Nutrition as Therapy:
Strategies for the Delivery of Enteral Nutrition
Stephen A. McClave, MD
Professor of Medicine
University of Louisville School of Medicine
Louisville, Kentucky USA
Disclosures
As it pertains to this CME activity, I have the
following disclosures to report:
• Grant/Research Support-Covidien, Nestle
• Consultant-Nestle, Abbott, Covidien
• Speaker’s Bureau-Nestle, Abbott
Stephen A. McClave, MD
What’s Driving Nutrition Therapy?
Nutrition Rx
This Way
Caloric deficit; Timing of EN initiation; Who benefits from EN Rx?
Effect of Caloric Deficit
•
•
•
Ramp-Up
10,000 kcal
Bartlett (1982) 1
Mortality increases 27% →76%
Mault (2000) 2
Durat MV increases
10 → 20 days
ICU LOS increases
16 → 25 days
Caloric
Deficit
5,000 kcal Villet (2005) 3
* p<0.05
Hosp LOS (p=0.0001) Complics (p=0.0003)
Infections (p=0.004) Durat MV (p=0.0002)
4,000 kcal Dvir, Singer (2006) 4
ARDS (p=0.0003) Renal failure (p=0.0001)
Sepsis (p=0.003) Need for surgery (p=0.0001)
Total complications (0.0001)
1
Surg 1982;92:771
2
JPEN 2000;24:S4
3
CCM 2005
4 Clin
Nutrit 2006;25:37
Effect of Early Initiation of Nutrition Therapy
•
•
Meta-Analysis of 6 PRCTs (n=234)
Early (within 24 hrs) vs Later Rx (1- 4 days after admission)
Results:
Mortality (OR = 0.34, 95%CI 0.14-0.85)
Pneumonia (OR = 0.31, 95%CI 0.12-0.78)
Mortality
Int Care Med 2009;35:2018
Who Benefits from
Enteral Nutrition?
•
•
Jie B et al
Nutrition 2012
Prospective Multicenter cohort study n=1085
Pre-op Nutrition therapy NRS-2002 (n=512 at risk)
102 with NRS ≥ 5
Results
When NRS ≥ 5 complications 50.6 vs 25.6 %
When NRS ≥ 5 length of stay
17 to 13 days
No benefit in NRS < 5
Jie B et al Nutrition 2012
Miller KR et al JPEN 2011
Who Benefits from Enteral Nutrition?
Rx Effect on High Risk Pts
p=0.01
Heyland DK (Crit Care 2011;6:1)
Value of EN
in the ICU
•
•
•
Rationale:
Prevents gut permeability and cytokine storm
Stimulates anti-inflammatory Th-2 CD4 Helper lymphocyte cell line
Promotes role of commensal bacteria, anti-inflammatory
microbiota
Takes advantage of anti-inflammatory effects of oral tolerance
Delivers SCFAs to cecum, anti-inflam effect of butyrate receptors
Delivers LCFAs to duodenum causing vagal anti-inflam effect
Evidence:
Early vs delayed feeding PRCTs
Early EN vs Standard Rx PRCTs
Concern:
Underfeeding, difficulties in EN delivery
Providing EN in
ICU is Difficult
•
•
•
EN is hard work!
“Physician-directed Malnutrition”
QA Monitor over 3 mos (n= 1192)1
21.9% were NPO > 3 days
Durat NPO mean 5.2d (range 0-16)
Anticipate under-delivery of EN
Study
Required
Ibrahim 2
100%
McClave 3
100%
Arabi 4
100%
Intended
100%
65%
90-100%
Actual
27.9%
50%
71.4%
University of Louisville experience (% goal delivered)
CCU/Neuro ICU
50%
MICU
80%
SICU
20%
Burn ICU
100%
1 JPEN
2011;35(3):337 2 JPEN 2002;26:174
3 Crit Care Med 1999;27:1252-6
4 AJCN 2011;93:569
Value of PN
in the ICU
•
•
•
Rationale
Value of protein in critical illness
Neg outcome with loss of LBM
Increased protein turnover (mobilization, acute phase, wound
healing, gluconeogenesis, renal acid/base balance)
Conditionally essential AAs (glutamine, tryptophan,
phenylalanine, tyrosine)
Consistent adequacy of nutrition Rx and approp glucose control
Evidence - Conflicting
Concern
Few mechanisms of immune modulation
PN benefit should be more likely in high risk patients
Ineffective, may worsen outcome in moderate risk patients
Lawson CM (Curr Gastro Rep 2011)
Bistrian BR (CCM 2011;391533)
EPaNIC Trial
What is Best Way to Reduce Caloric Deficit?
