for futility after 272 patients (27%) had been recruited. The results of the trial by Rice et al7 cannot be used to conclude that trophic feeding is equivalent to full feeding in critically ill patients. This study was not designed or powered as an equivalence study and does not provide definitive data to inform clinicians about how much nutritional support is enough, how early it should be started, or even if there should be “no nutrition provision” in the initial phase of critical illness—a case that has been persistently argued and remains to be tested.9 The effect of nutrition on an end point such as VFDs does not simply depend on dose and duration but on several other factors. These may include a complex interaction of prior nutritional reserves; the effects of any initial or evolving nutritional deficiency; the extent and severity of the underlying illnesses; the processes of recovery interacting with the metabolic signaling and stress from the nutrients; and the burdens imposed by the complications of providing nutritional support. These factors suggest that not all patients may benefit equally.10 An important challenge is identifying patients at increased nutritional risk. In the study by Rice et al,7 patients were relatively young (mean, 52 years), apparently well nourished, and relatively overweight (body mass index of 30), and 29% had diabetes. All patients had a reasonably functional gastrointestinal tract and may not have been nutritionally challenged. The most severely ill patients with lung injury were probably excluded because of gastrointestinal failure, and 90% of patients in the full-feeding group in the study tolerated full feedings within little more than a day. It appears that the patients in this study were relatively less critically ill, such that more than half of patients no longer required mechanical ventilation within the 6-day nutrition test period. An important question is whether the relationship between nutrition and the risk of developing a new infection was the same among noninfected patients entering the study compared with the majority of patients who had pneumonia and sepsis at the time of admission. Although Rice et al enrolled a large number of patients, as with any large study conducted in ICU settings, there is always significant case-mix heterogeneity, such as variation in primary pathology, illness severity, age, or nutritional state. By studying only patients with ALI, the authors limited heterogeneity, although inevitably some mix of causative pathologies remains. It is possible that some inherent limitations hampered the ability to find a difference in outcomes. First, it is possible that the difference in the interventions was too modest. The full-feeding group was based on a calculated ideal body weight, which may have underestimated the nutritional requirements in many patients with higher body mass indices. Even though the investigators on average achieved 80% of the nutritional target in the full-feeding group, the data presentation may have concealed a wider variance that includes a proportion of patients with a lesser amount of nutritional support delivered. Some patients might have only received a more trophic feeding because of some gastrointestinal dysfunction, possibly the patients who theoretically may have benefited most from the intervention. Second, the hypothesis that trophic feeding has benefit in ALI may be incorrect. There was no evidence that any patient subgroup may have benefited. Neither the primary end point of VFDs nor any secondary end point, such as 60-day mortality, was different in relation to body mass index, shock, or severity of lung injury. There appears to be no strong biological mechanism to provide a firm pathophysiological explanation for how a few days of less enteral nutrition (amount and volume) might produce a reduced need for ventilation. Third, because nutritional support is not just about the acute state, longer-term end points, including functional outcomes, were not reported but may have been informative. For instance, in an earlier study, Rice et al11 had observed that significantly more patients receiving full feedings, compared with trophic feedings, were discharged directly home rather than to a rehabilitation facility. The 6 days of profoundly limited protein intake in the trophic-feeding group in the current study had no apparent short-term effects, although the effects on longer-term outcomes remain unknown. The evidence base with respect