Plasma concentrations following repeated rectal or intravenous administration of paracetamol after heart surgery

Abstract

Paracetamol is commonly used for post-operative pain management in combination with more potent analgesics. The best route of paracetamol administration after major surgery, when oral intake may not be optimal, is not known. Our primary purpose was to study plasma concentrations after the 1st and 4th dose of 1 g of paracetamol given either rectally or intravenously (i.v.) after major surgery. In this prospective, randomized study, 48 patients undergoing heart surgery were randomized upon arrival to the intensive care unit (ICU) to receive paracetamol every 6th hour either as suppositories or intravenous injections. In half the patients (n = 24), blood samples for paracetamol concentration were obtained before and 20, 40 and 80 min after the first dose. In the other patients (n = 24), additional samples were taken prior to, and at 20, 40, 80 min and 4 and 6 h after, the 4th dose. Plasma paracetamol concentration peaked (95 +/- 36 micromol/l) within 40 min after initial i.v. administration but did not increase within 80 min after the 1st suppository. Plasma concentration before the 4th dose was 74 +/- 51 and 50 +/- 27 in the rectal and i.v. groups, respectively. Paracetamol concentration peaked 20 min after the 4th dose for the i.v. patients (210 +/- 84 micromol/l) and declined to 99 +/- 27 micromol/l at 80 min as compared with the rectal patients 69 +/- 44 to 77 +/- 48 micromol/l. Both time course and peak plasma concentrations of paracetamol given rectally differ from the one seen after intravenous administration. The clinical impact of these differences needs further investigation.