Critical Care Nutrition A Case Study of Creating Knowledge and Moving it into Action! Daren K. Heyland Director of Clinical Evaluation Research Unit Queen’s University, Kingston General Hospital Kingston, ON Canada HARD TO READ YOUR NAME

Learning Objectives Understand key components of moving ‘knowledge’ into action List main updates of Canadian Critical Care Nutrition Guidelines

Learning Objectives Insert pic of me at home

Critical Care Nutrition The right nutrient/nutritional strategy The right timing The right patient The right intensity (dose/duration) With the right outcome! www.criticalcarenutrition.com

Lost in (Knowledge) Translation! Knowledge to Action Model by Graham Heyland DK, Cahill N, Dhaliwal R JPEN Nov 2010

Knowledge Creation

On behalf of the REDOXS Study Investigators A RANDOMIZED TRIAL OF HIGH-DOSE GLUTAMINE AND ANTIOXIDANTS IN CRITICALLY ILL PATIENTS WITH MULTIORGAN FAILURE   The REDOXS study On behalf of the REDOXS Study Investigators N Engl J Med 2013;368:1489-97.

R R R The REDOXS study antioxidants glutamine 1200 ICU patients Factorial 2x2 design Double blind treatment glutamine R 1200 ICU patients R Concealed Stratified by site Evidence of placebo Multi-organ failure antioxidants placebo R placebo

The Research Protocol Inclusion Criteria Adults (>18) With 2 or more organ failures related to their acute illness : Requiring mechanically ventilation (P/F<300) Clinical evidence of hypoperfusion defined by need for vasopressor agents for more than 2 hour Renal dysfunction : Cr>171 or <500ml/24 hrs platelet < 50

High dose associated with Optimizing the Dose of Glutamine Dipeptides and Antioxidants In Critically Ill Patients: A Phase I dose finding study Parenterally Enterally Glutamine/day 0.35 gms/kg 30 gms Antioxidants per day 500 mcg Selenium Vit C 1500 mg Vit E 500 mg B carotene 10 mg Zinc 20 mg Se 300 ug High dose appears safe High dose associated with no worsening of SOFA Scores greater resolution of oxidative stress greater preservation of glutathione Improved mitochondrial function Heyland JPEN Mar 2007

Mortality Outcomes Note: all P values pertain to GLN vs No GLN; no significant differences between AOX vs. No AOX

Other Clinical Outcomes No differences between groups SOFA Need for dialysis Duration of mechanical ventilation PODS infections ICU and Hospital LOS

Post-hoc Secondary Analyses

Adjusted Analysis The 28-day mortality rates in the placebo, glutamine, antioxidant and combination groups were 25%, 32%, 29% and 33% respectively. Compared to placebo, the unadjusted OR (95% CI) of mortality was Glutamine 1.4 (1.0-2.0, P =0.063), Antioxidant 1.2 (0.8-1.7, P =0.31), Both 1.4 (1.0-2.0, P=0.049). After adjusting for all statistically significant baseline characteristics, the corresponding adjusted ORs remained virtually unchanged at: Glutamine 1.4 (1.0-2.1, P =0.054) Antioxidant 1.2(0.8-1.8, P =0.34) Both 1.4 (0.9-2.0, P =0.10)

