The most important objectives of anesthesia (unconsciousness, somatic unresponsiveness to surgical stimulation, and autonomic unresponsiveness to surgical stimulation) are now achieved often with the combined administration of opioids and intravenous anesthetics. The proposal is based on the hypothesis that anesthetic action in fact represents several actions (components of anesthesia) with different mechanisms for various components of anesthesia induced by the same agent. It is hypothesized that the combination of an intravenous anesthetic with an opioid can result in different outcomes for different components of anesthesia.
The aim of the present proposal is to demonstrate that different intravenous anesthetics and opioids interact differently (addition, synergism or antagonism) regarding different components of anesthesia, and, therefore, some of the combinations that seem advantageous, according to the outcome for one component of anesthesia, may be detrimental for another component. Interactions between the most commonly used opioids and intravenous anesthetics will be studied in an attempt to demonstrate that some of the combinations may give much better constellation of interactions for various components of anesthesia than others. This may have implications for the selection of anesthetic combinations that interact favorably regarding all components of anesthesia. In rat experiments, morphine and fentanyl will be used as opioids, and thiopental, diazepam, and etomidate as intravenous anesthetics. Each opioid-intravenous anesthetic combination will be assessed regarding the following three objectives of anesthesia: hypnotic effect, the ability to block somatic response to noxious stimulation, and the ability to block cardiac acceleration response to noxious stimulation. An interaction for each objective of anesthesia will be studied in separate series of experiments. ED50 and ED95 values for the agents given separately and jointly in binary combinations will be determined with a probit procedure and compared with an isobolographic analysis.
