Displaying publications 21 - 40 of 91 in total

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  1. Ng KT, Sarode D, Lai YS, Teoh WY, Wang CY
    Paediatr Anaesth, 2019 12;29(12):1163-1172.
    PMID: 31587414 DOI: 10.1111/pan.13752
    BACKGROUND: Ketamine is believed to reduce the incidence of emergence agitation in children undergoing surgery or procedure. However, recent randomized controlled trials reported conflicting findings.

    AIMS: To investigate the effect of ketamine on emergence agitation in children.

    METHODS: Databases of MEDLINE, EMBASE, and CENTRAL were systematically searched from their start date until February 2019. Randomized controlled trials comparing intravenous ketamine and placebo in children were sought. The primary outcome was the incidence of emergence agitation. Secondary outcomes included postoperative pain score, duration of discharge time, and the adverse effects associated with the use of ketamine, namely postoperative nausea and vomiting, desaturation, and laryngospasm.

    RESULTS: Thirteen studies (1125 patients) were included in the quantitative meta-analysis. The incidence of emergence agitation was 14.7% in the ketamine group and 33.3% in the placebo group. Children receiving ketamine had a lower incidence of emergence agitation, with an odds ratio being 0.23 (95% confidence interval: 0.11 to 0.46), certainty of evidence: low. In comparison with the placebo, ketamine group achieved a lower postoperative pain score (odds ratio: -2.42, 95% confidence interval: -4.23 to -0.62, certainty of evidence: very low) and lower pediatric anesthesia emergence delirium scale at 5 minutes after operation (odds ratio: -3.99, 95% confidence interval: -5.03 to -2.95; certainty of evidence: moderate). However, no evidence was observed in terms of incidence of postoperative nausea and vomiting, desaturation, and laryngospasm.

    CONCLUSION: In this meta-analysis of 13 randomized controlled trials, high degree of heterogeneity and low certainty of evidence limit the recommendations of ketamine for the prevention of emergence agitation in children undergoing surgery or imaging procedures. However, the use of ketamine is well-tolerated without any notable adverse effects across all the included trials.

    PROSPERO REGISTRATION: CRD42019131865.

