• 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.

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)

Early and Adequate Nutrition is therapy that modulates the underlying disease process and impacts patient outcomes
Adjunctive
Supportive
Care
Proactive
Primary
Therapy

Early 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

Updated 2009 www.criticalcarenutrition.com

Updated 2009 www.criticalcarenutrition.com

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

Increasing Calorie Debt Associated with worse Outcomes
Adequacy of EN
2000
1800
1600
1400
1200
1000
800
600
400
200
0
Caloric Debt
Prescribed Engergy
Energy Received From Enteral Feed
1 3 5 7 9 11 13 15 17 19 21
Days
 
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 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

10
0
60
Relationship of Caloric Intake, 60 day Mortality and BMI
50
40
30
BMI
All Patients
< 20
20-25
25-30
30-35
35-40
>40
20
0 500 1000
Calories Delivered
1500 2000

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
Multicenter RCT of glutamine and antioxidants (REDOXS Study)
First 364 patients with SF 36 at 3 months and/or 6 months
Model *
Estimate (CI)
(A) Increased energy intake
PHYSICAL FUNCTIONING (PF) at 3 months 3.2 (-1.0, 7.3)
P values
P=0.14
ROLE PHYSICAL (RP) at 3 months 4.2 (-0.0, 8.5)
STANDARDIZED PHYSICAL COMPONENT
SCALE (PCS) at 3 months
1.8 (0.3, 3.4)
P=0.05
P=0.02
PHYSICAL FUNCTIONING (PF) at 6 months 0.8 (-3.6, 5.1) P=0.73
ROLE PHYSICAL (RP) at 6 months 2.0 (-2.5, 6.5) P=0.38
STANDARDIZED PHYSICAL COMPONENT
0.70 (-1.0, 2.4) P=0.41
for increase of 30 gram/day, OR of infection at 28 days
Heyland Unpublished Data

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

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

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*
Unadjusted
Adjusted
0.4
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

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

JAMA
1994;271:56

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
What other outcomes might be important?
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

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!

Trophic vs. Full enteral feeding in critically ill patients with acute respiratory failure

Randomized
 Good follow up
 ITT

No blinding
Internally valid
1.
How representative are these patients to ALL the patients in your
ICU? May miss an important negative effect in ‘high risk’ patients
2.
What about the physically recovery of underfed patients?
No benefit, potential harm, minimal cost advantage=
Do not use routinely!

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

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

• 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

• 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.

“We must develop and validate diagnostic criteria for appropriate assignment of the described malnutrition syndromes to individual patients.”

A Conceptual Model for Nutrition Risk
Assessment in the Critically Ill
Acute
-Reduced po intake
-pre ICU hospital stay
Chronic
-Recent weight loss
-BMI?
Starvation
Acute
-IL-6
-CRP
-PCT
Nutrition Status micronutrient levels - immune markers - muscle mass
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)
Non-survivors by day 28
(n=138)
Age
Baseline APACHE II score
Baseline SOFA
# of days in hospital prior to ICU admission
71.7 [60.8 to 77.2]
26.0 [21.0 to 31.0]
9.0 [6.0 to 11.0]
0.9 [0.1 to 4.5]
Baseline Body Mass Index
Body Mass Index
26.0 [22.6 to 29.9]
<20
≥20
# of co-morbidities at baseline
Co-morbidity
Patients with 0-1 co-morbidity
Patients with 2 or more co-morbidities
C-reactive protein
¶
Procalcitionin
¶
Interleukin-6
¶
171 patients had data of recent oral intake and weight loss
6 ( 4.3%)
122 ( 88.4%)
3.0 [2.0 to 4.0]
20 (14.5%)
118 (85.5%)
135.0 [73.0 to 214.0]
4.1 [1.2 to 21.3]
158.4 [39.2 to 1034.4]
Non-survivors by day 28
(n=32)
% Oral intake (food) in the week prior to enrolment
% of weight loss in the last 3 month
4.0[ 1.0 to 70.0]
0.0[ 0.0 to 2.5]
Survivors by day 28
(n=460)
61.7 [49.7 to 71.5]
20.0 [15.0 to 25.0]
6.0 [4.0 to 8.5]
0.3 [0.0 to 2.2]
26.8 [23.4 to 31.5] p values
<.001
<.001
<.001
<.001
0.13
0.66
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]
1.0 [0.3 to 5.1]
72.0 [30.2 to 189.9]
0.07
<.001
<.001
Survivors by day 28
(n=139)
50.0[ 1.0 to 100.0]
0.0[ 0.0 to 0.0] p values
0.10
0.06

