Metalloproteinase expression after desflurane preconditioning in hepatectomies:A randomized clinical trial

BACKGROUND Hepatectomy with inflow occlusion results in ischemia-reperfusion injury;however,pharmacological preconditioning can prevent such injury and optimize the postoperative recovery of hepatectomized patients.The normal inflammatory response after a hepatectomy involves increased expression of metalloproteinases,which may signal pathologic hepatic tissue reformation.AIM To investigate the effect of desflurane preconditioning on these inflammatory indices in patients with inflow occlusion undergoing hepatectomy.METHODS This is a single-center,prospective,randomized controlled trial conducted at the 4th Department of Surgery of the Medical School of Aristotle University of Thessaloniki,between August 2016 and December 2017.Forty-six patients were randomized to either the desflurane treatment group for pharmacological preconditioning(by replacement of propofol with desflurane,administered 30 min before induction of ischemia)or the control group for standard intravenous propofol.The primary endpoint of expression levels of matrix metalloproteinases and their inhibitors was determined preoperatively and at 30 min posthepatic reperfusion.The secondary endpoints of neutrophil infiltration,coagulation profile,activity of antithrombin III(AT III),protein C(PC),protein S and biochemical markers of liver function were determined for 5 d postoperatively and compared between the groups.RESULTS The desflurane treatment group showed significantly increased levels of tissue inhibitor of metalloproteinases 1 and 2,significantly decreased levels of matrix metalloproteinases 2 and 9,decreased neutrophil infiltration,and less profound changes in the coagulation profile.During the 5-d postoperative period,all patients showed significantly decreased activity of AT III,PC and protein S(vs baseline values,P<0.05).The activity of AT III and PC differed significantly between the two groups from postoperative day 1 to postoperative day 5(P<0.05),showing a moderate drop in activity of AT III and PC in the desflurane treatment group and a dramatic drop in the control group.Compared to the control group,the desflurane treatment group also had significantly lower international normalized ratio values on all postoperative days(P<0.005)and lower serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase values on postoperative days 2 and 3(P<0.05).Total length of stay was significantly less in the desflurane group(P=0.009).CONCLUSION Desflurane preconditioning can lessen the inflammatory response related to ischemia-reperfusion injury and may shorten length of hospitalization.

Effect of diltiazem and lidocaine on arterial pressure or heart rate and the quality of extubation in patients undergoing uvulopalatopharyngoplasty

Objective：To evaluate the effect of diltiazem and lidocaine on arterial pressure or heart rate and the quality of extubation in patients undergoing uvulopalatopharyngoplasty. Methods： Sixty patients were randomly divided into 4 groups： In the control group patients were given saline; in the lidocaine group patients were given 1.0 mg/kg lidocaine ; in the diltiazem group patients were given 0. 2 mg/kg diltiazem; and in the lidocaine plus diltiazem group patients were given 1.0 mg/kg lidocaine and 0. 2 mg/kg diltiazem. These drugs were given 2 rain before tracheal extuhation. Values for SBP, DBP, and HR were recorded, on arriving at the operating room, immediately at the end of the surgery, at the time of injection of the study drugs, at tracheal extubation, at 1 min and 5 min after extubation. The quality of extubation according to the Sebel＇s grading scale were compared among the 4 groups. Results：During extubation in the control group HR, SBP and DBP increased significantly when compared to baseline levels. Both lidocaine （1.0 mg/kg） and diltiazem （0. 2 mg/kg） successfully alleviated these increases. The suppressive effect of diltiazem was greater than that of lidocaine. The combinative use of the two drugs minimized the increases. The administration of lidocaine significantly suppressed bucking or coughing compared with the other groups. Conclusions： The pressor responses and tachycardia occurring in patients with uvulopalatopharyngoplasty during emergence from anesthesia and tracheal extubation, can be easily blocked by a bolus dose of 1.0 mg/kg lidocaine, 0. 2 mg/kg diltiazem or the comhinative use of the two drugs. And the concurrent use of lidocaine and diltiazem alleviated the hemodynamic changes more obviously.