to nutritional issues in critically ill patients is limited. Studies evaluating drugs or other interventions among patients who only require short ICU stays often assume that only 1 factor is being assessed in a predictably consistent manner and in an attempt to modify a single pathology (as a drug action). These studies also attempt to recruit a sufficient number of patients so that other important differences between intervention groups are evenly distributed. However, this has not been the case with nutrition studies in critically ill patients and has contributed to widely differing interpretations in nutrition guidelines.12 The outcomes from nutrition interventions need to be assessed over longer time frames and with consideration of the nature and type of patient and presence of gastrointestinal tract dysfunction.13 For studies of critically ill patients, individual patient requirements might have to be more accurately assessed or even measured to provide optimal therapy. Providing effective nutritional support for critically ill patients represents a difficult aspect of the overall management of complex patients. The current study by Rice et al,7 taken together with existing data from other recent rigorous studies, highlights the need to challenge commonly used nutritional support practices and to achieve an individualized, evidence-based approach for optimal nutritional therapy in patients with ALI. Back to top Article Information Corresponding Author: Richard D. Griffiths, BSc, MBBS, MD, FRCP, FFICM, Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, Duncan Bldg, Daulby Street, Liverpool, L69 3GA, United Kingdom (rdg@liverpool.ac.uk). Published Online: February 5, 2012. doi:10.1001/jama.2012.168 Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and reported that he has no direct conflict of interest but as a clinical academic researcher has in the past received modest lecture travel expenses, has benefitted from independent research grants paid to the University of Liverpool from Fresenius Kabi GmbH, and has received grant support from the Medical Research Council and National Institute of Health Research, United Kingdom. Editorials represent the opinions of the authors and JAMA and not those of the American Medical Association. References 1. Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860-86717167474PubMedGoogle ScholarCrossref 2. Soeters PB, Grimble RF. Dangers, and benefits of the cytokine mediated response to injury and infection. Clin Nutr. 2009;28(6):583-59619556039PubMedGoogle ScholarCrossref 3. Lundholm K, Hyltander A, Sandström R. Nutrition and multiple organ failure. Nutr Res Rev. 1992;5(1):97-11319094315PubMedGoogle ScholarCrossref 4. Griffiths RD. Too much of a good thing: the curse of overfeeding. Crit Care. 2007;11(6):17618036266PubMedGoogle ScholarCrossref 5. Casaer MP, Mesotten D, Hermans G, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011;365(6):506-51721714640PubMedGoogle ScholarCrossref 6. Vanhorebeek I, Gunst J, Derde S, et al. Insufficient activation of autophagy allows cellular damage to accumulate in critically ill patients. J Clin Endocrinol Metab. 2011;96(4):E633-E64521270330PubMedGoogle ScholarCrossref 7. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. [published online February 5, 2012]. JAMA. 2012;307(8):795-803Google ScholarCrossref 8. Rice TW, Wheeler AP, Thompson BT, et al; NHLBI ARDS Clinical Trials Network. Enteral omega-3 fatty acid, γ-linolenic acid, and antioxidant supplementation in acute lung injury. JAMA. 2011;306(14):1574-158121976613PubMedGoogle ScholarCrossref 9. Koretz RL. Breathing and feeding: can you have one without the other? Chest. 1984;85(3):298-2996583052PubMedGoogle ScholarCrossref 10. Heyland DK, Dhaliwal R, Jiang X, Day AG. Identifying critically ill patients who benefit the most from nutrition therapy. Crit Care. 2011;15(6):R26822085763PubMedGoogle ScholarCrossref 11. Rice TW, Mogan S, Hays MA, et al. Randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure. Crit Care Med. 2011;39(5):967-97421242788PubMedGoogle ScholarCrossref 12. Griffiths RD. Guidelines for nutrition in the critically ill: are we altogether or in-the-altogether? JPEN J Parenter Enteral Nutr. 2010;34(6):595-59721097754PubMedGoogle ScholarCrossref 13. Griffiths RD. Nutrition and survival in intensive care. Med Klin Intensivmed Notfmed. 1998;35(1):3-9Google Scholar http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Nutrition for Critically Ill Patients: How Much Is Enough?

