Comparison of the recovery profile of sufentanil and remifentanil in total intravenous anesthesia: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Remifentanil is a short-acting opioid and can be administered during surgery without the risk of delayed postoperative recovery but concerns about hyperalgesia and the shortages of remifentanil lead anesthetists to consider long-acting opioids for Total Intravenous Anesthesia (TIVA). Sufentanil is a more potent opioid with a longer context-sensitive half-life but can promote good postoperative analgesia due to its residual effect. This meta-analysis aimed to compare the recovery profile of remifentanil and sufentanil for TIVA. METHODS: The search strategy was performed in PubMed, CENTRAL, and Web of Science for RCTs comparing sufentanil and remifentanil as part of TIVA in adults undergoing noncardiac surgery. Risk of bias and the quality of evidence were performed using RoB2 and GRADEpro, respectively. The primary outcome was time to tracheal extubation. Secondary analyses included postoperative analgesia, respiratory depression, and Postoperative Nausea and Vomiting (PONV). RESULTS: Sufentanil increases the time to extubate, MD = 4.29 min; 95% CI: 2.33 to 6.26; p = 0.001. It also reduces the need for postoperative rescue analgesia, logOR = -1.07; 95% CI: -1.62 to -0.52; p = 0.005. There were no significant differences between both opioids for PONV, logOR = 0.50; 95% CI: -0.10 to 1.10; p = 0.10 and respiratory depression, logOR = 1.21; 95% CI: -0.42 to 2.84; p = 0.15. CONCLUSION: Sufentanil delays the time to tracheal extubation compared with remifentanil but is associated with a reduced need for postoperative rescue analgesia. No significant differences were observed between the two opioids in terms of postoperative respiratory depression or PONV.

Assessing the Analgesic Efficacy of Lumbosacral Epidural Morphine in Cats Undergoing Ovariohysterectomy: A Comparative Study of Two Doses.

Opioids are administered epidurally (PV) to provide trans- and postoperative analgesia. Twenty healthy female cats aged between 6 and 24 months and weighing between 2 and 3.7 kg, undergoing elective ovariohysterectomy (OVH), were induced with propofol (8 mg/kg), followed by continuous infusion (0.1-0.4 mg/kg/min). Three groups were defined: CG (0.1 mL/kg of iodinated contrast, n = 6), G0.1 (0.1 mg/kg of morphine, n = 7), and G0.2 (0.2 mg/kg of morphine, n = 7) per VP. All received 0.1 mL/kg of iodinated contrast per VP and injection water to obtain a total of 0.3 mL/kg. Heart rate (HR), systolic blood pressure (SBP), temperature, expired CO2, oxygen saturation, and number of rescue analgesics were monitored. Postoperatively, a multidimensional scale was used to assess acute pain in cats for 12 h. The mean HR and SBP in the CG were higher at the time of maximum noxious stimulation and required fentanyl in all groups. Postoperatively, 83%, 28%, and 7% of the animals in CG, G0.1, and G0.2, respectively, received rescue analgesia. In cats undergoing OVH, epidural morphine at doses of 0.1 and 0.2 mg/kg did not prevent the need for intraoperative rescue analgesia but reduced the postoperative analgesic needed.

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.

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.

Remimazolam versus propofol for sedation in gastrointestinal endoscopic procedures: a systematic review and meta-analysis.

