Andexanet alpha versus four-factor prothrombin complex concentrate in DOACs anticoagulation reversal: an updated systematic review and meta-analysis.

BACKGROUND: There is currently a lack of evidence for the comparative effectiveness of Andexanet alpha and four-factor prothrombin complex concentrate (4F-PCC) in anticoagulation reversal of direct oral anticoagulants (DOACs). The primary aim of our systematic review was to verify which drug is more effective in reducing short-term all-cause mortality. The secondary aim was to determine which of the two reverting strategies is less affected by thromboembolic events. METHODS: A systematic review and meta-analysis was performed. RESULTS: Twenty-two studies were analysed in the systematic review and quantitative synthesis. In all-cause short-term mortality, Andexanet alpha showed a risk ratio (RR) of 0.71(95% CI 0.37-1.34) in RCTs and PSMs, compared to 4F-PCC (I2 = 81%). Considering the retrospective studies, the pooled RR resulted in 0.84 (95% CI 0.69-1.01) for the common effects model and 0.82 (95% CI 0.63-1.07) for the random effects model (I2 = 34.2%). Regarding the incidence of thromboembolic events, for RCTs and PSMs, the common and the random effects model exhibited a RR of 1.74 (95% CI 1.09-2.77), and 1.71 (95% CI 1.01-2.89), respectively, for Andexanet alpha compared to 4F-PCC (I2 = 0%). Considering the retrospective studies, the pooled RR resulted in 1.21 (95% CI 0.87-1.69) for the common effects model and 1.18 (95% CI 0.86-1.62) for the random effects model (I2 = 0%). CONCLUSION: Considering a large group of both retrospective and controlled studies, Andexanet alpha did not show a statistically significant advantage over 4F-PCC in terms of mortality. In the analysis of the controlled studies alone, Andexanet alpha is associated with an increased risk of thromboembolic events. CLINICAL TRIAL REGISTRATION: PROSPERO: International prospective register of systematic reviews, 2024, CRD42024548768.

Distal Reoperations after Repair of Acute Type A Aortic Dissection-Incidence, Causes and Outcomes.

Background and Aim of the Study: In patients with acute type A aortic dissection (A-AAD) whether initial repair should include also aortic arch replacement is still debated. We aimed to assess if extensive aortic repair prevents from reoperations patients with A-AAD. Methods: Outcomes after distal reoperation following repair of A-AAD (n = 285; 1977 to 2018) were analysed in 22 of 226 who underwent ascending aorta/hemiarch replacement (Group 1 R ) and 7 of 59 who had ascending aorta/arch replacement (Group 2 R ). Results: Distal reoperation was more common in Group 1 R (n = 22) than in Group 2 R (n = 0) (p < 0.001) while thoracic endovascular stenting was more frequent in Group 2 R (7 vs 3, p < 0.001). Indications for reoperation were pseudoaneurysm at distal anastomosis (n = 4, 18%) and progression of aortic dissection (n = 18, 82%) in Group 1 R . Indication for thoracic endovascular stenting was progressive aortic dissection in 3 patients of Group 1 R and in 6 of Group 2 R . Second reoperation was required in 2 patients from Group 1 R (2%) during a mean follow-up of 5 years. Median follow-up was 4 years in Group 1 R and 7 years in Group 2 R (p = 0.36). Hospital mortality was 14% in Group 1 R and 0% in Group 2 R (p = 0.3). Actuarial survival is 68 ± 10%, and 62 ± 11% for Group 1 R and 100% for Group 2 R at 5 and 10 years (p = 0.076). Conclusions: Distal reoperations after A-AAD repair have an acceptable mortality. An extensive initial repair has lower rate of reoperation and better mid-term survival and should be indicated especially for young patients in experienced centers.

Multiple Electrode Aggregometry After Cardiopulmonary Bypass to Assess Platelet (Dys)-Function and Transfusion Threshold: A Concordance Study.

