Department of Anaesthesiology, Medical Centre of the Johannes Gutenberg-University, Mainz, Germany.
PeerJ. 2023 Aug 21;11:e15875. doi: 10.7717/peerj.15875. eCollection 2023.
Sepsis is a common disease in intensive care units worldwide, which is associated with high morbidity and mortality. This process is often associated with multiple organ failure including acute lung injury. Although massive research efforts have been made for decades, there is no specific therapy for sepsis to date. Early and best treatment is crucial. Lidocaine is a common local anesthetic and used worldwide. It blocks the fast voltage-gated sodium (Na) channels in the neuronal cell membrane responsible for signal propagation. Recent studies show that lidocaine administered intravenously improves pulmonary function and protects pulmonary tissue in pigs under hemorrhagic shock, sepsis and under pulmonary surgery. The aim of this study is to show that lidocaine inhalative induces equivalent effects as lidocaine intravenously in pigs in a lipopolysaccharide (LPS)-induced sepsis with acute lung injury.
After approval of the local State and Institutional Animal Care Committee, to induce the septic inflammatory response a continuous infusion of lipopolysaccharide (LPS) was administered to the pigs in deep anesthesia. Following induction and stabilisation of sepsis, the study medication was randomly assigned to one of three groups: (1) lidocaine intravenously, (2) lidocaine per inhalation and (3) sham group. All animals were monitored for 8 h using advanced and extended cardiorespiratory monitoring. Postmortem assessment included pulmonary mRNA expression of mediators of early inflammatory response (IL-6 & TNF-alpha), wet-to-dry ratio and lung histology.
Acute respiratory distress syndrome (ARDS) was successfully induced after sepsis-induction with LPS in all three groups measured by a significant decrease in the PaO/FiO ratio. Further, septic hemodynamic alterations were seen in all three groups. Leucocytes and platelets dropped statistically over time due to septic alterations in all groups. The wet-to-dry ratio and the lung histology showed no differences between the groups. Additionally, the pulmonary mRNA expression of the inflammatory mediators IL-6 and TNF-alpha showed no significant changes between the groups. The proposed anti-inflammatory and lung protective effects of lidocaine in sepsis-induced acute lung injury could not be proven in this study.
脓毒症是全球重症监护病房的常见疾病，与高发病率和死亡率相关。这一过程通常与包括急性肺损伤在内的多器官衰竭有关。尽管数十年来进行了大量研究，但迄今为止尚无针对脓毒症的特定疗法。早期和最佳治疗至关重要。利多卡因是一种常见的局部麻醉剂，在全球范围内使用。它阻断神经元细胞膜上负责信号传导的快速电压门控钠（Na）通道。最近的研究表明，静脉内给予利多卡因可改善失血性休克、脓毒症和肺外科手术下猪的肺功能并保护肺组织。本研究旨在表明，在脂多糖（LPS）诱导的伴有急性肺损伤的脓毒症中，吸入利多卡因可产生与静脉内利多卡因相当的效果。
在当地州和机构动物护理委员会批准后，通过深麻醉向猪持续输注脂多糖（LPS）以诱导脓毒症炎症反应。在诱导和稳定脓毒症后，将研究药物随机分配到以下三组之一：（1）静脉内利多卡因，（2）吸入利多卡因和（3）假手术组。所有动物均通过先进和扩展的心肺监测进行 8 小时监测。尸检评估包括早期炎症反应介质（IL-6 和 TNF-α）的肺 mRNA 表达、湿重/干重比和肺组织学。
所有三组均成功通过 LPS 诱导的脓毒症诱导出急性呼吸窘迫综合征（ARDS），通过 PaO/FiO 比值的显著降低来衡量。此外，三组均出现脓毒症性血液动力学改变。由于所有组的败血症改变，白细胞和血小板随时间呈统计学下降。湿重/干重比和肺组织学显示各组之间无差异。此外，炎症介质 IL-6 和 TNF-α的肺 mRNA 表达在各组之间也没有明显变化。在本研究中，未能证明利多卡因在脓毒症诱导的急性肺损伤中的抗炎和肺保护作用。
