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

2022 ◽  
pp. 106002802110691
Author(s):  
Hannah L. Niss ◽  
Adham Mohamed ◽  
Timothy P. Berry ◽  
Timothy M. Saettele ◽  
Michelle M. Haines ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Response Rate ◽  
Positive Response ◽  
Pulmonary Vasodilators ◽  
Lower Baseline ◽  
Secondary Endpoints ◽  
Positive Response Rate

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.

scholarly journals Immunosuppression is associated with a lower risk of moderate to severe acute respiratory distress syndrome in COVID-19.

2020 ◽  
Author(s):  
Enric Monreal ◽  
Susana Sainz de la Maza ◽  
Pedro Gullón ◽  
Elena Natera-Villalba ◽  
Juan Luis Chico-García ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Lower Risk ◽  
Distress Syndrome ◽  
Drug Discontinuation ◽  
Risk Of Death ◽  
Non Invasive Ventilation ◽  
Secondary Endpoints ◽  
Male Patients

Abstract BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has spread rapidly worldwide. The role of immunosuppression among COVID-19 patients has not been elucidated and management may be challenging.OBJECTIVE: To assess differences in severe outcomes of hospitalized patients with COVID-19 according to immune system state.DESIGN: Retrospective single-center observational study with confirmed COVID-19 patients admitted to Hospital Universitario Ramón y Cajal from March 18, 2020 to April 04, 2020. The final date of follow-up was April 09, 2020.PARTICIPANTS: Confirmed COVID-19 patients.MAIN MEASURES: The primary endpoint was development of moderate-severe acute respiratory distress syndrome (ARDS). Time to moderate-severe ARDS, the need for mechanical or non-invasive ventilation (MV/NIV), death, and a composite of death or MV/NIV were secondary endpoints.KEY RESULTS: Of 138 patients included, 29 (21%) were immunocompromised (IC), with 95 (68.8%) male patients and a median (IQR) age of 68 (54 – 78) years. Among the baseline characteristics, no relevant or significant differences were observed between IC and non-immunocompromised (non-IC) patients. A significantly lower proportion of IC patients (24.1% [95% CI, 11.4 – 44.0%]) compared to non-IC patients (49.5% [95% CI, 40.1 – 59.0%]) developed moderate-severe ARDS, in both unadjusted (OR 0.32 [95% CI, 0.13 – 0.82], p=0.018) and adjusted (aOR 0.16 [95% CI, 0.05 – 0.52], p=0.003) analyses. A positive non-significant trend toward a longer time to moderate or severe ARDS, a lower need for MV/NIV, and a lower risk of death or MV/NIV were detected in IC. A trend toward a shorter- hospitalization in IC was observed.CONCLUSIONS: In our cohort of COVID-19 patients, immunosuppression was associated with a lower risk of moderate-severe ARDS. This suggests a potential protective effect from a hypothesized host hyper-inflammatory response and warrants reconsideration of drug discontinuation in IC patients.

scholarly journals HIGH VERSUS STANDARD DOSES OF CORTICOSTEROIDS IN COVID-19 PATIENTS WITH AN ACUTE RESPIRATORY DISTRESS SYNDROME: a controlled observational comparative study.

2020 ◽  
Author(s):  
Enric Monreal ◽  
Susana Sainz de la Maza ◽  
Elena Natera-Villalba ◽  
Alvaro Beltran-Corbellini ◽  
Fernando Rodriguez-Jorge ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Interaction Analysis ◽  
Increased Risk ◽  
Secondary Endpoints ◽  
Older Subjects ◽  
High Doses

INTRODUCTION: Despite the increasing evidence of the benefit of corticosteroids for the treatment of moderate-severe Coronavirus disease 2019 (COVID-19) patients, no data are available about the potential role of high doses of steroids for these patients. METHODS: All consecutive confirmed COVID-19 patients admitted to a single center were selected, including those treated with steroids and an acute respiratory distress syndrome (ARDS). Patients were allocated to the high doses (HD, 250mg/day or more of methylprednisolone) of corticosteroids or the standard doses (SD, 1.5mg/kg/day or more of methylprednisolone) at discretion of treating physician. The primary endpoint was the mortality between both cohorts and secondary endpoints were the risk of need for mechanical ventilation (MV) or death and the risk of developing a severe ARDS. RESULTS: 573 patients were included: 428 (74.7%) men, with a median (IQR) age of 64 (54-73) years. In HD cohort, a worse baseline respiratory situation was observed and male sex, older age and comorbidities were significantly more common. After adjusting by baseline characteristics, HD were associated with a higher mortality than SD (adjusted-OR 2.46, 95% CI 1.58-3.83, p<0.001) and with an increased risk of needing MV or death (adjusted-OR 2.50, p=0.001). Conversely, the risk of developing a severe ARDS was similar between groups. Interaction analysis showed that HD increased mortality exclusively in elderly patients. CONCLUSION: Our real-world experience advises against exceeding 1-1.5mg/kg/day of corticosteroids for severe COVID-19 with an ARDS, especially in older subjects. This reinforces the rationale of modulating rather than suppressing immune responses in these patients.

scholarly journals Non-severe immunosuppression might be associated with a lower risk of moderate-severe acute respiratory distress syndrome in COVID-19.

