Right displacement of trachea to reduce right bronchial misplacement of left double lumen tube: a prospective, double-blind, randomized study.

BACKGROUND: Misplacement of double-lumen endobronchial tubes (DLTs) during bronchial intubation, especially when bronchoscopy guidance is not applicable, threatens effective lung isolation and brings about airway injury during reposition. We aimed to examine whether a novel maneuver called right tracheal displacement (RTD) can reduce left-sided DLT misplacement during first-attempt intubation without bronchoscopy guidance. METHODS: Patients that underwent thoracic surgeries requiring one-lung ventilation during November 2020 to January 2021 were recruited and randomized into control and RTD group, with 54 cases in each group. The primary outcomes included the incidence of DLT misplacement and the time to complete desired bronchial intubation. The secondary outcomes included mucosal injury, sore throat and hoarseness upon emergence and at 24 h post-operatively. RESULT: The incidence of DLT misplacement in RTD group was significantly lower compared to control group (0% vs. 16.7%) The time to complete bronchial intubation was also significantly shortened in RTD group compared to control (52.88 ± 9.36 s vs. 63.04 ± 20.02 s). The incidence of mucosal injury, sore throat and hoarseness were comparable between two groups. CONCLUSION: RTD maneuver can effectively improve the success rate of first-attempt proper DLT positioning and shorten the time required by bronchial intubation. TRIAL REGISTRATION: This prospective, double-blind, randomized study has completed the registration of the Chinese Clinical Trial Center at 2/11/2020 with the registration number ChiCTR2000040212. It was conducted from 26/11/2020 to 31/7/2021 in third affiliated hospital of Sun Yat-sen university.

Intertruncal versus classical approach to the ultrasound-guided supraclavicular brachial plexus block for upper extremity surgery: study protocol for a randomized non-inferiority trial.

BACKGROUND: Ultrasound-guided intertruncal approach (IA) to the supraclavicular block (SB) is recently proposed as a new approach for local anesthetic (LA) injection in terms of the classical approach (CA) at the level of the first rib. The CA-SB has been proven to result in satisfying sensorimotor block, but associate with a high risk of intraneural injection. The aim of this randomized non-inferiority study is to explore whether IA-SB can obtain similar block dynamics, as the CA-SB, but avoiding an intraneural injection during the whole nerve block procedure. METHODS: The total 122 patients undergoing elective upper extremity surgery will be randomly allocated to receive either an IA-SB or a CA-SB using a double-injection (DI) technique. In the IA-SB group, a portion of LA (15 mL) is injected accurately to the intertruncal plane between the middle and lower trunks under real-time ultrasound guidance; then, the remaining volume (10 mL) is carefully distributed to the other intertruncal plane between the upper and middle trunks. In the CA-SB group, the DI technique will be carried out as described in Tran's study. The primary outcome is the percentage of patients with a complete sensory blockade at 20 min with a predefined non-inferiority margin of - 5%. The secondary outcomes include the sensory-motor blockade of all 4 terminal nerves, onset times of the individual nerves within 30 min, block-related variables, and adverse events. DISCUSSION: The results will provide sensory-motor blockade-related parameters and safety of the ultrasound-guided intertruncal approach to the supraclavicular block, thereby promoting clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000040199 . Registered on 25 November 2020.

Neutrophil Elastase Inhibitors Suppress Oxidative Stress in Lung during Liver Transplantation.

