{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T23:31:40Z","timestamp":1788823900972,"version":"build-2803163510"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Epinephrine is the only recommended vasopressor during neonatal cardiopulmonary resuscitation. However, there are concerns about the potential adverse effects of epinephrine, which might hamper efficacy during cardiopulmonary resuscitation. An alternative might be vasopressin, which has a preferable adverse effect profile, however, its optimal dose and route of administration is unknown. We aimed to compare the pharmacodynamics and pharmacokinetics of various vasopressin doses administered via intravenous (IV), intraosseous (IO), endotracheal (ETT), and intranasal (IN) routes in healthy neonatal piglets. Forty-four post-transitional piglets (1\u20133 days of age) were anesthetized, intubated via a tracheostomy, and randomized to receive vasopressin via intravenous (control), IO, ETT, or IN route. Heart rate (HR), arterial blood pressure, carotid blood flow, and cardiac function (e.g., stroke volume, ejection fraction) were continuously recorded throughout the experiment. Blood was collected prior to drug administration and throughout the observation period for pharmacodynamics and pharmacokinetic analysis. Significant changes in hemodynamic parameters were observed following IO administration of vasopressin while pharmacokinetic parameters were not different between IV and IO vasopressin. Administration of vasopressin via ETT or IN did not change hemodynamic parameters and had significantly lower maximum plasma concentrations and systemic absorption compared to piglets administered IV vasopressin (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). The IV and IO routes appear the most effective for vasopressin administration in neonatal piglets, while the ETT and IN routes appear unsuitable for vasopressin administration.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-74188-9","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T08:01:48Z","timestamp":1728028908000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacokinetic and pharmacodynamic evaluation of various vasopressin doses and routes of administration in a neonatal piglet model"],"prefix":"10.1038","volume":"14","author":[{"given":"Marwa","family":"Ramsie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Yin","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"O\u2019Reilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tze-Fun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg M.","family":"Schm\u00f6lzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,4]]},"reference":[{"key":"74188_CR1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.3390\/children6010004","volume":"6","author":"C Garcia-Hidalgo","year":"2019","unstructured":"Garcia-Hidalgo, C. & Schm\u00f6lzer, G. M. Chest compressions in the delivery room. Children6, 4 (2019).","journal-title":"Children"},{"key":"74188_CR2","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.resuscitation.2020.10.007","volume":"158","author":"C Halling","year":"2021","unstructured":"Halling, C. et al. Neonatal delivery room CPR: An analysis of the get with the Guidelines\u00ae\u2014Resuscitation Registry. Resuscitation158, 236\u2013242 (2021).","journal-title":"Resuscitation"},{"key":"74188_CR3","doi-asserted-by":"publisher","first-page":"S185","DOI":"10.1161\/CIR.0000000000000895","volume":"142","author":"MH Wyckoff","year":"2020","unstructured":"Wyckoff, M. H. et al. Neonatal life support: 2020 International consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation142, S185\u2013S221 (2020).","journal-title":"Circulation"},{"key":"74188_CR4","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1177\/1060028014537037","volume":"48","author":"DW Turner","year":"2014","unstructured":"Turner, D. W., Attridge, R. L. & Hughes, D. W. Vasopressin Associated with an increase in return of spontaneous circulation in Acidotic cardiopulmonary arrest patients. Ann. Pharmacother.48, 986\u2013991 (2014).","journal-title":"Ann Pharmacother"},{"key":"74188_CR5","doi-asserted-by":"publisher","first-page":"815857","DOI":"10.1155\/2012\/815857","volume":"2012","author":"A Papastylianou","year":"2012","unstructured":"Papastylianou, A. & Mentzelopoulos, S. Current pharmacological advances in the treatment of cardiac arrest. Emerg. Med. Int.2012, 815857 (2012).","journal-title":"Emerg. Med. Int."},{"key":"74188_CR6","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/BF00587170","volume":"347","author":"H Schaer","year":"1974","unstructured":"Schaer, H. Influence of respiratory and metabolic acidosis on epinephrine-inotropic effect in isolated guinea pig atria. Pflugers Arch.347, 297\u2013307 (1974).","journal-title":"Pflugers Arch."},{"key":"74188_CR7","doi-asserted-by":"publisher","first-page":"A56","DOI":"10.1097\/00003246-200412001-00209","volume":"32","author":"M Fries","year":"2004","unstructured":"Fries, M., Tang, W., Chang, Y.