Effect of intraoperative paravertebral or intravenous lidocaine versus control during lung resection surgery on postoperative complications: A randomized controlled trial.

BACKGROUND: Use of minimally invasive surgical techniques for lung resection surgery (LRS), such as video-assisted thoracoscopy (VATS), has increased in recent years. However, there is little information about the best anesthetic technique in this context. This surgical approach is associated with a lower intensity of postoperative pain, and its use has been proposed in programs for enhanced recovery after surgery (ERAS). This study compares the severity of postoperative complications in patients undergoing LRS who have received lidocaine intraoperatively either intravenously or via paravertebral administration versus saline. METHODS/DESIGN: We will conduct a single-center randomized controlled trial involving 153 patients undergoing LRS through a thoracoscopic approach. The patients will be randomly assigned to one of the following study groups: intravenous lidocaine with more paravertebral thoracic (PVT) saline, PVT lidocaine with more intravenous saline, or intravenous remifentanil with more PVT saline. The primary outcome will be the comparison of the postoperative course through Clavien-Dindo classification. Furthermore, we will compare the perioperative pulmonary and systemic inflammatory response by monitoring biomarkers in the bronchoalveolar lavage fluid and blood, as well as postoperative analgesic consumption between the three groups of patients. We will use an ANOVA to compare quantitative variables and a chi-squared test to compare qualitative variables. DISCUSSION: The development of less invasive surgical techniques means that anesthesiologists must adapt their perioperative management protocols and look for anesthetic techniques that provide good analgesic quality and allow rapid rehabilitation of the patient, as proposed in the ERAS protocols. The administration of a continuous infusion of intravenous lidocaine has proven to be useful and safe for the management of other types of surgery, as demonstrated in colorectal cancer. We want to know whether the continuous administration of lidocaine by a paravertebral route can be substituted with the intravenous administration of this local anesthetic in a safe and effective way while avoiding the risks inherent in the use of regional anesthetic techniques. In this way, this technique could be used in a safe and effective way in ERAS programs for pulmonary resection. TRIAL REGISTRATION: EudraCT, 2016-004271-52; ClinicalTrials.gov, NCT03905837 . Protocol number IGGFGG-2016 version 4.0, 27th April 2017.

The effect of anesthetic preconditioning with sevoflurane on intracellular signal-transduction pathways and apoptosis, in a lung autotransplant experimental model / O efeito do pré-condicionamento anestésico com sevoflurano sobre as vias de transdução de sinal intracelular e a apoptose, em modelo experimental de autotransplante pulmonar

Abstract Background: Anesthetic pre-conditioning attenuates inflammatory response during ischemia-reperfusion lung injury. The molecular mechanisms to explain it are not fully understood. The aim of our investigation was to analyze the molecular mechanism that explain the anti-inflammatory effects of anesthetic pre-conditioning with sevoflurane focusing on its effects on MAPKs (mitogen-activated protein kinases), NF-κB (nuclear factor kappa beta) pathways, and apoptosis in an experimental lung autotransplant model. Methods: Twenty large white pigs undergoing pneumonectomy plus lung autotransplant were divided into two 10-member groups on the basis of the anesthetic received (propofol or sevoflurane). Anesthetic pre-conditioning group received sevoflurane 3% after anesthesia induction and it stopped when one-lung ventilation get started. Control group did not receive sevoflurane in any moment during the whole study period. Intracellular signal-transduction pathways (MAPK family), transcription factor (NF-κB), and apoptosis (caspases 3 and 9) were analyzed during experiment. Results: Pigs that received anesthetic pre-conditioning with sevoflurane have shown significant lower values of MAPK-p38, MAPK-P-p38, JNK (c-Jun N-terminal kinases), NF-κB p50 intranuclear, and caspases (p < 0.05) than pigs anesthetized with intravenous propofol. Conclusions: Lung protection of anesthetic pre-conditioning with sevoflurane during experimental lung autotransplant is, at least, partially associated with MAPKs and NF κB pathways attenuation, and antiapoptotic effects.

