Project description:Delirium is a common postoperative complication among older patients with many adverse outcomes. Due to lack of validated biomarkers, prediction and monitoring of delirium by biological testing is not currently feasible. Circulating proteins in cerebrospinal fluid (CSF) may reflect biological processes causing delirium. Our goal was to discover and investigate candidate protein biomarkers in preoperative CSF that were associated with development of postoperative delirium in older surgical patients. We employed a nested case–control study design coupled with high multiplex affinity proteomics analysis to measure 1305 proteins in preoperative CSF. Twenty-four matched delirium cases and non-delirium controls were selected from the Healthier Postoperative Recovery (HiPOR) cohort and the associations between preoperative protein levels and postoperative delirium were assessed using t-test statistics with further analysis by systems biology to elucidate delirium pathophysiology. Proteomics analysis identified 32 proteins in preoperative CSF that significantly associate with delirium (t-test p<0.05). Due to the limited sample size these proteins did not remain significant by multiple hypothesis testing using the Benjamini-Hochberg correction and q-value method. Three algorithms were applied to separate delirium cases from non-delirium controls. Hierarchical clustering classified 40/48 case-control samples correctly, principal components analysis separated 43/48. The receiver operating characteristic curve yielded an area under the curve [95% confidence interval] of 0.91 [0.80-0.97]. Systems biology analysis identified several key pathways associated with risk of delirium: inflammation, immune cell migration, apoptosis, angiogenesis, synaptic depression and neuronal cell death. Proteomics analysis of preoperative CSF identifies 32 proteins that might discriminate individuals who subsequently develop postoperative delirium from matched control samples. These proteins are potential candidate biomarkers for delirium and may play a role in its pathophysiology.

Project description:PurposePostoperative delirium (POD) is considered the most common postoperative neurological complication in elderly patients. The aim of this study was to evaluate the efficacy of the administration of ketofol versus dexmedetomidine (DEX) for minimizing POD in elderly patients undergoing urgent exploration for intestinal obstruction.MethodsThis prospective double-blinded randomized clinical trial was conducted on 120 elderly patients undergoing urgent exploration for intestinal obstruction. Patients were randomly allocated to one of the three groups: Group C (control group) patients received normal saline 0.9%, group D received dexmedetomidine, and group K received ketofol (ketamine: propofol was 1:4). The primary outcome was the incidence of POD. Secondary outcomes were incidence of emergence agitation, postoperative pain, consumption of rescue opioids, hemodynamics, and any side effects.ResultsThe incidence of POD was statistically significantly lower in ketofol and DEX groups than in the control group at all postoperative time recordings. Additionally, VAS scores were statistically significantly decreased in the ketofol and DEX groups compared to the control group at all time recordings except at 48 and 72 h postoperatively, where the values of the three studied groups were comparable. The occurrence of emergence agitation and high-dose opioid consumption postoperatively were found to be significant predictors for the occurrence of POD at 2 h and on the evening of the 1st postoperative day.ConclusionThe administration of ketofol provides a promising alternative option that is as effective as DEX in reducing the incidence of POD in elderly patients undergoing urgent exploration for intestinal obstruction.Trial registrationThis clinical trial was approved by the Institutional Review Board (IRB) at Zagazig University (ZU-IRB# 6704// 3/03/2021) and ClinicalTrials.gov (NCT04816162, registration date 22/03/ 2021). The first research participant was enrolled on 25/03/2021).