  2. Lim SM, Ng BK, Wilson A, Cheong CC, Ng TY, Wang CY
    J Clin Monit Comput, 2021 Jan 02.
    PMID: 33387155 DOI: 10.1007/s10877-020-00623-7
    The primary objective of this study is to compare the effectiveness of cricoid pressure (CP) and paralaryngeal pressure (PLP) on occlusion of eccentric esophagus in patients under general anesthesia (GA). Secondary objectives include the prevalence of patients with central or eccentric esophagus both before and after GA, and the success rate of CP in occluding centrally located esophagus in patients post GA. Fifty-one ASA physical status I and II patients, undergoing GA for elective surgery were enrolled in this study. Ultrasonography imaging were performed to determine the position of the esophagus relative to the trachea: (i) before induction of GA, (ii) after GA before external CP maneuver, (iii) after GA with CP, and (iv) after GA with PLP. CP was applied to all patients whilst PLP via fingertip technique was only applied to patients with an eccentric esophagus. Among a total of 51 patients, 28 of them (55%) had eccentric esophagus pre GA, while this number increase to 33 (65%) after induction of GA. CP success rate was 100% in 18 patients with central esophagus post GA versus 27% in 33 patients with eccentric esophagus post GA (P<0.00001). Overall success rate for CP was 53%. In 33 patients with eccentric esophagus anatomy post GA, PLP success rate was 30% compared with 27% with CP (P=1.000). Ultrasound guided PLP fingertips technique was not effective in patients with an eccentrically located esophagus post GA. Ultrasound guided CP achieved 100% success rate in patients with a centrally located esophagus post GA.
  3. Monaco F, Di Prima AL, Kim JH, Plamondon MJ, Yavorovskiy A, Likhvantsev V, et al.
    J Cardiothorac Vasc Anesth, 2020 Jun;34(6):1622-1635.
    PMID: 32276758 DOI: 10.1053/j.jvca.2020.02.038
    SEPARATION from cardiopulmonary bypass (CPB) after cardiac surgery is a progressive transition from full mechanical circulatory and respiratory support to spontaneous mechanical activity of the lungs and heart. During the separation phase, measurements of cardiac performance with transesophageal echocardiography (TEE) provide the rationale behind the diagnostic and therapeutic decision-making process. In many cases, it is possible to predict a complex separation from CPB, such as when there is known preoperative left or right ventricular dysfunction, bleeding, hypovolemia, vasoplegia, pulmonary hypertension, or owing to technical complications related to the surgery. Prompt diagnosis and therapeutic decisions regarding mechanical or pharmacologic support have to be made within a few minutes. In fact, a complex separation from CPB if not adequately treated leads to a poor outcome in the vast majority of cases. Unfortunately, no specific criteria defining complex separation from CPB and no management guidelines for these patients currently exist. Taking into account the above considerations, the aim of the present review is to describe the most common scenarios associated with a complex CPB separation and to suggest strategies, pharmacologic agents, and para-corporeal mechanical devices that can be adopted to manage patients with complex separation from CPB. The routine management strategies of complex CPB separation of 17 large cardiac centers from 14 countries in 5 continents will also be described.
  4. Ng CC, Sybil Shah MHB, Chaw SH, Mansor MB, Tan WK, Koong JK, et al.
    Expert Rev Med Devices, 2021 Feb;18(2):203-210.
    PMID: 33322949 DOI: 10.1080/17434440.2021.1865796
    Background: Supraglottic airway devices have increasingly been used as the airway technique of choice in laparoscopic surgeries. This study compared the efficacy and safety of the Baska Mask with endotracheal tube (ETT) in patients undergoing elective laparoscopic cholecystectomy.Research design and methods: This single-center, prospective, randomized controlled trial recruited 60 patients aged 18-75 years with American Society of Anesthesiologists' classifications I to III. The time taken to achieve effective airway, number of attempts, ease of insertion, ventilation parameters, hemodynamics data, and pharyngolaryngeal complications were recorded.Results: The time taken to achieve effective airway was shorter for the Baska group (26.6 ± 4.7 vs. 47.2 ± 11.8 s; p
  5. Chien CS, Chien Y, Lin YY, Tsai PH, Chou SJ, Yarmishyn AA, et al.
    Front Cell Dev Biol, 2021;9:634190.
    PMID: 34422789 DOI: 10.3389/fcell.2021.634190
    Non-viral gene delivery holds promises for treating inherited diseases. However, the limited cloning capacity of plasmids may hinder the co-delivery of distinct genes to the transfected cells. Previously, the conjugation of maleimide-functionalized polyurethane grafted with small molecular weight polyethylenimine (PU-PEI600-Mal) using 1,6-hexanedithiol (HDT) could promote the co-delivery and extensive co-expression of two different plasmids in target cells. Herein, we designed HDT-conjugated PU-PEI600-Mal for the simultaneous delivery of CRISPR/Cas9 components to achieve efficient gene correction in the induced pluripotent stem cell (iPSC)-derived model of Fabry cardiomyopathy (FC) harboring GLA IVS4 + 919 G > A mutation. This FC in vitro model recapitulated several clinical FC features, including cardiomyocyte hypertrophy and lysosomal globotriaosylceramide (Gb3) deposition. As evidenced by the expression of two reporter genes, GFP and mCherry, the addition of HDT conjugated two distinct PU-PEI600-Mal/DNA complexes and promoted the co-delivery of sgRNA/Cas9 and homology-directed repair DNA template into target cells to achieve an effective gene correction of IVS4 + 919 G > A mutation. PU-PEI600-Mal/DNA with or without HDT-mediated conjugation consistently showed neither the cytotoxicity nor an adverse effect on cardiac induction of transfected FC-iPSCs. After the gene correction and cardiac induction, disease features, including cardiomyocyte hypertrophy, the mis-regulated gene expressions, and Gb3 deposition, were remarkably rescued in the FC-iPSC-differentiated cardiomyocytes. Collectively, HDT-conjugated PU-PEI600-Mal-mediated dual DNA transfection system can be an ideal approach to improve the concurrent transfection of non-viral-based gene editing system in inherited diseases with specific mutations.
  6. Ng KT, Lee ZX, Ang E, Teoh WY, Wang CY
    J Clin Anesth, 2020 Jun;62:109731.
    PMID: 31986433 DOI: 10.1016/j.jclinane.2020.109731
    OBJECTIVES: The repetitive hypoxic and hypercapnia events of obstructive sleep apnea (OSA) are believed to adversely affect cardiopulmonary function, which make them vulnerable to a higher incidence of postoperative complications. The primary aim of this systematic review and meta-analysis was to examine the association of OSA and the composite endpoints of postoperative cardiac or cerebrovascular complications in adult undergoing non-cardiac surgery.

