Intraoperative Troponin Elevation in Liver Transplantation Is Independently Associated With Mortality: A Prospective Observational Study.

Intraoperative factors implicated in postoperative mortality after liver transplantation (LT) are poorly understood. Because LT is a particularly demanding procedure, we hypothesized that intraoperative myocardial injury may be frequent and independently associated with early postoperative outcomes. We aimed to determine the association between intraoperative high-sensitivity troponin (hsTn) elevation during LT and 30-day postoperative mortality. A total of 203 adult patients undergoing LT were prospectively included in the cohort and followed during 1 year. Advanced hemodynamic parameters and serial high-sensitivity troponin T (hsTnT) measurements were assessed at 6 intraoperative time points. The optimal hsTnT cutoff level for intraoperative troponin elevation (ITE) was identified. Patients were classified into 2 groups according to the presence of ITE. Independent impact of ITE on survival was assessed through survival curves and multivariate Cox regression analysis. Intraoperative cardiac function was compared between groups. Troponin levels increased early during surgery in the ITE group. Troponin values at abdominal closure were associated with 30-day mortality (area under the receiver operating caracteristic curve, [AUROC], 0.73; P = 0.005). Patients with ITE showing values of hsTnT ≥61 ng/L at abdominal closure presented higher 30-day mortality (29.6% versus 3.4%; P < 0.001). ITE was independently associated with 30-day mortality (hazard ratio, 3.8; 95% confidence interval, 1.1-13.8; P = 0.04) and with worse overall intraoperative cardiac function. The hsTnT upper reference limit showed no discriminant capacity during LT. Intraoperative myocardial injury identified by hsTn elevation is frequently observed during LT, and it is associated with myocardial dysfunction and short-term mortality. Determinations of hsTn may serve as a valuable intraoperative monitoring tool during LT.

Protective Role of Hepatocyte Cyclooxygenase-2 Expression Against Liver Ischemia-Reperfusion Injury in Mice.

Liver ischemia and reperfusion injury (IRI) remains a serious clinical problem affecting liver transplantation outcomes. IRI causes up to 10% of early organ failure and predisposes to chronic rejection. Cyclooxygenase-2 (COX-2) is involved in different liver diseases, but the significance of COX-2 in IRI is a matter of controversy. This study was designed to elucidate the role of COX-2 induction in hepatocytes against liver IRI. In the present work, hepatocyte-specific COX-2 transgenic mice (hCOX-2-Tg) and their wild-type (Wt) littermates were subjected to IRI. hCOX-2-Tg mice exhibited lower grades of necrosis and inflammation than Wt mice, in part by reduced hepatic recruitment and infiltration of neutrophils, with a concomitant decrease in serum levels of proinflammatory cytokines. Moreover, hCOX-2-Tg mice showed a significant attenuation of the IRI-induced increase in oxidative stress and hepatic apoptosis, an increase in autophagic flux, and a decrease in endoplasmic reticulum stress compared to Wt mice. Interestingly, ischemic preconditioning of Wt mice resembles the beneficial effects observed in hCOX-2-Tg mice against IRI due to a preconditioning-derived increase in endogenous COX-2, which is mainly localized in hepatocytes. Furthermore, measurement of prostaglandin E2 (PGE2 ) levels in plasma from patients who underwent liver transplantation revealed a significantly positive correlation of PGE2 levels and graft function and an inverse correlation with the time of ischemia. Conclusion: These data support the view of a protective effect of hepatic COX-2 induction and the consequent rise of derived prostaglandins against IRI.

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.

Systemic and alveolar inflammatory response in the dependent and nondependent lung in patients undergoing lung resection surgery: A prospective observational study.

