title: Bronchoconstriction induced by inhaled methacholine delays desflurane uptake and elimination in a piglet model.
abstract: 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.
authors.affiliation: 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.
authors.forename: Moritz
authors.initials: M
authors.lastname: Kretzschmar
authors.affiliation: 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.
authors.forename: Alf
authors.initials: A
authors.lastname: Kozian
authors.affiliation: Oscillogy (®) LLC, Folsom, PA, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Baumgardner
authors.affiliation: Professor of Pneumonology and Head of the Department of Pneumonology, Otto-von-Guericke-University Magdeburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Schreiber
authors.affiliation: Senior Professor in Clinical Physiology, Department of Medical Sciences, Clinical Physiology, Uppsala University, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Hedenstierna
authors.affiliation: Professor of Anesthesiology and Intensive Care Medicine, Head of Hedenstierna Laboratory, Department of Surgical Sciences, Anesthesia and Intensive Care, Uppsala University, Uppsala, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Professor of Anesthesia and Chair of the Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hachenberg
authors.affiliation: Assistant Professor in Vascular and 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. Electronic address: Thomas.Schilling@med.ovgu.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schilling
mesh_terms: D000280:Administration, Inhalation; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics*; D000818:Animals; D001249:Asthma; D001774:Blood Chemical Analysis; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage*; D000077335:Desflurane; D006439:Hemodynamics / Q000187:drug effects; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013058:Mass Spectrometry; D016210:Methacholine Chloride / Q000008:administration & dosage*; D011446:Prospective Studies; D012119:Respiration / Q000187:drug effects; D034421:Sus scrofa
chemical_list: D018685:Anesthetics, Inhalation; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D000077335:Desflurane; D007530:Isoflurane
keywords: Alveolar ventilation; Animal model; Arterial blood gas concentration; Bronchoconstriction; Desflurane; Ventilation-/perfusion-mismatch