Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial.

BACKGROUND: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared to intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients. METHODS: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass. Between September 17, 2019, and November 28, 2023, a total of 3242 patients from 16 hospitals in 6 countries were randomly assigned (1:1 ratio) to receive either intravenous tranexamic acid (control) through surgery or topical tranexamic acid (treatment) at the end of surgery. The primary outcome was seizure, and the secondary outcome was red blood cell transfusion. After the last planned interim analysis-when 75% of anticipated participants had completed follow up-the Data and Safety Monitoring Board recommended to terminate the trial, and upon unblinding, the Operations Committee stopped the trial for safety. RESULTS: Among 3242 randomized patients (mean age, 66.0 years; 77.7% male), in-hospital seizure occurred in 4 of 1624 patients (0.2%) in the topical group and in 11 of 1628 patients (0.7%) in the intravenous group (absolute risk difference, -0.5%; 95% CI, -0.9 to 0.03; P = .07). Red blood cell transfusion occurred in 570 patients (35.1%) in the topical group and in 433 (26.8%) in the intravenous group (absolute risk difference, 8.3%; 95% CI, 5.2 to 11.5; P = .007). The absolute risk difference in transfusion of ≥4 units of red blood cells in the topical group compared to the intravenous group was 8.2% (95% CI, 3.4 to 12.9). CONCLUSIONS: Among patients having cardiac surgery, topical administration of tranexamic acid resulted in an 8.3% absolute increase in transfusion without reducing the incidence of seizure, compared to intravenous tranexamic acid.

Closing the care gap: combining enhanced recovery with minimally invasive valve surgery.

PURPOSE OF REVIEW: Patients with advanced age and frailty require interventions for structural heart disease at an increasing rate. These patients typically experience higher rates of postoperative morbidity, mortality and prolonged hospital length of stay, loss of independence as well as associated increased costs to the healthcare system. Therefore, it is becoming critically important to raise awareness and develop strategies to improve clinical outcomes in the contemporary, high-risk patient population undergoing cardiacprocedures. RECENT FINDINGS: Percutaneous options for structural heart disease have dramatically improved the therapeutic options for some older, frail, high-risk patients; however, others may still require cardiac surgery. Minimally invasive techniques can reduce some of the physiologic burden experienced by patients undergoing surgery and improve recovery. Enhanced Recovery After Cardiac Surgery (ERAS Cardiac) is a comprehensive, interdisciplinary, evidence-based approach to perioperative care. It has been shown to improve recovery and patient satisfaction while reducing complications and length of stay. SUMMARY: Combining minimally invasive cardiac surgery with enhanced recovery protocols may result in improved patient outcomes for a patient population at high risk of morbidity and mortality following cardiac surgery.

Hemorrhage, Disseminated Intravascular Coagulopathy, and Thrombosis Complications Among Critically Ill Patients with COVID-19: An International COVID-19 Critical Care Consortium Study.

OBJECTIVES: To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19. DESIGN: Prospective, observational study. SETTING: Two hundred twenty-nine ICUs across 32 countries. PATIENTS: Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: HECTOR complications occurred in 1,732 of 11,969 study eligible patients (14%). Acute thrombosis occurred in 1,249 patients (10%), including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial ischemia, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic strokes. Hemorrhagic complications were reported in 579 patients (4.8%), including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, 77 (13%) with pulmonary hemorrhage, and 68 (12%) with hemorrhage associated with extracorporeal membrane oxygenation (ECMO) cannula site. Disseminated intravascular coagulation occurred in 11 patients (0.09%). Univariate analysis showed that diabetes, cardiac and kidney diseases, and ECMO use were risk factors for HECTOR. Among survivors, ICU stay was longer (median days 19 vs 12; p < 0.001) for patients with versus without HECTOR, but the hazard of ICU mortality was similar (hazard ratio [HR] 1.01; 95% CI 0.92-1.12; p = 0.784) overall, although this hazard was identified when non-ECMO patients were considered (HR 1.13; 95% CI 1.02-1.25; p = 0.015). Hemorrhagic complications were associated with an increased hazard of ICU mortality compared to patients without HECTOR complications (HR 1.26; 95% CI 1.09-1.45; p = 0.002), whereas thrombosis complications were associated with reduced hazard (HR 0.88; 95% CI 0.79-0.99, p = 0.03). CONCLUSIONS: HECTOR events are frequent complications of severe COVID-19 in ICU patients. Patients receiving ECMO are at particular risk of hemorrhagic complications. Hemorrhagic, but not thrombotic complications, are associated with increased ICU mortality.

