{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T04:28:28Z","timestamp":1780806508644,"version":"3.54.1"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Clin Monit Comput"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nitric oxide (NO), a selective pulmonary vasodilator, can be delivered via conventional ICU and anesthesia machine ventilators. Anesthesia machines are designed for rebreathing of circulating gases, reducing volatile anesthetic agent quantity used. Current cylinder- and ionizing-based NO delivery technologies use breathing circuit flow to determine NO delivery and do not account for recirculated gases; therefore, they cannot accurately dose NO at FGF below patient minute ventilation (MV). A novel, cassette-based NO delivery system (GENOSYL<jats:sup>\u00ae<\/jats:sup> DS, Vero Biotech Inc.) uses measured NO concentration in the breathing circuit as an input to an advanced feedback control algorithm, providing accurate NO delivery regardless of FGF and recirculation of gases. This study evaluated GENOSYL<jats:sup>\u00ae<\/jats:sup> DS accuracy with different anesthesia machines, ventilation parameters, FGFs, and volatile anesthetics. GENOSYL<jats:sup>\u00ae<\/jats:sup> DS was tested with GE Aisys and Dr\u00e4ger Fabius anesthesia machines to determine NO dose accuracy with FGF\u2009&lt;\u2009patient MV, and with a Getinge Flow-i anesthesia machine to determine NO dose accuracy when delivering various volatile anesthetic agents. Neonatal and adult mechanical ventilation parameters and circuits were used. GENOSYL\u00ae DS maintained accurate NO delivery with all three anesthesia machines, at low FGF with recirculation of gases, and with all volatile anesthetic agents at different concentrations. Measured NO<jats:sub>2<\/jats:sub> levels remained acceptable at\u2009\u2264\u20091\u00a0ppm with set NO dose\u2009\u2264\u200940\u00a0ppm. GENOSYL<jats:sup>\u00ae<\/jats:sup> DS, with its advanced feedback control algorithm, is the only NO delivery system capable of accurately dosing NO with anesthesia machines with rebreathing ventilation parameters (FGF\u2009&lt;\u2009MV) regardless of anesthetic agent.<\/jats:p>","DOI":"10.1007\/s10877-024-01143-4","type":"journal-article","created":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T12:01:28Z","timestamp":1717243288000},"page":"1155-1162","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A novel, cassette-based nitric oxide delivery system with an advanced feedback control algorithm accurately delivers nitric oxide via the anesthesia machine independent of fresh gas flow rate and volatile anesthetic agent"],"prefix":"10.1007","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4204-4450","authenticated-orcid":false,"given":"Mark D.","family":"Twite","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron W.","family":"Roebuck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie R.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,1]]},"reference":[{"key":"1143_CR1","doi-asserted-by":"publisher","first-page":"9265","DOI":"10.1073\/pnas.84.24.9265","volume":"84","author":"LJ Ignarro","year":"1987","unstructured":"Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA. 1987;84:9265\u20139. https:\/\/doi.org\/10.1073\/pnas.84.24.9265.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1143_CR2","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1097\/00000542-199303000-00005","volume":"78","author":"CG Frostell","year":"1993","unstructured":"Frostell CG, Blomqvist H, Hedenstierna G, Lundberg J, Zapol WM. Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation. Anesthesiology. 1993;78:427\u201335. https:\/\/doi.org\/10.1097\/00000542-199303000-00005.","journal-title":"Anesthesiology"},{"key":"1143_CR3","doi-asserted-by":"publisher","first-page":"CD000399","DOI":"10.1002\/14651858.CD000399.pub3","volume":"1","author":"KJ Barrington","year":"2017","unstructured":"Barrington KJ, Finer N, Pennaforte T, Altit G. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst Rev. 2017;1:CD000399. https:\/\/doi.org\/10.1002\/14651858.CD000399.pub3.","journal-title":"Cochrane Database Syst Rev"},{"key":"1143_CR4","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1056\/NEJM200002173420704","volume":"342","author":"RH Clark","year":"2000","unstructured":"Clark RH, Kueser TJ, Walker MW, et al. Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn: clinical inhaled nitric oxide research group. N Engl J Med. 2000;342:469\u201374. https:\/\/doi.org\/10.1056\/NEJM200002173420704.","journal-title":"N Engl J Med"},{"key":"1143_CR5","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1097\/00000539-200002000-00045","volume":"90","author":"P Ceccarelli","year":"2000","unstructured":"Ceccarelli P, Bigatello LM, Hess D, Kwo J, Melendez L, Hurford WE. Inhaled nitric oxide delivery by anesthesia machines. Anesth Analg. 2000;90:482\u20138. https:\/\/doi.org\/10.1097\/00000539-200002000-00045.","journal-title":"Anesth Analg"},{"key":"1143_CR6","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.4187\/respcare.08799","volume":"66","author":"PN Austin","year":"2021","unstructured":"Austin PN, Branson RD. Using anesthesia machines as critical care ventilators during the covid-19 pandemic. Respir Care. 2021;66:1184\u201395. https:\/\/doi.org\/10.4187\/respcare.08799.","journal-title":"Respir Care"},{"key":"1143_CR7","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1213\/ANE.0000000000005137","volume":"132","author":"JM Feldman","year":"2021","unstructured":"Feldman JM, Hendrickx J, Kennedy RR. Carbon dioxide absorption during inhalation anesthesia: a modern practice. Anesth Analg. 2021;132:993\u20131002. https:\/\/doi.org\/10.1213\/ANE.0000000000005137.","journal-title":"Anesth Analg"},{"key":"1143_CR8","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1093\/bja\/81.3.404","volume":"81","author":"L Lindberg","year":"1998","unstructured":"Lindberg L, Rydgren G. Evaluation of nitrogen dioxide scavengers during delivery of inhaled nitric oxide. Br J Anaesth. 1998;81:404\u20138. https:\/\/doi.org\/10.1093\/bja\/81.3.404.","journal-title":"Br J Anaesth"},{"key":"1143_CR9","first-page":"54","volume":"37","author":"JMLS Feldman","year":"2022","unstructured":"Feldman JMLS. Patient safety and low-flow anesthesia. APSF Newsletter. 2022;37:54\u20136.","journal-title":"APSF Newsletter"},{"key":"1143_CR10","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1007\/s001010070108","volume":"49","author":"J Baum","year":"2000","unstructured":"Baum J, Zuchner K, Holscher U, et al. climatization of anesthetic gases using different breathing hose systems. Anaesthesist. 2000;49:402\u201311. https:\/\/doi.org\/10.1007\/s001010070108.","journal-title":"Anaesthesist"},{"key":"1143_CR11","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1093\/bja\/63.4.453","volume":"63","author":"JP Bengtson","year":"1989","unstructured":"Bengtson JP, Bengtson A, Stenqvist O. The circle system as a humidifier. Br J Anaesth. 1989;63:453\u20137. https:\/\/doi.org\/10.1093\/bja\/63.4.453.","journal-title":"Br J Anaesth"},{"key":"1143_CR12","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1177\/0310057X9402200414","volume":"22","author":"Kleemann pp.","year":"1994","unstructured":"Kleemann pp. Humidity of anaesthetic gases with respect to low flow anaesthesia. Anaesth Intensive Care. 1994;22:396\u2013408. https:\/\/doi.org\/10.1177\/0310057X9402200414.","journal-title":"Anaesth Intensive Care"},{"key":"1143_CR13","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1097\/EJA.0b013e3283414cb7","volume":"28","author":"M Bilgi","year":"2011","unstructured":"Bilgi M, Goksu S, Mizrak A, et al. Comparison of the effects of low-flow and high-flow inhalational anaesthesia with nitrous oxide and desflurane on mucociliary activity and pulmonary function tests. Eur J Anaesthesiol. 2011;28:279\u201383. https:\/\/doi.org\/10.1097\/EJA.0b013e3283414cb7.","journal-title":"Eur J Anaesthesiol"},{"key":"1143_CR14","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1186\/s12871-020-01140-5","volume":"20","author":"Y Cui","year":"2020","unstructured":"Cui Y, Wang Y, Cao R, Li G, Deng L, Li J. The low fresh gas flow anesthesia and hypothermia in neonates undergoing digestive surgeries: a retrospective before-after study. BMC Anesthesiol. 2020;20:223. https:\/\/doi.org\/10.1186\/s12871-020-01140-5.","journal-title":"BMC Anesthesiol"},{"key":"1143_CR15","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1007\/s12630-012-9736-2","volume":"59","author":"M Brattwall","year":"2012","unstructured":"Brattwall M, Warren-Stomberg M, Hesselvik F, Jakobsson J. Brief review: theory and practice of minimal fresh gas flow anesthesia. Can J Anaesth. 