<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/NCT03024697</url>
  </required_header>
  <id_info>
    <org_study_id>PECS 123</org_study_id>
    <nct_id>NCT03024697</nct_id>
  </id_info>
  <brief_title>Single-shot Pectoral Plane(PECs) Block Versus Continuous Local Anaesthetic Infusion Analgesia or Both PECS Block and Local Anaesthetic Infusion After Breast Surgery: A Prospective Randomised, Double-blind Trial</brief_title>
  <official_title>Single-shot Pectoral Plane (PECs) Blocks Versus Continuous Local Anaesthetic Infusion Analgesia or Both PECs Block and Local Anaesthetic Infusion After Non-ambulatory Breast Cancer Surgery: A Prospective, Randomised, Double-blind Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mater Misericordiae University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mater Misericordiae University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this proposed study, the investigators are looking to conduct a prospective, randomised,&#xD;
      double-blind, non-inferiority trial, to study single-shot pectoral plane (PECs) blocks versus&#xD;
      continuous local anaesthetic infusion analgesia versus a combination of PECs blocks and local&#xD;
      anaesthetic infusion analgesia, when it comes to providing analgesia for most forms of breast&#xD;
      surgery.&#xD;
&#xD;
      Breast surgery is common, and the optimal form of analgesia is currently unknown. Techniques&#xD;
      involving local anaesthetic, such as pectoral plane (PECs) blocks and infusion pumps, are&#xD;
      growing in popularity, as they reduce the amount of opioid medications used. Opioids are&#xD;
      associated with nausea, vomiting, low blood pressure, drowsiness and constipation, and as&#xD;
      such, opioid-sparing analgesic regimens postoperatively are becoming more common. These&#xD;
      regimens will typically involve paracetamol, a NSAID (non-steroidal anti-inflammatory drug),&#xD;
      and a local anaesthetic technique.&#xD;
&#xD;
      Pectoral plane blocks involve a once-off injection of local anaesthetic at two locations&#xD;
      within the chest wall, typically done after the patient undergoes general anaesthesia, but&#xD;
      before the commencement of surgery. Local anaesthetic infusion pumps involve the insertion of&#xD;
      a catheter into the wound at the end of surgery, before the patient emerges from general&#xD;
      anaesthesia, that constantly emit local anaesthetic over a defined period of time. Each&#xD;
      technique is considered extremely safe, and is considered acceptable as a form of pain relief&#xD;
      in patients undergoing breast surgery.&#xD;
&#xD;
      There are no published works comparing pectoral plane blocks with local anaesthetic infusion&#xD;
      pump analgesia, and the investigators see a gap in the knowledge base that can be addressed.&#xD;
      This study will allow efficacy, safety and cost of the three techniques to be compared. The&#xD;
      investigators feel the study design is robust, and statistical analysis based on previously&#xD;
      published works in the area of postoperative analgesia has allowed the study to be powered&#xD;
      appropriately.&#xD;
&#xD;
      Patients undergoing breast surgery are a vulnerable group, and this is recognised via the&#xD;
      provision of a comprehensive Patient Information Leaflet and a commitment to respecting the&#xD;
      process of Informed Consent. The investigators also recognise this is a stressful period in a&#xD;
      woman's life, and the study will be conducted in a sensitive and compassionate manner.&#xD;
&#xD;
      The study has been designed to be prospective, randomised, and double-blinded. The&#xD;
      anaesthetic will be standardised in relation to analgesic and anti-emetic agents&#xD;
      administered, in order to minimise variables. Chronic post-surgical pain is a growing area of&#xD;
      research, and the follow-up telephone interview at 3-months will allow investigation of this.&#xD;
&#xD;
      A Data Record Form will be utilised for data collection, which will subsequently be analysed&#xD;
      statistically. Data will be handled sensitively, securely, and by the minimum number of&#xD;
      researchers. A plan is in place for destruction of data at an appropriate time.&#xD;
&#xD;
      While there will be no direct benefit to participants, including monetary considerations,&#xD;
      this research study will add to the knowledge-base surrounding analgesia for breast surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Methods The Mater Misericordiae University Hospital's Institutional Review Board (IRB)&#xD;
      approved this study; reference number 1/378/1840, dated December 21st, 2016. It was&#xD;
      registered with clinicaltrials.gov; reference number NCT03024697, dated February 15th, 2017.&#xD;
      Forty-five ASA I-III female patients aged 18 years or older, undergoing non-ambulatory breast&#xD;
      cancer surgery under general anaesthesia between January and May 2017 were included. All&#xD;
      participants provided informed written consent.&#xD;
&#xD;
      Non-ambulatory breast cancer surgery encompassed wide-local excision with lymph node&#xD;
      resection, simple mastectomy, and mastectomy with lymph node resection. Those undergoing&#xD;
      latissimus dorsi or DIEP (deep inferior epigastric perforator) flap reconstruction were&#xD;
      excluded. Patients with chronic pain syndromes, local anaesthetic allergy, contraindication&#xD;
      to simple analgesics, local infection over the proposed block site, coagulopathy, or&#xD;
      co-morbid conditions precluding the provision of informed consent, were excluded. All&#xD;
      patients were day of surgery admission and attended a preoperative anaesthetic assessment&#xD;
      clinic.&#xD;
&#xD;
      Patients were allocated into three groups using computer-generated randomisation, with the&#xD;
      study number and group allocation concealed in sealed envelopes. Blocked randomisation in&#xD;
      groups of 9 was applied, giving similar numbers in each group as the study progressed. Groups&#xD;
      were named 'PECs', 'Local anaesthetic infusion (LA infusion)' , and 'Both (PECS &amp; LA&#xD;
      infusion)', which were evenly distributed to opaque envelopes numbered one to forty-five in&#xD;
      accordance with randomisation. The randomisation key was held by an independent party, and&#xD;
