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  1. 1. GLBL/MG17/20-0019 04/2020 © 2020 Baxter Healthcare Corporation Nutrition and Metabolic Needs in Critical Care and COVID-19 Twitter: @Paul_Wischmeyer Paul Wischmeyer M.D., E.D.I.C., FASPEN, FCCM Professor of Anesthesiology and Surgery Associate Vice Chair, Clinical Research Director, Nutrition Support Service Duke University School of Medicine Instagram: @Paul_WischmeyerMD
  2. 2. NIH Funding (Past/Pres) NIA, NIDDK, NIGMS, NHLBI, NICHD CIHR Funding RE-ENERGIZE Trial Mentee Research Grants ASPEN, IARS, FAER, SCCM Dept of Defense: SendHOME Trial RE-ENERGIZE Trial Cardiac Surgery Care Industry Financial Relationships: Consultant/Grant Support: Abbott, Baxter, Cosmed, Fresenius, Musclesound, Nestle, Nutricia, Takeda, DSM Paul Wischmeyer “Alignment” of Interests
  3. 3. We Must Take Responsibility For Not Just Outcomes in ICU... But…What Happens After ICU as Well!
  4. 4. “Creating Survivors...
  5. 5. ...not Victims!”
  6. 6. Courtesy :Arthur Van Zanten MD CRRT Paralyzed Norepinephrine Prone Position Often Obese How to give Nutrition? Often Male Mechanical Ventilation (Prolonged) Physical Therapy?
  7. 7. Pharmacological treatments during acute COVID-19 Antiretroviral 102 (71.3) Hydroxychloroquine 104 (72.7) Azithromycin 59 (41.3) Anti–IL-6 drugs (tocilizumab) 44 (30.8) Length of hospital stay, mean (SD), d 13.5 (9.7) Post–acute COVID-19 follow-up characteristics Days since symptoms onset, mean (SD) 60.3 (13.6) Days since discharge, mean (SD) 36.1 (12.9) Persistent symptoms, No. (%) None 18 (12.6) 1 or 2 46 (32.2) ≥3 79 (55.2) Worsened quality of life, No. (%)b 63 (44.1) Only 5% in ICU Fatigue - 53% of post- COVID pts at 60 days..
  8. 8. Mortality Related to Severe Sepsis and Septic Shock Among Critically Ill Patients in Australia and New Zealand, 2000-2012 Kirsi-Maija Kaukonen, MD, PhD, EDIC; Michael Bailey, PhD; Satoshi Suzuki, MD; David Pilcher, FCICM; Rinaldo Bellomo, MD, PhD IMPORTANCE Severe sepsis and septic shock are major causes of mortality in intensive care unit (ICU) patients. It is unknown whether progress has been made in decreasing their mortality rate. OBJECTIVE To describe changes in mortality for severe sepsis with and without shock in ICU patients. DESIGN, SETTING, AND PARTICIPANTS Retrospective, observational study from 2000 to 2012 including 101 064 patients with severe sepsis from 171 ICUs with various patient case mix in Australia and New Zealand. MAIN OUTCOMES AND MEASURES Hospital outcome (mortality and discharge to home, to other hospital, or to rehabilitation). RESULTS Absolute mortality in severe sepsis decreased from 35.0% (95% CI, 33.2%-36.8%; 949/2708) to 18.4% (95% CI, 17.8%-19.0%; 2300/12 512; P < .001), representing an overall decrease of 16.7% (95% CI, 14.8%-18.6%), an annual rate of absolute decrease of 1.3%, and a relative risk reduction of 47.5% (95% CI, 44.1%-50.8%). After adjusted analysis, mortality decreased throughout the study period with an odds ratio (OR) of 0.49 (95% CI, 0.46-0.52) in 2012, using the year 2000 as the reference (P < .001). The annual decline in mortality did Editorial Supplemental content at jama.com Mortality Related to Severe Sepsis and Septic Shock Among Critically Ill Patients in Australia and New Zealand, 2000-2012 Kirsi-Maija Kaukonen, MD, PhD, EDIC; Michael Bailey, PhD; Satoshi Suzuki, MD; David Pilcher, FCICM; Rinaldo Bellomo, MD, PhD IMPORTANCE Severe sepsis and septic shock are major causes of mortality in intensive care unit (ICU) patients. It is unknown whether progress has been made in decreasing their mortality rate. OBJECTIVE To describe changes in mortality for severe sepsis with and without shock in ICU patients. DESIGN, SETTING, AND PARTICIPANTS Retrospective, observational study from 2000 to 2012 including 101 064 patients with severe sepsis from 171 ICUs with various patient case mix in Australia and New Zealand. MAIN OUTCOMES AND MEASURES Hospital outcome (mortality and discharge to home, to other hospital, or to rehabilitation). RESULTS Absolute mortality in severe sepsis decreased from 35.0% (95% CI, 33.2%-36.8%; 949/2708) to 18.4% (95% CI, 17.8%-19.0%; 2300/12 512; P < .001), representing an overall decrease of 16.7% (95% CI, 14.8%-18.6%), an annual rate of absolute decrease of 1.3%, and a relative risk reduction of 47.5% (95% CI, 44.1%-50.8%). After adjusted analysis, mortality decreased throughout the study period with an odds ratio (OR) of 0.49 (95% CI, 0.46-0.52) in 2012, using the year 2000 as the reference (P < .001). The annual decline in mortality did not differ significantly between patients with severe sepsis and those with all other diagnoses (OR, 0.94 [95% CI, 0.94-0.95] vs 0.94 [95% CI, 0.94-0.94]; P = .37). The annual increase in Editorial Supplemental content at jama.com JAMA, 2014. ICU Mortality Decreasing ...over last 10 years!
  9. 9. Will We Win Some Battles? But…Lose the War!! In Critical Care…Especially in COVID-19
  10. 10. Sometimes, success leads to tragedy PYRRHIC VICTORY
  11. 11. JAMA, Online March 18, 2014 Although Sepsis Deaths Fall By Half…
  12. 12. JAMA, Online March 18, 2014 …Many More Patients to Rehab!
  13. 13. JAMA, Online March 18, 2014 Improved Hospital Survival..But... How many survive even a year?
  14. 14. > 40% of Mortality at 12 Month Follow-up Occurs Post-ICU Discharge Shiell AM, Griffiths RD et al Clinical Intensive Care 1990;1 (6): 256-262
  15. 15. Mortality Related to Severe Sepsis and Septic Shock Among Critically Ill Patients in Australia and New Zealand, 2000-2012 Kirsi-Maija Kaukonen, MD, PhD, EDIC; Michael Bailey, PhD; Satoshi Suzuki, MD; David Pilcher, FCICM; Rinaldo Bellomo, MD, PhD IMPORTANCE Severe sepsis and septic shock are major causes of mortality in intensive care unit (ICU) patients. It is unknown whether progress has been made in decreasing their mortality rate. OBJECTIVE To describe changes in mortality for severe sepsis with and without shock in ICU patients. DESIGN, SETTING, AND PARTICIPANTS Retrospective, observational study from 2000 to 2012 including 101 064 patients with severe sepsis from 171 ICUs with various patient case mix in Australia and New Zealand. MAIN OUTCOMES AND MEASURES Hospital outcome (mortality and discharge to home, to other hospital, or to rehabilitation). RESULTS Absolute mortality in severe sepsis decreased from 35.0% (95% CI, 33.2%-36.8%; 949/2708) to 18.4% (95% CI, 17.8%-19.0%; 2300/12 512; P < .001), representing an overall decrease of 16.7% (95% CI, 14.8%-18.6%), an annual rate of absolute decrease of 1.3%, and a relative risk reduction of 47.5% (95% CI, 44.1%-50.8%). After adjusted analysis, mortality decreased throughout the study period with an odds ratio (OR) of 0.49 (95% CI, 0.46-0.52) Editorial Supplemental content at jama.com Original Investigation | CARING FOR THE CRITICALLY ILL PATIENT Mortality Related to Severe Sepsis and Septic Shock Among Critically Ill Patients in Australia and New Zealand, 2000-2012 Kirsi-Maija Kaukonen, MD, PhD, EDIC; Michael Bailey, PhD; Satoshi Suzuki, MD; David Pilcher, FCICM; Rinaldo Bellomo, MD, PhD IMPORTANCE Severe sepsis and septic shock are major causes of mortality in intensive care unit (ICU) patients. It is unknown whether progress has been made in decreasing their mortality rate. OBJECTIVE To describe changes in mortality for severe sepsis with and without shock in ICU patients. DESIGN, SETTING, AND PARTICIPANTS Retrospective, observational study from 2000 to 2012 including 101 064 patients with severe sepsis from 171 ICUs with various patient case mix in Australia and New Zealand. MAIN OUTCOMES AND MEASURES Hospital outcome (mortality and discharge to home, to other hospital, or to rehabilitation). RESULTS Absolute mortality in severe sepsis decreased from 35.0% (95% CI, 33.2%-36.8%; 949/2708) to 18.4% (95% CI, 17.8%-19.0%; 2300/12 512; P < .001), representing an overall Editorial Supplemental content at jama.com JAMA, Online March 18, 2014. “Given low ICU mortality… Quality of Life …will become focus of future trials”
  16. 16. “Are we creating survivors... or Victims?” GLBL/MG17/20-0019 04/2020 © Baxter Healthcare Corporation
  17. 17. • 50% pts • Not Back At Work At 1 yr • • 33% pts • Never Return To Work (including young pts) Post-Hospital Weakness In ICU Survivors....or VICTIMS?? G
  18. 18. Latronico Lancet Neurol 2011; 10: 931 60-80% Functionally Impaired Courtesy: Wes Ely M.D.
  19. 19. This is an EPIDEMIC... COVID-19 Will Make Worse!
  20. 20. Average time on ventilator in COVID-19: 8-21 days The Challenge is…
  21. 21. Copyright
  22. 22. Why Are We Losing the Quality of Life War?
  23. 23. ICU & Major Surgery Patients Can Lose Up to 1 kg of Lean Body Mass Daily! Hypermetabolism & Catabolism Can Persist for Months - 2 Years! Wischmeyer PE, San-Millan I. Crit Care. 2015;19(suppl 3):S6. May Be Worse in COVID-19!
  24. 24. This is an EPIDEMIC
  25. 25. We Must Do Better! But How??
  26. 26. Courtesy :Arthur Van Zanten MD CRRT Paralyzed Norepinephrine Prone Position Often Obese How to give Nutrition? Often Male Mechanical Ventilation (Prolonged)
  27. 27. One Size Does NOT Fit All...
  28. 28. Right Nutrition Dose… In Right Patient… At Right Time… Personalized ICU Nutrition Stratagy We Must Measure!
  29. 29. Current Opinion in Critical Care: Online, May, 2021
  30. 30. How Do We Put This Data Into Practice? What do new ASPEN/SCCM/ESPEN Guidelines say? And…Can We Learn From Worldwide Experience...
