<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02237664</url>
  </required_header>
  <id_info>
    <org_study_id>UD-2015-16-P1Anesth</org_study_id>
    <secondary_id>GPAnesth-1</secondary_id>
    <nct_id>NCT02237664</nct_id>
  </id_info>
  <brief_title>Patient-Controlled Thoracic Paravertebral Block After Video-Assisted Thoracoscopic Surgery</brief_title>
  <official_title>Patient-Controlled Thoracic Paravertebral Block for Postoperative Analgesia After Video-Assisted Thoracoscopic Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imam Abdulrahman Bin Faisal University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Imam Abdulrahman Bin Faisal University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Thoracic surgery is commonly associated with severe postoperative pain and marked impairment&#xD;
      of respiratory function.1 Minimally invasive video-assisted thoracic surgery (VATS) is&#xD;
      assumed to result in better quality of life and less postoperative pain compared with&#xD;
      standard open thoracotomy, other investigators have reported comparable patient-reported&#xD;
      physical component summary and pain scores after VATS and thoracotomy during the first 12&#xD;
      months after lung resection.2 That study was non-randomized and 41% of the included patients&#xD;
      did not complete the follow-up period.2 VATS has recently been increasing in popularity as a&#xD;
      fast-track surgery with potential enhanced recovery after surgery.&#xD;
&#xD;
      Variety of approaches exist to manage pain after thoracotomy which could attenuate&#xD;
      post-thoracotomy pulmonary dysfunction. Epidural analgesia has been considered for many&#xD;
      decades to be the best method of pain relief after major thoracic surgery. In previous&#xD;
      meta-analyses,3-5 many investigators have reported that thoracic paravertebral blockade (PVB)&#xD;
      has comparable analgesic effects to thoracic epidural analgesia (TEA) in patients undergoing&#xD;
      thoracotomy.&#xD;
&#xD;
      Additionally, PVB has a better side-effect profile, lower rates of failed block and is&#xD;
      associated with a reduction in pulmonary complications.3-5 This could be extended to VATS to&#xD;
      enhance recovery after surgery owing to effective analgesia and fewer side effects.6-7&#xD;
&#xD;
      Patient-controlled analgesia (PCA) has been advocated as a favourable model for postoperative&#xD;
      analgesia, that allows a perfect match between intensity of pain and analgesic delivery,&#xD;
      improves the quality of analgesia and decreases the cumulative analgesic consumption.&#xD;
      Furthermore, the introduction of patient-controlled epidural analgesia (PCEA) with background&#xD;
      infusion during labour gave patients a sense of control over their analgesia, reduced the&#xD;
      total dose of local anesthetic administered, and had less motor block than those who receive&#xD;
      continuous epidural analgesia.8-9Patient-controlled epidural analgesia (PCEA) has become&#xD;
      increasingly popular for pain control after thoracotomy.10-12 In a previous preliminary&#xD;
      study, McElwain et al.13 have reported satisfactory analgesia after breast cancer surgery&#xD;
      with the use of PC-PVB, using either 15-min or 30-min lockout, that study did not include a&#xD;
      comparative arm with a continuous paravertebral infusion. Furthermore, Abou Zeid et al. have&#xD;
      reported comparable analgesia after thoracic surgery with the use of either&#xD;
      patient-controlled PVB had with the use of intrathecal morphine, that study was not&#xD;
      controlled and included few patients.14&#xD;
&#xD;
      The efficacy of the patient-controlled paravertebral blockade (PC-PVB) on the quality of&#xD;
      postoperative analgesia and pulmonary function after VATS has not yet been studied.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      We hypothesizes that the use of patient-controlled paravertebral blockade (PC-PVB) after VATS&#xD;
      will be associated with lower pain scores and less pulmonary dysfunction than continuous&#xD;
      paravertebral blockade (PVB).&#xD;
&#xD;
      Following obtaining of the Local Ethics Committee approval and informed patient consent, 62&#xD;
      patients, aged 18 -70 years, American Society of Anesthesiologists (ASA) physical status&#xD;
      II-III, undergoing elective VATS using postoperative thoracic paravertebral analgesia will be&#xD;
      included in this prospective, randomized, controlled, double-blind study.&#xD;
&#xD;
