Effect of postoperative application of esketamine on postoperative depression and postoperative analgesia in patients undergoing pancreatoduodenectomy: a randomized controlled trial protocol.

BACKGROUND: Pancreatoduodenectomy (PD) is traumatic, difficult to perform, and has a high incidence of postoperative complications and perioperative mortality. Postoperative complications and pain occur frequently and seriously affect the psychological status of patients. Esketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has analgesic and antidepressant effects. In this study, we aim to investigate the effect of esketamine on postoperative depression and pain in patients undergoing PD. METHODS/DESIGN: This prospective, single-center, randomized control trial will include 80 patients who will undergo elective PD. The patients will be randomly assigned to two groups: the experimental group that will receive esketamine (n = 40) and the control group (n = 40). In the esketamine group, the analgesic pump will be connected immediately after surgery. A solution of esketamine 1.5 mg/kg + sufentanil 2 µg/kg, diluted to 150 mL, will be administered continuously for 72 h at the background infusion and impact doses of 1 mL/h and 2 mL/time, respectively; the locking time will be 10 min. The control group will receive sufentanil 2 µg/kg that will be administered as per the esketamine group. The primary outcome will be the Hamilton Depression Scale (HAMD-17) score on the third day post-surgery (POD3). Secondary study indicators will include (1) visual analog scale (VAS) score and HAMD-17 score prior to surgery, immediately after entering the postanesthesia care unit (PACU) and 1, 2, 3, 4, and 5 days after surgery; (2) Richmond Agitation-Sedation Scale (RASS) score at 1, 2, 3, 4, and 5 days after surgery; (3) consumed doses of sufentanil and esketamine after surgery; (4) postoperative analgesia pump effective press times, rescue analgesia times, and rescue drug dosage, recording the number of rescue analgesia and rescue drug dosage at 6, 24, 48, and 72 h after the patient enters the PACU; (5) postoperative complications and adverse events; (6) postoperative hospital stay; (7) concentrations of brain-derived neurotrophic factor (BDNP), 5-hydroxytryptamine (5-HT), tumor necrosis factor (TNF-α) and interleukin-6, at 1, 3, and, 5 days post-surgery; and (8) the patient survival rate at 6 and 12 months post-surgery. DISCUSSION: The study hypothesis is that the postoperative HAMD-17 and VAS scores, incidence of postoperative adverse reactions, and concentration of serum markers BDNP, 5-HT, TNF-α, and IL-6 in the experimental group will be lower than those in the control group. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2200066303. Registered on November 30, 2022. PROTOCOL VERSION: 1.0.

[Effect of lidocaine precondition on hepatocytes calcium overload and apoptosis induced by cell hypoxia-reoxygenation].

OBJECTIVE: To investigate the effect and possible mechanism of lidocaine precondition on calcium overload and apoptosis of the hepatocytes induced by cell hypoxia-reoxygenation. METHODS: The cultured L02 hepatocytes were randomly divided into 3 groups: a hypoxia-reoxygenation group (Group I), a lidocaine precondition group (Group II), and a normal control group (Group III). After 4 hours of cell hypoxia and 10 hours of reoxygenation, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations in the nutritive medium were detected. The cytoplasm ionic calcium concentration was measured by fluoro spectrophotometer. The apoptosis was measured by flow cytometry and fluorescent microscope. The appearance and ultra-microstructure changes of hepatocytes were observed by inverted microscope and electronic microscope. RESULTS: Cytoplasm ionic calcium concentration and apoptosis was positively correlated (r=0.7652, R(2)=0.5855, P< 0.05). The ALT concentration in the nutritive medium, AST concentration in the nutritive medium, cytoplasm ionic calcium concentration and the ratio of apoptosis of Group I and II were significantly higher than those of Group III(P< 0.05).The appearance and ultra-microstructure changes of Group I and II were worse than those of Group III. The ALT concentration in the nutritive medium, AST concentration in the nutritive medium, cytoplasm ionic calcium concentration and the ratio of apoptosis of Group II were significantly lower than those of Group I (P< 0.05). The ultra-microstructure injury of hepatocytes of Group II were less serious than those of Group I. CONCLUSION: Precondition with lidocaine can attenuate calcium overload of hepatocytes induced by hypoxia-reoxygenation in vitro,and decrease the ratio of apoptosis.