Safety and efficacy of remifentanil target-controlled infusion for conscious sedation in a pregnant woman: a case report.

BACKGROUND: Every year 2% of pregnant women undergo nonobstetric surgical interventions worldwide. According to the American College of Obstetricians and Gynecologists Committee on Obstetric Practice, pregnant women should never be denied the most appropriate surgical treatment, regardless of the trimester of pregnancy. However, additional attention should be paid during the first trimester since it has the highest risk of inducing teratogenic mutations; additionally, during the third trimester, due to the possibility of preterm birth and low birth weight of the newborn, great care should be paid. CASE PRESENTATION: We present the case of a Caucasian 36-year-old woman during her 21st week of pregnancy, with a normal-sized fetus, according to the gestational age on ultrasound exam, and with no additional risk factors. The patient referred to an increasing nasal obstruction associated with rhinorrhea of the left nasal cavity. She also reported episodes of sleep apnea and hyposmia. The patient received a detailed otolaryngological examination, which allowed for identification of a mass within the left nasal cavity. The subsequent nasal endoscopy confirmed a grayish polypoid mass lesion with a multinodular surface occupying the entire left nasal fossa. The lesion totally obliterated the left maxillary sinus, resulting in obstruction of the anterior osteomeatal unit and ethmoidal sinusitis. She was referred for a functional endoscopic sinus surgery using analgosedation with remifentanil target-controlled infusion. DISCUSSION AND CONCLUSION: To the very best of our knowledge, this is the first case described in English literature about the use of analgosedation with remifentanil target-controlled infusion for otolaryngology surgery, specifically in functional endoscopic sinus surgery. It could be an interesting option to avoid the use of inhaled anesthetics that could induce fetal damage, especially during the first months of pregnancy. Furthermore, patient intubation is not necessary, which avoids cases of difficult intubation or any trauma to the airways. An adequate informed consent and appropriate compliance are elements of paramount importance in tailoring the anesthetic strategy for pregnant women who need nonobstetric surgical management.

Continuous vs intermittent Non-Invasive blood pressure MONitoring in preventing postoperative organ failure (niMON): study protocol for an open-label, multicenter randomized trial.

BACKGROUND: Blood pressure has become one of the most important vital signs to monitor in the perioperative setting. Recently, the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) recommended, with low level of evidence, continuous monitoring of blood pressure during the intraoperative period. Continuous monitoring allows for early detection of hypotension, which may potentially lead to a timely treatment. Whether the ability to detect more hypotension events by continuous noninvasive blood pressure (C-NiBP) monitoring can improve patient outcomes is still unclear. Here, we report the rationale, study design, and statistical analysis plan of the niMON trial, which aims to evaluate the effect of intraoperative C-NiBP compared with intermittent (I-NiBP) monitoring on postoperative myocardial and renal injury. METHODS: The niMon trial is an investigator-initiated, multicenter, international, open-label, parallel-group, randomized clinical trial. Eligible patients will be randomized in a 1:1 ratio to receive C-NiBP or I-NiBP as an intraoperative monitoring strategy. The proportion of patients who develop myocardial injury in the first postoperative week is the primary outcome; the secondary outcomes are the proportions of patients who develop postoperative AKI, in-hospital mortality rate, and 30 and 90 postoperative days events. A sample size of 1265 patients will provide a power of 80% to detect a 4% absolute reduction in the rate of the primary outcome. CONCLUSIONS: The niMON data will provide evidence to guide the choice of the most appropriate intraoperative blood pressure monitoring strategy. CLINICAL TRIAL REGISTRATION: Clinical Trial Registration: NCT05496322, registered on the 5th of August 2023.

The role of beta-blocker drugs in critically ill patients: a SIAARTI expert consensus statement.