BACKGROUND: Propofol has a favourable efficacy profile in gastrointestinal endoscopic procedures, however adverse events remain frequent. Emerging evidence supports remimazolam use in gastrointestinal endoscopy. This systematic review and meta-analysis compares remimazolam and propofol, both combined with a short-acting opioid, for sedation of adults in gastrointestinal endoscopy. METHODS: We searched MEDLINE, Embase, and Cochrane databases for randomised controlled trials comparing efficacy-, safety-, and satisfaction-related outcomes between remimazolam and propofol, both combined with short-acting opioids, for sedation of adults undergoing gastrointestinal endoscopy. We performed sensitivity analyses, subgroup assessments by type of short-acting opioid used and age range, and meta-regression analysis using mean patient age as a covariate. We used R statistical software for statistical analyses. RESULTS: We included 15 trials (4516 subjects). Remimazolam was associated with a significantly lower sedation success rate (risk ratio [RR] 0.991; 95% confidence interval [CI] 0.984-0.998; high-quality evidence) and a slightly longer induction time (mean difference [MD] 9 s; 95% CI 4-13; moderate-quality evidence), whereas there was no significant difference between the sedatives in other time-related outcomes. Remimazolam was associated with significantly lower rates of respiratory depression (RR 0.41; 95% CI 0.30-0.56; high-quality evidence), hypotension (RR 0.43; 95% CI 0.35-0.51; moderate-quality evidence), hypotension requiring treatment (RR 0.25; 95% CI 0.12-0.52; high-quality evidence), and bradycardia (RR 0.42; 95% CI 0.30-0.58; high-quality evidence). There was no difference in patient (MD 0.41; 95% CI -0.07 to 0.89; moderate-quality evidence) and endoscopist satisfaction (MD -0.31; 95% CI -0.65 to 0.04; high-quality evidence) between both drugs. CONCLUSIONS: Remimazolam has clinically similar efficacy and greater safety when compared with propofol for sedation in gastrointestinal endoscopies.

Accuracy of closed-loop and open-loop propofol delivery systems by bispectral index monitoring in breast surgery patients: a prospective randomized trial.

BACKGROUND: This randomized and controlled prospective study tested the hypothesis that closed-loop Target-Controlled Infusion (TCI) of propofol would be associated with better system performance when compared with open-loop controlled delivery of propofol. METHODS: Patients scheduled for elective breast surgery were randomly assigned to two groups: a closed-loop group, in which propofol infusion was performed by a closed-loop TCI system that used the Bispectral Index (BIS) as a feedback parameter to titrate the rate of propofol infusion, and an open-loop group, in which propofol infusion was performed manually and guided by the bispectral index. RESULTS: A total of 156 patients were recruited for this study (closed-loop group n = 79; open-loop group n = 77). The Global Score (GS) of the closed-loop group was lower than that of the open-loop group (34.3 and 42.2) (p = 0.044). The proportions of time with a BIS value between 40 and 60 were almost identical in the closed-loop group and the open-loop group (68.7 ± 10.6% and 66.7 ± 13.3%) (p = 0.318). The individuals in the closed-loop group consumed more propofol compared with those in the open-loop group (7.20 ± 1.65 mg.kg-1.h-1 vs. 6.03 ± 1.31 mg.kg-1.h-1, p < 0.001). No intraoperative recall, somatic events or adverse events occurred. No significant difference in heart rate was observed between the two groups (p = 0.169). CONCLUSION: The closed-loop protocol was associated with lower BIS variability and lower out-of-range BIS values, at the cost of a greater consumption of propofol when compared to the open loop group. REGISTER NUMBER: ChiCTR-INR-17010399.

Hemodynamic impact of increasing time between fentanyl and propofol administration during anesthesia induction: a randomised, clinical trial

Abstract Background and objective: Anesthesia induction can produce severe propofol dose-dependent hypotension. Fentanyl coadministration reduces the catecholaminergic response to orotracheal intubation allowing propofol dose reduction. The aim of this study is to determine whether the hemodynamic response is improved by increasing the time between fentanyl and propofol administration and reducing the dose of the latter without increasing the time to achieve optimal hypnosis. Methods: After approval by the Research Ethics Committee, patients undergoing non-cardiac surgery with endotracheal intubation were randomized by a computer-generated table into six time-dose groups (1 or 2 minutes/1, 1.5, or 2mg.kg-1 of propofol). Patients with high bronchoaspiration risk, a difficult airway, hemodynamic instability, or anesthetic allergies were excluded. After giving intravenous fentanyl (2 μg.kg-1 ), each group received different doses of propofol after 1 or 2 minutes. Non-invasive blood pressure (BP) and heart rate (HR) were measured at pre-induction, pre-intubation, and post-intubation. Time to hypnosis (bispectral index < 60) was also recorded. Results: Of the 192 recruited patients, 186 completed the study (1 min group n = 94; 2 min group n = 92). It was observed that HR and BP decreased after propofol administration and increased after intubation in all groups (p<0.0001). In patients over 55 years, the 2 min - 2 mg.kg-1 group showed the greatest systolic BP reduction (36 ± 12%) at pre-intubation, while the 1 min - 1.5 mg.kg-1 group showed the least hemodynamic alteration between pre- and post-intubation (-4 ± 13%). No significant differences were found in younger patients or in the time to reach hypnosis between the six groups. While no cases of severe bradycardia were recorded, 5,4% of the sample required vasopressors. Conclusion: Increasing the time between the administration of fentanyl and propofol by up to two minutes results in greater hypotension in patients over 55 years.

