Dargent Auguste, Bourredjem Abderrahmane, Argaud Laurent, Levy Bruno, Fournel Isabelle, Cransac Amélie, Badie Julio, Quintin Luc, Quenot Jean-Pierre
Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Médecine Intensive-Réanimation, Lyon, France.
APCSe VetAgro Sup UPSP 2016.A101, Marcy l'Etoile, France.
Front Med (Lausanne). 2022 Aug 9;9:968274. doi: 10.3389/fmed.2022.968274. eCollection 2022.
Refractory septic shock (RSS) is characterized by high vasopressor requirements, as a consequence of vasopressor resistance, which may be caused or enhanced by sympathetic hyperactivation. Experimental models and clinical trials show a reduction in vasopressor requirements and improved microcirculation compared to conventional sedation. Dexmedetomidine did not reduce mortality in clinical trials, but few septic shock patients were enrolled. This pilot trial aims to evaluate vasopressor re-sensitization with dexmedetomidine and assess the effect size, in order to design a larger trial.
This is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, comparing dexmedetomidine versus placebo in RSS patients with norepinephrine dose ≥0.5μg/kg/min. The primary outcome is blood pressure response to phenylephrine challenge, 6 hours after completion of a first challenge, after study treatment initiation. Secondary outcomes include feasibility and safety outcomes (bradycardia), mortality, vasopressor requirements, heart rate variability, plasma and urine catecholamines levels. The sample size is estimated at 32 patients to show a 20% improvement in blood pressure response to phenylephrine. Randomization (1:1) will be stratified by center, sedation type and presence of liver cirrhosis. Blood pressure and ECG will be continuously recorded for the first 24 h, enabling high-quality data collection for the primary and secondary endpoints. The study was approved by the ethics committee "Sud-Est VI" (2019-000726-22) and patients will be included after informed consent.
The present study will be the first randomized trial to specifically address the hemodynamic effects of dexmedetomidine in patients with septic shock. We implement a high-quality process for data acquisition and recording in the first 24 h, ensuring maximal quality for the evaluation of both efficacy and safety outcomes, as well as transparency of results. The results of the study will be used to elaborate a full-scale randomized controlled trial with mortality as primary outcome in RSS patients.
Registered with ClinicalTrials.gov (NCT03953677). Registered 16 May 2019, https://clinicaltrials.gov/ct2/show/NCT03953677.
难治性感染性休克（RSS）的特征是由于血管升压药抵抗导致对血管升压药的需求量很大，而这种抵抗可能由交感神经过度激活引起或加剧。实验模型和临床试验表明，与传统镇静相比，使用血管升压药的需求量减少，微循环得到改善。右美托咪定在临床试验中并未降低死亡率，但纳入的感染性休克患者很少。这项试点试验旨在评估右美托咪定对血管升压药的重新致敏作用并评估效应大小，以便设计一项更大规模的试验。
这是一项由研究者发起的多中心、随机、双盲、安慰剂对照试验，在去甲肾上腺素剂量≥0.5μg/kg/分钟的RSS患者中比较右美托咪定与安慰剂。主要结局是在开始研究治疗后，首次激发完成6小时后，对苯肾上腺素激发的血压反应。次要结局包括可行性和安全性结局（心动过缓）、死亡率、血管升压药需求量、心率变异性、血浆和尿儿茶酚胺水平。样本量估计为32例患者，以显示对苯肾上腺素的血压反应有20%的改善。随机分组（1:1）将按中心、镇静类型和肝硬化的存在情况进行分层。前24小时将持续记录血压和心电图，以便为主要和次要终点收集高质量的数据。该研究已获得伦理委员会“东南部第六区”（2019-000726-22）的批准，患者将在获得知情同意后纳入。
本研究将是第一项专门针对右美托咪定对感染性休克患者血流动力学影响的随机试验。我们在前24小时实施了高质量的数据采集和记录流程，确保对疗效和安全性结局评估的最大质量以及结果的透明度。该研究的结果将用于精心设计一项以死亡率为主要结局的RSS患者全规模随机对照试验。
已在ClinicalTrials.gov（NCT03953677）注册。2019年5月16日注册，https://clinicaltrials.gov/ct2/show/NCT03953677。
