Learning Objectives • Define iatrogenic malnutrition • Describe the nature of the evidence related to optimal amount of calories/protein • List key variables to consider in assessing nutritional risk in ICU patients • List strategies to improve nutritional adequacy in the critical care setting. A different form of malnutrition? 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) Early EN (within 24-48 hrs of admission) is recommended! Optimal Amount of Protein and Calories for Critically Ill Patients? Adequacy of EN kcal Increasing Calorie Debt Associated with worse Outcomes Prescribed Engergy 2000 1800 1600 1400 1200 1000 800 600 400 200 0 Energy Received From Enteral Feed Caloric Debt 1 3 5 7 9 11 13 15 17 19 21 Days 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 • 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 Relationship of Caloric Intake, 60 day Mortality and BMI 60 BMI All Patients < 20 20-25 25-30 30-35 35-40 >40 Mortality (%) 50 40 30 20 10 0 0 500 1000 1500 Calories Delivered 2000 Effect of Increasing Amounts of Calories from EN on Infectious Complications Multicenter observational study of 207 patients >72 hrs in ICU followed prospectively for development of infection for increase of 1000 cal/day, OR of infection at 28 days Heyland Clinical Nutrition 2010 Relationship between increased nutrition intake and physical function (as defined by SF-36 scores) following critical illness For every 1000 kcal/day received: Model * Estimate (CI) P values PHYSICAL FUNCTIONING 3.2 (-1.0, 7.3) P=0.14 ROLE PHYSICAL 4.2 (-0.0, 8.5) P=0.05 STANDARDIZED PHYSICAL COMPONENT SCALE 1.8 (0.3, 3.4) P=0.02 PHYSICAL FUNCTIONING 0.8 (-3.6, 5.1) P=0.73 ROLE PHYSICAL 2.0 (-2.5, 6.5) P=0.38 STANDARDIZED PHYSICAL COMPONENT SCALE 0.70 (-1.0, 2.4) P=0.41 At 3 months At 6 months for increase of 30 gram/day, OR of infection at 28 days Unpublished data from Multicenter RCT of glutamine and antioxidants (REDOXS Study); n=364 Mechancially Vent’d patients >7days (average ICU LOS 28 days) Faisy BJN 2009;101:1079 • 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…… Clinical Nutrition 2012 More (and Earlier) is Better! If you feed them (better!) They will leave (sooner!) 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 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) 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.* Unadjusted Adjusted D. In ICU at least 12 days prior to permanent progression to exclusive oral feeding* 0.4 0.6 0.8 1.0 1.2 1.4 1.6 Odds ratios with 95% confidence intervals *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. Association Between 12-day Caloric Adequacy and 60-Day Hospital Mortality Optimal amount= 80-85% Heyland CCM 2011 More (and Earlier) is Better! If you feed them (better!) They will leave (sooner!) Rice et al. JAMA 2012;307 Rice et al. JAMA 2012;307 Enrolled 12% of patients screened Rice et al. JAMA 2012;307 Trophic vs. Full enteral feeding in critically ill patients with acute respiratory failure • • • • • Average age 52 Few comorbidities Average BMI 29-30 All fed within 24 hrs (benefits of early EN) Average duration of study intervention 5 days No effect in young, healthy, overweight patients who have short stays! Nutritional Management of ICU Patients: Are these both 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 – 72 women – BMI 35 – PMHx COPD, poor functional status – Admitted to hospital 1 week ago with CAP – Now presents in respiratory failure requiring intubation and ICU admission ICU-acquired Weakness (ICUAW) Muscle weakness develops in 25%-60% of patients who have been mechanically ventilated for > 1 week1 Prolongs:1-4 – mechanical ventilation – weaning from the ventilator – ICU stay • ICUAW main clinical manifestation of critical illness neuromyopathy (CINM)5 1. 2. 3. 4. 