1. Feeding the Obese Critically Ill
Daren K. Heyland
Professor of Medicine
Queen’s University, Kingston General Hospital
Kingston, ON Canada

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

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

6. Feeding the Obese Critically Ill (BMI>30)
Canadians
Insufficient evidence
Americans*
Based on expert consensus, the goal should not exceed 65%–70% of target energy requirements as measured by IC.
If IC is unavailable, use weight-based equation 11–14 kcal/kg actual body weight per day for patients with BMI in the range of 30–50 and 22–25 kcal/kg ideal body weight per day for patients with BMI >50.
Protein should be provided in a range from 2.0 g/kg ideal body weight per day for patients with BMI of 30–40 up to 2.5 g/kg ideal body weight per day for patients with BMI ≥40.
Europeans
(silent)
*McClave CCM 2016

7. 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
Burge JPEN 1994

8. 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
Choban et al, Am J Clin Nutr Sep;66(3)

9. 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.
Burge JPEN 1994
Choban et al, Am J Clin Nutr Sep;66(3)

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

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

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

13. 2 or more co- morbidities
Not all critically ill obese patients are the same: the influence of prior co-morbidities.
0-1 co-morbidity
(n=38)
2 or more co- morbidities
(n=145)
p values
Discharged alive from ICU by day 28
36 (94.7%)
112 (77.2%)
0.02
Maximum SOFA score
7.5[5.0 to 11.0]
9.0[6.0 to 13.0]
0.04
Delta SOFA score
1.5[0.0 to 3.0]
2.0[1.0 to 5.0]
0.07
Number of days on MV
4.0[2.0 to 7.0]
0.09
Number of days in ICU
3.0[3.0 to 11.0]
6.0[3.0 to 10.0]
ICU free days in the first 28 days
24.5[17.0 to 25.0]
20.0[3.0 to 24.0]
0.003
Mortality at Day 14
2 (5.3%)
24 (16.6%)
0.08
Mortality at Day 28
30 (20.7%)
0.03
Raham ISRN Obesity 2012

14. Not all critically ill obese patients are the same: the influence of prior co-morbidities.
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).
Raham ISRN Obesity 2012

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

16. Not all Obest ICU Patient the same!
Low Risk
34 year former football player,
BMI 35
otherwise healthy
involved in motor vehicle accident
Mild head injury and fractured R leg requiring ORIF
High Risk
79 women
BMI 35
PMHx COPD, poor functional status, frail
Admitted to hospital 1 week ago with CAP
Now presents in respiratory failure requiring intubation and ICU admission

17. 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 were reviewed.
Muscle cross-sectional area at the 3rd 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

18. Body Composition Lab CT Imaging Analysis
Skeletal Muscle
Adipose Tissue

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

20. Sarcopenic Patients (n=106) Non-sarcopenic Patients (n=43)
BMI Characteristics
All Patients
Sarcopenic Patients (n=106)
Non-sarcopenic Patients (n=43)
BMI (kg/m2)
25.8 (22.7, 28.2)
24.4 (21.7, 27.3)
27.6 (25.5, 30.4)
Underweight, % 7 9 2
Normal Weight, % 37 44 19
Overweight, % 42 38 51
Obese, % 15 28
Almost half the sarcopenic patients were overweight

21. Low muscle mass associated with mortality
Proportion of Deceased Patients
P-value
Sarcopenic patients
32%
0.018
Non-sarcopenic patients
14%

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

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

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

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

26. Bias and accuracy of common estimation methods for
resting metabolic rate in
mechanically ventilated critically ill patients
Indirect calorimetry is the comparator.
Bias is the 95th percentile of the difference between estimated and measured. Negative values represent underestimates. Intervals that exclude zero indicate
statistically significant bias.
Accuracy is the percentage of patients whose estimated value falls within 10% of the measured value by indirect calorimetry.
ACCP, American College of Chest Physicians (25 kcal/kg body wt); HBE, Harris Benedict equation; MAW, metabolically active body weight [(Actual wt – Ideal
wt) 0.25þIdeal wt]; Faisy, Wt (8)þHt (14)þMinute ventilation (32)þTemperature (94) – 4834; Penn State, Mifflin (0.96)þMaximum body temperature
(167)þMinute ventilation (31) – 6212; Penn State modified, Mifflin (0.71)þMaximum body temperature (85)þMinute ventilation (64) – 3085.
For the Penn State equation, overall accuracy improves to 73% if the modified equation results in older obese patients are substituted for the results of the original
equation in this group.
Penn State or modified Penn State if >60 recommended by experts*
Curr Opin Crit Care 2012, 18:174–177
*Choban JPEN 2013

