Arterial and ventricular CSF pharmacokinetics after intrathecal meperidine in humans

In order to investigate the mechanisms leading to respiratory depression after lumbar administration of opioids, plasma and ventricular CSF pharmacokinetics of intrathecal meperidine (1 mg.kg-1) were studied in five head-injured patients undergoing surgery for lower limb fracture. Meperidine was detected both in the plasma (arterial catheter) and in the ventricular CSF (intracranial catheter) soon after intrathecal administration: 45 +/- 17 min and 100 +/- 14 min, respectively. The maximal plasma concentration was 341 +/- 133 ng.ml-1, whereas, in ventricular CSF, it was 64.5 +/- 14.9 ng.ml-1. The ventricular CSF-plasma ratio increased with time (r = 0.82) from 0.18 +/- 0.04 at the first hour to 0.38 +/- 0.1 at 16th hour. It is concluded that the putative risk of respiratory depression appears to be mainly related to the absorption into the systemic circulation and to redistribution back into CSF.