Ignacio Garutti

The effects of anesthetic preconditioning with sevoflurane in an experimental lung autotransplant model in pigs.

BACKGROUND:Ischemia–reperfusion lung injury is doubly important in thoracic surgery because of the associated ventilation damage to 1 lung. In this study we evaluated the cytoprotective effects of sevoflurane in a pulmonary autotransplant model in pigs. METHODS:Twenty Large White pigs undergoing pneumonectomy plus lung autotransplant were divided into 2 10-member groups on the basis of the anesthetic received (propofol or sevoflurane). Proinflammatory mediators, oxidative stress, nitric oxide metabolism, and hemodynamic and blood variables were measured at 5 different time points. RESULTS:There was an increase of oxidative stress markers and proinflammatory mediators in the propofol group, whereas the hemodynamic variables were similar in both groups. CONCLUSIONS:We demonstrated that sevoflurane decreased the inflammatory response and oxidative stress in a live ischemia–reperfusion lung model.

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 &agr; (TNF-&agr;) 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) 1&bgr;, IL-2, IL-10, TNF-&agr;, nuclear factor &kgr;B, 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-&agr; expression in BAL, plasma, and lung samples. Other inflammatory (IL-1&bgr;, nuclear factor &kgr;B, 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-&agr; 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.

Early Measurement of Indocyanine Green Clearance Accurately Predicts Short-Term Outcomes After Liver Transplantation.

Background There are no accurate tools to predict short-term mortality or the need for early retransplantation after liver transplantation (LT). A noninvasive measurement of indocyanine green clearance, the plasma disappearance rate (PDR), has been associated with initial graft function. Methods We evaluated the ability of PDR to predict early mortality or retransplantation after LT. In this observational prospective study, 332 LT were analyzed. Donor, recipient, and intraoperative data were investigated. The ensuing score was prospectively evaluated in a validation cohort of 77 patients. Results Thirty-three patients reached the main endpoint. By multivariate analysis, the only independent predictors of the endpoint were PDR (odds ratio [OR], 0.85; 95% confidence interval, 0.79-0.92) and international normalized ratio (OR, 1.45; 95% confidence interval, 1.17-1.82). A risk score weighted by the OR was built using cutoff values of 2.2 or greater for international normalized ratio (1 point) and less than 10%/min for PDR (2 points). Four categories (0 to 3) were possible. The risk of early death or retransplantation was associated with the score (0, 4.4%; 1, 6.5%; 2, 12%; and 3, 50%; &khgr;2 for trend, P < 0.001). The score was also associated with duration of mechanical ventilation and intensive care unit stay. The score had a good diagnostic performance in the validation cohort (sensitivity, 60%; specificity, 95.5%; positive predictive value, 66.7%; negative predictive value, 94.1%). Conclusions A simple score obtained within the first day after LT predicts short-term survival and need for retransplantation and may prove useful when selecting diagnostic and therapeutic strategies.

Sevoflurane prevents liver inflammatory response induced by lung ischemia-reperfusion.

Background Transplants cause ischemia-reperfusion (IR) injury that can affect distant organs. Liver is particularly sensitive to IR injury. The present randomized experimental study was designed to investigate a possible protective effect of sevoflurane against liver inflammatory response to lung IR in a lung upper lobe left autotransplant model. Methods Two groups (sevoflurane and control) of eight swines each were submitted to upper lobe left lung autotransplant. Hypnotic maintenance was performed with sevoflurane 3% or propofol 8 to 10 mg/kg per hr until pneumonectomy was done; then propofol was used for all animals. Blood and liver samples were taken in four different moments: prepneumonectomy, prereperfusion, 10 min postreperfusion and 30 min postreperfusion to measure levels of interleukin (IL)-1&bgr;, IL-10, tumor necrosis factor (TNF)-&agr;, monocyte chemotactic protein (MCP)-1, nuclear factor (NF)-&kgr;B, C-reactive protein, ferritin and caspase 3. Non-parametric test was used to find statistical meaning. Results Lung IR markedly increased the expression of TNF-&agr;, IL-1&bgr;, MCP-1, NF-&kgr;B and caspase activity in control livers compared with basal levels, whereas liver IL-10 expression decreased 10 and 30 min post-reperfusion. Sevoflurane significantly decreased TNF-&agr;, IL-1&bgr;, MCP-1, NF-&kgr;B liver expression and caspase 3 activity. Sevoflurane also reverted the lung IR-induced decrease in IL-10 expression. Conclusions The present results indicate that lung IR caused hepatic injury. Sevoflurane attenuated liver injury in a model of upper lobe left lung autotransplant in pigs.

