"The Effect of Stellate Ganglion Block in Severe Brain Injury"
Condition: Traumatic Brain Injury; Brain Inflammation; Cerebral Vasospasm
MeSH terms: Ganglion Cysts; Brain Injuries; Brain Injuries, Traumatic; Vasospasm, Intracranial; Encephalitis; Inflammation; Wounds and Injuries
Study type: Interventional

Summary: 
      Blood flow through the brain is reduced after brain damage. Secondary brain ischemia caused
      by hypoxia and hypotension, further increase the susceptibility of the ischemically
      compromised brain to secondary impairment during this period. In order to determine whether
      and to what extent blockage of the stellate ganglion (BSG) affects the blood flow to the
      injured brain, the investigators will measure the variables of brain blood flow before and
      after BSG using computed tomography angiography (CTA), trans-cranial Doppler ultrasound
      (TCD), intracranial pressure (ICP) and perfusion computed tomography (PCT) of the brain. At
      the same time, the investigators would like to evaluate whether and to what extent BSG
      affects the aseptic inflammatory brain injury response and the biochemical indicators of
      brain damage in patients with moderate and severe brain injury.
    

Detailed description: 
      Hypothesis

      Stellate ganglion blockade in patients with moderate and severe brain damage:

        1. Increases the diameter of the brain arteries and blood flow through the brain

        2. Do not interfere with intracranial pressure

        3. Reduces aseptic inflammatory reaction of the damaged brains measured by IL-6 and reduces
           damage of the brain tissue measured by protein S100B (S100B), neuron specific enolase
           (NSE) and glial fibrillary acidic protein (GFAP).

      Study design and method description

      The study will include 40 subjects of both sexes (18-70 years old) with moderate and severe
      head injury who will be treated surgically and/or conservatively at the Intensive Care Center
      (CIT) of the Department of Anesthesiology and Intensive Care UKC Ljubljana. The study will
      include patients who underwent computed tomography angiography of the brain (CTA) and
      received an intra-parenchymal intracranial pressure monitor electrode (ICP) at admission to
      the UKC Ljubljana Emergency Center or during CIT treatment. After primary conservative or
      surgical care, the subjects will be transferred for further treatment at CIT. Subjects will
      be sedated and mechanically ventilated. To maintain target cerabral perfusion pressure (CPP),
      the investigators will give an infusion of noradrenaline as needed. The study will not
      include subjects with primary decompression craniectomy and radiological signs of progression
      of intracranial hematomas, subjects in a barbiturate coma, and subjects with a norepinephrine
      dose greater than 0.2 mcg/kg/min. The study will not include pregnant women, children,
      patients with known hypersensitivity to iodine contrast media and local anesthetics, and
      patients with poor renal function (estimated glomerular filtration below 30ml / min /
      1.73m2).

      The research will be conducted during patient treatment at CIT. The investigators will begin
      the investigation after positive positive opinions from the Medical Ethics Commission of the
      Republic of Slovenia, and obtained written consent form patient's family members or official
      legal representatives.

      The effect of BSG on brain blood flow and the diameter of brain vessels will be evaluated by
      CTA, PCT, TCD.

      BSG will be done during the first week after admission at CIT on the same patient's side of
      the ICP position. One hour after BSG, control CTA in PCT will be done. TCD od the left and
      right middle brain artery (ACM) will be performed one hour before and after BSG.

      TCD will be used to measure the rate of blood flow through ACM in systole-Vs in diastole-Vd
      and pulsatility index (PI). The investigators will compare Vs, Vd values and PI before and
      after BSG.

      Possible changes in the diameter of large brain vessels after BSG will be compared between
      CTA done at the emergency center or during CIT treatment and a control CTA after BSG. For
      standard diameter measurement sites, the investigators will take the middle third of M1 and
      the proximal part of the M2 segment of the ACM, the middle third of the A1 and A2 segments of
      the anterior brain artery (ACA), the P1 segment and the first part of P2 segment of the
      posterior brain artery (ACP), the terminal part of the interior carotid artery (ACI), the
      middle third of the intradural part of the vertebral artery and middle third of the basilar
      artery. Changes in the diameter of the brain vessels will be presented numerically and
      descriptively.

