Effect of surfactant administration on outcomes of adult patients in acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

Meng, Shanshan; Chang, Wei; Lu, Zhonghua; Xie, Jianfeng; Qiu, Haibo; Yang, Yi; Guo, Fengmei

doi:10.1186/s12890-018-0761-y

Cited by 50 publications

(38 citation statements)

References 21 publications

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“…Zhang et al (2013): Exogenous pulmonary surfactant for acute respiratory distress syndrome in adults (Table 1). Meng et al (2019): Effect of surfactant administration on outcomes of adult patients in acute respiratory distress syndrome (Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…Surfactant replacement therapy for adult ARDS have been the subject of several clinical trials and meta-analyses. Most recently, Meng et al (2019) reported a meta-analysis of randomized controlled trials related to surfactant administration in adult ARDS (RCTs: 11, patients: 3038, and surfactants: Exosurf/Venticute/Pneumasurf/HL-10/natural extracts) and listed the mechanism of action of pulmonary surfactant in ARDS as (1) maintenance of lower alveolar tension and stabilization of the alveolar volume, (2) promotion of gas exchange and distribution, (3) reduction of edema in alveoli and interstitium, (4) modulation of systemic inflammatory reactions, and (5) reduction of local mechanical forces (Meng et al, 2019). Davidson et al (2006) (RCTs: 06, patients: 1323, and surfactants: Exosurf/Survanta/Venticute), reported that exogenous surfactant intervention may improve oxygenation but may not have significant effect on the mortality outcome.…”

Section: Ards Pulmonary Surfactants and Ambroxolmentioning

confidence: 99%

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Co-aerosolized Pulmonary Surfactant and Ambroxol for COVID-19 ARDS Intervention: What Are We Waiting for?

Kumar

2020

Front. Bioeng. Biotechnol.

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After more than 225 days of the first reports of the novel coronavirus from China, COVID-19 pandemic is still on surge. The search for an effective and efficient therapeutic and pharmaceutical intervention is as important and urgent now as it was on Day 1. Majority of the efforts in this direction are toward finding small molecule interventions via repurposing or redirecting the therapeutic approaches. This hypothesis proposes a physical intervention approach directed toward rescuing the complex lung pathology observed in COVID-19 related acute respiratory distress syndrome (CARDS). The loss of content as well as the synthesis and turnover of the surfactant in ARDS has been termed as a "collateral damage." A synergistic, early stage, cost-effective, pharmaceutically viable, safe, and immediately available solution is hence required. The effectiveness of exogenous surfactant treatment in ARDS has been marred with several limitations as pointed out in various clinical trials and require revised protocols related to surfactant dose and mode of delivery. This hypothesis proposes aerosolized surfactant delivery taking the optimal dosing and coating costs into account along with co-delivery of ambroxol to provide synergistic benefits. Ambroxol is reported to have anti-inflammatory,-oxidant,-viral, and-bacterial activities and has a direct impact on the production and secretion of the surfactant from the alveolar Type 2 cells. If aerosolized, atomized, or nebulized in the form of ambroxol-loaded phospholipid nanovesicles at the early stages of ARDS, depleted surfactant levels may be reinstated and surfactant turnover can be initiated and maintained. The ability to deliver both the components in aerosolized-nebulized form may have a huge impact on alleviating the healthcare burden in low resource settings where the availability of ventilators is limited. In conclusion, the surfactant-ambroxol co-aerosolized intervention approach hypothesized here has implications reaching to clinical and pharmaceutical translation worldwide.

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Section: Resultsmentioning

confidence: 99%

Section: Ards Pulmonary Surfactants and Ambroxolmentioning

confidence: 99%

Co-aerosolized Pulmonary Surfactant and Ambroxol for COVID-19 ARDS Intervention: What Are We Waiting for?

Kumar

2020

Front. Bioeng. Biotechnol.

