ISRCTN46621916.

Trial name or title	Study protocol for a double blind, randomised, placebo‐controlled trial of continuous subpectoral local anaesthetic infusion for pain and shoulder function following mastectomy: SUB‐pectoral Local anaesthetic Infusion following MastEctomy (SUBLIME) study
Methods	Single‐blinded (outcome observer) clinical RCT Sequence generation via computer‐generated randomization list follow‐up: 6 months
Participants	Participants: all women presenting for unilateral mastectomy surgery at the Royal Cornwall Hospitals NHS Trust and Royal Devon and Exeter NHS Foundation Trust, aged ≥ 18 years Operation: mastectomy with or without axillary involvement 2 groups, size: N/A Age (range), groups 1, 2: N/A All female participants Exclusion criteria: inability to give informed consent; primary reconstructive surgery; hypotension, hypovolaemia or any form of shock; known allergy or sensitivity to LA agents, morphine, paracetamol or ondansetron; pregnancy; daily opioid analgesic use; inability to understand or use a PCA device; inability to understand or complete the visual analogue assessment tools; concurrent participation in another interventional study that might conflict with this study
Interventions	Group 1 (saline, control arm): 0.9% sodium chloride, is sourced from standard NHS supplies at the participating sites, delivered by means of an infusion catheter and device, supplied as a sterile prepacked kit and licensed for the delivery of LA. At the end of the surgical procedure the surgeon inserts the infusion catheter percutaneously into the subpectoral plane under direct vision within the surgical field. After skin closure, a 20 mL bolus of comparator treatment is given via the catheter, which is then connected to the infusion device to provide an infusion of study treatment at a continuous rate of 5 mL/h for 24 h. Group 2 (levobupivacaine): 0.25% levobupivacaine (chirocaine), an established LA infusion agent, prepared as a 2.5 mg/mL solution and packaged by the manufacturer (Abbott) delivered by means of an infusion catheter and device, supplied as a sterile prepacked kit and licensed for the delivery of LA. At the end of the surgical procedure the surgeon inserts the infusion catheter percutaneously into the subpectoral plane under direct vision within the surgical field. After skin closure, a 20 mL bolus of active or comparator treatment is given via the catheter, which is then connected to the infusion device to provide an infusion of study treatment at a continuous rate of 5 mL/h for 24 h. In the active treatment arm this equates to a 50 mg bolus of levobupivacaine followed by an infusion of 12.5 mg/h. Both groups: paracetamol 1 g IV, ondansetron 4 mg IV, and dexamethasone 3.3 mg (+/‐ 0.1 mg) IV unless clinically contraindicated. Intubation and ventilation at anaesthetist’s discretion ‐ with muscle relaxant of anaesthetist’s choice. Sevoflurane in air: depth of anaesthesia at anaesthetist’s discretion. Fentanyl: 3 µg/kg to 6 µg/kg IV during surgery. Fluids: at anaesthetist’s discretion. All other nonopiate and nonantiemetic drugs: at anaesthetist’s discretion. IV rescue morphine in recovery unit, 2 mg increments IV morphine PCA, 1 mg bolus, 5 min lockout. Paracetamol 1 g 6‐hourly orally. Ibuprofen 400 mg 8‐hourly orally unless contraindicated as needed: ondansetron 4 mg (IV) 8‐hourly and cyclizine 50 mg (IV) 8‐hourly Adjuvants: none Immediate postop pain control: data not available
Outcomes	Dichotomous: none Continuous: VAS pain scores at rest at 24 h, 14 days and 6 months after surgery; BPI at 6 months. Secondary: total morphine consumption (mg) in the first 24 h (defined as the 24 h following start of the subpectoral infusion), including all morphine given in the recovery unit and cumulative PCA use as recorded by the PCA device and (2) total pain over the first 24 h, as defined by measurement of the area‐under‐the‐curve of each participant’s self‐reported pain scores at rest, measured using a VAS. VAS pain scores are recorded in the recovery unit and then at 4‐hourly intervals for the first 24 h. Secondary outcome measures include the number of PCA attempts in the first 24 h following start of infusion. Incidence of postoperative nausea and/or vomiting and use of supplemental analgesics and postoperative antiemetics in the first 24 h; self‐reported analgesia use at 14 days and 6 months; duration of hospital stay; shoulder movement assessed by goniometry at 24 h, 14 days and 6 months following surgery; shoulder function (as measured by the validated 31) at 6 months. Following the participant’s discharge, the length of stay in hospital is recorded by the research nurse. Adverse events reported: data not available
Starting date	15 October 2012
Contact information	Dr Roger Langford, roger.langford@rcht.cornwall. nhs.uk
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