Optimal Provision of EN Nutrition in the ICU Daren K. Heyland Professor of Medicine Queen’s University, Kingston General Hospital Kingston, ON Canada Add pep up slides

Early and Adequate Nutrition is therapy that modulates the underlying disease process and impacts patient outcomes Adjunctive Supportive Care Proactive Primary Therapy

 Caloric debt associated with: Increasing Calorie Debt Associated with worse Outcomes Caloric Debt Adequacy of EN  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

Early vs. Delayed EN: Effect on Infectious Complications R-make sure up to date. DONE Updated 2009 www.criticalcarenutrition.com

Early vs. Delayed EN: Effect on Mortality R- make sure up to date. DONE Updated 2009 www.criticalcarenutrition.com

Feeding the Hypotensive Patient? Prospectively collected multi-institutional ICU database of 1,174 patients who required mechanical ventilation for more than two days and were on vasopressor agents to support blood pressure. The beneficial effect of early feeding is more evident in the sickest patients, i.e, those on multiple vasopressor agents. DiGiovine et al. AJCC 2010

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

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

Hypothesis There is a relationship between amount of energy and protein received and clinical outcomes (mortality and # of days on ventilator) The relationship is influenced by nutritional risk BMI is used to define chronic nutritional risk

What Study Patients Actually Rec’d Average Calories in all groups: 1034 kcals and 47 gm of protein Result: Average caloric deficit in Lean Pts: 7500kcal/10days Average caloric deficit in Severely Obese: 12000kcal/10days

Relationship Between Increased Calories and 60 day Mortality BMI Group Odds Ratio 95% Confidence Limits P-value Overall 0.76 0.61 0.95 0.014 <20 0.52 0.29 0.033 20-<25 0.62 0.44 0.88 0.007 25-<30 1.05 0.75 1.49 0.768 30-<35 1.04 0.64 1.68 0.889 35-<40 0.36 0.16 0.80 0.012 >=40 0.63 0.32 1.24 0.180 Legend: Odds of 60-day Mortality per 1000 kcals received per day adjusting for nutrition days, BMI, age, admission category, admission diagnosis and APACHE II score.

Relationship Between Increased Energy and Ventilator-Free days BMI Group Adjusted Estimate 95% CI P-value LCL UCL Overall 3.5 1.2 5.9 0.003 <20 2.8 -2.9 8.5 0.337 20-<25 4.7 1.5 7.8 0.004 25-<30 0.1 -3.0 3.2 0.958 30-<35 -1.5 -5.8 2.9 0.508 35-<40 8.7 2.0 15.3 0.011 >=40 6.4 -0.1 12.8 0.053 Legend: # of VFD per 1000 kcals received per day adjusting for nutrition days, BMI, age, admission category, admission diagnosis and APACHE II score.

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

for increase of 30 gram/day, OR of infection at 28 days 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 gram/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 Multicenter RCT of glutamine and antioxidants (REDOXS Study) First 364 patients with SF 36 at 3 months and/or 6 months Model * Estimate (CI) P values (B) Increased protein intake PHYSICAL FUNCTIONING (PF) at 3 months 2.9 (-0.7, 6.6) P=0.11 ROLE PHYSICAL (RP) at 3 months 4.4 (0.7, 8.1) P=0.02 STANDARDIZED PHYSICAL COMPONENT SCALE (PCS) at 3 months 1.9 (0.5, 3.2) P=0.007 PHYSICAL FUNCTIONING (PF) at 6 months 0.2 (-3.9, 4.3) P=0.92 ROLE PHYSICAL (RP) at 6 months 1.7 (-2.5, 5.9) P=0.43 STANDARDIZED PHYSICAL COMPONENT SCALE (PCS) at 6 months 0.7 (-0.9, 2.2) P=0.39 for increase of 30 gram/day, OR of infection at 28 days Heyland Unpublished Data

More (and Earlier) is Better! If you feed them (better!) They will leave (sooner!)

