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.

Association of Impedance Aggregometry-Measured Platelet Aggregation With Thromboembolic Events in Patients Who Undergo Carotid Endarterectomy: A Pilot Study.

OBJECTIVES: The aim of the current study was to assess the relationship among thrombin receptor activator peptide 6 (TRAP test), adenosine-5'-diphosphate (ADP test), arachidonic acid (ASPI test), and stroke/transient ischemic attack (TIA), using the multiple electrode aggregometry (Multiplate) in patients undergoing carotid thromboendarterectomy (CEA). DESIGN: A retrospective study. SETTING: Vascular surgery operating rooms of a university hospital. PARTICIPANTS: One hundred thirty-one out of 474 patients undergoing CEA between November 2020 and October 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A preoperative blood sample of all enrolled patients was analyzed using the Multiplate analyzer. Receiver operating characteristics curves, were generated to test the ability of TRAP, ADP, and ASPI in discriminating perioperative thromboembolic stroke/TIA. A logistic LASSO regression model was used to identify factors independently associated with stroke/TIA. Eight patients experienced a perioperative stroke/TIA. Although all the platelet functional assays showed excellent predictive performance, an ADP value exceeding 72 U showed the highest specificity (87%) and sensitivity (68%) in discriminating patients who had a perioperative thromboembolic stroke/TIA, with a negative predictive value of 99% and a positive predictive value of 15%. After LASSO regression, an ADP >72 U and the need for a shunt during CEA were the only 2 variables independently associated with perioperative stroke/TIA. CONCLUSION: Because the ADP test was independently associated with perioperative stroke/TIA, the assessment of platelet reactivity using Multiplate may offer potential utility in monitoring patients undergoing CEA.

Esmolol in Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVE: To assess whether the administration of the ultra-short-acting ß-blocker esmolol in cardiac surgery could have a cardioprotective effect that translates into improved postoperative outcomes. DESIGN: Single-center, double-blinded, parallel-group randomized controlled trial. SETTING: A tertiary care referral center. PARTICIPANTS: Patients undergoing elective cardiac surgery with preoperative evidence of left ventricular end-diastolic diameter >60 mm and/or left ventricular ejection fraction <50%. INTERVENTIONS: Patients were assigned randomly to receive either esmolol (1 mg/kg as a bolus before aortic cross-clamping and 2 mg/kg mixed in the cardioplegia solution) or placebo in a 1:1 allocation ratio. MEASUREMENTS AND MAIN RESULTS: The primary composite endpoint of prolonged intensive care unit stay and/or in-hospital mortality occurred in 36/98 patients (36%) in the placebo group versus 27/102 patients (27%) in the esmolol group (p = 0.13). In the esmolol group, a reduction in the maximum inotropic score during the first 24 postoperative hours was observed (10 [interquartile range 5-15] v 7 [interquartile range 5-10.5]; p = 0.04), as well as a trend toward a reduction in postoperative low-cardiac-output syndrome (13/98 v 6/102; p = 0.08) and the rate of hospital admission at one year (26/95 v 16/96; p = 0.08). A trend toward an increase in the number of patients with ejection fraction ≥60% at hospital discharge also was observed (4/95 v 11/92; p = 0.06). CONCLUSIONS: In the present trial, esmolol as a cardioplegia adjuvant enhanced postoperative cardiac performance but did not reduce a composite endpoint of prolonged intensive care unit stay and/or mortality.

Long-term outcome of perioperative low cardiac output syndrome in cardiac surgery: 1-year results of a multicenter randomized trial.