BACKGROUND: Measurement of inflammatory mediators in bronchoalveolar lavage (BAL) during lung resection surgery with periods of one-lung ventilation (OLV) has revealed an intense local pulmonary response. The role of each lung in the inflammation that occurs during this procedure has never been investigated. OBJECTIVE(S): The primary objective of our study was to compare the inflammatory response in the dependent lung with that of the nondependent lung by measuring inflammatory markers in BAL. Our secondary objective was to assess the behaviour of these inflammatory mediators in patients with and without postoperative pulmonary complications (PPCs). DESIGN: A prospective, observational study. SETTING: Department of Anaesthesiology in a university hospital. PATIENTS: Forty-six consecutive patients undergoing lung resection surgery. INTERVENTION(S): BAL samples were taken from dependent and nondependent lung 10 min before initiating OLV and at the end of OLV (once two-lung ventilation was established). All patients were followed up until 30 days after surgery. MAIN OUTCOME MEASURES: The concentration of cytokines [interleukin (IL)-1, IL-2, IL-6, IL-10, tumour necrosis factor-alpha (TNF-α)], nitric oxide, carbon monoxide and matrix metalloproteinase 2 (MMP-2) was analysed in both lungs before and after OLV. PPCs were recorded. RESULTS: In BAL fluid, all measured biomarkers, apart from IL-10, were significantly greater (P < 0.05) at the end of OLV than those obtained before OLV, both for the dependent and nondependent lung. The increase in measured biomarkers was similar in both lungs. Eight patients developed PPC. Patients who developed PPC had higher levels of TNF-α (P < 0.05) in BAL from the nondependent lung before and after OLV than patients who did not have PPC. Patients who developed PPC had a smaller increase in MMP-2 levels (P < 0.05) in the dependent lung than patients who did not have PPC. CONCLUSION: In lung resection surgery, the inflammatory response is similar in both lungs. However, the greater increase in TNF-α levels in the nondependent lung and the smaller increase of MMP-2 concentration in the dependent lung may increase the susceptibility to develop PPC.

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.

The link between high factor VIII to protein C ratio values and poor liver function after major hepatectomy.

Our goal was to assess the coagulation profile in the immediate postoperative time after major liver surgery and its association with the liver function. Our hypothesis is that a decreased synthesis of the coagulation factor levels reflects an impaired liver synthesis following hepatic resection and will be associated with poor outcomes. This is a prospective, observational study recruiting consecutive patients scheduled for major liver resection in a tertiary hospital. Coagulation profile was assessed by conventional assays, viscoelastic assays and coagulation factor levels preoperatively and, on postoperative days 1, 2 and 6. Factor VIII to protein C (FVIII/PC) ratio has been used as a surrogate marker of hemostatic imbalance. Liver function was measured with conventional and indocyanine green (ICG) clearance tests, which were obtained preoperatively and on postoperative days 1 and 2. Sixty patients were recruited and 51 were included in the study. There is a clear increase in FVIII/PC ratio after surgery, which was significantly associated with low liver function, being more pronounced beyond postoperative day 2 and in patients with poorer liver function ( P  < 0.001). High FVIII/PC ratio values were significantly associated with higher postoperative morbidity, prolonged ICU and hospital stay and less survival ( P  < 0.05). High FVIII/PC ratio on postoperative day 2 was found to be predictor of posthepatectomy liver failure (PHLF; area under the ROC curve = 0.8129). Early postoperative high FVIII/PC ratio values are associated with low liver function, PHLF and poorer outcomes in patients undergoing major hepatic resection.

Usefulness of Indocyanine Green Plasma Disappearance Rate in Liver Donors and Recipients: A Prospective Observational Study.

BACKGROUND: Determination of indocyanine green (ICG) plasma disappearance rate (PDR) is a simple, inexpensive, and noninvasive tool to assess liver perfusion, absorption, and elimination. Its application in the liver transplant process has not been widely incorporated in clinical practice. This study aims to assess the usefulness of ICG PDR in the donor selection setting and in the early post-transplant phase and to analyze its variation between these 2 time points. METHODS: We performed a single-center prospective observational study. ICG clearance test was performed in 50 brain-dead donors (T0-PDR) to assess concordance with graft suitability. Rejected grafts biopsy specimens were analyzed to correlate histology with T0-PDR. In the recipients, ICG PDR was performed before wound closure (T1-PDR). The association of T0, T1, and T0-T1 variation with the development of early allograft dysfunction (EAD) was investigated. RESULTS: A total of 23 of 50 grafts were discarded because of poor macroscopic quality. A T0-PDR below 15.5%/min could predict graft rejection with 100% specificity and 69.6% sensitivity. All the biopsy specimens from donors with PDR < 10 %/min showed liver fibrosis. A total of 25 of the remaining 27 grafts were implanted; 5 patients (20%) developed EAD. T1-PDR performed better than T0-T1 variation to predict dysfunction. CONCLUSIONS: ICG PDR could be used in the donors as a filter to discard poor-quality grafts before procurement and, in the early post-transplant phase, to predict EAD.

