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• 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
kcal
Adequacy
of EN
Prescribed Engergy
2000
1800
1600
1400
1200
1000
800
600
400
200
0
Energy Received From Enteral Feed
1
3
5
7
9
11
13
15
17
19
21
Days
Prolonged ICU stay, discharged weak and
debilitated. Dies on day 43 in hospital from
massive PE
To what extent did
nutrition therapy (or lack
thereof) play a role in
this patient’s demise?
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
Contribution related to
misapplication or non application
of artificial nutrition?
Institute of Medicine 1999
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: 0-100%)
Cahill N Crit Care Med 2010 (in press)
Average time to start of EN was 46.5 hours
(site average range: 8.2-149.1 hours)
Cahill NE CCM 2010 (in press)
Underlying Pathophysiology
of Critical Illness
Loss of Gut Epithelial Integrity
Bacteria
INTESTINAL EPITHELIUM
SIRS
DISTAL ORGAN
INJURY
(Lung, Kidneys)
via thoracic duct
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
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)
Effect of Early Enteral Feeding on the
Outcome of Critically ill Mechanically
Ventilated Medical Patients
• Retrospective analysis of
multiinstitutional database
35
• 4049 patients requiring mech
vent > 2 days
25
• Categorized as “Early EN” if
rec’d feeds within 48 hours of
admission (n=2537, 63%)
15
30
20
Early
Late
10
5
0
VAP
ICU
Mort
Hosp
Mort
P=0.007
P=0.02
P=0.0005
Artinian Chest 2006:129;960
Effect of Early Enteral Feeding on the
Outcome of Critically ill Mechanically
Ventilated Medical Patients
Artinian Chest 2006:129;960
Early vs. Delayed EN:
Effect on Infectious Complications
Updated 2009
www.criticalcarenutrition.com
Early vs. Delayed EN:
Effect on Mortality
Updated 2009
www.criticalcarenutrition.com
What About Feeding the
Hypotensive Patient?
• Resuscitation is the priority
• No sense in feeding someone dying of
progressive circulatory failure
• However, if resuscitated yet remaining on
vasopressors:
Safety and Efficacy of
Enteral Feeding??
Effect of Early Enteral Feeding on
Hemodynamic Variables
• Animal model of sepsis and lung injury
– Splanchnic hemodynamics decline with endotoxemia
– Feeding reverses this decine and improves intestinal perfusion compared to
placebo fed
Purcell Am J Surg 1993;165:188
Kazamias World J Surgery 1998;22:6-11
• Anesthesia/Operative Model of stress
– Surgical insult induces inflammatory mediators and markers of oxidative
stress
– Feeding attenuates oxidative stress and chemokine production
Kotzampassi Mol Nutr Food Res 2009;53:770
9 patients day 1 Post-op following CPB
requiring inotropes and vasopressors
Feed enterally; metabolic response
consistent with substrates being utilized
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
Khalid Am J Crit Care 2010;19:261-268
Feeding the Hypotensive Patient?
The beneficial effect of early feeding is more
evident in the sickest patients:
-those on multiple vasopressor agents
-those on persistent circulatory failure (> 2days).
Khalid Am J Crit Care 2010;19:261-268
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 (0.1-30 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
Adequacy
of EN
kcal
Increased Caloric Debt Associated with Bad Clinical
Outcomes
Prescribed Engergy
2000
1800
1600
1400
1200
1000
800
600
400
200
0
Energy Received From Enteral Feed
Caloric Debt
1
3
5
7
9
11
13
15
17
19
21
Days
 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
• 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
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
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
Relationship Between Increased Calories
and 60 day Mortality
BMI Group
P-value
Odds
95%
Ratio Confidence
Limits
Overall
0.76
0.61
0.95
0.014
<20
0.52
0.29
0.95
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.
Relationship of Caloric Intake, 60 day Mortality and BMI
60
BMI
All Patients
< 20
20-25
25-30
30-35
35-40
>40
Mortality (%)
50
40
30
20
10
0
0
500
1000
1500
Calories Delivered
2000
Relationship Between Increased Energy and
Ventilator-Free days
Adjusted
95% CI
BMI Group
P-value
Estimate
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.
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)
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)
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)
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
www.criticalcarenutrition.com
More is Better!
Our Field of Dream
If you feed them (better!)
They will leave (sooner!)
ICU patients are not all created equal…should
we expect the impact of nutrition therapy to be
the same across all patients?
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 150-500x2.
Patients followed for development of VAP
(diagnosed invasively)
Mentec CCM 2001;29:1955
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
43
24
41
25
23
15
Pneumonia
ICU LOS
(days)
Intolerance
%Mortality
none
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 www.criticalcarenutrition.com
“Use of a feeding protocol that incorporates motility
agents and small bowel feeding tubes should be
considered”
Updated 2009, see www.criticalcarenutrition.com
Initial Efficacy and Tolerability of Early
Enteral Nutrition with Immediate or Gradual
Introduction in Intubated Patients
• RCT
• 100 mechanically
ventilated patients
(not in shock)
• 2 Med/surg ICUs
• All had target 25 kcal/kg
• All had early EN (within
24 hrs)
• Immediate goal rate vs
gradual ramp up
Desachy ICM 2008;34:1054
Initial Efficacy and Tolerability of Early
Enteral Nutrition with Immediate or Gradual
Introduction in Intubated Patients
Desachy ICM 2008;34:1054
Pro-motility agents?

