Displaying publications 41 - 60 of 90 in total

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  1. Kong APS, Lim S, Yoo SH, Ji L, Chen L, Bao Y, et al.
    Diabetes Res Clin Pract, 2023 Jul;201:110718.
    PMID: 37196707 DOI: 10.1016/j.diabres.2023.110718
    Glucose monitoring has evolved from self-monitoring of blood glucose to glycated hemoglobin, and the latest continuous glucose monitoring (CGM). A key challenge to adoption of CGM for management of diabetes in Asia is the lack of regional CGM recommendations. Hence, thirteen diabetes-specialists from eight Asia-Pacific (APAC) countries/regions convened to formulate evidence-based, APAC-specific CGM recommendations for individuals with diabetes. We defined CGM metrics/targets and developed 13 guiding-statements on use of CGM in: (1) people with diabetes on intensive insulin therapy, and (2) people with type 2 diabetes on basal insulin with/without glucose lowering drugs. Continual use of CGM is recommended in individuals with diabetes on intensive insulin therapy and suboptimal glycemic control, or at high risk of problematic hypoglycemia. Continual/intermittent CGM may also be considered in individuals with type 2 diabetes on basal insulin regimen and with suboptimal glycemic control. In this paper, we provided guidance for optimizing CGM in special populations/situations, including elderly, pregnancy, Ramadan-fasting, newly diagnosed type 1 diabetes, and comorbid renal disease. Statements on remote CGM, and stepwise interpretation of CGM data were also developed. Two Delphi surveys were conducted to rate the agreement on statements. The current APAC-specific CGM recommendations provide useful guidance for optimizing use of CGM in the region.
  2. Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.
    Autophagy, 2021 Jan;17(1):1-382.
    PMID: 33634751 DOI: 10.1080/15548627.2020.1797280
    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
  3. Xiang YT, Dickerson F, Kreyenbuhl J, Ungvari GS, Wang CY, Si TM, et al.
    Int Psychogeriatr, 2012 Jun;24(6):1002-8.
    PMID: 22300452 DOI: 10.1017/S1041610211002791
    This study examined the use of low doses of antipsychotic medications (300 mg/day CPZeq or less) in older Asian patients with schizophrenia and its demographic and clinical correlates.
  4. Xiang YT, Kreyenbuhl J, Dickerson FB, Ungvari GS, Wang CY, Si TM, et al.
    Aust N Z J Psychiatry, 2012 Dec;46(12):1159-64.
    PMID: 22790175 DOI: 10.1177/0004867412453625
    This study examined the prescribing patterns of several first- (FGAs) and second-generation antipsychotic (SGAs) medications administered to older Asian patients with schizophrenia during the period between 2001 and 2009.
  5. Xiang YT, Kreyenbuhl J, Dickerson FB, Ungvari GS, Wang CY, Si TM, et al.
    Int J Clin Pharmacol Ther, 2012 Jul;50(7):500-4.
    PMID: 22541750 DOI: 10.5414/CP201683
    This study surveyed the prescribing patterns of antipsychotic medications in Asian older schizophrenia patients with extrapyramidal side effects (EPS) during the period between 2001 and 2009.
  6. Xiang YT, Ungvari GS, Correll CU, Chiu HF, Lai KY, Wang CY, et al.
    Psychiatry Clin Neurosci, 2015 Aug;69(8):489-96.
    PMID: 25708964 DOI: 10.1111/pcn.12283
    Little is known about electroconvulsive therapy (ECT) use in Asian inpatients with schizophrenia. This study examined trends of ECT use for schizophrenia patients in Asia between 2001 and 2009 and its independent demographic and clinical correlates.
  7. Wang CY, Chiu CL, Har KO, Chan C, Rahman ZA
    Int J Oral Maxillofac Surg, 2002 Oct;31(5):506-10.
    PMID: 12418566
    This study compares the use of inhalation sedation using sevoflurane (group S) with inhalation sedation using nitrous oxide (group N) in patients undergoing bilateral extraction of third molar teeth under local anaesthesia. The study was designed as a cross-over study. Seventeen ASA I, day surgery patients were studied. Patients were randomly allocated to receive either 8 l/min 50% nitrous oxide in oxygen (group N) or same flow of 1% sevoflurane (group S) for the first procedure. Each patient then had the alternate method of sedation for the second procedure. There were no significant differences between the methods in patient co-operation and surgeon's satisfaction with sedation. Psychomotor tests were comparable in both groups. The patients were significantly more sedated in the group S compared to group N (P=0.004). Significantly more patients complained of an unpleasant odour group S (P<0.01) but none withdrew from the study for this reason. No adverse cardiorespiratory effects resulted from sevoflurane or nitrous oxide sedation. Both methods gave good amnesia during the procedure. There was high acceptance of both methods and the patients rated the technique as equally satisfactory. We conclude that inhalation sedation with sevoflurane is a suitable alternative method to nitrous oxide sedation.
  8. Chan MTV, Wang CY, Seet E, Tam S, Lai HY, Chew EFF, et al.
    JAMA, 2019 May 14;321(18):1788-1798.
    PMID: 31087023 DOI: 10.1001/jama.2019.4783
    IMPORTANCE: Unrecognized obstructive sleep apnea increases cardiovascular risks in the general population, but whether obstructive sleep apnea poses a similar risk in the perioperative period remains uncertain.

