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

Abstract

ObjectiveTo characterize the shape of the relationship between plasma ketamine concentration and minimum alveolar concentration (MAC) of isoflurane in dogs. Study designRetrospective analysis of previous data. AnimalsFour healthy adult dogs. MethodsThe 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 MACc=MAC0-(MAC0-MACmin)×CγEC50γ+Cγ, where C is the plasma ketamine concentration, MACc is the MAC of isoflurane at plasma ketamine concentration C, MAC0 is the MAC of isoflurane without ketamine, MACmin 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 MACmin, EC50, and γ. ResultsMean ± SEM MACmin, 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%. ConclusionsThe 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 relevanceThe 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.