Severe pulmonary hypertension-interstitial lung disease presenting as right ventricular failure: stabilisation with intravenous prostacyclin and maintenance with inhaled prostacyclin.

Background: Pulmonary hypertension (PH) leads to increased morbidity and mortality in interstitial lung disease (ILD). While the INCREASE trial highlighted the use of inhaled prostacyclin in PH-ILD patients, such therapy may be inadequate when right ventricular failure (RVF) is also present. In this study, we report the use of intravenous prostacyclin in three PH-ILD patients to stabilise right ventricular (RV) function, with a subsequent transition to maintenance therapy with inhaled prostacyclin. Methods: We evaluated three consecutive PH-ILD patients with RVF. RV afterload and pulmonary vascular resistance (PVR) were treated with intravenous prostacyclin during the induction phase of the therapy. Patients transitioned from intravenous prostacyclin to the maintenance phase of the treatment with inhaled prostacyclin once three transition criteria were met: cardiac index (CI) >2 L·min-1·m-2, PVR <7 Wood units (WU) and tricuspid annular plane systolic excursion (TAPSE) change >1 mm or TAPSE >1.6 cm. Results: Pre-treatment parameters for the three patients were a mean PVR of 14.3 WU, a mean Fick CI of 1.8 L·min-1·m-2 and a mean TAPSE of 1.4 cm. The average intravenous prostacyclin dose at the time of transition to maintenance therapy was 20.7 ng·kg-1·m-2 of treprostinil. At 3-months follow-up, the mean PVR was 6.3 WU, Fick CI 2.2 L·min-1·m-2 and TAPSE 1.7 cm. Conclusion: This case series of three PH-ILD patients with RVF introduces the concept of an initial intravenous prostacyclin induction phase, followed by a transition to maintenance therapy with inhaled prostacyclin. Further development of this treatment algorithm with a refinement of the transition criteria, potential testing in a clinical trial and a longer-term follow-up period is warranted to improve the outcomes of advanced PH-ILD patients with concomitant RVF.

Assessing the optimal MAP target in pre-capillary PH patients with RV failure: A retrospective analysis.

Right ventricular failure (RVF) in pre-capillary pulmonary hypertension (PH) is associated with high morbidity and mortality. While mean arterial pressure (MAP) goals have been well established in critical care literature, the optimal MAP target for patients with RVF secondary to pre-capillary PH remains unknown. The objective of this study was to evaluate the difference in outcomes between patients who were managed with different MAP targets. We retrospectively analyzed records of 60 patients who were admitted to the intensive care unit for decompensated RVF secondary to pre-capillary PH. The records were stratified into two groups: 30 patients who were treated with a static MAP goal of either 65 or 70 mmHg (MAP65/70) and 30 patients who received a dynamic MAP goal (MAPCVP) determined by invasively obtained central venous pressure or right atrial pressure. The dynamic MAP group had a statistically significant decrease in in-hospital mortality and incidence of acute kidney injury compared to the static MAP cohort.

Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19.

N-acetylcysteine (NAC) is an abundantly available antioxidant with a wide range of antidotal properties currently best studied for its use in treating acetaminophen overdose. It has a robustly established safety profile with easily tolerated side effects and presents the Food and Drug Administration's approval for use in treating acetaminophen overdose patients. It has been proven efficacious in off-label uses, such as in respiratory diseases, heart disease, cancer, human immunodeficiency virus infection, and seasonal influenza. Clinical trials have recently shown that NAC's capacity to replenish glutathione stores may significantly improve coronavirus disease 2019 (COVID-19) outcomes, especially in high risk individuals. Interestingly, individuals with glucose 6-phosphate dehydrogenase deficiency have been shown to experience even greater benefit. The same study has concluded that NAC's ability to mitigate the impact of the cytokine storm and prevent elevation of liver enzymes, C-reactive protein, and ferritin is associated with higher success rates weaning from the ventilator and return to normal function in COVID-19 patients. Considering the background knowledge of biochemistry, current uses of NAC in clinical practice, and newly acquired evidence on its potential efficacy against COVID-19, it is worthwhile to investigate further whether this agent can be used as a treatment or adjuvant for COVID-19.