Ischaemic preconditioning prevents the liver inflammatory response to lung ischaemia/reperfusion in a swine lung autotransplant model †

OBJECTIVES Lung ischaemia/reperfusion (IR) induces a systemic inflammatory response that causes damage to remote organs. The liver is particularly sensitive to circulating inflammatory mediators that occur after IR of remote organs. Recently, remote ischaemic preconditioning has been proposed as a surgical tool to protect several organs from IR. The present study was designed to investigate a possible protective effect of lung ischaemic preconditioning (IP) against the liver inflammatory response to lung IR. METHODS Two groups [IP and control (CON)] of 10 Large White pigs underwent lung autotransplants (left pneumonectomy, ex situ cranial lobectomy and caudal lobe reimplantation). Before pneumonectomy was performed in the study group, IP was induced with two 5-min cycles of left pulmonary arterial occlusion and a 5-min interval of reperfusion between the two occlusions. Five animals underwent sham surgery. Liver biopsies were obtained during surgery at (i) prepneumonectomy, (ii) prereperfusion, (iii) 10 min after reperfusion of the implanted lobe and (iv) 30 min after reperfusion. The expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-10 and inducible form of nitric oxide synthase (iNOS) was analysed by western blotting. The expression of mRNA for TNF-α, IL1, IL-10, monocyte chemoattractant protein-1 (MCP-1), nuclear factor kappa beta and iNOS was analysed by reverse transcription-polymerase chain reaction. Caspase-3 activity was determined by enzyme-linked immunosorbent assay. Non-parametric tests were used to compare differences between and within groups. RESULTS Lung IR markedly increased expression of TNF-α (P = 0.0051) and IL-1 (P = 0.0051) and caspase-3 activity (P = 0.0043) in the CON group compared with the prepneumonectomy levels. A decrease of IL-10 mRNA expression was observed in the CON group after lung reperfusion. In the IP group, TNF-α (P = 0.0011) and IL-1 (P = 0.0001) expression and caspase-3 activity (P < 0.0009) were lower after reperfusion than in the CON group. IP caused reversion of the observed decrease of IL-10 mRNA expression (P = 0.016) induced in liver tissue by lung IR. Lung IR markedly increased the expression of mRNA MCP-1 after 10 min (P = 0.0051) and 30 min (P = 0.0051) of reperfusion. These increases were not observed in the IP or sham groups. CONCLUSIONS IP prevented liver injury induced by lung IR through the reduction of proinflammatory cytokines and hepatocyte apoptosis.

Thoracic paravertebral block after thoracotomy: comparison of three different approaches §

BACKGROUND Thoracic paravertebral block (TPVB) is a regional block technique increasingly used for the early management of post-thoracotomy pain. We compare three different postoperative analgesic approaches based on TPVB: anesthetist, anesthetist plus surgeon, and surgeon. MATERIALS AND METHODS We randomized 54 patients undergoing elective thoracotomy to three different postoperative analgesia groups: paravertebral percutaneous catheter (PVA group), paravertebral percutaneous catheter plus incisional (subcutaneous) catheter (PVA+Inc), and paravertebral catheter under direct vision (PVS group). During early postoperative 48h, we measured pain intensity, intravenous morphine afforded by the patient-controlled analgesia pump, and the spirometric test. RESULTS There were no statistically significant differences among the collected preoperative data. No significant differences were observed on postoperative spirometric values. Analgesic quality was better in PVA+Inc group at 12 and 24 postoperative hours. In this group, intravenous morphine use to improve analgesia was significantly lower from 8h until 48h postoperative. CONCLUSIONS Association of thoracic paravertebral block to continuous infusion of a local anesthetic in the surgical incision area affords a better pain relief than paravertebral block alone (introduced by the surgeon or the anesthetist).

Extravascular Lung Water and Pulmonary Vascular Permeability Index Measured at the End of Surgery Are Independent Predictors of Prolonged Mechanical Ventilation in Patients Undergoing Liver Transplantation.

