<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Russian Journal of Pediatric Surgery, Anesthesia and Intensive Care</journal-id><journal-title-group><journal-title xml:lang="en">Russian Journal of Pediatric Surgery, Anesthesia and Intensive Care</journal-title><trans-title-group xml:lang="ru"><trans-title>Российский вестник детской хирургии, анестезиологии и реаниматологии</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2219-4061</issn><issn publication-format="electronic">2587-6554</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">1947</article-id><article-id pub-id-type="doi">10.17816/psaic1947</article-id><article-id pub-id-type="edn">BLYWQD</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Original Study Articles</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Оригинальные исследования</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Subanesthetic doses of ketamine infusion for neuroprotection in the postoperative period of pediatric cardiac surgery: a prospective randomized study</article-title><trans-title-group xml:lang="ru"><trans-title>Инфузия кетамина в субанестетических дозах с целью нейропротекции в послеоперационном периоде кардиохирургических операций у детей: проспективное рандомизированное исследование</trans-title></trans-title-group><trans-title-group xml:lang="zh"><trans-title>亚麻醉剂量氯胺酮持续输注用于儿童心脏外科术后神经保护：一项前瞻性随机研究</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3899-1642</contrib-id><contrib-id contrib-id-type="spin">7708-9960</contrib-id><name-alternatives><name xml:lang="en"><surname>Ivkin</surname><given-names>Artem A.</given-names></name><name xml:lang="ru"><surname>Ивкин</surname><given-names>Артём Александрович</given-names></name><name xml:lang="zh"><surname>Ivkin</surname><given-names>Artem A.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci. (Medicine)</p></bio><bio xml:lang="ru"><p>канд. мед. наук</p></bio><bio xml:lang="zh"><p>MD, Cand. Sci. (Medicine)</p></bio><email>ivkiaa@kemcardio.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8370-3083</contrib-id><contrib-id contrib-id-type="spin">2316-2287</contrib-id><name-alternatives><name xml:lang="en"><surname>Grigoriev</surname><given-names>Evgeny V.</given-names></name><name xml:lang="ru"><surname>Григорьев</surname><given-names>Евгений Валерьевич</given-names></name><name xml:lang="zh"><surname>Grigoriev</surname><given-names>Evgeny V.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Dr. Sci. (Medicine)</p></bio><bio xml:lang="ru"><p>д-р мед. наук</p></bio><bio xml:lang="zh"><p>MD, Dr. Sci. (Medicine)</p></bio><email>grigorievev@hotmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0246-3466</contrib-id><contrib-id contrib-id-type="spin">9805-5758</contrib-id><name-alternatives><name xml:lang="en"><surname>Mikhailova</surname><given-names>Alena A.</given-names></name><name xml:lang="ru"><surname>Михайлова</surname><given-names>Алена Александровна</given-names></name><name xml:lang="zh"><surname>Mikhailova</surname><given-names>Alena A.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>carfagenez@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4467-8732</contrib-id><contrib-id contrib-id-type="spin">3195-7252</contrib-id><name-alternatives><name xml:lang="en"><surname>Sinitskaya</surname><given-names>Anna V.</given-names></name><name xml:lang="ru"><surname>Синицкая</surname><given-names>Анна Викторовна</given-names></name><name xml:lang="zh"><surname>Sinitskaya</surname><given-names>Anna V.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>annacepokina@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Research Institute of Complex Problems of Cardiovascular Diseases</institution></aff><aff><institution xml:lang="ru">Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний</institution></aff><aff><institution xml:lang="zh">Research Institute of Complex Problems of Cardiovascular Diseases</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2025-12-15" publication-format="electronic"><day>15</day><month>12</month><year>2025</year></pub-date><pub-date date-type="pub" iso-8601-date="2025-12-30" publication-format="electronic"><day>30</day><month>12</month><year>2025</year></pub-date><volume>15</volume><issue>4</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><issue-title xml:lang="zh"/><fpage>469</fpage><lpage>482</lpage><history><date date-type="received" iso-8601-date="2025-08-08"><day>08</day><month>08</month><year>2025</year></date><date date-type="accepted" iso-8601-date="2025-11-26"><day>26</day><month>11</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2025, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2025, Эко-Вектор</copyright-statement><copyright-statement