Pharmacokinetics of L-theanine and the effect on amino acid composition in mice administered with L-theanine.

L-theanine, an amino acid component of the tea leaves of Camellia sinensis, is sold in Japan as a supplement for good sleep. Although several studies in humans and mice have reported the effects of L-theanine on brain function, only a few reports have comprehensively clarified the disposition of theanine administered to mice and its effects on concentrations of other blood amino acids. In this study, we aimed to determine the changes in the blood levels of L-theanine administered to mice and amino acid composition of the serum. L-theanine were administered to four-week-old Std-ddY male mice orally or via tail vein injection. L-theanine and other amino acids in serum prepared from blood collected at different time points post-dose were labeled with phenylisothiocyanate and quantified. The serum concentration of orally administered L-theanine peaked 15 min after administration. The area under the curve for tail vein injection revealed the bioavailability of L- theanine to be approximately 70%. L-theanine administration did not affect any amino acid levels in the serum, but a significant increase in the peak area overlapping the Glycine (Gly) peak was observed 30 min after administration. L-theanine administered to mice was rapidly absorbed and eliminated, suggesting that taking L-theanine as a supplement is safe without affecting its own levels or serum levels of other amino acids. However, considering that Gly, similar to L-theanine, is used as a dietary supplement for its anxiolytic effects and to improve sleep, determining the effects of L-theanine administration on Gly is important and needs further research.

Prophylactic clipping not effective in preventing post-polypectomy bleeding for < 20-mm colon polyps: A multicenter, open-label, randomized controlled trial.

BACKGROUND AND AIM: Prophylactic clipping (PC) after polypectomy has the potential to prevent post-polypectomy bleeding (PPB). We aimed to evaluate the effectiveness of PC in preventing PPB for < 20-mm polyps. METHODS: This multicenter, open-label, randomized controlled trial conducted from December 2013 to June 2017 at 10 institutions randomly assigned 1080 patients with < 20-mm colon polyps to the non-PC and PC groups. Allocation factors were institution, antiplatelet drug use, and polyp number. The primary endpoint was differences in PPB rates between the groups. The severity of PPB and post-procedural abdominal symptoms were also investigated. These endpoints in intention-to-treat and per-protocol (PP) analyses were evaluated. RESULTS: We investigated 1039 patients with 2960 lesions. There was no significant difference between the groups in characteristics including age, sex, hypertension, diabetes, hyperlipidemia, antiplatelet drug use, and lesion characteristics such as type and size. Excluding the clip used in the non-PC group, intraoperative bleeding, and deviation of protocol, 903 patients were investigated in PP analysis. There was no significant difference in the PPB rate between the non-PC and PC groups (2.7% vs 2.3%, P = 0.6973 [intention-to-treat analysis]; 3.0 vs 2.4%, P = 0.7353 [PP analysis]). Severe PPB (≥ grade 3) was similar between the groups. Total procedure time was significantly shorter in the non-PC group than in the PC group (31 vs 36 min, P = 0.0002). Post-procedural abdominal fullness was less common in the non-PC group than in the PC group (20.8% vs 25.6%, P = 0.0833). CONCLUSION: Prophylactic clipping is not effective in preventing PBB for < 20-mm colon polyps (UMIN000012163).

Changes in stroke volume induced by lung recruitment maneuver can predict fluid responsiveness during intraoperative lung-protective ventilation in prone position.

BACKGROUND: The present study aimed to evaluate the reliability of hemodynamic changes induced by lung recruitment maneuver (LRM) in predicting stroke volume (SV) increase after fluid loading (FL) in prone position. METHODS: Thirty patients undergoing spine surgery in prone position were enrolled. Lung-protective ventilation (tidal volume, 6-7 mL/kg; positive end-expiratory pressure, 5 cmH2O) was provided to all patients. LRM (30 cmH2O for 30 s) was performed. Hemodynamic variables including mean arterial pressure (MAP), heart rate, SV, SV variation (SVV), and pulse pressure variation (PPV) were simultaneously recorded before, during, and at 5 min after LRM and after FL (250 mL in 10 min). Receiver operating characteristic curves were generated to evaluate the predictability of SVV, PPV, and SV decrease by LRM (ΔSVLRM) for SV responders (SV increase after FL > 10%). The gray zone approach was applied for ΔSVLRM. RESULTS: Areas under the curve (AUCs) for ΔSVLRM, SVV, and PPV to predict SV responders were 0.778 (95% confidence interval: 0.590-0.909), 0.563 (0.371-0.743), and 0.502 (0.315-0.689), respectively. The optimal threshold for ΔSVLRM was 30% (sensitivity, 92.3%; specificity, 70.6%). With the gray zone approach, the inconclusive values ranged 25 to 75% for ΔSVLRM (including 50% of enrolled patients). CONCLUSION: In prone position, LRM-induced SV decrease predicted SV increase after FL with higher reliability than traditional dynamic indices. On the other hand, considering the relatively large gray zone in this study, future research is needed to further improve the clinical significance. TRIAL REGISTRATION: UMIN Clinical Trial Registry UMIN000027966 . Registered 28th June 2017.