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“…A meta-analysis that included 11 RCTs with 3038 patients indicated that surfactant administration does not improve mortality but improves oxygenation in adult ARDS patients [ 57 ]. However, some data suggest that the transcription of the surfactant genes, production of active surfactant proteins, and their turnover might be deregulated in the lung of the COVID-19 patient [ 58 ].…”

Section: Exogenous Surfactant Therapymentioning

confidence: 99%

Pharmacological management of COVID-19 patients with ARDS (CARDS): A narrative review

Matera

Rogliani

Calzetta

et al. 2020

Respiratory Medicine

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Coronavirus disease 2019 (COVID-19) is highly infectious. It has been highlighted that if not expertly and individually managed with consideration of the vasocentric features, a COVID-19 patient with an acute respiratory distress syndrome (CARDS) may eventually develop multiorgan failure. Unfortunately, there is still no definite drug for CARDS that is capable of reducing either short-term or long-term mortality and no specific treatments for COVID-19 exist right now. In this narrative review, based on a selective literature search in EMBASE, MEDLINE, Scopus, The Cochrane Library, Web of Science, and Google Scholar and ClinicalTrials.gov , we have examined the emerging evidence on the possible treatment of CARDS. Although numerous pharmacologic therapies to improve clinical outcomes in CARDS have been studied also in clinical trials, none have shown efficacy and there is great uncertainty about their effectiveness. There is still no recommendation for the therapeutic use of any specific agent to treat CARDS because no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale trials. However, there exist a number of drugs that may be useful at least in some patients. The real challenge now is to link the right patient to the right treatment.

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“…Methaemoglobin was monitored during iNO administration. [23,24] In both L and H Type, the prone position was applied when P/F ≤ 150 for at least 16 hours with 4-8 hours of the supine position. [25] When patients did not respond to any of the previous medical approaches, and extracorporeal circulation was not applicable (especially for the limited resources available), off-label Curosurf surfactant was administered.…”

Section: Patients Selectionmentioning

confidence: 99%

Surfactant Therapy for COVID-19 Related ARDS: A Retrospective Case-Control Pilot Study.

Piva

Robert

Slee

et al. 2020

Preprint

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Background. COVID-19 causes acute respiratory distress syndrome (ARDS) and depletes the lungs of surfactant, leading to prolonged mechanical ventilation and death. The feasibility and safety of surfactant delivery in COVID-19 ARDS patients have not been established. Methods. We performed retrospective analyses of data from patients receiving off-label use of natural surfactant during the COVID-19 pandemic. Seven COVID-19 PCR positive ARDS patients received liquid Curosurf (720 mg) in 150 ml normal saline, divided into five 30 ml aliquots) and delivered via a bronchoscope into second-generation bronchi. Patients were matched with 14 comparable subjects receiving supportive care for ARDS during the same time period. Feasibility and safety were examined as well as the duration of mechanical ventilation and mortality. Results. Patients showed no evidence of acute decompensation following surfactant installation into minor bronchi and lung retention for up to 2 hours. Cox regression showed a reduction of 28-days mortality within the surfactant group, though not significant. The surfactant did not increase the duration of ventilation, and health care providers did not convert to COVID-19 positive. Conclusions. Surfactant delivery through bronchoscopy at a dose of 720 mg in 150 ml normal saline is feasible and safe for COVID-19 ARDS patients and health care providers during the pandemic. Surfactant administration does not cause acute decompensation, and it could be related to improved survival and reduction of mechanical ventilation duration. This study supports the future performance of randomized clinical trials evaluating the efficacy of meticulous surfactant delivery.

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Effect of surfactant administration on outcomes of adult patients in acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

Cited by 50 publications

References 21 publications

Co-aerosolized Pulmonary Surfactant and Ambroxol for COVID-19 ARDS Intervention: What Are We Waiting for?

Co-aerosolized Pulmonary Surfactant and Ambroxol for COVID-19 ARDS Intervention: What Are We Waiting for?

Pharmacological management of COVID-19 patients with ARDS (CARDS): A narrative review

Surfactant Therapy for COVID-19 Related ARDS: A Retrospective Case-Control Pilot Study.

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