Mechanisms of regenerative preconditioning in pigs with subtotal hepatectomies.

BACKGROUND: Portal vein occlusion shortly before extended hepatic resections has hepatoprotective properties, but its molecular effects have not been elucidated. We characterized the impact of regenerative preconditioning by portal vein embolization (PVE) on hepatic energy metabolism and cytokine expression. MATERIALS AND METHODS: About 90% hepatectomies were performed in normal pigs (Control) and in pigs that underwent a PVE 24 h before the surgery (n = 10/group). Blood biochemistry and coagulation, liver damage, liver function (ICG), hepatic content of adenine nucleotides, and hepatic expression of inflammatory mediators (RT-PCR and WB) were determined before the hepatectomy, 15 min, and 24 h later. RESULTS: All PVE and hepatectomies were successfully accomplished. The 90% hepatectomy resulted in: Immediate reduction of ATP, leading to persistent decreases of energy load and ATP/ADP ratio up to the 24-h time-point; and pro-inflammatory expression profile of cytokines in the remnant liver. Prior performance of PVE attenuated the bioenergetic alterations and prevented many of the changes in hepatic cytokine expression. CONCLUSIONS: Regenerative preconditioning by PVE improved hepatic energy metabolism and modulated inflammatory mediators in the remnant liver in pigs undergoing major hepatectomies, potentially contributing to its hepatoprotective effects.

INTRODUCCIÓN: la oclusión de la vena porta precoz antes de hepatectomías extendidas tiene propiedades hepatoprotectoras, pero sus efectos moleculares no se han aclarado. Caracterizamos el impacto del preacondicionamiento regenerativo por embolización de la vena porta (PVE) sobre el metabolismo energético hepático y la expresión de citocinas. MATERIALES Y MÉTODOS: Realizamos hepatectomías del 90% en cerdos (Control) y en cerdos sometidos a PVE 24 horas antes de la cirugía (n = 10/grupo). La bioquímica y la coagulación, el daño hepático, la función hepática (ICG), los nucleótidos de adenina y la expresión de mediadores inflamatorios (RT-PCR y WB) fueron determinado antes de la hepatectomía, quince minutos y 24 horas después. RESULTADOS: Las PVE y las hepatectomías se realizaron con éxito. La hepatectomía del 90% resultó en: una reducción del ATP, lo que disminuye la carga energética y la relación ATP/ADP a las 24 horas; y en la expresión de citocinas proinflamatorias. La realización previa de PVE atenuó las alteraciones bioenergéticas y evitó muchos de los cambios en la expresión de citocinas. CONCLUSIONES: El preacondicionamiento regenerativo con PVE mejoró el metabolismo energético y moduló los mediadores inflamatorios en el hígado remanente en cerdos sometidos a hepatectomías subtotales, contribuyendo potencialmente a sus efectos hepatoprotectores.

"Small-for-Flow" Syndrome: Concept Evolution.

BACKGROUND: The "Small-for-Size" syndrome is defined as a liver failure after a liver transplant with a reduced graft or after a major hepatectomy. The later coined "Small-for-Flow" syndrome describes the same situation in liver resections but based on hemodynamic intraoperative parameters (portal pressure > 20 mmHg and/or portal flow > 250 ml/min/100 g). This focuses on the damage caused by the portal hyperafflux related to the volume of the remnant. METHODS: Relevant studies were reviewed using Medline, PubMed, and Springer databases. RESULTS: Portal hypertension after partial hepatectomies also leads to a higher morbidity and mortality. There are plenty of experimental studies focusing on flow rather than size. Some of them also perform different techniques to modulate the portal inflow. The deleterious effect of high posthepatectomy portal venous pressure is known, and that is why the idea of portal flow modulation during major hepatectomies in humans is increasing in everyday clinical practice. CONCLUSIONS: Considering the extensive knowledge obtained with the experimental models and good results in clinical studies that analyze the "Small-for-Flow" syndrome, we believe that measuring portal flow and portal pressure during major liver resections should be performed routinely in extended liver resections. Applying these techniques, the knowledge of hepatic hemodynamics would be improved in order to advance against posthepatectomy liver failure.

