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. Early and Adequate Nutrition is therapy that modulates the underlying disease process and impacts patient outcomes
Adjunctive
Supportive
Care
Proactive
Primary
Therapy

6. Early Feeding Supports Gastrointestinal Structure and Function
Maintenance of gut barrier function
Increased secretion of mucus, bile, IgA
Maintenance of peristalsis and blood flow
Attenuates oxidative stress and inflammation
Supports GALT
Improves glucose absorption
Alverdy (CCM 2003;31:598)
Kotzampassi Mol Nutr Food Research 2009
Nguyen CCM 2011

7. Early vs. Delayed EN: Effect on Infectious Complications
R-make sure up to date. DONE
Updated 2009

8. Early vs. Delayed EN: Effect on Mortality
R- make sure up to date. DONE
Updated 2009

9. Feeding the Hypotensive Patient?
Prospectively collected multi-institutional ICU database of 1,174 patients who required mechanical ventilation for more than two days and were on vasopressor agents to support blood pressure.
The beneficial effect of early feeding is more evident in the sickest patients, i.e, those on multiple vasopressor agents.
DiGiovine et al. AJCC 2010

10. 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?

11.  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

12. 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

14. 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

15. Relationship 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)  
P=0.14
ROLE PHYSICAL (RP) at 3 months
4.2 (-0.0, 8.5)
P=0.05
STANDARDIZED PHYSICAL COMPONENT SCALE (PCS) at 3 months
1.8 (0.3, 3.4)
P=0.02
PHYSICAL FUNCTIONING (PF) at 6 months
0.8 (-3.6, 5.1)
P=0.73
ROLE PHYSICAL (RP) at 6 months
2.0 (-2.5, 6.5)
P=0.38
STANDARDIZED PHYSICAL COMPONENT SCALE (PCS) at 6 months
0.70 (-1.0, 2.4)
P=0.41
for increase of 30 gram/day, OR of infection at 28 days
Heyland Unpublished Data

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

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

18. Permissive Underfeeding (Starvation)?
187 critically ill patients
Tertiles according to ACCP recommended levels of caloric intake
Highest tertile (>66% recommended calories) vs. Lowest tertile (<33% 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

20. 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

21. 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.

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

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

25. JAMA 1994;271:56

26. Trophic 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 2011;39:967

27. What other outcomes might be important?
Trophic vs. Full enteral feeding in critically ill patients with acute respiratory failure
What other outcomes might be important?
Rice CCM 2011;39:967

28. Trophic 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 2011;39:967

29. Rice et al. JAMA 2012;307

30. Still no measure of physical function!
Rice et al. JAMA 2012;307

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

32. 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!

33. What about the physically recovery of underfed patients?
Trophic vs. Full enteral feeding in critically ill patients with acute respiratory failure
Randomized
Good follow up
ITT
No blinding
Internally valid
How representative are these patients to ALL the patients in your ICU? May miss an important negative effect in ‘high risk’ patients
What about the physically recovery of underfed patients?
No benefit, potential harm, minimal cost advantage= Do not use routinely!

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

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

36. 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)

38. All ICU patients treated the same

39. 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

40. Subjective Global Assessment?

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

42. 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.

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

45. 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

46. Multi institutional data base of 598 patients
The 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, 15:R28

47. What are the nutritional risk factors associated with clinical outcomes? (validation of our candidate variables)
Non-survivors by day 28
(n=138)
Survivors by day 28
(n=460)
p values
Age
71.7 [60.8 to 77.2]
61.7 [49.7 to 71.5]
<.001
Baseline APACHE II score
26.0 [21.0 to 31.0]
20.0 [15.0 to 25.0]
Baseline SOFA
9.0 [6.0 to 11.0]
6.0 [4.0 to 8.5]
# of days in hospital prior to ICU admission
0.9 [0.1 to 4.5]
0.3 [0.0 to 2.2]
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
<20
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]
<0.001
Co-morbidity
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]
Interleukin-6¶
158.4 [39.2 to ]
72.0 [30.2 to 189.9]
171 patients had data of recent oral intake and weight loss
(n=32)
(n=139)
% Oral intake (food) in the week prior to enrolment
4.0[ to ]
50.0[ to ]
0.10
% of weight loss in the last 3 month
0.0[ to ]
0.0[ to ]
0.06

48. Spearman correlation with VFD within 28 days Number of observations
What 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
<.0001
598
Baseline APACHE II score
Baseline SOFA
594
% Oral intake (food) in the week prior to enrollment
0.1676
0.0234
183
number of days in hospital prior to ICU admission
0.0007
% of weight loss in the last 3 month
0.0130
184
Baseline BMI
0.0581
0.1671
567
# of co-morbidities at baseline
0.0420
Baseline CRP
0.0002
589
Baseline Procalcitionin
582
Baseline IL-6
581

49. The 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 <20 versus other
Comorbidities was left as integer values range 0-5
The remaining candidate variables were categorized into five equal sized groups (quintiles).

50. The 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
referent
0.780 1
0.949
1.272
1.907 2

51. 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.

