Sedation with propofol and isoflurane differs in terms of microcirculatory parameters: A randomized animal study using dorsal skinfold chamber mouse model.

OBJECTIVE: This study aimed to explore the effects of sedative doses of propofol and isoflurane on microcirculation in septic mice compared to controls. Isoflurane, known for its potential as a sedation drug in bedside applications, lacks clarity regarding its impact on the microcirculation system. The hypothesis was that propofol would exert a more pronounced influence on the microvascular flow index, particularly amplified in septic conditions. MATERIAL AND METHODS: Randomized study was conducted from December 2020 to October 2021 involved 60 BALB/c mice, with 52 mice analyzed. Dorsal skinfold chambers were implanted, followed by intraperitoneal injections of either sterile 0.9 % saline or lipopolysaccharide for the control and sepsis groups, respectively. Both groups received propofol or isoflurane treatment for 120 min. Microcirculatory parameters were obtained via incident dark-field microscopy videos, along with the mean blood pressure and heart rate at three time points: before sedation (T0), 30 min after sedation (T30), and 120 min after sedation (T120). Endothelial glycocalyx thickness and syndecan-1 concentration were also analyzed. RESULTS: In healthy controls, both anesthetics reduced blood pressure. However, propofol maintained microvascular flow, differing significantly from isoflurane at T120 (propofol, 2.8 ± 0.3 vs. isoflurane, 1.6 ± 0.9; P < 0.001). In the sepsis group, a similar pattern occurred at T120 without statistical significance (propofol, 1.8 ± 1.1 vs. isoflurane, 1.2 ± 0.7; P = 0.023). Syndecan-1 levels did not differ between agents, but glycocalyx thickness index was significantly lower in the isoflurane-sepsis group than propofol (P = 0.001). CONCLUSIONS: Propofol potentially offers protective action against microvascular flow deterioration compared to isoflurane, observed in control mice. Furthermore, a lower degree of sepsis-induced glycocalyx degradation was evident with propofol compared to isoflurane.

Impaired Capillary Recruitment Capacity in Obesity: A Subgroup Analysis of Prospective Observational Study on Anesthesia Effects.

BACKGROUND This subgroup analysis of prospective observational research, involving 71 participants, compared the effects of anesthesia on microvascular reactivity in obese vs lean individuals using near-infrared spectroscopy and vascular occlusion tests. The correlation between the body mass index (BMI) and microvascular reactivity under general anesthesia was also investigated. MATERIAL AND METHODS This study enrolled adult patients classified as American Society of Anesthesiologists physical status I or II, undergoing elective surgery under general anesthesia. The microcirculatory variables measured before (Tpre) and 30 min following the induction of anesthesia (Tpost) were as follows: baseline tissue oxygen saturation (StO2), occlusion slope (∇occl), and recovery slope (∇recov). The patients were grouped according to their BMI (lean [BMI <25 kg/m²] vs obese [BMI ≥25 kg/m²]). Data are presented as medians and interquartile ranges. RESULTS There were 43 patients in the lean group and 28 in the obese group. At Tpre, baseline StO2, ∇occl, and ∇recov were not different between the 2 groups (P=0.860, 0.659, and 0.518, respectively). At Tpost, the baseline StO2 and ∇occl were not different between the 2 groups (P=0.343 and 0.791); however, the ∇recov was lower in the obese group than in the lean group (3.245 [2.737, 3.977] vs 4.131 [3.491, 4.843], P=0.003). At Tpost, BMI showed a moderate correlation with ∇recov (correlation coefficient: -0.319, P=0.007). CONCLUSIONS In obese patients, capillary recruitment capacity during general anesthesia is compromised compared to lean patients.

Honokiol inhibits epithelial-mesenchymal transition and hepatic fibrosis via activation of Ecadherin/GSK3ß/JNK and inhibition of AKT/ERK/p38/ß-catenin/TMPRSS4 signaling axis.

