Fish oil omega-3 Fatty Acids Alleviate Postoperative delirium-like Behavior in aged mice by Attenuating Neuroinflammation and Oxidative Stress.

Postoperative delirium (POD) is a common and serious neuropsychiatric syndrome among older patients, and lacks effective therapies. Omega-3 fatty acids, possessing anti-inflammatory and antioxidant properties, have shown potent neuroprotective effects in several diseases. The present study investigated whether omega-3 fatty acids could exert a neuroprotective role against POD in aged mice. A mouse model of POD was established to explore the role of omega-3 fatty acids in laparotomy-induced delirium-like behavior by evaluating systemic inflammatory changes, neuroinflammation, oxidative stress, and behavior at different time points in aged mice. Oral gavage with omega-3 fatty acids (300 mg/kg) for 3 weeks before surgery significantly attenuated anesthesia/surgery-induced POD-like behavior and the accumulation of proinflammatory cytokines from the peripheral blood in aged mice. Moreover, it also remarkably mitigated neuroinflammation and the oxidative stress response (malondialdehyde [MDA] and superoxide dismutase [SOD]) in the prefrontal cortex and hippocampus of surgical mice. Our findings provided evidence that pretreatment with omega-3 fatty acids may play a vital role in the treatment of POD through mechanisms involving its anti-inflammatory and antioxidant effects, which may be a promising prevention strategy for POD in aged patients.

Intravenous Lidocaine Decreased the Median Effective Concentration of Sufentanil for Tracheal Intubation in Obese Patients.

Purpose: Sufentanil has been widely used to inhibit the hemodynamic responses caused by tracheal intubation. Using intravenous lidocaine may reduce the dose of sufentanil and better maintain the hemodynamics. This study aimed to determine the effects of intravenous lidocaine on the median effective concentration (EC50) of sufentanil for endotracheal intubation in obese patients. Patients and Methods: This is a randomized, double-blind, up-and-down sequential allocation study. Fifty obese patients undergoing bariatric surgery were randomly allocated in a 1:1 ratio into the lidocaine group and the saline group. Anesthesia was induced using a target-controlled infusion of propofol and sufentanil. The effect-site concentration (Ce) of propofol was 3.5 µg/mL. The Ce of sufentanil for the first patient was 0.4 ng/mL, and the sufentanil dose for the next patient was determined according to the responses of the previous patient, using Dixon's up-and-down sequential method with an interval of 0.05 ng/mL. When the target concentration of propofol and sufentanil was reached, lidocaine 1.5 mg/kg or the same volume of normal saline was infused over 3 min. Tracheal intubation was performed 3 min after the end of the lidocaine or normal saline infusion. Probit regression was used to calculate the EC50 and 95% confidence interval (CI) of sufentanil. Results: Thirty-eight patients completed this study. The EC50 of sufentanil was 0.36 ng/mL (95% CI: 0.31-0.41 ng/mL) in the lidocaine group, which was significantly lower than 0.50 ng/mL (95% CI: 0.43-0.62 ng/mL) in the saline group. In addition, compared with saline group, the dosage of sufentanil in lidocaine group decreased significantly during the test. The hemodynamics of the two groups were stable during the study period. Conclusion: Intravenous lidocaine 1.5 mg/kg decreased the EC50 of sufentanil required for tracheal intubation in obese patients undergoing bariatric surgery.

The pharmacokinetics and safety of lidocaine in liver cancer patients undergoing hepatic resection.

