1. The REDOXS© Study REducing Deaths from OXidative Stress
Dietitian and Pharmacy Training
Study Chair
Dr. Daren Heyland, MD, FRCPC
Project Leader
Rupinder Dhaliwal, BASc, RD

2. Administration of Study Supplements
Duration of study supplements
Maximum 28 days
Minimum 5 days: In patients with ICU LOS < 5 days and get discharged to ward

3. Parenteral Supplement
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
SC blinded Pharmacist unblinded

4. Enteral Study Supplement
EN REDOXS © Formula

5. US Product: selenium injection
Parenteral Study Supplements (Dipeptiven and Selenium) +
US Product: selenium injection

6. Study Supplements Pharmacist is unblinded Supplements to start ASAP
SS Manual p 4-10
Pharmacist is unblinded
Supplements to start ASAP
within 24 hrs of admission to ICU
within 2 hrs of randomization
Duration: 28 days or death or ICU discharge
min of 5 days IF transferred to ward, if not until ICU d/c
Continuous infusion X 24 hrs but can be doubled up (12 hrs max)

7. Infusion of Supplements
REDOXS Training
Infusion of Supplements
Parenteral supplements
as soon as patient resuscitated
10 ml/hr DEDICATED central port (eg. one of a triple lumen)
can run peripherally if needed (watch for phlebitis)
Do NOT infuse with medications
May piggyback with IV fluids, albumin, PN (no heparin/insulin)
Enteral supplement
NG tube OK or feeding tube
20 ml/hr, can be given via Y connector
start regardless of whether MDs want to start enteral nutrition
nutrients vs. nutrition
October 2007 7

8. Minimize interruptions, make up volume
SS Manual p 10-16
Minimize interruptions, make up volume
Infuse at double rate for 12 hrs maximum on Day 1
Intolerance to enteral feeding ( refer to feeding protocol)
Other enteral formulas, vitamins, minerals
Renal Dysfunction
Switch to lower protein formula
Restrict fluid
Refer to appendix
If received volumes < Prescribed = Protocol Violation……….notify Methods Centre !!

9. Template of Study Orders Study Supplement Manual Page 11
Imp. Manual: Tools
To optimize delivery of supplements
Study day 1= ICU admission until end of your flowsheet

10. Enteral Nutrition (EN)
ENTERAL REDOXS formula
PARENTERAL REDOXS formula (but will be in a normal saline type bag)
EN and ENTERAL REDOXS being “Y”-ed in

11. Role of the Dietitian

12. Optimizing Enteral Nutrition
Canadian CPGs
Feeding Protocol
Glycemic Protocol
Elevate the Head of the Bed
Motility Agents
Small Bowel Feeding

13. RD manual p 13
SS Manual p 16

14. Baseline Nutrition Dietitian to collect:
RD Manual p 5,6
Imp Manual p 29,30
Dietitian to collect:
Prescribed kcal and protein (baseline)
Type of nutrition support
Start and stop date and times
Refer to Dietitian Manual

15. Collection in real time essential !
Daily Nutrition Data
RD Manual p 7,11
Imp Manual p 37-39
Dietitian to collect
(for max 30 days):
Energy protein intake
Add propofol
Interruptions
Type of enteral formula
+ location of feeding tube (daily data)
Collection in real time essential !

16. Dietitian Checklist
Imp Manual: Tools
RD Manual: 19,20
Checklist is a tool…refer to webpage for data to be entered in eCRF
July 31st version online

17. Propofol ≥ 6 hrs Include in daily calories received as follows:
If on EN only, add to EN calories
If on PN only, add to PN calories
If on EN + PN, add to PN calories
Do not add if not receiving EN or PN

18. Study Supplement Compliance
Study Coordinator
Volumes must be monitored DAILY in real time by Study Coordinator.
If volumes < prescribed, need to report to CERU or provide explanation and take action to prevent recurrence.
Protocol Violation
Protocol Deviation
Study Coordinator to ensure compliance
Dietitian to help
Imp Manual p 34

19. Maximize EN nutrient and nutrition delivery
use of feeding protocols
small bowel feeding
Minimize interruptions, make up volume
Other enteral formulas with supplemental glutamine, vitamins, minerals not allowed
No supplements with high amounts of Zinc (5 mg max)
Renal Dysfunction
Switch to lower protein formula
Restrict fluid
Refer to appendix
If received volumes < Prescribed = Protocol Violation……….Study Coordinator to notify Methods Centre !!
Pilot study: Interruptions due to high urea only in
2% patient days (9% patients)
RD Manual p 12-17

20. Case study: High GRVs
Mr. Smith who is 4 days post laporotomy (findings show bowel is not compromised) has had high gastric residual volumes > 500 mls for the last 48 hours. His enteral feeds have been interrupted several times and are now on hold. The MD in charge has also stopped the enteral study supplements to give the gut a rest and he now wishes to start parenteral nutrition.
What to do?

21. FAQs
What if the prescribed calories and protein changes over the 28 days of the study duration?
How do I get a prescribed calorie/protein level if the dietitian has not assessed this?

