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Nutrition support during adult critical illness
Many critically ill patients you care for cannot maintain volitional oral intake. Therefore, nutrition support, through enteral or parenteral routes, remains a cornerstone in ensuring our critically ill patients receive substrates like glucose and protein. To understand the supportive role of nutrition during critical illness, let’s identify and contextualize the different phases of critical illness.
Phases of critical illness
The European Society of Parenteral and Enteral Nutrition’s (ESPEN) 2018 critical care nutrition guideline incorporates stages of critical illness in making nutrition recommendations (Singer P et al. Clin Nutr. 2019;38:48-79). The first week of critical illness is the acute phase and hallmarked by catabolism and metabolic and hemodynamic instability. The late phase is thereafter and hallmarked by rehabilitation and anabolism or chronic critical illness. The acute phase is further divided into early (days 1-2) and late acute phase (days 3-7). The time-points are arbitrary and merely serve as placeholders. An objective marker to distinguish phases does not exist and transition periods will be different for each patient.
Acute phase
Critical illness defining conditions like circulatory shock, respiratory failure, and trauma are stressors and lead to two key acute phase perturbations that nutrition may have a role in altering:
The first is hypercatabolism. Critical illness defining conditions activate neuroendocrine, inflammatory/immune, adipokine, and GI tract hormone pathways that increase serum glucagon, cortisol, and catecholamines to promote glycogenolysis, gluconeogenesis, insulin resistance, protein catabolism, and restricted/impaired anabolism.
The second is gut dysfunction. During health, there is cross-talk signaling that occurs between commensal bacteria, epithelium, and the immune system, which maintains gut barrier functions, achieved, for example, by promoting tight junction protein production. Acute critical illness pathophysiology loosens epithelial tight junctions, and the gut barrier is breached, creating an opportunity for downstream migration of pancreatic enzymes and cytokines. Furthermore, the microbiome morphs into a virulent pathobiome, which induces gut-derived inflammation.
When, where, and how much should we feed critically ill patients?
Since the acute phase of critical illness begins a series of events leading to negative energy balance and gut dysfunction, you might find early nutrition provision intuitive. Indeed, the 2016 ASPEN/SCCM and 2018 ESPEN critical care nutrition guidelines recommend early (within 24-48 hours of ICU admission) enteral nutrition (EN), delivered into the stomach, for all critically ill patients unable to maintain volitional intake. Meta-analyses of randomized controlled trials (RCT) conducted between1979 and 2013 show early EN reduces both mortality and infectious complications, compared with no early nutrition (McClave SA et al. JPEN. 2016;40:159-211).
RCT level data do not show superiority of EN over parenteral nutrition (PN). Nonetheless, early EN is recommended over PN because it maintains epithelial barrier function and supports immunity.
What is the optimal nutrition dose? The 2016 ASPEN/SCCM guideline recommends getting to >80% estimated energy goal within 48-72 hours in patients with high nutrition risk while the 2018 ESPEN guideline suggests maintaining a hypocaloric, or not exceeding 70% of prescribed energy goal, during the early acute phase. The recommendation is based on meta-analyses of RCTs conducted between 2011 and 2017, which shows no mortality difference between hypocaloric and isocaloric nutrition.
Biologically plausible rationale for starting hypocaloric, as opposed to full dose nutrition, during the acute phase of critical illness includes: (a) the acute phase represents a period of hemodynamic instability and mitochondrial dysfunction, and full-dose EN may lead to feeding intolerance and lack of substrate utilization, respectively; (b) in those with risk factors (like pre-existing malnutrition), starting full dose nutrition may lead to refeeding syndrome; and (c) endogenous glucose production occurs during the acute phase, and full dose nutrition may worsen hyperglycemia.
Therefore, during the early acute phase of critical illness, hypocaloric feeding using an isosmotic formula, with a slow up-titration to goal rate thereafter, while monitoring for feeding intolerance and refeeding syndrome is a reasonable starting point.
What is the role of parenteral nutrition in critical illness?
