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.

Prospective, randomized comparison of two supplemental oxygen methods during gastroscopy with propofol mono-sedation in obese patients.

BACKGROUND: Hypoxemia is a common complication in obese patients during gastroscopy with sedation. The Wei nasal jet tube (WNJT) is a new special nasopharyngeal airway with the ability to provide supraglottic jet ventilation and oxygen insufflation via its built-in wall channels. The aim of this study was to compare the efficacy and safety of the WNJT vs a nasal cannula for supplemental oxygen during gastroscopy with propofol mono-sedation in obese patients. AIM: To compare the efficacy and safety of the WNJT vs a nasal cannula for supplemental oxygen during gastroscopy with propofol mono-sedation in obese patients. METHODS: A total of 103 obese patients with a body mass index of 30 kg/m2 or more undergoing elective gastroscopy under propofol mono-sedation were randomly assigned to receive supplemental oxygen at 5 L/min through either a WNJT (WNJT group, n = 51) or a nasal cannula (nasal cannula group, n = 52). The lowest pulse oxygen saturation (SpO2) and mild and severe hypoxemia during gastroscopy were recorded. The primary outcome was the incidence of hypoxemia. RESULTS: The lowest SpO2 during gastroscopy with propofol mono-sedation was significantly increased in the WNJT group compared with the nasal cannula group. The incidence of mild hypoxemia and total incidence of hypoxemia were significantly lower in the WNJT group than in the nasal cannula group. Other than a higher incidence of epistaxis in the WNJT group, the occurrence of adverse events was similar between the devices. While neither device demonstrated a statistically significant difference in satisfaction among patients, the WNJT did result in improved satisfaction among anesthetists and physicians. CONCLUSION: During gastroscopy with propofol mono-sedation in obese patients, the WNJT, when compared with a nasal cannula for supplemental oxygen, can significantly reduce the occurrence of hypoxemia and improve both arterial oxygenation and satisfaction among anesthetists and physicians. The use of the WNJT may, however, lead to epistaxis in a few patients. In view of this clinically acceptable risk-benefit ratio, the WNJT may be recommended as an alternative tool for supplemental oxygen for the prevention of hypoxemia during gastroscopy with propofol mono-sedation in obese patients.

Comparison of two supplemental oxygen methods during gastroscopy with propofol mono-sedation in patients with a normal body mass index.

BACKGROUND: Hypoxemia due to respiratory depression and airway obstruction during upper gastrointestinal endoscopy with sedation is a common concern. The Wei nasal jet tube (WNJT) is a new nasopharyngeal airway with the ability to provide supraglottic jet ventilation and oxygen insufflation via its built-in wall channel. The available evidence indicates that with a low oxygen flow, compared with nasal cannula, the WNJT does not decrease the occurrence of hypoxemia during upper gastrointestinal endoscopy with propofol sedation. To date, there has been no study assessing the performance of WNJT for supplemental oxygen during upper gastrointestinal endoscopy with sedation when a moderate oxygen flow is used. AIM: To determine whether the WNJT performs better than the nasal prongs for the prevention of hypoxemia during gastroscopy with propofol mono-sedation when a moderate oxygen flow is provided in patients with a normal body mass index. METHODS: This study was performed in 291 patients undergoing elective gastroscopy with propofol mono-sedation. Patients were randomized into one of two groups to receive either the WNJT (WNJT group, n = 147) or the nasal cannula (nasal cannula group, n = 144) for supplemental oxygen at a 5-L/min flow during gastroscopy. The lowest SpO2 during gastroscopy was recorded. The primary endpoint was the incidence of hypoxemia or severe hypoxemia during gastroscopy. RESULTS: The total incidence of hypoxemia and severe hypoxemia during gastroscopy was significantly decreased in the WNJT group compared with the nasal cannula group (P = 0.000). The lowest median SpO2 during gastroscopy was significantly higher (98%; interquartile range, 97-99) in the WNJT group than in the nasal cannula group (96%; interquartile range, 93-98). Epistaxis by device insertion in the WNJT group occurred in 7 patients but stopped naturally without any treatment. The two groups were comparable in terms of the satisfaction of physicians, anesthetists and patients. CONCLUSION: With a moderate oxygen flow, the WNJT is more effective for the prevention of hypoxemia during gastroscopy with propofol mono-sedation compared with nasal prongs, but causing slight epistaxis in a few patients.

Ginsenoside Rb1 Attenuates Isoflurane/surgery-induced Cognitive Dysfunction via Inhibiting Neuroinflammation and Oxidative Stress.

OBJECTIVE: Anesthetic isoflurane plus surgery has been reported to induce cognitive impairment. The underlying mechanism and targeted intervention remain largely to be determined. Ginsenoside Rb1 was reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rb1 can attenuate isoflurane/surgery-induced cognitive dysfunction via inhibiting neuroinflammation and oxidative stress. METHODS: Five-months-old C57BL/6J female mice were treated with 1.4% isoflurane plus abdominal surgery for two hours. Sixty mg/kg ginsenoside Rb1 were given intraperitoneally from 7 days before surgery. Cognition of the mice were assessed by Barnes Maze. Levels of postsynaptic density-95 and synaptophysin in mice hippocampus were measured by Western blot. Levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in mice hippocampus were measured by ELISA. RESULTS: Here we show for the first time that the ginsenoside Rb1 treatment attenuated the isoflurane/surgery-induced cognitive impairment. Moreover, ginsenoside Rb1 attenuated the isoflurane/surgery-induced synapse dysfunction. Finally, ginsenoside Rb1 mitigated the isoflurane/surgery-induced elevation levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in the mice hippocampus. CONCLUSION: These results suggest that ginsenoside Rb1 may attenuate the isoflurane/surgery-induced cognitive impairment by inhibiting neuroinflammation and oxidative stress pending future studies.