Effect of Systemic Vascular Resistance on the Reliability of Noninvasive Hemodynamic Monitoring in Cardiac Surgery.

OBJECTIVE: To assess the effect of systemic vascular resistance (SVR) on the reliability of the ClearSight system (Edwards Lifesciences, Irvine, CA) for measuring blood pressure (BP) and cardiac output (CO). DESIGN: Observational study. SETTING: University hospital. PARTICIPANTS: Twenty-five patients undergoing cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: BP, measured using ClearSight and an arterial line, and CO, measured using ClearSight and a pulmonary artery catheter, were recorded before (T1) and two minutes after phenylephrine or ephedrine administration. Bland-Altman analysis was used to compare BP and CO measurements at T1. A polar plot was used to assess trending abilities. Patients were divided into the following three groups according to the SVR index (SVRI) at T1: low (<1,200 dyne s/cm5/m2), normal (1,200-25,00 dyne s/cm5/m2), and high (>2,500 dyne s/cm5/m2). The bias in BP and CO was -4.8 ± 8.9 mmHg and 0.10 ± 0.81 L/min, respectively, which was correlated significantly with SVRI (p < 0.05). The percentage error in CO was 40.6%, which was lower in the normal SVRI group (33.3%) than the low and high groups (46.3% and 47.7%, respectively). The angular concordance rate was 96.3% and 95.4% for BP and 87.0% and 92.5% for CO after phenylephrine and ephedrine administration, respectively. There was a low tracking ability for CO changes after phenylephrine administration in the low-SVRI group (angular concordance rate 33.3%). CONCLUSION: The ClearSight system showed an acceptable accuracy in measuring BP and tracking BP changes in various SVR states; however, the accuracy of CO measurement and its trending ability in various SVR states was poor.

Endoscopic alterations in Peyer's patches in patients with ulcerative colitis: A prospective, multicenter study.

BACKGROUND AND AIM: Peyer's patches (PPs) play a major role in intestinal mucosal immunity; however, their role in ulcerative colitis (UC) is not well investigated. We evaluated endoscopic features of PPs on narrow-band imaging with magnifying endoscopy (NBI-ME) and investigated their association with clinical factors. METHODS: We prospectively recruited 105 patients with UC, 18 with Crohn's disease, 16 with disease control, and 33 healthy control subjects at three institutions from 2014 to 2017. NBI-ME images of the villi of PPs were evaluated according to the Villi Index, and patients were divided into the Villi Index low (L) and high (H) types. The 1-year sustained clinical remission rate was evaluated between L-type and H-type PPs in patients with UC. RESULTS: The proportions of patients with H-type PPs were significantly higher among UC, Crohn's disease, and disease control patients than among healthy control patients (P = 0.0125, 0.018, 0.0007). In UC, age, gender, endoscopic score, and extent of disease involvement were not significantly different between L-type and H-type PPs, whereas the sustained clinical remission rate was significantly higher in L-type PPs than in H-type PPs (88% [57/65] vs 65% [17/26], P = 0.019). Multivariate analysis revealed that the L type of PPs was a significant factor for sustained clinical remission (odds ratio 3.8, 95% confidence interval 1.1-12.9, P = 0.033). CONCLUSIONS: Patients with UC showed endoscopic alterations in PPs on NBI-ME, and highly altered appearance of PPs can be associated with a high risk of clinical relapse in patients with UC.

Impact of intraoperative goal-directed fluid therapy on major morbidity and mortality after transthoracic oesophagectomy: a multicentre, randomised controlled trial.