Morbid obesity's impact on COVID-19 patients requiring venovenous extracorporeal membrane oxygenation: The covid-19 critical care consortium database review.

Introduction: Obesity is associated with a worse prognosis in COVID-19 patients with acute respiratory distress syndrome (ARDS). Veno-venous (V-V) Extracorporeal Membrane Oxygenation (ECMO) can be a rescue option, however, the direct impact of morbid obesity in this select group of patients remains unclear.Methods: This is an observational study of critically ill adults with COVID-19 and ARDS supported by V-V ECMO. Data are from 82 institutions participating in the COVID-19 Critical Care Consortium international registry. Patients were admitted between 12 January 2020 to 27 April 2021. They were stratified based on Body Mass Index (BMI) at 40 kg/m2. The endpoint was survival to hospital discharge.Results: Complete data available on 354 of 401 patients supported on V-V ECMO. The characteristics of the high BMI (>40 kg/m2) and lower BMI (≤40 kg/m2) groups were statistically similar. However, the 'high BMI' group were comparatively younger and had a lower APACHE II score. Using survival analysis, older age (Hazard Ratio, HR 1.49 per-10-years, CI 1.25-1.79) and higher BMI (HR 1.15 per-5 kg/m2 increase, CI 1.03-1.28) were associated with a decreased patient survival. A safe BMI threshold above which V-V ECMO would be prohibitive was not apparent and instead, the risk of an adverse outcome increased linearly with BMI.Conclusion: In COVID-19 patients with severe ARDS who require V-V ECMO, there is an increased risk of death associated with age and BMI. The risk is linear and there is no BMI threshold beyond which the risk for death greatly increases.

It's not all about ISCHEMIA: the case for coronary artery bypass grafting in stable coronary artery disease.

PURPOSE OF REVIEW: The recent American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions Guidelines for Coronary Artery Revascularization have raised concerns on the survival benefits of coronary artery bypass grafting (CABG) over guideline-directed medical therapy (GDMT) in stable coronary artery disease (CAD) and appropriate conduit selection for CABG. This review summarizes the evidence supporting CABG for stable CAD and use of the radial artery as a conduit for CABG. RECENT FINDINGS: CABG has consistently demonstrated a survival benefit over GDMT for patients with stable multivessel CAD. These benefits were more pronounced in patients with diabetes and/or anatomically complex coronary artery disease. The recently published International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial was not designed to and did not include an appropriate patient population to compare revascularization with CABG to GDMT. These results should thus be viewed in the context of previously published studies. Furthermore, increasing evidence suggests that use of a radial artery in CABG is associated with reduced myocardial infarction and repeat revascularization. This should be considered when selecting the appropriate conduits based on underlying patient factors. SUMMARY: Readers should be cautious when applying these guidelines broadly. Appropriate consideration of patient and anatomic factors, and in consultation with a multidisciplinary heart team, is important to achieve the best outcomes for patients.

Impact of renin-angiotensin-aldosterone system inhibition on mortality in critically ill COVID-19 patients with pre-existing hypertension: a prospective cohort study.

BACKGROUND: The influence of renin-angiotensin-aldosterone system (RAAS) inhibitors on the critically ill COVID-19 patients with pre-existing hypertension remains uncertain. This study examined the impact of previous use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on the critically ill COVID-19 patients. METHODS: Data from an international, prospective, observational cohort study involving 354 hospitals spanning 54 countries were included. A cohort of 737 COVID-19 patients with pre-existing hypertension admitted to intensive care units (ICUs) in 2020 were targeted. Multi-state survival analysis was performed to evaluate in-hospital mortality and hospital length of stay up to 90 days following ICU admission. RESULTS: A total of 737 patients were included-538 (73%) with pre-existing hypertension had received ACEi/ARBs before ICU admission, while 199 (27%) had not. Cox proportional hazards model showed that previous ACEi/ARB use was associated with a decreased hazard of in-hospital death (HR, 0.74, 95% CI 0.58-0.94). Sensitivity analysis adjusted for propensity scores showed similar results for hazards of death. The average length of hospital stay was longer in ACEi/ARB group with 21.2 days (95% CI 19.7-22.8 days) in ICU and 6.7 days (5.9-7.6 days) in general ward compared to non-ACEi/ARB group with 16.2 days (14.1-18.6 days) and 6.4 days (5.1-7.9 days), respectively. When analysed separately, results for ACEi or ARB patient groups were similar for both death and discharge. CONCLUSIONS: In critically ill COVID-19 patients with comorbid hypertension, use of ACEi/ARBs prior to ICU admission was associated with a reduced risk of in-hospital mortality following adjustment for baseline characteristics although patients with ACEi/ARB showed longer length of hospital stay. Clinical trial registration The registration number: ACTRN12620000421932; The date of registration: 30, March 2020; The URL of the registration: https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12620000421932 .