BACKGROUND: The role of ß-blockers in the critically ill has been studied, and data on the protective effects of these drugs on critically ill patients have been repeatedly reported in the literature over the last two decades. However, consensus and guidelines by scientific societies on the use of ß-blockers in critically ill patients are still lacking. The purpose of this document is to support the clinical decision-making process regarding the use of ß-blockers in critically ill patients. The recipients of this document are physicians, nurses, healthcare personnel, and other professionals involved in the patient's care process. METHODS: The Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) selected a panel of experts and asked them to define key aspects underlying the use of ß-blockers in critically ill adult patients. The methodology followed by the experts during this process was in line with principles of modified Delphi and RAND-UCLA methods. The experts developed statements and supportive rationales in the form of informative text. The overall list of statements was subjected to blind votes for consensus. RESULTS: The literature search suggests that adrenergic stress and increased heart rate in critically ill patients are associated with organ dysfunction and increased mortality. Heart rate control thus seems to be critical in the management of the critically ill patient, requiring careful clinical evaluation aimed at both the differential diagnosis to treat secondary tachycardia and the treatment of rhythm disturbance. In addition, the use of ß-blockers for the treatment of persistent tachycardia may be considered in patients with septic shock once hypovolemia has been ruled out. Intravenous application should be the preferred route of administration. CONCLUSION: ß-blockers protective effects in critically ill patients have been repeatedly reported in the literature. Their use in the acute treatment of increased heart rate requires understanding of the pathophysiology and careful differential diagnosis, as all causes of tachycardia should be ruled out and addressed first.

Unplanned admissions after day-case surgery in an Italian third-level pediatric hospital: a retrospective study.

BACKGROUND: Increasing procedures in day-case surgery can mitigate the costs of health service, without reducing safety and quality standards. The Ospedale Pediatrico Bambino Gesù has adopted an educational program for healthcare personnel and patients' families to increase the number of day-case surgery procedures performed without reducing the level of safety. The unplanned admission rate after day-case surgery can be a quality benchmark for pediatric day-case surgery, and in literature, there are no Italian data. METHODS: We made a retrospective analysis of the hospital database and focused on children requiring unplanned admission to the central venue of the hospital for the night. The audit covered the period from September 2012 to April 2018. RESULTS: We performed general anesthesia for 8826 procedures (urology 33.60%, plastic surgery 30.87%, general surgery 17.44%, dermatology 11.66%, dentistry 3.16%, orthopedics 1.64%, digestive endoscopy 1.63%). Unplanned admission for anesthetic reasons resulted in two cases: one case of syncope and one case of vomit (0.023% rate). No one major complication. CONCLUSIONS: Good quality of patient selection, the safety of the structure, family education, and an efficient organizational model combined with an educational program for anesthesiologists can improve the safety of anesthesia for day-case surgery.

Burnout in Italian anesthesiologists and intensivists during the COVID-19 pandemic: a national survey.

BACKGROUND: COVID-19 pandemic added additional burden upon healthcare systems and anesthesiology and intensive care physicians (AI) who possessed crucial expertise for dealing with the pandemic. Aim of the study was to uncover specific burnout patterns among Italian AI, exploring the hypothesis that burnout has a multicluster structure. Differences in social and professional characteristics between burnout patterns were explored. METHODS: One thousand and nine AI (658 women) members of the Società Italiana di Anestesia Analgesia Rianimazione e Terapia Intensiva (SIAARTI) working during COVID-19 pandemic participated. Sociodemographic, working information and burnout levels evaluated through Maslach Burnout Inventory (MBI) were collected. RESULTS: According to the MBI cutoff, 39.7% and 25.8% of participants scored high in emotional exhaustion and depersonalization respectively, and 44.2% scored low in personal accomplishment. Cluster analysis highlighted four burnout profiles: resilience, detachment, burnout, and emotional reserve. The results showed that AI in the Resilience and Emotional Reserve groups were significantly older and more experienced than those in the Detachment and Burnout groups. Additionally, more of the individuals in the Resilience group were working in intensive care units and departments dedicated to COVID-19 patients. The Detachment group was comprised of more AI working in operating units, while the Burnout group contained a higher number of AI working in COVID-19 departments. CONCLUSIONS: These findings highlight different burnout patterns in Italian AI: older age, more professional experience, and work in intensive care units and departments dedicated to COVID-19 seemed to be protective factors during the pandemic. This appears a first step to promote focused interventions.

Tracheostomy in critically ill patients with SARS 2 COVID-19 infection: a prospective observational multi-center study of short- and long-term outcomes.

