The CHARTER-Ireland trial: can nebulised heparin reduce acute lung injury in patients with SARS-CoV-2 requiring advanced respiratory support in Ireland: a study protocol and statistical analysis plan for a randomised control trial.

BACKGROUND: COVID-19 pneumonia is associated with the development of acute respiratory distress syndrome (ARDS) displaying some typical histological features. These include diffuse alveolar damage with extensive pulmonary coagulation activation. This results in fibrin deposition in the microvasculature, leading to the formation of hyaline membranes in the air sacs. Well-conducted clinical trials have found that nebulised heparin limits pulmonary fibrin deposition, attenuates progression of ARDS, hastens recovery and is safe in non-COVID ARDS. Unfractionated heparin also inactivates the SARS-CoV-2 virus and prevents entry into mammalian cells. Nebulisation of heparin may therefore limit fibrin-mediated lung injury and inhibit pulmonary infection by SARS-CoV-2. Based on these findings, we designed the CHARTER-Ireland Study, a phase 1b/2a randomised controlled study of nebulised heparin in patients requiring advanced respiratory support for COVID-19 pneumonia. METHODS: This is a multi-centre, phase 1b/IIa, randomised, parallel-group, open-label study. The study will randomise 40 SARs-CoV-2-positive patients receiving advanced respiratory support in a critical care area. Randomisation will be via 1:1 allocation to usual care plus nebulised unfractionated heparin 6 hourly to day 10 while receiving advanced respiratory support or usual care only. The study aims to evaluate whether unfractionated heparin will decrease the procoagulant response associated with ARDS up to day 10. The study will also assess safety and tolerability of nebulised heparin as defined by number of severe adverse events; oxygen index and respiratory oxygenation index of intubated and unintubated, respectively; ventilatory ratio; and plasma concentration of interleukin (IL)-1ß, IL6, IL-8, IL-10 and soluble tumour necrosis factor receptor 1, C-reactive protein, procalcitonin, ferritin, fibrinogen and lactate dehydrogenase as well as the ratios of IL-1ß/IL-10 and IL-6/IL-10. These parameters will be assessed on days 1, 3, 5 and 10; time to separation from advanced respiratory support, time to discharge from the intensive care unit and number tracheostomised to day 28; and survival to days 28 and 60 and to hospital discharge, censored at day 60. Some clinical outcome data from our study will be included in the international meta-trials, CHARTER and INHALE-HEP. DISCUSSION: This trial aims to provide evidence of potential therapeutic benefit while establishing safety of nebulised heparin in the management of ARDS associated with SARs-CoV-2 infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT04511923 . Registered on 13 August 2020. Protocol version 8, 22/12/2021 Protocol identifier: NUIG-2020-003 EudraCT registration number: 2020-003349-12 9 October 2020.

The use of Lean Methodology to reduce personal protective equipment wastage in children undergoing congenital cardiac surgery, during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has compounded many existing healthcare delivery challenges including long waiting lists and cost containment. New challenges have arisen, such as demand on supply of personal protective equipment (PPE) and the implications of social distancing on staff, patients, and their families. Despite the pandemic, the need to deliver safe, urgent congenital cardiac surgery has remained. OBJECTIVE: To demonstrate how Lean methodology can improve PPE supply chain demand and reduce staff exposure to children with unknown SARS-CoV-2 status undergoing congenital cardiac surgery, during the COVID-19 pandemic. METHODS: We implemented the define, measure, analyze, improve, and control method (DMAIC) and Value Stream Maps to eliminate waste steps during testing for SARS-CoV-2 for children undergoing congenital cardiac surgery. RESULTS: Following a 3-week period of implementation of this new value stream map, we reduced PPE set usage from 13 to 1 per patient, resulting in an annual saving of over €36,000 and reducing single-use plastic waste by nearly 70 000 pieces per annum. We reduced numbers of staff exposed to patients with an unknown SARS-CoV-2 status from 13 to 1. CONCLUSION: The use of Lean methodology can reduce waste of PPE and plastic, resulting in cost savings, while reducing staff exposure when testing patients with congenital cardiac disease for SARS-CoV-2. By preventing admission of SARS-CoV-2-positive patients, we can reduce use of isolation beds and prevent cancellation of surgery, improving patient flow and departmental efficiency. Other departments in our institution are implementing similar admission pathways to allow surgical services to restart during the ongoing pandemic.