Though Honokiol was known to have anti-inflammatory, antioxidant, anticancer, antithrombotic, anti-viral, metabolic, antithrombotic, and neurotrophic activities, the underlying mechanisms of Honokiol on epithelial-mesenchymal transition (EMT) mediated liver fibrosis still remain elusive so far. Anti-EMT and antifibrotic effects of Honokiol were explored in murine AML-12 hepatocyte cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, wound healing assay, Western blotting and also in CCl4-induced liver injury mouse model by immunohistochemistry. Honokiol significantly suppressed transforming growth factor ß1 (TGF-ß1)-induced EMT and migration of AML-12 cells along with decreased EMT phenotypes such as loss of cell adhesion and formation of fibroblast like mesenchymal cells in TGF-ß1-treated AML-12 cells. Consistently, Honokiol suppressed the expression of Snail and transmembrane protease serine 4 (TMPRSS4), but not p-Smad3, and activated E-cadherin in TGF-ß1-treated AML-12 cells. Additionally, Honokiol reduced the expression of ß-catenin, p-AKT, p-ERK, p-p38 and increased phosphorylation of glycogen synthase kinase 3 beta (GSK3ß) and JNK in TGF-ß1-treated AML-12 cells via TGF-ß1/nonSmad pathway. Conversely, GSK3ß inhibitor SB216763 reversed the ability of Honokiol to reduce Snail, ß-catenin and migration and activate E-cadherin in TGF-ß1-treated AML-12 cells. Also, Honokiol suppressed hepatic steatosis and necrosis by reducing the expression of TGF-ß1 and α-SMA in liver tissues of CCl4 treated mice. These findings provide scientific evidence that Honokiol suppresses EMT and hepatic fibrosis via activation of E-cadherin/GSK3ß/JNK and inhibition of AKT/ERK/p38/ß-catenin/TMPRSS4 signaling axis.

Ultrasonographic Carotid Artery Flow Measurements as Predictors of Spinal Anesthesia-Induced Hypotension in Elderly Patients: A Prospective Observational Study.

BACKGROUND In elderly patients, spinal anesthesia-induced hypotension (SAH) can be frequently caused by reduced preload and stiff ventricles. The primary purpose of this study was to investigate the ability of ultrasonographic carotid artery flow measurements during the passive leg raise (PLR) test to predict SAH in elderly patients. The correlation between preoperative transthoracic echocardiography (TTE) measurements and SAH was also investigated. MATERIAL AND METHODS The patients aged over 65 years scheduled for elective surgery under spinal anesthesia were recruited. Preoperative TTE was performed in all patients. Corrected carotid flow time and carotid blood flow were measured in the supine, semirecumbent, and PLR positions. Ultrasonographic carotid artery flow and preoperative TTE measurements were compared between patients who developed SAH and those who did not. Receiver operating characteristic (ROC) curve analysis and logistic regression analysis were used to test the association with SAH. RESULTS SAH occurred in 17 of 50 patients. Carotid blood flow in the semirecumbent position and preoperative mitral inflow E velocity could predict SAH, showing an area under the ROC curve of 0.754 (95% CI, 0.612-0.865) and 0.775 (95% CI, 0.634-0.881), respectively. However, according to the multivariate analysis, the independent risk factor for SAH was mitral inflow E velocity (OR 0.918, 95% CI 0.858-0.982, P=0.013). CONCLUSIONS In elderly patients, ultrasonographic carotid artery flow measurements failed to predict the occurrence of SAH. Only preoperative mitral inflow E velocity of TTE was selected as an independent risk factor for SAH.

Changes in the microvascular reactivity during spinal anesthesia.

PURPOSE: Anesthesia alters microcirculation and tissue oxygen saturation (StO2). We sought to examine changes in StO2 using near-infrared spectroscopy and a vascular occlusion test (VOT) during spinal anesthesia. METHODS: This prospective observational study was included 51 patients without comorbidities who underwent elective surgery under spinal anesthesia. We measured the StO2 in the lower extremity during VOT before and after intrathecal injection. RESULTS: The baseline, minimum, and maximum StO2 values during VOT significantly increased after intrathecal injection (baseline StO2 from 68.6 ± 7.3% to 77.1 ± 10.1%, minimum StO2 from 39.7 ± 14.9% to 48.8 ± 17.6%, and maximum StO2 from 74.2 ± 7.5% to 80.2 ± 10.0%, all P < 0.0001). The occlusion slope and ischemic stimulus did not significantly change after intrathecal injection. The reperfusion slope was 1.38 ± 0.69%/sec before intrathecal injection and significantly decreased to 1.15 ± 0.61%/sec after intrathecal injection (P = 0.0001). CONCLUSIONS: Our results showed that despite an increased perfusion, reperfusion rate was significantly decreased by spinal anesthesia. Further studies are required to confirm how these contradictory results (improving oxygenation while reducing microvascular reactivity) actually affect the clinical impact of spinal anesthesia on microvascular function.

