Relationship between preinduction electroencephalogram patterns and propofol sensitivity in adult patients.

PURPOSE: To determine the precise induction dose, an objective assessment of individual propofol sensitivity is necessary. This study aimed to investigate whether preinduction electroencephalogram (EEG) data are useful in determining the optimal propofol dose for the induction of general anesthesia in healthy adult patients. METHODS: Seventy healthy adult patients underwent total intravenous anesthesia (TIVA), and the effect-site target concentration of propofol was observed to measure each individual's propofol requirements for loss of responsiveness. We analyzed preinduction EEG data to assess its relationship with propofol requirements and conducted multiple regression analyses considering various patient-related factors. RESULTS: Patients with higher relative delta power (ρ = 0.47, p < 0.01) and higher absolute delta power (ρ = 0.34, p = 0.01) required a greater amount of propofol for anesthesia induction. In contrast, patients with higher relative beta power (ρ = -0.33, p < 0.01) required less propofol to achieve unresponsiveness. Multiple regression analysis revealed an independent association between relative delta power and propofol requirements. CONCLUSION: Preinduction EEG, particularly relative delta power, is associated with propofol requirements during the induction of general anesthesia. The utilization of preinduction EEG data may improve the precision of induction dose selection for individuals.

Safety and efficacy of a low-dose combination of midazolam, alfentanil, and propofol for deep sedation of elderly patients undergoing ERCP.

BACKGROUND: Proper sedation of patients, particularly elderly individuals, who are more susceptible to sedation-related complications, is of significant importance in endoscopic retrograde cholangiopancreatography (ERCP). This study aims to assess the safety and efficacy of a low-dose combination of midazolam, alfentanil, and propofol for deep sedation in elderly patients undergoing ERCP, compared to a group of middle-aged patients. METHODS: The medical records of 610 patients with common bile duct stones who underwent elective ERCP under deep sedation with a three-drug regimen, including midazolam, alfentanil, and propofol at Shandong Provincial Third Hospital from January 2023 to September 2023 were retrospectively reviewed in this study. Patients were categorized into three groups: middle-aged (50-64 years, n = 202), elderly (65-79 years, n = 216), and very elderly (≥ 80 years, n = 192). Intraoperative vital signs and complications were compared among these groups. RESULTS: The three groups showed no significant difference in terms of intraoperative variation of systolic blood pressure (P = 0.291), diastolic blood pressure (P = 0.737), heart rate (P = 0.107), peripheral oxygen saturation (P = 0.188), bispectral index (P = 0.158), and the occurrence of sedation-related adverse events including hypotension (P = 0.170) and hypoxemia (P = 0.423). CONCLUSION: The results suggest that a low-dose three-drug regimen consisting of midazolam, alfentanil, and propofol seems safe and effective for deep sedation of elderly and very elderly patients undergoing ERCP procedures. However, further studies are required to verify these findings and clarify the benefits and risks of this method.

Dexmedetomidine as an Adjunct to Propofol in Patients Undergoing Elective Endoscopic Retrograde Cholangio-Pancreaticography - A Double-blind Randomized Controlled Study.

Background: Propofol is the drug of choice for procedural sedation. The addition of α2 agonist dexmedetomidine may improve the safety profile of the procedure by providing stable hemodynamics, better sedation quality, and decreasing the side effects of each drug during elective endoscopic retrograde cholangio-pancreaticography (ERCP). Materials and Methods: Eighty patients aged between 18 and 60 years were distributed randomly into two groups. The dexmedetomidine + propofol group (group DP) received an injection of dexmedetomidine at the dose of 1 mcg/kg in 100 mLsaline, and the propofol group (group P) received plain 100 mL normal saline over 10 min. Subsequently, both groups received a bolus dose of injection propofol 1 mg/kg as sedation, and a modified observer's assessment of alertness/sedation score (MOASS) score was assessed, followed by infusion at the rate of 50 mcg/kg/min during the procedure. A rescue bolus dose (20 mg) of propofol was administered when the patient showed signs of inadequate sedation or analgesia in both groups. Cardiovascular and respiratory parameters were recorded every 10 min throughout the procedure. Post-procedure modified Aldrete score was evaluated for 30 min, and the endoscopist's score was noted at the end of the procedure. Results: There was a significant difference (P = 0.001) in the additional number of rescue doses of propofol administered in group DP (3.47 ± 0.77) as compared to group P (8.78 ± 1.11). The total dose of propofol was lower in group DP (316.59 ± 43.29 mg) than in group P (443 ± 41.1 mg) with P value = 0.001. Statistically significant differences in the hemodynamic values were observed in group DP during infusion (P value < 0.05) of dexmedetomidine and throughout the procedure (P < 0.05) when compared with group P. Endoscopists graded the satisfaction score as very high (3.477 ± 0.77) in group DP. Conclusion: The addition of dexmedetomidine to propofol during ERCP provided better and safer sedation.

