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Guidelines and Current Practices in the ICU in 2013: Are There Still Gaps? Rupinder 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

Conflict of interest/Disclosures Co-author of Canadian Clinical Practice Guidelines I have received speaker honoraria 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 None for this project 1

Learning Objectives Become familiar with the updated recommendations from the Canadian CPGs üTrophic feeds Learning Objectives Become familiar with the updated recommendations from the Canadian CPGs üTrophic feeds üGRVs üEnteral Fish oils üProbiotics üParenteral glutamine üParenteral Selenium üPN Type of Lipids üSupplemental 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

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

International Nutrition Survey (INS) 2013 Purpose illuminate gaps between current practice & guidelines identify 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

Methods • Each ICU enrolled 20 consecutive patients • ICU LOS> 72 hrs • 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

www. criticalcarenutrition. com www. criticalcarenutrition. com

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

ICU Characteristics Total (n =202) Hospital Type Teaching Non-teaching Size of Hospital (beds) Mean ICU Characteristics Total (n =202) Hospital Type Teaching Non-teaching Size of Hospital (beds) Mean (Range) ICU Structure Open Closed Other Size of ICU (beds) Mean (Range) Designated Medical Director Presence of Dietitian(s) 170 (84. 2%) 32( 15. 8%) 581 (50 -2500) 51 (25. 2%) 148 (73. 3%) 3 (1. 5%) 17(4 -86) 185 (91. 6%) 164 (81. 2%)

Patient Characteristics n = 4040 Age (years) Median [Q 1, Q 3] 63 [50 Patient Characteristics n = 4040 Age (years) Median [Q 1, Q 3] 63 [50 -74] BMI Median [Q 1, Q 3] 25. 7 [22. 5 - 30] Admission Category 2588 (64%) Surgical: Elective 428 (10. 6%) Surgical: Emergency Apache II Score Medical 1024 (25. 3%) Median [Q 1, Q 3] Presence of ARDS 22 [16 -27] 365/4040 (9%)

Clinical Outcomes n=4040 Length of Mechanical Ventilation (days) Median [Q 1, Q 3] 6. Clinical Outcomes n=4040 Length of Mechanical Ventilation (days) Median [Q 1, Q 3] 6. 6 [3. 1, 13. 6] Median [Q 1, Q 3] 10 [5. 8, 18. 9] Length of ICU Stay (days) Length of Hospital Stay (days) Median [Q 1, Q 3] 21 [10. 8, 44. 9. ] Patient Died (within 60 days) Yes 991 (24. 5%)

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

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

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

Canadian CPGs 2013 Topic new topics 2013 RCTs Total RCTs Fish Oils/Borage Oils 4 Canadian CPGs 2013 Topic new topics 2013 RCTs Total RCTs Fish Oils/Borage Oils 4 8 Probiotics 12 23 Combination EN + PN 3 8 PN Type of lipids 4 9 PN Glutamine 11 28 PN Selenium 7 18 Intentional Underfeeding: Trophic vs Full Feeds 2 Threshold of GRVs 2 Early Supplemental PN vs Late 1 1 PN + EN Glutamine 1 1 2 Available online now NCP Feb 2014 2

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

INS 2013: Trophic Feeds* 8. 4% all patients 6. 4% all ARDS pts * INS 2013: Trophic Feeds* 8. 4% all patients 6. 4% all ARDS pts * At initiation of EN, pts on EN prior to ICU excluded

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

INS 2013: GRVs threshold 1 INS 2013: GRVs threshold 1

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

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

Enteral Fish Oils* *Product enhanced with fish oils +borage oils + antioxidants 2009 Recommendation 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

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

INS 2013: Use of Enteral Fish Oils Formula (enteral) Patients receiving these formulas* Fish 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

Probiotics 1 Probiotics 1

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

Probiotics with 12 new RCTs Canadian CPGs Internal Committee 2013 Recommendation Probiotics q stronger Probiotics with 12 new RCTs Canadian CPGs Internal Committee 2013 Recommendation Probiotics q stronger signal for reduction in infections (2009: no reduction) q higher quality studies do NOT show a reduction in infections q trend towards a reduction in VAP (p=0. 06) q still trend towards reduction inbe considered” Upgrade to “should ICU mortality q no risk with use (exception of Saccharomyces boulardii) 1

INS 2013: Use of Probiotics Formula (enteral) Supplemental Probiotics 1 Patients receiving these formulas INS 2013: Use of Probiotics Formula (enteral) Supplemental Probiotics 1 Patients receiving these formulas (of all patients) 4. 9% (0. 0%-100%)

