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Daren K. Heyland Professor of Medicine Queen’s University, Kingston General Hospital

Iatrogenic Underfeeding in the Critically ill: Time for a change!. Daren K. Heyland Professor of Medicine Queen’s University, Kingston General Hospital Kingston, ON Canada. Iatrogenic Underfeeding is Harmful to ‘High-Risk’ Critically ill Patients!. Daren K. Heyland Professor of Medicine

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Daren K. Heyland Professor of Medicine Queen’s University, Kingston General Hospital

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  1. Iatrogenic Underfeeding in the Critically ill: Time for a change! Daren K. Heyland Professor of Medicine Queen’s University, Kingston General Hospital Kingston, ON Canada

  2. Iatrogenic Underfeeding is Harmful to ‘High-Risk’ Critically ill Patients! Daren K. Heyland Professor of Medicine Queen’s University, Kingston General Hospital Kingston, ON Canada

  3. Statements like this are a problem! “Our results suggest that, irrespective of the route of administration, the amount of macronutrients administered early during critical illness may worsen outcome.” Cesar Am J Respir Crit Care Med 2013;187:247–255 “The most notable findings, however, were that loss of muscle mass not only occurred despite enteral feeding but, paradoxically, was accelerated with higher protein delivery..” Batt JAMA Published online October 9, 2013 “Avoid mandatory full caloric feeding in the first week but rather suggest low dose feeding (e.g., up to 500 calories per day), advancing only as tolerated (grade 2B)..” SSC Guidelines CCM Feb 2013; Cesar NEJM 2014

  4. My Big Idea! • Underfeeding in some ICU patients results in increased morbidity and mortality! • Driven by misinterpretation of clinical data • Not all patients will benefit the same; need better tools to risk stratify • There are effective tools to overcome iatrogenic malnutrition

  5. Learning Objectives • Define Iatrogenic malnutrition • Review the evidentiary basis for the amount of macronutrients provided to critically ill patients • List strategies to improve nutritional adequacy in the critical care setting

  6. A different form of malnutrition?

  7. Health Care Associated Malnutrition Nutrition deficiencies associated with physiological derangement and organ dysfunction that occurs in a health care facility Patients who will benefit the most from nutrition therapy and who will be harmed the most from by iatrogenic malnutrition (underfeeding)

  8. RCTs of Early vs. Delayed EN Mortality RR 0.68 (0.46, 1.01) Infection RR 0.76 (0.69, 0.98)

  9. Nutritional and Non-nutritional benefits of Early Enteral Nutrition Attenuate oxidative stress↓ Systemic Inflammatory Response Syndrome (SIRS) Reduce gut/lung axis of inflammationMaintain MALT tissue↑Production of Secretory IgA at epithelial surfaces ↑Dominance of anti-inflammatory Th2 over pro-inflammatory Th1 responsesModulate adhesion molecules to ↓ transendothelial migration of macrophages and neutrophils ↑ Muscle function, mobility, return to baseline function Provide micro & macronutrients, antioxidantsMaintain lean body mass↓Muscle and tissue glycosylation↑ Mitochondrial function↑ Protein synthesis to meet metabolic demand Maintain gut integrity↓Gut permeabilitySupport commensal bacteriaStimulate oral tolerance↑Butyrate productionPromote insulin sensitivity, ↓hyperglycemia (AGEs) ↑ Absorptive capacity Influence anti-inflammatory receptors in GI tract↓ Virulence of pathogenic organisms↑ Motility, contractility McClave CCM 2015

  10. Pragmatic RCT in 33 ICUs in England • 2400 patients expected to require nutrition support for at least 2 days after unplanned admission • Early EN vs Early PN • According to local products and policies • Powered to detect a 6.4% ARR in 30 day mortality NEJM Oct 1 2014

  11. No difference in 30 day or 90 day mortality or infection nor 14 other secondary outcomes Suboptimal method of determining infection Protein Delivered: EN 0.7 gm/kg; PN 1.0 gm/kg

  12. Updated Meta-analysis of EN vs PNEffect on Infection RR 0.64 (95%CI 0.48, 0.87) Unpublished data

  13. Early EN (within 24-48 hrs of admission) is recommended! Optimal Amount of Protein and Calories for Critically Ill Patients?

