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.

Conditions

• Septic Shock
• Stress Response
• Cerebral Hemodynamics

Interventions

DRUG

Dexmedetomidine Hydrochloride

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..

DRUG

Esmolol Hydrochloride

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..

Sponsors & Collaborators

• Tibet Autonomous Region People's Hospital

  collaborator OTHER

• Xinchen Wang

  lead OTHER

Principal Investigators

• Wei Du, M.D. · Peking Union Medical College Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-11-01

Primary Completion

2021-11-01

Completion

2023-11-01

Countries

• China

Study Locations