Background: We report the characteristics, timing, and factors related to the decision to perform a tracheostomy in patients with confirmed COVID-19 infection admitted to eight Italian intensive care units (ICUs). Materials and methods: Prospective observational cohort study of patients with COVID-19 disease on mechanical ventilation. Long-term functional impairment (up to 180 days' post-hospital discharge) was assessed using the Karnofsky scale. Kaplan-Meier analysis assessed differences in survival and freedom from tracheostomy in relation to ICU stay. Cox regression model was used to assess which variables impacted on tracheostomy as a categorical outcome. Results: A total of 248 patients were recruited in the eight participating ICUs. Patients undergoing tracheostomy (n = 128) had longer ICU (25 (18-36) vs. 10 (7-16), P = 0.001) and hospital (37 (26.5-50) vs. 19 (8.5-34.5) P = 0.02) stays. ICU and hospital mortality of patients tracheostomized was 34% and 37%, respectively. Cumulative survival Kaplan-Meier analysis documented improved survival rates in patients undergoing tracheostomy (Log-Rank, Mantel-Cox = 4.8, P = 0.028). Median Karnofsky scale values improved over time but were similar between survivors receiving or not receiving tracheostomy. No healthcare worker involved in the tracheostomy procedure developed COVID-19 infection during the study period. Conclusions: Patients with COVID-19 infection who underwent tracheostomy had a better cumulative survival but similar long-term functional outcomes at 30, 60, and 180 days after hospital discharge.

Enhanced recovery after bariatric surgery: an Italian consensus statement.

BACKGROUND: Enhanced recovery after bariatric surgery (ERABS) is an approach developed to improve outcomes in obese surgical patients. Unfortunately, it is not evenly implemented in Italy. The Italian Society for the Surgery of Obesity and Metabolic Diseases and the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care joined in drafting an official statement on ERABS. METHODS: To assess the effectiveness and safety of ERABS and to develop evidence-based recommendations with regard to pre-, intra-, and post-operative care for obese patients undergoing ERABS, a 13-member expert task force of surgeons and anesthesiologists from Italian certified IFSO center of excellence in bariatric surgery was established and a review of English-language papers conducted. Oxford 2011 Levels of Evidence and U.S. Preventive Services Task Force Grade Definitions were used to grade the level of evidence and the strength of recommendations, respectively. The supporting evidence and recommendations were reviewed and discussed by the entire group at meetings to achieve a final consensus. RESULTS: Compared to the conventional approach, ERABS reduces the length of hospital stay and does not heighten the risk of major post-operative complications, re-operations, and hospital re-admissions, nor does it increase the overall surgical costs. A total of 25 recommendations were proposed, covering pre-operative evaluation and care (7 items), intra-operative management (1 item, 11 sub-items), and post-operative care and discharge (6 items). CONCLUSIONS: ERABS is an effective and safe approach. The recommendations allow the proper management of obese patients undergoing ERABS for a better outcome.

Which Surgery for Stage II-III Empyema Patients? Observational Single-Center Cohort Study of 719 Consecutive Patients.

OBJECTIVE: Recent guidelines support the use of thoracoscopic surgery in stage II-III empyema; however, there is still debate regarding the best surgical approach. The aim of our study is to compare postoperative outcomes of VATS and open surgical approaches for the treatment of post-pneumonic empyema. METHODS: Observational cohort study on prospectively collected cases of post-pneumonic empyema surgically treated in a single center (2000-2020). Patients were divided into an open group (OT, posterolateral muscle sparing thoracotomy) and VATS group (VT, 2 or 3 port ± utility incision). The primary outcome of the study was empyema resolution, assessed by the recurrence rate. Secondary outcomes were mortality, complications, pain and return to daily life. All patients were followed up at 1, 3 and 6 months after surgery in the outpatient clinic with a chest radiograph/CT scan. RESULTS: In total, 719 consecutive patients were surgically treated for stage II-III empyema, with 644 belonging to the VT group and 75 to the OT group. All patients had a clinical history of pneumonia lasting no more than 6 months before surgery, and 553 (76.9%) had stage II empyema. Operative time was 92.7 ± 6.8 min for the OT group and 112.2 ± 7.4 for the VT group. The conversion rate was 8.4% (46/545) for stage II and 19.2% (19/99) for stage III. Twelve patients (1.86%) in the VT group and four patients (5.3%) in the OT group underwent additional surgery for bleeding. Postoperative mortality was 1.25% (9/719): 5.3% (4/75) in OT and 0.77% (5/644) in VT. Postoperative stay was 10 ± 6.5 days in OT and 8 ± 2.4 in VT. Overall morbidity was 14.7% (106/719): 21.3% (16/75) in OT and 13.9% (90/644) in VT. In VT, six patients (0.93%) showed recurrent empyema: five were treated with chest drainage and one with additional open surgery. CONCLUSIONS: Our findings suggest that the VATS approach, showing a 99% success rate, shorter length of stay and lower postoperative morbidity, should be considered the treatment of choice for thoracic empyema.

