Evaluation of Continuous Inhaled Epoprostenol in the Treatment of Acute Respiratory Distress Syndrome, Including Patients With SARS-CoV-2 Infection

Background Acute respiratory distress syndrome (ARDS) management is primarily supportive. Pulmonary vasodilators, such as inhaled epoprostenol (iEPO), have been shown to improve PaO2:FiO2 (PF) and are used as adjunctive therapy. Objective To identify the positive response rate and variables associated with response to iEPO in adults with ARDS. A positive response to iEPO was defined as a 10% improvement in PF within 6 hours. Methods This retrospective study included adults with ARDS treated with iEPO. The primary endpoint was the variables associated with a positive response to iEPO. Secondary endpoints were positive response rate and the change in PF and SpO2:FiO2 within 6 hours. Statistical analysis included multivariable regression. Results Three hundred thirty-one patients were included. As baseline PF increased, the odds of responding to iEPO decreased (odds ratio [OR], 0.752, 95% CI, 0.69-0.819, p < 0.001). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related ARDS (OR 0.478, 95% CI, 0.281-0.814, p = 0.007) was associated with decreased odds of a positive response to iEPO. The total population had a 68.3% positive response rate to iEPO. SARS-CoV-2-related ARDS and non-SARS-CoV-2-related ARDS had a 59.5% and 72.7% positive response rate, respectively. iEPO significantly improved PF (71 vs 95, P < 0.001) in the whole population. Conclusion and Relevance iEPO was associated with a positive effect in a majority of moderate-to-severe ARDS patients, including patients with SARS-CoV-2-related ARDS. Lower baseline PF and non-SARS-CoV-2-related ARDS were significantly associated with a positive response to iEPO. The ability to predict which patients will respond to iEPO can facilitate better utilization.

Pharmacologic therapies for the low cardiac output syndrome in children after cardiac surgery: evidence of their efficacy and trends in their use

The low cardiac output syndrome describes the phenomenon of the reduction of cardiac output that can occur following cardiac surgery requiring cardiopulmonary bypass. If unrecognized or untreated, this condition can result in significant morbidity and mortality. Along with non-pharmacologic therapies, pharmacologic agents used to help manage the low cardiac output syndrome include catecholamine inotropes, inodilators, systemic vasodilators, pulmonary vasodilators, and other classes of medications. We summarize the rationale and key evidence supporting the use of these therapies in children. In addition, utilizing provider surveys and registry reviews, we describe the current trends in the use of these medications and the variation demonstrated between providers and centers. Given the heterogeneous etiology of low cardiac output syndrome, successful management requires that pharmacologic therapies be tailored to the physiologic derangements of each patient.

Transition from epoprostenol to selexipag in a patient with systemic sclerosis and pulmonary hypertension during the postoperative period of colon cancer surgery: A case report

Introduction: Most pulmonary vasodilators are administered orally; however, in patients with pulmonary hypertension undergoing gastrointestinal surgery, a switch to parenteral drugs is needed. Parenteral pulmonary vasodilators carry a risk of infection and reduced quality of life owing to long-term central venous catheterization; therefore, it is preferable to switch them to oral vasodilators after surgery. Here, we present the case of a patient with systemic sclerosis complicated by pulmonary hypertension and colon cancer, for which treatment was successfully switched from epoprostenol to selexipag postoperatively. Case Description: A 59-year-old woman, who was diagnosed with mixed group I and III pulmonary hypertension and systemic sclerosis, was on oral triple pulmonary vasodilators for pulmonary hypertension and Raynaud’s phenomenon. She was diagnosed as having colon cancer 3 months before admission. Despite the severe pulmonary condition and treatment with oral triple pulmonary vasodilators, colon cancer resection surgery was performed with the management for pulmonary hypertension through multidisciplinary treatments in collaboration with cardiology specialists. Medications for patients with pulmonary hypertension undergoing gastrointestinal surgery need to be switched from oral vasodilators to epoprostenol perioperatively. On postoperative day 19, 0.4 mg/day of selexipag was administered with epoprostenol. Subsequently, the epoprostenol dosage was gradually decreased, and selexipag was increased. On postoperative day 30, the dose of selexipag was increased to 1.2 mg/day and epoprostenol was discontinued. The patient was discharged on postoperative day 40. Conclusion: In our case, transition from epoprostenol to selexipag contributed to a more useful management strategy for systemic sclerosis and pulmonary hypertension in the postoperative period.