xml:lang="zh">Copyright ©; 2025,</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc-nd/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://rps-journal.ru/jour/article/view/1947">https://rps-journal.ru/jour/article/view/1947</self-uri><abstract xml:lang="en"><p><bold>BACKGROUND:</bold> Children with congenital heart disease are at high risk of cerebral injury in the postoperative period owning to age-related anatomical and physiological characteristics and a wide range of cardiac surgery–related factors detrimental to the brain. With its neuroprotective properties, ketamine may reduce these risks. However, its optimal dosing and effectiveness in pediatric patients require further investigation.</p> <p><bold>AIM:</bold> This study aimed to evaluate the effect of subanesthetic doses of ketamine on the brain in pediatric patients during the postoperative period after cardiac surgery with cardiopulmonary bypass.</p> <p><bold>METHODS:</bold> A prospective randomized study included 91 patients (aged 1–60 months). Patients were divided into a control group and three intervention groups receiving ketamine at 0.1, 0.2, or 0.3 mg/(kg · h), respectively, for 16 hours after surgery. Serum biomarkers of brain injury (S-100β, NSE, GFAP, occludin, and claudin-1), postoperative delirium (assessed using the CAPD scale), and adverse effects were evaluated.</p> <p><bold>RESULTS: </bold>No differences in intraoperative or postoperative parameters were observed between groups. At 16 hours after surgery, S-100β and NSE levels were significantly lower in intervention groups 2 and 3. CAPD scores were also statistically lower in all ketamine infusion groups.</p> <p><bold>CONCLUSION:</bold> In pediatric patients undergoing cardiac surgery, ketamine infusion at doses of 0.2–0.3 mg/(kg · h) resulted in lower levels of brain injury biomarkers S-100β and NSE, as well as reduced severity of postoperative delirium. The optimal ketamine dose requires further clarification in future studies.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Обоснование.</bold> Дети с врожденными пороками сердца подвержены высокому риску церебральных повреждений в послеоперационном периоде из-за своих анатомо-физиологических особенностей и широкого набора факторов кардиохирургических операций, негативных для головного мозга. Кетамин, обладающий нейропротективными свойствами, может снизить эти риски, но его оптимальные дозы и эффективность у детей требуют дальнейшего изучения.</p> <p><bold>Цель.</bold> Оценить эффект субанестетических доз кетамина в послеоперационном периоде на головной мозг у пациентов детского возраста после кардиохирургических операций в условиях искусственного кровообращения.</p> <p><bold>Методы. </bold>Проведено проспективное рандомизированное исследование с участием 91 пациента (возраст 1–60 мес.), разделенных на контрольную группу и три исследуемые группы, получавшие кетамин в дозах 0,1, 0,2 и 0,3 мг/(кг × ч) соответственно в течение 16 ч после операции. Оценивали сывороточные маркеры повреждения мозга (S-100-β, NSE, GFAP, окклюдин, клаудин-1), послеоперационный делирий (шкала CAPD) и побочные эффекты.</p> <p><bold>Результаты.</bold> Группы не различались по интра- и послеоперационным параметрам. Через 16 ч после операции уровни S-100-β и NSE были значимо ниже в исследуемых группах 2 и 3. Баллы по шкале CAPD также были статистически ниже во всех группах с инфузией кетамина.</p> <p><bold>Заключение.</bold> В группе пациентов с инфузией кетамина в дозах 0,2–0,3 мг/(кг × ч) у детей после кардиохирургических операций зарегистрирован более низкий уровень маркеров повреждения мозга S-100-β и NSE, а также меньшая выраженность послеоперационного делирия. Оптимальная доза кетамина требует уточнения в дальнейших исследованиях.</p></trans-abstract><trans-abstract xml:lang="zh"><p><bold>论证。</bold>由于其解剖生理特点以及心脏外科手术过程中存在的多种对脑组织不利的因素，先天性心脏病患儿在术后阶段面临较高的脑损伤风险。氯胺酮具有神经保护特性，可能降低上述风险，但其在儿童中的最佳剂量及疗效仍需进一步研究。</p> <p><bold>目的。</bold>评估在体外循环条件下接受心脏外科手术的儿童患者中，术后应用亚麻醉剂量氯胺酮对脑组织的影响。</p> <p><bold>方法。</bold>开展一项前瞻性随机研究，共纳入91例患者（年龄1–60个月），分为对照组和3个研究组。研究组在术后连续16 h静脉输注氯胺酮，剂量分别为0.1、0.2和0.3 mg/(kg · h)。评估血清脑损伤标志物（S-100-β、NSE、GFAP、Occludin、Claudin-1）、术后谵妄情况（CAPD量表）及不良反应。</p> <p><bold>结果。</bold>各组在术中及术后参数方面未见差异。术后16 h，研究组2和研究组3的S-100-β和NSE水平呈显著降低。所有接受氯胺酮输注的研究组CAPD评分亦降低。</p> <p><bold>结论。</bold>在接受心脏外科手术的儿童患者中，术后持续输注氯胺酮剂量为0.2–0.3 mg/(kg · h)与较低的脑损伤标志物S-100-β和NSE水平及较轻的术后谵妄程度相关。氯胺酮的最佳剂量仍需在后续研究中进一步明确。