1. Iatrogenic Malnutrition in the ICU: Time for a Change!
Daren K. Heyland
Professor of Medicine
Queen’s University, Kingston General Hospital
Kingston, ON Canada
Add data from iatrogenic malnutrition slides

2. Learning Objectives Define iatrogenic malnutrition
Describe the nature of the evidence related to optimal amount of calories/protein
List key variables to consider in assessing nutritional risk in ICU patients
List strategies to improve nutritional adequacy in the critical care setting.

3. A different form of malnutrition?
Need picture of malnourshed child

4. Health Care Associated Malnutrition
Nutrition deficiencies associated with physiological derangement and organ dysfunction that occurs in a health care facility
Patients who will benefit the most from nutrition therapy and who will be harmed the most from by iatrogenic malnutrition (underfeeding)

5. Optimal Amount of Protein and Calories for Critically Ill Patients?
Early EN (within hrs of admission) is recommended!
Optimal Amount of Protein and Calories for Critically Ill Patients?

6.  Caloric debt associated with:
Increasing Calorie Debt Associated with worse Outcomes
Caloric Debt
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

7. 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

9. for increase of 1000 cal/day, OR of infection at 28 days
Effect of Increasing Amounts of Calories from EN on Infectious Complications
Multicenter observational study of 207 patients >72 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

10. Relationship between increased nutrition intake and physical function (as defined by SF-36 scores) following critical illness
For every 1000 kcal/day received:
Model *
Estimate (CI)
P values
At 3 months
PHYSICAL FUNCTIONING
3.2 (-1.0, 7.3)  
P=0.14
ROLE PHYSICAL
4.2 (-0.0, 8.5)
P=0.05
STANDARDIZED PHYSICAL COMPONENT SCALE
1.8 (0.3, 3.4)
P=0.02
At 6 months
0.8 (-3.6, 5.1)
P=0.73
2.0 (-2.5, 6.5)
P=0.38
0.70 (-1.0, 2.4)
P=0.41
for increase of 30 gram/day, OR of infection at 28 days
Unpublished data from Multicenter RCT of glutamine and antioxidants
(REDOXS Study); n=364

11. Mechancially Vent’d patients >7days (average ICU LOS 28 days)
Faisy BJN 2009;101:1079

12. 113 select ICU patients with sepsis or burns
On average, receiving 1900 kcal/day and 84 grams of protein
No significant relationship with energy intake but……
Clinical Nutrition 2012

13. More (and Earlier) is Better!
If you feed them (better!)
They will leave (sooner!)

15. 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

16. 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.*
D. In ICU at least 12 days prior to permanent progression to exclusive oral feeding*
Remove the 1/3-2/3 data
*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.

17. Association Between 12-day Caloric Adequacy and 60-Day Hospital Mortality
Optimal amount=
80-85%
Heyland CCM 2011

18. More (and Earlier) is Better!
If you feed them (better!)
They will leave (sooner!)

20. Rice et al. JAMA 2012;307

21. Rice et al. JAMA 2012;307

22. Enrolled 12% of patients screened
Rice et al. JAMA 2012;307

23. No effect in young, healthy, overweight patients who have short stays!
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!

24. Nutritional Management of ICU Patients: Are these both 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
72 women
BMI 35
PMHx COPD, poor functional status
Admitted to hospital 1 week ago with CAP
Now presents in respiratory failure requiring intubation and ICU admission

25. ICU-acquired Weakness (ICUAW)
Muscle weakness develops in 25%-60% of patients who have been mechanically ventilated for > 1 week1
Prolongs:1-4
mechanical ventilation
weaning from the ventilator
ICU stay
ICUAW main clinical manifestation of critical illness neuromyopathy (CINM)5
de Jonghe B, et al. Crit Care Med ;30:
Garnacho-Montero J, et al. Crit Care Med ;33:
van den Berghe G, et al. Crit Care Med ;31:
Hermans G, et al. Am J Respir Crit Care Med ;175:
de Jonghe B, et al. Crit Care Med ;37(suppl.):S309-S315.