What are the nutritional risk factors associated with clinical outcomes?
(validation of our candidate variables)
Variable
Age
Baseline APACHE II score
Baseline SOFA
% Oral intake (food) in the week prior to enrollment
Spearman correlation with
VFD within 28 days
-0.1891
-0.3914
-0.3857
0.1676
p values
<.0001
<.0001
<.0001
0.0234
Number of observations
598
598
594
183 number of days in hospital prior to ICU admission
% of weight loss in the last 3 month
Baseline BMI
# of co-morbidities at baseline
Baseline CRP
Baseline Procalcitionin
Baseline IL-6
-0.1387
-0.1828
0.0581
-0.0832
-0.1539
-0.3189
-0.2908
0.0007
0.0130
0.1671
0.0420
0.0002
<.0001
<.0001
598
184
567
598
589
582
581

The Development of the NUTrition Risk in the
Critically ill Score (NUTRIC Score).
• % oral intake in the week prior was dichotomized into patients who reported less than 100% versus everyone else
• Weight loss was dichotomized as patients who reported any weight loss versus everyone else.
• BMI was dichotomized as <20 versus other
• Comorbidities was left as integer values range 0-5
• The remaining candidate variables were categorized into five equal sized groups (quintiles).

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
48.9-59.7
referent
0.780
0
1
59.7-67.4
67.5-75.3
0.949
1.272
1
1
75.4-89.4
1.907
2

The Development of the NUTrition Risk in the
Critically ill Score (NUTRIC Score).
Variable
Age
APACHE II
SOFA
# Comorbidities
Range
<50
50-<75
>=75
<15
15-<20
20-28
>=28
<6
6-<10
>=10
0-1
2+
Points
0
1
2
2
3
0
1
2
0
0
1
1
Days from hospital to ICU admit 0-<1
1+
0
1
IL6
AUC
Gen R-Squared
Gen Max-rescaled R-Squared
0-<400
400+
0.783
0.169
0.256
0
1
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).
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
0 1 2 3 4 5 6
Nutrition Risk Score
7 8 9 10

The Validation of the NUTrition Risk in the
Critically ill Score (NUTRIC Score).
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
0 1 2 3 4 5 6
Nutrition Risk Score
7 8 9 10

The Validation of the NUTrition Risk in the
Critically ill Score (NUTRIC Score).
Interaction between NUTRIC Score and nutritional adequacy (n=211) *
0
9
9
4
2
9
9
5
4
8 9
5
6
4
7
3
4
5
9
7 7
4
7
7
7
7
8
8
8
8 8
8
9
7 7
8
8
8
8
8
8
6
6 6 6 6 6 6 6 6
6 6 6 6 6
7
7
7
5
2
6 6 6 6
6 6
3
5 5 5 5
4
1
3
4 4
11
4
3
5 5
1
5
4 4 4
5
3 3 3
1
5
4
2
4 4
3
1
5 5 5 5 5
4 44
2 2
4 4
5 5 5 5 5 5 5 5 5
4
3 3
1
2
3
2
4 4
3
4
3
1
9
4
6
4
5
3
2
7
P value for the interaction=0.01
5
3
9
8
3
50 100
Nutrition Adequacy Levles (%)
150
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?

Overall Performance: Kcals
120
100
80
60
40
20
0
1 2 3 4
Mean of All Sites
5 6
ICU Day
7
Best Performing Site
8 9 10 11 12
Worst Performing Site
84%
56%
15%
N=211

% patients who failed to meet minimal quality targets (80% overall energy adequacy)

Strategies to Maximize the Benefits and
Minimize the Risks of EN weak evidence
• feeding protocols
• motility agents
• elevation of HOB
• small bowel feeds stronger evidence
Canadian CPGs www.criticalcarenutrition.com

Use of Nurse-directed Feeding Protocols
Start feeds at 25 ml/hr
> 250 ml
•hold feeds
•add motility agent
•reassess q 4h
Check
Residuals q4h
< 250 ml
•advance rate by 25 ml
•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
Feeding Protocol
Total n=269 15.2% using the recommended
Yes 208 (78%) threshold volume of 250 ml
Gastric Residual Volume
Tolerated in Protocol
Mean (range) 217 ml (50, 500)
Elements included in Protocol
Motility agents 68.5%
Small bowel feeding 55.2%
HOB Elevation 71.2 %
Heyland JPEN 2010

The Impact of Enteral Feeding Protocols on Enteral Nutrition Delivery:
Results of a multicenter observational study
80
60
40
20
0
Protocol
No Protocol
Calories from EN Total Calories
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 rec’ing motility agents 61.3% in protocolized sites vs 49.0% in those without
P<0.05
Heyland JPEN 2010

