6 A Continuous Quality Improvement Effort What ought to be done?RCTs, Systematic Reviews, and Evidence-based practice guidelinesHow to change?“KT strategies”What is done?Survey resultsWhat do we need to do differently?“Gaps” - site reports
7 Early and Adequate EN Best for the Patient! Role of Supplemental PN
8 Loss of Gut Epithelial Integrity Underlying Pathophysiology of Critical IllnessLoss of Gut Epithelial IntegrityINTESTINAL EPITHELIUMSIRSBacteriaDISTAL ORGAN INJURY(Lung, Kidneys)via thoracic ductlymphocytes
9 Disuse Causes Loss of Functional and Stuctural Integrity Increased Gut Permeability Characteristics : Time dependentCorrelation to disease severityConsequences: Risk of infectionRisk of MOFS
10 Feeding Supports Gastrointestinal Structure and Function Maintenance of gut barrier functionIncreased secretion of mucus, bile, IgAMaintenance of peristalsis and blood flowAttenuates oxidative stress and inflammationSupports GALTImproves glucose absorptionAlverdy (CCM 2003;31:598)Kotzampassi Mol Nutr Food Research 2009Nguyen CCM 2011
11 Effect of Early Enteral Feeding on the Outcome of Critically ill Mechanically Ventilated Medical PatientsRetrospective analysis of multiinstitutional database4049 patients requiring mech vent > 2 daysCategorized as “Early EN” if rec’d feeds within 48 hours of admission (n=2537, 63%)P=0.007P=0.02P=0.0005Artinian Chest 2006:129;960
12 Effect of Early Enteral Feeding on the Outcome of Critically ill Mechanically Ventilated Medical PatientsData evaluating the effect of n-3 FFAs on clinical outcomes is relatively sparse, and in this study, is confounded by the fact that they combined fish oils with antioxidants.Artinian Chest 2006:129;96012
13 Early EN (within 24-48 hrs of admission) is recommended! …associated with large reductions in infections and mortalityUpdated CPGs, see
14 Optimal Amount of Protein and Calories for Critically Ill Patients
16 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 continentsIncluded ventilated adult patients who remained in ICU >72 hours
18 for increase of 1000 cal/day, OR of infection at 28 days Effect of Increasing Amounts of Calories from EN on Infectious ComplicationsMulticenter observational study of 207 patients >72 hrs in ICU followed prospectively for development of infectionfor increase of 1000 cal/day, OR of infection at 28 daysHeyland Clinical Nutrition 2010
19 Relationship between increased nutrition intake and physical function (as defined by SF-36 scores) following critical illnessFor every 1000 kcal/day received:Model *Estimate (CI)P valuesAt 3 monthsPHYSICAL FUNCTIONING3.2 (-1.0, 7.3) P=0.14ROLE PHYSICAL4.2 (-0.0, 8.5)P=0.05STANDARDIZED PHYSICAL COMPONENT SCALE1.8 (0.3, 3.4)P=0.02At 6 months0.8 (-3.6, 5.1)P=0.732.0 (-2.5, 6.5)P=0.380.70 (-1.0, 2.4)P=0.41for increase of 30 gram/day, OR of infection at 28 daysUnpublished data from Multicenter RCT of glutamine and antioxidants(REDOXS Study); n=364
24 Methods to Determine Energy Requirements 60% Weight based39% Complex formula1% Indirect calorimetryUnpublished observations INS 2011
25 Small intestinal glucose absorption in the critically ill and health ICU patientsn = 28Healthy subjectsn = 16Median (IQR)3-OMG(mmol/L)P<0.05glucose absorption (using 3-OMG as a marker; 3-OMG absorbed via same transporters as glucose, but renally excreted. Acccordingly, this OVERESTIMATES glucose absorption in the critically ill.Time (mins)Deane, et al. Crit. Care Med .(2011)
26 Malabsorption studies: faeces Strack van Schijndel, et al. Clin. Nutr. 2006
27 More (and Earlier) is Better! If you feed them (better!)They will leave (sooner!)
29 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 auditSetting: 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
30 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.*D. In ICU at least 12 days prior to permanent progression to exclusive oral feeding*Remove the 1/3-2/3 data*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.