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

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

54. 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

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

56. Do we have a problem?

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

58. Failure Rate % patients who failed to meet minimal quality targets (80% overall energy adequacy)

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. Get a copy of the one nestle uses for their tool kit

63. 15.2% using the recommended threshold volume of 250 ml
The Impact of Enteral Feeding Protocols on Enteral Nutrition Delivery: Results of a multicenter observational study
Characteristics
Total n=269
Feeding Protocol
Yes
208 (78%)
Gastric Residual Volume Tolerated in Protocol
Mean (range)
217 ml (50, 500)
Elements included in Protocol
Motility agents
68.5%
Small bowel feeding
55.2%
HOB Elevation
71.2 %
15.2% using the recommended threshold volume of 250 ml
Heyland JPEN 2010

64. 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

65. 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!

66. Reasons for Inadequate Intake
Slow starts and slow ramp ups
Interruptions
Mostly related to procedures
Not related to GI dysfunction
Can be overcome by better feeding protocols
Impaired motility
Medications
Metabolic, electrolyte abnormalities
Underlying disease
Prophylactic use of motility agents

67. Protocol to Manage Interruptions to EN due to non-GI Reasons
Add slide on interrruptions to EN re procedures.
Can be downloaded from

68. Daren K. Heyland Enhanced Protein-Energy Provision
via the Enteral Route
in Critically Ill Patients:
The PEP uP Protocol
Daren K. Heyland
Professor of Medicine
Queen’s University, Kingston General Hospital
Kingston, ON Canada

69. 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 (250 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

70. The PEP uP Protocol
Stable patients should be able to tolerate goal rate
We use a concentrated solution to maximize calories per ml
Begin 24 hour volume-based feeds. After initial tube placement confirmed, start Pepatmen Total volume to receive in 24 hours is 17ml x weight (kg)= <write in 24 target volume>. Determine initial rate as per Volume Based Feeding Schedule. Monitor gastric residual volumes as per Adult Gastric Flow Chart and Volume Based Feeding Schedule. OR
Begin Peptamen 1.5 at 10 mL/h after initial tube placement confirmed. Hold if gastric residual volume >500 ml and ask Doctor to reassess. Reassess ability to transition to 24 hour volume-based feeds next day. {Intended for patient who is hemodynamically unstable (on high dose or escalating doses of vasopressors, or inadequately resuscitated) or not suitable for high volume enteral feeding (ruptured AAA, upper intestinal anastomosis, or impending intubation)}
NPO. Please write in reason: __________________ ______ (only if contraindication to EN present: bowel perforation, bowel obstruction, proximal high output fistula. Recent operation and high NG output not a contraindication to EN.) Reassess ability to transition to 24 hour volume-based feeds next day.
If unstable or unsuitable, just use trophic feeds
Note indications for trophic feeds
Drs need to justify why there are keeping patients NPO
We want to minimize the use of NPO but if selected, need to reassess next day
Note, there are only a few absolute contraindications to EN

71. It’s not just about calories...
Inadequate protein intake
Loss of lean muscle mass
Immune dysfunction
Weak
Prolonged mechanical ventilation
So in order to minimize this, we order:
Protein supplement Beneprotein® 14 grams mixed in 120 mls sterile water
administered bid via NG

72. Other Strategies to Maximize the Benefits and Minimize the Risks of EN
Motility agents started at initiation of EN rather that waiting till problems with High GRV develop.
Maxeran 10 mg IV q 6h (halved in renal failure)
If still develops high gastric residuals, add Erythromycin 200 mg q 12h.
Can be used together for up to 7 days but should be discontinued when not needed any more
Reassess need for motility agents daily

73. 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

74. % calories received/prescribed
Change of nutritional intake from baseline to follow-up of all the study sites (all patients)
% calories received/prescribed
Xuran, I need these redone without distinguishing commuinty from academic. Just one summary slope per figure.

75. % protein received/prescribed
Change of nutritional intake from baseline to follow-up of all the study sites (all patients)
% protein received/prescribed
Xuran, Re do as previous

76. Small Bowel vs. Gastric Feeding: A meta-analysis
Other Strategies to Maximize the Benefits and Minimize the Risks of EN
Small Bowel vs. Gastric Feeding: A meta-analysis
Effect on VAP
Updated 2011,

77. Does Postpyloric Feeding Reduce Risk of GER and Aspiration?
Tube Position
# of patients
% positive for GER
% positive for Aspiration
Stomach 21 32
5.8 D1 8 27
4.1 D2 3 11
1.8 D4 1 5
Total 33 75
11.7
P=0.004
P=0.09
Heyland CCM 2001;29:

78. FRICTIONAL ENTERAL FEEDING TUBE (TIGER TUBETM)
Flaps to allow peristalsis to pull tube passively forward
Sucessful jejunal placement >95%

79. CORTRAK® A new paradigm in feeding tube placement
Aid to placement of feeding tubes into the stomach or small bowel
The tip of the stylet is a transmitter.
Signal is picked up by an external receiver unit.
Signal is fed to an attached Monitor unit.
Provides user with a real-time, graphic display that represents the path of the feeding tube.

80. A Change to Nursing Report
Please report this % on rounds as part of the GI systems report
Adequacy of Nutrition Support =
24 hour volume of EN received
Volume prescribed to meet caloric requirements in 24 hours

81. When performance is measured, performance improves.
When performance is measured and reported back, the rate of improvement accelerates.
Thomas Monson

82. 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!

83. 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

84. 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

85. 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

86. 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

87. 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!
PEP uP protocol in all
Selective use of small bowel feeds then sPN in high risk patients

88. Not tolerating EN at 96 hrs?
Start PEP UP
Day 3
>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
Not tolerating EN at 96 hrs? No NO
Yes
Supplemental PN?

90. Questions?