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

Early and Adequate EN Best

for the Patient!

Role of Supplemental PN

Underlying Pathophysiology
of Critical Illness
Loss of Gut Epithelial Integrity

Bacteria

INTESTINAL EPITHELIUM

DISTAL ORGAN
INJURY
(Lung, Kidneys)

lymphocytes

SIRS

via thoracic duct

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

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

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
recd feeds within 48 hours of
admission (n=2537, 63%)

P=0.007

P=0.02

P=0.0005

Artinian Chest 2006:129;960

Effect of Early Enteral Feeding on

the Outcome of Critically ill
Mechanically Ventilated Medical
Patients

Artinian Chest 2006:129;960

Early EN (within 24-48 hrs of

admission) is recommended!

associated with large reductions in

infections and mortality
Updated CPGs, see www.criticalcarenutrition.com

Optimal Amount of Protein and

Calories for Critically Ill Patients

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

 Point prevalence survey of nutrition

practices in ICUs around the world
conducted Jan. 27, 2007
Enrolled 2772 patients from 158 ICUs over
5 continents
Included ventilated adult patients who
remained in ICU >72 hours

Effect of Increasing Amounts of

Calories from EN on Infectious
Complications
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

Heyland Clinical Nutrition 2010

Relationship between increased nutrition intake and

physical function (as defined by SF-36 scores)
following critical illness
For every 1000 kcal/day received:
Model *
Estimate (CI)

P values

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

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

At 3 months

At 6 months

for increase of 30 gram/day, OR of infection at 28 days

Unpublished data from Multicenter RCT of glutamine and antioxidants
(REDOXS Study); n=364

Mechancially Ventd patients >7days

(average ICU LOS 28 days)

Faisy BJN 2009;101:1079

 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

More (and Earlier) is

Better!

If you feed them (better!)

They will leave (sooner!)

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

Association between 12 day average caloric

adequacy and
60 day hospital mortality
(Comparing patients recd >2/3 to those who recd
<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
D. In ICU at least 12 days prior to
calculation.*
permanent progression to
exclusive oral feeding*

0.4

Unadjusted
Adjusted

0.6

0.8

1.0

1.2

1.4

1.6

Odds ratios with 95% confidence intervals

*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.

Association Between 12-day Caloric

Adequacy and 60-Day Hospital
Mortality

Optimal
amount=
80-85%

Heyland CCM 2011

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

More (and Earlier) is

Better!

If you feed them (better!)

They will leave (sooner!)

Rice et al. JAMA 2012;307

Still no measure of physical function!

Rice et al. JAMA 2012;307

Enrolled 12% of patients screened

Rice et al. JAMA 2012;307

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!

ICU patients are not all created equal

should we expect the impact of nutrition
therapy to be the same across all patients?

How do we figure out who will

benefit the most from Nutrition
Therapy?

A Conceptual Model for Nutrition Risk

Assessment in the Critically Ill
Acute

Chronic

-Reduced po intake
-pre ICU hospital stay

-Recent weight loss

-BMI?

Starvation
Nutrition Status
micronutrient levels - immune markers - muscle mass

Acute
-IL-6
-CRP
-PCT

Inflammation
Chronic
-Comorbid illness

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

What are the nutritional risk factors

associated with clinical outcomes?
(validation of our candidate variables)
Age
Baseline APACHE II score
Baseline SOFA
# of days in hospital prior to ICU admission
Baseline Body Mass Index
Body Mass Index

Non-survivors by day 28
(n=138)

Survivors by day 28
(n=460)

p values

71.7 [60.8 to 77.2]

61.7 [49.7 to 71.5]

<.001

26.0 [21.0 to 31.0]

20.0 [15.0 to 25.0]

<.001

9.0 [6.0 to 11.0]

6.0 [4.0 to 8.5]

<.001

0.9 [0.1 to 4.5]

0.3 [0.0 to 2.2]

<.001

26.0 [22.6 to 29.9]

26.8 [23.4 to 31.5]

0.13
0.66

<20
20

6 ( 4.3%)
122 ( 88.4%)
3.0 [2.0 to 4.0]

# of co-morbidities at baseline
Co-morbidity
Patients with 0-1 co-morbidity
20 (14.5%)
Patients with 2 or more co-morbidities
118 (85.5%)

135.0 [73.0 to 214.0]

C-reactive protein

4.1 [1.2 to 21.3]

Procalcitionin
158.4 [39.2 to 1034.4]
Interleukin-6
171 patients had data of recent oral intake and weight loss

% Oral intake (food) in the week prior to enrolment

% of weight loss in the last 3 month

25 ( 5.4%)
414 ( 90.0%)
3.0 [1.0 to 4.0]

<0.001
<0.001

140 (30.5%)
319 (69.5%)
108.0 [59.0 to 192.0]

0.07

1.0 [0.3 to 5.1]

<.001

72.0 [30.2 to 189.9]

<.001

Non-survivors by day 28
(n=32)

Survivors by day 28
(n=139)

p values

4.0[ 1.0 to 70.0]

50.0[ 1.0 to 100.0]

0.10

0.0[ 0.0 to 2.5]

0.0[ 0.0 to

0.0]

0.06

The Development of the NUTrition Risk

in the Critically ill Score (NUTRIC
Score).
Variable
Range
Points
Age

<50
50-<75
>=75
<15
15-<20
20-28
>=28
<6
6-<10
>=10
0-1
2+

0
1
2
0
1
2
3
0
1
2
0
1

Days from hospital to ICU admit

0-<1
1+

0
1

IL6

0-<400
400+

0
1

APACHE II

SOFA

# Comorbidities

AUC
Gen R-Squared
Gen Max-rescaled R-Squared

0.783
0.169
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.