</p></trans-abstract><kwd-group xml:lang="en"><kwd>congenital heart defects</kwd><kwd>cardiac surgery</kwd><kwd>ketamine</kwd><kwd>neuroprotection</kwd><kwd>neurovascular unit</kwd><kwd>children</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>врожденные пороки сердца</kwd><kwd>кардиохирургия</kwd><kwd>кетамин</kwd><kwd>нейропротекция</kwd><kwd>нейроваскулярная единица</kwd><kwd>дети</kwd></kwd-group><kwd-group xml:lang="zh"><kwd>先天性心脏病</kwd><kwd>心脏外科</kwd><kwd>氯胺酮</kwd><kwd>神经保护</kwd><kwd>神经血管单元</kwd><kwd>儿童</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Hansen TG. Anesthesia-related neurotoxicity and the developing animal brain is not a significant problem in children. Paediatr Anaesth. 2015;25(1):65–72. doi: 10.1111/pan.12548</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Jevtovic-Todorovic V. General anesthetics and neurotoxicity: how much do we know? Anesthesiol Clin. 2016;34(3):439–451. doi: 10.1016/j.anclin.2016.04.001</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Derbyshire E, Obeid R. Choline, neurological development and brain function: a systematic review focusing on the first 1000 days. Nutrients. 2020;12(6):1731. doi: 10.3390/nu12061731</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Sadhwani A, Wypij D, Rofeberg V, et al. Fetal brain volume predicts neurodevelopment in congenital heart disease. Circulation. 2022;145(15):1108–1119. doi: 10.1161/CIRCULATIONAHA.121.056305</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Aguet J, Fakhari N, Nguyen M, et al. Impact of cardiopulmonary bypass on cerebrovascular autoregulation assessed by ultrafast ultrasound imaging. J Physiol. 2023;601(6):1077–1093. doi: 10.1113/JP284070</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Ivkin AA, Grigoryev EV, Balakhnin DG, Chermnykh II. Intraoperative transfusion is a risk factor for cerebral injury after cardiac surgery in children: a prospective observational study. Annals of Critical Care. 2023;(1):101–114. doi: 10.21320/1818-474X-2023-1-101-114 EDN: TZRUWP</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Fu M, Yuan Q, Yang Q, et al. Risk factors and incidence of postoperative delirium after cardiac surgery in children: a systematic review and meta-analysis. Ital J Pediatr. 2024;50(1):24. doi: 10.1186/s13052-024-01603-2</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Hirata Y. Cardiopulmonary bypass for pediatric cardiac surgery. Gen Thorac Cardiovasc Surg. 2018;66(2):65–70. doi: 10.1007/s11748-017-0870-1</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Engelman R, Baker RA, Likosky DS, et al. The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical practice guidelines for cardiopulmonary bypass — temperature management during cardiopulmonary bypass. J Extra Corpor Technol. 2015;47(3):145–154. doi: 10.1051/ject/201547145</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Ivkin AA, Grigoriev EV. Role of hypothermia in cerebral protection in surgical correction of congenital heart defects. Complex Issues of Cardiovascular Diseases. 2023;12(4):228–234. doi: 10.17802/2306-1278-2023-12-4-228-234 EDN: TJQPVX</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Köditz H, Drouche A, Dennhardt N, et al. Depth of anesthesia, temperature, and postoperative delirium in children and adolescents undergoing cardiac surgery. BMC Anesthesiol. 2023;23(1):148. doi: 10.1186/s12871-023-02102-3</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Patel AK, Biagas KV, Clarke EC, et al. Delirium in children after cardiac bypass surgery. Pediatr Crit Care Med. 2017;18(2):165–171. doi: 10.1097/PCC.0000000000001032</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Staveski SL, Pickler RH, Khoury PhR, et al. Prevalence of ICU delirium in postoperative pediatric cardiac surgery patients. Pediatr Crit Care Med. 2021;22(1):68–78. doi: 10.1097/PCC.0000000000002591 EDN: MCYIOC</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Ivkin АА, Grigoriev EV, Tsepokina АV, Shukevich DL. Postoperative delirium in children in undergoing treatment of congenital septal heart defects. Messenger of Anesthesiology and Resuscitation. 2021;18(2):62–68. doi: 10.21292/2078-5658-2021-18-2-62-68 EDN: CKJRRS</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Saylan S, Akbulut UE. A comparison of ketamine-midazolam combination and propofol-fentanyl combination on procedure comfort and recovery process in pediatric colonoscopy procedures. Pak J Med Sci. 2021;37(2):483–488. doi: 10.12669/pjms.37.2.2787</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Kim K-S, Jeon MT, Kim ES, et al. Activation of NMDA receptors in brain endothelial cells increases transcellular permeability. Fluids Barriers CNS. 2022;19(1):70. doi: 10.1186/s12987-022-00364-6</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Ivkin AA, Grigoriev EV, Balakhnin DG, Sinitskaya AV. Subanesthetic dose infusion of ketamine in the postoperative period as a means of cerebroprotection in children during surgical correction of congenital heart defects: A prospective randomized study. Annals of Critical Care. 2024;(4):115–126. doi: 10.21320/1818-474X-2024-4-115-126 EDN: CXQZIJ</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Patent RF No. 2773741/06/08/20, IPC A61M 1/36 (2006.01). Method for vacuum ultrafiltration of extracorporeal circuit perfusate in children with blood reinfusion. (In Russ).