31 Association Between 12-day Caloric Adequacy and 60-Day Hospital Mortality Optimal amount=80-85%Heyland CCM 2011
32 RCT Level of Evidence that More EN= Improved Outcomes RCTs of aggressive feeding protocolsResults in better protein-energy intakeAssociated with reduced complications and improved survivalTaylor et al Crit Care Med 1999; Martin CMAJ 2004Meta-analysis of Early vs Delayed ENReduced infections: RR 0.76 (.59,0.98),p=0.04Reduced Mortality: RR 0.68 (0.46, 1.01) p=0.06
33 More (and Earlier) is Better! If you feed them (better!)They will leave (sooner!)
36 Still no measure of physical function! Rice et al. JAMA 2012;307
37 Enrolled 12% of patients screened Rice et al. JAMA 2012;307
38 No effect in young, healthy, overweight patients who have short stays! Trophic vs. Full enteral feeding in critically ill patients with acute respiratory failureAverage age 52Few comorbiditiesAverage BMI 29-30All fed within 24 hrs (benefits of early EN)Average duration of study intervention 5 daysNo effect in young, healthy, overweight patients who have short stays!
39 ICU patients are not all created equal…should we expect the impact of nutrition therapy to be the same across all patients?
40 How do we figure out who will benefit the most from Nutrition Therapy? Need picture of malnourshed child
41 A Conceptual Model for Nutrition Risk Assessment in the Critically Ill ChronicRecent weight lossBMI?AcuteReduced po intakepre ICU hospital stayStarvationNutrition Statusmicronutrient levels - immune markers - muscle massInflammationAcuteIL-6CRPPCTChronicComorbid illness
42 Multi institutional data base of 598 patients The Development of the NUTrition Risk in the Critically ill Score (NUTRIC Score).When adjusting for age, APACHE II, and SOFA, what effect of nutritional risk factors on clinical outcomes?Multi institutional data base of 598 patientsHistorical po intake and weight loss only available in 171 patientsOutcome: 28 day vent-free days and mortalityHeyland Critical Care 2011, 15:R28
43 What are the nutritional risk factors associated with clinical outcomes? (validation of our candidate variables)Non-survivors by day 28(n=138)Survivors by day 28(n=460)p valuesAge71.7 [60.8 to 77.2]61.7 [49.7 to 71.5]<.001Baseline APACHE II score26.0 [21.0 to 31.0]20.0 [15.0 to 25.0]Baseline SOFA9.0 [6.0 to 11.0]6.0 [4.0 to 8.5]# of days in hospital prior to ICU admission0.9 [0.1 to 4.5]0.3 [0.0 to 2.2]Baseline Body Mass Index26.0 [22.6 to 29.9]26.8 [23.4 to 31.5]0.13Body Mass Index0.66<206 ( 4.3%)25 ( 5.4%)≥20122 ( 88.4%)414 ( 90.0%)# of co-morbidities at baseline3.0 [2.0 to 4.0]3.0 [1.0 to 4.0]<0.001Co-morbidityPatients with 0-1 co-morbidity20 (14.5%)140 (30.5%)Patients with 2 or more co-morbidities118 (85.5%)319 (69.5%)C-reactive protein¶135.0 [73.0 to 214.0]108.0 [59.0 to 192.0]0.07Procalcitionin¶4.1 [1.2 to 21.3]1.0 [0.3 to 5.1]Interleukin-6¶158.4 [39.2 to ]72.0 [30.2 to 189.9]171 patients had data of recent oral intake and weight loss(n=32)(n=139)% Oral intake (food) in the week prior to enrolment4.0[ to ]50.0[ to ]0.10% of weight loss in the last 3 month0.0[ to ]0.0[ to ]0.06
44 The Development of the NUTrition Risk in the Critically ill Score (NUTRIC Score). VariableRangePointsAge<5050-<751>=752APACHE II<1515-<2020-28>=283SOFA<66-<10>=10# Comorbidities0-12+Days from hospital to ICU admit0-<11+IL60-<400400+AUC0.783Gen R-Squared0.169Gen Max-rescaled R-Squared 0.256BMI, 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.
45 The Validation of the NUTrition Risk in the Critically ill Score (NUTRIC Score).
46 The Validation of the NUTrition Risk in the Critically ill Score (NUTRIC Score).
47 Interaction between NUTRIC Score and nutritional adequacy (n=211)* 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=0.01Heyland Critical Care 2011, 15:R28
