Early Dexmedetomidine and Sympathetic Regulation in Sepsis

Summary

The goal of this clinical trial is to learn whether early administration of dexmedetomidine can improve autonomic nervous system regulation and clinical outcomes in adult patients with septic shock. It will also evaluate the safety of dexmedetomidine in this population. The main questions it aims to answer are: Does early dexmedetomidine improve sympathetic nervous system activity, as measured by heart rate variability (HRV) and blood pressure variability (BPV)? Does dexmedetomidine reduce endogenous catecholamine levels and vasopressor requirements? Does early autonomic modulation improve organ function and survival outcomes in septic shock? Researchers will compare dexmedetomidine to a placebo (normal saline) to determine whether dexmedetomidine improves hemodynamic stability and prognosis in patients with septic shock. Participants will: Be randomly assigned to receive dexmedetomidine (0.5 μg/kg/h) or placebo by continuous intravenous infusion for 48 hours Undergo continuous ECG and invasive blood pressure monitoring Have blood samples collected at predefined time points to measure inflammatory markers and endogenous catecholamine levels Be assessed for organ function, vasopressor use, and perfusion parameters during the first 48 hours Be followed up for 28-day and 90-day survival outcomes

Timeline

Start

2026-03-01

Primary completion

2028-03-01

Completion

2028-03-01

Publications

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• Results Carrara M, Ferrario M, Bollen Pinto B, Herpain A. The autonomic nervous system in septic shock and its role as a future therapeutic target: a narrative review. Ann Intensive Care. 2021 May 17;11(1):80. doi: 10.1186/s13613-021-00869-7.
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• Results Ammar MA, Sacha GL, Welch SC, Bass SN, Kane-Gill SL, Duggal A, Ammar AA. Sedation, Analgesia, and Paralysis in COVID-19 Patients in the Setting of Drug Shortages. J Intensive Care Med. 2021 Feb;36(2):157-174. doi: 10.1177/0885066620951426. Epub 2020 Aug 26.
• Results Dargent A, Bourredjem A, Jacquier M, Bohe J, Argaud L, Levy B, Fournel I, Cransac A, Badie J, Quintin L, Quenot JP. Dexmedetomidine to Reduce Vasopressor Resistance in Refractory Septic Shock: alpha2 Agonist Dexmedetomidine for REfractory Septic Shock (ADRESS): A Double-Blind Randomized Controlled Pilot Trial. Crit Care Med. 2025 Apr 1;53(4):e884-e896. doi: 10.1097/CCM.0000000000006608. Epub 2025 Feb 28.
• Results Shehabi Y, Howe BD, Bellomo R, Arabi YM, Bailey M, Bass FE, Bin Kadiman S, McArthur CJ, Murray L, Reade MC, Seppelt IM, Takala J, Wise MP, Webb SA; ANZICS Clinical Trials Group and the SPICE III Investigators. Early Sedation with Dexmedetomidine in Critically Ill Patients. N Engl J Med. 2019 Jun 27;380(26):2506-2517. doi: 10.1056/NEJMoa1904710. Epub 2019 May 19.
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• Results Dardalas I, Stamoula E, Rigopoulos P, Malliou F, Tsaousi G, Aidoni Z, Grosomanidis V, Milonas A, Papazisis G, Kouvelas D, Pourzitaki C. Dexmedetomidine effects in different experimental sepsis in vivo models. Eur J Pharmacol. 2019 Aug 5;856:172401. doi: 10.1016/j.ejphar.2019.05.030. Epub 2019 May 17.
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• Results Geloen A, Chapelier K, Cividjian A, Dantony E, Rabilloud M, May CN, Quintin L. Clonidine and dexmedetomidine increase the pressor response to norepinephrine in experimental sepsis: a pilot study. Crit Care Med. 2013 Dec;41(12):e431-8. doi: 10.1097/CCM.0b013e3182986248.
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• Results Stolk RF, van der Pasch E, Naumann F, Schouwstra J, Bressers S, van Herwaarden AE, Gerretsen J, Schambergen R, Ruth MM, van der Hoeven JG, van Leeuwen H, Pickkers P, Kox M. Norepinephrine Dysregulates the Immune Response and Compromises Host Defense during Sepsis. Am J Respir Crit Care Med. 2020 Sep 15;202(6):830-842. doi: 10.1164/rccm.202002-0339OC.
• Results Chirinos JA, Sweitzer N. Ventricular-Arterial Coupling in Chronic Heart Failure. Card Fail Rev. 2017 Apr;3(1):12-18. doi: 10.15420/cfr.2017:4:2.
• Results Carrara M, Herpain A, Baselli G, Ferrario M. Vascular Decoupling in Septic Shock: The Combined Role of Autonomic Nervous System, Arterial Stiffness, and Peripheral Vascular Tone. Front Physiol. 2020 Jul 7;11:594. doi: 10.3389/fphys.2020.00594. eCollection 2020.
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• Results Deutschman CS, Hellman J, Ferrer Roca R, De Backer D, Coopersmith CM; Research Committee of the Surviving Sepsis Campaign. The Surviving Sepsis Campaign: Basic/Translational Science Research Priorities. Crit Care Med. 2020 Aug;48(8):1217-1232. doi: 10.1097/CCM.0000000000004408.
• Results Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Hylander Moller M, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021 Nov 1;49(11):e1063-e1143. doi: 10.1097/CCM.0000000000005337. No abstract available.

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