Effect of Dexmedetomidine vs Esmolol or Placebo on Cerebral Hemodynamics in Septic Shock

Summary

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Some researchers proposed that the dysregulated response or organ dysfunction can be lessened by reducing the stress response, which further reduce complication and mortality rates of sepsis. Dexmedetomidine is alpha adrenergic receptor agonist, presenting sympatholytic action in certain parts of the brain with anxiolytic, sedative, and pain killing effects. In the experiments of sepsis animal model, dexmedetomidine have been proved to improve serum lactate clearance and the microcirculation. Dexmedetomidine may inhibit inflammation, as it enhances the activity of the immune system while reducing its systemic reaction and lowering cytokine concentrations. There are also evidences in clinical trials with definite safety that dexmedetomidine reduced inflammation, reduced vasopressor requirements and improved organ function. The beta antagonist esmolol has been proposed as a therapy to lower heart rate, thereby improving diastolic filling time, and improving cardiac output, resulting in a reduction in vasopressor support. A recent meta-analysis of 8 randomized studies using esmolol suggested that the 32% risk ratio decreased 28-day mortality, and a meta-analysis of 7 studies using esmolol in patients with sepsis and septic shock was associated with 32% lower 28-day mortality. However, the effect of anti-stress drugs on cerebral hemodynamics is unknown. In this study, investigators are going to apply the technique of transcranial Doppler to assess the reaction of cerebral blood flow in anti-stress group and control group.

Timeline

Start

2020-11-01

Primary completion

2021-11-01

Completion

2023-11-01

Publications

• Background Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
• Background Du W, Liu D, Long Y, Wang X. The beta-Blocker Esmolol Restores the Vascular Waterfall Phenomenon After Acute Endotoxemia. Crit Care Med. 2017 Dec;45(12):e1247-e1253. doi: 10.1097/CCM.0000000000002721.
• Background 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.
• Background Ohta Y, Miyamoto K, Kawazoe Y, Yamamura H, Morimoto T. Effect of dexmedetomidine on inflammation in patients with sepsis requiring mechanical ventilation: a sub-analysis of a multicenter randomized clinical trial. Crit Care. 2020 Aug 10;24(1):493. doi: 10.1186/s13054-020-03207-8.
• Background Scibelli G, Maio L, Sasso M, Lanza A, Savoia G. Dexmedetomidine: Current Role in Burn ICU. Transl Med UniSa. 2017 Jul 1;16:1-10. eCollection 2017 Jan.
• Background Nakashima T, Miyamoto K, Shima N, Kato S, Kawazoe Y, Ohta Y, Morimoto T, Yamamura H; DESIRE Trial Investigators. Dexmedetomidine improved renal function in patients with severe sepsis: an exploratory analysis of a randomized controlled trial. J Intensive Care. 2020 Jan 2;8:1. doi: 10.1186/s40560-019-0415-z. eCollection 2020.
• Background Zhang J, Chen C, Liu Y, Yang Y, Yang X, Yang J. Benefits of esmolol in adults with sepsis and septic shock: An updated meta-analysis of randomized controlled trials. Medicine (Baltimore). 2022 Jul 8;101(27):e29820. doi: 10.1097/MD.0000000000029820.

Drugs

Indications