      was not used to reveal participant group allocations until data analysis commenced. 'PECs'&#xD;
      patients received PECS I &amp; II blocks and a sham wound infiltration catheter. 'LA infusion'&#xD;
      patients received a continuous local anaesthetic wound infusion catheter. 'PECs &amp; LA&#xD;
      infusion' patients received a combination of techniques, without the initial local&#xD;
      anaesthetic bolus via the wound infusion catheter. PECs blocks were performed while patients&#xD;
      were under general anaesthesia, prior to the commencement of surgery. The operative surgeon&#xD;
      sited wound infusion catheters during skin closure at the end of surgery.&#xD;
&#xD;
      Patients were induced with fentanyl 1-2 μg.kg-1, followed by propofol titrated to the absence&#xD;
      of verbal response. Anaesthesia was maintained using an oxygen, air and sevoflurane&#xD;
      combination. Airway management and lung ventilation strategies were at the discretion of the&#xD;
      supervising anaesthetist. Patients received a standard intraoperative analgesic regimen of&#xD;
      paracetamol 1g and dexketoprofen 50mg intravenously (IV), with rescue morphine as deemed&#xD;
      necessary. Combination antiemetics, including ondansetron 0.1-0.15 mg.kg-1 IV, dexamethasone&#xD;
      0.1-0.2 mg.kg-1 IV or droperidol 0.01-0.015 mg.kg-1 IV, were administered according to&#xD;
      patient risk factors. Intraoperative management was otherwise left to the discretion of the&#xD;
      supervising anaesthetist. Routine monitoring was used in accordance with AAGBI guidelines15.&#xD;
      An electronic anaesthetic record was used to document physiological parameters. Perioperative&#xD;
      events, such as induction of anaesthesia, initial skin incision, and end of surgery, were&#xD;
      annotated on the record.&#xD;
&#xD;
      PECs I &amp; II blocks were performed on the side of surgery, using the ultrasound-guided&#xD;
      technique described by Blanco et al9, 10. The patient was placed in the supine, head-up,&#xD;
      position with the arm abducted. The skin was prepared with chlorhexidine gluconate&#xD;
      2%/isopropyl alcohol 70% (BD, ChloraPrep, NJ, USA). PECs blocks were performed with a&#xD;
      22-gauge echogenic needle (B. Braun, Ultraplex 360 cannula, Hessen, Germany; 50-80mm), using&#xD;
      the same ultrasound machine (Sonosite Edge, Sonosite, Inc., Bothwell, WA, USA) and transducer&#xD;
      (Sonosite HFL 50x, Sonosite, Inc., Bothwell, WA, USA). The ultrasound probe was placed&#xD;
      inferolaterally at the mid-clavicular level. The axillary artery and vein were identified,&#xD;
      and the probe moved laterally until pectoralis major, pectoralis minor and serratus anterior&#xD;
      muscles were located at the level of the 3rd rib. A needle in-plane approach was taken until&#xD;
      the needle tip was positioned in the plane between pectoralis major and minor muscles, and&#xD;
      levobupivacaine 0.25% 10ml was injected. The needle was advanced until it occupied the space&#xD;
      between pectoralis minor and serratus anterior muscles, and a further 20ml of levobupivacaine&#xD;
      0.25% was injected.&#xD;
&#xD;
      Blinding was not considered necessary for 'LA infusion' group patients, as PECs blocks were&#xD;
      performed under general anaesthesia. All patients had a wound infusion catheter sited and&#xD;
      attached to an elastometric pump (B. Braun, ON-Q PainBuster, Hessen, Germany), which was&#xD;
      placed by the operating surgeon during skin closure at the end of surgery. For blinding&#xD;
      purposes, patients in the 'PECs' group received a sham wound infiltration catheter system.&#xD;
      'LA infusion' and 'PECS &amp; LA infusion' patients received levobupivacaine 0.1% at 10ml.hr-1&#xD;
      for 24 hours postoperatively, while 'PECs' patients received sodium chloride 0.9% at the same&#xD;
      rate. 'LA infusion' patients were administered an initial bolus of levobupivacaine 0.25% 20ml&#xD;
      at the end of surgery. Those who performed the procedures, or were involved in the&#xD;
      perioperative management, were not involved in postoperative pain assessment or data&#xD;
      collection. Study interventions as described occurred while patients were under general&#xD;
      anaesthesia.&#xD;
&#xD;
      Patients were monitored for 24 hours after surgery, initially in the post-anaesthesia care&#xD;
      unit (PACU), and then at ward level once PACU discharge criteria were met. Oxycodone 1-2mg IV&#xD;
      as required was prescribed for rescue analgesia in the PACU. A standard analgesic protocol of&#xD;
      paracetamol 1g PO/IV 6-hourly regular, ibuprofen 400mg PO 8-hourly regular, and oxycodone&#xD;
      immediate release (oxynorm) 5-10mg 1-hourly as required for rescue analgesia, was prescribed&#xD;
      for all patients. Ondansetron 4-8mg IV 8-hourly as required was prescribed, to be&#xD;
      administered in the event of postoperative nausea and vomiting (PONV).&#xD;
&#xD;
      The primary outcome measure of the study was area under curve of verbal rating score (VRS) of&#xD;
      pain moving versus time, (AUC) where VRS pain was measured at 1 hour, 4-6 hours, 10-14 hours,&#xD;
      and 20-24 hours postoperatively. At each assessment, patients were invited to report their&#xD;
      pain VRS pain at rest. Pain while moving was defined as pain experienced while sitting&#xD;
      forward from a recumbent position. Secondary outcome measures were total opioid consumption&#xD;
      over a 24-hour period and presence of adverse events. An investigator masked to group&#xD;
      allocations recorded vital signs, pain scores, antiemetic administration and opioid use&#xD;
      postoperatively. Adverse events such as sedation, respiratory depression, hypotension,&#xD;
      pruritus and PONV were also recorded.&#xD;
&#xD;
      Statistical Analysis&#xD;
&#xD;
      Data was analysed by Graph Pad Prism v6 (Salt Lake City, UH). The primary end-point was area&#xD;
      under the VRS moving versus time curve (AUC). We powered the study to detect a 25% difference&#xD;
      in AUC from an internal pilot study which indicated mean AUC of 60 cm.hr-1 (SD 5-10) among&#xD;
      patients receiving PECs or LA infusion in our clinical service, to 45 cm.hr-1. We had&#xD;
      observed the standard deviation of the AUC to be in the order of 15 cm.hr-1. Assuming a Type&#xD;
