Overview
• Importance of preserving muscle
mass/function
• Optimal nutrition positively influences
subsequent physical function
• Role of early rehabilition/mobilization
• Need both optimal nutrition and optimal
mobilization to optimize outcome!
Moving Beyond Survival!
Clinical Scenario
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79 yo male admitted to hospital with AMI
Progressive respiratory failure
Aspirates
ARDS
Low volume ventilation, high PEEP, NO
Course complicated by line sepsis resulting in
need for pressors and renal failure
• @ 3 weeks, family asks “how much longer do we
prolong this?”
• “not just about survival; what will he be like?”
Muscle Matters!
Skeletal muscle mass predicts ventilator-free days, ICUfree days, and mortality in elderly ICU patients
• Patients > 65 years with an admission abdominal
computed tomography scan and requiring intensive care
unit stay at a Level I trauma center in 2009-2010 were
reviewed.
• Muscle cross-sectional area at the 3rd lumbar vertebra was
calculated and sarcopenia identified using sex-specific cutpoints.
• Muscle cross-sectional area was then related to clinical
parameters including ventilator-free days, ICU-free days,
and mortality.
Moisey Critical Care 2013
Skeletal Muscle
Adipose Tissue
Physical Characteristics of
Patients
•
•
•
•
•
N=149 patients
Median age: 79 years old
57% males
ISS: 19
Prevalence of sarcopenia: 71%
BMI Characteristics
All Patients
Sarcopenic
Patients (n=106)
Non-sarcopenic
Patients (n=43)
25.8 (22.7, 28.2)
24.4 (21.7, 27.3)
27.6 (25.5, 30.4)
Underweight, %
7
9
2
Normal Weight, %
37
44
19
Overweight, %
42
38
51
Obese, %
15
9
28
BMI (kg/m2)
Not all sarcopenics
underweight!!
Low muscle mass associated
with mortality
Proportion of Deceased
Patients
Sarcopenic patients
32%
Non-sarcopenic patients
14%
P-value
0.018
Muscle mass is associated with
ventilator-free and ICU-free days
All Patients
Sarcopenic
Patients
NonSarcopenic
Patients
P-value
Ventilator-free
days
25 (0,28)
19 (0,28)
27 (18,28)
0.004
ICU-free days
19 (0,25)
16 (0,24)
23 (14,27)
0.002
Determinants to Lean Body Mass
PROTEIN REQUIREMENT IN CRITICAL ILLNESS
AT ADEQUATE ENERGY INTAKE
Wolfe et al., Ann Surg 1983; Ishibashi et al., Crit Care Med 1998
Hoffer Am J Clin Nutr 2003
g protein / kg IBW per day
Whole-body protein loss
(kg / 2 weeks)
 0.7
0
-0.5
-1
-1.5
-2
 1.0
 1.5
 2.2
Protein balance improved with optimal
caloric feeding
Whole body protein synthesis
Phenylalanine oxidation
Whole body protein degradation
Whole body protein balance
Berg Crit Care 2013;17:R158
Nutritional Adequacy and Health-related
Quality of Life in Critically Ill Patients
Requiring Prolonged Mechanical Ventilation
• Sub study of the REDOXS study
• 302 patients survived to 6-months follow-up and were
mechanically ventilated for more than eight days in the
intensive care unit were included.
• Nutritional adequacy was obtained from the average
proportion of prescribed calories received during the first
eight days of mechanical ventilation in the ICU.
• HRQoL was prospectively assessed using Short-Form 36
Health Survey (SF-36) questionnaire at three-months and
six-months post ICU admission.
Estimates of association between nutritional adequacy
and SF-36 scores
Nutritional Adequacy per 25% increase
SF-36
Crude Estimate
p-value
(95% CI)
Physical
3-month
Functioning
(n=179)
6-month
Adjusted Estimate*
p-value
(95% CI)
7.71 (2.29, 13.14)
0.006
7.29 (1.43, 13.15)
0.02
5.25 (0.03, 10.47)
0.05
4.16 (-1.32, 9.64)
0.14
8.27 (3.03, 13.52)
0.002
8.30 (2.65, 13.95)
0.004
5.00 (-0.16, 10.16)
0 .06
3.15 (-2.25, 8.54)
0.25
1.82 (-0.07, 3.70)
0.06
1.82 (-0.18, 3.81)
0.07
1.77 (-0.15, 3.69)
0.07
1.33 (-0.65, 3.31)
0.19
(n=202)
Role
3-month
Physical
(n=178)
6-month
(n=202)
Physical
3-month
Component
(n=175)
Scale
6-month
(n=200)
*Adjusted for age, APACHE II score, baseline SOFA, Functional Comorbidity Index,
admission category, primary ICU diagnosis, body mass index, and region
Subgroup analysis by admission category
Nutritional Adequacy per 25% increase
Medical Patients
SF-36
N
Adjusted Estimate*
Surgical Patients
P
b
N
(95% CI)
Adjusted Estimate*
P
(95% CI)
PF: 3-mo
128
10.94 (4.33, 17.56)
0.001
51
-1.22 (-13.74, 11.30,)
0.84
PF: 6-mo
144
6.70 (0.19, 13.21)
0.04
58
-0.25 (-11.78, 11.28)
0.97
RP: 3-mo
127
13.13 (6.66, 19.59)
0.0001
51
-2.95 (-15.17, 9.26)
0.63
RP: 6-mo
144
7.15 (0.87, 13.44)
0.03
58
-3.37 (-15.44, 8.72)
0.58
PCS: 3-mo
125
3.48 (1.19, 5.77)
0.003
50
-1.55 (-5.90, 2.81)
0.47
PCS: 6-mo
142
2.53 (0.19, 4.87)
0.03
58
-0.36 (-4.38, 3.66)
0.86
*Adjusted for age, APACHE II score, baseline SOFA,
Functional Comorbidity Index, admission category, primary
ICU diagnosis, body mass index, and region
More (and Earlier) is Better!