Selected Subgroup Analyses   OR (95% CI) compared to placebo P-values* Subgroup Deaths/n (%) GLN alone AOX alone GLN+AOX Overall 363/1218 (30%) 1.40 (0.98-2.00) 1.20 (0.84-1.72) 1.42 (1.00-2.03) Study Setting Region 0.37 Canada 303/1044 (29%) 1.41 (0.96-2.07) 1.14 (0.77-1.67) 1.29 (0.88-1.89) USA 44/131 (34%) 1.56 (0.51-4.81) 1.43 (0.47-4.38) 3.43 (1.17-10.07) Europe 16/43 (37%) 0.86 (0.12-5.9) 2.40 (0.39-14.88) 0.89 (0.14-5.48) Baseline Patient Characteristics Admission category 0.52 Surgical 59/255 (23%) 2.16 (0.91-5.15) 1.94 (0.78-4.82) 1.58 (0.67-3.76) Medical 304/963 (32%) 1.28 (0.87-1.89) 1.08 (0.73-1.60) 1.43 (0.97-2.12) Cancer patients 0.74 No 297/1048 (28%) 1.48 (1.01-2.18) 1.15 (0.77-1.71) 1.42 (0.97-2.10) Yes 66/170 (39%) 1.05 (0.41-2.73) 1.43 (0.60-3.40) 1.38 (0.58-3.27) Etiology of Shock 0.71 Cardiogenic 74/240 (31%) 1.24 (0.56-2.79) 1.62 (0.75-3.51) 2.19 (1.03-4.67) Septic 256/826 (31%) 1.43 (0.93-2.19) 1.06 (0.69-1.63) 1.21 (0.79-1.86) Other/Unkown/None 33/152 (22%) 1.45 (0.46-4.57) 1.45 (0.43-4.86) 1.83 (0.60-5.78) Vasopressors <15 mcg/min 162/595 (27%) 1.58 (0.92-2.70) 1.66 (0.97-2.84) 1.50 (0.87-2.58) >=15 mcg/min 201/623 (32%) 1.32 (0.82-2.13) 0.92 (0.57-1.51) 1.39 (0.87-2.22) Renal dysfunction 0.035 216/776 (28%) 0.93 (0.59-1.46) 0.90 (0.58-1.40) 1.14 (0.74-1.77) 147/442 (33%) 2.75 (1.50-5.03) 2.16 (1.15-4.07) 2.15 (1.17-3.94) OR-odds ratio; CI-confidence interval; GLN-Glutamine; AOX-antioxidants

Conclusions Glutamine and antioxidants at doses studied in this study do not improve clinical outcomes in critically ill patients with multi-organ failure Glutamine may be harmful For both glutamine and antioxidants, the greatest signal of harm was in patients with multi-organ failure that included renal dysfunction upon study enrollment.

A RandomizEd trial of ENtERal Glutamine to minimIZE thermal injury Double blind treatment EN glutamine 2700 Burn Injury patients R 6 month mortality Concealed Stratified by site placebo

SodiUm SeleniTe Adminstration IN Cardiac Surgery (SUSTAIN CSX®-trial) Double blind treatment IV Selenium Alive and free of POD Or Time to freedom from life-sustain treatments 1400 high-risk patients undergoing cardiac surgery R Concealed Stratified by site placebo

Knowledge To Action Model Knowledge Synthesis Knowledge To Action Model Since 1980, 275 randomized trials of nutrition interventions studying >2000 critically ill patients Rupinder, please update the number of RCTs: done n = 275 RCTs!

Knowledge – To- Action Model Knowledge Synthesis Knowledge – To- Action Model Systematic reviews and meta-analyses of 45 nutrition related topics Please update numbers..done! n = 45 topics

What does the evidence show about Alternative Lipid Emulsions in the Critically Ill?

Therapeutic Options for PN Lipids Soybean Oil (ω-6) PN without Lipids Olive Oil (ω-9) MCT Fish Oils (ω-3) More Pro-Inflammatory Less Pro-Inflammatory

Overall effect on Mortality of ω-6 Reducing Strategy (n= 12 RCT) Ω-6 Sparing Strategies were associated with a reduction in Mortality (RR= 0.83, 95 % CI 0.62, 1.11, P= 0.20, heterogeneity I2 =0%) Manzanares W, et al. Int Care Med 2013

Overall effect on Ventilation Days (n= 5 RCT) Ω-6 Sparing Strategies were associated with a trend towards a reduction in Ventilation Days (WMD -2.57, 95% CI -5.51, 0.37, P=0.09) Manzanares W, et al. Int Care Med 2013

Overall effect on ICU Length of Stay (n= 8 RCT) Ω-6 Reducing Strategies were associated with a trend towards a reduction in ICU LOS (WMD -2.31, 95% CI -5.28, 0.66, P=0.13) Manzanares W, et al. Int Care Med 2013

