Lidocaine pretreatment attenuates inflammatory response and protects against sepsis-induced acute lung injury via inhibiting potassium efflux-dependent NLRP3 activation.

OBJECTIVE: Sepsis may often result in acute lung injury (ALI), with a high mortality and morbidity. Available evidence indicates that activation of NLRP3 inflammasome to induce macrophage inflammation plays a crucial role in the inflammation progression of ALI and lidocaine can attenuate inflammatory responses. We hypothesized that lidocaine may attenuate inflammatory response and sepsis-induced ALI by inhibiting potassium efflux-dependent NLRP3 activation. METHODS: C57BL/6N mice were randomized and divided into six groups (n = 6) receiving different treatments. Lung vascular permeability and histological changes in the lungs were evaluated by Evans blue dye, bronchoalveolar lavage analysis and hematoxylin and eosin staining. J774A.1 macrophages were divided into 12 groups receiving different treatments. The expression of both NLRP3 inflammasome activation-related protein and P2X7 in the macrophages was measured by immunofluorescence staining and Western blots. The whole cell currents were determined by a voltage-patch clamp technique. RESULTS: Challenge with LPS led to ALI in mice with an increased lung injury score (0.54 ± 0.09), which was significantly attenuated by lidocaine pretreatment (0.20 ± 0.08, P < 0.0001). Lidocaine pretreatment significantly decreased the NLRP3 activation and IL-1ß release in the macrophages. Furthermore, lidocaine pretreatment down-regulated the expression of P2X7 receptors, inhibited LPS- and ATP-induced sodium (Na+) inward flow, and maintained the intracellular K+ level in the macrophages. In addition, activation of Na+ influx did not eliminate anti-inflammatory effect of lidocaine. The activation of NLRP3 could be suppressed by extracellular K+ level in a dose-dependent model. However, lidocaine pretreatment eliminated NLRP3 activation and IL-1ß release induced by K+ efflux, and decreased outward K+ current and extracellular K+ level in the macrophages challenged by LPS/ATP. CONCLUSIONS: Lidocaine pretreatment can attenuate the sepsis-induced ALI by an anti-inflammatory mechanism of inhibiting K+ efflux-dependent NLRP3 activation.

Remimazolam Tosilate Sedation with Adjuvant Sufentanil in Chinese Patients with Liver Cirrhosis Undergoing Gastroscopy: A Randomized Controlled Study.

BACKGROUND This prospective, randomized, controlled study evaluated the efficacy and safety of remimazolam tosilate sedation with adjuvant sufentanil, relative to propofol, for Chinese patients with liver cirrhosis undergoing gastroscopy. MATERIAL AND METHODS Patients with liver cirrhosis (n=148) aged 18-65 years and undergoing gastroscopy were randomly and equally allocated to receive either 0.107 mg/kg remimazolam tosilate (remimazolam group) or 2 mg/kg propofol. Patients received intravenous sufentanil 0.15 µg/kg before the study drug. If necessary, an additional dose of propofol 20 mg was used and repeated. The primary outcome was the satisfaction rating (satisfactory, fair, or unsatisfactory) of the endoscopist with the sedation. Secondary outcomes were complications (respiratory depression, apnea, body movement, bradycardia, hypotension, nausea or vomiting, somnolence, dizziness, and fever) and patient satisfaction. RESULTS Compared with the propofol group, the remimazolam group required a longer time to sedation and a shorter time to emergence. The percentage of remimazolam sedations the endoscopist rated satisfactory (90.5%) was higher than that for propofol (77.0%; P=0.026). Patients given remimazolam experienced lower rates of respiratory depression, body movement, and hypotension (2.7, 8.1, 4.1%, respectively), than did the propofol group (17.6, 23.0, 14.9%; P=0.003, 0.013, 0.025). The 2 groups were comparable regarding the other secondary outcomes. CONCLUSIONS For Chinese patients with liver cirrhosis undergoing gastroscopy, remimazolam tosilate with adjuvant sufentanil provides a satisfactory level of sedation with a good safety profile.

Errate: Remimazolam Tosilate Sedation with Adjuvant Sufentanil in Chinese Patients with Liver Cirrhosis Undergoing Gastroscopy: A Randomized Controlled Study.

The results in Table 3 (highlighted) have been corrected to be consistent with the results reported in the text. Reference: YingHao Cao, Ping Chi, Chen Zhou, WenFei Lv, ZheFen Quan, Fu Shan Xue: Remimazolam Tosilate Sedation with Adjuvant Sufentanil in Chinese Patients with Liver Cirrhosis Undergoing Gastroscopy: A Randomized Controlled Study. Med Sci Monit, 2022; 28: e936580. DOI: 10.12659/MSM.936580.

Elevated effluent potassium concentrations predict the development of postreperfusion hyperkalemia in deceased liver transplantation: a retrospective cohort study.