</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Kuhn JE, Pareja Zabala MC, Chavez MM, et al. Utility of brain injury biomarkers in children with congenital heart disease undergoing cardiac surgery. Pediatr Neurol. 2023;148:44–53. doi: 10.1016/j.pediatrneurol.2023.06.024</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Smok B, Domagalski K, Pawłowska M. Diagnostic and prognostic value of IL-6 and sTREM-1 in SIRS and sepsis in children. Mediators Inflamm. 2020;2020:8201585. doi: 10.1155/2020/8201585</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Rothoerl RD, Brawanski A, Woertgen C. S100B protein serum levels after controlled cortical impact injury in the rat. Acta Neurochir (Wien). 2000;142(2):199–203. doi: 10.1007/s007010050024</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Silver G, Kearney J, Traube C, Hertzig M. Delirium screening anchored in child development: The Cornell Assessment for Pediatric Delirium. Palliat Support Care. 2015;13(4):1005–1011. doi: 10.1017/S1478951514000947</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166(10):1338–1344. doi: 10.1164/rccm.2107138</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Kain ZN, Mayes LC, Cicchetti DV, et al. The yale preoperative anxiety scale: how does it compare with a “gold standard”? Anesth Analg. 1997;85(4):783–788. doi: 10.1097/00000539-199710000-00012</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Cohen SP, Bhatia A, Buvanendran A, et al. Consensus guidelines on the use of intravenous ketamine infusions for chronic pain from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018;43(5):521–546. doi: 10.1097/AAP.0000000000000808</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Alanazi E. The effectiveness of ketamine compared to opioid analgesics for management of acute pain in children in the emergency department: systematic review. Am J Emerg Med. 2022;61:143–151. doi: 10.1016/j.ajem.2022.08.004</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Sperotto F, Giaretta I, Mondardini MC, et al. Ketamine prolonged infusions in the pediatric intensive care unit: a tertiary-care single-center analysis. J Pediatr Pharmacol Ther. 2021;26(1):73–80. doi: 10.5863/1551-6776-26.1.73</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Barbu M, Jónsson K, Zetterberg H, et al. Serum biomarkers of brain injury after uncomplicated cardiac surgery: Secondary analysis from a randomized trial. Acta Anaesthesiol Scand. 2022;66(4):447–453. doi: 10.1111/aas.14033</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Abdelhalim AA, Alarfaj AM. The effect of ketamine versus fentanyl on the incidence of emergence agitation after sevoflurane anesthesia in pediatric patients undergoing tonsillectomy with or without adenoidectomy. Saudi J Anaesth. 2013;7(4):392–398. doi: 10.4103/1658-354X.121047</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Costi D, Cyna AM, Ahmed S, et al. Effects of sevoflurane versus other general anaesthesia on emergence agitation in children. Cochrane Database Syst Rev. 2014;9:CD007084. doi: 10.1002/14651858.CD007084.pub2</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Schmitz A, Weiss M, Kellenberger C, et al. Sedation for magnetic resonance imaging using propofol with or without ketamine at induction in pediatrics-A prospective randomized double-blinded study. Paediatr Anaesth. 2018;28(3):264–274. doi: 10.1111/pan.13315</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Ng KT, Sarode D, Lai YS, et al. The effect of ketamine on emergence agitation in children: A systematic review and meta-analysis. Paediatr Anaesth. 2019;29(12):1163–1172. doi: 10.1111/pan.13752</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Park S, Choi AY, Park E, et al. Effects of continuous ketamine infusion on hemodynamics and mortality in critically ill children. PLoS One. 2019;14(10):e0224035. doi: 10.1371/journal.pone.0224035</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Abdelfattah M, Abdelbaser I, Awad KA, et al. Effect of low-dose ketamine infusion on opioid consumption in children undergoing open cardiac surgery: a randomized controlled double-blind study. J Cardiothorac Vasc Anesth. 2024;38(10):2349–2355. doi: 10.1053/j.jvca.2024.04.039</mixed-citation></ref></ref-list></back></article>