Accuracy of closed-loop and open-loop propofol delivery systems by bispectral index monitoring in breast surgery patients: a prospective randomized trial

Abstract Background: This randomized and controlled prospective study tested the hypothesis that closed-loop Target-Controlled Infusion (TCI) of propofol would be associated with better system performance when compared with open-loop controlled delivery of propofol. Methods: Patients scheduled for elective breast surgery were randomly assigned to two groups: a closed-loop group, in which propofol infusion was performed by a closed-loop TCI system that used the Bispectral Index (BIS) as a feedback parameter to titrate the rate of propofol infusion, and an open-loop group, in which propofol infusion was performed manually and guided by the bispectral index. Results: A total of 156 patients were recruited for this study (closed-loop group n = 79; open-loop group n = 77). The Global Score (GS) of the closed-loop group was lower than that of the open-loop group (34.3 and 42.2) (p = 0.044). The proportions of time with a BIS value between 40 and 60 were almost identical in the closed-loop group and the open-loop group (68.7 ± 10.6% and 66.7 ± 13.3%) (p = 0.318). The individuals in the closed-loop group consumed more propofol compared with those in the open-loop group (7.20 ± 1.65 mg.kg−1.h−1 vs. 6.03 ± 1.31 mg.kg−1.h−1, p < 0.001). No intraoperative recall, somatic events or adverse events occurred. No significant difference in heart rate was observed between the two groups (p = 0.169). Conclusion: The closed-loop protocol was associated with lower BIS variability and lower out-of-range BIS values, at the cost of a greater consumption of propofol when compared to the open loop group. Register number:ChiCTR-INR-17010399.

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

ABSTRACT 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.

Effects of different rates of propofol with or without S-ketamine on ventricular function in healthy cats - a randomized study.

Propofol is used for anesthetic induction in cats and procedural sedation in countries where alfaxalone is not available. Studies have reported propofol-related effects in echocardiography variables in dogs and humans. However, there is a lack of echocardiography studies investigating propofol-related effects on cats. This study aimed to use echocardiography to investigate echocardiographic changes in three protocols using propofol: propofol-slow (2 mg/kg/min, PS); propofol-fast (8 mg/kg/min, PF); propofol-ketamine (S-ketamine 2 mg/kg bolus followed by propofol 2 mg/kg/min; PK) in healthy premedicated (gabapentin-buprenorphine-acepromazine; 200 mg/cat, 0.4, and 0.1 mg/kg, respectively), non-intubated cats. Echocardiographic measurements were obtained at three time points: baseline (before the administration of propofol), end of propofol titration (end-point, T0), and 15 min after T0 (T15). Propofol at a lower rate continued from T0 to T15. Echocardiographic and physiological variables included fractional shortening (FS%), ejection fraction (EF%), HR, BP, and others. Propofol requirements at T0 for PF, PS, and PK groups were 5.0 ± 0.9, 3.8 ± 0.7, and 2.4 ± 0.5 mg/kg, respectively. EF% neither change over time nor between groups. PF and PK showed a reduction in FS% at T0 (47 ± 6 to 34 ± 6 and 42 ± 6 to 36 ± 5, respectively). BP reduced significantly in PF and PS groups (136 ± 26 to 105 ± 13 and 137 ± 22 to 115 ± 15 mmHg, respectively). It is unclear whether changes in echocardiography variables were of clinical relevance related to treatment groups or a result of within-group individual responses.

