Clinical dosage of lidocaine does not impact the biomedical outcome of sepsis-induced acute respiratory distress syndrome in a porcine model

Abstract

Background 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. Methods 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. Results Acute respiratory distress syndrome (ARDS) was successfully induced after sepsis-induction with LPS in all three groups measured by a significant decrease in the PaO2/FiO2 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.