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Acute Respiratory Distress Syndrome and the Use of Inhaled Pulmonary Vasodilators in the COVID-19 Era: A Narrative Review.

ABSTRACT: The Coronavirus disease (COVID-19) pandemic of 2019 has resulted in significant morbidity and mortality, especially from severe acute respiratory distress syndrome (ARDS). As of September 2022, more than 6.5 million patients have died globally, and up to 5% required intensive care unit treatment. COVID-19-associated ARDS (CARDS) differs from the typical ARDS due to distinct pathology involving the pulmonary vasculature endothelium, resulting in diffuse thrombi in the pulmonary circulation and impaired gas exchange. The National Institute of Health and the Society of Critical Care Medicine recommend lung-protective ventilation, prone ventilation, and neuromuscular blockade as needed. Further, a trial of pulmonary vasodilators is suggested for those who develop refractory hypoxemia. A review of the prior literature on inhaled pulmonary vasodilators in ARDS suggests only a transient improvement in oxygenation, with no mortality benefit. This narrative review aims to highlight the fundamental principles in ARDS management, delineate the fundamental differences between CARDS and ARDS, and describe the comprehensive use of inhaled pulmonary vasodilators. In addition, with the differing pathophysiology of CARDS from the typical ARDS, we sought to evaluate the current evidence regarding the use of inhaled pulmonary vasodilators in CARDS.

SUBMITTER: Nasrullah A

PROVIDER: S-EPMC9695622 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Acute Respiratory Distress Syndrome and the Use of Inhaled Pulmonary Vasodilators in the COVID-19 Era: A Narrative Review.

Nasrullah Adeel A Virk Shiza S Shah Aaisha A Jacobs Max M Hamza Amina A Sheikh Abu Baker AB Javed Anam A Butt Muhammad Ali MA Sangli Swathi S

Life (Basel, Switzerland) 20221102 11

The Coronavirus disease (COVID-19) pandemic of 2019 has resulted in significant morbidity and mortality, especially from severe acute respiratory distress syndrome (ARDS). As of September 2022, more than 6.5 million patients have died globally, and up to 5% required intensive care unit treatment. COVID-19-associated ARDS (CARDS) differs from the typical ARDS due to distinct pathology involving the pulmonary vasculature endothelium, resulting in diffuse thrombi in the pulmonary circulation and im ...[more]

PMID: 36362921

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Project description:IntroductionAssessment of treatments for acute respiratory distress syndrome (ARDS) has focused on short-term outcomes (for example, mortality); little information exists regarding long-term effects of ARDS treatment. Survivors of ARDS episodes may have long-term obstructive/restrictive pulmonary abnormalities and pulmonary gas exchange impairment. A 2004 prospective randomized placebo-controlled trial assessed the efficacy and safety of inhaled nitric oxide (iNO) in patients with non-septic ARDS; the primary endpoint was days alive and off assisted breathing. This analysis examined potential effects of iNO or placebo on pulmonary function six months post-treatment in ARDS survivors from that original study.MethodsARDS survivors (N = 92) from a large-scale randomized, placebo-controlled study evaluating mortality after either 5 ppm iNO or placebo for up to 28 days were assessed six months post-treatment. Pulmonary function testing across seven parameters was conducted.ResultsAt 6 months post-treatment, results indicated significantly better absolute values for iNO versus placebo for mean ± SD total lung capacity (TLC, 5.54 ± 1.42 vs. 4.81 ± 1.00; P = 0.026). There were also significantly better values for mean ± SD percent predicted values for a) forced expiratory volume in 1 second (FEV1, 80.23 ± 21.21 vs. 69.51 ± 28.97; P = 0.042), b) forced vital capacity (FVC, 83.78 ± 19.37 vs. 69.84 ± 27.40; P = 0.019), c) FEV1/FVC (96.14 ± 13.79 vs. 87.92 ± 19.77; P = 0.033), and d) TLC (93.33 ± 18.21 vs. 76.10 ± 21.84; P < 0.001). Nonsignificant differences were found in absolute FEV1, FEV1/FVC, FVC, forced expiratory flow from 25% to 75% of FVC, functional residual capacity, and CO diffusion.ConclusionsARDS patients surviving after treatment with low-dose iNO had significantly better values for select pulmonary function tests at six months post-treatment than placebo-treated patients. Further trials are warranted to determine the effects of iNO on chronic lung function in ARDS survivors, a factor in long-term morbidity and quality of life in this population.Trial registrationA Double-blind, Randomized, Placebo-controlled, Dose-response Study of Inhaled Nitric Oxide in the Treatment of Acute Respiratory Distress Syndrome. NCT number: ISRCTN53268296.