Safety and efficacy of target-controlled infusion versus intermittent bolus administration of propofol for sedation in colonoscopy: a randomized controlled trial

Abstract Background: Our objective was to compare the safety and efficacy of Target-Controlled Infusion (TCI) versus intermittent bolus of propofol for colonoscopy sedation. Methods: We conducted a randomized (1:1), single-blind, parallel-group superiority trial with fifty ASA I or II patients, both sexes, aged 18 to 65 years, Body Mass Index ≤ 30 kg.mr-2, undergoing colonoscopy, allocated to receive propofol by TCI (effect-site, 2 μg.mL-1 plus 0.5 μg.mL-1 until unconsciousness and as necessary for agitation) or intermittent bolus (1 mg.kg-1 plus 0.5 mg.kg-1 every 5 minutes or as above). The primary safety outcome was the need for airway maneuvers and the primary efficacy outcome was the need for interventions to adjust the level of sedation. Secondary outcomes included incidence of agitation, propofol dose, and time to recovery. Results: The median (IQR) number of airway maneuvers and interventions needed to adjust sedation was 0 (0-0) vs. 0 (0-0) (p = 0.239) and 1 (0-1) vs. 3 (1-4) (p < 0.001) in the TCI and control groups, respectively. Agitation was more common in the intermittent bolus group - 2 (0-2) vs. 1 (0-1), p < 0.001. The mean ± SD time to recovery was 4.9 ± 1.4 minutes in the TCI group vs. 2.3 ± 1.6 minutes in the control group (p < 0.001). The total propofol dose was higher in the TCI group (234 ± 46 μg.kg-1.min-1 vs. 195 ± 44 μg.kg-1.min-1 (p = 0.040)). Conclusions: During colonoscopy, TCI is as safe as intermittent bolus of propofol while reducing the incidence of agitation and the need for dose adjustments. However, intermittent bolus administration was associated with lower total propofol dose and earlier recovery.

Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study

Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

Increasing the aqueous solubility of the anesthetic propofol through wormlike micelle formation.

Propofol, a phenol derivative, is commonly employed as an intravenous anesthetic during clinical procedures, formulated as an oil/water emulsion due to its poor solubility in water. The stability limitations associated with emulsions have prompted research efforts towards developing aqueous formulations of propofol. In this work, we investigate the solubility enhancement of propofol in anionic and cationic surfactants. Our findings reveal that the solubility of propofol can increase significantly, up to 100-fold, depending on the nature of the micellar aggregate, as observed for alkylammonium halogenates CnTAB (for n = 12, 14 and 16), contrasting with the lower solubility with SDS. Interestingly, C14TAB and C16TAB demonstrate significantly higher solubility than C12TAB. This was attributed to the formation of wormlike micelles, in which the propofol molecules are positioned between the cationic heads of the surfactant molecules, changing the micellar curvature and the morphology of the aggregate. Therefore, the aromatic molecules in the micellar environment can be partitioned into the micellar cores and their palisades. Regarding C12TAB, the alkyl chain is too short to form wormlike micelles, thus, concentrating propofol molecules mainly into the micellar core, and consequently, leading to their aggregation. Solubility diagrams of propofol were constructed in conjunction with different surfactants. The systems exhibiting viscoelastic behavior, indicative of wormlike micelle formation, were further investigated using rheology. Additionally, the fluorescent properties of propofol enabled the examination of the anesthetic molecule within diverse micellar environments.

Presentación de un caso y revisión de literatura: anestesia total intravenosa en cirugía de estesioneuroblastoma / Presentation of a case and literature review: total intravenous anesthesia in estesioneuroblastoma surgery

Resumen: El estesioneuroblastoma es una neoplasia de las células del neuroepitelio olfatorio. Tiene una baja incidencia de 0.4 por cada millón de habitantes. Se caracteriza por síntomas como sinusitis, epistaxis, cefalea, discapacidad visual, obstrucción nasal, hiposmia y rinorrea. En este reporte se presenta el caso de un paciente masculino de 29 años con estesioneuroblastoma estadio Kadish C, quien fue programado para resección quirúrgica bajo anestesia total intravenosa con resultados satisfactorios durante el procedimiento quirúrgico.

Abstract: Esthesioneuroblastoma is a neoplasm of the olfactory neuroepithelium cells, it has a low incidence of 0.4 per million inhabitants. It is characterized by symptoms such as sinusitis, epistaxis, headache, visual impairment, nasal obstruction, hyposmia, and rhinorrhea. We present the case of a 29-year-old male patient with Kadish C stage esthesioneuroblastoma, who was scheduled for surgical resection under total intravenous anesthesia with satisfactory results during the surgical procedure.