Screening of potential biomarkers in propofol-induced neurotoxicity via bioinformatics prediction and experimental verification.

OBJECTIVES: To identify hub genes and biological processes of propofol-induced neurotoxicity and promote the development of pediatric anesthesiology. METHODS: We downloaded the GSE106799 dataset from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened, then Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Gene Set Enrichment analyses were performed on all DEGs. We identified potential ferroptosis genes in the pathogenesis of propofol-induced neurotoxicity. A key module was obtained after performing weighted gene co-expression network analysis (WGCNA) on the GSE106799 dataset. Hub genes were identified after the least absolute shrinkage and selection operator (LASSO) regression analysis of the intersection of DEGs and genes from the key module. We established a competing endogenous RNA network and predicted potential drugs according to the hub genes. Total RNA and proteins were extracted for real-time quantitative polymerase chain reaction and Western blotting, respectively. RESULTS: A total of 112 DEGs, including 76 upregulated and 36 downregulated ones were screened out. Propofol-induced neurotoxicity involved processes such as nervous system development, activation of JAK/STAT and MAPK signaling pathways, vascular regeneration, and oxidative stress. The results of WGCNA suggested that the tan module was the most strongly associated with propofol-induced neurotoxicity. We identified 4 hub genes (EGR4, HAO1, ITK and GM14446) after LASSO regression analysis. Animal experiments demonstrated that propofol caused overexpression of the protein levels of HAO1, ITK and inflammatory factors in the brain, as well as the mRNA levels of HAO1, ITK and GM14446. Propofol inhibited expression of EGR4 at mRNA and protein levels. CONCLUSIONS: Previous studies have demonstrated that EGR4, HAO1, ITK and GM14446 play a role in intellectual development, neuroinflammation and neuronal differentiation. These hub genes may help us to find new preventive and therapeutic targets for propofol-induced neurotoxicity.

Bispectral index-guided comparison of dexmedetomidine and fentanyl as an adjuvant with propofol to achieve an adequate depth for endotracheal intubation - A double-blind randomised controlled trial.

Background and Aims: Laryngoscopy and tracheal intubation require an adequate depth of anaesthesia. The study's primary objective was to compare the time needed to achieve the bispectral index (BIS)-guided adequate depth of anaesthesia for endotracheal intubation using fentanyl and dexmedetomidine. Methods: After institutional ethics committee clearance and written informed consent, this randomised study was conducted on 140 patients of either gender between 18 and 60 years who were scheduled for elective surgeries under general anaesthesia. Patients were randomised to intravenous dexmedetomidine 1 µg/kg (Group D) or fentanyl 2 µg/kg (Group F). The drugs were given as an intravenous infusion over 10 min before induction of anaesthesia. The primary outcome was the time required to achieve BIS 50. Normally distributed variables were compared using Student's t-test, and non-normally distributed variables were compared using the Mann-Whitney U test. Qualitative data were analysed using Chi-square/Fisher's exact test. A P value <0.05 was considered significant. Results: The time to achieve BIS 50 was lesser in Group F, 1546 (27) as compared to Group D, 1558 (11) s [mean difference (95% confidence interval (CI) 12[5.11, 18.89]), P < 0.001]. Haemodynamic parameters were comparable at all time points between both the groups, except heart rate, which was significantly lower. Propofol consumption was significantly less in group D than in group F [125.9 (25.36) versus 157.3 (42.80) mg, respectively, mean difference (95% CI) 31.4 (-44.16 to -20.63) P < 0.001)]. Conclusion: Dexmedetomidine achieves BIS 50 faster and has a propofol-sparing effect as compared to fentanyl.

