Preoperative forced expiratory volume in one second and postoperative respiratory outcomes in nonpulmonary and noncardiac surgery: a retrospective cohort study.

BACKGROUND: Although the usefulness of pulmonary function tests has been established for lung resection and coronary artery bypass surgeries, the association between preoperative pulmonary function test and postoperative respiratory complications in nonpulmonary and noncardiac surgery is inconclusive. The purpose of this study was to determine the association between preoperative forced expiratory volume in one second (FEV1) on pulmonary function test and the development of postoperative respiratory failure and/or death in patients undergoing major nonpulmonary and noncardiac surgery. METHODS: Adult patients aged ≥ 18 years and who underwent nonpulmonary and noncardiac surgery with expected moderate to high risk of perioperative complications from June 2012 to March 2019 were included. The primary exposure was preoperative FEV1 measured by pulmonary function test within six months before surgery. The primary outcome was respiratory failure (i.e., invasive positive pressure ventilation for at least 24 h after surgery or reintubation) and/or death within 30 days after surgery. A logistic regression model was used to adjust for the respiratory failure risk index, which is a scoring system that predicts the probability of postoperative respiratory failure based on patient and surgical factors, and to examine the association between preoperative FEV1 and the development of postoperative respiratory failure and/or death. RESULTS: Respiratory failure and/or death occurred within 30 days after surgery in 52 (0.9%) of 5562 participants. The incidence of respiratory failure and/or death in patients with FEV1 ≥ 80%, 70%- < 80%, 60%- < 70%, and < 60% was 0.9%, 0.6%, 1.7%, and 1.2%, respectively. Multivariable logistic regression analysis showed no significant association between preoperative FEV1 and postoperative respiratory failure and/or death (adjusted odds ratio per 10% decrease in FEV1: 1.01, 95% confidence interval: 0.88-1.17, P = 0.838). Addition of FEV1 information to the respiratory failure risk index did not improve the prediction of respiratory failure and/or death [area under the receiver operating characteristics curve: 0.78 (95% confidence interval: 0.72-0.84) and 0.78 (95% confidence interval: 0.72-0.84), respectively; P = 0.84]. CONCLUSION: We found no association between preoperative FEV1 and postoperative respiratory failure and/or death in patients undergoing major nonpulmonary and noncardiac surgery.

Prior exposure to stress exacerbates neuroinflammation and causes long-term behavior changes in sepsis.

Background: Neuroinflammation can occur during sepsis and is now regarded as the main mechanism underlying various related central nervous system (CNS) disorders. Another well-known factor causing neuroinflammation is psychological stress. In the current study, we examined the effects of prior exposure to stress on sepsis-induced neuroinflammation and CNS symptoms. Experimental procedure: Balb/c mice were subjected to wet bedding stress for 2 days, then lipopolysaccharide (LPS) was intraperitoneally administered. For examining the neuroinflammation, the expression of proinflammatory cytokines and NF-κB activity in the brain was analyzed by RT-PCR and ELISA-based assay. Additionally, immunohistochemical study using Iba-1 was performed. Finally, behavior tests were examined one month after LPS treatment. Result and conclusion: Stress exposure induced the upregulation of IL-1ß, IL-6 and TNFα mRNA in the cerebral cortex 4 h after LPS administration. Suggesting an underlying mechanism, LPS-induced NF-κB activation was significantly upregulated with stress in the brain. Histologically, microglia in the cerebral cortex were reactive and became more abundant with stress, while these effects were further increased with LPS injection. Behavioral analysis conducted showed a significant increase of anxiety-like behaviors in the stressed mice. These results suggest that prior exposure to stress exacerbates neuroinflammation during sepsis and induces long-term behavior changes.

Association between intraoperative end-tidal carbon dioxide and postoperative organ dysfunction in major abdominal surgery: A cohort study.

