Repurposing propofol for breast cancer therapy through promoting apoptosis and arresting cell cycle.

Breast cancer is the most prevalent cancer among women worldwide, characterized by a high mortality rate and propensity for metastasis. Although surgery is the standard treatment for breast cancer, there is still no effective method to inhibit tumor metastasis and improve the prognosis of patients with breast cancer after surgery. Propofol, one of the most widely used intravenous anesthetics in surgery, has exhibited a positive association with improved survival outcomes in patients with breast cancer post­surgery. However, the underlying molecular mechanism remains to be elucidated. The present study revealed that triple negative breast cancer cells, MDA­MB­231 and 4T1, exposed to propofol exhibited a significant decrease in cell viability. Notably, propofol exhibited minimal cytotoxic effects on HUVECs under the same conditions. Furthermore, propofol significantly inhibited the migration and invasion ability of MDA­MB­231 and 4T1 cells. Propofol promoted apoptosis in 4T1 cells through upregulation of Bax and cleaved caspase 3, while downregulating B­cell lymphoma­extra large. Concomitantly, propofol induced cell cycle arrest of 4T1 cells by downregulating cyclin E2 and phosphorylated cell division cycle 6. Furthermore, propofol exhibited excellent anticancer efficacy in a 4T1 breast cancer allograft mouse model. The present study sheds light on the potential of propofol as an old medicine with a novel use for breast cancer treatment.

Survival benefits of propofol-based versus inhalational anesthesia in non-metastatic breast cancer patients: a comprehensive meta-analysis.

Whether the anesthesia technique, inhalational general anesthesia (IGA) or propofol-based anesthesia (PBA), influences the long-term survival of non-metastatic breast cancer (eBC) remain unclear and controversial. We carried out a literature search on 16thJuly, 2022 for studies comparing IGA and PBA in eBC undergoing standard surgery, according to PRISMA 2020. The major endpoint in our study was overall survival (OS). Seventeen studies including four randomized clinical trials and thirteen retrospective cohort studies were included in the meta-analysis. Ten studies provided data for crude OS in unweighted eBC patients (imbalance in baseline characteristics). The summarized estimate HRs of the PBA group versus the IGA group (ten studies, N = 127,774, IGA group: 92,592, PBA group: 35,182.) was 0.83 (95%CI: 0.78-0.89). Compared with IGA, PBA was associated with both better 1-year OS (two studies, N = 104,083, IGA group: 84,074, PBA group: 20,009. Pooled HR = 0.80, 0.73-0.89) and 5-year OS (six studies, N = 121,580, IGA group: 89,472, PBA group: 32,108. HR = 0.80, 0.74-0.87). Ten studies applied PSM method to balance the baseline characteristics. In these weighted patients, PBA still showed a better OS (ten studies, N = 105,459, IGA group: 79,095, PBA group: 26,364. HR = 0.93, 0.87-1.00), a better 1-year OS (two studies, N = 83,007, IGA group: 67,609, PBA group: 15,398. HR = 0.88, 0.78-0.98) and a trend towards a better 5-year OS (nine studies, N = 121,580, IGA group: 76,797, PBA group: 24,066. HR = 0.95, 0.88-1.03). Loco-regional recurrence-free survival (LRRFS) was also better in PBA group (HR = 0.73, 0.61-0.86). The present study is the first comprehensive meta-analysis to demonstrate that propofol-based anesthesia could significantly improve OS and LRRFS in non-metastatic breast cancer patients, compared with inhalational anesthesia.

Efficacy and Safety of Remimazolam Versus Etomidate for Induction of General Anesthesia: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Postinduction hypotension (PIHO) is a hemodynamic abnormality commonly observed during the induction of general anesthesia. Etomidate is considered a safer drug for the induction of anesthesia because it has only minor adverse effects on the cardiovascular and pulmonary systems. Recent evidence indicates that the novel benzodiazepine remimazolam has minimal inhibitory effects on the circulation and respiration. However, the efficacy and safety of remimazolam versus etomidate in the induction of anesthesia are unclear. OBJECTIVE: To further understand the potential of remimazolam in anesthesia induction, it is necessary to design a meta-analysis to compare its effects versus the classic safe anesthetic etomidate. The aim of this study is to determine which drug has more stable hemodynamics and a lower incidence of PIHO. Our study will also yield data on sedation efficiency, time to loss of consciousness, time to awakening, incidence of injection pain, and postoperative nausea and vomiting with the two drugs. METHODS: We plan to search the Web of Science, Cochrane Library, Embase, PubMed, China National Knowledge Infrastructure, and Wanfang databases from the date of their creation until March 31, 2025. The language is limited to English and Chinese. The search terms are "randomized controlled trials," "etomidate," and "remimazolam." The incidence of PIHO is the primary outcome measure. Secondary outcomes include depth of anesthesia after induction, sedation success rate, time to loss of consciousness, hemodynamic profiles, recovery time, incidence of injection pain, and postoperative nausea and vomiting. Reviews, meta-analyses, case studies, abstracts from conferences, and commentaries will not be included. The heterogeneity of the results will be evaluated by sensitivity and subgroup analyses. RevMan software and Stata software will be used for data analysis. We will evaluate the quality of included studies using version 2 of the Cochrane risk-of-bias tool. The confidence of the evidence will be assessed through the Grading of Recommendations, Assessments, Developments, and Evaluations system. RESULTS: The protocol was registered in the international PROSPERO (Prospective Register of Systematic Reviews) registry in November 2023. As of June 2024, we have performed a preliminary article search and retrieval for further review. The review and analyses are expected to be completed in March 2025. We expect to submit manuscripts for peer review by the end of June 2025. CONCLUSIONS: By synthesizing the available evidence and comparing remimazolam and etomidate, we hope to provide valuable insights into the selection of anesthesia-inducing drugs to reduce the incidence of PIHO and improve patient prognosis. TRIAL REGISTRATION: PROSPERO CRD42023463120; https://tinyurl.com/333jb8bm. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55948.

