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

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 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: hours)

Loss of Gut Epithelial Integrity INTESTINAL EPITHELIUM SIRS Bacteria DISTAL ORGAN INJURY (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 function Increased secretion of mucus, bile, IgA Increased secretion of mucus, bile, IgA Maintenance of peristalsis and blood flow Maintenance of peristalsis and blood flow Favorable effects on GALT/MALT 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 4049 patients requiring mech vent > 2 days Categorized as “Early EN” if rec’d feeds within 48 hours of admission (n=2537, 63%) Artinian Chest 2006:129;960 P=0.007 P= P=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

Early vs. Delayed EN: Effect on Mortality Updated

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 vasopressors Feed 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:

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:

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

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 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 GroupOdds Ratio 95% Confidence Limits P-value Overall < < < < < >= 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% CIP-value LCLUCL Overall < < < < < >= 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 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

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 x2.  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 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

Updated 2009, see “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 StomachSmall BowelColon Cerulein0/(-)+++ Cisapride++(+) Domperidone+(+)0 Erythromycin+++0 Metoclopramide+++0 Neostigmine0(+)+ 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 Canadian CPGs

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 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 D D D4150 Total P=0.004P=0.09 Heyland CCM 2001;29:

FRICTIONAL ENTERAL FEEDING TUBE (TIGER TUBE TM ) 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