latest evidence on nutrition in the icu: will it change existing guidelines? rupinder dhaliwal, rd...
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Latest Evidence on Nutrition in the ICU: Latest Evidence on Nutrition in the ICU: Will it Change Existing Guidelines?Will it Change Existing Guidelines?
Rupinder Dhaliwal, RD
Clinical Evaluation Research Unit
Critical Care Nutrition
Kingston ON, Canada
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Outline of Session
New RCTs in select area of critical care nutrition (adult)
Fish oilsParenteral glutamineAntioxidantsProbiotics
Updated analyses of Canadian Guidelines
Impact on evidentiary basis
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www.criticalcarenutrition.com
JPEN 2003
1980-2003 n > 200 RCTs 34 topics 17 recommendations
2005 update2005 update20072007 updateupdate2009 update 2009 update
Development of Guidelines
Validity
HomogeneitySafety
FeasibilityCost
evidence integration of values+
practiceguidelines
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Inclusion Criteria
Updated to 2012• Randomized controlled trials• Critically ill patients (not elective surgery)• Clinical Outcomes• EMBASE, Medline, Cinhal, reference lists
Topic # RCTs 2009 # new RCTs 2012
Early vs. delayed 14 2
Target dose EN 2 2
Fish Oils/Borage Oils 5 4
Protein/peptides 4 1
Fibre 6 1
Small Bowel vs. Feeding 11 5
Protocols/GRVs 3 2
Probiotics 12 7
Supplemental PN 5 5
PN Type of lipids 5 4
PN Glutamine 17 11
Antioxidants 16 6
PN Selenium 11 5
New RCTs per Topic (n = 66)
New Topic # new RCTs
Trophic vs. Full feeds 2
Hypocaloric EN 1
Fish Oils only 1
PN + EN Glutamine 1
Threshold of GRVs 1
Discarding GRVs 1
Early Supplemental PN vs Late 1
Vitamin D 1
New Topics (n=8) and RCTs
Enteral Fish Oils**Product enhanced with fish oils +borage oils + antioxidants
2009 RecommendationBased on 5 studies, we recommend the use of
enteral formula with fish oils, borage oils, and
antioxidants in patients with ALI/ARDS
New RCTs = 3New RCTs = 3
Rice 2011Grau-Carmona 2011Thiella 2011+ Pontes Arruda 2011+ Stapleton 2011 (fish oil only)
Multicenter, RCT, 14 ICUs in Brazil
N = 200, early stages of sepsis (no organ failures; within 36 hrs from onset of sepsis).
Fish oil/borage oil/antioxidant vs. standard polymeric X 7 days
Outcomes:
• Evolution to more severe forms of sepsis (severe sepsis or septic shock
• 28 day all-cause mortality, organ failure development, hyper/hypoglycemic events, insulin use, hospital stay, ICU stay
Pontes-Arruda Crit Care 2011;15:R144
Variable Study (n=53)
Control (n=53)
P Value
Use of mechanical ventilation, n (%)
Development of sepsis 5.7% 13.3%0.022
Development of septic shock 20.7 % 37.7%
Invasive 10 (18.9%) 18 (34%) .039
Non-invasive 5 (9.4%) 6 (11.3%) NS
Number of days using mechanical ventilation
7 (4-12) 15 (9-21) .0033
Number of ICU days 7 (4-12) 13 (9-18) <.0001
Number of hospital days 9 (6-14) 19 (13-24) <.0001
Outcomes
No difference in survival between the groups
Pontes-Arruda Crit Care 2011;15:R144
PREVENTION VS. TREATMENT< 50 % patients ventilated
Exclude from CPGs
11 Spanish ICUs 89 patients with diagnosis of Sepsis on admission Randomized to:
• Fish Oil/Borage Oil formula OR• Standard polymeric formula
Outcomes: new organ dysfunction
Grau-Carmona Clin Nutr 2011
Timing of FeedingTiming of Feeding
SSUUPPPPLLEEMMEENNTT
““Early Early Full”Full”Fast ramp upFast ramp up
““Early Early Trophic”Trophic”(10 ml/hr)(10 ml/hr)
N-3 + GLA +N-3 + GLA +AntioxidantsAntioxidants(Module delivered (Module delivered as as bolusbolus bid) bid)
ControlControlStandard ENStandard EN(480 cal/ 20 g pro)(480 cal/ 20 g pro)
n = 250 n = 250
n = 250 n = 250
NIH NHLBI
……..Because of different study design, difficult to combine with other studies of continuous administration in moderately well fed patients…..