    DATA SOURCES: MEDLINE, EMBASE and CENTRAL were systematically searched from its inception until May 2019.

    REVIEW METHODS: All observational studies were included.

    RESULTS: Twenty-two studies (n = 3,033,814; 184,968 OSA vs 2,848,846 non-OSA) were included for quantitative meta-analysis. In non-cardiac surgery, OSA was significantly associated with a higher incidence of the composite endpoints of postoperative cardiac or cerebrovascular complications (odd ratio: 1.44, 95%CI: 1.17 to 1.78, ρ = 0.007, trial sequential analysis = conclusive; certainty of evidence = very low). In comparison to non-OSA, OSA patients were reported to have nearly 2.5-fold risk of developing pulmonary complications (odd ratio: 2.52, 95%CI: 1.92 to 3.31, ρ 

  7. Ang E, Ng KT, Lee ZX, Ti LK, Chaw SH, Wang CY
    J Clin Anesth, 2020 Dec;67:110023.
    PMID: 32805685 DOI: 10.1016/j.jclinane.2020.110023
    OBJECTIVES: There is growing evidence on the influence of general anaesthesia (GA) in promoting the proliferation of cancer cells. The benefits of regional anaesthesia (RA) on cancer recurrence rate in cancer surgery remains unclear in the literature. The primary objective of this review was to examine the effect of RA on the incidence of post-operative cancer recurrence rate in cancer resection surgery.

    DESIGN: Systematic review and meta-analysis with trial sequential analysis.

    DATA SOURCES: Medline, EMBASE and CENTRAL were systematically searched from its inception until April 2020.

    ELIGIBILITY CRITERIA: All randomized control trials and observational studies comparing RA only versus GA in cancer resection surgery were included. Case report, case series and editorials were excluded.

    RESULTS: Ten retrospective observational studies (n = 9708; 4567 GA vs 5141 RA) were included for qualitative and quantitative meta-analysis. In comparison to GA, RA was not significantly associated with a lower cancer recurrence rate in cancer resection surgery (odds ratio 1.01, 95% CI 0.67 to 1.53, p = 0.95, certainty of evidence = very low). However, the trial sequential analysis for cancer recurrence rate was inconclusive. Our analysis demonstrated no significant difference between the RA and GA groups in the overall survival rate (odds ratio 1.51, 95% CI 0.65 to 3.51, p = 0.34, certainty of evidence = very low), time to cancer recurrence (mean difference 1.45 months, 95% CI -8.69 to 11.59, p = 0.78, certainty of evidence = very low), cancer-related mortality (odds ratio 1.79, 95% CI 0.57 to 5.62, p = 0.32, certainty of evidence = very low).

    CONCLUSIONS: Given the low level of evidence and underpowered trial sequential analysis, our review neither support nor oppose that the use of RA was associated with lower incidence of cancer recurrence rate than GA in cancer resection surgery.

    TRIAL REGISTRATION: CRD42020163780.

