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Early and Adequate Nutrition is therapy

that modulates the underlying disease


process and impacts patient outcomes

Adjunctive
Supportive
Care

Proactive
Primary
Therapy

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

Early vs. Delayed EN:


Effect on Infectious
Complications

Updated 2009
www.criticalcarenutrition.com

Early vs. Delayed EN:


Effect on Mortality

Updated 2009
www.criticalcarenutrition.com

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

Early EN (within 24-48 hrs of


admission) is recommended!

Optimal Amount of Protein and


Calories for Critically Ill
Patients?

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

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

What Study Patients Actually Recd


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

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

0.95

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.

Relationship Between Increased Energy


and Ventilator-Free days
Adjusted
BMI Group

95% CI

P-value

Estimate

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.

Mechancially Ventd patients >7days


(average ICU LOS 28 days)

Faisy BJN 2009;101:1079

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

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

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

(B) Increased protein intake

for

STANDARDIZED PHYSICAL COMPONENT


1.9 (0.5, 3.2)
SCALE (PCS) at 3 months

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


0.7 (-0.9, 2.2)
P=0.39
SCALE (PCS)
at 6gram/day,
months
increase
of 30
OR of infection at 28 days

Heyland Unpublished Data

More (and Earlier) is


Better!

If you feed them (better!)


They will leave (sooner!)

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

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

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:
1.
2.
3.

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:
1.
2.
3.

ICU length of stay (LOS),


Evaluable nutrition days and
Relevant baseline patient characteristics or some combination thereof.

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

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

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

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

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

ICU patients are not all created equalshould 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

What are the nutritional risk factors


associated with clinical outcomes?
(validation of our candidate variables)
Spearman
correlation with
VFD within 28
days

p values

Number of
observations

Age
Baseline APACHE II score
Baseline SOFA

-0.1891
-0.3914
-0.3857

<.0001
<.0001
<.0001

598
598
594

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

0.1676

0.0234

183

number of days in hospital prior to ICU admission

-0.1387

0.0007

598

% of weight loss in the last 3 month


Baseline BMI
# of co-morbidities at baseline
Baseline CRP
Baseline Procalcitionin
Baseline IL-6

-0.1828
0.0581
-0.0832
-0.1539
-0.3189
-0.2908

0.0130
0.1671
0.0420
0.0002
<.0001
<.0001

184
567
598
589
582
581

Variable

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

19.3-48.8

referent

48.9-59.7

0.780

59.7-67.4

0.949

67.5-75.3

1.272

75.4-89.4

1.907

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?

Can we do better?

The same thinking that got you into


this mess wont get you out of it!

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 150-500x2.
Patients followed for development of VAP
(diagnosed invasively)
Mentec CCM 2001;29:1955

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

Strategies to Maximize the Benefits


and Minimize the Risks of EN

feeding protocols
motility agents
elevation of HOB
small bowel feeds

weak evidence

stronger evidence
Canadian CPGs www.criticalcarenutrition.com

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
Characteristics

Total
15.2% using the
recommended
threshold volume
of 250 ml

n=269
Feeding Protocol
Yes 208 (78%)
Gastric Residual Volume
Tolerated in Protocol
Mean (range)
Elements included in Protocol
Motility agents
Small bowel feeding
HOB Elevation

217 ml (50, 500)


68.5%
55.2%
71.2 %

Heyland JPEN Nov 2010

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

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

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 recd
more calories with no increase in
complications

Desachy ICM 2008;34:1054

Initial Efficacy and Tolerability of Early


Enteral Nutrition with Immediate or
Gradual Introduction in Intubated Patients

Desachy ICM 2008;34:1054

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

Protocol to Manage
Interruptions to EN due to nonGI Reasons

Can be downloaded from www.criticalcarenutrition.com

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

Change of nutritional intake from


baseline to follow-up of all the study
sites
(Efficacy Analysis)
80

80

% calories
Intervention
sites
Control sites
received/prescribed

371
331

60

376

378

50

390

404

359

379

40

40

374
373
360

375

% calories received/prescribed

60

326

372

50

70

Academic
Community

380

30

30

362

Baseline

377
327
p value for Academic sites=0.20
p value for Community sites=0.78

20

p value for Academic sites=0.001


p value f or Community sites=0.07

20

% calories received/prescribed

70

Academic
Community

Follow-up

Baseline

Follow-up

Change of nutritional intake from


baseline to follow-up of all the
study sites
(Efficacy
Analysis)
% protein
received/prescribed
Intervention sites

Control sites
80

80

326

331
371

60

376
378

50

360
374
373

404

359
379

40

375

% protein received/prescribed

390

40

50

60

372

380

30

30

362

Baseline

377
327
p value for Academic sites=0.15
p value for Community sites=0828

20

p value for Academic sites=0.002


p value for Community sites=0.009

20

% protein received/prescribed

70

Academic
Community

70

Academic
Community

Follow-up

Baseline

Follow-up

Other Strategies to Maximize the


Benefits and Minimize the Risks of
EN
Small Bowel vs. Gastric Feeding: A metaanalysis
Effect on VAP

Updated 2011,www.criticalcarenutrition.com

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

27

4.1

D2

11

1.8

D4

Total

33

75

11.7

P=0.004

P=0.09

Heyland CCM 2001;29:1495-1501

Health Care Associated


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

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 24-48
hours if EN is contraindicated or if they can not tolerate
adequate amounts of EN.

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

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

The TOP UP Trial


PN for 7 days

ICU patients
BMI <25
BMI >35
Fed enterally

Stratified by:
Site
BMI
Med vs Surg

Control

Primary
Outcome
60-day
mortality

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!

www.criticalcarenutrition.com

Questions?

www.criticalcarenutrition.com

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