Transcript A Randomized Trial of Empiric Antibiotics and Invasive

kcal
Consequences of Iatrogenic Malnutrition
Adequacy
of EN
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; Alberda ICM 2009
• 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
• 60% medical; 40% surgical
• Average APACHE II 22; BMI 27
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
More is Better!
Our Field of Dream
If you feed them (better!)
They will leave (sooner!)
2007 International Nutrition
Practice Survey
Cahill NE CCM 2010 (in press)
ICU patients are not all created equal…should
we expect the impact of nutrition therapy to be
the same across all patients?
After so many years of trying to improve care…we
still can’t feed adequately the enteral route!
Results of 2008 International Survey
n=156 ICUs
What if you can’t provide
adequate early enteral
nutrition?
… to TPN or not to TPN,
that is the question!
Canadian Recommendations
Enteral vs. Parenteral Nutrition
• Based on one level 1 and 12 level 2 studies,
when considering nutrition support for critically ill
patients, we strongly recommend the use of
Enteral Nutrition over Parenteral Nutrition.
www.criticalcarenutrition.com
Canadian Recommendations
Combined EN and PN
• Based on 5 level 2 studies, for critically ill
patients starting on enteral nutrition we
recommend that parenteral nutrition not be
started at the same time as enteral nutrition.
www.criticalcarenutrition.com
Canadian Recommendations
Combined EN and PN
• Based on 5 level 2 studies, for critically ill
patients starting on enteral nutrition we
recommend that parenteral nutrition not be
started at the same time as enteral nutrition.
www.criticalcarenutrition.com
ASPEN/SCCM ICU Nutrition CPGs
PN vs Standard Care
• In the patient who was previously healthy prior to critical
illness with no evidence of protein-calorie malnutrition,
use of PN should be reserved and initiated only after
the first 7 days of hospitalization (when EN is not
available).
Supplemental PN
• 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.
McClave JPEN 2009;33:277
Beth Taylorj
• 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.
Clinical Nutrition 2009
A Leap of Faith?
Significant
decrease
in mortality
yet
significant
increase in
infection
Simpson Int Care Med 2005;31:12
Beneficial Effect of Early PN?
Simpson Int Care Med 2005;31:12
Beneficial Effect of Early PN?
• Flaws in this meta-analysis of early PN
– Select studies were included (validity filter excluded
trials with 4-21% lost to follow up)
– Heterogeneous studies were included (elective surgical
patients)
– Used a fixed effects model rather than more
conservative random effects model
– Subgroup analysis at best is a hypothesis generating
analysis
– What is the biological rationale as to how PN causes
increased infection and yet reduces mortality?
Simpson Int Care Med 2005;31:12
Beneficial Effect of Early PN?
Simpson Int Care Med 2005;31:12
The favorable effect of early parenteral
feeding on survival in head-injured patients
•
•
•
•
RCT of 38 patients
EN vs PN
Methods score 6/14
Patients prescribed 2600 cal
– EN rec’d 26% vs PN 65%
When study
repeated years later,
no difference in
mortality
Rapp J Neurosurg 1983:58:906
Combined 2007 and 2008
International Nutrition Practice
Survey Databases
• Point prevalence survey of nutrition practices in
ICU’s around the world conducted Jan. 25, 2007
and May 14, 2008.