BACKGROUND: Transthoracic oesophagectomy is associated with major morbidity and mortality, which may be reduced by goal-directed therapy (GDT). The aim of this multicentre, RCT was to evaluate the impact of intraoperative GDT on major morbidity and mortality in patients undergoing transthoracic oesophagectomy. METHODS: Adult patients undergoing transthoracic oesophagectomy were randomised to receive either minimally invasive intraoperative GDT (stroke volume variation <8%, plus systolic BP maintained >90 mm Hg by pressors as necessary) or haemodynamic management left to the discretion of attending senior anaesthetists (control group; systolic BP >90 mm Hg alone). The primary outcome was the incidence of death or major complications (reoperation for bleeding, anastomotic leakage, pneumonia, reintubation, >48 h ventilation). A Cox proportional hazard model was used to examine whether the effects of GDT on morbidity and mortality were independent of other potential confounders. RESULTS: A total of 232 patients (80.6% male; age range: 36-83 yr) were randomised to either GDT (n=115) or to the control group (n=117). After surgery, major morbidity and mortality were less frequent in 22/115 (19.1%) subjects randomised to GDT, compared with 41/117 (35.0%) subjects assigned to the control group {absolute risk reduction: 15.9% (95% confidence interval [CI]: 4.7-27.2%); P=0.006}. GDT was also associated with fewer episodes of atrial fibrillation (odds ratio [OR]: 0.18 [95% CI: 0.05-0.65]), respiratory failure (OR: 0.27 [95% CI: 0.09-0.83]), use of mini-tracheotomy (OR: 0.29 [95% CI: 0.10-0.81]), and readmission to ICU (OR: 0.09 [95% CI: 0.01-0.67]). GDT was independently associated with morbidity and mortality (hazard ratio: 0.51 [95% CI: 0.30-0.87]; P=0.013). CONCLUSIONS: Intraoperative GDT may reduce major morbidity and mortality, and shorten hospital stay, after transthoracic oesophagectomy. CLINICAL TRIAL REGISTRATION: UMIN000018705.

Impact of deep breathing on predictability of stroke volume variation in spontaneous breathing patients.

BACKGROUND: This study investigated the ability of stroke volume variation (SVV) during deep breathing to discriminate fluid responders among spontaneously breathing patients. METHODS: Thirty patients undergoing general anaesthesia were enrolled and assessed before anaesthetic induction. Haemodynamic variables, including stroke volume (SV) and SVV, were measured using the ClearSight system during normal breathing. After these measurements, each patient was required to maintain deep breathing (6 breaths min-1 ) and haemodynamic variables were recorded. Then, the table was adjusted to the Trendelenburg position (15°) for 2 minutes, and haemodynamic variables were measured. Receiver operating characteristic curves were created for SVV during normal and deep breathing, and the difference in SVV between normal and deep breathing (ΔSVV) to discriminate fluid responders (SV increase >10% after changing position). The correlation between SV increase and ΔSVV was examined using Pearson's correlation coefficient. The grey zone approach was used to assess the inconclusive range of the haemodynamic variables. RESULTS: Receiver operating characteristic curve analysis indicated that ΔSVV showed good reliability in predicting fluid responsiveness (AUC: 0.850; 95% CI: 0.672-0.953; threshold: 4%, sensitivity: 75.0%, specificity: 88.9%], while SVV during normal breathing did not (AUC: 0.579; 95% CI: 0.386-0.756)]. Although SVV during deep breathing exhibited acceptable predictability (AUC: 0.778; 95% CI: 0.589-0.908), the sensitivity was not good (58.3%). With the grey zone approach, the inconclusive range of ΔSVV was small with the range of 1.4%-4.2% (23% of patients). CONCLUSION: Deep breathing could improve the reliability of dynamic indices in spontaneously breathing patients. TRIAL REGISTRATION: UMIN-CTR, identifer: UMIN000027970. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000032040.

Comparison of the venous-arterial CO2 to arterial-venous O2 content difference ratio with the venous-arterial CO2 gradient for the predictability of adverse outcomes after cardiac surgery.