If you feed them (better!)
They will leave (sooner!)
• 63 critically ill patients
• Muscle loss determined by serial US of
rectus femoris (CSA) on days 1, 3, 5, 7 and
10
• Histopathologic analysis also performed
• Protein signal pathways analyzed
JAMA Published online Oct 9, 2013
JAMA Published online Oct 9, 2013
• “In a multivariable linear analysis, change
in rectus femoris CSA was positively
associated with the degree of organ failure,
CRP level and amount of protein delivered”
JAMA Published online Oct 9, 2013
Clinical Implications
• “…increasing protein delivery was
associated with increased muscle wasting.”
JAMA Published online Oct 9, 2013
Guilty by Association
• Patients who stay longer in the ICU has
worse outcomes
• Patients who stay longer in the ICU will
have more muscle loss
• Patients in the ICU will have greater
opportunity to tolerate more protein/calories
Error to assume that protein causes
muscle loss or adverse outcomes
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
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 Nutrition in the ICU: Less is more!
Post-hoc analysis of EPANIC
Treatment effect persisted in all subgroups
Casaer Am J Respir Crit Care Med 2013;187:247–255
Early Nutrition in the ICU: Less is more!
Post-hoc analysis of EPANIC
Protein is the
bad guy!!
Indication bias:
1) patients with longer
projected stay would have
been fed more aggressively;
hence more protein/calories is
associated with longer lengths
of stay. (remember this is an
unblinded study).
2) 90% of these patients are
elective surgery. there would
have been little effort to feed
them and they would have
categorically different
outcomes than the longer stay
patients in which their were
efforts to feed
Casaer Am J Respir Crit Care Med 2013;187:247–255
Early vs. Late Parenteral
Nutrition in Critically ill Adults
How do you explain the early signal, present by day 3
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
– 2 other recent large scales trials (Swiss and Australian) confirm
safety of early PN
Cesaer NEJM 2011
No comment on protein intake
Factorialized with OMEGA where half patients
received extra 20 grams/day
Rice et al. JAMA 2012;307
Rice et al. JAMA 2012;307
Needham
BMJ 2013
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!
Not all ICU Patient the same!
• Low Risk
– 34 year former football
player,
– BMI 35
– otherwise healthy
– involved in motor
vehicle accident
– Mild head injury and
fractured R leg
requiring ORIF
• High Risk
– 79 women
– BMI 35
– PMHx COPD, poor
functional status, frail
– Admitted to hospital 1
week ago with CAP
– Now presents in
respiratory failure
requiring intubation and
ICU admission
Who might benefit the most from
nutrition therapy?
• High NUTRIC Score?
• Clinical
– BMI
– Projected long length of stay
•
•
•
•
Nutritional history variables
Sarcopenia
Medical vs. Surgical
Others?
More (and Earlier) is Better!
Particularly in ‘High-risk’ patients
If you feed them (better!)
They will leave (sooner!)
Failure Rate
% high risk patients who failed to meet minimal
quality targets (80% overall energy adequacy)
91.2
75.6
78.1
87.0
75.1
79.9
69.8
Unpublished observations.
Results of 2011 International Nutrition Survey (INS).
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, rather than started when there is a problem.
A Major Paradigm Shift in How we Feed Enterally
Heyland Crit Care 2010;
see www.criticalcarenutrition.com for more information on the PEP uP collaborative
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
Lancet 2009;273:
Early
Rehabilitation
Mobility
Inflammation
?
Duration of
mechanical
ventilation
Critical Illness
Nutrition
Therapy
Nutrition
Muscle Atrophy
&
Muscular Weakness
ICU/hospital
LOS
?
Functional
status
?
QOL
Questions?