Acute normovolemic hemodilution in cardiac surgery: Rationale and design of a multicenter randomized trial.

BACKGROUND: Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. METHODS: This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 ml as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. RESULTS: The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. CONCLUSION: The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.

A Randomized Trial of Intravenous Amino Acids for Kidney Protection.

BACKGROUND: Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. METHODS: In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. RESULTS: We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events. CONCLUSIONS: Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.).

Acute normovolemic hemodilution in cardiac surgery: rationale and design of a multicenter randomized trial

BACKGROUND: Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. METHODS: This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 mL as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. RESULTS: The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. CONCLUSION: The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. STUDY Registration: This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.

Feasibility of continuous non-invasive delivery of oxygen monitoring in cardiac surgical patients: a proof-of-concept preliminary study.

PURPOSE: Oxygen delivery (DO2) and its monitoring are highlighted to aid postoperative goal directed therapy (GDT) to improve perioperative outcomes such as acute kidney injury (AKI) after high-risk cardiac surgeries associated with multiple morbidities and mortality. However, DO2 monitoring is neither routine nor done postoperatively, and current methods are invasive and only produce intermittent DO2 trends. Hence, we proposed a novel algorithm that simultaneously integrates cardiac output (CO), hemoglobin (Hb) and oxygen saturation (SpO2) from the Edwards Life Sciences ClearSight System® and Masimo SET Pulse CO-Oximetry® to produce a continuous, real-time DO2 trend. METHODS: Our algorithm was built systematically with 4 components - machine interface to draw data with PuTTY, data extraction with parsing, data synchronization, and real-time DO2 presentation using a graphic-user interface. Hb readings were validated. RESULTS: Our algorithm was implemented successfully in 93% (n = 57 out of 61) of our recruited cardiac surgical patients. DO2 trends and AKI were studied. CONCLUSION: We demonstrated a novel proof-of-concept and feasibility of continuous, real-time, non-invasive DO2 monitoring, with each patient serving as their own control. Our study also lays the foundation for future investigations aimed at identifying personalized critical DO2 thresholds and optimizing DO2 as an integral part of GDT to enhance outcomes in perioperative cardiac surgery.

Paramedian versus midline approach of spinal anesthesia: a systematic review and meta-analysis with trial sequential analysis.

PURPOSE: Midline approach of spinal anesthesia has been widely used for patients undergoing surgical procedures. However, it might not be effective for obstetric patients and elderly with degenerative spine changes. Primary objective was to examine the success rate at the first attempt between the paramedian and midline spinal anesthesia in adults undergoing surgery. METHODS: Databases of MEDLINE, EMBASE, and CENTRAL were searched from their starting date until February 2023. Randomized clinical trials (RCTs) comparing the paramedian versus midline approach of spinal anesthesia were included. The primary outcome was the success rate at the first attempt of spinal anesthesia. RESULTS: Our review included 36 RCTs (n = 5379). Compared to the midline approach, paramedian approach may increase success rate at the first attempt but the evidence is very uncertain (OR: 0.47, 95% CI 0.27-0.82, ρ = 0.007, level of evidence:very low). Our pooled data indicates that the paramedian approach likely reduced incidence of post-spinal headache (OR: 2.07, 95% CI 1.51-2.84, ρ < 0.00001, level of evidence:moderate). The evidence suggests that the paramedian approach may result in a reduction in the occurrence of paresthesia (OR: 1.61, 95% CI 1.06-2.45, ρ = 0.03, level of evidence:low). CONCLUSIONS: Our meta-analysis of 36 RCTs showed that paramedian approach may result in little to no difference in success rate at the first attempt owing to its very low level of evidence. However, given the low level of evidence and studies with small sample sizes, these findings need to be interpreted with caveat. CLINICAL TRIAL REGISTRATION NUMBER: CRD42023397781.

Preoperative anemia and anemia treatment in cardiac surgery: a systematic review and meta-analysis.