5. de Jonghe B, et al. Crit Care Med. 2004;30:1117-1121. Garnacho-Montero J, et al. Crit Care Med. 2005;33:349-354. van den Berghe G, et al. Crit Care Med. 2003;31:359-366. Hermans G, et al. Am J Respir Crit Care Med. 2007;175:480-489. de Jonghe B, et al. Crit Care Med. 2009;37(suppl.):S309-S315. Determinants to Lean Body Mass Muscle Matters! Skeletal muscle mass predicts ventilator-free days, ICUfree days, and mortality in elderly ICU patients • Patients > 65 years with an admission abdominal computed tomography scan and requiring intensive care unit stay at a Level I trauma center in 2009-2010 were reviewed. • Muscle cross-sectional area at the 3rd lumbar vertebra was calculated and sarcopenia identified using sex-specific cutpoints. • Muscle cross-sectional area was then related to clinical parameters including ventilator-free days, ICU-free days, and mortality. Kozar (in submission) Skeletal Muscle Adipose Tissue Physical Characteristics of Patients • • • • • N=149 patients Median age: 79 years old 57% males ISS: 19 Prevalence of sarcopenia: 71% BMI Characteristics All Patients Sarcopenic Patients (n=106) Non-sarcopenic Patients (n=43) 25.8 (22.7, 28.2) 24.4 (21.7, 27.3) 27.6 (25.5, 30.4) Underweight, % 7 9 2 Normal Weight, % 37 44 19 Overweight, % 42 38 51 Obese, % 15 9 28 BMI (kg/m2) Low muscle mass associated with mortality Proportion of Deceased Patients Sarcopenic patients 32% Non-sarcopenic patients 14% P-value 0.018 Muscle mass is associated with ventilator-free and ICU-free days All Patients Sarcopenic Patients NonSarcopenic Patients P-value Ventilator-free days 25 (0,28) 19 (0,28) 27 (18,28) 0.004 ICU-free days 19 (0,25) 16 (0,24) 23 (14,27) 0.002 • Prospective multicenter observational trial of 136 patients requiring min 5 days of mechanical ventilation • After day 5, when awake, performed muscle testing Am J Respir CCM 2008;178:261-268 PROTEIN REQUIREMENT IN CRITICAL ILLNESS AT ADEQUATE ENERGY INTAKE Wolfe et al., Ann Surg 1983; Ishibashi et al., Crit Care Med 1998 Hoffer Am J Clin Nutr 2003 g protein / kg IBW per day Whole-body protein loss (kg / 2 weeks) 0.7 0 -0.5 -1 -1.5 -2 1.0 1.5 2.2 ICU patients are not all created equal…should we expect the impact of nutrition therapy to be the same across all patients? How do we figure out who will benefit the most from Nutrition Therapy? Health Care Associated Malnutrition Do Nutrition Screening tools help us discriminate those ICU patients that will benefit the most from artificial nutrition? Patients who will benefit the most from nutrition therapy and who will be harmed the most from by iatrogenic malnutrition (underfeeding) All ICU patients treated the same Albumin: a marker of malnutrition? • Low levels very prevalent in critically ill patients • Negative acute-phase reactant such that synthesis, breakdown, and leakage out of the vascular compartment with edema are influenced by cytokine-mediated inflammatory responses • Proxy for severity of underlying disease (inflammation) not malnutrition • Pre-albumin shorter half life but same limitation Subjective Global Assessment? • When training provided in advance, can produce reliable estimates of malnutrition • Note rates of missing data • mostly medical patients; not all ICU • rate of missing data? • no difference between well-nourished and malnourished patients with regard to the serum protein values on admission, LOS, and mortality rate. Mostly surgical patients; 100% data available for SGA “We must develop and validate diagnostic criteria for appropriate assignment of the described malnutrition syndromes to individual patients.” A Conceptual Model for Nutrition Risk Assessment in the Critically Ill Acute Chronic -Reduced po intake -pre ICU hospital stay -Recent weight loss -BMI? Starvation Nutrition Status micronutrient levels - immune markers - muscle mass Inflammation Acute -IL-6 -CRP -PCT Chronic -Comorbid illness The Development of the NUTrition Risk in the Critically ill Score (NUTRIC Score). Variable Age APACHE II SOFA # Comorbidities Range <50 50-<75 >=75 <15 15-<20 20-28 >=28 <6 6-<10 >=10 0-1 2+ Points 0 1 2 0 1 2 3 0 1 2 0 1 Days from hospital to ICU admit 0-<1 1+ 0 1 IL6 0-<400 400+ 0 1 AUC Gen R-Squared Gen Max-rescaled R-Squared 0.783 0.169 0.256 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. Observed Model-based 40 20 n=12 n=33 0 1 n=55 n=75 n=90 n=114 n=82 n=72 n=46 n=17 2 3 4 5 6 7 8 9 n=2 0 Mortality Rate (%) 60 80 The Validation of the NUTrition Risk in the Critically ill Score (NUTRIC Score). Nutrition Risk Score 10 Observed Model-based 10 8 6 4 2 n=12 n=33 n=55 n=75 n=90 n=114 n=82 n=72 n=46 n=17 n=2 0 1 2 3 4 5 6 7 8 9 10 0 Days on Mechanical Ventilator 12 14 The Validation of the NUTrition Risk in the Critically ill Score (NUTRIC Score). Nutrition Risk Score The Validation of the NUTrition Risk in the Critically ill Score (NUTRIC Score). 