Neil Mclean March 12, 2009

Case  You are working in the ICU and receive a patient from the OR. He is a 25 year old male who was involved in an MVC. His injuries include a severe closed head injury, a L hemopneumothorax with a chest tube in place, a splenic rupture (splenectomy performed) a grade 1 liver laceration, a L femur fracture (fixed). He is intubated and has an EVD in place. Upon admission, he is hemodynamically stable and you have done all the other right things.  You are now at the section in the pre-printed orders about options for feeding, You can choose between Parenteral Nutrition or Enteral Nutrition

Question #1 Does enteral nutrition compared to parenteral nutrition result in better results in critically ill adult patients? (MARIOS)

An ongoing saga… “…parenteral nutrition was an independent predictor of death (odds ratio of 2.09). The adverse sequelae associated with parenteral nutrition result from 1) not directly feeding the bowel; 2) the metabolic, immunologic, endocrine, and infective complications associated with parenteral nutrition; and 3) the fact that parenteral nutrition is infused into the patient’s systemic venous system, bypassing the liver.” Critical Care Medicine, 36(6) pp

This is all very confusing… Let’s turn to meta-analyses of RCTs for more clarity on the matter…

Thomson A. The enteral versus parenteral nutrition debate revisited. JPEN J. Parenter Enteral Nutr.2008; 32:

Is TPN really protective? Simpson F, Doig G. Parenteral vs enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle. Intensive Care Med. 2005;31(1):12-23

Is TPN really protective? Simpson F, Doig G. Parenteral vs enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle. Intensive Care Med. 2005;31(1):12-23

Thomson A. The enteral versus parenteral nutrition debate revisited. JPEN J. Parenter Enteral Nutr.2008; 32:

MORTALITY

MORTALITY PN calories > EN calories

MORTALITY PN calories = EN calories

MORTALITY PN blood sugars > EN blood sugars

INFECTIOUS COMPLICATIONS ARR = 0.17; NNT = 5.7

INFECTIONS PN calories > EN calories

INFECTIONS PN calories = EN calories

INFECTIONS PN blood sugars > EN blood sugars

GUIDELINE CONCLUSIONS 1. The use of EN compared to PN is not associated with a reduction in mortality in critically ill patients. 1. The use of EN compared to PN is associated with a significant reduction in the number of infectious complications in the critically ill. 1. No difference found in ventilator days or LOS between groups receiving EN or PN. 1. Insufficient data to comment on other complications; hyperglycemia or higher calories not found to result in higher mortality of infections. 1. EN is associated with a cost savings when compared to PN.

WHAT DOES THIS TELL ME?  Despite having clinical practice guidelines, route of nutrition is a topic that remains controversial.  As far as I can tell, the take home message should be: 1. Try to use EN if you can as it will decrease infectious complications, is cheaper, and will instantaneously give you another lumen. 1. Supplementing inadequate EN with PN has not been shown to be beneficial. 1. If you can’t use EN, PN is fine, though it may increase your rate of infections but not your LOS or mortality (this may only occur in patients that are overfed with PN however).

 You decide to feed this patient enterally via an NG tube. You ask your resident about starting to feed the patient and he says, “you know he has had a really tough day, why don’t we wait until the morning to start his feeds”

Why feed early?  Early EN improves wounds healing and host immune function  Decreases hypermetabolic response to tissue injury  Preserves intestinal mucosal integrity  Two meta-analysis recently published evalu Crit Care Med 2001;29(12):

 15 studies  All surgical patients  Early defined as < 36Hrs post admission or surgery Crit Care Med 2001;29(12):

Mean Reduction in length of stay 2.2 days (CI )

Mortality in early 8 % vs 11.5% in delayed EN. Not statistically significant: RR 0.74 (0, ) Crit Care Med 2001;29(12):

8 “level 2” RCTs Defined early as within feeds started within 24-48hrs of admission Only mechanically ventilated patients

Heyland et al, JPEN, 2003; 27: Trend towards decrease mortality

Heyland et al, JPEN, 2003; 27: Trend toward decrease infectious complications Final Recommendation: Recommend early EN within 24-48H after admission to ICU

Conclusion  Early EN is associated with a trend towards a reduction in mortality in critically ill patients.  Early EN is associated with a significant reduction in infectious complications  Early EN has no effect on ICU or hospital length of stay  Early EN improves nutritional intake. CriticalcareNutrition.com

Early aggressive vs early lower EN? CMAJ, 2004; 170 (2):

Intervention groups received more calories per day: 1264 Kcal vs 998 Kcal Achieve 80% of goal feeds: 5.1 vs 4.8 days! Significant shorter hospital stay Trend toward decrease mortality CMAJ, 2004; 170 (2):

Conclusions: May be associated with a reduction in mortality in the critically ill patient May be associated with a reduction in hospital lengths of stay in the critically ill patient Is associated with a trend towards a reduction in the # infections and complications in head injured patients. Results in a significantly higher calorie intake/lower calorie deficit in head injured patients and other critically ill patients.

