Analgesic Duration of Long Acting Local Anesthetics for Low Volume Ultrasound-guided Interscalene Brachial Plexus Block
Condition: Brachial Plexus Block; Anesthetics, Local
Study type: Interventional

Summary: 
      Severe pain following shoulder surgery is common and remains a major challenge. The
      interscalene nerve block is well suited for operations on the shoulder or upper arm, for
      providing surgical anesthesia as well as prolonged effective postoperative analgesia.

      Modern ultrasound guided ISB (US-ISB) allows for more accurate, targeted deposition of local
      anesthetic. The current trend is to lower the volume of local anesthetic for
      ultrasound-guided interscalene block in order to reduce potential complications such as
      phrenic nerve paralysis and local anesthetic toxicity. However, at low volumes the analgesic
      duration of the block could be compromised. Studies to elucidate the best local anesthetic
      agent, concentration and adjuncts to prolong analgesia at low volumes are needed. Ropivacaine
      and Bupivacaine are long acting local anesthetics commonly used for peripheral nerve blocks,
      however, there are no studies comparing their analgesic duration in the setting of low volume
      interscalene block to date.

      This study will investigate the analgesic duration of 0.5% Ropivacaine versus 0.5%
      Bupivacaine with 1:200,000 epinephrine versus 1% Ropivacaine for low volume US-ISB.

      This study aims to conduct a comparison of the duration of post operative analgesia achieved
      by these agents, hence allowing the appropriate local anesthetic agent and concentration
      selection in low-volume techniques.
    

Detailed description: 
      Hypothesis:

      0.5 % Bupivacaine with 1:200,000 epinephrine and 1% Ropivicaine provide longer duration
      analgesia than 0.5% Ropivicaine following a low dose ultrasound guided interscalene brachial
      plexus block (US-ISB)

      Background and Rationale:

      Severe pain following shoulder surgery is common and remains a major challenge. The
      interscalene approach to the brachial plexus is particularly well suited for operations on
      the shoulder or upper arm for providing surgical anesthesia as well as prolonged effective
      postoperative analgesia.

      Despite the benefits, the interscalene approach may present risks and complications. Common
      complications of the interscalene nerve block include phrenic nerve blockade , Horner's
      syndrome, recurrent laryngeal nerve blockade, and vasculature puncture. Rare, but potentially
      devastating, complications include carotid artery puncture and intervertebral artery
      injection, pneumothorax, subdural injection, intervertebral foramina injection resulting in
      spinal or epidural anesthesia, nerve injury and local anesthetic toxicity have been reported.

      The use of ultrasound (US) in regional anesthesia has allowed for easy visualization of the
      nerve, the needle, and the dispersion of the anesthetic, facilitating adequate injection in
      the perineural region. US-guided blocks have been associated with high success rates, reduced
      latencies, and reduced LA doses. A number of recent studies have confirmed that the use of
      ultrasound (US) also allows for a significant reduction in the local anesthetic volume for an
      effective interscalene nerve block. This reduction in volume of local anesthetic not only
      translates into reduced risk of local anesthetic toxicity but also a substantial reduction in
      the incidence of phrenic nerve paralysis.

      Based on the available research to date it appears that an effective interscalene block can
      be performed with a small volume of 5 ml of local anesthetic while minimizing the incidence
      of phrenic nerve palsy and local anesthetic toxicity. Based on the limited data available
      thus far the analgesic duration of the block does not appear to be compromised with the low
      volume techniques. However the critics of the low volume US-ISB persist with the belief that
      low-volume techniques, with their reduced local anesthetic dose, inherently produce a shorter
      duration block of lesser quality compared to higher volume. To date there are no studies
      comparing the analgesic duration of available and commonly used long acting local anesthetics
      in the setting of low-volume ISB technique.

      Bupivacaine and ropivicaine are the preferred long acting local anesthetics as they provide
      prolonged analgesia in the postoperative period. However, ropivacaine due to its reduced
      lipophilicity is generally considered less potent than bupivacaine with a shorter duration of
      action . The magnitude of this potency difference however is not clearly quantified and
      differs with varying techniques. In some studies, the potency difference amounts up to 50%
      whereas in other studies the difference is negligible. This may be due to the fact that this
      potency difference is dose dependent phenomenon. Ropivacaine has similar potency to
      bupivacaine at higher doses (e.g., doses required for peripheral nerve blocks for surgical
      anesthesia), ropivacaine is less potent than bupivacaine at lower doses, such as those used
      for epidural or intrathecal analgesia .