Comparison of efficacy and safety of equivalent doses of remimazolam versus propofol for gastroscopy anesthesia in elderly patients.

Remimazolam, a novel intravenous anesthetic, has been proven to be safe and efficacious in the gastroscopy setting among the elderly. However, reports comparing the effectiveness and safety of using equivalent doses of remimazolam with propofol have not been seen. The aim of this study was to compare the sedation efficacy and safety of the 95% effective doses (ED95) of remimazolam versus propofol combined with sufentanil in the gastroscopy setting among the elderly. In the first step of this two-step study, a modified up-and-down method was used to calculate the ED95 of remimazolam and propofol when combined with 0.1 µg/kg sufentanil in inhibiting body movement of elderly patients undergoing gastroscopy. In the second step, ED95 of both agents calculated in the first step were administered, endpoints of efficacy, safety, and incidence of adverse events were compared. A total of 46 individuals completed the first step. The ED95 of remimazolam was 0.163 mg/kg (95% CI 0.160-0.170 mg/kg), and that of propofol was 1.042 mg/kg (95% CI 1.007-1.112 mg/kg). In the second step, 240 patients completed the trial. The anesthetic effective rates of the remimazolam group and the propofol group were 78% and 83%, respectively, with no statistical difference (P = 0.312). Patients in the remimazolam group had more stable circulatory functions (P < 0.0001) and a lower incidence of pain on injection (3.3% vs. 19.5%, P < 0.0001). The incidence of hypotension was low in the remimazolam versus propofol group (15.6% vs. 39.0%, P < 0.0001). Overall adverse event was low in the remimazolam versus propofol group (21.3% vs. 62.7%, P < 0.0001).In this study, we found that when anesthesia was administered to elderly gastroscopy patients based on 95% effective doses of remimazolam and propofol, remimazolam was as effective as propofol, but was safer with a lower incidence of adverse events.Study registration: Chinese Clinical Trial Registry, ChiCTR2000034234. Registered 29/06/2020, https://www.chictr.org.cn .

The Inhibitory Effects of Propofol on Colorectal Cancer Progression through the NF-κB/HIF-1α Signaling Pathway.

BACKGROUND AND OBJECTIVE: Colorectal cancer (CRC) is a neoplastic disease that gradually develops due to genetic variations and epigenetic changes. Surgical excision is the first-line treatment for CRC. Accumulating evidence has shown that total intravenous anesthesia has beneficial effects for CRC patients as it decreases the probability of tumor recurrence and metastasis. Propofol is one of the most frequently used intravenous anesthetics in clinical practice. However, it remains unknown whether it can reduce recurrence and metastasis after surgery in cancer patients. METHODS: CRC cell lines (HCT116 and SW480) were cultured in vitro, and different concentrations of propofol were added to the cell culture medium. The proliferation effect of propofol on CRC cell lines was evaluated by CCK-8 assay. The effect of propofol on the migration and invasion of CRC cells was evaluated by scratch healing and Transwell experiments. The inhibitory effects of propofol on NF-κB and HIF-1α expressions in CRC cell lines were determined by Western blotting and immunofluorescence assays to further clarify the regulatory effects of propofol on NF-κB and HIF-1α. RESULTS: Compared to the control, propofol significantly inhibited the proliferation, migration, and invasion abilities of CRC cells (HCT116 and SW480) (P < 0.0001). The expression levels of NF-κB and HIF-1α gradually decreased with increasing propofol concentration in both cell lines. After activation and inhibition of NF-κB, the expression of HIF-1α changed. Further studies showed that propofol inhibited LPS-activated NF-κB-induced expression of HIF-1α, similar to the NF-κB inhibitor Bay17083 (P < 0.0001). CONCLUSION: In vitro, propofol inhibited the proliferation, migration, and invasion of CRC cells (HCT116 and SW480) in a dose-dependent manner, possibly by participating in the regulation of the NF-κB/HIF-1α signaling pathway.