1.0 Interaction between NUTRIC Score and nutritional adequacy (n=211)* 9 0.8 9 9 0.6 8 88 0.2 0.4 77 7 2 0 9 9 7 4 0.0 28 Day Mortality P value for the interaction=0.01 9 8888 7 7 7 8888 8 9 10 10 888 77 88 77 7 77 7 88 7 77 6 7 7777 6 66666 6 9 66666 6 6 66 6 666666666 666 6 6 66 7 5 555 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 4 4 3 5 55 555 55 555 55 5 5 5 44 4 43 4 4 4 2 4 4 4 3 44444444 33 444 4444 3 4 3 4 1 4 22 3 4 4 3 3 33 2 22 2 1 3 11 33 3 2 1 11 1 1 50 100 3 3 5 9 8 150 Nutrition Adequacy Levles (%) Heyland Critical Care 2011, 15:R28 • Multicenter prospective study of nutrition practice in abdominal surgery • All patients had nutrition screening, not all patients had peri op nutrition support • Benefit of nutrition support seen in NRS>5 compared to controls, no benefit seen in low risk patients (NRS<5). P=0.008 P=0.04 P=0.04 Patients with NRS >5 Who might benefit the most from nutrition therapy in the ICU? • High NUTRIC Score? • Clinical – BMI – Projected long length of stay • Others? Do we have a problem? Preliminary Results of INS 2011 Overall Performance: Kcals 120 % received/prescribed 100 84% 56% 80 60 40 15% 20 0 1 2 3 4 5 6 7 8 9 10 11 12 ICU Day Mean of All Sites Best Performing Site Worst Performing Site N=211 Nutritional Adequacy of High Risk Patients compared to Low Risk Patients Failure Rate % high risk patients who failed to meet minimal quality targets (80% overall energy adequacy) 91.2 75.6 78.1 87.0 79.9 75.1 69.8 Unpublished observations. Results of 2011 International Nutrition Survey (INS). Strategies to Maximize the Benefits and Minimize the Risks of EN • • • • feeding protocols motility agents elevation of HOB small bowel feeds weak evidence stronger evidence Canadian CPGs www.criticalcarenutrition.com Use of Nurse-directed Feeding Protocols Start feeds at 25 ml/hr > 250 ml •hold feeds •add motility agent Check Residuals q4h < 250 ml •advance rate by 25 ml •reassess q 4h •reassess q 4h “Should be considered as a strategy to optimize delivery of enteral nutrition in critically ill adult patients.” 2009 Canadian CPGs www.criticalcarenutrition.com The Impact of Enteral Feeding Protocols on Enteral Nutrition Delivery: Results of a multicenter observational study 80 60 40 Protocol 20 No Protocol 0 Calories from EN Total Calories P<0.05 • Time to start EN from ICU admission 41.2 in protocolized sites vs 57.1 hours in those without a protocol • Patients rec’ing motility agents 61.3% in protocolized sites vs 49.0% in those without P<0.05 Heyland JPEN 2010 Can we do better? The same thinking that got you into this mess won’t get you out of it! The Efficacy of Enhanced Protein-Energy Provision via the Enteral Route in Critically Ill Patients: The PEP uP Protocol! • • • • • • • 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 Nurse reports daily on nutritional adequacy. A Major Paradigm Shift in How we Feed Enterally The Efficacy of Enhanced Protein-Energy Provision via the Enteral Route in Critically Ill Patients: The PEP uP Protocol! Adequacy of Calories from EN (Before Group vs. After Group on Full Volume Feeds) P-value Day 1 0.08 Day 2 0.0003 Day 3 0.10 Day 4 0.19 Day 5 0.48 Day 6 0.18 Day 7 0.11 Total <0.0001 Heyland Crit Care 2010 100 100 Change of nutritional intake from baseline to followup of all the study sites (intervention group only) n ITT n Efficacy n FVF n E@Base 90 80 70 60 50 40 30 20 % protein received/prescribed 60 50 40 30 20 10 ITT Efficacy Full volume feeds Baseline intervention 0 10 ITT Efficacy Full volume feeds Baseline intervention 0 % calories received/prescribed 70 80 90 % calories received/prescribed 243 113 57 