PURPOSE: The purpose of this study was to explore the pharmacokinetics (PK) characteristics and safety of continuous lidocaine infusion during hepatectomy in liver cancer patients. METHODS: This study included thirty-five patients undergoing laparoscopic hepatectomy from January 2021 to December 2021. Patients received a short infusion of 1% lidocaine at a dose of 1.5 mg/kg based on ideal body weight, followed by a continuous infusion of 1 mg/kg/h during the operation. The plasma concentrations of lidocaine and its active metabolites were measured using validated ultra-performance liquid chromatography-tandem mass spectrometry. Safety was evaluated by monitoring and recording all adverse events (AEs). RESULTS: The concentrations of lidocaine were within the safe range, except one patient's concentration of lidocaine which reached the toxic range (> 5 µg/mL). The mean half-life (T1/2), the mean time to maximum observed concentration (Tmax), and the mean maximum observed concentration (Cmax) of lidocaine were 3.96 h, 2.85 h, and 2030 ng/mL, respectively; the mean T1/2, Tmax, and Cmax (n = 32) of MEGX were 6.59 h, 5.05 h, and 333.28 ng/mL, respectively; and the mean T1/2, Tmax, and Cmax of GX (n = 18) were 25.98 h, 7.33 h, and 75.81 ng/mL. Although eight subjects with AEs were reported, there were no serious AEs or deaths. No patients had serious postoperative complications. No deaths occurred within 30 days after the operation. CONCLUSIONS: Under the administration regimen of this study, intravenous infusion of lidocaine is safe and tolerable for liver cancer patients with laparoscopic hepatectomy. Fine safety and PK characteristics support the application of lidocaine in such patients and further clinical research. TRIAL REGISTRATION: China Clinical Trial Registration Center (ChiCTR2100042730), Registered 27 January 2021.

Carotid artery corrected flow time and respiratory variations of peak blood flow velocity for prediction of hypotension after induction of general anesthesia in elderly patients.

BACKGROUND: Postinduction hypotension is closely related to postoperative complications. Elderly patients with compromised cardiovascular compensatory reserve are more susceptible to hypotension after induction of general anesthesia. This study investigated whether the carotid artery corrected flow time (FTc) and respiratory variation of peak blood flow velocity in the common carotid artery (ΔVpeak) could predict postinduction hypotension in elderly patients. METHODS: This prospective observational study included elderly patients aged 65 to 75 who were scheduled for elective surgery under general anesthesia with ASA physical status class of I-II, without cardiovascular disease, hypertension, diabetes, or obesity. Anesthesia was induced by midazolam, sufentanil, and etomidate and was maintained by sevoflurane. The carotid artery FTc and ΔVpeak were measured by ultrasound before induction of anesthesia. Hemodynamic data were recorded before induction and then during the first 10 min after induction. RESULTS: Ninety-nine patients were included in the final analysis, of whom 63 developed postinduction hypotension. The area under the receiver operating characteristic curves was 0.87 (0.78 to 0.93) for carotid artery FTc and 0.67 (0.56 to 0.76) for ΔVpeak, respectively. The optimal cutoff value for predicting postinduction hypotension was 379.1 ms for carotid artery FTc, with sensitivity and specificity of 72.2 and 93.7%, respectively. The best cutoff value was 7.5% for ΔVpeak, with sensitivity and specificity of 55.6 and 75.0%, respectively. CONCLUSIONS: The carotid artery FTc is a reliable predictor of postinduction hypotension in elderly patients with ASA status of I or II, without cardiovascular disease, hypertension, diabetes, or obesity. Elderly patients with a carotid artery FTc less than 379.1 ms before anesthesia have a higher risk of postinduction hypotension. TRIAL REGISTRATION: Clinical Trial Registry on August 2nd, 2020 ( www.chictr.org.cn ; ChiCTR2000035190).

Simultaneous determination of lidocaine and its active metabolites in plasma by UPLC-MS/MS and application to a clinical pharmacokinetic study in liver cancer patients with laparoscopic hepatectomy.