  8. Ng KT, Chan XL, Tan W, Wang CY
    J Clin Anesth, 2019 Feb;52:37-47.
    PMID: 30172838 DOI: 10.1016/j.jclinane.2018.08.019
    OBJECTIVES: Patients with preoperative low left ventricular ejection fraction (LVEF) are known to be associated with high morbidities and mortality in cardiac surgery. The primary aim of this review was to examine the clinical outcomes of levosimendan versus placebo in patients with preoperative low LVEF ≤ 50% undergoing cardiac surgery.

    DATA SOURCES: MEDLINE, EMBASE, PubMed and CENTRAL were searched systematically from their inception until June 2018.

    REVIEW METHODS: All the randomised clinical trials (RCTs) were included.

    RESULTS: Twelve trials were eligible (n = 1867) for inclusion in the data synthesis. In comparison to the placebo cohort, the levosimendan cohort showed a significant reduction in mortality (TSA = inconclusive; ρ = 0.002; I2 = 0%; FEM: OR 0.56; 95% CI 0.39, 0.80), especially in the subgroups of preoperative severe low LVEF ≤ 30% (ρ = 0.003; OR 0.33; 95% CI 0.16, 0.69), preoperative administering of levosimendan (ρ = 0.001; OR 0.46; 95% CI 0.29, 0.74) and patients who had bolus followed by infusion of levosimendan (ρ = 0.005; OR 0.50; 95% CI 0.30, 0.81). However, the effect on mortality was not significant in the subgroup analysis of high quality trials (ρ = 0.14; OR 0.73; 95% CI 0.47, 1.12). The levosimendan cohort showed a significantly lower incidence of low-cardiac-output-syndrome (ρ 

  9. Tsan SEH, Ng KT, Lau J, Viknaswaran NL, Wang CY
    Braz J Anesthesiol, 2020 11 09;70(6):667-677.
    PMID: 33288219 DOI: 10.1016/j.bjan.2020.08.009
    OBJECTIVES: Positioning during endotracheal intubation (ETI) is critical to ensure its success. We aimed to determine if the ramping position improved laryngeal exposure and first attempt success at intubation when compared to the sniffing position.

    METHODS: PubMed, EMBASE, and Cochrane CENTRAL databases were searched systematically from inception until January 2020. Our primary outcomes included laryngeal exposure as measured by Cormack-Lehane Grade 1 or 2 (CLG 1/2), CLG 3 or 4 (CLG 3/4), and first attempt success at intubation. Secondary outcomes were intubation time, use of airway adjuncts, ancillary maneuvers and complications during ETI.

    RESULTS: Seven studies met our inclusion criteria, of which 4 were RCTs and 3 were cohort studies. The meta-analysis was conducted by pooling the effect estimates for all 4 included RCTs (n=632). There were no differences found between ramping and sniffing positions for odds of CLG 1/2, CLG 3/4, first attempt success at intubation, intubation time, use of ancillary airway maneuvers and use of airway adjuncts, with evidence of high heterogeneity across studies. However, the ramping position in surgical patients is associated with increased likelihood of CLG 1/2 (OR=2.05, 95% CI 1.26 to 3.32, p=0.004) and lower likelihood of CLG 3/4 (OR=0.49, 95% CI 0.30 to 0.79, p=0.004), moderate quality of evidence.

    CONCLUSION: Our meta-analysis demonstrated that the ramping position may benefit surgical patients undergoing ETI by improving laryngeal exposure. Large-scale well-designed multicentre RCTs should be carried out to further elucidate the benefits of the ramping position in the surgical and intensive care unit patients.

  10. Shariffuddin II, Teoh WH, Wahab S, Wang CY
    BMC Anesthesiol, 2018 01 05;18(1):3.
    PMID: 29304735 DOI: 10.1186/s12871-017-0464-6
    BACKGROUND: Ambulatory surgery has recently gain popularity, as it is a good method of optimizinghospital resources utilization. To support ambulatory surgery, anaesthetic goals nowrevolve around patients' early recovery with minimal pain and nausea, expedientdischarge home and prompt resumption of activities of daily living. In this study, weevaluated the effect of a single pre-induction dose of dexmedetomidine on anaestheticrequirements, postoperative pain and clinical recovery after ambulatory ureteroscopy andureteric stenting under general anaesthesia.