Resumo Justificativa: O pré-condicionamento anestésico atenua a resposta inflamatória durante a lesão de isquemia-reperfusão do pulmão. Os mecanismos moleculares para explicá-lo não são totalmente compreendidos. O objetivo de nossa investigação foi analisar o mecanismo molecular que explica os efeitos anti-inflamatórios do pré-condicionamento anestésico com sevoflurano, enfocar seus efeitos sobre as proteínas quinases ativadas por mitógenos (MAPKs), o fator nuclear kappa beta (NF-κB) e a apoptose em modelo experimental de autotransplante pulmonar. Métodos: Vinte porcos Large White submetidos à pneumonectomia e autoimplante de pulmão foram divididos em dois grupos de 10 membros com base no anestésico recebido (propofol ou sevoflurano). O grupo de pré-condicionamento anestésico recebeu sevoflurano a 3% após a indução da anestesia, que foi descontinuado quando a ventilação monopulmonar foi iniciada. O grupo controle não recebeu sevoflurano em qualquer momento durante todo o período do estudo. As vias de transdução de sinal intracelular (família MAPK), o fator de transcrição (NF-κB) e a apoptose (caspases 3 e 9) foram analisados durante o experimento. Resultados: Os suínos que receberam pré-condicionamento anestésico com sevoflurano apresentaram valores mais baixos de MAPK-p38, MAPK-P-p38, c-Jun N-terminal quinases (JNK), NF-κB p50 intranuclear e caspases (p < 0,05) do que os suínos anestesiados com propofol intravenoso. Conclusões: A proteção pulmonar do pré-condicionamento anestésico com sevoflurano durante o autotransplante pulmonar experimental está, pelo menos, parcialmente associada à atenuação das vias de MAPKs e NF κB e aos efeitos antiapoptóticos.

[The effect of anesthetic preconditioning with sevoflurane on intracellular signal-transduction pathways and apoptosis, in a lung autotransplant experimental model]. / O efeito do pré­condicionamento anestésico com sevoflurano sobre as vias de transdução de sinal intracelular e a apoptose, em modelo experimental de autotransplante pulmonar.

BACKGROUND: Anesthetic pre-conditioning attenuates inflammatory response during ischemia-reperfusion lung injury. The molecular mechanisms to explain it are not fully understood. The aim of our investigation was to analyze the molecular mechanism that explain the anti-inflammatory effects of anesthetic pre-conditioning with sevoflurane focusing on its effects on MAPKs (mitogen-activated protein kinases), NF-κB (nuclear factor kappa beta) pathways, and apoptosis in an experimental lung autotransplant model. METHODS: Twenty large white pigs undergoing pneumonectomy plus lung autotransplant were divided into two 10-member groups on the basis of the anesthetic received (propofol or sevoflurane). Anesthetic pre-conditioning group received sevoflurane 3% after anesthesia induction and it stopped when one-lung ventilation get started. Control group did not receive sevoflurane in any moment during the whole study period. Intracellular signal-transduction pathways (MAPK family), transcription factor (NF-κB), and apoptosis (caspases 3 and 9) were analyzed during experiment. RESULTS: Pigs that received anesthetic pre-conditioning with sevoflurane have shown significant lower values of MAPK-p38, MAPK-P-p38, JNK (c-Jun N-terminal kinases), NF-κB p50 intranuclear, and caspases (p<0.05) than pigs anesthetized with intravenous propofol. CONCLUSIONS: Lung protection of anesthetic pre-conditioning with sevoflurane during experimental lung autotransplant is, at least, partially associated with MAPKs and NF κB pathways attenuation, and antiapoptotic effects.

Glycocalyx Degradation after Pulmonary Transplantation Surgery.

PURPOSE: Ischaemia-reperfusion injury (IRI) is a main cause of morbidity after pulmonary resection surgery. The degradation of glycocalyx, a dynamic layer of macromolecules at the luminal surface of the endothelium, seems to participate in tissue dysfunction after IRI. Lidocaine has a proven anti-inflammatory activity in several tissues but its modulation of glycocalyx has not been investigated. This work aimed to investigate the potential involvement of glycocalyx in lung IRI in a lung auto-transplantation model and the possible effect of lidocaine in modulating IRI. METHODS: Three groups (sham-operated, control, and lidocaine), each consisting of 6 Large White pigs, were subjected to lung auto-transplantation. All groups received the same anaesthesia. In addition, the lidocaine group received a continuous IV administration of lidocaine (1.5 mg/kg/h). Lung tissue and plasma samples were taken before pulmonary artery clamp, before reperfusion, and 30 and 60 min post-reperfusion in order to analyse pulmonary oedema, glycocalyx components, adhesion molecules, and myeloperoxidase level. RESULTS: Ischaemia caused pulmonary oedema, which was greater after reperfusion. This effect was accompanied by decreased levels of syndecan-1 and heparan sulphate in the lung samples, together with increased levels of both glycocalyx components in the plasma samples. After reperfusion, neutrophil activation and the expression of adhesion molecules were increased. All these alterations were significantly lower or absent in the lidocaine group. CONCLUSION: Lung IRI caused glycocalyx degradation that contributed to neutrophil activation and adhesion. The administration of lidocaine was able to protect the lung from glycocalyx degradation.

