Richard Beale1, Jacqueline Beddoe Rosendo2, Christos Bergeles2, Anair Beverly3, Luigi Camporota1, Alfonso A Castrejón-Pita3, Douglas C Crockett4, John N Cronin5, Timothy Denison6, Sebastian East3, Chantal Edwardes7, Andrew D Farmery8, Filiberto Fele3, James Fisk6, Carla V Fuenteslópez6, Michael Garstka3, Paul Goulart3, Clare Heaysman2, Azad Hussain9, Prashant Jha2, Idris Kempf3, Adhithya Senthil Kumar3, Annika Möslein3, Andrew C J Orr3, Sebastien Ourselin2, David Salisbury6, Carlo Seneci2, Robert Staruch10, Harrison Steel3, Mark Thompson6, Minh C Tran11, Valentina Vitiello2, Miguel Xochicale2, Feibiao Zhou3, Federico Formenti12, Thomas Kirk13. 1. Centre for Human and Applied Physiological Sciences, King's College London, UK; Intensive Care Unit, Guy's and St Thomas' NHS Foundation Trust, London, UK. 2. School of Biomedical Engineering and Imaging Sciences, King's College London, UK. 3. Department of Engineering Science, University of Oxford, UK. 4. Nuffield Department of Clinical Neurosciences, University of Oxford, UK; Milton Keynes University Hospital NHS Foundation Trust, Milton Keynes, UK. 5. Centre for Human and Applied Physiological Sciences, King's College London, UK; Department of Anaesthesia, Guy's and St Thomas' NHS Foundation Trust, London, UK. 6. Department of Engineering Science, Institute of Biomedical Engineering, University of Oxford, UK. 7. Medical Sciences Division, University of Oxford, UK. 8. Nuffield Department of Clinical Neurosciences, University of Oxford, UK. 9. OxVent Ltd, Abingdon, UK. 10. Department of Engineering Science, Institute of Biomedical Engineering, University of Oxford, UK; Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK; The Academic Department of Military Surgery and Trauma, Birmingham, UK. 11. Department of Engineering Science, University of Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, UK. 12. Centre for Human and Applied Physiological Sciences, King's College London, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, UK; Department of Biomechanics, University of Nebraska Omaha, Omaha, NE, USA. Electronic address: federico.formenti@outlook.com. 13. Nuffield Department of Clinical Neurosciences, University of Oxford, UK; Department of Engineering Science, Institute of Biomedical Engineering, University of Oxford, UK. Electronic address: tomfrankkirk@gmail.com.
Abstract
BACKGROUND: The manufacturing of any standard mechanical ventilator cannot rapidly be upscaled to several thousand units per week, largely due to supply chain limitations. The aim of this study was to design, verify and perform a pre-clinical evaluation of a mechanical ventilator based on components not required for standard ventilators, and that met the specifications provided by the Medicines and Healthcare Products Regulatory Agency (MHRA) for rapidly-manufactured ventilator systems (RMVS). METHODS: The design utilises closed-loop negative feedback control, with real-time monitoring and alarms. Using a standard test lung, we determined the difference between delivered and target tidal volume (VT) at respiratory rates between 20 and 29 breaths per minute, and the ventilator's ability to deliver consistent VT during continuous operation for >14 days (RMVS specification). Additionally, four anaesthetised domestic pigs (3 male-1 female) were studied before and after lung injury to provide evidence of the ventilator's functionality, and ability to support spontaneous breathing. FINDINGS: Continuous operation lasted 23 days, when the greatest difference between delivered and target VT was 10% at inspiratory flow rates >825 mL/s. In the pre-clinical evaluation, the VT difference was -1 (-90 to 88) mL [mean (LoA)], and positive end-expiratory pressure (PEEP) difference was -2 (-8 to 4) cmH2O. VT delivery being triggered by pressures below PEEP demonstrated spontaneous ventilation support. INTERPRETATION: The mechanical ventilator presented meets the MHRA therapy standards for RMVS and, being based on largely available components, can be manufactured at scale. FUNDING: Work supported by Wellcome/EPSRC Centre for Medical Engineering,King's Together Fund and Oxford University.