Cook, Heyland JAMA Oct 2011
OMEGA: 60-Day MortalityOMEGA: 60-Day Mortality
P=0.05P=0.14P=0.14
Rice et al JAMA Oct 2011
bolusnot formula
select patients
include but analyze without
89 patients from 5 centres in US
Mechanically ventilated patients with Acute lung injury (ALI)
Randomized to (separate from EN):• BOLUS fish oils 7.5 mls q 6 hrs, 9.75g EPA & 6.75 gm DHA/day OR• placebo i.e. normal saline X 14 days
EN or PN as per MDs discretion
Stapleton CCM 2011
Clinical Outcomes
Stapleton CCM 2011
Fish Oils ONLYBolus
Separate from EN
X aggregate with RCTs of fish oil,
borage oil
Fish Oils: Effect on mortality (n = 6)
2009: RR 0.67, 95% CI 0.51, 0.97, p = 0.003
No effect , statistical heterogeneity!
INTERSEPT, Stapleton data not included
EN fish oils: with new RCTs
Effect on mortality disappears when bolus study is included• statistical heterogeneity present
Effect on mortality is significant when bolus study excluded
2012 Recommendation
Fish Oils/borage oil:
Downgrade recommendation to “should be considered”
Fish Oils alone: insufficient data
Arginine
2009 Recommendation
Based on 22 studies, we recommend arginine and other
select nutrients not be used for critically ill patients
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New RCTs = 0New RCTs = 0 Elective surgery patients many RCTs
Drover et al Am Coll Surg 2011
significant reduction in infections p <0.0001 significant shorter HLOS p <0.0001
EN Glutamine
2009 Recommendation
Based on 2 level 1 and 7 level 2 studies, enteral glutamine
should be considered in burn and trauma patients. There
are insufficient data to support the routine use of enteral
glutamine in other critically ill patients
No changes in No changes in recommendationrecommendation
New RCTs = 0New RCTs = 0
PN Glutamine2009 Recommendation Based on 17 studies, when parenteral nutrition is prescribed to critically
ill patients, parenteral supplementation with glutamine, where available, is strongly recommended. There are insufficient data to generate recommendations for intravenous glutamine in critically ill patients receiving enteral nutrition
Ozgultekin 2008 Ozgultekin 2008 Eroglu 2009Eroglu 2009Perez Barcena 2010Perez Barcena 2010Grau 2011Grau 2011Andrews 2011Andrews 2011Wernerman 2011Wernerman 2011Cekman 2011Cekman 2011Zeigler 2012 (in press)Zeigler 2012 (in press)+ 3 Chinese RCTs+ 3 Chinese RCTs+ Heyland 2012 REDOXS (EN + PN)+ Heyland 2012 REDOXS (EN + PN)
New RCTs = 11 New RCTs = 11
• 10 centres in Scotland • 502 Patients expected to be in ICU for at least 48h and required PN
meet at least half their requirements (only 50% received PN)• Randomized 2.6 days after admission to ICU• Trial PN isocaloric and isonitrogenous, given for up to 7 days
unless died or stopped PN» Glutamine 20g/d ( too small of a dose?)» Selenium 500μg/d» Both» Neither
• Median duration of study PN was 4-5 days
Andrews BMJ 2011:342
The SIGNET Trial – RESULTSThe SIGNET Trial – RESULTS
Effect of GlutamineEffect of Glutamine
No significant differences
Confirmed infections within 14 daysMortality
No significant differences
Multicenter trial in Spain
127 patients with APACHE II score >12 and requiring PN for 5–9 days
Standard PN vs. Supplemented with 0.5 g/kg/d of Ala-Gln dipeptide
Enrolled patients received only 5-6 days of PN
Grau CCM 2011; 39
413 Patients given nutrition by EN and/or PN route
