1. REducing Deaths due to OXidative Stress: The REDOXS© Study: Can we provide adequate enteral nutrition to patients with Shock?
Rupinder Dhaliwal
John Drover
John Muscedere
Xuran Jiang
Daren Heyland
Critical Care Nutrition, Kingston ON, Canada 1

2. Background Delivery of adequate EN in critically ill patients
with shock is problematic due to interruptions:
high illness acuity
other treatment priorities
hesitancy to feed unstable patients requiring vasopressors
Paucity of data from RCTs on feeding practices
in this acutely ill population from multicentre trials
Cresci NCP, McClave NCP 2003, Berger Am J Clin Nutr 2005 1

3. Purpose
To report on the delivery of enteral nutrition in patients with shock in The REDOXS© study, a multicentre, randomized controlled trial of pharmaconutrition
*high dose glutamine and antioxidants are dissociated from enteral/parenteral nutrition. Given via enteral and parenteral route 1

4. R R R REDOXS© Study Design antioxidants glutamine 1200 ICU patients
Factorial 2x2 design
glutamine R
1200 ICU patients R
Evidence of
placebo
organ failure
antioxidants
placebo R
placebo

5. Study Groups Enteral Supplement Parenteral Supplement GLN +AOX
Glutamine + AOX
Dipeptiven + Selenium
AOX
AOX only
Placebo + Selenium
GLN
Glutamine only
Dipeptiven + Placebo
Placebo
Placebo + Placebo
Duration of intervention: 28 days (min 5 days) 1

6. Enteral Nutrition (EN)
ENTERAL REDOXS formula
PARENTERAL REDOXS formula
EN and ENTERAL REDOXS being “Y”-ed in

7. Dosing Study High dose appears safe High dose associated with
Parenterally
Enterally
Glutamine/day
0.35 gms/kg
30 gms
Antioxidants
per day
500 mcg Selenium
Vit C 1500 mg
Vit E 500 mg
B carotene 10 mg
Zinc 20 mg
Se 300 ug
High dose appears safe
High dose associated with
no worsening of SOFA Scores
greater resolution of oxidative stress
greater preservation of glutathione
Improved mitochondrial function
Heyland JPEN Mar 2007

8. Inclusion Criteria mechanically ventilated adults, in ICU
two or more of following organ failures related to acute illness
P/F ratio ≤ 300
Renal dysfunction
Platelet count < 50 mm3
Hypoperfusion requiring vasopressors for  2 hours
Any dose norepinephrine, epinephrine, vasopressin OR
 5 ug/kg/minute of dopamine OR
> 50 ug/min phenylephrine OR
Randomized to one of 4 groups within 24 hrs admission to ICU
“Shock” defined as:
Hypoperfusion requiring vasopressors for  2 hours
Any dose norepinephrine, epinephrine, vasopressin or
 5 ug/kg/minute of dopamine or
> 50 ug/min phenylephrine 1

9. Exclusion Criteria 1

10. Methods
Daily data collected from ICU admission to a minimum of 5 days and a maximum of 30 days
timing of EN and volumes received
incidence of high GRVs, GRV in mls
use and timing of motility and small bowel feeding 1

11. Methods
Sites were instructed to monitor the volumes of study supplements received daily and to make up for interruptions by infusing at double the hourly infusion rate
Enteral and parenteral nutrition was initiated and maintained independently as per the Canadian Clinical Practice Guidelines
Dietitians and Research Coordinators were asked to monitor delivery of enteral nutrition daily
The use of motility agents and small bowel feeding was also encouraged for patients with gastrointestinal intolerance (feeding protocol) 1

13. Results: Patients
May 2007 to July 2008 across 20 ICUs (Canada, Europe)
205 patients with shock were randomized
N = 205
Cohort: 159 patients locked data 1

14. Results: Route of Nutrition
Reasons for None: Extubation (11), Death (5), Withdrawal of life sustaining therapies (1), GI contraindication (5), Aspiration (n=1) 1

15. Results: Delivery of EN
Start of Enteral Nutrition from ICU admit
20.2 hours (median, range )
Duration of EN
9.2 days (median 6.8, range days)
Mean Volume of EN received
67% (range %) of prescribed (mean 1800 Kcals)
Patients received < 80% prescribed mean volumes EN
97/135 (73%)
Patients received <80% prescribed EN ≥ 1 day
133/135 (98.5%) 1

16. Results: Incidence of high GRVs
N = 133 (< 80% on at least 1 day)
N = 73/133 (55%)
For 45% patients, reasons are based on reasons for witholding enteral study supplement 1

17. Results: motility agents
Of those that had high GRV
57/73 (78%) got
motility agents
N = 57
% mean prescribed volume
received
24 hr pre motility agents = 35.1%
vs.
24 hr post motility agents = 55.9%
(p=0.009)
N= 57 motility agents
Timing of Motility agents
12/57 (21%) started motility agents
before high GRV
23/57 (40%) on the same day
22/57 (39%) started motility agents
1.6  0.9 days (mean, SD)
after the first GRV> 250 mls 1

18. Results: small bowel feeding
Of those that had high GRV
30/73 (41%) got
Small bowel feeds
N = 30
% mean prescribed volume
received
24 hr pre small bowel = 54.2%
vs.
24 hr post small bowel = 67.3%
(p=0.36)
N= 30 small bowel feeds
Timing of small bowel feeds
6/30 (20%) started before high GRV
4/30 (14%) on the same day
20/30 (67%) started
4.7  3.5 days (mean, SD)
after the first GRV> 250 mls 1

19. Conclusions In critically ill patients with shock, EN can be
provided in the early phases of acute illness to majority of patients
In some, delivery of EN is interrupted/compromised by non physiologic factors
The delivery of EN in this population can be maximized by
better adoption and earlier initiation of motility agents and small bowel feeding.
close monitoring of the delivered volumes of EN 1

20. Acknowledgements J. Drover J. Muscedere
D. K. Heyland
J. Drover
J. Muscedere
A. Day
X. Jiang
D. Cook
G. Pagliarello
M. Albert
for the REDOXS© Steering Committee and the Canadian Critical Care Trials Group
Kingston General Hospital,
St. Joseph’s Hospital, Hamilton,
The Ottawa Hospital,
Hopital du Sacre-Coeur, Montreal, Canada 1