Effects of Combined Spinal Epidural Anaesthesia and Spinal Anaesthesia on Peri-Operative Pulmonary Status in Geriatric Patients in Lower Extremity Surgery

Background: Lower extremity surgeries performed in elderly people usually have high prevalence of peri-operative medical problems related to anaesthesia. The overall objective of peri-operative care of geriatric population is to fast recovery from anaesthesia and avoid functional decline. Objective: To compare the peri-operative pulmonary status of combined spinal epidural anaesthesia (CSEA) and spinal anaesthesia (SA) in geriatric patients underwent lower extremity surgeries. Methods: This prospective comparative study was conducted at Department of Anaesthesia, Analgesia and Intensive Care Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2016 to June 2018. A total of 70 geriatric cases that underwent lower extremity surgeries were included in this study. Cases were randomly allocated into two groups;35 in Group A (CSEA) and 35 in Group B (SAB). The different outcome variables between the groups like-duration of anaesthesia, respiratory rates (RR), oxygen saturation (SpO2), end tidal CO2 (EtCO2), peak expiratory flow rate (PEFR), breath holding test (BHT), peri-operative side effects of anaesthesia and post-operative visual analogue score (VAS) were analyzed and compared by statistical tests. Results: The mean age, weight, BMI of Group A and Group B patients were not significantly different (p > 0.05). No significant differences were observed in duration of surgery, gender and ASA grade between the groups (p > 0.05). Mean duration of anaesthesia, mean time to achieve target level of sensory block and mean time to achieve complete motor block were significantly higher in Group A (p < 0.001). Mean RR, SpO2, EtCO2, PEFR and BHT of both groups were not significantly different (p > 0.05). Peri-operative side effects of anaesthesia and post-operative VAS were significantly less in group A patients (p < 0.05). Conclusion: Combined spinal epidural anaesthesia is effective and safe;produces stable peri-operative pulmonary status with prolonging analgesia and fewer side effects as compared to spinal anaesthesia in geriatric patients.

Perioperative thromboprophylaxis in liver transplant patients

Improvements in surgical and anesthetic procedures have increased patient survival after liver transplantation(LT). However, the perioperative period of LT can still be affected by several complications. Among these, thromboembolic complications(intracardiac thrombosis, pulmonary embolism, hepatic artery and portal vein thrombosis) are relatively common causes of increased morbidity and mortality. The benefit of thromboprophylaxis in general surgical patients has already been established, but it is not the standard of care in LT recipients. LT is associated with a high bleeding risk, as it is performed in a setting of already unstable hemostasis. For this reason, the role of routine perioperative prophylactic anticoagulation is usually restricted. However, recent data have shown that the bleeding tendency of cirrhotic patients is not an expression of an acquired bleeding disorder but rather of coexisting factors(portal hypertension, hypervolemia and infections). Furthermore, in cirrhotic patients, the new paradigm of ‘‘rebalanced hemostasis' ' can easily tip towards hypercoagulability because of the recently described enhanced thrombin generation, procoagulant changes in fibrin structure and platelet hyperreactivity. This new coagulation balance, along with improvements in surgical techniques and critical support, has led to a dramatic reduction in transfusion requirements, and the intraoperative thromboembolic-favoring factors(venous stasis, vessels clamping, surgical injury) have increased the awareness of thrombotic complications and led clinicians to reconsider the limited use of anticoagulants or antiplatelets in the postoperative period of LT.

Predictive factors of short term outcome after liver transplantation: A review

Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse outcomes. Little is known about the early postoperative parameters that can be used as valid predictive indices for early graft function, retransplantation or surgical reintervention, secondary complications, long intensive care unit stay or death. In this review, we present state-of-the-art knowledge regarding the early post-transplantation tests and scores that can be applied during the first postoperative week to predict liver allograft function and patient outcome, thereby guiding the therapeutic and surgical decisions of the medical staff. Post-transplant clinical and biochemical assessment of patients through laboratory tests (platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1) and scores (model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment and model of early allograft function) have been reported to have good performance, but they only allow late evaluation of patient status and graft function, requiring days to be quantified. The indocyanine green plasma disappearance rate has long been used as a liver function assessment technique and has produced interesting, although not univocal, results when performed between the 1th and the 5th day after transplantation. The liver maximal function capacity test is a promising method of metabolic liver activity assessment, but its use is limited by economic cost and extrahepatic factors. To date, a consensual definition of early allograft dysfunction and the integration and validation of the above-mentioned techniques, through the development of numerically consistent multicentric prospective randomised trials, are necessary. The medical and surgical management of transplanted patients could be greatly improved by using clinically reliable tools to predict early graft function.