  31. 31. Elijah W. - 49 y.o. African- American (AA) male (Science Professor) with cough, fever x 7 days Wife and Brother both COVID (+)…
  32. 32. Admitted to hospital on 3L Nasal Cannula Oxygen... History of recent surgery for diverticulitis…
  33. 33. Within 6 h of admit…Rapid Respiratory Decompensation, RR-45, Sat 78% on 8 L FM Elijah W. - 49 y.o. Found to be COVID (+)
  34. 34. Paralysis Started… In ICU… Tachypnea Dyssynchrony With Ventilator PaO2- 52 FiO2 100%
  35. 35. Prone Positoning
  36. 36. In ICU- Paralyzed and Prone- Day 1 -Blood pressure: 100/60 on 0.07 ug/kg/min levophed -On Ventilator…Peep 10, Fio2 60% -CVP 12 -MV O2 sat- 77%, Lactate 1.2
  37. 37. Nutrition Therapy in the Patient with COVID-19 Disease Requiring ICU Care Updated April 1, 2020 Robert Martindale, PhD, MD –Professor of Surgery, Department of Surgery, Oregon Health and Science University, Portland Oregon Jayshil J. Patel MD– Associate Professor of Medicine, Division of Pulmonary & Critical Care Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin Beth Taylor DCN, RD-AP- Research Scientist/Nutrition Support Dietitian, Barnes-Jewish Hospital, St. Louis, Missouri Malissa Warren, RD - Advanced Practice Nutrition Support Dietitian, Oregon Health and Science University and Portland VA Health Care Center, Portland Oregon Stephen A McClave MD - Professor of Medicine, Division of Gastroenterology Hepatology and Nutrition, University of Louisville, School of Medicine, Louisville Kentucky Reviewed and Approved by the Society of Critical Care Medicine and the American Recommendation 2: Timing of Nutrition Delivery -Early EN Within 24-36 h of ICU admission and 12 h of intubation - Use NG Tube- avoid post-pyloric typically Martindale et al. SCCM/ ASPEN Guidelines Apr 2020 SCCM/ASPEN COVID-19 Nutrition Guidelines
  38. 38. What About... ...Enteral Feeding On Pressors? Key Words: critical care; enteral nutrition; gastrointestinal; gut; intensive care unit; nutrition; parenteral nutrition; shock; trophic feeding; vasopressor period of starvation, lack of enteral nutrients and prebi fiber delivery, and the presence of exogenous/endogen vasopressorswilldrivedysbiosis(2,7).Recentdatashowsp Enteral Nutrition Can Be Given to Patients on Vasopressors PaulE.Wischmeyer,MD,EDIC,FASPEN Crit Care Med. 2020, 48(1): 122-125
  39. 39. Key Words: critical care; enteral nutrition; gastrointestinal; gut; intensive care unit; nutrition; parenteral nutrition; shock; trophic feeding; vasopressor T he gut has long been felt to play a central role in the progression and pathogenesis of critical illness. In fact, seminal papers have described the gut as the “motor for systemic inflammation and organ failure”(1). Perturbations of intestinal epithelial homeostasis in critical illness can lead to increased pro-inflammatory cytokine production, gut barrier dysfunction, and cellular apoptosis which is felt to contribute to multiple organ failure (1). This is felt to be driven by a range of factors including rapid change in the microbiome, known as dysbiosis (2), and intestinal permeability changes (1). Further, inflammatory signaling changes via the vagus nerve (3) and period of starvation, lack of enteral nutrients and prebiotic fiber delivery, and the presence of exogenous/endogenous vasopressors will drive dysbiosis (2, 7). Recent data shows pro- vision of even 20% of nutrition via EN can prevent dysbiosis, attenuate loss of gut barrier function, and innate immunity (7). In addition, a body of experimental and human critical care data demonstrates that EN can trigger activation of an- ti-inflammatory vagal-cholinergic pathway via Cholecystoki- nin-mediated receptor stimulation in shock states (3). Thus, outside of the obvious need for protein/energy delivery to pro- mote recovery, the mechanistic benefits of EN in critical care settings are long established. Specific to the effects of nutrition delivery on gut blood flow duringshock,benefitsofENonsplanchnicischemiaduetoshock have been long described in laboratory models of shock (8). Human studies of cardiogenic shock reveal EN increases car- diac index, splanchnic blood flow, and preserves bowel ab- Enteral Nutrition Can Be Given to Patients on Vasopressors Paul E. Wischmeyer, MD, EDIC, FASPEN Feeding On Vasopressors May Not Only Be Safe in Many Patients… ...But Also Saves Lives! Crit Care Med. Jan;48(1):122-125, 2020 Wischmeyer PE, Enteral Nutrition Can Be Given to Patients on Vasopressors. Crit Care Med. 2020 Jan;48(1):122-125
  40. 40. 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* Hiroyuki Ohbe a, * , Taisuke Jo b , Hiroki Matsui a , Kiyohide Fushimi c , Hideo Yasunaga a a Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan b Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan c Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan a r t i c l e i n f o Article history: Received 4 November 2018 Accepted 9 February 2019 Keywords: Early enteral nutrition Bowel ischemia Shock Vasopressors Noradrenaline s u m m a r y Background & aims: Despite extensive research on early enteral nutrition (EEN), it remains unclear whether EEN is effective for patients with shock requiring vasopressors. This study aimed to compare outcomes between EEN and late enteral nutrition (LEN) in ventilated patients with shock requiring low-, medium-, or high-dose noradrenaline. Methods: Using a national inpatient database in Japan, we identified ventilated patients admitted to intensive care units who had shock requiring catecholamines (noradrenaline or dobutamine) from July 2010 to March 2016. We defined patients who started enteral nutrition within 2 days after starting mechanical ventilation as EEN group and the others as LEN group. Propensity score matching was performed between patients undergoing EEN and LEN in each of the low- (<0.1 mg/kg/min), medium- (0.1e0.3 mg/kg/min), and high-dose (!0.3 mg/kg/min) noradrenaline groups. Results: We identified 52,563 eligible patients during the 69-month study period, including 38,488, Original article 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* Hiroyuki Ohbe a, * , Taisuke Jo b , Hiroki Matsui a , Kiyohide Fushimi c , Hideo Yasunaga a a Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan b Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan c Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan a r t i c l e i n f o Article history: Received 4 November 2018 Accepted 9 February 2019 Keywords: Early enteral nutrition Bowel ischemia Shock Vasopressors Noradrenaline s u m m a r y Background & aims: Despite extensive research on early enteral nutrition (EEN), it remains unclear whether EEN is effective for patients with shock requiring vasopressors. This study aimed to compare outcomes between EEN and late enteral nutrition (LEN) in ventilated patients with shock requiring low-, medium-, or high-dose noradrenaline. Methods: Using a national inpatient database in Japan, we identified ventilated patients admitted to intensive care units who had shock requiring catecholamines (noradrenaline or dobutamine) from July 2010 to March 2016. We defined patients who started enteral nutrition within 2 days after starting mechanical ventilation as EEN group and the others as LEN group. Propensity score matching was performed between patients undergoing EEN and LEN in each of the low- (<0.1 mg/kg/min), medium- (0.1e0.3 mg/kg/min), and high-dose (!0.3 mg/kg/min) noradrenaline groups. Results: We identified 52,563 eligible patients during the 69-month study period, including 38,488, 11,042, and 3033 patients in the low-, medium-, and high-dose noradrenaline groups, respectively. One-to-two propensity score matching created 5,969, 2,162, and 477 one-to-two matched pairs in the low-, medium-, and high-dose noradrenaline groups, respectively. The 28-day mortality rate was significantly lower in the EEN than LEN group in the low-dose noradrenaline group (risk difference, "2.9%; 95% confidence interval [CI], "4.5% to "1.3%) and in the medium-dose noradren- aline group (risk difference, "6.8%; 95% CI, "9.6% to "4.0%). In the high-dose noradrenaline group, 28-day mortality did not differ significantly between the EEN and LEN groups (absolute risk difference, "1.4%; 95% CI, "7.4%e4.7%). Conclusions: Although the size of the subgroup requiring high-dose noradrenaline may have been too small to demonstrate a significant difference, the results suggest that EEN was associated with a reduction in mortality in ventilated adults treated with low- or medium-dose noradrenaline but not in 2 groups: -Patients started EN within 2 days- EEN group -Pts started post 2 days - LEN group 52,563 patients identified & matched Ohbe H1, Jo T2, Matsui H3, Fushimi K4, Yasunaga H3. 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. 2019 Feb 15. pii: S0261-5614(19)30074-3. doi: 10.1016/j.clnu.2019.02.020. [Epub ahead of print] Clin Nutr 2019 Feb 15. [Epub] Large Health Ouctome Study: National Inpatient Database MV'd ICU patients with shock on norepinephrine or dobutamine
  41. 41. 52,563 ICU patients with shock on vasopressors Primary Outcomes: 28-d mortality rate significantly lower in EEN vs LEN in: No difference observed between EEN & LEN in High-Dose NE group (>0.3 mg/kg/min) (OR 0.96; 95% CI, 0.81-1.14) -Low-Dose Norepinephrine group (<0.1 mg/kg/min) (OR 0.84; 95% CI, 0.77 - 0.93) -Medium-Dose Norepinephrine group (0.1-0.3 mg/kg/min) (OR 0.77; 95% CI, 0.68- 0.86) 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* Hiroyuki Ohbe a, * , Taisuke Jo b , Hiroki Matsui a , Kiyohide Fushimi c , Hideo Yasunaga a a Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan b Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan c Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan a r t i c l e i n f o Article history: Received 4 November 2018 Accepted 9 February 2019 Keywords: Early enteral nutrition Bowel ischemia Shock Vasopressors Noradrenaline s u m m a r y Background & aims: Despite extensive research on early enteral nutrition (EEN), it remains unclear whether EEN is effective for patients with shock requiring vasopressors. This study aimed to compare outcomes between EEN and late enteral nutrition (LEN) in ventilated patients with shock requiring low-, medium-, or high-dose noradrenaline. Methods: Using a national inpatient database in Japan, we identified ventilated patients admitted to intensive care units who had shock requiring catecholamines (noradrenaline or dobutamine) from July 2010 to March 2016. We defined patients who started enteral nutrition within 2 days after starting mechanical ventilation as EEN group and the others as LEN group. Propensity score matching was performed between patients undergoing EEN and LEN in each of the low- (<0.1 mg/kg/min), medium- (0.1e0.3 mg/kg/min), and high-dose (!0.3 mg/kg/min) noradrenaline groups. Results: We identified 52,563 eligible patients during the 69-month study period, including 38,488, Original article 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* Hiroyuki Ohbe a, * , Taisuke Jo b , Hiroki Matsui a , Kiyohide Fushimi c , Hideo Yasunaga a a Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan b Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan c Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan a r t i c l e i n f o Article history: Received 4 November 2018 Accepted 9 February 2019 Keywords: Early enteral nutrition Bowel ischemia Shock Vasopressors Noradrenaline s u m m a r y Background & aims: Despite extensive research on early enteral nutrition (EEN), it remains unclear whether EEN is effective for patients with shock requiring vasopressors. This study aimed to compare outcomes between EEN and late enteral nutrition (LEN) in ventilated patients with shock requiring low-, medium-, or high-dose noradrenaline. Methods: Using a national inpatient database in Japan, we identified ventilated patients admitted to intensive care units who had shock requiring catecholamines (noradrenaline or dobutamine) from July 2010 to March 2016. We defined patients who started enteral nutrition within 2 days after starting mechanical ventilation as EEN group and the others as LEN group. Propensity score matching was performed between patients undergoing EEN and LEN in each of the low- (<0.1 mg/kg/min), medium- (0.1e0.3 mg/kg/min), and high-dose (!0.3 mg/kg/min) noradrenaline groups. Results: We identified 52,563 eligible patients during the 69-month study period, including 38,488, 11,042, and 3033 patients in the low-, medium-, and high-dose noradrenaline groups, respectively. One-to-two propensity score matching created 5,969, 2,162, and 477 one-to-two matched pairs in the low-, medium-, and high-dose noradrenaline groups, respectively. The 28-day mortality rate was significantly lower in the EEN than LEN group in the low-dose noradrenaline group (risk difference, "2.9%; 95% confidence interval [CI], "4.5% to "1.3%) and in the medium-dose noradren- aline group (risk difference, "6.8%; 95% CI, "9.6% to "4.0%). In the high-dose noradrenaline group, 28-day mortality did not differ significantly between the EEN and LEN groups (absolute risk difference, "1.4%; 95% CI, "7.4%e4.7%). Conclusions: Although the size of the subgroup requiring high-dose noradrenaline may have been too small to demonstrate a significant difference, the results suggest that EEN was associated with a reduction in mortality in ventilated adults treated with low- or medium-dose noradrenaline but not in Clin Nutr 2019 Feb 15. [Epub]