• Each site aimed to enroll 20 patient each
• Included ventilated adult patients who remained in
ICU >72 hours
• Enrolled 5771 patients from 351 ICUs from >20
countries
Heyland (unpublished data)
What is the effect of supplemental PN in
critically ill patients receiving early EN:
Results of a multicenter observational study
2920 patients receiving
early EN
What is the effect of supplemental PN in
critically ill patients receiving early EN:
Results of a multicenter observational study
Adequacy of Calories from Total Nutrition
(EN+PN+propofol)
% calories received/prescribed
100
90
80
70
60
50
40
30
20
10
1
2
3
4
5
6
7
8
9
10
11
ICU day
Early EN
Early Suppl. PN
Late Suppl. PN
12
What is the effect of supplemental PN in
critically ill patients receiving early EN:
Results of a multicenter observational study
Adequacy of Calories from EN only
% calories received/prescribed
80
70
60
50
40
30
20
10
0
1
2
3
4
5
6
7
8
9
10
11
ICU day
Early EN
Early Suppl. PN
Late Suppl. PN
12
What is the effect of supplemental PN in
critically ill patients receiving early EN:
Results of a multicenter observational study
Clinical Outcomes: All Patients
Proportion dead or remaining in hospital
P=0.0003
Regression model: Time to Discharge Alive
Single Predictor
Multiple Predictor
What is the effect of supplemental PN in
critically ill patients receiving early EN:
Results of a multicenter observational study
Clinical Outcomes: Patients with low BMI (<20)
Proportion dead or remaining in hospital
P=0.43
What is the effect of supplemental PN in
critically ill patients receiving early EN:
Results of a multicenter observational study
Clinical Outcomes: Patients with GI admission diagnosis
Proportion dead or remaining in hospital
P=0.06
What is the effect of supplemental PN in
critically ill patients receiving early EN:
Results of a multicenter observational study
Clinical Outcomes: Patients with persistent early GI dysfunction
Proportion dead or remaining in hospital
P=0.04
What is the effect of supplemental PN in
critically ill patients receiving early EN:
Results of a multicenter observational study
Conclusions
In mechanically ventilated ICU patients
receiving early EN, supplemental PN is
associated with greater provision of calories
and protein but no beneficial effect on
clinical outcomes, even in high risk patients
(low BMI, GI admission diagnosis,
persistent early GI dysfunction)
What to do when early enteral feeding is
not possible in critically ill patients:
A multicenter observational study
• Focus in medical ICU patients only
• Excluded all those who rec’d early EN
What to do when early enteral feeding is
not possible in critically ill patients:
A multicenter observational study
Adequacy of Calories from Total Nutrition
(EN+PN+propofol)
% calories received/prescribed
100
90
80
70
60
50
40
30
20
10
0
1
2
3
4
5
6
7
8
9
10
ICU day
Early PN
Late PN
Late EN
11
12
What to do when early enteral feeding is
not possible in critically ill patients:
A multicenter observational study
Adequacy of Calories from EN only
% calories received/prescribed
80
70
60
50
40
30
20
10
0
1
2
3
4
5
6
7
8
9
10
ICU day
Early PN
Late PN
Late EN
11
12
What to do when early enteral feeding is
not possible in critically ill patients:
A multicenter observational study
Clinical Outcomes: All Patients
Proportion dead or remaining in hospital
Survival Distribution Function
1.00
0.75
P=0.01
0.50
0.25
0.00
0
10
20
30
40
50
60
70
Days to Hospital Discharge
STRATA:
group=1.Early PN
group=2.Late PN
group=3.Late EN
Censored group=1.Early PN
Censored group=2.Late PN
Censored group=3.Late EN
Multivariable regression model:
No effect of timing of nutrition on outcome
What to do when early enteral feeding is
not possible in critically ill patients:
A multicenter observational study
Clinical Outcomes: Only Patients with low BMI (<25)
Proportion dead or remaining in hospital
Survival Distribution Function
1.00
0.75
P=0.01
0.50
0.25
0.00
0
10
20
30
40
50
60
70
Days to Hospital Discharge
STRATA:
group=1.Early PN
group=2.Late PN
group=3.Late EN
Censored group=1.Early PN
Censored group=2.Late PN
Censored group=3.Late EN
What to do when early enteral feeding is
not possible in critically ill patients:
A multicenter observational study
Conclusions
In medical ICU patients, when early EN is
not possible, early PN is associated with
greater provision of calories and protein but
no beneficial effect on clinical outcomes,
even in high risk patients (low BMI)
Current Evidence for use of PN in critically ill patients:
Results of prospective, observational multicenter
German Study
• Point prevalence study
• 454 ICUs from 310
hospitals in Germany
• 399 patients septic
patients included
–
–
–
–
EN only
PN only
EN +PN
none
Median APACHE II 26
68% had no GI pathology
46% in shock
Overall mortality 55.2%
Elke CCM 2008;36:1762
Current Evidence for use of PN in critically ill patients:
Results of prospective, observational multicenter
German Study
• Point prevalence study
• 454 ICUs from 310
hospitals in Germany
• 399 patients septic
patients included
–
–
–
–
Median APACHE II 26
68% had no GI pathology
46% in shock
Overall mortality 55.2%
70
P=0.005
60
50
40
%
mortality
30
20
10
0
EN only PN only EN +
PN
none
Multivariate analysis:
PN independent predictor for mortality
(OR 2.09, 95% CI 1.29-3.37)
Current Evidence for use of PN in critically ill patients:
Observational study in Critically Ill Trauma Patients
• Retrospective, multicenter, cohort study of 597
severely injured patients
• Compared those that rec’d PN within 7 to those
who did not.