Thromboelastographic reference ranges for a cirrhotic patient population undergoing liver transplantation

AIM To describe the thromboelastography(TEG) "reference" values within a population of liver transplant(LT) candidates that underline the differences from healthy patients.METHODS Between 2000 and 2013, 261 liver transplant patients with a model for end-stage liver disease(MELD) score between 15 and 40 were studied. In particular the adult patients(aged 18-70 years) underwent to a first LT with a MELD score between 15 and 40 were included, while all patients with acute liver failure, congenital bleeding disorders, and anticoagulant and/or antiplatelet drug use were excluded. In this population of cirrhotic patients, preoperative haematological and coagulation laboratory tests were collected, and the pretransplant thromboelastographic parameters were studied and compared with the parameters measured in a previously studied population of 40 healthy subjects. The basal TEG parameters analysed in the cirrhotic population of liver candidates were as follows: Reaction time(r), coagulation time(k), Angle-Rate of polymerization of clot(α Angle), Maximum strenght of clot(MA), Amplitudes of the TEG tracing at 30 min and 60 min after MA is measured(A30 and A60), and Fibrinolysis at 30 and 60 min after MA(Ly30 and Ly60). The possible correlation between the distribution of the reference range and the gender, age, MELD score(higher or lower than 20) and indications for transplantation(liver pathology) were also investigated. In particular, a MELD cut-off value of 20 was chosen to verify the possible correlation between the thromboelastographic reference range and MELD score. RESULTS Most of the TEG reference values from patients with end-stage liver disease were significantly different from those measured in the healthy population and were outside the suggested normal ranges in up to 79.3% of subjects. Wide differences were found among all TEG variables, including r(41.5% of the values), k(48.6%), α(43.7%), MA(79.3%), A30(74.4%) and A60(80.9%), indicating a prevailing trend to hypocoagulability. The differences between the mean TEG values obtained from healthy subjects and the cirrhotic population were statistically significant for r(P = 0.039), k(P < 0.001), MA(P < 0.001), A30(P < 0.001), A60(P < 0.001) and Ly60(P = 0.038), indicating slower and less stable clot formation in the cirrhotic patients. In the cirrhotic population, 9.5% of patients had an r value shorter than normal, indicating a tendency for faster clot formation. Within the cirrhotic patient population, gender, age and the presence of hepatocellular carcinoma or alcoholic cirrhosis were not significantly associated with greater clot firmness or enhanced whole blood clot formation, whereas greater clot strength was associated with a MELD score < 20, hepatitis C virus and cholestaticrelated cirrhosis(P < 0.001; P = 0.013; P < 0.001).CONCLUSION The range and distribution of TEG values in cirrhotic patients differ from those of healthy subjects, suggesting that a specific thromboelastographic reference range is required for liver transplant candidates.

Intraoperative thromboelastography as a tool to predict postoperative thrombosis during liver transplantation

