Extradural morphine: influence of adrenaline admixture.
The influence of the addition of adrenaline on extradural morphine analgesia and pharmacokinetics was investigated in a double-blind study. Morphine 2 mg was administered to 14 patients undergoing thoracotomy. In addition, adrenaline 50 micrograms added to the extradural solution, was administered to half of the patients, selected randomly. Morphine concentrations in serial plasma and cerebrospinal fluid (CSF) samples were measured. Postoperative analgesia was estimated by determining the requirement for additional analgesics. Following extradural administration of plain morphine, the peak morphine concentrations in CSF were 22 +/- 5 (SEM) times those in plasma; during the elimination phase the CSF concentrations exceeded those in plasma by about 150 times. The area under the concentration v. time curve (AUC) was 162 +/- 27 (SEM) times larger in CSF than in plasma. The admixture of adrenaline with the extradural morphine increased the individual variability in CSF and plasma concentrations. However, compared with the plain morphine group, adrenaline did not significantly increase the concentrations of morphine in CSF, nor were the morphine concentrations in plasma significantly decreased. The duration of analgesia was related to the amount of morphine in CSF, that is AUC (P less than 0.05) and peak concentrations of morphine in CSF (P less than 0.05).