Anaesthesiological strategies to improve outcome in liver transplantation recipients.

Graft and patients survival are the main goal of anesthesiological management in patients undergoing liver transplantation (LT). Even if anesthesiological practice sustained major developments over time, some evidence-based intraoperative strategies have not yet been widely applied. The aim of this review was to summarize intraoperative anesthesiological strategies which could have the potential to improve LT graft and/or recipient survival. Monitoring must be as accurate as possible in order to manage intraoperative hemodynamic changes. The pulmonary artery catheter still represents the more reliable method to monitor cardiac output by using the intermittent bolus thermodilution technique. Minimally invasive hemodynamic monitoring devices may be considered only in stable cirrhotic patients. Goal-directed fluid-therapy has not yet defined for LT, but it could have a role in optimizing the long-term sequelae associated with volume depletion or overload. The use of vasopressor may affect LT recipient's outcome, by preventing prolonged hypotension, decreasing blood products transfusion and counteracting hepato-renal syndrome. The use of viscoelastic point of care is also warranted in order to reduce blood products requirements. Decreasing mechanical ventilation time, when it is feasible, may considerably improve survival. Finally, monitoring the depth of anesthesia when integrated into an early extubation protocol might have a positive effect on graft function.

Auditory cortex involvement in emotional learning and memory.

Emotional memories represent the core of human and animal life and drive future choices and behaviors. Early research involving brain lesion studies in animals lead to the idea that the auditory cortex participates in emotional learning by processing the sensory features of auditory stimuli paired with emotional consequences and by transmitting this information to the amygdala. Nevertheless, electrophysiological and imaging studies revealed that, following emotional experiences, the auditory cortex undergoes learning-induced changes that are highly specific, associative and long lasting. These studies suggested that the role played by the auditory cortex goes beyond stimulus elaboration and transmission. Here, we discuss three major perspectives created by these data. In particular, we analyze the possible roles of the auditory cortex in emotional learning, we examine the recruitment of the auditory cortex during early and late memory trace encoding, and finally we consider the functional interplay between the auditory cortex and subcortical nuclei, such as the amygdala, that process affective information. We conclude that, starting from the early phase of memory encoding, the auditory cortex has a more prominent role in emotional learning, through its connections with subcortical nuclei, than is typically acknowledged.

Minimum alveolar concentration threshold of sevoflurane for postoperative dream recall.

BACKGROUND: Many factors affect postoperative dream recall, including patient characteristics, type of anesthesia, timing of postoperative interview and stress hormone secretion. Aims of the study were to determine whether Bispectral Index (BIS)-guided anesthesia might decrease sevoflurane minimum alveolar concentration (MAC) when compared with hemodynamically-guided anesthesia, and to search for a MAC threshold useful for preventing arousal, dream recall and implicit memory. METHODS: One hundred thirty patients undergoing elective thyroidectomy were enrolled. Anesthesia was induced with propofol 2 mg kg(-1), fentanyl 3 mcg kg(-1) and cis-atracurium 0.15 mg kg(-1). For anesthesia maintenance, patients were randomly assigned to one of two groups: a BIS-guided group in which sevoflurane MAC was adjusted on the basis of BIS values, and a hemodynamic parameters (HP)-guided group in which MAC was adjusted based on HP. An auditory recording was presented to patients during anesthesia maintenance. Dream recall and explicit/implicit memory were investigated upon awakening and approximately after 24 h. RESULTS: Mean sevoflurane MAC during auditory presentation was similar in the two groups (0.85 ± 0.16 and 0.87 ± 0.17 [P = 0.53] in BIS-guided and HP-guided groups, respectively). Frequency of dream recall was similar in the two groups: 27% (N. = 17) in BIS-guided group, 18% (N. = 12) in HP-guided group, P = 0.37. In both groups, dream recall was less probable in patients anesthetized with MAC values ≥ 0.9 (area under ROC curve = 0.83, sensitivity = 90%, and specificity = 49%). CONCLUSION: BIS-guided anesthesia was not able to generate different MAC values compared to HP-guided anesthesia. Independent of the guide used for anesthesia, a sevoflurane MAC over 0.9 was required to prevent postoperative dream recall.