Bacterial infections in critically ill patients with SARS-2-COVID-19 infection: results of a prospective observational multicenter study.

PURPOSE: To investigate the prevalence, incidence and characteristics of bacterial infections and their impact on outcome in critically ill patients infected with COVID-19. METHODS: We conducted a prospective observational study in eight Italian ICUs from February to May 2020; data were collected through an interactive electronic database. Kaplan-Meier analysis (limit product method) was used to identify the occurrence of infections and risk of acquisition. RESULTS: During the study period 248 patients were recruited in the eight participating ICUs. Ninety (36.3%) patients developed at least one episode of secondary infection. An ICU length of stay between 7 and 14 days was characterized by a higher occurrence of infectious complications, with ventilator-associated pneumonia being the most frequent. At least one course of antibiotic therapy was given to 161 (64.9%) patients. Overall ICU and hospital mortality were 33.9% and 42.9%, respectively. Patients developing bacteremia had a higher risk of ICU mortality [45.9% vs. 31.6%, odds ratio 1.8 (95% CI 0.9-3.7), p = 0.069] and hospital mortality [56.8% vs. 40.3%, odds ratio 1.9 (95% CI 1.1-3.9), p = 0.04]. CONCLUSION: In critically ill patients infected with COVID-19 the incidence of bacterial infections is high and associated with worse outcomes. Regular microbiological surveillance and strict infection control measures are mandated.

Can we think of a TAT, that is a "tailored antiplatelet therapy"?

What can be seen from the case report by Verzelloni et al. has a double value, beyond the case itself. First of all, the use of platelet aggregation assessment tests, such as TEG-PM, allows clinicians to verify the exact timing between the suspension of thienopyridines and the possibility of surgery without further temporal delays and is also able to favor the evolution of ischemic problems or hemodynamic instability not easily treatable. It, therefore, allows clinicians to optimize the bleeding/thrombosis matching. Second, the use of point of care methodologies for the evaluation of platelet aggregation allows us to evaluate the adequacy of the antiaggregation, facilitating, where resistance or percentages of antiaggregation are lower than expected, modification of the therapeutic regimen.

Orthogeriatric co-management for the care of older subjects with hip fracture: recommendations from an Italian intersociety consensus.

BACKGROUND: Health outcomes of older subjects with hip fracture (HF) may be negatively influenced by multiple comorbidities and frailty. An integrated multidisciplinary approach (i.e. the orthogeriatric model) is, therefore, highly recommended, but its implementation in clinical practice suffers from the lack of shared management protocols and poor awareness of the problem. The present consensus document has been implemented to address these issues. AIM: To develop evidence-based recommendations for the orthogeriatric co-management of older subjects with HF. METHODS: A 20-member Expert Task Force of geriatricians, orthopaedics, anaesthesiologists, physiatrists, physiotherapists and general practitioners was established to develop evidence-based recommendations for the pre-, peri-, intra- and postoperative care of older in-patients (≥ 65 years) with HF. A modified Delphi approach was used to achieve consensus, and the U.S. Preventive Services Task Force system was used to rate the strength of recommendations and the quality of evidence. RESULTS: A total of 120 recommendations were proposed, covering 32 clinical topics and concerning preoperative evaluation (11 topics), perioperative (8 topics) and intraoperative (3 topics) management, and postoperative care (10 topics). CONCLUSION: These recommendations should ease and promote the multidisciplinary management of older subjects with HF by integrating the expertise of different specialists. By providing a convenient list of topics of interest, they might assist in identifying unmet needs and research priorities.