380 Left heart disease phenotype and use of pulmonary vasodilators in elderly patients with pulmonary arterial hypertension: the Patriarca registry

Aims The prevalence of occult left heart disease (LHD) and the feasibility of vasodilator therapy in the progressively growing population of elderly subjects with pulmonary arterial hypertension (PAH) are under scrutiny. We evaluated the presence of a LHD phenotype and the patterns of vasodilator treatment in such patients. Methods and results The PATRIARCA registry collected cross-sectional data from 180 subjects with PAH or chronic thromboembolic pulmonary hypertension and ≥70 years of age in 11 Italian centres between 1 December 2019 and 15 September 2020. After excluding patients with CTEPH or incomplete follow-up haemodynamic parameters, 77 individuals with PAH diagnosed at ≥ 65 years of age according to current guidelines were included in the analysis. A LHD phenotype was defined as follows, expanding the criteria adopted in the AMBITION trial: (i) ≥3 among body mass index ≥30 kg/m2, systemic hypertension, diabetes, and significant coronary artery disease; (ii) 2 of the risk factors for LHD above and ≥1 among permanent atrial fibrillation, left ventricular (LV) hypertrophy, LV ejection fraction &lt;50%, at least moderate mitral or aortic valve disease, and left atrial dilation; (iii) pulmonary vascular resistance (PVR) between 3 and 3.75 WU or PVR between 3.75 and 6.25 WU in the presence of a pulmonary artery wedge pressure (PAWP) of 13–15 mmHg. Forty-one (53%) patients had a LHD phenotype according to the most recent clinical and haemodynamic evaluation, which was performed 16 (4–35) months after diagnosis (Figure). As per definition, they had higher rates of comorbidities and more often echocardiographic signs of LHD (not shown). The frequency of NYHA classes I–II was comparable between the two groups, while the 6 min-walking distance tended to be lower in subjects with a LHD phenotype than in those without (Figure, left panel). Furthermore, these latter had lower PVR and higher PAWP. No differences were seen in treatment with pulmonary vasodilators, with around 50% of patients receiving double oral combination therapy in both groups (Figure, right panel). During the study period, 7 (17%) and 4 (11%) patients died in the LHD and no-LHD groups, respectively (P = 0.40). Conclusions In this real-world cohort of elderly patients, a LHD phenotype was common despite an initial haemodynamic diagnosis of PAH. However, it did not appear to cause simplification or discontinuation of pulmonary vasodilator therapy. Longitudinal studies are needed to determine whether and how a LHD phenotype affects the use and effects of PAH drugs in the elderly.

Oxidative Stress and Respiratory Diseases in Preterm Newborns

Premature infants are exposed to increased generation of reactive oxygen species, and on the other hand, they have a deficient antioxidant defense system. Oxidative insult is a salient part of lung injury that begins as acute inflammatory injury in respiratory distress disease and then evolves into chronic and structural scarring leading to bronchopulmonary dysplasia. Oxidative stress is also involved in the pathogenesis of pulmonary hypertension in newborns through the modulation of the vascular tone and the response to pulmonary vasodilators, with consequent decrease in the density of the pulmonary vessels and thickening of the pulmonary arteriolar walls. Oxidative stress has been recognized as both a trigger and an endpoint for several events, including inflammation, hypoxia, hyperoxia, drugs, transfusions, and mechanical ventilation, with impairment of pulmonary function and prolonged lung damage. Redoxomics is the most fascinating new measure to address lung damage due to oxidative stress. The new challenge is to use omics data to discover a set of biomarkers useful in diagnosis, prognosis, and formulating optimal and individualized neonatal care. The aim of this review was to examine the most recent evidence on the relationship between oxidative stress and lung diseases in preterm newborns. What is currently known regarding oxidative stress-related lung injury pathogenesis and the available preventive and therapeutic strategies are also discussed.