Comparison between sevoflurane and propofol on immunomodulation in an in vitro model of sepsis.

Introduction: Patients with sepsis often require sedation and/or anesthesia. Although the immunomodulatory effects of anesthetics have been increasingly recognized, the molecular mechanisms require better elucidation. We compared the effects of sevoflurane with propofol on the expression of pro- and anti-inflammatory biomarkers released by monocytes/macrophages and blood/bronchoalveolar lavage fluid (BALF) neutrophils, the phagocytic capacity of monocytes/ macrophages, and neutrophil migration, as well as mediators associated with alveolar epithelial and endothelial cells obtained from rats with sepsis. Methods: Polymicrobial sepsis was induced by cecal ligation and puncture in nine male Wistar rats. After 48 h, animals were euthanized and their monocytes/alveolar macrophages, blood and BALF neutrophils, as well as alveolar epithelial and endothelial cells were extracted, and then exposed to (1) sevoflurane (1 minimal alveolar concentration), (2) propofol (50 µM), or (3) saline, control (CTRL) for 1 h. Results: Sevoflurane reduced interleukin (IL)-6 mRNA expression in monocytes and alveolar macrophages (p = 0.007, p = 0.029), whereas propofol decreased IL-6 mRNA only in alveolar macrophages (p = 0.027) compared with CTRL. Sevoflurane increased IL-10 expression (p = 0.0002) in monocytes compared with propofol and increased IL-10 mRNA and transforming growth factor (TGF)-ß mRNA (p = 0.037, p = 0.045) compared with CTRL. Both sevoflurane and propofol did not affect mRNA expression of IL-10 and TGF-ß in alveolar macrophages. The phagocytic capacity of monocytes (p = 0.0006) and alveolar macrophages (p = 0.0004) was higher with sevoflurane compared with propofol. Sevoflurane, compared with CTRL, reduced IL-1ß mRNA (p = 0.003, p = 0.009) and C-X-C chemokine receptor 2 mRNA (CXCR2, p = 0.032 and p = 0.042) in blood and BALF neutrophils, and increased CXCR4 mRNA only in BALF neutrophils (p = 0.004). Sevoflurane increased blood neutrophil migration (p = 0.015) compared with propofol. Both sevoflurane and propofol increased zonula occludens-1 mRNA (p = 0.046, p = 0.003) in alveolar epithelial cells and reduced Toll-like receptor 4 mRNA (p = 0.043, p = 0.006) in alveolar endothelial cells compared with CTRL. Only propofol reduced surfactant protein B mRNA (p = 0.028) in alveolar epithelial cells. Discussion: Sevoflurane, compared with propofol, increased anti-inflammatory biomarkers in monocytes, but not in alveolar macrophages, enhanced monocyte/alveolar macrophage phagocytic capacity and increased neutrophil migration in in vitro experimental sepsis. Both propofol and sevoflurane protected lung epithelial and endothelial cells.

Propofol inhibits myocardial injury induced by microvesicles derived from hypoxia-reoxygenated endothelial cells via lncCCT4-2/CCT4 signaling.