BACKGROUND:Pulmonary edema (PE) after orthotopic liver transplantation (OLT) may compromise the postoperative course and prolong the duration of mechanical ventilation (MV) and intensive care unit length of stay. Hemodynamic monitoring with transpulmonary thermodilution permits quantification of extravascular lung water index (ELWI) and calculation of the pulmonary vascular permeability index (PVPI), which is the ratio between the ELWI and the pulmonary blood volume. This ratio can discriminate between PE hydrostatic and nonhydrostatic PE. We investigated the relationship between ELWI and PVPI values, measured at the end of surgery, and prolonged MV (PMV) in patients after OLT. METHODS:We retrospectively studied 93 consecutive patients who underwent OLT. We recorded preoperative data including spirometry, echocardiography, severity liver disease with the Model for End-Stage Liver Disease score, and the Child-Pugh classification scores. Intraoperatively, we performed hemodynamic measurements with transpulmonary thermodilution and pulmonary arterial catheters after the induction of anesthesia, 10 minutes before reperfusion, and at the end of surgery. Moreover, we recorded the length of surgery, the amount of IV volume infused, the results of blood coagulation analyses, and blood transfusion. Postoperatively, we recorded the duration of MV and intensive care unit length of stay, mortality, and graft function. Patients were then classified as requiring PMV (>48 hours after surgery) or not. Statistical analyses, preoperative and intraoperative variables between patients with and without PMV, were compared using Mann-Whitney U tests. Receiver-operating characteristic curves were used to evaluate the ability of preoperative and intraoperative variables to predict PMV. RESULTS:Twelve patients required PMV after surgery. Patients who required PMV exhibited increased ELWI (11.6 ± 3 mL/kg vs 9.3 ± 2 mL/kg, P = 0.0099) and PVPI values (2.94 ± 1 vs 1.8 ± 0.6, P = 0.000015) at the end of surgery. The areas under the receiver-operating characteristic curve were 0.890 ± 0.04 for PVPI with a 99% confidence interval of 0.782 to 0.958 and 0.730 ± 0.08 for ELWI with a 99% confidence interval of 0.594 to 0.839. Using a cutoff of 2.3 for PVPI allowed a sensitivity = 91.7%, a specificity = 83.8, a positive predictive value = 45.8%, and a negative predictive value = 98.5% for predicting PMV. A cutoff of 12 for ELWI allowed a sensitivity of 50%, specificity of 85%, positive predictive value of 33.3%, and negative predictive value of 91.9% for PMV. CONCLUSIONS:PVPI and ELWI values obtained at the end of OLT are useful for predicting the need for postoperative PMV.

Lidocaine Administration Controls MicroRNAs Alterations Observed After Lung Ischemia-Reperfusion Injury.

BACKGROUND:Ischemia–reperfusion injury (IRI) is associated with morbidity and mortality. MicroRNAs (miRNAs) have emerged as regulators of IRI, and they are involved in the pathogenesis of organ rejection. Lidocaine has proven anti-inflammatory activity in several tissues but its modulation of miRNAs has not been investigated. This work aims to investigate the involvement of miRNAs in lung IRI in a lung auto-transplantation model and to investigate the effect of lidocaine. METHODS:Three groups (sham, control, and Lidocaine), each comprising 6 pigs, underwent a lung autotransplantation. All groups received the same anesthesia. In addition, animals of lidocaine group received a continuous intravenous administration of lidocaine (1.5 mg/kg/h) during surgery. Lung biopsies were taken before pulmonary artery clamp, before reperfusion, 30 minutes postreperfusion (Rp-30), and 60 minutes postreperfusion (Rp-60). Samples were analyzed for different miRNAs (miR-122, miR-145, miR-146a, miR-182, miR-107, miR-192, miR-16, miR-21, miR-126, miR-127, miR142-5p, miR152, miR155, miR-223, and let7) via the use of reverse-transcription quantitative polymerase chain reaction. Results were normalized with miR-103. RESULTS:The expression of miR-127 and miR-16 did not increase after IRI. Let-7d, miR-21, miR-107, miR-126, miR-145, miR-146a, miR-182, and miR-192 significantly increased at the Rp-60 (control versus sham P < .001). miR-142-5p, miR-152, miR-155, and miR 223 significantly increased at the Rp-30 (control versus sham P < .001) and at the Rp-60 (control versus. sham P < .001). The administration of lidocaine was able to attenuate these alterations in a significant way (control versus Lidocaine P < .001). CONCLUSIONS:Lung IRI caused dysregulation miRNA. The administration of lidocaine reduced significantly miRNAs alterations.

