This document discusses optimal nutrition strategies for critically ill patients. It emphasizes the importance of early enteral nutrition within 48 hours of admission, and achieving adequate calorie and protein intake levels. Higher calorie and protein intake levels are associated with better outcomes like reduced infections, shorter hospital stays and lower mortality. The development of the NUTRIC risk score is summarized, which can help identify patients most likely to benefit from aggressive nutrition therapy based on factors like age, illness severity and comorbidities. Validation studies showed higher risk patients based on NUTRIC score had worse outcomes with low nutrition adequacy levels. Nurse-directed feeding protocols are recommended to help optimize enteral nutrition delivery.

3. Critical Care Nutrition
The right nutrient/nutritional strategy
The right timing
The right patient
The right intensity (dose/duration)
With the right outcome!
www.criticalcarenutrition.com

6. Early and Adequate EN Best for
the Patient!
Role of Supplemental PN

7. Loss of Gut Epithelial Integrity
INTESTINAL EPITHELIUM
SIRS
Bacteria
DISTAL ORGANDISTAL ORGAN
INJURYINJURY
(Lung, Kidneys)(Lung, Kidneys)
via thoracic duct
Underlying Pathophysiology
of Critical Illness
lymphocytes

8. Disuse Causes Loss of Functional and Stuctural Integrity
Increased Gut Permeability
Characteristics : Time dependent
Correlation to disease severity
Consequences: Risk of infection
Risk of MOFS

9. Feeding Supports Gastrointestinal
Structure and Function
• Maintenance of gut barrier function
• Increased secretion of mucus, bile, IgA
• Maintenance of peristalsis and blood flow
•Attenuates oxidative stress and inflammation
•Supports GALT
•Improves glucose absorption
Alverdy (CCM 2003;31:598)
Kotzampassi Mol Nutr Food Research 2009
Nguyen CCM 2011

10. Effect of Early Enteral Feeding on the
Outcome of Critically ill Mechanically
Ventilated Medical Patients
• Retrospective analysis of
multiinstitutional database
• 4049 patients requiring mech
vent > 2 days
• Categorized as “Early EN” if
rec’d feeds within 48 hours of
admission (n=2537, 63%)
0
5
10
15
20
25
30
35
VAP ICU
Mort
Hosp
Mort
Early
Late
Artinian Chest 2006:129;960
P=0.007 P=0.0005P=0.02

11. Effect of Early Enteral Feeding on the
Outcome of Critically ill Mechanically
Ventilated Medical Patients
Artinian Chest 2006:129;960

12. Early EN (within 24-48 hrs of admission)
is recommended!
…associated with large reductions in
infections and mortality
Updated CPGs, see www.criticalcarenutrition.com

13. Optimal Amount of Protein and
Calories for Critically Ill Patients

14. 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
0
200
400
600
800
1000
1200
1400
1600
1800
2000
1 3 5 7 9 11 13 15 17 19 21
Days
kcal
Prescribed Engergy
Energy Received From Enteral Feed
Caloric Debt

15. • 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

17. Effect of Increasing Amounts of Calories
from EN on Infectious Complications
Heyland Clinical Nutrition 2010
Multicenter observational study of 207 patients >72 hrs in ICU
followed prospectively for development of infection
for increase of 1000 cal/day, OR of infection at 28 days

18. Relationship between increased nutrition intake and
physical function (as defined by SF-36 scores)
following critical illness
Unpublished data from Multicenter RCT of glutamine and antioxidants
(REDOXS Study); n=364
for increase of 30 gram/day, OR of infection at 28 days
Model *
Estimate (CI)
P values
At 3 months
PHYSICAL FUNCTIONING 3.2 (-1.0, 7.3) P=0.14
ROLE PHYSICAL 4.2 (-0.0, 8.5) P=0.05
STANDARDIZED PHYSICAL COMPONENT SCALE 1.8 (0.3, 3.4) P=0.02
At 6 months
PHYSICAL FUNCTIONING 0.8 (-3.6, 5.1) P=0.73
ROLE PHYSICAL 2.0 (-2.5, 6.5) P=0.38
STANDARDIZED PHYSICAL COMPONENT SCALE 0.70 (-1.0, 2.4) P=0.41
For every 1000 kcal/day received:

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

20. • 113 select ICU patients
with sepsis or burns
• On average, receiving
1900 kcal/day and 84
grams of protein
• No significant
relationship with
energy intake but……
Clinical Nutrition 2012

