Suppression of the human spinal H-reflex by propofol: a quantitative analysis.

BACKGROUND: The spinal cord is an important site of anaesthetic action because it mediates surgical immobility. During anaesthesia with volatile anaesthetics, it has been shown that the suppression of the spinal H-reflex correlates with surgical immobility. To evaluate whether the H-reflex could also be a possible candidate for monitoring immobility during propofol anaesthesia, this study assessed the concentration-dependent suppression of the H-reflex by propofol. To discriminate different effect sites, the individual concentration response-curves and the t(1/2ke0) of the H-reflex have been compared with those of two EEG parameters. METHODS: In 18 patients, anaesthesia was induced and maintained with propofol infused using a target-controlled infusion pump at stepwise increasing and decreasing plasma concentrations between 0.5 and 4.5 mg/l. The H-reflex of the soleus muscle was recorded at a frequency of 0.1 Hz. Calculated propofol concentrations and H-reflex amplitude were analysed in terms of a pharmacokinetic-pharmacodynamic (PKPD) model with a sigmoid concentration-response function. RESULTS: For slowly increasing propofol concentrations, computer fits of the PKPD model for H-reflex suppression by propofol yielded the following median parameters: EC50 1.1 (0.8-1.7) mg/l, slope parameter 2.4 (2.0-3.7), and a t(1/2ke0) of 6.7 (2.8-7.5, 25-75% quantiles) min. For the bispectral index, the t(1/2ke0) was 2.2 (1.8-3.1) min and for the spectral edge frequency at the 95th percentile of the power spectrum 2.8 (1.9-3.2) min. CONCLUSIONS: Propofol, unlike sevoflurane, suppresses the spinal H-reflex at concentrations far lower than the C50 skin incision. The differences in t(1/2ke0)-values indicate the presence of different effect compartments for effects on the H-reflex and the EEG.

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 (BIS). 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 EC(50tetanus) 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 EC(50) 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.

Concentration-dependent suppression of F-waves by sevoflurane does not predict immobility to painful stimuli in humans.

BACKGROUND: Decreased spinal excitability contributes to the immobilizing effects of halogenated ethers during general anaesthesia. Recurrent spinal responses such as F-waves reflect spinal excitability and are suppressed by volatile anaesthetics. To evaluate whether F-waves are suitable for monitoring immobility, the concentration-dependent effects of sevoflurane on F-waves were compared with effects on the Bispectral Index (BIS). The predictive power of all parameters for movement responses to noxious stimuli was tested. In addition, the effect of the noxious stimulus itself on F-waves was investigated. METHODS: In 28 patients, F-waves were recorded during sevoflurane anaesthesia at a frequency of 0.2 Hz at the lower limb. To insert a laryngeal mask, the sevoflurane concentration was initially increased to approximately 4%, which caused a complete extinction of F-waves. The sevoflurane concentration was then reduced until the F-waves recovered. BIS and spectral edge frequency (SEF(95)) were recorded continuously. The t(1/2ke0) and EC(50) values of the F-wave persistence and amplitude were calculated using a standard pharmacokinetic-pharmacodynamic model. During decreasing sevoflurane concentration motor responses to tetanic electrical stimulation (50 Hz, 60 mA, 5 s, volar forearm) were tested in seven patients and MAC(tetanus) was calculated using logistic regression. RESULTS: Sevoflurane reduces the F-wave amplitude with an EC(50) of 0.79 vol% at a far lower concentration than the calculated MAC(tetanus) (1.5 vol%), whereas the F-wave persistence yields an EC(50) of 1.4 vol%. Spinal and EEG parameters predicted the motor responses to movement better than chance alone, but did not differ significantly from each other. CONCLUSION: F-waves, especially the F-wave amplitude, cannot be used to predict movement to noxious stimuli during sevoflurane anaesthesia because they are almost completely suppressed at subclinical sevoflurane concentrations. Either the particular motoneurone pool (the largest motoneurones) assessed by F-waves is not involved in generating movement to painful stimuli or direct effects on motoneurone excitability are not involved in the suppression of movement to painful stimuli by sevoflurane.