    METHODS: Sixty patients were randomised to receive IV dexmedetomidine 0.5 μg.kg-1 (Group DEX, n = 30) or IV saline (Group P, n = 30). General anaesthesia was maintained with Sevoflurane: oxygen: air, titrated to BIS 40-60. Pain intensity, sedation, rescue analgesics, nausea/vomiting and resumption of daily activities were recorded at 1 h, and postoperative day (POD) 1-5.

    RESULTS: Group DEX patients had significant reduction in sevoflurane minimum alveolar concentration (MAC), mean (SD) DEX vs. Placebo 0.6 (0.2) vs. 0.9 (0.1), p = 0.037; reduced postoperative resting pain at 1 h (VAS 0-10) (mean (SD) 1.00 (1.84) vs. 2.63 (2.78), p = 0.004), POD 1 (mean (SD) 1.50 (1.48) vs. 2.87 (2.72), p = 0.002), POD 2 (0.53 (0.97) vs. 1.73 (1.96), p = 0.001) and POD 3 (0.30 (0.75) vs. 0.89 (1.49), p = 0.001). DEX patients also had less pain on movement POD 1 (3.00 (2.12) vs. 4.30 (3.10), p = 0.043) and POD 2 (2.10 (1.98) vs. 3.10 (2.46), p = 0.040), with higher resumption of daily activities by 48 h compared to placebo, 87% vs. 63%, p = 0.04.

    CONCLUSIONS: We conclude that a single dose of dexmedetomidine was a useful adjuvant in reducing MAC and postoperative pain (at 1 h and POD 1-3), facilitating faster return to daily activities by 48 h.

    TRIAL REGISTRATION: The Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617001120369 , 31st July 2017, retrospectively registered.

  11. Tsan SEH, Wang CY
    Anesth Analg, 2021 02 01;132(2):e33-e34.
    PMID: 33449571 DOI: 10.1213/ANE.0000000000005307
  12. Tsan SEH, Lim SM, Abidin MFZ, Ganesh S, Wang CY
    Anesth Analg, 2020 07;131(1):210-219.
    PMID: 31348051 DOI: 10.1213/ANE.0000000000004349
    BACKGROUND: Approximately half of all difficult tracheal intubations (DTIs) are unanticipated; hence, proper positioning during intubation is critical to increase the likelihood of success. The bed-up-head-elevated (BUHE) intubation position has been shown to improve laryngeal view, reduce airway complications, and prolong safe apneic time during intubation. In this study, we sought to determine whether the BUHE intubation position is noninferior to Glidescope (GLSC)-assisted intubation with regard to laryngeal exposure.

    METHODS: A total of 138 American Society of Anesthesiologists (ASA) I to III patients were randomly assigned into 2 groups and underwent baseline laryngoscopy in the sniffing position. Group BUHE patients (n = 69) were then intubated in the BUHE position, while group GLSC patients (n = 69) were intubated using GLSC laryngoscopy. Laryngeal exposure was measured using Percentage of Glottic Opening (POGO) score and Cormack-Lehane (CL) grading, and noninferiority will be declared if the difference in mean POGO scores between both groups do not exceed -15% at the lower limit of a 98% confidence interval (CI). Secondary outcomes measured included time required for intubation (TRI), number of intubation attempts, use of airway adjuncts, effort during laryngoscopy, and complications during intubation.

    RESULTS: Mean POGO score in group BUHE was 80.14% ± 22.03%, while in group GLSC it was 86.45% ± 18.83%, with a mean difference of -6.3% (98% CI, -13.2% to 0.6%). In both groups, there was a significant improvement in mean POGO scores when compared to baseline laryngoscopy in the sniffing position (group BUHE, 25.8% ± 4.7%; group GLSC, 30.7% ± 6.8%) (P < .0001). The mean TRI was 36.23 ± 14.41 seconds in group BUHE, while group GLSC had a mean TRI of 44.33 ± 11.53 seconds (P < .0001). In patients with baseline CL 3 grading, there was no significant difference between mean POGO scores in both groups (group BUHE, 49.2% ± 19.6% versus group GLSC, 70.5% ± 29.7%; P = .054).