Observed
Model-based

40
20

n=12

n=33

n=55

n=75

n=90

n=114

n=82

n=72

n=46

n=17

n=2

Mortality Rate (%)

60

80

The Validation of the NUTrition Risk in

the Critically ill Score (NUTRIC Score).

Nutrition Risk Score

10

Observed
Model-based

10
8
6
4
2

n=12

n=33

n=55

n=75

n=90

n=114

n=82

n=72

n=46

n=17

n=2

10

Days on Mechanical Ventilator

12

14

The Validation of the NUTrition Risk in

the Critically ill Score (NUTRIC Score).

Nutrition Risk Score

The Validation of the NUTrition Risk in

the Critically ill Score (NUTRIC Score).
1.0

Interaction between NUTRIC Score and nutritional adequacy (n=211)*

0.8

8 88
0.6

77 7

9
9

8888
7 7

8888

0.2

0.4

77

4
0.0

28 Day Mortality

P value for the

interaction=0.01

2
0

9
8

10
10

888

8
77 7
8
77 7
88
7
77
6
7
7777
6 66666 6
9
66666 6 6 6
66 666666666
666 6 6 66
7
5
555
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
4 4 3
5 55 555 55 555 55
5
5 5
444 4 43
4
4
2
4
4
4
3
44444444
33
444 4444
3
4
3
1
4 4
22
3
4 4
3 3 33 2 22 2 1
3
11
33 3
2
1 11 1 1
50

100

3
3
5

150

Nutrition Adequacy Levles (%)

Heyland Critical Care 2011, 15:R28

Who might benefit the most from

nutrition therapy?
High NUTRIC Score?
Clinical
BMI
Projected long length of stay

Others?

Do we have a problem?

Preliminary Results of INS

2011
Overall Performance: Kcals
84%
56%
15%

N=211

Failure Rate
% high risk patients who failed to meet minimal
quality targets (80% overall energy adequacy)

Unpublished observations, Results of 2011 INS

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

Use of a feeding protocol that incorporates motility

agents and small bowel feeding tubes should be
considered
www.criticalcarenutrition.com

Use of Nurse-directed Feeding

Protocols
Start feeds at 25
ml/hr
> 250 ml
hold feeds
add motility
agent

Check
Residuals
q4h

< 250 ml
advance rate by 25 ml
reassess q 4h

reassess q 4h

Should be considered as a strategy to optimize delivery of

enteral nutrition in critically ill adult patients.
2009 Canadian CPGs www.criticalcarenutrition.com

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 recing motility agents:

61.3%
in protocolized sites vs 49.0% in those
P<0.05
without
Heyland JPEN Nov 2010

Can we do better?

The same thinking that got you into

this mess wont get you out of it!

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

The Efficacy of Enhanced Protein-Energy Provision via

the Enteral Route in Critically Ill Patients:
The PEP uP Protocol!

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.

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!
Adequacy of Calories from EN
(Before Group vs. After Group on Full Volume Feeds)

P-value

Day 1
0.08

Day 2
0.0003

Day 3
0.10

Day 4
0.19

Day 5
0.48

Day 6
0.18

Day 7
0.11

Total
<0.0001

Heyland Crit Care 2010

100

100

Change of nutritional intake from baseline

to follow-up of all the study sites
(intervention group only)

n
n
n
n

ITT
Ef ficacy
FVF
E@Base

70
60
50
40
30
10

ITT
Efficacy
Full volume feeds
Baseline intervention

10

ITT
Efficacy
Full volume feeds
Baseline intervention

20

% protein received/prescribed

20

30

40

50

60

% calories received/prescribed

70

80

80

90

90

% calories
received/prescribed

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

10

59
40
17
71

52
35
14
62

12

n ITT
n Eff icacy
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

10

59
40
17
71

52
35
14
62

12

Heyland CCM 2013 (in press)

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

Health Care Associated

Malnutrition
What if you cant provide
adequate nutrition enterally?
to add PN or not to add PN,
that is the question!

Early vs. Late Parenteral

Nutrition in Critically ill Adults
4620 critically ill patients
Randomized to early PN
Recd 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

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 recd PN for 1-2 days on average
Late group only recd any PN

Cesaer NEJM 2011

Lancet Dec 2012

Lancet Dec 2012

Lancet Dec 2012

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 shortterm relative contraindication and were not
expected to PN or oral nutrition

Doig, ANZICS, JAMA May 2013

Who were these patients?

Overall, standard
care group
remained unfed for
2.8 days after
randomization
40% of standard
care group never
recd any artificial
nutrition; remained
in ICU 3.5 days

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

Main inference: No harm by early PN

(in contrast to EPaNIC)
Doig, ANZICS, JAMA May 2013

What if you cant 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

Start PEP UP within 24-48 hrs

At 72 hrs

YES

>80% of Goal
Calories?

NO

No

Yes

Anticipated
Long Stay?

High Risk?

Carry on!

Yes

No

Maximize EN with
motility agents and
small bowel feeding

YES

No
Supplemental PN?

Tolerating
EN at 96
hrs?

No problem

NO

Yes
No problem

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

Questions?