Allopurinol dosage and effect on ischemia-reperfusion damage in elective and acute aortic surgery.
To study the effect of a safe dosage of allopurinol on ischemia-reperfusion damage following aortic surgery, 24 patients undergoing either elective or acute aortic reconstruction, were randomized to receive allopurinol or placebo, yielding four groups: elective/placebo (EP), elective/allopurinol (EA), acute/placebo (AP) and acute/allopurinol (AA). Blood concentrations of allopurinol, oxypurinol, uric acid, malondialdehyde, ascorbic acid, and 99mTc-albumin were determined perioperatively. Adequate concentrations and biochemical activity of allopurinol and oxypurinol were obtained, without side-effects. Malondialdehyde did not increase perioperatively, but was significantly higher in acute surgery than in elective surgery intraoperatively. Yet, ascorbic acid levels and 99mTc-albumin disappearance were not different from groups EP and EA. No influence of allopurinol was found on malondialdehyde, ascorbic acid and 99mTc-albumin. An influence of allopurinol may have been obscured, as patients in group AA were more hypotensive than in group AP. In conclusion, adequate allopurinol concentration can be obtained with a safe dosage in abdominal aortic surgery. Signs of ischemia-reperfusion injury were found in acute surgery, not in elective surgery. Therefore, further investigation on the clinical effect of allopurinol is only useful in acute aortic surgery.
Smeets
H J
HJ
Department of Surgery, University Hospital, Leiden, The Netherlands.
Dulfer
F T
FT
van Milligen de Wit
A W
AW
Camps
J
J
Kievit
J
J
Van Bockel
J H
JH
Hermans
J
J
Berger
H M
HM
D000368:Aged; D000493:Allopurinol / Q000008:administration & dosage* / Q000097:blood; D000975:Antioxidants / Q000008:administration & dosage*; D001012:Aorta, Abdominal / Q000601:surgery*; D001205:Ascorbic Acid / Q000097:blood; D017558:Elective Surgical Procedures; D006801:Humans; D008315:Malondialdehyde / Q000097:blood; D010117:Oxypurinol / Q000097:blood; D015427:Reperfusion Injury / Q000188:drug therapy*; D013668:Technetium Tc 99m Aggregated Albumin; D014527:Uric Acid / Q000097:blood
D000975:Antioxidants; D013668:Technetium Tc 99m Aggregated Albumin; D014527:Uric Acid; D008315:Malondialdehyde; D000493:Allopurinol; D010117:Oxypurinol; D001205:Ascorbic Acid