Analgesic and Hemodynamic Effects of Dexmedetomidine-Ketamine vs Fentanyl-Ketamine in Healthy Volunteers: A Randomized Trial.

IF 2.5 3区 医学 Q2 CLINICAL NEUROLOGY
Journal of Pain Research Pub Date : 2025-05-16 eCollection Date: 2025-01-01 DOI:10.2147/JPR.S514277
Maja Green, Amie C Hayley, Luke A Downey, Michael Keane, Michaela Elise Kenneally, Krishnan Chakravarthy, Yahya Shehabi
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引用次数: 0

Abstract

Background: Dexmedetomidine is an α2-agonist sedative with opioid-sparing properties, is limited by dose-dependent hypotension and bradycardia. Ketamine, an NMDA receptor antagonist, has sympathomimetic effects and may attenuate these cardiovascular effects while contributing analgesia. Whether low-dose ketamine can stabilize dexmedetomidine-induced hemodynamic changes and provide comparable analgesia to an opioid-based regimen is uncertain.

Methods: In this open-label trial, we enrolled 41 healthy volunteers aged 18 to 45 years. All participants received a ketamine infusion (0.3 mg/kg bolus, then 0.15 mg/kg/hour for 3 hours). At 90 minutes, participants were randomized to receive either dexmedetomidine (0.7 µg/kg/hour for 90 minutes, KET/DEX group) or fentanyl (three 25 µg boluses, KET/FENT group). The primary outcomes were change in blood pressure and pain tolerance (measured by pressure algometry). Secondary outcomes included heart rate, subjective mood and sedation, and adverse events. Data were analyzed using mixed-effects models and Fisher's exact tests.

Results: Of 41 randomized participants, 39 completed the protocol (KET/DEX, 19; KET/FENT, 20). KET/DEX resulted in greater reductions in systolic blood pressure (mean decrease 35-40 mm Hg; ~25-30%) compared to KET/FENT (mean change minimal; between-group P<0.001). Heart rate declined modestly with KET/DEX but did not differ significantly between groups. Both regimens increased pain tolerance to a similar degree (mean threshold rise ~30-50 kPa; between-group P=0.80). Participants in the KET/DEX group reported greater sedation and transient negative mood effects (eg, disinterest), while KET/FENT was associated with mild nausea in a minority. Clinically significant hypotension occurred in 4 participants (21%) in the KET/DEX group and in none of the KET/FENT group (P=0.047). All events were transient and responsive to fluid boluses. No respiratory depression occurred in either group.

Conclusion: Ketamine plus dexmedetomidine produced analgesia equivalent to ketamine plus fentanyl but with more pronounced hypotension and deeper sedation. The hemodynamic effects of dexmedetomidine were not fully offset by low-dose ketamine. These findings suggest that while ketamine-dexmedetomidine may offer an opioid-sparing alternative, careful dose selection and monitoring are required to ensure tolerability. (Funded by Monash University and Monash Health; ACTRN12617000787381).

Clinical trial number and registry url: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372916.

右美托咪定-氯胺酮与芬太尼-氯胺酮在健康志愿者中的镇痛和血流动力学作用:一项随机试验
背景:右美托咪定是一种α - 2激动剂镇静剂,具有阿片类药物节约特性,但受剂量依赖性低血压和心动过缓的限制。氯胺酮是一种NMDA受体拮抗剂,具有拟交感神经效应,可以减轻这些心血管效应,同时起到镇痛作用。低剂量氯胺酮是否可以稳定右美托咪定引起的血流动力学变化,并提供与阿片类药物方案相当的镇痛尚不确定。方法:在这项开放标签试验中,我们招募了41名年龄在18至45岁之间的健康志愿者。所有参与者均接受氯胺酮输注(0.3 mg/kg丸,然后0.15 mg/kg/小时,持续3小时)。在90分钟时,参与者被随机分配接受右美托咪定(0.7µg/kg/小时,持续90分钟,KET/DEX组)或芬太尼(3次25µg, KET/FENT组)。主要结局是血压和疼痛耐受性的变化(通过压力测量法测量)。次要结局包括心率、主观情绪和镇静以及不良事件。使用混合效应模型和Fisher精确检验分析数据。结果:41名随机受试者中,39名完成了方案(KET/DEX, 19名;尿酮体/零头布料,20)。KET/DEX可显著降低收缩压(平均降低35-40 mm Hg;~25-30%)与KET/FENT相比(平均变化最小;群体间的PP = 0.80)。KET/DEX组的参与者报告了更大的镇静作用和短暂的负面情绪影响(例如,无兴趣),而KET/FENT组的少数参与者与轻度恶心有关。在KET/DEX组中有4名参与者(21%)出现临床显著性低血压,而在KET/FENT组中没有出现(P=0.047)。所有事件都是短暂的,对液体丸有反应。两组均未发生呼吸抑制。结论:氯胺酮加右美托咪定的镇痛效果与氯胺酮加芬太尼相当,但低血压更明显,镇静程度更深。低剂量氯胺酮不能完全抵消右美托咪定的血流动力学效应。这些发现表明,虽然氯胺酮-右美托咪定可能提供一种节省阿片类药物的替代方案,但需要仔细选择剂量和监测以确保耐受性。(由莫纳什大学和莫纳什健康资助;ACTRN12617000787381)。临床试验编号和注册网址:https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372916。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Pain Research
Journal of Pain Research CLINICAL NEUROLOGY-
CiteScore
4.50
自引率
3.70%
发文量
411
审稿时长
16 weeks
期刊介绍: Journal of Pain Research is an international, peer-reviewed, open access journal that welcomes laboratory and clinical findings in the fields of pain research and the prevention and management of pain. Original research, reviews, symposium reports, hypothesis formation and commentaries are all considered for publication. Additionally, the journal now welcomes the submission of pain-policy-related editorials and commentaries, particularly in regard to ethical, regulatory, forensic, and other legal issues in pain medicine, and to the education of pain practitioners and researchers.
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