Pharmacokinetic modeling of tranexamic acid for patients undergoing cardiac surgery with normal renal function and model simulations for patients with renal impairment

Tranexamic acid (TXA), an effective anti-fibrinolytic agent that is cleared by glomerular filtration, is used widely for cardiopulmonary bypass (CPB) surgery. However, an effective dosing regimen has not been fully developed in patients with renal impairment. The aims of this study were to characterize the inter-patient variability associated with pharmacokinetic parameters and to recommend a new dosing adjustment based on the BART dosing regimen for CPB patients with chronic renal dysfunction (CRD). Recently published data on CPB patients with normal renal function (n = 15) were re-examined with a two-compartment model using the ADAPT5® and NONMEMVII® to identify covariates that explain inter-patient variability and to ascertain whether sampling strategies might affect parameter estimation. A series of simulations was performed to adjust the BART dosing regimen for CPB patients with renal impairment. Based on the two-compartmental model, the number of samples obtained after discontinuation of TXA infusion was found not to be critical in parameter estimation (p > 0.05). Both body weight and creatinine clearance were identified as significant covariates (p < 0.005). Simulations showed significantly higher than normal TXA concentrations in CRD patients who received the standard dosing regimen in the BART trial. Adjustment of the maintenance infusion rate based on the percent reduction in renal clearance resulted in predicted plasma TXA concentrations that were safe and therapeutic (~100 mg·L(-1) ). Our proposed dosing regimen, with consideration of renal function, is predicted to maintain effective target plasma concentrations below those associated with toxicity for patients with renal failure for CPB

Effect of sedation with inhaled anaesthetics on cognitive and psychiatric outcomes in critically ill adults: a systematic review protocol

Introduction The COVID-19 pandemic has renewed interest in the use of inhaled anaesthetics for sedation of ventilated critically ill patients. Preliminary data show that inhaled anaesthetics reduce lung inflammation, time to extubation and intensive care unit length of stay compared with intravenous sedatives. However, the impact of inhaled anaesthetics on cognitive and psychiatric outcomes is not well described in this setting. Randomised controlled trials are underway to establish if inhaled anaesthetics affect these and other patient and health system outcomes. Our aim is to summarise the known effects of inhaled sedatives on cognitive and psychiatric outcomes. Methods and analysis In this systematic review, we will use MEDLINE, EMBASE, and PsycINFO to identify studies from 1970 to 2021 that assessed cognitive and psychiatric outcomes in critically ill adult patients sedated with inhaled anaesthetics. We will include case series, observational and cohort studies and randomised controlled trials. We will exclude case studies due to the heterogeneity of reporting in these studies. For randomised controlled trials comparing inhaled to intravenous sedation, we will report cognitive and psychiatric outcomes for both study arms. Studies will be selected based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Data will be extracted using a standardised data extraction tool by two independent reviewers. Studies will be assessed for bias using the Cochrane risk of bias tool for randomised controlled trials, or the Newcastle-Ottawa Scale for cohort and case-control studies. Findings will be reported according to outcome and descriptive statistics will be used to illustrate findings in a narrative fashion. Ethics and dissemination The systematic review uses published data and therefore does not require ethics approval. Results will be disseminated via publication in peer-reviewed journals and presentation at conferences related to the field. PROSPERO registration number CRD42021236455

Postoperative Discharge Destination Impacts 30-Day Outcomes: A National Surgical Quality Improvement Program Multi-Specialty Surgical Cohort Analysis

Surgical patients can be discharged to a variety of facilities which vary widely in intensity of care. Postoperative readmissions have been found to be more strongly associated with post-discharge events than pre-discharge complications, indicating the importance of discharge destination. We sought to evaluate the association between discharge destination and 30-day outcomes. A retrospective cohort study was conducted using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Patients were dichotomized based on discharge destination: home versus non-home. The main outcome of interest was 30-day unplanned readmission. The secondary outcomes included post-discharge pulmonary, infectious, thromboembolic, and bleeding complications, as well as death. In this cohort study of over 1.5 million patients undergoing common surgical procedures across eight surgical specialties, we found non-home discharge to be associated with adverse 30-day post-operative outcomes, namely, unplanned readmissions, post-discharge pulmonary, infectious, thromboembolic, and bleeding complications, as well as death. Non-home discharge is associated with worse 30-day outcomes among patients undergoing common surgical procedures. Patients and caregivers should be counseled regarding discharge destination, as non-home discharge is associated with adverse post-operative outcomes

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

American College of Rheumatology Provisional Criteria for Clinically Relevant Improvement in Children and Adolescents With Childhood-Onset Systemic Lupus Erythematosus

10.1002/acr.23834ARTHRITIS CARE & RESEARCH715579-59

Surgical Critical Care Utilization in Adult patients undergoing Major Non-Cardiac Surgery in Ontario: A Population Based Study