PURPOSE: We aimed to conduct a systematic review and meta-analysis to assess the effects of anemia and anemia severity on patient outcomes in cardiac surgery and determine whether preoperative treatments confer postoperative benefit. SOURCE: We searched four international databases for observational and randomized studies published until 1 October 2022. Study quality was assessed via Newcastle-Ottawa scores and the Cochrane Risk-of-Bias 2 tool and certainty of evidence was rated with the Grading of Recommendations, Assessment, Development and Evaluations approach. We conducted random-effects meta-analyses for our primary outcome of mortality, for secondary outcomes including length of stay (LOS) in the hospital and intensive care unit, and for postsurgical complications. As part of a secondary analysis, we analyzed short-term preoperative anemia treatments and conducted trial sequential analysis of randomized trials to assess the efficacy of these treatment programs. PRINCIPAL FINDINGS: We included 35 studies (159,025 patients) in our primary meta-analysis. Preoperative anemia was associated with increased mortality (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.2 to 2.9; P < 0.001, high certainty). Study-level meta-regression revealed lower hemoglobin levels and studies with lower proportions of male patients to be associated with increased risk of mortality. Preoperative anemia was also associated with an increase in LOS and postsurgical complications. Our secondary analysis (seven studies, 1,012 patients) revealed short-term preoperative anemia treatments did not significantly reduce mortality (OR, 1.1; 95% CI, 0.65 to 1.9; P = 0.69). Trial sequential analysis suggested that there was insufficient evidence to conclude if treatment programs yield any benefit or harm. CONCLUSIONS: Preoperative anemia is associated with mortality and morbidity after cardiac surgery. More research is warranted to test the efficacy of current anemia treatment programs. STUDY REGISTRATION: PROSPERO (CRD42022319431); first submitted 17 April 2023.

RéSUMé: OBJECTIF: Notre objectif était de mener une revue systématique et une méta-analyse pour évaluer les effets de l'anémie et de la gravité de l'anémie sur les devenirs des patient·es en chirurgie cardiaque et déterminer si les traitements préopératoires conféraient un bénéfice postopératoire. SOURCES: Nous avons réalisé des recherches dans quatre bases de données internationales pour en extraire des études observationnelles et randomisées publiées jusqu'au 1er octobre 2022. La qualité des études a été évaluée à l'aide des scores de Newcastle-Ottawa et de l'outil Cochrane 2 sur le risque de biais, et la certitude des données probantes a été évaluée selon l'approche GRADE (Grading of Recommendations, Assessment, Development and Evaluations). Nous avons réalisé des méta-analyses à effets aléatoires pour notre critère d'évaluation principal de mortalité, pour les critères d'évaluation secondaires, notamment la durée du séjour à l'hôpital et à l'unité de soins intensifs, et pour les complications postopératoires. Dans le cadre d'une analyse secondaire, nous avons examiné les traitements préopératoires de l'anémie à court terme et effectué une analyse séquentielle d'études randomisées afin d'évaluer l'efficacité de ces modalités de traitement. CONSTATATIONS PRINCIPALES: Nous avons inclus 35 études portant sur 159 025 patient·es dans notre méta-analyse. L'anémie préopératoire était associée à une augmentation de la mortalité (rapport de cotes [RC], 2,5; intervalle de confiance [IC] à 95 %, 2,2 à 2,9; P < 0,001, certitude élevée). La méta-régression au niveau de l'étude a révélé que des taux d'hémoglobine plus faibles et des études avec des proportions plus faibles de patients masculins étaient associées à un risque accru de mortalité. L'anémie préopératoire était également associée à une augmentation de la durée de séjour et des complications postopératoires. Notre analyse secondaire (sept études, 1012 patient·es) a révélé que les traitements préopératoires de l'anémie à court terme ne réduisaient pas significativement la mortalité (RC, 1,1; IC 95 %, 0,65 à 1,9; P = 0,69). L'analyse séquentielle des études a suggéré qu'il n'y avait pas suffisamment de données probantes pour conclure si les modalités de traitement entraînaient un bénéfice ou un préjudice. CONCLUSION: L'anémie préopératoire est associée à la mortalité et à la morbidité après une chirurgie cardiaque. D'autres recherches sont justifiées pour tester l'efficacité des programmes actuels de traitement de l'anémie. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42022319431); première soumission le 17 avril 2023.