BACKGROUND: The manufacturing of any standard mechanical ventilator cannot rapidly be upscaled to several thousand units per week, largely due to supply chain limitations. The aim of this study was to design, verify and perform a pre-clinical evaluation of a mechanical ventilator based on components not required for standard ventilators, and that met the specifications provided by the Medicines and Healthcare Products Regulatory Agency (MHRA) for rapidly-manufactured ventilator systems (RMVS). METHODS: The design utilises closed-loop negative feedback control, with real-time monitoring and alarms. Using a standard test lung, we determined the difference between delivered and target tidal volume (VT) at respiratory rates between 20 and 29 breaths per minute, and the ventilator's ability to deliver consistent VT during continuous operation for >14 days (RMVS specification). Additionally, four anaesthetised domestic pigs (3 male-1 female) were studied before and after lung injury to provide evidence of the ventilator's functionality, and ability to support spontaneous breathing. FINDINGS: Continuous operation lasted 23 days, when the greatest difference between delivered and target VT was 10% at inspiratory flow rates >825 mL/s. In the pre-clinical evaluation, the VT difference was -1 (-90 to 88) mL [mean (LoA)], and positive end-expiratory pressure (PEEP) difference was -2 (-8 to 4) cmH2O. VT delivery being triggered by pressures below PEEP demonstrated spontaneous ventilation support. INTERPRETATION: The mechanical ventilator presented meets the MHRA therapy standards for RMVS and, being based on largely available components, can be manufactured at scale. FUNDING: Work supported by Wellcome/EPSRC Centre for Medical Engineering,King's Together Fund and Oxford University.
Authors: Jan Buytaert; Paula Collins; Adam Abed Abud; Phil Allport; Antonio Pazos Álvarez; Kazuyoshi Akiba; Oscar Augusto de Aguiar Francisco; Aurelio Bay; Florian Bernard; Sophie Baron; Claudia Bertella; Josef X Brunner; Themis Bowcock; Martine Buytaert-De Jode; Wiktor Byczynski; Ricardo De Carvalho; Victor Coco; Ruth Collins; Nikola Dikic; Nicolas Dousse; Bruce Dowd; Kārlis Dreimanis; Raphael Dumps; Paolo Durante; Walid Fadel; Stephen Farry; Antonio Fernàndez Prieto; Arturo Fernàndez Tèllez; Gordon Flynn; Vinicius Franco Lima; Raymond Frei; Abraham Gallas Torreira; Tonatiuh García Chàvez; Evangelos Gazis; Roberto Guida; Karol Hennessy; Andre Henriques; David Hutchcroft; Stefan Ilic; Artūrs Ivanovs; Aleksandar Jevtic; Emigdio Jimenez Dominguez; Christian Joram; Kacper Kapusniak; Edgar Lemos Cid; Jana Lindner; Rolf Lindner; M Ivàn Martínez Hernàndez; Mirko Meboldt; Marko Milovanovic; Sylvain Mico; Johan Morant; Michel Morel; Georg Männel; Dónal Murray; Irina Nasteva; Niko Neufeld; Igor Neuhold; Francisco Pardo-Sobrino López; Eliseo Pèrez Trigo; Gonzalo Pichel Jallas; Edyta Pilorz; Lise Piquilloud; Xavier Pons; David Reiner; Hector David Règules Medel; Saul Rodríguez Ramírez; Mario Rodíguez Cahuantzi; Carl Roosens; Philipp Rostalski; Freek Sanders; Eric Saucet; Marianne Schmid Daners; Burkhard Schmidt; Patrick Schoettker; Rainer Schwemmer; Heinrich Schindler; Archana Sharma; Derick Sivakumaran; Christophe Sigaud; Vasilios Spitas; Nicola Steffen; Peter Svihra; Guillermo Tejeda Muñoz; Nikolaos Tachatos; Efstratios Tsolakis; Jan van Leemput; Laurence Vignaux; Francois Vasey; Hamish Woonton; Ken Wyllie Journal: R Soc Open Sci Date: 2022-03-16 Impact factor: 2.963