Safety and efficacy of remimazolam versus propofol during endoscopic ultrasound: A multicenter randomized controlled study.

BACKGROUND AND AIMS: Propofol, a widely used sedative in gastrointestinal endoscopic procedures, is associated with cardiorespiratory suppression. Remimazolam is a novel ultra-short-acting benzodiazepine sedative with rapid onset and minimal cardiorespiratory depression. This study aimed to compare the safety and efficacy of remimazolam and propofol during endoscopic ultrasound (EUS) procedures. METHODS: A multicenter randomized controlled study was conducted between October 2022 and March 2023 in patients who underwent EUS procedures. Patients were randomly assigned to receive either remimazolam or propofol as a sedative agent. The primary endpoint was cardiorespiratory adverse events during the procedure, including desaturation, respiratory depression, hypotension, and tachycardia. Secondary endpoints included the time to achieve sedation, recovery time, quality of sedation, pain at the injection site, and satisfaction of both the endoscopists and patients. RESULTS: Four hundred patients enrolled in the study: 200 received remimazolam (10.8±7.7 mg) and 200 received propofol (88.0±49.1 mg). For cardiorespiratory adverse events, the remimazolam group experienced fewer occurrences than the propofol group (8.5% vs. 16%, p=0.022). There was a non-significant trend toward less oxygen desaturation (1.0% vs 3.5%, p= 0.09), respiratory depression (0.5% vs 1.5%, p= 0.62), hypotension (2.5% vs 5.5%, p=0.12) and tachycardia (4.5% vs 5.5%, p=0.68) with remimazolam than with propofol. Remimazolam showed a shorter induction time than propofol, while maintaining comparable awakening and recovery times. Injection site pain was significantly lower in the remimazolam group than in the propofol group. The remimazolam group demonstrated a significantly higher quality of sedation and satisfaction scores than the propofol group, as evaluated by both endoscopists and patients. CONCLUSION: Remimazolam was superior to propofol in terms of safety and efficacy during EUS examinations.

Neutrophils and Anesthetic Drugs: Implications in Onco-Anesthesia.

Apart from being a significant line of defense in the host defense system, neutrophils have many immunological functions. Although there are not many publications that accurately present the functions of neutrophils in relation to oncological pathology, their activity and implications have been studied a lot recently. This review aims to extensively describe neutrophils functions'; their clinical implications, especially in tumor pathology; the value of clinical markers related to neutrophils; and the implications of neutrophils in onco-anesthesia. This review also aims to describe current evidence on the influence of anesthetic drugs on neutrophils' functions and their potential influence on perioperative outcomes.

Propofol and salvianolic acid A synergistically attenuated cardiac ischemia-reperfusion injury in diabetic mice via modulating the CD36/AMPK pathway.

