Transcript A Randomized Trial of Empiric Antibiotics and Invasive

Critical Care Nutrition
The right nutrient/nutritional strategy
The right timing
The 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
Underlying Pathophysiology
of Critical Illness
Loss of Gut Epithelial Integrity
Bacteria
INTESTINAL EPITHELIUM
DISTAL ORGAN
INJURY
(Lung, Kidneys)
lymphocytes
SIRS
via thoracic duct
Disuse Causes Loss of Functional and Stuctural Integrity
Increased 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
35
• 4049 patients requiring mech
vent > 2 days
25
• Categorized as “Early EN” if
rec’d feeds within 48 hours of
admission (n=2537, 63%)
15
30
20
Early
Late
10
5
0
VAP
ICU
Mort
Hosp
Mort
P=0.007
P=0.02
P=0.0005
Artinian Chest 2006:129;960
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
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
• 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
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
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
For every 1000 kcal/day received:
Model *
Estimate (CI)
P values
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
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
At 3 months
At 6 months
for increase of 30 gram/day, OR of infection at 28 days
Unpublished data from Multicenter RCT of glutamine and antioxidants
(REDOXS Study); n=364
Mechancially Vent’d patients >7days
(average ICU LOS 28 days)
Faisy BJN 2009;101:1079
• 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.*
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
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
survival
Taylor 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
www.criticalcarenutrition.com
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!
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!
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
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?
Do we have a problem?
Preliminary Results of INS 2011
Overall Performance: Kcals
120
% received/prescribed
100
84%
56%
80
60
40
15%
20
0
1
2
3
4
5
6
7
8
9
10
11
12
ICU Day
Mean of All Sites
Best Performing Site
Worst Performing Site
N=211
Failure Rate
% high risk patients who failed to meet minimal quality targets
(80% overall energy adequacy)
Unpublished observations, Results of 2011 INS
In resuscitated, hemodynamically stable patients, other aspects of patient care take… 50.0
No or not enough feeding pumps on the unit.
48.6
Enteral formula not available on the unit.
46.9
Delays and difficulties in obtaining small bowel access in patients not tolerating… 43.1
No or not enough dietitian coverage during weekends and holidays.
42.4
No feeding tube in place to start feeding.
41.4
Delay in physicians ordering the initiation of EN.
40.7
Non-ICU physicians (i.e. surgeons, gastroenterologists) requesting patients not be… 37.8
Delays in initiating motility agents in patients not tolerating enteral nutrition.
37.2
The current national guidelines for nutrition are not readily accessible.
35.2
Waiting for the dietitian to assess the patient.
34.0
Feeding being held too far in advance of procedures or operating room visits.
31.3
No feeding protocol in place to guide the initiation and progression of enteral… 31.0
Fear of adverse events due to aggressively feeding patients.
29.9
The language of the recommendations of the current national guidelines for… 29.0
Nurses failing to progress feeds as per the feeding protocol.
29.0
Not enough time dedicated to education and training on how to optimally feed… 28.0
Not enough dietitian time dedicated to the ICU during regular weekday hours.
27.8
Not enough nursing staff to deliver adequate nutrition.
23.4
Current feeding protocol is outdated.
23.4
Current scientific evidence supporting some nutrition interventions is inadequate to… 21.3
Lack of agreement among ICU team on the best nutrition plan of care for the patient.
19.3
10.0 15.0 20.0 25.0 30.0 35.0 40.0 45.0 50.0 55.0 60.0 65.0 70.0 75.0 80.0 85.0 90.0
Cahill, J Crit Care 2012 Dec;27(6):727-
Proportion that responded "important" or "very important"
“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
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%P<0.05
in protocolized sites vs 49.0% in those without
Heyland JPEN Nov 2010
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 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 (300 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
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
100
100
Change of nutritional intake from baseline to followup of all the study sites (intervention group only)
n ITT
n Efficacy
n FVF
n E@Base
90
80
70
60
50
40
30
20
% protein received/prescribed
60
50
40
30
20
10
ITT
Efficacy
Full volume feeds
Baseline intervention
0
10
ITT
Efficacy
Full volume feeds
Baseline intervention
0
% calories received/prescribed
70
80
90
% calories
received/prescribed
243
113
57
260
219
113
57
236
194
113
57
209
171
108
54
175
153
105
52
152
138
96
46
136
118
83
40
113
107
75
35
102
83
59
26
90
76
52
23
80
1
2
3
4
5
6
7
8
9
10
59
40
17
71
52
35
14
62
12
n ITT
n Efficacy
n FVF
n E@Base
243
113
57
260
219
113
57
236
194
113
57
209
171
108
54
175
153
105
52
152
138
96
46
136
118
83
40
113
107
75
35
102
83
59
26
90
76
52
23
80
1
2
3
4
5
6
7
8
9
10
59
40
17
71
52
35
14
62
12
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
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!
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
Lancet Dec 2012
Lancet Dec 2012
Lancet Dec
2012
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 shortterm relative contraindication and were not
expected to PN or oral nutrition
Doig, ANZICS, JAMA May 2013
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
•
Main inference: No harm by early PN
(in contrast to EPaNIC)
Doig, ANZICS, JAMA May 2013
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
Start PEP UP within 24-48 hrs
At 72 hrs
YES
>80% of Goal
Calories?
NO
No
Yes
Anticipated
Long Stay?
High Risk?
Carry on!
Yes
No
Maximize EN with
motility agents and
small bowel feeding
YES
No
Supplemental PN?
Tolerating
EN at 96
hrs?
No problem
NO
Yes
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?