Three-level Injection Paravertebral Block vs General Anesthesia in Mastectomy
Condition: Radical Mastectomy
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of the study is to investigate if paravertebral block for breast surgery may
      improve postoperative analgesia and shorten length of hospital stay. Within a prospective
      clinical trial sixty women (ASA I - III) undergoing unilateral mastectomy surgery with
      axillary dissection are enrolled. Exclusion criteria are general infection and local
      infection at the site of planned puncture, anatomic deformities of the thoracic spine,
      coagulation disorders, allergy against local anesthetics or contrast agents, pregnancy or
      breast-feeding and BMI ≥ 30 kg/m2.

      Patients are randomly assigned to two groups, 30 patients each, by using block of four
      method. Group I patients receive paravertebral block at spine level Th 4 via catheter; Group
      II patients will have general anesthesia without nitrous oxide.

      Paravertebral block (PVB) will be entirely performed by one person (1st author) with the
      patient in prone position. In randomly selected patients the catheter localization will be
      detected by fluoroscopy after injection of 0.5 ml contrast agent. The catheter positioned at
      about 8 cm from skin level, a mixture of 10 ml bupivacaine 0.5% plus 20 ml lidocaine 2% with
      adrenaline 1:200,000 will be injected sequentially 10 ml each while withdrawing the catheter
      2 cm after the first and again 2 cm after the second injection. Then the catheter will be
      removed. Low dose intraoperative sedation is provided with IV midazolam 2-3 mg, ketamine 0.5
      mg/kg bolus and continuous propofol using target-controlled infusion (TCI) system aiming at
      effect site concentration (Ce) of 1 - 1.5 mcg/mL to allow spontaneous breathing. In case
      surgical approach is not tolerated, the regional block is graded insufficient, and it is
      switched to general anesthesia.

      At postoperative care unit (PACU) the pain score using visual rating scale (VRS) from 0 to 10
      (worst imaginable pain) is assessed at rest and on movement of the shoulder every 15 minutes
      until 60 minutes. Analgesia is provided by IV morphine 0.04 mg/kg boluses with a 15-min
      dosing interval to maintain VRS - score < 3. Time to first analgesic demand and 24-hr
      analgesics consumption is recorded as well as postoperative nausea and vomiting (PONV).
      Complications are recorded including those related to the paravertebral block, such as
      Horner's syndrome, epidural spreading, hypotension that is not related to another. Patients
      will be checked 6, 12, and 24hr postoperatively for adverse effects, pain scores, and
      satisfaction scores.
    

Detailed description: 
      Multiple studies have shown that breast surgery is associated with significant postoperative
      pain, nausea, vomiting, and development of chronic pain. General anaesthesia is associated
      with a 50% incidence of nausea and vomiting among breast cancer surgery patients. The
      proposed benefits of regional anesthesia including paravertebral block compared to general
      anaesthesia are decreasing stress response, improving postoperative pain control and
      postoperative pulmonary function, decreasing cancer recurrence, and reducing thromboembolic
      events. However, the debate about these benefits is still controversial.

      Paravertebral block for breast surgery, either alone or additional to general anaesthesia is
      favored by many investigators, due to better postoperative analgesia and shorter hospital
      stay. In an elder investigation thermographic imaging was used to apply paravertebral block.
      After a single injection of 15 ml 0.5% bupivacaine at spine level Th9-Th10 there was a mean
      distribution of somatic block of five and of sympathetic block of eight dermatomes without
      any hemodynamic side effects. No bilateral spread was found. The authors contradicted the
      suggestions paravertebral block being ineffective and sometimes hazardous. However, their
      patients were chronic pain patients with a number of six only.

      Single-injection paravertebral block may not be sufficient to cover the relevant dermatomes
      C6 - Th6 for radical mastectomy with axillary dissection, when applied as the sole anesthetic
      technique. Some study groups performed paravertebral block with several injections. Four
      injections resulted in sufficient anaesthesia in 97% of these patients, whereas one injection
      was effective in only 11%. Though there is limited published evidence yet, a single injection
      for paravertebral block may be insufficient for extensive breast surgery, such as mastectomy
      including axillary evisceration. However, considering the potential risks of deep
      paravertebral puncture a limitation of punctures would be preferable. Inserting a
      paravertebral catheter far enough and in proper position offers the opportunity to apply the
      anesthetic agent at different sites, by moving the catheter backwards after each injection.

      The purpose of our study is to find out if injections via paravertebral catheter at three
      different levels are advantageous and efficient compared to general anesthesia in patients
      having mastectomy with axillary dissection.

      In addition, instead of 4 cm catheter insertion inside the paravertebral space (PVS) as the
      recommended, we used ultrasound-guided PVB (transverse view, out of plane technique), to
      facilitate further insertion of the catheter (8 cm) in the PVS. A contrast agent will be used
      in randomly selected patients to prove the exact site of the inserted catheter and to
      exclude/detect obstructions such as kinking.

      Methods: This is a prospective clinical trial. Patients have to agree documented by written
      informed consent. Sixty women, ASA I - III undergoing unilateral mastectomy surgery with
      axillary dissection, including radical lymph node removal or sentinel node biopsy are
      enrolled.

      Patients are randomly assigned to two groups, 30 patients each, by using block of four
      method. Group I patients receive paravertebral block at spine level Th 4 via catheter with
      injections at three different levels; Group II patients will have general anesthesia.