Objective: Assess the inter-hospital variation and factors associated with intensive care unit (ICU) admission for adult elective non-cardiac surgical patients in Ontario. Methodology: Population databases identified 13 surgical groups between January 2006-December 2014. Primary outcome assessed early ICU utilization within 24 hours post-surgery. I described the inter-hospital variation in proportion of patients admitted to ICU, patient and hospital-level factors associated with ICU admission using multilevel logistic regression for each group. Intra-class correlation coefficient (ICC) and median odds ratio (MOR) assessed the association of individual hospitals with ICU admission. Results: 541,524 patients across 93 hospitals were studied. Early ICU admission varied between 0.9% (hysterectomy) and 90.8% (open abdominal aortic aneurysm repair). ICC ranged between 18% for hysterectomy (MOR 2.3) to 75.9% for endovascular aortic aneurysm repair (MOR 21.5). Conclusion: Ontario hospitals showed wide inter-hospital variation in early ICU admission with a large proportion of this variation attributable to the admitting hospital.M.Sc

Tranexamic acid: a clinical review

  Blood loss and subsequent transfusions are associated with major morbidity and mortality. The use of antifibrinolytics can reduce blood loss in cardiac surgery, trauma, orthopedic surgery, liver surgery and solid organ transplantation, obstetrics and gynecology, neurosurgery and non-surgical diseases. The evidence of their efficacy has been mounting for years. Tranexamic acid (TXA), a synthetic lysine-analogue antifibrinolytic, was first patented in 1957 and its use has been increasing in contrast to aprotinin, a serine protease inhibitor antifibrinolytic. This review aims to help acute care physicians navigate through the clinical evidence available for TXA therapy, develop appropriate dose regimens whilst minimizing harm, as well as understand its broadening scope of applications. Many questions remain unanswered regarding other clinical effects of TXA such as anti-inflammatory response to cardiopulmonary bypass, the risk of thromboembolic events, adverse neurological effects such as seizures, and its morbidity and mortality, all of which necessitate further clinical trials on its usage and safety in various clinical settings.  Blood loss and subsequent transfusions are associated with major morbidity and mortality. The use of antifibrinolytics can reduce blood loss in cardiac surgery, trauma, orthopedic surgery, liver surgery and solid organ transplantation, obstetrics and gynecology, neurosurgery and non-surgical diseases. The evidence of their efficacy has been mounting for years. Tranexamic acid (TXA), a synthetic lysine-analogue antifibrinolytic, was first patented in 1957 and its use has been increasing in contrast to aprotinin, a serine protease inhibitor antifibrinolytic. This review aims to help acute care physicians navigate through the clinical evidence available for TXA therapy, develop appropriate dose regimens whilst minimizing harm, as well as understand its broadening scope of applications. Many questions remain unanswered regarding other clinical effects of TXA such as anti-inflammatory response to cardiopulmonary bypass, the risk of thromboembolic events, adverse neurological effects such as seizures, and its morbidity and mortality, all of which necessitate further clinical trials on its usage and safety in various clinical settings

Real-Time Three-Dimensional Transesophageal EchocardiographyA Step-by-Step Guide /

XVII, 234p. 188 illus., 185 illus. in color.onlin

Early versus late tracheostomy in cardiovascular intensive care patients

Background: Benefits of tracheostomy have been well established. Most of the literature, refers these benefits to general intensive care population, excluding cardiac surgery or including only small number of these patients. On the other hand, there is no clear definition describing the proper time to perform the procedure and defining what are potential benefits of early compared to late tracheostomy. This retrospective cohort aims to assess the potential benefits of early tracheostomy on post-operative outcomes, length of stay and post-tracheostomy complications within cardiac surgical population. Methods: After obtaining REB approval, we conducted a retrospective chart review in a single, tertiary care institution, identifying patients who underwent tracheostomy after cardiac surgery from 1999 to 2006. Time-to-tracheostomy was defined as “early” if &lt; 7 days or “late” if ≥ 7 days post-cardiac surgery). Results: 14,101 patients underwent cardiac surgery over the 7-year study period; from those, 147 (1.36%) received tracheostomy. 32 (22%) patients underwent early tracheostomy and 115 (78%) late tracheostomy. Incidence of atrial fibrillation (31.2% vs 61.7%; P = 0.003), kidney dysfunction (6.3% vs 27.2%; P=0.015) and kidney failure 18.8% vs 43.5%; P = 0.013) were lower in the early tracheostomy group. There were no differences on post tracheostomy infection or presence of acute respiratory distress syndrome. Both the ICU and hospital length of stay were significantly shorter in early tracheostomy group, 21.5 (ET) vs 36.9 (LT) days and 37.5 (ET) vs 57.6 (LT) days respectively. There were no differences in mortality between groups. Conclusions: There are significant benefits in reduction of postoperative morbidities with overall shorter ICU and hospital stay. These benefits may promote faster patient rehabilitation with reduced healthcare costs