Perioperative Quality Initiative and Enhanced Recovery After Surgery-Cardiac Society Consensus Statement on the Management of Preoperative Anemia and Iron Deficiency in Adult Cardiac Surgery Patients.

Preoperative anemia is common in patients presenting for cardiac surgery, with a prevalence of approximately 1 in 4, and has been associated with worse outcomes including increased risk of blood transfusion, kidney injury, stroke, infection, and death. Iron deficiency, a major cause of anemia, has also been shown to have an association with worse outcomes in patients undergoing cardiac surgery, even in the absence of anemia. Although recent guidelines have supported diagnosing and treating anemia and iron deficiency before elective surgery, details on when and how to screen and treat remain unclear. The Eighth Perioperative Quality Initiative (POQI 8) consensus conference, in conjunction with the Enhanced Recovery after Surgery-Cardiac Surgery Society, brought together an international, multidisciplinary team of experts to review and evaluate the literature on screening, diagnosing, and managing preoperative anemia and iron deficiency in patients undergoing cardiac surgery, and to provide evidence-based recommendations in accordance with Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria for evaluating biomedical literature.

Frailty-aware care: giving value to frailty assessment across different healthcare settings.

Healthcare systems need to adapt to better serve an aging population with complex presentations. Frailty assessments are a potential means to address this heterogeneity in aging to identify individuals at increased risk for adverse health outcomes. Furthermore, frailty assessments offer an opportunity to optimize patient care in various healthcare settings. While the vast number of frailty assessment tools available can be a source of confusion for clinicians, each tool has features adaptable to the constraints and goals of different healthcare settings. This review discusses and compares barriers, facilitators, and the application of frailty assessments in primary care, the emergency department/intensive care unit and surgical care to cover a breadth of settings with different frailty assessment considerations. The implementation of frailty-aware care across healthcare settings potentiates better healthcare outcomes for older adults.

Fabrication of Smart Tantalum Carbide MXene Quantum Dots with Intrinsic Immunomodulatory Properties for Treatment of Allograft Vasculopathy.

MXene nanomaterials have sparked significant interest among interdisciplinary researchers to tackle today's medical challenges. In particular, colloidal MXene quantum dots (MQDs) offer the high specific surface area and compositional flexibility of MXene while providing improvements to aqueous stability and material-cell interactions. The current study for the first time reports the development and application of immunoengineered tantalum-carbide (Ta4C3T x ) MQDs for in vivo treatment of transplant vasculopathy. This report comes at a critical juncture in the field as poor long-term safety of other MXene compositions challenge the eventual clinical translatability of these materials. Using rational design and synthesis strategies, the Ta4C3T x MQDs leverage the intrinsic anti-inflammatory and antiapoptotic properties of tantalum to provide a novel nanoplatform for biomedical engineering. In particular, these MQDs are synthesized with high efficiency and purity using a facile hydrofluoric acid-free protocol and are enriched with different bioactive functional groups and stable surface TaO2 and Ta2O5. Furthermore, MQDs are spontaneously uptaken into antigen-presenting endothelial cells and alter surface receptor expression to reduce their activation of allogeneic T-lymphocytes. Finally, when applied in vivo, Ta4C3T x MQDs ameliorate the cellular and structural changes of early allograft vasculopathy. These findings highlight the robust potential of tailored Ta4C3T x MQDs for future applications in medicine.

Ischemic and Hemorrhagic Stroke Among Critically Ill Patients With Coronavirus Disease 2019: An International Multicenter Coronavirus Disease 2019 Critical Care Consortium Study.