PN can be exclusive or supplemental (in a patient receiving EN). Historically, providers may have been reluctant to utilize PN for fear of infectious morbidity; however, contemporary pragmatic-design RCTs demonstrate safety with exclusive PN (Harvey SE et al. N Engl J Med. 2014;371:1673-84). When your patient has a contraindication for EN or does not tolerate it despite a trial of small bowel feeding, meta-analyses have shown a mortality benefit of early exclusive PN in malnourished patients, as compared with no nutrition (Braunschweig C et al. Am J Clin Nutr.2001;74:534-42).
As for supplemental PN (SPN), the 2016 ASPEN/SCCM guideline does not recommend it until day 7 in all critically ill patients, while the 2018 ESPEN guideline recommends its use on a case-by-case basis. Since, two trials inform SPN use. The EAT-ICU trial showed no difference in 6-month physical function between EN group and early-goal-directed nutritiongroup, which included SPN to achieve estimated energy requirement during the first week of critical illness (Allingstrup MJ et al. Intensive Care Med. 2017;43:1637-47). The TOP-UP trial compared EN alone with EN plus SPN in nutritionally high risk patients (ie, those who stand to have more complications as a result of undernutrition) and found those with a BMI < 25 kg/m2 and those with a NUTRIC score >5 who received supplemental PN atop EN had improved 30-day mortality, as compared with EN alone (Wischmeyer P et al. Crit Care. 2017;21:142). Mortality was a secondary outcome, and further study of supplemental PN in nutritionally high-risk patients is warranted. Until further data are available, supplemental PN should probably be restricted during the acute phase of critical illness.
Protein may be the important substrate
Proteolysis is the rule during critical illness, and amino acids are liberated from skeletal muscle breakdown. Using ultrasound, Puthucheary et al found a 17.7% reduction in rectus femoris cross-sectional area in 63 critically ill adults and identified muscle cellular infiltration at ICU day 10, suggesting critical illness leads to quantitative and qualitative muscle defects (Puthucheary Z et al. JAMA. 2013;15:1591-1600).
Since survivorship from critical illness is increasing, acquired loss of muscle mass may contribute to post-ICU physical functioning impairments. Thus, protein may be the most important substrate to deliver during critical illness. The 2016 ASPEN/SCCM guideline recommends 1.2 – 2.0 g/kg actual body weight (ABW)/day in nonobese critically ill patients.
Unfortunately, the optimal protein dose and the timing of intake are unknown. Observational studies suggest benefit with lower and higher doses, which creates equipoise for protein dose. The signal may be lost in heterogeneity, and observational data suggest higher protein dose may benefit patients with high nutritional risk. In terms of timing, one observational study found lower (<0.8 g/kg/d) protein dose before day 3 followed by higher (>0.8 g/kg/d) dose thereafter was associated with mortality benefit (Koekkoek WAC et al. Clin Nutr.2019;38:883-890).
Until stronger data are available to guide optimal protein dose and timing, it is reasonable to observe the 2016 ASPEN/SCCM guideline protein recommendation of at least 1.2 g/kg/day. The 2018 ESPEN guideline recommends a similar dose of 1.3 g/kg/day.
Future research and summary
Many questions remain unanswered and present opportunities for future research. Priorities for critical care nutrition research include studying the impact of combined nutrition and exercise in the acute and late phases of critical illness and identifying best tools to differentiate responses to caloric and protein intake.
In summary, critical illness has acute and late phases. The acute phase is a hypercatabolic state leading to negative energy and nitrogen balance and gut dysfunction. Take-home points for nutrition support in the acute phase of critical illness are:
1. It is reasonable to start early hypocaloric EN with an isosmotic formula with slow up-titration over the first week of critical illness while monitoring for refeeding syndrome and feeding intolerance.
2. Use exclusive PN in ICU patients with pre-existing malnutrition when EN is contraindicated or not tolerated.
3. Supplemental PN should probably be restricted during the acute phase of critical illness.
4. Optimal protein dose and timing are unknown. It is reasonable to start with at least 1.2 g/kg ABW/day in non-obese patients.
Dr. Patel is with the Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Dr. Rice is with the Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Vanderbilt University, Nashville, Tennessee.
