{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:10:33Z","timestamp":1790143833105,"version":"4.0.1"},"reference-count":41,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>The effects of concurrent ketamine and propofol (ketofol) constant rate infusion (CRI) were examined in six dogs. The K:P ratio was 1:2, with an initial CRI of 0.25\/0.5 mg\/kg\/min over ten minutes, followed by a 0.5 mg\/kg ketamine bolus for induction. During induction, a comprehensive EEG frequency spectrum from delta to gamma was observed, accompanied by subanesthetic-dose ketofol-induced behavioral excitation, including nystagmus, tongue flicking, salivation and active muscle activity. The dogs were maintained on three 15 min decremental doses of ketofol CRI (0.8\/1.6, 0.4\/0.8 and 0.2\/0.4 mg\/kg\/min). This phase featured a significant decrease in the Patient State Index, electromyographic activity and a shift to low beta waves (SEF95: 13\u201318 Hz). Additionally, profound antinociception to electric stimulation and a stable heart rate and blood pressure (MBP 81.5\u2013110 mmHg) were observed, as well as a merging of ketamine and propofol EEG characteristics during maintenance. In the recovery phase, a return to beta and gamma EEG patterns and excitement behavior occurred, accompanied by a significant reduction in antinociception, highlighting features of low doses of ketofol. This study reveals biphasic EEG dynamic changes, associated behaviors and robust antinociception and cardiovascular function, suggesting the utility of ketofol as a total intravenous anesthetic combination in dogs.<\/jats:p>","DOI":"10.3390\/ani13213391","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T07:24:04Z","timestamp":1698823444000},"page":"3391","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ketamine\u2013Propofol Coadministration for Induction and Infusion Maintenance in Anesthetized Dogs: Effects on Electroencephalography and Antinociception"],"prefix":"10.3390","volume":"13","author":[{"given":"Jeff C.","family":"Ko","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Murillo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann B.","family":"Weil","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2472-3556","authenticated-orcid":false,"given":"Matthias","family":"Kreuzer","sequence":"additional","affiliation":[{"name":"School of Medicine, Technical University of Munich, 80333 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George E.","family":"Moore","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1093\/bja\/52.8.731","article-title":"Animal studies of the anaesthetic activity of ICI 35 868","volume":"52","author":"Glen","year":"1980","journal-title":"Br. J. Anaesth."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1097\/00000542-198908000-00015","article-title":"Propofol: A new intravenous anesthetic","volume":"71","author":"Sebel","year":"1989","journal-title":"Anesthesiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.2174\/1381612043382846","article-title":"Propofol: Therapeutic Indications and Side-Effects","volume":"10","author":"Marik","year":"2004","journal-title":"Curr. Pharm. Des."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1007\/s40262-018-0672-3","article-title":"Clinical Pharmacokinetics and Pharmacodynamics of Propofol","volume":"57","author":"Sahinovic","year":"2018","journal-title":"Clin. Pharmacokinet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejphar.2009.01.007","article-title":"Propofol: A review of its non-anaesthetic effects","volume":"605","author":"Vasileiou","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"612","DOI":"10.3389\/fnhum.2016.00612","article-title":"Ketamine: 50 Years of Modulating the Mind","volume":"10","author":"Li","year":"2016","journal-title":"Front. Hum. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/00000542-198202000-00007","article-title":"Ketamine\u2014Its Pharmacology and Therapeutic Uses","volume":"56","author":"White","year":"1982","journal-title":"Anesthesiology"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Andolfatto, G., Abu-Laban, R.B., Zed, P.J., Staniforth, S.M., Stackhouse, S., Moadebi, S., and Willman, E. (2012). Ketamine-Propofol Combination (Ketofol) Versus Propofol Alone for Emergency Department Procedural Sedation and Analgesia: A Randomized Double-Blind Trial. Ann. Emerg. Med., 59.","DOI":"10.1016\/j.annemergmed.2012.01.017"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1097\/TA.0b013e318250cdb8","article-title":"Ketamine\/propofol admixture (ketofol) is associated with improved hemodynamics as an induction agent: A randomized, controlled trial","volume":"73","author":"Smischney","year":"2012","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.ajem.2015.12.074","article-title":"Ketamine-propofol combination (ketofol) vs propofol for procedural sedation and analgesia: Systematic review and meta-analysis","volume":"34","author":"Jalili","year":"2016","journal-title":"Am. J. Emerg. Med."