BENEFICIAL-EFFECTS OF VERAPAMIL IN RENAL-RISK SURGICAL PATIENTS

Objective: To test whether the administration of calcium channel antagonists, such as verapamil (V), on the day before, during, and for 24-36 h after an important abdominal intervention, can lower the onset of acute renal failure (ARF), mostly in renal-risk patients, such as the aged. Design: Randomized, nonblinded study. Setting: Three surgical care university departments and two intensive care units of the same hospital (S. Anna, Ferrara, Italy). Patients: Thirty-five elderly patients (61-83 years old) entered the study: 18 of them were given V; 17 were not treated and were considered as controls. The two study groups were overlapping as regards age, renal risk, and surgical challenge. The patients who underwent ARF (5 in the treated group, 7 among the controls) were rejected from the study. Interventions: V was given on the eve of surgery at a dose of 80 mg/8 h per os and then through slow infusion (5 mg/4-6 h) during the next intra- and postoperative 24-36 h. Abdominal surgery was performed owing to gastric cancer (8 cases), colorectal neoplasia (10 cases), gallstone disease (4 cases), subrenal aortic aneurysm (6 cases), and iliofemoral obstructive arteriopathy (7 cases). Measurements: Serum creatinine (s(Cr)) was assessed to test renal function; 24-h urinary levels of brush-border enzymes (gamma glutamyl transferase, or gGT), lysosomal enzym es (N-acetyl-beta-D-glucosaminidase, or NAG), and beta(2)-microglobulin (or beta(2)M) were determined at T-0 (on the eve of surgery), T-1 (first and second day after), and T-2 (7th and 8th day after) to demonstrate possible tubule cell damage. Results: In the evaluated patients (13 treated with V and 10 untreated): (a) the 24-h urinary levels of gGt and NAG persisted unchanged throughout the study in the treated patients, whereas in the controls the same indices exhibited significant (p < 0.01) increases at T-1 and T-2; (b) the 24-h urinary levels of beta(2)M showed significant (p < 0.01) increases in both groups from T-0 to T-1; however, at T-2 these values tended to return to normal ranges in the treated patients, whereas they continued to be elevated in the untreated group. As regards the patients who underwent postoperative ARF, in the treated group urine output was significantly larger (p < 0.01 at T-1 and p < 0.001 at T-2), S-Cr was significantly (p < 0.05) lower, and the renal function recovered earlier (within 10 +/- 3 vs. 22 +/- 9 days) than in the controls. Conclusions: The administration of calcium channel antagonists to renal-risk patients during surgery and immediately before and after it has failed to prevent the onset of postoperative ARF. Nevertheless this procedure has been shown to somehow reduce surgery-mediated lesions of the tubule cells, as demonstrated by the finding of elevated urinary enzymes only in the untreated group.