Van den Berghe
Europe
USA
Casaer MP, Van den Berghe G (NEJM 2011;365:506)
SCCM/ASPEN (USA) vs ESPEN (Europe)
versus
Results of
EPaNIC Study
•
•
PRCT 4640 adult ICU pts multicenter
Received 2009 Stoutenbeek Award for study design
All pts started on EN, tight glucose control
Results
Early PN (ESPEN)
(n=2312)
Infection
26.2%
ICU LOS
4.0 d
Hosp LOS
14.0 d
Durat CRRT
10.0 d
MV > 2 days
40.2%
Hosp mortality
10.9%
ICU dschg alive
71.7%
Healthcare cost
17,973 E
* p<0.05
Late PN (ASPEN)
(n=2328)
22.8% *
3.0 d *
12.0 d *
7.0 d *
36.3% *
10.4% (p=NS)
75.2%*
16,863 E *
MP Casear, G Van Den Berghe (NEJM 2011;365:506 )
Swiss Study Supplemental PN
•
•
•
PRCT in high risk Med ICU patients (n=275)
Functional gut, expected ICU LOS>5d
Study pts: Add PN after 3 days if <60% Measured REE
Controls: EN alone
Results (EN vs SPN)
Coefficient
New infection -0.27
Mech vent hrs -87.4
Hosp LOS
-2.70d
Signif
0.019
0.001
0.009
Key issues:
Wait longer to add PN (at 72 hrs)
Only add if EN feeds <60% goal
M Berger, C Pichard (24th ESICM Congress, Berlin, Germany, October 1-5, 2011)
Issue of Supplemental PN
Re-Analysis of EPaNIC Study in
Patients With Greatest Dz Severity
What have
we learned?
APACHE II vs Mort, LOS, MOF
< 10
10-20
20-30
>30
Favors Early PN
•
Favors Late PN
Tremendous adverse effect from PN use
outside the setting of intestinal failure
Greet Van den Berghe (DDW 2012 Presentation)
When Do We Feed?
•
•
•
Recognize true contraindications to EN
Don’t misinterpret mild-moderate degree of intolerance, dysfunction
Consider judicious use of PN if EN insufficient
•
•
Take advantage of opportunity to deliver early EN
Have skill set, expertise, protocols, strategies in place to activate
Today’s
Total
Volume
Reduce Deficit with EN:
Volume-Based
#1
Feeding
Rate-Based
Feeding
Volume-Based Feeding
Chart to Calculate Adjusted Rate
Volume-Based Protocol
Rate for hours remaining
University
EN Vol of Louisville Hospital - Volume Based Feeding Schedule
Gastric Enteral Feeding Guidelines to Provide Goal Rate Ordered
Goal Goal Total
mL/hr ml formula
/ 24hrs per 24 hrs
100
2400
95
2280
90
2160
85
2040
80
1920
75
1800
70
1680
65
1560
60
1440
55
1320
50
1200
45
1080
40
960
35
840
30
720
25
600
20
480
15
360
24
23
100 104
95
99
90
94
85
89
80
83
75
78
70
73
65
68
60
63
55
57
50
52
45
47
40
42
35
37
30
31
25
26
20
21
15
16
Color Key:
22
109
104
98
93
87
82
76
71
65
60
55
49
44
38
33
27
22
16
21
114
109
103
97
91
86
80
74
69
63
57
51
46
40
34
29
23
17
Hours Remaining in Day to Refeed Withheld Enteral Formula (Due to Feeding on Hold for Test or Procedure)
20
19
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
120 126 133 141 150 160 171 185 200 218 240 267 280 280 280 280 280 280 280
114 120 127 134 143 152 163 175 190 207 228 253 280 280 280 280 280 280 280
108 114 120 127 135 144 154 166 180 196 216 240 270 280 280 280 280 280 280
102 107 113 120 128 136 146 157 170 185 204 227 255 280 280 280 280 280 280