Ginsenoside Rg1 Attenuates Isoflurane-induced Caspase-3 Activation via Inhibiting Mitochondrial Dysfunction.

OBJECTIVE: The inhalation anesthetic isoflurane has been shown to induce mitochondrial dysfunction and caspase activation, which may lead to learning and memory impairment. Ginsenoside Rg1 is reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rg1 can attenuate isoflurane-induced caspase activation via inhibiting mitochondrial dysfunction. METHODS: We investigated the effects of ginsenoside Rg1 at concentrations of 12.5, 25, and 50 µmol/L and pretreatment times of 12 h and 24 h on isoflurane-induced caspase-3 activation in H4 naïve and stably transfected H4 human neuroglioma cells that express full-length human amyloid precursor protein (APP) (H4-APP cells). For mitochondrial dysfunction, we assessed mitochondrial permeability transition pore (mPTP) and adenosine-5'-triphosphate (ATP) levels. We employed Western blot analysis, chemiluminescence, and flowcytometry. RESULTS: Here we show that pretreatment with 50 µmol/L ginsenoside Rg1 for 12 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in H4-APP cells, while pretreatment with 25 and 50 µmol/L ginsenoside Rg1 for 24 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in both H4 naïve and H4-APP cells. CONCLUSION: These data suggest that ginsenoside Rg1 may ameliorate isoflurane-induced caspase-3 activation by inhibiting mitochondrial dysfunction. Pending further studies, these findings might recommend the use of ginsenoside Rg1 in preventing and treating isoflurane-induced neurotoxicity.

Relationship between depth of anesthesia and effect-site concentration of propofol during induction with the target-controlled infusion technique in elderly patients.

BACKGROUND: There are few studies to assess whether the effect-site concentration of propofol can predict anesthetic depth during the target-controlled infusion (TCI) induction in elderly patients. This study aimed to evaluate the relationship between effect-site concentration of propofol and depth of anesthesia during the TCI induction in elderly patients. METHODS: Ninety patients (60 - 80 years) with an American Society of Anesthesiologists (ASA) physical status of 1 - 3, undergoing scheduled abdominal and thoracic surgery under general anesthesia were randomly allocated into one of three groups, Group S1, S2 and S3 (30 patients in each group). The patients in Group S1 received propofol with a target plasma concentration of 4.0 microg/ml; patients in Group S2 received propofol with an initial target plasma concentrations of 2.0 microg/ml that was raised to 4.0 microg/ml 3 minutes later; patients in Group S3 received an infused scheme of 3 steps; starting from a target plasma concentration of 2.0 microg/ml that was increased stepwised by 1 microg/ml until a target plasma concentration of 4.0 microg/ml was achieved, the interval between the two steps was 3 minutes. When an Observer's Assessment of Alertness/Sedation (OAA/S) score of 1 was achieved, remifentanil (effect-site concentration (Ce) of 4.0 ng/ml) and rocuronium 0.9 mg/kg were administered. Tracheal intubation was started 2 minutes after rocuronium injection. Changes of propofol Ce, blood pressure (BP), heart rate (HR), and bispectral index (BIS) were recorded. RESULTS: When an OAA/S score of 1 was achieved, Ce of propofol were (1.7 +/- 0.4) microg/ml, (1.9 +/- 0.3) microg/ml, (1.9 +/- 0.4) microg/ml and the BIS values were 64 +/- 5, 65 +/- 8, and 62 +/- 8 in Groups S1, S2 and S3. Before intubation, Ce of propofol was (2.8 +/- 0.2) microg/ml, (2.8 +/- 0.3) microg/ml, (2.7 +/- 0.3) microg/ml, and the BIS values were 48 +/- 7, 51 +/- 7, and 47 +/- 5 in Groups S1, S2 and S3. By linear regression analysis, a significant correlation between Ce of propofol and BIS values was found (r = -0.580, P < 0.01). Systolic blood pressure (SBP) before intubation was significantly lower in Group S1 than in Groups S2 and S3. SBP and HR after intubation in the three groups were significantly increased when compared with pre-intubation values, but they did not exceed baseline values. CONCLUSIONS: During the TCI induction, Ce of propofol with (1.9 +/- 0.3) microg/ml may make the elderly patients unconscious. When remifentanil with a Ce of 4.0 ng/ml is added a Ce of propofol with (2.8 +/- 0.3) microg/ml is suitable for intubation. The Ce of propofol has a close correlation with the BIS values. Also, a two-step TCI technique seems to be a more suitable method of anesthesia induction in elderly patients compared with the no-stepwise TCI technique and three-step TCI technique.