Griffiths, Richard D.
JAMA , Volume 307 (8) – Feb 22, 2012
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References (16)

Publisher
American Medical Association
Copyright
Copyright © 2012 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.2012.168
Publisher site
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Abstract

Healthy adults have a closely interrelated nutritional, metabolic, and immune system that regulates food requirements and responds well to short-term nutritional deprivation but not to nutrient excess.1 However, when critically ill, patients no longer have control over their food intake, and clinicians may administer nutritional support with little understanding of individual patient needs in the light of inflammatory demands, injury responses, and the underlying influences of genotype and age.2 Because robust evidence about the nutritional requirements for critically ill patients at the various stages of their illness is lacking, particularly when they are acutely ill,3 clinicians often base nutritional support on “requirements” based on averages and guesswork. Nutritional support in excess of actual requirements may contribute to metabolic stress.4 In the intensive care unit (ICU), parenteral nutrition can facilitate excessive early provision of nutrients during a period of considerable uncertainty about requirements. This was illustrated in the study by Casaer et al,5 in which very early targeting of full feeding requirements with parenteral nutrition in the first few days was not beneficial. The authors of that study suggested the possibility that nutrition might suppress the normal activation of acute mechanisms necessary to remove cellular damage.6 In patients receiving mechanical ventilation, enteral feeding rarely delivers consistently more than 80% of the target full feeding, but it is still reasonable to question whether further restriction of enteral nutrition would be preferable during the early stages of an acute illness. In this issue of JAMA, Rice and colleagues, writing for the National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network,7 report findings examining whether there is any advantage to restricting the amount of initial enteral intake among mechanically ventilated patients with acute lung injury (ALI). The EDEN study was a large, unblinded trial from 44 sites that recruited 1000 patients soon after starting ventilation and developing ALI (about 80% of which was attributable to primary pneumonias or sepsis). The study hypothesis was that administration of considerably reduced, trophic feeding (about 25% of the target full feeding) during the first 6 days would increase ventilator-free days (VFDs) compared with a more actively advanced conventional full enteral nutrition regimen achieving a target intake of 80%. This hypothesis was not supported by the study findings: there was no difference between trophic feedings vs full enteral feedings in VFDs or any important secondary end points, including ICU stay, organ failure–free days, 28-day mortality, and 60-day mortality. Nonetheless, this study highlights several important practical points. The majority of these patients can be fed nasogastrically; the majority tolerate gastric residual volumes of 400 mL, measured at 6-hour intervals, without high rates of aspiration or increased ventilator-associated pneumonia; and using a protocolized approach for feeding allows clinicians to deliver a greater volume of the target feeding amounts than prior groups have reported. One potentially confounding factor was that the study was initially combined in a factorial design with another study, the OMEGA trial,8 which randomized patients to receive a supplement containing omega-3 fatty acids, γ-linolenic acid, and antioxidants until stopped for futility after 272 patients (27%) had been recruited. The results of the trial by Rice et al7 cannot be used to conclude that trophic feeding is equivalent to full feeding in critically ill patients. This study was not designed or powered as an equivalence study and does not provide definitive data to inform clinicians about how much nutritional support is enough, how early it should be started, or even if there should be “no nutrition provision” in the initial phase of critical illness—a case that has been persistently argued and remains to be tested.9 The effect of nutrition on an end point such as VFDs does not simply depend on dose and duration but on several other factors. These may include a complex interaction of prior nutritional reserves; the effects of any initial or evolving nutritional deficiency; the extent and severity of the underlying illnesses; the processes of recovery interacting with the metabolic signaling and stress from the nutrients; and the burdens imposed by the complications of providing nutritional support. These factors suggest that not all patients may benefit equally.10 An important challenge is identifying patients at increased nutritional risk. In the study by Rice et al,7 patients were relatively young (mean, 52 years), apparently well nourished, and relatively overweight (body mass index of 30), and 29% had diabetes. All patients had a reasonably functional gastrointestinal tract and may not have been nutritionally challenged. The most severely ill patients with lung injury were probably excluded because of gastrointestinal failure, and 90% of patients in the full-feeding group in the study tolerated full feedings within little more than a day. It appears that the patients in this study were relatively less critically ill, such that more than half of patients no longer required mechanical ventilation within the 6-day nutrition test period. An important question is whether the relationship between nutrition and the risk of developing a new infection was the same among noninfected patients entering the study compared with the majority of patients who had pneumonia and sepsis at the time of admission. Although Rice et al enrolled a large number of patients, as with any large study conducted in ICU settings, there is always significant case-mix heterogeneity, such as variation in primary pathology, illness severity, age, or nutritional state. By studying only patients with ALI, the authors limited heterogeneity, although inevitably some mix of causative pathologies remains. It is possible that some inherent limitations hampered the ability to find a difference in