Title: A Randomized Trial of Empiric Antibiotics and Invasive Diagnostic Techniques in the setting of Ventilator-Associated Pneumonia
1Iatrogenic Malnutrition in the ICU Time for a
Change!
Daren K. Heyland Professor of Medicine Queens
University, Kingston General Hospital Kingston,
ON Canada
2A different form of malnutrition?
3Health Care Associated Malnutrition
- Nutrition deficiencies associated with
physiological derangement and organ dysfunction
that occurs in a health care facility
4Increasing Calorie Debt Associated with worse
Outcomes
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 Petros Clin Nutr 2006
5- 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
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7Mechancially Ventd patients gt7days (average ICU
LOS 28 days)
Faisy BJN 20091011079
8Effect of Increasing Amounts of Calories from EN
on Infectious Complications
Multicenter observational study of 207 patients
gt72 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
9Relationship 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
(A) Increased energy intake
PHYSICAL FUNCTIONING (PF) at 3 months 3.2 (-1.0, 7.3) P0.14
ROLE PHYSICAL (RP) at 3 months 4.2 (-0.0, 8.5) P0.05
STANDARDIZED PHYSICAL COMPONENT SCALE (PCS) at 3 months 1.8 (0.3, 3.4) P0.02
PHYSICAL FUNCTIONING (PF) at 6 months 0.8 (-3.6, 5.1) P0.73
ROLE PHYSICAL (RP) at 6 months 2.0 (-2.5, 6.5) P0.38
STANDARDIZED PHYSICAL COMPONENT SCALE (PCS) at 6 months 0.70 (-1.0, 2.4) P0.41
for increase of 30 gram/day, OR of infection at
28 days
Heyland Unpublished Data
10More (and Earlier) is Better!
If you feed them (better!) They will leave
(sooner!)
11Permissive Underfeeding(Starvation)?
- 187 critically ill patients
- Tertiles according to ACCP recommended levels of
caloric intake - Highest tertile (gt66 recommended calories) vs.
Lowest tertile (lt33 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
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13Optimal 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
14- Association between 12 day average caloric
adequacy and - 60 day hospital mortality
- (Comparing patients recd gt2/3 to those who recd
lt1/3)
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.
D. In ICU at least 12 days prior to permanent
progression to exclusive oral feeding
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.
15Association Between 12-day Caloric Adequacy and
60-Day Hospital Mortality
Heyland CCM 2011
16More (and Earlier) is Better!
If you feed them (better!) They will leave
(sooner!)
17Trophic 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 201139967
18Trophic vs. Full enteral feeding in critically
ill patients with acute respiratory failure
Did not measure infection nor physical function!
Rice CCM 201139967
19Trophic 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 201139967
20Trophic 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
21ICU patients are not all created equalshould we
expect the impact of nutrition therapy to be the
same across all patients?
22How do we figure out who will benefit the most
from Nutrition Therapy?
23Health Care Associated Malnutrition
- Do Nutrition Screening tools help us discriminate
those ICU patients that will benefit the most
from artificial nutrition?
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26Albumin a marker of malnutrition?
- Low levels very prevalent in critically ill
patients - Negative acute-phase reactant such that
synthesis, breakdown, and leakage out of the
vascular compartment with edema are influenced by
cytokine-mediated inflammatory responses - Proxy for severity of underlying disease
(inflammation) not malnutrition - Pre-albumin shorter half life but same limitation
27Subjective Global Assessment?
28- When training provided in advance, can produce
reliable estimates of malnutrition - Note rates of missing data
29- mostly medical patients not all ICU
- rate of missing data?
- no difference between well-nourished and
malnourished patients with regard to the serum
protein values on admission, LOS, and mortality
rate.
30We must develop and validate diagnostic criteria
for appropriate assignment of the described
malnutrition syndromes to individual patients.