This study aimed to compare the prognostic performance of the ratio of mixed and central venous-arterial CO2 tension difference to arterial-venous O2 content difference (Pv-aCO2/Ca-vO2 and Pcv-aCO2/Ca-cvO2, respectively) with that of the mixed and central venous-to-arterial carbon dioxide gradient (Pv-aCO2 and Pcv-aCO2, respectively) for adverse events after cardiac surgery. One hundred and ten patients undergoing cardiac surgery with cardiopulmonary bypass were enrolled. After catheter insertion, three blood samples were withdrawn simultaneously through arterial pressure, central venous, and pulmonary artery catheters, before and at the end of the operation, and preoperative and postoperative values were determined. The primary end-point was set as the incidence of postoperative major organ morbidity and mortality (MOMM). Receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were performed to evaluate the prognostic reliability of Pv-aCO2, Pcv-aCO2, Pv-aCO2/Ca-vO2, and Pcv-aCO2/Ca-cvO2 for MOMM. MOMM events occurred in 25 patients (22.7%). ROC curve analysis revealed that both postoperative Pv-aCO2/Ca-vO2 and Pcv-aCO2/Ca-cvO2 were significant predictors of MOMM. However, postoperative Pv-aCO2 was the best predictor of MOMM (area under the curve [AUC]: 0.804; 95% confidence interval [CI] 0.688-0.921), at a 5.1-mmHg cut-off, sensitivity was 76.0%, and specificity was 74.1%. Multivariate analysis revealed that postoperative Pv-aCO2 was an independent predictor of MOMM (odds ratio [OR]: 1.42, 95% CI 1.01-2.00, p = 0.046) and prolonged ICU stay (OR: 1.45, 95% CI 1.05-2.01, p = 0.024). Pv-aCO2 at the end of cardiac surgery was a better predictor of postoperative complications than Pv-aCO2/Ca-vO2 and Pcv-aCO2/Ca-cvO2.

Tumor suppressor KIF1Bß regulates mitochondrial apoptosis in collaboration with YME1L1.

KIF1Bß, a member of the kinesin superfamily of motor proteins, is a haploinsufficient tumor suppressor mapped to chromosome 1p36.2, which is frequently deleted in neural crest-derived tumors, including neuroblastoma and pheochromocytoma. While KIF1Bß acts downstream of the nerve growth factor (NGF) pathway to induce apoptosis, further molecular functions of this gene product have largely been unexplored. In this study, we report that KIF1Bß destabilizes the morphological structure of mitochondria, which is critical for cell survival and apoptosis. We identified YME1L1, a mitochondrial metalloprotease responsible for the cleavage of the mitochondrial GTPase OPA1, as a physical interacting partner of KIF1Bß. KIF1Bß interacted with YME1L1 through its death-inducing region, as initiated the protease activity of YME1L1 to cleave the long forms of OPA1, resulting in mitochondrial fragmentation. Overexpression of YME1L1 promoted apoptosis, while knockdown of YME1L1 promoted cell growth. High YME1L1 expression was significantly associated with a better prognosis in neuroblastoma. Furthermore, in NGF-deprived PC12 cells, KIF1Bß and YME1L1 were upregulated, accompanied by mitochondrial fragmentation and apoptotic cell death. Small interfering RNA-mediated knockdown of either protein alone, however, remarkably inhibited the NGF depletion-induced apoptosis. Our findings indicate that tumor suppressor KIF1Bß plays an important role in intrinsic mitochondria-mediated apoptosis through the regulation of structural and functional dynamics of mitochondria in collaboration with YME1L1. Dysfunction of the KIF1Bß/YME1L1/OPA1 mechanism may be involved in malignant biological features of neural crest-derived tumors as well as the initiation and progression of neurodegenerative diseases.

Usefulness of intestinal real-time virtual sonography in patients with inflammatory bowel disease.

