Frequency, characteristics, and outcome of patients with COVID-19 pneumonia and "silent hypoxemia" at admission: a severity-matched analysis.

BACKGROUND: An aspect of COVID-19 baffling physicians is the presentation of patients with acute respiratory failure, but normal mental faculties and no perception of dyspnea (i.e. "silent hypoxemia"). The aim of this study was to investigate the frequency, characteristics, and outcome of COVID-19 patients with silent hypoxemic status and comparing them with a symptomatic severity-matched group. METHODS: This is a retrospective monocentric observational study involving all patients with PCR confirmed SARS-CoV-2 pneumonia, admitted at Papa Giovanni XXIII Hospital, Bergamo (Italy) from Emergency Department due to acute respiratory failure, during the first Italian pandemic peak (February-April 2020). RESULTS: Overall 28-day mortality in 1316 patients was 26.9%. Patients who did not report dyspnea at admission (N 469, 35.6%) had a lower 28-day mortality (22.6 vs. 29.3%, P=0.009). The severity matching analysis (i.e. PaO2/FiO2 and imaging) led to the identification of two groups of 254 patients that did not differ for sex prevalence, age, BMI, smoking history, comorbidities, and PaCO2 at admission. The use of CPAP during the first 24 hours, such as the need of endotracheal intubation (ETI) during the overall admission were significantly lower in matched patients with silent hypoxemia, whereas 28-day mortality resulted similar (P=0.21). CONCLUSIONS: Lack of dyspnea is common in patients suffering from severe COVID-19 pneumonia leading to respiratory failure, since up to a third of them could be asymptomatic on admission. Dyspnea per se correlates with pneumonia severity, and prognosis. However, dyspnea loses its predictive relevance once other findings to evaluate pneumonia severity are available such as PaO2/FiO2 and imaging. Silent hypoxemic patients are less likely to receive CPAP during the first 24 hours and ETI during the hospitalization, in spite of a comparable mortality to the dyspneic ones.

Antecedent use of renin-angiotensin system inhibitors is associated with reduced mortality in elderly hypertensive Covid-19 patients.

OBJECTIVES: The effect of renin-angiotensin system inhibitors (RASIs) on mortality in patients with coronavirus disease (Covid-19) is debated. From a cohort of 1352 consecutive patients admitted with Covid-19 to Papa Giovanni XXIII Hospital in Bergamo, Italy, between February and April 2020, we selected and studied hypertensive patients to assess whether antecedent (prior to hospitalization) use of RASIs might affect mortality from Covid-19 according to age. METHODS AND RESULTS: Arterial hypertension was present in 688 patients. Overall mortality (in-hospital or shortly after discharge) was 35% (N = 240). After adjusting for 26 medical history variables via propensity score matching, antecedent use of RASIs (N = 459, 67%) was associated with a lower mortality in older hypertensive patients (age above the median of 68 years in the whole series), whereas no evidence of a significant effect was found in the younger group of the same population (P interaction = 0.001). In an analysis of the subgroup of 432 hypertensive patients older than 68 years, we considered two RASI drug subclasses, angiotensin-converting enzyme inhibitors (ACEIs, N = 156) and angiotensin receptor blockers (ARBs, N = 140), and assessed their respective effects by taking no-antecedent-use of RASIs as reference. This analysis showed that both antecedent use of ACEIs and antecedent use of ARBs were associated with a lower Covid-19 mortality (odds ratioACEI = 0.57, 95% confidence interval 0.36--0.91, P = 0.018) (odds ratioARB = 0.49, 95% confidence interval 0.29--0.82, P = 0.006). CONCLUSION: In the population of over-68 hypertensive Covid-19 patients, antecedent use of ACEIs or ARBs was associated with a lower all-cause mortality, whether in-hospital or shortly after discharge, compared with no-antecedent-use of RASIs.

A 57-year-old man with rapidly progressive pulmonary hypertension.

Pulmonary Tumor Thrombotic Microangiopathy (PTTM) is a rare condition associated with neoplastic disorders, predominantly gastric cancer, leading to pre-capillary Pulmonary Hypertension (PH). The pathologic mechanism involved is a fibrocellular intimal proliferation of small pulmonary vessels sustained by nests of carcinomatous cells lodged in pulmonary vasculature. Clinical presentation is nonspecific, including progressive dyspnea and dry cough. Diagnosis of PTTM is extremely challenging ante-mortem and prognosis is poor. Here we describe the case of a middle-aged man, without known previous cancer history. The clinical course was rapidly unfavorable, with progressive dyspnea and PH associated with hemodynamic instability, eventually culminating in patient's death. PTTM diagnosis was made post-mortem. PTTM should be considered in any patient presenting with unexplained PH, especially if it is rapidly progressive, poorly responsive to standard approaches or there is suspected history of malignancy. A prompt diagnosis of PTTM could help in bringing light into this still under-recognized condition.