Non-invasive mid-term electrocardiogram patch monitoring is effective in detecting atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a cause of serious morbidity such as stroke. Early detection and treatment of AF is important. Current guidelines recommend screening via opportunistic pulse taking or 12­lead electrocardiogram. Mid-term ECG patch monitors increases the sensitivity of AF detection. METHODS: The Singapore Atrial Fibrillation Study is a prospective multi-centre study aiming to study the incidence of AF in patients with no prior AF and a CHA2DS2-VASc score of at least 1, with the use of a mid-term continuous ECG monitoring device (Spyder ECG). Consecutive patients from both inpatient and outpatient settings were recruited from 3 major hospitals from May 2016 to December 2019. RESULTS: Three hundred and fifty-five patients were monitored. 6 patients (1.7%) were diagnosed with AF. There were no significant differences in total duration of monitoring between the AF and non-AF group (6.39 ± 3.19 vs 5.42 ± 2.46 days, p = 0.340). Patients with newly detected AF were more likely to have palpitations (50.0% vs 11.8%, p = 0.027). Half of the patients (n = 3, 50.0%) were diagnosed on the first day of monitoring and the rest were diagnosed after 24 h. On univariate analysis, only hyperlipidemia was associated with reduced odds of being diagnosed with AF (OR HR 0.08 CI 0.01-0.74, p = 0.025). In a group of 128 patients who underwent coronary artery bypass grafting and had post-operative ECG monitoring, 9 patients (7.0%) were diagnosed with post-operative AF. CONCLUSIONS: The use of non-invasive mid-term patch-based ECG monitoring is an effective modality for AF screening.

Predictors of unplanned hospital readmission after non-cardiac surgery in Singapore: a 2-year retrospective review.

INTRODUCTION: Unplanned hospital readmissions after surgery contribute significantly to healthcare costs and potential complications. Identifying predictors of readmission is inherently complex and involves an intricate interplay between medical factors, healthcare system factors and sociocultural factors. Therefore, the aim of this study was to elucidate the predictors of readmissions in an Asian surgical patient population. METHODS: A two-year single-institution retrospective cohort study of 2744 patients was performed in a university-affiliated tertiary hospital in Singapore, including patients aged 45 and above undergoing intermediate or high-risk non-cardiac surgery. Unadjusted analysis was first performed, followed by multivariable logistic regression. RESULTS: Two hundred forty-nine patients (9.1%) had unplanned 30-day readmissions. Significant predictors identified from multivariable analysis include: American Society of Anaesthesiologists (ASA) Classification grades 3 to 5 (adjusted OR 1.51, 95% CI 1.10-2.08, p = 0.01), obesity (adjusted OR 1.66, 95% CI 1.18-2.34, p = 0.04), asthma (OR 1.70, 95% CI 1.03-2.81, p = 0.04), renal disease (OR 2.03, 95% CI 1.41-2.92, p < 0.001), malignancy (OR 1.68, 95% CI 1.29-2.37, p < 0.001), chronic obstructive pulmonary disease (OR 2.46, 95% CI 1.19-5.11, p = 0.02), cerebrovascular disease (OR 1.73, 95% CI 1.17-2.58, p < 0.001) and anaemia (OR 1.45, 95% CI 1.07-1.96, p = 0.02). CONCLUSION: Several significant predictors of unplanned readmissions identified in this Asian surgical population corroborate well with findings from Western studies. Further research will require future prospective studies and development of predictive risk modelling to further address and mitigate this phenomenon.