PURPOSE: Perioperative myocardial dysfunction occurs frequently in cardiac surgery, and is a risk factor for morbidity and mortality. Levosimendan has been suggested to reduce mortality of patients with perioperative myocardial dysfunction. However, long-term outcome data on its efficacy in cardiac surgery are lacking. MATERIALS AND METHODS: Cardiac surgery patients with perioperative myocardial dysfunction were randomized to levosimendan or placebo, in addition to standard inotropic care. One-year mortality data were collected. RESULTS: We randomized 506 patients (248 to levosimendan 258 to placebo). At 1-year follow-up, 41 patients (16.5%) died in the levosimendan group, while 47 (18.3%) died in the placebo group (absolute risk difference -1.8; 95% CI -8.4 to 4.9; P = .60). Female sex, history of chronic obstructive pulmonary disease, previous myocardial infarction, serum creatinine, hematocrit, mean arterial pressure, and duration of cardiopulmonary bypass were independently associated with 1-year mortality. CONCLUSIONS: Levosimendan administration does not improve 1-year survival in cardiac surgery patients with perioperative myocardial dysfunction. One-year mortality in these patients is 17%. Six predictive factors for long-term mortality were identified. STUDY REGISTRATION NUMBER: NCT00994825 (ClinicalTrials.gov).

Fast reshaping of intensive care unit facilities in a large metropolitan hospital in Milan, Italy: facing the COVID-19 pandemic emergency

At the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak spread from China all around the world, causing thousands of deaths. In Italy, the hardest hit region was Lombardy, with the first reported case on 20 February 2020. San Raffaele Scientific Institute ­ a large tertiary hospital and research centre in Milan, Italy ­ was immediately involved in the management of the public health emergency. Since the beginning of the outbreak, the elective surgical activity of the hospital was rapidly reduced and large areas of the hospital were simultaneously reorganised to admit and assist patients with coronavirus disease 2019 (COVID-19). In addition, the hospital became the regional referral hub for cardiovascular emergencies in order to keep ensuring a high level of health care to non-COVID-19 patients in northern Italy. In a few days, a COVID-19 emergency department was created, improving the general ward capacity to a total number of 279 beds dedicated to patients with COVID-19. Moreover, the number of intensive care unit (ICU) beds was increased from 28 to 72 (54 of them dedicated to patients with COVID-19, and 18 to cardiology and cardiac surgery hub emergencies), both converting pre-existing areas and creating new high technology spaces. All the involved health care personnel were rapidly trained to use personal protection equipment and to manage this particular category of patients both in general wards and ICUs. Furthermore, besides clinical activities, continuously important research projects were carried out in order to find new strategies and more effective therapies to better face an unprecedented health emergency in Italy.

Differences in Biomarkers Pattern Between Severe Isolated Right and Left Ventricular Dysfunction After Cardiac Surgery.

OBJECTIVE: To find out if there are any differences in biomarkers between severe isolated right ventricular (RV) dysfunction and severe isolated left ventricular (LV) dysfunction after cardiac surgery using cardiopulmonary bypass. DESIGN: Observational study. SETTING: Teaching hospital. PARTICIPANTS: A total of 46 patients who had severe isolated RV or LV dysfunction after cardiac surgery. INTERVENTION: The authors collected perioperative clinical and biomarker data. MEASUREMENTS AND MAIN RESULTS: Severe isolated RV dysfunction patients (n = 20) had higher postoperative direct bilirubin (p = 0.030), total bilirubin (p = 0.044), glucose (p = 0.011), and international normalized ratio (INR) (p = 0.050) by repeated measure analysis of variance when compared with patients with severe isolated LV dysfunction (n = 26). The RV group also showed lower preoperative alanine transferase (19.3 ± 1.5 v 32.7 ± 4.2, p = 0.001), higher 4-hour INR (1.5 ± 0.3 v 1.4 ± 0.2, p = 0.008), and higher 48-hour INR (1.8 ± 0.4 v 1.4 ± 0.1, p < 0.001). None in the LV group died, whereas 4 patients in the RV group died (all of them had preoperative atrial fibrillation and underwent double valve replacement surgery). CONCLUSION: The authors observed biomarkers differences between severe isolated RV dysfunction and severe isolated RV dysfunction.

Adrenergic Downregulation in Critical Care: Molecular Mechanisms and Therapeutic Evidence.