      Anesthetic preparation: After arrival at the OR standard monitoring is applied including ECG,
      noninvasive blood pressure and pulse oxymetry. Midazolam 0.05 mg per kilogram bodyweight is
      given intravenously to all patients to achieve mild sedation.

      Paravertebral block (Group I). Paravertebral block will be entirely performed by one person
      (first author) with the patient in prone position. The superior aspect of the Th4 spinous
      process is marked. After skin disinfection an 18-gauge Tuohy needle including attached saline
      filled syringe is inserted perpendicular to the skin at the Th3-Th4 interspace, using the
      area 2.5 cm lateral to T4 spinous process as Landmark. Under ultrasound guidance, the needle
      is advanced by out of plane technique, angled anteriorly until contact with the transverse
      process, and then redirected either caudal or cephalad and parallel to the spine advanced
      further until loss of resistance. After placement of the needle an end-hole 20 gauge catheter
      is inserted and advanced 8 cm beyond needlepoint into the paravertebral space. The catheter
      insertion is scored as 'easy', 'difficult' or 'impossible'. In randomly selected patients the
      catheter localization will be detected by fluoroscopy after injection of 0.5 ml contrast
      agent. The catheter positioned, a mixture of 10 ml bupivacaine 0.5% plus 20 ml lidocaine 2%
      with adrenaline 1:200,000 will be slowly injected sequentially 10 ml each while withdrawing
      the catheter 2 cm after the first and again 2 cm after the second injection. Then the
      catheter will be removed. Patients are returned to the supine position and remain for at
      least 30 minutes in the preoperative area. Sensory blockade is assessed by using pin-prick
      method.

      When analgesia is adequate patients are moved into the operating room. Intraoperative
      sedation is provided with low dose IV midazolam, ketamine bolus and continuous propofol using
      target-controlled infusion system to allow spontaneous breathing. In case skin incision or
      further surgical approach is not tolerated, the regional block is graded insufficient, and it
      is switched to general anesthesia.

      General Anaesthesia (Group II): Anesthesia is induced intravenously with propofol and
      fentanyl. Atracurium is used to facilitate tracheal intubation. Anesthesia is maintained with
      sevoflurane and 50% oxygen in air. Additional Fentanyl will be administered on discretion of
      the anesthesiologist.

      Data collection: Patients' biometric data, details of the clinical course, such as amount of
      anesthetics used, operation time, surgical difficulties, hemodynamic instability (if any) and
      similar are recorded. At postoperative care unit (PACU) the pain score using visual rating
      scale from 0 (no pain) to 10 (worst imaginable pain) is assessed at rest and on movement of
      the shoulder every 15 minutes until 60 minutes. Analgesia is provided by IV morphine boluses
      with a 15-min dosing interval to maintain VRS - score < 3. Time to first analgesic demand and
      24-hr analgesics consumption is recorded. Postoperative nausea and vomiting is assessed using
      a 3-point scale; Ondansetron is administered to treat it. Any complications are recorded
      including those related to paravertebral block, such as Horner's syndrome, epidural
      spreading, hypotension that is not related to another reason, pneumothorax and adverse effect
      of local anesthetics. Patients will be checked 6, 12, and 24hr postoperatively for adverse
      effects, pain scores, and satisfaction scores. During hospital stay, the patients receive one
      tablet of Ultracet (tramadol plus acetaminophen) and Celebrex 200 mg two times a day for pain
      relief and oral lorazepam before bedtime. Residents or nurses on postoperative care station
      and surgical ward both are blinded to the treatment groups.

      Sample size estimation: According to the data from a previous study paravertebral block
      compared to general anesthesia can reduce postoperative analgesia requirement (opioids +
      non-steroidal analgesics) up to 80%. Taking a 5% significance level as basis 30 patients per
      group is adequate.

      Statistical analyses: Parametric data are expressed as mean and analyzed using Student's T
      test. The non-parametric data are expressed as median (range) and analyzed using Mann-Whitney
      U Test. Repeated analysis of variance is used to compare VAS between groups. The association
      between the techniques and incidence of complications are evaluated by chi-square or Fisher's
      exact test as appropriate. Statistical analyses will be performed using SPSS v20.0 for
      Windows (SPSS Inc., Chicago, USA). All tests are two-sided and a p-value of < 0.05 is
      accepted as statistically significant.
    

Intervention name(s): paravertebral block; fentanyl, propofol, atracurium; lidocaine , adrenaline, ketamine bolus, midazolam; catheter with 3-level-injection; sevoflurane and 50% oxygen in air
Intervention type(s): Procedure; Drug; Drug; Device; Drug
Intervention description(s): catheter with 3-level-injection; endotracheal intubation; a mixture of 10 ml bupivacaine 0.5% plus 20 ml lidocaine 2% with adrenaline 1:200,000, ketamine bolus 0.5 mg/kg, midazolam 2-3 mg and continuous propofol using target-controlled infusion (TCI) system aiming at effect site concentration (Ce) of 1-1.5 mcg/mL
Other intervention name(s): 10 ml bupivacaine 0.5% plus 20 ml lidocaine 2% with adrenaline 1:200,000, ketamine bolus 0.5 mg/kg, midazolam 2-3 mg and TCI propofol at Ce of 1-1.5 mcg/ml
Intervention MeSH terms: Lidocaine; Epinephrine; Racepinephrine; Midazolam; Fentanyl; Ketamine; Bupivacaine; Propofol; Sevoflurane; Epinephryl borate; Atracurium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: paravertebral block, mastectomy, efficiency