Association between maternal labour epidural analgesia and autistic traits in offspring.

STUDY OBJECTIVE: Studies investigating associations between maternal epidural analgesia (MEA) and autism spectrum disorder (ASD) in the offspring are conflicting and lack prospective neurobehavioral follow-up assessments for autistic traits. We aim to prospectively investigate associations between MEA and autistic traits in the offspring. DESIGN: Prospective neurobehavioral observational cohort study. SETTING: Singaporean tertiary healthcare institutions. PATIENTS: Participants recruited were singleton non-IVF children, >36 weeks gestation, delivered via normal vaginal delivery by mothers >18 years of age, delivered in Singapore from June 2009-September 2010 and followed up over 7 years. INTERVENTIONS: Exposure to maternal epidural analgesia during delivery. MEASUREMENTS: The primary outcome is an abnormal Social Responsiveness Scale (SRS) T score at 7 years (≥60 points). Secondary outcomes include the diagnosis of ASD and abnormal scores for autistic traits assessed via a neurobehavioral battery comprising: CBCL (child behavioural checklist), Q-CHAT (Quantitative Checklist for Autism in Toddlers), and Bayley-III. Multivariable analyses adjusting for maternal and offspring characteristics were performed. MAIN RESULTS: 704 out of 769 mother-child dyads recruited fulfilled the criteria for analysis. 365/704 mothers received MEA. The incidence of an abnormal SRS score at 7 years in offspring exposed to MEA was 19.9%, and 26.1% in non-exposed offspring (p = 0.154). Multivariable analysis did not demonstrate a significant association between MEA and abnormal SRS scores at 7 years (O.R.0.726, 95% C·I. 0.394-1.34, p = 0.305). After adjustment for maternal and fetal demographics, exposure to MEA was not significantly associated with an abnormal screen in all other tests for autistic traits. The clinical incidence of ASD was 1.76% in children without exposure to MEA, and 2.32% in children with MEA exposure (p = 0.506). CONCLUSIONS: MEA is not significantly associated with the development of ASD and autistic traits in offspring, assessed over 7 years. Results should be taken into perspective given our wide confidence intervals and small cohort size.

Thoracic Epidural Anesthesia in Cardiac Surgery: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis of Randomized Controlled Trials.

BACKGROUND: Research on fast-track recovery protocols postulates that thoracic epidural anesthesia (TEA) in cardiac surgery contributes to improved postoperative outcomes. However, concerns about TEA's safety hinder its widespread usage. We conducted a systematic review and meta-analysis to assess the benefits and risks of TEA in cardiac surgery. METHODS: We searched 4 databases for randomized controlled trials (RCTs) assessing the use of TEA against only general anesthesia (GA) in adults undergoing cardiac surgery, up till June 4, 2022. We conducted random-effects meta-analyses, evaluated risk of bias using the Cochrane Risk-of-Bias 2 tool, and rated certainty of evidence via the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Primary outcomes were intensive care unit (ICU), hospital length of stay, extubation time (ET), and mortality. Other outcomes included postoperative complications. Trial sequential analysis (TSA) was conducted on all outcomes to elicit statistical and clinical benefit. RESULTS: Our meta-analysis included 51 RCTs (2112 TEA patients and 2220 GA patients). TEA significantly reduced ICU length of stay (-6.9 hours; 95% confidence interval [CI], -12.5 to -1.2; P = .018), hospital length of stay (-0.8 days; 95% CI, -1.1 to -0.4; P < .0001), and ET (-2.9 hours; 95% CI, -3.7 to -2.0; P < .0001). However, we found no significant change in mortality. TSA found that the cumulative Z-curve passed the TSA-adjusted boundary for ICU length of stay, hospital length of stay, and ET, suggesting a clinical benefit. TEA also significantly reduced pain scores, pooled pulmonary complications, transfusion requirements, delirium, and arrhythmia, without additional complications such as epidural hematomas, of which the risk was estimated to be <0.14%. CONCLUSIONS: TEA reduces ICU and hospital length of stay, and postoperative complications in patients undergoing cardiac surgery with minimal reported complications such as epidural hematomas. These findings favor the use of TEA in cardiac surgery and warrant consideration for use in cardiac surgeries worldwide.

