Detecting Compartment Syndrome Pain in the Presence of Regional Anesthesia in Healthy Volunteers
Condition: Compartment Syndrome of Leg; Healthy
MeSH terms: Compartment Syndromes; Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      The goal of the study is to determine how different types of Regional Anesthesia (nerve
      blocks) can be helpful to patients with lower extremity trauma who develop compartment
      syndrome (an increased pressure in the fascial compartments) which can occur after injury to
      the leg.

      This is a prospective, randomized study in healthy volunteers, who will undergo testing of
      the leg using a cuff inflation system, involving quantitative sensory testing (QST),
      questionnaire completion, with ultrasound scanning and nerve blocks in a supervised,
      monitored setting (BWH Clinical Investigation Center).

      Specific Aims

        1. Determine the effect of adductor canal-saphenous nerve block (ACB) and popliteal-fossa
           nerve block (SNB-PF) vs no block on pressure and ischemic pain in a model of compartment
           syndrome.

             1. Hypothesis: There will be minimal or no change in pressure pain threshold and
                tolerance and pain ratings with ACB alone

             2. Hypothesis: There will be an increase in pressure pain threshold and tolerance and
                decrease in pain ratings with ACB plus popliteal-fossa nerve block (SNB-PF),
                compared to no block

        2. Determine the concentration dependence of SNB-PF effect on pressure and ischemic pain by
           comparing increasing doses of local anesthetic.

             1. Hypothesis: There will be a greater increase in pressure pain threshold and
                tolerance and great decrease in pain ratings with 1.5% mepivacaine than with 0.375%
                mepivacaine.
    

Detailed description: 
      Please complete the survey (copy and paste into new link).
      https://redcap.partners.org/redcap/surveys/?s=D4A4TN9TDL We will not contact you if the
      survey is incomplete.

      Please contact us via email (ykchen@partners.org) about this study with subject line
      "Interested in participating in Compartment Syndrome Study"

      Screening and Enrollment:

      Healthy volunteers will be recruited, and all interested individuals will be invited to
      contact study staff to hear more about the study requirements and undergo a brief phone
      screen to determine eligibility. After their initial phone screen with study staff,
      interested subjects meeting eligibility requirements will be provided with an electronic copy
      of the consent form, perform a video consent, and schedule a study visit, to be conducted in
      the Clinical Investigation Center at Brigham and Women's Hospital. A 5 hour, 1 office visit
      is required.

      All subjects will also undergo a survey-based COVID screen within 24 hours prior to the
      study.

      Study day:

      Immediately upon arrival for their study appointment, the physician investigator will go
      through the consent form in detail with each potential participant, and they will also be
      given a chance to read it thoroughly and have questions answered. Special care will be taken
      during the consent process to ensure subjects are fully competent and understand the nature
      of the questionnaires and testing procedures, including a brief demonstration of the devices
      and testing done. If agreeable to the study procedures after having questions answered,
      participants will provide informed consent. Each participant will be assigned a random ID
      number, and data will be collected, entered, and analyzed by ID number only. The subject's
      status as a patient will be unaffected by his/her decision to participate. If subject decides
      against participation at this point, they will be reimbursed for their time ($20).

      Enrolled participants will complete basic deidentified demographic, clinical, psychosocial,
      and pain questionnaires. Brief validated questionnaires will include the PROMIS anxiety,
      depression, and sleep disturbance short forms, Pain Catastrophizing Scale (PCS), situational
      pain catastrophizing scale (sPCS), Brief Symptom Index, Fibromyalgianess scale, Brief Pain
      Inventory, Positive and Negative Affect Schedule, and pain coping strategies questionnaire.

      After completing questionnaires, subjects will lie on a stretcher, with head of bed elevated
      to 30-45 degree angle according to comfort, with legs and feet exposed for testing.