      With PCT-produced color maps beside qualitative evaluation od the possible changes of the
      brain blood flow on the left and right brain hemisphere after BSG, the investigators will
      also evaluate changes in regional brain blood volume (rCBV), regional brain blood flow
      (rCBF), mean transition time (MTT). Outside the contusion regions, the investigators will
      mark the region of interest (ROI) of 500 mm2 for ACA, ACM and ACP perfusion areas. Siemens
      SyngoVia software will be used.

      PCT and CTA will be done by the helical CT tomogram (Somatom, Siemens, Erlangen, Germany). A
      40 ml non-ionic low-osmolar iodine contrast medium, 370 mg/ml iopromide (Ultravist; Bayer
      HealthCare, Berlin, Germany) will be used. It will be injected at a flow rate of 5 ml/s into
      a cubital vein. Perfusion imaging will be initiated 7 seconds after the injection of
      contrast.

      Blood samples for the determination of IL6, NSE, S100B in GFAP will be drawn from the right
      external jugular vein and peripheral artery (radial or femoral artery) one hour before and 1,
      6, 12, 24 hours after BSG. The investigators will compare IL6, NSE, S100B, GFAP values in
      venous blood from right jugular vein before v after BSG. A comparation of the values of IL6,
      NSE, S100B, GFAP in venous blood from the right internal jugular vein in arterial blood taken
      from the peripheral artery will be done as well. Blood samples will be sent for analysis to
      the central laboratory of UKC Ljubljana.

      Brain oxygenation will be measured with a non-invasive method on both fronts using Near
      Infrared Spectroscopy (NIRS). NIRS measurement values will be measured immediately before BSG
      and within 5, 10, 15, 20, 25 and 30 minutes after BSG.

      BSG will be done ipsilaterally to the inserted ICP electrode. BSG will be done under
      ultrasound control at the C6-C7 level, with a lateral approach with a Stimulplex Ultra 360
      5cm needle (B.Brown). A 6-15 MHz high frequency probe will be used. BSG will be done always
      by the same anesthesiologist. The injection site and the ultrasound probe will be aseptically
      prepared. The ultrasound probe will be placed transversely to the neck axis at the height of
      the sixth cervical vertebra. After preliminary verification of the needle tip position over
      the long cervical muscle and under the prevertebral fascia and after negative aspiration, 8
      ml of 0.5% levobupivacaine will be injected. Because het investigator's subjects will be
      sedated, onset of the BSG will be confirmed 10 minutes after the blockade, by the onset of
      three signs of Horner's syndrome (ptosis, myosis, enophthalmus, anhydrosis, conjunctival
      hyperemia): enophthalmus, anhydrosis, conjunctival hyperemia.

      ICP in CPP will be continuously measured before and after BSG. The data will be analyzed in
      graphical display using IBM SPSS Statistics statistical programs, ver. 25 and Microsoft
      Excel. The variables will be presented as mean values with standard deviation or as median
      with interquartile range. Using the paired t-test, the investigators will compare the average
      values of the sample's numerically variables. Significant differences will be defined as
      p<0,05.

      Expected results

      When investigating the effect of BSG on the brain circulation and inflammatory response in
      subjects with moderate and severe brain damage, the investigators expect a significant
      increase in the diameter of the large brain arteries, and thus a positive effect of BSG on
      the brain circulation of the injured brain (decreased mean blood transition time, increased
      blood volume in the brain, and increased blood flow through the brain). The investigators
      estimate that BSG will not change the intracranial pressure. The investigators expect NIRS
      values to be significantly higher after the blockade than before the blockade. Due to the
      positive effects of BSG on the aseptic inflammatory response of non-injured brain, BSG is
      expected to have the same effect in the injured brain. The investigators also expect BSG will
      decrease the concentration of biochemical indicators of inflammation and damage to neurons
      and glia.
    

Intervention name(s): one site blockade of the stellate ganglion
Intervention type(s): Procedure
Intervention description(s): Ultrasound guided one site blockade of the stellate ganglion.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stellate ganglion block; brain hemodynamics; brain inflammatory response