Impaired motility




Dysmotility linked to



Medications
Metabolic, electrolyte abnormalities
Underlying disease
decreased tolerance of EN
gastropulmonary route of infection
Trials of Cisapride, Erythromycin,
Metoclopramide,
Prokinetic drugs and their sites of action
Stomach
Small Bowel
Colon
Cerulein
0/(-)
++
+
Cisapride
+
+
(+)
Domperidone
+
(+)
0
Erythromycin
++
+
0
Metoclopramide
++
+
0
Neostigmine
0
(+)
+
Octreotide
(-)
+
0
Tegaserod
+
(+)
(+)
(0 no effect, – possible negative effect, (+) possible positive effect,
+/++ good and very good prokinetic effect)
Pro-motility Agents
Conclusion:
1) Motility agents have no effect on mortality or infectious
complications in critically ill patients.
2) Motility agents may be associated with an increase in gastric
emptying, a reduction in feeding intolerance and a greater caloric
intake in critically ill patients.
• “Based on 1 level 1 study and 5 level 2 studies, in
critically ill patients who experience feed intolerance
(high gastric residuals, emesis), we recommend the use
of a promotility agent. Given the safety concerns
associated with erythromycin, the recommendation is
made for metoclopramide. There are insufficient data
to make a recommendation about the use of combined
use of metoclopramide and erythromycin.”
2009 Canadian CPGs www.criticalcarenutrition.com
Other Strategies to Maximize the
Benefits and Minimize the Risks of EN
• Head of Bed elevation to 45 (or at least 30 if
the patient doesn’t tolerate 45)
– This will reduce regurgitation, aspiration and
subsequent pneumonia
List of Contraindications
to HOB Elevation
• unstable c-spine
• hemodynamically unstable
• Pelvic fractures with
instability
•Prone position
•Intra-aortic ballon pump
•Procedures
•Unable because of obesity
Small Bowel vs. Gastric Feeding:
A meta-analysis
Effect on Nutritional Endpoints
• 4 studies that document increased delivery of
protein and calories with small bowel
feeding; 2 show no difference
• One study that documents time goal quicker
with small bowel
• Fewer interruptions with high gastric
residuals with small bowel
• 2 studies document delay in initiating feeds
secondary to delay in obtaining small bowel
access
Small Bowel vs. Gastric Feeding:
A meta-analysis (9)
Effect on VAP
www.criticalcarenutrition.com
Does Postpyloric Feeding Reduce
Risk of GER and Aspiration?
Tube
Position
# of
patients
% positive
for GER
Stomach
21
32
% positive
for
Aspiration
5.8
D1
8
27
4.1
D2
3
11
1.8
D4
1
5
0
Total
33
75
11.7
P=0.004
P=0.09
Heyland CCM 2001;29:1495-1501
FRICTIONAL ENTERAL FEEDING TUBE
(TIGER TUBETM)
Flaps to allow
peristalsis to
pull tube
passively
forward
Sucessful jejunal placement >95%
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 realtime, graphic display that
represents the path of the
feeding tube.
Conclusions
• Early EN associated with improvement in
clinically important outcomes
• Audits suggest lots of opportunities for
improvement
• Second generation feeding protocols,
motility agents, and small bowel feeding
may address unmet need to help with
nutritional adequacy