Canadian Clinical Practice Guidelines in 2013 February 10th 2012 PN Type of Lipids 2009 Recommendation There are insufficient data to make a recommendation on the type of lipids to be used in critically ill patients receiving parenteral nutrition. 2013 Recommendation: IV lipids that reduce the load of omega-6 fatty acids/soybean oil emulsions should be considered. There are insufficient data on type of soybean reducing lipids Rupinder Dhaliwal

Which Alternative Lipid Emulsion to Use? No head to head trials (and not likely to be) We analyzed our International Nutrition Survey database to evaluate effect of Alternative Lipids on outcomes. Analyzed adjusted for key confounding variables. Edmunds CCM 2014 epub

Which Alternative Lipid Emulsion to Use? Edmunds CCM 2014 epub

Which Alternative Lipid Emulsion to Use? Fish Oil Olive Oil Lipid Free MCT Soybean Edmunds CCM 2014 epub

Clinical Practice Guidelines Knowledge – To- Action Model Development of Critical Care Nutrition Clinical Practice Guidelines

Clinical Practice Guidelines for Nutrition published initially in 2003 updated 2005, 2007, 2009 and 2013

How to Narrow the Gap? First Define the Gap International audits of nutrition practice

Objectives of International Survey Quality Improvement To determine current nutrition practice in the adult critical care setting (overall and subgroups) Illuminate gaps between best practice and current practice To identify nutrition practices to target for quality improvement initiatives Generate New Knowledge To determine factors associated with optimal provision of nutrition To determine what nutrition practices are associated with best clinical outcomes

Australia & New Zealand: 36 Participation: INS 2013 202 ICUs 26 nations 4040 patients 37,872 days Canada: 24 Europe & Africa: 35 Asia: 41 USA: 52 Japan: 21 India: 9 Singapore: 5 Philippines:2 China: 2 Iran : 1 Thailand: 1 Turkey: 11 UK: 8 Ireland: 4 Norway: 4 Switzerland: 3 Italy: 1 Sweden: 1 Spain: 1 South Africa: 2 Colombia:6 Uruguay:4 Venezuela:2 Peru:1 Mexico: 1 Added 2013 slide Latin America: 14 Australia & New Zealand: 36 37

Australia & New Zealand: 40 Participation Across the 5 Years of the Survey : 355 Distinct ICUs Canada: 69 Europe: 51 USA: 126 Asia: 52 Rupinder, please update this slide to be summative over all 5 years . Miao is combining the database now and can tell you these numbers. Latin America: 17 Australia & New Zealand: 40 38

Value of Bench-marked Site Reports Recommendations: Based on 8 level 2 studies, we recommend early enteral nutrition (within 24-48 hrs following resuscitation) in critically ill patients. Early vs Delayed Nutrition Intake

In patients with high gastric residual volumes: use of motility agents 58.7% (site average range: 0-100%) use of small bowel feeding 14.7% (range: 0-100%) Cahill N Crit Care Med 2010

Need to Understand Local Barriers Assess Barriers

Implementation Process Institutional Factors Understanding Adherence to Guidelines in the ICU: Development of a Comprehensive Framework ADHERENCE CPG Characteristics Patient Characteristics Provider Intent Implementation Process Institutional Factors Provider Characteristics - Profession Critical care expertise Educational background Personality System characteristics Hospital characteristics Structure Processes Resources Knowledge Attitudes Familiarity Agreement Outcome expectancy ICU characteristics Structure Processes Resources Culture Motivation Self-efficacy Awareness Jones N, Suurdt J, Ouellette-Kuntz H, Heyland DK JPEN Nov 2010

NO ONE COULD SEE THIS SLIDE AT CNW NO ONE COULD SEE THIS SLIDE AT CNW..PERHAPS YOU COULD PICK SOME AND ENLARGE?

Can we do better with our current feeding protocols? The same thinking that got you into this mess won’t get you out of it!

