Importance of Early Diagnosis and Treatment of Perioperative Catatonia: A Case Report.

Symptoms of catatonia include silence, motionlessness, and postural retention. Although it is important to detect and treat catatonia early, before it becomes severe, postoperative cases have inherent risks that hinder diagnosis and treatment. A 60-year-old man with schizophrenia underwent endoscopic/thoracoscopic esophagectomy and was extubated in the operating room. In the intensive care unit (ICU), he had stiffness in the neck, ankles, and knees, catalepsy during passive knee flexion, mild disturbance of consciousness, mild creatine kinase elevation, and respiratory depression. Intravenous diazepam was administered for diagnosis, and the patient's rapid improvement indicated catatonia. He was intubated and started on lorazepam; tapering produced no recurrence of symptoms. The patient was extubated and transferred to the general ward on postoperative Day 2. Because this patient was extubated in the operating room and was managed postoperatively in the ICU with a full-time doctor, his symptoms were easily recognized and early diagnosis was possible. Thus, we were able to administer drug therapy quickly and adequately and perform forward management that accounted for postoperative risks, thereby achieving a favorable outcome.

Intraoperative cardiac arrest caused by unexpected vasospastic angina requiring prolonged resuscitation using extracorporeal membrane oxygenation: a case report.

BACKGROUND: Vasospastic angina (VSA) occurring during surgery is rare but can lead to sudden intraoperative cardiac arrest. CASE PRESENTATION: A 77-year-old man with hypertension, and no history of coronary artery disease, displayed an abrupt ST-segment elevation on the electrocardiogram (ECG) during laparoscopic inguinal hernia surgery under general anesthesia. Subsequently, ventricular fibrillation (VF) occurred, with a finding suggesting ischemic myocardial contracture by transesophageal echocardiography. VF was refractory to cardiopulmonary resuscitation (CPR), and veno-arterial extracorporeal membrane oxygenation (VA ECMO) was introduced. Spontaneous circulation resumed 77 min post-cardiac arrest. VSA was confirmed through the patient's clinical course and coronary angiography. Subsequently, VA ECMO was terminated, and the patient was discharged uneventfully. CONCLUSIONS: Extracorporeal CPR may be a valuable alternative to extended resuscitation for refractory ventricular arrhythmias by VSA.

Dexmedetomidine Might Exacerbate Acute Kidney Injury, While Midazolam Might Have a Postconditioning Effect: A Rat Model of Lipopolysaccharide-Induced Acute Kidney Injury.

BACKGROUND: The preconditioning effects of dexmedetomidine and propofol on septic acute kidney injury (AKI) have been reported, but the postconditioning effects remain unknown. This study investigated the postconditioning effects of dexmedetomidine, midazolam, and propofol on septic AKI. METHODS: Forty-eight male Wistar rats were intraperitoneally administered lipopolysaccharide (LPS; 8.3 mg kg-1) or normal saline. Twenty-four hours later, rats were allocated to specific anesthetic groups (n=6 each) and exposed for 6 h, as follows: C, control (no anesthetic); D, dexmedetomidine (5 µg kg-1 h-1); M, midazolam (0.6 mg kg-1 h-1); or P, propofol (10 mg kg-1 h-1). Serum creatinine (Cr) and cystatin C (CysC) were measured at the end of anesthesia. Western blot and immunofluorescent analyses of kidney samples were performed. RESULTS: Among LPS-treated groups, D group showed worsened renal dysfunction (L-C vs L-D: Cr, P=0.002, effect size (η2) =0.83; CysC, P=0.004, η2=0.71), whereas M group showed improved renal function (L-C vs L-M: Cr, P=0.009, η2=0.55). In immunofluorescent analysis of renal tubules, D group showed increased expression of nuclear factor κB (NFκΒ) (L-C vs L-D: NFκΒ, P=0.002, η2=0.75; phospho-NFκΒ, P=0.018, η2=0.66) and inhibitor of κ light polypeptide gene enhancer in B-cell kinase ß (IKKß) (L-C vs L-D: IKKß, P=0.002, η2=0.59; phospho-IKKα/ß, P=0.004, η2=0.59), whereas M group showed decreased NFκB expression (L-C vs L-M: NFκB, P=0.003, η2=0.55; phospho-NFκB, P=0.013, η2=0.46). CONCLUSIONS: Dexmedetomidine administration might worsen septic AKI, while midazolam might preserve kidney function via the NFκΒ pathway.