Microvascular Reactivity Measured by Dynamic Near-infrared Spectroscopy Following Induction of General Anesthesia in Healthy Patients: Observation of Age-related Change.

Background: The purpose of this study was to investigate the effect of general anesthesia on microvascular reactivity and tissue oxygen saturation (StO2) using near-infrared spectroscopy in conjunction with vascular occlusion tests (VOT). Age-related changes of microvascular reactivity, that is, the capacity of capillary recruitment, were examined. Methods: This prospective observational study was performed on 60 patients without comorbidities who underwent elective surgery under general anesthesia. Baseline StO2 on thenar eminence, hemodynamics, and laboratory profile were monitored before (T0) and 30 min after general anesthesia (T1). During VOT, occlusion slope representing oxygen consumption of muscle and recovery slope representing microvascular reactivity were also collected at T0 and T1. Results: Baseline StO2 and minimum / maximum StO2 during VOT increased under general anesthesia. Occlusion slope decreased while the recovery slope increased under general anesthesia. To observe aging effect, Receiver operating characteristic analysis was performed and age less than 65 years old showed a fair performance in predicting the increase of microvascular reactivity after the induction of anesthesia (AUC 0.733, 95% CI 0.594-0.845, P= 0.003). For age-related analyses, 27 patients of younger group (< 65 years) and 26 patients of older group (≥ 65 years) were divided. Recovery slope significantly increased under general anesthesia in younger group (2.44 [1.91-2.81] % ∙ sec-1 at T0 and 3.59 [2.58-3.51] % ∙ sec-1 at T1, P <0.001), but not in older group (2.61 [2.21-3.20] % ∙ sec-1 at T0, 2.63 [1.90-3.60] % ∙ sec-1 at T1, P = 0.949). Conclusions: General anesthesia could improve StO2 through increase of microvascular reactivity and decrease of tissue metabolism. However, microvascular reactivity to capillary recruitment under general anesthesia significantly improves in younger patients, not in older patients.

Apoptotic effect of compound K in hepatocellular carcinoma cells via inhibition of glycolysis and Akt/mTOR/c-Myc signaling.

Since the AKT/mammalian target of rapamycin (mTOR)/c-Myc signaling plays a pivotal role in the modulation of aerobic glycolysis and tumor growth, in the present study, the role of AKT/mTOR/c-Myc signaling in the apoptotic effect of Compound K (CK), an active ginseng saponin metabolite, was explored in HepG2 and Huh7 human hepatocellular carcinoma cells (HCCs). Here, CK exerted significant cytotoxicity, increased sub-G1, and attenuated the expression of pro-Poly (ADP-ribose) polymerase (pro-PARP) and Pro-cysteine aspartyl-specific protease (pro-caspase3) in HepG2 and Huh7 cells. Consistently, CK suppressed AKT/mTOR/c-Myc and their downstreams such as Hexokinase 2 (HK2) and pyruvate kinase isozymes M2 (PKM2) in HepG2 and Huh7 cells. Additionally, CK reduced c-Myc stability in the presence or absence of cycloheximide in HepG2 cells. Furthermore, AKT inhibitor LY294002 blocked the expression of p-AKT, c-Myc, HK2, PKM2, and pro-cas3 in HepG2 cells. Pyruvate blocked the ability of CK to inhibit p-AKT, p-mTOR, HK2, and pro-Cas3 in treated HepG2 cells. Overall, these findings provide evidence that CK induces apoptosis via inhibition of glycolysis and AKT/mTOR/c-Myc signaling in HCC cells as a potent anticancer candidate for liver cancer clinical translation.

