1. Guidelines and Current Practices in the ICU in 2013: Are There Still Gaps? Rupinder Dhaliwal, RD Manager, Research & Networking Clinical Evaluation Research Unit Queen’s University, Kingston, Canada 1

2. Conflict of interest/Disclosures Co-author of Canadian Clinical Practice Guidelines I have received speaker honoraria and/or I have been paid from grants from the following companies: –Nestlé –Fresenius Kabi –Baxter –Abbott 1 None for this project

3. Learning Objectives Become familiar with the updated recommendations from the Canadian CPGs Trophic feeds GRVs Enteral Fish oils Probiotics Parenteral glutamine Parenteral Selenium PN Type of Lipids Supplemental PN Review the current nutrition practices in ICUs around the World (International Nutrition Survey 2013) To identify areas in current practices that need to be improved 1

4. Knowledge To Action Model Identify the Problem How are ICU pts around the World being fed ?

5. International Nutrition Survey (INS) 2013 Purpose illuminate gaps between current practice & guidelines identify practice areas to target for change History started in Canada in 2001 5 th International audit (2007, 2008, 2009, 2011 & 2013) Methods Observational, point prevalence study

6. Methods Each ICU enrolled 20 consecutive patients ICU LOS> 72 hrs vented within first 48 hrs Data abstracted from chart Hospital and ICU characteristics –Patient information –Baseline Nutrition Assessment –Daily Nutrition data –Patient outcomes (e.g. mortality, length of stay) Benchmarking Report provided Best of the Best Competition if n ≥ 20 patients

7. www.criticalcarenutrition.com

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

9. ICU Characteristics CharacteristicsTotal (n =202) Hospital Type Teaching170 (84.2%) Non-teaching32( 15.8%) Size of Hospital (beds) Mean (Range)581 (50-2500) ICU Structure Open51 (25.2%) Closed148 (73.3%) Other3 (1.5%) Size of ICU (beds) Mean (Range)17(4-86) Designated Medical Director185 (91.6%) Presence of Dietitian(s)164 (81.2%)

10. Patient Characteristics Characteristicsn = 4040 Age (years) Median [Q1,Q3]63 [50-74] BMI Median [Q1, Q3]25.7 [22.5 - 30] Admission Category Medical2588 (64%) Surgical: Elective428 (10.6%) Surgical: Emergency1024 (25.3%) Apache II Score Median [Q1, Q3]22 [16-27] Presence of ARDS365/4040 (9%)

11. Clinical Outcomes Outcomes n=4040 Length of Mechanical Ventilation (days) Median [Q1, Q3]6.6 [3.1, 13.6] Length of ICU Stay (days) Median [Q1, Q3]10 [5.8, 18.9] Length of Hospital Stay (days) Median [Q1,Q3]21 [10.8, 44.9.] Patient Died (within 60 days) Yes991 (24.5%)

12. Knowledge To Action Model Synthesizing Knowledge (evidence) Canadian Nutrition Guidelines

13. www.criticalcarenutrition.com JPEN 2003  1980-2003 2005 update 2007 update 2009 update 2013 update

14. New Evidence 2009 207 RCTs 34 Topics 17 recommendations 2013 275 RCTS 45 Topics 22 recommendations 68 new RCTs across 27 topics!

15. Topic new topics 2013 RCTsTotal RCTs Fish Oils/Borage Oils 48 Probiotics 1223 Combination EN + PN 38 PN Type of lipids 49 PN Glutamine 1128 PN Selenium 718 Intentional Underfeeding: Trophic vs Full Feeds 22 Threshold of GRVs 22 Early Supplemental PN vs Late 11 PN + EN Glutamine 11 Available online now NCP Feb 2014 Canadian CPGs 2013

16. EN: Trophic Feeds Effect of Trophic feeds on mortality Canadian CPGs Internal Committee  no effect on mortality or VAP  maybe better gastrointestinal tolerance but underfeeding  no safety concerns if trophic feeds for 5 days  long term effects of this strategy (muscle mass, function, functional recovery)?  patients age ~ 52 yrs, high BMIs, no comorbidities: represent pt that would benefit?  recommendation based on values other than the treatment effect alone 2013 Recommendation In patients with Acute Lung Injury, an initial strategy of trophic feeds for 5 days should not be considered