TSLP in DRG neurons causes the development of neuropathic pain through T cells.

BACKGROUND: Peripheral nerve injury to dorsal root ganglion (DRG) neurons develops intractable neuropathic pain via induction of neuroinflammation. However, neuropathic pain is rare in the early life of rodents. Here, we aimed to identify a novel therapeutic target for neuropathic pain in adults by comprehensively analyzing the difference of gene expression changes between infant and adult rats after nerve injury. METHODS: A neuropathic pain model was produced in neonatal and young adult rats by spared nerve injury. Nerve injury-induced gene expression changes in the dorsal root ganglion (DRG) were examined using RNA sequencing. Thymic stromal lymphopoietin (TSLP) and its siRNA were intrathecally injected. T cells were examined using immunofluorescence and were reduced by systemic administration of FTY720. RESULTS: Differences in changes in the transcriptome in injured DRG between infant and adult rats were most associated with immunological functions. Notably, TSLP was markedly upregulated in DRG neurons in adult rats, but not in infant rats. TSLP caused mechanical allodynia in adult rats, whereas TSLP knockdown suppressed the development of neuropathic pain. TSLP promoted the infiltration of T cells into the injured DRG and organized the expressions of multiple factors that regulate T cells. Accordingly, TSLP caused mechanical allodynia through T cells in the DRG. CONCLUSION: This study demonstrated that TSLP is causally involved in the development of neuropathic pain through T cell recruitment.

Intraoperative serum lactate levels as a prognostic predictor of outcome for emergency abdominal surgery: a retrospective study.

BACKGROUND: The relationship between intraoperative lactate levels and prognosis after emergency gastrointestinal surgery remains unclear. The purpose of this study was to investigate the prognostic value of intraoperative lactate levels for predicting in-hospital mortality, and to examine intraoperative hemodynamic managements. METHODS: We conducted a retrospective observational study of emergency GI surgeries performed at our institution between 2011 and 2020. The study group comprised patients admitted to intensive care units postoperatively, and whose intraoperative and postoperative lactate levels were available. Intraoperative peak lactate levels (intra-LACs) were selected for analysis, and in-hospital mortality was set as the primary outcome. The prognostic value of intra-LAC was assessed using logistic regression and receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 551 patients included in the study, 120 died postoperatively. Intra-LAC in the group who survived and the group that died was 1.80 [interquartile range [IQR], 1.19-3.01] mmol/L and 4.22 [IQR, 2.15-7.13] mmol/L (P < 0.001), respectively. Patients who died had larger volumes of red blood cell (RBC) transfusions and fluid administration, and were administered higher doses of vasoactive drugs. Logistic regression analysis showed that intra-LAC was an independent predictor of postoperative mortality (odds ratio [OR] 1.210, 95% CI 1.070 -1.360, P = 0.002). The volume of RBCs, fluids transfused, and the amount of vasoactive agents administered were not independent predictors. The area under the curve (AUC) of the ROC curve for intra-LAC for in-hospital mortality was 0.762 (95% confidence interval [CI], 0.711-0.812), with a cutoff value of 3.68 mmol/L by Youden index. CONCLUSIONS: Intraoperative lactate levels, but not hemodynamic management, were independently associated with increased in-hospital mortality after emergency GI surgery.

Lateral position does not cause an interhemicerebral difference of cerebral hemodynamic in healthy adult volunteers.

Cerebral perfusion is maintained at a consistent value irrespective of changes in systemic blood pressure or disease-induced changes in general physical condition. This regulatory mechanism is effective despite postural changes, working even during changes in posture, such as those from sitting to standing or from the head-down to the head-up position. However, no study has addressed changes in perfusion separately in the left and right cerebral hemispheres, and there has been no specific investigation of the effect of the lateral decubitus position on perfusion in each hemisphere. Surgery, particularly respiratory surgery, is often performed with the patient in the lateral decubitus position, and since intraoperative anesthesia may also have an effect, it is important to ascertain the effect of the lateral decubitus position on perfusion in the left and right cerebral hemispheres in the absence of anesthesia. The effects of the lateral decubitus position on heart rate, blood pressure, and hemodynamic in the left and right cerebral hemispheres assessed by regional saturation of oxygen measured by near-infrared spectroscopy were investigated in healthy adult volunteers. Although the lateral decubitus position causes systemic circulatory changes, it may not cause any difference in hemodynamic between the left and right cerebral hemispheres.