      Before operation, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and&#xD;
      peak expiratory flow rate (PEFR), were measured. On the morning before surgery, the patients&#xD;
      will be instructed in the use of the PCA pump and a VAS. The patients will be asked to rate&#xD;
      their experienced pain using the VAS from 0 to 100 mm with 0 representing no pain and 100&#xD;
      representing the worst imaginable pain.&#xD;
&#xD;
      Prior to the procedure an 18 to 20 G intravenous access will be established. Patient monitors&#xD;
      includes electrocardiograph, non-invasive blood pressure, and pulse oximeter. All patients&#xD;
      will be premedicated with iv midazolam 0.01-0.03 mg kg-1.&#xD;
&#xD;
      Before the induction of general anesthesia, paravertebral space ipsilateral to the&#xD;
      thoracostomy will be identified 3 cm lateral to the spinous process of T5-8 with&#xD;
      ultrasound-guidance (USG) using a high-frequency linear array probe of a Sonosite MTurbo&#xD;
      ultrasound machine (MicroMaxxs ultrasound system, Sonosite Inc, Bothell, WA). After the probe&#xD;
      was placed at the level of the T5-6 interspace, the apex of the paravertebral space will be&#xD;
      visualized as a wedge-shaped hypoechoic space surrounded by the hyperechoic line of the&#xD;
      pleura below and the internal intercostal membrane above. An 18 G Tuohy needle (B. Braun,&#xD;
      Germany) will be inserted in a lateral-to-medial direction using an in-plane approach and&#xD;
      will be kept advancing until the needle tip penetrates the internal intercostal membrane.7 A&#xD;
      20-G epidural catheter (B. Braun, Germany) will be introduced through Tuohy needle and&#xD;
      advanced 3 cm into the paravertebral space. After gentle aspiration, a test dose of 3 mL of&#xD;
      bupivacaine 0.25% with epinephrine 5 µg mL-1 will be administered through the catheter. If no&#xD;
      significant rise in heart rate or arterial pressure will be observed, a bolus of 0.3 mL kg-1&#xD;
      of bupivacaine 0.25% with epinephrine (5 µg mL-1), followed by continuous paravertebral&#xD;
      infusion of bupivacaine 0.25% and fentanyl 2 µg mL-1 at 0.1 mL kg-1 h-1 intraoperatively.15&#xD;
&#xD;
      In all patients, standard monitors and state and response entropy (SE and RE, respectively,&#xD;
      GE Healthcare, Helsinki, Finland) based-depth of anesthesia will be applied. The radial&#xD;
      artery will be catheterized. Anesthetic technique will be standardized in all studied&#xD;
      patients. After preoxygenation, general anesthesia will be induced with propofol 1.5-3 mg&#xD;
      kg-1 and target-controlled infusion (TCI) of remifentanil at an effect-site concentration&#xD;
      (Ce) of 4 ng mL-1, to achieve the SE values below 50 and the difference between RE and SE&#xD;
      below 10. Rocuronium (0.5 mg kg-1) will be given to facilitate the endobronchial intubation&#xD;
      with a left-double lumen endobronchial tube and the correct position of its tip will be&#xD;
      confirmed with a fiberoptic bronchoscope.&#xD;
&#xD;
      Anaesthesia will be maintained with 0.7-1.5 minimum alveolar concentration of sevoflurane and&#xD;
      remifentanil Ce of 2-4 ng mL-1 to maintain the SE values below 50, the difference between RE&#xD;
      and SE below 10 and the mean arterial blood pressure (MAP) and heart rate &lt;20% of baseline&#xD;
      values. Rocuronium increments will be used to maintain surgical relaxation.&#xD;
&#xD;
      Two lung ventilation (TLV) will be instituted using fraction of inspired oxygen (FiO2) of 0.4&#xD;
      in air, tidal volume (VT) of 8 mL kg-1, inspiratory to expiratory (I: E) ratio of 1:2.5 and&#xD;
      PEEP of 5 cm H2O, and respiratory rate will be adjusted to achieve an arterial carbon dioxide&#xD;
      tension (PaCO2) of 4.7-6 kPa. During one-lung ventilation (OLV), the dependent lung will be&#xD;
      ventilated with a FiO2 of 1.0, VT of 6 mL kg-1 and I: E ratio, PEEP, and respiratory rate,&#xD;
      will be maintained as during TLV. The dependent lung will be recruited at 30-minute intervals&#xD;
      by increasing the inspiratory pressure to 40 cmH2O for 10 seconds.&#xD;
&#xD;
      All surgical procedures will be performed by the same surgeons who will be blinded for the&#xD;
      study group. The VATS procedure will begin with the exploration of the pleural cavity using a&#xD;
      30° video thoracoscopic camera through 1.5 cm single skin incision with the use of 1-3&#xD;
      trocars which enables the thoracoscopic instruments to move the lung.&#xD;
&#xD;