  42. 42. Authors Conclude: “Results show EEN is associated with reduction in mortality in ventilated adults treated with low- or medium-dose norepinephrine but not high-dose norepinephrine” 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* Hiroyuki Ohbe a, * , Taisuke Jo b , Hiroki Matsui a , Kiyohide Fushimi c , Hideo Yasunaga a a Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan b Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan c Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan a r t i c l e i n f o Article history: Received 4 November 2018 Accepted 9 February 2019 Keywords: Early enteral nutrition Bowel ischemia Shock Vasopressors Noradrenaline s u m m a r y Background & aims: Despite extensive research on early enteral nutrition (EEN), it remains unclear whether EEN is effective for patients with shock requiring vasopressors. This study aimed to compare outcomes between EEN and late enteral nutrition (LEN) in ventilated patients with shock requiring low-, medium-, or high-dose noradrenaline. Methods: Using a national inpatient database in Japan, we identified ventilated patients admitted to intensive care units who had shock requiring catecholamines (noradrenaline or dobutamine) from July 2010 to March 2016. We defined patients who started enteral nutrition within 2 days after starting mechanical ventilation as EEN group and the others as LEN group. Propensity score matching was performed between patients undergoing EEN and LEN in each of the low- (<0.1 mg/kg/min), medium- (0.1e0.3 mg/kg/min), and high-dose (!0.3 mg/kg/min) noradrenaline groups. Results: We identified 52,563 eligible patients during the 69-month study period, including 38,488, Original article 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* Hiroyuki Ohbe a, * , Taisuke Jo b , Hiroki Matsui a , Kiyohide Fushimi c , Hideo Yasunaga a a Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan b Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan c Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan a r t i c l e i n f o Article history: Received 4 November 2018 Accepted 9 February 2019 Keywords: Early enteral nutrition Bowel ischemia Shock Vasopressors Noradrenaline s u m m a r y Background & aims: Despite extensive research on early enteral nutrition (EEN), it remains unclear whether EEN is effective for patients with shock requiring vasopressors. This study aimed to compare outcomes between EEN and late enteral nutrition (LEN) in ventilated patients with shock requiring low-, medium-, or high-dose noradrenaline. Methods: Using a national inpatient database in Japan, we identified ventilated patients admitted to intensive care units who had shock requiring catecholamines (noradrenaline or dobutamine) from July 2010 to March 2016. We defined patients who started enteral nutrition within 2 days after starting mechanical ventilation as EEN group and the others as LEN group. Propensity score matching was performed between patients undergoing EEN and LEN in each of the low- (<0.1 mg/kg/min), medium- (0.1e0.3 mg/kg/min), and high-dose (!0.3 mg/kg/min) noradrenaline groups. Results: We identified 52,563 eligible patients during the 69-month study period, including 38,488, 11,042, and 3033 patients in the low-, medium-, and high-dose noradrenaline groups, respectively. One-to-two propensity score matching created 5,969, 2,162, and 477 one-to-two matched pairs in the low-, medium-, and high-dose noradrenaline groups, respectively. The 28-day mortality rate was significantly lower in the EEN than LEN group in the low-dose noradrenaline group (risk difference, "2.9%; 95% confidence interval [CI], "4.5% to "1.3%) and in the medium-dose noradren- aline group (risk difference, "6.8%; 95% CI, "9.6% to "4.0%). In the high-dose noradrenaline group, 28-day mortality did not differ significantly between the EEN and LEN groups (absolute risk difference, "1.4%; 95% CI, "7.4%e4.7%). Conclusions: Although the size of the subgroup requiring high-dose noradrenaline may have been too small to demonstrate a significant difference, the results suggest that EEN was associated with a reduction in mortality in ventilated adults treated with low- or medium-dose noradrenaline but not in Clin Nutr 2019 Feb 15. [Epub]
  43. 43. How to Feed Safely… ...Enteral Nutrition On Vasopressors Key Words: critical care; enteral nutrition; gastrointestinal; gut; intensive care unit; nutrition; parenteral nutrition; shock; trophic feeding;vasopressor period of starvation, lack of enteral nutrients and prebiotic fiber delivery, and the presence of exogenous/endogenous vasopressorswilldrivedysbiosis(2,7).Recentdatashowspro- EnteralNutritionCanBeGiventoPatientson Vasopressors PaulE.Wischmeyer,MD,EDIC,FASPEN Crit Care Med. 2020, 48(1): 122-125 Wischmeyer PE, Enteral Nutrition Can Be Given to Patients on Vasopressors. Crit Care Med. 2020 Jan;48(1):122-125
  44. 44. Wischmeyer PE, Crit Care Med. 2020, 48(1): 122-125
  45. 45. How to Safely Give EN On Vasopressors... Wischmeyer PE, Enteral Nutrition Can Be Given to Patients on Vasopressors. Crit Care Med. 2020 Jan;48(1):122-125 FEED STOMACH! Not Small Bowel! Best monitor for gut perfusion and safety! -Watch for residual >500 cc or other intolerance signs
  46. 46. What about Bolus/ Intermittent Feeding?
  47. 47. CURRENT OPINION Continuous or intermittent feeding: pros and cons Danielle E. Beara,b,c,d,e,! , Nicholas Hartc,d,e , and Zudin Puthuchearye,f,g,! Purpose of review There has been a recent shift in the focus of providing nutrition support to critically ill adults towards enhancing recovery and promoting survivorship. With this has come an evaluation of our current approaches to nutrition support, which includes whether continuous feeding is optimal, particularly for reducing muscle wasting, but also for managing blood glucose levels and feeding intolerance and at the organizational level. This review will discuss the pros and cons of using intermittent and continuous feeding relating to several aspects of the management of critically ill adults. Recent findings Few studies have investigated the effect of intermittent feeding over continuous feeding. Overall, intermittent feeding has not been shown to increase glucose variability or gastrointestinal intolerance, two of the reasons continuous feeding is the preferred method. A current study investigating the effect of intermittent vs. continuous feeding is awaited to provide insight into the effect of muscle wasting. Summary Although there are limited studies investigating the safety and efficacy of an intermittent rather than continuous feeding regimen in critically ill adults, there are several theoretical advantages. Further studies should investigate these and in the meantime, feeding regimens should be devised based on individual patient factors. Keywords er Health, Inc. All rights reserved. Bridge Rd, London SE1 7EH, UK. Tel: +44 207 188 5642; e-mail: Danielle.Bear@gstt.nhs.uk ! Danielle E. Bear and Zudin Puthucheary have contributed equally to the article. Curr Opin Crit Care 2018, 24:256–261 DOI:10.1097/MCC.0000000000000513 Volume 24 " Number 4 " August 2018 CURRENT OPINION Intermittent versus continuous feeding in critically ill adults Jayshil J. Patela , Martin D. Rosenthalb , and Daren K. Heylandc Purpose of review Early enteral nutrition is recommended in critically ill adult patients. The optimal method of administering enteral nutrition remains unknown. Continuous enteral nutrition administration in critically ill patients remains the most common practice worldwide; however, its practice has recently been called into question in favor of intermittent enteral nutrition administration, where volume is infused multiple times per day. This review will outline the key differences between continuous and intermittent enteral nutrition, describe the metabolic responses to continuous and intermittent enteral nutrition administration and outline recent studies comparing continuous with intermittent enteral nutrition administration on outcomes in critically ill adults. Recent findings In separate studies, healthy humans and critically ill patients receiving intermittent nutrition (infused over 3 h) had improved whole body protein balance from negative to positive. These studies did not have an isonitrogenous control group. A randomized controlled trial of intermittent bolus versus continuous enteral nutrition in healthy REVIEW lters Kluwer Health, Inc. All rights reserved. ts of early g gut integ- d responses 2 && ]. ne research highlighted e nutrition, al nutrition g, the effect ing on out- al nutrition ntermittent) nutrition expert panel identified the need for a a Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, b Division of Acute Care Surgery, University of Florida, Gainesville, Florida, USA and c Division of Critical Care Medicine, Queen’s University, Kingston, Ontario, Canada Correspondence to Jayshil J. Patel, MD, Associate Professor of Medi- cine, Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, 9200 West Wisconsin Avenue Suite E5200, Milwaukee, WI 53226, USA. Tel: +1 414 955 7042; e-mail: jpatel2@mcw.edu Curr Opin Clin Nutr Metab Care 2018, 21:116–120 DOI:10.1097/MCO.0000000000000447 Volume 21 ! Number 2 ! March 2018 REVIEW Open Access Feeding critically ill patients the right ‘whey’: thinking outside of the box. A personal view Paul E Marik Marik Annals of Intensive Care (2015) 5:11 DOI 10.1186/s13613-015-0051-2 Marik Annals of Intensive Care (2015) 5:11 DOI 10.1186/s13613-015-0051-2
  48. 48. Intermittent/bolus feeding in ICU- • Is safe • Is associated with similar levels of gastric intolerance as for continuous feeding • Intermittent/bolus feeding may be potential tool for preventing muscle loss & functional debility Existing data indicates that bolus/Intermit feeding is: See new data→ Effect of Intermittent or Continuous Feed on Muscle Wasting in Critical Illness A Phase 2 Clinical Trial Angela S. McNelly, PhD; Danielle E. Bear, MRes; Bronwen A. Connolly, PhD; Gill Arbane, BSc; Lau [ Critical Care Original Research ] control group (standard continuous enteral feeding, n ¼ 59). The primary outcome was 10- day loss of rectus femoris muscle cross-sectional area determined by ultrasound. Secondary outcomes included nutritional target achievements, plasma amino acid concentrations, gly- cemic control, and physical function milestones. RESULTS: Muscle loss was similar between arms (–1.1% [95% CI, –6.1% to –4.0%]; P ¼ .676). More intermittently fed patients received 80% or more oftarget protein (OR, 1.52 [1.16-1.99]; P < .001) and energy (OR, 1.59 [1.21-2.08]; P ¼ .001). Plasma branched-chain amino acid concen- trations before and after feeds were similar between arms on trial day 1 (71 mM [44-98 mM]; P ¼ .547) and trial day 10 (239 mM [33-444 mM]; P ¼ .178). During the 10-day intervention period the coefficient of variation for glucose concentrations was higher with intermittent feed (17.84 [18.6- 20.4]) vs continuous feed (12.98 [14.0-15.7]; P < .001). However, days with reported hypogly- cemia and insulin usage were similar in both groups. Safety profiles, gastric intolerance, physical function milestones, and discharge destinations did not differ between groups. INTERPRETATION: Intermittent feeding in early critical illness is not shown to preserve muscle mass in this trial despite resulting in a greater achievement of nutritional targets than continuous feeding. However, it is feasible and safe. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02358512; URL: www.clinicaltrials.gov CHEST 2020; 158(1):183-194