BACKGROUND: Neutrophil infiltration plays a critical role in the pathogenesis of acute lung injury following liver transplantation (LT). Neutrophil elastase is released from neutrophils during pulmonary polymorphonuclear neutrophil activation and sequestration. The aim of the study was to investigate whether the inhibition of neutrophil elastase could lead to the restoration of pulmonary function following LT. METHODS: In in vivo experiments, lung tissue and bronchoalveolar lavage fluid (BALF) were collected at 2, 4, 8, and 24 h after rats were subjected to orthotopic autologous LT (OALT), and neutrophil infiltration was detected. Next, neutrophil elastase inhibitors, sivelestat sodium hydrate (exogenous) and serpin family B member 1 (SERPINB1) (endogenous), were administered to rats before OALT, and neutrophil infiltration, pulmonary oxidative stress, and barrier function were measured at 8 h after OALT. RESULTS: Obvious neutrophil infiltration occurred from 2 h and peaked at 8 h in the lungs of rats after they were subjected to OALT, as evidenced by an increase in naphthol-positive cells, BALF neutrophil elastase activity, and lung myeloperoxidase activity. Treatment with neutrophil elastase inhibitors, either sivelestat sodium hydrate or SERPINB1, effectively reduced lung naphthol-positive cells and BALF inflammatory cell content, increased expression of lung HO-1 and tight junction proteins ZO-1 and occludin, and increased the activity of superoxide dismutase. CONCLUSION: Neutrophil elastase inhibitors, sivelestat sodium hydrate and SERPINB1, both reduced lung neutrophil infiltration and pulmonary oxidative stress and finally restored pulmonary barrier function.

Intravenous Anesthetic Protects Hepatocyte from Reactive Oxygen Species-Induced Cellular Apoptosis during Liver Transplantation In Vivo.

BACKGROUND: Liver transplantation leads to liver ischemia/reperfusion (I/R) injury, resulting in early graft dysfunction and failure. Exacerbations of oxidative stress and inflammatory response are key processes in the development of liver I/R injury. Intravenous anesthetic propofol potent effects on free radical scavenging and protects livers against I/R injury. However, the role and mechanism of propofol-mediated hepatic protection in liver transplantation is poorly understood. The aim of this study was to evaluate the role of propofol postconditioning in the liver I/R injury after liver transplantation. METHODS: Forty-eight rats were randomly divided into six groups: rats receiving either sham operation or orthotopic autologous liver transplantation (OALT) in the absence or presence of propofol (high dose and low dose) postconditioning or intralipid control or VAS2870 (Nox2 special inhibitor). Eight hours after OALT or sham operation, parameters of organ injury, oxidative stress, inflammation, and NADPH-associated proteins were assessed. RESULTS: After OALT, severe liver pathological injury was observed that was associated with increases of serum AST and ALT, which were attenuated by propofol postconditioning. In addition, especially high dose of propofol postconditioning reduced TNF-α, IL-1ß, IL-6, TLR4, and NF-κB inflammatory pathway, accompanied with decrease of neutrophil elastase activity, MPO activity, 8-isoprotane, p47phox and gp91phox protein expressions, and increase of SOD activity. Inhibition of Nox2 by VAS2870 conferred similar protective effects in liver transplantation. CONCLUSION: Liver transplantation leads to severe inflammation and oxidative stress with NADPH oxidase activation. Propofol postconditioning reduces liver I/R injury after liver transplantation partly via inhibiting NADPH oxidase Nox2 and the subsequent inflammation and oxidative stress.

ONO-5046 suppresses reactive oxidative species-associated formation of neutrophil extracellular traps.

BACKGROUND: Neutrophil extracellular traps (NETs) have been identified as a non-apoptosis cell death pattern that leads to the release of granular contents into the extracellular space and subsequent excessive inflammatory response. The present study aims to investigate whether ONO-5046, a novel neutrophil elastase inhibitor, could affect NETs formation and promote inflammation resolution. METHODS: Neutrophils were separated and identified. Cell survival rate was analyzed using the trypan blue stain-resistance method. Different concentrations of lipopolysaccharide (LPS) (0.01 µg/mL, 0.1 µg/mL, and 1.0 µg/mL) were used to stimulate NETs formation. ONO-5046 (0.1 µg/mL and 1 µg/mL) was administered after high-dose LPS stimulation and NETs formation. Moreover, tBHP was used to further investigate the relationships between the effects of ONO-5046 and reactive oxygen species (ROS) release. ROS was detected by DCFH-DA fluorescent staining and NETs formation was demonstrated via immunofluorescence staining for neutrophil elastase and citrullinated histone H3 (H3Cit). RESULTS: NETs formation was stimulated by LPS in a dose-dependent manner. High doses of LPS induced ROS generation and decreased cellular survival. ONO-5046 reduced LPS-induced NETs formation in a dose-dependent manner, as evidenced by immunofluorescence staining for neutrophil elastase and H3Cit whereby the fluorescence intensity decreased and neutrophil ROS generation was attenuated. However, the effects of ONO-5046 on NETs reduction were reversed by ROS inducer tBHP. CONCLUSIONS: The neutrophil elastase inhibitor ONO-5046 suppresses ROS-associated NETs formation, which may lead to inflammation resolution.