BACKGROUND AND AIM: Transabdominal ultrasonography (US) examination for the intestine is often difficult, and its precedence for intestinal examination depends on accessibility to experienced ultrasonographers. Real-time virtual sonography (RVS) assists examination of US as a fusion method by synchronizing US images with pre-captured computed tomography or magnetic resonance images. We aimed to evaluate the feasibility to use RVS for the examination of the intestine. METHODS: The time to scan three parts of the intestine was compared between conventional US and RVS in seven participants without intestinal diseases. Whether RVS accurately synchronized US images with reference images of intestinal target lesions was judged in 20 patients with inflammatory bowel disease. RESULTS: Examination time to scan the ascending colon and the ileocecum using intestinal RVS was significantly shorter than that using conventional US alone (36.7 vs 50.0 s [P = 0.0313] and 35.4 vs 66.4 s [P = 0.0156], respectively) in participants without intestinal diseases. Well-synchronized US images of the intestinal lesions, such as stenosis, with reference computed tomography/magnetic resonance images were obtained by RVS in all the lesions in the fixed parts of the colon (ascending and descending colon), and images of nine lesions in 12 lesions (75%) were well synchronized in the unfixed part of the intestine in Crohn's disease patients. CONCLUSION: Real-time virtual sonography significantly reduced the examination time of intestinal US. Intestinal RVS can help the ultrasonographer to guide the US probe to detect and monitor intestinal lesions by synchronizing reference images, especially in inflammatory bowel disease patients (UMIN Clinical Trials Registry number: UMIN000011571).

The Sum of Early Diastolic Annulus Velocities in the Mitral and Tricuspid Valve Can Predict Adverse Events After Cardiac Surgery.

OBJECTIVES: To assess whether a tissue Doppler imaging (TDI)-based parameter consisting of the sum of early diastolic velocities of the mitral annulus (Me') and tricuspid annulus (Te') can serve as a predictor of adverse outcomes after cardiac surgery. DESIGN: Prospective, observational study. SETTING: University hospital. PARTICIPANTS: The study comprised 100 patients undergoing cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After anesthetic induction, transesophageal echocardiography was performed to obtain the values of the early transmitral flow velocity (E), Me', and Te'. The primary endpoint was the incidence of postoperative major organ morbidity and mortality (MOMM) events, including death, redo surgery, prolonged ventilation, stroke, sternal infection, and dialysis. Receiver operating characteristic and multivariate logistic analyses were used to examine the prognostic performance of TDI-based parameters for predicting MOMM incidence. The secondary endpoint was the incidence of death or rehospitalization for cardiovascular disease within 1 year post-discharge. TDI-based parameters were measured in 87 of the 100 patients enrolled. Me' plus Te' had better prognostic ability (area under the curve 0.771; threshold 13 cm/s; sensitivity 86.7%; specificity 64.9%) than that of Me' or E to Me' (E/Me')% and was an independent predictor of MOMM (odds ratio 0.45; 95% confidence interval 0.28-0.74, p = 0.001), whereas Me' was not. Lower Me' plus Te' (≤13 cm/s) was associated with a significantly higher incidence and earlier onset of cardiovascular events within 1 year post-discharge (p = 0.012). CONCLUSIONS: Compared with Me' and E/Me', which traditionally are used for assessing diastolic function, Me' plus Te' showed better prognostic ability for both short- and long-term outcomes of cardiac surgery.

Long-term efficacy of comprehensive multidisciplinary antibiotic stewardship programs centered on weekly prospective audit and feedback.

OBJECTIVE: To evaluate the long-term effects of comprehensive antibiotic stewardship programs (ASPs) on antibiotic use, antimicrobial-resistant bacteria, and clinical outcomes. DESIGN: Before-after study. SETTING: National university hospital with 934 beds. INTERVENTION: Implementation in March 2010 of a comprehensive ASPs including, among other strategies, weekly prospective audit and feedback with multidisciplinary collaboration. METHODS: The primary outcome was the use of antipseudomonal antibiotics as measured by the monthly mean days of therapy per 1000 patient days each year. Secondary outcomes included overall antibiotic use and that of each antibiotic class, susceptibility of Pseudomonas aeruginosa, the proportion of patients isolated methicillin-resistant Staphylococcus aureus (MRSA) among all patients isolated S. aureus, the incidence of MRSA, and the 30-day mortality attributable to bacteremia. RESULTS: The mean monthly use of antipseudomonal antibiotics significantly decreased in 2011 and after as compared with 2009. Susceptibility to levofloxacin was significantly increased from 2009 to 2016 (P = 0.01 for trend). Its susceptibility to other antibiotics remained over 84% and did not change significantly during the study period. The proportion of patients isolated MRSA and the incidence of MRSA decreased significantly from 2009 to 2016 (P < 0.001 and = 0.02 for trend, respectively). There were no significant changes in the 30-day mortality attributable to bacteremia during the study period (P = 0.57 for trend). CONCLUSION: The comprehensive ASPs had long-term efficacy for reducing the use of the targeted broad-spectrum antibiotics, maintaining the antibiotic susceptibility of P. aeruginosa, and decreasing the prevalence of MRSA, without adversely affecting clinical outcome.

