Muroya Kenji, Ueda Kenta, Wada Keiichi, Kotoda Masakazu, Matsukawa Takashi
Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Surgical Center, University of Yamanashi Hospital, University of Yamanashi, Yamanashi, Japan.
Front Pharmacol. 2022 Oct 14;13:1019114. doi: 10.3389/fphar.2022.1019114. eCollection 2022.
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 ( = 6 each). Thirty minutes after discontinuation of the drugs, cooling was initiated by perfusing 10°C water 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, = 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, = 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 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.
术后或治疗性低温期间的寒战可导致严重并发症，如心肌梗死和呼吸衰竭。尽管几种麻醉剂和阿片类药物显示有抗寒战作用，但其镇静和呼吸副作用削弱了这些药物预防寒战的效用。在本研究中，我们使用低温兔模型探讨了新型超短效苯二氮䓬类药物瑞马唑仑预防寒战的潜力。成年雄性日本白兔用异氟烷麻醉。兔子接受生理盐水（对照组）、瑞马唑仑（0.1或1mg/kg/h）或瑞马唑仑+氟马西尼（一种选择性γ-氨基丁酸（GABA）A型受体拮抗剂，每组n = 6）。停药30分钟后，通过将10°C的水灌注到置于结肠的塑料管中开始降温，直至动物出现寒战。记录核心体温以及血流动力学和生理参数。1mg/kg/h的瑞马唑仑显著降低了寒战期间的核心体温变化（-2.50±0.20°C vs.对照组：-1.00±0.12°C，P = 0.0009）。给予氟马西尼后，1mg/kg/h瑞马唑仑对核心体温变化的作用消失（-0.94±0.16°C vs.对照组：-1.00±0.12°C，P = 0.996）。降温期间，大多数血流动力学和生理参数在各组之间无显著差异。即使其麻醉作用可能消失后，临床相关剂量的瑞马唑仑仍能通过GABA途径成功抑制兔的寒战。瑞马唑仑可能有预防手术或治疗性低温患者寒战的潜力。