17. INS 2013: Trophic Feeds* 8.4% all patients 6.4% all ARDS pts * At initiation of EN, pts on EN prior to ICU excluded

18. Not checking gastric residual volumes was associated with:  increased rates of vomiting  better nutritional adequacy Reignier 2013 Canadian CPGs Internal Committee  no differences in clinical outcomes  nutritional adequacy improvement was minimal  does not include difficult to feed pts (MOF, surgical)  vomiting associated with increased infection, length of stay and mortality (Metheny Am J Crit Care 2008)  opposing views of risks of higher GRVs (Mentec CCM 2001, McClave CCM 2005)  Montejo 2010: hemodynamic stability of patients unknown. Gastric Residual Volumes 2013 Recommendation There are insufficient data to make a recommendation for not checking gastric residual volumes or a specific gastric residual volume threshold. Based on 2 level 2 studies, a gastric residual volume of either 250 or 500 mLs (or somewhere in between) is acceptable as a strategy to optimize delivery of enteral nutrition in critically ill patients.

19. INS 2013: GRVs threshold 1

20. INS 2013: EN interruptions % pt days on EN Need to explore protocols to manage these interruptions

21. Enteral Fish Oils* *Product enhanced with fish oils +borage oils + antioxidants 1

22. Enteral Fish Oils * *Product enhanced with fish oils +borage oils + antioxidants 2009 Recommendation Based on 5 studies, we recommend the use of enteral formula with fish oils, borage oils, and antioxidants in patients with ALI/ARDS New RCTs = 4 Rice 2011 (bolus) Grau-Carmona 2011 Thiella 2011 Elamin 2012

23. EN Fish oils with new RCTs Canadian CPGs Internal Committee  mortality disappears when bolus study is include (statistical heterogeneity)  effect on mortality is significant when bolus study excluded  infections (2 RCTs): no effect  reduction in ICU LOS still significant (heterogeneity)  concerns of control group, negative results of large studies 2013 2013 Recommendation Fish Oils/borage oil: Downgraded recommendation to “should be considered” Fish Oils alone: insufficient data 1

24. INS 2013: Use of Enteral Fish Oils Formula (enteral)Patients receiving these formulas* Fish oil enriched formula (all patients) 10.0% (0.0%-100%) Fish oil enriched formula (in ARDS patients) 20.2% (0.0%-100%) * Of those patients on EN or EN+PN 1

25. Probiotics 1

26. 2009 Recommendation There are insufficient data to make a recommendation on the use of Prebiotics/Probiotics/Synbiotics in critically ill patients Schlotterer 1987 Kecskes 2003 Lu 2004 Li 2007 Klarin 2008 Knight 2009 Barraud 2010 Morrow 2010 Frohmader 2010 Ferrie 2011 Sharma 2011 Tan 2011 New RCTs = 12 (only probiotics) Petrof et al Critical Care 2012

27. Probiotics with 12 new RCTs 1 Canadian CPGs Internal Committee  stronger signal for reduction in infections (2009: no reduction)  higher quality studies do NOT show a reduction in infections  trend towards a reduction in VAP (p=0.06)  still trend towards reduction in ICU mortality  no risk with use (exception of Saccharomyces boulardii) 2013 Recommendation Probiotics Upgrade to “should be considered”

28. INS 2013: Use of Probiotics Formula (enteral)Patients receiving these formulas (of all patients) Supplemental Probiotics4.9% (0.0%-100%) 1

29. Glutamine supplementation? 1

30. PN Glutamine 2009 Recommendation Based on 17 studies, when parenteral nutrition is prescribed to critically ill patients, parenteral supplementation with glutamine, where available, is strongly recommended. There are insufficient data to generate recommendations for intravenous glutamine in critically ill patients receiving enteral nutrition Tian 2006 Zhang 2007 Yang 2008 Ozgultekin 2008 Eroglu 2009 Perez Barcena 2010 Grau 2011 Andrews 2011 Wernerman 2011 Cekman 2011 Zeigler 2013 (in press) + Heyland 2013 (EN + PN) New RCTs = 11

31. less effect on overall mortality & infections, now a trend hospital mortality and ICU LOS significant reduction (heterogeneity) large scale multicenter randomized trials of IV glutamine have failed to demonstrate a convincing positive effect (Andrews, Wernerman, Ziegler) safety concerns from REDOXS can not be ignored 2013 Recommendation: PN Glutamine Downgraded to “ should be considered” CAUTION: do not use PN glutamine in patients with shock and MOF PN GLN with 11 new RCTs

32. PN + EN Glutamine REDOXS: largest multicentre trial patients with at least 2 organ failures increase in mortality across all time points 2013 Recommendation: strongly recommend that high dose combined parenteral and enteral glutamine supplementation NOT be used in critically ill patients with multi-organ failure 1