      At the end of surgery, the nondependent lung will be re-expanded, the remifentanil and&#xD;
      sevoflurane will be discontinued after chest closure and skin closure, respectively, and the&#xD;
      residual neuromuscular blockade will be antagonized.&#xD;
&#xD;
      During working hours of the first 48 hours, the patients will be visited by an acute pain&#xD;
      nurse and/or a consultant anesthesiologist, who will interview each patient regarding&#xD;
      satisfaction with postoperative analgesia. After hours, an anesthetic registrar will be&#xD;
      available to review analgesia management. All patients will receive multimodal analgesia&#xD;
      consisting of regular IV paracetamol (1 g four times a day) and IV lornoxicam (8 mg two times&#xD;
      a day) for postoperative pain relief.&#xD;
&#xD;
      Breakthrough pain, defined as pain VAS &gt; 30 mm, will be treated with a bolus of 0.1 mL kg-1&#xD;
      of paravertebral medication administered through the pump. No additional medication will be&#xD;
      given if the pain VAS &lt; 30 mm. If after 15 minutes pain VAS persists greater than 30,&#xD;
      additional 0.1 mL kg-1 of the paravertebral medication will be given. If the patient still&#xD;
      has a pain VAS &gt; 30 despite breakthrough pain intervention, then the patient will be&#xD;
      connected to PCA with intravenous morphine 1 mg, with a lockout interval of 8 minutes and a&#xD;
      maximum 4-hourly limit of 30 mg.5&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2015</start_date>
  <completion_date type="Anticipated">June 2020</completion_date>
  <primary_completion_date type="Anticipated">February 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pain scores</measure>
    <time_frame>48 hours after surgery</time_frame>
    <description>Pain scores on a 100-mm-long visual analog score (VAS) at rest and on cough</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hemodynamic variables</measure>
    <time_frame>48 hours after surgery</time_frame>
    <description>Heart rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of bolus demands</measure>
    <time_frame>48 after surgery</time_frame>
    <description>The number of bolus demands</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Actual number of boluses</measure>
    <time_frame>48 hours after surgery</time_frame>
    <description>the actual number of on demand boluses of the patient-controlled analgesia received by the patient</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total volume of administered bupivacaine</measure>
    <time_frame>48 hours after surgery</time_frame>
    <description>total volume of bupivacaine administered during the first 48 hours after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rescue analgesic requirements</measure>
    <time_frame>48 hours after surgery</time_frame>
    <description>rescue analgesic requirements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Requirement for antiemetic medication</measure>
    <time_frame>48 hours after surgery</time_frame>
    <description>Requirement for antiemetic medications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall patient satisfaction</measure>
    <time_frame>48 hours after surgery</time_frame>
    <description>Overall patient satisfaction will be recorded on a 100-mm visual analog scale (VAS) (0 mm = completely dissatisfied, 100 mm = completely satisfied) after catheter removal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sedation scores</measure>
    <time_frame>48 hours after surgery</time_frame>
    <description>Patient sedation will be assessed 4 hourly on a five-point sedation score (1, wide awake; 2, drowsy or dozing intermittently; 3, mostly sleeping but easily awakened; 4, asleep, difficulty responding to verbal commands; 5, awakened only by shaking).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary function tests</measure>
    <time_frame>24 hours before surgery, 72 hours after surgery</time_frame>
    <description>, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEFR) will be recorded</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">62</enrollment>
  <condition>Video-assisted Thoracoscopic Surgery</condition>
  <arm_group>
    <arm_group_label>Patient-controlled paravertebral analgesia (PC-PVB)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patient-controlled paravertebral analgesia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Continuous paravertebral analgesia (C-PVB)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Continuous paravertebral analgesia</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Continuous paravertebral analgesia (C-PVB)</intervention_name>