Many critically ill patients you care for cannot maintain volitional oral intake. Therefore, nutrition support, through enteral or parenteral routes, remains a cornerstone in ensuring our critically ill patients receive substrates like glucose and protein. To understand the supportive role of nutrition during critical illness, let’s identify and contextualize the different phases of critical illness.
Phases of critical illness
The European Society of Parenteral and Enteral Nutrition’s (ESPEN) 2018 critical care nutrition guideline incorporates stages of critical illness in making nutrition recommendations (Singer P et al. Clin Nutr. 2019;38:48-79). The first week of critical illness is the acute phase and hallmarked by catabolism and metabolic and hemodynamic instability. The late phase is thereafter and hallmarked by rehabilitation and anabolism or chronic critical illness. The acute phase is further divided into early (days 1-2) and late acute phase (days 3-7). The time-points are arbitrary and merely serve as placeholders. An objective marker to distinguish phases does not exist and transition periods will be different for each patient.
Acute phase
Critical illness defining conditions like circulatory shock, respiratory failure, and trauma are stressors and lead to two key acute phase perturbations that nutrition may have a role in altering:
The first is hypercatabolism. Critical illness defining conditions activate neuroendocrine, inflammatory/immune, adipokine, and GI tract hormone pathways that increase serum glucagon, cortisol, and catecholamines to promote glycogenolysis, gluconeogenesis, insulin resistance, protein catabolism, and restricted/impaired anabolism.
The second is gut dysfunction. During health, there is cross-talk signaling that occurs between commensal bacteria, epithelium, and the immune system, which maintains gut barrier functions, achieved, for example, by promoting tight junction protein production. Acute critical illness pathophysiology loosens epithelial tight junctions, and the gut barrier is breached, creating an opportunity for downstream migration of pancreatic enzymes and cytokines. Furthermore, the microbiome morphs into a virulent pathobiome, which induces gut-derived inflammation.
When, where, and how much should we feed critically ill patients?
Since the acute phase of critical illness begins a series of events leading to negative energy balance and gut dysfunction, you might find early nutrition provision intuitive. Indeed, the 2016 ASPEN/SCCM and 2018 ESPEN critical care nutrition guidelines recommend early (within 24-48 hours of ICU admission) enteral nutrition (EN), delivered into the stomach, for all critically ill patients unable to maintain volitional intake. Meta-analyses of randomized controlled trials (RCT) conducted between1979 and 2013 show early EN reduces both mortality and infectious complications, compared with no early nutrition (McClave SA et al. JPEN. 2016;40:159-211).
RCT level data do not show superiority of EN over parenteral nutrition (PN). Nonetheless, early EN is recommended over PN because it maintains epithelial barrier function and supports immunity.
What is the optimal nutrition dose? The 2016 ASPEN/SCCM guideline recommends getting to >80% estimated energy goal within 48-72 hours in patients with high nutrition risk while the 2018 ESPEN guideline suggests maintaining a hypocaloric, or not exceeding 70% of prescribed energy goal, during the early acute phase. The recommendation is based on meta-analyses of RCTs conducted between 2011 and 2017, which shows no mortality difference between hypocaloric and isocaloric nutrition.
Biologically plausible rationale for starting hypocaloric, as opposed to full dose nutrition, during the acute phase of critical illness includes: (a) the acute phase represents a period of hemodynamic instability and mitochondrial dysfunction, and full-dose EN may lead to feeding intolerance and lack of substrate utilization, respectively; (b) in those with risk factors (like pre-existing malnutrition), starting full dose nutrition may lead to refeeding syndrome; and (c) endogenous glucose production occurs during the acute phase, and full dose nutrition may worsen hyperglycemia.
Therefore, during the early acute phase of critical illness, hypocaloric feeding using an isosmotic formula, with a slow up-titration to goal rate thereafter, while monitoring for feeding intolerance and refeeding syndrome is a reasonable starting point.
What is the role of parenteral nutrition in critical illness?