},{"key":"ref_11","first-page":"278","article-title":"Corticoadrenal and Cardiorespiratory Responses to Administration of Propofol Combined with Dexmedetomidine or Ketamine in Rabbits","volume":"57","author":"Gonz","year":"2018","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.vaa.2023.02.002","article-title":"Ketamine\u2013propofol for total intravenous anaesthesia in rabbits: A comparison of premedication with acepromazine\u2013medetomidine, acepromazine\u2013midazolam or acepromazine\u2013morphine","volume":"50","author":"Hashemi","year":"2023","journal-title":"Vet. Anaesth. Analg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.1476-4431.2012.00722.x","article-title":"A comparison of 3 anesthetic protocols for 24 h of mechanical ventilation in cats","volume":"22","author":"Boudreau","year":"2012","journal-title":"J. Vet. Emerg. Crit. Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.2460\/javma.241.10.1307","article-title":"Evaluation of a ketamine-propofol drug combination with or without dexmedetomidine for intravenous anesthesia in cats undergoing ovariectomy","volume":"241","author":"Ravasio","year":"2012","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2460\/javma.253.1.101","article-title":"Recovery of horses from general anesthesia after induction with propofol and ketamine versus midazolam and ketamine","volume":"253","author":"Jarrett","year":"2018","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/vaa.12218","article-title":"A comparison of cardiopulmonary function, recovery quality, and total dosages required for induction and total intravenous anesthesia with propofol versus a propofol-ketamine combination in healthy Beagle dogs","volume":"42","author":"Kennedy","year":"2015","journal-title":"Vet. Anaesth. Analg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/j.1467-2995.2009.00500.x","article-title":"A comparison of the effects of two different doses of ketamine used for co-induction of anaesthesia with a target-controlled infusion of propofol in dogs","volume":"36","author":"Mair","year":"2009","journal-title":"Vet. Anaesth. Analg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"234","DOI":"10.17555\/jvc.2017.08.34.4.234","article-title":"Anesthetic Effect of Different Ratio of Ketamine and Propofol in Dogs","volume":"34","author":"Lee","year":"2017","journal-title":"J. Vet. Clin."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1136\/vr.146.20.571","article-title":"Comparative study of propofol or propofol and ketamine for the induction of anaesthesia in dogs","volume":"146","author":"Lerche","year":"2000","journal-title":"Vet. Rec."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/vaa.12171","article-title":"Comparison of propofol with ketofol, a propofol-ketamine admixture, for induction of anaesthesia in healthy dogs","volume":"41","author":"Leece","year":"2014","journal-title":"Vet. Anaesth. Analg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"231","DOI":"10.2460\/ajvr.75.3.231","article-title":"Comparison of the cardiorespiratory effects of a combination of ketamine and propofol, propofol alone, or a combination of ketamine and diazepam before and after induction of anesthesia in dogs sedated with acepromazine and oxymorphone","volume":"75","year":"2014","journal-title":"Am. J. Vet. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"215","DOI":"10.5455\/javar.2019.f335","article-title":"Evaluation of anesthesia produced by ketofol in acepromazine- or medetomidine-sedated dogs","volume":"6","author":"Wamaitha","year":"2019","journal-title":"J. Adv. Vet. Anim. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1136\/vr.160.3.85","article-title":"Total intravenous anaesthesia with propofol or propofol\/ketamine in spontaneously breathing dogs premedicated with medetomidine","volume":"160","author":"Nemec","year":"2007","journal-title":"Vet. Rec."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1258\/la.2012.011135","article-title":"Electroencephalogram-based anaesthetic depth monitoring in laboratory animals","volume":"46","author":"Silva","year":"2012","journal-title":"Lab. Anim."