Update on post-traumatic stress syndrome after anesthesia.

BACKGROUND: Between 0.5% and 2% of surgical patients undergoing general anesthesia may experience awareness with explicit recall. These patients are at a risk for developing anxiety symptoms which may be transient or can lead to post-traumatic stress disorder (PTSD). AIM: The aim of this review was to assess the prevalence of PTSD after intraoperative awareness episodes and analyze patients' complaints, type and timing of assessment used. METHODS: PubMed, MEDLINE and The Cochrane Library were searched up until October 2012. Prospective and retrospective studies on human adult subjects describing prevalence of PTSD and/or psychological sequalae after awareness episodes were included. RESULTS: Seven studies were identified. Prevalence of PTSD ranged from 0 to 71%. Acute emotions such as fear, panic, inability to communicate and feeling of helplessness were the only patients' complaints that were significantly correlated to psychological sequelae including PTDS. There were cases that reported psychological symptoms after 2-6 hours from awakening (%) or 30 days after (%). Previous studies used psychological scales lacking of dissociation assessment. CONCLUSIONS: Whenever an awareness episode is suspected, a psychological assessment with at least three interviews at 2-6 h, 2-36 h and 30 days must be performed in order to collect symptoms associated with both early and delayed retrieval of traumatic event. As a dissociative state could hide the expression of reactive symptoms after intraoperative awareness, future studies should be focused on detecting dissociative symptoms in order to carry out a prompt and appropriate treatment aimed at avoiding long-term psychological disability.

Effects of training periodization on cardiac autonomic modulation and endogenous stress markers in volleyball players.

We investigated the effects of selective loads of periodization model (SLPM) on autonomic modulation of heart rate variability (HRV) and endogenous stress markers before and after a competition period in volleyball players (N=32). The experimental protocol for the evaluation of HRV consisted of using spectral analysis of time series composed of the R-R intervals derived from electrocardiogram obtained in the supine position and during the tilt test. Stress marker levels were determined by quantifying the plasma concentration of endogenous catecholamines, cortisol and free testosterone. The results showed no changes between the levels of HRV before and after a competition period. In contrast, the quantification of the plasma concentration of endogenous stress markers revealed reductions in the levels of total catecholamines, noradrenaline and cortisol. These changes were accompanied by increases in the concentration of free testosterone and in the testosterone/cortisol ratio. In conclusion, our results demonstrate that the SLPM did not change the cardiac autonomic modulation of HRV, but promoted beneficial adaptations in athletes, including positive changes in the plasma concentration of the endogenous stress markers. The absence of changes in HRV indicates that there is no direct relationship between cardiac autonomic modulation and endogenous stress markers in the present study.

Low values of left ventricular ejection time in the post-anhepatic phase may be associated with occurrence of primary graft dysfunction after orthotopic liver transplantation: results of a single-centre case-control study.

BACKGROUND: Previous investigations on risk factors for orthotopic liver transplantation (OLT) surgery have not analyzed hemodynamic aberrations in great detail. Moreover, the usefulness of esophageal Doppler monitoring has not been extensively studied in this clinical setting. The aim of this study was to evaluate if the occurrence of primary graft dysfunction (PGD) may be anticipated by hemodynamic indexes measured by esophageal Doppler (ED) monitoring system as well as by pulmonary artery catheter (PAC) in patients undergoing OLT. MATERIALS AND METHODS: 38 OLT recipients were studied. Patients with acute liver failure or having non treated esophageal varices and those transplanted with marginal donors were excluded from the study. The haemodynamic data - measured by ED monitoring system (HemosonicTM 100, Arrow, OK, USA) and PAC - collected at the following 3 time points were considered for statistical analysis: 30 minutes after the induction of anesthesia but before skin incision, T0; 20 minutes after liver dissection, T1; at the beginning of biliary reconstruction, T2. On the basis of early outcome (72 hours after OLT), patients were distinguished into two groups: those with PGD (grade III-IV of Toronto classification) and those without PGD (grade I-II). RESULTS: LVETc (left ventricular ejection time) values, registered at the beginning of biliary reconstruction (T2), were lower in patients with PGD compared to those without PGD (p < 0.000), while there were no differences in hemodynamic parameters derived from PAC between the two groups. CONCLUSIONS: Since LVETc is related to preload, the results of this study would suggest that normovolemia could be the end point of a fluid replacement strategy in OLT setting.

