Learning Objectives• Define iatrogenic malnutrition• Describe the nature of the evidence related

to optimal amount of calories/protein• List key variables to consider in assessing

nutritional risk in ICU patients• List strategies to improve nutritional

adequacy in the critical care setting.

A different form of malnutrition?

Health Care Associated Malnutrition

Nutrition deficiencies associated with physiological derangement and organ

dysfunction that occurs in a health care facility

Patients who will benefit the most from nutrition therapy and who will be harmed the most from

by iatrogenic malnutrition (underfeeding)

Optimal Amount of Protein and Calories for Critically Ill

Patients?

Early EN (within 24-48 hrs of admission) is recommended!

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

0200400600800

100012001400160018002000

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Unpublished data from Multicenter RCT of glutamine and antioxidants (REDOXS Study); n=364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

More (and Earlier) is Better!

If you feed them (better!)They will leave (sooner!)

Rice et al. JAMA 2012;307

Rice et al. JAMA 2012;307

Rice et al. JAMA 2012;307

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!

Nutritional Management of ICU Patients: Are these both the same?

• Low Risk– 34 year former football

player,– BMI 35– otherwise healthy– involved in motor

vehicle accident– Mild head injury and

fractured R leg requiring ORIF

• High Risk– 72 women– BMI 35– PMHx COPD, poor

functional status– Admitted to hospital 1

week ago with CAP– Now presents in respiratory

failure requiring intubation and ICU admission

ICU-acquired Weakness (ICUAW)

Muscle weakness develops in 25%-60% of patients who have been mechanically ventilated for > 1 week1

Prolongs:1-4 – mechanical ventilation– weaning from the ventilator– ICU stay

• ICUAW main clinical manifestation of critical illness neuromyopathy (CINM)5

1. de Jonghe B, et al. Crit Care Med. 2004;30:1117-1121.2. Garnacho-Montero J, et al. Crit Care Med. 2005;33:349-354.3. van den Berghe G, et al. Crit Care Med. 2003;31:359-366.4. Hermans G, et al. Am J Respir Crit Care Med. 2007;175:480-489.5. de Jonghe B, et al. Crit Care Med. 2009;37(suppl.):S309-S315.

Determinants to Lean Body Mass

Muscle Matters!Skeletal muscle mass predicts ventilator-free days, ICU-

free days, and mortality in elderly ICU patients

• Patients > 65 years with an admission abdominal computed tomography scan and requiring intensive care unit stay at a Level I trauma center in 2009-2010 were reviewed.

• Muscle cross-sectional area at the 3rd lumbar vertebra was calculated and sarcopenia identified using sex-specific cut-points.

• Muscle cross-sectional area was then related to clinical parameters including ventilator-free days, ICU-free days, and mortality.

Kozar (in submission)

Skeletal Muscle

Adipose Tissue

Physical Characteristics of Patients

• N=149 patients• Median age: 79 years old• 57% males• ISS: 19• Prevalence of sarcopenia: 71%

BMI CharacteristicsAll Patients Sarcopenic

Patients (n=106)Non-sarcopenic Patients (n=43)

BMI (kg/m2) 25.8 (22.7, 28.2) 24.4 (21.7, 27.3) 27.6 (25.5, 30.4)

Underweight, % 7 9 2

Normal Weight, % 37 44 19

Overweight, % 42 38 51

Obese, % 15 9 28

Low muscle mass associated with mortality

Proportion of Deceased Patients

P-value

Sarcopenic patients 32%0.018

Non-sarcopenic patients 14%

Muscle mass is associated with ventilator-free and ICU-free

daysAll Patients Sarcopenic

PatientsNon-

Sarcopenic Patients

P-value

Ventilator-free days

25 (0,28) 19 (0,28) 27 (18,28) 0.004

ICU-free days 19 (0,25) 16 (0,24) 23 (14,27) 0.002

Am J Respir CCM 2008;178:261-268

• Prospective multicenter observational trial of 136 patients requiring min 5 days of mechanical ventilation• After day 5, when awake, performed muscle testing

PROTEIN REQUIREMENT IN CRITICAL ILLNESSAT ADEQUATE ENERGY INTAKE

Wolfe et al., Ann Surg 1983; Ishibashi et al., Crit Care Med 1998Hoffer Am J Clin Nutr 2003

-2

-1.5

-1

-0.5

0

Who

le-b

ody

prot

ein

loss

(kg

/ 2 w

eeks

)

g protein / kg IBW per day

0.7 1.0 1.5 2.2

PROTEIN REQUIREMENT IN CRITICAL ILLNESSAT ADEQUATE ENERGY INTAKE

Wolfe et al., Ann Surg 1983; Ishibashi et al., Crit Care Med 1998Hoffer Am J Clin Nutr 2003

-2

-1.5

-1

-0.5

0

Who

le-b

ody

prot

ein

loss

(kg

/ 2 w

eeks

)

g protein / kg IBW per day

0.7 1.0 1.5 2.2

-2

-1.5

-1

-0.5

0

Who

le-b

ody

prot

ein

loss

(kg

/ 2 w

eeks

)

g protein / kg IBW per day

0.7 1.0 1.5 2.2

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?