BACKGROUND: Ischemia-reperfusion (IR) induces increased release of extracellular vesicles in the heart and exacerbates myocardial IR injury. We have previously shown that propofol attenuates hypoxia/reoxygenation (HR)-induced injury in human umbilical vein endothelial cells (HUVECs) and that microvesicles derived from propofol-treated HUVECs inhibit oxidative stress in endothelial cells. However, the role of microvesicles derived from propofol post-treated HUVECs ((HR + P)-EMVs) in IR-injured cardiomyocytes is unclear. In this study, we aimed to investigate the role of (HR + P)-EMVs in cardiac IR injury compared to microvesicles derived from hypoxic/reoxygenated HUVECs (HR-EMVs) and to elucidate the underlying mechanisms. METHODS: Hypoxia/reoxygenation (HR) models of HUVECs and AC16 cells and a mouse cardiac IR model were established. Microvesicles from HR-injured HUVECs, DMSO post-treated HUVECs and propofol post-treated HUVECs were extracted by ultra-high speed centrifugation, respectively. The above EMVs were co-cultured with HR-injured AC16 cells or injected intracardially into IR mice. Flow cytometry and immunofluorescence were used to determine the levels of oxidative stress and apoptosis in cardiomyocytes. Apoptosis related proteins were detected by Western blot. Echocardiography for cardiac function and Evans blue-TTC staining for myocardial infarct size. Expression of lncCCT4-2 in EMVs and AC16 cells was analysed by whole transcriptome sequencing of EMVs and RT-qPCR. The molecular mechanism of inhibition of myocardial injury by (HR + P)-EMVs was elucidated by lentiviral knockdown of lncCCT4-2, plasmid overexpression or knockdown of CCT4, and actinomycin D assay. RESULTS: In vitro and in vivo experiments confirmed that HR-EMVs exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes, leading to increased infarct size and worsened cardiac function. Notably, (HR + P)-EMVs induced significantly less oxidative stress and apoptosis in IR-injured cardiomyocytes compared to HR-EMVs. Mechanistically, RNA sequencing of EMVs and RT-qPCR showed that lncCCT4-2 was significantly upregulated in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs. Reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. Furthermore, the anti-apoptotic activity of lncCCT4-2 from (HR + P)-EMVs was achieved by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in cardiomyocytes. CONCLUSIONS: Our study showed that (HR + P)-EMVs uptake by IR-injured cardiomyocytes upregulated lncCCT4-2 in cardiomyocytes and promoted CCT4 expression, thereby inhibiting HR-EMVs induced oxidative stress and apoptosis.

Anesthetic effects of isoflurane and fentanyl infusion in capuchin monkeys (Sapajus sp) undergoing salpingectomy or deferentectomy, previously chemically restrained with ketamine-midazolam or ketamine-dexmedetomidine.

BACKGROUND: This study evaluated the anesthetic and cardiorespiratory effects of two anesthetic protocols for salpingectomy or deferentectomy in capuchin monkeys (Sapajus sp). MATERIALS AND METHODS: Five capuchin monkeys (5 per group) received ketamine (20 mg/kg) combined with midazolam (0.5 mg/kg; group KM) or dexmedetomidine (5 µg/kg; group KD) intramuscularly. Anesthesia is induced with propofol intravenously and maintained with isoflurane. Before the start of surgery, fentanyl 3 µg/kg was administered IV, and continuous infusion (10 µg/kg/min) IV was started. Times and quality of anesthetic recovery were evaluated postoperatively. RESULTS: KM and KD resulted in adequate chemical restraint. KD resulted in bradycardia. Intraoperative heart rate and systolic blood pressure were higher in KM than in KD. Both groups had smooth recovery. Time to standing was longer in KM than in KD. CONCLUSION: Both protocols allowed the performance of surgeries, with few cardiorespiratory effects. Anesthetic recovery was smooth and shorter in KD group.

Síndrome de infusión de propofol y COVID-19. Reporte de caso / Propofol and COVID-19 infusion syndrome. Case report

Resumen: La forma grave de neumonía por SARS-CoV-2 (COVID-19) cursa en la mayoría de los casos con un síndrome de dificultad respiratoria aguda (SDRA). Es necesario emplear sedación durante su ventilación mecánica, el propofol es el que más de utiliza por su farmacocinética y farmacodinamia. El propofol es un anestésico que se usa ampliamente en las unidades de cuidados intensivos. Su empleo puede provocar un efecto adverso poco frecuente, pero en extremo grave, conocido como síndrome por infusión de propofol (SIP), el cual se encuentra estrechamente asociado a la velocidad de infusión aunado a factores de riesgos propios del paciente. Se caracteriza principalmente por inestabilidad hemodinámica, acidosis láctica y por progresión a disfunción multiorgánica. Se presenta un caso de SIP en paciente con síndrome de dificultad respiratoria aguda (SDRA) secundario a SARS-CoV-2 que desarrolla esta complicación asociada a la sedación. Se discute fisiopatológica clínica y consideraciones que deberán tomarse en cuenta al momento de su utilización en infusión continua.

