Post-traumatic stress disorder (PTSD) is a debilitating anxiety disorder that may develop after an individual has experienced or witnessed a severe traumatic event. It has been shown that the 18 kDa translocator protein (TSPO) may be correlated with PTSD and that the TSPO ligand improved the behavioral deficits in a mouse model of PTSD. Midazolam, a ligand for TSPO and central benzodiazepine receptor (CBR), induces anxiolytic- and anti-depressant-like effects in animal models. The present study aimed to determine whether midazolam ameliorates PTSD behavior in rats as assessed by the single prolonged stress (SPS) model. The SPS rats received daily Sertraline (Ser) (15 mg/kg, p.o.) and midazolam (0.125, 0.25, 0.5, and 1 mg/kg, p.o.) during the exposure to SPS and behavioral assessments, which included the open field (OF) test, the contextual fear paradigm (CFP), and the elevated plus-maze (EPM). The results showed that, like Ser (15 mg/kg, p.o.), midazolam (0.25 and 0.5 mg/kg, p.o.) significantly reversed the behavioral deficiencies of the SPS rats, including PTSD-associated freezing and anxiety-like behavior but not the effects on spontaneous locomotor activity. In addition, the anti-PTSD effects of midazolam (0.5 mg/kg, p.o.) were antagonized by the TSPO antagonist PK11195 (3 mg/kg, i.p.), the CBR antagonist flumazenil (15 mg/kg, p.o.) and the inhibitor of steroidogenic enzymes finasteride (30 mg/kg, p.o.), which by themselves had no effect on PTSD-associated freezing and anxiety-like behavior. In summary, this study demonstrated that midazolam improves the behavioral deficits in the SPS model through dual TSPO and CBR and neurosteroidogenesis.
Postoperative cognitive dysfunction (POCD) is recognized as a complication after surgery in the elderly. The exact pathogenic mechanisms of POCD are still unknown. In this study, we investigated the role of iron accumulation within the central nervous system in the development of cognitive dysfunction in rats following splenectomy. Cognitive function was assessed using a Morris water maze on postoperative days 1, 3, and 7. Impaired cognitive function was observed on days 1 and 3 after splenectomy, while an anesthesia-alone group showed no significant difference from the control. Serum iron levels decreased and brain iron content increased on days 1 and 3 after surgery, which was in parallel with the impairment of cognitive function. Furthermore, the levels of proteins involved in the maintenance of brain iron homeostasis, including ferritin, transferrin receptor 1, and iron regulatory protein 2, were significantly different at postoperative days 1 and 3 in the hippocampus of splenectomized animals when compared with those of the control. The alterations in iron homeostasis were accompanied by intensified oxidative stress as measured by increases in the lipid peroxidation product, malondialdehyde, and a decrease in the levels of superoxide dismutase activity. Overall, these findings suggest that the impaired cognitive function was primarily due to surgical trauma rather than anesthesia. Increased iron accumulation and oxidative stress in the brain, especially in the hippocampus, may be involved in the pathogenesis of POCD.
Posterior spinal instrumentation and fusion surgery in school-aged children and adolescents is associated with the potential for massive intraoperative blood loss, which requires significant allogeneic blood transfusion. Until now, the intraoperative use of the cell saver has been extensively adopted; however, its efficacy and cost-effectiveness have not been well established. Therefore, the aim of this study is to determine the efficacy and cost-effectiveness of intraoperative cell saver use. This study was a single-center, retrospective study of 247 school-aged and adolescent patients who underwent posterior spinal instrumentation and fusion surgery between August 2007 and June 2013. A cell saver was used intraoperatively in 67 patients and was not used in 180 patients. Matched case-control pairs were selected using a propensity score to balance potential confounders in baseline characteristics. Allogeneic red blood cell (RBC) and plasma transfusions as well as blood transfusion costs were analyzed. The propensity score matching produced 60 matched pairs. Compared to the control group, the cell saver group had significantly fewer intraoperative allogeneic RBC transfusions (P = 0.012). However, when the combined postoperative and total perioperative periods were evaluated for the use of allogeneic RBC transfusion, no significant differences were observed between the two groups (P = 0.813 and P = 0.101, respectively). With regard to the total cost of perioperative transfusion of all blood products (RBC and plasma), costs for the control group were slightly lower than those of the cell saver group, but this variance did not reach statistical significance (P = 0.095). The use of the cell saver in posterior spinal instrumentation and fusion surgery in school-aged children and adolescents was able to decrease the amount of intraoperative allogeneic RBC transfusion but failed to decrease total perioperative allogeneic RBC transfusion. Moreover, the use of the cell saver was not cost-effective.
The objective of this review was to systematically assess the effect of thoracic epidural analgesia (TEA) vs. systemic analgesia (SA) on the recovery of gastrointestinal (GI) function in patients following GI surgery. We performed a comprehensive literature search to identify randomized controlled trials of adult patients undergoing GI surgery, comparing the effect of two postoperative analgesia regimens. Patients postoperatively receiving local anesthesia-based TEA with or without opioids were compared to patients receiving opioid-based SA. The outcomes considered were times to GI function recovery, GI complications, and specific side effects. Twelve studies with 331 patients in the TEA group and 319 in the SA group were included. Compared to SA, TEA improved the GI recovery after GI procedures by shortening the time to first passage of flatus by 31.3 h, 95% confidence intervals (CIs): -33.2 to -29.4, P < 0.01; and shortening the time to first passage of stool by 24.1 h, 95% CIs: -27.2 to -20.9, P < 0.001. There was no difference between the groups in the incidence of anastomotic leakage and ileus. The occurrence of postoperative hypotension was relatively higher in the TEA group, risk ratio: 7.9, 95% CIs: 2.4 to 26.5, P = 0.001; other side effects (such as pruritus and vomiting) were similar in the two groups. There is evidence that TEA (compared to SA) improves the recovery of GI function after GI procedures without any increased risk of GI complications. To further confirm these effects, larger, better quality randomized controlled trials with standard outcome measurements are needed.
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