PN can be exclusive or supplemental (in a patient receiving EN). Historically, providers may have been reluctant to utilize PN for fear of infectious morbidity; however, contemporary pragmatic-design RCTs demonstrate safety with exclusive PN (Harvey SE et al. N Engl J Med. 2014;371:1673-84). When your patient has a contraindication for EN or does not tolerate it despite a trial of small bowel feeding, meta-analyses have shown a mortality benefit of early exclusive PN in malnourished patients, as compared with no nutrition (Braunschweig C et al. Am J Clin Nutr.2001;74:534-42).
As for supplemental PN (SPN), the 2016 ASPEN/SCCM guideline does not recommend it until day 7 in all critically ill patients, while the 2018 ESPEN guideline recommends its use on a case-by-case basis. Since, two trials inform SPN use. The EAT-ICU trial showed no difference in 6-month physical function between EN group and early-goal-directed nutritiongroup, which included SPN to achieve estimated energy requirement during the first week of critical illness (Allingstrup MJ et al. Intensive Care Med. 2017;43:1637-47). The TOP-UP trial compared EN alone with EN plus SPN in nutritionally high risk patients (ie, those who stand to have more complications as a result of undernutrition) and found those with a BMI < 25 kg/m2 and those with a NUTRIC score >5 who received supplemental PN atop EN had improved 30-day mortality, as compared with EN alone (Wischmeyer P et al. Crit Care. 2017;21:142). Mortality was a secondary outcome, and further study of supplemental PN in nutritionally high-risk patients is warranted. Until further data are available, supplemental PN should probably be restricted during the acute phase of critical illness.
Protein may be the important substrate
Proteolysis is the rule during critical illness, and amino acids are liberated from skeletal muscle breakdown. Using ultrasound, Puthucheary et al found a 17.7% reduction in rectus femoris cross-sectional area in 63 critically ill adults and identified muscle cellular infiltration at ICU day 10, suggesting critical illness leads to quantitative and qualitative muscle defects (Puthucheary Z et al. JAMA. 2013;15:1591-1600).
Since survivorship from critical illness is increasing, acquired loss of muscle mass may contribute to post-ICU physical functioning impairments. Thus, protein may be the most important substrate to deliver during critical illness. The 2016 ASPEN/SCCM guideline recommends 1.2 – 2.0 g/kg actual body weight (ABW)/day in nonobese critically ill patients.
Unfortunately, the optimal protein dose and the timing of intake are unknown. Observational studies suggest benefit with lower and higher doses, which creates equipoise for protein dose. The signal may be lost in heterogeneity, and observational data suggest higher protein dose may benefit patients with high nutritional risk. In terms of timing, one observational study found lower (<0.8 g/kg/d) protein dose before day 3 followed by higher (>0.8 g/kg/d) dose thereafter was associated with mortality benefit (Koekkoek WAC et al. Clin Nutr.2019;38:883-890).
Until stronger data are available to guide optimal protein dose and timing, it is reasonable to observe the 2016 ASPEN/SCCM guideline protein recommendation of at least 1.2 g/kg/day. The 2018 ESPEN guideline recommends a similar dose of 1.3 g/kg/day.
Future research and summary
Many questions remain unanswered and present opportunities for future research. Priorities for critical care nutrition research include studying the impact of combined nutrition and exercise in the acute and late phases of critical illness and identifying best tools to differentiate responses to caloric and protein intake.
In summary, critical illness has acute and late phases. The acute phase is a hypercatabolic state leading to negative energy and nitrogen balance and gut dysfunction. Take-home points for nutrition support in the acute phase of critical illness are:
1. It is reasonable to start early hypocaloric EN with an isosmotic formula with slow up-titration over the first week of critical illness while monitoring for refeeding syndrome and feeding intolerance.
2. Use exclusive PN in ICU patients with pre-existing malnutrition when EN is contraindicated or not tolerated.
3. Supplemental PN should probably be restricted during the acute phase of critical illness.
4. Optimal protein dose and timing are unknown. It is reasonable to start with at least 1.2 g/kg ABW/day in non-obese patients.
Dr. Patel is with the Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Dr. Rice is with the Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Vanderbilt University, Nashville, Tennessee.
