Optimizing Nutrition Delivery in the Critically Ill

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Critical Care NutritionThe right nutrient/nutritional strategy

The right timingThe 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

Loss of Gut Epithelial Integrity

INTESTINAL EPITHELIUM

SIRS

Bacteria

DISTAL ORGAN DISTAL ORGAN INJURY INJURY (Lung, Kidneys)(Lung, Kidneys)

via thoracic duct

Underlying Pathophysiology of Critical Illness

lymphocytes

Disuse Causes Loss of Functional and Stuctural IntegrityIncreased 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 rec’d feeds within 48 hours of admission (n=2537, 63%)

0

5

10

15

20

25

30

35

VAP ICUMort

HospMort

EarlyLate

Artinian Chest 2006:129;960

P=0.007 P=0.0005P=0.02

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 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

0200

400600

8001000

12001400

16001800

2000

1 3 5 7 9 11 13 15 17 19 21

Days

kcal

Prescribed Engergy

Energy Received From Enteral Feed

Caloric Debt

• 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

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

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:

Faisy BJN 2009;101:1079

Mechancially Vent’d patients >7days (average ICU LOS 28 days)

• 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 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

UnadjustedAdjusted

Odds ratios with 95% confidence intervals

Association Between 12-day Caloric Adequacy and 60-Day Hospital

Mortality

Heyland CCM 2011

Optimal amount= 80-85%

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

survivalTaylor 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


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!


Enrolled 12% of patients screened

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?

Nutrition Statusmicronutrient levels - immune markers - muscle mass

Starvation

Acute-Reduced po intake

-pre ICU hospital stay

Chronic-Recent weight loss

-BMI?

InflammationAcute

-IL-6-CRP-PCT

Chronic-Comorbid illness

A Conceptual Model for Nutrition Risk Assessment in the Critically Ill

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)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

The Development of the NUTrition Risk in the Critically ill Score (NUTRIC

Score). Variable Range PointsAge <50 0

50-<75 1>=75 2

APACHE II <15 015-<20 120-28 2>=28 3

SOFA <6 06-<10 1>=10 2

# Comorbidities 0-1 02+ 1

Days from hospital to ICU admit 0-<1 01+ 1

IL6 0-<400 0400+ 1

AUC 0.783Gen R-Squared 0.169Gen 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.

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

Mo

rta

lity

Ra

te (

%)

02

04

06

08

0

ObservedModel-based

n=12 n=33 n=55 n=75 n=90 n=114 n=82 n=72 n=46 n=17 n=2


0 1 2 3 4 5 6 7 8 9 10

Nutrition Risk Score

Da

ys o

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ech

an

ica

l Ve

ntil

ato

r

02

46

81

01

21

4 ObservedModel-based

n=12 n=33 n=55 n=75 n=90 n=114 n=82 n=72 n=46 n=17 n=2


0 50 100 150

0.0

0.2

0.4

0.6

0.8

1.0

Nutrition Adequacy Levles (%)

28

Da

y M

ort

alit

y

11 111

1

111

22

2

22 2

22

2

33

333

33

3

3

333

3

3

33

33

444444

4444

4

444

44 4444

44

4

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4 444 4 44

44

4

55 5555 5 55 5 5 5 5 5

5 55555 5

5

55

555 55 55555

55

5 555 555

66 66 6666666

6 66

6

666 666 66 6

6

66

66

6 6

666

6 66

66

77

7

77

7

7

7

7

7

7

7

7

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77

7

7

77

7

7

7 7

7

88

8

8

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8

88

88

8

88

8

8

88

8

8

8

99

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

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):727-734


“Use of a feeding protocol that incorporates motility agents and small bowel feeding tubes should be considered”

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.”

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 withoutHeyland JPEN Nov 2010

P<0.05

P<0.05

Can we do better?

The same thinking that got you into this mess won’t get you out of it!

Enhanced Protein-Energy Provision

via the Enteral Routein 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.

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

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 TotalP-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

Change of nutritional intake from baseline to follow-up of all the study sites (intervention group only)

% calories received/prescribed

% c

alo

rie

s re

ceiv

ed

/pre

scri

be

d

1 2 3 4 5 6 7 8 9 10 12

01

02

03

04

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06

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09

01

00

n ITTn Eff icacyn FVFn E@Base

24311357260

21911357236

19411357209

17110854175

15310552152

1389646136

1188340113

1077535102

83592690

76522380

59401771

52351462

ITTEfficacyFull volume feedsBaseline intervention

% p

rote

in r

ece

ive

d/p

resc

rib

ed

1 2 3 4 5 6 7 8 9 10 12

01

02

03

04

05

06

07

08

09

01

00

n ITTn Eff icacyn FVFn E@Base

24311357260

21911357236

19411357209

17110854175

15310552152

1389646136

1188340113

1077535102

83592690

76522380

59401771

52351462

ITTEfficacyFull volume feedsBaseline intervention

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

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

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

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

Lancet Dec 2012

Lancet Dec 2012

Lancet Dec 2012

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

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

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

•

Doig, ANZICS, JAMA May 2013

Main inference: No harm by early PN (in contrast to EPaNIC)

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

Yes

YESAt 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

YESTolerating

EN at 96 hrs? Yes

NO

Start PEP UP within 24-48 hrs

High Risk?

Carry on!

Supplemental PN? 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?

Documents

Optimizing Nutrition Delivery in the Critically Ill