    <description>Patients will receive continuous paravertebral infusion of bupivacaine 0.2% and fentanyl 2 μg mL-1 at rate of 8 mL h-1</description>
    <arm_group_label>Continuous paravertebral analgesia (C-PVB)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Patient-controlled paravertebral analgesia (PC-PVB)</intervention_name>
    <description>Patients will receive background continuous paravertebral infusion of bupivacaine 0.2% and fentanyl 2 μg mL-1 at rate of 8 mL h-1 with patient demand bolus dose of 3 mL and lockout time of 15 min with a 20 mL h-1 maximum dose, irrespective of their age</description>
    <arm_group_label>Patient-controlled paravertebral analgesia (PC-PVB)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  American Society of Anesthesiologists (ASA) physical status II-III.&#xD;
&#xD;
          -  Use of postoperative thoracic paravertebral analgesia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cardiac disease&#xD;
&#xD;
          -  Pulmonary disease&#xD;
&#xD;
          -  Renal disease&#xD;
&#xD;
          -  Hepatic disease&#xD;
&#xD;
          -  Neuropsychiatric disease&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Bleeding disorder&#xD;
&#xD;
          -  Severe anatomical abnormalities of the vertebral column or ribs&#xD;
&#xD;
          -  Allergy to study medications&#xD;
&#xD;
          -  Other contraindications to paravertebral analgesia&#xD;
&#xD;
          -  Body mass index (BMI) ≥ 35 kg m-2&#xD;
&#xD;
          -  Body weight less than 50 kg&#xD;
&#xD;
          -  Emergency surgery&#xD;
&#xD;
          -  Preoperative pain score &gt; 70 mm on visual analogue scale (VAS)&#xD;
&#xD;
          -  Drug or alcohol abuse&#xD;
&#xD;
          -  Chronic pain condition requiring daily intake of analgesics&#xD;
&#xD;
          -  Language or mental disorders&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yasser Al Jehani, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chairman of Surgery Dept</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mohamed R El Tahan, MD</last_name>
    <role>Study Director</role>
    <affiliation>Imam Abdulrahman Bin Faisal University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mohamed R El Tahan, MD</last_name>
    <phone>+966 13 865 1193</phone>
    <email>mohamedrefaateltahan@yahoo.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Abdulmohsin A Al Ghamdi, MD</last_name>
    <phone>+966 50 581 4737</phone>
    <email>mohsenkfu@hotmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>King Fahd Hospital of the University</name>
      <address>
        <city>Khobar</city>
        <state>Eastern</state>
        <zip>31952</zip>
        <country>Saudi Arabia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Abdulmohsen A Al Ghamdi, MD</last_name>
      <phone>+966 13 8966666</phone>
      <phone_ext>2021</phone_ext>
      <email>mohsenkfu@hotmail.com</email>
    </contact>
    <investigator>
      <last_name>Alaa M Khidr, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Abdulmohsen A Al Ghamdi, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Saudi Arabia</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>September 8, 2014</study_first_submitted>
  <study_first_submitted_qc>September 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2014</study_first_posted>
  <last_update_submitted>March 19, 2019</last_update_submitted>
  <last_update_submitted_qc>March 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 20, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Thoracoscopy</keyword>
  <keyword>Patient-controlled analgesia</keyword>
  <keyword>Paravertebral analgesia</keyword>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02237664
org study id: UD-2015-16-P1Anesth
secondary id: GPAnesth-1
nct id: NCT02237664
lead sponsor: 
has dmc: Yes
Thoracic surgery is commonly associated with severe postoperative pain and marked impairment
      of respiratory function.1 Minimally invasive video-assisted thoracic surgery (VATS) is
      assumed to result in better quality of life and less postoperative pain compared with
      standard open thoracotomy, other investigators have reported comparable patient-reported
      physical component summary and pain scores after VATS and thoracotomy during the first 12
      months after lung resection.2 That study was non-randomized and 41% of the included patients
      did not complete the follow-up period.2 VATS has recently been increasing in popularity as a
      fast-track surgery with potential enhanced recovery after surgery.