    OBJECTIVES: To determine the association between obstructive sleep apnea and 30-day risk of cardiovascular complications after major noncardiac surgery.

    DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study involving adult at-risk patients without prior diagnosis of sleep apnea and undergoing major noncardiac surgery from 8 hospitals in 5 countries between January 2012 and July 2017, with follow-up until August 2017. Postoperative monitoring included nocturnal pulse oximetry and measurement of cardiac troponin concentrations.

    EXPOSURES: Obstructive sleep apnea was classified as mild (respiratory event index [REI] 5-14.9 events/h), moderate (REI 15-30), and severe (REI >30), based on preoperative portable sleep monitoring.

    MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, and stroke within 30 days of surgery. Proportional-hazards analysis was used to determine the association between obstructive sleep apnea and postoperative cardiovascular complications.

    RESULTS: Among a total of 1364 patients recruited for the study, 1218 patients (mean age, 67 [SD, 9] years; 40.2% women) were included in the analyses. At 30 days after surgery, rates of the primary outcome were 30.1% (41/136) for patients with severe OSA, 22.1% (52/235) for patients with moderate OSA, 19.0% (86/452) for patients with mild OSA, and 14.2% (56/395) for patients with no OSA. OSA was associated with higher risk for the primary outcome (adjusted hazard ratio [HR], 1.49 [95% CI, 1.19-2.01]; P = .01); however, the association was significant only among patients with severe OSA (adjusted HR, 2.23 [95% CI, 1.49-3.34]; P = .001) and not among those with moderate OSA (adjusted HR, 1.47 [95% CI, 0.98-2.09]; P = .07) or mild OSA (adjusted HR, 1.36 [95% CI, 0.97-1.91]; P = .08) (P = .01 for interaction). The mean cumulative duration of oxyhemoglobin desaturation less than 80% during the first 3 postoperative nights in patients with cardiovascular complications (23.1 [95% CI, 15.5-27.7] minutes) was longer than in those without (10.2 [95% CI, 7.8-10.9] minutes) (P 

  9. Chung F, Waseem R, Wang CY, Seet E, Suen C, Chan MTV, et al.
    J Clin Anesth, 2022 Feb 04;78:110653.
    PMID: 35131555 DOI: 10.1016/j.jclinane.2022.110653
    STUDY OBJECTIVE: Obstructive sleep apnea (OSA) is known to be associated with postoperative cardiovascular events in patients undergoing major non-cardiac surgery. The objective of the study is to determine whether preoperative oximetry-derived hypoxemia predicts postoperative cardiovascular events in surgical patients with unrecognized obstructive sleep apnea.

    DESIGN AND SETTING: The study was a planned post hoc analyses of a multicenter prospective cohort study.

    PATIENTS: The inclusion criteria were patients ≥45 years old undergoing major non-cardiac surgery with cardiovascular risk factors.

    INTERVENTIONS AND MEASUREMENTS: All patients underwent pre-operative pulse oximetry (PULSOX-300i, Konica-Minolta Sensing, Inc). The severity of OSA was classified based on oxygen desaturation index (ODI) (mild: ≥5 to <15, moderate: ≥15 to <30, and severe OSA: ≥30 events/h). The 30 days cardiovascular events were a composite of myocardial injury, cardiac death, congestive heart failure, thromboembolism, atrial fibrillation, and stroke.