Treatment of Refractory Status Epilepticus With Continuous Intravenous Anesthetic Drugs: A Systematic Review.

Importance: Multiple continuous intravenous anesthetic drugs (CIVADs) are available for the treatment of refractory status epilepticus (RSE). There is a paucity of data comparing the different types of CIVADs used for RSE. Objective: To systematically review and compare outcome measures associated with the initial CIVAD choice in RSE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Evidence Review: Data sources included English and non-English articles using Embase, MEDLINE, PubMed, and Web of Science (January 1994-June 2023) as well as manual search. Study selection included peer-reviewed studies of 5 or more patients and at least 1 patient older than 12 years with status epilepticus refractory to a benzodiazepine and at least 1 standard antiseizure medication, treated with continuously infused midazolam, ketamine, propofol, pentobarbital, or thiopental. Independent extraction of articles was performed using prespecified data items. The association between outcome variables and CIVAD was examined with an analysis of variance or χ2 test where appropriate. Binary logistic regressions were used to examine the association between outcome variables and CIVAD with etiology, change in mortality over time, electroencephalography (EEG) monitoring (continuous vs intermittent), and treatment goal (seizure vs burst suppression) included as covariates. Risk of bias was addressed by listing the population and type of each study. Findings: A total of 66 studies with 1637 patients were included. Significant differences among CIVAD groups in short-term failure, hypotension, and CIVAD substitution during treatment were observed. Non-epilepsy-related RSE (vs epilepsy-related RSE) was associated with a higher rate of CIVAD substitution (60 of 120 [50.0%] vs 11 of 43 [25.6%]; odds ratio [OR], 3.11; 95% CI, 1.44-7.11; P = .006) and mortality (98 of 227 [43.2%] vs 7 of 63 [11.1%]; OR, 17.0; 95% CI, 4.71-109.35; P < .001). Seizure suppression was associated with mortality (OR, 7.72; 95% CI, 1.77-39.23; P = .005), but only a small subgroup was available for analysis (seizure suppression: 17 of 22 [77.3%] from 3 publications vs burst suppression: 25 of 98 [25.5%] from 12 publications). CIVAD choice and EEG type were not predictors of mortality. Earlier publication year was associated with mortality, although the observation was no longer statistically significant after adjusting SEs for clustering. Conclusions and Relevance: Epilepsy-related RSE was associated with lower mortality compared with other RSE etiologies. A trend of decreasing mortality over time was observed, which may suggest an effect of advances in neurocritical care. The overall data are heterogeneous, which limits definitive conclusions on the choice of optimal initial CIVAD in RSE treatment.

Efficacy and safety of Ciprofol compared with Propofol during general anesthesia induction: A systematic review and meta-analysis of randomized controlled trials (RCT).