Management of Pulmonary Thromboembolism

Pulmonary thrombo-embolism (PTE) is a major cause of cardiovascular morbidity and mortality. Incidence of PTE and its associated mortality is affected by the Prescence of associated risk factors, comorbid conditions and advancement in the treatment options. Clinical probability, D-Dimer, echocardiography and CT pulmonary angiography are used in the diagnosis. Management starts with stratification, with high-risk category being benefited from the thrombolytic therapy. Catheter directed therapy may be used in ineligible or failed cases with surgical embolectomy being used as final salvage therapy. Patients with persistent hemodynamic stability can be started on anticoagulation alone. Supportive therapy with fluid expansion and inhalational Nitric oxide may provide benefit in few. Patients with PTE should receive secondary preventive anticoagulation to prevent recurrences. High risk patients with sub-segmental PTE may benefit from anticoagulation. For early detection of long-term complications of PTE a patient cantered follow-up is needed. Chronic thrombo-embolic pulmonary hypertension (CTEPH) is a dreaded complication with pulmonary end-arterectomy being a gold standard management option in eligible patients with non-surgical therapy (balloon pulmonary angioplasty and pulmonary vasodilators) also being used in many cases.

A CASE OF PULMONARY THROMOEMBOLISM OCCURRED IMMEDIATELY AFTER THE FIRST DOSE OF CHADOX1 NCOV- 19 VACCINATION.

In the recent studies, COVID-19 vaccines, especially Covishield has been associated with the reports of Vaccine-Induced pulmonary thromboembolism. pulmonary thromboembolism is a complication that can occur after the rst dose of the vaccine causing the thrombosis in veins at specic sites like lungs, Brain and Deep Veins and Arteries. It presents commonly as the Pulmonary Embolism (PE), within 7-10 days of vaccination. Patients taking vaccinations under the age of 45 presents at the high risk. Mortality rate in such post vaccination thrombosis is considered to be 50% in some cases. Thus, it is far more important to understand and identify the early signs and symptoms for early diagnosis, proper treatment and interventions. In the following case presented. A 29-year-old male patient was presented with the complaints of High Fever, Cough and Extreme Breathlessness after receiving the rst dose of ChADOx1 nCoV-19 Vaccination against the Corona Virus Disease 2019 (COVID-19). He had history of Exertional Dyspnoea for 2-3 weeks. He was diagnosed to have Pulmonary Embolism with severe PAH. 2D ECHO was done which showed Severe Pulmonary Hypertension Likely Pulmonary Thromboembolism, Good biventricular systolic function, Mild TR. CT Chest with Pulmonary Angiography was done which showed Eccentric lling defect seen in bilateral arteries at hila with extension in lower lobe segment branches- likely thrombus. CT Scan of Thorax (Plain & Contrast) was also done which showed bilateral small patchy ground glass haze with superimposed Reticular thickening mainly in Subpleural region. He was immediately thrombolysed with Intrapulmonary TNK after doing Check angiography. He was then managed with Oxygen support, NIV support, Inj. Fondaparinux, Anti biotics, Anti-coagulant, diuretics, Pulmonary vasodilators, Anti-hypertensive, and other supportive drugs. He responded well to the given treatment and was gradually weaned off NIV and oxygen support. Serial D-dimer, CBC, Chest X ray monitoring was done. Repeat CT chest was done in view of fresh lesions on Chest X ray which showed cavitatory lesion in Right mid zone with moderate Pleural effusion. Chest Physician consultation was taken and advice followed accordingly. He was discharged after 19 days, later he was then taken up for follow up every 2 weeks