Antitumor Effect of Morusin via G1 Arrest and Antiglycolysis by AMPK Activation in Hepatocellular Cancer.

Though Morusin isolated from the root of Morus alba was known to have antioxidant, anti-inflammatory, antiangiogenic, antimigratory, and apoptotic effects, the underlying antitumor effect of Morusin is not fully understood on the glycolysis of liver cancers. Hence, in the current study, the antitumor mechanism of Morusin was explored in Hep3B and Huh7 hepatocellular carcninomas (HCC) in association with glycolysis and G1 arrest. Herein, Morusin significantly reduced the viability and the number of colonies in Hep3B and Huh7 cells. Moreover, Morusin significantly increased G1 arrest, attenuated the expression of cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and cyclin-dependent kinase 6 (CDK6) and upregulated p21 and p27 in Hep3B and Huh7 cells. Interestingly, Morusin significantly activated phosphorylation of the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) but attenuated the expression of the p-mammalian target of protein kinase B (AKT), rapamycin (mTOR), c-Myc, hexokinase 2(HK2), pyruvate kinases type M2 (PKM2), and lactate dehydrogenase (LDH) in Hep3B and Huh7 cells. Consistently, Morusin suppressed lactate, glucose, and adenosine triphosphate (ATP) in Hep3B and Huh7 cells. Conversely, the AMPK inhibitor compound C reduced the ability of Morusin to activate AMPK and attenuate the expression of p-mTOR, HK2, PKM2, and LDH-A and suppressed G1 arrest induced by Morusin in Hep3B cells. Overall, these findings suggest that Morusin exerts an antitumor effect in HCCs via AMPK mediated G1 arrest and antiglycolysis as a potent dietary anticancer candidate.

Anti-inflammatory effects of dexmedetomidine on human amnion-derived WISH cells.

Background: To maintain the normal pregnancy, suppression of inflammatory signaling pathway is a crucial physiologic response. Dexmedetomidine has been used for labor analgesia or supplement of inadequate regional analgesia during delivery. And it has been reported that dexmedetomidine has an anti-inflammatory effect. In this study, we examined the influence of dexmedetomidine on the expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and inflammatory cytokines in lipopolysaccharide (LPS)-stimulated human amnion-derived WISH cells. In addition, we evaluated the association of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathway in anti-inflammatory effect of dexmedetomidine. Methods: Human amnion-derived WISH cells were pretreated with various concentrations of dexmedetomidine (0.001-1 µg/ml) for 1 h and after then treated with LPS (1 µg/ml) for 24 h. MTT assay was conducted to evaluate the cytotoxicity. Nitric oxide (NO) production was analyzed using Griess-reaction microassay. RT-PCR was performed for analysis of mRNA expressions of COX-2, PGE2, tumor necrosis factor (TNF)-α and interlukin (IL)-1ß. Protein expressions of COX-2, PGE2, p38 and NF-κB were analyzed by western blotting. Results: LPS and dexmedetomidine had no cytotoxic effect on WISH cells. There was no difference in NO production after dexmedetomidine pretreatment. The mRNA and protein expressions of COX-2 and PGE2 were decreased by dexmedetomidine pretreatment in LPS-treated WISH cells. Dexmedetomidine also attenuated the LPS-induced mRNA expression of TNF-α and IL-1ß. The activation of p38 and NF-κB was suppressed by dexmedetomidine pretreatment in LPS-treated WISH cells. Conclusion: We demonstrated that dexmedetomidine pretreatment suppressed the expressions of inflammatory mediators increased by LPS. In addition, this study suggests that anti-inflammatory effect of dexmedetomidine on WISH cells was mediated by the inhibitions of p38 and NF-κB activation.

The effect of combined Epidural-general Anesthesia on Hemodynamic Instability during Pheochromocytoma and Paraganglioma Surgery: A multicenter retrospective cohort study.