Catecholamines remain the mainstay of therapy for acute cardiovascular dysfunction. However, adrenergic receptors quickly undergo desensitization and downregulation after prolonged stimulation. Moreover, prolonged exposure to high circulating catecholamines levels is associated with several adverse effects on different organ systems. Unfortunately, in critically ill patients, adrenergic downregulation translates into progressive reduction of cardiovascular response to exogenous catecholamine administration, leading to refractory shock. Accordingly, there has been a growing interest in recent years toward use of noncatecholaminergic inotropes and vasopressors. Several studies investigating a wide variety of catecholamine-sparing strategies (eg, levosimendan, vasopressin, ß-blockers, steroids, and use of mechanical circulatory support) have been published recently. Use of these agents was associated with improvement in hemodynamics and decreased catecholamine use but without a clear beneficial effect on major clinical outcomes. Accordingly, additional research is needed to define the optimal management of catecholamine-resistant shock.

Noninvasive ventilation during left atrial appendage closure under sedation: Preliminary experience with the Janus Mask.

Background: Percutaneous left atrial appendage occlusion (LAAO) is indicated in subjects with atrial fibrillation who cannot receive oral anticoagulants. This procedure requires transesophageal echocardiography guidance and is usually performed under general anesthesia. The Janus Mask is a new device designed to allow upper endoscopic procedures during noninvasive ventilation (NIV). Aims: This study aims to assess the possibility of performing LAAO under sedation and NIV. Setting: Cardiac electrophysiology laboratory. Design: Case-control study. Materials and Methods: Data from 11 subjects undergoing LAAO under sedation and NIV with the Janus Mask were retrospectively collected. Procedure duration, outcomes, and physicians' satisfaction were compared with those of 11 subjects who underwent LAAO under general anesthesia in the same period. Statistical Analysis: Univariate analysis and analysis of variance for between-groups comparison. Results: The 11 subjects treated with sedation experienced a good outcome, with a high degree of satisfaction from the medical team. An increase in arterial partial pressure of carbon dioxide in the Janus group (45 [43-62] mmHg vs. 33 [30-35] mmHg in the general anesthesia group, P < 0.001) led to a transient pH decrease 45 min after the beginning of the procedure (7.30 [7.18-7.36] vs. 7.40 [7.39-7.46], P = 0.014). No differences in arterial partial pressure of oxygen, FiO2, and hemodynamic parameters were observed. The subjects' conditions at discharge from the recovery room were comparable. No difference in procedure duration was registered. Conclusions: LAAO procedure under sedation and NIV through the Janus Mask is safe and feasible. This strategy might represent a valuable alternative to manage such a compromised and fragile population.

Anesthetic Management of Cardioband Implantation: Data From a Preliminary Experience and New Insights.

OBJECTIVE: Percutaneous procedures for the treatment of mitral valve disease represent valuable therapeutic options for high-risk patients. The anesthetic management of these patients is complex, as they often suffer from cardiac failure and present multiple comorbidities. A recently developed device for transcatheter mitral valve annuloplasty (Cardioband - Valtech Cardio, Or Yehuda, Israel) is now available in clinical practice. The aim of this study was to present the authors' experience with Cardioband device implantation and to describe their anesthetic strategy. DESIGN: Retrospective study. SETTING: Cardiac catheterization laboratory of a teaching hospital. PARTICIPANTS: Thirteen patients undergoing Cardioband implantation. INTERVENTIONS: All the procedures were performed under general anesthesia with continuous transesophageal echocardiographic monitoring. Three-dimensional echocardiography, inotropic therapy, cardiac pacing, and mechanical circulatory support always were available and performed as needed. MEASUREMENTS AND MAIN RESULTS: Mean age was 73±7.1 years, and mean preoperative ejection fraction was 38±7.4%. No complications related to anesthetic management were recorded. The authors observed 1 episode of device malfunction and 1 case of accidental damage to the circumflex artery. Postoperative complications were observed in 3 patients, involving detachment of the anchors, anemia requiring transfusions, vascular injury, and new-onset atrial fibrillation. Six patients (46%) required ICU admission. All patients (100%) were discharged from the hospital. CONCLUSIONS: Cardioband device implantation under general anesthesia is a feasible approach when performed by skilled physicians with all the expertise and the resources of high-volume centers used to dealing with severely ill patients.