-T., Castillo, C. & Weil, M. H. Detrimental effects of epinephrine on microcirculatory blood flow in a porcine model of cardiac arrest: 212. Crit. Care Med.32, A56 (2004).","journal-title":"Crit. Care Med."},{"key":"74188_CR8","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1097\/CCM.0b013e31819cedc9","volume":"37","author":"G Ristagno","year":"2009","unstructured":"Ristagno, G. et al. Epinephrine reduces cerebral perfusion during cardiopulmonary resuscitation*. Crit. Care Med.37, 1408 (2009).","journal-title":"Crit. Care Med."},{"key":"74188_CR9","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1097\/00005344-199208000-00014","volume":"20","author":"AW Fox","year":"1992","unstructured":"Fox, A. W., May, R. E. & Mitch, W. E. Comparison of peptide and nonpeptide receptor-mediated responses in rat tail artery. J. Cardiovasc. Pharmacol.20, 282\u2013289 (1992).","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"74188_CR10","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1056\/NEJMoa025431","volume":"350","author":"V Wenzel","year":"2004","unstructured":"Wenzel, V. et al. A comparison of Vasopressin and Epinephrine for Out-of-hospital cardiopulmonary resuscitation. N. Engl. J. Med.350, 105\u2013113 (2004).","journal-title":"N. Engl. J. Med."},{"key":"74188_CR11","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/S0300-9572(01)00470-1","volume":"52","author":"K Mann","year":"2002","unstructured":"Mann, K., Berg, R. A. & Nadkarni, V. Beneficial effects of vasopressin in prolonged pediatric cardiac arrest: A case series. Resuscitation52, 149\u2013156 (2002).","journal-title":"Resuscitation"},{"key":"74188_CR12","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1097\/PCC.0b013e31819a36f2","volume":"10","author":"JM Duncan","year":"2009","unstructured":"Duncan, J. M. et al. Vasopressin for in-hospital pediatric cardiac arrest: Results from the American Heart Association National Registry of Cardiopulmonary Resuscitation*. Pediatr. Crit. Care Med.10, 191\u2013195 (2009).","journal-title":"Pediatr. Crit. Care Med."},{"key":"74188_CR13","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1097\/PCC.0b013e31822f1569","volume":"13","author":"TG Carroll","year":"2012","unstructured":"Carroll, T. G., Dimas, V. V. & Raymond, T. T. Vasopressin rescue for in-pediatric intensive care unit cardiopulmonary arrest refractory to initial epinephrine dosing: A prospective feasibility pilot trial. Pediatr. Crit. Care Med.13, 265\u2013272 (2012).","journal-title":"Pediatr Crit Care Med"},{"key":"74188_CR14","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1186\/s12917-020-02451-y","volume":"16","author":"N Percie du Sert","year":"2020","unstructured":"Percie du Sert, N. et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. BMC Vet. Res.16, 242 (2020).","journal-title":"BMC Veterinary Research"},{"key":"74188_CR15","doi-asserted-by":"publisher","first-page":"2495","DOI":"10.1161\/CIRCULATIONAHA.113.002289","volume":"128","author":"GM Schm\u00f6lzer","year":"2013","unstructured":"Schm\u00f6lzer, G. M. et al. Cardiopulmonary resuscitation with chest compressions during sustained inflations: A new technique of neonatal resuscitation that improves recovery and survival in a neonatal porcine model. Circulation128, 2495\u20132503 (2013).","journal-title":"Circulation"},{"key":"74188_CR16","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.resuscitation.2013.10.011","volume":"85","author":"GM Schm\u00f6lzer","year":"2014","unstructured":"Schm\u00f6lzer, G. M. et al. 3:1 compression to ventilation ratio versus continuous chest compression with asynchronous ventilation in a porcine model of neonatal resuscitation. Resuscitation85, 270\u2013275 (2014).","journal-title":"Resuscitation"},{"key":"74188_CR17","doi-asserted-by":"publisher","unstructured":"Cheung, P.-Y., Gill, R. S. & Bigam, D. L. A swine model of neonatal asphyxia. J. Vis. Exp. 3166. https:\/\/doi.org\/10.3791\/3166 (2011).","DOI":"10.3791\/3166"},{"key":"74188_CR18","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1038\/pr.2017.316","volume":"83","author":"M Wagner","year":"2018","unstructured":"Wagner, M. et al. Effects of epinephrine on hemodynamic changes during cardiopulmonary resuscitation in a neonatal piglet model. Pediatr. Res.83, 897\u2013903 (2018).","journal-title":"Pediatr. Res."},{"key":"74188_CR19","doi-asserted-by":"publisher","first-page":"525","DOI":"10.3389\/fphys.2019.00525","volume":"10","author":"W Shen","year":"2019","unstructured":"Shen, W., Xu, X., Lee, T.-F., Schm\u00f6lzer, G. & Cheung, P.-Y. The relationship between heart rate and left ventricular isovolumic relaxation during normoxia and hypoxia-asphyxia in newborn piglets. Front. Physiol.10, 525 (2019).","journal-title":"Front. Physiol."