      I error of 0.05 and a Type II error of 0.1, then n=11 patients would be required each group&#xD;
      to detect this difference with 90% power. We obtained IRB permission for n=15 each group to&#xD;
      allow for protocol violations or patient drop-out.&#xD;
&#xD;
      Data was collected at 1, 4-6, 12-14 and 20-24 hr, post-operatively. It was tested for&#xD;
      distribution initially using the Kolmogorov-Smirnov test. For each patient, their AUC both&#xD;
      moving and at rest was calculated by plotting their pain VRS versus time using Graph Pad&#xD;
      Prism v.6. The mean AUC according to the three study groups was then calculated and inspected&#xD;
      for distribution as described above, and all AUC data was found to be normally distributed.&#xD;
      Therefore, AUC data is expressed as mean ± SD and was compared using ANOVA with post hoc&#xD;
      Bonferroni correction. Non-normally distributed data was compared using the Kruskal-Wallis&#xD;
      test for repeated measurements. Categorical data (e.g. the incidence of potential adverse&#xD;
      effects) were compared using Fischer's exact test where appropriate. P&lt;0.05 was deemed&#xD;
      statistically significant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">May 2017</completion_date>
  <primary_completion_date type="Actual">May 2017</primary_completion_date>
  <phase>Phase 4</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>Supportive Care</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under curve of verbal rating score (VRS) of pain moving versus time</measure>
    <time_frame>VRS pain was measured at 1 hour, 4-6 hours, 10-14 hours, and 20-24 hours postoperatively</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total postoperative opioid consumption</measure>
    <time_frame>Over first 24 postoperative hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative nausea and vomiting</measure>
    <time_frame>Recorded at the following time points after surgery: 1 hour, 2-4 hours, 6-8 hours, 10-14 hours 20-24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative sedation score</measure>
    <time_frame>Recorded at the following time points after surgery: 1 hour, 2-4 hours, 6-8 hours, 10-14 hours 20-24 hours</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Breast Diseases</condition>
  <condition>Anesthesia</condition>
  <condition>Block</condition>
  <arm_group>
    <arm_group_label>PECs Block</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomised to receive pectoral plane blocks and a sham local anaesthetic infusion wound catheter</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LA Infusion</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomised to receive a local anaesthetic infusion wound catheter; No sham pectoral plane block performed as patients usually under general anaesthetic at time of block.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PECs Block &amp; LA Infusion</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomised to receive pectoral plane blocks and a local anaesthetic infusion wound catheter.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Pectoral Plane Block</intervention_name>
    <arm_group_label>PECs Block</arm_group_label>
    <arm_group_label>PECs Block &amp; LA Infusion</arm_group_label>
    <other_name>PECs Block</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Local Anaesthetic Wound Infusion Catheter</intervention_name>
    <description>Levobupivicaine 0.1% @10ml/hr via a wound infusion catheter</description>
    <arm_group_label>LA Infusion</arm_group_label>
    <arm_group_label>PECs Block &amp; LA Infusion</arm_group_label>
    <other_name>Local Anaesthetic Infusion</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female&#xD;
&#xD;
          -  Undergoing breast surgery, including wide local excision (WLE) and sentinel lymph node&#xD;
             biopsy (SLNB), mastectomy +- SLNB&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Male&#xD;
&#xD;
          -  Undergoing flap reconstruction breast surgery, implant surgery or bilateral breast&#xD;
             surgery&#xD;
&#xD;
          -  Chronic pain syndrome&#xD;
&#xD;
          -  Local anaesthetic allergy&#xD;
&#xD;
          -  Contraindication to routine postoperative analgesia, e.g. paracetamol&#xD;
&#xD;
          -  Contraindication to regional anaesthesia, i.e. localised infection&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Donal Buggy</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mater Misericordiae University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Anaesthesia, Mater Misericordiae University Hospital</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ireland</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>January 15, 2017</study_first_submitted>
  <study_first_submitted_qc>January 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 19, 2017</study_first_posted>
  <last_update_submitted>September 6, 2017</last_update_submitted>
  <last_update_submitted_qc>September 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mater Misericordiae University Hospital</investigator_affiliation>
    <investigator_full_name>Sean Keane</investigator_full_name>
    <investigator_title>Dr. Sean Keane; Anaesthesia SpR</investigator_title>
  </responsible_party>
  <keyword>Breast surgery</keyword>
  <keyword>Pectoral plane block</keyword>
  <keyword>PECs</keyword>
  <keyword>Local anaesthesia infusion</keyword>
  <keyword>Analgesia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anesthetics</mesh_term>
    <mesh_term>Anesthetics, Local</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>IPD will not be made available to other researchers as this has been pre-determined with patients as part of the process of informed consent.</ipd_description>
  </patient_data>
  <!-- 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/NCT03024697
org study id: PECS 123
nct id: NCT03024697
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In this proposed study, the investigators are looking to conduct a prospective, randomised,
      double-blind, non-inferiority trial, to study single-shot pectoral plane (PECs) blocks versus
      continuous local anaesthetic infusion analgesia versus a combination of PECs blocks and local
      anaesthetic infusion analgesia, when it comes to providing analgesia for most forms of breast
      surgery.