48 Who might benefit the most from nutrition therapy? High NUTRIC Score?ClinicalBMIProjected long length of stayOthers?
53 “Use of a feeding protocol that incorporates motility agents and small bowel feeding tubes should be considered”
54 Use of Nurse-directed Feeding Protocols Start feeds at 25 ml/hr< 250 mladvance rate by 25 mlreassess q 4h> 250 mlhold feedsadd motility agentreassess q 4hCheck Residuals q4h“Should be considered as a strategy to optimize delivery of enteral nutrition in critically ill adult patients.”2009 Canadian CPGs
55 Time to start EN from ICU admission: The Impact of Enteral Feeding Protocols on Enteral Nutrition Delivery: Results of a multicenter observational studyP<0.05Time to start EN from ICU admission:41.2 in protocolized sites vs 57.1 hours in those without a protocolPatients rec’ing motility agents:61.3% in protocolized sites vs 49.0% in those withoutP<0.05Heyland JPEN Nov 2010
56 The same thinking that got you into this mess won’t get you out of it! Can we do better?The same thinking that got you into this mess won’t get you out of it!
57 Daren K. Heyland Enhanced Protein-Energy Provision via the Enteral Routein Critically Ill Patients:The PEP uP ProtocolDaren K. HeylandProfessor of MedicineQueen’s University, Kingston General HospitalKingston, ON Canada
58 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!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 polymericTolerate higher GRV threshold (300 ml or more)Motility agents and protein supplements are started immediatelyNurse reports daily on nutritional adequacy.A Major Paradigm Shift in How we Feed Enterally
59 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)Day 1Day 2Day 3Day 4Day 5Day 6Day 7TotalP-value0.080.00030.100.190.480.180.11<0.0001Heyland Crit Care 2010
60 % calories received/prescribed Change of nutritional intake from baseline to follow-up of all the study sites (intervention group only)% calories received/prescribedHeyland CCM 2013 (in press)
61 Other Strategies to Maximize the Benefits and Minimize the Risks of EN Liberalization of gastric residual volumesMotility agents started at initiation of EN rather that waiting till problems with High GRV develop.Small bowel feeding tubesElevation of head of the bedHave nurse report on nutritional adquacy during daily ward rounds
62 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!
63 Early vs. Late Parenteral Nutrition in Critically ill Adults 4620 critically ill patientsRandomized to early PNRec’d 20% glucose 20 ml/hr then PN on day 3OR late PND5W IV then PN on day 8All patients standard EN plus ‘tight’ glycemic controlResults:Late PN associated with6.3% likelihood of early discharge alive from ICU and hospitalShorter ICU length of stay (3 vs 4 days)Fewer infections (22.8 vs 26.2 %)No mortality differenceCesaer NEJM 2011
64 Early vs. Late Parenteral Nutrition in Critically ill Adults ? Applicability of dataNo one give so much IV glucose in first few daysNo one practice tight glycemic controlRight 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 overweightNot an indictment of PNEarly group only rec’d PN for 1-2 days on averageLate group –only ¼ rec’d any PNCesaer NEJM 2011
68 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 short-term relative contraindication and were not expected to PN or oral nutritionDoig, ANZICS, JAMA May 2013
69 Who were these patients? Overall, standard care group remained unfed for 2.8 days after randomization40% of standard care group never rec’d any artificial nutrition; remained in ICU 3.5 days
70 Intervention not intense enough? 40% of both groups got EN (delayed)40% of standard care group got PN for an average of 3.0 daysAverage PN use in early PN group was 6.0 days
71 Main inference: No harm by early PN (in contrast to EPaNIC) Doig, ANZICS, JAMA May 2013
72 What if you can’t provide adequate nutrition enterally? … to TPN or not to TPN,that is the question!Case by case decisionMaximize EN delivery prior to initiating PNUse early in high risk cases
73 Start PEP UP within 24-48 hrs At 72 hrs>80% of Goal Calories?YESNoNOYesAnticipated Long Stay?High Risk?YesCarry on!NoMaximize EN with motility agents and small bowel feedingNo problemYESYesNOTolerating EN at 96 hrs?NoSupplemental PN?No problem
74 R The TOP UP Trial Primary Outcome 60-day mortality PN for 7 days Stratified by:SiteBMIMed vs SurgICU patientsRBMI <2560-day mortalityBMI >35Fed enterallyControl
75 Muscle Outcome Assessments in TOP UP Measures of muscle mass and functionmitochondrial complex I activityUS of femoral quad (baseline and follow up CTs when available)Hand grip strength6 min walk testSF 36 (RP and PCS)
76 Reliability of US measure of Quad Muscle Layer Thickness 46 pairs of within operator measurements with an ICC of .9873 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) = cm ( to ), p=
78 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 riskNeed to do something to reduce iatrogenic malnutrition in your ICU!Audit your practice first!PEP uP protocol in allSelective use of small bowel feeds then sPN in high risk patients