An update on levosimendan in acute cardiac care: applications and recommendations for optimal efficacy and safety.

Introduction: In the 20 years since its introduction to the palette of intravenous hemodynamic therapies, the inodilator levosimendan has established itself as a valuable asset for the management of acute decompensated heart failure. Its pharmacology is notable for delivering inotropy via calcium sensitization without an increase in myocardial oxygen consumption.Areas covered: Experience with levosimendan has led to its applications expanding into perioperative hemodynamic support and various critical care settings, as well as an array of situations associated with acutely decompensated heart failure, such as right ventricular failure, cardiogenic shock with multi-organ dysfunction, and cardio-renal syndrome. Evidence suggests that levosimendan may be preferable to milrinone for patients in cardiogenic shock after cardiac surgery or for weaning from extracorporeal life support and may be superior to dobutamine in terms of short-term survival, especially in patients on beta-blockers. Positive effects on kidney function have been noted, further differentiating levosimendan from catecholamines and phosphodiesterase inhibitors.Expert opinion:Levosimendan can be a valuable resource in the treatment of acute cardiac dysfunction, especially in the presence of beta-blockers or ischemic cardiomyopathy. When attention is given to avoiding or correcting hypovolemia and hypokalemia, an early use of the drug in the treatment algorithm is preferred.

Good clinical practice for the use of vasopressor and inotropic drugs in critically ill patients: state-of-the-art and expert consensus.

Vasopressors and inotropic agents are widely used in critical care. However, strong evidence supporting their use in critically ill patients is lacking in many clinical scenarios. Thus, the Italian Society of Anesthesia and Intensive Care (SIAARTI) promoted a project aimed to provide indications for good clinical practice on the use of vasopressors and inotropes, and on the management of critically ill patients with shock. A panel of 16 experts in the field of intensive care medicine and hemodynamics has been established. Systematic review of the available literature was performed based on PICO questions. Basing on available evidence, the panel prepared a summary of evidence and then wrote the clinical questions. A modified semi-quantitative RAND/UCLA appropriateness method has been used to determine the appropriateness of specific clinical scenarios. The panel identified 29 clinical questions for the use of vasopressors and inotropes in patients with septic shock and cardiogenic shock. High level of agreement exists among the panel members about appropriateness of inotropes/vasopressors' use in patients with septic shock and cardiogenic shock.

Perioperative goal-directed therapy and postoperative complications in different kind of surgical procedures: an updated meta-analysis.

BACKGROUND: Goal-directed therapy (GDT) aims to assure tissue perfusion, by optimizing doses and timing of fluids, inotropes, and vasopressors, through monitoring of cardiac output and other basic hemodynamic parameters. Several meta-analyses confirm that GDT can reduce postoperative complications. However, all recent evidences focused on high-risk patients and on major abdominal surgery. OBJECTIVES: The aim of the present meta-analysis is to investigate the effect of GDT on postoperative complications (defined as number of patients with a least one postoperative complication) in different kind of surgical procedures. DATA SOURCES: Randomized controlled trials (RCTs) on perioperative GDT in adult surgical patients were included. The primary outcome measure was complications, defined as number of patients with at least one postoperative complication. A subgroup-analysis was performed considering the kind of surgery: major abdominal (including also major vascular), only vascular, only orthopedic surgery. and so on. STUDY APPRAISAL AND SYNTHESIS METHODS: Meta-analytic techniques (analysis software RevMan, version 5.3.5, Cochrane Collaboration, Oxford, England, UK) were used to combine studies using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In 52 RCTs, 6325 patients were enrolled. Of these, 3162 were randomized to perioperative GDT and 3153 were randomized to control. In the overall population, 2836 patients developed at least one complication: 1278 (40%) were randomized to perioperative GDT, and 1558 (49%) were randomized to control. Pooled OR was 0.60 and 95% CI was 0.49-0.72. The sensitivity analysis confirmed the main result. The analysis enrolling major abdominal patients showed a significant result (OR 0.72, 95% CI 0.59-0.87, p = 0.0007, 31 RCTs, 4203 patients), both in high- and low-risk patients. A significant effect was observed in those RCTs enrolling exclusively orthopedic procedures (OR 0.53, 95% CI 0.35-0.80, p = 0.002, 7 RCTs, 650 patients. Also neurosurgical procedures seemed to benefit from GDT (OR 0.40, 95% CI 0.21-0.78, p = 0.008, 2 RCTs, 208 patients). In both major abdominal and orthopedic surgery, a strategy adopting fluids and inotropes yielded significant results. The total volume of fluid was not significantly different between the GDT and the control group. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The present meta-analysis, within the limits of the existing data, the clinical and statistical heterogeneity, suggests that GDT can reduce postoperative complication rate. Moreover, the beneficial effect of GDT on postoperative morbidity is significant on major abdominal, orthopedic and neurosurgical procedures. Several well-designed RCTs are needed to further explore the effect of GDT in different kind of surgeries.