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

 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

Protocol to Manage Interruptions to EN due to non-GI Reasons
Can be downloaded from www.criticalcarenutrition.com

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 (250 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

Stable patients should be able to tolerate goal rate
Begin 24 hour volume-based feeds. After initial tube placement confirmed, start Pepatmen
1.5. Total volume to receive in 24 hours is 17ml x weight (kg)= <write in 24 target volume>.
Determine initial rate as per Volume Based Feeding Schedule. Monitor gastric residual volumes as per Adult Gastric Flow Chart and Volume Based Feeding Schedule.
OR
Begin Peptamen 1.5 at 10 mL/h after initial tube placement confirmed. Hold if gastric residual volume >500 ml and ask Doctor to reassess. Reassess ability to transition to 24 hour volume-based feeds next day. {Intended for patient who is hemodynamically unstable
(on high dose or escalating doses of vasopressors, or inadequately resuscitated) or not suitable for high volume enteral feeding (ruptured AAA, upper intestinal anastomosis, or impending intubation)}
OR
NPO. Please write in reason: __________________ ______. (only if contraindication to EN present: bowel perforation, bowel obstruction, proximal high output fistula. Recent operation and high NG output not a contraindication to EN.) Reassess ability to transition to 24 hour volume-based feeds next day.
We want to minimize the use of NPO but if selected, need to reassess next day
We use a concentrated solution to maximize calories per ml
If unstable or unsuitable, just use trophic feeds
Note indications for trophic feeds
Drs need to justify why there are keeping patients
NPO
Note, there are only a few absolute contraindications to
EN

It’s not just about calories...
Inadequate protein intake
Loss of lean muscle mass
Immune dysfunction
Weak
Prolonged mechanical ventilation
So in order to minimize this, we order:

Protein supplement Beneprotein® 14 grams mixed in 120 mls sterile water administered bid via NG

Other Strategies to Maximize the Benefits and Minimize the Risks of EN
• Motility agents started at initiation of EN rather that waiting till problems with High
GRV develop.
– Maxeran 10 mg IV q 6h (halved in renal failure)
– If still develops high gastric residuals, add
Erythromycin 200 mg q 12h.
– Can be used together for up to 7 days but should be discontinued when not needed any more
– Reassess need for motility agents daily

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

Change of nutritional intake from baseline to follow-up of all the study sites (all patients)
% calories received/prescribed
Intervention sites Control sites p value <0.0001
373
360
Baseline
390
375
Follow-up Baseline Follow-up

Change of nutritional intake from baseline to follow-up of all the study sites (all patients)
% protein received/prescribed
Intervention sites Control sites p value <0.0001
p value=0.78
331
371
Baseline
390
373
Follow-up Baseline
378
379
380
362
359
Follow-up

Other Strategies to Maximize the Benefits and Minimize the Risks of EN
Small Bowel vs. Gastric Feeding: A meta-analysis
Effect on VAP
Updated 2011,www.criticalcarenutrition.com

Does Postpyloric Feeding Reduce
Risk of GER and Aspiration?
Tube
Position
Stomach
D1
D2
D4
Total
# of patients
21
8
3
1
33
% positive for GER
32
27
11
5
% positive for
Aspiration
5.8
4.1
1.8
0
75 11.7
P=0.004
P=0.09
Heyland CCM 2001;29:1495-1501

FRICTIONAL ENTERAL FEEDING TUBE
(TIGER TUBE TM )
Flaps to allow peristalsis to pull tube passively forward
Sucessful jejunal placement >95%

®
A new paradigm in feeding tube placement
– Aid to placement of feeding tubes into the stomach or small bowel
– The tip of the stylet is a transmitter.
– Signal is picked up by an external receiver unit.
– Signal is fed to an attached
Monitor unit.
– Provides user with a realtime, graphic display that represents the path of the feeding tube.

Adequacy of Nutrition Support =
Please report this
% on rounds as part of the GI systems report
24 hour volume of EN received
Volume prescribed to meet caloric requirements in 24 hours

Thomas Monson

What if you can’t provide adequate nutrition enterally?
… to add PN or not to add PN, that is the question!

• 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
• 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

• ? 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

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

ICU patients
BMI <25
BMI >35
Fed enterally
R
PN for 7 days
Stratified by:
Site
BMI
Med vs Surg
Control
Primary
Outcome
60-day mortality

• 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

Yes
YES
Start PEP UP
Day 3
>80% of
Goal
Calories
NO
No
Anticipated
Long Stay?
Carry on!
Yes
Maximize EN with motility agents and small bowel feeding
YES
Yes
Supplemental PN?
Not tolerating
EN at 96 hrs?
High Risk?
NO
No
No
No problem

www.criticalcarenutrition.com

Questions?