      Clearly for low volume US-ISB, ropivicaine's potentially improved safety profile becomes
      clinically insignificant, and the dose dependent reduced potency may play an important role
      in decreasing the duration of analgesia. Previous studies looking at the performance of
      ropivicaine and bupivicaine for upper extremity peripheral nerve blocks have only been done
      in high volume settings. In these studies the high dose of local anesthetic used may have
      masked any difference in potency of bupivacaine and ropivicaine.

      Clearly future studies are needed to better define the analgesic duration of low volumes
      US-ISB and determine the effects of different local anesthetics, different concentrations and
      adjuncts on the duration and quality of the block at these low volumes.

      Specific Objective

      To investigate the analgesic duration of 0.5% ropivacaine versus 0.5% bupivacaine with
      1:200,000 epinephrine versus 1% ropivacaine for low volume US-ISB.

      Protocol:

      Patients scheduled for arthroscopic shoulder surgery will be approached for participation by
      research assistants in the pre-operative anesthetic clinic. Patients providing informed
      consent will be allocated to one of three groups using a computer generated random number
      table and blinding of group allocation will be maintained with sequentially numbered, sealed,
      opaque envelopes.

      On the day of surgery, patients will be pre-medicated with oral acetaminophen 1000mg (650mg
      if < 60kg), and oral celecoxib 400mg (200mg if < 60kg). Once intravenous access is secure and
      standard monitors applied (electrocardiogram, non-invasive blood pressure cuff, continuous
      oxygen saturation), patients will receive sedation with intravenous midazolam (1-2mg). The
      lateral aspect of the neck including the supraclavicular fossa ipsilateral to the surgical
      site will be cleansed with an isopropyl alcohol/chlorhexidine gluconate solution. The
      US-guided ISB will be performed under sterile conditions by a staff regional
      anesthesiologist, or regional anesthesia fellow. The ISB will be performed using a 13-6 MHz
      38-mm linear US probe with appropriate sterile barrier (M-Turbo®; SonoSite Inc., Bothell, WA)
      at the upper trunk level via posterior approach with a 22-gauge insulated 50-mm regional
      block needle (Stimuplex®; B.Braun Medical, Bethlehem, PA). After satisfactory position of the
      needle tip is achieved and visualized, the injectate will be administered slowly.

      The local anesthetic injectate will be prepared in a blinded syringe by trained anesthesia
      assistants that are aware of group allocation but will take no further part in study
      procedures or assessments. This individual will prepare the injectate in a 5ml syringe.

      All other personnel - patients, anesthesiologists performing the ISB or caring for the
      patient in the operating theatre, surgeons, research assistants performing outcome measures,
      and statisticians - will remain blinded.

      The block will be assessed at 20 minute intervals, using loss of pinprick sensation to C5/C6
      dermatome and strength of shoulder abduction. Patients will be excluded if there is no
      evidence of both sensory and motor block at 20 minutes.

      Patients will undergo general anesthesia with a standardized induction technique using
      fentanyl 1mcg/kg, and propofol 1-3mg /kg. Endotracheal intubation will be facilitated with
      rocuronium 0.6mg/kg if necessary or a laryngeal mask airway can be placed for spontaneously
      breathing patients. Anesthesia will be maintained using the inhalational anesthetic
      sevoflurane (Abbott Corp) with an end-tidal concentration of 1.4 - 2%. Muscle relaxation will
      be reversed using a combination of neostigmine (0.04mg/kg) and glycopyrrolate (0.007mg/kg) in
      necessary. Supplementary intraoperative opioids for pain (systolic blood pressure or heart
      rate increase from baseline of greater than 10% from surgical stimulus) will be given at the
      discretion of the attending anesthesiologist (intravenous hydromorphone [0.2 mg per bolus] or
      fentanyl [25 ug per bolus]) intravenous . Standard anti-emetic prophylaxis with the serotonin
      antagonist ondansetron will be given.