Initiation time of renal replacement therapy on patients with acute kidney injury: A systematic review and meta-analysis of 8179 participants.

The early initiation of renal replacement therapy has been recommended for patients with acute renal failure by some studies, but its effects on mortality and renal recovery are unknown. We conducted an updated meta-analysis to provide quantitative evaluations of the association between the early initiation of renal replacement therapy and mortality for patients with acute kidney injury. After applying inclusion/exclusion criteria, 51 studies, including 10 randomized controlled trials, with a total of 8179 patients were analyzed. Analysis of the included trials showed that patients receiving early renal replacement therapy had a 25% reduction in all-cause mortality compared to those receiving late renal replacement therapy (risk ratio [RR] 0.75, 95% CI [0.69, 0.82]). We also noted a 30% increase in renal recovery (RR 1.30, 95% CI [1.07, 1.56]), a reduction in hospitalization of 5.84 days (mean difference [MD], 95% CI [-10.27, -1.41]) and a reduction in the duration of mechanical ventilation of 2.33 days (MD, 95% CI [-3.40, -1.26]) in patients assigned to early renal replacement therapy. The early initiation of renal replacement therapy was associated with a decreased risk of all-cause mortality compared with the late initiation of RRT in patients with acute kidney injury. These findings should be interpreted with caution given the heterogeneity between studies. Further studies are needed to identify the causes of mortality and to assess whether mortality differs by dialysis dose.

Intestinal injury following liver transplantation was mediated by TLR4/NF-κB activation-induced cell apoptosis.

Intestinal motility and barriers are often impaired due to intestinal congestion during liver transplantation. Intestinal bacteria and enterogenous endotoxins enter into the blood stream or lymphatic system and translocate to other organs, which can result in postoperative multi-organ dysfunction (MODF) and systemic inflammatory reaction syndrome (SIRS) severely affecting patient survival. However, the mechanisms underlying liver transplantation-induced intestinal injury remain unclear and effective therapies are lacking. Thus, the present study investigated whether these effects were associated with endotoxin-mediated apoptosis. Rat autologous orthotopic liver transplantation (AOLT) models were established to observe dynamic intestinal injuries at different time-points following reperfusion. Changes in the levels of endotoxins and the primary receptor, toll-like receptor 4 (TLR4), as well as its downstream signaling molecule, nuclear factor-κB (NF-κB) were all determined. Finally, immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling assays were conducted to detect caspase-3 expression and intestinal cell apoptosis, respectively. AOLT resulted in significant pathological intestinal injury, with the most serious intestine damage apparent four or eight hours following reperfusion. Furthermore, the levels of endotoxins and inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, peaked during this time period and gradually decreased to the normal level. Notably, TLR4 and downstream NF-κB expression, as well as NF-κB-mediated caspase-3 activation and intestinal cell apoptosis coincided with the intestinal pathological damage. Thus, the possible mechanism of post-liver transplantation intestinal injury was demonstrated to be associated with NF-κB activation-induced cell apoptosis.

Intestinal mucosal injury induced by tryptase-activated protease-activated receptor 2 requires ß-arrestin-2 in vitro.