      Breast surgery is common, and the optimal form of analgesia is currently unknown. Techniques
      involving local anaesthetic, such as pectoral plane (PECs) blocks and infusion pumps, are
      growing in popularity, as they reduce the amount of opioid medications used. Opioids are
      associated with nausea, vomiting, low blood pressure, drowsiness and constipation, and as
      such, opioid-sparing analgesic regimens postoperatively are becoming more common. These
      regimens will typically involve paracetamol, a NSAID (non-steroidal anti-inflammatory drug),
      and a local anaesthetic technique.

      Pectoral plane blocks involve a once-off injection of local anaesthetic at two locations
      within the chest wall, typically done after the patient undergoes general anaesthesia, but
      before the commencement of surgery. Local anaesthetic infusion pumps involve the insertion of
      a catheter into the wound at the end of surgery, before the patient emerges from general
      anaesthesia, that constantly emit local anaesthetic over a defined period of time. Each
      technique is considered extremely safe, and is considered acceptable as a form of pain relief
      in patients undergoing breast surgery.

      There are no published works comparing pectoral plane blocks with local anaesthetic infusion
      pump analgesia, and the investigators see a gap in the knowledge base that can be addressed.
      This study will allow efficacy, safety and cost of the three techniques to be compared. The
      investigators feel the study design is robust, and statistical analysis based on previously
      published works in the area of postoperative analgesia has allowed the study to be powered
      appropriately.