    CONCLUSIONS: In the general population, BUHE intubation position provides a noninferior laryngeal view to GLSC intubation. The laryngeal views obtained in both approaches were superior to the laryngeal view obtained in the sniffing position. In view of the many advantages of the BUHE position for intubation, the lack of proven adverse effects, the simplicity, and the cost-effectiveness, we propose that clinicians should consider the BUHE position as the standard intubation position for the general population.

  13. Lai HY, Foo LL, Lim SM, Yong CF, Loh PS, Chaw SH, et al.
    Clin Auton Res, 2020 Feb;30(1):53-60.
    PMID: 29196938 DOI: 10.1007/s10286-017-0485-8
    PURPOSE: Comparison of hemodynamic profiles and pain scores in diabetic patients undergoing diabetic foot surgery receiving peripheral nerve block (PNB) or spinal anesthesia [subarachnoid block (SAB)].

    METHODS: This was a prospective, randomised controlled trial. We recruited diabetic patients aged > 18 years, American Society of Anesthesiologists class II-III, who were scheduled for unilateral diabetic foot surgery below the knee. All patients were assessed for autonomic dysfunction using the Survey of Autonomic Symptoms score. Participants were randomly assigned to receive either PNB or SAB for the surgery. Hemodynamic data, including usage of vasopressors, were recorded at 5-min intervals for up to 1 h after the induction of anesthesia. Pain scores were recorded postoperatively, and follow-up was done via telephone 6 months later.

    RESULTS: Compared to the PNB group, the SAB group had a larger number of patients with significant hypotension (14 vs. 1; p = 0.001) and more patients who required vasopressor boluses (6 vs. 0 patients). Compared to SAB group, the patients in the PNB group had a longer postoperative pain-free duration (9 vs. 4.54 h; p = 0.002) and lower pain scores 1 day after surgery (3.63 vs. 4.69; p = 0.01).

    CONCLUSION: Peripheral nerve block should be considered, whenever possible, as the first option of anesthesia for lower limb surgery in diabetic patients as it provides hemodynamic stability and superior postoperative pain control compared to SAB.

    TRIAL REGISTRATION: Clinical trial registry: ClinicalTrials.gov. ID NCT02727348.