Lidocaine, widely used as a local anesthetic, has anti-inflammatory and inhibitory effects on tumor recurrence and metastasis. To investigate the pharmacokinetics of lidocaine in liver cancer patients undergoing laparoscopic hepatectomy, a fast and sensitive analytical technique was developed. The method was adequately validated with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to simultaneously determine the concentration of lidocaine and its metabolites in plasma. The chromatographic separation was achieved on an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm) by gradient elution with a mobile phase of A (formic acid-water (1:1000, v/v)) and B (formic acid-acetonitrile (1:1000, v/v)). The accuracy and precision were verified within the concentration ranges of 10-5000 ng/mL for lidocaine, 2-1000 ng/mL for monoethylglycinexylidide (MEGX) and 2-500 ng/mL for glycinexylidide (GX). The selectivity, carry-over effect, interference between the analytes and internal standard (IS), precision and accuracy, matrix effect extraction recovery, dilution integrity and stability were satisfactory for the relevant guideline standards. The method was successfully applied to the pharmacokinetic study of lidocaine in liver cancer patients undergoing laparoscopic hepatectomy. After receiving a bolus and continuous infusion, the mean peak concentration of lidocaine was 2097 ng/mL for lidocaine, 336.6 ng/mL for MEGX and 72.66 ng/mL for GX, respectively. The mean peak time was 2.89 h for lidocaine, 5.14 h for MEGX and 9.88 h for GX, respectively. In addition, the mean half-life was 4.19 h for lidocaine and 6.92 h for MEGX. In this study, we found that the metabolism of lidocaine and MEGX might be affected by the hepatic blood flow occlusion or liver injury.

Effect of low-dose ketamine on MACBAR of sevoflurane in laparoscopic cholecystectomy: A randomized controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Low-dose ketamine can reduce the minimum alveolar concentration of sevoflurane necessary to block the adrenergic response (MACBAR ) in animals. However, the effects of low-dose ketamine on the sevoflurane MACBAR in patients undergoing laparoscopic surgery are unclear. The aim of this study was to investigate the effects of three different low doses of ketamine on the MACBAR of sevoflurane in patients undergoing laparoscopic cholecystectomy. METHODS: One hundred patients who underwent laparoscopic cholecystectomy were enrolled. After general anaesthesia induction and tracheal intubation, patients received sevoflurane anaesthesia in combination with a loading dose of saline followed by infusion or a loading dose of 0.5 mg/kg ketamine followed by a continuous infusion of 5 (K1 group), 10 (K2 group) and 20 µg/kg/min (K3 group). The target concentration of end-tidal sevoflurane was maintained for at least 20 minutes before carbon dioxide pneumoperitoneum stimulus. The MACBAR of sevoflurane in each group was determined by using an up-and-down sequential allocation technique. RESULTS AND DISCUSSION: Seventy-one patients completed the study. The values of MACBAR for sevoflurane were 5.3% in the K0 , 4.8% in K1 , 3.3% in K2 and 3.2% in K3 groups. The use of ketamine significantly reduced the MACBAR of sevoflurane compared to sevoflurane alone. The K2 and K3 groups showed significantly lower values of MACBAR than that in the K1 group. However, a higher dose of ketamine in the K3 group did not further reduce the sevoflurane MACBAR . The mean arterial blood pressure (MAP) values before pneumoperitoneum in the K2 and the K3 groups were significantly higher compared to those in the K0 and K1 groups. Compared with the values before pneumoperitoneum, the heart rate and MAP after pneumoperitoneum were significantly increased. Overall, the haemodynamics remained stable during the study period in all groups. WHAT IS NEW AND CONCLUSION: A loading dose of 0.5 mg/kg ketamine followed by a continuous infusion of 10.0 µg/kg/min led to a significant decrease in the MACBAR of sevoflurane in patients undergoing laparoscopic cholecystectomy.

Effects of hydrogen sulfide on cognitive dysfunction and NR2B in rats.

BACKGROUND: Hepatic ischemia/reperfusion (hepatic I/R) has been found to induce cognitive dysfunction. The NR2B subunit of N-methyl-D-aspartate (NMDA) receptors is a major factor in memory and learning processes, and hydrogen sulfide (H2S) may modulate this NMDA receptor. Therefore, in this study, sodium hydrosulfide (NaHS, a donor of H2S) was administered in an animal model of hepatic I/R to investigate the effects of H2S on cognitive impairment and expression of NR2B. MATERIALS AND METHODS: NaHS (5 mg/kg) or normal saline was administered intraperitoneally once a day for 11 consecutive days, during which a rat model of 70% hepatic I/R was established on the fourth day. Cognitive function was evaluated using a Morris water maze, mRNA and protein levels of the NR2B subunit were detected in the hippocampus by RT-PCR and Western blotting. All these tests were performed on postoperative days 1, 3, 5, and 7. RESULTS: Cognitive dysfunction was detected in the hepatic I/R group, and this dysfunction was associated with a decrease in the mRNA and protein levels of the NR2B subunit of the NMDA receptors in the hippocampus. In contrast, treatment with NaHS significantly ameliorated the impairment of cognitive function caused by hepatic I/R, and an increase in mRNA and protein levels of the NR2B subunit was detected in the corresponding hippocampus tissues. CONCLUSIONS: The present data suggest that H2S exerts a protective effect on hepatic I/R-induced cognitive impairment, and this effect may be associated with the NR2B subunit of the NMDA receptors. H2S may represent a novel therapeutic agent for the treatment of postoperative cognitive dysfunction after liver surgery.

