Effect of P2Y12 Inhibitors on Survival Free of Organ Support Among Non-Critically Ill Hospitalized Patients With COVID-19: A Randomized Clinical Trial.

Importance: Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. Objective: To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021. Interventions: Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis. Results: Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15). Conclusions and Relevance: Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.

Primary cardiac angiosarcoma: a rare cause of diffuse alveolar haemorrhage.

Primary cardiac angiosarcoma is a rare disease with a dismal prognosis. We report a case of a 50-year-old man who presented with haemoptysis, cough and worsening dyspnoea. An intracardiac mass was visualised on echocardiogram. He was treated for diffuse alveolar haemorrhage and acute respiratory distress syndrome but died from refractory hypoxaemic respiratory failure leading to cardiac arrest. The diagnosis of primary cardiac angiosarcoma with haemorrhagic pulmonary metastases leading to diffuse alveolar damage was confirmed on autopsy.

Defining a Ventilation Strategy for Flexible Bronchoscopy on Mechanically Ventilated Patients in the Medical Intensive Care Unit.

BACKGROUND: Flexible bronchoscopy (FB) in intubated patients on mechanical ventilation increases airway resistance. During FB, two ventilatory strategies are possible: maintaining tidal volume (VT) while maintaining baseline CO2 or allowing reduction of VT. The former strategy carries risk of hyperinflation due to expiratory flow limitation with FB. The aim of the authors was too study end expiratory lung volume (EELV) during FB of intubated subjects while limiting VT. METHODS: We studied 16 subjects who were intubated on mechanical ventilation and required FB. Changes in EELV were measured by respiratory inductance plethysmography. Ventilator mechanics, EELV, and arterial blood gases, were measured. RESULTS: FB insertions decreased EELV in 64% of cases (-325±371 mL) and increased it in 32% of cases (65±59 mL). Suctioning decreased EELV in 76% of cases (-120±104 mL) and increased it in 16% of cases (29±33 mL). Respiratory mechanics were unchanged. Pre-FB and post-FB, PaO2 decreased by 61±96 mm Hg and PaCO2 increased by 15±7 mm Hg. CONCLUSIONS: There was no clinically significant increase in EELV in any subject during FB. Decreases in EELV coincided with FB-suctioning maneuvers. Peak pressure limiting ventilation protected the subject against hyperinflation with a consequent, well-tolerated reduction in VT, and hypercapnea. Suctioning should be limited, especially in patients vulnerable to derecruitment effect.