27.  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

28. 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

29. How are Obese Patients Actually Being Fed?
Total
25-<30
30-<35
35<-40
>=40
P-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)
Nutrition Received
14.0 (7.6)
13.6 (6.7)
11.2 (5.9)
9.8 (5.1)
8.1 (4.4)
0.6 (0.4)
0.6 (0.3)
0.5 (0.3)
0.4 (0.3)
Received EN protein supplements
173 (6.2%)
50 (6.1%)
28 (7.1%)
17 (10.5%)
22 (12.9%)
0.0002

30. 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

32. How do we increase nutrition delivery in the Obese Patient?
Enterally
High protein (low NPC:N ratio solutions)
Protein supplements
PEP uP protocol
Parenterally
IV amino acids
Supplemental PN?

33. R The TOP UP Trial Primary Outcome 60-day mortality PN for 7 days
High-risk
ICU patients
Stratified by:
Site
BMI
Med vs Surg R
BMI <25
60-day mortality
BMI >35
EN Alone

34. HYPOTHESIS
Increased early energy and protein delivery with PN+EN to underweight (BMI < 25) and obese (BMI> 35) critically ill patients will result in improved survival at 60 day versus standard EN alone 34

35. Objectives of the Pilot Study
Not powered to look at clinical outcomes
Primary Aim:
Difference in the calories and protein received between the control and intervention groups
Secondary Aims
Confirm the feasibility of the trial (estimate recruitment rate)
Confirm feasibility of the intervention.
Tertiary Aim
explore the effect of differential effects of calorie and protein delivery on muscle mass and physical function

36. Eligibility Criteria Inclusion Criteria
Critically ill adult patients (>18 years old)
Expected to require mechanical ventilation > 48 hrs
Expected ICU dependency of 5 or more days
Are on enteral nutrition or are to be initiated on enteral nutrition within 7 days of ICU admission and
Have a BMI < 25 or >35, based on pre-ICU actual or estimated dry weight.

37. Study Intervention Olimel N9 in 3 Chamber bag 1000 ml size
20% lipid emulsion containing a mixture of refined olive oil (80%) and refined soya oil (20%).
High nitrogen concentration (14% AA)
27.5% glucose solution
1.1 cal/ml

38. Study Intervention
Both groups fed enterally started as early as possible (as per standard care)
EN solution will be cal/ml
EN started at 25 ml/hr and increased by at least 25 mls q 4 hrs until goal achieved
Upon enrollment, study dietitians calculated the total volume/24 hours of either EN or PN required to receive goal calories and protein.
The PN solution was started at 25 ml/hr and increase by 25ml/hr increments every 4 hours as tolerated (monitoring blood glucose every 4 hours and electrolytes every twelve hours) till 100% of goal calories are reached.
As PN rate increased, EN rate decreased (paired feeding)

39. Results

40. Patient Demographics, BMI >35
EN (N=35)
EN+PN (N=25)
p value
Age
56.0±13.4 ( )
56.9±17.6 ( )
0.67
Sex
0.46
Male
13 (37.1%)
7 (28.0%)
Female
22 (62.9%)
18 (72.0%)
APACHEII score
20.8± 7.3 ( )
20.9± 5.2 ( )
0.98
BMI
46.9± 9.5 ( )
47.1± 9.7 ( )
0.96
Charlson Comorbidity Index
1.9± 2.1 ( )
1.4± 1.7 ( )
0.49
Type of Admission
0.93
Medical
20 (57.1%)
14 (56.0%)
Surgical
15 (42.9%)
11 (44.0%)
Primary Diagnosis
0.08
Other
3 (8.6%)
1 (4.0%)
Cardiovascular/Vascular
1 (2.9%)
5 (20.0%)
Respiratory
11 (31.4%)
6 (24.0%)
Gastrointestinal
4 (11.4%)
Neurologic
5 (14.3%)
0 (0.0%)
Sepsis
7 (20.0%)
Trauma
2 (5.7%)
Metabolic
Hematologic