    MAIN RESULTS: For 1218 patients with mild, moderate, or severe OSA (mean age: 67.2 ± 9.3 years; body mass index: 27.0 ± 5.3 kg/m2), the rate of postoperative cardiovascular events was 16.4%, 25.2%, and 29.8% respectively. The multivariable analysis showed that preoperative oxygen desaturation index (ODI) ≥30 events per hour {adjusted hazard ratio (aHR) 1.63 [95% confidence interval (CI): 1.05-2.53]}, and cumulative time spent during sleep with oxygen saturation below 80% (CT80) ≥10 min {aHR 1.79 [95% CI: 1.28-2.50]} were independent predictors of 30-day postoperative cardiovascular events.

    CONCLUSIONS: Preoperative ODI ≥30 events per hour and CT80 ≥ 10 min are associated with increased risk of postoperative cardiovascular events. Preoperative screening using oximetry helps in risk stratification for unrecognized sleep apnea.

    CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01494181.

  10. Sessler DI, Conen D, Leslie K, Yusuf S, Popova E, Graham M, et al.
    Anesthesiology, 2020 04;132(4):692-701.
    PMID: 32022771 DOI: 10.1097/ALN.0000000000003158
    BACKGROUND: The authors previously reported that perioperative aspirin and/or clonidine does not prevent a composite of death or myocardial infarction 30 days after noncardiac surgery. Moreover, aspirin increased the risk of major bleeding and clonidine caused hypotension and bradycardia. Whether these complications produce harm at 1 yr remains unknown.

    METHODS: The authors randomized 10,010 patients with or at risk of atherosclerosis and scheduled for noncardiac surgery in a 1:1:1:1 ratio to clonidine/aspirin, clonidine/aspirin placebo, clonidine placebo/aspirin, or clonidine placebo/aspirin placebo. Patients started taking aspirin or placebo just before surgery; those not previously taking aspirin continued daily for 30 days, and those taking aspirin previously continued for 7 days. Patients were also randomly assigned to receive clonidine or placebo just before surgery, with the study drug continued for 72 h.

    RESULTS: Neither aspirin nor clonidine had a significant effect on the primary 1-yr outcome, a composite of death or nonfatal myocardial infarction, with a 1-yr hazard ratio for aspirin of 1.00 (95% CI, 0.89 to 1.12; P = 0.948; 586 patients [11.8%] vs. 589 patients [11.8%]) and a hazard ratio for clonidine of 1.07 (95% CI, 0.96 to 1.20; P = 0.218; 608 patients [12.1%] vs. 567 patients [11.3%]), with effect on death or nonfatal infarction. Reduction in death and nonfatal myocardial infarction from aspirin in patients who previously had percutaneous coronary intervention at 30 days persisted at 1 yr. Specifically, the hazard ratio was 0.58 (95% CI, 0.35 to 0.95) in those with previous percutaneous coronary intervention and 1.03 (95% CI, 0.91to 1.16) in those without (interaction P = 0.033). There was no significant effect of either drug on death, cardiovascular complications, cancer, or chronic incisional pain at 1 yr (all P > 0.1).

    CONCLUSIONS: Neither perioperative aspirin nor clonidine have significant long-term effects after noncardiac surgery. Perioperative aspirin in patients with previous percutaneous coronary intervention showed persistent benefit at 1 yr, a plausible sub-group effect.

  11. Marcucci M, Painter TW, Conen D, Lomivorotov V, Sessler DI, Chan MTV, et al.
    Ann Intern Med, 2023 May;176(5):605-614.
    PMID: 37094336 DOI: 10.7326/M22-3157
    BACKGROUND: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively.

    OBJECTIVE: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery.

    DESIGN: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723).

    SETTING: 110 hospitals in 22 countries.

    PATIENTS: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications.

    INTERVENTION: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery.

    MEASUREMENTS: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment.

    RESULTS: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term.

    LIMITATION: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels.

    CONCLUSION: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications.

    PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong.

  12. Devereaux PJ, Marcucci M, Painter TW, Conen D, Lomivorotov V, Sessler DI, et al.
    N Engl J Med, 2022 May 26;386(21):1986-1997.
    PMID: 35363452 DOI: 10.1056/NEJMoa2201171
    BACKGROUND: Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding.

    METHODS: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025.

    RESULTS: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority).

    CONCLUSIONS: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.).