26. Determinants to Lean Body Mass

27. Muscle Matters! Skeletal muscle mass predicts ventilator-free days, ICU-free 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 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.
Kozar (in submission)

28. Body Composition Lab CT Imaging Analysis
Skeletal Muscle
Adipose Tissue
To date we have used weight/BMI as a descriptor of patient body composition and we have looked at change in weight as a marker of change in nutritional status or to evaluate success/failure of nutritional intervention
However, with weight, we cannot discern specific body composition profile or changes in profile;
Use of already existing CT scans can provide this information…
-L3 bony landmark – literature; longitudinal

29. Physical Characteristics of Patients
N=149 patients
Median age: 79 years old
57% males
ISS: 19
Prevalence of sarcopenia: 71%

30. Sarcopenic Patients (n=106) Non-sarcopenic Patients (n=43)
BMI Characteristics
All Patients
Sarcopenic Patients (n=106)
Non-sarcopenic Patients (n=43)
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 28

31. Low muscle mass associated with mortality
Proportion of Deceased Patients
P-value
Sarcopenic patients
32%
0.018
Non-sarcopenic patients
14%

32. 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

34. After day 5, when awake, performed muscle testing
Prospective multicenter observational trial of 136 patients requiring min 5 days of mechanical ventilation
After day 5, when awake, performed muscle testing
Am J Respir CCM 2008;178:

36. ICU patients are not all created equal…should we expect the impact of nutrition therapy to be the same across all patients?

37. How do we figure out who will benefit the most from Nutrition Therapy?
Need picture of malnourshed child

38. Health Care Associated Malnutrition
Do Nutrition Screening tools help us discriminate those ICU patients that will benefit the most from artificial nutrition?
Patients who will benefit the most from nutrition therapy and who will be harmed the most from by iatrogenic malnutrition (underfeeding)

40. All ICU patients treated the same

41. Albumin: 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

42. Subjective Global Assessment?

43. When training provided in advance, can produce reliable estimates of malnutrition
Note rates of missing data

44. 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.

45. Mostly surgical patients; 100% data available for SGA

47. “We must develop and validate
diagnostic criteria for appropriate assignment of the
described malnutrition syndromes to individual patients.”

48. A Conceptual Model for Nutrition Risk Assessment in the Critically Ill
Chronic
Recent weight loss
BMI?
Acute
Reduced po intake
pre ICU hospital stay
Starvation
Nutrition Status
micronutrient levels - immune markers - muscle mass
Inflammation
Acute
IL-6
CRP
PCT
Chronic
Comorbid illness

49. The Development of the NUTrition Risk in the Critically ill Score (NUTRIC Score).
Variable
Range
Points
Age
<50
50-<75 1
>=75 2
APACHE II
<15
15-<20
20-28
>=28 3
SOFA
<6
6-<10
>=10
# Comorbidities
0-1 2+
Days from hospital to ICU admit
0-<1 1+
IL6
0-<400
400+
AUC
0.783
Gen R-Squared
0.169
Gen Max-rescaled R-Squared 
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.

50. The Validation of the NUTrition Risk in the Critically ill Score (NUTRIC Score).

51. The Validation of the NUTrition Risk in the Critically ill Score (NUTRIC Score).

52. Interaction between NUTRIC Score and nutritional adequacy (n=211)*
The Validation of the NUTrition Risk in the Critically ill Score (NUTRIC Score).
Interaction between NUTRIC Score and nutritional adequacy (n=211)*
P value for the interaction=0.01
Heyland Critical Care 2011, 15:R28

53. P=0.008
P=0.04
P=0.04
Multicenter prospective study of nutrition practice in abdominal surgery
All patients had nutrition screening, not all patients had peri op nutrition support
Benefit of nutrition support seen in NRS>5 compared to controls, no benefit seen in low risk patients (NRS<5).
Patients with NRS >5

54. Who might benefit the most from nutrition therapy in the ICU?
High NUTRIC Score?
Clinical
BMI
Projected long length of stay
Others?

55. Do we have a problem?

56. Preliminary Results of INS 2011 Overall Performance: Kcals
84%
56%
15%
N=211

57. Nutritional Adequacy of High Risk Patients compared to Low Risk Patients

58. Failure Rate
% high risk patients who failed to meet minimal quality targets (80% overall energy adequacy)
91.2
87.0
78.1
79.9
75.6
75.1
69.8
Unpublished observations. Results of 2011 International Nutrition Survey (INS).