Incidence of gastric adenocarcinoma among lesions diagnosed as low-grade adenoma/dysplasia on endoscopic biopsy: A multicenter, prospective, observational study.

BACKGROUND AND AIM: Differentiation between gastric adenocarcinoma and low-grade adenoma/dysplasia (LGA) on endoscopic forceps biopsy is difficult. We aim to clarify the incidence of carcinoma in specimens, obtained by endoscopic resection (ER), from cases that had been diagnosed as LGA (Vienna category 3) on endoscopic biopsy. METHODS: In this multicenter, prospective, observational study, patients with gastric adenoma (Vienna category 3 or 4.1) diagnosed on endoscopic forceps biopsy were enrolled. All the specimens were subjected to histopathological central review. Primary endpoint was the incidence of carcinoma (Vienna category 4.2 or over) among the biopsy-proven gastric LGA. Secondary endpoints were the histological findings of resected specimens, clinicopathological features of carcinoma, and short-term outcomes of all ER cases. RESULTS: Ninety-five patients with 104 lesions diagnosed as gastric adenoma were enrolled. After central review of the biopsy specimens, 47 lesions were diagnosed as LGA and seven lesions (15%) as adenocarcinoma (95% confidence interval, 7.6-28%). Carcinoma was detected in lesions that had a minimum size of 6 mm; the incidence of carcinoma was higher in the larger lesions. There was a histological discrepancy between biopsy and ER material in more than 60% of the cases. CONCLUSIONS: A substantial proportion of biopsy-proven gastric LGA specimens were diagnosed as adenocarcinoma after ER. This indicated histological discrepancy between biopsy-proven gastric LGA and histology of the resected material.

Impact of continuous non-invasive blood pressure monitoring on hemodynamic fluctuation during general anesthesia: a randomized controlled study.

This study assessed the ability of a continuous non-invasive blood pressure (BP) monitoring system to reduce intra-anesthetic hemodynamic fluctuation compared with intermittent BP cuff measurement. Forty patients undergoing total knee arthroplasty under general anesthesia were enrolled and randomly divided into two groups (Control and CS group). BP management was performed using the same protocol with BP measured by intermittent BP cuff in the Control and that by continuous non-invasive BP monitoring in the CS group. We assessed the accuracy and precision of the continuous non-invasive BP monitoring compared with BP cuff measurement using Bland-Altman, four-quadrant plot, and polar-plot analyses. Additionally, the occurrence of hypotension and hypertention during general anesthesia was compared between the two groups. The continuous non-invasive BP monitoring showed excellent accuracy of - 1.1 ± 8.1 mmHg during surgery and an acceptable trending ability with a concordance rate of 95.1% according to the four-quadrant plot analysis and an angular concordance rate of 86.7% by polar-plot analysis. Hypotension was less common in the CS group during induction of anesthesia (p = 0.002) and surgery (p = 0.008). Hypertension occurred more frequently in the Control group during emergence from anesthesia (p = 0.037). The duration of hemodynamic stability (systolic BP 80-110% of baseline) intraoperatively was longer in the CS group than in the Control group (87.7 vs. 61.9%; p < 0.001). Accuracy and trending ability of the continuous non-invasive BP monitoring was clinically acceptable, and lead to hemodynamic stability and reduction of intra-anesthetic hypotension and hypertension intraoperatively.

Pre-anesthetic stroke volume variation can predict cardiac output decrease and hypotension during induction of general anesthesia.