Glutamine supplementation? 1 Glutamine supplementation? 1

PN Glutamine 2009 Recommendation Based on 17 studies, when parenteral nutrition is prescribed to 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 New RCTs = 11 Grau 2011 Andrews 2011 Wernerman 2011 Cekman 2011 Zeigler 2013 (in press) + Heyland 2013 (EN + PN)

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

PN + EN Glutamine ü REDOXS: largest multicentre trial ü patients with at least PN + EN Glutamine ü REDOXS: largest multicentre trial ü patients with at least 2 organ failures ü 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

EN Glutamine 2009 Recommendation Based on 2 level 1 and 7 level 2 studies, 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 multiorgan failure

INS 2013: Use of Glutamine Supplementation Patients receiving supplementation EN patients Enteral glutamine supplementation* INS 2013: Use of Glutamine Supplementation Patients receiving supplementation EN patients Enteral glutamine supplementation* 5. 3% (0. 0% -100%) IV/PN glutamine supplementation 2. 0 % (0. 0% - 36. 4%) PN patients Enteral glutamine supplementation* 8. 8 % (0. 0% - 100%) IV/PN glutamine supplementation 9. 2% (0. 0% - 33. 3%) Burn patients Any glutamine supplementation 4. 9% (0. 0 %-33. 3%) Trauma patients Any glutamine supplementation 14. 1% (9. 9%-100%) In patients with Shock or MOF ? * Over and beyond standard formula

Parenteral Selenium 1 Parenteral Selenium 1

Parenteral Selenium 2009 Recommendation: There are insufficient data to make a recommendation regarding IV/PN Parenteral Selenium 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

PN Selenium with new RCTs PN selenium ü no effect on mortality (was a PN Selenium with new RCTs PN selenium ü no effect on mortality (was a trend p =0. 13) ü reduction in infections, p =0. 04 (was no effect) ü no effect on LOS (same) 2013 Recommendation: Upgraded to “should be considered” 1

INS 2013: Use of PN Se Selenium Supplementation Patients receiving supplementation EN patients IV/PN INS 2013: Use of PN Se Selenium Supplementation Patients receiving supplementation EN patients IV/PN supplementation PN patients IV/PN supplementation 6. 4% (0. 0% - 100%) Any IV/PN Selenium supplementation 1. 7% (0. 0 %- 65%) Any Enteral Selenium supplementation 1 1. 7% (0. 0% - 63. 2 %) 0. 3 % (0. 0%-66. 7%)

PN Type of Lipids 2009 Recommendation There are insufficient data to make a recommendation 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

2013 CPGs Internal Committee Canadian. Recommendation (Upgrade) q new signals for • reduction in 2013 CPGs Internal Committee Canadian. Recommendation (Upgrade) q new signals for • reduction in mortality (p =0. 20) IV lipids that reduce the load of omega-6 fatty • ICU LOS (p = 0. 13), statistical heterogeneity present • duration of ventilation (p=0. 09) acids/soybean oil emulsions should be considered. There are insufficient data on type of soybean reducing lipids q no effect on infections (p=0. 58) 2009 same q no direct comparisons so not clear on what type of omega-6 sparing strategy

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

EN + PN Lancet 2012 Combined EN + PN üused indirect calorimetry üNo difference EN + PN Lancet 2012 Combined EN + PN üused indirect calorimetry üNo difference mortality üreduced infections day 4 -28 + Abrishami 2010 + Chen 2011 No change from 2009 we recommend that PN not be started at the same time as EN. Insufficient evidence in those who are not tolerating EN (case by case) NEJM 2011 Early Supplemental PN vs. Late ülarge multicentre üearly PN: worse infections, LOS üearly PN: no diff mortality ühigh glucose loading ülow risk patients 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)

INS 2013: EN + PN % ICU days EN + PN = 4. 5% INS 2013: EN + PN % ICU days EN + PN = 4. 5%

INS 2013: use of Early vs Late PN Timing of PN start in patients INS 2013: use of Early vs Late PN Timing of PN start in patients on EN (n =189 ICUs) PN start from ICU admit 5. 1 days

INS 2013: Overall Adequacy Calories Prescribed 1741 [1500 -1997] Kcals 24. 9 [20. 2 INS 2013: Overall Adequacy Calories Prescribed 1741 [1500 -1997] Kcals 24. 9 [20. 2 -26. 7] Kcal/kg/day Average across all days: 62% (0 -185%)

INS 2013: Overall Adequacy Protein Prescribed 82 [68 -100] gms 1. 1 [1. 0 INS 2013: Overall Adequacy Protein Prescribed 82 [68 -100] gms 1. 1 [1. 0 -1. 3] gms/kg/day Average across all days: 58% (0 -165%)

Summary • Several gaps exist in current nutrition practices when compared to the latest 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

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

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