  49. 49. Acknowledge I acknowledge to trial the inte allowing us to the best bedsid Disclosure Figure 1 and T other sources. Received: 3 M References Table 2 Intermittent feeding schedule Time (h) Volume (ml) Duration of infusion (min) 0 100 20 4 150 20 8 150 20 12 200 30 16 200 30 20 250 40 24 Target Marik Annals of Intensive Care (2015) 5:11 R E V I E W Open Access Feeding critically ill patients the right ‘whey’: thinking outside of the box. A personal view Paul E Marik Abstract Atrophy of skeletal muscle mass is an almost universal problem in survivors of critical illness and is associated with significant short- and long-term morbidity. Contrary to common practice, the provision of protein/amino acids as a continuous infusion significantly limits protein synthesis whereas intermittent feeding maximally stimulates skeletal muscle synthesis. Furthermore, whey-based protein (high in leucine) increases muscle synthesis compared to soy or casein-based protein. In addition to its adverse effects on skeletal muscle synthesis, continuous feeding is unphysiological and has adverse effects on glucose and lipid metabolism and gastrointestinal function. I propose that critically ill patients’ be fed intermittently with a whey-based formula and that such an approach is likely to be associated with better glycemic control, less hepatic steatosis and greater preservation of muscle mass. This paper provides the scientific basis for my approach to intermittent feeding of critically ill patients. Keywords: Nutrition; Whey; Muscle mass; Muscle atrophy; Intermittent feeding; Continuous feeding; Metabolic function; Insulin; Incretin; MTOR; Autophagy; Ubiquitin–proteasome complex Review Survivors of critical illness suffer from marked muscle wasting which may take years to recover. The loss of muscle mass is associated with muscle weakness, pro- longed mechanical ventilatory support, fatigue and de- layed recovery [1–3]. This disorder is known as critical illness myopathy (CIM) or intensive care unit-acquired weakness (ICUAW) [1–3]. CIM is characterized by a diffuse non-necrotizing myopathy accompanied by fiber atrophy, fatty degeneration of muscle fibers and fibrosis [4]. Multiple factors are likely to play a role in inducing CIM including muscle inactivity, inflammation, cellular energy stress, corticosteroids, hyperglycemia, neuro- muscular blocking agents and inadequate nutritional support [2, 4]. CIM is exceedingly common in ICU survi- vors, being reported in up to 46 % of cases [5]. Herridge et al. followed 109 survivors of ARDS for up to 5 years after discharge from the ICU [6, 7]. All patients reported poor functional status with proximal weakness and fatigue at discharge. At 1 year, the distance walked in 6 minutes Muscle breakdown during acute illness In health, net muscle synthesis is stimulated in the post- prandial state while net muscle breakdown occurs be- tween meals with muscle mass being maintained through balanced protein synthesis and breakdown [8]. Distinct metabolic pathways are involved in the synthesis and breakdown of muscle. Figure 1 provides an overview of these pathways. Muscle protein synthesis and not break- down is more responsive to anabolic stimuli [9]. In healthy individuals, the anabolic effects of feeding occurs due to an increase in the synthetic rate of muscle protein synthe- sis of approximately 300 % with a concomitant 50 % de- crease in the rate of protein breakdown [8, 10]. In healthy young men following an oral bolus of essential amino acids, there is a lag period of 45–90 min followed by an increase in the muscle protein synthetic response which continues for about 90 min then rapidly returns to base- line [8, 10, 11]. The duration and degree of the muscle protein synthetic response following protein ingestion is influenced by exercise, age and the dose and type of pro- REVIEW Feeding criticall thinking outside Paul E Marik Abstract Atrophy of skeletal muscle mass is Marik Annals of Intensive Care (2015) 5:11 DOI 10.1186/s13613-015-0051-2 Intermittent Feeding Strategy
  50. 50. In ICU- Paralyzed and Prone- Day 1 -Blood pressure: 100/60 on 0.07 ug/kg/min levophed -On Ventilator…Peep 10, Fio2 60% -CVP 12 -MV O2 sat- 77%, Lactate 1.2
  51. 51. Enteral Feeding in Proned Patients is Safe... SCCM/ASPEN COVID-19 Guidelines Recommendation 7: Nutrition for Patient in Prone Positioning Retrospective/small prospective trials show EN in prone pts not associated w/ increased risk of GI/ pulmonary complications, thus we recommend early EN in prone pts (JPEN J Parenter Enteral Nutr. 2016 Feb;40(2):250-5) Most prone pts tolerate EN delivered to stomach. When EN used in prone pts elevate HOB (reverse Trendelenburg) to >10 -25 deg to decrease aspiration risk Martindale et al.. SCCM/ ASPEN Guidelines Apr 2020
  52. 52. How Much to Feed in Acute Phase of Critical Illness? n
  53. 53. Nutrition Therapy in the Patient with COVID-19 Disease Requiring ICU Care Updated April 1, 2020 Robert Martindale, PhD, MD –Professor of Surgery, Department of Surgery, Oregon Health and Science University, Portland Oregon Jayshil J. Patel MD– Associate Professor of Medicine, Division of Pulmonary & Critical Care Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin Beth Taylor DCN, RD-AP- Research Scientist/Nutrition Support Dietitian, Barnes-Jewish Hospital, St. Louis, Missouri Malissa Warren, RD - Advanced Practice Nutrition Support Dietitian, Oregon Health and Science University and Portland VA Health Care Center, Portland Oregon Stephen A McClave MD - Professor of Medicine, Division of Gastroenterology Hepatology and Nutrition, University of Louisville, School of Medicine, Louisville Kentucky Reviewed and Approved by the Society of Critical Care Medicine and the American Recommendation 4: Nutrition Dose Start low dose EN (hypocaloric /trophic) advancing to full EN slow over first ICU week to meet energy goal of 15-20 kcal/kg actual body weight (ABW)/d (70-80% of caloric requirements) & protein goal of 1.2-2.0 gm/kg ABW/d Martindale et al. SCCM/ ASPEN Guidelines Apr 2020 SCCM/ASPEN COVID-19 Nutrition Guidelines
  54. 54. Catabolic Response to Stress and Injury Body Can Generate 50-75% of Pts Glucose Requirements! Exogenous Glucose Kcal Delivery? Text Adapted from: Anesthesiology 2015; 123:1455-72
  55. 55. Catabolic Response to Critical Illness and Trauma Body Can Generate 50-75% of Pts Glucose Requirements! Exogenous Glucose Kcal Delivery? Text Adapted from: Anesthesiology 2015; 123:1455-72
  56. 56. Resting energy expenditure, calorie and protein consumption in critically ill patients: a retrospective cohort study Oren Zusman1* , Miriam Theilla2,3 , Jonathan Cohen2,4 , Ilya Kagan2 , Itai Bendavid2 and Pierre Singer2,4 Abstract Background: Intense debate exists regarding the optimal energy and protein intake for intensive care unit (ICU) patients. However, most studies use predictive equations, demonstrated to be inaccurate to target energy intake. We sought to examine the outcome of a large cohort of ICU patients in relation to the percent of administered calories divided by resting energy expenditure (% AdCal/REE) obtained by indirect calorimetry (IC) and to protein intake. Methods: Included patients were hospitalized from 2003 to 2015 at a 16-bed ICU at a university affiliated, tertiary care hospital, and had IC measurement to assess caloric targets. Data were drawn from a computerized system and included the % AdCal/REE and protein intake and other variables. A Cox proportional hazards model for 60-day mortality was used, with the % AdCal/REE modeled to accommodate non-linearity. Length of stay (LOS) and length of ventilation (LOV) were also assessed. Results: A total of 1171 patients were included. The % AdCal/REE had a significant non-linear (p < 0.01) association with mortality after adjusting for other variables (p < 0.01). Increasing the percentage from zero to 70 % resulted in a hazard ratio (HR) of 0.98 (CI 0.97–0.99) pointing to reduced mortality, while increases above 70 % suggested an increase in mortality with a HR of 1.01 (CI 1.01–1.02). Increasing protein intake was also associated with decreased mortality (HR 0.99, CI 0.98–0.99, p = 0.02). An AdCal/REE >70 % was associated with an increased LOS and LOV. Conclusions: The findings of this study suggest that both underfeeding and overfeeding appear to be harmful to critically ill patients, such that achieving an Adcal/REE of 70 % had a survival advantage. A higher caloric intake may also be associated with harm in the form of increased LOS and LOV. The optimal way to define caloric goals therefore requires an exact estimate, which is ideally performed using indirect calorimetry. These findings may provide a basis for future randomized controlled trials comparing specific nutritional regimens based on indirect calorimetry measurements. Keywords: Indirect calorimetry, Nutrition, Protein, Resting energy expenditure, Calorie consumption Background The provision of nutritional support for critically ill pa- tients continues to be the subject of intense debate, with described [6, 7]. Importantly, for many reasons either by design or default, many critically ill patients do not re- ceive their full energy requirements and the proportion 1171 patients Zusman et al. Critical Care (2016) 20:367 RESEARCH Resting energy expenditure, c protein consumption in critica Zusman et al. Critical Care (2016)20:367 DOI 10.1186/s13054-016-1538-4 1171 pts in ICU > 96 h & Measured Energy Expenditure. Lowest Mortality ~70% of REE Delivered
  57. 57. We Need Actual Data on Measured Energy Needs in COVID-19!... ...This is A New Pandemic Disease!
  58. 58. ICU Nutrition Guidelines If available, energy expenditure should be measured by indirect calorimetry Singer et al. Clin Nutr 2019; 38: 48-79
  59. 59. IC in ESPEN COVID-19 Updates 62 ESPEN expert statements and practical guidance for nutritional management of individuals with SARS-CoV-2 infection. March, 2020 Indirect Calorimetry Can Be Done Safely in COVID-19 With Precautions! ESPEN expert statements and practical guidance for nutritional management of individuals with SARS-CoV-2 infection March 24, 2020 2.2. Statement 2 … Energy needs can be assessed using indirect calorimetry if safely available with ensured sterility of the measurement system…
  60. 60. Energy delivery guided by indirect calorimetry in critically ill patients: a systematic review and meta-analysis Jing-Yi Duan1 , Wen-He Zheng2 , Hua Zhou1 , Yuan Xu1 and Hui-Bin Huang1* Abstract Background: The use of indirect calorimetry (IC) is increasing due to its precision in resting energy expenditure (REE) measurement in critically ill patients. Thus, we aimed to evaluate the clinical outcomes of an IC-guided nutrition therapy compared to predictive equations strategy in such a patient population. Methods: We searched PubMed, EMBASE, and Cochrane library databases up to October 25, 2020. Randomized controlled trials (RCTs) were included if they focused on energy delivery guided by either IC or predictive equations in critically ill adults. We used the Cochrane risk-of-bias tool to assess the quality of the included studies. Short-term mortality was the primary outcome. The meta-analysis was performed with the fixed-effect model or random-effect model according to the heterogeneity. Results: Eight RCTs with 991 adults met the inclusion criteria. The overall quality of the included studies was moder- ate. Significantly higher mean energy delivered per day was observed in the IC group, as well as percent delivered energy over REE targets, than the control group. IC-guided energy delivery significantly reduced short-term mortality compared with the control group (risk ratio=0.77; 95% CI 0.60 to 0.98; I2 =3%, P=0.03). IC-guided strategy did not significantly prolong the duration of mechanical ventilation (mean difference [MD]=0.61 days; 95% CI − 1.08 to 2.29; P=0.48), length of stay in ICU (MD=0.32 days; 95% CI − 2.51 to 3.16; P=0.82) and hospital (MD=0.30 days; 95% CI − 3.23 to 3.83; P=0.87). Additionally, adverse events were similar between the two groups. Conclusions: This meta-analysis indicates that IC-guided energy delivery significantly reduces short-term mortality in critically ill patients. This finding encourages the use of IC-guided energy delivery during critical nutrition support. But more high-quality studies are still needed to confirm these findings. Duan et al. Crit Care (2021) 25:88 https://doi.org/10.1186/s13054-021-03 RESEARCH Energy delive Page 8 of 10 Duan et al. Crit Care (2021) 25:88 Fig. 2 Forest plot showing the effects of energy delivery guided by indirect calorimetry on short-term mortality rate in critically ill patients Eight RCTs with 991 adults in ICU 23% ⬇ICU Mortality with IC Use IC Guided “Isocaloric Feeding” Improves Mortality
  61. 61. Original article The clinical evaluation of the new indirect calorimeter developed by the ICALIC project Taku Oshima a , Marta Delsoglio b , Yves M. Dupertuis b , Pierre Singer c , Elisabeth De Waele d, e, f , Cecilia Veraar g , Claudia-Paula Heidegger h , Jan Wernermann i , Paul E. Wischmeyer j , Mette M. Berger k , Claude Pichard b, * a Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana Chuou-ku, Chiba City, Chiba, 260- 8677, Japan b Nutrition Unit, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211, Geneva, Switzerland c Critical Care Medicine, Institute for Nutrition Research, Rabin Medical Center, Beilison Hospital, Petah Tikva, 49100, Israel d Department of Intensive Care, Vrije Universiteit Brussel, Brussels, Belgium e Department of Intensive Care, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium f Department of Nutrition, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium g Division of Cardiac Thoracic Vascular Anesthesia and Intensive Care Medicine, University Hospital of Vienna, Waehrihger Guertel 18-20, 1090 Vienna, Austria h Department of Acute Medicine, Division of Intensive Care, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva, Switzerland i Department of Anesthesiology and Intensive Care Medicine, Karolinska University Hospital Huddinge, Sweden j Department of Anesthesiology, Duke University, Durham, NC, USA k Service of Adult Intensive Care, Lausanne University Hospital, 1011 Lausanne, Switzerland Contents lists available at ScienceDirect Clinical Nutrition journal homepage: http://www.elsevier.com/locate/clnu
  62. 62. Q-NRG+ Calorimeter : Innovations Accurate • < 3% Rapid measurements • No warm-up • Monthly calibration Easy to use • Touchscreen operation • Easy disinfection Compact, easy handling • Battery operation • 4 kg Affordable COSMED Q-NRG Metabolic Monitor User Manual 2018.