2012;59:785\u201397. https:\/\/doi.org\/10.1007\/s12630-012-9736-2.","journal-title":"Can J Anaesth"},{"key":"1143_CR16","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1097\/ACO.0000000000000887","volume":"33","author":"GA Van Norman","year":"2020","unstructured":"Van Norman GA, Jackson S. The anesthesiologist and global climate change: An ethical obligation to act. Curr Opin Anaesthesiol. 2020;33:577\u201383. https:\/\/doi.org\/10.1097\/ACO.0000000000000887.","journal-title":"Curr Opin Anaesthesiol"},{"key":"1143_CR17","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1023\/a:1009971712989","volume":"15","author":"E Sieffert","year":"1999","unstructured":"Sieffert E, Ducros L, Losser MR, Payen DM. Inhaled nitric oxide fraction is influenced by both the site and the mode of administration. J Clin Monit Comput. 1999;15:509\u201317. https:\/\/doi.org\/10.1023\/a:1009971712989.","journal-title":"J Clin Monit Comput"},{"key":"1143_CR18","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/cc118","volume":"2","author":"L Puybasset","year":"1998","unstructured":"Puybasset L, Rouby JJ. Pulmonary uptake and modes of administration of inhaled nitric oxide in mechanically-ventilated patients. Crit Care. 1998;2:9\u201317. https:\/\/doi.org\/10.1186\/cc118.","journal-title":"Crit Care"},{"key":"1143_CR19","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.4187\/respcare.08856","volume":"66","author":"S Gianni","year":"2021","unstructured":"Gianni S, Carroll RW, Kacmarek RM, Berra L. Inhaled nitric oxide delivery systems for mechanically ventilated and nonintubated patients: a review. Respir Care. 2021;66:1021\u20138. https:\/\/doi.org\/10.4187\/respcare.08856.","journal-title":"Respir Care"},{"key":"1143_CR20","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1111\/j.1460-9592.2009.02948.x","volume":"19","author":"T Uejima","year":"2009","unstructured":"Uejima T, Urban R, Verhagen J. Sevoflurane interferes with inhaled nitric oxide (ino) delivery from the inomax ds machine. Paediatr Anaesth. 2009;19:404. https:\/\/doi.org\/10.1111\/j.1460-9592.2009.02948.x.","journal-title":"Paediatr Anaesth"},{"key":"1143_CR21","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.niox.2014.02.001","volume":"37","author":"MA Lovich","year":"2014","unstructured":"Lovich MA, Fine DH, Denton RJ, et al. Generation of purified nitric oxide from liquid n2o4 for the treatment of pulmonary hypertension in hypoxemic swine. Nitric Oxide. 2014;37:66\u201372. https:\/\/doi.org\/10.1016\/j.niox.2014.02.001.","journal-title":"Nitric Oxide"},{"key":"1143_CR22","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.niox.2016.06.001","volume":"58","author":"MJ Pezone","year":"2016","unstructured":"Pezone MJ, Wakim MG, Denton RJ, et al. Nitrogen dioxide reducing ascorbic acid technologies in the ventilator circuit leads to uniform no concentration during inspiration. Nitric Oxide. 2016;58:42\u201350. https:\/\/doi.org\/10.1016\/j.niox.2016.06.001.","journal-title":"Nitric Oxide"},{"key":"1143_CR23","unstructured":"US Department of Health and Human Services, Food and Drug Administration, Center for Devices and Radiological Health. Guidance Document for Premarket Notification Submissions for Nitric Oxide Delivery Apparatus, Nitric Oxide Analyzer and Nitrogen Dioxide Analyzer. January 24, 2000. Accessed November 7, 2022. https:\/\/www.fda.gov\/media\/71766\/download."},{"key":"1143_CR24","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1097\/00000539-200110000-00029","volume":"93","author":"EI Eger 2nd","year":"2001","unstructured":"Eger EI 2nd. Age, minimum alveolar anesthetic concentration, and minimum alveolar anesthetic concentration-awake. Anesth Analg. 2001;93:947\u201353. https:\/\/doi.org\/10.1097\/00000539-200110000-00029.","journal-title":"Anesth Analg"},{"key":"1143_CR25","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1213\/ANE.0000000000005504","volume":"133","author":"S Varughese","year":"2021","unstructured":"Varughese S, Ahmed R. Environmental and occupational considerations of anesthesia: a narrative review and update. Anesth Analg. 2021;133:826\u201335. https:\/\/doi.org\/10.1213\/ANE.0000000000005504.","journal-title":"Anesth Analg"},{"key":"1143_CR26","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1111\/pan.13994","volume":"30","author":"TA Glenski","year":"2020","unstructured":"Glenski TA, Levine L. The implementation of low-flow anesthesia at a tertiary pediatric center: a quality improvement initiative. Paediatr Anaesth. 