BACKGROUND: Ciprofol, a newer entrant with similarities to propofol, has shown promise with a potentially improved safety profile, making it an attractive alternative for induction of general anesthesia. This meta-analysis aimed to assess the safety and efficacy of ciprofol compared with propofol during general anesthesia induction. METHODS: A comprehensive literature search was conducted using PubMed, Clinical Trial.gov, and Cochrane Library databases from inception to July 2023 to identify relevant studies. All statistical analyses were conducted using R statistical software version 4.1.2. RESULTS: Thirteen Randomized Controlled Trials (RCTs) encompassing a total of 1998 participants, were included in our analysis. The pooled analysis indicated that Ciprofol was associated with a notably lower incidence of pain upon injection [RR: 0.15; 95% CI: 0.10 to 0.23; I^2 = 43%, p < 0.0000001] and was non-inferior to propofol in terms of anesthesia success rate [RR: 1.00; 95% CI: 0.99 to 1.01; I^2 = 0%; p = 0.43]. In terms of safety, the incidence of hypotension was significantly lower in the ciprofol group [RR:0.82; 95% CI:0.68 to 0.98; I^2 = 48%; p = 0.03]. However, no statistically significant differences were found for postoperative hypertension, bradycardia, or tachycardia. CONCLUSION: In conclusion, Ciprofol is not inferior to Propofol in terms of its effectiveness in general anesthesia. Ciprofol emerges as a valuable alternative sedative with fewer side effects, especially reduced injection pain, when compared to Propofol. SUMMARY: Propofol, frequently utilized as an anesthetic, provides swift onset and quick recovery. However, it has drawbacks such as a narrow effective dosage range and a high occurrence of adverse effects, particularly pain upon injection. Ciprofol, a more recent drug with propofol-like properties, has demonstrated promise and may have an improved safety profile, making it a compelling alternative for inducing general anesthesia. This meta-analysis compared the safety and effectiveness of Ciprofol with Propofol for general anesthesia induction in a range of medical procedures, encompassing thirteen Randomized Controlled Trials (RCTs) and 1998 individuals. The pooled analysis indicated that Ciprofol was associated with a notably lower incidence of pain upon injection [RR: 0.15; 95% CI: 0.10 to 0.23; I^2 = 43%, p < 0.0000001] and was non-inferior to propofol in terms of anesthesia success rate [RR: 1.00; 95% CI: 0.99 to 1.01; I^2 = 0%; p = 0.43]. In terms of safety, the incidence of hypotension was significantly lower in the ciprofol group [RR:0.82; 95% CI:0.68 to 0.98; I^2 = 48%; p = 0.03]. However, no statistically significant differences were found for hypertension, bradycardia, or tachycardia. In conclusion, ciprofol is equally effective at inducing and maintaining general anesthesia as propofol. When compared to propofol, ciprofol is a better alternative sedative for operations including fiberoptic bronchoscopy, gynecological procedures, gastrointestinal endoscopic procedures, and elective surgeries because it has less adverse effects, most notably less painful injections.

Efficacy of remimazolam tosilate versus propofol for total intravenous anaesthesia in urological surgery: A randomised clinical trial.

BACKGROUND: Remimazolam is a novel ultra-short-acting benzodiazepine sedative that acts on the gamma-aminobutyric acid type A receptor (GABAAR). OBJECTIVE: To compare the efficacies of remimazolam (RMZ), and propofol (PROP) combined with remifentanil and cisatracurium for total intravenous anaesthesia (TIVA) in patients undergoing urological surgery. DESIGN: A prospective, single-blind, randomised, noninferiority clinical trial. SETTING: Single centre from 1 January 2022 to 30 March 2022. PATIENTS: A total of 146 adult patients undergoing elective urological surgery. INTERVENTION: Patients were randomly allocated in a 1 : 1 ratio to the PROP or RMZ groups. In the PROP group, anaesthesia was induced with propofol at 100 mg min -1 to reach a bispectral index score (BIS) of 40 to 60. After loss of consciousness (LOC), intravenous fentanyl 3 µg kg -1 was administered, followed by cisatracurium 0.3 mg kg -1 . Patients were intubated 3 min after cisatracurium administration. Anaesthesia was maintained with the combination of propofol (plasma concentration: 2.5 to 4 µg ml -1 ) and remifentanil (plasma concentration: 2.5 to 4 ng ml -1 ). In the RMZ group, anaesthesia was induced with remimazolam tosilate starting at 10 mg kg -1  h -1 to reach a BIS of 40 to 60 and maintained between 0.2 and 2 mg kg -1  h -1 . After LOC, fentanyl and cisatracurium were administered and intubation was performed as in the PROP group. Anaesthesia was maintained with a combination of remimazolam (0.2 to 2 mg kg -1  h -1 ) and remifentanil (plasma concentration: 2.5 to 4 ng ml -1 ). MAIN OUTCOME MEASURES: The primary outcome was the TIVA success rate. The predefined noninferiority margin considered an absolute difference of 6% in the primary outcome between the groups. The secondary outcomes were vital signs, anaesthesia and surgery characteristics, and adverse events. RESULTS: All patients completed the trial. The success rates of TIVA with remimazolam and propofol were 100 and 98.6%, respectively. The incidence of hypotension during anaesthesia was lower in the RMZ group (26%) than in the PROP group (46.6%) ( P  = 0.016). The median [IQR] total consumption of ephedrine during anaesthesia was higher in the PROP group 10 [0 to 12.5] mg than in the RMZ group 0 [0 to 10] mg ( P  = 0.0002). The incidence of injection pain was significantly higher in the PROP group (76.7%) than in the RMZ group (0; P  < 0.001). No significant differences in the controllability of the anaesthesia depth, anaesthesia and surgery characteristics, or vital signs were observed between the groups. CONCLUSION: Remimazolam demonstrated noninferior efficacy to propofol combined with remifentanil and cisatracurium for TIVA in patients undergoing urological surgery. TRIAL REGISTRATION: Chictr.org.cn, identifier: ChiCTR2100050923. CLINICAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100050923, Principal investigator: Xuehai Guan, Date of registration: 8 November 2021, https://www.chictr.org.cn/showproj.html?proj=133466 ).

