Modification of central nervous system effects of laudanosine by inhalation anaesthetics

To determine the effect of inhalation anaesthetics on the plasma concentration of laudanosine necessary to produce CNS excitation, we administered laudanosine 0.5 mg kg-1 min-1 i.v. to 40 rabbits under eight study conditions: 1.0 or 0.7% halothane, 1.6% isoflurane, 2.0% enflurane, during normocapnia and hypocapnia; 70% nitrous oxide, alone and with 1.0% halothane, and room air (control). At the onset of purposeless, unco-ordinated movements of the entire body, blood samples were obtained to determine the CNS excitation-threshold plasma concentration (ETPC) of laudanosine. During normocapnia, 1.0% halothane, 1.6% isoflurane and 2.0% enflurane increased ETPC (mean (SD) 11.8 (2.5), 11.3 (2.8) and 9.1 (1.4) micrograms ml-1, respectively) from control (5.0 (0.9) microgram ml-1). ETPC during enflurane anaesthesia did not change significantly with hypocapnia. Nitrous oxide, alone or in combination with halothane, did not change ETPC. The combination of nitrous oxide with 1.0% halothane significantly decreased ETPC to less than that for halothane alone (6.7 (1.2) v. 11.8 (2.5) micrograms ml-1, respectively).