BACKGROUND: Postreperfusion hyperkalemia (PRHK) has garnered increasing attention in regard to deceased liver transplantation (LT), especially for LT using the expanded criteria donor grafts. However, the impact of the effluent potassium (eK+) concentration on PRHK has been largely overlooked. We evaluated whether elevated eK+ concentrations are associated with PRHK in deceased LT. METHODS: In this single-institution, retrospective cohort study, we included all adults who underwent deceased LT with intraoperative eK+ concentration monitoring between November 2016 and December 2018. The eK+ concentrations were obtained from the effluent samples collected following a standard portal vein flush. PRHK was defined as any serum potassium (sK+) level of > 5.5 mmol/L following reperfusion. Logistic regression was performed to identify predictors for PRHK, and linear regression was used to examine predictors of the maximum percentage increase in the sK+ level following reperfusion. RESULTS: Of the 86 patients who met the inclusion criteria, 54 (62.8%) developed PRHK. Independent predictors for PRHK included greater graft weight (OR 1.283 [95% CI 1.029-1.599] per 100 g, P = 0.027), an elevated eK+ concentration (OR 1.291 [95% CI 1.068-1.561] per mol/L, P = 0.008), and a higher sK+ level before reperfusion (OR 4.459 [95% CI 1.543-12.884] per mol/L, P = 0.006). An eK+ concentration of more than 6.9 mmol/L had a sensitivity of 59.26% and a specificity of 78.12% for predicting PRHK (area under the receiver operating characteristic curve, 0.694). Multiple linear regression analyses indicated that the eK+ and sK+ levels before reperfusion were significant predictors of the maximum percentage increase in the sK+ level following reperfusion. In addition, PRHK was associated with an increased risk of postreperfusion significant arrhythmias, severe postreperfusion syndrome, and postoperative early allograft dysfunction. CONCLUSIONS: This study shows that the eK+ concentration could predict the risk of PRHK in deceased LT. Further prospective studies are warranted to clarify these associations.

Long-term high-risk drinking does not change effective doses of propofol for successful insertion of gastroscope in Chinese male patients.

BACKGROUND: Available literature indicates that long-term drinkers demand a higher dose of propofol for induction of anesthesia than non-drinkers. However, there is no study having assessed the influence of long-term high-risk drinking (LTHRD) on the effective doses of propofol for successful insertion of gastroscope with sedation. This study was designed to compare the effective doses of propofol for successful insertion of gastroscope between LTHRD and non-drinking (ND) Chinese male patients. METHODS: Thirty-one LTHRD patients and 29 ND male patients undergoing elective gastroscopy with propofol sedation were enrolled. The modified Dixon's up-and-down method was applied to determine the calculated median effective dose (ED50) of propofol for successful insertion of gastroscope. Furthermore, the isotonic regression analysis was used to establish the dose-response curve of propofol and assess the effective doses of propofol where 50% (ED50) and 95% (ED95) of gastroscope insertions were successful. RESULTS: The calculated ED50 of propofol for successful insertion of gastroscope was 1.55 ± 0.10 mg/kg and 1.44 ± 0.11 mg/kg in the LTHRD and ND patients. The isotonic regression analysis further showed that ED50 and ED95 of propofol for successful insertion of gastroscope was 1.50 mg/kg (95%CI, 1.40-1.63) and 1.80 mg/kg (95%CI, 1.74-1.90) in the LTHRD patients, respectively; 1.40 mg/kg (95% CI, 1.27-1.57) and 1.60 mg/kg (95%CI, 1.56-1.65) in the ND patients. The ED50 of propofol for successful insertion of gastroscope was not significantly different between LTHRD and ND patients. CONCLUSIONS: This study demonstrates that the difference in the estimated ED50 of propofol for successful insertion of gastroscope between LTHRD and ND Chinese male patients was not statistically significant. TRIAL REGISTRATION: The study was registered on November 28, 2020 ( ChiCTR2000040382 ) in the Chinese Clinical Trial Registry.

The 50% and 95% effective doses of remimazolam tosilate with adjuvant sufentanil for sedation in patients with liver cirrhosis undergoing oesophagogastric varices screening endoscopy.

WHAT IS ALREADY KNOWN AND OBJECTIVE: Sedation is routinely provided for patients undergoing gastrointestinal endoscopy. Remimazolam tosilate is a novel and short-acting sedative agent that has been used for sedation during endoscopic procedures. The optimal dose of remimazolam in gastrointestinal endoscopy for patients with liver cirrhosis has not been elucidated. BACKGROUND: To determine the effective dose of remimazolam tosilate with adjuvant sufentanil for sedation in patients with liver cirrhosis undergoing oesophagogastric varices screening endoscopy. MATERIAL AND METHODS: Patients aged 18-65 years with liver cirrhosis undergoing screening endoscopy for oesophagogastric varices were recruited. Sufentanil 0.15 µg/kg was given intravenously at 2 min before administration of remimazolam tosilate. The initial dose of remimazolam was 0.1 mg/kg and adjusted by 0.025 mg/kg as a step size, based on the Dixon and Massay up-and-down sequential method. Inclusion of patients was stopped after eight crossovers and the calculated median effective dose (ED50 ) of remimazolam for successful endoscopy was obtained by calculating the mean of midpoint of all crossovers. Furthermore, a probit regression was applied to establish the dose-response curve of remimazolam and further assess the 95% effective dose (ED95 ) of remimazolam. RESULTS: The calculated ED50 of remimazolam for successful endoscopy using the mean of midpoint of all crossovers was 0.097 mg/kg (95% CI, 0.004-0.099 mg/kg). Using the probit regression analysis, the ED50 and ED95 of remimazolam for successful endoscopy was 0.097 mg/kg (95% CI, 0.004-0.099 mg/kg) and 0.107 mg/kg (95% CI, 0.103-0.336 mg/kg), respectively. No adverse events were observed throughout the study period. CONCLUSIONS: This pilot study suggests that the ED50 and ED95 of remimazolam tosilate with adjuvant sufentanil for sedation in liver cirrhosis patients undergoing oesophagogastric varices screening endoscopy was 0.097 and 0.107 mg/kg, respectively.