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

23. 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

24. 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*
*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.
0.4 0.6 0.8 1.0 1.2 1.4 1.6
Unadjusted
Adjusted
Odds ratios with 95% confidence intervals

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

26. RCT Level of Evidence that
More EN= Improved Outcomes
 RCTs of aggressive feeding protocols
 Results in better protein-energy intake
 Associated with reduced complications and improved
survival
Taylor et al Crit Care Med 1999; Martin CMAJ 2004
 Meta-analysis of Early vs Delayed EN
 Reduced infections: RR 0.76 (.59,0.98),p=0.04
 Reduced Mortality: RR 0.68 (0.46, 1.01) p=0.06
www.criticalcarenutrition.com

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

29. Rice et al. JAMA 2012;307

30. Rice et al. JAMA 2012;307
Still no measure of physical function!

31. Rice et al. JAMA 2012;307
Enrolled 12% of patients screened

32. Trophic vs. Full enteral feeding in critically ill
patients with acute respiratory failure
• Average age 52
• Few comorbidities
• Average BMI 29-30
• 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!

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

34. How do we figure out who will benefit
the most from Nutrition Therapy?

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

36. 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

37. 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] <.001
Baseline SOFA 9.0 [6.0 to 11.0] 6.0 [4.0 to 8.5] <.001
# of days in hospital prior to ICU admission 0.9 [0.1 to 4.5] 0.3 [0.0 to 2.2] <.001
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 <0.001
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] <.001
Interleukin-6¶ 158.4 [39.2 to 1034.4] 72.0 [30.2 to 189.9] <.001
171 patients had data of recent oral intake and weight loss
Non-survivors by day 28
(n=32)
Survivors by day 28
(n=139)
p values
% Oral intake (food) in the week prior to enrolment 4.0[ 1.0 to 70.0] 50.0[ 1.0 to 100.0] 0.10
% of weight loss in the last 3 month 0.0[ 0.0 to 2.5] 0.0[ 0.0 to 0.0] 0.06

38. The Development of the NUTrition Risk in the
Critically ill Score (NUTRIC Score).
Variable Range Points
Age <50 0
50-<75 1
>=75 2
APACHE II <15 0
15-<20 1
20-28 2
>=28 3
SOFA <6 0
6-<10 1
>=10 2
# Comorbidities 0-1 0
2+ 1
Days from hospital to ICU admit 0-<1 0
1+ 1
IL6 0-<400 0
400+ 1
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.

39. The Validation of the NUTrition Risk in the
Critically ill Score (NUTRIC Score).
0 1 2 3 4 5 6 7 8 9 10
Nutrition Risk Score
MortalityRate(%)
020406080
Observed
Model-based
n=12 n=33 n=55 n=75 n=90 n=114 n=82 n=72 n=46 n=17 n=2

40. The Validation of the NUTrition Risk in the
Critically ill Score (NUTRIC Score).
0 1 2 3 4 5 6 7 8 9 10
Nutrition Risk Score
DaysonMechanicalVentilator
02468101214
Observed
Model-based
n=12 n=33 n=55 n=75 n=90 n=114 n=82 n=72 n=46 n=17 n=2

41. The Validation of the NUTrition Risk in the
Critically ill Score (NUTRIC Score).
0 50 100 150
0.00.20.40.60.81.0
Nutrition Adequacy Levles (%)
28DayMortality
11
11
1
1
1
11
2
2
2
2
2 2
2
2
2
3
3
3
33
3
3
3
3
33
3
3
3
3
3
3
3
444
4
44
4444
4
44
4
44 44
44
4
4
4
4
4
4 4
44 4 44
4
4
4
55 5555 5 5
5 5 5 5 5 5
5 55
555 5
5
5
5
555 55 555
55
5
5
5
555 5
55
66 66 66
666
66
6 6
6
6
66
6 666 66 6
6
6
6
6
6
6 6
6
66
6 6
6
6
6
7
7
7
7
7
7
7
7
7
7
7
7
7
7
77
7
7
7
7
7
7
7 7
7
8
8
8
8
8
8
8
8
88
8
8
8
88
8
8
8
8
8
8
8
9
9
9
9
9
9
9
9
9
1010
Interaction between NUTRIC Score and nutritional adequacy (n=211)*
P value for the
interaction=0.01
Heyland Critical Care 2011, 15:R28