96 101 107 113 120 128 137 148 160 175 192 213 240 274 280 280 280 280 280
90
95 100 106 113 120 129 138 150 164 180 200 225 257 280 280 280 280 280
84
88
93
99 105 112 120 129 140 153 168 187 210 240 280 280 280 280 280
78
82
87
92
98 104 111 120 130 142 156 173 195 223 260 280 280 280 280
72
76
80
85
90
96 103 111 120 131 144 160 180 206 240 280 280 280 280
66
69
73
78
83
88
94 102 110 120 132 147 165 189 220 280 280 280 280
60
63
67
71
75
80
86
92 100 109 120 133 150 171 200 240 280 280 280
54
57
60
64
68
72
77
83
90
98 108 120 135 154 180 216 270 280 280
48
51
53
56
60
64
69
74
80
87
96 107 120 137 160 192 240 280 280
42
44
47
49
53
56
60
65
70
76
84
93 105 120 140 168 210 280 280
36
38
40
42
45
48
51
55
60
65
72
80
90 103 120 144 180 240 280
30
32
33
35
38
40
43
46
50
55
60
67
75
86 100 120 150 200 280
24
25
27
28
30
32
34
37
40
44
48
53
60
69
80
96 120 160 240
18
19
20
21
23
24
26
28
30
33
36
40
45
51
60
72
90 120 180
White=Tolerated by G Tube
Green=Arbitrary Maximum Rate Tolerated by G Tube
1
280
280
280
280
280
280
280
280
280
280
280
280
280
280
280
280
280
280
Small Bowel Enteral Feeding Guidelines to Provide Goal Rate Ordered
Goal Goal Total
mL/hr ml formula
/ 24hrs per 24 hrs
100
2400
95
2280
90
2160
85
2040
80
1920
24
100
95
90
85
80
23
104
99
94
89
83
22
109
104
98
93
87
Arbitrary maximum rate set :
Hours Remaining in Day to Refeed Withheld Enteral Formula (Due to Feeding on Hold for Test or Procedure)
21
20
19
18 Stomach
17
16
15
14
13
12
11
10
9
8
7
6
5
4
(280
mL/hr)
114 120 126 133 141 150 150 150 150 150 150 150 150 150 150 150 150 150
109 114 120 127 Small
134 143 150
150 150 150(150
150 150mL/hr)
150 150 150 150 150 150
bowel
103 108 114 120 127 135 144 150 150 150 150 150 150 150 150 150 150 150
97
91
102
96
107
101
113
107
120
113
128
120
136
128
146
137
150
148
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
3
150
150
150
150
150
2
150
150
150
150
150
1
150
150
150
150
150
Today’s
EN Volume
Reduce Deficit with EN:
Volume-Based
Feeding
%Goal kcals overall
81% → 93%
Calorie deficit
-1934 kcal → -776 kcal
%Goal kcals/day
Uninterrupted EN
No difference (102-103%)
Interrupted EN
61% → 95%
(Compliance in only a third of pts )
SA McClave, DK Heyland [JPEN 2011;35(1):134-135]
Reduce Deficit with EN: Top-Down Therapy
•
Come out at the start with guns blazing!!
Rapid advancement (start at goal)
Initiate prokinetics
Volume-based feeds
Chart cumulative caloric balance
Small peptide formula
Protein supplements
Small bowel feeds
Elevate head of bed
•
Back off as tolerance develops
•
Example: Canadian Pep-Up Study
Goal EN calories 59%→83% (p<0.02)
Heyland, McClave
[JPEN 2010;34(2):208]
TopDown
Conventional
#2
#3
•
•
•
Reduce Deficit With EN:
Use of Nurse-Driven EN Protocols
Elements
Tube access
Elevate HOB
Oral care
Cal balance
Rate ramp-up
GRVs
Prokinetics
How to enforce?
Impact on outcome?
Nurse’s hand
on spigot!
