Propofol Anesthesia Research Articles

Comparative assessment of the effect of anesthetics (propofol, sevoflurane, desflurane) on hemodynamics and gas exchange in the lungs during operations for acute pulmonary embolism

Introduction. To date, single studies have been published on the anesthesiological support of operations for acute pulmonary embolism. The issues of the influence of basic anesthetics on central hemodynamics and the functional state of lung tissue are not covered.The objective was to conduct a comparative assessment of the effect of anesthesia based on propofol, sevoflurane and desflurane on the parameters of central hemodynamics, myocardial contractility and functional state of the lungs during operations for acute pulmonary embolism.Materials and methods. The study included 75 patients (42 men and 33 women) aged 42.3 ± 14.3 years. All patients were operated for massive pulmonary embolism under cardiopulmonary bypass. The patients were randomized into three groups: in the first group (25 patients), propofol was used as the main anesthetic; in the secondgroup (25 patients) - sevoflurane; in the third group (25 patients) - desflurane. The indicators of central hemodynamics, myocardial contractile function and the functional state of the lungs during the operation were studied.Results. The comparative analysis of the anesthesia revealed that propofol had a more pronounced depressive effect on hemodynamics (a statistically significant decrease in blood pressure and EF LV), and desflurane had a moderate hyperdynamic effect (a statistically significant increase in heart rate). Anesthesia with propofol caused a statistically significant increase in the AAPO2 index (by 32.1%), a decrease in the PaO2/FiO2 index (by 24.1%) before cardiopulmonary bypass. After CPB, the oxygenation index decreased, intrapulmonary blood shunting increased, and pulmonary compliance decreased statistically significantly. The use of inhalation anesthetics (sevoflurane, desflurane) effectively preserved the functional parameters of the lungs: there were no statistically significant changes in the studied parameters.Conclusion. The inclusion of inhaled anesthetics (sevoflurane and desflurane) in the anesthesia regimen during surgery for acute pulmonary embolism ensures the stability of hemodynamic parameters and contractile function of the myocardium. The use of inhaled anesthetics maintains high lung function during surgery.

Assessing different brain oxygenation components in elderly patients under propofol or sevoflurane anesthesia: A randomized controlled study

Study objectiveElderly patients undergoing pathophysiological changes necessitate clinical tools for cerebral monitoring. This prospective randomized controlled study aimed to explore how cerebral monitoring using Δo2Hbi, ΔHHbi, and ΔcHbi manifests in elderly patients under either propofol or sevoflurane anesthesia. DesignSingle-center, prospective, randomization. SettingA single tertiary hospital (Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea). PatientsEnrolled 100 patients scheduled for urologic surgery under general anesthesia. Inclusion criteria were (a) age 70–80 years, (b) American Society of Anesthesiologists (ASA) physical status I-II. InterventionPatients were double-blind randomized to receive propofol-based or sevoflurane anesthesia. Cerebral oximetry-related parameters were measured at 5, 10, 15, 20, and 30 min in a setting devoid of surgery-related factors. MeasurementsThe primary outcome focused on the Δo2Hbi pattern in the left and right sides within the propofol and sevoflurane groups. Main resultsWe analyzed 100 patients, 50 patients in each group. In the propofol group, the left Δo2Hbi decreased from 1.4 (3.7) at 5 min to −0.1 (1.8) at 30 min (P < 0.0001), and the right Δo2Hbi decreased from 2.9 (4.2) at 5 min to −0.06 (2.3) at 30 min (P < 0.0001). In the sevoflurane group, the left Δo2Hbi decreased from 1.1 (3.4) at 5 min to −1.4 (4.4) at 30 min (P < 0.0001), and the right Δo2Hbi decreased from 2.0 (3.2) at 5 min to −1.2 (3.9) at 30 min (P < 0.0001). There were no significant differences between the two groups. ΔHHbi did not exhibit significant changes after an initial decrease at 5 min and showed no significant differences between the two groups. ConclusionsIn cerebral oximetry, Δo2Hbi and ΔHHbi could emerge as a valuable approach for discerning changes in the underlying baseline status of the brain in elderly patients during anesthesia.

Comparative Effects of Target-Controlled Infusion of Propofol Versus Spinal and Thiopental-Sevoflurane Anesthesia on Lipid Peroxidation in Elective Cesarean Section: A Prospective, Open-Label Study.