Factor XII Silencing Using siRNA Prevents Thrombus Formation in a Rat Model of Extracorporeal Life Support.

Heparin anticoagulation increases the bleeding risk during extracorporeal life support (ECLS). This study determined whether factor XII (FXII) silencing using short interfering RNA (siRNA) can provide ECLS circuit anticoagulation without bleeding. Adult male, Sprague-Dawley rats were randomized to four groups (n = 3 each) based on anticoagulant: (1) no anticoagulant, (2) heparin, (3) FXII siRNA, or (4) nontargeting siRNA. Heparin was administered intravenously before and during ECLS. FXII or nontargeting siRNA were administered intravenously 3 days before the initiation of ECLS via lipidoid nanoparticles. The rats were placed on pumped, arteriovenous ECLS for 8 hours or until the blood flow resistance reached three times its baseline resistance. Without anticoagulant, mock-oxygenator resistance tripled within 7 ± 2 minutes. The resistance in the FXII siRNA group did not increase for 8 hours. There were no significant differences in resistance or mock-oxygenator thrombus volume between the FXII siRNA and the heparin groups. However, the bleeding time in the FXII siRNA group (3.4 ± 0.6 minutes) was significantly shorter than that in the heparin group (5.5 ± 0.5 minutes, p < 0.05). FXII silencing using siRNA provided simpler anticoagulation of ECLS circuits with reduced bleeding time as compared to heparin. http://links.lww.com/ASAIO/A937.

Increased extracellular release of microRNAs from dorsal root ganglion cells in a rat model of neuropathic pain caused by peripheral nerve injury.

microRNAs (miRNAs) are extracellularly released by cells for intercellular communication, while intracellularly, they inhibit the expression of specific genes. An increasing number of studies suggest that extracellular miRNAs have great potential as both therapeutic targets and disease-specific biomarkers in a variety of diseases, including pain disorders. However, little is known about miRNA release from dorsal root ganglion (DRG) neurons in neuropathic pain caused by peripheral nerve injury. In this study, we investigated the changes in the extracellular release of miRNAs from DRG neurons in a rat model of neuropathic pain induced by chronic constriction injury of the sciatic nerve. We found increased release of six miRNAs (let-7d, miR-21, miR-142-3p, miR-146b, miR-203-3p and miR-221) from primary cultured DRG neurons prepared from rats 7 days after nerve injury. Among these, miR-221 was also increased in serum from days 7 to 28 after nerve injury. In contrast, serum miR-221 levels and its release from DRG neurons were unchanged in an inflammatory pain model produced by intraplantar injection of complete Freund's adjuvant. These results suggest that the increased release of specific miRNAs by DRG neurons may be involved in the pathophysiology of neuropathic pain through extracellular as well as intracellular mechanisms. Furthermore, serum miR-221 may be useful as a biomarker of neuropathic pain caused by peripheral nerve injury.

The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence.

Anaesthetics may modify colorectal cancer cell biology which potentially affects long-term survival. This study aims to compare propofol and sevoflurane regarding with the direct anaesthetic effects on cancer malignancy and the indirect effects on host immunity in a cancer xenograft mode of mice. Cultured colon cancer cell (Caco-2) was injected subcutaneously to nude mice (day 1). Mice were exposed to either 1.5% sevoflurane for 1.5 h or propofol (20 µg g-1; ip injection) with or without 4 µg g-1 lipopolysaccharide (LPS; ip) from days 15 to 17, compared with those without anaesthetic exposure as controls. The clinical endpoints including tumour volumes over 70 mm3 were closely monitored up to day 28. Tumour samples from the other cohorts were collected on day 18 for PCR array, qRT-PCR, western blotting and immunofluorescent assessment. Propofol treatment reduced tumour size (mean ± SD; 23.0 ± 6.2mm3) when compared to sevoflurane (36.0 ± 0.3mm3) (p = 0.008) or control (23.6 ± 4.7mm3). Propofol decreased hypoxia inducible factor 1α (HIF1α), interleukin 1ß (IL1ß), and hepatocyte growth factor (HGF) gene expressions and increased tissue inhibitor of metalloproteinases 2 (TIMP-2) gene and protein expression in comparison to sevoflurane in the tumour tissue. LPS suppressed tumour growth in any conditions whilst increased TIMP-2 and anti-cancer neutrophil marker expressions and decreased macrophage marker expressions compared to those in the LPS-untreated groups. Our data indicated that sevoflurane increased cancer development when compared with propofol in vivo under non-surgical condition. Anaesthetics tested in this study did not alter the effects of LPS as an immune modulator in changing immunocyte phenotype and suppressing cancer development.

