The EEG burst suppression threshold test for the determination of CNS sensitivity to intravenous anesthetics in rats

The electroencephalographic (EEG) threshold test was developed to determine the central nervous system (CNS) sensitivity to several depressant drugs, mainly intravenous anesthetic agents. Test drugs were administered to the rats by continuous intravenous infusion until a defined EEG criterion indicating deep anesthesia was reached. The criterion was a burst suppression which lasted 1 s or more, the 'silent second' (SS). The dose of the drug needed to induce the SS, the threshold dose, was the dependent variable. In the intact animal, it is influenced by the potency of the drug and dose administration rate of the infusion (mg/kg/min). The method has several advantages over the commonly used anesthesia times (misnomer: sleeping time) where the duration is influenced by several pharmacokinetic properties such as metabolism and redistribution. With the method it is possible under in vivo conditions to monitor continuously the electrical changes in the CNS. No interruptions are necessary. The pharmacological end-point is well defined, easy to monitor and detect. The threshold doses of the drugs applied remained stable with repetitive testing of the same individual. Thus, it can be used effectively to determine the CNS sensitivity to a number of drugs and to follow changes in this sensitivity after several physiological, pharmacological or pathological interventions.