Background: Prevention of diabetic heart myocardial ischemia-reperfusion (IR) injury (MIRI) is challenging. Propofol attenuates MIRI through its reactive oxygen species scavenging property at high doses, while its use at high doses causes hemodynamic instability. Salvianolic acid A (SAA) is a potent antioxidant that confers protection against MIRI. Both propofol and SAA affect metabolic profiles through regulating Adenosine 5'-monophosphate-activated protein kinase (AMPK). The aim of this study was to investigate the protective effects and underlying mechanisms of low doses of propofol combined with SAA against diabetic MIRI. Methods: Diabetes was induced in mice by a high-fat diet followed by streptozotocin injection, and MIRI was induced by coronary artery occlusion and reperfusion. Mice were treated with propofol at 46 mg/kg/h without or with SAA at 10 mg/kg/h during IR. Cardiac origin H9c2 cells were exposed to high glucose (HG) and palmitic acid (PAL) for 24 h in the absence or presence of cluster of differentiation 36 (CD36) overexpression or AMPK gene knockdown, followed by hypoxia/reoxygenation (HR) for 6 and 12 h. Results: Diabetes-exacerbated MIRI is evidenced as significant increases in post-ischemic infarction with reductions in phosphorylated (p)-AMPK and increases in CD36 and ferroptosis. Propofol moderately yet significantly attenuated all the abovementioned changes, while propofol plus SAA conferred superior protection against MIRI to that of propofol. In vitro, exposure of H9c2 cells under HG and PAL decreased cell viability and increased oxidative stress that was concomitant with increased levels of ferroptosis and a significant increase in CD36, while p-AMPK was significantly reduced. Co-administration of low concentrations of propofol and SAA at 12.5 µM in H9c2 cells significantly reduced oxidative stress, ferroptosis and CD36 expression, while increasing p-AMPK compared to the effects of propofol at 25 µM. Moreover, either CD36 overexpression or AMPK silence significantly exacerbated HR-induced cellular injuries and ferroptosis, and canceled propofol- and SAA-mediated protection. Notably, p-AMPK expression was downregulated after CD36 overexpression, while AMPK knockdown did not affect CD36 expression. Conclusions: Combinational usage of propofol and SAA confers superior cellular protective effects to the use of high-dose propofol alone, and it does so through inhibiting HR-induced CD36 overexpression to upregulate p-AMPK.

Efficacy and safety of ciprofol versus propofol for induction and maintenance of general anesthesia: a systematic review and meta-analysis.

BACKGROUND: Propofol has been the gold standard for anesthesia induction and maintenance due to its rapid onset and favorable pharmacokinetic properties. However, the search for alternative agents with improved safety and efficacy has led to the emergence of ciprofol (HSK3486), a structural analog of propofol. This systematic review and meta-analysis aim to comprehensively assess the safety and efficacy of ciprofol compared to propofol for anesthesia induction and maintenance in adult patients undergoing surgical procedures. METHODS: This study included only double-arm RCTs in which participants were aged eighteen or older undergoing surgery. For the statistical analysis of the extracted data, we employed RevMan 5.4.1. RESULTS: Ciprofol demonstrated a promising trend of higher anesthesiologists' satisfaction during the induction phase (MD 0.14, 95%, CI - 0.28 to 0.56, p = 0.51), whereas Propofol was favored during maintenance. Propofol also exhibited advantages with a shorter time to successful anesthesia induction (MD 0.08 min, 95% CI 0.00 to 0.15, p = 0.04), and quicker attainment of full alertness (MD 0.11 min, 95% CI - 1.29 to 1.52, p = 0.87), suggesting its efficiency in clinical practice. Importantly, there were no significant disparities in the success rate of anesthesia. CONCLUSION: Both ciprofol and propofol demonstrate comparable efficacy and safety for anesthesia induction and maintenance in adult patients undergoing surgery. While propofol provides a faster onset of induction, ciprofol exhibits advantages in terms of pain management. Clinicians should consider these findings when selecting anesthetic agents, and tailoring choices to individual patient needs and clinical scenarios.

PRESS (Propofol, Remifentanil, Electricity/EEG, Setup and Setting) to Start: Introducing a Total Intravenous Anaesthesia Checklist at a Large Teaching Hospital.

Total intravenous anaesthesia (TIVA) is becoming more widely used, and as of yet there are few safety checks for the use of TIVA when compared to inhaled anaesthesia. This study aims to assess the feasibility and utility of introducing a TIVA checklist at a large teaching hospital. Methods A survey was sent out to all consultant and trainee anaesthetists at our hospital regarding their use of TIVA and errors in practice related to its use. A checklist was created based on common errors reported in the survey, errors described in NAP5 and our hospital's standard operating procedure. The checklist was introduced, and another survey was distributed a month later to assess compliance and utility and to gain feedback. Results In the first survey, there were 39 responses. A total of 64% had seen an error with the use of TIVA. For those using TIVA 70% of the time or more, 31% had seen an error in the last three months. Twelve per cent of those who had seen errors found that the errors led to patient harm. Only 33% used a method to double-check for errors prior to commencing TIVA. In the follow-up survey, 80% of those who used the checklist had found it useful, and 30% had corrected an error while using the checklist. Eighty-seven per cent felt the checklist would prevent errors from being made. Eighty per cent of respondents said they would use the checklist in their future practice. The checklist was found to be more useful for trainees, and for those who use TIVA less often. Discussion The 'PRESS to start TIVA" checklist has been shown to be a useful tool to prevent errors and a majority of anaesthetists at our hospital plan to use it going forward. Our data suggests that anaesthetists who are less experienced with TIVA benefit more from having a checklist. There was a marked increase in the number of anaesthetists who would use a checklist in the future, compared to those who used one in the initial survey. This shows that introducing a checklist is feasible and is likely to reduce errors going forward.

