Abstract
The general anesthetic propofol has been in clinical use for more than 30 years and has become the agent of choice for rapid intravenous induction. While its hypnotic and anti-convulsant properties are well known, the propensity for propofol to promote seizure activity is less well characterised. Electroencephalogram-confirmed reports of propofol-induced seizure activity implicate a predisposition in epileptic subjects. The aim of this study was to investigate the seizure-promoting action of propofol in mouse brain slices—with the goal of establishing an in vitro model of propofol pro-convulsant action for future mechanistic studies. Coronal slices were exposed to either normal artificial cerebrospinal fluid (aCSF) or no-magnesium (no-Mg) aCSF—and extracellular field potential recordings made from the hippocampus, entorhinal cortex and neocortex. Propofol (and etomidate for comparison) were delivered at three stepwise concentrations corresponding to clinically relevant levels. The main finding was that propofol induced ictal-like seizures in seven out of ten hippocampal recordings (p = 0.004 compared to controls) following pre-exposure to no-Mg aCSF—but strongly inhibited seizure-like event (SLE) activity in the neocortex. Propofol did not induce seizure activity in slices exposed to normal aCSF. The results support the contention that propofol has the capacity to promote seizure activity, particularly when there is an underlying seizure predisposition. This study establishes an in vitro model for exploring the mechanisms by which propofol promotes subcortical seizure activity.
Highlights
Propofol was introduced to clinical practice as a general anesthetic in 1977 and has become the agent of choice for rapid intravenous induction
It is noteworthy that subcortical seizure activity, which may present as myoclonic convulsive-like movements (Gale 1992), can be difficult to detect in the EEG (Borgeat et al 1993; Kiloh and Osselton 1961; Makela et al 1993)
We have shown in unrelated experiments that the GABAB agonist baclofen enhances the length of seizure-like event (SLE) activity in the neocortex
Summary
Propofol was introduced to clinical practice as a general anesthetic in 1977 and has become the agent of choice for rapid intravenous induction. Myoclonic activity during propofol anesthesia is common (Walder et al 2002) and many case-studies report convulsive-like muscle activity, during. Abnormal posturing and convulsive-like movements during propofol anesthesia are not universally associated with EEG changes consistent with cortical seizure activity (Borgeat et al 1993). These could be instances of non-seizure-related muscle dystonia and/or epileptiform activity originating from deeper structures (Borgeat et al 1993). It is noteworthy that subcortical seizure activity, which may present as myoclonic convulsive-like movements (Gale 1992), can be difficult to detect in the EEG (Borgeat et al 1993; Kiloh and Osselton 1961; Makela et al 1993). A normal EEG does not necessarily preclude an epileptiform aetiology
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