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 polymeric. Motility agents and protein supplements are started immediately, rather than started when there is a problem. Tolerate higher GRV* threshold (300 ml or more). A major paradigm shift in how we feed enterally * GRV: gastric residual volume Heyland DK. Crit Care. 2010;14(2):R78 Heyland DK CCM 2013.

Tools to Operationalize the PEP uP Protocol Bedside Written Materials Description EN initiation orders Physician standardized order sheet for starting EN. Gastric feeding flow chart Flow diagram illustrating the procedure for management of gastric residual volumes. Volume-based feeding schedule Table for determining goal rates of EN based on the 24 hour goal volume. Daily monitoring checklist Excel spreadsheet used to monitor the progress of EN. Materials to Increase Knowledge and Awareness Study information sheets Information about the study rationale and guidelines for implementation of the PEP uP protocol. Three versions of the sheets were developed targeted at nurses, physicians, and patients’ family, respectively. PowerPoint presentations Information about the study rationale and how to implement the PEP uP protocol. A long (30-40 minute) and short (10-15 minute) version were available. Self-learning module Information about the PEP uP protocol and case example to work through independently. Posters A variety of posters were available to hang in the ICU during the study. Frequently Asked Questions (FAQ) document Document addresses common questions about the PEP uP Protocol. Electronic reminder messages Animated reminder messages about key elements of the PEP uP protocol to be displayed on a monitor in the ICU. Monthly newsletters Monthly circular with updates about the study.

% Protein Received/Prescribed Change of Nutritional Intake from Baseline to Follow-up of All the Study Sites (All patients) % Protein Received/Prescribed p value=0.005 p value=0.81 Heyland DK CCM 2013.

Results of the Canadian PEP uP Collaborative 8 ICUs implemented PEP uP protocol through Fall of 2012-Spring 2013 Compared to 16 ICUs (concurrent control group) All evaluated their nutrition performance in the context of INS 2013 Heyland JPEN 2014 (in submission)

Results of the Canadian PEP uP Collaborative

Results of the Canadian PEP uP Collaborative Proportion of Prescribed Energy From EN According to Initial EN Delivery Strategy Just say no to NPO*

New Collaborative: PEP UP US? Want to add a slide here re: this? Do you want to do this ?

Need for a Tailored Approach Select Intervention(s)

Bridging the Guideline – Practice Gap In Critical Care Nutrition: A Review of Guideline Implementation Studies 3 Cluster RCTs 14 ICUs in Canada 60 ICUs in Canada 27 ICUs in Australia Guidelines Bedside Cahill N, Heyland DK

Practice Changing Interventions Protocolize/automate care Improve organizational culture Develop local opinion leaders Audit and feedback with bench-marked site reports Assess barriers and have interactive workshops with small group problem solving Implement strategies with rapid cycle change (PDSA) Educational reminders (checklists, manuals, posters, pocket cards) One on one academic detailing

What works best at your site? (barriers and enablers will vary site to site) What is already working well at your site? (strengths and weakness are different across sites)

REPEATED SLIDE, CANNOT SEE THIS AT ALL

Tailored Intervention: Vs. Tailored Intervention: Change strategies specifically chosen to address the barriers identified at a specific setting at a specific time

Systematic Review of Tailored Interventions 26 studies of tailored interventions Pooled OR 1.52 (95% CI 1.27-1.82), p=0.001 Variation in methodology None in clinical nutrition Baker et al Cochrane Database Syst Rev 2010

PERFormance Enhancement of the Canadian nutrition guidelines through a Tailored Implementation Strategy: The PERFECTIS Study Hypothesis Barriers are inversely related to nutrition performance and tailoring change strategies to overcome barriers to change will reduce the presence of these barriers and lead to improvements in nutrition practice.