Rationale for and Practical Use of Sacubitril/Valsartan in the Patient's Journey with Heart Failure and Reduced Ejection Fraction.

Sacubitril with valsartan (sacubitril/valsartan) is a relatively novel compound that has become a milestone in the treatment of patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) in the last decade. Contemporary data suggest that sacubitril/valsartan is associated with improved outcomes compared with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, and has a greater beneficial effect on myocardial reverse remodelling. Additionally, two recent trials have shown that sacubitril/valsartan is well-tolerated even in the acute HF setting, thus enabling a continuum of use in the patient's journey with HFrEF. This article summarises available data on the effectiveness and tolerability of sacubitril/valsartan in patients with HFrEF, and provides the clinician with practical insights to facilitate the use of this drug in every setting, with an emphasis on acute HF, hypotension, electrolyte imbalance and renal insufficiency.

Sublingual sufentanil tablet system for the management of acute postoperative pain in a hospital setting: an observational study.

BACKGROUND: The use of a strong opioid with intravenous patient-controlled analgesia (IV-PCA) is recommended for postoperative pain, but its use is restricted due to technical problems. Other delivery systems, like sublingual PCA, with the sufentanil tablet system (SSTS) device, could overcome the safety concerns related to IV-PCA. METHODS: This prospective observational study evaluated the efficacy, safety and usability of SSTS for post-surgical analgesia in the real-life setting. RESULTS: Two-hundred-ninety-eight subjects (125 males), ranging 18-87 years who were undergoing a surgical intervention with a necessity for postoperative analgesia in a hospital setting, were analyzed for SSTS efficacy and safety. The primary end point (success of treatment according to Patient Global Assessment of the Method of Pain Control [PGA] on the second postoperative day) was achieved in 89.8% (95% CI: 85.6-93.1%, P≤0.001 from a presumed value of 60%). During the first 24 hours, pain was below the baseline score (1.2±1.4 after four hours and 1.8±1.6 after 20 hours). The mean impairment in quality of sleep was 1.7±1.7 on postoperative day 1. The overall nurse ease of care (EOC) and nurses' satisfaction questionnaire score was 4.6±0.6, and 4.1±0.9, respectively. The overall patient EOC score was 4.3±0.5; 93.5% patients were extremely satisfied/satisfied with pain control and 93.2% were extremely satisfied/satisfied with the way of the administration. CONCLUSIONS: Under a real-life clinical practice setting, SSTS provides effective pain management and is easy to use for patients and nurses.

At the peak of COVID-19 age and disease severity but not comorbidities are predictors of mortality: COVID-19 burden in Bergamo, Italy.

BACKGROUND: Findings from February 2020, indicate that the clinical spectrum of COVID-19 can be heterogeneous, probably due to the infectious dose and viral load of SARS-CoV-2 within the first weeks of the outbreak. The aim of this study was to investigate predictors of overall 28-day mortality at the peak of the Italian outbreak. METHODS: Retrospective observational study of all COVID-19 patients admitted to the main hospital of Bergamo, from February 23 to March 14, 2020. RESULTS: Five hundred and eight patients were hospitalized, predominantly male (72.4%), mean age of 66±15 years; 49.2% were older than 70 years. Most of patients presented with severe respiratory failure (median value [IQR] of PaO2/FiO2: 233 [149-281]). Mortality rate at 28 days resulted of 33.7% (N.=171). Thirty-nine percent of patients were treated with continuous positive airway pressure (CPAP), 9.5% with noninvasive ventilation (NIV) and 13.6% with endotracheal intubation. 9.5% were admitted to Semi-Intensive Respiratory Care Unit, and 18.9% to Intensive Care Unit. Risk factors independently associated with 28-day mortality were advanced age (≥78 years: odds ratio [OR], 95% confidence interval [CI]: 38.91 [10.67-141.93], P<0.001; 70-77 years: 17.30 [5.40-55.38], P<0.001; 60-69 years: 3.20 [1.00-10.20], P=0.049), PaO2/FiO2<200 at presentation (3.50 [1.70-7.20], P=0.001), need for CPAP/NIV in the first 24 hours (8.38 [3.63-19.35], P<0.001), and blood urea value at admission (1.01 [1.00-1.02], P=0.015). CONCLUSIONS: At the peak of the outbreak, with a probable high infectious dose and viral load, older age, the severity of respiratory failure and renal impairment at presentation, but not comorbidities, are predictors of 28-day mortality in COVID-19.

