2. Objective

3. Key Points Not all obese patients are the same Nutritional approach may need to vary Challenge to the prevailing dogma that hypocaloric feeding (undernourishment) is acceptable

4. 2000 Obesity Trends* Among U.S. Adults BRFSS, 1990, 2000, 2010 (*BMI 30, or about 30 lbs. overweight for 5’4” person) 2010 1990 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

5. Relative Trends Sturm, Pub Health, 2007, 121:492 (BRFSS data)

6. What to do when the obese patient becomes critically ill?

7. Feeding the Obese Critically Ill (BMI>30) Provide 50-70% of target energy requirements (>14 kcal/kg actual body weight) and >2.0-2.5 g/kg IBW/d protein)* Americans Insufficient evidence Canadians (silent) Europeans *Choban JPEN 2013

8. Burge JPEN 1994 RCTs of Hypocaloric Nutrition in Obesity (1) 16 hospitalized obese patients requiring PN (? ICU, ‘mild-moderate stress’) Defined obesity as >130% IBW Goal was to show equal nitrogen balance in hypocaloric group (14 kcals/kg actual wt) vs control (25 kcals/kg actual wt) Protein intake was the same (2.0g/kg IBW) Outcomes: –No difference in % of patients achieving positive Nitrogen Balance –Weight change did not differ significantly between groups –Infections not measured –No difference in LOS or mortality

9. Choban et al, Am J Clin Nutr. 1997 Sep;66(3) RCTs of Hypocaloric Nutrition in Obesity (2) 30 hospitalized obese patients (13 in the ICU) Defined obesity as BMI >35 Hypocaloric group -13.6kcals/kg actual wt Control group – 22.5 kcals/kg actual wt Protein intake was the same (2 g/kg IBW) Outcomes: –No difference in % of patients achieving positive Nitrogen Balance –Weight change did not differ significantly between groups –Infections not measured –No difference in LOS or mortality

10. Clinical Inferences to ICU Patients? N=46 (13 ICU patients) Focus was on patients requiring PN, says nothing about patients on EN Focus was on NB, other outcomes not assessed or underpowered.

11. Is there sufficient evidence that should inform one prescription on how ALL obese patients should be fed?

12. Extreme Obesity and Outcomes in Critically Ill Patients Martino Chest 2011;140:1198 Analysis of data from multicenter international observational study of ICU nutrition practices in 2007 and 2008 Increased obesity= increased risk of prolongation of stay

13. Not all critically ill obese patients are the same: the influence of prior co-morbidities. Raham ISRN Obesity 2012 Prospective observational study of 183 critically ill patients had a BMI ≥ 30

14. Not all critically ill obese patients are the same: the influence of prior co-morbidities. Raham ISRN Obesity 2012 0-1 co-morbidity (n=38) 2 or more co- morbidities (n=145) p values Discharged alive from ICU by day 2836 (94.7%)112 (77.2%)0.02 Maximum SOFA score7.5[5.0 to 11.0]9.0[6.0 to 13.0]0.04 Delta SOFA score1.5[0.0 to 3.0]2.0[1.0 to 5.0]0.07 Number of days on MV2.0[1.0 to 5.0]4.0[2.0 to 7.0]0.09 Number of days in ICU3.0[3.0 to 11.0]6.0[3.0 to 10.0]0.04 ICU free days in the first 28 days24.5[17.0 to 25.0] 20.0[3.0 to 24.0] 0.003 Mortality at Day 142 (5.3%)24 (16.6%)0.08 Mortality at Day 282 (5.3%)30 (20.7%)0.03

15. Not all critically ill obese patients are the same: the influence of prior co-morbidities. Raham ISRN Obesity 2012 In the adjusted analysis, compared to patients with limited co-morbidities, obese patients with multiple co-morbidities were: more likely to die at 28 days (OR 4.28, 95%CI, CI 0.92, 20.02, p=0.06) tended to have longer ICU duration (3.06 days, standard error [SE] 2.28, p=0.18) and had significantly fewer ICU free days in the first 28 days (-3.92 days, SE 1.83, p=0.03).

16. ICU Obese patients are not all created equal…should we expect the impact of nutrition therapy to be the same across all patients?

17. Start EN within 24-48 hrs of admission to ICU Optimal Amount of Protein and Calories for Critically Ill Patients

18. Bias and accuracy of common estimation methods for resting metabolic rate in mechanically ventilated critically ill patients Curr Opin Crit Care 2012, 18:174–177 Penn State or modified Penn State if >60 recommended by experts* * Choban JPEN 2013

19. Increasing Calorie Debt Associated with worse Outcomes   Caloric debt associated with:   Longer ICU stay   Days on mechanical ventilation   Complications   Mortality Adequacy of EN Rubinson CCM 2004; Villet Clin Nutr 2005; Dvir Clin Nutr 2006; Petros Clin Nutr 2006 Caloric Debt

20. 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

21. How are Obese Patients Actually Being Fed? Total25-<3030-<3535<-40>=40P-value Nutritional Prescription Mean Energy [Kcal/kg/day] (SD) 24.0 (5.8) 23.8 (3.7) 20.2 (3.4) 17.9 (2.8) 15.0 (4.0)<0.0001 Mean Protein [grams/kg/day] (SD) 1.2 (0.3) 1.0 (0.2) 0.9 (0.2) 0.8 (0.3)<0.0001 Nutrition Received Mean Energy [Kcal/kg/day] (SD) 14.0 (7.6) 13.6 (6.7) 11.2 (5.9) 9.8 (5.1) 8.1 (4.4)<0.0001 Mean Protein [grams/kg/day] (SD) 0.6 (0.4) 0.6 (0.3) 0.5 (0.3) 0.4 (0.3) <0.0001 Received EN protein supplements 173 (6.2%)50 (6.1%)28 (7.1%)17 (10.5%)22 (12.9%)0.0002