Reduce Deficit With EN:
Use of EN Protocols
Studies (year)
Design
Taylor (1999)1
Pinilla (2001)2
Martin (2004)3
Doig (2008)4
PRCT
PRCT
PRCT
PRCT
Spain (2001)5 B/A Implt
Arabi (2004)6 B/A Implt
Barr (2004)7
B/A Implt
1CCM
Feed Rx
Outcome
37→59%
↓Infect, complics, LOS
70 → 76%
no ∆
2.16→1.6 d to EN ↓Mortality, hosp LOS
1.37→0.75 d to EN
no ∆
52→68%
(nutrit endpts only)
53.9→64.5%
no ∆
68→78% pts on EN ↓Mortality, durat MV
1999;27:2525 2JPEN 2001;25:81 3CMAJ 2004;170:197 4JAMA 2008;300:2731
5JPEN 1999;23:288-92 6NCP 2004;19:523 7Chest 2004;125:1446
Initiating and Enforcing
a New EN Protocol
•
•
Prospective interventional study
(n=5800 ICU days)
NUTSIA Protocol over 3 three-month periods (2005, 2006, 2007)
Before Protocol After Protocol With Enforcement
(n=198 pts)
(n=179 pts)
(n=195 pts)
Results
Rx (kcal/kg/d)
11.4 +7.9
ICU kcal balance -7180 +5008
Hosp LOS (days) 31.1 +52.2
13.9 +8.0
-6133 +3854
24.1 +21.0
15.4 +9.6 **
-5568 +5194 **
23.2 +22.1**
Soguel L, Revelly JP, Berger MM (CCM 2012;40;1-7)
#4
Reduce Deficit with EN:
Modify Existing Protocols
•
•
American Society of Anesthesiologists 2011 1
Practice Guidelines for preoperative fasting in the healthy
patients undergoing elective procedure
(standard NPO policy):
2 hour fast for clear liquids
6 hour fast for light meals
•
Meta Analysis of 22 PRCTs showed no evidence that
shortened fluid restriction changed risk of aspiration or
morbidity vs standard NPO policy 2
1 Anesthesiology
2011;114: 495-511
2 McLeod
Can J Surg 2005
Modifying Protocols:
PRCT Modifying NPO Past MN
NPO at
MN
(n = 27)
Clear Liqs
240 ml
2 hr fast
(n = 17)
Formula
240 ml
4 hr fast
(n = 24)
Formula
240 ml
2 hr fast
(n = 25)
Signif
P
value
Gastric Vol
(mean ± SD)
38 ± 40
ml
48 ± 47
ml
29 ± 30
ml
70 ± 77*
ml
0.042
Clear view
No. (%)
21 (78%)
10 (63%)
17 (74%)
10 (40%) *
0.026
Obscured
View No. (%)
2 (7%)
2 (13%)
2 (9%)
9 (36%) *
0.035
Regurgitation
No. (%)
1 (4%)
0 (0%)
3 (13%)
1 (4%)
0.470
SA McClave, CC Lowen (JPEN 2001;25:S14)
#5
#5
Reduce Deficit with EN:
Nutrition Bundle
•
Bundle: New concept in ICU care
Set of few (5-7) short action statements
Strength comes from doing all actions on the list
Full compliance with bundle actions improves outcome
•
Bundles derived in directed way
Review of literature → derive guidelines →
pick bundle elements → intervention trial
•
Effective bundles developed for:
VAP, DVT, Pressure Sores, Surgical Site Infection, BSIs
•
Could a bundle be developed for Nutrition therapy?
Reduce Deficit
with EN:
Nutrition Bundle
Targeted MD Education
•
•
•
•
•
•
PRCT with 2 Trauma Teams
Posted daily patient cumulative caloric deficit
Immediate feeding tube placement for mech ventilated patients
Elimination of clear liquid diet orders (order full liquids instead)
Pre-op and post-op reduction of NPO fasting period
Volume-based feeding
Minimize fasting period before diagnostic tests
GA Franklin, SA McClave (JPEN 2007; 31:S7-8)
Reduce Deficit
with EN:
Nutrition Bundle
Target Team
(n=66)
Control Team
(n=55)
Mean NPO days
Mean Clear Liq days
Mean Caloric Deficit
Mean % Goal kcal infused
2.44 (+/-1.3)d
0.14 (+/-0.8)d *
-6795.8 kcal *
30.1 (+/-0.3)% *
2.85 (+/-1.8)d
0.62 (+/-0.8)d
-8817 kcal
22.2 (+/-0.2)%
ICU days
Vent days
MOF SOFA Score
Infection ( % patients )
3.5 (+/-5.6)d #
1.6 (+/-3.7)d #
0.20 (+/-0.8) *
10.6%
5.2 (+/-6.8)d
2.8 (+/-5.0)d
0.45 (+/-0.1)
23.6%
GA Franklin, SA McClave (JPEN 2007; 31:S7-8) *p < 0.05, # p = 0.13
How Much Should Patients Be Fed?
Some studies upset the apple cart….
Can We Dismiss
Some Studies?
These studies
make me so
nervous…
Is There Some Fatal Flaw?