      Patients undergoing breast surgery are a vulnerable group, and this is recognised via the
      provision of a comprehensive Patient Information Leaflet and a commitment to respecting the
      process of Informed Consent. The investigators also recognise this is a stressful period in a
      woman's life, and the study will be conducted in a sensitive and compassionate manner.

      The study has been designed to be prospective, randomised, and double-blinded. The
      anaesthetic will be standardised in relation to analgesic and anti-emetic agents
      administered, in order to minimise variables. Chronic post-surgical pain is a growing area of
      research, and the follow-up telephone interview at 3-months will allow investigation of this.

      A Data Record Form will be utilised for data collection, which will subsequently be analysed
      statistically. Data will be handled sensitively, securely, and by the minimum number of
      researchers. A plan is in place for destruction of data at an appropriate time.

      While there will be no direct benefit to participants, including monetary considerations,
      this research study will add to the knowledge-base surrounding analgesia for breast surgery.
Methods The Mater Misericordiae University Hospital's Institutional Review Board (IRB)
      approved this study; reference number 1/378/1840, dated December 21st, 2016. It was
      registered with clinicaltrials.gov; reference number NCT03024697, dated February 15th, 2017.
      Forty-five ASA I-III female patients aged 18 years or older, undergoing non-ambulatory breast
      cancer surgery under general anaesthesia between January and May 2017 were included. All
      participants provided informed written consent.

      Non-ambulatory breast cancer surgery encompassed wide-local excision with lymph node
      resection, simple mastectomy, and mastectomy with lymph node resection. Those undergoing
      latissimus dorsi or DIEP (deep inferior epigastric perforator) flap reconstruction were
      excluded. Patients with chronic pain syndromes, local anaesthetic allergy, contraindication
      to simple analgesics, local infection over the proposed block site, coagulopathy, or
      co-morbid conditions precluding the provision of informed consent, were excluded. All
      patients were day of surgery admission and attended a preoperative anaesthetic assessment
      clinic.

      Patients were allocated into three groups using computer-generated randomisation, with the
      study number and group allocation concealed in sealed envelopes. Blocked randomisation in
      groups of 9 was applied, giving similar numbers in each group as the study progressed. Groups
      were named 'PECs', 'Local anaesthetic infusion (LA infusion)' , and 'Both (PECS & LA
      infusion)', which were evenly distributed to opaque envelopes numbered one to forty-five in
      accordance with randomisation. The randomisation key was held by an independent party, and
      was not used to reveal participant group allocations until data analysis commenced. 'PECs'
      patients received PECS I & II blocks and a sham wound infiltration catheter. 'LA infusion'
      patients received a continuous local anaesthetic wound infusion catheter. 'PECs & LA
      infusion' patients received a combination of techniques, without the initial local
      anaesthetic bolus via the wound infusion catheter. PECs blocks were performed while patients
      were under general anaesthesia, prior to the commencement of surgery. The operative surgeon
      sited wound infusion catheters during skin closure at the end of surgery.