Early noninvasive measurement of the indocyanine green plasma disappearance rate accurately predicts early graft dysfunction and mortality after deceased donor liver transplantation.

Early diagnosis of graft dysfunction in liver transplantation is essential for taking appropriate action. Indocyanine green clearance is closely related to liver function and can be measured noninvasively by spectrophotometry. The objectives of this study were to prospectively analyze the relationship between the indocyanine green plasma disappearance rate (ICGPDR) and early graft function after liver transplantation and to evaluate the role of ICGPDR in the prediction of severe graft dysfunction (SGD). One hundred seventy-two liver transplants from deceased donors were analyzed. Ten patients had SGD: 6 were retransplanted, and 4 died while waiting for a new graft. The plasma disappearance rate was measured 1 hour (PDRr60) and within the first 24 hours (PDR1) after reperfusion, and it was significantly lower in the SGD group. PDRr60 and PDR1 were excellent predictors of SGD. A threshold PDRr60 value of 10.8%/minute and a PDR1 value of 10%/minute accurately predicted SGD with areas under the receiver operating curve of 0.94 (95% confidence interval, 0.89-0.97) and 0.96 (95% confidence interval, 0.92-0.98), respectively. In addition, survival was significantly lower in patients with PDRr60 values below 10.8%/minute (53%, 47%, and 47% versus 95%, 94%, and 90% at 3, 6, and 12 months, respectively) and with PDR1 values below 10%/minute (62%, 62%, and 62% versus 94%, 92%, and 88%). In conclusion, very early noninvasive measurement of ICGPDR can accurately predict early severe graft dysfunction and mortality after liver transplantation.

The impact of lung recruitment on hemodynamics during one-lung ventilation.

OBJECTIVE: The objective of the present study was to investigate respiratory and hemodynamic changes by measuring continuous cardiac output, cardiac filling, and stroke volume variation after lung recruitment in thoracic surgery. DESIGN: A prospective, observational study. SETTING: A tertiary care university hospital single institution. PARTICIPANTS: Forty patients undergoing thoracotomy for lung resection with at least 1 hour of one-lung ventilation (OLV). INTERVENTIONS: During OLV, an alveolar recruitment maneuver (ARM) was performed. MEASUREMENTS AND MAIN RESULTS: Based on Edwards Vigileo/FloTrac system (Edwards Lifesciences, Irvine, CA), the arterial pressure-based cardiac output, cardiac index, systemic vascular resistance, stroke volume variation, and central venous oxygen saturation were recorded immediately before the maneuver and 1, 2, 3, 4, 5, and 10 minutes after the maneuver. Stroke volume variation was the parameter most affected during and after the maneuver; it increased to 50% and 40% in the first and second minute, respectively (p < 0.01). The cardiac index was also affected and decreased 9.4% (p < 0.05) in the first minute after the maneuver. ScvO2 decreased significantly during the first 2 minutes (7% and 6.5%, respectively). However, after 3 minutes, all values recorded were similar to prerecruitment values. The PaO2 and PcvO2 from samples taken 10 minutes after the maneuver improved considerably with respect to the values before alveolar recruitment. CONCLUSIONS: The authors concluded that during open-chest surgery with OLV, an ARM effectively improved oxygenation without inducing important circulatory changes.

Effects of ventilatory mode during one-lung ventilation on intraoperative and postoperative arterial oxygenation in thoracic surgery.