OBJECTIVES: Stroke has been reported in observational series as a frequent complication of coronavirus disease 2019, but more information is needed regarding stroke prevalence and outcomes. We explored the prevalence and outcomes of acute stroke in an international cohort of patients with coronavirus disease 2019 who required ICU admission. DESIGN: Retrospective analysis of prospectively collected database. SETTING: A registry of coronavirus disease 2019 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with acute stroke during their stay. PATIENTS: Patients older than 18 years old with acute coronavirus disease 2019 infection in ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 2,699 patients identified (median age 59 yr; male 65%), 59 (2.2%) experienced acute stroke: 0.7% ischemic, 1.0% hemorrhagic, and 0.5% unspecified type. Systemic anticoagulant use was not associated with any stroke type. The frequency of diabetes, hypertension, and smoking was higher in patients with ischemic stroke than in stroke-free and hemorrhagic stroke patients. Extracorporeal membrane oxygenation support was more common among patients with hemorrhagic (56%) and ischemic stroke (16%) than in those without stroke (10%). Extracorporeal membrane oxygenation patients had higher cumulative 90-day probabilities of hemorrhagic (relative risk = 10.5) and ischemic stroke (relative risk = 1.7) versus nonextracorporeal membrane oxygenation patients. Hemorrhagic stroke increased the hazard of death (hazard ratio = 2.74), but ischemic stroke did not-similar to the effects of these stroke types seen in noncoronavirus disease 2019 ICU patients. CONCLUSIONS: In an international registry of ICU patients with coronavirus disease 2019, stroke was infrequent. Hemorrhagic stroke, but not ischemic stroke, was associated with increased mortality. Further, both hemorrhagic stroke and ischemic stroke were associated with traditional vascular risk factors. Extracorporeal membrane oxygenation use was strongly associated with both stroke and death.

Improving outcomes after low-risk coronary artery bypass grafting: understanding phase of care mortality analysis, failure to rescue and recent perioperative recommendations.

PURPOSE OF REVIEW: Avoidable adverse events are responsible for up to 50% of deaths after low-risk coronary artery bypass grafting. This article reviews recent quality improvement efforts to improve outcomes after cardiac surgery. RECENT FINDINGS: Systematic quality improvement methodology in cardiac surgery has improved significantly over the past decade. Contemporary efforts with phase of care mortality analysis (POCMA) focus on identifying and addressing root causes for mortality. Each patient's perioperative course is an interconnected sequence of clinical events, decisions, interventions, and treatment responses occurring across five perioperative phases. A single seminal event within a specific phase of care has been found to often trigger the eventual death of a patient. Several groups have made significant improvements to perioperative outcomes by addressing these avoidable mortality trigger events. Failing that, failure to rescue (FTR) metrics can be used to identify institutional factors responsible for poor perioperative outcomes. This ongoing focus on quality improvement serves to further improve outcomes after low-risk cardiac surgery. SUMMARY: Modern quality improvement methodology, including POCMA and FTR analysis, has the potential to significantly improve outcomes after cardiac surgery. Larger future studies with multiinstitutional data sharing will be key to facilitate ongoing quality improvement and knowledge translation in this field.

Two-year outcomes from the PARTNER 3 trial: where do we stand?

PURPOSE OF REVIEW: The PARTNER 3 trial was conducted to compare outcomes after transcatheter aortic valve replacement (TAVR) with a balloon-expandable valve and surgical aortic valve replacement (SAVR) in individuals at low surgical risk with aortic stenosis. Recently reported rates of death, stoke and valve thrombosis in the TAVR arm have raised concerns about the longevity of this intervention in low-risk individuals. It is incumbent on all members of the Heart Team to understand the potential consequences of these findings. RECENT FINDINGS: TAVR was initially superior to SAVR at 1 year for a primary composite endpoint of death, stroke and rehospitalization. Results at 2 years now indicate noninferiority. Potential causative factors, comparisons with other transcatheter valves and implications for patients, providers and trainees are explored. Recommendations are additionally provided regarding TAVR and SAVR in individuals with aortic stenosis. SUMMARY: Concerns regarding the longevity of TAVR in low-risk individuals notwithstanding, results from PARTNER 3 indicate that TAVR is at least noninferior to SAVR out to 2 years. Longer follow-up will be required to determine whether these newly founded concerns are justifiable.

Diagnostic accuracy of the 4AT for delirium detection in older adults: systematic review and meta-analysis.