      Patients were induced with fentanyl 1-2 μg.kg-1, followed by propofol titrated to the absence
      of verbal response. Anaesthesia was maintained using an oxygen, air and sevoflurane
      combination. Airway management and lung ventilation strategies were at the discretion of the
      supervising anaesthetist. Patients received a standard intraoperative analgesic regimen of
      paracetamol 1g and dexketoprofen 50mg intravenously (IV), with rescue morphine as deemed
      necessary. Combination antiemetics, including ondansetron 0.1-0.15 mg.kg-1 IV, dexamethasone
      0.1-0.2 mg.kg-1 IV or droperidol 0.01-0.015 mg.kg-1 IV, were administered according to
      patient risk factors. Intraoperative management was otherwise left to the discretion of the
      supervising anaesthetist. Routine monitoring was used in accordance with AAGBI guidelines15.
      An electronic anaesthetic record was used to document physiological parameters. Perioperative
      events, such as induction of anaesthesia, initial skin incision, and end of surgery, were
      annotated on the record.

      PECs I & II blocks were performed on the side of surgery, using the ultrasound-guided
      technique described by Blanco et al9, 10. The patient was placed in the supine, head-up,
      position with the arm abducted. The skin was prepared with chlorhexidine gluconate
      2%/isopropyl alcohol 70% (BD, ChloraPrep, NJ, USA). PECs blocks were performed with a
      22-gauge echogenic needle (B. Braun, Ultraplex 360 cannula, Hessen, Germany; 50-80mm), using
      the same ultrasound machine (Sonosite Edge, Sonosite, Inc., Bothwell, WA, USA) and transducer
      (Sonosite HFL 50x, Sonosite, Inc., Bothwell, WA, USA). The ultrasound probe was placed
      inferolaterally at the mid-clavicular level. The axillary artery and vein were identified,
      and the probe moved laterally until pectoralis major, pectoralis minor and serratus anterior
      muscles were located at the level of the 3rd rib. A needle in-plane approach was taken until
      the needle tip was positioned in the plane between pectoralis major and minor muscles, and
      levobupivacaine 0.25% 10ml was injected. The needle was advanced until it occupied the space
      between pectoralis minor and serratus anterior muscles, and a further 20ml of levobupivacaine
      0.25% was injected.

      Blinding was not considered necessary for 'LA infusion' group patients, as PECs blocks were
      performed under general anaesthesia. All patients had a wound infusion catheter sited and
      attached to an elastometric pump (B. Braun, ON-Q PainBuster, Hessen, Germany), which was
      placed by the operating surgeon during skin closure at the end of surgery. For blinding
      purposes, patients in the 'PECs' group received a sham wound infiltration catheter system.
      'LA infusion' and 'PECS & LA infusion' patients received levobupivacaine 0.1% at 10ml.hr-1
      for 24 hours postoperatively, while 'PECs' patients received sodium chloride 0.9% at the same
      rate. 'LA infusion' patients were administered an initial bolus of levobupivacaine 0.25% 20ml
      at the end of surgery. Those who performed the procedures, or were involved in the
      perioperative management, were not involved in postoperative pain assessment or data
      collection. Study interventions as described occurred while patients were under general
      anaesthesia.

      Patients were monitored for 24 hours after surgery, initially in the post-anaesthesia care
      unit (PACU), and then at ward level once PACU discharge criteria were met. Oxycodone 1-2mg IV
      as required was prescribed for rescue analgesia in the PACU. A standard analgesic protocol of
      paracetamol 1g PO/IV 6-hourly regular, ibuprofen 400mg PO 8-hourly regular, and oxycodone
      immediate release (oxynorm) 5-10mg 1-hourly as required for rescue analgesia, was prescribed
      for all patients. Ondansetron 4-8mg IV 8-hourly as required was prescribed, to be
      administered in the event of postoperative nausea and vomiting (PONV).

