Kretzschmar Moritz, Kozian Alf, Baumgardner James E, Schreiber Jens, Hedenstierna Göran, Larsson Anders, Hachenberg Thomas, Schilling Thomas
Research Anesthesiologist, Department of Surgical Sciences, Hedenstierna Laboratory, Uppsala University, Uppsala, Sweden; Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
Assistant Professor in Cardiothoracic Anesthesia, Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany; Department of Surgical Sciences, Hedenstierna Laboratory, Uppsala University, Uppsala, Sweden.
Respir Physiol Neurobiol. 2016 Jan;220:88-94. doi: 10.1016/j.resp.2015.09.014. Epub 2015 Oct 9.
Bronchoconstriction is a hallmark of asthma and impairs gas exchange. We hypothesized that pharmacokinetics of volatile anesthetics would be affected by bronchoconstriction. Ventilation/perfusion (VA/Q) ratios and pharmacokinetics of desflurane in both healthy state and during inhalational administration of methacholine (MCh) to double peak airway pressure were studied in a piglet model. In piglets, MCh administration by inhalation (100 μg/ml, n=6) increased respiratory resistance, impaired VA/Q distribution, increased shunt, and decreased paO2 in all animals. The uptake and elimination of desflurane in arterial blood was delayed by nebulization of MCh, as determined by Micropore Membrane Inlet Mass Spectrometry (wash-in time to P50, healthy vs. inhalation: 0.5 min vs. 1.1 min, to P90: 4.0 min vs. 14.8 min). Volatile elimination was accordingly delayed. Inhaled methacholine induced severe bronchoconstriction and marked inhomogeneous VA/Q distribution in pigs, which is similar to findings in human asthma exacerbation. Furthermore, MCh-induced bronchoconstriction delayed both uptake and elimination of desflurane. These findings might be considered when administering inhalational anesthesia to asthmatic patients.
支气管收缩是哮喘的一个标志，会损害气体交换。我们假设挥发性麻醉剂的药代动力学受支气管收缩的影响。在一个仔猪模型中，研究了健康状态下以及吸入乙酰甲胆碱（MCh）使气道压力达到双峰时地氟烷的通气/灌注（VA/Q）比值和药代动力学。在仔猪中，吸入MCh（100μg/ml，n = 6）会增加呼吸阻力，损害VA/Q分布，增加分流，并使所有动物的动脉血氧分压（PaO2）降低。通过微孔膜进样质谱法测定，MCh雾化延迟了地氟烷在动脉血中的摄取和消除（达到P50的吸入时间，健康状态与吸入MCh时：0.5分钟对1.1分钟，达到P90：4.0分钟对14.8分钟）。挥发性物质的消除相应延迟。吸入乙酰甲胆碱在猪中诱发了严重的支气管收缩和明显的VA/Q分布不均，这与人类哮喘发作时的发现相似。此外，MCh诱导的支气管收缩延迟了地氟烷的摄取和消除。在给哮喘患者实施吸入麻醉时可能需要考虑这些发现。
