QUANTIFYING THE RESPIRATORY DYNAMICS OF SEVOFLURANE IN THE CAT

Abstract

S434 Inhalational anesthetics depress ventilation (VI) in a dose-dependent fashion. In this study we determined the dynamics of changes in VI due to changes in end-tidal sevoflurane tension (PETSEVO) in a cat model. METHODS: Approval from the Animal Ethics Board was obtained. Experiments were performed in seven alpha-chloralose-urethan anesthetized cats. The end-tidal PCO2 (PET CO2) was kept constant at 8 mmHg above resting values throughout the studies. The PETSEVO pattern applied was: (1) 5 to 10 min at 0 mmHg; (2) a stepwise increase to 8 mmHg ([similar] 1%), in 4 cats, or to 3.5 mmHg ([similar]0.5%), in 3 other cats; (3) 15 to 20 min at 8 or 3.5 mmHg; and (4) 20 min at 0 mmHg. The VI - PETSEVO data were analyzed using an inhibitory sigmoid-EMAX pharmacodynamic model together with a kinetic model that postulates an "effect" compartment: [1,2]Equation 1 and Equation 2 where VO is VI at zero PETSEVO, Delta VMAX the maximal decrease in VI, PEC 50 the steady-state sevoflurane tension at which 50% of the maximal decrease in VI occurred, gamma a shape parameter, PECSEVO (t) the estimated sevofurane tension in the effect compartment at time t and tau a time constant. We assumed that VI is linked directly to PECSEVO. Values are mean +/- SE. RESULTS: Inspection of individual data fits showed that the model adequately describes the ventilatory dynamics of sevoflurane. VI and PETSEVO data and model output of one cat are shown in Figure 1. There was an evident time lag between the changes in PETSEVO and VI. Since the pharmacodynamic parameters did not differ between the sevoflurane step changes to 3.5 and 8 mmHg we pooled the data. The mean values of the parameters were: VO = 670 +/- 116 ml/min; Delta VMAX = 633 +/- 117 ml/min; PEC 50 = 2.9 +/- 0.7 mmHg (- 0.4%); gamma = 1.0 +/- 0.2; and tau = 6.4 +/- 0.7 min (corresponds to an effect site equilibration half-life of 4.4 min).Figure 1: Left. Breath-to-breath data from one cat: VI (each dot is one breath) and PET SEVO vs. time, model output (line through VI data). Right. Closing the loop: PEC SEVO vs. VI, model output.CONCLUSIONS: Application of the model permits the prediction of the temporal and steady-state respiratory depressive effects of sevoflurane. Baseline anesthesia, which may have affected the value of the dynamic parameters, and the evident species differences, makes extrapolation to humans difficult. However, there are no reasons to doubt that the model is not applicable to describe the respiratory effects of inhalational anesthetics in humans when PET CO2 is kept constant.