During pregnancy, physiological changes can increase oxidative stress (OS) in both mothers and fetuses. The use of anesthesia for cesarean sections (CSs) could exacerbate this stress due to its impact on the ischemia-reperfusion effect. Our study aimed to explore the effects of target-controlled infusion of propofol on OS during CSs, and to compare these effects with those of spinal and thiopental-sevoflurane anesthesia. The study included ninety parturients undergoing elective CS, allocated into three groups: Group S (spinal) (n = 30), Group P (propofol) (n = 30), and Group TS (thiopental-sevoflurane) (n = 30). Venous blood samples were taken from mothers at three time points, before, during, and after surgery, and one sample was taken from the umbilical vein after delivery. Blood samples were analyzed with the thiobarbituric acid reactive substances (TBARS) assay and blood gas analysis. A statistical comparison between groups was obtained by one-way analysis of variance (ANOVA) and the Wilcoxon test where appropriate. Levels of TBARS after the induction of anesthesia were lower in all groups compared to values preoperatively. In Group P, TBARS levels started to decrease in the first five minutes after the induction (1.90 ± 0.47; P < 0.001) and had significantly lower values compared to Group S (2.22 ± 0.21) and Group TS (2.40 ± 0.20). Two hours after surgery, TBARS values were the lowest in Group P (1.76 ± 0.15, P<0.001), compared to Group S (2.18 ± 0.24) and Group TS (2.41 ± 0.21). TBARS value in umbilical venous blood was significantly lower in Group P (1.56 ± 0.16, P < 0.001) compared to Group S (2.18 ± 0.17) and Group TS (2.09 ± 0.09). Umbilical cord venous blood gas values (pH, PCO2, HCO3, lactates, and base excess (BE)) were not different between the groups, except for PO2, which was significantly lower in Group S (20.5 ± 5.0; P < 0.001) compared to Group P (36.5 ± 19.2) and Group TS (33.5 ± 10.1). Target-controlled infusion of propofol anesthesia could beadvantageous for parturients with compromised oxidative status, especially those undergoing emergency CSs when general anesthesia is required.

Regulating the activity of GABAergic neurons in the ventral pallidum alters the general anesthesia effect of propofol

The full mechanism of action of propofol, a commonly administered intravenous anesthetic drug in clinical practice, remains elusive. The focus of this study was the role of GABAergic neurons which are the main neuron group in the ventral pallidum (VP) closely associated with anesthetic effects in propofol anesthesia. The activity of VP GABAergic neurons following propofol anesthesia in Vgat-Cre mice was observed via detecting c-Fos immunoreactivity by immunofluorescence and western blotting. Subsequently, chemogenetic techniques were employed in Vgat-Cre mice to regulate the activity of VP GABAergic neurons. The role of VP GABAergic neurons in generating the effects of general anesthesia induced by intravenous propofol was further explored through behavioral tests of the righting reflex. The results revealed that c-Fos expression in VP GABAergic neurons in Vgat-Cre mice dramatically decreased after propofol injection. Further studies demonstrated that chemogenetic activation of VP GABAergic neurons during propofol anesthesia shortened the duration of anesthesia and promoted wakefulness. Conversely, the inhibition of VP GABAergic neurons extended the duration of anesthesia and facilitated the effects of anesthesia. The results obtained in this study suggested that regulating the activity of GABAergic neurons in the ventral pallidum altered the effect of propofol on general anesthesia.

Role of scalp nerve block in improving the quality of rehabilitation in patients after meningioma resection: A randomized controlled clinical trial.