A case of severe respiratory failure due to interstitial pneumonia successfully bridged to lung transplantation from a brain-dead donor using 109-day veno-arterial extracorporeal membrane oxygenation.

In Japan, successful cases of a bridge to lung transplantation (BTT) by extracorporeal membrane oxygenation (ECMO) are rare. We present the case of a man in his thirties, diagnosed with interstitial pneumonia 6 years prior and registered for lung transplant 1 year prior due to disease progression despite treatment. Due to the patient's worsening respiratory failure, he was transferred to our hospital for BTT by ECMO. Since long-term management was expected and pulmonary hypertension was present, veno-arterial (V-A) ECMO was conducted using the right atrial blood outflow via the right internal jugular vein and right axillary artery inflow via a vascular graft. After tracheostomy, he was managed as "Awake ECMO". In addition, interprofessional collaboration such as physiotherapist rehabilitation, nurses, and liaison teams prevented muscle weakness and supported the mental aspect. We were able to minimize complications such as severe infections and bleeding. A compatible brain-dead donor was found on day 108 after introducing ECMO, and the patient was transferred to a transplant facility on day 109. The peripheral upper V-A ECMO is one of the configurations suitable for long-term BTT management.

The neutrophil to lymphocyte ratio and serum albumin as predictors of acute kidney injury after coronary artery bypass grafting.

Postoperative acute kidney injury (AKI) is a highly prevalent and serious complication after cardiac surgery. The aim of this study is to identify the predictors of AKI and the cut-off values after isolated off-pump coronary artery bypass grafting (OPCAB). A total of 329 adult patients, who underwent isolated OPCAB between December 2008 and February 2021, were retrospectively analyzed. The patients were divided into three groups: non-AKI, early AKI and late AKI groups. The early AKI group or the late AKI group were defined as 'having AKI that occurred before or after 48 h postoperatively', respectively. Multivariate logistic regression analysis was performed to identify the predictors of AKI. Receiver operating characteristic (ROC) curve analysis was used to evaluate the cutoff value, the sensitivity, and the specificity of the predictors. On the multivariate analysis, the emergency surgery, the preoperative serum albumin, and the postoperative day 1 neutrophil to lymphocyte ratio (NL ratio) were identified as the independent predictors of AKI. However, neither albumin nor the NL ratio predicted late AKI. The present study showed the preoperative albumin and the postoperative day 1 NL ratio were the robust and independent predictors of postoperative early AKI in isolated OPCAB.

Hyaluronic acid restored protein permeability across injured human lung microvascular endothelial cells.

Lung endothelial permeability is a key pathological feature of acute respiratory distress syndrome. Hyaluronic acid (HA), a major component of the glycocalyx layer on the endothelium, is generated by HA synthase (HAS) during inflammation and injury and is critical for repair. We hypothesized that administration of exogenous high molecular weight (HMW) HA would restore protein permeability across human lung microvascular endothelial cells (HLMVEC) injured by an inflammatory insult via upregulation of HAS by binding to CD44. A transwell coculture system was used to study the effects of HA on protein permeability across HLMVEC injured by cytomix, a mixture of IL-1ß, TNFα, and IFNγ, with or without HMW or low molecular weight (LMW) HA. Coincubation with HMW HA, but not LMW HA, improved protein permeability following injury at 24 h. Fluorescence microscopy demonstrated that exogenous HMW HA partially prevented the increase in "actin stress fiber" formation. HMW HA also increased the synthesis of HAS2 mRNA expression and intracellular HMW HA levels in HLMVEC following injury. Pretreatment with an anti-CD44 antibody or 4-methylumbelliferone, a HAS inhibitor, blocked the therapeutic effects. In conclusion, exogenous HMW HA restored protein permeability across HLMVEC injured by an inflammatory insult in part through upregulation of HAS2.