      Variety of approaches exist to manage pain after thoracotomy which could attenuate
      post-thoracotomy pulmonary dysfunction. Epidural analgesia has been considered for many
      decades to be the best method of pain relief after major thoracic surgery. In previous
      meta-analyses,3-5 many investigators have reported that thoracic paravertebral blockade (PVB)
      has comparable analgesic effects to thoracic epidural analgesia (TEA) in patients undergoing
      thoracotomy.

      Additionally, PVB has a better side-effect profile, lower rates of failed block and is
      associated with a reduction in pulmonary complications.3-5 This could be extended to VATS to
      enhance recovery after surgery owing to effective analgesia and fewer side effects.6-7

      Patient-controlled analgesia (PCA) has been advocated as a favourable model for postoperative
      analgesia, that allows a perfect match between intensity of pain and analgesic delivery,
      improves the quality of analgesia and decreases the cumulative analgesic consumption.
      Furthermore, the introduction of patient-controlled epidural analgesia (PCEA) with background
      infusion during labour gave patients a sense of control over their analgesia, reduced the
      total dose of local anesthetic administered, and had less motor block than those who receive
      continuous epidural analgesia.8-9Patient-controlled epidural analgesia (PCEA) has become
      increasingly popular for pain control after thoracotomy.10-12 In a previous preliminary
      study, McElwain et al.13 have reported satisfactory analgesia after breast cancer surgery
      with the use of PC-PVB, using either 15-min or 30-min lockout, that study did not include a
      comparative arm with a continuous paravertebral infusion. Furthermore, Abou Zeid et al. have
      reported comparable analgesia after thoracic surgery with the use of either
      patient-controlled PVB had with the use of intrathecal morphine, that study was not
      controlled and included few patients.14