In this study, we analyzed whether scalp nerve block with ropivacaine can improve the quality of rehabilitation in patients after meningioma resection. We included 150 patients who were undergoing craniotomy in our hospital and categorized them into 2 groups - observation group (patients received an additional regional scalp nerve block anesthesia) and control group (patients underwent intravenous general anesthesia for surgery), using the random number table method approach (75 patients in each group). The main indicator of the study was the Karnofsky Performance Scale scores of patients at 3 days postoperatively, and the secondary indicator was the anesthesia satisfaction scores of patients after awakening from anesthesia. The application value of different anesthesia modes was studied and compared in the 2 groups. Patients in the observation group showed better anesthesia effects than those in the control group, with significantly higher Karnofsky Performance Scale scores at 3 days postoperatively (75.02 vs 66.43, P < .05) and anesthesia satisfaction scores. Compared with patients in the control group, patients in the observation group had lower pain degrees at different times after the surgery, markedly lower dose of propofol and remifentanil for anesthesia, and lower incidence of adverse reactions and postoperative complications. In addition, the satisfaction score of the patients and their families for the treatment was higher and the results of all the indicators were better in the observation group than in the control group, with statistically significant differences (P < .05). Scalp nerve block with ropivacaine significantly improves the quality of short-term postoperative rehabilitation in patients undergoing elective craniotomy for meningioma resection. This is presumably related to the improvements in intraoperative hemodynamics, relief from postoperative pain, and reduction in postoperative nausea and vomiting.

Uncovering essential anesthetics-induced exosomal miRNAs related to hepatocellular carcinoma progression: a bioinformatic investigation

BackgroundAnesthetic drugs may alter exosomal microRNA (miRNA) contents and mediate cancer progression and tumor microenvironment remodeling. Our study aims to explore how the anesthetics (sevoflurane and propofol) impact the miRNA makeup within exosomes in hepatocellular carcinoma (HCC), alongside the interconnected signaling pathways linked to the tumor immune microenvironment.MethodsIn this prospective study, we collected plasma exosomes from two groups of HCC patients (n = 5 each) treated with either propofol or sevoflurane, both before anesthesia and after hepatectomy. Exosomal miRNA profiles were assessed using next-generation sequencing (NGS). Furthermore, the expression data from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) was used to pinpoint the differentially expressed exosomal miRNAs (DEmiRNAs) attributed to the influence of propofol or sevoflurane in the context of HCC. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to dissect the signaling pathways and biological activities associated with the identified DEmiRNAs and their corresponding target genes.ResultsA total of 35 distinct DEmiRNAs were exclusively regulated by either propofol (n = 9) or sevoflurane (n = 26). Through TCGA-LIHC database analysis, 8 DEmiRNAs were associated with HCC. These included propofol-triggered miR-452-5p and let-7c-5p, as well as sevoflurane-induced miR-24-1-5p, miR-122-5p, miR-200a-3p, miR-4686, miR-214-3p, and miR-511-5p. Analyses revealed that among these 8 DEmiRNAs, the upregulation of miR-24-1-5p consistently demonstrated a significant association with lower histological grades (p < 0.0001), early-stage tumors (p < 0.05) and higher survival (p = 0.029). Further analyses using GSEA and GSVA indicated that miR-24-1-5p, along with its target genes, were involved in governing the tumor immune microenvironment and potentially inhibiting tumor progression in HCC.ConclusionsThis study provided bioinformatics evidence suggesting that sevoflurane-induced plasma exosomal miRNAs may have a potential impact on the immune microenvironment of HCC. These findings established a foundation for future research into mechanistic outcomes in cancer patients.

The effect of propofol versus thiopentone on APGAR score of babies delivered and recovery of pregnant mothers undergoing elective cesarean section

Background and objectives: The Apgar score is a vital indicator of the baby's well-being. This study aims to compare the effects of propofol and thiopental anesthetics on babies' Apgar scores and mothers' recovery times, this study was carried out. Methods: This single-arm interventional study was conducted in Zhyan and Soma Hospital in Sulaimani, Kurdistan Region of Iraq from February 2022 to July 2022. Separate doses of propofol and thiopental were given to 140 pregnant women who were candidates for elective cesarean section in two separate groups. Apgar scores at 1 and 5 minutes after birth, recovery time, and hemodynamic changes before and after the intervention were evaluated and compared. Results: The results of the diastolic pressure variable after the intervention and the hemodynamic variables were significantly different in each group before and after the intervention (P&lt;0.001). The mean recovery time in propofol and thiopental groups was 21.4 ± 2.4 and 26.0 ± 1.8 minutes, respectively, and they were statistically significantly different (p&lt;0.001). There was a statistically significant difference in the Apgar score at the 5th minute between the two groups (p=0.03). In terms of the need for resuscitation after the first minute, the results were in favor of the propofol group (p&lt;0.001). Conclusion: Propofol can be used more safely since patients who had anesthesia with it had better hemodynamics, quicker recovery times, neonates with higher Apgar scores, and less need for postpartum resuscitation.

