1. Optimal Provision of EN Nutrition in the ICU
Daren K. Heyland
Professor of Medicine
Queen’s University, Kingston General Hospital
Kingston, ON Canada
Add pep up slides

2. Early and Adequate Nutrition is therapy that modulates the underlying disease process and impacts patient outcomes
Adjunctive
Supportive
Care
Proactive
Primary
Therapy

3.  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

4. Early vs. Delayed EN: Effect on Infectious Complications
R-make sure up to date. DONE
Updated 2009

5. Early vs. Delayed EN: Effect on Mortality
R- make sure up to date. DONE
Updated 2009

6. Feeding the Hypotensive Patient?
Prospectively collected multi-institutional ICU database of 1,174 patients who required mechanical ventilation for more than two days and were on vasopressor agents to support blood pressure.
The beneficial effect of early feeding is more evident in the sickest patients, i.e, those on multiple vasopressor agents.
DiGiovine et al. AJCC 2010

7. Optimal Amount of Protein and Calories for Critically Ill Patients?
Early EN (within hrs of admission) is recommended!
Optimal Amount of Protein and Calories for Critically Ill Patients?

8. 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

9. 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

10. 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

11. Relationship Between Increased Calories and 60 day Mortality
BMI Group
Odds Ratio
95% Confidence Limits
P-value
Overall
0.76
0.61
0.95
0.014
<20
0.52
0.29
0.033
20-<25
0.62
0.44
0.88
0.007
25-<30
1.05
0.75
1.49
0.768
30-<35
1.04
0.64
1.68
0.889
35-<40
0.36
0.16
0.80
0.012
>=40
0.63
0.32
1.24
0.180
Legend: Odds of 60-day Mortality per 1000 kcals received per day adjusting for nutrition days, BMI, age, admission category, admission diagnosis and APACHE II score.

13. Relationship Between Increased Energy and Ventilator-Free days
BMI Group
Adjusted
Estimate
95% CI
P-value
LCL
UCL
Overall
3.5
1.2
5.9
0.003
<20
2.8
-2.9
8.5
0.337
20-<25
4.7
1.5
7.8
0.004
25-<30
0.1
-3.0
3.2
0.958
30-<35
-1.5
-5.8
2.9
0.508
35-<40
8.7
2.0
15.3
0.011
>=40
6.4
-0.1
12.8
0.053
Legend: # of VFD per 1000 kcals received per day adjusting for nutrition days, BMI, age, admission category, admission diagnosis and APACHE II score.

14. Mechancially Vent’d patients >7days (average ICU LOS 28 days)
Faisy BJN 2009;101:1079

15. for increase of 30 gram/day, OR of infection at 28 days
Effect of Increasing Amounts of Protein from EN on Infectious Complications
Multicenter observational study of 207 patients >72 hrs in ICU followed prospectively for development of infection
for increase of 30 gram/day, OR of infection at 28 days
Heyland Clinical Nutrition 2010

16. Relationship between increased nutrition intake and physical function (as defined by SF-36 scores) following critical illness
Multicenter RCT of glutamine and antioxidants (REDOXS Study)
First 364 patients with SF 36 at 3 months and/or 6 months
Model *
Estimate (CI)
P values
(B) Increased protein intake
PHYSICAL FUNCTIONING (PF) at 3 months
2.9 (-0.7, 6.6)
P=0.11
ROLE PHYSICAL (RP) at 3 months
4.4 (0.7, 8.1)
P=0.02
STANDARDIZED PHYSICAL COMPONENT SCALE (PCS) at 3 months
1.9 (0.5, 3.2)
P=0.007
PHYSICAL FUNCTIONING (PF) at 6 months
0.2 (-3.9, 4.3)
P=0.92
ROLE PHYSICAL (RP) at 6 months
1.7 (-2.5, 5.9)
P=0.43
STANDARDIZED PHYSICAL COMPONENT SCALE (PCS) at 6 months
0.7 (-0.9, 2.2)
P=0.39
for increase of 30 gram/day, OR of infection at 28 days
Heyland Unpublished Data

