Clinical trial NCT06169475: Effect of Dexmedetomidine vs Esmolol or Placebo on Cerebral Hemodynamics in Septic Shock
Official title: Effect of Dexmedetomidine vs Esmolol or Placebo on Cerebral Hemodynamics in Septic Shock: A Randomized Clinical Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Septic Shock
Stress Response
Cerebral Hemodynamics
Keywords: Septic shock
Stress response
Trans-cranial Doppler
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Tibet Autonomous Region People's Hospital
First posted: 2023-12-13
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The cerebral hemodynamic change caused by the anti-stress therapy
timeFrame: Hour 0, Hour 6, Hour 12, Hour 18 and Hour 24.
Secondary outcomes:
measure: The systemic hemodynamic change caused by anti-stress therapy
timeFrame: Hour 0, Hour 6, Hour 12, Hour 18 and Hour 24
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital, Chinese Academy of Medical Science
Study officials:
affiliation: Peking Union Medical College Hospital
name: Wei Du, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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