GABAergic neurons of anterior thalamic reticular nucleus regulate states of consciousness in propofol- and isoflurane-mediated general anesthesia.

The thalamus system plays critical roles in the regulation of reversible unconsciousness induced by general anesthetics, especially the arousal stage of general anesthesia (GA). But the function of thalamus in GA-induced loss of consciousness (LOC) is little known. The thalamic reticular nucleus (TRN) is the only GABAergic neurons-composed nucleus in the thalamus, which is composed of parvalbumin (PV) and somatostatin (SST)-expressing GABAergic neurons. The anterior sector of TRN (aTRN) is indicated to participate in the induction of anesthesia, but the roles remain unclear. This study aimed to reveal the role of the aTRN in propofol and isoflurane anesthesia. We first set up c-Fos straining to monitor the activity variation of aTRNPV and aTRNSST neurons during propofol and isoflurane anesthesia. Subsequently, optogenetic tools were utilized to activate aTRNPV and aTRNSST neurons to elucidate the roles of aTRNPV and aTRNSST neurons in propofol and isoflurane anesthesia. Electroencephalogram (EEG) recordings and behavioral tests were recorded and analyzed. Lastly, chemogenetic activation of the aTRNPV neurons was applied to confirm the function of the aTRN neurons in propofol and isoflurane anesthesia. c-Fos straining showed that both aTRNPV and aTRNSST neurons are activated during the LOC period of propofol and isoflurane anesthesia. Optogenetic activation of aTRNPV and aTRNSST neurons promoted isoflurane induction and delayed the recovery of consciousness (ROC) after propofol and isoflurane anesthesia, meanwhile chemogenetic activation of the aTRNPV neurons displayed the similar effects. Moreover, optogenetic and chemogenetic activation of the aTRN neurons resulted in the accumulated burst suppression ratio (BSR) during propofol and isoflurane GA, although they represented different effects on the power distribution of EEG frequency. Our findings reveal that the aTRN GABAergic neurons play a critical role in promoting the induction of propofol- and isoflurane-mediated GA.

Unveiling the protective role of sevoflurane in video-assisted thoracoscopic surgery associated-acute lung injury: Inhibition of ferroptosis

Acute lung injury (ALI) frequently occurs after video-assisted thoracoscopic surgery (VATS). Ferroptosis is implicated in several lung diseases. Therefore, the disparate effects and underlying mechanisms of the two commonly used anesthetics (sevoflurane (Sev) and propofol) on VATS-induced ALI need to be clarified. In the present study, enrolled patients were randomly allocated to receive Sev (group S) or propofol anesthesia (group P). Intraoperative oxygenation, morphology of the lung tissue, expression of ZO-1, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), superoxide dismutase (SOD), glutathione (GSH), Fe2+, glutathione peroxidase 4 (GPX4), and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in the lung tissue as well as the expression of TNF-α and IL-6 in plasma were measured. Postoperative complications were recorded. Of the 85 initially screened patients scheduled for VATS, 62 were enrolled in either group S (n = 32) or P (n = 30). Compared with propofol, Sev substantially (1) improved intraoperative oxygenation; (2) relieved histopathological lung injury; (3) increased ZO-1 protein expression; (4) decreased the levels of TNF-α and IL-6 in both the lung tissue and plasma; (5) increased the contents of GSH and SOD but decreased Fe2+ concentration; (6) upregulated the protein expression of p-AKT, Nrf2, HO-1, and GPX4. No significant differences in the occurrence of postoperative outcomes were observed between both groups. In summary, Sev treatment, in comparison to propofol anesthesia, may suppress local lung and systemic inflammatory responses by activating the PI3K/Akt/Nrf2/HO-1 pathway and inhibiting ferroptosis. This cascade of effects contributes to the maintenance of pulmonary epithelial barrier permeability, alleviation of pulmonary injury, and enhancement of intraoperative oxygenation in patients undergoing VATS.

Activation of Ventral Tegmental Area Dopaminergic Neurons Projecting to the Parabrachial Nucleus Promotes Emergence from Propofol Anesthesia in Male Rats.