41. Nutritional Adequacy* (%), BMI >35
Primary Outcome
Nutritional Adequacy* (%), BMI >35
EN (n=34)
EN+PN (n=24)
Difference mean
(95% CI)
p-value
Adequacy by EN route
Calories first week
68±24
69±24
1 (-12 to 13)
0.915
Protein in first week
62±21
61±19
-2 (-12 to 9)
0.754
Adequacy by EN or PN route
99±10
31 (22 to 40)
<.001
87±13
25 (16 to 34)
*refers to % prescribed volume received

42. Enteral Nutrition Only (n=35)
Clinical Outcomes
Enteral Nutrition Only (n=35)
Enteral Nutrition plus Supplemental PN
(n=25)
p values
Duration of Mechanical Ventilation (days)
8.3 [6.3 to 13.2]
7.7 [3.3 to 14.7]
0.68
Length of stay in ICU (days)
14.5 [9.0 to 18.7]
12.9 [7.9 to 17.0]
0.62
Length of stay in hospital (days)
21.0 [16.6 to 33.0]
23.9 [20.9 to 29.7]
0.53
ICU mortality
6 (17.1%)
4 (16.0%)
0.91
Hospital mortality
Time to discharge alive from hospital
30.5 [17.1, 82.7]
27.1 [22.0, 83.9]
0.80
6 months mortality
7 (20.0%)
6 (24.0%)
0.71
Double check ICU and hospital mortality- it is the same
ANSWER FROM XURAN: Yes, I double checked the data and confirmed that the ICU and hospital mortality rate are the same.

43. Performance-based Measures
Enteral Nutrition Only (n=35)
EN+PN
(n=25)
P-value
Hand Grip at Hospital discharge
Patient died
6 (17.1%)
4 (16.0%)
Unable to do
5 (14.3%)
1 (4.0%)
Refused to Do
0 (0.0%)
Done
12 (34.3%)
12 (48.0%)
Missed
9 (25.7%)
3 (12.0%)
Unknown reason
1 (2.9%)
Use ICU
2 (5.7%)
Hand grip strength
4 [unable-19]
20 [unable-40]
0.16
6-min Walk test at hospital discharge
16 (45.7%)
4 (11.4%)
7 (20.0%)
2 (8.0%)
2 (8.0 %)
6-min walk test
unable [unable-unable]
unable [unable-123]
0.75
Values that were missed or have unknown reason for not done are excluded. The remaining values are ranked as died<unable<refused=0<other non-zero values. The p-values are calculated by the rank-based Wilcoxon-Rank Sum tests.

44. Enteral Nutrition Only (n=35)
Other Outcomes
Enteral Nutrition Only (n=35)
EN+PN
(n=25)
Difference mean
(95% CI) p
values
Barthel index (change from baseline)
-32.2±36.6
( )
-31.3±27.0
( )
1 (-24,22)
0.90
SF 36 score (changes from baseline to 6 months)
PHYSICAL FUNCTIONING
-12.1±49.0 ( )
3.5±29.3 ( )
16 (-51, 20)
0.51
ROLE-PHYSICAL
-5.0±54.3 ( )
-10.0±54.3 ( )
-5 (-41, 51)
0.76
STANDARDIZED PHYSICAL COMPONENT SCALE
-1.6±16.1 ( )
1.6±7.7 ( )
3 (-15,8)
0.35
US thickness
Baseline
1.9± 0.7 ( )
1.7± 0.7 ( )
0 (0,1)
0.12
Week #2
1.7± 0.7 ( )
1.6± 0.8 ( )
0.41
Week #3
1.8± 0.7 ( )
1.7± 1.1 ( )
0 (-1,1)
0.75
Week #4
1.3± 0.4 ( )
1.4± 0.3 ( )
0.81
Change from Baseline
-0.1±0.6 ( )
-0.2±0.5 ( )
0 (0,0)
0.71

45. Conclusions of TOP uP study
Topping UP obese critically ill patient feasible
Possible signals of benefit
Hand grip strength
SF 36 PF
need to reduce missing data

46. 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