Health Care Associated Malnutrition

Do Nutrition Screening tools help us discriminate those ICU patients that will benefit the most from artificial nutrition?

Patients who will benefit the most from nutrition therapy and who will be harmed the most from

by iatrogenic malnutrition (underfeeding)

All ICU patients treated the same

Albumin: a marker of malnutrition?

• Low levels very prevalent in critically ill patients• Negative acute-phase reactant such that synthesis,

breakdown, and leakage out of the vascular compartment with edema are influenced by cytokine-mediated inflammatory responses

• Proxy for severity of underlying disease (inflammation) not malnutrition

• Pre-albumin shorter half life but same limitation

Subjective Global Assessment?

• When training provided in advance, can produce reliable estimates of malnutrition

• Note rates of missing data

• mostly medical patients; not all ICU• rate of missing data?• no difference between well-nourished and malnourished patients with regard to the serum protein values on admission, LOS, and mortality rate.

Mostly surgical patients; 100% data available for SGA

“We must develop and validatediagnostic criteria for appropriate

assignment of thedescribed malnutrition syndromes

to individual patients.”

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). 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

Mor

talit

y R

ate

(%)

020

4060

80

ObservedModel-based

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

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

Day

s on

Mec

hani

cal V

entil

ator

02

46

810

1214 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

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

0 50 100 150

0.0

0.2

0.4

0.6

0.8

1.0

Nutrition Adequacy Levles (%)

28 D

ay M

orta

lity

11 111

1

111

22

2

22 2

22

2

33

333

33

3

3

333 3

3

33

33

444444

44444

444

44 4444

44

4

44

4 444 4 444

4

4

55 5555 5 55 5 5 5 5 5

5 55 5 55 55

5 5555 55 555 55 55

5 555 555

66 66 6666666

6 66

666

6 666 66 6

6

66

66

6 6

666

6 666

67

77

77

7

7

7

7

7

7

7

7

7

77

7

7

77

7

7

7 7

7

88

8

8

8

8

8

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

• Multicenter prospective study of nutrition practice in abdominal surgery

• All patients had nutrition screening, not all patients had peri op nutrition support

• Benefit of nutrition support seen in NRS>5 compared to controls, no benefit seen in low risk patients (NRS<5).

P=0.008 P=0.04 P=0.04

Patients with NRS >5

Who might benefit the most from nutrition therapy in the ICU?

• 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

Nutritional Adequacy of

High Risk Patients

compared to Low Risk

Patients

Failure Rate

Unpublished observations. Results of 2011 International Nutrition Survey (INS).

75.6 78.1

91.2

75.1

87.0

69.8

79.9

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 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 without

Heyland JPEN 2010

0

20

40

60

80

Calories from EN Total Calories

ProtocolNo Protocol

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!

• 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

alor

ies

rece

ived

/pre

scrib

ed

1 2 3 4 5 6 7 8 9 10 12

010

2030

4050

6070

8090

100

n ITTn Efficacyn FVFn E@Base

24311357260

21911357236

19411357

209

17110854175

15310552

152

1389646

136

1188340113

1077535102

83592690

76522380

59401771

52351462

ITTEfficacyFull volume feedsBaseline intervention

% p

rote

in re

ceiv

ed/p

resc

ribed

1 2 3 4 5 6 7 8 9 10 12

010

2030

4050

6070

8090

100

n ITTn Eff icacyn FVFn E@Base

24311357260

21911357236

19411357

209

17110854175

15310552152

1389646136

1188340113

1077535

102

83592690

76522380

59401771

52351462

ITTEfficacyFull volume feedsBaseline intervention

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

ICU patientsBMI <25 R

PN for 7 days

Control

The TOP UP Trial

Fed enterally

Primary Outcome

60-day mortality

BMI >35

Stratified by:SiteBMI

Med vs Surg

Muscle Outcome Assessments

in TOP UP• Measures of muscle mass and function

– mitochondrial complex I activity– US of femoral quad (baseline and follow up CTs when available) – Hand grip strength– 6 min walk test– SF 36 (RP and PCS)

Reliability of US measure of Quad Muscle Layer Thickness

• 46 pairs of within operator measurements with an ICC of .98• 73 pairs of operator 1 to operator 2 measurements with an ICC of .94. •There was a small but statistically significant difference between the operator 1 and 2 results Mean (operator 1-2) (95% CI) = -0.061 cm (-0.100 to -0.022), p= 0.0028. 

Lancet 2009;273:

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! (JOIN International Critical Care Nutrition Survey in 2013)– PEP uP protocol in all– Selective use of small bowel feeds then sPN in high risk patients

Questions?