Project description:BackgroundThere have been over 200 million cases and 4.4 million deaths from COVID-19 worldwide. Despite the lack of robust evidence one potential treatment for COVID-19 associated severe hypoxaemia is inhaled pulmonary vasodilator (IPVD) therapy, using either nitric oxide (iNO) or prostaglandins. We describe the implementation of, and outcomes from, a protocol using IPVDs in a cohort of patients with severe COVID-19 associated respiratory failure receiving maximal conventional support.MethodsProspectively collected data from adult patients with SARS-CoV-2 admitted to the intensive care unit (ICU) at a large teaching hospital were analysed for the period 14th March 2020 - 11th February 2021. An IPVD was considered if the PaO2/FiO2 (PF) ratio was less than 13.3kPa despite maximal conventional therapy. Nitric oxide was commenced at 20ppm and titrated to response. If oxygenation improved Iloprost nebulisers were commenced and iNO weaned. The primary outcome was percentage changes in PF ratio and Alveolar-arterial (A-a) gradient.ResultsFifty-nine patients received IPVD therapy during the study period. The median PF ratio before IPVD therapy was commenced was 11.33kPa (9.93-12.91). Patients receiving an IPVD had a lower PF ratio (14.37 vs. 16.37kPa, p = 0.002) and higher APACHE-II score (17 vs. 13, p = 0.028) at ICU admission. At 72 hours after initiating an IPVD the median improvement in PF ratio was 33.9% (-4.3-84.1). At 72 hours changes in PF ratio (70.8 vs. -4.1%, p < 0.001) and reduction in A-a gradient (44.7 vs. 14.8%, p < 0.001) differed significantly between survivors (n = 33) and non-survivors (n = 26).ConclusionsThe response to IPVDs in patients with COVID-19 associated acute hypoxic respiratory failure differed significantly between survivors and non-survivors. Both iNO and prostaglandins may offer therapeutic options for patients with severe refractory hypoxaemia due to COVID-19. The use of inhaled prostaglandins, and iNO where feasible, should be studied in adequately powered prospective randomised trials.

Project description:Studies evaluating inhaled prostacyclins for the management of acute respiratory distress syndrome (ARDS) have produced inconsistent results regarding their effect on oxygenation. The purpose of this systematic review and meta-analysis was to evaluate the change in the Pao2/Fio2 ratio after administration of an inhaled prostacyclin in patients with ARDS.Data sourcesWe searched Ovid Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane, Scopus, and Web of Science.Study selectionWe included abstracts and trials evaluating administration of inhaled prostacyclins in patients with ARDS.Data extractionChange in the Pao2/Fio2 ratio, Pao2, and mean pulmonary artery pressure (mPAP) were extracted from included studies. Evidence certainty and risk of bias were evaluated using Grading of Recommendations Assessment, Development, and Evaluation and the Cochrane Risk of Bias tool.Data synthesisWe included 23 studies (1,658 patients) from 6,339 abstracts identified by our search strategy. The use of inhaled prostacyclins improved oxygenation by increasing the Pao2/Fio2 ratio from baseline (mean difference [MD], 40.35; 95% CI, 26.14-54.56; p < 0.00001; I2 = 95%; very low quality evidence). Of the eight studies to evaluate change in Pao2, inhaled prostacyclins also increased Pao2 from baseline (MD, 12.68; 95% CI, 2.89-22.48 mm Hg; p = 0.01; I2 = 96%; very low quality evidence). Only three studies evaluated change in mPAP, but inhaled prostacyclins were found to improve mPAP from baseline (MD, -3.67; 95% CI, -5.04 to -2.31 mm Hg; p < 0.00001; I2 = 68%; very low quality evidence).ConclusionsIn patients with ARDS, use of inhaled prostacyclins improves oxygenation and reduces pulmonary artery pressures. Overall data are limited and there was high risk of bias and heterogeneity among included studies. Future studies evaluating inhaled prostacyclins for ARDS should evaluate their role in ARDS subphenotypes, including cardiopulmonary ARDS.

Dataset Information

Acute Respiratory Distress Syndrome and the Use of Inhaled Pulmonary Vasodilators in the COVID-19 Era: A Narrative Review.

Publications

Acute Respiratory Distress Syndrome and the Use of Inhaled Pulmonary Vasodilators in the COVID-19 Era: A Narrative Review.

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