Abstract: The severe form of SARS-CoV-2 pneumonia (COVID-19) occurs in most cases with acute respiratory distress syndrome (ARDS), requiring the use of sedation during mechanical ventilation, with propofol being the most widely used for its pharmacokinetics and pharmacodynamics. Propofol is a widely used anesthetic in intensive care units (ICU). Its use can cause an infrequent but extremely serious adverse effect, known as propofol infusion syndrome (PRIS), which is closely associated with the speed of infusion coupled with risk factors specific to the patient, the clinical features of PRIS are hemodynamic instability, lactic acidosis and with progression to multi-organ dysfunction. We present a case of SIP in a patient with acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 who develops this complication associated with sedation, discusses clinical pathophysiology and considerations that should be taken into account when using it in continuous infusion.

Safety and efficacy of target-controlled infusion versus intermittent bolus administration of propofol for sedation in colonoscopy: a randomized controlled trial.

BACKGROUND: Our objective was to compare the safety and efficacy of Target-Controlled Infusion (TCI) versus intermittent bolus of propofol for colonoscopy sedation. METHODS: We conducted a randomized (1:1), single-blind, parallel-group superiority trial with fifty ASA I or II patients, both sexes, aged 18 to 65 years, Body Mass Index ≤ 30 kg.m-2, undergoing colonoscopy, allocated to receive propofol by TCI (effect-site, 2 µg.mL-1 plus 0.5 µg.mL-1 until unconsciousness and as necessary for agitation) or intermittent bolus (1 mg.kg-1 plus 0.5 mg.kg-1 every 5 minutes or as above). The primary safety outcome was the need for airway maneuvers and the primary efficacy outcome was the need for interventions to adjust the level of sedation. Secondary outcomes included incidence of agitation, propofol dose, and time to recovery. RESULTS: The median (IQR) number of airway maneuvers and interventions needed to adjust sedation was 0 (0‒0) vs. 0 (0‒0) (p = 0.239) and 1 (0‒1) vs. 3 (1‒4) (p < 0.001) in the TCI and control groups, respectively. Agitation was more common in the intermittent bolus group ‒ 2 (0‒2) vs. 1 (0‒1), p < 0.001. The mean ± SD time to recovery was 4.9 ± 1.4 minutes in the TCI group vs. 2.3 ± 1.6 minutes in the control group (p < 0.001). The total propofol dose was higher in the TCI group (234 ± 46 µg.kg-1.min-1 vs. 195 ± 44 µg.kg-1.min-1 (p = 0.040)). CONCLUSIONS: During colonoscopy, TCI is as safe as intermittent bolus of propofol while reducing the incidence of agitation and the need for dose adjustments. However, intermittent bolus administration was associated with lower total propofol dose and earlier recovery.

Role of melatonin in attenuation of hemodynamic response to intubation and anesthetic requirements: a randomized, controlled, double-blind study.

BACKGROUND: Melatonin has been studied to have anxiolytic, sedative, and analgesic effects. However, there is limited data on the effect of melatonin in the attenuation of hemodynamic response to intubation. We aimed to study whether preanesthetic oral melatonin attenuates hemodynamic responses to intubation and anesthetic requirements. METHODS: Sixty-four patients scheduled for laparoscopic cholecystectomy were randomized into melatonin or placebo group (n...=...32 each). Melatonin group received two tablets (3...mg each) of melatonin, and the placebo group received two tablets of vitamin D3 120...min before induction. Hemodynamic parameters were recorded during induction and postintubation for 15...minutes. Total induction dose of propofol, total intraoperative fentanyl consumption, and adverse effects of melatonin were also noted. RESULTS: Postintubation rise in heart rate (HR) was less in the melatonin group compared to the placebo group (10.59% vs. 37.08% at 1...min, respectively) (p...<...0.0001). Maximum percentage increase in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) was lesser in melatonin group than placebo group (SBP 9.25% vs. 37.73%, DBP 10.58% vs. 35.51%, MBP 9.99% vs. 36.45% at 1 min postintubation. respectively) (p...<...0.0001). Induction dose of propofol (1.42 mg.kg-1 vs. 2.01...mg.kg-1) and the number of patients requiring additional fentanyl intraoperatively (3 vs. 11) were also significantly reduced in the melatonin group. CONCLUSION: Premedication with 6...mg of oral melatonin resulted in significant attenuation of postintubation rise in HR, SBP, DBP, and MBP. It also reduced the induction dose of propofol, total intraoperative fentanyl consumption without any adverse effects.