Comparison of propofol and desflurane for postoperative neurocognitive function in patients with aneurysmal subarachnoid hemorrhage: A prospective randomized trial.

Background: Following aneurysmal subarachnoid hemorrhage, 40-50% of survivors experience cognitive dysfunction, which affects their quality of life. Anesthetic agents play a pivotal role in aneurysm surgeries. However, substantial evidence regarding their effects on neurocognitive function is lacking. This study evaluated the effects of propofol and desflurane on postoperative neurocognitive function and serum S-100B levels. Methods: One hundred patients were equally randomized to receive either propofol (Group P) or desflurane (Group D). Cognitive function was assessed using the Montreal Cognitive Assessment scale at three different time points: Preoperatively, at the time of discharge, and one month after surgery. Perioperative serum levels of S-100B were also measured. Results: The preoperative mean cognitive score in Group P was 21.64 + 4.46 and in Group D was 21.66 + 4.07 (P = 0.79). At discharge, a significant decrease in cognitive scores was observed compared to preoperative scores (Group P- 20.91 + 3.94, P = 0.03 and Group D-19.28 + 4.22, P = 0.00); however, scores were comparable between the two groups (P = 0.09). One month following surgery, mean cognitive scores were 22.63 + 3.57 in Group P and 20.74 + 3.89 in Group D, and the difference was significant (P = 0.04). Higher memory and orientation scores were observed in Group P than in Group D at one month (P < 0.05) in the subgroup analysis. Both groups had similar serum S-100B levels. Conclusion: The mean cognitive scores one month after surgery improved significantly with propofol compared with desflurane, but without clinical significance. Individual domain analysis demonstrated that orientation and memory scores were better preserved with propofol.

Comparison Between the Protective Effect of Isoflurane and Propofol on Myocardium During Coronary Artery Bypass Grafting: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Intravenous non-volatile anaesthetics like propofol are commonly used in cardiac surgeries across several countries. Volatile anaesthetics like isoflurane may help in protecting the myocardium and minimize ischaemia-reperfusion injury. Hence, we did this review to compare the cardioprotective effect of isoflurane and propofol among patients undergoing coronary artery bypass grafting (CABG). METHODS: We conducted a search in the databases Medical Literature Analysis and Retrieval System Online (or MEDLINE), Embase, PubMed Central®, ScienceDirect, Google Scholar, and Cochrane Library from inception until April 2021. We carried out a meta-analysis with random-effects model and reported pooled risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI) depending on the type of outcome. RESULTS: We analysed 13 studies including 808 participants. Almost all were low-quality studies. For cardiac index, the pooled SMD was 0.14 (95% CI: -0.22 to 0.50); for cardiac troponin I, pooled SMD was 0.10 (95% CI: -0.28 to 0.48). For mortality, the RR was 3.00 (95% CI: 0.32 to 28.43); for MI, pooled RR was 1.58 (95% CI: 0.59 to 4.20); and for inotropic drug use, pooled RR was 1.04 (95% CI: 0.90 to 1.21). For length of intensive care unit stay, the pooled SMD was 0.13 (95% CI: -0.29 to 0.55), while pooled SMD for mechanical ventilation time was -0.02 (95% CI: -0.54 to 0.51). CONCLUSION: Isoflurane did not have significant cardioprotective effect compared to propofol following CABG. Hence, the anaesthetists need to check some viable alternatives to manage these patients and reduce the rate of postoperative complications.