},{"key":"74188_CR20","doi-asserted-by":"publisher","first-page":"464","DOI":"10.3390\/children8060464","volume":"8","author":"D Sankaran","year":"2021","unstructured":"Sankaran, D. et al. Effect of a larger flush volume on bioavailability and efficacy of umbilical venous epinephrine during neonatal resuscitation in Ovine Asphyxial arrest. Children8, 464 (2021).","journal-title":"Children"},{"key":"74188_CR21","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1136\/archdischild-2020-321034","volume":"106","author":"D Sankaran","year":"2021","unstructured":"Sankaran, D. et al. Randomised trial of epinephrine dose and flush volume in term newborn lambs. Arch. Dis. Child Fetal. Neonatal. Ed.106, 578\u2013583 (2021).","journal-title":"Arch. Dis. Child Fetal Neonatal Ed."},{"key":"74188_CR22","doi-asserted-by":"publisher","first-page":"18011","DOI":"10.1038\/s41598-018-36332-0","volume":"8","author":"Y Jiang","year":"2018","unstructured":"Jiang, Y. & Platt, M. L. Oxytocin and vasopressin increase male-directed threats and vocalizations in female macaques. Sci. Rep.8, 18011 (2018).","journal-title":"Sci. Rep."},{"key":"74188_CR23","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1161\/01.RES.66.3.710","volume":"66","author":"WA Boyle","year":"1990","unstructured":"Boyle, W. A. & Segel, L. D. Attenuation of vasopressin-mediated coronary constriction and myocardial depression in the hypoxic heart. Circ. Res.66, 710\u2013721 (1990).","journal-title":"Circ. Res."},{"key":"74188_CR24","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1097\/00003246-199908000-00027","volume":"27","author":"V Wenzel","year":"1999","unstructured":"Wenzel, V. et al. Intraosseous vasopressin improves coronary perfusion pressure rapidly during cardiopulmonary resuscitation in pigs. Crit. Care Med.27, 1565\u20131569 (1999).","journal-title":"Crit. Care Med."},{"key":"74188_CR25","doi-asserted-by":"publisher","first-page":"237","DOI":"10.5055\/ajdm.2016.0245","volume":"11","author":"H Mark","year":"2016","unstructured":"Mark H. Wimmer, B. S. N. et al. The comparison of humeral intraosseous and intravenous administration of vasopressin on return of spontaneous circulation and pharmacokinetics in a hypovolemic cardiac arrest swine model. Am. J. Disaster Med.11, 237\u2013242 (2016).","journal-title":"Am. J. Disaster Med."},{"key":"74188_CR26","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1038\/s41390-023-02858-x","volume":"95","author":"M Ramsie","year":"2023","unstructured":"Ramsie, M., Cheung, P.-Y., Lee, T.-F., O\u2019Reilly, M. & Schm\u00f6lzer, G. M. Comparison of various vasopressin doses to epinephrine during cardiopulmonary resuscitation in asphyxiated neonatal piglets. Pediatr. Res.95, 1265\u20131272 (2023).","journal-title":"Pediatr. Res."},{"key":"74188_CR27","doi-asserted-by":"publisher","first-page":"S-71","DOI":"10.1089\/jamp.2010.0836","volume":"23","author":"JS Patton","year":"2010","unstructured":"Patton, J. S. et al. The particle has landed\u2014characterizing the fate of Inhaled Pharmaceuticals. J. Aerosol Med. Pulm. Drug Deliv.23, S-71 (2010).","journal-title":"J. Aerosol Med. Pulm. Drug Deliv."},{"key":"74188_CR28","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1016\/j.apsb.2021.05.015","volume":"11","author":"Y Guo","year":"2021","unstructured":"Guo, Y. et al. Pharmaceutical strategies to extend pulmonary exposure of inhaled medicines. Acta Pharm. Sin. B11, 2565\u20132584 (2021).","journal-title":"Acta Pharm. Sin. B"},{"key":"74188_CR29","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/0306-3623(86)90198-9","volume":"17","author":"H Vilhardt","year":"1986","unstructured":"Vilhardt, H. & Lundin, S. Biological effect and plasma concentrations of DDAVP after intranasal and peroral administration to humans. Gen. Pharmaco. Vasc. Syst.17, 481\u2013483 (1986).","journal-title":"Gen. Pharmacol. Vasc. Syst."},{"key":"74188_CR30","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/0002-9378(74)90587-0","volume":"120","author":"HE Cohn","year":"1974","unstructured":"Cohn, H. E., Sacks, E. J., Heymann, M. A. & Rudolph, A. M. Cardiovascular responses to hypoxemia and acidemia in fetal lambs. Am. J. Obstetr. Gynecol.120, 817\u2013824 (1974).","journal-title":"Am. J. Obstetr. Gynecol."},{"key":"74188_CR31","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1161\/01.RES.57.6.811","volume":"57","author":"AM Rudolph","year":"1985","unstructured":"Rudolph, A. M. Distribution and regulation of blood flow in the fetal and neonatal lamb. Circ. Res.57, 811\u2013821 (1985).","journal-title":"Circ Res"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-74188-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-74188-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-74188-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T08:06:16Z","timestamp":1728029176000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-74188-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,4]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["74188"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-74188-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-4637657\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,4]]},"assertion":[{"value":"25 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 October 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":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"23096"}}