  63. 63. Summary - New Indirect Calorimetry Device • Accurate • Easy to use • Compact - portable • Easy maintenance • Easy disinfection • Affordable Rapid measurements
  64. 64. Longitudinal Evaluation of Energy Expenditure and Metabolic Pathophysiology of COVID-19 (LEEP-COVID) Whittle J…Wischmeyer PE for LEEP-COVID Group Crit Care. 24: 581, 2020 PMID: 32988390 ClinicalTrials.Gov: NCT04350073
  65. 65. Are COVID-19 ICU Patients Hypermetabolic in Acute Phase?
  66. 66. GLBL/MG17/20-0019 04/2020 © Baxter Healthcare Corporation This is an mid-50’s LTAC patient COVID (+) (60 kg) early in care (day 2): - Spont breathing on vent (not paralyzed) - 15 kcal/kg is determined by indirect calorimetry -On Trophic Tube Feeds GLBL/MG17/20-0019 04/2020 © Baxter Healthcare Corporation
  67. 67. GLBL/MG17/20-0019 04/2020 © Baxter Healthcare Corporation 49 yo COVID (+) patient early in care (day 4): -Being fed 1440 kcal/d- based on 18 kcal/kg - Proned and Paralyzed when test was done on PEEP of 12
  68. 68. What About Chronic and Recovery Phase? Beyond Day 5-7… G
  69. 69. -COVID (+) 49 yo pt (ICU Day 12) -Being underfed 1440 kcal/d- based on 20-25 kg/kg -35 kg/kg/d by IC -We changed feeding to 2400 kcal/d as patient weaned on vent on pressure support ICU Day 12
  70. 70. -COVID (+) 49 yo pt (ICU Day 15) -Febrile at time of cart (> 70% of day) -44 kcal/kg via IC -Changed feeding to 2400 kcal/d w/ improved RQ & increased REE as patient weaned on vent on pressure support ICU Day 15
  71. 71. -COVID (+) 49 yo pt (ICU Day 18) (Now Afebrile-previous IC measures pt febrile much of day) -28 kcal/kg measured by IC -We changed feeding to 2100 kcal/d to account for febrile & non-febrile periods as pt weaned on vent on pressure support ICU Day 18
  72. 72. -COVID (+) 49 yo pt (ICU Day 23) -Being fed < 50% of goal x 7 days - RQ showing underfeeding and continued protein breakdown -34 kcal/kg measured by IC -Feeding needs continue to be 156% of predicted and EN+SPN being considered ICU Day 23
  73. 73. Caloric Need Vs Predicted in COVID-19 40 60 80 100 120 140 160 180 200 0 - 2 3 - 5 6 - 8 9 - 11 12 - 14 15 - 17 18 - 20 21 - 23 24 - 26 27 - 30 > 30 RESTING ENERGY EXPENDITURE PREDICTED (%) REE Expon. (REE) DAYS Whittle J…Wischmeyer PE for LEEP-COVID Group Crit Care. 24: 581, 2020 PMID: 32988390
  74. 74. - In first 3-7 days: COVID-19 patients are NormoMETABOLIC (80-100% of predicted/ 17-20 kcal/kg/d) - After day 7: COVID-19 patients are HYPERMETABOLIC - 120-200% of equation predicted even paralyzed… (25->35+ kcal/kg/d) Indirect Calorimetry Data in COVID-19 NCT:04350073 Initial LEEP-COVID Data Whittle J…Wischmeyer PE for LEEP-COVID Group Crit Care. 24: 581, 2020 PMID: 32988390
  75. 75. How Well Do Existing Predictive Equations Perform Versus Measured Energy Needs via Indirect Calorimetry? Hint…POORLY! NEW PUBLISHED DATA!
  76. 76. Q-NRG Indirect Calorimeter (IC) longitudinal measures compared to Harris-Benedict (HB), Mifflin St-Jeor (MSJ), & Penn State University (PSU) 2003b & PSU 2010 equations from ICU WEEK 1-7. Methods: Population: From LEEP-COVID Study- 38 Intubated COVID-19 patients in ICU Prolonged progressive hypermetabolism during COVID-19 hospitalization undetected by common predictive energy equations Laura E. Niederer a, b , Hilary Miller a, b , Krista L. Haines c , Jeroen Molinger d , John Whittle e , David B. MacLeod d , Stephen A. McClave f , Paul E. Wischmeyer d, * a Duke Office of Clinical Research, Duke University School of Medicine, Durham, NC, USA b Duke Nutrition Services, Duke University Hospital, Durham, NC, USA c Department of Surgery, Division of Trauma Critical Care, and Acute Care Surgery, Duke University School of Medicine, Durham, NC, USA d Department of Anesthesiology, Duke University School of Medicine, Division of Critical Care, Durham, NC, USA e Centre for Perioperative Medicine, Division of Surgery & Interventional Science, University College London, London, UK f Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA a r t i c l e i n f o Article history: Received 30 June 2021 Accepted 23 July 2021 Keywords: Critical care Intensive care unit Nutrition status Indirect calorimetry SARS-CoV-2 Energy expenditure s u m m a r y Background & aims: Indirect calorimetry (IC) is the gold-standard for determining measured resting energy expenditure (mREE) in critical illness. When IC is not available, predicted resting energy expenditure (pREE) equations are commonly utilized, which often inaccurately predict metabolic de- mands leading to over- or under-feeding. This study aims to longitudinally assess mREE via IC in critically ill patients with SARS-CoV-2 (COVID-19) infection throughout the entirety of, often prolonged, intensive care unit (ICU) stays and compare mREE to commonly utilized pREE equations. Methods: This single-center prospective cohort study of 38 mechanically ventilated COVID-19 patients from April 1, 2020 to February 1, 2021. The Q-NRG® Metabolic Monitor was used to obtain IC data. The Harris-Benedict (HB), Mifflin St-Jeor (MSJ), Penn State University (PSU), and weight-based equations from the American Society of Parenteral and Enteral Nutrition e Society of Critical Care Medicine (ASPEN-SCCM) Clinical Guidelines were utilized to assess the accuracy of common pREE equations and their ability to predict hypo/hypermetabolism in COVID-19 ICU patients. Results: The IC measures collected revealed a relatively normometabolic or minimally hypermetabolic Original article Prolonged progressive hypermetabolism during COVID-19 hospitalization undetected by common predictive energy equations Laura E. Niederer a, b , Hilary Miller a, b , Krista L. Haines c , Jeroen Molinger d , John Whittle e , David B. MacLeod d , Stephen A. McClave f , Paul E. Wischmeyer d, * a Duke Office of Clinical Research, Duke University School of Medicine, Durham, NC, USA b Duke Nutrition Services, Duke University Hospital, Durham, NC, USA c Department of Surgery, Division of Trauma Critical Care, and Acute Care Surgery, Duke University School of Medicine, Durham, NC, USA d Department of Anesthesiology, Duke University School of Medicine, Division of Critical Care, Durham, NC, USA e Centre for Perioperative Medicine, Division of Surgery & Interventional Science, University College London, London, UK f Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA a r t i c l e i n f o Article history: Received 30 June 2021 Accepted 23 July 2021 s u m m a r y Background & aims: Indirect calorimetry (IC) is the gold-standard for determining measured resting energy expenditure (mREE) in critical illness. When IC is not available, predicted resting energy expenditure (pREE) equations are commonly utilized, which often inaccurately predict metabolic de- Contents lists available at ScienceDirect Clinical Nutrition ESPEN journal homepage: http://www.clinicalnutritionespen.com Published Online: Clinical Nutrition ESPEN, 8/2021
  77. 77. Comparison of Predictive Energy Expenditure Equations to Measured Energy Expenditure Via IC in Critically Ill COVID-19 Patients ICU= Intensive CareUnit, IC= Indirect Calorimetry,MSJ= Mifflin St. Jeor,HB= Harris Benedict,PSU= PennState University,SEM=StandardErrorof Mean Indirect calorimetry REE in COVID-19 ICU patients by Intubation week Week 1 (n=27) Week 2 (n=16) Week 3 (n=8) Weeks 4-7 (n=8) IC kcal/kg admit wt (mean, SEM) 21.6 (1.1) 23.1 (2.4) 28.0 (1.9) 27.9 (2.1) % of Harris Benedict 113.1 (4.3) 122.3 (9.9) 142.1 (9.8) 147.2 (10.5)
  78. 78. 15 20 25 30 MV Week 1 MV Week 2 MV Week 3 MV Weeks 4-7 IC mREE ASPEN-SCCM (Upper-End- 30 kcal/kg) PSU ASPEN-SCCM Lower-End (25 kcal/kg) Harris-Benedict MSJ Kcal/Kg/Day Measured REE Via Indirect Calorimetry Versus Commonly Used Predictive Equations in COVID-19 ICU Patients
  79. 79. Measured REE Via Indirect Calorimetry in OBESE vs. NON-OBESE COVID-19 ICU Patients