 So the resident agrees to start feeding and now asks you how much do I order?  Question #3 Discuss the tools for estimating enteral feeding requirements in the critically ill adult patient. Please include a discussion of indirect calorimetry (TODD)

 You initiate enteral feeding. A few hours later the nurse calls you to tell you that the patient gastric residuals are high.  Question #4 Does the use of a promotility agent impact patient outcome? ( please discuss some of the options for promotility agents) (SCOTT)

 40-50% of critically ill patients experience some degree of slow gastric emptying Increases risk of reflux and aspiration, as well as suboptimal nutrition.  Options are prokinetics (maxeran, erythromycin, naloxone, ?methylnaltrexone), postpyloric feeding, or TPN.  Regarding prokinetics little (if any) evidence exists regarding impact on “hard” outcomes.

 Metoclopramide (maxeran), a dopamine antagonist has been shown to: Improve gastric emptying in critically ill patients after a single dose. Effect on the longer term success of feeding unknown.

 Erythromycin (3mg/kg) has been shown to: Increase gastric emptying. Improve feeding success in previously feed intolerant patients.

Erythromycin vs. metoclopromide vs. both Single double blind RCT (Nguyen, 2007) showed erythromycin 200 mg bid was more effective in reducing gastric residuals than maxeran 10 mg IV bid, but both treatments had rapid tachyphylaxis. Combination rescue therapy was highly effective and had less tachyphylaxis. A separate study confirmed that combination therapy was more effective than erythromycin alone in reducing gastric residuals. Combination therapy has also been found to result in a significant higher calorie intake, lower gastric residual volumes and lower need for post pyloric feeds. Concerns around routine erythromycin use include bacterial resistance, the potential for cardiac toxicity and tachyphylaxis.

Other outcomes  Multiple studies show benefit of promotility agents on overall nutritional intake.  In five studies of either maxeran or erythromycin used alone, no mortality benefit has been demonstrated.  In three studies looking at pneumonia or infection rates, only one (using naloxone), showed a significant reduction in pneumonia. The other two (using maxeran) showed no difference in pneumonia or infection rates.

Other outcomes - cont’d.  LOS, ventilator days - no differences have been shown in three studies that looked at these outcomes.  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.

Recommendation  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.  Other steps to reduce feeding intolerance and aspiration risk include head of bed elevation, control of pain and other contributing factors like hypotension and sepsis, avoidance of opiates.

 Question #5 Are there other techniques to ensure adequate nutrition? Please discuss the utility of small bowel feeding, use of feeding protocols, body position. (NAISAN)

Question #5 Are there other techniques to ensure adequate nutrition?  If serious concern about GI tract not working then TPN  Already heard not the best option  Other options include a feeding protocol with early use of duodenal tube, and prokinetics

Duodenal tube  Based on 11 level 2 studies, small bowel feeding compared to gastric feeding may be associated with a reduction in pneumonia in critically ill patients.  Mortality: Based on the 9 studies that reported on mortality, no significant differences between the groups were found (RR 0.93, , p = 0.6)

Duodenal tube  infections: Based on the 9 studies that reported on infections, the meta-analysis showed that small bowel feeding was associated with a significant reduction in infections (RR 0.77, , p = 0.05)

Duodenal feeding  Based on the 5 studies that reported the LOS, a trend towards a reduction in ICU LOS with gastric feeding was seen. The presence of significant statistical heterogeneity weakens this estimate

Head Injuries  The group that had a more aggressive feeding regimen and small bowel feeding (Taylor) had fewer major complications and a better neurological outcome at 3 months than the group receiving gastric feeds Taylor SJ et al. Prospective, randomized, controlled trial to determine the effect of early enhanced enteral nutrition on clinical outcome in mechanically ventilated patients suffering head injury. Crit Care Med 1999;27:

Duodenal feeding  Conclusions:  1) Small bowel feeding, compared to gastric feeding maybe associated with a reduction in pneumonia in critically ill patients.  2) No difference in mortality or ventilator days in critically ill patients receiving small bowel vs.gastric feedings.  3) Small bowel feeding improves calorie and protein intake and is associated with less time taken to reach target rate of enteral nutrition when compared to gastric feeding.

