Title: A Randomized Trial of Empiric Antibiotics and Invasive Diagnostic Techniques in the setting of Ventilator-Associated Pneumonia
1Early Parenteral Nutrition Should NOT be Used In
Critically ILL Patients
Daren K. Heyland Professor of Medicine Queens
University, Kingston General Hospital Kingston,
ON Canada
2Consequences of Iatrogenic Malnutrition
Adequacy of EN
Adequacy of EN
- ? 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
3- Point prevalence survey of nutrition practices in
ICUs around the world conducted Jan. 27, 2007 - Enrolled 2772 patients from 158 ICUs over 5
continents - Included ventilated adult patients who remained
in ICU gt72 hours - 60 medical 40 surgical
- Average APACHE II 22 BMI 27
4Hypothesis
- 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
5What Study Patients Actually Recd
- 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
6Relationship Between Increased Calories and 60
day Mortality
BMI Group Odds Ratio 95 Confidence Limits 95 Confidence Limits P-value
Overall 0.76 0.61 0.95 0.014
lt20 0.52 0.29 0.95 0.033
20-lt25 0.62 0.44 0.88 0.007
25-lt30 1.05 0.75 1.49 0.768
30-lt35 1.04 0.64 1.68 0.889
35-lt40 0.36 0.16 0.80 0.012
gt40 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.
7(No Transcript)
8More is Better!
Our Field of Dream
If you feed them (better!) They will leave
(sooner!)
92007 International Nutrition Practice Survey
Cahill NE CCM 2010 (in press)
10ICU patients are not all created equalshould we
expect the impact of nutrition therapy to be the
same across all patients?
11Results of 2008 International Surveyn156 ICUs
After so many years of trying to improve carewe
still cant feed adequately the enteral route!
12- What if you cant provide adequate early enteral
nutrition? - to TPN or not to TPN,
- that is the question!
13Canadian RecommendationsEnteral 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
14Canadian RecommendationsCombined 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
15Canadian RecommendationsCombined 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
16ASPEN/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 200933277
17Beth 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
18A Leap of Faith?
19Significant decrease in mortality yet significant
increase in infection
Simpson Int Care Med 20053112
20Beneficial Effect of Early PN?
Simpson Int Care Med 20053112
21Beneficial 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 20053112
22Beneficial Effect of Early PN?
Simpson Int Care Med 20053112
23The 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 recd 26 vs PN 65
When study repeated years later, no difference in
mortality
Rapp J Neurosurg 198358906
24Combined 2007 and 2008 International Nutrition
Practice Survey Databases
- Point prevalence survey of nutrition practices in
ICUs 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 gt72 hours - Enrolled 5771 patients from 351 ICUs from gt20
countries
Heyland (unpublished data)
25What is the effect of supplemental PN in
critically ill patients receiving early EN
Results of a multicenter observational study
2920 patients receiving early EN
26What 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
(ENPNpropofol)
27What 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
28What 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
P0.0003
Regression model Time to Discharge Alive
Multiple Predictor
Single Predictor
29What 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
(lt20) Proportion dead or remaining in hospital
P0.43
30What 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
P0.06
31What 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
P0.04
32What 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)
33What 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 recd early EN
34What to do when early enteral feeding is not
possible in critically ill patients A
multicenter observational study
Adequacy of Calories from Total Nutrition
(ENPNpropofol)
35What to do when early enteral feeding is not
possible in critically ill patients A
multicenter observational study
Adequacy of Calories from EN only
36What 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
P0.01
Multivariable regression model No effect of
timing of nutrition on outcome
37What to do when early enteral feeding is not
possible in critically ill patients A
multicenter observational study
Clinical Outcomes Only Patients with low BMI
(lt25) Proportion dead or remaining in hospital
P0.01
38What 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)
39Current Evidence for use of PN in critically ill
patientsResults 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
Elke CCM 2008361762
40Current Evidence for use of PN in critically ill
patientsResults of prospective, observational
multicenter German Study
P0.005
- 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
Multivariate analysis PN independent predictor
for mortality (OR 2.09, 95 CI 1.29-3.37)
41Current 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 recd 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 2008207459
42Early Supplemental PN is Associated with
Increased Infection in Critically Ill Trauma
Patients
No Early PN Early PN Odds Ratio P value
Overall Adjusted
Nosocomial Infections 27 56 2.1 (1.3-3.5) P0.003
Late ARDS 1 8 3.4 (1.0-11.0) P0.04
Death 8 23 1.5 (0.8-3.0) P0.24
EN tolerant analysis
Nosocomial Infections 42 69 2.5 (1.1-5.9) P0.03
Late ARDS 2 9 5.4 (1.1-27.4) P0.04
Death 8 19 2.7 (0.8-9.3) P0.10
Differences not due to differences in glycemic
control
43International Multicenter Observational Study of
Nutrition Practices
- 351 ICUs around the world
- 5771 mechanically ventilated patients gt 3days in
ICU
5.1
Heyland (unpublished data)
44- What if you cant provide adequate early enteral
nutrition? - to TPN or not to TPN,
- that is the question!
45(No Transcript)
46The 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
47The Efficacy of Enhanced Protein-Energy Provision
via the Enteral Route in Critically Ill Patients
The PEP uP Protocol!
Heyland (in submission)
48The Efficacy of Enhanced Protein-Energy Provision
via the Enteral Route in Critically Ill Patients
The PEP uP Protocol!
Heyland (in submission)
49Conclusions
- 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
50Questions?