Risk factors of post-anaesthesia care unit delirium in patients undergoing non-cardiac surgery in Singapore.

Introduction: Post-anaesthesia care unit (PACU) delirium affects 5%-45% of patients after surgery and is associated with postoperative delirium and increased mortality. Up to 40% of PACU delirium is preventable, but it remains under-recognised due to a lack of awareness of its diagnosis. The nursing delirium screening scale (Nu-DESC) has been validated for diagnosing PACU delirium, but is not routinely used locally. This study aimed to use Nu-DESC to establish the incidence and risk factors of PACU delirium in patients undergoing non-cardiac surgery in the surgical population. Methods: We conducted an audit of eligible patients undergoing major surgery in three public hospitals in Singapore over 1 week. Patients were assessed for delirium 30-60 min following their arrival in PACU using Nu-DESC, with a total score of ≥2 indicative of delirium. Results: A total of 478 patients were assessed. The overall incidence rate of PACU delirium was 18/478 (3.8%), and the incidence was 9/146 (6.2%) in patients aged > 65 years. Post-anaesthesia care unit delirium was more common in females, patients with malignancy and those who underwent longer operations. Logistic regression analysis showed that the use of bispectral index (P < 0.001) and the presence of malignancy (P < 0.001) were significantly associated with a higher incidence of PACU delirium. Conclusion: In this first local study, the incidence of PACU delirium was 3.8%, increasing to 6.2% in those aged > 65 years. Understanding these risk factors will form the basis for which protocols can be established to optimise resource management and prevent long-term morbidities and mortality in PACU delirium.

Point-of-care platelet function testing for guided transfusion in neurosurgical management of intracranial hemorrhage: a systematic review.

Given the rising prevalence of antiplatelet therapy, rapid preoperative identification of patients with bleeding diathesis is necessary for the guidance of blood product administration. This is especially relevant in neurosurgery for intracranial hemorrhage (ICH), where indiscriminate transfusions may lead to further hemorrhagic or thromboembolic injury. Point-of-care (POC) testing of platelet function is a promising solution to this dilemma, as it has been proven effective in cardiac surgery. However, to date, POC platelet function testing in neurosurgery has not been extensively evaluated. This systematic review appraises the use of POC platelet function test (PFT) in emergency neurosurgery in terms of its impact on patient outcomes.A comprehensive search was conducted on four electronic databases (Pubmed, MEDLINE, Embase, and Cochrane) for relevant English language articles from their respective inceptions until 1 June 2022. We included all randomized controlled trials and cohort studies that met the following inclusion criteria: (i) involved adult patients undergoing neurosurgery for ICH; (ii) evaluated platelet function via POC PFT; (iii) reported a change in perioperative blood loss; and/or (iv) reported data on treatment-related adverse events and mortality. Assessment of study quality was conducted using the Newcastle Ottawa Quality Assessment Scale for Cohort Studies and Case-Control Studies, and the JBI Critical Appraisal Checklist for Case Series.The search yielded 2,835 studies, of which seven observational studies comprising 849 patients met the inclusion criteria for this review. Overall, there is evidence that the use of POC PFT to assess bleeding risk reduced bleeding events, thromboembolic adverse outcomes, and the length of hospitalization. However, there is currently insufficient evidence to suggest that using POC PFT improves blood product use, functional outcomes or mortality.

Intravenous amino acid therapy for kidney protection in cardiac surgery a protocol for a multi-centre randomized blinded placebo controlled clinical trial. The PROTECTION trial.

