Bupivacaine Versus Ropivacaine on Diaphragmatic Motility and Ventilatory Function
Condition: Paresis
MeSH terms: Paresis
Study type: Interventional

Summary: 
      Background: Outpatient continuous interscalene brachial plexus blocks are used to control
      pain after shoulder surgery, with infusions of 0.125% bupivacaine or 0.2% ropivacaine. There
      have been no studies comparing the effects of these two formulations. The major concern is
      hemidiaphragmatic paresis, and since ropivacaine preferentially blocks sensory fibers, it may
      cause less blockade of the phrenic nerve. This study was to evaluate the effects of
      continuous interscalene brachial plexus infusions, with the hypothesis that respiratory
      function is more affected by 0.125% bupivacaine than 0.2% ropivacaine, with equal effects on
      pain relief.

      Methods: All patients underwent baseline spirometry and ultrasound evaluation of
      diaphragmatic excursion, followed by interscalene catheter placement for their surgery, then
      randomized to receive a pump containing 0.2% ropivacaine or 0.125% bupivacaine. Patients
      returned to the hospital the following day for spirometry, ultrasound reevaluation, and
      evaluation of their pain level since discharge.
    

Detailed description: 
      INTRODUCTION

      Shoulder surgery is associated with severe postoperative pain and continuous interscalene
      brachial plexus blocks can control this pain. Compared to single-shot injections, continuous
      interscalene blocks can increase patient satisfaction, decrease narcotic requirements, which
      then decreases postoperative nausea and vomiting , improve quality of sleep and decrease
      hospital length of stay .

      The concept of continuous peripheral nerve blocks at home (CPNBH) with disposable pumps began
      in 1998 in Sweden. The authors chose 0.125% bupivacaine for interscalene catheters and their
      choice was not based on any evidence in the literature, but rather "because this
      concentration was already available at the institution for epidural infusions" (personal
      communication, Dr. Narinder Rawal, January 2013). Two years later, as ropivacaine became more
      widely available, others chose to evaluate the safety and efficacy of 0.2% ropivacaine for
      continuous interscalene infusions. Again, the choice of this specific concentration was not
      evidence-based, but rather "because the company made it in this concentration" (personal
      communication, Dr. Stephen Klein, January 2013). To date, published reviews show that most
      studies use either of those formulations, yet there have been no studies comparing the
      effects of these two drugs and concentrations, particularly on pain relief and on major side
      effects of CPNBH.

      One of those major side effects is ipsilateral phrenic nerve paresis. This is because
      blockade of the brachial plexus at the interscalene groove with a single large-volume
      injection causes diaphragmatic hemiparesis in 100% of patients. This incidence is decreased
      to 20% with a continuous infusion of a dilute solution11, where 9% of patients have a
      subjective feeling of shortness of breath. An ideal infusate in CPNBH would control
      postoperative pain and have minimal effects on the phrenic nerve.

      Ropivacaine has been shown to have blockade properties that differ from bupivacaine;
      specifically, ropivacaine seems to preferentially block sensory nerve fibers, while weakly
      blocking motor fibers. It is not known whether this translates into a more attenuated block
      of the phrenic nerve with ropivacaine. Therefore, the purpose of this study was to evaluate
      the effects of continuous interscalene peripheral nerve blocks with 0.125% bupivacaine versus
      0.2% ropivacaine, comparing their effect on pain relief and respiratory function. The primary
      hypothesis is that respiratory function is more affected by bupivacaine than ropivacaine,
      with equal effects on pain relief.

      METHODS

      Patients who were scheduled for moderately to severely painful unilateral shoulder surgery
      who agreed to continuous interscalene catheter placement were enrolled in the study and gave
      written consent.

      All patients underwent baseline studies, which included ultrasonic evaluation of
      diaphragmatic excursion and bedside spirometry. All were placed in a 45-degree upright
      position on a hospital stretcher. Assessment of the range of motion of both hemidiaphragms
      was performed with a curvilinear low frequency ultrasound probe The probe was placed
      subcostaly in the mid-axillary line, angled 45 degrees cephalad on both sides, using the
      liver on the right and the spleen on the left as acoustic windows. If there was difficulty in
      obtaining a satisfactory image (frequently the case on the left side), the probe was moved
      laterally toward the anterior axillary line until the diaphragm was visualized. Range of
      motion of the diaphragm with normal respiration was assessed visually to exclude any
      pre-existing diaphragmatic motion abnormalities, followed by sigh and sniff tests. During the
      'sniff test', movement of the diaphragm was evaluated from the resting expiratory position
      during quick inspirations of air taken through the nose. During the 'sigh test', the range of
      diaphragmatic motion from the resting expiratory position to deep inspiration was measured.
      The normal caudad movement of the diaphragm was recorded with the distance traveled in
      centimeters. Each measurement was performed 3 times and the best value was recorded. A mark
      was placed on the patients' skin where measurements were taken, to ascertain that the
      diaphragm was assessed from the same site during the follow-up visit.

      Bedside spirometry was performed for each patient, again in a 45-degree upright position in a
      hospital stretcher. After instructing the patient, forced expiratory volume at 1 second
      (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF) were measured three times,
      and the best measurement was recorded.

