Estimation of the Number of General Anesthesia Cases Based on a Series of Nationwide Surveys on Twitter during COVID-19 Pandemic in Japan: A Statistical Analysis.

Background and objectives: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread to more than 200 countries. In light of this situation, the Japanese Government declared a state of emergency in seven regions of Japan on 7 April 2020 under the provisions of the law. The medical care delivery system has been under pressure. Although various surgical societies have published guidelines on which to base their surgical decisions, it is not clear how general anesthesia has been performed and will be performed in Japan. Materials and Methods: One of the services provided by the social network service Twitter is a voting function-Twitter Polls-through which anonymous surveys were conducted. We analyzed the results of a series of surveys 17 times over 22 weeks on Twitter on the status of operating restrictions using quadratic programming to solve the mathematical optimizing problem, and public data provided by the Japanese Government were used to estimate the current changes in the number of general anesthesia performed in Japan. Results: The minimum number of general anesthesia cases per week was estimated at 67.1% compared to 2015 on 27 April 2020. The timeseries trend was compatible with the results reported by the Japanese Society of Anesthesiologists (correlation coefficient r = 0.69, p < 0.001). Conclusions: The number of general anesthesia was reduced up to two-thirds during the pandemic of COVID-19 in Japan and was successfully quantitatively estimated using a quick questionnaire on Twitter.

Preoperative Hypercapnia as a Predictor of Hypotension During Anesthetic Induction in Lung Transplant Recipients.

OBJECTIVE: To determine the incidence and predisposing factors of hypotension during anesthetic induction in lung transplant recipients. DESIGN: Retrospective study. SETTING: University hospital. PARTICIPANTS: Patients who underwent lung transplantation between 2008 and 2013 (n = 68). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors analyzed the mean arterial pressure (MAP) from administration of anesthetic drugs to 10 minutes after endotracheal intubation (ie, the anesthetic induction) among participants who underwent lung transplantation. Patients were considered to have clinically significant hypotension (CSH) when the following criteria were fulfilled: An MAP decrease of>40% from baseline and MAP of<60 mmHg. Overall, 41.2% of patients experienced CSH during the induction of anesthesia. The preoperative partial pressure of carbon dioxide (PaCO2) was significantly higher in patients who experienced CSH during anesthetic induction than in those who did not (p = 0.005). Preoperative PaCO2 predicted the development of CSH during anesthetic induction (area under the curve = 0.702; p = 0.002), with an optimal cut-off point of 55 mmHg determined by maximizing the Youden index. The incidences of CSH during anesthetic induction for patients with (PaCO2 ≥ 55) and without (PaCO2<55) preoperative hypercapnia were 75.0% (95% confidence interval [CI] [53.8-89.2]) and 30.8% (95% CI 26.4-37.3), respectively. After adjustment for known predicting factors, the odds ratio for the relationship between preoperative hypercapnia and CSH during anesthetic induction was 12.54 (95% CI 3.10-66.66). CONCLUSIONS: Hypotension during anesthetic induction is common in lung transplant recipients, and is independently predicted by preoperative hypercapnia.

The clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation.

PURPOSE: We examined the clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation (post-HSCT), focusing on ventilatory management. We aimed to determine the incidence of oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction in post-HSCT lung transplant recipients, and to explore factors associated with their development. METHODS: Nineteen consecutive patients who underwent lung transplantation post-HSCT at Kyoto University Hospital (Japan) were retrospectively studied. Data regarding patient characteristics, preoperative examination, and clinical course during anesthetic induction were analyzed. RESULTS: The incidence of oxygen desaturation (SpO2 < 90 %) during anesthetic induction and severe respiratory acidosis (pH < 7.2) after anesthetic induction were 21.1 and 26.3 %, respectively. Reduced dynamic compliance (Cdyn) during mechanical ventilation was significantly associated with oxygen desaturation during anesthetic induction (p = 0.01), as well as severe respiratory acidosis after anesthetic induction (p = 0.01). The preoperative partial pressure of carbon dioxide in arterial blood (PaCO2; r = -0.743, p = 0.002) and body mass index (BMI; r = 0.61, p = 0.021) significantly correlated with Cdyn, and multivariate analysis revealed that both PaCO2 and BMI were independently associated with Cdyn. CONCLUSIONS: Oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction frequently occur in post-HSCT lung transplant recipients. Low Cdyn may, at least partially, explain oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction. Moreover, preoperative hypercapnia and low BMI were predictive of low Cdyn.