Early predictors of oxygenator exchange during veno-venous extracorporeal membrane oxygenation: A retrospective analysis.

INTRODUCTION: Oxygenator exchange during extracorporeal membrane oxygenation (ECMO) is a life-threatening procedure. D-dimer has been used to predict oxygenator failure, but it is a parameter used a few days before oxygenator exchange. This study investigated parameters before and immediately after ECMO initiation that predict oxygenator exchange. METHODS: This was a single-center, retrospective study of 28 patients who received veno-venous ECMO with heparin/silicone-coated polypropylene oxygenator (NSH-R HPO-23WH-C; Senko Medical Inc., Tokyo, Japan), due to acute respiratory failure, from April 2015 to March 2020. Clinical data before ECMO initiation and during the first 3 days on ECMO were compared between the patients with oxygenator exchange (exchange group) and those without oxygenator exchange (non-exchange group). RESULTS: Nine (32%) patients required oxygenator exchange. The exchange group had significantly higher white blood cell count (WBC) (16,944 ± 2423/µL vs 10,342 ± 1442/µL, p < 0.05) and Acute Physiology and Chronic Health Evaluation (APACHE) II score (31 ± 5 vs 25 ± 8, p < 0.05) before ECMO initiation than the non-exchange group. The partial pressure of oxygen at the outlet of the oxygenator (PO2 outlet) and activated partial thromboplastin time (aPTT) during the first 3 days on ECMO were significantly lower in the exchange group than in the non-exchange group. CONCLUSIONS: High WBC and APACHE II score before ECMO initiation, low PO2 outlet, and aPTT during the first 3 days on ECMO were associated with oxygenator exchange during veno-venous ECMO. These parameters could be used to avoid unexpected oxygenator exchange.

Anaesthetic management of an abdominal aortic aneurysmorrhaphy in Klippel-Trenaunay-Weber syndrome: a case report.

BACKGROUND: Klippel-Trenaunay-Weber syndrome (KTWS) is a rare congenital malformation. Although there have been few reports on anaesthetic management of patients with KTWS, there is a lack of data on anaesthetic management for abdominal aortic aneurysm (AAA) surgeries in these patients. CASE PRESENTATION: A 74-year-old man (height, 160 cm and body weight, 51.5 kg) with KTWS was scheduled for AAA replacement. Abdominal computed tomography (CT) showed prominent tortuosity below the abdominal aorta with an infrarenal abdominal aortic aneurysm, right common iliac artery aneurysm, and right external iliac artery aneurysm. Moreover, a remarkably noted arteriovenous fistula had developed between the aneurysm and peripheral artery. General anaesthesia was induced. Furthermore, a central venous catheter and an 8.5 French sheath in the left internal jugular vein were inserted. During the operation, bleeding from a collateral vessel in the cross-clamped aorta led the surgeon to decide to perform aneurysmorrhaphy. Intraoperatively, blood loss was 1500 ml, and 20 units of red blood cell concentrate were used. CONCLUSIONS: Regarding AAA procedures in patients with KTWS, aortic cross-clamping may not sufficiently intercept blood flow due to collateral vessels. In these patients, the anaesthesiologist must be prepared to transfuse blood more rapidly and frequently than during normal AAA procedures.

The Need for an Adult Intensive Care Unit Boot Camp for Residents and Fellows: A Cross-Sectional Survey among Intensive Care Unit Directors.

BACKGROUND: The concept of "see one, do one, teach one" raises concerns regarding patient safety in the intensive care unit (ICU) and highlights the need for prior preparation of residents/fellows for ICU rotation. This study assessed the need for an adult pre-ICU "boot camp" training course. METHODS: An online questionnaire regarding the current ICU training and desirable course framework was distributed via e-mail to the ICU directors of 269 educational centers certified by the Japanese Society of Intensive Care Medicine. RESULTS: The response rate was 39% (106/269). The number of residents/fellows undergoing ICU rotation was 5.5 (IQR 2-12) /ICU/year, and the majority (63%) were second to fourth year post-graduate residents and fellows. ICU directors opined that of the fundamental critical care skills, residents/fellows performed well or very well in only seven out of 29 skills (24%). Only 18% of the ICU directors had an established ICU training curriculum. Overall, 72% of the directors were interested in the boot camp. The desirable course framework was 3-5 hours per day with simulations and lectures. The core skills that directors considered as important to acquire during ICU rotation were central venous catheter insertion, tracheal intubation, defibrillation, initiation of mechanical ventilation, physical examination of critically ill patients, and shock assessment. CONCLUSIONS: Residents/fellows began ICU rotations with suboptimal skills as reported by ICU directors. In addition, most of the ICUs had not established a training curriculum. Therefore, having an ICU boot camp is necessary to enhance critical care skills and to decrease medical errors.