BACKGROUND: Postoperative acute kidney injury (AKI) is frequent in cardiac surgery patients. Its pathophysiology is complex and involves decreased renal perfusion. Preliminary clinical evidence in critically ill patients shows that amino acids infusion increases renal blood flow and may decrease the incidence and severity of AKI. We designed a study to evaluate the effectiveness of perioperative continuous infusion of amino acids in decreasing AKI. METHODS: This is a phase III, multi-center, randomized, double-blind, placebo-controlled trial. Adults undergoing cardiac surgery with cardiopulmonary bypass (CPB) are included. Patients are randomly assigned to receive either continuous infusion of a balanced mixture of amino acids in a dose of 2 g/kg ideal body weight/day or placebo (balanced crystalloid solution) from the operating room up to start of renal replacement therapy (RRT), or ICU discharge, or 72 h after the first dose. The primary outcome is the incidence of AKI during hospital stay defined by KDIGO (Kidney Disease: Improving Global Outcomes). Secondary outcomes include the need for, and duration of, RRT, mechanical ventilation; ICU and hospital length of stay; all-cause mortality at ICU, hospital discharge, 30, 90, and 180 days after randomization; quality of life at 180 days. Data will be analyzed in 3500 patients on an intention-to-treat basis. DISCUSSION: The trial is ongoing and currently recruiting. It will be one of the first randomized controlled studies to assess the relationship between amino acids use and kidney injury in cardiac surgery. If our hypothesis is confirmed, this practice could reduce morbidity in the studied population. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov with the trial identification NCT03709264 in October 2018.

Bispectral Index (BIS) Monitoring and Postoperative Delirium in Elderly Patients Undergoing Surgery: A Systematic Review and Meta-Analysis With Trial Sequential Analysis.

OBJECTIVE: To examine the effect of bispectral index (BIS)-guided anesthesia on the incidence of postoperative delirium (POD) in elderly patients undergoing surgery. DESIGN: A systematic review, meta-analysis, and trial sequential analysis (TSA). SETTING: In the operating room, postoperative anesthesia care units (PACU), and ward. PARTICIPANTS: Elderly patients (>60 years old) undergoing surgery. INTERVENTIONS: The EMBASE, MEDLINE, and CENTRAL databases were searched systematically from their inception until December 2020 for randomized controlled trials comparing BIS and usual care or blinded BIS. MEASUREMENTS AND MAIN RESULTS: Ten trials (N = 3,891) were included for quantitative meta-analysis. In comparison to the control group, there was no significant difference in the incidence of POD in elderly patients randomized to BIS-guided anesthesia (odds ratio [OR] 0.71, 95% CI 0.47-1.08, I2 = 76%, p = 0.11, level of evidence = very low, TSA = inconclusive). The authors' review demonstrated that elderly patients with BIS-guided anesthesia were significantly associated with a lower incidence of postoperative cognitive dysfunction (POCD) (OR 0.64, 95% CI 0.46-0.88, p = 0.006), extubation time (mean difference [MD] -3.38 minutes, 95% CI -4.38 to -2.39, p < 0.00001), time to eye opening (MD -2.17 minutes, 95% CI -4.21 to -0.14, p = 0.04), and time to discharge from the PACU (MD -10.77 minutes, 95% CI -11.31 to - 10.23, p < 0.00001). CONCLUSION: The authors' meta-analysis demonstrated that BIS-guided anesthesia was not associated with a reduced incidence of POD, but it was associated with a reduced incidence of POCD and improved recovery parameters.

Nocturnal Oxygen Desaturation Index Correlates with Respiratory Depression in Post-Surgical Patients Receiving Opioids - A Post-Hoc Analysis from the Prediction of Opioid-Induced Respiratory Depression in Patients Monitored by Capnography (PRODIGY) Study.