OBJECTIVE: Cardiac surgery patients have a high risk of postoperative bleeding. Historically, the platelet count has been one of the main parameters used to establish the need for platelet transfusions, and the recent introduction of point-of-care tests for platelet function has allowed clinicians to rationalize platelet transfusion needs by assessing the platelet (dys-)function of the patient. For the present study, the authors evaluated how the introduction of one of these systems-the adenosine diphosphate (ADP) test, performed using a Multiplate electrode analyzer (Roche Diagnostics, Basel, Switzerland)-into their clinical practice had modified their platelet transfusion practice. The relationship between the platelet count and the functional evaluation of platelet aggregation (via the ADP test) also was examined. DESIGN: This was a retrospective, single-center, observational study. SETTING: Cardiac surgery department of a tertiary care center in North-east Italy. PARTICIPANTS: Cardiac surgery patients requiring cardiac bypass in 2017 and 2019. INTERVENTIONS: The primary outcome was to compare platelet transfusion practice before and after the implementation of a platelet function test (the ADP test) into the institution's transfusion algorithm, which replaced the platelet count as the trigger. Secondary outcomes were assessing whether the incorporation of the ADP test into their transfusion algorithm brought about a reduction in the frequency of platelet transfusions compared with previous rates (when only platelets counts were used); assessing patient blood loss in the first 12 postoperative hours; and ascertaining the percentage of patients requiring surgical reexplorations. MEASUREMENTS AND MAIN RESULTS: The study comprised 110 patients undergoing cardiac surgery from the platelet count period (2017) and 110 patients from the ADP test period (2019). Agreement between platelet counts versus ADP tests in determining the need for platelet transfusion was moderate (κ = 0.483; 95% confidence interval [CI] 0.239-0.728), and the general linear regression relationship between platelet counts and the ADP test (Akaike information criterion = 2536; p < 0.001) was determined. Since the introduction of ADP testing, a highly significant reduction in platelet transfusions has occurred: 41.82% (platelet count period) versus 13.64% (ADP test period) (p < 0.001); average blood loss in the 12 hours postsurgery also was less in the ADP test period (p < 0.001) at 300 mL (95% CI 150-730) compared with 440 mL in the platelet count period (95% CI 135-900). Furthermore, a decreasing trend was observed in the number of patients requiring reexploration to optimize hemostasis in the first 12 hours postsurgery (6.36% v 2.73%); however, this trend did not achieve statistical significance (p = 0.195). CONCLUSION: The application of new Multiplate analyzer technologies, like the ADP test, have the potential to reduce platelet transfusion rates in cardiac surgery patients compared with the use of platelet counts alone; this point-of-care test may constitute an important strategy to help spare the use of allogeneic blood products. Additional studies are needed to confirm this trend and establish the best cutoff values to apply.

Transesophageal ultrasonography during orthotopic liver transplantation: Show me more.

The first perioperative transesophageal echocardiography (TEE) guidelines published 21 years ago were mainly addressed to cardiac anesthesiologists. TEE has since expanded its role outside this setting and currently represents an invaluable tool to assess chamber sizes, ventricular hypertrophy, and systolic, diastolic, and valvular function in patients undergoing orthotopic liver transplantation (OLT). Right-sided microemboli, right ventricular dysfunction, and patent foramen ovale (PFO) are the most common intra-operative findings described during OLT. However, left ventricular outflow tract obstruction and left ventricular ballooning syndrome are more difficult to recognize and less frequent. Transesophageal ultrasonography (TEU) during OLT is also underused. Its applications are as follows: (1) assistance in the difficult placement of pulmonary arterial catheters; (2) help with catheterization of great vessels for external veno-venous bypass placement; (3) intra-operative evaluation of surgical liver anastomosis patency, if feasible, through the liver window; and (4) intra-operative investigation of "acute hypoxemia" due to pulmonary and cardiac issues using trans-esophageal lung ultrasound (TELU). The aims of this review are as follows: (1) to summarize the uses of TEE and TEU throughout all phases of OLT, and (2) to describe other new feasible applications.

A randomized controlled trial of levosimendan to reduce mortality in high-risk cardiac surgery patients (CHEETAH): Rationale and design.

OBJECTIVE: Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes. DESIGN: Double-blind, placebo-controlled, multicenter randomized trial. SETTING: Tertiary care hospitals. INTERVENTIONS: Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 µg/[kg min]) or placebo for 24-48 hours. MEASUREMENTS AND MAIN RESULTS: The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction. CONCLUSIONS: This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery.