Thoracic aorta aneurysm open repair in heart transplant recipient; the anesthesiologist's perspective.

Many years following transplantation, heart transplant recipients may require noncardiac major surgeries. Anesthesia in such patients may be challenging due to physiological and pharmacological problems regarding allograft denervation and difficult immunosuppressive management. Massive hemorrhage, hypoperfusion, renal, respiratory failure, and infections are some of the most frequent complications related to thoracic aorta aneurysm repair. Understanding how to optimize hemodynamic and infectious risks may have a substantial impact on the outcome. This case report aims at discussing risk stratification and anesthetic management of a 54-year-old heart transplant female recipient, affected by Marfan syndrome, undergoing thoracic aorta aneurysm repair.

Swallowing Impairment During Propofol Target-Controlled Infusion.

BACKGROUND: Sedatives can impair the swallowing process. We assessed the incidence and severity of swallowing impairment in patients sedated with propofol at clinically relevant doses. We also identified factors that were predictive of swallowing impairment. METHODS: In 80 patients scheduled to undergo elective gastrointestinal endoscopy under target-controlled infusion (TCI) propofol sedation, swallowing was evaluated by glottis videoendoscopy, using the Dysphagia Severity Score (DSS) and the Penetration and Aspiration Scale (PAS). The level of sedation was assessed with the Observer's Assessment of Alertness/Sedation (OAAS) scale. Evaluations were obtained within each patient at 3 target effect-site propofol concentrations of 2, 3, and 4 µg/mL (Marsh model). RESULTS: At 2 µg/mL TCI, the OAAS score was 2 in 21 (26.25%) patients and 1 in 59 (73.75%). The OAAS score was 1 in all patients at 3 and 4 µg/mL TCI target. At 3 µg/mL TCI target, 19 (24.36%) patients had a DSS = 3 and 18 patients (23.08%) had a PAS = 7-8 (severe swallowing impairment). DSS was associated with increasing age (5-year odds ratio [OR] 1.53 [1.22-1.93]; P < 0.001), body mass index (BMI; OR 1.24 [1.08-1.42]; P = 0.002), and TCI target (OR 15.80 [7.76-32.20]; P < 0.001). In an alternative model incorporating OAAS instead of TCI target, DSS was associated with increasing age (5-year OR 1.13 [1.02-1.24]; P = 0.014) and BMI (OR 1.08 [1.02-1.15]; P = 0.006) and decreasing OAAS (OR 0.05 [0.006-0.36]; P = 0.003). PAS was associated with increasing age (5-year OR 1.09 [1.04-1.15]; P < 0.001), BMI (OR 1.23 [1.07-1.41]; P = 0.003), and TCI target (OR 15.23 [7.45-31.16]; P < 0.001). In an alternative model incorporating OAAS instead of TCI target, PAS was associated with increasing age (5-year OR 1.14 [1.04-1.26]; P = 0.007) and BMI (OR 1.09 [1.02-1.15]; P = 0.006) and decreasing OAAS (OR 0.05 [0.006-0.41]; P = 0.005). CONCLUSIONS: Aspiration due to swallowing impairment may occur during deep sedation produced by propofol at commonly used TCI targets. TCI targets are predictors of swallowing impairment; increased age and high BMI are concomitant risk factors.

Levosimendan reduces mortality in patients with severe sepsis and septic shock: A meta-analysis of randomized trials.