Perioperative Predictors of Acute Kidney Injury after Liver Transplantation and its Impact on Postoperative Outcome

Background and Goal of Study Liver transplantation (LT) is the best treatment for patients with end-stage liver disease. It is a very complex surgery with high rates of morbidity and mortality. Acute kidney injury (AKI) is a common and serious complication after LT. The ability to early identify those patients at high risk of post-LT AKI is crucial, and could provide invaluable help for their proper management during and after LT surgery. The aim of this study was to identify perioperative predictors of post-LT AKI and to assess the impact of AKI on postoperative outcome. Materials and Methods After approval by the Ethical Review Board, we conducted a prospective, single-center study of 242 consecutive adult patients undergoing LT between December 2010 and February 2017. Early AKI was defined according to KDIGO criteria (Kidney Disease Improving Global Outcomes). Serum creatinine was measured at baseline and up to 3 post-LT days. Patients with and without AKI were compared to identify perioperative predictors for this complication. Perioperative variables were collected, including demographic data, baseline creatinine, MELD and Child-Pugh scores, intraoperative hemodynamic data, and transfusion and fluid therapy. Length of intensive care unit (ICU) stay, hospital-stay, 30-day mortality and one-year mortality were studied as postoperative outcomes. For data analysis Man Whitney, Chi-square or Fisher exact tests were used. Results and Discussion The incidence of AKI at 72 h post-LT was 63.6% (154 patients). Only four variables were identified as predictors of post-LT AKI: higher recipient weight, hemodynamic data at end of surgery (cardiac index [CI] and renal perfusion pressure [RPP=mean arterial pressure minus inferior vena cava pressure]) and the amount of intraoperative colloid administration (table 1). The remaining pre- and intra-operative variables did not differ significantly between the two groups. Table. No title available. AKI after liver transplantation was associated with worse post-LT course, with longer ICU and hospital stay, and reduced 30-day and one-year survival (table 2). Table. No title available. Conclusions In patients undergoing LT there was a high incidence of early AKI. Development of AKI after LT was associated with a remarkably worse postoperative outcome. These results suggest that higher intraoperative colloid administration, lower CI and lower RPP had a negative impact on post-LT renal function. Thus, targeting modifiable risk factors, such as fluid therapy and hemodynamic derangements may reduce the incidence of AKI.

Comportamento da variação do volume sistólico em pacientes hemodinamicamente estáveis durante cirurgia torácica com períodos de ventilação monopulmonar

INTRODUCTION In last few years, emphasis was placed in goal-directed therapy in order to optimize patients hemodynamic status and improve their prognosis. Parameters based on the interaction between heart and lungs have been questioned in situations like low tidal volume and open chest surgery. The goal of the study was to analyze the changes that one-lung ventilation can produce over stroke volume variation and to assess the possible impact of airway pressures and lung compliance over stroke volume variation. METHODS Prospective observational study, 112 patients undergoing lung resection surgery with one-lung ventilation periods were included. Intravenous fluid therapy with crystalloids was set at 2mL.kg-1.h-1. Hypotension episodes were treated with vasoconstrictive drugs. Two-lung ventilation was implemented with a TV of 8mL.kg-1 and one-lung ventilation was managed with a TV of 6mL.kg-1. Invasive blood pressure was monitored. We recorded the following cardiorespiratory values: heart rate, mean arterial pressure, cardiac index, stroke volume index, airway peak pressure, airway plateau pressure and static lung compliance at 3 different times during surgery: immediately after lung collapse, 30minutes after initiating one-lung ventilation and after restoration of two-lung ventilation. RESULTS Stroke volume variation values were influenced by lung collapse (before lung collapse14.6 (DS) vs. OLV 9.9% (DS), p < 0.0001); or after restoring two-lung ventilation (11.01 (DS), p < 0.0001). During two-lung ventilation there was a significant correlation between airwaypressures and stroke volume variation, however this correlation lacks during one-lung ventilation. CONCLUSION The decrease of stroke volume variation values during one-lung ventilation with protective ventilatory strategies advices not to use the same threshold values to determine fluid responsiveness.