BACKGROUND: Data on the effects of intraoperative end-tidal carbon dioxide (EtCO2) levels on postoperative organ dysfunction are limited. Thus, this study was designed to investigate the relationship between the intraoperative EtCO2 level and postoperative organ dysfunction in patients who underwent major abdominal surgery under general anesthesia. METHODS: We conducted a cohort study involving patients who underwent major abdominal surgery under general anesthesia at Kyoto University Hospital. We classified those with a mean EtCO2 of less than 35 mmHg as low EtCO2. The time effect was determined as the minutes when the EtCO2 value was below 35 mmHg, whereas the cumulative effect was evaluated by measuring the area below the 35-mmHg threshold. The outcome was postoperative organ dysfunction, defined as a composite of at least one organ dysfunction among acute renal injury, circulatory dysfunction, respiratory dysfunction, coagulation dysfunction, and liver dysfunction within 7 days after surgery. RESULTS: Of the 4,171 patients, 1,195 (28%) had low EtCO2, and 1,428 (34%) had postoperative organ dysfunction. An association was found between low EtCO2 and increased postoperative organ dysfunction (adjusted risk ratio, 1.11; 95% confidence interval [CI], 1.03-1.20; p = 0.006). Additionally, long-term exposure to EtCO2 values of less than 35 mmHg (≥224 min) was associated with postoperative organ dysfunction (adjusted risk ratio, 1.18; 95% CI, 1.06-1.32; p = 0.003) and low EtCO2 severity (area under the threshold) (adjusted risk ratio, 1.13; 95% CI, 1.02-1.26; p = 0.018). CONCLUSIONS: Intraoperative low EtCO2 of below 35 mmHg was associated with increased postoperative organ dysfunction.

Utility of thromboelastogram in cardiac surgery in Jacobsen syndrome associated with platelet dysfunction: a case report.

BACKGROUND: Jacobsen syndrome is a rare genetic disorder with multiple congenital anomalies and platelet abnormalities caused by chromosome 11 deletion. CASE PRESENTATION: A 7-month-old boy with thrombocytopenia underwent ventricular septal defect closure. At the beginning of surgery, the platelet count was 168 × 103/µL, and heparinized kaolin with heparinase reaction time (HKH-R), which represents clot formation time, was prolonged at 30.4 min. Platelet transfusion was continued, and at the end of surgery, the platelet count and HKH-R values improved to 215 × 103/µL and 15 min, respectively. CONCLUSIONS: As anesthetic management of patients with abnormal platelet function, the viscoelasticity test might be useful in evaluating hemostatic capacity.

Sepsis-associated neuroinflammation in the spinal cord.

Septic patients commonly present with central nervous system (CNS) disorders including impaired consciousness and delirium. Today, the main mechanism regulating sepsis-induced cerebral disorders is believed to be neuroinflammation. However, it is unknown how another component of the CNS, the spinal cord, is influenced during sepsis. In the present study, we intraperitoneally injected mice with lipopolysaccharide (LPS) to investigate molecular and immunohistochemical changes in the spinal cord of a sepsis model. After LPS administration in the spinal cord, pro-inflammatory cytokines including interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha mRNA were rapidly and drastically induced. Twenty-four-hour after the LPS injection, severe neuronal ischemic damage spread into gray matter, especially around the anterior horns, and the anterior column had global edematous changes. Immunostaining analyses showed that spinal microglia were significantly activated and increased, but astrocytes did not show significant change. The current results indicate that sepsis induces acute neuroinflammation, including microglial activation and pro-inflammatory cytokine upregulation in the spinal cord, causing drastic neuronal ischemia and white matter edema in the spinal cord.

Relationship between the Use of Fentanyl-Based Intravenous Patient-Controlled Analgesia and Clinically Significant Events in Laparoscopic Gynecological Surgery: A Single-Center Retrospective Cohort Study.

Background: This study examined the relationship between the use of fentanyl-based intravenous patient-controlled analgesia (ivPCA) and the incidence of a clinically significant event (CSE), while considering both the analgesic effects and side effects in laparoscopic gynecological surgery. Methods: This study included 816 patients undergoing laparoscopic gynecological surgery under general anesthesia at Kyoto University Hospital between 2012 and 2018. The primary exposure was the use of fentanyl-based ivPCA. We defined an outcome measure­CSE­that integrates severe wound pain and vomiting assumed to negatively affect patient recovery. We performed multivariable logistic regression analysis to assess the independent relationship between ivPCA use and CSE. Results: Multivariable logistic regression analysis revealed that fentanyl-based ivPCA was independently associated with increased CSE (adjusted odds ratio (95% confidence interval): 1.80 (1.24−2.61), p = 0.002). Use of ivPCA was associated with a reduced incidence of postoperative severe wound pain (adjusted odds ratio (95% confidence interval): 0.50 (0.27−0.90), p = 0.022), but was also associated with an increased incidence of vomiting (adjusted odds ratio (95% confidence interval): 2.65 (1.79−3.92), p < 0.001). Conclusion: The use of fentanyl-based ivPCA in laparoscopic gynecological surgery is associated with increased CSE.

