1. Early Enteral Nutrition in the ICU: The Clock is Ticking!
Daren K. Heyland
Professor of Medicine
Queen’s University, Kingston General Hospital
Kingston, ON Canada

2. Case Scenario Mr KT 76 per’d diverticulum Septic shock, ARDS, MODS
Day 1- high NG drainage, distended abdomen
Day 3- trickle feeds
Feeds on and off again for
whole first week
No PN, no small bowel feeds,
no specialized nutrients

3. Case Scenario Adequacy of EN Adequacy of EN
Prolonged ICU stay, discharged weak and debilitated. Dies on day 43 in hospital from massive PE

4. To what extent did nutrition therapy (or lack thereof) play a role in this patient’s demise?

5. Medical Error 44,000 to 98,000 deaths per year in the US
October 9th, 2002
Medical Error
44,000 to 98,000 deaths per year in the US
total heath care costs of errors resulting in injury between $17 to $29 billion
On an annual basis More people die from medical error than traffic accidents, breast cancer, or AlDs.
Contribution related to misapplication or non application of artificial nutrition?
Institute of Medicine 1999
Rupinder Dhaliwal, RD

6. In patients with high gastric residual volumes:
use of motility agents 58.7% (site average range: 0-100%)
use of small bowel feeding 14.7% (range: %)
Cahill N Crit Care Med 2010 (in press)

7. Average time to start of EN was 46. 5 hours (site average range: 8
Average time to start of EN was 46.5 hours (site average range: hours)
Cahill NE CCM (in press)

8. Loss of Gut Epithelial Integrity
Underlying Pathophysiology of Critical Illness (1)
Loss of Gut Epithelial Integrity
INTESTINAL EPITHELIUM
SIRS
Bacteria
DISTAL ORGAN INJURY
(Lung, Kidneys)
via thoracic duct

9. Disuse Causes Loss of Functional and Stuctural Integrity Increased Gut Permeability
Characteristics : Time dependent
Correlation to disease severity
Consequences: Risk of infection
Risk of MOFS

10. Feeding Supports Gastrointestinal Structure and Function
Maintenance of gut barrier function
Increased secretion of mucus, bile, IgA
Maintenance of peristalsis and blood flow
Favorable effects on GALT/MALT
Alverdy (CCM 2003;31:598)

11. Effect of Early Enteral Feeding on the Outcome of Critically ill Mechanically Ventilated Medical Patients
Retrospective analysis of multiinstitutional database
4049 patients requiring mech vent > 2 days
Categorized as “Early EN” if rec’d feeds within 48 hours of admission (n=2537, 63%)
P=0.007
P=0.02
P=0.0005
Artinian Chest 2006:129;960

12. Effect of Early Enteral Feeding on the Outcome of Critically ill Mechanically Ventilated Medical Patients
Data evaluating the effect of n-3 FFAs on clinical outcomes is relatively sparse, and in this study, is confounded by the fact that they combined fish oils with antioxidants.
Artinian Chest 2006:129;960 12

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

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

15. What About Feeding the Hypotensive Patient?
Resuscitation is the priority
No sense in feeding someone dying of progressive circulatory failure
However, if on stable or declining doses of vasopressors:
Safety and Efficacy of
Enteral Feeding??

16. Dog Model with IV oleic acid lung injury
Purcell Am J Surg 1993;165:188

17. 9 patients day 1 Post-op following CPB requiring inotropes and vasopressors
Feed enterally; metabolic response consistent with substrates being utilized
ICG clearance suggestive of increase mesenteric blood flow

18. Feeding the Hypotensive Patient?
Retrospective analysis of a prospectively collected multi-institutional medical intensive care unit (ICU) database.
A total of 1,174 patients were identified who required mechanical ventilation for more than two days and were placed on vasopressor agents to support their blood pressure.
Patients divided according to whether or not they received enteral nutrition within 48 hours of mechanical ventilation onset.
707 patients (60%) who did were labeled as the “early enteral nutrition group” and the remaining 467 patients (40%) were labeled as “late enteral nutrition group”.
The primary endpoints were overall ICU and hospital mortality.
Data also analyzed after controlling for confounding by matching for propensity score
DiGiovine et al. AJCC 2009 (in press)

19. Feeding the Hypotensive Patient?
The beneficial effect of early feeding is more evident in the sickest patients, i.e, those on multiple vasopressor agents.
DiGiovine et al. AJCC 2009 (in press)

20. Feeding enterally the hemodynamically unstable critically ill patient: Experience with a multicenter trial (The REDOXS study)
20 ICUs enrolling patients on vasopressors into REDOXS study
159 patients [28 day mortality- 31%]
85% started on EN (2% PN, 13% none)
Time from ICU admission to start of EN: 20.2 hrs (0-204 hrs)
Duration of EN 9.2 days ( days)
Overall, rec’d 68% of goal calories and protein
55% had high gastric residual volumes
Of those, 78% got motility agents
Daily adequacy pre and post motility agents improved (35% vs. 56%, p=0.009)
Heyland ESICM Brussels 2009

21. Underlying Pathophysiology (2)
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

22. 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
60% medical; 40% surgical
Average APACHE II 22; BMI 27