Role of surgical manipulation in lung inflammatory response in a model of lung resection surgery.

OBJECTIVES: Lung resection surgery with one-lung ventilation leads to an inflammatory response. Surgical manipulation can play a key role in this response. Sevoflurane, a commonly used volatile anaesthetic, has a proven anti-inflammatory effect. Our main goal was to evaluate the segregated effect of surgical manipulation during lung resection surgery and the protective role of sevoflurane with regard to this response. METHODS: Fifteen pigs underwent left thoracotomy for caudal lobectomy under general anaesthesia. The animals were divided into 3 groups: control, sevoflurane and sham. The animals in the sham group underwent left thoracotomy and one-lung ventilation over 120 min, without lobectomy. The animals in the sevoflurane group received anaesthetic maintenance with sevoflurane. The animals in the sham group and the control group received propofol during the procedure. Lung biopsies were collected before the procedure (left caudal lobe) and 24 h later (right mediastinal lobe and left upper lobe). The samples were stored to measure levels of inflammatory markers (IL-1, TNF-α and ICAM-1), apoptotic mediators (BAD, BAX, BCL-2 and Caspase-3), Syndecan-1, MicroRNAs 182, 145 and lung oedema. RESULTS: Surgical manipulation increased the expression of inflammation (IL-1, TNF-α and ICAM-1) and proapoptotic mediators (BAX, BAD and Caspase-3). It also caused degradation of endothelial glycocalyx (Syndecan-1) and pulmonary oedema. Administration of sevoflurane reduced the elevation of inflammatory markers, degradation of glycocalyx and pulmonary oedema observed in the control group. CONCLUSIONS: Surgical manipulation of the collapsed lung could increase the expression of inflammation and proapoptotic mediators and cause tissue damage in the form of pulmonary oedema. Sevoflurane could attenuate this molecular response and pulmonary oedema.

Intravenous lidocaine decreases tumor necrosis factor alpha expression both locally and systemically in pigs undergoing lung resection surgery.

BACKGROUND: Lung resection surgery is associated with an inflammatory reaction. The use of 1-lung ventilation (OLV) seems to increase the likelihood of this reaction. Different prophylactic and therapeutic measures have been investigated to prevent lung injury secondary to OLV. Lidocaine, a commonly used local anesthetic drug, has antiinflammatory activity. Our main goal in this study was to investigate the effect of IV lidocaine on tumor necrosis factor α (TNF-α) lung expression during lung resection surgery with OLV. METHODS: Eighteen pigs underwent left caudal lobectomy. The animals were divided into 3 groups: control, lidocaine, and sham. All animals received general anesthesia. In addition, animals in the lidocaine group received a continuous IV infusion of lidocaine during surgery (1.5 mg/kg/h). Animals in the sham group only underwent thoracotomy. Samples of bronchoalveolar lavage (BAL) fluid and plasma were collected before initiation of OLV, at the end of OLV, at the end of surgery, and 24 hours after surgery. Lung biopsy specimens were collected from the left caudal lobe (baseline) before surgery and from the mediastinal lobe and the left cranial lobe 24 hours after surgery. Samples were flash-frozen and stored to measure levels of the following inflammatory markers: interleukin (IL) 1ß, IL-2, IL-10, TNF-α, nuclear factor κB, monocyte chemoattractant protein-1, inducible nitric oxide synthase, and endothelial nitric oxide synthase. Markers of apoptosis (caspase 3, caspase 9, Bad, Bax, and Bcl-2) were also measured. In addition, levels of metalloproteinases and nitric oxide metabolites were determined in BAL fluid and in plasma samples. A nonparametric test was used to examine statistical significance. RESULTS: OLV caused lung damage with increased TNF-α expression in BAL, plasma, and lung samples. Other inflammatory (IL-1ß, nuclear factor κB, monocyte chemoattractant protein-1) and apoptosis (caspase 3, caspase 9, and BAX) markers were also increased. With the use of IV lidocaine there was a significant decrease in the levels of TNF-α in the same samples compared with the control group. Lidocaine administration also reduced the inflammatory and apoptotic changes observed in the control group. Hemodynamic values, blood gas values, and airway pressure were similar in all groups. CONCLUSIONS: Our results suggest that lidocaine can prevent OLV-induced lung injury through reduced expression of proinflammatory cytokines and lung apoptosis. Administration of lidocaine may help to prevent lung injury during lung surgery with OLV.