OBJECTIVE: Detection of delirium in hospitalised older adults is recommended in national and international guidelines. The 4 'A's Test (4AT) is a short (<2 minutes) instrument for delirium detection that is used internationally as a standard tool in clinical practice. We performed a systematic review and meta-analysis of diagnostic test accuracy of the 4AT for delirium detection. METHODS: We searched MEDLINE, EMBASE, PsycINFO, CINAHL, clinicaltrials.gov and the Cochrane Central Register of Controlled Trials, from 2011 (year of 4AT release on the website www.the4AT.com) until 21 December 2019. Inclusion criteria were: older adults (≥65 years); diagnostic accuracy study of the 4AT index test when compared to delirium reference standard (standard diagnostic criteria or validated tool). Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled estimates of sensitivity and specificity were generated from a bivariate random effects model. RESULTS: Seventeen studies (3,702 observations) were included. Settings were acute medicine, surgery, a care home and the emergency department. Three studies assessed performance of the 4AT in stroke. The overall prevalence of delirium was 24.2% (95% CI 17.8-32.1%; range 10.5-61.9%). The pooled sensitivity was 0.88 (95% CI 0.80-0.93) and the pooled specificity was 0.88 (95% CI 0.82-0.92). Excluding the stroke studies, the pooled sensitivity was 0.86 (95% CI 0.77-0.92) and the pooled specificity was 0.89 (95% CI 0.83-0.93). The methodological quality of studies varied but was moderate to good overall. CONCLUSIONS: The 4AT shows good diagnostic test accuracy for delirium in the 17 available studies. These findings support its use in routine clinical practice in delirium detection. PROSPERO REGISTRATION NUMBER: CRD42019133702.

Cardiac surgeons' concerns, perceptions, and responses during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on health care and cardiac surgery. We report cardiac surgeons' concerns, perceptions, and responses during the COVID-19 pandemic. METHODS: A detailed survey was sent to recruit participating adult cardiac surgery centers in North America. Data regarding cardiac surgeons' perceptions and changes in practice were analyzed. RESULTS: Our study comprises 67 institutions with diverse geographic distribution across North America. Nurses were most likely to be redeployed (88%), followed by advanced care practitioners (69%), trainees (28%), and surgeons (25%). Examining surgeon concerns in regard to COVID-19, they were most worried with exposing their family to COVID-19 (81%), followed by contracting COVID-19 (68%), running out of personal protective equipment (PPE) (28%), and hospital resources (28%). In terms of PPE conservation strategies among users of N95 respirators, nearly half were recycling via decontamination with ultraviolet light (49%), followed by sterilization with heat (13%) and at home or with other modalities (13%). Reuse of N95 respirators for 1 day (22%), 1 week (21%) or 1 month (6%) was reported. There were differences in adoption of methods to conserve N95 respirators based on institutional pandemic phase and COVID-19 burden, with higher COVID-19 burden institutions more likely to resort to PPE conservation strategies. CONCLUSIONS: The present study demonstrates the impact of COVID-19 on North American cardiac surgeons. Our study should stimulate further discussions to identify optimal solutions to improve workforce preparedness for subsequent surges, as well as facilitate the navigation of future healthcare crises.

The COMPASS trial: practical considerations for application after coronary artery bypass surgery.

PURPOSE OF REVIEW: We review the cardiovascular outcomes for people using anticoagulation strategies (COMPASS) trial with particular emphasis on patients with a history of remote coronary artery bypass grafting (CABG) and those who were enrolled 4-14 days after CABG. We provide practical guidance for selecting patients with the greatest potential to benefit who have acceptable bleeding risk. In particular, we address concerns about postoperative bleeding and discuss the relative merits of rivaroxaban and aspirin versus P2Y12 inhibition and aspirin. RECENT FINDINGS: The COMPASS trial demonstrated that rivaroxaban and aspirin reduce myocardial infarction, stroke, and cardiovascular death in patients with coronary artery disease, without a demonstrated effect on bypass graft patency in the first postoperative year. SUMMARY: After CABG, cardiac surgeons should consider using the COMPASS regimen in patients at high risk of thrombosis whose risk of bleeding is acceptable. If used, the COMPASS regimen should be continued indefinitely in conjunction with other pharmacological risk reduction therapies to prevent long-term atherothrombotic events.

Outcomes of extracorporeal membrane oxygenation support in the cardiac catheterization laboratory.