OBJECTIVE: The purpose of this study was to investigate the relationship between the ventilatory mode used during one-lung ventilation (OLV) and intraoperative and early postoperative arterial oxygenation in patients undergoing thoracic surgery. METHODS: A prospective, randomized clinical trial. SETTING: A tertiary care university hospital single institution. PARTICIPANTS: One hundred ten patients scheduled for thoracic surgery with at least 1 hour of OLV. INTERVENTIONS: Patients were prospectively randomized into 2 groups depending on the ventilatory mode used during OLV: volume-controlled ventilation (VCV) or pressure-controlled ventilation (PCV). In VCV, the authors used a tidal volume (Vt) of 8 mL/kg and in the PCV group an inspiratory pressure to provide a tidal volume of 8 mL/kg. MEASUREMENTS AND MAIN RESULTS: Airway pressures and arterial blood gases were obtained at 20, 30, and 40 minutes after OLV. The authors recorded the ratio of arterial oxygen tension to inspired oxygen fraction (PaO(2)/F(I)O(2)) at 4 hours (RU1) and 24 hours (RU2) after surgery. During OLV, there were no differences in arterial oxygenation, airway plateau pressure, and mean pressure between groups, although peak pressure was higher in the VCV group (p < 0.01). The PaO(2)/F(I)O(2) ratio at RU1 was 312.6 +/- 106 in the VCV group and 322.1 +/- 104. In the PCV group at RU2, it was 402.4 +/- 105 and 389.6 +/- 114, respectively, and there were no significant differences between the groups. CONCLUSIONS: In patients undergoing thoracic surgery, the use of PCV compared with VCV during OLV with the same Vt of 8 mL/kg does not affect arterial oxygenation during OLV or early postoperative oxygenation.

Hepatic flow is an intraoperative predictor of early allograft dysfunction in whole-graft deceased donor liver transplantation: An observational cohort study.

BACKGROUND: Early allograft dysfunction (EAD) after liver transplantation (LT) is an important cause of morbidity and mortality. To ensure adequate graft function, a critical hepatocellular mass is required in addition to an appropriate blood supply. We hypothesized that intraoperative measurement of portal venous and hepatic arterial flow may serve as a predictor in the diagnosis of EAD. AIM: To study whether hepatic flow is an independent predictor of EAD following LT. METHODS: This is an observational cohort study in a single institution. Hepatic arterial blood flow and portal venous blood flow were measured intraoperatively by transit flow. EAD was defined using the Olthoff criteria. Univariate and multivariate analyses were used to determine the intraoperative predictors of EAD. Survival analysis and prognostic factor analysis were performed using the Kaplan-Meier and Cox regression models. RESULTS: A total of 195 liver transplant procedures were performed between January 2008 and December 2014 in 188 patients. A total of 54 (27.7%) patients developed EAD. The median follow-up was 39 mo. Portal venous flow, hepatic arterial flow (HAF) and total hepatic arterial flow were associated with EAD in both the univariate and multivariate analyses. HAF is an independent prognostic factor for 30-d patient mortality. CONCLUSION: Intraoperative measurement of blood flow after reperfusion appears to be a predictor of EAD; Moreover, HAF should be considered a predictor of 30-d patient mortality.

Comprehensive Characterization of a Porcine Model of The "Small-for-Flow" Syndrome.

INTRODUCTION: The term "Small-for-Flow" reflects the pathogenetic relevance of hepatic hemodynamics for the "Small-For-Size" syndrome and posthepatectomy liver failure. We aimed to characterize a large-animal model for studying the "Small-for-Flow" syndrome. METHODS: We performed subtotal (90%) hepatectomies in 10 female MiniPigs using a simplified transection technique with a tourniquet. Blood tests, hepatic and systemic hemodynamics, and hepatic function and histology were assessed before (Bas), 15 min (t-15 min) and 24 h (t-24 h) after the operation. Some pigs underwent computed tomography (CT) scans for hepatic volumetry (n = 4) and intracranial pressure (ICP) monitoring (n = 3). Postoperative care was performed in an intensive care unit environment. RESULTS: All hepatectomies were successfully performed, and hepatic volumetry confirmed liver remnant volumes of 9.2% [6.2-11.2]. The hepatectomy resulted in characteristic hepatic hemodynamic alterations, including portal hyperperfusion, relative decrease of hepatic arterial blood flow, and increased portal pressure (PP) and portal-systemic pressure gradient. The model reproduced major diagnostic features including the development of cholestasis, coagulopathy, encephalopathy with increased ICP, ascites, and renal failure, hyperdynamic circulation, and hyperlactatemia. Two animals (20%) died before t-24 h. Histological liver damage was observed at t-15 min and at t-24 h. The degree of histological damage at t-24 h correlated with intraoperative PP (r = 0.689, p = 0.028), hepatic arterial blood flow (r = 0.655, p = 0.040), and hepatic arterial pulsatility index (r = 0.724, p = 0.066). All animals with intraoperative PP > 20 mmHg presented liver damage at t-24 h. CONCLUSION: The present 90% hepatectomy porcine experimental model is a feasible and reproducible model for investigating the "Small-for-Flow" syndrome.