23. Hypothesis
There is a relationship between amount of energy and protein received and clinical outcomes (mortality and # of days on ventilator)
The relationship is influenced by nutritional risk
BMI is used to define chronic nutritional risk

24. What Study Patients Actually Rec’d
Average Calories in all groups:
1034 kcals and 47 gm of protein
Result:
Average caloric deficit in Lean Pts:
7500kcal/10days
Average caloric deficit in Severely Obese:
12000kcal/10days

25. Relationship Between Increased Calories and 60 day Mortality
BMI Group
Odds Ratio
95% Confidence Limits
P-value
Overall
0.76
0.61
0.95
0.014
<20
0.52
0.29
0.033
20-<25
0.62
0.44
0.88
0.007
25-<30
1.05
0.75
1.49
0.768
30-<35
1.04
0.64
1.68
0.889
35-<40
0.36
0.16
0.80
0.012
>=40
0.63
0.32
1.24
0.180
Legend: Odds of 60-day Mortality per 1000 kcals received per day adjusting for nutrition days, BMI, age, admission category, admission diagnosis and APACHE II score.

27. Relationship Between Increased Energy and Ventilator-Free days
BMI Group
Adjusted
Estimate
95% CI
P-value
LCL
UCL
Overall
3.5
1.2
5.9
0.003
<20
2.8
-2.9
8.5
0.337
20-<25
4.7
1.5
7.8
0.004
25-<30
0.1
-3.0
3.2
0.958
30-<35
-1.5
-5.8
2.9
0.508
35-<40
8.7
2.0
15.3
0.011
>=40
6.4
-0.1
12.8
0.053
Legend: # of VFD per 1000 kcals received per day adjusting for nutrition days, BMI, age, admission category, admission diagnosis and APACHE II score.

28. Effect of increasing amounts of EN on infectious complications
Multicenter observational database
597 patients prospectively followed for development of ICU-acquired infection
2 independent adjudicators
Examined the relationship between nutritional adequacy and infection
Heyland (in submission)

29. for increase of 1000 cal/day, OR of ICU-acquired infection
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 ICU-acquired infection
Heyland (in submission)

30. for increase of 30 gram/day, OR of ICU-acquired infection
Effect of Increasing Amounts of Protein from EN on Infectious Complications
Multicenter observational study of 207 patients >72 hrs in ICU followed prospectively for development of infection
for increase of 30 gram/day, OR of ICU-acquired infection
Heyland (in submission)

31. RCT Level of Evidence that More EN= Improved Outcomes
RCTs of aggressive feeding protocols
Results in better protein-energy intake
Associated with reduced complications and improved survival
Taylor et al Crit Care Med 1999; Martin CMAJ 2004
Meta-analysis of Early vs Delayed EN
Reduced infections: RR 0.76 (.59,0.98),p=0.04
Reduced Mortality: RR 0.68 (0.46, 1.01) p=0.06

32. More is Better! Our Field of Dream If you feed them (better!)
They will leave (sooner!)

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

34. Aggressive Gastric Feeding may be a BAD THING!
Observational study of 153 medical/surgical ICU patients receiving EN in stomach
Intolerance= residual volume>500ml, vomiting, or residual volume x2.
Patients followed for development of VAP (diagnosed invasively)
Mentec CCM 2001;29:1955

35. Aggressive Gastric Feeding may be a BAD THING!
Incidence of Intolerance= 46%
Statistically associated with worse clinical outcomes!
Risk factors for Intolerance
Sedation
Catecholamines
High residuals before and during EN

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

37. Updated 2009, see www.criticalcarenutrition.com
Rupinder to update
“Use of a feeding protocol that incorporates motility agents and small bowel feeding tubes should be considered”
Updated 2009, see

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

40. Sites recorded the presence or absence of a feeding protocol
The Impact of Enteral Feeding Protocols on Enteral Nutrition Delivery: Results of a multicenter observational study
International, prospective, observational, cohort studies conducted in 2007 and 2008 from 269 Intensive Care Units (ICUs) in 28 countries
Included 5497 mechanically ventilated adult patients > 3 days in ICU
Sites recorded the presence or absence of a feeding protocol
Sites provided nutritional data on enrolled patients from ICU admission to ICU discharge for a max of 12 days.
Heyland JPEN ( in press)

41. 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 ( in press)

42. 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 ( in press)

43. Initial Efficacy and Tolerability of Early Enteral Nutrition with Immediate or Gradual Introduction in Intubated Patients
This study randomized 100 mechanically ventilated patients (not in shock) to Immediate goal rate vs gradual ramp up (our usual standard).
The immediate goal group rec’d more calories with no increase in complications
Desachy ICM 2008;34:1054

44. 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!
Not all critically ill patients are the same; we have 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.
Tolerate higher GRV threshold (250 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

45. The Efficacy of Enhanced Protein-Energy Provision via the Enteral Route in Critically Ill Patients: The PEP uP Protocol!
Heyland (in submission)

46. The Efficacy of Enhanced Protein-Energy Provision via the Enteral Route in Critically Ill Patients: The PEP uP Protocol!
Heyland (in submission)

47. Conclusions
Early EN associated with improvement in clinically important outcomes
Audits suggest lots of opportunities for improvement
Second generation feeding protocols may address unmet need to help with nutritional adequacy

48. Questions?