Since the clinical introduction of general anesthesia, its underlying mechanisms have not been fully elucidated. The ventral tegmental area (VTA) and parabrachial nucleus (PBN) play pivotal roles in the mechanisms underlying general anesthesia. However, whether dopaminergic (DA) projections from the VTA to the PBN play a role in mediating the effects of general anesthesia is unclear. We microinjected 6-hydroxydopamine into the PBN to damage tyrosine hydroxylase positive (TH+) neurons and found a prolonged recovery time from propofol anesthesia. We used calcium fiber photometry recording to explore the activity of TH + neurons in the PBN. Then, we used chemogenetic and optogenetic approaches either activate the VTADA-PBN pathway, shortening the propofol anesthesia emergence time, or inhibit this pathway, prolonging the emergence time. These data indicate the crucial involvement of TH + neurons in the PBN in regulating emergence from propofol anesthesia, while the activation of the VTADA-PBN pathway facilitates the emergence of propofol anesthesia.

#242 Incidence of postoperative acute kidney injury is twice as high in men than women following radical colorectal surgery—key findings from PROSACC

Abstract Background and Aims Acute kidney injury (AKI) affects approximately 8% of the general surgical population. Additionally, AKI increases the risk for morbidity and mortality by 8- and 3-fold respectively. It was earlier believed that women had a greater risk for postoperative AKI. However, recent literature indicates that the incidence of AKI is actually higher in hospitalized men than women (2.2 odds ratio). Hence the male sex is currently discussed to be a risk factor for AKI. We therefore hypothesized that the incidence of postoperative AKI will be higher amongst men than women after radical colorectal surgery. Method We conducted a post hoc analysis (PROSACC: Propofol or Sevoflurane Anesthesia in Colon Cancer, NCT05585866) on the database from the CAN-study (Cancer and Anesthesia: Survival After Radical Surgery, NCT01975064). The CAN-study included cancer patients undergoing radical surgery at several sites in China, Croatia, Poland, and Sweden. Patients included in PROSACC were those undergoing colorectal surgery at any predefined site. Primary outcome was incidence of AKI by changes in plasma creatinine, secondary outcome was AKI in association to gender (women/men). The KDIGO criteria was used for classifying AKI on postoperative days 1-3 and 4-10. Database management and statistical analysis was performed by Uppsala Research Centre. Men vs women AKI outcome at day 1-3 and 4-10 was statistically compared with the Pearson's chi-square test. Results A total of 3254 patients (n = 1900 men; n = 1354 women) were included in the analysis with their preoperative plasma creatinine. Demographics showed that of the women, 39% had hypertension, 12% had diabetes and 2% had pre-existing kidney disease. In comparison, amongst the men, 24% had hypertension, 9% had diabetes and 1% pre-existing kidney disease. Postoperative plasma creatinine values were obtainable from the database in 2741 patients (n = 1578 men; n = 1163 women) on postoperative day 1-3. One hundred and ninety patients (7%) of this group had developed AKI. Separated by gender, 6% of the women (n = 72) and 8% of the men (n = 118) had established AKI according to KDIGO (p = 0.190). Plasma creatinine values were obtainable in 986 patients (n = 582 men; n = 404 women) on postoperative day 4-10 whereas 87 patients (9%) in this group had developed AKI. Separated by gender, 6% of the women (n = 23) but 11% of the men (n = 64) had established AKI at this timepoint (p = 0.004). Conclusion With this post hoc analysis of a global, multicentre, randomized controlled trial we conclude that the incidence of postoperative AKI is twice as high in men compared with women after 4-10 postoperative days following radical colorectal surgery. Since the women had higher rate of pronounced preoperative risk factors yet still had lower incidence of AKI, this study aligns with the conclusion that the male sex is a risk factor for postoperative AKI.

Sodium Leak Channel in Glutamatergic Neurons of the Lateral Parabrachial Nucleus Helps to Maintain Respiratory Frequency Under Sevoflurane Anesthesia.