  14. Liu CY, Lin HF, Lai WY, Lin YY, Lin TW, Yang YP, et al.
    J Chin Med Assoc, 2022 Apr 01;85(4):409-413.
    PMID: 35383703 DOI: 10.1097/JCMA.0000000000000703
    Lung carcinoma (LC) is the third most common cancer diagnosis and accounted for the most cancer-related mortality worldwide in 2018. Based on the type of cells from which it originates, LC is commonly classified into non-small cell lung cancers (NSCLC) and small cell lung cancers (SCLC). NSCLC account for the majority of LC and can be further categories into adenocarcinoma, large cell carcinoma, and squamous cell carcinoma. Accurate classification of LC is critical for its adequate treatment and therapeutic outcome. Since NSCLC express more epidermal growth factor receptor (EGFR) with activation mutations, targeted therapy EGFR-tyrosine kinase inhibitors (TKIs) have been considered as primary option of NSCLC patients with activation EGFR mutation. In this review, we present the genetic alterations, reported mutations in EGFR, and TKIs treatment in NSCLC patients with an emphasis on the downstream signaling pathways in NSCLC progression. Among the signaling pathways identified, mitogen activation protein kinase (MAPK), known also as extracellular signal-regulated protein kinase (Erk) pathway, is the most investigated among the related pathways. EGFR activation leads to the autophosphorylation of its kinase domain and subsequent activation of Ras, phosphorylation of Raf and MEK1/2, and the activation of ERK1/2. Phosphatidylinositol 3-kinase (PI3K)/Akt is another signal pathway that regulates cell cycle and has been linked to NSCLC progression. Currently, three generations of EGFR TKIs have been developed as a first-line treatment of NSCLC patients with EGFR activation and mutation in which these treatment options will be further discussed in this review. The Supplementary Appendix for this article is available at http://links.lww.com/JCMA/A138.
  15. Tsan SEH, Viknaswaran NL, Cheong CC, Cheah S, Ng KT, Mong SXY, et al.
    Anaesthesia, 2023 Sep;78(9):1153-1161.
    PMID: 37314744 DOI: 10.1111/anae.16058
    Tranexamic acid is an antifibrinolytic drug that is widely used during surgery, but there are concerns about its thromboembolic effects. We aimed to investigate the effect of prophylactic intravenous tranexamic acid on thromboembolic outcomes in patients undergoing non-cardiac surgery. The MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched. Randomised controlled trials comparing intravenous tranexamic acid with placebo or no treatment in patients undergoing non-cardiac surgery were included. The primary outcome was a composite of peri-operative cardiovascular thromboembolic events, defined as any deep vein thrombosis, pulmonary embolism, myocardial ischaemia/infarction or cerebral ischaemia/infarction. A total of 191 randomised controlled trials (40,621 patients) were included in the review. The primary outcome occurred in 4.5% of patients receiving intravenous tranexamic acid compared with 4.9% of patients in the control group. Our analysis showed that there was no difference between groups for composite cardiovascular thromboembolic events (risk ratio 1.02, 95%CI 0.94-1.11, p = 0.65, I2 0%, n = 37,512). This finding remained robust when sensitivity analysis was performed with continuity correction and in studies with a low risk of bias. However, in trial sequential analysis, our meta-analysis only achieved 64.6% of the required information size. There was no association between intravenous tranexamic acid and seizure rate or mortality rate within 30 days. Intravenous tranexamic acid was associated with a reduced blood transfusion rate compared with control (9.9% vs. 19.4%, risk ratio 0.46, 95%CI 0.41-0.51, p 
  16. Teoh WY, Tan TG, Ng KT, Ong KX, Chan XL, Hung Tsan SE, et al.
    Ann Surg, 2021 Apr 01;273(4):676-683.
    PMID: 32282377 DOI: 10.1097/SLA.0000000000003896
    OBJECTIVES: Perioperative bleeding remains a major concern to all clinicians caring for perioperative patients. Due to the theoretical risk of thromboembolic events associated with tranexamic acid (TXA) when administered intravenously, topical route of TXA has been extensively studied, but its safety and efficacy profile remain unclear in the literature. The primary aim of this review was to assess the effect of topical TXA on incidence of blood transfusion and mortality in adults undergoing surgery.

    DATA SOURCES: EMBASE, MEDLINE, CENTRAL, and ISI Web of Science were systematically searched from their inception until May 31, 2019.

    REVIEW METHODS: Parallel-arm randomized controlled trials were included.

    RESULTS: Seventy-one trials (7539 participants: orthopedics 5450 vs nonorthopedics 1909) were included for quantitative meta-analysis. In comparison to placebo, topical TXA significantly reduced intraoperative blood loss [mean difference (MD) -36.83 mL, 95% confidence interval (CI) -54.77 to -18.88, P < 0.001], total blood loss (MD -319.55 mL, 95% CI -387.42 to -251.69, P < 0.001), and incidence of blood transfusion [odds ratio (OR) 0.30, 95% CI 0.26-0.34, P < 0.001]. Patients who received topical TXA were associated with a shorter length of hospital stay (MD -0.28 days, 95% CI -0.47 to -0.08, P = 0.006). No adverse events associated with the use of topical TXA were observed, namely mortality (OR 0.78, 95% CI 0.45-1.36, P = 0.39), pulmonary embolism (OR 0.73, 95% CI 0.27-1.93, P = 0.52), deep vein thrombosis (OR 1.07, 95% CI 0.65-1.77, P = 0.79), myocardial infarction (OR 0.79, 95% CI 0.21-2.99, P = 0.73), and stroke (OR 0.85, 95% CI 0.28-2.57, P = 0.77). Of all included studies, the risk of bias assessment was "low" for 20 studies, "unclear" for 26 studies and "high" for 25 studies.

