Early and Adequate Nutrition is therapy that
modulates the underlying disease process
and impacts patient outcomes
Adjunctive
Supportive
Care
Proactive
Primary
Therapy
Adequacy
of EN
kcal
Increasing Calorie Debt Associated with worse Outcomes
Prescribed Engergy
2000
1800
1600
1400
1200
1000
800
600
400
200
0
Energy Received From Enteral Feed
Caloric Debt
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
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 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
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 Rec’d
• 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
P-value
Odds
95%
Ratio Confidence
Limits
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 of Caloric Intake, 60 day Mortality and BMI
60
BMI
All Patients
< 20
20-25
25-30
30-35
35-40
>40
Mortality (%)
50
40
30
20
10
0
0
500
1000
1500
Calories Delivered
2000
Relationship Between Increased Energy
and Ventilator-Free days
Adjusted
95% CI
BMI Group
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 Vent’d 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 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.*
Unadjusted
Adjusted
D. In ICU at least 12 days prior to
permanent progression to exclusive oral
feeding*
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
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 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
Inflammation
Acute
-IL-6
-CRP
-PCT
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
0
48.9-59.7
0.780
1
59.7-67.4
0.949
1
67.5-75.3
1.272
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
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
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
0
1
n=55
n=75
n=90
n=114
n=82
n=72
n=46
n=17
2
3
4
5
6
7
8
9
n=2
0
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
0
1
2
3
4
5
6
7
8
9
10
0
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)*
9
0.8
9
9
0.6
8 88
0.2
0.4
77 7
2
0
9
9
7
4
0.0
28 Day Mortality
P value for the
interaction=0.01
9
8888
7 7
7
8888
8
9
10
10
888
77
88
77 7
77 7
88
7
77
6
7
7777
6 66666 6
9
66666 6 6 66
6 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
44 4 43
4
4
4
2
4
4
4
3
44444444
33
444 4444
3
4
3
4
1
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
9
8
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 won’t 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
during EN


43
24
41
25
23
15
Pneumonia
ICU LOS
(days)
Intolerance
%Mortality
none
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
n=269
15.2% using the
recommended
threshold volume
of 250 ml
Feeding Protocol
Yes 208 (78%)
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 Nov 2010
The Impact of Enteral Feeding Protocols
on Enteral Nutrition Delivery:
Results of a multicenter observational study
80
60
40
Protocol
20
No Protocol
0
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
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 rec’d
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 non-GI 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)
% calories received/prescribed
80
Control sites
80
Intervention sites
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 for 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 meta-analysis
Effect on VAP
Updated 2011,www.criticalcarenutrition.com
Does Postpyloric Feeding Reduce
Risk of GER and Aspiration?
Tube
Position
# of
patients
% positive
for GER
Stomach
21
32
% positive
for
Aspiration
5.8
D1
8
27
4.1
D2
3
11
1.8
D4
1
5
0
Total
33
75
11.7
P=0.004
P=0.09
Heyland CCM 2001;29:1495-1501
Health Care Associated
Malnutrition
What if you can’t 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
• Results:
• Randomized to early PN
Late PN associated with
– Rec’d 20% glucose 20
• 6.3% likelihood of early
ml/hr then PN on day 3
discharge alive from ICU
and hospital
• OR late PN
• Shorter ICU length of
– D5W IV then PN on day
stay (3 vs 4 days)
8
• Fewer infections (22.8 vs
• All patients standard EN plus
26.2 %)
‘tight’ glycemic control
• 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 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
The TOP UP Trial
PN for 7 days
Primary
Outcome
ICU patients
BMI <25
BMI >35
Fed enterally
R
Stratified by:
Site
BMI
Med vs Surg
Control
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