Use of an esophageal echo-Doppler device during liver transplantation: preliminary report.

Determination of cardiac output (CO) is crucial for perioperative monitoring of orthotopic liver transplant (OLT) recipients. A pulmonary artery catheter (PAC) has always been considered the "gold standard" of hemodynamic monitoring. The aim of this study was to evaluate the suitability of a transesophageal echo-Doppler device (ED) as a minimally invasive device to measure CO in OLT. ED was compared with the standard PAC technique taking into account the disease severity of OLT recipients as defined by the model for end-stage liver disease (MELD) score. We enrolled 42 cirrhotic patients scheduled for OLT 3 thermodilution CO measurements were taken by a PAC and the most recent ED measurement (CO(ED)) was also recorded. Paired measurements of CO were performed at standard times, unless there were additional clinical needs. Recipients were stratified into 3 groups according to MELD score: MELD score < or = 15 (14 patients); MELD score between 16 and 28 (17 patients); and MELD score > or = 29 (11 patients). We performed 495 paired measurements of CO. Mean bias was 0.34 +/- 0.9 L/min and limits of agreement were -1.46 and 2.14 L/min. In patients with MELD score <15, the bias was 0.12 +/- 0.55. The ED results were not interchangeable with PAC, because of the large limits of agreement. However, in cirrhotic patients with MELD scores <15, the precision of the new method was similar to that of PAC; therefore, in this subset of patients, it may represent a reliable alternative to PAC.

Weight loss and quality of life improvement in obese subjects treated with sibutramine: a double-blind randomized multicenter study.

BACKGROUND AND AIM: Obesity affects cardiovascular risk and also quality of life (QoL). The aim of this study was to test weight loss and impact on QoL after sibutramine treatment in obese subjects. METHODS: Double-blind randomized trial on 309 outpatients (51 males, 258 females; age 41.8 +/- 10.9 years, BMI 35.0 +/- 3.1 kg/m(2)) randomized to sibutramine (n = 154) or to placebo (n = 155) treatment. A combination of sibutramine 10 mg or matching placebo and a balanced hypocaloric diet was given for 6 months with monthly evaluations. The main outcome measures were weight loss, the impact of weight on QoL, BMI, and waist circumference. RESULTS: The mean weight reduction was 8.2 kg in the sibutramine group and 3.9 in the placebo group at 6 months (p < 0.01). 40% of the sibutramine subjects and 14% of the control subjects lost > or =10% of their body weight (p < 0.01). The improvement in the impact of weight on QoL was statistically significant only in the sibutramine group at 6 months (mean -12.5 vs. -4.5 points; p < 0.01). In the sibutramine group the reduction in BMI (-3.1 vs. -1.4 kg/m(2)) and waist circumference (7.7 vs. 3.5 cm) was significantly greater (p < 0.001). The incidence of adverse events was low and similar to the placebo. CONCLUSIONS: This study confirmed that sibutramine significantly enhances the effect of diet on weight loss, BMI and waist circumference reduction, and showed a significant improvement of QoL.

Ischemic stroke with cardiac involvement in aortic thromboembolism.

An aortic thrombus may be detected by using transesophageal echocardiography after an embolic event. Clinical features are variable and may include cardiac and neurologic symptoms, such as the stroke. We report a case of a woman with an acute ischemic stroke, a myocardial infarction and a free floating aortic thrombus.

Balanced anestesia versus total intravenous anestesia for kidney transplantation.