[Extracorporeal Membrane Oxygenation for Anesthesia Induction in a Patient with Severe Cardiorespiratory Impairment due to Mediastinal Angiosarcoma].

BACKGROUND: Mediastinal angiosarcoma is a rare intrathoracic tumor that can cause severe pleural and pericardial fibrosis. CASE REPORT: We report the anesthetic management for pericardiectomy and pleurolysis in a 33-year-old patient with a mediastinal angiosarcoma. He presented with severe restrictive ventilatory impairment and heart failure due to fibrosis of the pleura and pericardium. Spirometry indicated a forced vital capacity of 0.66 l, while arterial blood gas analysis under noninvasive positive pressure ventilation indicated hypercapnia (pH 7.44; Pa(CO2) 59.2 mmHg). His cardiac index was 1.36 l x min(-1) x m(-2). Anesthesia induction and positive pressure ventilation are associated with an extremely high cardiorespiratory risk; therefore, veno-arterial-extracorporeal membrane oxygenation (VA-ECMO) with femoral cannulation was started prior to anesthesia induction. After achieving a stable circulation and adequate gas exchange, anesthesia was induced, and mechanical ventilation with intratracheal intubation was initiated. With ECMO and inotropic support stable hemodynamics was maintained throughout anesthesia induction and the operation was performed uneventfully under cardiopulmonary bypass. The patient was extubated on the first postoperative day and discharged one month after the operation. CONCLUSION: ECMO is a useful option to secure adequate gas exchange and circulation during anesthesia induction in patients with severe cardiopulmonary problems due to mediastinal tumors.

[Evaluation of postoperative pain intensity after ear, nose, and throat surgery--the effect of intraoperative fentanyl use].

BACKGROUND: This study was designed to determine postoperative pain levels after ear, nose, and throat (ENT) surgery, and also to examine whether intraoperative fentanyl use during ENT surgery enhances the quality of postoperative pain control. METHODS: The distribution of pain scores and rescue analgesic requirements among 198 patients undergoing ENT surgery were examined. Multivariate logistic regression analysis was performed to identify independent factors associated with moderate to severe postoperative pain (maximal pain score ≥ 5 on the numerical rating scale) and postoperative nausea and vomiting (PONV). RESULTS: 27.8% of patients experienced moderate to severe postoperative pain after ENT surgery. The distribution of postoperative pain levels was similar among procedures performed on different anatomical regions. Intraoperative fentanyl use was not associated with moderate to severe postoperative pain (adjusted odds ratio (95% confidence interval) :1.03 (0.51-2.13))]. On the other hand, intraoperative fentanyl use was independently associated with PONV [3.10 (1.25-8.92); P = 0.0138]. CONCLUSIONS: Prevalence of moderate to severe postoperative pain after ENT surgery was approximately 28%. Intraoperative fentanyl use was not associated with a decreased incidence of moderate to severe postoperative pain, but was significantly associated with PONV.

Orthostatic intolerance during early mobilization following video-assisted thoracic surgery.

