Novel ultrashort-acting benzodiazepine remimazolam lowers shivering threshold in rabbits
Shivering after surgery or during therapeutic hypothermia can lead to serious complications, such as myocardial infarction and respiratory failure. Although several anesthetics and opioids are shown to have anti-shivering effects, their sedative and respiratory side effects dampen the usefulness of...
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| Format: | Article |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1019114/full |
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| author | Kenji Muroya Kenta Ueda Keiichi Wada Masakazu Kotoda Takashi Matsukawa |
| author_facet | Kenji Muroya Kenta Ueda Keiichi Wada Masakazu Kotoda Takashi Matsukawa |
| author_sort | Kenji Muroya |
| collection | DOAJ |
| description | Shivering after surgery or during therapeutic hypothermia can lead to serious complications, such as myocardial infarction and respiratory failure. Although several anesthetics and opioids are shown to have anti-shivering effects, their sedative and respiratory side effects dampen the usefulness of these drugs for the prevention of shivering. In the present study, we explored the potential of a novel ultrashort-acting benzodiazepine, remimazolam, in the prevention of shivering using a rabbit model of hypothermia. Adult male Japanese white rabbits were anesthetized with isoflurane. The rabbits received saline (control), remimazolam (either 0.1 or 1 mg/kg/h), or remimazolam + flumazenil, a selective γ-aminobutyric acid (GABA) type A receptor antagonist (n = 6 each). Thirty minutes after discontinuation of the drugs, cooling was initiated by perfusing 10°C water via a plastic tube positioned in the colon until the animal shivered. Core body temperature and hemodynamic and physiological parameters were recorded. Remimazolam at 1 mg/kg/h significantly lowered the core temperature change during shivering (−2.50 ± 0.20°C vs. control: −1.00 ± 0.12°C, p = 0.0009). The effect of 1 mg/kg/h remimazolam on the core temperature change was abolished by flumazenil administration (−0.94 ± 0.16°C vs. control: −1.00 ± 0.12°C, p = 0.996). Most of the hemodynamic and physiological parameters did not differ significantly among groups during cooling. Remimazolam at a clinically relevant dose successfully suppressed shivering in rabbits via the GABA pathway even after its anesthetic effects likely disappeared. Remimazolam may have the potential to prevent shivering in patients undergoing surgery or therapeutic hypothermia. |
| first_indexed | 2024-04-11T09:25:55Z |
| format | Article |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T09:25:55Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-90cfd2eda9be47d89d62c13e62b951572022-12-22T04:32:02ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.10191141019114Novel ultrashort-acting benzodiazepine remimazolam lowers shivering threshold in rabbitsKenji Muroya0Kenta Ueda1Keiichi Wada2Masakazu Kotoda3Takashi Matsukawa4Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, Yamanashi, JapanDepartment of Anesthesiology, Faculty of Medicine, University of Yamanashi, Yamanashi, JapanSurgical Center, University of Yamanashi Hospital, University of Yamanashi, Yamanashi, JapanDepartment of Anesthesiology, Faculty of Medicine, University of Yamanashi, Yamanashi, JapanDepartment of Anesthesiology, Faculty of Medicine, University of Yamanashi, Yamanashi, JapanShivering after surgery or during therapeutic hypothermia can lead to serious complications, such as myocardial infarction and respiratory failure. Although several anesthetics and opioids are shown to have anti-shivering effects, their sedative and respiratory side effects dampen the usefulness of these drugs for the prevention of shivering. In the present study, we explored the potential of a novel ultrashort-acting benzodiazepine, remimazolam, in the prevention of shivering using a rabbit model of hypothermia. Adult male Japanese white rabbits were anesthetized with isoflurane. The rabbits received saline (control), remimazolam (either 0.1 or 1 mg/kg/h), or remimazolam + flumazenil, a selective γ-aminobutyric acid (GABA) type A receptor antagonist (n = 6 each). Thirty minutes after discontinuation of the drugs, cooling was initiated by perfusing 10°C water via a plastic tube positioned in the colon until the animal shivered. Core body temperature and hemodynamic and physiological parameters were recorded. Remimazolam at 1 mg/kg/h significantly lowered the core temperature change during shivering (−2.50 ± 0.20°C vs. control: −1.00 ± 0.12°C, p = 0.0009). The effect of 1 mg/kg/h remimazolam on the core temperature change was abolished by flumazenil administration (−0.94 ± 0.16°C vs. control: −1.00 ± 0.12°C, p = 0.996). Most of the hemodynamic and physiological parameters did not differ significantly among groups during cooling. Remimazolam at a clinically relevant dose successfully suppressed shivering in rabbits via the GABA pathway even after its anesthetic effects likely disappeared. Remimazolam may have the potential to prevent shivering in patients undergoing surgery or therapeutic hypothermia.https://www.frontiersin.org/articles/10.3389/fphar.2022.1019114/fullbenzodiazepineremimazolamshiveringγ-aminobutyric acidhypothermia |
| spellingShingle | Kenji Muroya Kenta Ueda Keiichi Wada Masakazu Kotoda Takashi Matsukawa Novel ultrashort-acting benzodiazepine remimazolam lowers shivering threshold in rabbits Frontiers in Pharmacology benzodiazepine remimazolam shivering γ-aminobutyric acid hypothermia |
| title | Novel ultrashort-acting benzodiazepine remimazolam lowers shivering threshold in rabbits |
| title_full | Novel ultrashort-acting benzodiazepine remimazolam lowers shivering threshold in rabbits |
| title_fullStr | Novel ultrashort-acting benzodiazepine remimazolam lowers shivering threshold in rabbits |
| title_full_unstemmed | Novel ultrashort-acting benzodiazepine remimazolam lowers shivering threshold in rabbits |
| title_short | Novel ultrashort-acting benzodiazepine remimazolam lowers shivering threshold in rabbits |
| title_sort | novel ultrashort acting benzodiazepine remimazolam lowers shivering threshold in rabbits |
| topic | benzodiazepine remimazolam shivering γ-aminobutyric acid hypothermia |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1019114/full |
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