Duodenal feeds  In units where obtaining access is difficult, small bowel feedings should be considered for patients at high risk for intolerance (on inotropes, continuous infusion of sedatives, or paralytic agents, or patients with high nasogastric drainage) or at high risk for regurgitation and aspiration (nursed in supine position)

Feeding Protocols  There were 3 trials that demonstrated an improvement in nutritional outcomes (i.e. residual volumes, time to reach goal rate of EN, etc) with the use of a feeding protocol

Feeding Protocols  There was 1 level 2 study that compared outcomes of a protocol with a higher gastric residual volume threshold (250 ml) + mandatory prokinetics to a feeding protocol with a lower gastric residual volume threshold (150 mls) (Pinilla 2001)  two cluster RCTs evaluated the effect of an enhanced feeding protocol as one of several interventions geared towards optimizing nutrition (Martin 2004, Doig 2008)

Feeding Protocols  Mortality: Only one study reported on mortality (Martin 2004) and there was a trend towards a reduction in hospital mortality (p=0.058)  Infections: The incidence did not differ between groups in the study that reported on this outcome (Pinilla 2001)

 LOS and Ventilator days: In both cluster randomized controlled trials, no differences in ICU length of stay was observed,  however, the hospital length of stay was significantly lower in the ICUs that received the evidence based algorithms in one trial (p=0.003, Martin 2004)

Feeding Protocols  in the study by Pinilla et al, there was a lower number of elevated gastric residuals in the group that received the protocol with higher residual volume threshold + prokinetics (p<0.005)  Also a trend towards less time taken to reach goal rate of feeding(p<0.09)

Feeding Protocol  The # days 100% goal calories were met was higher in the ICUs that were randomized to the feeding protocol group in the Doig study (p=0.03)  The time from ICU admission to start of feeds was lower in the ICUs that were randomized to the algorithm group/practice change group in both cluster trials (Martin 2004 p=0.17, Doig 2008 p<0.001)

Feeding Protocols  Conclusions:  1) Feeding protocols/algorithms with prokinetics, post-pyloric tubes may be associated with a trend towards a reduction in hospital mortality and a significant reduction in hospital length of stay.  2) Feeding protocols with prokinetics and a higher gastric residual threshold (250 mls) are associated with a trend towards a reduction in gastric residual aspirations and less time taken to reach goal feeding rate in the critically ill.

Patient Positioning  Summary of evidence: There was 1 level 1 study and 1 level 2 study that compared the frequency of pneumonia in critically ill patients assigned to semi- recumbent or supine position.  In one study (Nieuwenhoven 2006) the target of the intervention (45 degrees head of the bed elevation) was never achieved

Patient Positioning  Mortality: There was no significant difference between the groups in either study.  Infections: There was a significant reduction in the incidence of pneumonia in patients in the semi recumbent vs. supine position (p = 0.018, RR =0.22, 95% CI 0.05,0.9) in one study (Drakulovic 1999) but no effect on pneumonia in the other study that did not achieve the target intervention(Nieuwenhoven 2006)

Patient Positioning  LOS, Ventilator days: There were no statistically significant differences between the groups in either study.

Patient Positioning  Conclusions:  1) Semirecument position may be associated with a significant reduction in pneumonia in critically ill patients.  2) Semirecument position has no effect on mortality, ICU length of stay or duration of mechanical ventilation.

 The residuals improve and the next day on rounds the dietician students makes a comment that she read about the use of probiotics in the critically ill patient and was wondering if we should use them in this case.  Question #6 Does the addition of prebiotics/probiotics/symbiotics result in any improvement in outcome in critically ill adult patients? (YOAN)

What are prebiotics/probiotics/symbiotics?  ‘Live microorganisms which when administered in adequate amounts confer a health benefit on the host’  Endogenous bacteria in the gut  Eg. Lactobacillus, Bifidobacterium

Why give probiotics?  Improve intestinal mucosal barrier  Improve immune function  Decrease load of gram – bacteria  ?decrease diarrhea and translocation

 3 groups Placebo Viable probiotics Non viable probiotics  Looked at immune response via IgA IgG  Compared MODS

Canadian recommendations  1 level 1 and 10 level 2 trials  Mortality No improvement PROPATRIA – increased mortality

Infections

 LOS One study (Symbiotic 2000) showed decreased LOS others are equivical  Mechanical ventilation Decrease also seen in Symbiotic 2000, but not in others

Recommendations  NO effect or overall mortality  MAY improve ICU mortality  NO affect on infectious complications  MAY reduce diarrhea