PURPOSE: Early postoperative mobilization is crucial for early ambulation to reduce postoperative pulmonary complications after lung resection. However, orthostatic intolerance (OI) may delay patient recovery, leading to complications. It is therefore important to understand the prevalence of and predisposing factors for OI following video-assisted thoracic surgery (VATS), which have not been established. This study evaluated the incidence of OI, impact of OI on delayed ambulation, and predisposing factors associated with OI in patients after VATS. METHODS: This retrospective cohort study consecutively analyzed data from 236 patients who underwent VATS. The primary outcome was defined as OI with symptoms associated with ambulatory challenge on postoperative day 1 (POD1), including dizziness, nausea and vomiting, feeling hot, blurred vision, or transient syncope. Multivariate logistic regression was performed to identify independent factors associated with OI. RESULTS: Of the 236 patients, 35.2 % (83) experienced OI; 45.8 % of these could not ambulate at POD1, compared with 15.7 % of patients without OI (P < 0.001). Factors independently associated with OI included advanced age [odds ratio 2.83 (1.46-5.58); P = 0.002], female gender [odds ratio 2.40 (1.31-4.46); P = 0.004], and postoperative opioid use [odds ratio 2.61 (1.23-5.77); P = 0.012]. Use of thoracic epidural anesthesia was not independently associated with OI [odds ratio 0.72 (0.38-1.37); P = 0.318]. CONCLUSION: Postoperative OI was common in patients after VATS and significantly associated with delayed ambulation. Advanced age, female gender, and postoperative opioid use were identified as independent predisposing factors for OI.

Persisting mild hypothermia suppresses hypoxia-inducible factor-1alpha protein synthesis and hypoxia-inducible factor-1-mediated gene expression.

The transcription factor hypoxia-inducible factor-1 (HIF-1) plays an essential role in regulating gene expression in response to hypoxia-ischemia. Ischemia causes the tissue not only to be hypoxic but also to be hypothermic because of the hypoperfusion under certain circumstances. On the other hand, the induced hypothermia is one of the most common therapeutic modalities to extend tolerance to hypoxia. Although hypoxia elicits a variety of cellular and systemic responses at different organizational levels in the body, little is known about how hypoxia-induced responses are affected by low temperature. We examined the influence of mild hypothermic conditions (28-32 degrees C) on HIF-1 in both in vitro and in vivo settings. In vitro experiments adopting cultured cells elucidated that hypoxia-induced HIF-1 activation was resistant to 4-h exposure to the low temperature. In contrast, exposure to the low temperature as long as 24 h suppressed HIF-1 activation and the subsequent upregulation of HIF-1 target genes such as VEGF or GLUT-1. HIF-1alpha protein stability in the cell was not affected by hypothermic treatment. Furthermore, intracellular ATP content was reduced under 1% O(2) conditions but was not largely affected by hypothermic treatment. The evidence indicates that reduction of oxygen consumption is not largely involved in suppression of HIF-1. In addition, we demonstrated that HIF-1 DNA-binding activity and HIF-1-dependent gene expressions induced under 10% O(2) atmosphere in mouse brain were not influenced by treatment under 3-h hypothermic temperature but were inhibited under 5-h treatment. On the other hand, we indicated that warming ischemic legs of mice for 24 h preserved HIF-1 activity. In this report we describe for the first time that persisting low temperature significantly reduced HIF-1alpha neosynthesis under hypoxic conditions, leading to a decrease in gene expression for adaptation to hypoxia in both in vitro and in vivo settings.

Unexpectedly difficult intubation caused by subglottic stenosis in Wegener's granulomatosis.

A 76-year-old woman was scheduled to undergo abdominal aortic repair for progressive abdominal aortic aneurysm. After inducing general anesthesia, the 7.5-mm internal diameter (ID) tracheal tube could not be advanced below the level of the vocal cords because of resistance, and intubation was re-attempted several times using smaller tubes. An otolaryngologist was consulted and subglottic stenosis of unknown origin was suggested. The aortic repair was cancelled and tracheostomy was performed instead. She was diagnosed with Wegener's granulomatosis 46 days after the operation because she developed symptoms of renal dysfunction, hemoptysis, gastrointestinal bleeding, and presence of anti-neutrophil cytoplasmic autoantibodies (c-ANCA). The patient was treated with steroids but died 89 days after the operation because of pulmonary bleeding and renal dysfunction. Tracheal stenosis is a rare presenting feature of Wegener's granulomatosis that usually occurs late in the disease; however, anesthesiologists around the world need to bear in mind that the disease can present airway symptoms and can be the cause of airway obstruction.