Many critically ill patients you care for cannot maintain volitional oral intake. Therefore, nutrition support, through enteral or parenteral routes, remains a cornerstone in ensuring our critically ill patients receive substrates like glucose and protein. To understand the supportive role of nutrition during critical illness, let’s identify and contextualize the different phases of critical illness.
Phases of critical illness
The European Society of Parenteral and Enteral Nutrition’s (ESPEN) 2018 critical care nutrition guideline incorporates stages of critical illness in making nutrition recommendations (Singer P et al. Clin Nutr. 2019;38:48-79). The first week of critical illness is the acute phase and hallmarked by catabolism and metabolic and hemodynamic instability. The late phase is thereafter and hallmarked by rehabilitation and anabolism or chronic critical illness. The acute phase is further divided into early (days 1-2) and late acute phase (days 3-7). The time-points are arbitrary and merely serve as placeholders. An objective marker to distinguish phases does not exist and transition periods will be different for each patient.
Acute phase
Critical illness defining conditions like circulatory shock, respiratory failure, and trauma are stressors and lead to two key acute phase perturbations that nutrition may have a role in altering:
The first is hypercatabolism. Critical illness defining conditions activate neuroendocrine, inflammatory/immune, adipokine, and GI tract hormone pathways that increase serum glucagon, cortisol, and catecholamines to promote glycogenolysis, gluconeogenesis, insulin resistance, protein catabolism, and restricted/impaired anabolism.
The second is gut dysfunction. During health, there is cross-talk signaling that occurs between commensal bacteria, epithelium, and the immune system, which maintains gut barrier functions, achieved, for example, by promoting tight junction protein production. Acute critical illness pathophysiology loosens epithelial tight junctions, and the gut barrier is breached, creating an opportunity for downstream migration of pancreatic enzymes and cytokines. Furthermore, the microbiome morphs into a virulent pathobiome, which induces gut-derived inflammation.
When, where, and how much should we feed critically ill patients?
Since the acute phase of critical illness begins a series of events leading to negative energy balance and gut dysfunction, you might find early nutrition provision intuitive. Indeed, the 2016 ASPEN/SCCM and 2018 ESPEN critical care nutrition guidelines recommend early (within 24-48 hours of ICU admission) enteral nutrition (EN), delivered into the stomach, for all critically ill patients unable to maintain volitional intake. Meta-analyses of randomized controlled trials (RCT) conducted between1979 and 2013 show early EN reduces both mortality and infectious complications, compared with no early nutrition (McClave SA et al. JPEN. 2016;40:159-211).
RCT level data do not show superiority of EN over parenteral nutrition (PN). Nonetheless, early EN is recommended over PN because it maintains epithelial barrier function and supports immunity.
What is the optimal nutrition dose? The 2016 ASPEN/SCCM guideline recommends getting to >80% estimated energy goal within 48-72 hours in patients with high nutrition risk while the 2018 ESPEN guideline suggests maintaining a hypocaloric, or not exceeding 70% of prescribed energy goal, during the early acute phase. The recommendation is based on meta-analyses of RCTs conducted between 2011 and 2017, which shows no mortality difference between hypocaloric and isocaloric nutrition.
Biologically plausible rationale for starting hypocaloric, as opposed to full dose nutrition, during the acute phase of critical illness includes: (a) the acute phase represents a period of hemodynamic instability and mitochondrial dysfunction, and full-dose EN may lead to feeding intolerance and lack of substrate utilization, respectively; (b) in those with risk factors (like pre-existing malnutrition), starting full dose nutrition may lead to refeeding syndrome; and (c) endogenous glucose production occurs during the acute phase, and full dose nutrition may worsen hyperglycemia.
Therefore, during the early acute phase of critical illness, hypocaloric feeding using an isosmotic formula, with a slow up-titration to goal rate thereafter, while monitoring for feeding intolerance and refeeding syndrome is a reasonable starting point.
What is the role of parenteral nutrition in critical illness?