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32A Conceptual Model for Nutrition Risk Assessment
in the Critically Ill
Starvation
33The 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, 15R28
34What are the nutritional risk factors associated
with clinical outcomes?(validation of our
candidate variables)
Non-survivors by day 28 (n138) Survivors by day 28 (n460) p values
Age 71.7 60.8 to 77.2 61.7 49.7 to 71.5 lt.001
Baseline APACHE II score 26.0 21.0 to 31.0 20.0 15.0 to 25.0 lt.001
Baseline SOFA 9.0 6.0 to 11.0 6.0 4.0 to 8.5 lt.001
of days in hospital prior to ICU admission 0.9 0.1 to 4.5 0.3 0.0 to 2.2 lt.001
Baseline Body Mass Index 26.0 22.6 to 29.9 26.8 23.4 to 31.5 0.13
Body Mass Index 0.66
lt20 6 ( 4.3) 25 ( 5.4)
20 122 ( 88.4) 414 ( 90.0)
of co-morbidities at baseline 3.0 2.0 to 4.0 3.0 1.0 to 4.0 lt0.001
Co-morbidity lt0.001
Patients with 0-1 co-morbidity 20 (14.5) 140 (30.5)
Patients with 2 or more co-morbidities 118 (85.5) 319 (69.5)
C-reactive protein 135.0 73.0 to 214.0 108.0 59.0 to 192.0 0.07
Procalcitionin 4.1 1.2 to 21.3 1.0 0.3 to 5.1 lt.001
Interleukin-6 158.4 39.2 to 1034.4 72.0 30.2 to 189.9 lt.001
171 patients had data of recent oral intake and weight loss 171 patients had data of recent oral intake and weight loss 171 patients had data of recent oral intake and weight loss 171 patients had data of recent oral intake and weight loss
Non-survivors by day 28 (n32) Survivors by day 28 (n139) p values
Oral intake (food) in the week prior to enrolment 4.0 1.0 to 70.0 50.0 1.0 to 100.0 0.10
of weight loss in the last 3 month 0.0 0.0 to 2.5 0.0 0.0 to 0.0 0.06
35What are the nutritional risk factors associated
with clinical outcomes?(validation of our
candidate variables)
Variable Spearman correlation with VFD within 28 days p values Number of observations
Age -0.1891 lt.0001 598
Baseline APACHE II score -0.3914 lt.0001 598
Baseline SOFA -0.3857 lt.0001 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 -0.1828 0.0130 184
Baseline BMI 0.0581 0.1671 567
of co-morbidities at baseline -0.0832 0.0420 598
Baseline CRP -0.1539 0.0002 589
Baseline Procalcitionin -0.3189 lt.0001 582
Baseline IL-6 -0.2908 lt.0001 581
36The Development of the NUTrition Risk in the
Critically ill Score (NUTRIC Score).
- oral intake in the week prior was dichotomized
into patients who reported less than 100 versus
everyone else - Weight loss was dichotomized as patients who
reported any weight loss versus everyone else. - BMI was dichotomized as lt20 versus other
- Comorbidities was left as integer values range
0-5 - The remaining candidate variables were
categorized into five equal sized groups
(quintiles).
37The 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
38The Development of the NUTrition Risk in the
Critically ill Score (NUTRIC Score).
Variable Range Points
Age lt50 0
50-lt75 1
gt75 2
APACHE II lt15 0
15-lt20 1
20-28 2
gt28 3
SOFA lt6 0
6-lt10 1
gt10 2
Comorbidities 0-1 0
2 1
Days from hospital to ICU admit 0-lt1 0
1 1
IL6 0-lt400 0
400 1
AUC 0.783 0.783
Gen R-Squared 0.169 0.169
Gen Max-rescaled R-Squared 0.256 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.
39The Validation of the NUTrition Risk in the
Critically ill Score (NUTRIC Score).
40The Validation of the NUTrition Risk in the
Critically ill Score (NUTRIC Score).
41The Validation of the NUTrition Risk in the
Critically ill Score (NUTRIC Score).
Interaction between NUTRIC Score and nutritional
adequacy (n211)
P value for the interaction0.01
Heyland Critical Care 2011, 15R28
42Who might benefit the most from nutrition therapy?
- High NUTRIC Score?
- Clinical
- BMI
- Projected long length of stay
- Others?
43Do we have a problem?
44Preliminary Results of INS 2011Overall
Performance Kcals
84
56
15
N211
45Failure Rate patients who failed to meet
minimal quality targets (80 overall energy
adequacy)
46Can we do better?
The same thinking that got you into this mess
wont get you out of it!
47The 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
48In 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!
49www.criticalcarenutrition.com
50Questions?
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