Anesthesia management for emergency laparotomy in a pediatric patient with suspected hereditary angioedema.

Hereditary angioedema (HAE) is caused by complement factor 1 inhibitor (C1-INH) deficiency, and its mode of inheritance is autosomal dominant. We present a case of an 8-year-old patient who required emergency laparotomy after a traffic accident. General anesthesia with tracheal intubation was necessary. The patient's mother and maternal grandmother had been diagnosed with HAE. HAE is associated with high mortality when airway edema is caused by tracheal intubation. It was impossible to rule out HAE preoperatively in the patient. Therefore, we presumed that he had HAE and treated him with pasteurized C1-INH concentrate. The patient underwent laparotomy uneventfully. Several days after the operation, the laboratory data revealed that the perioperative plasma complement 1 q subunit (C1q) protein level and C1-INH function were not lowered. The diagnosis of HAE was not confirmed, but it was not possible to rule out the diagnosis either. The prophylactic use of a C1-INH in this case may be justified, because the procedure was an emergency and because of the high mortality associated with tracheal intubation in patients with HAE.

The intravenous anesthetic propofol inhibits lipopolysaccharide-induced hypoxia-inducible factor 1 activation and suppresses the glucose metabolism in macrophages.

PURPOSE: Hypoxia-inducible factor 1 (HIF-1) is a master transcription factor of hypoxia-induced gene expression. Anesthetics and perioperative drugs have been reported to affect HIF-1 activity. However, the effect of propofol on HIF-1 activity is not well documented. In this study, we investigated the effect of propofol on HIF-1 activation using macrophage-differentiated THP-1 cells. METHODS: Cells were exposed to lipopolysaccharide (LPS) under 20 or 1% O(2) conditions with or without propofol treatment. The cell lysate was subjected to Western blot analysis using anti-HIF-1alpha and HIF-1beta antibodies. HIF-1-dependent gene expression was investigated by quantitative real-time reverse-transcriptase PCR analysis and luciferase assay. The amount of cellular lactate and ATP was assayed. RESULTS: Propofol suppressed HIF-1alpha protein accumulation induced by LPS, but not by hypoxia in the THP-1 cells in a dose-dependent manner by inhibiting the neo-synthesis of HIF-1alpha protein. Induction of the HIF-1 downstream gene expression including glucose transporter 1, enolase 1, lactate dehydrogenase A, pyruvate dehydrogenase kinase-1 and vascular endothelial growth factor was inhibited by propofol. Propofol suppressed LPS-induced lactate accumulation and ATP content in THP-1 cells. CONCLUSION: Our experimental results indicate that propofol inhibits HIF-1 activation and downstream gene expression induced by LPS and suppressed HIF-1-dependent glucose metabolic reprogramming. HIF-1 suppression by propofol in macrophages may explain molecular mechanisms behind the inhibitory effect of propofol on cellular inflammatory responses.

[Postextubation laryngeal edema seven years after undergoing neck dissection].

We report a case of upper airway obstruction after extubation in a 69-year-old female patient who underwent transurethral ureterolithotripsy (TUL). She had underwent bilateral modified radical neck dissection 7 years previously. TUL went smoothly in Trenderenburg position, and the extubation was performed after antagonism of neuromuscular block. The patient was closely observed in the operating theater, but about 10 minutes after extubation, she was noted to have dyspnea and tracheal tug. Dexamathasone 2 mg IV was given but was unsuccessful. Although we could support the airway with bag-mask ventilation, continuous stridor required re-intubation. Direct laryngoscopy revealed severe obstruction caused by laryngeal edema. An otolaryngologist was consulted and he performed tracheostomy. We transferred the patient to the intensive care unit for observation. Flexible fiberoptic scope examination performed on postoperative day (POD) 1 showed the decrease of the laryngeal edema. Tacheal tube was removed on POD 7 and she was discharged from the hospital POD 10 without further complications. Patients after a neck dissection may be at elevated risk for postoperative laryngeal edema caused by lymphatic destruction or venous congestion of the neck.

