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

Not Applicable

Completed

• Conditions: Septic Shock; Stress Response; Cerebral Hemodynamics
• Interventions: Drug: Dexmedetomidine Hydrochloride; Drug: Esmolol Hydrochloride

• Registration Number: NCT06169475
• Lead Sponsor: Xinchen Wang

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.

Detailed Description

It is a single-blinded, single-center, randomized trial. Patients with septic shock established within 24 hours in the ICU of Tibet Autonomous Region People's Hospital will be screened for recruitment. After adequate fluid resuscitation, continuous infusion of norepinephrine is given to the patients to maintain a mean arterial pressure (MAP) of 65-75 millimeter of mercury (mmHg). Midazolam and fentanyl are given to achieve the goal sedation of bispectral index (BIS) 40-60, patients who are still with tachycardia (heart rate over 100 b.p.m.) will be recruited. After recruitment, patients in accordance with the random number table are divided into dexmedetomidine group, esmolol group and control group (T0). Patients in the two experimental groups are required to achieve the heart rate goal of 75-95 b.p.m. in one hour by adjusting the dose of dexmedetomidine or esmolol every twenty minutes. All patients acquired the hemodynamic evaluation at T1, T2, T3, T4 (6, 12, 18, 24hours after enrollment). The hemodynamic evaluation including transcranial Doppler of middle cerebral artery(MCA), deep middle cerebral vein (DMCV), basal vein Rosenthal (BVR) and transverse sinus (TS), hemodynamic parameters acquired by the pressure-recording analytical method through peripheral arterial with Mostcare. Demographic characteristics, diagnosis, laboratory reports and drug dose are collected during the study.

Study Timeline

• Study Start: 2020-11-01
• Primary Completion: 2021-11-01
• Study Completion: 2023-11-01
• Study First Submitted: 2023-11-27
• Status Verified: 2023-12
• Study First Submitted QC: 2023-12-05
• Last Update Submitted: 2023-12-05
• Study First Posted: 2023-12-13
• Last Update Posted: 2023-12-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

1. 18 ~ 80 years old.
2. Patients established septic shock according to sepsis 3.0 criteria.
3. Under deep sedation of BIS 40-60 with midazolam and fentanyl.
4. After achieving the goal sedation, patients are still with tachycardia (heart rate over 100 b.p.m..

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
dexmedetomidine group	Dexmedetomidine Hydrochloride	-
esmolol group	Esmolol Hydrochloride	-

Primary Outcome Measures

Name	Time	Method
The cerebral hemodynamic change caused by the anti-stress therapy	Hour 0, Hour 6, Hour 12, Hour 18 and Hour 24.	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.

Secondary Outcome Measures

Name	Time	Method
The systemic hemodynamic change caused by anti-stress therapy	Hour 0, Hour 6, Hour 12, Hour 18 and Hour 24	The systemic hemodynamic changes will be acquired through the pressure-recording analytical method with Mostcare, blood pressure and electro cardiac monitor, central venous pressure (CVP) monitor, trans thoracic echocardiography, and blood gas 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

Trial Locations

Locations (1)

Peking Union Medical College Hospital, Chinese Academy of Medical Science; 🇨🇳 Beijing, China