Objectives: The purpose of this study was to compare the effects of combined epidural-general anesthesia with those of general anesthesia alone on hemodynamic instability (intraoperative hypotension and hypertensive crisis) during pheochromocytoma and sympathetic paraganglioma surgery. Methods: A total of 119 patients' medical records were reviewed who were diagnosed as having pheochromocytoma and sympathetic paraganglioma on the basis of histological findings. Intraoperative hypotension was defined as a mean blood pressure < 60 mmHg or a decrease > 30% in baseline systolic blood pressure after adrenal vein ligation. Hypertensive crisis was defined as a systolic blood pressure > 200 mmHg or an increase > 30% in baseline systolic blood pressure during the operation. The predictor variables for intraoperative hypotension and hypertensive crisis were analyzed with logistic regression models. Data were presented as adjusted odds ratio with 95% confidence interval. Results: The independent predictors of intraoperative hypotension were an increased attenuation number on unenhanced computed tomography (1.112 [1.009-1.226], p = 0.033), a high baseline mean blood pressure (1.063 [1.012-1.117], p = 0.015), and the combined epidural-general anesthesia (5.439 [1.410-20.977], p = 0.014). In contrast, an increased attenuation number on unenhanced computed tomography was the only independent predictor of hypertensive crisis (1.087 [1.021-1.158], p = 0.009). Conclusions: The combined epidural-general anesthesia was not effective in attenuating hypertensive responses, but could have exacerbated intraoperative hypotension. These findings should be taken into account before selecting the anesthetic technique in pheochromocytoma and sympathetic paraganglioma surgery.

Effect of sensor location on regional cerebral oxygen saturation measured by INVOS 5100 in on-pump cardiac surgery.

PURPOSE: Near-infrared spectroscopy sensors often cannot be attached at the commercially recommended locations because combined use of neurological monitoring systems is common during on-pump cardiac surgery. The primary purpose of this study was to compare the incidence of regional cerebral oxygen desaturation and regional cerebral oxygen saturation values detected using near-infrared spectroscopy between the upper and lower forehead during on-pump cardiac surgery. METHODS: A prospective observational study was conducted with 25 adult patients scheduled for elective on-pump cardiac surgery. Regional cerebral oxygen saturations at the left upper and lower forehead and other clinical measurements were monitored intraoperatively. McNemar's test was used to analyze differences in the incidence of cerebral regional oxygen desaturation between the left upper and lower forehead. Two-way repeated measures ANOVA with post hoc Bonferroni correction was used to compare the regional cerebral oxygen saturation at each time point. RESULTS: There was a significantly higher incidence of regional cerebral oxygen desaturation at the upper than lower forehead only at 1 h after initiation of aortic cross-clamping. There were significant differences between the left upper and lower regional cerebral oxygen saturation values throughout the observation period. CONCLUSION: Regional cerebral oxygen saturation was significantly lower at the upper than lower forehead during on-pump cardiac surgery. However, disagreements in detection of cerebral regional oxygen desaturation were only significant at 1 h after initiation of aortic cross-clamping. TRIAL REGISTRATION: WHO-ICTRP, Clinical Research Information Service (CRiS). ID: KCT0000971. URL: https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=3678&type=my .

Comparisons of recursive partitioning analysis and conventional methods for selection of uncuffed endotracheal tubes for pediatric patients.

BACKGROUND: Numerous studies have investigated the best method of selecting the appropriate size of endotracheal tube (ETT) for children. However, none of the methods or formulae for selection of ETT size have shown better prediction over another, and they have required complex formulae calculation or even use of cumbersome equipment. Recursive partitioning analysis creates a decision tree that is more likely to enable clearer and easier visualization of decision charts compared to other data mining methods. OBJECTIVES: The aim of the current study was to develop a clinically practical and intuitive chart for prediction of ETT size. METHODS: Pediatric patients aged 2-9 years undergoing general anesthesia were intubated with uncuffed ETT. The tube size was considered optimal when a tracheal leak was detected at an inflation pressure between 10 and 25 cmH2 O. The observed ETT size was compared with the predicted ETT size calculated using Cole's formula, multivariate regression analysis, ultrasonographic measurements, and recursive partitioning tree structure analysis. Preference among the prediction methods was also investigated by asking physicians about their preference of methods. RESULTS: Correct prediction rates were 33.3%, 50%, 61.9%, and 59.5%, and close prediction rates were 61.9%, 83.3%, 88.1%, and 93.7% for Cole's formulae, multivariate regression analysis, ultrasonographic measurements, and recursive partitioning tree model, respectively. Fourteen of 16 physicians prefer to use the easy-to-interpret tree model. CONCLUSIONS: Analysis of the tree model by recursive partitioning structure analysis accomplished a high correct and close prediction rate for selection of an appropriate ETT size. The intuitive and easy-to-interpret tree model would be a quick and helpful tool for selection of an ETT tube for pediatric patients.