Tryptase exacerbates intestinal ischemia-reperfusion injury, however, the direct role of tryptase in intestinal mucosal injury and the underlying mechanism remains largely unknown. Protease-activated receptor 2 (PAR­2), commonly activated by tryptase, interacts with various adaptor proteins, including ß­arrestin­2. The present study aimed to determine whether tryptase is capable of inducing intestinal mucosal cell injury via PAR­2 activation and to define the role of ß­arrestin­2 in the process of injury. The IEC­6 rat intestinal epithelial cell line was challenged by tryptase stimulation. Cell viability, lactate dehydrogenase (LDH) activity and apoptosis were analyzed to determine the severity of cell injury. Injury was also evaluated following treatments with specific PAR­2 and extracellular signal­related kinases (ERK) inhibitors, and knockdown of ß­arrestin­2. PAR­2, ERK and ß­arrestin­2 protein expression levels were evaluated. Tryptase treatment (100 and 1,000 ng/ml) resulted in IEC­6 cell injury, as demonstrated by significant reductions in cell viability, accompanied by concomitant increases in LDH activity and levels of cleaved caspase­3 protein expression. Furthermore, tryptase treatment led to a marked increase in PAR­2 and phosphorylated­ERK expression, and exposure to specific PAR­2 and ERK inhibitors eliminated the changes induced by tryptase. Knockdown of ß­arrestin­2 blocked tryptase­mediated cell injury, whereas tryptase exerted no influence on ß­arrestin­2 expression in IEC­6 cells. These data indicate that tryptase may directly damage IEC­6 cells via PAR-2 and the downstream activation of ERK, and demonstrate that the signaling pathway requires ß-arrestin-2.

Dexmedetomidine ameliorates acute lung injury following orthotopic autologous liver transplantation in rats probably by inhibiting Toll-like receptor 4-nuclear factor kappa B signaling.

BACKGROUND: To investigate whether pretreatment with dexmedetomidine (Dex) has a protective effect against acute lung injury (ALI) in an orthotopic autologous liver transplantation (OALT) rat model and to explore the mechanisms responsible for the protective effect of Dex against lung injury. METHODS: Forty-eight rats underwent OALT and were randomly divided into six groups (n = 8 in each group) that received 10 µg/kg Dex, 50 µg/kg Dex, 50 µg/kg Dex + nonspecific α2-adrenergic receptor (AR) antagonist atipamezole, 50 µg/kg Dex + specific α2B/C-AR antagonist ARC-239, 50 µg/kg Dex + specific α2A-AR antagonist BRL-44408, or the same amount of normal saline. The sham rats (n = 8) underwent anesthesia induction, laparotomy, and separation of the portal vein without liver ischemia and reperfusion. Lung tissue sections were stained with hematoxylin and eosin (HE) to visualize the damage. The expression of Toll-like receptor 4 (TLR4) and the phospho-nuclear factor (NF)-κB p65 subunit as well as inflammatory cytokines was measured. RESULTS: Rats exhibited increased histological lung injury scores and pulmonary edema following OALT. Pretreatment with 50 µg/kg Dex attenuated OALT-induced lung injury in rats, probably by inhibiting the activation of the TLR4-NF-κB signaling pathway. The protective effect of Dex could be blocked by atipamezole or BRL-44408, but not by ARC-239, suggesting these effects of Dex were mediated, at least in part, by the α2A-AR. CONCLUSIONS: Dex exerts protective effects against ALI following OALT, and this protection is associated with the suppression of TLR4-NF-κB signaling. Thus, pretreatment with Dex may be a useful method for reducing lung damage caused by liver transplantation.

[Protective effects of ulinastatin during orthotopic liver transplantation on kidney function with decreasing acute renal failure after liver transplantation in patients with severe hepatitis].