BACKGROUND Thromboembolic complications are relatively common causes of increased morbidity and mortality in the perioperative period in liver transplant patients.Early postoperative portal vein thrombosis(PVT,incidence 2%-2.6%)and early hepatic artery thrombosis(HAT,incidence 3%-5%)have a poor prognosis in transplant patients,having impacts on graft and patient survival.In the present study,we attempted to identify the predictive factors of these complications for early detection and therefore monitor more closely the patients most at risk of thrombotic complications.AIM To investigate whether intraoperative thromboelastography(TEG)is useful in detecting the risk of early postoperative HAT and PVT in patients undergoing liver transplantation(LT).METHODS We retrospectively collected thromboelastographic traces,in addition to known risk factors(cold ischemic time,intraoperative requirement for red blood cells and fresh-frozen plasma transfusion,prolonged operating time),in 27 patients,selected among 530 patients(≥18 years old),who underwent their first LT from January 2002 to January 2015 at the Liver University Transplant Center and developed an early PVT or HAT(case group).Analyses of the TEG traces were performed before anesthesia and 120 min after reperfusion.We retrospectively compared these patients with the same number of nonconsecutive control patients who underwent LT in the same study period without developing these complications(1:1 match)(control group).The chosen matching parameters were:Patient graft and donor characteristics[age,sex,body mass index(BMI)],indication for transplantation,procedure details,United Network for Organ Sharing classification,BMI,warm ischemia time(WIT),cold ischemia time(CIT),the volume of blood products transfused,and conventional laboratory coagulation analysis.Normally distributed continuous data are reported as the mean±SD and compared using one-way Analysis of Variance(ANOVA).Nonnormally distributed continuous data are reported as the median(interquartile range)and compared using the Mann-Whitney test.Categorical variables were analyzed with Chi-square tests with Yates correction or Fisher’s exact test depending on best applicability.IBM SPSS Statistics version 24(SPSS Inc.,Chicago,IL,United States)was employed for statistical analysis.Statistical significance was set at P<0.05.RESULTS Postoperative thrombotic events were identified as early if they occurred within 21 d postoperatively.The incidence of early hepatic artery occlusion was 3.02%,whereas the incidence of PVT was 2.07%.A comparison between the case and control groups showed some differences in the duration of surgery,which was longer in the case group(P=0.032),whereas transfusion of blood products,red blood cells,fresh frozen plasma,and platelets,was similar between the two study groups.Thromboelastographic parameters did not show any statistically significant difference between the two groups,except for the G value measured at basal and 120’postreperfusion time.It was higher,although within the reference range,in the case group than in the control group(P=0.001 and P<0.001,respectively).In addition,clot lysis at 60 min(LY60)measured at 120’postreperfusion time was lower in the case group than in the control group(P=0.035).This parameter is representative of a fibrinolysis shutdown(LY60=0%-0.80%)in 85%of patients who experienced a thrombotic complication,resulting in a statistical correlation with HAT and PVT.CONCLUSION The end of surgery LY60 and G value may identify those recipients at greater risk of developing early HAT or PVT,suggesting that they may benefit from intense surveillance and eventually anticoagulation prophylaxis in order to prevent these serious complications after LT.

Anaesthetic perioperative management of patients with pancreatic cancer

Pancreatic cancer remains a significant and unresolved therapeutic challenge.Currently,the only curative treatment for pancreatic cancer is surgical resection.Pancreatic surgery represents a technically demanding major abdominal procedure that can occasionally lead to a number of pathophysiological alterations resulting in increased morbidity and mortality.Systemic,rather than surgical complications,cause the majority of deaths.Because patients are increasingly referred to surgery with at advanced ages and because pancreatic surgery is extremely complex,anaesthesiologists and surgeons play a crucial role in preoperative evaluations and diagnoses for surgical intervention.The anaesthetist plays a key role in perioperative management and can significantly influence patient outcome.To optimise overall care,patients should be appropriately referred to tertiary centres,where multidisciplinary teams(surgical,medical,radiation oncologists,gastroenterologists,interventional radiologists and anaesthetists)work together and where close cooperation between surgeons and anaesthesiologists promotes the safe performance of major gastrointestinal surgeries with acceptable morbidity and mortality rates.In this review,we sought to provide simple daily recommendations to the clinicians who manage pancreatic surgery patients to make their work easier and suggest a joint approach between surgeons and anaesthesiologists in daily decision making.

Perioperative effects of high doses of intraoperative thymoglobulin induction in liver transplantation

