Temporary Celiac Ganglion Block as a Test Before Celiac Ganglion Resection for Dysautonomia-Related Bowel Dysmotility
Condition: Dysautonomia
MeSH terms: Ganglion Cysts; Synovial Cyst; Primary Dysautonomias; Autonomic Nervous System Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      Dysautonomia is malfunction of the autonomic nervous system. It usually results from
      overactivity of the sympathetic portion and over-secretion of acetylcholine. Symptoms depend
      on the organ involved by this sympathetic overstimulation. Involvement of the
      gastrointestinal system results in chronic dysmotility, nausea, vomiting, food intolerance,
      weight loss and need for feeding tube placement and/or parenteral feeding. Autonomic celiac
      ganglia resection has been shown to alleviate symptoms as it interrupts the sympathetic
      stimulation to the gastrointestinal (GI) system, however there is no pre surgery test to
      confirm the diagnosis. The investigators' objective is to temporarily block the celiac
      ganglion with a long acting anesthetic (liposomal bupivacaine). If symptoms abate the
      diagnosis is confirmed and patient will proceed to surgery.
    

Detailed description: 
      Problem:

      Dysautonomia is malfunction of the autonomic nervous system. It usually results from
      overactivity of the sympathetic portion and over-secretion of acetylcholine. Symptoms depend
      on the organ involved by this sympathetic overstimulation. A partial list of
      dysautonomia-related conditions is shown below:

      Affected Level Manifestation Cardiac innervation Postural Orthostatic Tachycardia Syndrome
      Skin Hyperhidrosis Arteries Raynaud's phenomenon Kidneys Hypertension Small nerve fibers
      Reflex Sympathetic Dystrophy Pain fibers Complex regional pain syndrome GI system Chronic GI
      dysmotility/irritable bowel syndrome (IBS) The last one (Chronic GI dysmotility) usually
      affects young females, presenting after puberty. Symptoms include chronic abdominal pain,
      intestinal angina, chronic nausea/vomiting, inability to take po, need for total parenteral
      nutrition (TPN) or G-tube feeding. Further, the patients' condition is often complicated by
      opioid dependence, malnutrition, weight loss, social isolation etc. Many such patients are
      misdiagnosed as having Median Arcuate Ligament Syndrome (MALS) and are referred to surgery
      for ligament release. Though some of the patients do get partial relief, this temporary
      relief is due to the partial interruption of the sympathetic nerves during surgery. Repeat
      surgery to complete celiac ganglion resection is often necessary. Occasionally surgeons refer
      patients for a Computer Tomography (CT) guided temporary celiac ganglion block to confirm (or
      exclude) sympathetic system dysfunction as the cause of the patients symptoms. However
      negative or positive predictive value of this test has not been studies rigorously.

      Research Hypothesis:

      The investigators' hypothesis is that a low-risk, outpatient test can confirm (or exclude)
      dysautonomia as the cause of the patient's symptoms. The experimental test is CT-guided,
      celiac ganglion temporary block with liposomal bupivacaine.

      Importance of the Research:

      Some of the patients who are diagnosed as having MALS have in fact dysautonomia and have the
      wrong surgery. Many other patients with dysautonomia-related GI symptoms are not diagnosed at
      all and offered only symptomatic treatment. The development of CT-guided, celiac ganglion
      temporary block with liposomal bupivacaine as a low-risk confirmatory test for
      dysautonomia-related GI symptoms, will improve surgical outcomes and afford a novel treatment
      option to many patients.

      2. Objectives

      CT-guided, celiac ganglion temporary block with liposomal bupivacaine will eliminate
      sympathetic input to the bowel. Its half-life is 24 hours and therefore symptom relief can be
      distinguished from overlap due to procedural sedation.

      Primary:

        1. Improved tolerance to per os (PO) solid food intake

        2. Decrease in abdominal pain (both at baseline and that associated with PO intake)

      Secondary:

        1. Decrease/elimination of pre-existing nausea/vomiting frequency and severity

        2. Decrease/elimination of analgesic use

        3. Background

           Experience with Procedure:

           CT-guided, celiac ganglion temporary block with liposomal bupivacaine. The PI, Dr.
           Georgiades has performed CT-guided nerve blocks hundreds of times, including celiac
           ganglion block, over the past 15 years. Nerve and specifically celiac ganglion block is
           an approved procedure for abdominal pain treatment, and is performed by Interventional
           Radiology at Johns Hopkins. Dr. Georgiades is a full time faculty in the Division of
           Interventional Radiology. He has privileges for performing CT-guided Celiac Ganglion
           block, as well as conscious sedation. Dr. Georgiades will be the only investigator
           performing this procedure in the test population.