OBJECTIVE: To study whether using ulinastatin (UTI) during orthotopic liver transplantation (OLT) can decrease acute renal failure after liver transplantation in patients with Severe Hepatitis. METHOD: Thirty-one patients with Severe Hepatitis undergoing orthotopic liver transplantation (OLT) were studied. They were devided into two groups: determination of serumbeta(2) microglobulin (beta(2) MG), BUN and Cr before operation and 24 h after operation, at the same time, urine samples were taken for determination of urine beta(2) MG. Data of HR, ABPM, CVP, CO were recorded during operation. The Incidence of renal failure affiliated liver transplantation (RFALT) and prognosis of these patients were also recorded in the two groups after operation. RESULTS: (1) 4 cases in group U while 10 cases in group C developed RFALT at 24 h after operation (P < 0.05). In these patients who developed RFALT at 24 h after operation, 4 cases were all rehabilitation discharge in group U, while in group C, 2 cases died, 3 cases didn't cure but required discharge, only 5 cases were rehabilitation discharge. (2) Compared with baseline before operation, serum beta(2) MG, Urine beta(2) MG, BUN and Cr increased significantly at 24 h after operation both in two groups, (P < 0.05, P < 0.01). (3) Compared with group C, serum beta(2) MG, Urine beta(2) MG, BUN increased significantly at 24 h after operation in group U (P < 0.05, P < 0.01). CONCLUSION: Protective effects of ulinastatin during orthotopic liver transplantation on kidney function in patients with Severe Hepatitis can decrease acute renal failure after liver transplantation.

Effects of propofol intravenous injection bolus on the left ventricular function and the myocardial beta-adrenoceptor in rats.

Propofol bolus injection has been reported to influence cardiovascular functions. However, the detailed mechanism underlying this action has not been elucidated. This study was designed to investigate the effects of propofol i.v. bolus on the left ventricular function, the myocardial beta-adrenoceptor (beta-AR) binding-site density (Bmax) and Kd (apparent dissociation constant) in a 30-minute period. One hundred and four male Wistar rats were randomly divided into four groups: group C (control group), group I (intralipid group), group P1 (5 mg/kg propofol) and group P2 (10 mg/kg propofol). The results showed a significant downregulation of HR, LVSP, +dp/dtmax and -dp/dtmax in both groups P1 and P2 (especially after bolus injection in 7 min) than those of group C (P < 0.05), whereas no significant difference was found between the P1 and P2 groups (P > 0.05). Likely, Bmax was remarkably upregulated in both groups P1 and P2 (P < 0.05, vs. groups C and I), and there was no significant difference between these two groups (P > 0.05). Of note, the Kd value in group P2 (10 mg/kg propofol) was found dramatically increased in 30 min than that in the low-dose propofol-treated group (group P1) as well as in groups C and I (P < 0.05). In conclusion, these results indicate that intravenous injection of propofol bolus can inhibit the cardiac function partially via upregulation of Bmax and downregulation of the beta-AR affinity at higher-dose injection of propofol bolus.

Prognostic values of serum cystatin C and beta2 microglobulin, urinary beta2 microglobulin and N-acetyl-beta-D-glucosaminidase in early acute renal failure after liver transplantation.

BACKGROUND: Acute renal failure (ARF) after liver transplantation is associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of early effective prognostic factors. Recent studies indicated that serum levels of cystatin C and beta2-microglobulin (beta2 MG) as well as urinary beta2 MG and N-acetyl-beta-D-glucosaminidase (NAG) would increase in patients with early and mild renal impairment. In this study, these factors were detected during the different stages in patients who accepted orthotopic liver transplantation (OLT), and their feasibilities to predict early ARF after OLT were also analyzed. METHODS: Sixty patients with normal blood urea nitrogen (BUN) and serum creatinine (SCr) who received modified piggyback liver transplantation without veno-venous bypass were prospectively studied. Blood samples were drawn from patients for the determination of serum beta2 MG (n = 60), SCr (n = 60) and serum Cystatin C (n = 39) at following 5 intervals: before operation (T0), 20 minutes before anhepatic phase (T1), 25 minutes in anhepatic (T2), 60 minutes after reperfusion (T3) and at the end of operation (T4). Urinary beta2 MG (n = 60) and NAG (n = 60) were also examined at following 3 intervals: before operation (T0), 60 minutes after reperfusion (T3) and at the end of operation (T4). According to the Rimola A criteria of ARF in 24 hours after operation, all the patients were divided into two groups: ARF group and non-ARF group. The data were statistically analyzed to evaluate the feasibiliy of regarding these factors as prognostic factors for early ARF after liver transplantation in patients with normal SCr and BUN before operation. RESULTS: Ten of sixty cases showed ARF (16.7%). The Logistic regression analysis showed that the levels of serum and urinary beta2 MG as well as serum cystatin C before operation were correlated with early ARF after liver transplantation (P < 0.05), while only serum levels of cystatin C and Cr at the end of operation correlated with early ARF (P < 0.05, P < 0.01) after liver transplantation. The serum beta2 MG, Cystatin C, SCr and urinary beta2 MG levels in ARF group were much more higher than that in non-ARF group (P < 0.05, P < 0.01). There were significant differences between the correct and false predictive positive ratios of serum cystatin C, serum and urinary beta2 MG levels before operation (P < 0.05, P < 0.01), while only SCr showed significant difference between these groups at the end of operation (P < 0.01). CONCLUSIONS: The results revealed that there was potential renal damage among those patients who demonstrated normal SCr and BUN before operation, and that liver transplantation could aggravate this damage and causing ARF. Here we provided the prognostic values of serum Cystatin C, beta2 MG, urinary beta2 MG and NAG in patients with early acute renal failure after liver transplantation.