Comparison of Gastric Emptying Time after the Ingestion of Whisky with Isocalorically Adjusted Glucose Solution.

Previous studies have shown that the liquid gastric emptying mainly depended on energy content, regardless of compositional differences. But the gastric emptying of alcoholic beverages remains unclear. Therefore, we performed the present study to compare gastric emptying times between whisky mixed with water and glucose solution with uniform energy contents and volumes. As a crossover study, 10 healthy male volunteers ingested one of 3 test solutions with a uniform volume of 150 ml, i.e., whisky with water-containing whisky 30 ml (67 kcal), sugar water containing glucose 16.8 g (67 kcal), and water (0 kcal), and the gastric emptying time of each beverage was then assessed by ultrasound measurements of the gastric antral cross-sectional area. The gastric emptying pattern of whisky with water was faster than that of isocaloric sugar water, but slower than that of water. Each antral cross-sectional area 20, 30, and 40 min after the ingestion of sugar water was significantly larger than that of whisky with water. Antral cross-sectional areas 10 and 20 min after the ingestion of water were significantly smaller than those of whisky with water. In conclusion, the gastric emptying time of whisky would be faster than that of isocaloric glucose solution and slower than that of water. Unlike the other beverages, the gastric emptying time of alcohol drinks does not purely depend on the energy content because alcohol itself has no calorie before absorption. This study is registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000034443).

Effects of general anesthesia on behavioral circadian rhythms and clock-gene expression in the suprachiasmatic nucleus in rats.

The suprachiasmatic nucleus (SCN) of the hypothalamus is a nucleus that regulates circadian rhythms through the cyclic expression of clock genes. It has been suggested that circadian-rhythm-related, adverse postoperative events, including sleep disturbances and delirium, are partly caused by anesthesia-induced disruption of clock-gene expression. We examined the effects of multiple general anesthetics on the expression cycle of Period2 (Per2), one of the clock genes that regulate circadian rhythms in the SCN, and on the behavioral rhythms of animals. Rats were treated with sevoflurane, propofol, and dexmedetomidine for 4 h. The expression of Per2 in SCN was analyzed using in situ hybridization, and the behavioral rhythm before and after anesthesia was analyzed. Per2 expression in the SCN decreased significantly immediately after anesthesia in all groups compared with corresponding control groups. However, Per2 returned to normal levels within 24 h, and there was no phase change in the gene expression cycle or behavioral rhythm. This study suggests that acute suppression of Per2 expression may be a general phenomenon induced by general anesthesia, but that the molecular mechanism of the body clock is resilient to disturbances to some extent.

Identification of Brain Regions Activated by Sevoflurane and Propofol and Regional Changes in Gene Expression.

General anesthetics have different efficacies and side effect incidences based on their mechanism of action. However, detailed comparative studies of anesthetics are incomplete. In this study, target brain regions and gene expression changes in these brain regions were determined for sevoflurane and propofol to understand the mechanisms that cause differences among anesthetics. Rats were anesthetized with sevoflurane or propofol for 1 hr, and brain regions with anesthesia-induced changes in neuronal activity were examined by immunohistochemistry and in situ hybridization for c-Fos. Among the identified target brain regions, gene expression analysis was performed in the habenula, the solitary nucleus and the medial vestibular nucleus from laser microdissected samples. Genes altered by sevoflurane and propofol were different and included genes involved in the incidence of postoperative nausea and vomiting and emergence agitation, such as Egr1 and Gad2. GO enrichment analysis showed that the altered genes tended to be evenly distributed in all functional category. The detailed profiles of target brain regions and induced gene expression changes of sevoflurane and propofol in this study will provide a basis for analyzing the effects of each anesthetic agent and the risk of adverse events.