PN can be exclusive or supplemental (in a patient receiving EN). Historically, providers may have been reluctant to utilize PN for fear of infectious morbidity; however, contemporary pragmatic-design RCTs demonstrate safety with exclusive PN (Harvey SE et al. N Engl J Med. 2014;371:1673-84). When your patient has a contraindication for EN or does not tolerate it despite a trial of small bowel feeding, meta-analyses have shown a mortality benefit of early exclusive PN in malnourished patients, as compared with no nutrition (Braunschweig C et al. Am J Clin Nutr.2001;74:534-42).
As for supplemental PN (SPN), the 2016 ASPEN/SCCM guideline does not recommend it until day 7 in all critically ill patients, while the 2018 ESPEN guideline recommends its use on a case-by-case basis. Since, two trials inform SPN use. The EAT-ICU trial showed no difference in 6-month physical function between EN group and early-goal-directed nutritiongroup, which included SPN to achieve estimated energy requirement during the first week of critical illness (Allingstrup MJ et al. Intensive Care Med. 2017;43:1637-47). The TOP-UP trial compared EN alone with EN plus SPN in nutritionally high risk patients (ie, those who stand to have more complications as a result of undernutrition) and found those with a BMI < 25 kg/m2 and those with a NUTRIC score >5 who received supplemental PN atop EN had improved 30-day mortality, as compared with EN alone (Wischmeyer P et al. Crit Care. 2017;21:142). Mortality was a secondary outcome, and further study of supplemental PN in nutritionally high-risk patients is warranted. Until further data are available, supplemental PN should probably be restricted during the acute phase of critical illness.
Protein may be the important substrate
Proteolysis is the rule during critical illness, and amino acids are liberated from skeletal muscle breakdown. Using ultrasound, Puthucheary et al found a 17.7% reduction in rectus femoris cross-sectional area in 63 critically ill adults and identified muscle cellular infiltration at ICU day 10, suggesting critical illness leads to quantitative and qualitative muscle defects (Puthucheary Z et al. JAMA. 2013;15:1591-1600).
Since survivorship from critical illness is increasing, acquired loss of muscle mass may contribute to post-ICU physical functioning impairments. Thus, protein may be the most important substrate to deliver during critical illness. The 2016 ASPEN/SCCM guideline recommends 1.2 – 2.0 g/kg actual body weight (ABW)/day in nonobese critically ill patients.
Unfortunately, the optimal protein dose and the timing of intake are unknown. Observational studies suggest benefit with lower and higher doses, which creates equipoise for protein dose. The signal may be lost in heterogeneity, and observational data suggest higher protein dose may benefit patients with high nutritional risk. In terms of timing, one observational study found lower (<0.8 g/kg/d) protein dose before day 3 followed by higher (>0.8 g/kg/d) dose thereafter was associated with mortality benefit (Koekkoek WAC et al. Clin Nutr.2019;38:883-890).
Until stronger data are available to guide optimal protein dose and timing, it is reasonable to observe the 2016 ASPEN/SCCM guideline protein recommendation of at least 1.2 g/kg/day. The 2018 ESPEN guideline recommends a similar dose of 1.3 g/kg/day.
Future research and summary
Many questions remain unanswered and present opportunities for future research. Priorities for critical care nutrition research include studying the impact of combined nutrition and exercise in the acute and late phases of critical illness and identifying best tools to differentiate responses to caloric and protein intake.
In summary, critical illness has acute and late phases. The acute phase is a hypercatabolic state leading to negative energy and nitrogen balance and gut dysfunction. Take-home points for nutrition support in the acute phase of critical illness are:
1. It is reasonable to start early hypocaloric EN with an isosmotic formula with slow up-titration over the first week of critical illness while monitoring for refeeding syndrome and feeding intolerance.
2. Use exclusive PN in ICU patients with pre-existing malnutrition when EN is contraindicated or not tolerated.
3. Supplemental PN should probably be restricted during the acute phase of critical illness.
4. Optimal protein dose and timing are unknown. It is reasonable to start with at least 1.2 g/kg ABW/day in non-obese patients.
Dr. Patel is with the Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Dr. Rice is with the Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Vanderbilt University, Nashville, Tennessee.