The lateral parabrachial nucleus (PBL) is implicated in the regulation of respiratory activity. Sodium leak channel (NALCN) mutations disrupt the respiratory rhythm and influence anesthetic sensitivity in both rodents and humans. Here, we investigated whether the NALCN in PBL glutamatergic neurons maintains respiratory function under general anesthesia. Our results showed that chemogenetic activation of PBL glutamatergic neurons increased the respiratory frequency (RF) in mice; whereas chemogenetic inhibition suppressed RF. NALCN knockdown in PBL glutamatergic neurons but not GABAergic neurons significantly reduced RF under physiological conditions and caused more respiratory suppression under sevoflurane anesthesia. NALCN knockdown in PBL glutamatergic neurons did not further exacerbate the respiratory suppression induced by propofol or morphine. Under sevoflurane anesthesia, painful stimuli rapidly increased the RF, which was not affected by NALCN knockdown in PBL glutamatergic neurons. This study suggested that the NALCN is a key ion channel in PBL glutamatergic neurons that maintains respiratory frequency under volatile anesthetic sevoflurane but not intravenous anesthetic propofol.

Postoperative liver injury after sevoflurane or propofol anesthesia in patients undergoing non-cardiac surgery: a retrospective cohort study

Although sevoflurane is generally considered safe, reports suggest that sevoflurane may cause postoperative liver injury more frequently than previously believed. Therefore, we aimed to compare the incidence of clinically significant postoperative liver injury following non-cardiac surgery between patients who underwent sevoflurane anesthesia and propofol-based total intravenous anesthesia. We retrospectively reviewed adult surgical patients from January 2010 to September 2022 who underwent general anesthesia in our center using sevoflurane or propofol over 3 h. After 1:1 propensity score matching, the incidence of postoperative liver injury was compared between the two groups. Out of 58,300 patients reviewed, 44,345 patients were included in the analysis. After propensity score matching, 7767 patients were included in each group. The incidence of postoperative liver injury was 1.4% in the sevoflurane group, which was similar to that in the propofol group (1.6%; p = 0.432). Comparison of the severity of postoperative alanine aminotransferase elevation showed that the incidence of borderline and mild elevation was higher in the sevoflurane group, but there was no difference in the incidence of moderate and severe elevation. In conclusion, sevoflurane anesthesia over 3 h was not associated with a higher incidence of clinically significant postoperative liver injury compared to propofol anesthesia.

Electroencephalographic Indices for Clinical Endpoints during Propofol Anesthesia in Infants: An Early-phase Propofol Biomarker-finding Study.

Unlike expired sevoflurane concentration, propofol lacks a biomarker for its brain effect site concentration, leading to dosing imprecision particularly in infants. Electroencephalography monitoring can serve as a biomarker for propofol effect site concentration, yet proprietary electroencephalography indices are not validated in infants. The authors evaluated spectral edge frequency (SEF95) as a propofol anesthesia biomarker in infants. It was hypothesized that the SEF95 targets will vary for different clinical stimuli and an inverse relationship existed between SEF95 and propofol plasma concentration. This prospective study enrolled infants (3 to 12 months) to determine the SEF95 ranges for three clinical endpoints of anesthesia (consciousness-pacifier placement, pain-electrical nerve stimulation, and intubation-laryngoscopy) and correlation between SEF95 and propofol plasma concentration at steady state. Dixon's up-down method was used to determine target SEF95 for each clinical endpoint. Centered isotonic regression determined the dose-response function of SEF95 where 50% and 90% of infants (ED50 and ED90) did not respond to the clinical endpoint. Linear mixed-effect model determined the association of propofol plasma concentration and SEF95. Of 49 enrolled infants, 44 evaluable (90%) showed distinct SEF95 for endpoints: pacifier (ED50, 21.4 Hz; ED90, 19.3 Hz), electrical stimulation (ED50, 12.6 Hz; ED90, 10.4 Hz), and laryngoscopy (ED50, 8.5 Hz; ED90, 5.2 Hz). From propofol 0.5 to 6 μg/ml, a 1-Hz SEF95 increase was linearly correlated to a 0.24 (95% CI, 0.19 to 0.29; P < 0.001) μg/ml decrease in plasma propofol concentration (marginal R2 = 0.55). SEF95 can be a biomarker for propofol anesthesia depth in infants, potentially improving dosing accuracy and utilization of propofol anesthesia in this population.

Influence of Clinical and Genetic Factors on Propofol Dose Requirements: A Genome-wide Association Study.