  14. Increasing Calorie Debt Associated with worse Outcomes Adequacy of EN Caloric Debt •  Caloric debt associated with: •  Longer ICU stay •  Days on mechanical ventilation •  Complications •  Mortality Rubinson CCM 2004; Villet Clin Nutr 2005; Dvir Clin Nutr 2006; Petros Clin Nutr 2006

  15. Optimal Amount of Calories for Critically Ill Patients: Depends on how you slice the cake! • Objective: To examine the relationship between the amount of calories recieved and mortality using various sample restriction and statistical adjustment techniques and demonstrate the influence of the analytic approach on the results. • Design: Prospective, multi-institutional audit • Setting: 352 Intensive Care Units (ICUs) from 33 countries. • Patients: 7,872 mechanically ventilated, critically ill patients who remained in ICU for at least 96 hours. Heyland Crit Care Med 2011

  16. A. In ICU for at least 96 hours. Days after permanent progression to exclusive oral feeding are included as zero calories* B. In ICU for at least 96 hours. Days after permanent progression to exclusive oral feeding are excluded from average adequacy calculation.* C. In ICU for at least 4 days before permanent progression to exclusive oral feeding. Days after permanent progression to exclusive oral feeding are excluded from average adequacy calculation.* Association between 12 day average caloric adequacy and 60 day hospital mortality (Comparing patients rec’d >2/3 to those who rec’d <1/3) D. In ICU at least 12 days prior to permanent progression to exclusive oral feeding* *Adjusted for evaluable days and covariates,covariates include region (Canada, Australia and New Zealand, USA, Europe and South Africa, Latin America, Asia), admission category (medical, surgical), APACHE II score, age, gender and BMI.

  17. Association Between 12-day Nutritional Adequacy and 60-Day Hospital Mortality Optimal amount= 80-85% Heyland CCM 2011

  18. Impact of Protein Intake on 60-day Mortality • Data from 2828 patients from 2013 International Nutrition Survey ¹ Adjusted for BMI, Gender, Admission Type, Age, Evaluable Days, APACHE II Score, SOFA Score ² Adjusted for all in model 1 plus for calories and protein Nicolo JPEN 2015 (in press)

  19. Rate of Mortality Relative to Adequacy of Protein and Energy Intake Delivered Nicolo JPEN 2015 (in press)

  20. 113 select ICU patients with sepsis or burns • On average, receiving 1900 kcal/day and 84 grams of protein • No significant relationship with energy intake but…… 1.45 gm/kg/d 1.06 gm/kg/d 0.79 gm/kg/d Clinical Nutrition 2012

  21. ICU patients are not all created equal…should we expect the impact of nutrition therapy to be the same across all patients?

  22. Point prevalence survey of nutrition practices in ICU’s around the world conducted Jan. 27, 2007 • Enrolled 2772 patients from 158 ICU’s over 5 continents • Included ventilated adult patients who remained in ICU >72 hours

  23. 75% 25% 100% 50%

  24. Mechancially Vent’d patients >7days (average ICU LOS 28 days) Faisy BJN 2009;101:1079

  25. Effect of Increasing Amounts of Protein from EN on Infectious Complications Multicenter observational study of 207 patients >72 hrs in ICU followed prospectively for development of infection for increase of 30 grams/day, OR of infection at 28 days Heyland Clinical Nutrition 2010

  26. Nutritional Adequacy and Long-term Outcomes in Critically Ill Patients Requiring Prolonged Mechanical Ventilation • Sub study of the REDOXS study • 302 patients survived to 6-months follow-up and were mechanically ventilated for more than eight days in the intensive care unit were included. • Nutritional adequacy was obtained from the average proportion of prescribed calories received during the first eight days of mechanical ventilation in the ICU. • HRQoL was prospectively assessed using Short-Form 36 Health Survey (SF-36) questionnaire at three-months and six-months post ICU admission.  Wei CCM 2015 (in press)

  27. Estimates of association between nutritional adequacy and SF-36 scores *Every 25% increase in nutritional adequacy; adjusted for age, APACHE II score, baseline SOFA, Functional Comorbidity Index, admission category, primary ICU diagnosis, body mass index, and region

  28. RCT Level of Evidence that More EN= Improved Outcomes • RCTs of aggressive feeding protocols • Results in better protein-energy intake • Associated with reduced complications and improved survival Taylor et al Crit Care Med 1999; Martin CMAJ 2004 • Meta-analysis of Early vs Delayed EN • Reduced infections: RR 0.76 (.59,0.98),p=0.04 • Reduced Mortality: RR 0.68 (0.46, 1.01) p=0.06 www.criticalcarenutrition.com

  29. Earlier and Optimal Nutrition (>80%) is Better! If you feed them (better!) They will leave (sooner!)

  30. Initial Tropic vs. Full EN in Patients with Acute Lung Injury The EDEN randomized trial Rice TW, et al. JAMA. 2012;307(8):795-803.