• Also compared early PN group to subgroup of
‘EN tolerant’ (tolerated 1000 kcal any day during
first week)
• Adjusted for differences in key baseline
demographics
Sena J Am Coll Surg 2008;207:459
Early Supplemental PN is Associated with Increased
Infection in Critically Ill Trauma Patients
No Early PN Early PN
Odds Ratio
P value
Nosocomial Infections
27%
56%
2.1 (1.3-3.5)
P=0.003
Late ARDS
1%
8%
3.4 (1.0-11.0)
P=0.04
Death
8%
23%
1.5 (0.8-3.0)
P=0.24
Nosocomial Infections
42%
69%
2.5 (1.1-5.9)
P=0.03
Late ARDS
2%
9%
5.4 (1.1-27.4)
P=0.04
Death
8%
19%
2.7 (0.8-9.3)
P=0.10
Overall Adjusted
EN tolerant analysis
Differences not due to differences in glycemic control
International Multicenter Observational
Study of Nutrition Practices
•351 ICUs around the world
•5771 mechanically ventilated patients > 3days in ICU
5.1%
Heyland (unpublished data)
What if you can’t provide
adequate early enteral
nutrition?
… to TPN or not to TPN,
that is the question!
Consider a newer,
second generation
feeding protocol...
The Efficacy of Enhanced Protein-Energy Provision via the
Enteral Route in Critically Ill Patients:
The PEP uP Protocol!
•
•
•
•
•
Not all critically ill patients are the same; we have
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.
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
The Efficacy of Enhanced Protein-Energy Provision via the
Enteral Route in Critically Ill Patients:
The PEP uP Protocol!
Figure 2.1 Adequacy of Calories from EN (Before Group vs. After Group on Full Volume
Feeds)
100
90
80
70
60
50
40
30
20
10
0
1
2
3
4
5
6
7
ICU Day
PLOT
P-value
Day 1
0.049
Before Group
Day 2
0.0005
Day 3
0.17
Day 4
0.31
After Group
Day 5
0.60
Day 6
0.34
Day 7
0.20
Total
0.015
Heyland (in submission)
% protein received/prescribed
The Efficacy of Enhanced Protein-Energy Provision via the
Enteral Route in Critically Ill Patients:
The PEP uP Protocol!
Figure 2.2 Adequacy of Protein from EN (Before Group vs. After Group on Full Volume
Feeds)
120
110
100
90
80
70
60
50
40
30
20
10
0
1
2
3
4
5
6
7
ICU Day
PLOT
P-value
Day 1
0.014
Before Group
Day 2
<0.0001
Day 3
0.0015
Day 4
0.13
After Group
Day 5
0.57
Day 6
0.62
Day 7
0.34
Total
0.002
Heyland (in submission)
Conclusions
• More EN is better
• Currently no role for routine use of PN in early
setting
• Potential for harm
• Need RCT level of evidence to establish role
Questions?