A Randomized Trial of Empiric Antibiotics and Invasive Diagnostic Techniques in the setting of Ventilator-Associated Pneumonia

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Optimizing Outcomes of Critically Ill
Patients The importance of adequate nutrition
and early mobilization
Daren K. Heyland Professor of Medicine Queens
University, Kingston General Hospital Kingston,
ON Canada
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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!

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Clinical Scenario
Moving Beyond Survival!

• 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
• _at_ 3 weeks, family asks how much longer do we
  prolong this?
• not just about survival what will he be like?

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Muscle Matters!Skeletal muscle mass predicts
ventilator-free days, ICU-free days, and
mortality in elderly ICU patients

• Patients gt 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 cut-points.
• Muscle cross-sectional area was then related to
  clinical parameters including ventilator-free
  days, ICU-free days, and mortality.

Moisey Critical Care 2013
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Body Composition Lab CT Imaging Analysis
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Physical Characteristics of Patients

• N149 patients
• Median age 79 years old
• 57 males
• ISS 19
• Prevalence of sarcopenia 71

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BMI Characteristics
All Patients Sarcopenic Patients (n106) Non-sarcopenic Patients (n43)
BMI (kg/m2) 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
Not all sarcopenics underweight!!
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Low muscle mass associated with mortality
Proportion of Deceased Patients P-value
Sarcopenic patients 32 0.018
Non-sarcopenic patients 14 0.018
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Muscle mass is associated with ventilator-free
and ICU-free days
All Patients Sarcopenic Patients Non-Sarcopenic 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
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Determinants to Lean Body Mass
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Protein balance improved with optimal caloric
feeding
Whole body protein synthesis
Whole body protein degradation
Phenylalanine oxidation
Whole body protein balance
Berg Crit Care 201317R158
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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. 

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Estimates of association between nutritional
adequacy and SF-36 scores
Adjusted for age, APACHE II score, baseline
SOFA, Functional Comorbidity Index, admission
category, primary ICU diagnosis, body mass index,
and region
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Subgroup analysis by admission category
Adjusted for age, APACHE II score, baseline
SOFA, Functional Comorbidity Index, admission
category, primary ICU diagnosis, body mass index,
and region
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More (and Earlier) is Better!
If you feed them (better!) They will leave
(sooner!)
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• 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
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JAMA Published online Oct 9, 2013
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• 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
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Clinical Implications

• increasing protein delivery was associated with
  increased muscle wasting.

JAMA Published online Oct 9, 2013
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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

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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
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• 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.
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Association Between 12-day Caloric Adequacy and
60-Day Hospital Mortality
Heyland CCM 2011
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Early vs. Late Parenteral Nutrition in Critically
ill Adults

• 4620 critically ill patients
• Randomized to early PN
• Recd 20 glucose 20 ml/hr then PN on day 3
• OR late PN
• D5W IV then PN on day 8
• All patients standard EN plus tight glycemic
  control

• Results
• Late PN associated with
• 6.3 likelihood of early discharge alive from ICU
  and hospital
• Shorter ICU length of stay (3 vs 4 days)
• Fewer infections (22.8 vs 26.2 )
• No mortality difference

Cesaer NEJM 2011
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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 2013187247255
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Early Nutrition in the ICU Less is
more!Post-hoc analysis of EPANIC
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
Protein is the bad guy!!
Casaer Am J Respir Crit Care Med 2013187247255
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Early vs. Late Parenteral Nutrition in Critically
ill Adults
How do you explain the early signal, present by
day 3
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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)
• gt70 normal to slightly overweight
• Not an indictment of PN
• Early group only recd PN for 1-2 days on average
• Late group only ¼ recd any PN
• 2 other recent large scales trials (Swiss and
  Australian) confirm safety of early PN

Cesaer NEJM 2011
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No comment on protein intakeFactorialized with
OMEGA where half patients received extra 20
grams/day
Rice et al. JAMA 2012307
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Rice et al. JAMA 2012307
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Needham BMJ 2013
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Enrolled 12 of patients screened
Rice et al. JAMA 2012307
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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!
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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

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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?

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More (and Earlier) is Better!Particularly in
High-risk patients
If you feed them (better!) They will leave
(sooner!)
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Failure Rate
high risk patients who failed to meet minimal
quality targets (80 overall energy adequacy)
91.2
87.0
79.9
78.1
75.6
75.1
69.8
Unpublished observations. Results of 2011
International Nutrition Survey (INS).
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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.criticalcarenutri
tion.com for more information on the PEP uP
collaborative
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At 72 hrs gt80 of Goal Calories?
YES
Anticipated Long Stay?
High Risk?
Carry on!
No
Maximize EN with motility agents and small bowel
feeding
YES
Tolerating EN at 96 hrs?
No
Supplemental PN?
No problem
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Lancet 2009273
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Critical Illness
Nutrition Therapy
Early Rehabilitation
Inflammation
Nutrition
Mobility
Muscle Atrophy Muscular Weakness
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Duration of mechanical ventilation
?
ICU/hospital LOS
Functional status
?
QOL
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In Conclusion

• Immobility and Inflammation erode lean muscle
  mass leading to weakness and impaired HRQOL
• Lean body mass key determinant to outcome
• Optimizing nutritional intake can attenuate
  erosion of lean mass and is associated with
  improved function
• Combination of activity and optimal nutrition
  will result in greatest preservation of lean
  muscle mass
• Need to do something to reduce iatrogenic
  underfeeding in your ICU!
• Audit your practice first (next international
  nutrition survey later 2014/early 2015)!
• PEP uP protocol in all
• TOP UP?

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Questions?