The Efficacy and Safety of Dexmedetomidine for Sedation During Surgery Under Epidural or Spinal Anesthesia: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: Only a few studies have been reported on the use of dexmedetomidine for sedating surgical patients requiring epidural or spinal anesthesia. We conducted a randomized, double-blind, placebo-controlled, parallel-group study at 12 hospitals in Japan. METHODS: Adult patients were randomly allocated to receive an intravenous administration of placebo or dexmedetomidine at 0.067, 0.25, 0.5 or 1.0 µg/kg over 10 min after epidural or spinal anesthesia. All dexmedetomidine groups received dexmedetomidine 0.2-0.7 µg/kg/h to maintain an Observer's Assessment of Alertness/Sedation Scale (OAA/S) score of ≤ 4; however, propofol was administered to rescue patients who exceeded this score. Surgery was then started 15 min after study drug infusion in patients with OAA/S score of ≤ 4. The primary endpoint was the percentage of patients not requiring rescue propofol to achieve and maintain an OAA/S score of ≤ 4. RESULTS: Of the 120 enrolled and randomized patients, 119 were treated the study: 22 received placebo and 97 received dexmedetomidine (23-25 patients per dose). Significantly more patients did not require propofol in the dexmedetomidine 0.5 and 1.0 µg/kg groups (68.0% and 80.0%, respectively) compared to the placebo group (22.7%) (P = 0.003 and P < 0.001, respectively). Common adverse events (AEs) were protocol-defined respiratory depression, bradycardia and hypotension. There was no significant difference in the incidence of AEs between the dexmedetomidine and the placebo groups. CONCLUSION: We concluded that loading doses of 0.5 and 1.0 µg/kg dexmedetomidine, followed by an infusion at a rate of 0.2-0.7 µg/kg/h, provide effective and well-tolerated sedation for surgical patients during epidural or spinal anesthesia.Clinical trials.gov identifier: NCT01438957.

Worse ECOG-PS Is Associated with Increased 30-Day Mortality among Adults Older than 90 Years Undergoing Non-Cardiac Surgery: A Single-Center Retrospective Study.

BACKGROUND: A growing number of older patients are undergoing surgeries. However, reliable preoperative predictors of surgical mortality among older patients have not been identified. This study compared predictive factors for 30-day survival in patients older than 90 years after non-cardiac surgery. METHODS: This retrospective study at Nippon Medical School Hospital investigated the records of patients aged >90 years who underwent non-cardiac surgeries between 2010 and 2020. The data collected included age, gender, American Society of Anesthesiologists physical status (ASA-PS), preoperative Charlson score, preoperative fall risk assessment, Eastern Cooperative Oncology Group performance status (ECOG-PS), modified 5-item frailty index (mFI-5), need for intraoperative transfusion, postoperative complications, and 30-day survival after surgery. RESULTS: A total of 327 cases of elective surgery and 149 cases of emergency surgery were examined. Nonsurvivors (n=20, 4.2%) had significantly worse preoperative ASA-PS (for emergency cases) (nonsurvivors vs. survivors, 2.8 [2-3] vs. 2.3 [1-4], p=0.045), ECOG-PS (3.0 [2-4] vs. 1.0 [0-4], p<0.001), and mFI-5 values (3.0 [1-4] vs. 1.0 [0-3], p<0.001), more emergency cases (75.0% vs. 36.2%, p=0.004), and a greater need for intraoperative transfusion (55.0% vs. 13.4%, p<0.001). Among frailty assessment methods, ECOG-PS was the most strongly associated with 30-day mortality (area under the curve, ECOG-PS: 0.98, p<0.001; mFI-5: 0.86, p<0.001; Charlson score: 0.53, p=0.71; fall risk assessment: 0.55, p=0.44). Kaplan-Maier curves and multivariate logistic regression analysis demonstrated that an ECOG-PS of >3 was significantly associated with 30-day mortality (ECOG-PS: Kaplan-Maier curve, p<0.001, Log-rank test; odds ratio 1.71, 95% confidence interval: 1.35-2.16, p<0.001). CONCLUSIONS: An ECOG-PS of >3 was significantly correlated with 30-day mortality after non-cardiac surgery in patients older than 90 years.