[Effect of urapidil combined with phentolamine on hypertension during extracorporeal circulation].

OBJECTIVE: To study the effect of urapidil combined with phentolamine in the management of hypertension during extracorporeal circulation. METHODS: Ninety patients undergoing aortic and mitral valve replacement were randomly divided into 3 equal groups to receive treatment with phentolamine (group A), urapidil (group B), or both (group C) during extracorporeal circulation. The mean arterial pressure (MAP) before and after drug administration, time interval of two administrations, spontaneous recovery of heart beat after aorta unclamping, ventricular arrhythmia, changes of ST-segment 1 min after the recovery of heart beat, ante-parallel cycle time, aorta clamping time, post-parallel cycle time, dopamine dose after cardiac resuscitation, and perioperative changes of plasma TNF-α and IL-6 levels were recorded. RESULTS: There was no significant difference in MAP between the 3 groups before or after hypotensive drug administration (P>0.05). The time interval of two hypotensive drug administrations was longer in group C than in groups A and B (P<0.05). The incidence of spontaneous recovery of heart beat after aorta unclamping, incidence of ventricular arrhythmia, changes of ST-segment 1 min after the recovery of heart beat, ante-parallel cycle time, aorta clamping time, and post-parallel cycle time were all comparable between the 3 groups. The dose of dopamine administered after cardiac resuscitation was significantly larger in group B than in groups A or group C (P<0.05). The plasma levels of TNF-α and IL-6 were significantly increased after CPB and after the operation in all the groups, but were lowed in group C than in groups A and B at the end of CPB and at 2 h and 12 after the operation. CONCLUSIONS: Urapidil combined with phentolamine can control hypertension during extracorporeal circulation without causing hypotension.

Incidence of unanticipated difficult airway in obstetric patients in a teaching institution.

PURPOSE: Our aim was to determine the incidence of difficult intubation during pregnancy-related surgery at a high-risk, high-volume teaching institution. METHODS: Airway experience was analyzed among patients who had pregnancy-related surgery under general anesthesia from January 2001 through February 2006. A difficult airway was defined as needing three or more direct laryngoscopy (DL) attempts, use of the additional airway equipment after the DL attempts, or conversion to regional anesthesia due to inability to intubate. Airway characteristics were compared between patients with and without a difficult airway. In addition, pre- and postoperative airway evaluations were compared to identify factors closely related to changes from pregnancy. RESULTS: In a total of 30,766 operations, 2,158 (7%) were performed with general anesthesia. Among these, 1,026 (47.5%) were for emergency cesarean delivery (CD), 610 (28.3%) for nonemergency CD, and 522 (24.2%) for non-CD procedures. A total of 12 patients (0.56%) were identified as having a difficult airway. Four patients were intubated with further DL attempts; others required mask ventilation and other airway equipment. Two patients were ventilated through a laryngeal mask airway without further intubation attempts. Ten of the 12 difficult airway cases were encountered by residents during their first year of clinical anesthesia training. There were no maternal or fetal complications except one possible aspiration. CONCLUSION: Unanticipated difficult airways accounted for 0.56% of all pregnancy-related surgical patients. More than 99.9% of all obstetric patients could be intubated. A difficult airway is more likely to be encountered by anesthesia providers with <1 year of experience. Proper use of airway equipment may help secure the obstetric airway or provide adequate ventilation. Emergency CD did not add an additional level of difficulty over nonemergency CD.