  80. 80. “This study shows a previously unreported & unique pattern of a prolonged hypermetabolic stress response to critical illness seen only in patients infected by the SARS-CoV-2 virus & perhaps in some severely burned patients” Conclusions: This prolonged hypermetabolic response pattern appeared more significant in non-obese verses obese patients. Prolonged progressive hypermetabolism during COVID-19 hospitalization undetected by common predictive energy equations Laura E. Niederer a, b , Hilary Miller a, b , Krista L. Haines c , Jeroen Molinger d , John Whittle e , David B. MacLeod d , Stephen A. McClave f , Paul E. Wischmeyer d, * a Duke Office of Clinical Research, Duke University School of Medicine, Durham, NC, USA b Duke Nutrition Services, Duke University Hospital, Durham, NC, USA c Department of Surgery, Division of Trauma Critical Care, and Acute Care Surgery, Duke University School of Medicine, Durham, NC, USA d Department of Anesthesiology, Duke University School of Medicine, Division of Critical Care, Durham, NC, USA e Centre for Perioperative Medicine, Division of Surgery & Interventional Science, University College London, London, UK f Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA a r t i c l e i n f o Article history: Received 30 June 2021 Accepted 23 July 2021 Keywords: Critical care Intensive care unit Nutrition status Indirect calorimetry SARS-CoV-2 Energy expenditure s u m m a r y Background & aims: Indirect calorimetry (IC) is the gold-standard for determining measured resting energy expenditure (mREE) in critical illness. When IC is not available, predicted resting energy expenditure (pREE) equations are commonly utilized, which often inaccurately predict metabolic de- mands leading to over- or under-feeding. This study aims to longitudinally assess mREE via IC in critically ill patients with SARS-CoV-2 (COVID-19) infection throughout the entirety of, often prolonged, intensive care unit (ICU) stays and compare mREE to commonly utilized pREE equations. Methods: This single-center prospective cohort study of 38 mechanically ventilated COVID-19 patients from April 1, 2020 to February 1, 2021. The Q-NRG® Metabolic Monitor was used to obtain IC data. The Harris-Benedict (HB), Mifflin St-Jeor (MSJ), Penn State University (PSU), and weight-based equations from the American Society of Parenteral and Enteral Nutrition e Society of Critical Care Medicine (ASPEN-SCCM) Clinical Guidelines were utilized to assess the accuracy of common pREE equations and their ability to predict hypo/hypermetabolism in COVID-19 ICU patients. Results: The IC measures collected revealed a relatively normometabolic or minimally hypermetabolic Original article Prolonged progressive hypermetabolism during COVID-19 hospitalization undetected by common predictive energy equations Laura E. Niederer a, b , Hilary Miller a, b , Krista L. Haines c , Jeroen Molinger d , John Whittle e , David B. MacLeod d , Stephen A. McClave f , Paul E. Wischmeyer d, * a Duke Office of Clinical Research, Duke University School of Medicine, Durham, NC, USA b Duke Nutrition Services, Duke University Hospital, Durham, NC, USA c Department of Surgery, Division of Trauma Critical Care, and Acute Care Surgery, Duke University School of Medicine, Durham, NC, USA d Department of Anesthesiology, Duke University School of Medicine, Division of Critical Care, Durham, NC, USA e Centre for Perioperative Medicine, Division of Surgery & Interventional Science, University College London, London, UK f Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA a r t i c l e i n f o Article history: Received 30 June 2021 Accepted 23 July 2021 s u m m a r y Background & aims: Indirect calorimetry (IC) is the gold-standard for determining measured resting energy expenditure (mREE) in critical illness. When IC is not available, predicted resting energy expenditure (pREE) equations are commonly utilized, which often inaccurately predict metabolic de- Contents lists available at ScienceDirect Clinical Nutrition ESPEN journal homepage: http://www.clinicalnutritionespen.com Published Online: Clinical Nutrition ESPEN, 8/2021
  81. 81. “Indirect calorimetry is essential for nutritional targets in COVID-19 ICU pts, preferably repeated measures longitudinally, as predictive energy equations do not accurately predict actual mREE and/or account for progressive hypermetabolism in COVID-19” Prolonged progressive hypermetabolism during COVID-19 hospitalization undetected by common predictive energy equations Laura E. Niederer a, b , Hilary Miller a, b , Krista L. Haines c , Jeroen Molinger d , John Whittle e , David B. MacLeod d , Stephen A. McClave f , Paul E. Wischmeyer d, * a Duke Office of Clinical Research, Duke University School of Medicine, Durham, NC, USA b Duke Nutrition Services, Duke University Hospital, Durham, NC, USA c Department of Surgery, Division of Trauma Critical Care, and Acute Care Surgery, Duke University School of Medicine, Durham, NC, USA d Department of Anesthesiology, Duke University School of Medicine, Division of Critical Care, Durham, NC, USA e Centre for Perioperative Medicine, Division of Surgery & Interventional Science, University College London, London, UK f Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA a r t i c l e i n f o Article history: Received 30 June 2021 Accepted 23 July 2021 Keywords: Critical care Intensive care unit Nutrition status Indirect calorimetry SARS-CoV-2 Energy expenditure s u m m a r y Background & aims: Indirect calorimetry (IC) is the gold-standard for determining measured resting energy expenditure (mREE) in critical illness. When IC is not available, predicted resting energy expenditure (pREE) equations are commonly utilized, which often inaccurately predict metabolic de- mands leading to over- or under-feeding. This study aims to longitudinally assess mREE via IC in critically ill patients with SARS-CoV-2 (COVID-19) infection throughout the entirety of, often prolonged, intensive care unit (ICU) stays and compare mREE to commonly utilized pREE equations. Methods: This single-center prospective cohort study of 38 mechanically ventilated COVID-19 patients from April 1, 2020 to February 1, 2021. The Q-NRG® Metabolic Monitor was used to obtain IC data. The Harris-Benedict (HB), Mifflin St-Jeor (MSJ), Penn State University (PSU), and weight-based equations from the American Society of Parenteral and Enteral Nutrition e Society of Critical Care Medicine (ASPEN-SCCM) Clinical Guidelines were utilized to assess the accuracy of common pREE equations and their ability to predict hypo/hypermetabolism in COVID-19 ICU patients. Results: The IC measures collected revealed a relatively normometabolic or minimally hypermetabolic Original article Prolonged progressive hypermetabolism during COVID-19 hospitalization undetected by common predictive energy equations Laura E. Niederer a, b , Hilary Miller a, b , Krista L. Haines c , Jeroen Molinger d , John Whittle e , David B. MacLeod d , Stephen A. McClave f , Paul E. Wischmeyer d, * a Duke Office of Clinical Research, Duke University School of Medicine, Durham, NC, USA b Duke Nutrition Services, Duke University Hospital, Durham, NC, USA c Department of Surgery, Division of Trauma Critical Care, and Acute Care Surgery, Duke University School of Medicine, Durham, NC, USA d Department of Anesthesiology, Duke University School of Medicine, Division of Critical Care, Durham, NC, USA e Centre for Perioperative Medicine, Division of Surgery & Interventional Science, University College London, London, UK f Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA a r t i c l e i n f o Article history: Received 30 June 2021 Accepted 23 July 2021 s u m m a r y Background & aims: Indirect calorimetry (IC) is the gold-standard for determining measured resting energy expenditure (mREE) in critical illness. When IC is not available, predicted resting energy expenditure (pREE) equations are commonly utilized, which often inaccurately predict metabolic de- Contents lists available at ScienceDirect Clinical Nutrition ESPEN journal homepage: http://www.clinicalnutritionespen.com Published Online: Clinical Nutrition ESPEN, 8/2021 Conclusions: If IC is unavailable, PSU 2003b & 2010 (2003b for <60 y, and PSU 2010 for >60 y) should be used to predict energy expenditure
  82. 82. 20 15 30 35 40 45 1.5 2.0 2.5 Kcal/kg/day Protein (g/kg/d) 25 0.5 Targeted Nutrition Delivery in Critical Illness ICU Intubations Total Kcal Delivery in Well Nourished Pt Activity/ Rehab Increases Severe Malnutrition BMI < 25? (0-5 d Post ICU-admit) Acute phase Chronic phase (5+ days Post ICU-admit) Recovery Phase (Post-ICU Discharge) 1.0 Wischmeyer PE. Crit Care Clin 34:107-125. 2018 “Traditional Patient Proposed Kcal Delivery” “COVID-19 Patient Proposed Kcal Delivery”
  83. 83. NEW 2021 ASPEN ICU Nutrition Guidelines There is no significant difference in clinical outcomes between early EN or PN (Strong Recommendation, Evidence Grade-High) J Parenter Enteral Nutr. 46: 12– 41, 2022. Because similar energy intake provided by PN or EN led to no differences in risk/harm: We recommend either PN or EN is acceptable When similar energy is delivered by PN or EN early in critical illness for relatively short periods of time, clinical outcomes are similar.
  84. 84. Using Indirect Calorimetry in Clinical Practice Wischmeyer PE et al, Indirect Calorimetry is Essential for Optimal Nutrition Therapy in the ICU, Accepted, Nutrition in Clinical Practice,2021
  85. 85. Using Indirect Calorimetry in Clinical Practice Wischmeyer PE et al, Indirect Calorimetry is Essential for Optimal Nutrition Therapy in the ICU, Accepted, Nutrition in Clinical Practice,2021
  86. 86. Carbohydrate Lipid Electrolytes, Trace Elements Protein Nutrition must be the complete package...
  87. 87. Can’t build a house without bricks... Protein is Fundamental...
  88. 88. Energy Expenditure and Protein Requirements 1.8-Fold Max Increase at Day 20 4-Fold Increase in Protein Loss Day 1 Fürst P, Protein and amino acid metabolism: Composition of stressed and nonstressed states, In Cresci G (ed), Nutrition support for the critically ill patient, Taylor & Francis (CRC), Boca Raton, 2005 pg 29
  89. 89. Catabolic Response to Stress and Injury Body Can Generate 50-75% of Pts Glucose Requirements! Exogenous Glucose Kcal Delivery? Text Adapted from: Anesthesiology 2015; 123:1455-72 Early Protein Delivery May be Essential Due to Catabolism!