22. Daily Monitoring Dietitian Study Coordinator
Enteral Nutrition Adequacy
Study Coordinator
Enteral Study Supplement Volumes
< 80 % prescribed: Protocol Violation Form
>= 80 and < 100 %: Provide explanation
Parenteral Study Supplement Volumes
< 90% prescribed: Protocol Violation Form
>=90 and < 100%: provide explanation

23. SS Manual p 16

24. Pharmacy

25. Password can be shared by all pharmacy staff
Pharmacy Web Access
Pharmacy Manual p 4
To be completed by 2 of the most responsible pharmacists or technicians
Password can be shared by all pharmacy staff

26. Pharmacy Log In
Pharmacy Manual p 5

27. Pharmacy Treatment assignment
Pharmacy Manual p 6
Pharmacy Treatment assignment
If error made in allocation,
contact CERU ASAP!
Note: this is not the randomization list that will be used for the study.

28. *US sites: refer to Work Instruction for Selenium
Supply of Supplements
Fresenius Kabi: Dipeptiven, EN REDOXS
Selenium: BIOSYN (EU), Baxter (Canada) or Pharmacy to purchase on own* (US)
Before start: Supplies to be shipped to sites once Ethics approval received
Need updated pharmacy contact and shipping address
*US sites: refer to Work Instruction for Selenium

29. If hypernatremia, can be mixed in with D5W instead of saline!
Dispensing
Pharm Manual p 12
ICU pharmacist  dispensing pharmacist
Sign signature log
Enteral supplements
no mixing needed
Parenteral supplements
Mixing required: Dipeptiven (Glutamine) + Selenium (AOX) + Normal Saline
If hypernatremia, can be mixed in with D5W instead of saline!

30. Enteral Products Obtain appropriate enteral product
Pharm Manual p 12, 29
Enteral Products
Obtain appropriate enteral product
Infuse at 20 ml/hour for all patients
Generate pharmacy label (need 2 labels)

31. Remove company label and staple to Form B
Pharm Manual p 12, 13
Remove company label and staple to Form B
Attach pharmacy label to bottle
(maintain blinding)

32. Enteral Dispensing Log
Pharm Manual p 14

33. Mixing of Parenteral Supplements
Pharm Manual p 15
Dipeptiven (Glutamine) + Selenium (AOX) + Normal Saline
Final volume = 250 mls, hourly rate = 10 ml/hr
1. Determine dose of Glutamine according to Normal weight
Normal Weight (kg) = height (cms) –100 cms
Dose of Dipeptiven = Normal wt. X 2.5 mls
(This equals to Normal wt. X 0.35 gms of Glutamine or Normal weight X 0.5 gms of L-alanyl-L-Glutamine)
2. Dose of Selenium = 12.5 ml (500 micrograms) = 1.25 vial EU sites: dose is 10 mls (500 micrograms) = 1 vial
3. Combine the Glutamine + Selenium and remove this volume from 250 ml of normal saline
4. Replace normal saline with this mixture. Final volume =250 mls

34. Dosages according to height (PN)
Pharm Manual p 18, 32
Dosages according to height (PN)
If > 6 feet 5 inches (>196 cms)
Final volume of parenteral solution will be between mls
Can still use 250 mls bag of saline
If no normal saline to be used, use an empty sterile bag and add supplements to the bag (instead of removing all normal saline)
Final rate of solution will exceed 10 ml/hr
Central line needed but peripheral may be used (72 hrs max)
Refer to
Revised
Worksheets
on web
Nov 2007
Pilot Study: no one > 190 cms (6’3”)

35. Parenteral Worksheet: GLN
Use
Revised
Worksheets
(for >196 cms)
on web
November 2007
Pharm Manual p 15, 31-41

36. Parenteral Worksheet: AOX
Use
Revised
Worksheets
(for >196 cms)
on web
November 2007

37. Parenteral Worksheet: AOX+GLN
Use
Revised
Worksheets
(for >196 cms)
on web
November 2007

38. Parenteral Worksheet: Placebo
Use
Revised
Worksheets
(for >196 cms)
on web
November 2007

39. Pharm Manual p 16, 42
Parenteral Label

40. Parenteral Study Supplement Log
Pharm Manual p 17
Parenteral Study Supplement Log

41. Expiration of Supplements
Pharm Manual p 10
Selenium once opened: 24 hrs if refrigerated
Dipeptiven once opened: mix immediately
Once mixed, parenteral solutions have an expiration of 96 hrs room temperature
Can make in batches to last 3 days!!
Enteral Supplements once opened: 24 hrs

42. Nutrient Accountability Logs
Pharm Manual p 19-25
Nutrient Accountability Logs
One log for each product except for normal saline

43. Monthly Site Inventory Log
Pharm Manual p 8,9
Monthly Site Inventory Log
Fax in to CERU monthly
US sites: Pharmacy stock vs. Baxter

44. Fax similar log to CERU monthly
Temperature Log
Pharm Manual p 10, 11
Fax similar log to CERU monthly

45. Delegation of Authority Log
Main pharmacist to sign this Delegation of Authority Log

46. Pharmacy Delegation Log
All pharmacy staff involved to sign

47. Case Study: Dosing error
REDOXS Pharmacist away for weekend and returns on Monday and after reviewing logs realizes that Mr. J.S accidentally received the wrong supplements. Should have received GLN but received GLN+AOX instead for the last 18 hours.
What to do?
Stop the infusion immediately
Inform research coordinator ASAP, maintain blinding
Notify CERU immediately, Note to File
Steps to prevent recurrence

48. FAQs Pharmacy Keep vials of returned/destroyed products?
One password for all Pharmacists/technicians?
Pharmacist or technician that dispenses the supplements?
P. Manual page 16

49. REDOXS© Circular and Bulletin
Questions??
Imp Manual Tools
REDOXS© Circular and Bulletin

50. Resources available www.criticalcarenutrition.com >REDOXS