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

18. Permissive Underfeeding (Starvation)?
187 critically ill patients
Tertiles according to ACCP recommended levels of caloric intake
Highest tertile (>66% recommended calories) vs. Lowest tertile (<33% recommended calories)
 in hospital mortality
 Discharge from ICU breathing spontaneously
Middle tertile (33-65% recommended calories) vs. lowest tertile
Discharge from ICU breathing spontaneously
Krishnan et al Chest 2003

20. Optimal Amount of Calories for Critically Ill Patients: Depends on how you slice the cake!
Objective: To examine the relationship between the amount of calories recieved and mortality using various sample restriction and statistical adjustment techniques and demonstrate the influence of the analytic approach on the results.
Design: Prospective, multi-institutional audit
Setting: 352 Intensive Care Units (ICUs) from 33 countries.
Patients: 7,872 mechanically ventilated, critically ill patients who remained in ICU for at least 96 hours.
Heyland Crit Care Med 2011

21. Optimal Amount of Calories for Critically Ill Patients: Depends on how you slice the cake!
Sample restriction approaches have included limiting analyzed patients to those:
In the ICU for at least 96 hours,
In the ICU at least 96 hours prior to progression to exclusive oral feeding and
Eliminating days after progression to exclusive oral feeding from the calculation of nutrition intake.
Statistical adjustment approaches have included using regression techniques to adjust for:
ICU length of stay (LOS),
Evaluable nutrition days and
Relevant baseline patient characteristics or some combination thereof.
Heyland Crit Care Med 2011

22. Association between 12 day average caloric adequacy and
60 day hospital mortality
(Comparing patients rec’d >2/3 to those who rec’d <1/3)
A. In ICU for at least 96 hours. Days after permanent progression to exclusive oral feeding are included as zero calories*
B. In ICU for at least 96 hours. Days after permanent progression to exclusive oral feeding are excluded from average adequacy calculation.*
C. In ICU for at least 4 days before permanent progression to exclusive oral feeding. Days after permanent progression to exclusive oral feeding are excluded from average adequacy calculation.*
D. In ICU at least 12 days prior to permanent progression to exclusive oral feeding*
Remove the 1/3-2/3 data
*Adjusted for evaluable days and covariates,covariates include region (Canada, Australia and New Zealand, USA, Europe and South Africa, Latin America, Asia), admission category (medical, surgical), APACHE II score, age, gender and BMI.

23. Association Between 12-day Caloric Adequacy and 60-Day Hospital Mortality
Optimal amount=
80-85%
Heyland CCM 2011

24. Trophic vs. Full enteral feeding in critically ill patients with acute respiratory failure
Single center study of 200 mechanically ventilated patients
Trophic feeds: 10 ml/hr x 5 days
Rice CCM 2011;39:967

25. Did not measure infection nor physical function!
Trophic vs. Full enteral feeding in critically ill patients with acute respiratory failure
Did not measure infection nor physical function!
Rice CCM 2011;39:967

26. Trophic vs. Full enteral feeding in critically ill patients with acute respiratory failure
“survivors who received initial full-energy enteral nutrition were more likely to be discharged home with or without help as compared to a rehabilitation facility (68.3% for the full-energy group vs. 51.3% for the trophic group; p = .04).”
Rice CCM 2011;39:967

27. Trophic vs. Full enteral feeding in critically ill patients with acute respiratory failure
Average age 51
Few comorbidities
Average BMI 29
All fed within 24 hrs (benefits of early EN)
Average duration of study intervention 5 days
No effect in young, healthy, overweight patients who have short stays!
Large multicenter trial of this concept
(EDEN study) by ARDSNET just finished

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

29. How do we figure out who will benefit the most from Nutrition Therapy?
Need picture of malnourshed child

30. A Conceptual Model for Nutrition Risk Assessment in the Critically Ill
Chronic
Recent weight loss
BMI?
Acute
Reduced po intake
pre ICU hospital stay
Starvation
Nutrition Status
micronutrient levels - immune markers - muscle mass
Inflammation
Acute
IL-6
CRP
PCT
Chronic
Comorbid illness

31. Multi institutional data base of 598 patients
The Development of the NUTrition Risk in the Critically ill Score (NUTRIC Score).
When adjusting for age, APACHE II, and SOFA, what effect of nutritional risk factors on clinical outcomes?
Multi institutional data base of 598 patients
Historical po intake and weight loss only available in 171 patients
Outcome: 28 day vent-free days and mortality
Heyland Critical Care 2011, 15:R28