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1159\/000443175","article-title":"Pharmaco-EEG Studies in Animals: A History-Based Introduction to Contemporary Translational Applications","volume":"72","author":"Drinkenburg","year":"2015","journal-title":"Neuropsychobiology"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Murillo, C., Weil, A.B., Moore, G.E., Kreuzer, M., and Ko, J.C. (2023). Electroencephalographic and Cardiovascular Changes Associated with Propofol Constant Rate of Infusion Anesthesia in Young Healthy Dogs. Animals, 13.","DOI":"10.3390\/ani13040664"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1093\/bja\/aem175","article-title":"Ketamine increases the frequency of electroencephalographic bicoherence peak on the \u03b1 spindle area induced with propofol","volume":"99","author":"Hayashi","year":"2007","journal-title":"Br. J. Anaesth."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1034\/j.1399-6576.1999.430216.x","article-title":"The effect of ketamine on clinical endpoints of hypnosis and EEG variables during propofol infusion","volume":"43","author":"Sakai","year":"1999","journal-title":"Acta Anaesthesiol. Scand."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Murillo, C., Weng, H.-Y., Weil, A.B., Kreuzer, M., and Ko, J.C. (2022). Perioperative Brain Function Monitoring with Electroencephalography in Horses Anesthetized with Multimodal Balanced Anesthetic Protocol Subjected to Surgeries. Animals, 12.","DOI":"10.3390\/ani12202851"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.2460\/ajvr.73.11.1707","article-title":"Evaluation of anesthetic, analgesic, and cardiorespiratory effects in dogs after intramuscular administration of dexmedetomidine\u2013butorphanol\u2013tiletamine-zolazepam or dexmedetomidine-tramadol-ketamine drug combinations","volume":"73","author":"Krimins","year":"2012","journal-title":"Am. J. Vet. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1007\/s10877-020-00578-9","article-title":"Technical considerations when using the EEG export of the SEDLine Root device","volume":"35","author":"Jurth","year":"2021","journal-title":"J. Clin. Monit. Comput."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1097\/ALN.0000000000000841","article-title":"Clinical Electroencephalography for Anesthesiologists","volume":"123","author":"Purdon","year":"2015","journal-title":"Anesthesiology"},{"key":"ref_33","first-page":"E1142","article-title":"Electroencephalogram signatures of loss and recovery of consciousness from propofol","volume":"110","author":"Purdon","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1146\/annurev-neuro-060909-153200","article-title":"General Anesthesia and Altered States of Arousal: A Systems Neuroscience Analysis","volume":"34","author":"Brown","year":"2011","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nchembio0208-91","article-title":"Losing inhibition with ketamine","volume":"4","author":"Seamans","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11496","DOI":"10.1523\/JNEUROSCI.2213-07.2007","article-title":"NMDA Receptor Hypofunction Produces Opposite Effects on Prefrontal Cortex Interneurons and Pyramidal Neurons","volume":"27","author":"Homayoun","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1097\/ALN.0b013e3181ed09a2","article-title":"Taming the Ketamine Tiger","volume":"113","author":"Domino","year":"2010","journal-title":"Anesthesiology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1016\/j.clinph.2016.03.005","article-title":"Electroencephalogram signatures of ketamine anesthesia-induced unconsciousness","volume":"127","author":"Akeju","year":"2016","journal-title":"Clin. Neurophysiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3389\/fncom.2013.00022","article-title":"Ketamine, Propofol, and the EEG: A Neural Field Analysis of HCN1-Mediated Interactions","volume":"7","author":"Bojak","year":"2013","journal-title":"Front. Comput. Neurosci."},{"key":"ref_40","first-page":"1","article-title":"Analgesia, Sedation and Anesthesia: Making the Switch from Medetomidine to Dexmedetomidine","volume":"31","author":"Ko","year":"2009","journal-title":"Compend. Contin. Educ. Vet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.2460\/javma.2000.216.1578","article-title":"Sedative and cardiorespiratory effects of medetomidine, medetomidine-butorphanol, and medetomidine-ketamine in dogs","volume":"216","author":"Ko","year":"2000","journal-title":"J. Am. Vet. Med. Assoc."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/13\/21\/3391\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:15:29Z","timestamp":1760130929000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/13\/21\/3391"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,1]]},"references-count":41,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["ani13213391"],"URL":"https:\/\/doi.org\/10.3390\/ani13213391","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,1]]}}}