outcomes. First, it is possible that the difference in the interventions was too modest. The full-feeding group was based on a calculated ideal body weight, which may have underestimated the nutritional requirements in many patients with higher body mass indices. Even though the investigators on average achieved 80% of the nutritional target in the full-feeding group, the data presentation may have concealed a wider variance that includes a proportion of patients with a lesser amount of nutritional support delivered. Some patients might have only received a more trophic feeding because of some gastrointestinal dysfunction, possibly the patients who theoretically may have benefited most from the intervention. Second, the hypothesis that trophic feeding has benefit in ALI may be incorrect. There was no evidence that any patient subgroup may have benefited. Neither the primary end point of VFDs nor any secondary end point, such as 60-day mortality, was different in relation to body mass index, shock, or severity of lung injury. There appears to be no strong biological mechanism to provide a firm pathophysiological explanation for how a few days of less enteral nutrition (amount and volume) might produce a reduced need for ventilation. Third, because nutritional support is not just about the acute state, longer-term end points, including functional outcomes, were not reported but may have been informative. For instance, in an earlier study, Rice et al11 had observed that significantly more patients receiving full feedings, compared with trophic feedings, were discharged directly home rather than to a rehabilitation facility. The 6 days of profoundly limited protein intake in the trophic-feeding group in the current study had no apparent short-term effects, although the effects on longer-term outcomes remain unknown. The evidence base with respect to nutritional issues in critically ill patients is limited. Studies evaluating drugs or other interventions among patients who only require short ICU stays often assume that only 1 factor is being assessed in a predictably consistent manner and in an attempt to modify a single pathology (as a drug action). These studies also attempt to recruit a sufficient number of patients so that other important differences between intervention groups are evenly distributed. However, this has not been the case with nutrition studies in critically ill patients and has contributed to widely differing interpretations in nutrition guidelines.12 The outcomes from nutrition interventions need to be assessed over longer time frames and with consideration of the nature and type of patient and presence of gastrointestinal tract dysfunction.13 For studies of critically ill patients, individual patient requirements might have to be more accurately assessed or even measured to provide optimal therapy. Providing effective nutritional support for critically ill patients represents a difficult aspect of the overall management of complex patients. The current study by Rice et al,7 taken together with existing data from other recent rigorous studies, highlights the need to challenge commonly used nutritional support practices and to achieve an individualized, evidence-based approach for optimal nutritional therapy in patients with ALI. Back to top Article Information Corresponding Author: Richard D. Griffiths, BSc, MBBS, MD, FRCP, FFICM, Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, Duncan Bldg, Daulby Street, Liverpool, L69 3GA, United Kingdom (rdg@liverpool.ac.uk). Published Online: February 5, 2012. doi:10.1001/jama.2012.168 Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and reported that he has no direct conflict of interest but as a clinical academic researcher has in the past received modest lecture travel expenses, has benefitted from independent research grants paid to the University of Liverpool from Fresenius Kabi GmbH, and has received grant support from the Medical Research Council and National Institute of Health Research, United Kingdom. Editorials represent the opinions of the authors and JAMA and not those of the American Medical Association. References 1. Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860-86717167474PubMedGoogle ScholarCrossref 2. Soeters PB, Grimble RF. Dangers, and benefits of the cytokine mediated response to injury and infection. Clin Nutr. 2009;28(6):583-59619556039PubMedGoogle ScholarCrossref 3. Lundholm K, Hyltander A, Sandström R. Nutrition and multiple organ failure. Nutr Res Rev. 1992;5(1):97-11319094315PubMedGoogle ScholarCrossref 4. Griffiths RD. Too much of a good thing: the curse of overfeeding. Crit Care. 2007;11(6):17618036266PubMedGoogle ScholarCrossref 5. Casaer MP, Mesotten D, Hermans G, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011;365(6):506-51721714640PubMedGoogle ScholarCrossref 6. Vanhorebeek I, Gunst J, Derde S, et al. Insufficient activation of autophagy allows cellular damage to accumulate in critically ill patients. J Clin Endocrinol Metab. 2011;96(4):E633-E64521270330PubMedGoogle ScholarCrossref 7. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. [published online February 5, 2012]. JAMA. 2012;307(8):795-803Google ScholarCrossref 8. Rice TW, Wheeler AP, Thompson BT, et al; NHLBI ARDS Clinical Trials Network. Enteral omega-3 fatty acid, γ-linolenic acid, and antioxidant supplementation in acute lung injury. JAMA. 2011;306(14):1574-158121976613PubMedGoogle ScholarCrossref 9. Koretz RL. Breathing and feeding: can you have one without the other? Chest. 1984;85(3):298-2996583052PubMedGoogle ScholarCrossref 10. Heyland DK, Dhaliwal R, Jiang X, Day AG. Identifying critically ill patients who benefit the most from nutrition therapy. Crit Care. 2011;15(6):R26822085763PubMedGoogle ScholarCrossref 11. Rice TW, Mogan S, Hays MA, et al. Randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure. Crit Care Med. 2011;39(5):967-97421242788PubMedGoogle ScholarCrossref 12. Griffiths RD. Guidelines for nutrition in the critically ill: are we altogether or in-the-altogether? JPEN J Parenter Enteral Nutr. 2010;34(6):595-59721097754PubMedGoogle ScholarCrossref 13. Griffiths RD. Nutrition and survival in intensive care. Med Klin Intensivmed Notfmed. 1998;35(1):3-9Google Scholar

Journal

JAMA – American Medical Association

Published: Feb 22, 2012

Keywords: critical illness,science of nutrition

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