      Following this, with standard noninvasive monitoring and oxygen via nasal cannula, all
      patients had interscalene catheter placement with midazolam sedation (up to 5 mg). All
      catheters were placed using and nerve. After draping the area and sheathing the ultrasound
      probe (SiteRite; Bard Access Systems, Salt Lake City, UT), a local anesthetic skin wheal was
      placed and a 17-gauge Tuohy insulated needle was inserted in-plane with a posterior approach,
      through the middle scalene muscle. The prevertebral fascial plane was punctured and the
      needle tip was placed in the area of connective tissue between the C5 and C6 nerve roots. A
      19-gauge stimulating catheter was then inserted through the needle and attached to the nerve
      stimulator, set at a current of 0.48 mA, 100 microsecond pulse duration and 2 Hz frequency.
      The nerve stimulator settings were kept constant throughout the procedure. With ultrasound
      visualization and muscle twitches of the upper arm (biceps, triceps or deltoid), the catheter
      was threaded 5-6 cm beyond the needle tip. If stimulation was lost during threading, the
      catheter was gently withdrawn, the needle was moved slightly and the catheter was threaded
      again with ultrasound visualization and visible muscle twitching. If this was not possible
      after five minutes (from the first catheter threading), the patient was removed from the
      study. Once the catheter was threaded successfully, the needle and catheter stylet were
      removed and the catheter was withdrawn until the skin marking was 2-3 cm beyond the needle
      depth. The nerve stimulator was reattached to the catheter to verify the presence of a muscle
      twitch at 0.48mA, and a 5 ml volume of 1.5% lidocaine with epinephrine 1:200,000 was injected
      under direct ultrasound vision, confirming local anesthetic spread.

      Prior to transport into the operating room and after negative aspiration, all catheters were
      injected with 30 ml plain mepivacaine 1.5%, followed by an assessment of the quality of the
      sensory and motor block. A general anesthetic was administered with propofol induction and
      maintenance with vecuronium and sevoflurane. No opioids or additional benzodiazepines were
      given. Three hours after the initial injection, whether patients were in the operating room
      or in the Post Anesthesia Care Unit (PACU), an additional 10 ml plain mepivacaine 1.5% was
      given through the catheter. Upon arrival to PACU, pain control was assessed (on a numerical
      scale from 0 to 10), catheter and dressing integrity were verified and patients were
      randomized by the pharmacists, using a computer-generated randomization table, to receive a
      disposable pump (On-Q CB004, I Flow Corporation, Lake Forrest, CA) containing 400 ml of 0.2%
      ropivacaine or 0.125% bupivacaine and set at a rate of 6 ml/hr. Except for the pharmacist,
      all other personnel were blinded to the content of the pumps.

      The following day (20-28 hours after discharge), patients returned to the hospital and were
      asked about their highest pain level (on a numerical scale from 0 to 10) since surgery and
      the number of pain pills taken since discharge, difficulty breathing, the amount of numbness
      in the hand, and any problems with the catheter or the pump. The catheter sites were examined
      and when necessary, the dressing was reinforced. After this, patients underwent pulmonary
      testing, again on a stretcher in a 45-degree upright position. Repeat ultrasonographic
      evaluation of diaphragmatic excursion (sniff and sigh tests) and bedside spirometry were
      performed. For the ultrasonographic evaluation, the previously marked sites were used for 3
      measurements, recording the best effort. If on the sigh and/or sniff test a caudad movement
      of the hemidiaphragm was seen, the distance was measured, recorded and assigned a positive
      value (+). If paradoxical cephalad movement of the diaphragm was observed, the distance was
      given a negative value (-). Following completion of the ultrasonographic evaluation,
      spirometry was performed. Again FEV1, FVC and PEF were measured and the best of 3 attempts
      was recorded. Patients were sent home with CPNBH for an additional two days. Per routine, an
      anesthesiologist called them every day to assess their pain level, shortness of breath,
      numbness, and integrity of the catheter site.

      Statistical Analysis Determining the study size was allowing for a 15% difference in forced
      expiratory volume at 1 second (FEV1) between the two. A non-inferiority power analysis was
      chosen to obtain an alpha error probability of 0.05 and a 1 minus beta error probability of
      0.8. A sample size of 30 patients (15 per group) was chosen to give the study sufficient
      power. A T-test (unmatched pairs) was used to compare continuous data between the two groups.
      If data had a non-normal distribution, a non-parametric Kruskal-Wallis ANOVA was used to
      examine differences between means. Categorical data was expressed as mean + standard error.
      Statistical significance was set at a p-value ≤ 0.05, two-tailed.
    

Intervention name(s): Ropivacaine; Bupivacaine
Intervention type(s): Drug; Drug
Intervention description(s): Post-operative epidural 0.125% Ropivacaine Interscalene brachial plexus block, 20-28 hrs post surgery.; Post-operative epidural 0.125% Bupivacaine Interscalene brachial plexus block, 20-28 hrs post surgery.
Other intervention name(s): Naropin; Marcaine
Intervention MeSH terms: Bupivacaine; Ropivacaine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: Nerve Block/adverse effects; Phrenic Nerve; Respiratory function; Pain measurement