This study aimed to assess the reliability of stroke volume variation (SVV) in predicting cardiac output (CO) decrease and hypotension during induction of general anesthesia. Forty-five patients undergoing abdominal surgery under general anesthesia were enrolled. Before induction of anesthesia, patients were required to maintain deep breathing (6-8 times/min), and pre-anesthetic SVV was measured for 1 min by electrical cardiometry. General anesthesia was induced with propofol, remifentanil, rocuronium, and sevoflurane. Study duration was defined from the start of fluid administration till 5 min after tracheal intubation. Blood pressure (BP) was measured every minute. Cardiac output was measured continuously by electrical cardiometry. Receiver operating characteristics (ROC) curves were made regarding the incidence of decreased CO (less than 70% of the baseline) and hypotension (mean BP <65 mmHg). The risk of developing decreased CO and hypotension was evaluated by multivariate logistic regression analysis. The time from the start of the procedure to onset of decreased CO was analyzed by the Kaplan-Meier method. The area under the ROC curve and optimal threshold value of pre-anesthetic SVV for predicting decreased CO and hypotension were 0.857 and 0.693. Patients with lower SVV exhibited a significantly slower onset and lower incidence of decreased CO than those with higher SVV (p = 0.003). Multivariate logistic regression analysis indicated high pre-anesthetic SVV as being an independent risk factor for decreased CO and hypotension (odds ratio, 1.43 and 1.16, respectively). In conclusions, pre-anesthetic SVV can predict incidence of decreased CO and hypotension during induction of general anesthesia.

Impact of non-invasive continuous blood pressure monitoring on maternal hypotension during cesarean delivery: a randomized-controlled study.

PURPOSE: This study aimed to investigate the efficacy of the ClearSight™ system (Edwards Lifesciences, Irvine, CA) for reducing the incidence of hypotension compared with the traditional oscillometric blood pressure monitoring in cesarean delivery under spinal anesthesia. METHODS: Forty patients undergoing cesarean delivery under spinal anesthesia were enrolled. The patients were randomly divided into two groups (Control and ClearSight groups). All patients received spinal anesthesia using 0.5% hyperbaric bupivacaine (11.5 mg) and fentanyl (10 µg). Blood pressure was managed with the same protocol using the ClearSight™ system (ClearSight group) and oscillometric blood pressure monitoring (Control group). Furthermore, we compared the accuracy of the ClearSight™ system with the traditional oscillometric monitoring for blood pressure measurement using Bland-Altman, four-quadrant plot, and polar plot analyses. RESULTS: The incidence of hypotension was significantly lower in the ClearSight group from induction to delivery (45% vs. 0%, p < 0.001) and to the end of surgery (50% vs. 20%, p = 0.049). Intraoperative nausea occurred more frequently in the Control group (45% vs. 10%, p = 0.012). The ClearSight™ system demonstrated acceptable accuracy with a bias of - 4.3 ± 11.7 mmHg throughout the procedure. Four-quadrant analysis revealed an excellent trending ability of the ClearSight™ system with a concordance rate of approximately 95%. In the polar plot analysis, the angular bias and concordance rate were - 13.5° ± 19.0° and 76.9%, respectively. CONCLUSIONS: The accuracy and trending ability of the ClearSight™ system for blood pressure measurement was clinically acceptable in cesarean delivery under spinal anesthesia, leading to reductions in maternal hypotension and nausea.

Transcutaneous near-infrared spectroscopy for monitoring spinal cord ischemia: an experimental study in swine.

We aimed to assess the ability of near-infrared spectroscopy (NIRS) to detect spinal cord ischemia, and to evaluate changes in regional oxygen saturation (rSO2) following recovery of spinal cord circulation and cerebrospinal fluid drainage. Four 12-month-old female swine weighing 28.7-29.5 kg were acquired for this study. NIRS probes were placed along the midline of the upper (T6/7) and lower (T9/T10) thoracic vertebrae. The thoracic aorta was clamped distal of the left subclavian artery to induce spinal ischemia. Aortic cross-clamping was maintained for 30 min. Fifteen minutes after aortic de-clamping, the cerebrospinal fluid drainage catheter was opened to air, and cerebrospinal fluid drainage was initiated. Following aortic clamping, rSO2 in both upper and lower regions of the spinal cord decreased by 15 % within 5 min and by 20 % within 10 min (relative change). After aortic de-clamping, rSO2 values in both regions returned to baseline within 5 min. No changes in rSO2 in either the upper or lower vertebrae were observed following initiation of cerebrospinal fluid drainage. Histological analysis revealed that ischemic changes had occurred in all spinal levels. NIRS may be used to detect decreases in and recovery of spinal cord circulation following aortic clamping and de-clamping, whereas it may not reflect minor changes in spinal cord circulation due to cerebrospinal fluid drainage. Further clinical studies are required to investigate the potential for NIRS as an index of spinal cord circulation.

Hydroxyethyl starch 130/0.4 versus crystalloid co-loading during general anesthesia induction: a randomized controlled trial.