Efficacy of Isoflurane-Remifentanil versus Propofol-Remifentanil on Controlled Hypotension and Surgeon Satisfaction in Rhinoplasty: A Single-Blind Clinical Trial Study.

Background: Rhinoplasty is a complex but popular surgery in Iran. The main complications of the surgery are post-operative bleeding and nasal septal hematoma due to poor intra-operative controlled hypertension. This study aimed to compare the efficacy of isoflurane-remifentanil (I-R) versus propofol-remifentanil (P-R) to induce controlled hypotension and to assess surgeon satisfaction with each of these combinations during rhinoplasty. Methods: In 2020-2021, a single-blind clinical study was conducted on 98 patients aged 18-50 years undergoing rhinoplasty at Mother and Child Hospital (Shiraz, Iran). Patients were randomly divided into P-R (n=48) and I-R (n=50) groups. Changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were assessed during surgery and in the recovery room. A questionnaire was used to evaluate the level of surgeon satisfaction. Data were analyzed using independent samples t test, Chi-square test, and repeated measures ANOVA with SPSS software. P<0.05 was considered statistically significant. Results: Five minutes after anesthesia induction, the P-R combination had a greater effect on reducing SBP (P=0.010), DBP (P=0.007), MAP (P=0.003), and HR (P=0.026) than I-R. However, from the 40th minute to the end of surgery and after 30 minutes of recovery, the I-R combination had a slightly better effect on blood pressure reduction than P-R. There was no difference in surgeon satisfaction with either of the two drug combinations. Conclusion: Both P-R and I-R combinations are recommended to induce hypotension during rhinoplasty. However, I-R is more effective than P-R in inducing the desired controlled hypotension.

Remimazolam Compared to Propofol for Total Intravenous Anesthesia with Remifentanil on the Recovery of Psychomotor Function: A Randomized Controlled Trial.

INTRODUCTION: This study aimed to compare remimazolam to propofol in psychomotor recovery after total intravenous anesthesia (TIVA) using the Trieger dot test. METHODS: Sixty-six patients who were scheduled to undergo endoscopic sinus surgery with American Society of Anesthesiologists (ASA) physical status I or II were randomly allocated to the remimazolam (group R) or propofol group (group P). In group R, all patients received flumazenil postoperatively. After discontinuation of anesthetic agents, the time to eye opening, response to verbal commands, extubation, and discharge from the operation room were measured. Psychomotor recovery was assessed using the Trieger dot test before induction and at 0, 30, 60, 90, 120, 150, and 180 min after anesthesia. RESULTS: The time to eye opening, response to verbal commands, extubation, and discharge from the operation room were significantly longer in group P compared to group R (group P: 9.8 ± 3.2 min, 11.5 ± 3.4 min, 12.7 ± 3.4 min, 18.1 ± 4.2 min; group R: 6.5 ± 2 min, 7.3 ± 2.6 min, 8.4 ± 2.9 min, 13.2 ± 3.2 min; respectively, p < 0.05). In the Trieger dot test, the number of dots missed was significantly increased in group R compared to group P at 30, 60, 90, and 120 min after discharge from the operation room (group R: 20.5 ± 9.3, 16 ± 8.8, 14.9 ± 11.1, 14.3 ± 10.8; group P: 14.6 ± 7.8, 10 ± 7.1, 8.7 ± 7.3, 7.3 ± 5.7; respectively, p < 0.05). The maximum distance of dots missed was significantly increased in group R compared to group P at 30 min after discharge from the operation room (group R: 3.9 ± 2.8; group P: 2.7 ± 1.6; p < 0.05). CONCLUSION: Our results suggest that remimazolam with flumazenil leads to rapid recovery following anesthesia; however, it may cause delayed psychomotor decline. CLINICAL TRIAL REGISTRATION: This trial is registered with the University Hospital Medical Information Network (registration number UMIN000044900).

Emergence Agitation with Earthquake-Related Traumatic Stress Symptoms After Intravenous Sedation. / Intravenöz Sedasyon Sonrasi Depremle Iliskili Travmatik Stres Belirtileri ile Seyreden Derlenme Ajitasyonu.

