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

NCT06169475 | Completed

• 1 other identifier: D-E-P-sepsis
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Septic Shock; Stress Response; Cerebral Hemodynamics

Keywords

Septic shock; Stress response; Trans-cranial Doppler

Outcome Measures

Primary Outcomes (1)

• The cerebral hemodynamic change caused by the anti-stress therapy

  The cerebral hemodynamics will be evaluated according to the features of the blood flow of MCA, DMCV, BVR and TS measured by transcranial doppler, as well as regional cerebral oxygen saturation measured by the near infrared spectroscopy at Hour 0, Hour 6, Hour 12, Hour 18 and Hour 24. The difference will be acquired by contrasting between two intervention group and one control group.

  Hour 0, Hour 6, Hour 12, Hour 18 and Hour 24.

Secondary Outcomes (1)

• The systemic hemodynamic change caused by anti-stress therapy

  Hour 0, Hour 6, Hour 12, Hour 18 and Hour 24

Study Arms (3)

dexmedetomidine group

EXPERIMENTAL

Drug: Dexmedetomidine Hydrochloride

esmolol group

EXPERIMENTAL

Drug: Esmolol Hydrochloride

control group

NO INTERVENTION

Interventions

Dexmedetomidine Hydrochloride DRUG

The continuous intravenous infusion of dexmedetomidine (0.1mg/ml) will start at 0.1ug/kg/h, increasing every 20 minutes by a step change of 0.05-0.2ug/kg/h to reach the target heart rate with the expectation that this should be within 12 hours. The infusion will be reduced by step change, and if necessary, ultimately stopped if the heart rate fall below 80b.p.m..

dexmedetomidine group

Esmolol Hydrochloride DRUG

The continuous intravenous infusion of esmolol (10mg/ml) will start at 20mg/h, increasing every 20 minutes by a step change of 20mg/h to reach the target heart rate with the expectation that this should be within 12 hours. The infusion will be reduced by step change, and if necessary, ultimately stop if the heart rate fall below 80b.p.m..

esmolol group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \~ 80 years old.
• Patients established septic shock according to sepsis 3.0 criteria.
• Under deep sedation of BIS 40-60 with midazolam and fentanyl.
• After achieving the goal sedation, patients are still with tachycardia (heart rate over 100 b.p.m..

You may not qualify if:

• Pregnancy.
• Patients with severe arrhythmia.
• Patients with aortic or aortic valve disease.
• Patients with mechanical circulatory assist device (e.g. extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP), etc).
• Patients with cerebral trauma.
• Any contraindication to the use of transcranial doppler.

Sponsors & Collaborators

• Xinchen Wang: lead
• Tibet Autonomous Region People's Hospital: collaborator

Study Sites (1)

Peking Union Medical College Hospital, Chinese Academy of Medical Science

Beijing, China

Location

Related Publications (7)

• 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.

  PMID: 26903338 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.

  PMID: 28991824 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.

  PMID: 31108055 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.

  PMID: 32778146 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.

  PMID: 28775963 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.

  PMID: 31908779 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.

  PMID: 35801730 BACKGROUND

MeSH Terms

Conditions

Shock, Septic; Fractures, Stress

Interventions

Dexmedetomidine; esmolol

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Fractures, Bone; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Wei Du, M.D.

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The participants who under deep sedation are blinded to the grouping.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Attending Doctor

Study Record Dates

• First Submitted: November 27, 2023
• First Posted: December 13, 2023
• Study Start: November 1, 2020
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2023
• Last Updated: December 13, 2023

Record last verified: 2023-12

Locations

CN (1)