Project description:Perioperative neurocognitive disorder (PND) is a common complication following thoracic surgery that frequently occurs in patients ?65 years. PND includes postoperative cognitive dysfunction (POCD) and postoperative delirium (POD). To investigate whether intravenous dexmedetomidine (DEX) is able to improve neurocognitive function in elderly male patients following thoracoscopic lobectomy, a randomized, double-blinded, placebo-controlled trial was performed at the Affiliated Hospital of Inner Mongolia Medical University (Hohhot, China). Patients aged ?65 years were enrolled and were subjected to thoracic surgery under general anesthesia. A computer-generated randomization sequence was used to randomly assign patients (at a 1:1 ratio) to receive either intravenous DEX (0.5 µg/kg per h, from induction until chest closure) or placebo (intravenous normal saline). The primary endpoint was the result of the Mini-Mental State Examination (MMSE). The secondary endpoints were the results of the Montreal Cognitive Assessment (MoCA) and those obtained with the Confusion Assessment Method (CAM), as well as the incidence of POCD and POD during the first 7 postoperative days. Other observational indexes included sleep quality at night, self-anxiety scale prior to the operation and 7 days following the operation and the visual analogue scale (VAS) score at rest and during movement on the first and third day following the operation. Furthermore, at 6 h following surgery, the MMSE score in the DEX group was significantly higher than that in the saline group. At 6 h and on the first day postoperatively, the MoCA score in the DEX group was significantly higher than that in the saline group. The incidence of POCD and POD in the DEX group was 13.2 and 7.5%, respectively, while that in the saline group was 35.8 and 11.3%, respectively. There was a significant difference in the incidence of POCD between the two groups (P<0.01). In the DEX group, mean sleep quality was increased, whereas the mean VAS was decreased compared with the corresponding values in the saline group. In conclusion, elderly male patients who underwent thoracoscopic lobectomy under continuous infusion of DEX (0.5 µg/kg/h) exhibited a reduced incidence of POCD during the first 7 postoperative days as compared with the placebo group. Furthermore, DEX improved the subjective sleep quality in the first postoperative night, reduced anxiety and alleviated postoperative pain. In addition, it increased the incidence of bradycardia. The present study was registered in the Chinese Clinical Trial Registry (www.chictr.org.cn; registration no. ChiCTR-IPR-17010958).

Project description:ImportancePostoperative delirium occurs in 10% to 60% of elderly patients having major surgery and is associated with longer hospital stays, increased hospital costs, and 1-year mortality. Emerging literature suggests that dexmedetomidine sedation in critical care units is associated with reduced incidence of delirium. However, intraoperative use of dexmedetomidine for prevention of delirium has not been well studied.ObjectiveTo evaluate whether an intraoperative infusion of dexmedetomidine reduces postoperative delirium.Design, setting, and participantsThis study was a multicenter, double-blind, randomized, placebo-controlled trial that randomly assigned patients to dexmedetomidine or saline placebo infused during surgery and for 2 hours in the recovery room. Patients were assessed daily for postoperative delirium (primary outcome) and secondarily for postoperative cognitive decline. Participants were elderly (>68 years) patients undergoing major elective noncardiac surgery. The study dates were February 2008 to May 2014.InterventionsDexmedetomidine infusion (0.5 µg/kg/h) during surgery and up to 2 hours in the recovery room.Main outcomes and measuresThe primary hypothesis tested was that intraoperative dexmedetomidine administration would reduce postoperative delirium. Secondarily, the study examined the correlation between dexmedetomidine use and postoperative cognitive change.ResultsIn total, 404 patients were randomized; 390 completed in-hospital delirium assessments (median [interquartile range] age, 74.0 [71.0-78.0] years; 51.3% [200 of 390] female). There was no difference in postoperative delirium between the dexmedetomidine and placebo groups (12.2% [23 of 189] vs 11.4% [23 of 201], P = .94). After adjustment for age and educational level, there was no difference in the postoperative cognitive performance between treatment groups at 3 months and 6 months. Adverse events were comparably distributed in the treatment groups.Conclusions and relevanceIntraoperative dexmedetomidine does not prevent postoperative delirium. The reduction in delirium previously demonstrated in numerous surgical intensive care unit studies was not observed, which underscores the importance of timing when administering the drug to prevent delirium.Trial registrationclinicaltrials.gov Identifier NCT00561678.

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