Clinical guidelines for perioperative hemodynamic management of non cardiac surgical adult patients.

Perioperative hemodynamic management, through monitoring and intervention on physiological parameters to improve cardiac output and oxygen delivery (goal-directed therapy, GDT), may improve outcome. However, an Italian survey has revealed that hemodynamic protocols are applied by only 29.1% of anesthesiologists. Aim of this paper is to provide clinical guidelines for a rationale use of perioperative hemodynamic management in non cardiac surgical adult patients, oriented for Italy and updated with most recent studies. Guidelines were elaborated according to NICE (National Institute for Health and Care Excellence) and GRADE system (Grading of Recommendations of Assessment Development and Evaluations). Key questions were formulated according to PICO system (Population, Intervention, Comparators, Outcome). Guidelines and systematic reviews were identified on main research databases and strategy was updated to June 2018. There is not enough good quality evidence to support the adoption of a GDT protocol in order to reduce mortality, although it may be useful in high risk patients. Perioperative GDT protocol to guide fluid therapy is recommended to reduce morbidity. Continuous monitoring of arterial pressure may help to identify short periods of hemodynamic instability and hypotension. Fluid strategy should aim to a near zero balance in normovolemic patients at the beginning of surgery, and a slight positive fluid balance may be allowed to protect renal function. Drugs such as inotropes, vasocostrictors, and vasodilatator should be used only when fluids alone are not sufficient to optimize hemodynamics. Perioperative GDT protocols are associated with a reduction in costs, although no economic study has been performed in Italy.

Periprocedural management of patients with subarachnoid hemorrhage.

PURPOSE OF REVIEW: Anesthesiologists and intensivists may be involved in the management of aneurysmal subarachnoid hemorrhage (aSAH) patients at various stages of care. This article will review the recent advances in the periprocedural management of aSAH patients. RECENT FINDINGS: New scoring systems to assess gravity and prognosis of aSAH patients have been evaluated and proposed. Rebleeding still remains, with early aneurysmal treatment, a major challenge in the first hours of aSAH management. In the last decades, the treatment of the aSAH has shifted from clipping to coiling and more recently, the use of flow diversion technique has been introduced in selected patients. Although these improvements allow treatment of more complex aneurysms, they have implications for the anesthesiologist, including requiring the management of anticoagulation with its inherent risks. Even though knowledge, monitoring, and management of postprocedural phase of aSAH patients has improved, vasospasm and cerebral-delayed ischemia still remain the major and devastating complications in the postoperative course of aSAH patients. SUMMARY: Despite recent progress in the scoring, diagnosis, and treatment of aSAH patients, the periprocedural management of these patients is still a major challenge for anesthesiologists and intensivists, who are involved from the first phase of the aneurysm rupture through the postoperative phases and vasospasm period.

Burnout in Cardiac Anesthesiologists: Results From a National Survey in Italy.

OBJECTIVE: There is increasing burnout incidence among medical disciplines, and physicians working in emergency settings seem at higher risk. Cardiac anesthesiology is a stressful anesthesiology subspecialty dealing with high-risk patients. The authors hypothesized a high risk of burnout in cardiac anesthesiologists. DESIGN: National survey conducted on burnout. SETTING: Italian cardiac centers. PARTICIPANTS: Cardiac anesthesiologists. INTERVENTIONS: The authors administered via email an anonymous questionnaire divided into 3 parts. The first 2 parts evaluated workload and private life. The third part consisted of the Maslach Burnout Inventory test with its 3 constituents: high emotional exhaustion, high depersonalization, and low personal accomplishment. MEASUREMENTS AND MAIN RESULTS: The authors measured the prevalence and risk of burnout through the Maslach Burnout Inventory questionnaire and analyzed factors influencing burnout. Among 670 contacts from 71 centers, 382 cardiac anesthesiologists completed the survey (57%). The authors found the following mean Maslach Burnout Inventory values: 14.5 ± 9.7 (emotional exhaustion), 9.1 ± 7.1 (depersonalization), and 33.7 ± 8.9 (personal accomplishment). A rate of 34%, 54%, and 66% of respondents scored in "high" or "moderate-high" risk of burnout (emotional exhaustion, depersonalization, and personal accomplishment, respectively). The authors found that, if offered to change subspecialty, 76% of respondents would prefer to remain in cardiac anesthesiology. This preference and parenthood were the only 2 investigated factors with a protective effect against all components of burnout. Significantly lower burnout scores were found in more experienced anesthesiologists. CONCLUSION: A relatively high incidence of burnout was found in cardiac anesthesiologists, especially regarding high depersonalization and low personal accomplishment. Nonetheless, most of the respondents would choose to remain in cardiac anesthesiology.