      QST testing Pressure pain threshold: Pressure algometry is the most commonly used test for
      static mechanical pressure sensation in the skin and in deep tissues. Pressure algometers
      deliver a firm and quantifiable pressure through a flat base applied to the skin. The
      electronic pressure algometer that we will use (Wagner Instruments) is a hand-held algometer
      utilizing a pressure-sensitive strain gauge, covered by a 0.5 cm2 circular probe. The probe
      is covered with a soft polypropylene disk, to avoid injury to the skin. The pressure applied
      through the probe is transduced, amplified, and converted to electrical reading on a digital
      display. The pressure will be slowly increased (1 lb/s) and the participant will be asked to
      note when they first feel pain and when they want the pressure to stop , which will be
      recorded as the pressure pain threshold and tolerance, respectively.120 This process will be
      repeated on the trapezius and the forearm, alternating between sides of the body with 20
      seconds between measurements.

      Pin Prick: This tests the detection and intensity of sharp type pain. In addition, it is
      often used as a modality to test temporal summation of pain with repeated stimuli. The
      conductor of the test will touch the participant on the finger with weighted mechanical
      probes in ascending order (64 mN, 128 mN, 256 mN, 512 mN), making sure to keep the probe
      perpendicular to the skin, and allowing the full weight to be resting on this point (i.e. the
      weight moves within the barrel), but without touching the barrel/cylinder itself to the skin.
      The participant will be instructed to rate the pain (0-10) of each stimulation. The conductor
      will make note of the lowest weight pin prick the participant indicated caused a 1-3 out of
      10 pain. Then the conductor will perform the test of temporal summation to repeated punctate
      stimuli, which is considered an index of central pain-faciliatory processes. The pin prick
      weight that the participant noted was a 1-3 out of 10 pain is applied to the skin of the
      dorsal fingers at a frequency of 1Hz. Ten stimuli are applied, and the patient will be asked
      to rate the sensation of pain from the fifth, and tenth stimulus, as well as 15 seconds after
      the end of the stimulus train (PAS). The wind-up phenomenon occurs with progressive increase
      evoked pain with repeated stimulation and represents an index of central sensitization.
      Testing order will be performed on each hand, bilaterally, and on each foot.

      Pressure Pain Threshold Assessment:

      Pressure pain will be assessed through response to cuff pressure algometry (CPA). Tonic,
      deep-tissue, mechanical stimulation will be applied using a Hokanson rapid cuff inflator,
      which allows specific calibrated pressures to by administered and held for defined time
      periods. Using an adjustable cuff (similar to standard blood pressure cuff) wrapped around
      the leg, centered around the largest diameter of the gastrocnemius muscle, pressure will be
      increased by turning a manual dial at a rate of approximately 10-20 mmHg/second until the
      subject first feels pressure, and thereafter at approximately 5-10 mmHg/s, at which time
      subject will be asked to note when they first start feeling pain and then when they feel as
      though the pain is a 4, 6, 8 and 10 out of 10 VAS score (0 = no pain, 10 = worst pain), after
      which the cuff will be immediately deflated. Participants will be given a break. Cuff
      pressure at each of these points will be recorded 3 times for each leg to determine baseline
      pain thresholds.

      Ischemic Pain Assessment:

      The cuff will be re-inflated to the subject's average pressure previously determined to
      produce 4 out of 10 pain for that leg, and held for 5 minutes. A pulse oximeter will be
      placed on the big toe to monitor ischemia (pulse oximetry wave expected to disappear).
      Subjects will be asked for pain score at rest every 30 seconds, and pain score on passive
      stretch of gastrocnemius every 60 seconds. The participant will be reminded immediately
      before cuff inflation that they may ask for the pressure cuff to be deflated at any time, in
      which case this time will be recorded. Subjects will be asked to indicate the presence of
      tingling (paresthesias), and will rate pain at rest 30 and 60 seconds following cuff
      deflation (painful after sensations), as well as pain with passive stretch of gastrocnemius
      at 60 seconds after cuff deflation.

      There will be a 1 minute break, then the cuff pressure will be inflated to a pressure
      corresponding to the next pain level as initially identified on the averaged baseline testing
      (ex: if pressure 4/10 was 100 mmHg and 6/10 was 150 mmHg, cuff pressure will first be held at
      100 mmHg and held for 5 minutes, followed by a 1 minute break, and then reinflated at 150
      mmHg and held for 5 minutes, followed by 1 minutes break, etc.). The above procedure will be
      repeated for cuff pressure at 6/10, 8/10, and 10/10. This will be done first on the "control
      leg" and then on the "block leg" prior to the nerve block placement. Subjects will be
      reminded that they may discontinue the cuff inflation at any point, and the time of cuff
      inflation recorded.