Airway management in a patient with severe tracheal stenosis: bilateral superficial cervical plexus block with dexmedetomidine sedation.

A 54-year-old woman with a history of severe tracheal stenosis caused by papillary thyroid cancer with tracheal invasion was admitted for an elective surgery. A bilateral superficial cervical plexus block with 0.5 % ropivacaine 14 ml (7 ml per side) under dexmedetomidine sedation was performed, followed by tracheal dissection and endotracheal tube (ETT) insertion. The patient continued spontaneous respiration without any hypoxic event, and the bispectral index was maintained at a range of 50-80. After ETT insertion, a total thyroidectomy and tracheal resection with end-to-end anastomosis were performed under general anesthesia. The patient was transferred to the surgical intensive care unit after extubation, and she recovered without any complications.

Preoperative echocardiography as a predictor of spinal anesthesia-induced hypotension in older patients with mild left ventricular diastolic dysfunction: a retrospective observational study.

BACKGROUND: Spinal anesthesia-induced hypotension (SAH) frequently occurs in older patients, many of whom have mild left ventricular (LV) diastolic dysfunction, often asymptomatic at rest. This study investigated the association between preoperative echocardiographic measurements and SAH in older patients with mild LV diastolic dysfunction. METHODS: We conducted a retrospective observational study using data from electronic medical records. The patients ≥ 65 years old who underwent spinal anesthesia for urologic surgery between January 2016 and December 2017 and whose preoperative echocardiography within 6 months before surgery revealed grade I LV diastolic dysfunction were recruited. SAH was investigated using the anesthesia records. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: A total of 163 patients were analyzed. SAH and significant SAH developed in 55 (33.7%) patients. The mitral inflow E velocity was an independent risk factor for SAH (odds ratio [OR], 0.886; 95% confidence interval [CI], 0.845-0.929; P < 0.001). The area under the ROC curve for mitral inflow E velocity to predict SAH was 0.819 (95% CI, 0.752-0.875; P < 0.001). If mitral inflow E velocity was ≤ 60 cm/s, SAH was predicted with a sensitivity of 83.6% and specificity of 70.4%. CONCLUSIONS: The preoperative mitral inflow E velocity demonstrated the greatest predictability of SAH in older patients with mild LV diastolic dysfunction. This may assist in identifying patients at high risk of SAH and guiding preventive strategies in the future.

Reducing the carbon footprint of operating rooms through education on the effects of inhalation anesthetics on global warming: A retrospective study.

Environmental concerns, especially global warming, have prompted efforts to reduce greenhouse gas emissions. Healthcare systems, including anesthesia practices, contribute to these emissions. Inhalation anesthetics have a significant environmental impact, with desflurane being the most concerning because of its high global warming potential. This study aimed to educate anesthesiologists on the environmental impact of inhalation anesthetics and assess changes in awareness and practice patterns, specifically reducing desflurane use. This study included data from patients who underwent surgery under general anesthesia 1 month before and after education on the effects of inhalation anesthetics on global warming. The primary endpoint was a change in inhalational anesthetic use. Secondary endpoints included changes in carbon dioxide equivalent (CO2e) emissions, driving equivalent, and medical costs. After the education, desflurane use decreased by 50%, whereas sevoflurane use increased by 50%. This shift resulted in a reduction in the overall amount of inhalational anesthetics used. The total CO2e and driving-equivalent values decreased significantly. The cost per anesthesia case decreased, albeit to a lesser extent than expected. Education on the environmental impact of inhalation anesthetics has successfully altered anesthesiologists' practice patterns, leading to reduced desflurane usage. This change has resulted in decreased CO2e emissions and has had a positive effect on mitigating global warming. However, further research is required to assess the long-term impact of such education and the variability in practice patterns across different institutions.