Acute acquired immune thrombocytopenia after cardiac surgery: A challenging case.

Thrombocytopenia is a common condition that recognizes an infinite number of possible causes, especially in specific settings like the one covered in this case report: the postoperative period of cardiac surgery. We report a case of an old male with multiple comorbidities who underwent a coronary angioplasty procedure and aortic valve replacement. He showed severe thrombocytopenia in the postoperative days. Differential diagnosis required a big effort, also for the experts in the field. Our goal was to aggressively treat the patient with prednisolone, platelets, and intravenous immunoglobulins to maximize the prognosis. Our patient developed no complications and was discharged successfully.

Influence of a regional network combined with a systematic multidisciplinary approach on the outcomes of patients with acute type A aortic dissection.

BACKGROUND: Whether in patients with acute type A aortic dissection reduction of intervals between onset of symptoms and diagnosis influences patient outcomes is still not completely defined. METHODS: In 199 patients with acute type A aortic dissection, the efficacy of a systematic multidisciplinary approach and institution of a regional network were evaluated; 90 patients operated before 2016 (Group1) were compared with 109 repaired after 2016 (Group2) for early and late outcomes. RESULTS: Mortality was reduced from 13% in Group1 to 4% in Group2 (p = 0.013). In Group2 a more patients (46%) had arch replacement compared to Group1 (29%)(p = 0.06). In Group2 axillary artery cannulation was almost routinely used (91% vs 67%, p < 0.001) with shorter circulatory arrest time (37 vs 44 min, p < 0.001). The interval from diagnosis to surgery dropped from 210 min in Group1 to 160 min in Group2 (p < 0.001); this reduction was evident both in patients admitted to the emergency department of a spoke and/or a hub center. Patients presenting with or developing shock were reduced from Group1 to Group2 and in particular those reaching the hub center from spoke centers. Survival at 1 and 5 years was 82 ± 4% and 70 ± 5% in Group1 vs 92 ± 3% and 87 ± 8% in Group2 (p = 0.007). CONCLUSIONS: Outcomes of patients with acute type A aortic dissection improved using a systematic multidisciplinary approach while a network between spoke and hub centers reduced intervals between diagnosis, transportation to hub center and repair, limiting the incidence of tamponade and shock.

Platelet Dysfunction in Cardiac Surgery: When is the Best Time to Assess It? An Observational Single Center Study.

Purpose. Cardiac surgery is characterized by a high risk of complications related to perioperative bleeding. Guidelines suggest the use of local algorithms based on perioperative point-of-care tests to assess and manage potential coagulation abnormalities. We investigated whether heparin reversal administration affects the adenosine-5-diphosphate (ADP) test values, thus identifying the earliest time point following cardio-pulmonary bypass that permits the promptest detection and treatment of potential platelet dysfunctions. Methods. This was a retrospective, single-center, observational study enrolling cardiac surgery patients requiring cardiac bypass. ADP-tests at 4 different time-points during surgery (T0: baseline, T1: at aortic de-clamping, T2: 10 minutes after protamine administration, and T3: at the end of surgery) were performed. Results. 63 patients undergoing elective cardiac surgery were studied. Baseline ADP-test values were almost constantly greater than intraoperative values, and end of surgery values were often greater than previous intraoperative values. The only difference that proved to be not statistically significant was between T1 and T2, with a clinically insignificant mean difference of -.2 U (95%CI of difference: -6.9 - 6.5 U). There was no correlation between the variation in ADP-test values pre- and post-protamine administration and the protamine-to-heparin ratio. Conclusion. The results of the present study support the hypothesis that the ADP-test could be performed early, at aortic de-clamping before protamine administration. This approach allows for the promptest assessment of a potential impairment in platelet function, and its timely correction.

Early awaking of patients following FET allows early recognition of paraplegia with prospects for complete recovery using prompt spinal drainage.

We report a patient who presented with paraplegia after ascending aorta and arch replacement using the frozen elephant trunk technique. Immediate postoperatively cerebrospinal fluid drainage allowed successful reversal of spinal cord injury. Early awakening of patients following a frozen elephant trunk technique is mandatory because it allows recognition and treatment of this complication by prompt cerebrospinal liquor drainage.