Permissive Underfeeding (Starvation)? 187 critically ill patients Tertiles according to ACCP recommended levels of caloric intake Highest tertile (>66% recommended calories) vs. Lowest tertile (<33% recommended calories)  in hospital mortality  Discharge from ICU breathing spontaneously Middle tertile (33-65% recommended calories) vs. lowest tertile Discharge from ICU breathing spontaneously Krishnan et al Chest 2003

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

Optimal Amount of Calories for Critically Ill Patients: Depends on how you slice the cake! Sample restriction approaches have included limiting analyzed patients to those: In the ICU for at least 96 hours, In the ICU at least 96 hours prior to progression to exclusive oral feeding and Eliminating days after progression to exclusive oral feeding from the calculation of nutrition intake. Statistical adjustment approaches have included using regression techniques to adjust for: ICU length of stay (LOS), Evaluable nutrition days and Relevant baseline patient characteristics or some combination thereof. 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.* 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.

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

Trophic vs. Full enteral feeding in critically ill patients with acute respiratory failure Single center study of 200 mechanically ventilated patients Trophic feeds: 10 ml/hr x 5 days Rice CCM 2011;39:967

Did not measure infection nor physical function! Trophic vs. Full enteral feeding in critically ill patients with acute respiratory failure Did not measure infection nor physical function! Rice CCM 2011;39:967

Trophic vs. Full enteral feeding in critically ill patients with acute respiratory failure “survivors who received initial full-energy enteral nutrition were more likely to be discharged home with or without help as compared to a rehabilitation facility (68.3% for the full-energy group vs. 51.3% for the trophic group; p = .04).” Rice CCM 2011;39:967

Trophic vs. Full enteral feeding in critically ill patients with acute respiratory failure Average age 51 Few comorbidities Average BMI 29 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! Large multicenter trial of this concept (EDEN study) by ARDSNET just finished

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? Need picture of malnourshed child

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

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 patients Historical po intake and weight loss only available in 171 patients Outcome: 28 day vent-free days and mortality Heyland Critical Care 2011, 15:R28

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 values Age 71.7 [60.8 to 77.2] 61.7 [49.7 to 71.5] <.001 Baseline APACHE II score 26.0 [21.0 to 31.0] 20.0 [15.0 to 25.0] Baseline SOFA 9.0 [6.0 to 11.0] 6.0 [4.0 to 8.5] # of days in hospital prior to ICU admission 0.9 [0.1 to 4.5] 0.3 [0.0 to 2.2] Baseline Body Mass Index 26.0 [22.6 to 29.9] 26.8 [23.4 to 31.5] 0.13 Body Mass Index 0.66 <20 6 ( 4.3%) 25 ( 5.4%) ≥20 122 ( 88.4%) 414 ( 90.0%) # of co-morbidities at baseline 3.0 [2.0 to 4.0] 3.0 [1.0 to 4.0] <0.001 Co-morbidity Patients with 0-1 co-morbidity 20 (14.5%) 140 (30.5%) Patients with 2 or more co-morbidities 118 (85.5%) 319 (69.5%) C-reactive protein¶ 135.0 [73.0 to 214.0] 108.0 [59.0 to 192.0] 0.07 Procalcitionin¶ 4.1 [1.2 to 21.3] 1.0 [0.3 to 5.1] Interleukin-6¶ 158.4 [39.2 to 1034.4] 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 enrolment 4.0[ 1.0 to 70.0] 50.0[ 1.0 to 100.0] 0.10 % of weight loss in the last 3 month 0.0[ 0.0 to 2.5] 0.0[ 0.0 to 0.0] 0.06

Spearman correlation with VFD within 28 days Number of observations What are the nutritional risk factors associated with clinical outcomes? (validation of our candidate variables) Variable Spearman correlation with VFD within 28 days p values Number of observations Age -0.1891 <.0001 598 Baseline APACHE II score -0.3914 Baseline SOFA -0.3857 594 % Oral intake (food) in the week prior to enrollment 0.1676 0.0234 183 number of days in hospital prior to ICU admission -0.1387 0.0007 % of weight loss in the last 3 month -0.1828 0.0130 184 Baseline BMI 0.0581 0.1671 567 # of co-morbidities at baseline -0.0832 0.0420 Baseline CRP -0.1539 0.0002 589 Baseline Procalcitionin -0.3189 582 Baseline IL-6 -0.2908 581