      The primary outcome measure of the study was area under curve of verbal rating score (VRS) of
      pain moving versus time, (AUC) where VRS pain was measured at 1 hour, 4-6 hours, 10-14 hours,
      and 20-24 hours postoperatively. At each assessment, patients were invited to report their
      pain VRS pain at rest. Pain while moving was defined as pain experienced while sitting
      forward from a recumbent position. Secondary outcome measures were total opioid consumption
      over a 24-hour period and presence of adverse events. An investigator masked to group
      allocations recorded vital signs, pain scores, antiemetic administration and opioid use
      postoperatively. Adverse events such as sedation, respiratory depression, hypotension,
      pruritus and PONV were also recorded.

      Statistical Analysis

      Data was analysed by Graph Pad Prism v6 (Salt Lake City, UH). The primary end-point was area
      under the VRS moving versus time curve (AUC). We powered the study to detect a 25% difference
      in AUC from an internal pilot study which indicated mean AUC of 60 cm.hr-1 (SD 5-10) among
      patients receiving PECs or LA infusion in our clinical service, to 45 cm.hr-1. We had
      observed the standard deviation of the AUC to be in the order of 15 cm.hr-1. Assuming a Type
      I error of 0.05 and a Type II error of 0.1, then n=11 patients would be required each group
      to detect this difference with 90% power. We obtained IRB permission for n=15 each group to
      allow for protocol violations or patient drop-out.

      Data was collected at 1, 4-6, 12-14 and 20-24 hr, post-operatively. It was tested for
      distribution initially using the Kolmogorov-Smirnov test. For each patient, their AUC both
      moving and at rest was calculated by plotting their pain VRS versus time using Graph Pad
      Prism v.6. The mean AUC according to the three study groups was then calculated and inspected
      for distribution as described above, and all AUC data was found to be normally distributed.
      Therefore, AUC data is expressed as mean ± SD and was compared using ANOVA with post hoc
      Bonferroni correction. Non-normally distributed data was compared using the Kruskal-Wallis
      test for repeated measurements. Categorical data (e.g. the incidence of potential adverse
      effects) were compared using Fischer's exact test where appropriate. P<0.05 was deemed
      statistically significant.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Area under curve of verbal rating score (VRS) of pain moving versus time
time frame: VRS pain was measured at 1 hour, 4-6 hours, 10-14 hours, and 20-24 hours postoperatively
measure: Total postoperative opioid consumption
time frame: Over first 24 postoperative hours
measure: Postoperative nausea and vomiting
time frame: Recorded at the following time points after surgery: 1 hour, 2-4 hours, 6-8 hours, 10-14 hours 20-24 hours
measure: Postoperative sedation score
time frame: Recorded at the following time points after surgery: 1 hour, 2-4 hours, 6-8 hours, 10-14 hours 20-24 hours
arm group label: PECs Block
arm group type: Active Comparator
description: Patients randomised to receive pectoral plane blocks and a sham local anaesthetic infusion wound catheter
arm group label: LA Infusion
arm group type: Active Comparator
description: Patients randomised to receive a local anaesthetic infusion wound catheter; No sham pectoral plane block performed as patients usually under general anaesthetic at time of block.
arm group label: PECs Block & LA Infusion
arm group type: Active Comparator
description: Patients randomised to receive pectoral plane blocks and a local anaesthetic infusion wound catheter.
intervention type: Procedure
intervention name: Pectoral Plane Block
arm group label: PECs Block
arm group label: PECs Block & LA Infusion
other name: PECs Block
intervention type: Procedure
intervention name: Local Anaesthetic Wound Infusion Catheter
description: Levobupivicaine 0.1% @10ml/hr via a wound infusion catheter
arm group label: LA Infusion
arm group label: PECs Block & LA Infusion
other name: Local Anaesthetic Infusion
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Donal Buggy
role: Principal Investigator
affiliation: Mater Misericordiae University Hospital
facility: 
country: Ireland
responsible party type: Principal Investigator
investigator affiliation: Mater Misericordiae University Hospital
investigator full name: Sean Keane
investigator title: Dr. Sean Keane; Anaesthesia SpR
mesh term: Breast Diseases
mesh term: Anesthetics
mesh term: Anesthetics, Local
sharing ipd: No
ipd description: IPD will not be made available to other researchers as this has been pre-determined with patients as part of the process of informed consent.