      The efficacy of the patient-controlled paravertebral blockade (PC-PVB) on the quality of
      postoperative analgesia and pulmonary function after VATS has not yet been studied.
We hypothesizes that the use of patient-controlled paravertebral blockade (PC-PVB) after VATS
      will be associated with lower pain scores and less pulmonary dysfunction than continuous
      paravertebral blockade (PVB).

      Following obtaining of the Local Ethics Committee approval and informed patient consent, 62
      patients, aged 18 -70 years, American Society of Anesthesiologists (ASA) physical status
      II-III, undergoing elective VATS using postoperative thoracic paravertebral analgesia will be
      included in this prospective, randomized, controlled, double-blind study.

      Before operation, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and
      peak expiratory flow rate (PEFR), were measured. On the morning before surgery, the patients
      will be instructed in the use of the PCA pump and a VAS. The patients will be asked to rate
      their experienced pain using the VAS from 0 to 100 mm with 0 representing no pain and 100
      representing the worst imaginable pain.

      Prior to the procedure an 18 to 20 G intravenous access will be established. Patient monitors
      includes electrocardiograph, non-invasive blood pressure, and pulse oximeter. All patients
      will be premedicated with iv midazolam 0.01-0.03 mg kg-1.

      Before the induction of general anesthesia, paravertebral space ipsilateral to the
      thoracostomy will be identified 3 cm lateral to the spinous process of T5-8 with
      ultrasound-guidance (USG) using a high-frequency linear array probe of a Sonosite MTurbo
      ultrasound machine (MicroMaxxs ultrasound system, Sonosite Inc, Bothell, WA). After the probe
      was placed at the level of the T5-6 interspace, the apex of the paravertebral space will be
      visualized as a wedge-shaped hypoechoic space surrounded by the hyperechoic line of the
      pleura below and the internal intercostal membrane above. An 18 G Tuohy needle (B. Braun,
      Germany) will be inserted in a lateral-to-medial direction using an in-plane approach and
      will be kept advancing until the needle tip penetrates the internal intercostal membrane.7 A
      20-G epidural catheter (B. Braun, Germany) will be introduced through Tuohy needle and
      advanced 3 cm into the paravertebral space. After gentle aspiration, a test dose of 3 mL of
      bupivacaine 0.25% with epinephrine 5 µg mL-1 will be administered through the catheter. If no
      significant rise in heart rate or arterial pressure will be observed, a bolus of 0.3 mL kg-1
      of bupivacaine 0.25% with epinephrine (5 µg mL-1), followed by continuous paravertebral
      infusion of bupivacaine 0.25% and fentanyl 2 µg mL-1 at 0.1 mL kg-1 h-1 intraoperatively.15

      In all patients, standard monitors and state and response entropy (SE and RE, respectively,
      GE Healthcare, Helsinki, Finland) based-depth of anesthesia will be applied. The radial
      artery will be catheterized. Anesthetic technique will be standardized in all studied
      patients. After preoxygenation, general anesthesia will be induced with propofol 1.5-3 mg
      kg-1 and target-controlled infusion (TCI) of remifentanil at an effect-site concentration
      (Ce) of 4 ng mL-1, to achieve the SE values below 50 and the difference between RE and SE
      below 10. Rocuronium (0.5 mg kg-1) will be given to facilitate the endobronchial intubation
      with a left-double lumen endobronchial tube and the correct position of its tip will be
      confirmed with a fiberoptic bronchoscope.

      Anaesthesia will be maintained with 0.7-1.5 minimum alveolar concentration of sevoflurane and
      remifentanil Ce of 2-4 ng mL-1 to maintain the SE values below 50, the difference between RE
      and SE below 10 and the mean arterial blood pressure (MAP) and heart rate <20% of baseline
      values. Rocuronium increments will be used to maintain surgical relaxation.

      Two lung ventilation (TLV) will be instituted using fraction of inspired oxygen (FiO2) of 0.4
      in air, tidal volume (VT) of 8 mL kg-1, inspiratory to expiratory (I: E) ratio of 1:2.5 and
      PEEP of 5 cm H2O, and respiratory rate will be adjusted to achieve an arterial carbon dioxide
      tension (PaCO2) of 4.7-6 kPa. During one-lung ventilation (OLV), the dependent lung will be
      ventilated with a FiO2 of 1.0, VT of 6 mL kg-1 and I: E ratio, PEEP, and respiratory rate,
      will be maintained as during TLV. The dependent lung will be recruited at 30-minute intervals
      by increasing the inspiratory pressure to 40 cmH2O for 10 seconds.

      All surgical procedures will be performed by the same surgeons who will be blinded for the
      study group. The VATS procedure will begin with the exploration of the pleural cavity using a
      30° video thoracoscopic camera through 1.5 cm single skin incision with the use of 1-3
      trocars which enables the thoracoscopic instruments to move the lung.

      At the end of surgery, the nondependent lung will be re-expanded, the remifentanil and
      sevoflurane will be discontinued after chest closure and skin closure, respectively, and the
      residual neuromuscular blockade will be antagonized.

