Characteristics of the relationship between plasma ketamine concentration and its effect on the minimum alveolar concentration of isoflurane in dogs

Objective To characterize the shape of the relationship between plasma ketamine concentration and minimum alveolar concentration (MAC) of isoflurane in dogs. Study design Retrospective analysis of previous data. Animals Four healthy adult dogs. Methods The MAC of isoflurane was determined at five to six different plasma ketamine concentrations. Arterial blood samples were collected at the time of MAC determination for measurement of plasma ketamine concentration. Plasma concentration/effect data from each dog were fitted to a sigmoid inhibitory maximum effect model in which MAC_c = MAC ₀ - (MAC₀-MAC_min)×C^γ/ EC₅₀ ^γ+C^γ, where C is the plasma ketamine concentration, MAC_c is the MAC of isoflurane at plasma ketamine concentration C, MAC₀ is the MAC of isoflurane without ketamine, MAC_min is the lowest MAC predicted during ketamine administration, EC₅₀ is the plasma ketamine concentration producing 50% of the maximal MAC reduction, and γ is a sigmoidicity factor. Nonlinear regression was used to estimate MAC_min, EC₅₀, and γ. Results Mean ± SEM MAC_min, EC₅₀ and γ were estimated to be 0.11 ± 0.01%, 2945 ± 710 ng mL ^-1 and 3.01 ± 0.84, respectively. Mean ± SEM maximal MAC reduction predicted by the model was 92.20 ± 1.05%. Conclusions The relationship between plasma ketamine concentration and its effect on isoflurane MAC has a classical sigmoid shape. Maximal MAC reduction predicted by the model is less than 100%, implying that high plasma ketamine concentrations may not totally abolish gross purposeful movement in response to noxious stimulation in the absence of inhalant anesthetics. Clinical relevance The parameter estimates reported in this study will allow clinicians to predict the expected isoflurane MAC reduction from various plasma ketamine concentrations in an average dog.