32. What are the nutritional risk factors associated with clinical outcomes? (validation of our candidate variables)
Non-survivors by day 28
(n=138)
Survivors by day 28
(n=460)
p values
Age
71.7 [60.8 to 77.2]
61.7 [49.7 to 71.5]
<.001
Baseline APACHE II score
26.0 [21.0 to 31.0]
20.0 [15.0 to 25.0]
Baseline SOFA
9.0 [6.0 to 11.0]
6.0 [4.0 to 8.5]
# of days in hospital prior to ICU admission
0.9 [0.1 to 4.5]
0.3 [0.0 to 2.2]
Baseline Body Mass Index
26.0 [22.6 to 29.9]
26.8 [23.4 to 31.5]
0.13
Body Mass Index
0.66
<20
6 ( 4.3%)
25 ( 5.4%)
≥20
122 ( 88.4%)
414 ( 90.0%)
# of co-morbidities at baseline
3.0 [2.0 to 4.0]
3.0 [1.0 to 4.0]
<0.001
Co-morbidity
Patients with 0-1 co-morbidity
20 (14.5%)
140 (30.5%)
Patients with 2 or more co-morbidities
118 (85.5%)
319 (69.5%)
C-reactive protein¶
135.0 [73.0 to 214.0]
108.0 [59.0 to 192.0]
0.07
Procalcitionin¶
4.1 [1.2 to 21.3]
1.0 [0.3 to 5.1]
Interleukin-6¶
158.4 [39.2 to ]
72.0 [30.2 to 189.9]
171 patients had data of recent oral intake and weight loss
(n=32)
(n=139)
% Oral intake (food) in the week prior to enrolment
4.0[ to ]
50.0[ to ]
0.10
% of weight loss in the last 3 month
0.0[ to ]
0.0[ to ]
0.06

33. Spearman correlation with VFD within 28 days Number of observations
What are the nutritional risk factors associated with clinical outcomes? (validation of our candidate variables)
Variable
Spearman correlation with VFD within 28 days
p values
Number of observations
Age
<.0001
598
Baseline APACHE II score
Baseline SOFA
594
% Oral intake (food) in the week prior to enrollment
0.1676
0.0234
183
number of days in hospital prior to ICU admission
0.0007
% of weight loss in the last 3 month
0.0130
184
Baseline BMI
0.0581
0.1671
567
# of co-morbidities at baseline
0.0420
Baseline CRP
0.0002
589
Baseline Procalcitionin
582
Baseline IL-6
581

34. The Development of the NUTrition Risk in the Critically ill Score (NUTRIC Score).
For example, exact quintiles and logistic parameters for age
Exact Quintile
Parameter
Points
referent
0.780 1
0.949
1.272
1.907 2

35. The Development of the NUTrition Risk in the Critically ill Score (NUTRIC Score).
Variable
Range
Points
Age
<50
50-<75 1
>=75 2
APACHE II
<15
15-<20
20-28
>=28 3
SOFA
<6
6-<10
>=10
# Comorbidities
0-1 2+
Days from hospital to ICU admit
0-<1 1+
IL6
0-<400
400+
AUC
0.783
Gen R-Squared
0.169
Gen Max-rescaled R-Squared 
0.256
BMI, CRP, PCT, weight loss, and oral intake were excluded because they were not significantly associated with mortality or their inclusion did not improve the fit of the final model.

36. The Validation of the NUTrition Risk in the Critically ill Score (NUTRIC Score).

37. The Validation of the NUTrition Risk in the Critically ill Score (NUTRIC Score).

38. Interaction between NUTRIC Score and nutritional adequacy (n=211)*
The Validation of the NUTrition Risk in the Critically ill Score (NUTRIC Score).
Interaction between NUTRIC Score and nutritional adequacy (n=211)*
P value for the interaction=0.01
Heyland Critical Care 2011, 15:R28

39. Who might benefit the most from nutrition therapy?
High NUTRIC Score?
Clinical
BMI
Projected long length of stay
Others?

