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Effect of Bronchoconstriction-induced Ventilation-Perfusion Mismatch on Uptake and Elimination of Isoflurane and Desflurane
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Otto von Guericke Univ, Dept Anesthesia & Intens Care Med, Magdeburg, Germany.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Otto von Guericke Univ, Dept Anesthesia & Intens Care Med, Magdeburg, Germany.
Oscill LLC, Pittsburgh, PA USA; Univ Pittsburgh, Med Ctr, Dept Anesthesiol, Pittsburgh, PA USA.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
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2017 (English)In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 127, no 5, p. 800-812Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Increasing numbers of patients with obstructive lung diseases need anesthesia for surgery. These conditions are associated with pulmonary ventilation/perfusion (VA/Q) mismatch affecting kinetics of volatile anesthetics. Pure shunt might delay uptake of less soluble anesthetic agents but other forms of VA/Q scatter have not yet been examined. Volatile anesthetics with higher blood solubility would be less affected by VA/Q mismatch. We therefore compared uptake and elimination of higher soluble isoflurane and less soluble desflurane in a piglet model.

METHODS: Juvenile piglets (26.7 ± 1.5 kg) received either isoflurane (n = 7) or desflurane (n = 7). Arterial and mixed venous blood samples were obtained during wash-in and wash-out of volatile anesthetics before and during bronchoconstriction by methacholine inhalation (100 μg/ml). Total uptake and elimination were calculated based on partial pressure measurements by micropore membrane inlet mass spectrometry and literature-derived partition coefficients and assumed end-expired to arterial gradients to be negligible. VA/Q distribution was assessed by the multiple inert gas elimination technique.

RESULTS: Before methacholine inhalation, isoflurane arterial partial pressures reached 90% of final plateau within 16 min and decreased to 10% after 28 min. By methacholine nebulization, arterial uptake and elimination delayed to 35 and 44 min. Desflurane needed 4 min during wash-in and 6 min during wash-out, but with bronchoconstriction 90% of both uptake and elimination was reached within 15 min.

CONCLUSIONS: Inhaled methacholine induced bronchoconstriction and inhomogeneous VA/Q distribution. Solubility of inhalational anesthetics significantly influenced pharmacokinetics: higher soluble isoflurane is less affected than fairly insoluble desflurane, indicating different uptake and elimination during bronchoconstriction.

Place, publisher, year, edition, pages
2017. Vol. 127, no 5, p. 800-812
National Category
Anesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:uu:diva-334179DOI: 10.1097/ALN.0000000000001847ISI: 000414634700010PubMedID: 28857808OAI: oai:DiVA.org:uu-334179DiVA, id: diva2:1158886
Funder
Swedish Research Council, X2015-99x-22731-01-04Available from: 2017-11-21 Created: 2017-11-21 Last updated: 2018-02-16Bibliographically approved
In thesis
1. Ventilation/Perfusion Matching and its Effect on Volatile Pharmacokinetics
Open this publication in new window or tab >>Ventilation/Perfusion Matching and its Effect on Volatile Pharmacokinetics
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The mismatching of alveolar ventilation and perfusion (VA/Q) is the major determinant of impaired gas exchange. The gold standard for analyzing VA/Q distribution is the multiple inert gas elimination technique (MIGET), conventionally based on gas chromatography (GC), and, although simple in principle, a technically demanding procedure limiting its use. A new technique based on micropore membrane inlet mass spectrometry (MMIMS) combined MIGET with mass spectrometry, simplifying the sample handling process, and potentially providing VA/Q distributions for a general clinical approach.

The kinetics of volatile anesthetics are well known in patients with healthy lungs. The uptake and distribution of inhaled anesthetics have usually been modeled by physiologic models. However, these models have limitations, and they do not consider ventilation/perfusion matching. Respiratory diseases account for a large part of morbidity and mortality and are associated with pulmonary VA/Q mismatch that may affect uptake and elimination of volatile anesthetics.

The objectives of the studies were firstly to investigate assessment of VA/Q mismatch by MMIMS and secondly to investigate the effects of asthma-like VA/Q mismatch on the kinetics of volatile anesthetics in an experimental porcine model.

Anesthetized and mechanically ventilated piglets were studied.

In study I, a direct comparison of MIGET by MMIMS with the conventional MIGET by GC in three animal models that covered a wide range of VA/Q distributions was preformed. The two methods agreed well, and parameters derived from both methods showed good agreement with externally measured references.

In studies II–IV, a stable method of inducing and maintaining asthma-like VA/Q mismatch with methacholine (MCh) administration was established, and the effect of VA/Q mismatch on the pharmacokinetics of desflurane and isoflurane was investigated. The present model of bronchoconstriction demonstrates a delay in volatile anesthetic uptake and elimination, related to the heterogeneity of MCh-inhalation induced ventilation. The difference in solubility of volatile anesthetics has a significant influence on their uptake and elimination under VA/Q mismatch. The higher blood soluble isoflurane is affected to a lesser degree than the fairly insoluble desflurane.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. p. 53
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1269
Keywords
Anesthesia, Animal models in research, Mass spectrometry, Gas chromatography, MIGET, Ventilation-perfusion, Desflurane, Isoflurane, Bronchoconstriction
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-304298 (URN)978-91-554-9732-3 (ISBN)
Public defence
2016-12-08, Enghoffsalen, Akademiska sjukhuset, Uppsala, 09:15 (English)
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Supervisors
Available from: 2016-11-14 Created: 2016-10-03 Last updated: 2018-02-16

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Kretzschmar, MoritzKozian, AlfBorges, João BatistaHedenstierna, GöranLarsson, AndersSchilling, Thomas

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