AIM: An ideal anesthetic regimen for kidney transplantation should be able to assure haemodynamic stability to obtain an optimal graft reperfusion. The aim of this study was to compare 2 regimens of anesthesia for patients submitted to kidney transplantation. METHODS: We studied 40 patients: 20 subjects (Group A) received balanced anesthesia with thiopental, fentanyl and isoflurane, to the others 20 (Group B), a total intravenous anesthesia (TIVA) with propofol and remifentanyl was given. In both groups muscle relaxation was obtained with a bolus of cisatracurium followed by a continuous infusion. We performed standard clinical, invasive blood pressure and central venous pressure monitoring. Hemodyna-mic data have been collected at standard times. During the postoperative period we evaluated the recovery (Aldrete Score) in the recovery room and the analgesia (VAS) at 1, 6, 24 h after the end of surgery. RESULTS: The trend of hemodynamic parameters did not show statistically significant differences between the 2 groups. We observed statistically significant differences concerning the quality of the recovery and the postoperative analgesia. The recovery in group B was faster than in group A, but in group A the pain control was better than in group B at least during the first postoperative hour. CONCLUSIONS: For their pharmacokinetic properties, propofol, remifentanyl and cisatracurium allow to obtain a good control of the hemodynamic parameters and a fast and safe recovery of consciousness. Total intravenous anesthesia regimen seems to be an alternative to the balanced anesthesia for patients undergoing kidney transplantation.

Acute pancreatitis in emergency department.

Acute abdominal pain is one of the most frequent conditions in patients presenting to the Emergency Department (ED). Acute pancreatitis (AP) is a common abdominal disorder with problematic diagnosis because of the lack of a gold standard diagnostic test. Determination of serum amylase levels was considered a screening test, but recent studies have shown an important group of emergency department patients who have normoamylasemia. Other clinical laboratory tests, such as urinary screening, could be useful to decrease misdiagnosed cases of AP in an emergency situation, whereas, to confirm the clinical suspicious, radiological imaging may add specificity. On admission in ED stratifying patients into different categories, according to severity score systems, may be helpful for an appropriate management.

Hepatic steatosis in obese patients: clinical aspects and prognostic significance.

Non-alcoholic fatty liver disease is a new clinicopathological condition of emerging importance, now recognized as the most common cause of abnormal liver tests. It is characterized by a wide spectrum of liver damage: simple steatosis may progress to advanced fibrosis and to cryptogenic cirrhosis through steatohepatitis, and ultimately to hepatocellular carcinoma. Obesity is the most significant single risk factor for the development of fatty liver, both in children and in adults; obesity is also predictive of the presence of fibrosis, potentially progressing to advanced liver disease. From a pathogenic point of view, insulin resistance plays a central role in the accumulation of triglycerides within the hepatocytes and in the initiation of the inflammatory cascade. Chronic hepatocellular injury, necroinflammation, stellate cell activation, progressive fibrosis and ultimately, cirrhosis may be initiated by peroxidation of hepatic lipids and injury-related cytokine release. In the last few years, several pilot studies have shown that treatment with insulin-sensitizing agents, anti-oxidants or cytoprotective drugs may be useful, but there is no evidence-based support from randomized clinical trials. Modifications in lifestyle (e.g. diet and exercise) to reduce obesity remain the mainstay of prevention and treatment of a disease, which puts a large number of individuals at risk of advanced liver disease in the near future.

Safety of interferon beta treatment for chronic HCV hepatitis.

Hepatitis C is a major cause of liver-related morbidity and mortality worldwide. In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirrhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicate infection and prevent progression of the disease. The treatment has evolved from the use of alpha-interferon (IFNalpha) alone to the combination of IFNalpha plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin. Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjects are not suitable owing to intolerance toward drugs. IFNbeta represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety of IFNbeta treatment in HCV-related chronic hepatitis. The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNbeta are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNbeta treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported. A more recent study, performed to compare IFNbeta alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event frequency have been observed in subpopulations such as patients with genotype-1b HCV hepatitis unresponsive to IFNalpha treatment or with HCV-related cirrhosis and patients with acute viral hepatitis. If further studies will confirm the efficacy of combined IFNbeta and ribavirin treatment, this regimen could represent a safe and alternative therapeutic option in selected patients.