AIM:To describe our single-centre experience in liver transplantation(LT)with the infusion of high perioperative thymoglobulin doses.The optimal dosage and timing of thymoglobulin[antithymocyte globulin(ATG)]administration during LT remains controversial.Cytokine release syndrome,haemolytic anaemia,thrombocytopenia,neutropenia,fever and serum sickness are potential adverse effects associated with ATG infusion.METHODS:Between December 2009 and December 2010,16 adult non-randomized patients(ATG group),receiving a liver graft from a deceased donor,received an intraoperative infusion(4-6 h infusion)of thymoglobulin(3 mg/kg,ATG:Thymoglobuline).These patients were compared(case control approach)with 16 patients who had a liver transplant without ATG treatment(control group)to evaluate the possible effects of intraoperative ATG infusion.The matching parameters were:Sex,recipient age(±5 years),LT indication including viral status,MELD score(±5 points),international normalized ratio and platelet count(as close as possible).The exclusion criteria for both groups included the following:Multi-organ or living donor transplant,immunosuppressive therapy before transplantation,contraindications to the administration of any thymocyte globulin,human immunodeficiency virus seropositivity,thrombocytopenia[platelet<50000/μL]or leukopenia[white blood cells<1000/μL].The perioperative side effects(haemodynamic alterations,core temperature variations,colloids and crystalloids requirements,and surgical time)possibly related to ATG infusion and the thromboelastographic(TEG)evaluation of the ATG effects on coagulation,blood loss and blood product transfusion were analysed during the operation and the first three postoperative days.RESULTS:Intraoperative ATG administration was associated with longer surgical procedures[560±88 min vs 480±83 min(control group),P=0.013],an intraoperative core temperature more than 37℃(50%of ATG patients vs 6.2%of control patients,P=0.015),major intraoperative blood loss[3953±3126 mL vs 1419±940 mL(control group),P=0.05],higher red blood cell[2092±1856 mL ATG group vs 472±632 mL(control group),P=0.02],fresh frozen plasma[671±1125 mL vs 143±349 mL(control group),P=0.015],and platelet[374±537 mL vs 15.6±62.5 mL(control group),P=0.017]transfusion,and a higher requirement for catecholamines(0.08±0.07μg/kg per minutes vs 0.01±0.38μg/kg per minutes,respectively,in the ATG and control groups)for haemodynamic support.The TEG tracings changed to a straight line during ATG infusion(preanhepatic and anhepatic phases)in 81%of the patients from the ATG group compared to 6.25%from the control group(P<0.001).Patients from the ATG group compared to controls had higher post-op core temperatures(38℃±1.0℃vs 37.3℃±0.5℃;P=0.02),an increased need of noradrenaline(43.7%vs 6.25%,P=0.037),received more platelet transfusions(31.5%vs 0%,P=0.04)and required continuous renal replacement therapy(4 ATG patients vs none in the control group;P=0.10).ATG infusion was considered the cause of a fatal anaphylactic shock and of a suspected adverse reaction that led to intravascular haemolysis and acute renal failure.CONCLUSION:The side effects and the coagulation imbalance observed in patients receiving a high dosage of ATG suggest caution in the use of thymoglobulin during LT.

Transoesophageal echocardiography during liver transplantation

Liver transplantation(LT) has become the standard of care for patients with end stage liver disease. The allocation of organs, which prioritizes the sickest patients, has made the management of liver trans-plant candidates more complex both as regards their comorbidities and their higher risk of perioperative complications. Patients undergoing LT frequently display considerable physiological changes during the pro-cedures as a result of both the disease process and the surgery. Transoesophageal echocardiography(TEE), which visualizes dynamic cardiac function and overall contractility, has become essential for perioperative LT management and can optimize the anaesthetic management of these highly complex patients. More-over, TEE can provide useful information on volume status and the adequacy of therapeutic interventions and can diagnose early intraoperative complications, such as the embolization of large vessels or development of pulmonary hypertension. In this review, directed at clinicians who manage TEE during LT, we show why the procedure merits a place in challenging anaesthetic environment and how it can provide essential information in the perioperative management of compromised patients undergoing this very complex surgical procedure.

HIV among people who inject drugs in Hungary

Background:Before 2014(the year of closure of the two largest needle exchange programs in Hungary,which halved the number of available syringes in the country despite increased injecting risk practices)no HIV was reportedly acquired in Hungary among people who inject drugs(PWIDs)who were not also men who had sex with other men(MSM).In 2014,one and in 2015 two non-MSM PWIDs were newly diagnosed with HIV who supposedly became infected in Hungary,and both incident HIV cases in 2015 were diagnosed in the AIDS stage.In addition,two new(albeit supposedly imported)non-MSM PWID cases were also registered in the first three quarters of 2016,one of which subsequently was diagnosed with and then died of AIDS.At the same time,the prevalence of HCV doubled among PWIDs(from 24%to 49%in Hungary and from 34%to 61%in Budapest).Case presentation:The case that we discuss in this paper is a male PWID,who was diagnosed with HIV and AIDS in May of 2015 and then died of AIDS the next month.His HIV infection status was detected with delay,and then appeared in the official statistics as an incident PWID HIV case and an incident PWID AIDS case,but not as an incident PWID AIDS death.No contact tracing followed,even though it would have been relatively easy considering the circumstances.To our knowledge,no HIV post-exposure protocol exists in hospitals,in case of HIV exposure due to an eventual needle-stick injury.Conclusions:Our paper draws attention to recently published HIV and AIDS surveillance data,and shows the failure of the system.While sounding the alarm based on three newly detected PWID HIV cases in the past 2 years may be premature,there are definitely serious problems in the HIV detection and tracing system among PWIDs in Hungary.