Purpose: Postoperative monitoring of respiratory status on general care wards typically consists of intermittent checks of oxyhemoglobin saturation and respiratory rate, allowing substantial unmonitored time for severe opioid induced respiratory depression (RD) to develop unnoticed. Oxygen desaturation index (ODI) can be computed solely by continuous pulse oximetry monitoring. In this post-hoc analysis, we evaluate whether nocturnal ODI correlates with RD. Patients and Methods: The PRODIGY trial (NCT02811302) was a multinational study conducted where adult patients receiving parenteral opioids on the general care floor were continuously monitored by blinded pulse oximetry and capnography monitoring to detect episodes of RD. An RD episode was defined as: respiratory rate ≤5 breaths/min (bpm) for ≥3 minutes, oxygen saturation (SpO2) ≤85% for ≥3 minutes, end-tidal carbon dioxide (EtCO2) ≤15 or ≥60 mm Hg for ≥3 minutes, apnea episode lasting >30 seconds, or any respiratory opioid-related adverse event. Data were used to calculate nocturnal (00:00 ─ 06:00) ODI4% based on desaturation episodes (4% decrease from mean oxyhemoglobin saturation in the past 120 seconds, lasting ≥10 seconds). Continuous monitoring began after a patient received parenteral opioids, allowing identification of potential RD and ODI4% episodes during opioid therapy. The average number of ODI4% episodes (≥1, ≥5, ≥10, ≥15 episodes/hour) were analyzed. Logistic regression and area under the receiver operating characteristic curve (AUC) were computed. Results: A final cohort of 1072 (out of 1335) patients had sufficient data, with 76% (N=817/1072) having ≥1 episode of ODI4%. Multivariable logistic regression showed that ODI4% was strongly associated with RD, with greater risk for higher ODI4% scores: ≥5 episodes/hour odds ratio 2.59 (95% CI 1.72-3.89, p<0.0001); ≥10 episodes/hour 3.39 (95% CI 1.80-6.39, p=0.0002); ≥15 episodes/hour 4.71 (95% CI 1.93-11.47, p=0.0006).There was no significant association between ODI4% and respiratory adverse events. Conclusion: Nocturnal ODI4% was highly correlated with RD among hospitalized patients receiving parenteral opioids. Patients with a high ODI4%, especially with ≥15 episodes/hour, are more likely to experience RD and should be evaluated for the need of closer monitoring after opioid administration.

Variant landscape of the RYR1 gene based on whole genome sequencing of the Singaporean population.

The RYR1 gene codes for a ryanodine receptor which is a calcium release channel in the skeletal muscle sarcoplasmic reticulum. It is associated with Malignant Hyperthermia (MH) and congenital myopathies including Central Core Disease (CCD), Multiminicore Disease (MMD) and Congenital Fibre-Type Disproportion (CFTD). There is currently little information on the epidemiology of RYR1 variants in Asians. Our study aims to describe the RYR1 variant landscape in a Singapore cohort unselected for RYR1-associated conditions. Data was retrieved from the SG10K pilot project, where whole genome sequencing was performed on volunteers unselected and undetermined for RYR1-associated conditions. Variants were classified based on pathogenicity using databases ClinVar and InterVar. Allele frequencies of pathogenic variants were compared between Chinese, Indians and Malays. Using databases ExAC, GnomAD and GenomeAsia 100k study, we further compared local allele frequencies to those in Europe, America and Asia. Data was analysed using R Commander. Significant P value was set at p < 0.05. Majority of the RYR1 variants were missense mutations. We identified four pathogenic and four likely pathogenic RYR1 variants. All were related to the aforementioned RYR1-associated conditions. There were 6 carriers of RYR1 pathogenic variants amongst 4810 individuals, corresponding to an allele frequency of 0.06%. The prevalence of pathogenic variants was the highest amongst Indians (4 in 1127 individuals) (p = 0.030). Majority of pathogenic and likely pathogenic mutations were missense and located in mutational hotspots. These variants also occurred at higher frequencies in Asians than globally. This study describes the variant landscape of the RYR1 gene in Singapore. This knowledge will facilitate genetic screening for RYR1-related conditions.