PURPOSE: Hypotension and decreased cardiac output (CO) are common adverse effects during anesthesia induction depending on the patient's pre-anesthetic cardiac condition. The aim of this study was to assess the ability of hydroxyethyl starch (HES) 130/0.4 to prevent hypotension and decreased CO during the induction of general anesthesia. METHODS: Ninety patients undergoing laparoscopic surgery were randomly divided into a HES group and a crystalloid group. Following the insertion of an intravenous line, fluid was administered to each patient at a rate of 25 ml/min using either crystalloid or HES 130/0.4. Five minutes after the initiation of fluid loading, anesthesia was induced using propofol (1.5 mg/kg), rocuronium (0.9 mg/kg), and remifentanil (0.3 mcg/kg/min). Tracheal intubation was performed 5 min after the induction of anesthesia. Following tracheal intubation, general anesthesia was maintained using remifentanil and sevoflurane. Non-invasive blood pressure (BP) level was measured at 1-min intervals and CO was measured continuously using electrical cardiometry from the start of fluid loading until 5 min after tracheal intubation. RESULTS: The number of patients with hypotension (systolic BP < 90 mmHg or 80% of baseline) was significantly lower in the HES group (p < 0.001) than in the crystalloid group. Patients in the HES group showed smaller CO decreases than did patients in the crystalloid group (p < 0.001). The Kaplan-Meier method showed a lower incidence and significantly slower onset of hypotension in the HES group (p = 0.009). Multivariate logistic regression models indicated that the use of HES is an independent factor for the prevention of both hypotension and decreased CO (below 85% of baseline; p < 0.005 for both). CONCLUSIONS: Co-loading using HES 130/0.4 prevented hypotension and decreased CO during general anesthesia induction.

Hemodynamic monitoring and management in high-risk surgery: a survey among Japanese anesthesiologists.

The aim of this study was to assess the current practices of hemodynamic management in high-risk surgical patients among Japanese anesthesiologists. An invitation letter to the survey, which included 35 questions related to hemodynamic monitoring in high-risk surgery, was mailed to every hospital approved by the Japanese Society of Anesthesiologists (JSA) (1260 hospitals). Of the 692 JSA respondents, 573 completed the survey. Despite reporting a high rate of cardiac output (CO) and stroke volume variation (SVV) monitoring in JSA members (70 and 74 %, respectively), fluid goal-directed therapy was poorly implemented in high-risk surgery (7.4 %). Also, 47 % of the JSA respondents did not consistently perform CO optimization. SVV was more commonly used (76 %) as an indicator of volume expansion among JSA respondents, while central venous pressure was less frequently used (48 %). Despite a broader use of advanced hemodynamic monitoring, optimization of CO is still poorly protocolized and applied in Japan. The development of guidelines and protocols for hemodynamic management, including the establishment of strong evidence aimed at improving clinical outcomes, is needed to assist anesthesiologists in more universal adoption of perioperative CO optimization.

Amelioration of small bowel injury by switching from nonselective nonsteroidal anti-inflammatory drugs to celecoxib in rheumatoid arthritis patients: a pilot study.

BACKGROUND/AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in patients with rheumatoid arthritis (RA) but have several side effects including mucosal damage in the small intestine. We aimed to evaluate whether the small bowel injury is ameliorated by switching from nonselective NSAIDs to celecoxib in patients with RA. METHODS: Sixteen patients with RA who were treated with nonselective NSAIDs were enrolled in this study. Nonselective NSAIDs were converted to celecoxib for 12 weeks. Capsule endoscopy was performed before and after treatment with celecoxib. Videos were screened by gastroenterologists blinded to the patients' treatment. RESULTS: Before the administration of celecoxib, reddened folds, denuded areas, petechiae/red spots and mucosal breaks were observed in 63, 63, 88 and 69% of the patients, respectively. In the 14 patients who completed this study, conversion to celecoxib significantly reduced the number of petechiae/red spots, the number of mucosal breaks, and Lewis scores. RA activity and cytokine levels in the peripheral blood were not significantly different before and after treatment with celecoxib. CONCLUSIONS: The incidence of small bowel injury by nonselective NSAIDs is high in patients with RA. Conversion from nonselective NSAIDs to celecoxib can be useful for protecting patients with RA from small bowel injury.