The effects of anesthetics on chronic pain after breast cancer surgery.

BACKGROUND: The incidence and predictive factors for chronic pain after breast cancer surgery have been widely studied. Because it negatively affects patients' daily lives, methods to prevent and reduce chronic pain and its severity should be developed. Our previous study showed that propofol anesthesia has an antihyperalgesic effect under remifentanil-induced hyperalgesia and reduced acute pain compared with sevoflurane anesthesia. In this study, we investigated the hypothesis that propofol would prevent the development and severity of chronic pain after breast cancer surgery, as in acute pain. METHODS: A retrospective study was conducted with 175 women (n = 86 in the propofol group and n = 89 in the sevoflurane group) aged 20 to 65 years who underwent breast cancer surgery between March 2007 and December 2008. Patients were followed up by telephone in July 2011. Analysis included incidence, severity, and duration of chronic pain between propofol and sevoflurane groups. Severity was categorized into mild, moderate, and severe pain. Duration of chronic pain was also divided into 3 categories by 1-year time interval. Risk factors associated with the incidence and severity of chronic pain after breast cancer surgery were also identified. RESULTS: Chronic pain after breast cancer surgery was more likely to occur in the sevoflurane group compared with the propofol group (95% confidence interval [CI] 1.146-1.809, P = 0.007). Among patients with chronic pain, neither the severity (95% CI 0.516-7.419) nor duration (95% CI 0.106-1.007) differed between patients receiving sevoflurane and propofol. Younger age (95% CI 0.907-0.992, P = 0.021), axillary lymph node dissection (95% CI 1.204-1.898, P = 0.003), 24-hour postoperative morphine consumption (95% CI 1.004-1.116, P = 0.036), and sevoflurane (95% CI 1.146-1.809, P = 0.007) were predictive factors for the development of chronic pain. Higher 24-hour postoperative morphine consumption (95% CI 1.001-1.379, P = 0.049) increased the severity of chronic pain. CONCLUSIONS: This study showed that propofol anesthesia was associated with a lower incidence of chronic pain after breast cancer surgery than sevoflurane anesthesia. However, propofol did not have a significant effect on severity and duration of chronic pain. Further prospective studies are needed to confirm the validity of these provocative findings.

What we need to know and do on sugammadex usage in pregnant and lactating women and those on hormonal contraceptives.

Sugammadex is a chemically modified γ-cyclodextrin that is used as a selective reversal agent for steroidal neuromuscular blockade. The use of sugammadex has greatly increased globally; however, little is known about its potential adverse effects in pregnant and lactating women or those using hormonal contraceptives. There are three important theoretical assumptions. Firstly, pregnancy-related physiological changes involve most organs and affect the pharmacokinetic profiles of medications. Considering the physiological changes in pregnant women and the pharmacokinetic properties of sugammadex, alterations in the dosage and safety profiles of sugammadex may occur during pregnancy. Secondly, very large and polarized sugammadex molecules are expected to have limited placental transfer to the fetus and excretion into breast milk. Finally, sugammadex can bind to steroidal neuromuscular blocking agents as well as other substances with similar structures, such as progesterone. As a result of using sugammadex, progesterone levels can be reduced, causing adverse effects such as early pregnancy cessation and failure of hormonal contraceptives. This narrative review aims to demonstrate the correlations between sugammadex and pregnancy, lactation, and reproductive potential based on previously published preclinical and clinical studies. This will bridge the gap between theoretical assumptions and currently unknown clinical facts. Moreover, this review highlights what anesthesia providers should be aware of and what actions to take while administering sugammadex to such patients.

A prospective double-blinded randomized control trial comparing erector spinae plane block to thoracic epidural analgesia for postoperative pain in video-assisted thoracic surgery.