    CONCLUSIONS: In the meta-analysis of 71 trials (7539 patients), topical TXA reduced the incidence of blood transfusion without any notable adverse events associated with TXA in adults undergoing surgery.

    PROSPERO: CRD 42018111762.

  17. Botto F, Alonso-Coello P, Chan MT, Villar JC, Xavier D, Srinathan S, et al.
    Anesthesiology, 2014 Mar;120(3):564-78.
    PMID: 24534856 DOI: 10.1097/ALN.0000000000000113
    BACKGROUND: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study's four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS.

    METHODS: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated "abnormal" laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria.

    RESULTS: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors' diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96-5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6-41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom.

    CONCLUSION: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

  18. Thomas S, Borges F, Bhandari M, De Beer J, Urrútia Cuchí G, Adili A, et al.
    J Bone Joint Surg Am, 2020 May 20;102(10):880-888.
    PMID: 32118652 DOI: 10.2106/JBJS.18.01305
    BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is common and of prognostic importance. Little is known about MINS in orthopaedic surgery. The diagnostic criterion for MINS was a level of ≥0.03 ng/mL on a non-high-sensitivity troponin T (TnT) assay due to myocardial ischemia.

    METHODS: We undertook an international, prospective study of 15,103 patients ≥45 years of age who had inpatient noncardiac surgery; 3,092 underwent orthopaedic surgery. Non-high-sensitivity TnT assays were performed on postoperative days 0, 1, 2, and 3. Among orthopaedic patients, we determined (1) the prognostic relevance of the MINS diagnostic criteria, (2) the 30-day mortality rate for those with and without MINS, and (3) the probable proportion of MINS cases that would go undetected without troponin monitoring because of a lack of an ischemic symptom.

    RESULTS: Three hundred and sixty-seven orthopaedic patients (11.9%) had MINS. MINS was associated independently with 30-day mortality including among those who had had orthopaedic surgery. Orthopaedic patients without and with MINS had a 30-day mortality rate of 1.0% and 9.8%, respectively (odds ratio [OR], 11.28; 95% confidence interval [CI], 6.72 to 18.92). The 30-day mortality rate was increased for patients with MINS who had an ischemic feature (i.e., symptoms, or evidence of ischemia on electrocardiography or imaging) (OR, 18.25; 95% CI, 10.06 to 33.10) and for those who did not have an ischemic feature (OR, 7.35; 95% CI, 3.37 to 16.01). The proportion of orthopaedic patients with MINS who were asymptomatic and in whom the myocardial injury would have probably gone undetected without TnT monitoring was 81.3% (95% CI, 76.3% to 85.4%).

    CONCLUSIONS: One in 8 orthopaedic patients in our study had MINS, and MINS was associated with a higher mortality rate regardless of symptoms. Troponin levels should be measured after surgery in at-risk patients because most MINS cases (>80%) are asymptomatic and would go undetected without routine measurements.

    LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

  19. Devereaux PJ, Lamy A, Chan MTV, Allard RV, Lomivorotov VV, Landoni G, et al.
    N Engl J Med, 2022 Mar 03;386(9):827-836.
    PMID: 35235725 DOI: 10.1056/NEJMoa2000803
    BACKGROUND: Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations.

    METHODS: We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex).

    RESULTS: Of 13,862 patients included in the study, 296 (2.1%) died within 30 days after surgery. Among patients who underwent isolated coronary-artery bypass grafting or aortic-valve replacement or repair, the threshold troponin level, measured within 1 day after surgery, that was associated with an adjusted hazard ratio of more than 1.00 for death within 30 days was 5670 ng per liter (95% confidence interval [CI], 1045 to 8260), a level 218 times the upper reference limit. Among patients who underwent other cardiac surgery, the corresponding threshold troponin level was 12,981 ng per liter (95% CI, 2673 to 16,591), a level 499 times the upper reference limit.

    CONCLUSIONS: The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.).

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