      Upon arrival to the recovery room, pain (Verbal Response Score ≥4 or patient request for
      analgesia) will be treated with hydromorphone in 0.2-0.4mg increments every 5 minutes as
      needed. Once oral intake is initiated, patients will receive one of two oral analgesic
      preparations as needed: Tylenol #3® (acetaminophen 325 mg/codeine 30 mg/caffeine 15 mg per
      tablet), or oxycocet (acetaminophen 325 mg/oxycodone HCl 5 mg per tablet) if intolerant to
      codeine. Upon discharge from hospital, patients will receive a prescription for Tylenol #3®
      as needed, or oxycocet if intolerant to codeine. After discharge, patients will complete a
      home diary and return to the study team using a stamped, return-addressed envelope. Patients
      will be asked to record the time at which they first experience pain at the surgical site,
      the time when they first consume prescribed opioid analgesics for surgical site pain and
      regain normal (or baseline equivalent) strength in their biceps and hand. On postoperative
      days (POD) 1, 2 at 12h00 patients will be requested to document interval oral analgesic
      consumption, presence of nausea or vomiting, presence of weakness in the operative arm, and
      presence of paresthesia (numbness or tingling) in the operative arm. The doses of oral
      codeine or oxycodone consumed by each patient will be converted into equianalgesic doses of
      conversion ratios will be employed according to the general monograph for opioids in the
      Canadian Pharmacists' Association Compendium of Pharmaceuticals and Specialties (36th ed.,
      2001) as follows: oral oxycodone: oral morphine sulphate = 1:2, and oral codeine: oral
      morphine sulphate = 6.6:1.

      Sample size calculation

      Based on the investigator's clinical experience with low dose US-ISB (Ropivacaine 0.5% 5ml)
      as well as previously published work, Investigators expect analgesic duration of 12 hours
      with a standard deviation of 4 hours. The sample size calculation is based on being able to
      detect a difference of 30% (3.6 hours ) in duration of analgesia between the three groups.

      It is estimated that 57 patients are required (19 per group) to achieve 80% power to detect
      differences among the means versus the alternative of equal means using an F test with a 0.05
      significance level. The size of the variation in the means is represented by their standard
      deviation, which is 1.70. The common standard deviation within a group is assumed to be 4.00.
      To account for incomplete data or loss to follow-up, the plan is to recruit 60 patients
      total.

      Data collection

      Data will be collected on a customized case report form that includes all relevant
      demographic and intra-operative data as well as each outcome sought. Patients will be
      provided with a home diary to complete that will capture all outcomes sought that are not
      obtained in hospital.

      Statistical analysis

      Demographic data will be summarized and expressed using appropriate measures of central
      tendency and dispersion for continuous data, and frequency for categorical data. The primary
      outcome, time to first sensation of pain at the surgical site, will be summarized as mean
      (SD) or median (IQR) after testing the data for normality with the Kolmogrov Smirnoff test.
      This will also determine whether groups will be compared with the t-test (for normally
      distributed data) or Kaplan Meier Survival Curves (for skewed data). Secondary outcomes that
      are time based will also be assessed in the above manner (time to first analgesic request,
      duration of motor block). Continuous secondary outcomes (opioid consumption, VRS, room air
      SpO2) will be assessed with repeated measures ANOVA or the Mann Whitney U-test for
      non-parametric data. Categorical outcomes will be compared with the Chi square or Fisher's
      exact test as necessary.
    

Intervention name(s): Ropivacaine 0.5%; Ropivacaine 1%; Bupivacaine 0.5% + epinephrine 1:200,000
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Ropivacaine 0.5% is used for low-volume ultrasound-guided interscalene brachial plexus block.; Ropivicaine 1% is used for low-volume ultrasound-guided interscalene brachial plexus block.; Bupivacaine 0.5% + epinephrine 1:200,000 is used for low-volume ultrasound-guided interscalene brachial plexus block.
Intervention MeSH terms: Epinephrine; Bupivacaine; Ropivacaine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Brachial Plexus Block; Anesthetics, Local