Study Schema: Pre-test Posttest

Example of Tailored Action Plan

Change in Prioritized Barriers Score Site Range -26.3% (SD 18.8%) To -4.6% (SD 28.6%) Overall Barriers Score Before = 30.5% After = 20.8% Change = -9.7 %

Change in Adequacy of Total Nutrition Before = 43% After = 49% Change = 6% Site Range = -2 to 18%

OPTimal nutrition by Informing and Capacitating family members of best practices: The OPTICs feasibility study Investigators Andrea Marshall, RN, MN, PhD Daren Heyland, MD, FRCPC, MSc Naomi Cahill, RD, PhD candidate Rupinder Dhaliwal, RD

Gap exists: best practice & current practice Evidence-based nutrition guidelines are inconsistently implemented Large scale, multi-faceted interventions have failed to improve nutrition practices & have not improved nutritional adequacy for the critically ill Engaging family members to act as advocates for nutrition may be a promising strategy to narrow the gap between best practice & current practice both in the ICU and post ICU

Objectives: Definitive study Hypothesis Educating families about the importance of nutrition and having them advocate for better nutrition for their loved one in the ICU will result in better nutrition delivery during critical illness and in the recovery phase

Evidence for Family Advocacy Literature supports family-centered care1,2,3,4 Families and ICU staff are very supportive of family involvement in patient care. Most patients are also favourable of family involvement in their care1 Garrouste-Orgeas M, Willems V, Timsit JF, Diaw F, Brochon S, Vesin A, et al. Opinions of families, staff, and patients about family participation in care in intensive care units. J Crit Care. 2010;25(4):634-40. Cypress BS. The lived ICU experience of nurses, patients and family members: a phenomenological study with Merleau-Pontian perspective. Intensive Crit Care Nurs. 2011;27(5):273-80 Kinsala EL. The Very Important Partner program: integrating family and friends into the health care experience. Prog Cardiovasc Nurs. 1999;14(3):103-10. Mitchell M, Chaboyer W, Burmeister E, Foster M. Positive effects of a nursing intervention on family-centered care in adult critical care. Am J Crit Care. 2009;18(6):543-52; quiz 53.

Objectives: Feasibility Study Primary aim: Evaluate the feasibility and acceptability of an intervention designed to educate family members about the importance of adequate nutrition in ICU and during recovery from critical illness

Intervention: Family education session & patient nutrition history Education session and booklet Information about nutrition therapy Nutrition therapy risks, side effects Initiating oral feeds following EN or PN How family members can be advocates for the best nutrition practices Nutrition history (Family member) Weight loss history Past diets, food intolerances/allergies, GI problems Chewing/swallowing difficulties Eating patterns Food preferences

Creating a Culture of Clinical Excellence in Critical Care Nutrition: The ‘Best of the Best’ Award Heyland JPEN 2010: in press

Recognition and Reward Recognition a powerful motivator of human performance

Determining the Best of the Best Determinant Weighting Overall Adequacy of EN plus appropriate PN 10 % patients receiving EN 5 % of patients with EN initiated within 48 hours 3 % of patients with high gastric residual volumes (HGRV) receiving motility agents 1 % of patients with HGRV receiving small bowel tubes % of patient glucose measurements greater than 10 mmol/L (excluding day 1; fewest is best) Rank all eligible ICUs by determinants Multiply ranking by weighting ICU with highest score is crowned ‘Best of the Best’

2008 Best of the Best Top 3 ICUs 1. Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand 2. Kingston General Hospital, Kingston, Canada 3. Regional Hospital A. Cardarelli, Italy   ADDED A NEW PICTURE FOR THE BOB..other one needs to retore! Top 3

The Team at the Alfred Hospital ICU, Melbourne, Australia Best of the Best 2011 ADDED 2011 BOB IN CASE YOU WANT THIS? The Team at the Alfred Hospital ICU, Melbourne, Australia

2013 Best of the Best 1. Kingston General Hospital, Kidd2 ICU Canada TOP 3 Sites 1. Kingston General Hospital, Kidd2 ICU Canada 2. Hospital General de Medellín, luz Castro de Gutiérrez Unidad de cuidados intensivos , Colombia 3. The Ministry of Health Ankara, Numune Research and Training Hospital Turkey Please fill this in and add some pics on the next slides…DONE! Top 3

Kingston General Hospital

Hospital General de Medellín Colombia

The Ministry of Health Ankara Turkey

And the Cycle continues...

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