Infective endocarditis following a valve-in-valve procedure.

An 83-year-old man had aortic valve replacement for aortic stenosis with a pericardial bioprosthesis and subsequent implantation of a CoreValve™ prosthesis as a valve-in-valve procedure. Approximately 4 years later, he developed endocarditis on the CoreValve™ with severe prosthetic stenosis, a periannular abscess and systemic embolization. At reoperation both prostheses were removed and another bioprosthesis inserted after reconstruction of the aortic root. Endocarditis after transaortic valve implantation is an uncommon event with dismal prognosis. Infection of a self-expandable device as a valve-in-valve has not been previously reported. This complication represents a surgical challenge which, however, can be successfully managed.

Experienced Use of Dexmedetomidine in the Intensive Care Unit: A Report of a Structured Consensus.

OBJECTIVE: Management of pain, agitation and delirium (PAD) remains to be a true challenge in critically ill patients. The pharmacological proprieties of dexmedetomidine (DEX) make it an ideal candidate drug for light and cooperative sedation, but many practical questions remain unanswered. This structured consensus from 17 intensivists well experienced on PAD management and DEX use provides indications for the appropriate use of DEX in clinical practice. METHODS: A modified RAND/UCLA appropriateness method was used. In four predefined patient populations, the clinical scenarios do not properly cope by the current recommended pharmacological strategies (except DEX), and the possible advantages of DEX use were identified and voted for agreement, after reviewing literature data. RESULTS: Three scenarios in medical patients, five scenarios in patients with acute respiratory failure undergoing non-invasive ventilation, three scenarios in patients with cardiac surgery in the early postoperative period and three scenarios in patients with overt delirium were identified as challenging with the current PAD strategies. In these scenarios, the use of DEX was voted as potentially useful by most of the panellists owing to its specific pharmacological characteristics, such as conservation of cognitive function, lack of effects on the respiratory drive, low induction of delirium and analgesia effects. CONCLUSION: DEX might be considered as a first-line sedative in different scenarios even though conclusive data on its benefits are still lacking.

Mid-term clinical outcomes in cardiac surgery of Jehovah's witnesses.

INTRODUCTION: Surgical treatment of Jehovah's witnesses is a special challenge for cardiac surgery. The purpose of this study was to evaluate perioperative management and mid-term clinical outcome of Jehovah's witnesses who underwent cardiac surgery. METHODS: Between January 1990 and June 2009, 34 Jehovah's witnesses (22 men, mean age 66 +/- 8 years) underwent cardiac surgery. Surgical procedures included 17 coronary artery bypass grafts (CABG): 3 CABG and aortic valve replacements (AVR); 1 CABG and mitral valve plasty (MVP); 6 AVR; 1 subaortic membrane resection; 2 mitral valve replacements (MVR) and 2 MVP; 1 mitro-aortic valve replacement; and 1 cardiac foreign body removal. There were four urgent operations; 14 patients had NYHA class II-III. Sixteen patients received erythropoietin preoperatively. Preoperative haemoglobin (Hb) value was 14.2 +/- 1.4 g/dl. RESULTS: Extracorporeal circulation time was 127 +/- 66 min, aortic cross-clamping 84 +/- 45 min. Haemoglobin value 24 h after surgery was 11.2 +/- 1.7 g/dl, haematocrit 34.1 +/- 5.2%. None required surgical reoperation for bleeding.Intensive care unit stay was 2.3 +/- 4.3 days, hospital stay 12.3 +/- 10.4 days; there was no hospital mortality. Postoperatively, erythropoietin was administered to 19 patients. Follow-up was completed in 100%. Reoperation was necessary 8 years later in one patient for mitral bioprosthesis degeneration; the patient died 8 months later. All other patients are alive 59 +/- 60 months after surgery; actuarial survival is 100% and 80 +/- 2% at 5 and 10 years, respectively. CONCLUSION: In our limited experience, early and late surgical results of Jehovah's witnesses patients are satisfactory. Appropriate preoperative management, optimization of Hb values, intraoperative measures to reduce the risk of bleeding and total blood loss recovery are the goals to achieve these results.