Propofol is a widely used intravenous hypnotic. Dosing is based mostly on weight, with great interindividual variation in consumption. Suggested factors affecting propofol requirements include age, sex, ethnicity, anxiety, alcohol consumption, smoking, and concomitant valproate use. Genetic factors have not been widely explored. This study considered 1,000 women undergoing breast cancer surgery under propofol and remifentanil anesthesia. Depth of anesthesia was monitored with State Entropy (GE Healthcare, Finland). Propofol requirements during surgery were recorded. DNA from blood was genotyped with a genome-wide array. A multivariable linear regression model was used to assess the relevance of clinical variables and select those to be used as covariates in a genome-wide association study. Imputed genotype data were used to explore selected loci further. In silico functional annotation was used to explore possible consequences of the discovered genetic variants. Additionally, previously reported genetic associations from candidate gene studies were tested. Body mass index, smoking status, alcohol use, remifentanil dose (ln[mg · kg-1 · min-1]), and average State Entropy during surgery remained statistically significant in the multivariable model. Two loci reached genome-wide significance (P < 5 × 10-8). The most significant associations were for single-nucleotide polymorphisms rs997989 (30 kb from ROBO3), likely affecting expression of another nearby gene, FEZ1, and rs9518419, close to NALCN (sodium leak channel); rs10512538 near KCNJ2 encoding the Kir2.1 potassium channel showed suggestive association (P = 4.7 × 10-7). None of these single-nucleotide polymorphisms are coding variants but possibly affect the regulation of nearby genes. None of the single-nucleotide polymorphisms previously reported as affecting propofol pharmacokinetics or pharmacodynamics showed association in the data. In this first genome-wide association study exploring propofol requirements, This study discovered novel genetic associations suggesting new biologically relevant pathways for propofol and general anesthesia. The roles of the gene products of ROBO3/FEZ1, NALCN, and KCNJ2 in propofol anesthesia warrant further studies.

Effect of Butorphanol-Medetomidine and Butorphanol-Dexmedetomidine on Echocardiographic Parameters during Propofol Anaesthesia in Dogs.

This study compared the effects of butorphanol-medetomidine and butorphanol-dexmedetomidine combinations on echocardiographic parameters during propofol anaesthesia in dogs. The dogs were randomly divided into two groups. In the butorphanol-medetomidine (BM) group, butorphanol (0.2 mg/kg) and medetomidine (15 μg/kg) were intravenously administered; in the butorphanol-dexmedetomidine (BD) group, butorphanol (0.2 mg/kg) and dexmedetomidine (7.5 μg/kg) was used. Anaesthesia was induced with propofol and maintained with a constant-rate infusion of propofol (0.2 mg/kg/min). The echocardiographic parameters were assessed in conscious dogs (T0). Echocardiography was conducted again at 10 min post premedication (T1), followed by assessments at 30 (T2), 60 (T3), and 90 (T4) mins. The dogs were subjected to diagnostic procedures (radiography, computed tomography) under anaesthesia. A significant reduction in heart rate and cardiac output was noted in both groups at T1. There was no significant difference in the stroke volume between the BM and BD groups. The application of butorphanol-dexmedetomidine caused a significant increase in the left ventricular internal diameter in diastole and the diameter of the left atrium compared to that caused by butorphanol-medetomidine. This study documented that butorphanol-medetomidine and butorphanol-dexmedetomidine combinations caused similar reductions in heart rate and cardiac output in both groups. 'New´ valvular regurgitation occurred following their administration.

Comparison between propofol and total inhalational anaesthesia on cardiovascular outcomes following on-pump cardiac surgery in higher-risk patients: a randomised controlled pilot and feasibility study

ObjectivesMyocardial revascularisation and cardiopulmonary bypass (CPB) can cause ischaemia-reperfusion injury, leading to myocardial and other end-organ damage. Volatile anaesthetics protect the myocardium in experimental studies. However, there is uncertainty about...

Comparison of Effects of Propofol Combined with Different Doses of Esketamine for ECT in the Treatment of Depression: A Randomized Controlled Trial Protocol.