           Clinical Data (with medication):

           Liposomal bupivacaine has long been used as an effective local analgesic, especially in
           orthopedic and plastic surgery.

           Clinical Data (Celiac ganglion block):

           Celiac ganglion block has been used for over a century for the treatment of abdominal
           pain. CT-guided celiac ganglion block has been introduced in the 1950s and most commonly
           performed with a combination of lidocaine and alcohol for permanent celiac ablation.

           Experience with Medication:

           Liposomal bupivacaine is an (food and drug administration) FDA approved drug and has
           long been used as a local anesthetic. It is simply a long acting formulation of
           bupivacaine. Bupivacaine's half-life is 2.7 hours. Since the procedure is performed
           under conscious sedation, the effects of bupivacaine cannot be distinguished from those
           of the medication given for sedation (Versed and fentanyl). The half-life of liposomal
           bupivacaine on the other hand, is approximately 24 hours. Therefore any symptom relief
           on post-test day #1 or 2 can be attributed to celiac ganglion blockade and not to
           sedation medication.

           Liposomal bupivacaine is available in 266 mg vials which is the maximum recommended
           single dose for adults.

        4. Study Procedures a. Study design, including the sequence and timing of study procedures
           (distinguish research procedures from those that are part of routine care). The research
           protocol is highlighted in light brown below. All else is part of the patient's standard
           of care treatment. There are two potential patient populations than are candidates for
           the research protocol. 1. those with dysautonomia-related GI dysmotility, misdiagnosed
           as having MALS after MALS surgery fails to relieve symptoms, and 2. those with known
           dysautonomia-related dysmotility and related symptoms. The research procedure includes
           the CT-guided celiac ganglion block only. This test will be used to confirm (or exclude)
           dysautonomia as the patient's cause of GI symptoms. Those who have symptom relief after
           the test block, will proceed with open celiac ganglion resection.

      Treatment Description:

      1. SELECTION/RECRUITMENT

      Potential Population Pool (PPP):

      Adolescents and adults with diagnosis of :

        1. Median Arcuate Ligament Syndrome (MALS)

        2. Both MALS & Postural orthostatic Tachycardia Syndrome (POTS)

        3. POTS or other Dysautonomia symptoms & bowel dysmotility

      Study Population (Subgroup of PPP):

        1. MALS patients with little or no improvement after laparoscopic arcuate ligament release

        2. MALS & POTS patients with little or no improvement after laparoscopic arcuate ligament
           release

        3. POTS/Dysautonomia patients with bowel dysmotility Symptoms: Required: Chronic nausea,
           food intolerance, abdominal pain, Additional: Chronic vomiting, need for enteral or
           parenteral Nutrition, hyperhidrosis, complex regional pain syndrome, Raynaud's Exclusion
           Criteria: Evidence for non-dysautonomia related causes of the patient's symptoms.

      Must Exclude: Chronic cholecystitis, gastritis, peptic ulcer disease, gastro esophageal
      reflux, celiac disease, mesenteric atherosclerotic disease, vasculitis, anorexia, depression,
      other psych issues, etc Complete Compass 31 (Validated Autonomic Function Score)
    

Intervention name(s): Celiac ganglion block; Liposomal bupivacaine
Intervention type(s): Procedure; Drug
Intervention description(s): The celiac ganglion block will be performed under CT guidance and with the patent under moderate sedation. With the patient prone the back will be prepped and draped sterility. Under CT guidance two 22 gauge needles will be placed with the tips on either side of the celiac artery. This is the location of the celiac ganglia. Liposomal bupivacaine will then be injected in that location. Maximum dose is 133 mg for 75 kg person. For lower weight patients, dose will be weight based. Then patient will be observed for 1-2 hours post procedure and then discharged to home; Liposomal bupivacaine will then be injected in that location. Maximum dose is 133 mg for 75 kg person. For lower weight patients, dose will be weight based.
Other intervention name(s): Exparel
Intervention MeSH terms: Bupivacaine
Intervention model: Single Group Assignment
Intervention model description: 10 patients with chronic GI dysmotility, chronic nausea/vomiting and feeding intolerance requiring G-J feeding and considered for Celiac Ganglion resection
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: celiac ganglion block; resection; bowel dysmotility