  90. 90. Early Catabolic Response to Critical Illness and Trauma Body Can Generate up to 50-75% of Glucose Requirements in Early Acute Phase ! Lower Early Exogenous Non- protein Kcal Delivery? Text Early Protein Delivery May be Essential Due to Catabolism! (Start at 0.8 g/kg/d -> 1.2-2.0 g/kkg/d Post ICU day 3)
  91. 91. Defining anabolic resista Defining anabolic resistance: implications for delivery of clinical care nutrition Robert W. Mortona , Daniel A. Traylora , Peter J.M. Weijsb,c,d , and Stuart M. Phillipsa Purpose of review Skeletal muscle mass with aging, during critical care, and following critical care is a determinant of quality of life and survival. In this review, we discuss the mechanisms that underpin skeletal muscle atrophy and recommendations to offset skeletal muscle atrophy with aging and during, as well as following, critical care. Recent findings Anabolic resistance is responsible, in part, for skeletal muscle atrophy with aging, muscle disuse, and during disease states. Anabolic resistance describes the reduced stimulation of muscle protein synthesis to a given dose of protein/amino acids and contributes to declines in skeletal muscle mass. Physical inactivity induces: anabolic resistance (that is likely exacerbated with aging), insulin resistance, systemic inflammation, decreased satellite cell content, and decreased capillary density. Critical illness results in rapid skeletal muscle atrophy that is a result of both anabolic resistance and enhanced skeletal muscle breakdown. Summary Insofar as atrophic loss of skeletal muscle mass is concerned, anabolic resistance is a principal determinant of age-induced losses and appears to be a contributor to critical illness-induced skeletal muscle atrophy. Older individuals should perform exercise using both heavy and light loads three times per week, ingest at least 1.2 g of protein/kg/day, evenly distribute their meals into protein boluses of 0.40 g/kg, and consume g anabolic resistance: implications very of clinical care nutrition Robert W. Mortona , Daniel A. Traylora , Peter J.M. Weijsb,c,d , and Stuart M. Phillipsa eview e mass with aging, during critical care, and following critical care is a determinant of quality vival. In this review, we discuss the mechanisms that underpin skeletal muscle atrophy and ons to offset skeletal muscle atrophy with aging and during, as well as following, critical care. ngs stance is responsible, in part, for skeletal muscle atrophy with aging, muscle disuse, and e states. Anabolic resistance describes the reduced stimulation of muscle protein synthesis to a protein/amino acids and contributes to declines in skeletal muscle mass. Physical inactivity bolic resistance (that is likely exacerbated with aging), insulin resistance, systemic decreased satellite cell content, and decreased capillary density. Critical illness results in muscle atrophy that is a result of both anabolic resistance and enhanced skeletal muscle ophic loss of skeletal muscle mass is concerned, anabolic resistance is a principal determinant d losses and appears to be a contributor to critical illness-induced skeletal muscle atrophy. uals should perform exercise using both heavy and light loads three times per week, ingest at protein/kg/day, evenly distribute their meals into protein boluses of 0.40 g/kg, and consume 2 h of retiring for sleep. During critical care, early, frequent, and multimodal physical ombination with early, enteral, hypocaloric energy (!10–15 kcal/kg/day), and high-protein day) provision is recommended. utor of age-induced, a major contributor of disuse- induced, and a secondary contributor to critical Curr Opin Crit Care 2018, 24:000–000 DOI:10.1097/MCC.0000000000000488 1070-5295 Copyright ! 2018 Wolters Kluwer Health, Inc. All rights reserved. www. Copyright © 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this
  92. 92. Protein Intake to Optimize Muscle Gain Frank Zane Age 70 Recommendations for maintaining skeletal muscle mass in healthy and cr Protein Delivery FIGURE 3. Recommendations for mainta Strength Training least 1.2 g of protein/kg/day, evenly distribute their meals into protein boluses of 0.40 g/kg, and cons protein within 2 h of retiring for sleep. During critical care, early, frequent, and multimodal physical therapies in combination with early, enteral, hypocaloric energy (!10–15 kcal/kg/day), and high-prot (>1.2 g/kg/day) provision is recommended. Keywords amino acids, muscle, protein turnover INTRODUCTION Aging results in progressive and slow loss of skeletal muscle (sarcopenia) [1]. In contrast, critical illness results in rapid skeletal muscle atrophy [2,3]. Skeletal muscle atrophy is a risk factor for all-cause morbidity and mortality both as we age [4,5] and during critical illness [6,7]. Skeletal muscle mass is determined by the balance in muscle protein turnover [e.g. the algebraic difference between muscle protein synthe- sis (MPS) and muscle protein breakdown (MPB)]. Anabolic resistance is the inability of an anabolic stimulus (e.g. protein provision, hormonal stimula- tion, and/or muscle contraction) to stimulate MPS and occurs with increasing age [8 & ,9,10 & ,11 & ,12], peri- ods of inactivity [13,14], and during critical illness [15,16,17 && ,18,19]. This review aims to provide evi- dence that anabolic resistance is a principal contrib- utor of age-induced, a major contributor of disuse- illness-induced skeletal muscle atrophy. We di how whole-body and muscle protein turnove altered with age, inactivity, and critical illness b elaborating on how insulin resistance, syst inflammation, satellite cells, and alterations in microvasculature contribute to anabolic resista The latter portion of the review prescribes strat a Department of Kinesiology, McMaster University, Hamilton, C b Department of Nutrition and Dietetics, VU University, c Departm Intensive Care Medicine, VU Medical Center and d Department o tion and Dietetics, Amsterdam University of Applied Sciences, A dam, The Netherlands Correspondence to Professor Stuart M. Phillips, PhD, Departm Kinesiology, McMaster University, 1280 Main Street West, Hamilt L8S 4L8, Canada. Tel: +1 905 525 9140 x24465; e-mail: phillis@mcmaster.ca Curr Opin Crit Care 2018, 24:000–000 Adapted from:
  93. 93. Defining anabolic resista Tx?: HMB Oxandrolone Propranolol Defining anabolic resistance: implications for delivery of clinical care nutrition Robert W. Mortona , Daniel A. Traylora , Peter J.M. Weijsb,c,d , and Stuart M. Phillipsa Purpose of review Skeletal muscle mass with aging, during critical care, and following critical care is a determinant of quality of life and survival. In this review, we discuss the mechanisms that underpin skeletal muscle atrophy and recommendations to offset skeletal muscle atrophy with aging and during, as well as following, critical care. Recent findings Anabolic resistance is responsible, in part, for skeletal muscle atrophy with aging, muscle disuse, and during disease states. Anabolic resistance describes the reduced stimulation of muscle protein synthesis to a given dose of protein/amino acids and contributes to declines in skeletal muscle mass. Physical inactivity induces: anabolic resistance (that is likely exacerbated with aging), insulin resistance, systemic inflammation, decreased satellite cell content, and decreased capillary density. Critical illness results in rapid skeletal muscle atrophy that is a result of both anabolic resistance and enhanced skeletal muscle breakdown. Summary Insofar as atrophic loss of skeletal muscle mass is concerned, anabolic resistance is a principal determinant of age-induced losses and appears to be a contributor to critical illness-induced skeletal muscle atrophy. Older individuals should perform exercise using both heavy and light loads three times per week, ingest at least 1.2 g of protein/kg/day, evenly distribute their meals into protein boluses of 0.40 g/kg, and consume g anabolic resistance: implications very of clinical care nutrition Robert W. Mortona , Daniel A. Traylora , Peter J.M. Weijsb,c,d , and Stuart M. Phillipsa eview e mass with aging, during critical care, and following critical care is a determinant of quality vival. In this review, we discuss the mechanisms that underpin skeletal muscle atrophy and ons to offset skeletal muscle atrophy with aging and during, as well as following, critical care. ngs stance is responsible, in part, for skeletal muscle atrophy with aging, muscle disuse, and e states. Anabolic resistance describes the reduced stimulation of muscle protein synthesis to a protein/amino acids and contributes to declines in skeletal muscle mass. Physical inactivity bolic resistance (that is likely exacerbated with aging), insulin resistance, systemic decreased satellite cell content, and decreased capillary density. Critical illness results in muscle atrophy that is a result of both anabolic resistance and enhanced skeletal muscle ophic loss of skeletal muscle mass is concerned, anabolic resistance is a principal determinant d losses and appears to be a contributor to critical illness-induced skeletal muscle atrophy. uals should perform exercise using both heavy and light loads three times per week, ingest at protein/kg/day, evenly distribute their meals into protein boluses of 0.40 g/kg, and consume 2 h of retiring for sleep. During critical care, early, frequent, and multimodal physical ombination with early, enteral, hypocaloric energy (!10–15 kcal/kg/day), and high-protein day) provision is recommended. utor of age-induced, a major contributor of disuse- induced, and a secondary contributor to critical Curr Opin Crit Care 2018, 24:000–000 DOI:10.1097/MCC.0000000000000488 1070-5295 Copyright ! 2018 Wolters Kluwer Health, Inc. All rights reserved. www. Copyright © 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this
  94. 94. Extra-Protein Reduces Mortality! Every additional 30 g/d protein given... Mortality decreased! Alberda,C, Heyland D et al Intensive Care Med.35:1728-37. 2009
  95. 95. Resting energy expenditure, calorie and protein consumption in critically ill patients: a retrospective cohort study Oren Zusman1* , Miriam Theilla2,3 , Jonathan Cohen2,4 , Ilya Kagan2 , Itai Bendavid2 and Pierre Singer2,4 Abstract Background: Intense debate exists regarding the optimal energy and protein intake for intensive care unit (ICU) patients. However, most studies use predictive equations, demonstrated to be inaccurate to target energy intake. We sought to examine the outcome of a large cohort of ICU patients in relation to the percent of administered calories divided by resting energy expenditure (% AdCal/REE) obtained by indirect calorimetry (IC) and to protein intake. Methods: Included patients were hospitalized from 2003 to 2015 at a 16-bed ICU at a university affiliated, tertiary care hospital, and had IC measurement to assess caloric targets. Data were drawn from a computerized system and included the % AdCal/REE and protein intake and other variables. A Cox proportional hazards model for 60-day mortality was used, with the % AdCal/REE modeled to accommodate non-linearity. Length of stay (LOS) and length of ventilation (LOV) were also assessed. Results: A total of 1171 patients were included. The % AdCal/REE had a significant non-linear (p < 0.01) association with mortality after adjusting for other variables (p < 0.01). Increasing the percentage from zero to 70 % resulted in a hazard ratio (HR) of 0.98 (CI 0.97–0.99) pointing to reduced mortality, while increases above 70 % suggested an increase in mortality with a HR of 1.01 (CI 1.01–1.02). Increasing protein intake was also associated with decreased mortality (HR 0.99, CI 0.98–0.99, p = 0.02). An AdCal/REE >70 % was associated with an increased LOS and LOV. Conclusions: The findings of this study suggest that both underfeeding and overfeeding appear to be harmful to critically ill patients, such that achieving an Adcal/REE of 70 % had a survival advantage. A higher caloric intake may also be associated with harm in the form of increased LOS and LOV. The optimal way to define caloric goals therefore requires an exact estimate, which is ideally performed using indirect calorimetry. These findings may provide a basis for future randomized controlled trials comparing specific nutritional regimens based on indirect calorimetry measurements. Keywords: Indirect calorimetry, Nutrition, Protein, Resting energy expenditure, Calorie consumption Background The provision of nutritional support for critically ill pa- tients continues to be the subject of intense debate, with described [6, 7]. Importantly, for many reasons either by design or default, many critically ill patients do not re- ceive their full energy requirements and the proportion RESEARCH Resting energy protein consum Zusman et al. Critical Care (2016) 20:367 DOI 10.1186/s13054-016-1538-4 1171 pts in ICU > 96 h & Measured Energy Expenditure. Lowest Mortality- 1.3 g/kg/d Protein
  96. 96. 20 15 30 35 40 45 1.5 2.0 2.5 Kcal/kg/day Protein (g/kg/d) 25 0.5 Nutrition Delivery Targets in COVID-19 from LEEP-COVID Data ICU Intubations Activity/ Rehab Increases (Day 0-7 post-ICU admit) Acute phase Chronic phase (2nd-3rd ICU week) Recovery Phase (Post-ICU Discharge) 1.0 Adapted from Wischmeyer PE. Crit Care Clin 34:107-125. 2018 “Traditional ICU Patient Proposed Kcal Delivery” “COVID-19 Patient Proposed Kcal Delivery” Protein Delivery
  97. 97. International ICU Nutrition Survey
  98. 98. % receive/prescribed 0 10 20 30 40 50 60 70 80 90 100 Canada Aust/NZ USA Europe Latin America Asia Total 54.5 54.5 51.3 60.7 48.9 61.1 58.9 54.5 54.5 51.3 60.7 48.9 61.1 58.9 We Underfeed For 2 Weeks... https://www.criticalcarenutrition.com
  99. 99. 0.6 g/kg/d for 2 weeks in ICU! Average Protein Delivery Guideline Protein: 1.2 -2.0 g/kg/d
  100. 100. “Are we creating survivors... or Victims?” GLBL/MG17/20-0019 04/2020 © Baxter Healthcare Corporation
  101. 101. Improved Protein and Kcal Delivery in 1st ICU Week Improves Survival in Hi-Risk Pts Wei X, et al. Crit Care Med. 2015;43(8):1569-1579. 0-50% Kcals N= 475 Pts on Ventilator > 8 Days 50 - < 80% Kcals > 80% Kcals
  102. 102. Improved Protein and Kcal in First Week in MICU Improves Quality of Life N= 475 Pts on Ventilator > 8 Days Subgroup Analysis of the Effect of Nutritional Adequacy on SF-36 scores ! ! Nutritional Adequacy a per 25% increase Medical Patients SF-36 N b Adjusted Estimate c, d (95% CI) P PF: 3-mo 128 10.9 (4.3, 17.6) 0.001 PF: 6-mo 144 6.7 (0.2, 13.2) 0.04 RP: 3-mo 127 13.1 (6.7, 19.6) <.001 RP: 6-mo 144 7.2 (0.9, 13.4) 0.03 PCS: 3-mo 125 3.5 (1.2, 5.8) 0.003 PCS: 6-mo 142 2.5 (0.2, 4.9) 0.03 Wei X, et al. Crit Care Med. 2015;43(8):1569-1579.
  103. 103. How you feed in the 1st week in ICU... Changes Pts QoL Months Later!! Wei X, et al. Crit Care Med. 2015;43(8):1569-1579.
  104. 104. -On Trophic EN at 15 cc/h - Stopped multiple times for proning, GRV > 500 -Receiving < 25% of protein/kcal needs In ICU- Paralyzed and Prone- Day 4 -BP: 100/60 on 0.04 ug/kg/min levophed -MV O2 sat- 81%, Lactate 1.0
  105. 105. Achieving Goal EN in COVID Patients is… VERY DIFFICULT! The Challenge is… And…GI Tract Involvement is Common in COVID-19
  106. 106. Courtesy :Arthur Van Zanten MD CRRT Paralyzed Norepinephrine Prone Position Often Obese EN often < 50% goal!