2020;30:1139\u201345. https:\/\/doi.org\/10.1111\/pan.13994.","journal-title":"Paediatr Anaesth"},{"key":"1143_CR27","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1093\/bja\/aes464","volume":"110","author":"S Singaravelu","year":"2013","unstructured":"Singaravelu S, Barclay P. Automated control of end-tidal inhalation anaesthetic concentration using the ge aisys carestation. Br J Anaesth. 2013;110:561\u20136. https:\/\/doi.org\/10.1093\/bja\/aes464.","journal-title":"Br J Anaesth"},{"key":"1143_CR28","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/s10877-015-9723-6","volume":"30","author":"R Carette","year":"2016","unstructured":"Carette R, De Wolf AM, Hendrickx JF. Automated gas control with the maquet flow-i. J Clin Monit Comput. 2016;30:341\u20136. https:\/\/doi.org\/10.1007\/s10877-015-9723-6.","journal-title":"J Clin Monit Comput"},{"key":"1143_CR29","doi-asserted-by":"publisher","first-page":"34","DOI":"10.5603\/AIT.2017.0008","volume":"49","author":"T Skalec","year":"2017","unstructured":"Skalec T, Gorecka-Dolny A, Zielinski S, Gibek M, Strozecki L, Kubler A. Comparison of anaesthetic gas consumption and stability of anaesthesia using automatic and manual control over the course of anaesthesia. Anaesthesiol Intensive Ther. 2017;49:34\u20139. https:\/\/doi.org\/10.5603\/AIT.2017.0008.","journal-title":"Anaesthesiol Intensive Ther"},{"key":"1143_CR30","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1111\/aas.12961","volume":"61","author":"AJ Wetz","year":"2017","unstructured":"Wetz AJ, Mueller MM, Walliser K, et al. End-tidal control vs. Manually controlled minimal-flow anesthesia: a prospective comparative trial. Acta Anaesthesiol Scand. 2017;61:1262\u20139. https:\/\/doi.org\/10.1111\/aas.12961.","journal-title":"Acta Anaesthesiol Scand"},{"key":"1143_CR31","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/s10877-013-9516-8","volume":"28","author":"U Lucangelo","year":"2014","unstructured":"Lucangelo U, Garufi G, Marras E, et al. End-tidal versus manually-controlled low-flow anaesthesia. J Clin Monit Comput. 2014;28:117\u201321. https:\/\/doi.org\/10.1007\/s10877-013-9516-8.","journal-title":"J Clin Monit Comput"},{"key":"1143_CR32","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1213\/ANE.0000000000002688","volume":"127","author":"JFA Hendrickx","year":"2018","unstructured":"Hendrickx JFA, De Wolf AM. The anesthesia workstation: Quo Vadis? Anesth Analg. 2018;127:671\u20135. https:\/\/doi.org\/10.1213\/ANE.0000000000002688.","journal-title":"Anesth Analg"}],"container-title":["Journal of Clinical Monitoring and Computing"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10877-024-01143-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10877-024-01143-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10877-024-01143-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T09:06:35Z","timestamp":1727341595000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10877-024-01143-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,1]]},"references-count":32,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["1143"],"URL":"https:\/\/doi.org\/10.1007\/s10877-024-01143-4","relation":{},"ISSN":["1387-1307","1573-2614"],"issn-type":[{"value":"1387-1307","type":"print"},{"value":"1573-2614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,1]]},"assertion":[{"value":"17 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 June 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statement on Human Rights"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statement on Welfare of Animals"}},{"value":"Mark D. Twite reports consulting fees from Vero Biotech Inc. Aaron W. Roebuck reports employment with and stock options in Vero Biotech Inc. Stephanie R. Anderson reports previous employment with Vero Biotech Inc.  Patents are planned for the GENOSYL<sup>\u00ae<\/sup> Delivery System by Vero Biotech Inc. A Dr\u00e4ger Fabius GS Premium anesthesia machine was also provided by Dr\u00e4ger. The authors declare that the work described is original research that has not been published previously. All authors have approved the manuscript.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}]}}