Example: Arabi Study
JPEN 2010;34(3):280
Artifactual Error by
Confounding Factor:
Hospital Mortality (OR= Odds Ratio)
Heyland
Outcome (tertiles)
1st
2nd
3rd
Signif
Arabi 1
All ICU patients
1.00
1.23
1.99
p=0.02
Heyland 2
All ICU patients
1.00
1.22
1.28
[ Exclude days of exclusive PO diet (no all PO) ]
No all PO days
1.00
1.08
1.04
NRx >4d, no all PO
1.00
0.77
0.73
NRx >12d, no all PO 1.00
0.69
0.68
1
JPEN 2010;34(3):280
2 CCM
p=0.0005
p=NS
p<0.0001
p=0.003
2011;39(12):1
Trophic vs Full Feeds
ARDSNet Multi-Center PRCT
Todd Rice
80% Goal calories
ALI/ARDS patients on MV
Trophic 20cc/hr x 6days (n=508)
vs Full feeds (n=492)
25% Goal
calories
No difference:
Mortality, vent-free days, MOF,
or infection
jama.ama-assn.org (Feb 9, 2012)
Response to Article: Recent Memo
“Initial Trophic vs Full Enteral Feeding
in Patients With Acute Lung Injury”
The ARDSNet Multicenter EDEN Randomized Trial
Rice T, et al JAMA 2012;307(8):1-9
Message sent from member of Surviving Sepsis Campaign (SSC)
Committee (who are revising their guidelines) to SCCM/ASPEN
Guidelines Committee member August 2012:
“The proposed recommendation on enteral nutrition
support may need modification. The recent ARDSNet
study, as well as earlier studies, suggest that full enteral
calorie/protein may not be necessary and could possibly
be harmful if given in the first week of critical illness. We
recommend that in the new version of the SSC guidelines,
feeding should begin in 5 to 7 days rather than 48 hours.”
Does This Study
Conflict With the Literature?
Does This Study
Conflict With the Literature?
• Early vs.
Delayed EN
Infection
PE Marik, GP Zaloga (CCM 2001;29:2264)
Does This Study
Conflict With the Literature?
•
EN vs Standard Rx (no specialized nutrition Rx) 3,4
Lewis 1,2 – Elective surgery and surgery critical care
Reduction infections by 28% (RR=0.72, p=0.03)
Reduction hospital LOS by 0.84 days (p=0.001)
Reduction mortality 6.8% to 2.4% (p=0.03)
Pupelis 3 – Severe acute pancreatitis post-op after complications
Reduction in mortality by 74% (RR=0.26, p=0.06)
SJ Lewis (BMJ 2001;323:1) 1 (J Gastro Surg 2009;13:569)
3 SA McClave (JPEN 2006;30:143)
2
•
Does This Study
Conflict With the Literature?
Effect of Nurse-driven EN protocols
Studies (year)
Design
Taylor (1999)1
Pinilla (2001)2
Martin (2004)3
Doig (2008)4
PRCT
PRCT
PRCT
PRCT
Spain (2001)5 B/A Implt
Arabi (2004)6 B/A Implt
Barr (2004)7
B/A Implt
1CCM
Feed Rx
Outcome
37→59%
↓Infect, complics, LOS
70 → 76%
no ∆
2.16→1.6 d to EN ↓Mortality, hosp LOS
1.37→0.75 d to EN
no ∆
52→68%
(nutrit endpts only)
53.9→64.5%
no ∆
68→78% pts on EN ↓Mortality, durat MV
1999;27:2525 2JPEN 2001;25:81 3CMAJ 2004;170:197 4JAMA 2008;300:2731
5JPEN 1999;23:288-92 6NCP 2004;19:523 7Chest 2004;125:1446
How Do We Resolve This?
•
•
•
Why would trophic feeds work?
25% Goals calories is sufficient
Dose is less important
Early initiation more important
Minimizing interruptions important
Less fluids in ARDS important 1
BMI range less nutrition effect 2
Findings unique to this population?
BMI 25-30
BMI 30-35
Is doing nothing just as good? No!!
How does this study affect my practice?
Start early
Avoid interruptions
Aggressive EN Rx, unless intolerance
Avoid setting low target at outset
1T
Rice (JAMA 2012)
2C
Alberda (Int Care Med 2009)
Looking Toward Building Nutrition
Therapy at Your Institution
•
Build EN program, get involved, re-evaluate policies
•
Protocols help move process in the right direction
•
Focus on issues optimizing delivery of EN, with judicious use of PN
•
Have skill set, expertise, strategies in place to activate
•
Take advantage of opportunities to deliver early EN
Questions?
Thank you for your time today