Antioxidantien - ein Irrweg? REDOXS & OMEGA Studie

Transcription

1 AKE Herbsttagung 2013 St. Wolfgang Antioxidantien - ein Irrweg? REDOXS & OMEGA Studie Friedrich Längle Chirurgische Abteilung

2 REDOX A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients Daren Heyland, M.D., John Muscedere, M.D., Paul E. Wischmeyer, M.D.,Deborah Cook, M.D., Gwynne Jones, M.D., Martin Albert, M.D.,Gunnar Elke, M.D., Mette M. Berger, M.D., Ph.D., and Andrew G. Day, M.Sc., for the Canadian Critical Care Trials Group N Engl J Med 2013, 368:

3 REDOX - Methods Blinded 2 by 2 factorial trial 1223 critically ill adults in 40 ICUs who had > 2 organ failure and receiving mechanical ventilation (APACHE II 25%, 93.5% shock, 36.3% renal insufficience) Groups: Glutamin 0.35 g/kg/day iv and 30 g enteral n=303 Antioxidants (500 µg selenium) iv and 300 µg selenium + 20 mg zink + 10 mg beta carotene mg vitamin E mg vitamin C enteral n=308 Both n=310 Placebo (iv and enteral) n=302 3

4 REDOX - Methods Supplements were started within 24 of admission (iv and enteral) for a maximum of 28 days, discharge or death Primary outcome: 28 day mortality Subgroup of pts in North America: measurement of plasma glutamin and selenium at baseline and day 4 and 7 4

5 REDOX - Results Overall mortality was 29.8% Glutamin vs no glutamin: mortality: 32.4% vs 27.2% OR 1.28 p=0.05 In hospital mortality and mortality 6 mos was higher in glutamin group Antioxidants vs no antioxidants: mortality: 30.8% vs 28.8% OR 1.09 p=0.48 no effect on secondary outcome 5

6 REDOX - Results 6

7 REDOX - Results 7

8 REDOX Laboratory Results In 66 pts baseline median plasma glutamin and selenium levels were within normal limits Glutamin and selenium levels increased significantly on day 4 and 7 However, glutamin and selenium levels remained in normal ranges at all time points 8

9 REDOX - Conclusions Early provision of glutamine or antioxidants did not improve clinical outcomes Glutamin was associated with an increase in mortality among critically ill patients with multiorgan failure 9

10 REDOX - Discussion Characteristics of study population Difference in selenium deficiency in European and North American ICU trials Insufficient dose of selenium and ineffective dosing schedule (Hochdosis Selen geringere Mortalität) Bedeutung des AO Cocktails? 10

11 OMEGA Enteral Omega-3 Fatty Acid, γ-linolenic Acid, and Antioxidant Supplementation in Acute Lung Injury Todd W. Rice, MD, MScArthur P. Wheeler, MD B. Taylor Thompson, MD Bennett P. deboisblanc, MD Jay Steingrub, MD Peter Rock, MD, MBA for the NIH NHLBI Acute Respiratory Distress Syndrome Network of Investigators JAMA. 2011;306(14):

12 OMEGA - Methods Objective To determine if dietary supplementation of omega-3 (n-3) fatty acids, along with γ -linolenic acid and antioxidants to patients with acute lung injury would increase ventilator-free days to study day 28. Design: randomized, doubleblind, placebo-controlled, multicenter trial Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition 12

13 OMEGA - Methods Interventions: Twice-daily enteral supplementation of n-3 fatty acids, γ -linolenic acid, and antioxidants compared with an isocaloric control. (pharmaconurition). Enteral nutrition, directed by a protocol, was delivered separately from the study supplement. Main Outcome Measure Ventilator-free days to study day

14 OMEGA - Methods

15 OMEGA - Results The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P=0.02) intensive care unit free days (14.0 vs 16.7; P=0.04) fewer nonpulmonary organ failure free days (12.3 vs 15.5; P=0.02). Sixty-day hospital mortality 26.6% in the n-3 group vs 16.3% in the control group (P=0.054) Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P=0.001) 15

16 OMEGA - Results

17 OMEGA - Results JAMA. 2011;306(14): doi: /jama

18 OMEGA - Conclusions This study suggests that twice-daily enteral supplementation of n-3 fatty acids, γ -LA, and antioxidants change plasma levels of n-3 fatty acids but do not improve clinical outcomes or biomarkers of systemic inflammation in patients with ALI and in fact may be harmful. 18

19 OMEGA - Discussion Bolus vs kontinuierliche Gabe von Lipiden (nicht in Phase II getestet, bei Durchfall geringere intestinale Resorption) Kontrollgruppe nicht isonitrogen (wenig fetthaltig, proteinreich, kohlenhydratreich, respiratorischer Quotient) Interaktion zw. Pharmakonutrition und Kalorienzufur Stellenwert der Antioxidantien (Zink proinflammatorisch, ) 19