Acute Kidney Injury in Coronavirus Disease 2019 Infected Patients: A Meta-Analytic Study.

INTRODUCTION: In clinical reports on coronavirus disease 2019 (COVID-19), the incidence of acute kidney injury (AKI) is extremely variable, although AKI is described as an independent risk factor for mortality. A meta-analysis was performed to clarify the incidence and the impact of COVID-19-related AKI on mortality. METHODS: All trials reporting the incidence of AKI in COVID-19 patients were searched using MEDLINE, the Cochrane Library, and EMBASE databases (last update April 26, 2020). RESULTS: Ten trials with a sample of 5,166 patients were included. AKI occurred in 947 out of 5,166 (18.3%) patients. AKI incidence was higher in severe cases: 62/305 severe patients developed AKI (20%) versus 27/1,268 nonsevere patients (2%) (p = 0.00001). AKI occurred in 475 out of 915 (52%) deceased patients versus 183 out of 2,678 (7%) survivors (p = 0.00001). Continuous renal replacement therapy was significantly more frequent in severe cases and in dead patients. CONCLUSION: A significant increase in mortality rate was observed in COVID patients who developed AKI, and AKI incidence was also higher in severe cases. Any supportive strategies to protect kidney could represent valuable intervention to reduce mortality in severe COVID-19 patients.

Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use.

Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use.

Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and non-cardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, UK and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute heart failure arena in recent times and charts a possible development trajectory for the next 20 years.

A randomized trial comparing the acute coronary, systemic, and environmental effects of electronic vaping cigarettes versus heat-not-burn cigarettes in smokers of combustible cigarettes undergoing invasive coronary assessment: rationale and design of the SUR-VAPES 3 trial.

BACKGROUND: Traditional combustible cigarette (TCC) smoking remains a major cause of preventable cardiovascular morbidity and mortality. Modified risk products (MRP) such as electronic vaping cigarettes (EVC) and heat-not-burn cigarettes (HNBC) may be safer than TCC but may still have detrimental oxidative, platelet and vascular effects of particular importance to people with symptomatic coronary artery disease (CAD). METHODS: We aimed to compare the acute coronary, systemic and environmental effects of two leading MRP in 20 TCC smokers admitted for invasive coronary assessment of CAD and willing to quit or after prior failed quitting attempts. After confirmation at angiography of an intermediate coronary stenosis, coronary flow reserve (CFR) will be appraised. Patients will then be randomized 1:1 to use a single EVC or a single HNBC in the catheterization laboratory, followed by repeat CFR measurement. The primary endpoint will be the change in CFR before and after product use. Quantitative coronary angiography, fractional flow reserve (FFR), and instantaneous wave-free ratio (iFR) will also be measured. RESULTS: We expected to accrue results able to: 1) test whether MRP have in general a detrimental impact on coronary vascular function in TCC smokers; 2) test whether EVC have a different impact than HNBC on coronary function; 3) provide ancillary pathophysiologic and translational insights on the acute risk and safety profile of MRP in TCC smokers with established cardiovascular disease, including complex correlations between coronary, cardiac, systemic and environmental effects. In addition, by directly informing participants of their individual results, they will be further empowered to quit TCC. CONCLUSIONS: The Sapienza University of Rome-Vascular Assessment of Proatherosclerotic Effects of Smoking (SUR-VAPES) 3 trial will provide important insights into the pathophysiologic cardiovascular impact of EVC and HNBC, also suitable to inform patients and individualize their smoking cessation strategy.