59. Strategies to Maximize the Benefits and Minimize the Risks of EN
weak evidence
feeding protocols
motility agents
elevation of HOB
small bowel feeds
stronger evidence
Canadian CPGs

60. Use of Nurse-directed Feeding Protocols
Start feeds at 25 ml/hr
< 250 ml
advance rate by 25 ml
reassess q 4h
> 250 ml
hold feeds
add motility agent
reassess q 4h
Check Residuals q4h
“Should be considered as a strategy to optimize delivery of enteral nutrition in critically ill adult patients.”
2009 Canadian CPGs

61. The Impact of Enteral Feeding Protocols on Enteral Nutrition Delivery: Results of a multicenter observational study
P<0.05
Time to start EN from ICU admission 41.2 in protocolized sites vs 57.1 hours in those without a protocol
Patients rec’ing motility agents 61.3% in protocolized sites vs 49.0% in those without
P<0.05
Heyland JPEN 2010

62. The same thinking that got you into this mess won’t get you out of it!
Can we do better?
The same thinking that got you into this mess won’t get you out of it!

63. 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!
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
Nurse reports daily on nutritional adequacy.
A Major Paradigm Shift in How we Feed Enterally

64. The Efficacy of Enhanced Protein-Energy Provision via the Enteral Route in Critically Ill Patients: The PEP uP Protocol!
Adequacy of Calories from EN
(Before Group vs. After Group on Full Volume Feeds)
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Total
P-value
0.08
0.0003
0.10
0.19
0.48
0.18
0.11
<0.0001
Heyland Crit Care 2010

65. % calories received/prescribed
Change of nutritional intake from baseline to follow-up of all the study sites (intervention group only)
% calories received/prescribed

66. Health Care Associated Malnutrition
What if you can’t provide adequate nutrition enterally?
… to add PN or not to add PN,
that is the question!

67. Early vs. Late Parenteral Nutrition in Critically ill Adults
4620 critically ill patients
Randomized to early PN
Rec’d 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

68. 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
Cesaer NEJM 2011

69. Lancet Dec 2012

70. Lancet Dec 2012

71. Lancet Dec 2012

72. Adult patients were eligible for enrollment within 24 hours of ICU admission if they were expected to remain in the ICU on the calendar day after enrollment, were considered ineligible for enteral nutrition by the attending clinician due to a short-term relative contraindication and were not expected to PN or oral nutrition
Doig, ANZICS, JAMA May 2013

73. Who were these patients?
Overall, standard care group remained unfed for 2.8 days after randomization
40% of standard care group never rec’d any artificial nutrition; remained in ICU 3.5 days

74. Intervention not intense enough?
40% of both groups got EN (delayed)
40% of standard care group got PN for an average of 3.0 days
Average PN use in early PN group was 6.0 days

75. Main inference: No harm by early PN (in contrast to EPaNIC)
Doig, ANZICS, JAMA May 2013

76. What if you can’t provide adequate nutrition enterally?
… to TPN or not to TPN,
that is the question!
Case by case decision
Maximize EN delivery prior to initiating PN
Use early in high risk cases

77. Start PEP UP within 24-48 hrs
At 72 hrs
>80% of Goal Calories?
YES No NO
Yes
Anticipated Long Stay?
High Risk?
Yes
Carry on! No
Maximize EN with motility agents and small bowel feeding
No problem
YES
Yes NO
Tolerating EN at 96 hrs? No
Supplemental PN?
No problem

78. R The TOP UP Trial Primary Outcome 60-day mortality PN for 7 days
Stratified by:
Site
BMI
Med vs Surg
ICU patients R
BMI <25
60-day mortality
BMI >35
Fed enterally
Control

79. Muscle Outcome Assessments in TOP UP
Measures of muscle mass and function
mitochondrial complex I activity
US of femoral quad (baseline and follow up CTs when available)
Hand grip strength
6 min walk test
SF 36 (RP and PCS)

80. Reliability of US measure of Quad Muscle Layer Thickness
46 pairs of within operator measurements with an ICC of .98
73 pairs of operator 1 to operator 2 measurements with an ICC of .94.
There was a small but statistically significant difference between the operator 1 and 2 results Mean (operator 1-2) (95% CI) = cm ( to ), p=  

81. Lancet 2009;273:

82. In 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! (JOIN International Critical Care Nutrition Survey in 2013)
PEP uP protocol in all
Selective use of small bowel feeds then sPN in high risk patients

85. Questions?