Sedation with intravenous anesthetics is a sedation method that is often preferred during minor surgical procedures for anxious patients. Among the anesthetic agents used are drugs such as midazolam and ketamine, which can cause psychiatric symptoms such as loss of control over the behavior of the person (disinhibition) or dissociation. In people with high anxiety levels, a paradoxical rise of anxiety may rarely occur with midazolam, and emergence agitation or delirium may occur after anesthesia with ketamine. Post-traumatic stress disorder is a known risk factor for emergence agitation. Accompanying traumatic stress symptoms are reported to have persisted for a long time in the case reports of emergence agitation with a past history of trauma. It is aimed to discuss the importance of traumatic stress symptoms in sedation management in the post-earthquake period by presenting a case with increased anxiety and emergence agitation with acute stress symptoms such as re-experiencing the earthquake after sedation with intravenous anesthetics for a local surgical procedure immediately after experiencing the Kahramanmaras earthquake on February 6 in Turkey. Keywords: Earthquakes, intravenous anesthetics, emergence, psychomotor agitation, acute stress disorder, post-traumatic stress disorder.

Application of Dexmedetomidine in Surgical Anesthesia for Gastric Cancer and Its Effects on IL-1ß, IL-6, TNF-α and CRP.

This study was performed to analyze the application of dexmedetomidine (Dex) in anesthesia for gastric cancer surgery and its effect on serum inflammatory factors in patients. In this regard, a total of 78 patients with gastric cancer who were hospitalized in our hospital from January 2020 to September 2023 and received general intravenous anesthesia were randomly divided into two groups (n=39 in each group). The conventional group was given the same volume of 0.9% sodium chloride solution 10min before induction of anesthesia, and the Dex group was given Dex1µg/kg intravenous pump 10min before induction of anesthesia. The hemodynamics, serum levels of IL-1ß, IL-6, TNF-α, CRP, propofol, remifentanil, and the total incidence of adverse reactions were compared between the two groups at different periods. The results showed that the mean arterial pressure (MAP), heart rate (HR), serum IL-1ß, IL-6, TNF-α and CRP in the Dex group were compared with those in the routine group (P>0.05). MAP and HR in T1, T2 and T3Dex groups were lower than those in the conventional group (P<0.05). The serum levels of IL-1ß, IL-6, TNF-α and CRP in T4 and T5 of the Dex group were lower than those of the routine group (P<0.05). The dosage of propofol and remifentanil in the Dex group was lower than those in the conventional group (P<0.05). The total incidence of adverse reactions in the Dex group (5.13%) was compared with that in the conventional group (10.26%), P>0.05. It was concluded that Dex can effectively maintain the stability of hemodynamics during gastric cancer surgery, reduce the dosage of propofol and other anesthetic drugs, reduce inflammation, and has a certain safety without obvious adverse reactions.

Ketofol as an Anesthetic Agent in Patients With Isolated Moderate to Severe Traumatic Brain Injury: A Prospective, Randomized Double-blind Controlled Trial.

BACKGROUND: The effects of ketofol (propofol and ketamine admixture) on systemic hemodynamics and outcomes in patients undergoing emergency decompressive craniectomy for traumatic brain injury (TBI) are unknown and explored in this study. METHODS: Fifty patients with moderate/severe TBI were randomized to receive ketofol (n=25) or propofol (n=25) for induction and maintenance of anesthesia during TBI surgery. Intraoperative hemodynamic stability was assessed by continuous measurement of mean arterial pressure (MAP) and need for rescue interventions to maintain MAP within 20% of baseline. Brain relaxation scores, serum biomarker-glial fibrillary acidic protein levels, and extended Glasgow Outcome Scale (GOSE) at 30 and 90 days after discharge were also explored. RESULTS: MAP was lower and hemodynamic fluctuations more frequent in patients receiving propofol compared with those receiving ketofol (P<0.05). MAP fell >20% below baseline in 22 (88%) patients receiving propofol and in 10 (40%) receiving ketofol (P=0.001), with a greater requirement for vasopressors (80% vs. 24%, respectively; P=0.02). Intraoperative brain relaxation scores and GOSE at 30 and 90 day were similar between groups. Glial fibrillary acidic protein was lower in the ketofol group (3.31±0.43 ng/mL) as compared with the propofol (3.41±0.17 ng/mL; P=0.01) group on the third postoperative day. CONCLUSION: Compared with propofol, ketofol for induction and maintenance of anesthesia during decompressive surgery in patients with moderate/severe TBI was associated with improved hemodynamic stability, lower vasopressor requirement, and similar brain relaxation.

Effect of common OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 polymorphisms on perioperative analgesic and propofol demands on patients subjected to thyroidectomy surgery.