Effect of propofol on androgen receptor activity in prostate cancer cells.

Androgen receptor is a nuclear receptor and transcription factor activated by androgenic hormones. Androgen receptor activity plays a pivotal role in the development and progression of prostate cancer. Although accumulating evidence suggests that general anesthetics, including opioids, affect cancer cell growth and impact patient prognosis, the effect of those drugs on androgen receptor in prostate cancer is not clear. The purpose of this study was to investigate the effect of the general anesthetic propofol on androgen receptor activity in prostate cancer cells. An androgen-dependent human prostate cancer cell line (LNCaP) was stimulated with dihydrotestosterone (DHT) and exposed to propofol. The induction of androgen receptor target genes was investigated using real-time reverse transcription polymerase chain reaction, and androgen receptor protein levels and localization patterns were analyzed using immunoblotting and immunofluorescence assays. The effect of propofol on the proliferation of LNCaP cells was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Propofol significantly inhibited DHT-induced expression of androgen receptor target genes in a dose- and time-dependent manner, and immunoblotting and immunofluorescence assays indicated that propofol suppressed nuclear levels of androgen receptor proteins. Exposure to propofol for 24h suppressed the proliferation of LNCaP cells, whereas 4h of exposure did not exert significant effects. Together, our results indicate that propofol suppresses nuclear androgen receptor protein levels, and inhibits androgen receptor transcriptional activity and proliferation in LNCaP cells.

Use of extracorporeal membrane oxygenation in complicated transcatheter aortic valve replacement.

OBJECTIVES: Although transcatheter aortic valve replacement (TAVR) is an excellent alternative procedure for high-risk patients with severe symptomatic aortic stenosis, it is often associated with life-threatening complications. We report on the emergency or elective use of veno-arterial extracorporeal membrane oxygenation (ECMO) to manage these complications. METHODS: Between December 2013 and February 2016, 46 patients underwent TAVR at our institution. Of these, 4 patients required emergency ECMO support and another 3 patients were electively placed on ECMO support at the start of the procedure. The mean age of the ECMO patients was 87.3 ± 3.6 years and all were female. The Society of Thoracic Surgeons-predicted risk of mortality score in these patients was 12.2 ± 6.2%. RESULTS: TAVR with ECMO was completed through the transapical approach in 6 patients, and the transfemoral approach in 1 patient. The arterial access route for ECMO was the femoral artery in 5, the external iliac artery in 1, and the subclavian artery in 1. Indications for the use of emergency ECMO were hemodynamic instability in 2, cardiogenic shock in 2, while indications for elective ECMO were severe pulmonary hypertension, impaired left ventricular function and a combination of these. There was no 30-day mortality, and the 1-year survival rate was 83.3% with no significant difference compared to patients without ECMO support. CONCLUSION: The use of ECMO in very high-risk patients undergoing TAVR may increase safety and contribute to excellent outcomes. Although ECMO support is rarely needed in TAVR, a well-prepared treatment strategy by the heart team is mandatory.

Cigarette smoke reversibly activates hypoxia-inducible factor 1 in a reactive oxygen species-dependent manner.

Cigarette smoke (CS) is a major contributor to the development of a large number of fatal and debilitating disorders. However, the precise molecular mechanisms underlying the effects of CS in lung disease are largely unknown. To elucidate these pathophysiological processes, we examined the in vitro and in vivo effects of CS extract (CSE) and CS on the transcription factor, hypoxia-inducible factor 1 (HIF-1). CSE induced concentration- and time-dependent accumulation of HIF-1α protein in human lung epithelial-like cells under non-hypoxic conditions. Genes upregulated by HIF-1, including vascular endothelial growth factor and regulated in development and DNA damage response 1, both of which are involved in smoking-induced emphysematous changes, were increased by CSE treatment under non-hypoxic conditions in vitro and in vivo. Further investigation revealed that reactive oxygen species were generated in cells exposed to CSE and were required for CSE-mediated induction of HIF-1α protein, as was activation of phosphoinositide 3-kinase and mitogen-activated protein kinase pathways. In conclusion, we demonstrated that CSE and CS induced HIF-1 activation in vitro and in vivo, respectively. The evidence warrants further investigation to indicate that HIF-1 plays an important role in CS-induced gene expression, which is deeply involved in pulmonary cellular stress and small airway remodelling.