Association between intraoperative end-tidal carbon dioxide and postoperative nausea and vomiting in gynecologic laparoscopic surgery.

Gynecologic laparoscopic surgery has a high incidence of postoperative nausea and vomiting (PONV). Studies suggest that low intraoperative end-tidal carbon dioxide (EtCO2) is associated with an increased incidence of PONV, but the results have not been consistent among studies. This study investigated the association between intraoperative EtCO2 and PONV in patients undergoing gynecologic laparoscopic surgeries under general anesthesia. This retrospective cohort study involved patients who underwent gynecologic laparoscopic surgeries under general anesthesia at Kyoto University Hospital. We defined low EtCO2 as a mean EtCO2 of < 35 mmHg. Multivariable modified Poisson regression analysis examined the association between low EtCO2 and PONV during postoperative two days and the postoperative length of hospital stay (PLOS). Of the 739 patients, 120 (16%) had low EtCO2, and 430 (58%) developed PONV during postoperative two days. There was no substantial association between low EtCO2 and increased incidence of PONV (adjusted risk ratio: 0.96; 95% confidence interval [CI] 0.80-1.14; p = 0.658). Furthermore, there was no substantial association between low EtCO2 and prolonged PLOS (adjusted difference in PLOS: 0.13; 95% CI - 1.00 to 1.28; p = 0.816). Intraoperative low EtCO2, specifically a mean intraoperative EtCO2 below 35 mmHg, was not substantially associated with either increased incidence of PONV or prolonged PLOS.

Incidence, clinical characteristics and long-term prognosis of postoperative symptomatic venous thromboembolism: a retrospective cohort study.

OBJECTIVES: The purpose of this study was to evaluate the incidence, clinical characteristics and prognosis of postoperative symptomatic venous thromboembolism (VTE) in Japan. DESIGN: Retrospective observational study. Two data sets, Contemporary ManageMent AND outcomes in patients with Venous ThromboEmbolism (COMMAND VTE) Registry and Japanese Society of Anesthesiologists (JSA) annual report, were used for current analyses. SETTING: Eighteen of 29 centres participated in the COMMAND VTE Registry. PARTICIPANTS: Acute symptomatic patients with VTE who had undergone surgery 2 months prior to the diagnosis at 18 centres from January 2010 to December 2013 were identified in the COMMAND VTE Registry. From each centre's JSA annual report, the overall population that had received anaesthetic management during this period was retrieved. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the incidences and clinical characteristics of postoperative symptomatic VTE. The secondary outcomes were recurrent VTE, major bleeding and all-cause death. RESULTS: We identified 137 patients with postoperative symptomatic VTE, including 57 patients with pulmonary embolism. The incidences of postoperative symptomatic VTE and pulmonary embolism were 0.067% and 0.028%, respectively, based on data from 2 03 943 patients who underwent surgery, managed by anaesthesiologists, during the study period. The incidences of postoperative symptomatic VTE varied widely, depending on surgical and anaesthetic characteristics. Postoperative symptomatic VTE occurred at a median of 8 days after surgery, with 58 patients (42%) diagnosed within 7 days. The cumulative incidence, 30 days after VTE, of recurrent VTE, major bleeding, and all-cause death was 3.0%, 5.2%, and 3.7%, respectively. CONCLUSION: This study, combining the large real-world VTE and anaesthesiology databases in Japan revealed the incidence, clinical features and prognosis of postoperative symptomatic VTE, providing useful insights for all healthcare providers involved in various surgeries. TRIAL REGISTRATION: Not applicable.

The inhibitory effects of Orengedokuto on inducible PGE2 production in BV-2 microglial cells.

