{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T22:26:40Z","timestamp":1781562400621,"version":"3.54.5"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T00:00:00Z","timestamp":1636934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","award":["18-580"],"award-info":[{"award-number":["18-580"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Heart Foundation","award":["PhD Scholarship"],"award-info":[{"award-number":["PhD Scholarship"]}]},{"DOI":"10.13039\/100008247","name":"University of Otago","doi-asserted-by":"crossref","award":["Health Sciences Career Development Fellowship"],"award-info":[{"award-number":["Health Sciences Career Development Fellowship"]}],"id":[{"id":"10.13039\/100008247","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Neonatal Trust Wellington","award":["PhD Scholarship"],"award-info":[{"award-number":["PhD Scholarship"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Non-invasive physiological monitoring can induce stress in laboratory animals. Sedation reduces the level of restraint required, thereby improving the validity of physiological signals measured. However, sedatives may alter physiological equilibrium introducing unintended bias and\/or, masking the experimental outcomes of interest. We aimed to investigate the cardiorespiratory effects of four short-acting sedatives in juvenile guinea pigs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Method<\/jats:title>\n<jats:p>12 healthy, 38 (26\u201346) day-old Dunkin Hartley guinea pigs were included in this blinded, randomised, crossover design study. Animals were sedated by intramuscular injection using pre-established minimum effective doses of either alfaxalone (5 mg\/kg), diazepam (5 mg\/kg), ketamine (30 mg\/kg), or midazolam (2 mg\/kg) administered in random order with a minimum washout period of 48 hours between agents. Sedative depth, a composite score comprised of five assessment criteria, was observed every 5-min from dosing until arousal. Physiological monitoring of cardiorespiratory status included measures of heart rate, blood pressure, respiratory rate, and peripheral microvascular perfusion.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Ketamine and alfaxalone were most effective in inducing stable sedation suitable for physiological monitoring, and diazepam less-so. Midazolam was unsuitable due to excessive hypersensitivity. All sedatives significantly increased heart rate above non-sedated control rates (<jats:italic>P<\/jats:italic>&lt;0.0001), without altering blood pressure or microvascular perfusion. Alfaxalone and ketamine reduced respiratory rate relative to their control condition (<jats:italic>P<\/jats:italic>&lt;0.0001, <jats:italic>P<\/jats:italic> = 0.05, respectively), but within normative ranges.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Ketamine and alfaxalone are the most effective sedatives for inducing short duration, stable sedation with minimal cardiorespiratory depression in guinea pigs, while diazepam is less-so. However, alfaxalone is the most appropriate sedative for longitudinal studies requiring multiple physiological timepoints.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0259559","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T18:33:11Z","timestamp":1637001191000},"page":"e0259559","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Differential effects of four intramuscular sedatives on cardiorespiratory stability in juvenile guinea pigs (Cavia porcellus)"],"prefix":"10.1371","volume":"16","author":[{"given":"Ryan P.","family":"Sixtus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cholawat","family":"Pacharinsak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clint 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experience","volume":"15","author":"CJ Green","year":"1981","journal-title":"Lab Anim"},{"issue":"3","key":"pone.0259559.ref023","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1647\/2011-037R.1","article-title":"Sedation and Physiologic Response to Manual Restraint After Intranasal Administration of Midazolam in Hispaniolan Amazon Parrots (Amazona ventralis)","volume":"26","author":"C Mans","year":"2012","journal-title":"Journal of Avian Medicine and Surgery"},{"key":"pone.0259559.ref024","article-title":"Schuster, Erhardt, Baumgartner. Cardiovascular effects of alfaxalone on hemodynamic function in pigs","author":"N Pfeiffer","year":"2013","journal-title":"Open Access Animal Physiology"},{"issue":"11","key":"pone.0259559.ref025","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.2460\/ajvr.69.11.1391","article-title":"Comparison of the anesthetic efficacy and cardiopulmonary effects of continuous rate infusions of alfaxalone-2-hydroxypropyl-beta-cyclodextrin and propofol in dogs","volume":"69","author":"B Ambrose","year":"2008","journal-title":"Am J Vet Res"},{"issue":"2","key":"pone.0259559.ref026","first-page":"393","article-title":"Midazolam Minimally Impairs Thermoregulatory Control","volume":"81","author":"A Kurz","year":"1995","journal-title":"Anesthesia and Analgesia"},{"issue":"1","key":"pone.0259559.ref027","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.clp.2008.09.007","article-title":"Drugs of choice for sedation and analgesia in the NICU","volume":"36","author":"RW Hall","year":"2009","journal-title":"Clinics in perinatology"},{"key":"pone.0259559.ref028","unstructured":"Pearson M, Best P, Patten B, editors. New therapeutic horizons: choosing a new drug for inducing anesthesia: propofol or alfaxalone. Proceedings of the American Academy of Veterinary Pharmacology and Therapeutics Thirteenth Biennial Symposium; 2003; Charlotte, NC."},{"key":"pone.0259559.ref029","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1053\/j.jepm.2012.09.011","article-title":"Therapeutic reviews: alfaxalone","volume":"21","author":"KL Jones","year":"2012","journal-title":"J Exotic Pet Med"},{"issue":"6","key":"pone.0259559.ref030","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1292\/jvms.18-0618","article-title":"Sedative and physiological effects of low-dose intramuscular alfaxalone in rabbits","volume":"81","author":"Y Ishikawa","year":"2019","journal-title":"J Vet Med Sci"},{"issue":"2","key":"pone.0259559.ref031","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1093\/toxsci\/kfh224","article-title":"Developmental neurotoxicity of ketamine: morphometric confirmation, exposure parameters, and multiple fluorescent labeling of apoptotic neurons","volume":"81","author":"AC Scallet","year":"2004","journal-title":"Toxicol Sci"},{"issue":"9","key":"pone.0259559.ref032","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/j.1751-0813.2012.00974.x","article-title":"Clinical evaluation of alfaxalone as an anaesthetic induction agent in dogs less than 12 weeks of age","volume":"90","author":"B O\u2019Hagan","year":"2012","journal-title":"Aust Vet J"},{"issue":"10","key":"pone.0259559.ref033","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/j.1751-0813.2012.00983.x","article-title":"Clinical evaluation of alfaxalone as an anaesthetic induction agent in cats less than 12 weeks of age","volume":"90","author":"BJ O\u2019Hagan","year":"2012","journal-title":"Aust Vet J"},{"issue":"3","key":"pone.0259559.ref034","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.anclin.2016.04.001","article-title":"General Anesthetics and Neurotoxicity: How Much Do We Know?","volume":"34","author":"V Jevtovic-Todorovic","year":"2016","journal-title":"Anesthesiol Clin"},{"issue":"6","key":"pone.0259559.ref035","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1111\/j.1365-2885.2008.00998.x","article-title":"The pharmacokinetics and pharmacodynamics of alfaxalone in cats after single and multiple intravenous administration of Alfaxan at clinical and supraclinical doses","volume":"31","author":"T Whittem","year":"2008","journal-title":"J Vet Pharmacol Ther"},{"key":"pone.0259559.ref036","first-page":"131","article-title":"Evaluation of a combination of alfaxalone with medetomidine and butorphanol for inducing surgical anesthesia in laboratory mice","volume":"64","author":"S Higuchi","year":"2016","journal-title":"Jpn J Vet Res"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0259559","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T18:33:38Z","timestamp":1637001218000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0259559"}},"subtitle":[],"editor":[{"given":"Dragan","family":"Hrncic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,11,15]]},"references-count":36,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0259559","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,15]]}}}