OBJECTIVES: The aims of this single-center retrospective study were to characterize and determine predictors of 30-day survival in a cohort of patients requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO) supported cardiopulmonary resuscitation (E-CPR) in the cardiac catheterization laboratory (CCL) for cardiac arrest (CA) or refractory cardiogenic shock (CS). BACKGROUND: While safety in the CCL has improved, periprocedural mortality from CA remains high. The application of VA-ECMO is an emerging form of resuscitation with a paucity of data evaluating its use in the CCL for CA or CS. METHODS: All consecutive patients aged 18 years or older presenting to a single CCL from October 2010 to May 2018 who required E-CPR for CA or refractory CS were included. The primary outcome of our study was overall survival 30 days from VA-ECMO initiation. Secondary outcomes included 1-year survival, hospital length of stay, and ECMO related complications. RESULTS: Sixty-two patients with a mean age of 60 ± 9 years, 63% male, were included. VA-ECMO was initiated for CA in 39 patients (63%) and for CS in 23 patients (37%). The median ECMO duration was 48 hr. Overall 30-day survival was 47% (CA group 44% vs. CS group 52%; p = .414). One-year survival was 44%. Initial serum creatinine (OR 1.18 per 10 µmol/L increase; p = .016; AUC = 0.65) was the only multivariate predictor of 30-day mortality. CONCLUSIONS: The use of VA-ECMO in the CCL is feasible, demonstrating 47% 30-day survival, largely persistent to 1 year, in a cohort that otherwise has extremely high mortality.

Dexmedetomidine versus propofol sedation in reducing delirium among older adults in the ICU: A systematic review and meta-analysis.

BACKGROUND: Delirium is common in the ICU, with incidence rates reported to be upwards of 70%. Due to the significant morbidity and mortality associated with delirium, it is hypothesised that a delirium-free sedative agent will improve outcomes in older adults admitted to the ICU. OBJECTIVES: To assess if dexmedetomidine sedation is associated with a reduction in ICU delirium among older adults, and to evaluate its risks and benefits compared with propofol sedation. DESIGN: Systematic review of randomised controlled trials and cohort studies with meta-analyses. DATA SOURCES: Articles published from database inception to 8 April 2019 were retrieved from Medline, EMBASE, Evidence-based Medicine Reviews, International Pharmaceutical Abstracts, Scopus, ClinicalTrials.gov and WHO Trials. ELIGIBILITY: Studies were included if they compared dexmedetomidine sedation with propofol in the ICU, reported the incidence of delirium as an outcome and had a mean/median sample age of at least 60. Studies that examined dexmedetomidine and propofol use intra-operatively or as part of general anaesthesia were excluded. RESULTS: Dexmedetomidine sedation was associated with a lower incidence of delirium when compared with propofol: seven studies, n=1249; risk ratio 0.70; 95% confidence interval (CI) 0.52 to 0.95; P = 0.02. There was no statistically significant difference in the incidence of bradycardia: three studies, n=278; risk ratio 1.52; 95% CI 0.85 to 2.72; P = 0.16, and hypotension: six studies, n=867 patients; risk ratio 1.12; 95% CI 0.86 to 1.45; P = 0.42. Dexmedetomidine sedation did not reduce hospital length of stay, ICU length of stay or duration of mechanical ventilation compared with propofol. CONCLUSION: Compared with propofol, dexmedetomidine sedation in the ICU is associated with lower delirium incidence among older adults with no significant increase in adverse events. In older adult ICU patients at risk of developing delirium, sedation with dexmedetomidine should be considered. Further research is warranted to elucidate and explain the mechanisms underlying this process, and to confirm our findings with large, multicentre trials. TRIAL REGISTRATION: The study protocol has been registered in PROSPERO (CRD42018099339).

Acute Effect of High-Intensity Interval Versus Moderate-Intensity Continuous Exercise on Blood Pressure and Arterial Compliance in Middle-Aged and Older Hypertensive Women With Increased Arterial Stiffness.