Within 72 hrs of ICU admission
Supplemented as IV L-Ala-Glutamine, 0.283 g/kg/day administered separate from PN vs. placebo (saline)
Primary endpoint SOFA; infections not recorded
No effect on SOFA
Wernerman Acta Anesthesiology 2011
GLND Ziegler et al (in press)
n =150 surgical ICU patients needing PN after cardiac, vascular, colonic surgery
no differences in mortality
trend towards increase in infections
The REDOXS© Study REducing Deaths due to OXidative Stress
The REDOXS© StudyREducing Deaths from OXidative Stress
Dr. Daren Heyland et al
N = 1223 patients with 2 or more organ failuresRandomized to high GLN EN + PN vs. placebo
within 24 hrs admission to ICUFactorial design: Antioxidants vs. placebo
Glutamine given via PN plus EN
Patients at least 2 Organ failure
X aggregate with other studies
less effect on mortality, now only a trend less effect on infections, still significant
2012 Recommendation:PN Glutamine
Downgrade to recommend or should be considered
CAUTION: do not use high dose PN in patients with acute MOF
PN + EN Glutamine (REDOXS)
Strongly recommend that high dose IV GLN + EN NOT be used in
patients with MOF
PN GLN with new RCTs
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Supplemental Antioxidant Nutrients
2009 Recommendation:Based on 16 studies, the use of supplemental vitamins and trace
elements should be considered
Parenteral Selenium
2009 Recommendation:
There are insufficient data to make a recommendation regarding IV/PN selenium supplementation, alone or in combination with other antioxidants, in critically ill patients
AOX/PN Se new RCTs
El Attar 2009Montoya 2009Andrews 2011Manzanares 2011Valenta 2011
New RCTs = 5
+ REDOXS Study 2012
Manzanares Critical Care 2012
AOX combined: mortality, n =22
2009 0.76 RR [0.64, 0.91]
p = 0.002
2012still significantweaker signal
AOX combined weaker significant effect on reduction on mortality stronger reduction in infections stronger signal for both in sicker patients
PN selenium still trend towards reduction in mortality stronger reduction in infections
2012 Recommendation (TO BE FINALIZED):AOX: no change ?
PN Se: no change ?
Antioxidants/PN Se with new RCTs
Probiotics
2009 Recommendation
There are insufficient data to make a recommendation on the use of Prebiotics/Probiotics/Synbiotics in critically ill patients
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Knight 2009Barraud 2010Morrow 2010Frohmader 2010Ferrie 2011Sharma 2011Tan 2011
New RCTs = 7Petrof et al Critical Care 2012
Probiotics with new RCTs
stronger signal for reduction in infections (2009: no reduction)– higher quality studies do NOT show a reduction in infections
significant reduction in VAP still trend towards reduction in ICU mortality
2012 Recommendation:Upgrade to should be considered
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Summary• Many recent RCTs in area of critical care nutrition • Careful review of the articles is recommended• Recommendations for following will probably not change
Arginine
EN glutamine
• Recommendations for the following will probably be downgradedEN Fish Oils/borage oils
PN Glutamine
PN + EN Glutamine (NEW TOPIC)
• Recommendations for following will probably be upgraded Probiotics
• Recommendations for following are pendingCombined AOX
PN Selenium
Updated recommendations will have an impact on practices in ICU