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.

Cardiac dysfunction during liver transplantation: incidence and preoperative predictors.

BACKGROUND: The aim was to investigate the cardiac response during liver transplantation (LT) and analyze its relationship with clinical factors, echocardiographic, and hemodynamic findings. METHODS: All patients undergoing LT for cirrhosis from 1998 to 2004 were included. Clinical data, comprehensive echocardiography, hepatic, and right heart hemodynamic measurements were analyzed. During LT patients underwent continuous right-heart pressure monitorization. Measurements 10 min after reperfusion were compared with baseline values. Abnormal cardiac response was defined as a decrease in left ventricular stroke work index despite a rise in pulmonary wedge capillary pressure. Predictors of abnormal cardiac response were investigated using logistic regression. RESULTS: Data were available from 209 patients (mean age 52 (9) yrs; Child A 27; B 93; C 89) with a mean model for end-stage liver disease score 16.3 (4.7). Abnormal cardiac response was observed in 47 (22.5%) patients after reperfusion. Patients who developed this response had hyponatremia, lower central venous pressure, lower pulmonary artery pressure, and lower pulmonary wedged capillary pressure. Abnormal cardiac response was related to a longer postoperative intubation time. CONCLUSION: Abnormal cardiac response is observed during LT and may be a manifestation of occult cirrhotic cardiomyopathy. This finding is underestimated with usual diagnostic tools and could be related to indirect signs of circulatory dysfunction of advanced liver disease.

Comparison of the hemodynamic effects of a single 5 mg/kg dose of lidocaine with or without epinephrine for thoracic paravertebral block.

BACKGROUND AND OBJECTIVES: Epinephrine is often added to local anesthetic solutions to minimize and slow the systemic absorption of local anesthetics, and thus reduce the possibility of adverse effects of these drugs. In an earlier study we found that the injection of 5 mg/kg of lidocaine via the paravertebral route depressed myocardial contractility by up to 30%, with practically no changes in heart rate or blood pressure. In the present study we investigated whether these alterations are due to systemic absorption of the local anesthetic, and whether such absorption can be minimized by adding epinephrine to the local anesthetic solution. METHODS: A prospective, blind, and randomized study was made of 50 patients subjected to lung resection surgery. The subjects were divided into two groups: Lid group (5 mg/kg bolus dose of lidocaine in the thoracic paravertebral space) and Lid+E group (addition of 5 mcg/mL of epinephrine to the local anesthetic). The anesthetic solution was administered through a paravertebral catheter ipsilateral to the operative side. In addition to routine hemodynamic monitoring (heart rate and radial artery blood pressure), an aortic transpulmonary thermodilution catheter was inserted into the femoral artery for recording of the following variables: cardiac index, cardiac function index, maximum pressure derivative, global end diastolic volume, and intrathoracic total blood volume index. Data collection was carried out immediately before administration of the anesthetic solution and 15, 30, and 45 minutes after administration. Measurements were made of the plasma lidocaine levels at those same postparavertebral injection time points. RESULTS: Prior to paravertebral dosing there were no differences in terms of the hemodynamic variables studied. However, 15 minutes after dosing in the Lid+E group, lesser reductions in contractility, cardiac function index, and cardiac index were recorded, compared with the Lid group, with a significant reduction in cardiac filling volumes. Blood lidocaine levels were 53% and 34% lower in Lid+E group, as recorded 15 and 30 minutes after injection. The patients who, 15 minutes after paravertebral injection, had blood lidocaine levels greater than 3 mcg/mL (independently of the type of anesthetic solution used) had a significant reduction in mean blood pressure, cardiac function index, cardiac index, and maximum pressure derivative, compared with the patients with lower blood lidocaine concentrations. CONCLUSIONS: Addition of epinephrine to lidocaine when performing thoracic paravertebral block, attenuates the cardiodepressive effects associated with the systemic absorption of lidocaine and also, as a result of the beta-adrenergic consequences of epinephrine, systemic absorption from the paravertebral space.