  13. Uyama Y, Yamazaki E, Clark K, Wang CY, Woro E, Tong FY, et al.
    Ther Innov Regul Sci, 2015 Mar;49(2):249-253.
    PMID: 30222411 DOI: 10.1177/2168479014551646
    In response to the globalization of drug development, regulatory inspection of Good Clinical Practice (GCP) has recently been conducted not only by International Conference on Harmonisation (ICH) regions but also non-ICH regions. To promote the international implementation of GCP, consistent understanding and interpretation of its concept among regions are important. This article summarizes the background and past activities of the E6 Discussion Group, established under the Regulators Forum.
  14. Wang CY, Ong GS
    Anaesthesia, 1993 Jun;48(6):514-5.
    PMID: 8322993
    A case of severe bronchospasm occurring during epidural anaesthesia in a patient undergoing Caesarean section is described. The aetiology of the bronchospasm may have been related to sympathetic nervous blockade allowing unopposed parasympathetically mediated bronchoconstriction.
  15. de Leon J, Schoretsanitis G, Smith RL, Molden E, Solismaa A, Seppälä N, et al.
    Pharmacopsychiatry, 2021 Dec 15.
    PMID: 34911124 DOI: 10.1055/a-1625-6388
    This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.
  16. Pedersen SS, Holse C, Mathar CE, Chan MTV, Sessler DI, Liu Y, et al.
    Anesth Analg, 2022 Nov 01;135(5):1021-1030.
    PMID: 35417425 DOI: 10.1213/ANE.0000000000006042
    BACKGROUND: Two trials reported that a high inspiratory oxygen fraction (F io2 ) does not promote myocardial infarction or death. Observational studies can provide larger statistical strength, but associations can be due to unobserved confounding. Therefore, we evaluated the association between intraoperative F io2 and cardiovascular complications in a large international cohort study to see if spurious associations were observed.

    METHODS: We included patients from the Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) study, who were ≥45 years of age, scheduled for overnight hospital admission, and had intraoperative F io2 recorded. The primary outcome was myocardial injury after noncardiac surgery (MINS), and secondary outcomes included mortality and pneumonia, all within 30 postoperative days. Data were analyzed with logistic regression, adjusted for many baseline cardiovascular risk factors, and illustrated in relation to findings from 2 recent controlled trials.

    RESULTS: We included 6588 patients with mean age of 62 years of whom 49% had hypertension. The median intraoperative F io2 was 0.46 (5%-95% range, 0.32-0.94). There were 808 patients (12%) with MINS. Each 0.10 increase in median F io2 was associated with a confounder-adjusted increase in odds for MINS: odds ratio (OR), 1.17 (95% confidence interval [CI], 1.12-1.23; P < .0001). MINS occurred in contrast with similar frequencies and no significant difference in controlled trials (2240 patients, 194 events), in which patients were given 80% vs 30% oxygen. Mortality was 2.4% and was not significantly associated with a median F io2 (OR, 1.07; 95% CI, 0.97-1.19 per 0.10 increase; P = .18), and 2.9% of patients had pneumonia (OR, 1.05; 95% CI, 0.95-1.15 per 0.10 increase; P = .34).

    CONCLUSIONS: We observed an association between intraoperative F io2 and risk of myocardial injury within 30 days after noncardiac surgery, which contrasts with recent controlled clinical trials. F io2 was not significantly associated with mortality or pneumonia. Unobserved confounding presumably contributed to the observed association between F io2 and myocardial injury that is not supported by trials.

  17. Landoni G, Lomivorotov VV, Nigro Neto C, Monaco F, Pasyuga VV, Bradic N, et al.
    N Engl J Med, 2019 03 28;380(13):1214-1225.
    PMID: 30888743 DOI: 10.1056/NEJMoa1816476
    BACKGROUND: Volatile (inhaled) anesthetic agents have cardioprotective effects, which might improve clinical outcomes in patients undergoing coronary-artery bypass grafting (CABG).

    METHODS: We conducted a pragmatic, multicenter, single-blind, controlled trial at 36 centers in 13 countries. Patients scheduled to undergo elective CABG were randomly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or to total intravenous anesthesia. The primary outcome was death from any cause at 1 year.

