Effect of Dexmedetomidine vs Esmolol or Placebo on Cerebral Hemodynamics in Septic Shock
Condition: Septic Shock; Stress Response; Cerebral Hemodynamics
MeSH terms: Shock, Septic; Shock
Study type: Interventional

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.
    

Intervention name(s): Dexmedetomidine Hydrochloride; Esmolol Hydrochloride
Intervention type(s): Drug; Drug
Intervention description(s): 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..; 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..
Intervention MeSH terms: Dexmedetomidine; Esmolol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Septic shock; Stress response; Trans-cranial Doppler