22. 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

23. 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

25. BMI Group Adjusted Estimate 95% CIP-value LCLUCL Overall3.51.25.90.003 <202.8-2.98.50.337 20-<254.71.57.80.004 25-<300.1-3.03.20.958 30-<35-1.5-5.82.90.508 35-<408.72.015.30.011 >=406.4-0.112.80.053 Relationship Between Increased Energy and Ventilator-Free days Legend: # of VFD per 1000 kcals received per day adjusting for nutrition days, BMI, age, admission category, admission diagnosis and APACHE II score.

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

27. ICU Obese patients are not all created equal…should we expect the impact of nutrition therapy to be the same across all patients?

28. Muscle Matters! Skeletal muscle mass predicts ventilator-free days, ICU- free days, and mortality in elderly ICU patients Patients > 65 years with an admission abdominal computed tomography scan and requiring intensive care unit stay at a Level I trauma center in 2009-2010 were reviewed. Muscle cross-sectional area at the 3 rd lumbar vertebra was calculated and sarcopenia identified using sex-specific cut- points. Muscle cross-sectional area was then related to clinical parameters including ventilator-free days, ICU-free days, and mortality. Moisey Crit Care 2013 Sept;17(5):R206

29. Skeletal Muscle Adipose Tissue

30. Physical Characteristics of Patients N=149 patients Median age: 79 years old 57% males ISS: 19 Prevalence of sarcopenia: 71%

31. BMI Characteristics All PatientsSarcopenic Patients (n=106) Non-sarcopenic Patients (n=43) BMI (kg/m 2 )25.8 (22.7, 28.2)24.4 (21.7, 27.3)27.6 (25.5, 30.4) Underweight, %792 Normal Weight, %374419 Overweight, %423851 Obese, %15928 Almost half the sarcopenic patients were overweight

32. Low muscle mass associated with mortality Proportion of Deceased Patients P-value Sarcopenic patients32% 0.018 Non-sarcopenic patients14%

33. Muscle mass is associated with ventilator-free and ICU-free days All PatientsSarcopenic Patients Non- Sarcopenic Patients P-value Ventilator-free days 25 (0,28)19 (0,28)27 (18,28)0.004 ICU-free days19 (0,25)16 (0,24)23 (14,27)0.002

34. Nutrition Status micronutrient levels - immune markers - muscle mass Acute Starvation (Reduced po intake, pre ICU hospital stay) Chronic Malnutrition (?Sarcopenia) Severity of Illness (APACHE, SOFA, IL-6) Pre-existing Co- morbidities (Metabolic consequences) What does Nutrition Risk Assessment look like for the obese critically ill? Functional Impairment (reduced mobility and strength) Risk Status High risk= high risk of death and greater likelihood of benefit from Nutrition Degree of Obesity (BMI)

35. A Proposed Clinical Staging System for Obesity (non-critically ill) Sharma Int J of Obesity 2009;33:289 Increasing complications Increasing aggressiveness We need to adapt this way of thinking to the ICU setting!

36. What if you can’t provide adequate nutrition enterally? … to add PN or not to add PN, that is the question! Role of PN in the Obese Patient?

37. 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 Cesaer NEJM 2011 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

38. 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

39. Lancet Dec 2012 Doig, ANZICS, JAMA May 2013

40. What if you can’t provide adequate nutrition enterally to critically ill obese patient?? … to supplement with PN or not to PN, that is the question! Case by Case Decision Maximize EN delivery prior to initiating PN

41. High-risk ICU patients BMI <25 R PN for 7 days EN Alone The TOP UP Trial Inadequately fed enterally in first 2 days (<60%) Primary Outcome 60-day mortality BMI >35 Stratified by: Site BMI Med vs Surg

42. HYPOTHESIS Increased early energy and protein delivery with PN+EN to underweight (BMI 35) critically ill patients will result in improved survival at 60 day versus standard EN alone

43. Key Methodological Features Only enrolling nutrition ‘at risk’ patients not tolerating EN within first 48 hrs. Paired EN/PN feeding to meet goal rate of protein/calories from initiation vs. EN alone x 7 days High nitrogen PN solution with olive oil (Olimel, 3 in 1, Baxter) Comprehensive assessment of muscle mass and muscle function

44. In Conclusion Not all Obese ICU patients are the same in terms of ‘risk’- need to develop and validate risk assessment tools in this population Iatrogenic underfeeding is harmful to some Obese ICU patients or some will benefit more from aggressive feeding (avoiding protein/calorie debt) Aggressive use of EN (high protein diets) and protein supplements indicated Supplemental PN may be beneficial in some

45. Yes YES High Risk Obese? No NO EN (hypocaloric OK) or nothing YES Anticipated Long Stay? Yes No NO EN (hypocaloric OK)Aggressive EN* Yes YES Not tolerating Early EN No NO Supplemental PN? *Aggressive EN= PEP uP protocols, high protein diets, protein supplements, motility agents and small bowel feeds