Costa, EC, Kent, DE, Boreskie, KF, Hay, JL, Kehler, DS, Edye-Mazowita, A, Nugent, K, Papadopoulos, J, Stammers, AN, Oldfield, C, Arora, RC, Browne, RAV, and Duhamel, TA. Acute effect of high-intensity interval versus moderate-intensity continuous exercise on blood pressure and arterial compliance in middle-aged and older hypertensive women with increased arterial stiffness. J Strength Cond Res 34(5): 1307-1316, 2020-Hypertension and arterial stiffness are common in middle-aged and older women. This study compared the acute effect of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) on blood pressure (BP) and arterial compliance in middle-aged and older hypertensive women with increased arterial stiffness. Nineteen women (67.6 ± 4.7 years) participated in this randomized controlled crossover trial. Subjects completed a control, MICE (30 minutes at 50-55% of heart rate reserve [HRR]), and HIIE (10 × 1 minute at 80-85% of HRR, 2 minutes at 40-45% of HRR) session in random order. Blood pressure and large and small arterial compliance (radial artery pulse wave analysis) were measured at baseline and 30, 60, 90, and 120 minutes after sessions. A p < 0.05 was considered statistically significant. Systolic BP was reduced in ∼10 mm Hg after MICE at 30 minutes and after HIIE at all time points (30, 60, 90, and 120 minutes) after exercise compared with the control session (p < 0.05). Only HIIE showed lower systolic BP levels at 60, 90, and 120 minutes after exercise compared with the control session (∼10 mm Hg; p < 0.05). No changes were observed in diastolic BP, or in large and small arterial compliance (p > 0.05). High-intensity interval exercise elicited a longer systolic postexercise hypotension than MICE compared with the control condition, despite the absence of acute modifications in large and small arterial compliance.

Malnutrition and Mortality in Frail and Non-Frail Older Adults Undergoing Aortic Valve Replacement.

BACKGROUND: Older adults undergoing aortic valve replacement (AVR) are at risk for malnutrition. The association between preprocedural nutritional status and midterm mortality has yet to be determined. METHODS: The FRAILTY-AVR (Frailty in Aortic Valve Replacement) prospective multicenter cohort study was conducted between 2012 and 2017 in 14 centers in 3 countries. Patients ≥70 years of age who underwent transcatheter or surgical AVR were eligible. The Mini Nutritional Assessment-Short Form was assessed by trained observers preprocedure, with scores ≤7 of 14 considered malnourished and 8 to 11 of 14 considered at risk for malnutrition. The Short Performance Physical Battery was simultaneously assessed to measure physical frailty, with scores ≤5 of 12 considered severely frail and 6 to 8 of 12 considered mildly frail. The primary outcome was 1-year all-cause mortality, and the secondary outcome was 30-day composite mortality or major morbidity. Multivariable regression models were used to adjust for potential confounders. RESULTS: There were 1158 patients (727 transcatheter AVR and 431 surgical AVR), with 41.5% females, a mean age of 81.3 years, a mean body mass index of 27.5 kg/m2, and a mean Society of Thoracic Surgeons-Predicted Risk of Mortality of 5.1%. Overall, 8.7% of patients were classified as malnourished and 32.8% were at risk for malnutrition. Mini Nutritional Assessment-Short Form scores were modestly correlated with Short Performance Physical Battery scores (Spearman R=0.31, P<0.001). There were 126 deaths in the transcatheter AVR group (19.1 per 100 patient-years) and 30 deaths in the surgical AVR group (7.5 per 100 patient-years). Malnourished patients had a nearly 3-fold higher crude risk of 1-year mortality compared with those with normal nutritional status (28% versus 10%, P<0.001). After adjustment for frailty, Society of Thoracic Surgeons-Predicted Risk of Mortality, and procedure type, preprocedural nutritional status was a significant predictor of 1-year mortality (odds ratio, 1.08 per Mini Nutritional Assessment-Short Form point; 95% CI, 1.01-1.16) and of the 30-day composite safety end point (odds ratio, 1.06 per Mini Nutritional Assessment-Short Form point; 95% CI, 1.001-1.12). CONCLUSIONS: Preprocedural nutritional status is associated with mortality in older adults undergoing AVR. Clinical trials are needed to determine whether pre- and postprocedural nutritional interventions can improve clinical outcomes in these vulnerable patients.

Inflammation in myocardial injury: mesenchymal stem cells as potential immunomodulators.

Ischemic heart disease is a growing worldwide epidemic. Improvements in medical and surgical therapies have reduced early mortality after acute myocardial infarction and increased the number of patients living with chronic heart failure. The irreversible loss of functional cardiomyocytes puts these patients at significant risk of ongoing morbidity and mortality after their index event. Recent evidence suggests that inflammation is a key mediator of postinfarction adverse remodeling in the heart. In this review, we discuss the cardioprotective and deleterious effects of inflammation and its mediators during acute myocardial infarction. We also explore the role of mesenchymal stem cell therapy to limit secondary injury and promote myocardial healing after myocardial infarction.