BACKGROUND AND AIM: Reactive microglia has been associated with neuroinflammation caused by the production of proinflammatory molecules such as cytokines, nitric oxide, and prostaglandins. The overexpression of these molecules may provoke neuronal damage that can cause neurodegenerative diseases. A traditional herbal medicine, Orengedokuto (OGT), has been widely used for treating inflammation-related diseases. However, how it influences neuroinflammation remains poorly understood. EXPERIMENTAL PROCEDURE: This study investigated the effects of OGT on inflammatory molecule induction in BV-2 microglial cells using real-time RT-PCR and ELISA. An in vivo confirmation of these effects was then performed in mice. RESULTS AND CONCLUSION: OGT showed dose-dependent inhibition of prostaglandin E2 (PGE2) production in BV-2 cells stimulated with lipopolysaccharide (LPS). To elucidate the mechanism of PGE2 inhibition, we examined cyclooxygenases (COXs) and found that OGT did not suppress COX-1 expression or inhibit LPS-induced COX-2 upregulation at either the transcriptional or translational levels. In addition, OGT did not inhibit COX enzyme activities within the concentration that inhibited PGE2 production, suggesting that the effect of OGT is COX-independent. The inhibitory effects of OGT on PGE2 production in BV-2 cells were experimentally replicated in primary cultured astrocytes and mice brains. OGT can be useful in the treatment of neuroinflammatory diseases by modulating PGE2 expression.

Maternal exposure to volatile anesthetics induces IL-6 in fetal brains and affects neuronal development.

Most clinically used general anesthetics have demonstrated neurotoxicity in animal studies, but the related mechanisms remain unknown. Previous studies suggest that anesthetics affect neuronal development through neuroinflammation, and significant effects of neuroinflammation on neurogenesis and neuronal disease have been shown. In the present study, we treated pregnant mice with 2% sevoflurane for 3 h at gestational day 15.5 and analyzed the expression of proinflammatory cytokines, including IL-6 and IL-17, in fetal mice brains. Sevoflurane induced IL-6 mRNA significantly, but did not upregulate IL-17. Other volatile anesthetics, including isoflurane, enflurane, and halothane, induced IL-6 mRNA in fetal brains as well as sevoflurane, but propofol did not. Sevoflurane and isoflurane showed the same effects in cultured microglia and astrocytes, but not in neurons. Because IL-6 induction in fetal brains may affect neuronal precursor cells (NPCs), numbers of NPCs in the subventricular zone were studied, revealing that maternal sevoflurane treatment significantly increases NPCs in offspring at 8 weeks after birth (p8wk). But this effect was absent in IL-6 knockout mice. Finally, behavioral experiments also revealed that maternal sevoflurane exposure causes learning impairments in p8wk offspring. These findings collectively demonstrate that maternal exposure to volatile anesthetics upregulates IL-6 in fetal mice brains, and the effects could result in long-lasting influences on neuronal development.

Neurological prognosis of 6 cases after chest compression during general anesthesia.

INTRODUCTION: Data on the outcomes after chest compression (CC) of patients who are under general anesthesia (GA) are limited. The present study aimed to evaluate the neurological outcomes in patients who received CC while under GA. METHODS: The patients who received CC while under GA, between 2010 and 2015, in Kyoto Medical Center were surveyed retrospectively. The primary outcome was poor neurologic function or death, as defined by a cerebral performance category score (CPC) score of 3-5 on day 28. RESULTS: Six patients received CC while under GA, and four patients had poor neurological outcomes with a CPC score of 4 or 5 on day 28. All these patients required emergency operation because of their primary disease. CONCLUSION: Even if the patients were monitored and immediately managed under GA, ineffective management of preoperative conditions tended to result in the poor neurological prognosis.

Successful perioperative management of living-donor liver transplantation for a patient with severe methylmalonic acidemia: a case report.

BACKGROUND: Methylmalonic acidemia (MMAemia) is a rare hereditary disease affecting organic acid metabolism. It causes recurrent metabolic acidosis and secondary mitochondrial dysfunction, resulting in a poor prognosis. Liver transplantation (LT) has been performed to facilitate the metabolism of organic acids and improve the prognosis of MMAemia. However, there have been few reports on perioperative management of LT. CASE PRESENTATION: A 22-month-old female with severe MMAemia was scheduled to receive LT to relieve recurrent metabolic acidosis despite dietary and pharmacological treatment. General anesthesia was maintained without propofol or nitrous oxide, which can worsen MMAemia-induced metabolic acidosis during anesthesia for LT. Strict metabolic and respiratory management enabled the operation to be successfully performed without metabolic acidosis. CONCLUSION: Perioperative management of LT for MMAemia is challenging for anesthesiologists because of the possibility of serious metabolic acidosis. We succeeded in preventing metabolic decompensation by avoiding the use of propofol and nitrous oxide.

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.