PURPOSE: There is controversy about the use of inotropes in the treatment of severe sepsis and septic shock. The objective of this study was to evaluate if levosimendan, as compared with standard inotropic therapy (eg, dobutamine), reduces mortality in septic patients. MATERIALS AND METHODS: BioMedCentral, PubMed, EMBASE, and the Cochrane Central Register were searched for pertinent studies, up to 1st May 2015. Randomized trials on the use of levosimendan in patients with severe sepsis and septic shock were included if reporting mortality data. The primary outcome was mortality, whereas secondary outcomes were blood lactate, cardiac index, total fluid infused, norepinephrine dosage, and mean arterial pressure. RESULTS: Seven studies for a total of 246 patients were included in the analysis. Levosimendan was associated with significantly reduced mortality compared with standard inotropic therapy (59/125 [47%] in the levosimendan group and 74/121 [61%] in the control group; risk difference = -0.14, risk ratio = 0.79 [0.63-0.98], P for effect = .03, I(2) = 0%, numbers needed to treat = 7). Blood lactate was significantly reduced in the levosimendan group, whereas cardiac index and total fluid infused were significantly higher in the levosimendan group. No difference in mean arterial pressure and norepinephrine usage was noted. CONCLUSIONS: In patients with severe sepsis and septic shock, levosimendan is associated with a significant reduction in mortality compared with standard inotropic therapy. A large ongoing multicenter randomized trial will have to confirm these findings.

Noninvasive ventilation and survival in acute care settings: a comprehensive systematic review and metaanalysis of randomized controlled trials.

OBJECTIVE: Noninvasive ventilation is increasingly applied to prevent or treat acute respiratory failure, but its benefit on survival is still controversial for many indications. We performed a metaanalysis of randomized controlled trials focused on the effect of noninvasive ventilation on mortality. DATA SOURCES: BioMedCentral, PubMed, Embase, and the Cochrane Central Register of clinical trials (updated December 31, 2013) were searched. STUDY SELECTION: We included all the randomized controlled trials published in the last 20 years performed in adults, reporting mortality, comparing noninvasive ventilation to any other treatment for prevention or treatment of acute respiratory failure or as a tool allowing an earlier extubation. Studies with unclear methodology, comparing two noninvasive ventilation modalities, or in palliative settings were excluded. DATA EXTRACTION: We extracted data on mortality, study design, population, clinical setting, comparator, and follow-up duration. DATA SYNTHESIS: Seventy-eight studies were analyzed. Noninvasive ventilation was associated with a reduction in mortality (12.6% in the noninvasive ventilation group vs 17.8% in the control arm; risk ratio=0.73 [0.66-0.81]; p<0.001; number needed to treat=19 with 7,365 patients included) at the longest available follow-up. Mortality was reduced when noninvasive ventilation was used to treat (14.2% vs 20.6%; risk ratio=0.72; p<0.001; number needed to treat=16, with survival improved in pulmonary edema, chronic obstructive pulmonary disease exacerbation, acute respiratory failure of mixed etiologies, and postoperative acute respiratory failure) or to prevent acute respiratory failure (5.3% vs 8.3%; risk ratio=0.64 [0.46-0.90]; number needed to treat=34, with survival improved in postextubation ICU patients), but not when used to facilitate an earlier extubation. Overall results were confirmed for hospital mortality. Patients randomized to noninvasive ventilation maintained the survival benefit even in studies allowing crossover of controls to noninvasive ventilation as rescue treatment. CONCLUSIONS: This comprehensive metaanalysis suggests that noninvasive ventilation improves survival in acute care settings. The benefit could be lost in some subgroups of patients if noninvasive ventilation is applied late as a rescue treatment. Whenever noninvasive ventilation is indicated, an early adoption should be promoted.

Acute normovolemic hemodilution.

Acute normovolemic hemodilution (AHN) is a well known but poorly used "blood saving" method. The authors, based on their own experience and on the "low hematocrit" physiology, present some concepts on AHN and a clinical experience to demonstrate the usefulness and affordability of this method. Consequently we offer several tools concerning both the realization of AHN and the safe use of such dilution, suggesting simple and exciting methods to determine if, when and how to apply this blood saving system.