2020 ◽  
Author(s):  
Enric Monreal ◽  
Susana Sainz de la Maza ◽  
Pedro Gullón ◽  
Elena Natera-Villalba ◽  
Juan Luis Chico-García ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Lower Risk ◽  
Distress Syndrome ◽  
Severe Immunosuppression ◽  
Risk Of Death ◽  
Non Invasive Ventilation ◽  
Secondary Endpoints ◽  
Male Patients

Abstract BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has spread rapidly worldwide. The role of immunosuppression among COVID-19 patients has not been elucidated and management may be challenging. OBJECTIVE: To assess differences in severe outcomes of hospitalized patients with COVID-19 according to immune system state. DESIGN: Retrospective single-center observational study with confirmed COVID-19 patients admitted to Hospital Universitario Ramón y Cajal from March 18, 2020 to April 04, 2020. The final date of follow-up was April 09, 2020.PARTICIPANTS: Confirmed COVID-19 patients. MAIN MEASURES: The primary endpoint was development of moderate-severe acute respiratory distress syndrome (ARDS). Time to moderate-severe ARDS, the need for mechanical or non-invasive ventilation (MV/NIV), death, and a composite of death or MV/NIV were secondary endpoints. KEY RESULTS: Of 138 patients included, 27 (19.6%) were immunosuppressed (IS), with 95 (68.8%) male patients and a median (Q1, Q3) age of 68 (54–78) years. Among the baseline characteristics, no relevant or significant differences were observed between IS and non-immunosuppressed (non-IS) patients, detecting a non-severe immunosupression among IS. A significantly lower proportion of IS patients (22.2% [95%CI, 9.8–43.0%]) compared to non-IS patients (49.5% [95%CI, 40.2–58.9%]) developed moderate-severe ARDS, in both unadjusted (OR 0.29 [95%CI, 0.11–0.76], p=0.014) and adjusted (aOR 0.16 [95%CI, 0.05–0.55], p=0.004) analyses. After stratifying by pathologies, only IS autoimmune diseases remained significant (aOR 0.12 [95%CI, 0.03–0.57], p=0.007). Non-significant trends toward a longer time to moderate or severe ARDS, a lower need for MV/NIV, and a lower risk of death or MV/NIV were detected in IS. CONCLUSIONS: In our cohort of COVID-19 patients, non-severe immunosuppression was associated with a lower risk of moderate-severe ARDS, especially among AD. This suggests a potential protective effect from a hypothesized host hyper-inflammatory response and warrants reconsideration of management of IS patients.

scholarly journals Inhaled Aerosolized Prostacyclin and Nitric Oxide as Selective Pulmonary Vasodilators in ARDS—A Pilot Study

1996 ◽  
Vol 24 (5) ◽  
pp. 564-568 ◽  
Author(s):  
P. V. Van Heerden ◽  
D. Blythe ◽  
S. A. R. Webb
Keyword(s):  
Nitric Oxide ◽  
Acute Respiratory Distress Syndrome ◽  
Pilot Study ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Shunt Fraction ◽  
Pulmonary Vasodilators ◽  
Haemodynamic Changes ◽  
Alveolar Oxygen

Nitric oxide 10 ppm and inhaled aerosolized prostacyclin 50 ng/kg/min were compared as selective pulmonary vasodilators in five patients with hypoxaemia secondary to acute respiratory distress syndrome. Neither agent resulted in systemic haemodynamic changes, indicating true pulmonary selectivity. Inhaled aerolized prostacyclin improved oxygenation to a degree comparable to nitric oxide, as measured by the arterial alveolar oxygen partial pressure gradient and shunt fraction.

Efficacy and Safety of Corticosteroids for Persistent Acute Respiratory Distress Syndrome

2018 ◽  
pp. 152-156
Author(s):  
Sean Levy ◽  
Ednan Bajwa
Keyword(s):  
Mechanical Ventilation ◽  
Acute Respiratory Distress Syndrome ◽  
Adverse Events ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Efficacy And Safety ◽  
Secondary Endpoints ◽  
Physiologic Parameters

The role of corticosteroids in the treatment of acute respiratory distress syndrome (ARDS), and in particular, those patients with persistent ARDS (defined as > 7 days since onset) has been controversial. In this ARDSNet study, subjects who received corticosteroids had similar outcomes as compared with placebo. Particular harm was seen in subjects with ARDS onset more than 14 days prior to treatment. Overall adverse events were similar between groups, although a higher rate of neuromyopathy was noted in those receiving steroids. Despite these findings, improvements in physiologic parameters and certain secondary endpoints suggest a possible role for steroids, perhaps with a more prolonged tapering of the drug following liberation from mechanical ventilation.

COVID-19 – eine vaskuläre Systemerkrankung

2020 ◽  
Vol 49 (10) ◽  
pp. 418-421
Author(s):  
Christopher Werlein ◽  
Peter Braubach ◽  
Vincent Schmidt ◽  
Nicolas J. Dickgreber ◽  
Bruno Märkl ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome

ZUSAMMENFASSUNGDie aktuelle COVID-19-Pandemie verzeichnet mittlerweile über 18 Millionen Erkrankte und 680 000 Todesfälle weltweit. Für die hohe Variabilität sowohl der Schweregrade des klinischen Verlaufs als auch der Organmanifestationen fanden sich zunächst keine pathophysiologisch zufriedenstellenden Erklärungen. Bei schweren Krankheitsverläufen steht in der Regel eine pulmonale Symptomatik im Vordergrund, meist unter dem Bild eines „acute respiratory distress syndrome“ (ARDS). Darüber hinaus zeigen sich jedoch in unterschiedlicher Häufigkeit Organmanifestationen in Haut, Herz, Nieren, Gehirn und anderen viszeralen Organen, die v. a. durch eine Perfusionsstörung durch direkte oder indirekte Gefäßwandschädigung zu erklären sind. Daher wird COVID-19 als vaskuläre Multisystemerkrankung aufgefasst. Vor dem Hintergrund der multiplen Organmanifestationen sind klinisch-pathologische Obduktionen eine wichtige Grundlage der Entschlüsselung der Pathomechanismen von COVID-19 und auch ein Instrument zur Generierung und Hinterfragung innovativer Therapieansätze.

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