[Behaviour of stroke volume variation in hemodynamic stable patients during thoracic surgery with one-lung ventilation periods]. / 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 patient's 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.

[Deep versus moderate neuromuscular block during one-lung ventilation in lung resection surgery]. / Bloqueio neuromuscular profundo versus moderado durante a ventilação monopulmonar em cirurgia de ressecção pulmonar.

BACKGROUND AND OBJECTIVES: Neuromuscular relaxants are essential during general anesthesia for several procedures. Classical anesthesiology literature indicates that the use of neuromuscular blockade in thoracic surgery may be deleterious in patients in lateral decubitus position in one-lung ventilation. The primary objective of our study was to compare respiratory function according to the degree of patient neuromuscular relaxation. Secondary, we wanted to check that neuromuscular blockade during one-lung ventilation is not deleterious. METHODS: A prospective, longitudinal observational study was made in which each patient served as both treated subject and control. 76 consecutive patients programmed for lung resection surgery in Gregorio Marañon Hospital along the year of 2013 who required one-lung ventilation in lateral decubitus were included. Ventilator data, hemodynamic parameters were registered in different moments according to train-of-four response (intense, deep and moderate blockade) during one-lung ventilation. RESULTS: Peak, plateau and mean pressures were significantly lower during the intense and deep blockade. Besides, compliance and peripheral oxygen saturation were significantly higher in those moments. Heart rate was significantly higher during deep blockade. No mechanical ventilation parameters were modified during measurements. CONCLUSIONS: Deep neuromuscular blockade attenuates the poor lung mechanics observed during one-lung ventilation.

Preconditioning by portal vein embolization modulates hepatic hemodynamics and improves liver function in pigs with extended hepatectomy.

BACKGROUND: Portal vein embolization is performed weeks before extended hepatic resections to increase the future liver remnant and prevent posthepatectomy liver failure. Portal vein embolization performed closer to the operation also could be protective, but worsening of portal hyper-perfusion is a major concern. We determined the hepatic hemodynamic effects of a portal vein embolization performed 24 hours prior to hepatic operation. METHODS: An extended (90%) hepatectomy was performed in swine undergoing (portal vein embolization) or not undergoing (control) a portal vein embolization 24 hours earlier (n = 10/group). Blood tests, hepatic and systemic hemodynamics, hepatic function (plasma disappearance rate of indocyanine green), liver histology, and volumetry (computed tomographic scanning) were assessed before and after the hepatectomy. Hepatocyte proliferating cell nuclear antigen expression and hepatic gene expression also were evaluated. RESULTS: Swine in the control and portal vein embolization groups maintained stable systemic hemodynamics and developed similar increases of portal blood flow (302 ± 72% vs 486 ± 92%, P = .13). Portal pressure drastically increased in Controls (from 9.4 ± 1.3 mm Hg to 20.9 ± 1.4 mm Hg, P < .001), while being markedly attenuated in the portal vein embolization group (from 11.4 ± 1.5 mm Hg to 16.1 ± 1.3 mm Hg, P = .061). The procedure also improved the preservation of the hepatic artery blood flow, liver function, and periportal edema. These effects occurred in the absence of hepatocyte proliferation or hepatic growth and were associated with the induction of the vasoprotective gene Klf2. CONCLUSION: Portal vein embolization preconditioning represents a potential hepato-protective strategy for extended hepatic resections. Further preclinical studies should assess its medium-term effects, including survival. Our study also supports the relevance of hepatic hemodynamics as the main pathogenetic factor of post-hepatectomy liver failure.