Esmolol reduces perioperative ischemia in cardiac surgery: a meta-analysis of randomized controlled studies.

OBJECTIVE: beta-Blockers were associated with a reduction of mortality and morbidity in noncardiac surgery until recently when the POISE trial showed that beta-blockers could be harmful in the perioperative period because of hypotension and bradycardia. Esmolol is an ultra-short-acting beta-blocker mostly used in emergency and high-risk patients. The authors performed a meta-analysis to evaluate the clinical effects of esmolol in cardiac surgery. DESIGN: Meta-analysis. SETTING: Hospitals. PARTICIPANTS: A total of 778 patients from 20 randomized trials. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULT: Three investigators independently searched BioMedCentral and PubMed. Inclusion criteria were random allocation to treatment and comparison of esmolol versus other drugs, placebo, or standard of care in cardiac surgery. Exclusion criteria were duplicate publications, nonhuman experimental studies, and no data on clinical outcomes. The use of esmolol was associated with a significant reduction of myocardial ischemia episodes (15/122 [12.2%] in the esmolol group v 36/140 [25.7%] in the control arm, odds ratio [OR] =0.42 [0.23-0.79], p = 0.007) and development of arrhythmias after cardiopulmonary bypass (15/65 [23.07%] v 23/64 [35.9%], OR = 0.42 [0.18-1.01], p = 0.05). The authors did not find a reduction in the use of inotropic drugs in esmolol-treated patients (29/153 [18.9%] v 48/146 [32.8%], OR = 0.43 [0.16-1.10], p = 0.08). Esmolol-treated patients had more episodes of bradycardia (19/129 [14.72%] v 3/133 [2.25%], OR = 5.49 [2.21-13.62], p = 0.0002) and hypotension (28/113 [24.77%] v 14/119 [11.76%], OR = 2.73 [0.83-9.04], p = 0.10). CONCLUSIONS: Esmolol reduces the incidence of myocardial ischemia and arrhythmias in cardiac surgery. An increase in bradycardia was noted as well.

[Panhypopituitarism from pituitary metastases of breast cancer]. / Panipopituitarismo da metastasi ipofisarie di carcinoma mammario.

Metastases to the pituitary gland are uncommon causes of hypopituitarism, to be particularly considered in patients affected with disseminated cancers, arising in the breast or in the lung. Differential diagnosis could be correctly addressed by the concomitant presence of diabetes insipidus, due to the prominent involvement of the posterior lobe, and by some neuroradiological findings. We report the case of a 58-year-old woman, suffering from advanced breast cancer, who developed diabetes insipidus and anterior hypopituitarism. Magnetic resonance images showed diffuse encephalic metastatic lesions, with a thickened pituitary stalk, loss of high signal intensity of posterior lobe and a mildly enlarged and inhomogeneously enhanced adenohypophysis. Substitutive hormonal therapy was started, but the patient died five months later due to the progression of the neoplastic disease.

[Elevated concentration of serum carcinoembryonic antigen in hypothyroidism]. / Elevate concentrazioni sieriche di antigene carcinoembrionario in corso di ipotiroidismo.

In this case-report we describe two patients with hypothyroidism and increased carcinoembryonic antigen (CEA) serum concentration. The former patient was a woman affected by primary autoimmune hypothyroidism, the latter by secondary hypothyroidism in empty sella syndrome. In both of the patients we found no evidence of neoplastic disease and CEA serum concentrations reverted almost completely to the normal range values after the patients were given the hormonal replacement therapy with L-thyroxine. Although the association of hypothyroidism with elevated CEA serum concentrations has been already reported in the literature, hypothyroidism is usually disregarded when a physician is facing with a patient with increased CEA levels. On the contrary, our data suggest that hypothyroidism should be taken into account in the diagnostic work-up of these patients, such as smoking, cholestasis, impaired liver function, chronic inflammatory bronchial and bowel disease.