260 219 113 57 236 194 113 57 209 171 108 54 175 153 105 52 152 138 96 46 136 118 83 40 113 107 75 35 102 83 59 26 90 76 52 23 80 1 2 3 4 5 6 7 8 9 10 59 40 17 71 52 35 14 62 12 n ITT n Efficacy n FVF n E@Base 243 113 57 260 219 113 57 236 194 113 57 209 171 108 54 175 153 105 52 152 138 96 46 136 118 83 40 113 107 75 35 102 83 59 26 90 76 52 23 80 1 2 3 4 5 6 7 8 9 10 59 40 17 71 52 35 14 62 12 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! Early vs. Late Parenteral Nutrition in Critically ill Adults • 4620 critically ill patients • Results: • Randomized to early PN Late PN associated with – Rec’d 20% glucose 20 • 6.3% likelihood of early ml/hr then PN on day 3 discharge alive from ICU and hospital • OR late PN • Shorter ICU length of – D5W IV then PN on day stay (3 vs 4 days) 8 • Fewer infections (22.8 vs • All patients standard EN plus 26.2 %) ‘tight’ glycemic control • No mortality difference Cesaer NEJM 2011 Early vs. Late Parenteral Nutrition in Critically ill Adults • ? Applicability of data – No one give so much IV glucose in first few days – No one practice tight glycemic control • Right patient population? – – – – Majority (90%) surgical patients (mostly cardiac-60%) Short stay in ICU (3-4 days) Low mortality (8% ICU, 11% hospital) >70% normal to slightly overweight • Not an indictment of PN – Early group only rec’d PN for 1-2 days on average – Late group –only ¼ rec’d any PN Cesaer NEJM 2011 Lancet Dec 2012 Lancet Dec 2012 Lancet Dec 2012 Adult patients were eligible for enrollment within 24 hours of ICU admission if they were expected to remain in the ICU on the calendar day after enrollment, were considered ineligible for enteral nutrition by the attending clinician due to a shortterm relative contraindication and were not expected to PN or oral nutrition Doig, ANZICS, JAMA May 2013 Who were these patients? Overall, standard care group remained unfed for 2.8 days after randomization 40% of standard care group never rec’d any artificial nutrition; remained in ICU 3.5 days Intervention not intense enough? • 40% of both groups got EN (delayed) • 40% of standard care group got PN for an average of 3.0 days • Average PN use in early PN group was 6.0 days • Main inference: No harm by early PN (in contrast to EPaNIC) Doig, ANZICS, JAMA May 2013 What if you can’t provide adequate nutrition enterally? … to TPN or not to TPN, that is the question! •Case by case decision •Maximize EN delivery prior to initiating PN •Use early in high risk cases Start PEP UP within 24-48 hrs At 72 hrs YES >80% of Goal Calories? NO No Yes Anticipated Long Stay? High Risk? Carry on! Yes No Maximize EN with motility agents and small bowel feeding YES No Supplemental PN? Tolerating EN at 96 hrs? No problem NO Yes No problem The TOP UP Trial PN for 7 days Primary Outcome ICU patients BMI <25 BMI >35 Fed enterally R Stratified by: Site BMI Med vs Surg Control 60-day mortality Muscle Outcome Assessments in TOP UP • Measures of muscle mass and function – – – – – mitochondrial complex I activity US of femoral quad (baseline and follow up CTs when available) Hand grip strength 6 min walk test SF 36 (RP and PCS) Reliability of US measure of Quad Muscle Layer Thickness • 46 pairs of within operator measurements with an ICC of .98 • 73 pairs of operator 1 to operator 2 measurements with an ICC of .94. •There was a small but statistically significant difference between the operator 1 and 2 results Mean (operator 1-2) (95% CI) = -0.061 cm (0.100 to -0.022), p= 0.0028. Lancet 2009;273: In Conclusion • Health Care Associate Malnutrition is rampant • Not all ICU patients are the same in terms of ‘risk’ • Iatrogenic underfeeding is harmful in some ICU patients or some will benefit more from aggressive feeding (avoiding protein/calorie debt) • BMI and/or NUTRIC Score is one way to quantify that risk • Need to do something to reduce iatrogenic malnutrition in your ICU! – Audit your practice first! (JOIN International Critical Care Nutrition Survey in 2013) – PEP uP protocol in all – Selective use of small bowel feeds then sPN in high risk patients Questions?