{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:47:19Z","timestamp":1760060839702,"version":"build-2065373602"},"reference-count":27,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Heart and Stroke Foundation of Canada","award":["G-22-0031980"],"award-info":[{"award-number":["G-22-0031980"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Neonatal resuscitation guidelines recommend the use of the vasopressor epinephrine during neonatal cardiopulmonary resuscitation (CPR); however, vasopressin may be a potential alternative. Successful neonatal CPR requires rapid vasopressor administration, but the current guideline-recommended routes can take several minutes to establish and require substantial skill and\/or training. The intramuscular (IM) route provides rapid drug administration and does not require special skills, training, or equipment. Objective: We aimed to compare two doses of IM vasopressin to intravenous (IV) vasopressin in a healthy neonatal piglet model to examine the hemodynamic and pharmacokinetic effects. Methods: Fifteen neonatal piglets (n = 5\/group; 1\u20133 days of age) were anesthetized, intubated via a tracheostomy, and randomized to 4 IU\/kg IM vasopressin, 8 IU\/kg IM vasopressin, or 0.4 IU\/kg IV vasopressin. Various hemodynamic and cardiac function parameters were continuously recorded throughout the experiment. Blood was collected prior to drug administration and throughout the experiment for pharmacokinetic and pharmacodynamic analysis. Results: The 4 IU\/kg IM vasopressin dose was ineffective in producing systemic changes in hemodynamics or cardiac function as it was poorly absorbed. The 8 IU\/kg IM vasopressin dose had comparable results to IV vasopressin and was rapidly distributed to systemic circulation. Conclusions: The higher IM vasopressin dose of 8 IU\/kg is effective in increasing systolic and diastolic blood pressure.<\/jats:p>","DOI":"10.3390\/children12101284","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:39:42Z","timestamp":1758710382000},"page":"1284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Intramuscular Vasopressin on Pharmacokinetics and Pharmacodynamics in Healthy Neonatal Piglets: A Dose\u2013Response Study"],"prefix":"10.3390","volume":"12","author":[{"given":"Marwa","family":"Ramsie","sequence":"first","affiliation":[{"name":"Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, 10240 Kingsway Avenue NW, Edmonton, AB T5H 3V9, Canada"},{"name":"Department of Pediatrics, University of Alberta, Edmonton, AB T5H 3V9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7141-1523","authenticated-orcid":false,"given":"Po-Yin","family":"Cheung","sequence":"additional","affiliation":[{"name":"Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, 10240 Kingsway Avenue NW, Edmonton, AB T5H 3V9, Canada"},{"name":"Department of Pediatrics, University of Alberta, Edmonton, AB T5H 3V9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raza","family":"Hyderi","sequence":"additional","affiliation":[{"name":"Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, 10240 Kingsway Avenue NW, Edmonton, AB T5H 3V9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shrieya","family":"Praveen","sequence":"additional","affiliation":[{"name":"Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, 10240 Kingsway Avenue NW, Edmonton, AB T5H 3V9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tze-Fun","family":"Lee","sequence":"additional","affiliation":[{"name":"Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, 10240 Kingsway Avenue NW, Edmonton, AB T5H 3V9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"O\u2019Reilly","sequence":"additional","affiliation":[{"name":"Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, 10240 Kingsway Avenue NW, Edmonton, AB T5H 3V9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9798-2415","authenticated-orcid":false,"given":"Georg M.","family":"Schm\u00f6lzer","sequence":"additional","affiliation":[{"name":"Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, 10240 Kingsway Avenue NW, Edmonton, AB T5H 3V9, Canada"},{"name":"Department of Pediatrics, University of Alberta, Edmonton, AB T5H 3V9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Garcia-Hidalgo, C., and Schm\u00f6lzer, G.M. (2019). Chest Compressions in the Delivery Room. Children, 6.","DOI":"10.3389\/fped.2018.00400"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.resuscitation.2021.05.029","article-title":"Epidemiology and Outcomes of Infants after Cardiopulmonary Resuscitation in the Neonatal or Pediatric Intensive Care Unit from a National Registry","volume":"165","author":"Handley","year":"2021","journal-title":"Resuscitation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S185","DOI":"10.1161\/CIR.0000000000000895","article-title":"Neonatal Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations","volume":"142","author":"Wyckoff","year":"2020","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S543","DOI":"10.1161\/CIR.0000000000000267","article-title":"Part 13: Neonatal Resuscitation","volume":"132","author":"Wyckoff","year":"2015","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.anai.2023.09.015","article-title":"Anaphylaxis: A 2023 Practice Parameter Update","volume":"132","author":"Golden","year":"2024","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1056\/NEJMoa025431","article-title":"A Comparison of Vasopressin and Epinephrine for Out-of-Hospital Cardiopulmonary Resuscitation","volume":"350","author":"Wenzel","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0300-9572(01)00470-1","article-title":"Beneficial Effects of Vasopressin in Prolonged Pediatric Cardiac Arrest: A Case Series","volume":"52","author":"Mann","year":"2002","journal-title":"Resuscitation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1097\/01.CCM.0000259377.64733.4C","article-title":"Beneficial Effects of Terlipressin in Prolonged Pediatric Cardiopulmonary Resuscitation: A Case Series","volume":"35","author":"Matok","year":"2007","journal-title":"Crit. Care Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/pr.2014.38","article-title":"Vasopressin Improves Survival Compared with Epinephrine in a Neonatal Piglet Model of Asphyxial Cardiac Arrest","volume":"75","author":"McNamara","year":"2014","journal-title":"Pediatr. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1038\/s41390-023-02858-x","article-title":"Comparison of Various Vasopressin Doses to Epinephrine during Cardiopulmonary Resuscitation in Asphyxiated Neonatal Piglets","volume":"95","author":"Ramsie","year":"2023","journal-title":"Pediatr. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"100427","DOI":"10.1016\/j.resplu.2023.100427","article-title":"Vasopressin versus Epinephrine during Neonatal Cardiopulmonary Resuscitation of Asphyxiated Post-Transitional Piglets","volume":"15","author":"Lee","year":"2023","journal-title":"Resusc. Plus"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1097\/FJC.0000000000000092","article-title":"Cardiac Effects of Vasopressin","volume":"64","author":"Pelletier","year":"2014","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Percie du Sert, N., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE Guidelines 2.0: Updated Guidelines for Reporting Animal Research. BMC Vet. Res., 16.","DOI":"10.1186\/s12917-020-02451-y"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ramsie, M., Cheung, P.-Y., O\u2019Reilly, M., Lee, T.-F., and Schm\u00f6lzer, G.M. (2024). Pharmacokinetic and Pharmacodynamic Evaluation of Various Vasopressin Doses and Routes of Administration in a Neonatal Piglet Model. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-74188-9"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1161\/CIRCULATIONAHA.113.002289","article-title":"Cardiopulmonary Resuscitation with Chest Compressions during Sustained Inflations: A New Technique of Neonatal Resuscitation That Improves Recovery and Survival in a Neonatal Porcine Model","volume":"128","author":"Labossiere","year":"2013","journal-title":"Circulation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.resuscitation.2013.10.011","article-title":"3:1 Compression to Ventilation Ratio versus Continuous Chest Compression with Asynchronous Ventilation in a Porcine Model of Neonatal Resuscitation","volume":"85","author":"Labossiere","year":"2014","journal-title":"Resuscitation"},{"key":"ref_17","first-page":"3166","article-title":"A Swine Model of Neonatal Asphyxia","volume":"56","author":"Cheung","year":"2011","journal-title":"J. Vis. Exp."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/pr.2017.316","article-title":"Effects of Epinephrine on Hemodynamic Changes during Cardiopulmonary Resuscitation in a Neonatal Piglet Model","volume":"83","author":"Wagner","year":"2018","journal-title":"Pediatr. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Shen, W., Xu, X., Lee, T.-F., Schm\u00f6lzer, G., and Cheung, P.-Y. (2019). The Relationship Between Heart Rate and Left Ventricular Isovolumic Relaxation During Normoxia and Hypoxia-Asphyxia in Newborn Piglets. Front. Physiol., 10.","DOI":"10.3389\/fphys.2019.00525"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1161\/CIRCULATIONAHA.117.033067","article-title":"Time to Epinephrine Administration and Survival From Nonshockable Out-of-Hospital Cardiac Arrest Among Children and Adults","volume":"137","author":"Hansen","year":"2018","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1210\/endo-107-6-1899","article-title":"Effects of Increases in Plasma Vasopressin Concentration on Plasma Renin Activity, Blood Pressure, Heart Rate, and Plasma Corticosteroid Concentration in Conscious Dogs","volume":"107","author":"Malayan","year":"1980","journal-title":"Endocrinology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1161\/01.RES.47.3.346","article-title":"Hemodynamic Effects of Exogenous and Endogenous Vasopressin at Low Plasma Concentrations in Conscious Dogs","volume":"47","author":"Montani","year":"1980","journal-title":"Circ. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.xjon.2022.01.008","article-title":"The Acute Influence of Vasopressin on Hemodynamic Status and Tissue Oxygenation Following the Norwood Procedure","volume":"9","author":"Bronicki","year":"2022","journal-title":"JTCVS Open"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0022-3565(25)27674-1","article-title":"Studies on the Cardiovascular Effects of Synthetic Vasopressin","volume":"157","author":"Nakano","year":"1967","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1161\/01.RES.66.3.710","article-title":"Attenuation of Vasopressin-Mediated Coronary Constriction and Myocardial Depression in the Hypoxic Heart","volume":"66","author":"Boyle","year":"1990","journal-title":"Circ. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"eabd5758","DOI":"10.1126\/scitranslmed.abd5758","article-title":"Importance of the Pig as a Human Biomedical Model","volume":"13","author":"Lunney","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ayuso, M., Buyssens, L., Stroe, M., Valenzuela, A., Allegaert, K., Smits, A., Annaert, P., Mulder, A., Carpentier, S., and Van Ginneken, C. (2021). The Neonatal and Juvenile Pig in Pediatric Drug Discovery and Development. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010044"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/10\/1284\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:48:46Z","timestamp":1760035726000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/10\/1284"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,24]]},"references-count":27,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["children12101284"],"URL":"https:\/\/doi.org\/10.3390\/children12101284","relation":{},"ISSN":["2227-9067"],"issn-type":[{"type":"electronic","value":"2227-9067"}],"subject":[],"published":{"date-parts":[[2025,9,24]]}}}