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

43. Do we have a problem?

44. Preliminary Results of INS 2011
Overall Performance: Kcals
84%
56%
15%
N=211

45. Failure Rate
% high risk patients who failed to meet minimal quality targets
(80% overall energy adequacy)
Unpublished observations, Results of 2011 INS

46. Cahill, J Crit Care 2012 Dec;27(6):727-

47. www.criticalcarenutrition.com
“Use of a feeding protocol that incorporates motility
agents and small bowel feeding tubes should be
considered”

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

49. The Impact of Enteral Feeding Protocols
on Enteral Nutrition Delivery:
Results of a multicenter observational study
• 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
Heyland JPEN Nov 2010
P<0.05
P<0.05

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

51. Enhanced Protein-Energy Provision
via the Enteral Route
in Critically Ill Patients:
The PEP uP Protocol

52. • Different feeding options based on hemodynamic
stability and suitability for high volume intragastric
feeds.
• 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
• Nurse reports daily on nutritional adequacy.
The Efficacy of Enhanced Protein-Energy Provision via the
Enteral Route in Critically Ill Patients:
The PEP uP Protocol!
A Major Paradigm Shift in How we Feed Enterally

53. The Efficacy of Enhanced Protein-Energy Provision via the
Enteral Route in Critically Ill Patients:
The PEP uP Protocol!
Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Total
P-value 0.08 0.0003 0.10 0.19 0.48 0.18 0.11 <0.0001
Adequacy of Calories from EN
(Before Group vs. After Group on Full Volume Feeds)
Heyland Crit Care 2010

54. Change of nutritional intake from baseline to follow-
up of all the study sites (intervention group only)
% calories
received/prescribed
%caloriesreceived/prescribed
1 2 3 4 5 6 7 8 9 10 12
0102030405060708090100
n ITT
n Efficacy
n FVF
n E@Base
243
113
57
260
219
113
57
236
194
113
57
209
171
108
54
175
153
105
52
152
138
96
46
136
118
83
40
113
107
75
35
102
83
59
26
90
76
52
23
80
59
40
17
71
52
35
14
62
ITT
Efficacy
Full volume feeds
Baseline intervention
%proteinreceived/prescribed
1 2 3 4 5 6 7 8 9 10 12
0102030405060708090100
n ITT
n Efficacy
n FVF
n E@Base
243
113
57
260
219
113
57
236
194
113
57
209
171
108
54
175
153
105
52
152
138
96
46
136
118
83
40
113
107
75
35
102
83
59
26
90
76
52
23
80
59
40
17
71
52
35
14
62
ITT
Efficacy
Full volume feeds
Baseline intervention
Heyland CCM 2013 (in press)

55. Other Strategies to Maximize the
Benefits and Minimize the Risks of EN
• Liberalization of gastric residual volumes
• Motility agents started at initiation of EN
rather that waiting till problems with High
GRV develop.
• Small bowel feeding tubes
• Elevation of head of the bed
• Have nurse report on nutritional adquacy
during daily ward rounds

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

57. 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

58. 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

59. Lancet Dec 2012

60. Lancet Dec 2012

61. Lancet Dec 2012

62. Doig, ANZICS, JAMA May 2013
Adult patients were eligible for enrollment within 24
hours of ICU admission if they were expected to
remain in the ICU on the calendar day after
enrollment, were considered ineligible for enteral
nutrition by the attending clinician due to a short-
term relative contraindication and were not
expected to PN or oral nutrition

63. Who were these patients?
Overall, standard
care group
remained unfed for
2.8 days after
randomization
40% of standard
care group never
rec’d any artificial
nutrition; remained
in ICU 3.5 days

64. Intervention not intense enough?
• 40% of both groups got EN (delayed)
• 40% of standard care group got PN for an
average of 3.0 days
• Average PN use in early PN group was 6.0 days
•

65. Doig, ANZICS, JAMA May 2013
Main inference: No harm by early PN
(in contrast to EPaNIC)

66. 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
•Use early in high risk
cases

67. Yes
YES
At 72 hrs
>80% of Goal
Calories?
No
NO
No problem
Anticipated
Long Stay?
Yes No
Maximize EN with
motility agents and
small bowel feeding
No
YES
Tolerating
EN at 96
hrs?
Yes
NO
Start PEP UP within 24-48 hrs
High Risk?
Carry on!
Supplemental PN? No problem

68. 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!
– PEP uP protocol in all
– Selective use of small bowel feeds then sPN in high risk patients

69. Questions?