[Changes in pulmonary gas exchange and intrapulmonary shunt during orthotopic liver transplantation with non-venovenous bypass].

OBJECTIVE: To study the changes in pulmonary gas exchange and intrapulmonary shunt during orthotopic liver transplantation (OLT) with non-venovenous bypass. METHODS: Nineteen American Society of Anesthesiologists (ASA) III-IV patients (male 17, female 2) with terminal liver diseases were enrolled for study. Their age ranged from 25-67 years. Anesthesia was induced with midazolam 0.05 mg/kg, propofol 0.5-1.0 mg/kg, fentanyl 4 microg/kg, with vecuronium 0.1 mg/kg, and it was maintained with isoflurane inhalation, fentanyl and vecuronium. All patients were mechanically ventilated with 100% O(2) during operation. After induction of anesthesia, Swan-Ganz catheter was inserted via right internal jugular vein. Cardiac output (CO), mixed venous oxygen saturation and core venous temperature were continuously monitored with continuous cardiac output monitor, and electrocardiogram (ECG), central venous pressure (CVP), pulmonary arterial wedge pressure (PAWP), pulse oxygen saturation (SpO(2)) and end-tidal carbon dioxide tension (P(ET)CO(2)) were also continuously monitored during operation. Radial artery was cannulated for continuous direct blood pressure monitoring. Arterial and mixed venous blood samples were taken after induction of anaesthesia, and partial pressure of oxygen (PaO(2)), partial pressure of carbon dioxide (PaCO(2)), and cardiac index(CI) were determined after induction of anaesthesia, 30 minutes before anhepatic stage, 30 minutes during anhepatic stage, 30 minutes during neohepatic stage and at the end of operation. Alveolar-arterial oxygen partial pressure difference (P(A-a)O(2)) and intrapulmonary shunt (Qs/Qt) were calculated according to the standard formula. RESULTS: After induction of anaesthesia, when the inspired oxygen flow (FiO(2)) was 1.00, PaO(2) was only (385.0+/-56.4) mm Hg (1 mm Hg=0.133 kPa), P(A-a)O(2) and Qs/Qt were all higher than normal values. There were no significant changes 30 minutes before anhepatic stage as compared with that after induction of anaesthesia. CO, CI and Qs/Qt were decreased significantly during anhepatic stage compared with that after induction of anaesthesia. PaO(2), PaCO(2), CO and CI were increased and P(A-a)O(2) decreased significantly, but there were no significant changes in Qs/Qt 30 minutes during neohepatic stage. CI and CO increased and Qs/Qt decreased significantly at the end of operation, but there were no significant difference in PaO(2), PaCO(2) and P(A-a)O(2). CONCLUSION: There are obvious changes in pulmonary gas exchange and intrapulmonary shunt during OLT with non-veno-venous bypass.