PLASMA-CONCENTRATIONS OF DILTIAZEM AND IT S ACTIVE METABOLITES IN CORONARY-ARTERY SURGERY - RELATIONSHIP WITH PREOPERATIVE TREATMENT

Preoperative oral administration of calcium channel blocking agents ha s been found ineffective to prevent perioperative myocardial ischaemia . Our hypothesis was that low plasma concentrations may account for th is inefficiency. Twenty-three male patients, scheduled for surgical my ocardial revascularisation, were administered their usual anti-anginal treatment, including 180 to 360 mg of diltiazem since more than one w eek. The usual dosage was given at 8.00 p.m. on the day before surgery . On the morning of surgery, after withdrawal of a first blood sample, 60 mg of diltiazem were administered per mouth before the induction o f anaesthesia. The anaesthesia was obtained with fentanyl, midazolam o r flunitrazepam, pancuronium and isoflurane as required. The cardiopul monary bypass (CPB) was associated with total haemodilution with Ringe r's Lactate and a membrane oxygenator. A second blood sample was withd rawn after CPB. Plasma concentrations of diltiazem and its two active metabolites, N-monodemethyldiltiazem (MA) and desacetyldiltiazem (M1), were assessed by HPLC. Plasma diltiazem concentrations decreased from 78 +/- 66 (mean +/- SD) to 51 +/- 42 mug . l-1 (p < 0.05) with wide i ndividual variations. These concentrations were under therapeutic leve ls in 18 out of 23 patients before (p < 0.05) with wide individual var iations. These concentrations were under therapeutic levels in 18 out of 23 patients before induction and in 22 patients after CPB. The meta bolite/diltiazem ratios remained constant. A dosage-plasma concentrati on relationship was observed preoperatively with diltiazem and MA. It is concluded that plasma concentrations of diltiazem should be optimiz ed preoperatively in order to prevent myocardial ischaemia.