      IV placement:

      A 20 g IV will be placed prior to the start of any nerve block procedure. Site of IV
      placement will be cleaned with alcohol swab and initially anesthetized with 1% lidocaine
      administered through a small needle to allow greater comfort with IV placement.

      Nerve Blocks:

      Saphenous Nerve Block (ACB):

      Subjects will lie supine with block leg slightly abducted. Standard monitors will be applied
      for vital monitoring (continuous pulse oximetry, EKG, blood pressure cuff every 5 minutes),
      and this monitoring continued until 20 minutes after block completion. Using sterile
      technique (cleaning of skin with chloroprep, sterile gloves, mask, sterile cap, sterile
      needle, sterile ultrasound probe cover and sterile gel), an ultrasound-guided approach will
      be used to identify the saphenous nerve and surrounding sonographic landmarks (sartorius
      muscle, vastus medialis, femoral artery, femoral vein, and adductor magnus). With a small
      needle, a small skin wheal of 1 cc of 1% lidocaine will be used to anesthetize the skin.
      Afterwards a standard 21 g, 10 cm block needle will be inserted and directed under ultrasound
      guidance to the saphenous nerve location. Aspiration on block syringe will be performed to
      confirm that needle tip is not within a vascular structure to avoid intraarterial or venous
      injection of local anesthetic. Incremental injection (5 cc at a time) of 1.5% mepivacaine
      will follow, with a total of 10 cc (150 mg) deposited around the saphenous nerve.

      Popliteal sciatic Nerve Block (SNB-PF): (for dual nerve block group only) Participant will
      lie supine, with leg elevated to allow access to posterior leg for US scanning. Using sterile
      technique, an ultrasound-guided approach will be used to identify the common peroneal nerve
      and tibial nerve at the level of the popliteal fossa, and surrounding sonographic landmarks
      (femur, popliteal artery, and popliteal vein). The common peroneal and tibial nerves will be
      followed proximally by scanning proximally along the leg with the ultrasound until they form
      a unitary nerve (sciatic). With a small needle, a small skin wheal of 1 cc of 1% lidocaine
      will be used to anesthetize the skin of the lateral level at this level. Afterwards a
      standard 21 g, 10 cm block needle will be inserted and directed under ultrasound guidance to
      the sciatic nerve. Aspiration on block syringe will be performed to confirm that needle tip
      is not within a vascular structure to avoid intraarterial or venous injection of local
      anesthetic. Incremental injection (5 cc at a time) of 0.375% or 1.5% mepivacaine will follow,
      with a total of 15 cc (56.25 mg or 225 mg) deposited around the sciatic nerve.

      Expected timeline Pressure pain threshold assessment will take approximately 3 minutes and
      Ischemic pain assessment approximately 30 minutes (5 minutes per inflation pressure with 1
      minute for rest in between). Each assessment will be taken at baseline and 20 minutes after
      nerve block completion to allow full effect. Ultrasound measures of compartment pressures
      will be assessed before, during, and after pressure and ischemic pain assessment.

      Resolution of Nerve block: Nerve blocks with mepivacaine are expected to be resolved within
      4-6 hours, but monitoring will continue beyond this time as some normal variation in
      resolution may occur between individuals. Subjects will only be given assistance with getting
      off stretcher/chair if needed for 4 hours after nerve block placement. Strength testing of
      target nerve groups in lower extremity will be confirmed before subject is allowed to walk
      independently. Subjects gait and walking will be assessed and confirmed to be ambulating
      safely before discharge.
    

Intervention name(s): Mepivacaine Injection; Mepivacaine Injection
Intervention type(s): Drug; Drug
Intervention description(s): Injection of 0.375% mepivacaine in nerve block; Injection of 1.5% mepivacaine in nerve block
Other intervention name(s): Prilocaine; Prilocaine
Intervention MeSH terms: Prilocaine; Mepivacaine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Our patients will be randomized to one of six arms.
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Healthy volunteer; Regional anesthesia; Compartment Syndrome