Propofol Alleviates Anxiety-Like Behaviors Associated with Pain by Inhibiting the Hyperactivity of PVNCRH Neurons via GABAA Receptor ß3 Subunits.

Pain, a comorbidity of anxiety disorders, causes substantial clinical, social, and economic burdens. Emerging evidence suggests that propofol, the most commonly used general anesthetic, may regulate psychological disorders; however, its role in pain-associated anxiety is not yet described. This study investigates the therapeutic potential of a single dose of propofol (100 mg kg-1) in alleviating pain-associated anxiety and examines the underlying neural mechanisms. In acute and chronic pain models, propofol decreased anxiety-like behaviors in the elevated plus maze (EPM) and open field (OF) tests. Propofol also reduced the serum levels of stress-related hormones including corticosterone, corticotropin-releasing hormone (CRH), and norepinephrine. Fiber photometry recordings indicated that the calcium signaling activity of CRH neurons in the paraventricular nucleus (PVNCRH) is reduced after propofol treatment. Interestingly, artificially activating PVNCRH neurons through chemogenetics interfered with the anxiety-reducing effects of propofol. Electrophysiological recordings indicated that propofol decreases the activity of PVNCRH neurons by increasing spontaneous inhibitory postsynaptic currents (sIPSCs). Further, reducing the levels of γ-aminobutyric acid type A receptor ß3 (GABAAß3) subunits in PVNCRH neurons diminished the anxiety-relieving effects of propofol. In conclusion, this study provides a mechanistic and preclinical rationale to treat pain-associated anxiety-like behaviors using a single dose of propofol.

[Retracted] Propofol modulates the proliferation, invasion and migration of bladder cancer cells through the miR­145­5p/TOP2A axis.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the tumour images shown in Fig. 6B on p. 8 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes, which had either already been published or were under consideration for publication at around the same time. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 23: 439, 2021; DOI: 10.3892/mmr.2021.12078].

Construction of preclinical evidence for propofol in the treatment of reperfusion injury after acute myocardial infarction: A systematic review and meta-analysis.

Propofol, a commonly used intravenous anesthetic, has demonstrated potential in protecting against myocardial ischemia/reperfusion injury (MIRI) based on preclinical animal studies. However, the clinical benefits of propofol in this context are subject to debate. We conducted a systematic search across eight databases to identify all relevant animal studies investigating the preventive effects of propofol on MIRI until October 30, 2023. We assessed the methodological quality of the included studies using SYRCLE's bias risk tool. Statistical analysis was performed using STATA 15.1. The primary outcome measures analyzed in this study were myocardial infarct size (IS) and myocardial injury biomarkers. This study presents a comprehensive analysis of 48 relevant animal studies investigating propofol's preventive effects on MIRI. Propofol administration demonstrated a reduction in myocardial IS and decreased levels of myocardial injury biomarkers (CK-MB, LDH, cTnI). Moreover, propofol improved myocardial function parameters (+dp/dtmax, -dP/dtmax, LVEF, LVFS), exhibited favorable effects on inflammatory markers (IL-6, TNF-α) and oxidative stress markers (SOD, MDA), and reduced myocardial cell apoptotic index (AI). These findings suggest propofol exerts cardioprotective effects by reducing myocardial injury, decreasing infarct size, and improving heart function. However, the absence of animal models that accurately represent comorbidities such as aging and hypertension, as well as inconsistent administration methods that align with clinical practice, may hinder its clinical translation. Further robust investigations are required to validate these findings, elucidate the underlying mechanisms of propofol, and facilitate its potential translation into clinical practice.

Comparison of arterial hypotension incidence during general anesthesia induction - target-controlled infusion vs. bolus injection of propofol: a randomized clinical trial.