BACKGROUND: Perioperative anesthetic and/or analgesic demand present considerable variation, and part of that variation appears to be genetic in origin. Here we investigate the impact of common polymorphisms in OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 genes, on the intra-operative consumption of remifentanil and propofol, as well as the postoperative analgesic needs, in patients subjected to thyroidectomy surgery. METHODS: We conducted a prospective cohort study with 90 patients scheduled to undergo elective thyroidectomy, under total intravenous anesthesia achieved by target control infusion (TCI) of propofol and remifentanil. Postoperative analgesics were administered by protocol and on-demand by the individual patient. Genotyping was established by PCR-RFLP methods. Genotyping data, intra-operative hemodynamics, and total consumption of remifentanil and propofol, as well as postoperative analgesic needs and pain perception, were recorded for each individual. RESULTS: Patients with the ABCB1 3435TT genotype appeared to experience significantly less pain within one hour post-operatively, compared to C carriers [mean VAS (SD) = 0.86 (1.22) vs. 2.42 (1.75); p = 0.017], a finding limited to those seeking rescue analgesic treatment. Intra-operatively, homozygotes patients for the minor allele of OPRM1 A118G and CYP2B6 G516T appeared to consume less remifentanil [mean (SD) = 9.12 (1.01) vs. 13.53 (5.15), for OPRM1 118GG and A carriers] and propofol [median (range) = 14.95 (11.53, 1359.5) vs. 121.4 (1.43, 2349.4), for CYP2B6 516TT and G carriers, respectively] but the difference was not statistically significant in our sample. CONCLUSIONS: The ABCB1 C3435T polymorphism appears to affect the postoperative perception of surgical pain among patients with low pain threshold. The small number of minor allele homozygotes for the OPRM1 A118G and CYP2B6 G516T polymorphisms precludes a definitive conclusion regarding the inclusion of the latter in a TCI-programming algorithm, based on the results of this study. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12616001598471.

Ciprofol: A Novel Alternative to Propofol in Clinical Intravenous Anesthesia?

Ciprofol is a novel compound that was independently developed in China. According to the Chinese product instructions approved by the China National Medical Products Administration and the information of official website, indications for ciprofol include sedation and anesthesia during the surgical/procedure of nontracheal intubation, induction and maintenance of general anesthesia, and sedation during intensive care. Ciprofol is a short-acting intravenous sedative based on the structural modification of propofol. Ciprofol has high efficacy, good selectivity, and fewer adverse reactions, indicating good clinical application potential. A series of clinical studies have been conducted to evaluate the sedative effect of ciprofol in various procedures and settings, including gastroscopy and colonoscopy, fiber-optic bronchoscopy, general anesthesia in elective surgeries, and mechanical ventilation in intensive care units. This review summarizes the chemical structure, pharmacodynamics, and pharmacokinetic properties of ciprofol. We also assessed the efficacy and safety of ciprofol by synthesizing the relevant clinical trial data.

The Anti-Inflammatory and Antioxidant Effects of Propofol and Sevoflurane in Children With Cyanotic Congenital Heart Disease.

OBJECTIVE: The authors aimed to compare the anti-inflammatory and antioxidant effects of propofol and sevoflurane in children with cyanotic congenital heart disease (CCHD) undergoing cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, randomized, double-blind study. SETTING: Single center, university hospital. PARTICIPANTS: Children ages 1-10 years with CCHD undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Children were randomized to receive general anesthesia with either sevoflurane (group S) or propofol (group P). Systemic inflammatory response syndrome (SIRS) occurrence was assessed at the end of the surgery and at the sixth, 12th, and 24th postoperative hours. Blood samples were obtained at 4 times: after anesthesia induction (T0), after release of the aortic cross-clamp (T1), at the end of the surgery (T2), and at the postoperative 24th hour (T3). The serum levels of interleukin 6 and tumor necrosis factor alpha, and the total antioxidant status (TAS) and total oxidant status, were analyzed. RESULTS: SIRS was more common in group S than in group P at all times (p = 0.020, p = 0.036, p = 0.004, p = 0.008). There were no significant differences between the groups in the mean tumor necrosis factor alpha and interleukin 6 levels at any time. The TAS level at T2 was higher in group P than group S (p = 0.036). The serum TAS level increased at T2 compared with T0 in group P, but it decreased in group S (p = 0.041). CONCLUSION: The results showed that propofol provided a greater antioxidant effect and reduced SIRS postoperatively more than sevoflurane in children with CCHD undergoing cardiac surgery.

Etomidate elicits anti-tumor capacity by disrupting the JAK2/STAT3 signaling pathway in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading malignancy of the digestive system, especially in China. Although radiotherapy, chemotherapy, and transarterial chemoembolization have achieved tremendous success, surgical resection remains the primary treatment for HCC patients. Recent studies have shown that intravenous anesthetic drugs may affect the malignant behaviors of tumor cells, ultimately leading to differences in the postoperative prognosis of patients. Etomidate is one of the most widely used intravenous anesthetic drugs for the induction and maintenance of anesthesia in tumor patients undergoing surgery. However, the effects and underlying mechanisms of etomidate on HCC cells have not yet been characterized. Our study indicated that etomidate significantly impedes the malignant progression of HCC cells. Mechanistically, etomidate inhibits phosphorylation and, ultimately, the activity of Janus kinase 2 (JAK2) by competing with ATP for binding to the ATP-binding pocket of JAK2. Thus, it suppresses the JAK2/STAT3 signaling pathway in HCC cells to exert its anti-tumor efficacy. Herein, we provide preclinical evidence that etomidate is the optimal choice for surgical treatment of HCC patients.