  107. 107. -GI symptoms occur in 20-70% of COVID-19 Pts -Include: Diarrhea, Nausea/Vomiting, Abd Pain, Liver Injury - ~50% of pts have stool w/ +COVID19 - SARS-COV-2 viral receptor angiotensin converting enzyme 2 highly expressed in GI epithelial cells REVIEW Covid-19 and the digestive system Sunny H Wong,*,† Rashid NS Lui*,† and Joseph JY Sung*,† *Institute of Digestive Disease, and † Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong Key words coronavirus, Covid-19, diarrhea, gastrointestinal infection, pneumonia. Accepted for publication 24 March 2020. Correspondence Professor Joseph JY Sung, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, Shatin, Hong Kong. Email: jjysung@cuhk.edu.hk Declaration of conflict of interest: The authors declare no conflict of interest. Abstract The novel coronavirus disease is currently causing a major pandemic. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a member of the Betacoronavirus genus that also includes the SARS-CoV and Middle East respiratory syn- drome coronavirus. While patients typically present with fever and a respiratory illness, some patients also report gastrointestinal symptoms such as diarrhea, vomiting, and ab- dominal pain. Studies have identified the SARS-CoV-2 RNA in stool specimens of in- fected patients, and its viral receptor angiotensin converting enzyme 2 was found to be highly expressed in gastrointestinal epithelial cells. These suggest that SARS-CoV-2 can actively infect and replicate in the gastrointestinal tract. This has important implications to the disease management, transmission, and infection control. In this article, we review the important gastrointestinal aspects of the disease. Journal of Gastroenterology of Hepatology Online: 3/2020: doi:10.1111/jgh.15047
  108. 108. Personalization of Early Nutrition Delivery by Disease Type? COVID-19 specific...? New Data!
  109. 109. Early EN Improves Clinical Outcomes in COVID-19 - Retrospective cohort study on timing of EN initiation in patients undergoing MV Methods: Population: - 851 patients from multiple U.S. hospitals with COVID-19 on MV - Early EN (within 3 days of MV) vs. Late EN (after 3 days post-ICU) - Premier Database- 75 U.S. Hospitals contributed COVID-19 data- 265,298 pts total - Inverse-probability-of-treatment weighting (IPTW) to control confounding variables - Multivariable logistic regression model DukeCAPER DukeCAPER Krista Haines, Virginia Parker, Tetsu Ohnuma, Vijay Krishnamoorthy, Karthik Raghunathan, Suela Sulo, Kirk W. Kerr, Beth Besecker, Bridget A. Cassady, Paul Wischmeyer Submitted for Publication: Under Review
  110. 110. Covid-19 Patients Are Being STARVED in ICU! Time to EN Start (N) Mean EN Start Std Dev Early EN < 3 d 513 2.4 0.8 Late EN > 3 d 348 9.9 8.4 > 40% of COVID-19 ICU Pts Not Fed Any EN for > 3 d Mean Time to EN Start in Late EN group was ~10 days!
  111. 111. Early EN Improves Clinical Outcomes in COVID-19 Early EN Reduces Mechanical Ventilation Days (HR=1.25, 95% CI:1.01-1.54) Early EN Reduces ICU LOS (Hazard Ratio [HR] =1.39, 95% CI:1.15-1.68) Early EN Reduces Hosp LOS (HR=1.53, 95% CI:1.23-1.91)
  112. 112. Early EN Improves Clinical Outcomes in COVID-19 No Difference in Mortality Early EN Reduces Hospital Costs (-$22,443, 95%CI:-$32,342 to -$12,534)
  113. 113. We Must Start EN and/or PN Sooner in COVID-19 ICU Patients to Optimize Outcomes!
  114. 114. SCCM/ASPEN Recommend Early TPN in COVID! “In contrast to other populations of critically ill patients... …a lower threshold for switching to PN in the patient with COVID-19 disease needs to be utilized.” Martindale et al.. SCCM/ ASPEN Guidelines Apr 2020
  115. 115. -On Trophic EN at 15 cc/h - Stopped multiple times for proning, GRV > 500 -Receiving < 25% of protein/kcal needs In ICU- Paralyzed and Prone- Day 4 -BP: 100/60 on 0.04 ug/kg/min levophed -MV O2 sat- 81%, Lactate 1.0
  116. 116. Does Parenteral Nutrition (TPN) lead to increased risk of infection in ICU pts? A. Yes B. No
  117. 117. Does Parenteral Nutrition (TPN) lead to increased risk of infection in ICU pts? A. Yes B. No
  118. 118. Four New Large Randomized Trials Show.... TPN Does Not Increase Infection Risk in 2022! Doig et al. JAMA, 2013 Heidegger et al, Lancet, 2013 CALORIES Trial, NEJM, 2014 NUTRIREA-2, Lancet, 2017
  119. 119. TPN No Longer Related To Infection in 2022! - No Longer “Hyperalimentation” - We Now Control Hyperglycemia - Improved Protein Delivery - Better Central Line Care Improved Lipids?
  120. 120. NEW 2021 ASPEN ICU Nutrition Guidelines There is no significant difference in clinical outcomes between early EN or PN (Strong Recommendation, Evidence Grade-High) J Parenter Enteral Nutr. 46: 12– 41, 2022. Because similar energy intake provided by PN or EN led to no differences in risk/harm: We recommend either PN or EN is acceptable When similar energy is delivered by PN or EN early in critical illness for relatively short periods of time, clinical outcomes are similar.
  121. 121. Finally!....New IV Lipids in U.S!
  122. 122. Lipid Choice Matters To Outcome!
  123. 123. If Your Hospital is Still Using Pure Soybean Oil in TPN... STOP!
  124. 124. If Your Hospital is Still Using Pure Soybean Oil in TPN... Your Patients Deserve Better!
  125. 125. Switch to Olive Oil or Fish Oil PN Lipid Now!
  126. 126. Rapidly developing severe hypertriglyceridemia in even low propofol does have been seen in COVID pts Monitor serum triglyceride levels in COVID-19 pts receiving propofol and/or IV lipids (w/in 24 h) post-initiation of lipids or propofol COVID-19 Hypertriglyceridemia SCCM/ASPEN COVID-19 Guidelines
  127. 127. New Oliguria... Urine Output - 10-15 cc/h Creatinine - 4.6 mg/dL Elijah W. - 49 y.o. Found to be COVID (+) CRRT Initiated...
  128. 128. Elijah W. - 49 y.o. Found to be COVID (+) ICU Day 21… Pt Develops Pancytopenia (Plts- 27, WBC-1.0) All drug-related etiologies ruled-out...
  129. 129. What CVVH related metabolic/ nutritional loss may be causing pancytopenia? Copper level < 10 umol/L Copper Chloride- 4 mg/d IV given
  130. 130. Vitamin/Nutrient Losses in CRRT
  131. 131. 2016 ASPEN/SCCM Guidelines [Quality of Evidence: Very Low] We recommend pts on CRRT or freq. HD receive increased protein, up to 2.5 g/kg/d Protein should not be restricted in AKI pts to avoid or delay initiating dialysis therapy!
  132. 132. Malnutrition, CVVH and Complications Wischmeyer PE. Nutrition in Sepsis Crit Care Clin 34:107-125. 2018 Pancytopenia/Neutropenia: Copper, Vitamin B12, Folate, Vitamin B6 Lactic Acidois: Thiamine Encephalopathy/Delerium: Vit. B6 (50 mg IV q day), Thiamine, Vit. B12, Folate Prolonged Weakness/Neuromuscular Dysfunction (Can Be Permanent!) Carnitine, Copper
  133. 133. Incidence & Role of Severe Micronutrient and Vitamin Deficiencies Caused by Continuous Renal Replacement Therapy (CRRT) in Critically Ill Patients Investigator Initiated Trial: Duke CAPER Health Outcomes Group
  134. 134. 89.6% of CRRT pts developed 1 deficiency in trace/water-soluble vitamins ≥
  135. 135. Conclusions A Majority of Patients on CRRT > 5-7 Days Develop Significant Nutrient Deficiencies Copper (71%), Vit B6 (71%) Selenium (43%), Carnitine (38%) is Most Common in CRRT Zinc (50%), Vit B6(40%), & Selenium (29%) Most Common in Nutritionally “At-Risk”
  136. 136. Conclusions Carnitine & Selenium Deficiency Show Signal for Increased Mortality in CRRT Any Nutrient Deficiency in Any Patient (CVVH or NOT) ↑ Mortality Risk 2.4-fold Other Nutrient Deficiencies Show Initial Trends for Increased Mortality in CRRT
  137. 137. Current Opinion in Critical Care: Online, May, 2021 CVVH and Malnutrition: Must Check…& Continue to Replete! Would also check Vitamin C, Folate, Vit B12, Vit D Copper, Carnitine, Zinc, Thiamine, Selenium, Vit. B6 Need Continuous Monitoring and Repletion While on CVVH q weekly
  138. 138. Started on Oral Nutrition... Will they eat enough on her own? Recovering COVID-19 Patients… Not Likely!! Average Post-ICU Intake: 700 kcal/d
  139. 139. Oral Nutrition Supplements (ONS) Only Way To Deliver Post-ICU Nutrition Needs!
  140. 140. ONS Reduces Hospital Mortality OR 0.61 [95% CI 0.48–0.78], p < 0.001 Meta-analysis of 11 trials, n = 1965; Control ONS Stratton et al, 2003 Book: Disease-related malnutrition: an evidence-based approach to treatment
  141. 141. SECTION 5 ONS Reduces Hospital Complications Stratton et al, 2003 Book: Disease-related malnutrition: an evidence-based approach to treatment OR 0.31; 95% CI 0.17–0.56, p < 0.001 Meta-analysis of 7 trials, n = 384 Control ONS
  142. 142. Every $1 spent on ONS... Saves $52.63 in hospital costs ONS Reduces Costs... Philipson et al. American Journal of Managed Care 19:121-128, 2013
  143. 143. HP-HMB ONS Reduces Death at 90 d Post-Hospital Discharge Deutz NE et al, Clinical Nutrition, 35:18-2, 2016 HP-HMB ONS Placebo 78 Center, RCT, n=652 pts
  144. 144. HP-HMB Associated with 50% Reduction in Mortality Day 30 Day 60 Day 90 0% 5% 10% 15% Mortality in all patients Placebo HP-HMB P=0.049 P=0.020 P=0.018 The number needed to treat (NNT) to prevent 1 death was 20.3 Deutz NE, et al., Clinical Nutrition (2016) 2016;35(1):18-26
  145. 145. Conclusions Use of ONS in Post-ICU pts is essential! Highly Effective Intervention To Improve Clinical Outcomes and Reduce Costs
  146. 146. Is “Right” Nutrition Enough to Win the War?
  147. 147. SRM SRM+NS Partial SRM Disease-related Malnutriion 60 70 80 90 100 1 2 3 4 5 6 7 Time Lean Body Mass (%) Calorie Delivery Alone Won’t Stop LBM Loss! Acute (ICU) Malnutrition Acute (ICU) Malnutrition + Nutrition Support Chronic Dz Malnutrition Chronic Dz Malnutrition + Nutrition Support Jensen et al, JPEN, 34:156-159, 2010
  148. 148. “Survival of the Fittest” We Are NOT Evolved For This! Hypermetabolism & Catabolism Can Persist for Months - > 2 Years!
  149. 149. Can We Learn From Elite Athletes… …To help our pts?
  150. 150. Take “Right” Anabolic Agents!?
  151. 151. Should NOT be given in “acute phase or early ICU” Post-acute phase testosterone much more promising! Testosterone and Analogs
  152. 152. Testosterone Levels in ICU: Must Check… Virtually All Testosterone Levels I Check Are: Wischmeyer PE. Nutrition in Sepsis Crit Care Clin 34:107-125. 2018 Severely Deficient After 3-5 days in ICU! Wischmeyer PE et al Curr Opin Crit Care. Online 8/2020

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