33. EN Glutamine 2009 Recommendation Based on 2 level 1 and 7 level 2 studies, enteral glutamine should be considered in burn and trauma patients. There are insufficient data to support the routine use of enteral glutamine in other critically ill patients New RCTs = 0 Heyland 2013 GLN EN + PN 2013 Recommendation: ……In addition, we strongly recommend that any glutamine NOT be used in critically ill patients with shock and multi- organ failure

34. Glutamine SupplementationPatients receiving supplementation EN patients Enteral glutamine supplementation* IV/PN glutamine supplementation 5.3% (0.0% -100%) 2.0 % (0.0% - 36.4%) PN patients Enteral glutamine supplementation* IV/PN glutamine supplementation 8.8 % (0.0% - 100%) 9.2% (0.0% - 33.3%) Burn patients Any glutamine supplementation4.9% (0.0 %-33.3%) Trauma patients Any glutamine supplementation14.1% (9.9%-100%) In patients with Shock or MOF? INS 2013: Use of Glutamine * Over and beyond standard formula

35. Parenteral Selenium 1

36. 2009 Recommendation: There are insufficient data to make a recommendation regarding IV/PN selenium supplementation, alone or in combination with other antioxidants, in critically ill patients New RCTs = 7 Lindner 2004 El Attar 2009 Gonzalez 2009 Andrews 2011 Manzanares 2011 Valenta 2011 Heyland 2013 removed Schneider 2011

37. PN selenium no effect on mortality (was a trend p =0.13) reduction in infections, p =0.04 (was no effect) no effect on LOS (same) 2013 Recommendation: Upgraded to “should be considered” PN Selenium with new RCTs 1

38. Selenium SupplementationPatients receiving supplementation EN patients IV/PN supplementation1.7% (0.0% - 63.2 %) PN patients IV/PN supplementation6.4% (0.0% - 100%) Any IV/PN Selenium supplementation1.7% (0.0 %- 65%) Any Enteral Selenium supplementation0.3 % (0.0%-66.7%) INS 2013: Use of PN Se 1

39. 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. New RCTs* =4 Wang 2009 Barbosa 2010 Umpierrez 2012 Pontes-Arruda 2012 X include studies that had no soybean oil in control *omega-6 fatty acid load (or soybean oil sparing strategy) vs. soybean emulsion

40. Canadian CPGs Internal Committee  new signals for reduction in mortality (p =0.20) ICU LOS (p = 0.13), statistical heterogeneity present duration of ventilation (p=0.09)  no effect on infections (p=0.58) 2009 same  no direct comparisons so not clear on what type of omega-6 sparing strategy 2013 Recommendation (Upgrade) 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

41. INS 2013: Type of PN lipids % of patient days on PN

42. EN + PN No change from 2009 we recommend that PN not be started not be started at the same time as EN. Insufficient evidence in those who are not tolerating EN (case by case) NEJM 2011 Lancet 2012 Early Supplemental PN vs. Late Combined EN + PN Strongly recommend that early PN & high IV glucose not be used in low risk, short ICU stay Insufficient evidence in those who are not tolerating EN (case by case) large multicentre early PN: worse infections, LOS early PN: no diff mortality high glucose loading low risk patients used indirect calorimetry No difference mortality reduced infections day 4-28 + Abrishami 2010 + Chen 2011

43. INS 2013: EN + PN % ICU days EN + PN = 4.5%

44. INS 2013: use of Early vs Late PN PN start from ICU admit 5.1 days Timing of PN start in patients on EN (n =189 ICUs)

45. INS 2013: Overall Adequacy Calories Average across all days: 62% (0-185%) Prescribed 1741 [1500-1997] Kcals 24.9 [20.2-26.7] Kcal/kg/day

46. INS 2013: Overall Adequacy Protein Average across all days: 58% (0-165%) Prescribed 82 [68-100] gms 1.1 [1.0-1.3] gms/kg/day

47. Summary Several gaps exist in current nutrition practices when compared to the latest recommendations Gastric Residual Volumes (interruptions) Probiotics PN Glutamine (in shock, MOF) PN Selenium Significant underfeeding still exists in ICUs around the World Barriers to adoption needs to be evaluated Need to explore innovative strategies to improve nutrition delivery in the ICU

48. Acknowledgements Margot Lemieux Jesse Gadon Miao Wang Project Assistance Electronic Data System Data Analyses 1 Canadian Clinical Practice Guidelines Internal Committee and

49. 1