40. The same thinking that got you into this mess won’t get you out of it!
Can we do better?
The same thinking that got you into this mess won’t get you out of it!

41. Aggressive Gastric Feeding may be a BAD THING!
Observational study of 153 medical/surgical ICU patients receiving EN in stomach
Intolerance= residual volume>500ml, vomiting, or residual volume x2.
Patients followed for development of VAP (diagnosed invasively)
Mentec CCM 2001;29:1955

42. Aggressive Gastric Feeding may be a BAD THING!
Incidence of Intolerance= 46%
Statistically associated with worse clinical outcomes!
Risk factors for Intolerance
Sedation
Catecholamines
High residuals before and during EN

43. Strategies to Maximize the Benefits and Minimize the Risks of EN
weak evidence
feeding protocols
motility agents
elevation of HOB
small bowel feeds
stronger evidence
Canadian CPGs

44. Rupinder to update
“Use of a feeding protocol that incorporates motility agents and small bowel feeding tubes should be considered”

45. Use of Nurse-directed Feeding Protocols
Start feeds at 25 ml/hr
< 250 ml
advance rate by 25 ml
reassess q 4h
> 250 ml
hold feeds
add motility agent
reassess q 4h
Check Residuals q4h
“Should be considered as a strategy to optimize delivery of enteral nutrition in critically ill adult patients.”
2009 Canadian CPGs

47. Get a copy of the one nestle uses for their tool kit

48. 15.2% using the recommended threshold volume of 250 ml
The Impact of Enteral Feeding Protocols on Enteral Nutrition Delivery: Results of a multicenter observational study
Characteristics
Total n=269
Feeding Protocol
Yes
208 (78%)
Gastric Residual Volume Tolerated in Protocol
Mean (range)
217 ml (50, 500)
Elements included in Protocol
Motility agents
68.5%
Small bowel feeding
55.2%
HOB Elevation
71.2 %
15.2% using the recommended threshold volume of 250 ml
Heyland JPEN Nov 2010

49. Time to start EN from ICU admission: Patients rec’ing motility agents:
The Impact of Enteral Feeding Protocols on Enteral Nutrition Delivery: Results of a multicenter observational study
P<0.05
Time to start EN from ICU admission:
41.2 in protocolized sites vs 57.1 hours in those without a protocol
Patients rec’ing motility agents:
61.3% in protocolized sites vs 49.0% in those without
P<0.05
Heyland JPEN 2010

50. Reasons for Inadequate Intake
Slow starts and slow ramp ups
Interruptions
Mostly related to procedures
Not related to GI dysfunction
Can be overcome by better feeding protocols
Impaired motility
Medications
Metabolic, electrolyte abnormalities
Underlying disease
Prophylactic use of motility agents

51. Initial Efficacy and Tolerability of Early Enteral Nutrition with Immediate or Gradual Introduction in Intubated Patients
This study randomized 100 mechanically ventilated patients (not in shock) to Immediate goal rate vs gradual ramp up (our usual standard).
The immediate goal group rec’d more calories with no increase in complications
Desachy ICM 2008;34:1054

52. Initial Efficacy and Tolerability of Early Enteral Nutrition with Immediate or Gradual Introduction in Intubated Patients
Desachy ICM 2008;34:1054

53. What Gastric Residual Volume Threshold Should I use?
329 patients randomized to GRV 200 vs. 500
>80% Medical
Average APACHE II 18
Similar nutritional adequacy:
85 vs 88% goal calories

54. Protocol to Manage Interruptions to EN due to non-GI Reasons
Add slide on interrruptions to EN re procedures.
Can be downloaded from

55. Other Strategies to Maximize the Benefits and Minimize the Risks of EN
Head of Bed elevation to 45 (or at least 30 if the patient doesn’t tolerate 45)
This will reduce regurgitation, aspiration and subsequent Pneumonia
List of Contraindications to HOB Elevation
unstable c-spine
hemodynamically unstable
Pelvic fractures with instability
Prone position
Intra-aortic ballon pump
Procedures
Unable because of obesity

56. Other Strategies to Maximize the Benefits and Minimize the Risks of EN
Impaired motility
Medications
Metabolic, electrolyte abnormalities
Underlying disease
Dysmotility linked to
decreased tolerance of EN
gastropulmonary route of infection
Trials of Cisapride, Erythromycin, Metoclopramide,