Comparison of positive end-expiratory pressure with reverse Trendelenburg position in morbidly obese patients undergoing bariatric surgery: effects on hemodynamics and pulmonary gas exchange.

BACKGROUND: Anesthetized morbidly obese patients often exhibit impaired pulmonary gas exchanges, mostly because of a reduction in functional residual capacity. At present, several approaches are suggested to ventilate these patients. METHODS: The efficiency of positive end-expiratory pressure (PEEP) and reverse Trendelenburg position (RTP) were compared in order to improve oxygenation in 20 morbidly obese patients undergoing bariatric surgery. RESULTS: Both PEEP and RTP determined a significant decrease in alveolar-arterial oxygen difference and an increase in total respiratory compliance (Ctot). RTP resulted in lower airway pressures than PEEP with similar improvements in Ctot and oxygenation. Concerning hemodynamic parameters, cardiac output (CO) significantly decreased with both PEEP and RTP. CONCLUSIONS: RTP and PEEP can be considered adequate ventilatory settings for morbidly obese patients, without any significant difference with regard to gas exchange improvement. However, the decrease in CO may partially counteract the beneficial effects on oxygenation of these ventilatory settings.

S-adenosil-L-methionine is able to reverse the immunosuppressive effects of chenodeoxycholic acid in vitro.

The study was conceived to evaluate if S-adenosil-L-methionine, a substance commonly used in the treatment of cholestasis in patients with cirrhosis and chronic hepatitis, exerts any immunological effect and of it is able to counterbalance bile acid-mediated immunosuppression. Proliferation and interleukin 2 and interferon-gamma secretion of human lymphocytes, collected from healthy subjects and exposed to mitogenic stimuli (phytohemagglutinin, pokeweed and anti-CD3 monoclonal antibodies), were analysed in the basal condition or after exposure to S-adenosil-L-methionine and/or chenodeoxycholic acid. Chenodeoxycholic acid inhibited phytohemagglutinin-induced lymphocyte proliferation and interferon-gamma secretion, and phytohemagglutinin and pokeweed-mediated interleukin 2 secretion. S-adenosil-L-methionine did not affect lymphocyte proliferation while it reduced interleukin 2 secretion upon phytohemagglutinin and pokeweed stimulation and interferon-gamma secretion upon all stimuli tested. Moreover, S-adenosil-L-methionine counteracted chenodeoxycholic acid-mediated inhibition of lymphocyte proliferation and interleukin 2 secretion. The results of our study confirm the immunosuppressive role of chenodeoxycholic acid on both secretive and proliferative lymphocyte functions and provide evidence of immunomodulatory activities of S-adenosil-L-methionine and its capacity to antagonize chenodeoxycholic acid-mediated inhibition of lymphocyte proliferation and interleukin 2 secretion.

[Reactivity of antigenic fractions obtained from Toxoplasma gondii evaluated with Western blotting]. / Reattivitá di frazioni antigeniche ottenute da Toxoplasma gondii valutate mediante Western blot.

A toxoplasma gondii antigen, has been obtained by sonication, separated by SDS gel electrophoresis system in 10% acrylamide and blotted onto nitrocellulose paper (Western Blot). The antigen has been tested against: serum samples from subjects T. gondii negative; serum samples from patients with acute Toxoplasma infection; serum samples from subjects who had serologic evidence of infection with T. gondii, but IgM negatives. IgG and IgM immune response has been evaluated. Gel stained with Coomassie Blue revealed 48 protein fractions; only twenty fractions reacted as antigen. In particular, we have observed that only one protein fraction has been recognized by IgM antibodies present in the serum of patient with acute Toxoplasma infection (with lymphoadenopathy); some protein fractions have been recognized only by IgG antibodies; some protein fractions have been recognized in the same time by IgG and IgM antibodies in the same serum sample.