The Development of the NUTrition Risk in the Critically ill Score (NUTRIC Score). For example, exact quintiles and logistic parameters for age Exact Quintile Parameter Points 19.3-48.8 referent 48.9-59.7 0.780 1 59.7-67.4 0.949 67.5-75.3 1.272 75.4-89.4 1.907 2

The Development of the NUTrition Risk in the Critically ill Score (NUTRIC Score). Variable Range Points Age <50 50-<75 1 >=75 2 APACHE II <15 15-<20 20-28 >=28 3 SOFA <6 6-<10 >=10 # Comorbidities 0-1 2+ Days from hospital to ICU admit 0-<1 1+ IL6 0-<400 400+ AUC 0.783 Gen R-Squared 0.169 Gen Max-rescaled R-Squared  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.

The Validation of the NUTrition Risk in the Critically ill Score (NUTRIC Score).

The Validation of the NUTrition Risk in the Critically ill Score (NUTRIC Score).

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=0.01 Heyland Critical Care 2011, 15:R28

Who might benefit the most from nutrition therapy? High NUTRIC Score? Clinical BMI Projected long length of stay Others?

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!

Aggressive Gastric Feeding may be a BAD THING! Observational study of 153 medical/surgical ICU patients receiving EN in stomach Intolerance= residual volume>500ml, vomiting, or residual volume 150-500x2. Patients followed for development of VAP (diagnosed invasively) Mentec CCM 2001;29:1955

Aggressive Gastric Feeding may be a BAD THING! Incidence of Intolerance= 46% Statistically associated with worse clinical outcomes! Risk factors for Intolerance Sedation Catecholamines High residuals before and during EN

Strategies to Maximize the Benefits and Minimize the Risks of EN weak evidence feeding protocols motility agents elevation of HOB small bowel feeds stronger evidence Canadian CPGs www.criticalcarenutrition.com

Rupinder to update “Use of a feeding protocol that incorporates motility agents and small bowel feeding tubes should be considered” www.criticalcarenutrition.com

Use of Nurse-directed Feeding Protocols Start feeds at 25 ml/hr < 250 ml advance rate by 25 ml reassess q 4h > 250 ml hold feeds add motility agent reassess q 4h Check Residuals q4h “Should be considered as a strategy to optimize delivery of enteral nutrition in critically ill adult patients.” 2009 Canadian CPGs www.criticalcarenutrition.com

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15.2% using the recommended threshold volume of 250 ml The Impact of Enteral Feeding Protocols on Enteral Nutrition Delivery: Results of a multicenter observational study Characteristics Total n=269 Feeding Protocol Yes 208 (78%) Gastric Residual Volume Tolerated in Protocol Mean (range) 217 ml (50, 500) Elements included in Protocol Motility agents 68.5% Small bowel feeding 55.2% HOB Elevation 71.2 % 15.2% using the recommended threshold volume of 250 ml Heyland JPEN Nov 2010

Time to start EN from ICU admission: Patients rec’ing motility agents: The Impact of Enteral Feeding Protocols on Enteral Nutrition Delivery: Results of a multicenter observational study 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

Reasons for Inadequate Intake Slow starts and slow ramp ups Interruptions Mostly related to procedures Not related to GI dysfunction Can be overcome by better feeding protocols Impaired motility Medications Metabolic, electrolyte abnormalities Underlying disease Prophylactic use of motility agents

Initial Efficacy and Tolerability of Early Enteral Nutrition with Immediate or Gradual Introduction in Intubated Patients This study randomized 100 mechanically ventilated patients (not in shock) to Immediate goal rate vs gradual ramp up (our usual standard). The immediate goal group rec’d more calories with no increase in complications Desachy ICM 2008;34:1054

Initial Efficacy and Tolerability of Early Enteral Nutrition with Immediate or Gradual Introduction in Intubated Patients Desachy ICM 2008;34:1054

What Gastric Residual Volume Threshold Should I use? 329 patients randomized to GRV 200 vs. 500 >80% Medical Average APACHE II 18 Similar nutritional adequacy: 85 vs 88% goal calories

Protocol to Manage Interruptions to EN due to non-GI Reasons Add slide on interrruptions to EN re procedures. Can be downloaded from www.criticalcarenutrition.com