Application of Propofol Target-Controlled Infusion for Optimized Hemodynamic Status in ESRD Patients Receiving Arteriovenous Access Surgery: A Randomized Controlled Trial.

Background and Objectives: End-stage renal disease (ESRD) is associated with increased anesthetic risks such as cardiovascular events resulting in higher perioperative mortality rates. This study investigated the perioperative and postoperative outcomes in ESRD patients receiving propofol target-controlled infusion with brachial plexus block during arteriovenous (AV) access surgery. Materials and Methods: We recruited fifty consecutive patients scheduled to receive AV access surgery. While all patients received general anesthesia combined with ultrasound-guided brachial plexus block, the patients were randomly assigned to one of two general anesthesia maintenance groups, with 23 receiving propofol target-controlled infusion (TCI) and 24 receiving sevoflurane inhalation. We measured perioperative mean arterial pressure (MAP), heart rate, and cardiac output and recorded postoperative pain status and adverse events in both groups. Results: ESRD patients receiving propofol TCI had significantly less reduction in blood pressure than those receiving sevoflurane inhalation (p < 0.05) during AV access surgery. Perioperative cardiac output and heart rate were similar in both groups. Both groups reported relatively low postoperative pain score and a low incidence of adverse events. Conclusions: Propofol TCI with brachial plexus block can be used as an effective anesthesia regimen for ESRD patients receiving AV access surgery. It can be used with less blood pressure fluctuation than inhalational anesthesia.

Factors Associated with Prolonged Extubation after Total Intravenous Anesthesia in Patients Undergoing Vestibular Schwannoma Resection.

OBJECTIVE: To identify factors associated with prolonged tracheal extubation after vestibular schwannoma resection in patients receiving propofol-remifentanil-based total intravenous anesthesia (TIVA). STUDY DESIGN: Single-center retrospective study of vestibular schwannoma resection performed by a single neurosurgeon between July 2018 and September 2021. SETTING: Tertiary academic medical center. PATIENTS: Adults receiving TIVA for vestibular schwannoma resection, classified according to extubation time: non-prolonged extubation (<15 min) and prolonged extubation (≥15 min). MAIN OUTCOME MEASURES: Time from end of surgery to extubation, demographic parameters, intraoperative variables, and familiarity between the anesthesia provider and the neurosurgeon were analyzed. Predictors for prolonged extubation were analyzed via multivariate analysis. The primary outcome was the incidence of prolonged extubation. The secondary outcome was factors associated with prolonged tracheal extubation. RESULTS: A total of 234 cases were analyzed. The median (interquartile range) extubation time was 9.4 minutes (7.2, 12.2 min). Extubation was prolonged in 39 patients (16.7%). Factors predicting prolonged extubation were significant blood loss (odds ratio [OR], 12.8; 95% confidence interval [CI], 2.6-61.7; p = 0.002), intraoperative neuromuscular blocking drug infusion (OR, 6.6; 95% CI, 2.8-15.7; p < 0.001), and lack of familiarity between the anesthesia provider and neurosurgeon (OR, 4.4; 95% CI, 1.5-12.3; p = 0.005). CONCLUSION: Significant blood loss, intraoperative neuromuscular blocking drug infusion, and lack of familiarity between anesthesia provider and neurosurgeon were associated with prolonged extubation following TIVA for vestibular schwannoma resection.

Expanding Indications for a Ketogenic Diet as an Adjuvant Therapy in Adult Refractory Status Epilepticus: an Exploratory Study Using Moderation Analysis.

Refractory status epilepticus (RSE) requires multimodal treatment approaches to achieve rapid seizure cessation and neuroprotection. A ketogenic diet (KD) has demonstrated efficacy as a nutritional therapeutic option for adult RSE. However, the group of adult RSE patients who would benefit from adopting a KD needs to be determined to appropriately select the patients indicated for a KD. Therefore, we conducted a nonrandomized retrospective cohort study to explore the therapeutic efficacy of a KD by investigating the moderation effect of a KD on the association between the clinical characteristics of RSE patients and their functional outcomes. This study investigated 140 RSE patients, including 32 patients treated with a KD; among these patients, 28 (81%) achieved seizure cessation. We found that KD moderated the reduction in the modified Rankin scale (mRS) score at discharge among patients who were older, had higher seizure severity scores, were under continuous intravenous anesthetic therapy (CIVAD), and had super-RSE. Age and seizure severity scores, but not CIVAD or super-RSE, were associated with a KD-moderated change in mRS score at 3 months. Thus, we consider that our study provides evidence of a neuroprotective effect of KD in the most severe RSE patients with very few remaining therapeutic options, but future randomized controlled trials in these subgroups of KD patients are necessary.