Association Between Race and Opioid-Induced Respiratory Depression: An International Post Hoc Analysis of the Prediction of Opioid-induced Respiratory Depression In Patients Monitored by Capnography Trial.

BACKGROUND: Opioid-induced respiratory depression (OIRD) is common on the medical and surgical wards and is associated with increased morbidity and health care costs. While previous studies have investigated risk factors for OIRD, the role of race remains unclear. We aim to investigate the association between race and OIRD occurrence on the medical/surgical ward. METHODS: This is a post hoc analysis of the PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial; a prospective multinational observational blinded study of 1335 general ward patients who received parenteral opioids and underwent blinded capnography and oximetry monitoring to identify OIRD episodes. For this study, demographic and perioperative data, including race and comorbidities, were analyzed and assessed for potential associations with OIRD. Univariable χ 2 and Mann-Whitney U tests were used. Stepwise selection of all baseline and demographic characteristics was used in the multivariable logistic regression analysis. RESULTS: A total of 1253 patients had sufficient racial data (317 Asian, 158 Black, 736 White, and 42 other races) for inclusion. The incidence of OIRD was 60% in Asians (N = 190/317), 25% in Blacks (N = 40/158), 43% in Whites (N = 316/736), and 45% (N = 19/42) in other races. Baseline characteristics varied significantly: Asians were older, more opioid naïve, and had higher opioid requirements, while Blacks had higher incidences of heart failure, obesity, and smoking. Stepwise multivariable logistic regression revealed that Asians had increased risk of OIRD compared to Blacks (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.54-4.04; P = .0002) and Whites (OR, 1.38; 95% CI, 1.01-1.87; P = .0432). Whites had a higher risk of OIRD compared to Blacks (OR, 1.81; 95% CI, 1.18-2.78; P = .0067). The model's area under the curve was 0.760 (95% CI, 0.733-0.787), with a Hosmer-Lemeshow goodness-of-fit test P value of .23. CONCLUSIONS: This post hoc analysis of PRODIGY found a novel association between Asian race and increased OIRD incidence. Further study is required to elucidate its underlying mechanisms and develop targeted care pathways to reduce OIRD in susceptible populations.

Evaluation of the Efficiency and Safety of a Safe Label System: A Prospective Simulation Study.

OBJECTIVES: Our study aims to investigate the safety and efficiency of the Codonics Safe Label System (SLS) in a prospective simulation study. METHODS: Three sets of simulated experiments involving 82 anesthetists were carried out on patient simulator mannequins. The primary outcome assessed through the simulated experiments was the effectiveness of the SLS in avoiding vial swap errors. Secondary outcomes analyzed included the efficacy of the SLS in preventing syringe swap and the difference in time taken to prepare standardized drugs as compared with conventional methods. RESULTS: The SLS was associated with a significant reduction in all 4 stages of vial swap error. The incidence of wrong ampoule breakage was significantly lower in the SLS group compared with the conventional group (12.1% versus 38.5%, P = 0.007). The number of staff who drew the wrong ampoule was similarly lower in the SLS group compared with the conventional group (4.9% versus 33.3%, P = 0.001). The proportions of staff who eventually wrongly labeled the loaded syringe were 0% in the SLS group and 17.9% in the conventional group (P = 0.005).Drug preparation time was longer for the SLS group than for the conventional group (239.6 ± 45.9 versus 160.3 ± 46.5 seconds, P < 0.001).There was no significant difference in the incidence of syringe swap with the use of the SLS. CONCLUSIONS: The use of the SLS is effective in reducing vial swap error, but not syringe swap errors, and is associated with increased time taken for anesthetic drug preparation.