Major depressive disorder (MDD) is a common mood disorder. Electroconvulsive therapy (ECT) has a significant effect on treatment-resistant MDD. Esketamine may have potential advantages in improving the efficacy of ECT, and the strong affinity of this compound for NMDAR renders it a viable therapeutic option for the management of depression. This study aims to compare the effects of different doses of esketamine combined with propofol anesthesia versus propofol anesthesia alone in ECT, aiming to provide further insights for optimizing ECT and enhancing comprehensive treatment outcomes for depression. This study was a prospective, randomized, controlled, double-blind trial involving subjects and evaluators. One hundred eleven patients scheduled for ECT were randomly assigned to three groups. In Group P, propofol at 1mg/kg was administered intravenously. In Group P+E, propofol at a dosage of 0.5mg/kg and esketamine at a dosage of 0.5mg/kg was administered intravenously. Patients in Group P+SE received propofol at a dosage of 0.75mg/kg and esketamine at a dosage of 0.25mg/kg. The same anesthesia protocol was used for the same patient until the end of the last treatment. The primary outcome measures were the Hamilton depression scale (HAMD) and the Patient Health Questionnaire-9 (PHQ-9), the Columbia-Suicide Severity Rating Scale (C-SSRS), and the Digit symbol substitution test (DSST). Secondary outcomes included length of hospital stay, readmission rate, hemodynamic status, recovery, and adverse events. This study aimed to compare the effects of propofol combined with different doses of esketamine for ECT. The results may provide a better choice for ECT anesthesia.

Propofol enhancement of slow wave sleep to target the nexus of geriatric depression and cognitive dysfunction: protocol for a phase I open label trial

IntroductionLate-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a risk factor for cognitive decline. Slow...

Incidence of postoperative acute kidney injury is twice as high in men than women following radical colorectal surgery — key findings from PROSACC, a posthoc analysis of a global, multicenter, randomized controlled trial

Acute kidney injury (AKI) affects approximately 8% of the general surgical population. Additionally, AKI increases the risk for morbidity and mortality by 8- and 3-fold respectively. It was earlier believed that women had a greater risk for postoperative AKI. However, recent literature indicates that the incidence of AKI is actually higher in hospitalized men than women (2.2 odds ratio). Hence the male sex is currently discussed to be a risk factor for AKI. We therefore hypothesized that the incidence of postoperative AKI will be higher amongst men than women after radical colorectal surgery. We conducted a posthoc analysis (PROSACC: Propofol or Sevoflurane Anesthesia in Colon Cancer, NCT05585866) on the database from the CAN-study (Cancer and Anesthesia: Survival After Radical Surgery, NCT01975064). The CAN-study included cancer patients undergoing radical surgery at several sites in China, Croatia, Poland, and Sweden. Patients included in PROSACC were those undergoing colorectal surgery at any predefined site. Primary outcome was incidence of AKI by changes in plasma creatinine, secondary outcome was AKI in association to gender (women/men). The KDIGO criteria was used for classifying AKI on postoperative days 1-3 and 4-10. Database management and statistical analysis was performed by Uppsala Research Centre. Men vs women AKI outcome at day 1-3 and 4-10 was statistically compared with the Pearson’s chi-square test. A total of 3254 patients (n=1900 men; n=1354 women) were included in the analysis with their preoperative plasma creatinine. Demographics showed that of the women, 39% had hypertension, 12% had diabetes and 2% had preexisting kidney disease. In comparison, amongst the men, 24% had hypertension, 9% had diabetes and 1% preexisting kidney disease. Postoperative plasma creatinine values were obtainable from the database in 2741 patients (n=1578 men; n=1163 women) on postoperative day 1-3. One hundred and ninety patients (7%) of this group had developed AKI. Separated by gender, 6% of the women (n=72) and 8% of the men (n=118) had established AKI according to KDIGO (p=0.190). Plasma creatinine values were obtainable in 986 patients (n=582 men; n=404 women) on postoperative day 4-10 whereas 87 patients (9%) in this group had developed AKI. Separated by gender, 6% of the women (n=23) but 11% of the men (n=64) had established AKI at this timepoint (p=0.004). With this posthoc analysis of a global, multicenter, randomized controlled trial we conclude that the incidence of postoperative AKI is twice as high in men compared with women after 4-10 postoperative days following radical colorectal surgery. Since the women had higher rate of pronounced preoperative risk factors yet still had lower incidence of AKI, this study aligns with the conclusion that the male sex is a risk factor for postoperative AKI. Funded by the Swedish Research Council (2014–02569 and 2014–07606). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.