Anestesia total intravenosa libre de opioides guiada por qCON y qNOX en paciente obesa / Total Intravenous anesthesia in patients with intestinal occlusive syndrome

Introducción: En los últimos años la anestesia libre de opioides ha constituido una alternativa más a las técnicas tradicionales de anestesia general. Con la exclusión de este grupo de fármacos se evitan los múltiples efectos adversos y complicaciones asociados al mismo. A pesar de que la anestesia libre de opioides tiene sus indicaciones y que ha demostrado sus beneficios en cierto grupo de pacientes, existen aún controversias en relación con su utilidad en el paciente obeso. Características como la obesidad hacen que los modelos multimodales empleados para programar la anestesia libre de opioides sean cada vez más complejos. Objetivos: Describir un caso clínico realizado con la técnica de anestesia libre de opioides que constituye la primera experiencia en Ecuador. Presentación del caso: Se presenta el caso de una paciente obesa intervenida de colecistectomía laparoscópica mediante infusión de propofol, ketamina, lidocaína, sulfato de magnesio, y dexmedetomidina. La titulación de estos fármacos se realizó mediante cálculo de concentraciones plasmáticas a través de modelos farmacocinéticos y guiada por monitorización de profundidad anestésica y analgésica, con lo cual se logró optimizar el consumo de fármacos, disminuir las complicaciones y una evolución clínica favorable. Hasta donde se conoce a nivel local y de país (Ecuador) es la primera experiencia que se reporta con esta técnica. Conclusiones: La anestesia libre de opioides puede resultar una elección en el paciente obeso ya que asegura una adecuada recuperación sin efectos adversos asociados(AU)

Introduction: In recent years, opioid-free anesthesia has become another alternative in front of traditional general anesthesia techniques. The exclusion of this group of drugs avoids the numerous adverse effects and complications associated with its usage. Although opioid-free anesthesia has its indications and has showed its benefits in a certain group of patients, there is still controversy regarding its usefulness in the obese patient. Characteristics such as obesity make the multimodal models used to program opioid-free anesthesia increasingly complex. Objectives: To describe a clinical case involving the opioid-free anesthesia technique, which is the first experience in Ecuador. Case presentation: The case is presented of a female obese patient who underwent laparoscopic cholecystectomy by infusion of propofol, ketamine, lidocaine, magnesium sulfate and dexmedetomidine. Titration of these drugs was carried out by calculating plasma concentrations through pharmacokinetic models and guided by monitoring of anesthetic and analgesic depth, thus optimizing drug consumption, reducing complications and achieving a favorable clinical evolution. As far as known locally and in the country (Ecuador), this is the first reported experience with this technique. Conclusions: Opioid-free anesthesia may be a choice in the obese patient, since it ensures adequate recovery without associated adverse effects(AU)

Volatile versus Propofol General Anesthesia and Long-term Survival after Breast Cancer Surgery: A National Registry Retrospective Cohort Study.

BACKGROUND: Several retrospective studies using administrative or single-center data have failed to show any difference between general anesthesia using propofol versus inhaled volatiles on long-term survival after breast cancer surgery. Although randomized controlled trials are ongoing, validated data from national clinical registries may advance the reliability of existing knowledge. METHODS: Data on breast cancer surgery performed under general anesthesia between 2013 and 2019 from the Swedish PeriOperative Registry and the National Quality Registry for Breast Cancer were record-linked. Overall survival was compared between patients receiving propofol and patients receiving inhaled volatile for anesthesia maintenance. RESULTS: Of 18,674 subjects, 13,873 patients (74.3%) received propofol and 4,801 (25.7%) received an inhaled volatile for general anesthesia maintenance. The two cohorts differed in most respects. Patients receiving inhaled volatile were older (67 yr vs. 65 yr), sicker (888 [19.0%] American Society of Anesthesiologists status 3 to 5 vs. 1,742 [12.8%]), and the breast cancer to be more advanced. Median follow-up was 33 months (interquartile range, 19 to 48). In the full, unmatched cohort, there was a statistically significantly higher overall survival among patients receiving propofol (13,489 of 13,873 [97.2%]) versus inhaled volatile (4,039 of 4,801 [84.1%]; hazard ratio, 0.80; 95% CI, 0.70 to 0.90; P < 0.001). After 1:1 propensity score matching (4,658 matched pairs), there was no statistically significant difference in overall survival (propofol 4,284 of 4,658 [92.0%]) versus inhaled volatile (4,288 of 4,658 [92.1%]; hazard ratio, 0.98; 95% CI, 0.85 to 1.13; P = 0.756). CONCLUSIONS: Among patients undergoing breast cancer surgery under general anesthesia, no association was observed between the choice of propofol or an inhaled volatile maintenance and overall survival.