A Narrative Review of Adherence to Subarachnoid Hemorrhage Guidelines.

Over the past 2 decades, a large number of guidelines for aneurysmal subarachnoid hemorrhage (aSAH) management have been proposed. The primary aim of these "evidence-based" guidelines is to improve the care of aSAH patients by summarizing and making current knowledge readily available to clinicians. However, an investigation into aSAH guidelines, their changes along time and their successful translation into clinical practice is still lacking.We performed a literature search of historical events and subarachnoid hemorrhage guidelines using the Entrez PubMed NIH, Embase, and Cochrane databases for articles published up to November of 2016. Data were summarized for guidelines on aSAH management and cross-sectional studies of their application. A total of 11 guidelines and 10 cross-sectional studies on aSAH management were analyzed. The use of nimodipine for the treatment of SAH is the only recommendation that remained consistent across guidelines over time (r=0.82; P<0.05). A shift in the definitive treatment for aneurysms from open surgical clipping to endovascular coiling was also noted (r=-0.91; r=0.96; P<0.005). In addition, definitive treatment for aneurysm is being performed earlier. The use of triple-H therapy and the long-term administration of anticonvulsive therapy has decreased. Finally, written protocols for aSAH management were not consistently used across tertiary care institutions (r=-0.46; P=0.43; confidence interval, -0.95 to -0.70).We conclude that guidelines related to the management of patients with SAH have evolved from a consensus-based approach into an evidence-based approach. Nevertheless, the translation into clinical practice is limited, suggesting that personalized approaches to care is inherent, and perhaps necessary for aSAH management.

Levosimendan for patients with severely reduced left ventricular systolic function and/or low cardiac output syndrome undergoing cardiac surgery: a systematic review and meta-analysis.

BACKGROUND: Previous studies have shown beneficial effects of levosimendan in high-risk patients undergoing cardiac surgery. Two large randomized controlled trials (RCTs), however, showed no advantages of levosimendan. METHODS: We performed a systematic review and meta-analysis (MEDLINE and Embase from inception until March 30, 2017), investigating whether levosimendan offers advantages compared with placebo in high-risk cardiac surgery patients, as defined by preoperative left ventricular ejection fraction (LVEF) ≤ 35% and/or low cardiac output syndrome (LCOS). The primary outcomes were mortality at longest follow-up and need for postoperative renal replacement therapy (RRT). Secondary postoperative outcomes investigated included myocardial injury, supraventricular arrhythmias, development of LCOS, acute kidney injury (AKI), duration of mechanical ventilation, intensive care unit and hospital lengths of stay, and incidence of hypotension during drug infusion. RESULTS: Six RCTs were included in the meta-analysis, five of which investigated only patients with LVEF ≤ 35% and one of which included predominantly patients with LCOS. Mortality was similar overall (OR 0.64 [0.37, 1.11], p = 0.11) but lower in the subgroup with LVEF < 35% (OR 0.51 [0.32, 0.82], p = 0.005). Need for RRT was reduced by levosimendan both overall (OR 0.63 [0.42, 0.94], p = 0.02) and in patients with LVEF < 35% (OR 0.55 [0.31, 0.97], p = 0.04). Among secondary outcomes, we found lower postoperative LCOS in patients with LVEF < 35% receiving levosimendan (OR 0.49 [0.27, 0.89], p = 0.02), lower overall AKI (OR 0.62 [0.42, 0.92], p = 0.02), and a trend toward lower mechanical support, both overall (p = 0.07) and in patients with LVEF < 35% (p = 0.05). CONCLUSIONS: Levosimendan reduces mortality in patients with preoperative severely reduced LVEF but does not affect overall mortality. Levosimendan reduces the need for RRT after high-risk cardiac surgery.

Neprilysin inhibition in heart failure: mechanisms and substrates beyond modulating natriuretic peptides.

The autonomic nervous system, the renin-angiotensin-aldosterone system, and the natriuretic peptide system represent critical regulatory pathways in heart failure and as such have been the major targets of pharmacological development. The introduction and approval of angiotensin receptor neprilysin inhibitors (ARNi) have broadened the available drug treatments of patients with chronic heart failure with reduced ejection fraction. Neprilysin catalyses the degradation of a number of vasodilator peptides, including the natriuretic peptides, bradykinin, substance P, and adrenomedullin, as well as vasoconstrictor peptides, including endothelin-1 and angiotensin I and II. We review the multiple, potentially competing, substrates for neprilysin inhibition, and the resultant composite clinical effects of ARNi therapy. A mechanistic understanding of this novel therapeutic class may provide important insights into the expected on-target and off-target effects when this agent is more widely prescribed.