Lack of renoprotective effect of theophylline during aortocoronary bypass surgery

Background. The incidence of acute renal failure (ARF) after cardiac surgery remains high, despite improvements in surgical techniques and perioperative care, and is associated with an inacceptably high mortality. The adenosine receptor antagonist theophylline has been shown to confer some benefit in experimental and clinical ARF due to ischaemia, contrast media and various nephrotoxic agents. Methods. In a double-blind, randomized, placebo-controlled trial, the effectiveness of theophylline for prevention of renal impairment after elective coronary artery bypass grafting (CABG) was evaluated. Fifty-six patients with normal renal function received a bolus of 4 mg/kg and a subsequent continuous infusion or 0.25 mg/kg/h theophylline (n = 28) or isotonic saline (n = 28) for up to 96 h. Serum creatinine concentrations were measured preoperatively and daily until day 5 after surgery, and the glomerular filtration rate (GFR) ([Cr-51]EDTA-clearance) was determined preoperatively, and at days 1, 3 and 5 after surgery. Results. Serum creatinine and GFR were the same in both groups. The number of patients with increases of serum creatinine greater than or equal to0.4 mg/dl were five in the theophylline group and four in the placebo group, Volumes of infused fluid and urine volumes were not different between groups, both ranging from similar to7.5 to 8.1 during the first 24 h after surgery. The number of patients with termination of study medication due to presumed side effects was not different between placebo and theophylline groups. Conclusions. Theophylline administration for renal protection after CABG appears to be ineffective in a pilot study in well-hydrated patients. However, the statistical power of our study was not sufficient to exclude a possible protective effect of theophylline. The present study demonstrated the feasability of a larger trial with theophylline or one of the new specific adenosine A1 receptor antagonists in the setting of ARF after cardiac surgery.