  31. Initial Tropic vs. Full EN in Patients with Acute Lung Injury The EDEN randomized trial Rice TW, et al. JAMA. 2012;307(8):795-803.

  32. Initial Tropic vs. Full EN in Patients with Acute Lung Injury The EDEN randomized trial Enrolled 12% of patients screened Rice TW, et al. JAMA. 2012;307(8):795-803.

  33. Trophic vs. Full EN in Critically Ill Patients with Acute Respiratory Failure • Average age 52 • Few comorbidities • Average BMI* 29-30 • All fed within 24 hours (benefits of early EN) • Average duration of study intervention 5 days No effect in young, healthy, overweight patients who have short stays! * BMI: body mass index Alberda C, et al. Intensive Care Med. 2009;35(10):1728-37.

  34. ICU patients are not all created equal…should we expect the impact of nutrition therapy to be the same across all patients?

  35. Not all ICU Patient the same! • Low Risk • 34 year former football player, • BMI 35 • otherwise healthy • involved in motor vehicle accident • Mild head injury and fractured R leg requiring ORIF • High Risk • 79 women • BMI 35 • PMHx COPD, poor functional status, frail • Admitted to hospital 1 week ago with CAP • Now presents in respiratory failure requiring intubation and ICU admission

  36. How do we figure out who will benefit the most from Nutrition Therapy?

  37. A Conceptual Model for Nutrition Risk Assessment in the Critically Ill Acute • Reduced po intake • pre ICU hospital stay Acute • IL-6 • CRP • PCT Chronic • Recent weight loss • BMI? Chronic • Comorbid illness Starvation Nutrition Status micronutrient levels - immune markers - muscle mass Inflammation

  38. The Development of the NUTrition Risk in the Critically ill Score (NUTRIC Score). BMI, CRP, PCT, weight loss, and oral intake were excluded because they were not significantly associated with mortality or their inclusion did not improve the fit of the final model.

  39. The Validation of the NUTrition Risk in the Critically ill Score (NUTRIC Score). Interaction between NUTRIC Score and nutritional adequacy (n=211)* P value for the interaction=0.01 Heyland Critical Care 2011, 15:R28

  40. Further validation of the “modified NUTRIC” nutritional risk assessment tool • In a second data set of 1200 ICU patients • Minus IL-6 levels Rahman Clinical Nutrition 2015

  41. Who might benefit the most from nutrition therapy? • High NUTRIC Score? • Clinical • BMI • Projected long length of stay • Nutritional history variables • Sarcopenia • Medical vs. Surgical • Others?

  42. Earlier and Optimal Nutrition (>80%) is Better! (For High Risk Patients) If you feed them (better!) They will leave (sooner!)

  43. Failure Rate The Prevalence of Iatrogenic Underfeeding in the Nutritionally ‘At-Risk’ Critically Ill Patient % high risk patients who failed to meet minimal quality targets (80% overall energy adequacy) Of all at-risk patients, 14% were ever prescribed volume-based feeds 15% ever received sPN Heyland Clinical Nutrition 2015

  44. Can we do better? The same thinking that got you into this mess won’t get you out of it!

  45. Different feeding options based on hemodynamic stability and suitability for high volume intragastric feeds. In select patients, we start the EN immediately at goal rate, not at 25 ml/hr. We target a 24 hour volume of EN rather than an hourly rate and provide the nurse with the latitude to increase the hourly rate to make up the 24 hour volume. Start with a semi elemental solution, progress to polymeric Tolerate higher GRV threshold (300 ml or more) Motility agents and protein supplements are started immediately, rather than started when there is a problem. The Efficacy of Enhanced Protein-Energy Provision via the Enteral Route in Critically Ill Patients: The PEP uP Protocol! A Major Paradigm Shift in How we Feed Enterally Heyland Crit Care 2010; see www.criticalcarenutrition.com for more information on the PEP uP collaborative

  46. Results of the Canadian PEP uP Collaborative Results of 2013 International Nutrition Survey Heyland JPEN 2014

  47. Health Care Associated Malnutrition What if you can’t provide adequate nutrition enterally? … to add PN or not to add PN, that is the question!

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