57. 2009 Canadian CPGs www.criticalcarenutrition.com
Pro-motility Agents
Conclusion:
1) Motility agents have no effect on mortality or infectious complications in critically ill patients.
2) Motility agents may be associated with an increase in gastric emptying, a reduction in feeding intolerance and a greater caloric intake in critically ill patients.
“Based on 1 level 1 study and 5 level 2 studies, in critically ill patients who experience feed intolerance (high gastric residuals, emesis), we recommend the use of a promotility agent. Given the safety concerns associated with erythromycin, the recommendation is made for metoclopramide. There are insufficient data to make a recommendation about the use of combined use of metoclopramide and erythromycin.”
2009 Canadian CPGs

58. Other Strategies to Maximize the Benefits and Minimize the Risks of EN
Motility agents started at initiation of EN rather that waiting till problems with High GRV develop.
Maxeran 10 mg IV q 6h (halved in renal failure)
If still develops high gastric residuals, add Erythromycin 200 mg q 12h.
Can be used together for up to 7 days but should be discontinued when not needed any more
Reassess need for motility agents daily

59. Daren K. Heyland Enhanced Protein-Energy Provision
via the Enteral Route
in Critically Ill Patients:
The PEP uP Protocol
Daren K. Heyland
Professor of Medicine
Queen’s University, Kingston General Hospital
Kingston, ON Canada

60. 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!
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
Tolerate higher GRV threshold (300 ml or more)
Motility agents and protein supplements are started immediately, rather than started when there is a problem.
A Major Paradigm Shift in How we Feed Enterally
Heyland Crit Care 2010

61. % calories received/prescribed
Change of nutritional intake from baseline to follow-up of all the study sites (Efficacy Analysis)
% calories received/prescribed 61

62. % protein received/prescribed
Change of nutritional intake from baseline to follow-up of all the study sites (Efficacy Analysis)
% protein received/prescribed 62

63. Small Bowel vs. Gastric Feeding: A meta-analysis
Other Strategies to Maximize the Benefits and Minimize the Risks of EN
Small Bowel vs. Gastric Feeding: A meta-analysis
Effect on VAP
Updated 2011,

64. Does Postpyloric Feeding Reduce Risk of GER and Aspiration?
Tube Position
# of patients
% positive for GER
% positive for Aspiration
Stomach 21 32
5.8 D1 8 27
4.1 D2 3 11
1.8 D4 1 5
Total 33 75
11.7
P=0.004
P=0.09
Heyland CCM 2001;29:

65. Health Care Associated Malnutrition
What if you can’t provide adequate nutrition enterally?
… to add PN or not to add PN,
that is the question!

66. Critical Care Nutrition CPGs
Canadians
Maximize EN (motility agents, small bowel feeds, etc.) prior to starting PN.
Americans
If unable to meet energy requirements after 7-10 days by the enteral route, consider initiating PN.
Initiating PN prior to this 7-10 day period does not improve outcome and may be detrimental to the patient.
Europeans
All patient who are not expected to be on normal nutrition within 3 days should receive PN within hours if EN is contraindicated or if they can not tolerate adequate amounts of EN.

67. 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
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
Cesaer NEJM 2011

68. 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

69. Maximize EN delivery prior to initiating PN
What if you can’t provide adequate nutrition enterally?
… to TPN or not to TPN,
that is the question!
Case by Case Decision
Maximize EN delivery prior to initiating PN

70. R The TOP UP Trial Primary Outcome 60-day mortality PN for 7 days
Stratified by:
Site
BMI
Med vs Surg
ICU patients R
BMI <25
60-day mortality
BMI >35
Fed enterally
Control

71. In Conclusion Health Care Associate Malnutrition is rampant
Not all ICU patients are the same in terms of ‘risk’
Iatrogenic underfeeding is harmful in some ICU patients or some will benefit more from aggressive feeding (avoiding protein/calorie debt)
BMI and/or NUTRIC Score is one way to quantify that risk
Need to do something to reduce iatrogenic malnutrition in your ICU!
Audit your practice first!
Consider updating your feeding protocol!

73. Questions?