BACKGROUND: The incidence of arterial hypotension during induction of general anesthesia is influenced by the method of propofol administration, but there is a dearth of randomized clinical trials comparing bolus injection and target-controlled infusion in relation to arterial hypotension. This study seeks to compare the incidence of arterial hypotension between these two methods of propofol administration. METHODS: This prospective, randomized, single-center, non-blinded study included 60 patients (aged 35 to 55-years), classified as ASA physical status I or II, who were undergoing non-cardiac surgeries. They were randomly allocated using a computer to two groups based on the method of propofol administration during the induction of general anesthesia: the Target Group, receiving target-controlled infusion at 4 µg.mL-1, and the Bolus Group, receiving a bolus infusion of 2 mg.kg-1. Both groups also received midazolam 2 mg, fentanyl 3 µg.kg-1, and rocuronium 0.6 mg.kg-1. Over the first 10 minutes of anesthesia induction, Mean Arterial Pressure (MAP), Heart Rate (HR), level of Consciousness (qCON), and Suppression Rate (SR) were recorded every 2 minutes. RESULTS: Twenty-seven patients remained in the TCI group, while 28 were in the Bolus group. Repeated measure analysis using mixed-effects models could not reject the null hypothesis for the effect of group-time interactions in MAP (p = 0.85), HR (p = 0.49), SR (p = 0.44), or qCON (p = 0.72). The difference in means for qCON (60.2 for TCI, 50.5 for bolus, p < 0.001), MAP (90.3 for TCI, 86.2 for bolus, p < 0.006), HR (76.2 for TCI, 76.9 for bolus, p = 0.93), and SR (0.01 for TCI, 5.5 for bolus, p < 0.001), irrespective of time (whole period means), revealed some significant differences. CONCLUSION: Patients who received propofol bolus injection exhibited a lower mean arterial pressure, a greater variation in the level of consciousness, and a higher suppression rate compared to those who received it as a target-controlled infusion. However, the interaction effect between groups and time remains inconclusive.

How Is the Nociceptive Withdrawal Reflex Influenced by Increasing Doses of Propofol in Pigs?

The nociceptive withdrawal reflex (NWR) is a physiological, polysynaptic spinal reflex occurring in response to noxious stimulations. Continuous NWR threshold (NWRt) tracking has been shown to be possibly useful in the depth of anesthesia assessment. The primary aim of this study was to describe how propofol modulates the NWRt over time in pigs. Five juvenile pigs (anesthetized three times) were included. An intravenous (IV) infusion of propofol (20 mg/kg/h) was started, and boli were administered to effect until intubation. Afterwards, the infusion was increased every ten minutes by 6 mg/kg/h, together with an IV bolus of 0.5 mg/kg, until reaching an electroencephalographic suppression ratio (SR) of between 10% and 30%. The NWRt was continuously monitored. For data analysis, the time span between 15 min following intubation and the end of propofol infusion was considered. Individual durations of propofol administration were divided into five equal time intervals for each pig (TI1-TI5). A linear regression between NWRt and TI was performed for each pig. Moreover, the baseline NWRt and slopes of the linear regression (b1) were compared among days using a Friedman Repeated Measures Analysis of Variance on Ranks. The NWRt always increased with the propofol dose (b1 = 4.71 ± 3.23; mean ± standard deviation). No significant differences were found between the baseline NWRt and the b1 values. Our results suggest that the NWRt may complement the depth of anesthesia assessment in pigs receiving propofol.

Decoding the Neurotoxic Effects of Propofol: Insights into the RARα-Snhg1-Bdnf Regulatory Cascade.

The potential neurotoxic effects of propofol, an extensively utilized anesthetic, underline the urgency to comprehend its influence on neuronal health. Insights into the role of the RARα-Snhg1-Bdnf network can offer significant advancements in minimizing these effects. The study targets the exploration of the RARα and Snhg1 regulatory network's influence on Bdnf expression in the realm of propofol-induced neurotoxicity. Harnessing the GEO database and utilizing JASPAR and RPISeq for projections, the study embarks on an in-depth analysis employing both in vitro and in vivo models. The findings draw a clear link between propofol-induced neurotoxicity and the amplification of RAR signaling pathways, impacting hippocampal development and apoptosis and leading to increased RARα and Snhg1 and decreased Bdnf. Propofol is inferred to accentuate neurotoxicity by heightening RARα and Snhg1 interactions, culminating in Bdnf suppression.