• 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
Prolonged ICU stay, discharged weak and debilitated. Dies on day 43 in hospital from
massive PE
Adequacy of EN
Adequacy of EN
0200
400600
8001000
12001400
16001800
2000
1 3 5 7 9 11 13 15 17 19 21
Days
kcal
Prescribed Engergy
Energy Received From Enteral Feed
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
Institute of Medicine 1999
Contribution related to misapplication or non application
of artificial nutrition?
Cahill N Crit Care Med 2010 (in press)
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 NE CCM 2010 (in press)
Average time to start of EN was 46.5 hours
(site average range: 8.2-149.1 hours)
Loss of Gut Epithelial Integrity
INTESTINAL EPITHELIUM
SIRS
Bacteria
DISTAL ORGAN DISTAL ORGAN INJURY INJURY (Lung, Kidneys)(Lung, Kidneys)
via thoracic duct
Underlying Pathophysiology of Critical Illness
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 functionMaintenance of gut barrier function
• Increased secretion of mucus, bile, IgAIncreased secretion of mucus, bile, IgA• Maintenance of peristalsis and blood flowMaintenance of peristalsis and blood flow
•Favorable effects on GALT/MALTFavorable 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
• 4049 patients requiring mech vent > 2 days
• Categorized as “Early EN” if rec’d feeds within 48 hours of admission (n=2537, 63%)
0
5
10
15
20
25
30
35
VAP ICUMort
HospMort
EarlyLate
Artinian Chest 2006:129;960
P=0.007 P=0.0005P=0.02
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 2009www.criticalcarenutrition.com
Early vs. Delayed EN: Effect on Mortality
Updated 2009www.criticalcarenutrition.com
• Resuscitation is the priority
• No sense in feeding someone dying of progressive circulatory failure
• However, if resuscitated yet remaining on vasopressors:
What About Feeding the Hypotensive Patient?
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
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
Purcell Am J Surg 1993;165:188
9 patients day 1 Post-op following CPB requiring inotropes and vasopressorsFeed enterally; metabolic response
consistent with substrates being utilized
• 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
Feeding the Hypotensive Patient?
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
Increased Caloric Debt Associated with Bad Clinical Outcomes
Caloric debt associated with: Longer ICU stay
Days on mechanical ventilation Complications
Mortality
Adequacy of EN
Rubinson CCM 2004; Villet Clin Nutr 2005; Dvir Clin Nutr 2006; Petros Clin Nutr 2006
0200
400600
8001000
12001400
16001800
2000
1 3 5 7 9 11 13 15 17 19 21
Days
kcal
Prescribed Engergy
Energy Received From Enteral Feed
Caloric Debt
• 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 Odds Ratio
95% Confidence
Limits
P-value
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.
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
Relationship Between Increased Energy and Ventilator-Free days
Legend: # of VFD per 1000 kcals received per day adjusting for nutrition days, BMI, age, admission category, admission diagnosis and APACHE II score.
• Multicenter observational database
• 597 patients prospectively followed for development of ICU-acquired infection
• 2 independent adjudicators
• Examined the relationship between nutritional adequacy and infection
Effect of increasing amounts of EN on infectious complications
Heyland (in submission)
Effect of Increasing Amounts of Calories from EN on Infectious
Complications
Heyland (in submission)
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
Effect of Increasing Amounts of Protein from EN on Infectious Complications
Heyland (in submission)
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
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
survivalTaylor 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
Incidence of Intolerance= 46%
Statistically associated with worse clinical outcomes!
Risk factors for Intolerance Sedation Catecholamines High residuals before and
during EN
43
23
41
24
15
25
Pneumonia ICU LOS(days)
%Mortality
Intolerance none
Aggressive Gastric Feeding may be a BAD
THING!
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
Updated 2009, see www.criticalcarenutrition.com
“Use of a feeding protocol that incorporates motility agents and small bowel feeding tubes should be considered”
Initial Efficacy and Tolerability of Early Enteral Nutrition with Immediate or
Gradual Introduction in Intubated Patients
Desachy ICM 2008;34:1054
• 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
Initial Efficacy and Tolerability of Early Enteral Nutrition with Immediate or
Gradual Introduction in Intubated Patients
Desachy ICM 2008;34:1054
Impaired motility Medications Metabolic, electrolyte abnormalities Underlying disease
Dysmotility linked to decreased tolerance of EN gastropulmonary route of infection
Trials of Cisapride, Erythromycin, Metoclopramide,
Pro-motility agents?
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
• “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.”
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.
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
• 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
Effect on Nutritional Endpoints
Effect on VAP
www.criticalcarenutrition.com
Small Bowel vs. Gastric Feeding: A meta-analysis (9)
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 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 real-time, 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