The suppression of spinal F-waves by propofol does not predict immobility to painful stimuli in humans

Background. The immobilizing effects of volatile anaesthetics are primarily mediated at the spinal level. A suppression of recurrent spinal responses (F-waves), which reflect spinal excitability, has been shown for propofol. We have assessed the concentration-dependent F-wave suppression by propofol and related it to the logistic regression curve for suppression of movement to noxious stimuli and the effect on the bispectral index (TM) (BIS (TM)). The predictive power of drug effects on F-waves and BIS for movement responses to noxious stimuli was tested. Methods. In 24 patients anaesthesia was induced and maintained with propofol infused by a target controlled infusion pump at stepwise increasing and decreasing plasma concentrations between 0.5 and 4.5 mg litre(-1). The F-waves of the abductor hallucis muscle were recorded at a frequency of 0.2 Hz. BIS values were recorded continuously. Calculated propofol concentrations and F-wave amplitude and persistence were analyzed in terms of a pharmacokinetic-pharmacodynamic (PK/PD) model with a simple sigmoid concentration-response function. Motor responses to tetanic electrical stimulation (50 Hz, 60 mA, 5 s, volar forearm) were tested and the EC50tetanus was calculated using logistic regression. Results. For slowly increasing propofol concentrations, computer fits of the PK/PD model for the suppression by propofol yielded a median EC50 of 1.26 (0.4-2.3) and 1.9 (1.0-2.8) mg litre(-1) for the F-wave amplitude and persistence, respectively. These values are far lower than the calculated EC50 for noxious electrical stimulation of 3.75 mg litre(-1). This difference results in a poor prediction probability of movement to noxious stimuli of 0.59 for the F-wave amplitude. Conclusions. F-waves are almost completely suppressed at subclinical propofol concentrations and they are therefore not suitable for prediction of motor responses to noxious stimuli under propofol mono-anaesthesia.