Midazolam inhibits the hypoxia-induced up-regulation of erythropoietin in the central nervous system.

Erythropoietin (EPO), a regulator of red blood cell production, is endogenously expressed in the central nervous system. It is mainly produced by astrocytes under hypoxic conditions and has proven to have neuroprotective and neurotrophic effects. In the present study, we investigated the effect of midazolam on EPO expression in primary cultured astrocytes and the mouse brain. Midazolam was administered to 6-week-old BALB/c male mice under hypoxic conditions and pregnant C57BL/6N mice under normoxic conditions. Primary cultured astrocytes were also treated with midazolam under hypoxic conditions. The expression of EPO mRNA in mice brains and cultured astrocytes was studied. In addition, the expression of hypoxia-inducible factor (HIF), known as the main regulator of EPO, was evaluated. Midazolam significantly reduced the hypoxia-induced up-regulation of EPO in BALB/c mice brains and primary cultured astrocytes and suppressed EPO expression in the fetal brain. Midazolam did not affect the total amount of HIF proteins but significantly inhibited the nuclear expression of HIF-1α and HIF-2α proteins. These results demonstrated the suppressive effects of midazolam on the hypoxia-induced up-regulation of EPO both in vivo and in vitro.

Successful surgical aortic valve replacement for prosthetic valve infective endocarditis following transcatheter aortic valve implantation.

An 80-year-old male underwent a transcatheter aortic valve implantation (TAVI) for severe senile aortic stenosis. Six weeks after the surgery, he was readmitted to our institution because of a high-grade fever. Transesophageal echocardiography revealed thickening of all three leaflets of the aortic prosthesis and mobile mass on the leaflet, and Streptococcus sanguis was identified from his blood culture. Therefore, he was diagnosed with prosthetic valve endocarditis (PVE) and received intensive intravenous antibiotic therapy. Because he did not respond to the pharmacological therapy, surgical aortic valve replacement (AVR) was indicated although it was considered a relatively high-risk procedure. Herein, we report on the successful surgical AVR in this patient using a pericardial valve after removal of the infected prosthetic valve, and discuss some issues related to this rare complication after TAVI. .

Successful balloon aortic valvuloplasty as a bridge therapy to transcatheter aortic valve implantation during the proctoring period.

In Japan, transcatheter aortic valve implantation (TAVI) with Edwards-SAPIEN XT valve (Edwards Lifesciences Inc., Irvine, CA, USA) started in October 2013. All institutions should undergo a training period to perform TAVI independently. Balloon aortic valvuloplasty (BAV) as a bridge to TAVI during the training period should be performed with caution to avoid severe aortic regurgitation (AR) because bailout TAVI is not possible. We present a case in which BAV was successfully performed as a bridge to TAVI during the training period. The patient was an 85-year-old man with medically uncontrollable congestive heart failure due to severe aortic valve stenosis. The aortic valve area was 0.60 cm2 with a left ventricular ejection fraction of 20%. TAVI was considered a safe but high-risk strategy owing to the unstable hemodynamic condition. We chose BAV as a bridge therapy to TAVI. The aortic annulus diameter was 25.3 mm on computed tomography scans. We chose a 20-mm balloon catheter to avoid BAV-induced AR. Transfemoral TAVI was performed successfully 16 days after BAV using a 26-mm SAPIEN XT valve. The postoperative course was uneventful. The case demonstrated BAV as a bridge therapy to TAVI can be safely and effectively performed during the training period. .