Effects of methacholine infusion on desflurane pharmacokinetics in piglets

摘要

The data of a corresponding animal experiment demonstrates that nebulized methacholine (MCh) induced severe bronchoconstriction and significant inhomogeneous ventilation and pulmonary perfusion (V? A /Q?) distribution in pigs, which is similar to findings in human asthma. The inhalation of MCh induced bronchoconstriction and delayed both uptake and elimination of desflurane (Kretzschmar et al., 2015) . The objective of the present data is to determine V? A /Q? matching by Multiple Inert Gas Elimination Technique (MIGET) in piglets before and during methacholine- (MCh-) induced bronchoconstriction, induced by MCh infusion, and to assess the blood concentration profiles for desflurane (DES) by Micropore Membrane Inlet Mass Spectrometry (MMIMS). Healthy piglets ( n =4) under general anesthesia were instrumented with arterial, central venous, and pulmonary artery lines. The airway was secured via median tracheostomy with an endotracheal tube, and animals were mechanically ventilated with intermittent positive pressure ventilation (IPPV) with a FiO 2 of 0.4, tidal volume ( V T )=10ml/kg and PEEP of 5cmH 2 O using an open system. The determination of V. A /Q. was done by MIGET: before desflurane application and at plateau in both healthy state and during MCh infusion. Arterial blood was sampled at 0, 1, 2, 5, 10, 20, and 30min during wash-in and washout, respectively. Bronchoconstriction was established by MCH infusion aiming at doubling the peak airway pressure, after which wash-in and washout of the anesthetic gas was repeated. Anesthesia gas concentrations were measured by MMIMS. Data were analyzed by ANOVA, paired t -test, and by nonparametric Friedman?s test and Wilcoxon?s matched pairs test. We measured airway pressures, pulmonary resistance, and mean paO 2 as well as hemodynamic variables in all pigs before desflurane application and at plateau in both healthy state and during methacholine administration by infusion. By MIGET, fractional alveolar ventilation and pulmonary perfusion in relation to the V.A/Q. compartments, data of logSDQ? and logSDV? (the second moments describing global dispersion, i.e. heterogeneity of distribution) were estimated prior to and after MCh infusion. The uptake and elimination of desflurane was determined by MMIMS.