      During working hours of the first 48 hours, the patients will be visited by an acute pain
      nurse and/or a consultant anesthesiologist, who will interview each patient regarding
      satisfaction with postoperative analgesia. After hours, an anesthetic registrar will be
      available to review analgesia management. All patients will receive multimodal analgesia
      consisting of regular IV paracetamol (1 g four times a day) and IV lornoxicam (8 mg two times
      a day) for postoperative pain relief.

      Breakthrough pain, defined as pain VAS > 30 mm, will be treated with a bolus of 0.1 mL kg-1
      of paravertebral medication administered through the pump. No additional medication will be
      given if the pain VAS < 30 mm. If after 15 minutes pain VAS persists greater than 30,
      additional 0.1 mL kg-1 of the paravertebral medication will be given. If the patient still
      has a pain VAS > 30 despite breakthrough pain intervention, then the patient will be
      connected to PCA with intravenous morphine 1 mg, with a lockout interval of 8 minutes and a
      maximum 4-hourly limit of 30 mg.5
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Pain scores
time frame: 48 hours after surgery
description: Pain scores on a 100-mm-long visual analog score (VAS) at rest and on cough
measure: Hemodynamic variables
time frame: 48 hours after surgery
description: Heart rate
measure: Number of bolus demands
time frame: 48 after surgery
description: The number of bolus demands
measure: Actual number of boluses
time frame: 48 hours after surgery
description: the actual number of on demand boluses of the patient-controlled analgesia received by the patient
measure: Total volume of administered bupivacaine
time frame: 48 hours after surgery
description: total volume of bupivacaine administered during the first 48 hours after surgery
measure: Rescue analgesic requirements
time frame: 48 hours after surgery
description: rescue analgesic requirements
measure: Requirement for antiemetic medication
time frame: 48 hours after surgery
description: Requirement for antiemetic medications
measure: Overall patient satisfaction
time frame: 48 hours after surgery
description: Overall patient satisfaction will be recorded on a 100-mm visual analog scale (VAS) (0 mm = completely dissatisfied, 100 mm = completely satisfied) after catheter removal.
measure: Sedation scores
time frame: 48 hours after surgery
description: Patient sedation will be assessed 4 hourly on a five-point sedation score (1, wide awake; 2, drowsy or dozing intermittently; 3, mostly sleeping but easily awakened; 4, asleep, difficulty responding to verbal commands; 5, awakened only by shaking).
measure: Pulmonary function tests
time frame: 24 hours before surgery, 72 hours after surgery
description: , forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEFR) will be recorded
arm group label: Patient-controlled paravertebral analgesia (PC-PVB)
arm group type: Active Comparator
description: Patient-controlled paravertebral analgesia
arm group label: Continuous paravertebral analgesia (C-PVB)
arm group type: Placebo Comparator
description: Continuous paravertebral analgesia
intervention type: Procedure
intervention name: Continuous paravertebral analgesia (C-PVB)
description: Patients will receive continuous paravertebral infusion of bupivacaine 0.2% and fentanyl 2 μg mL-1 at rate of 8 mL h-1
arm group label: Continuous paravertebral analgesia (C-PVB)
intervention type: Procedure
intervention name: Patient-controlled paravertebral analgesia (PC-PVB)
description: Patients will receive background continuous paravertebral infusion of bupivacaine 0.2% and fentanyl 2 μg mL-1 at rate of 8 mL h-1 with patient demand bolus dose of 3 mL and lockout time of 15 min with a 20 mL h-1 maximum dose, irrespective of their age
arm group label: Patient-controlled paravertebral analgesia (PC-PVB)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Yasser Al Jehani, MD
role: Principal Investigator
affiliation: Chairman of Surgery Dept
last name: Mohamed R El Tahan, MD
role: Study Director
affiliation: Imam Abdulrahman Bin Faisal University
last name: Mohamed R El Tahan, MD
phone: +966 13 865 1193
email: mohamedrefaateltahan@yahoo.com
last name: Abdulmohsin A Al Ghamdi, MD
phone: +966 50 581 4737
email: mohsenkfu@hotmail.com
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: Saudi Arabia
responsible party type: Sponsor