OBJECTIVES: To compare the analgesic efficacies of erector spinae plane (ESP) block and thoracic epidural analgesia (TEA) in video-assisted thoracic surgery (VATS). METHODS: Sixty patients undergoing VATS received patient-controlled TEA with a basal rate of 3 ml/hour (h), a bolus of 3 ml (Group E), or ESP block with programmed intermittent bolus infusions of 15 mL/3 h and a bolus of 5 ml (Group ES) for 2 postoperative days. The primary outcome was to compare pain scores at rest 24 h postoperatively between the 2 groups. Secondary outcomes included NRS score for 48 h, procedural time, dermatomal spread, use of rescue medication, adverse events, and patient satisfaction. RESULTS: Patients with continuous ESP block had a higher NRS score than those with TEA but no statistical difference at a specific time. The dermatomal spread was more extensive in the TEA group than in the ESP block group (p=0.016); cumulative morphine consumption was higher in the ESP block group (p=0.047). The incidence of overall adverse events in the TEA group was higher than in the ESP block group (p=0.045). CONCLUSION: Erector spinae plane block may be inferior to TEA for analgesia following VATS, but it could have tolerable analgesia and a better side effect profile than TEA. Therefore, it could be an alternative to TEA as a component of multimodal analgesia.

Microvascular reactivity as a predictor of major adverse events in patients with on-pump cardiac surgery.

BACKGROUND: Microcirculatory disturbances are typically most severe during cardiopulmonary bypass (CPB), which occurs during cardiac surgeries. If microvascular reactivity compensates for microcirculatory disturbances during CPB, tissue hypoxemia can be minimized. The primary aim of this study was to assess whether microvascular reactivity during CPB could predict major adverse events (MAE) after cardiac surgery. METHODS: This prospective observational study included 115 patients who underwent elective on-pump cardiac surgeries. A vascular occlusion test (VOT) with near-infrared spectroscopy was performed five times for each patient: before the induction of general anesthesia, 30 min after the induction of general anesthesia, 30 min after applying CPB, 10 min after protamine injection, and post-sternal closure. The postoperative MAE was recorded. The area under the receiver operating characteristic (AUROC) curve analysis was performed for the prediction of MAE using the recovery slope. RESULTS: Of the 109 patients, MAE occurred in 32 (29.4%). The AUROC curve for the recovery slope during CPB was 0.701 (P < 0.001; 95% CI [0.606, 0.785]). If the recovery slope during CPB was < 1.08%/s, MAE were predicted with a sensitivity of 62.5% and specificity of 72.7%. CONCLUSIONS: Our study demonstrated that the recovery slope of the VOT during CPB could predict MAE after cardiac surgery. These results support the idea that disturbances in microcirculation induced by CPB can predict the development of poor clinical outcomes, thereby demonstrating the potential role of microvascular reactivity as an early predictor of MAE after cardiac surgery.

Propofol attenuates odontogenic/osteogenic differentiation of human dental pulp stem cells in vitro.

Background/purpose: Various studies have used stem cells in the field of bone tissue engineering to repair bone defects. Dental pulp stem cells (DPSCs) have multipotent properties and can be acquired in a noninvasive manner; therefore, they are frequently used in experiments in regenerative medicine. The objective of this study was to investigate the odontogenic/osteogenic differentiation of human DPSCs (hDPSCs) using propofol, a widely used intravenous anesthetic agent. Materials and methods: Alkaline phosphatase (ALP) staining was used to investigate the effects of various concentrations of propofol (5, 20, 50 and 100 µM) on the osteogenic differentiation of hDPSCs. Real-time qPCR and Western blot analysis were used to detect the effect of propofol on the expression of odontogenic/osteogenic genes, such as DMP1, RUNX2, OCN, and BMP2. Odontogenic/osteogenic differentiation of hDPSCs was estimated at days 7 and 14. Results: ALP staining of hDPSCs was significantly decreased by propofol treatment. The mRNA expression of DMP1, RUNX2, OCN, and BMP2 decreased after propofol treatment for 14 days. The protein expression of DMP1 and BMP2 was decreased by propofol at days 7 and 14, and that of RUNX2 was decreased by propofol at day 14 only. Conclusion: Propofol attenuated odontogenic/osteogenic differentiation of hDPSCs in vitro. This result suggests that propofol, which is widely used for dental sedation, may inhibit the odontogenic/osteogenic differentiation of hDPSCs.