    RESULTS: A total of 5400 patients were randomly assigned: 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group. On-pump CABG was performed in 64% of patients, with a mean duration of cardiopulmonary bypass of 79 minutes. The two groups were similar with respect to demographic and clinical characteristics at baseline, the duration of cardiopulmonary bypass, and the number of grafts. At the time of the second interim analysis, the data and safety monitoring board advised that the trial should be stopped for futility. No significant difference between the groups with respect to deaths from any cause was seen at 1 year (2.8% in the volatile anesthetics group and 3.0% in the total intravenous anesthesia group; relative risk, 0.94; 95% confidence interval [CI], 0.69 to 1.29; P = 0.71), with data available for 5353 patients (99.1%), or at 30 days (1.4% and 1.3%, respectively; relative risk, 1.11; 95% CI, 0.70 to 1.76), with data available for 5398 patients (99.9%). There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events, including myocardial infarction.

    CONCLUSIONS: Among patients undergoing elective CABG, anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia. (Funded by the Italian Ministry of Health; MYRIAD ClinicalTrials.gov number, NCT02105610.).

  18. Zangrillo A, Lomivorotov VV, Pasyuga VV, Belletti A, Gazivoda G, Monaco F, et al.
    PMID: 35168907 DOI: 10.1053/j.jvca.2022.01.001
    OBJECTIVE: To investigate the effect of volatile anesthetics on the rates of postoperative myocardial infarction (MI) and cardiac death after coronary artery bypass graft (CABG).

    DESIGN: A post hoc analysis of a randomized trial.

    SETTING: Cardiac surgical operating rooms.

    PARTICIPANTS: Patients undergoing elective, isolated CABG.

    INTERVENTIONS: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or total intravenous anesthesia (TIVA). The primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48 hours from surgery. The secondary outcome was 1-year death due to cardiac causes.

    MEASUREMENTS AND MAIN RESULTS: A total of 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). The mean age was 62 ± 8.4 years, and the median baseline ejection fraction was 57% (50-67), without differences between the 2 groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14 of 2,530 [0.6%] v 27 of 2,501 [1.1%] in the TIVA group; p = 0.038) and as-treated analyses (16 of 2,708 [0.6%] v 29 of 2,617 [1.1%] in the TIVA group; p = 0.039), but not in the intention-to-treat analysis (17 of 2,663 [0.6%] v 28 of 2,667 [1.0%] in the TIVA group; p = 0.10). Overall, deaths due to cardiac causes were lower in the volatile group (23 of 2,685 [0.9%] v 40 of 2,668 [1.5%] than in the TIVA group; p = 0.03).

    CONCLUSIONS: An anesthetic regimen, including volatile agents, may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality.

  19. Goh PK, Chiu CL, Wang CY, Chan YK, Loo PL
    Anaesth Intensive Care, 2005 Apr;33(2):223-8.
    PMID: 15960405
    The aim of this prospective, double-blind, randomized, placebo-controlled clinical trial was to investigate whether the administration of ketamine before induction with propofol improves its associated haemodynamic profile and laryngeal mask airway (LMA) insertion conditions. Ninety adult patients were randomly allocated to receive either ketamine 0.5 mg x kg(-1) (n = 30), fentanyl 1 microg x kg(-1) (n = 30) or normal saline (n = 30), before induction of anaesthesia with propofol 2.5 mg x kg(-1). Insertion of the LMA was performed 60s after injection of propofol. Arterial blood pressure and heart rate were measured before induction (baseline), immediately after induction, immediately before LMA insertion, immediately after LMA insertion and every minute for three minutes after LMA insertion. Following LMA insertion, the following six subjective endpoints were graded by a blinded anaesthestist using ordinal scales graded 1 to 3: mouth opening, gagging, swallowing, movement, laryngospasm and ease of insertion. Systolic blood pressure was significantly higher following ketamine than either fentanyl (P = 0.010) or saline (P = 0.0001). The median (interquartile range) summed score describing the overall insertion conditions were similar in the ketamine [median 7.0, interquartile range (6.0-8.0)] and fentanyl groups [median 7.0, interquartile range (6.0-8.0)]. Both appeared significantly better than the saline group [median 8.0, interquartile range (6.75-9.25); P = 0.024]. The incidence of prolonged apnoea (> 120s) was higher in the fentanyl group [23.1% (7/30)] compared with the ketamine [6.3% (2/30)] and saline groups [3.3% (1/30)]. We conclude that the addition of ketamine 0.5 mg x kg(-1) improves haemodynamics when compared to fentanyl 1 microg x kg(-1), with less prolonged apnoea, and is associated with better LMA insertion conditions than placebo (saline).
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