Other Strategies to Maximize the Benefits and Minimize the Risks of EN Head of Bed elevation to 45 (or at least 30 if the patient doesn’t tolerate 45) This will reduce regurgitation, aspiration and subsequent Pneumonia List of Contraindications to HOB Elevation unstable c-spine hemodynamically unstable Pelvic fractures with instability Prone position Intra-aortic ballon pump Procedures Unable because of obesity

Other Strategies to Maximize the Benefits and Minimize the Risks of EN Impaired motility Medications Metabolic, electrolyte abnormalities Underlying disease Dysmotility linked to decreased tolerance of EN gastropulmonary route of infection Trials of Cisapride, Erythromycin, Metoclopramide,

2009 Canadian CPGs www.criticalcarenutrition.com Pro-motility Agents Conclusion: 1) Motility agents have no effect on mortality or infectious complications in critically ill patients. 2) Motility agents may be associated with an increase in gastric emptying, a reduction in feeding intolerance and a greater caloric intake in critically ill patients. “Based on 1 level 1 study and 5 level 2 studies, in critically ill patients who experience feed intolerance (high gastric residuals, emesis), we recommend the use of a promotility agent. Given the safety concerns associated with erythromycin, the recommendation is made for metoclopramide. There are insufficient data to make a recommendation about the use of combined use of metoclopramide and erythromycin.” 2009 Canadian CPGs www.criticalcarenutrition.com

Other Strategies to Maximize the Benefits and Minimize the Risks of EN Motility agents started at initiation of EN rather that waiting till problems with High GRV develop. Maxeran 10 mg IV q 6h (halved in renal failure) If still develops high gastric residuals, add Erythromycin 200 mg q 12h. Can be used together for up to 7 days but should be discontinued when not needed any more Reassess need for motility agents daily

Daren K. Heyland Enhanced Protein-Energy Provision via the Enteral Route in Critically Ill Patients: The PEP uP Protocol Daren K. Heyland Professor of Medicine Queen’s University, Kingston General Hospital Kingston, ON Canada

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! 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. A Major Paradigm Shift in How we Feed Enterally Heyland Crit Care 2010

% calories received/prescribed Change of nutritional intake from baseline to follow-up of all the study sites (Efficacy Analysis) % calories received/prescribed 61

% protein received/prescribed Change of nutritional intake from baseline to follow-up of all the study sites (Efficacy Analysis) % protein received/prescribed 62

Small Bowel vs. Gastric Feeding: A meta-analysis Other Strategies to Maximize the Benefits and Minimize the Risks of EN Small Bowel vs. Gastric Feeding: A meta-analysis Effect on VAP Updated 2011,www.criticalcarenutrition.com

Does Postpyloric Feeding Reduce Risk of GER and Aspiration? Tube Position # of patients % positive for GER % positive for Aspiration Stomach 21 32 5.8 D1 8 27 4.1 D2 3 11 1.8 D4 1 5 Total 33 75 11.7 P=0.004 P=0.09 Heyland CCM 2001;29:1495-1501

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!

Critical Care Nutrition CPGs Canadians Maximize EN (motility agents, small bowel feeds, etc.) prior to starting PN. Americans If unable to meet energy requirements after 7-10 days by the enteral route, consider initiating PN. Initiating PN prior to this 7-10 day period does not improve outcome and may be detrimental to the patient. Europeans All patient who are not expected to be on normal nutrition within 3 days should receive PN within 24-48 hours if EN is contraindicated or if they can not tolerate adequate amounts of EN.

Early vs. Late Parenteral Nutrition in Critically ill Adults 4620 critically ill patients Randomized to early PN Rec’d 20% glucose 20 ml/hr then PN on day 3 OR late PN D5W IV then PN on day 8 All patients standard EN plus ‘tight’ glycemic control Results: Late PN associated with 6.3% likelihood of early discharge alive from ICU and hospital Shorter ICU length of stay (3 vs 4 days) Fewer infections (22.8 vs 26.2 %) 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

Maximize EN delivery prior to initiating PN 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

R The TOP UP Trial Primary Outcome 60-day mortality PN for 7 days Stratified by: Site BMI Med vs Surg ICU patients R BMI <25 60-day mortality BMI >35 Fed enterally Control

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! Consider updating your feeding protocol!

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