Clinical trial NCT03708302: Serratus and Parasternal Infrapectoral Block for Breast Surgery.
Official title: Serratus and Parasternal Infrapectoral Block for Breast Surgery. A Randomized Controlled Double Blinded Study to Measure Impact on Time to Hospital Discharge in an Outpatient Setting.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Pain
Post-Op Complication
Keywords: breast surgery
serratus plane block
parasternal infrapectoral block
simple mastectomy
oncoplastic reduction mammoplasty
Lead sponsor: Western University, Canada
Sponsor class: OTHER
First posted: 2018-10-17
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Effective pain control is important following breast surgery as it improves quality of recovery, decreases the risk of chronic pain development and reduction of overall health care cost. Current strategies of pain management for breast surgery include use of opioid medication or addition of regional anesthesia along with general anesthesia. Serratus block and parasternal infrapectoral blocks are newly developed fascial plane blocks that are technically easy to perform, effective and safe based on our daily clinical practice and published evidence. We are comparing the addition of serratus and parasternal infrapectoral nerve block with general anesthesia to a combination of placebo and general anesthesia for breast reduction surgery. We propose that this would result in an improved efficiency resulting in early hospital discharge and improve quality of patient care, following breast reduction surgery.

Detailed description: Study Introduction:

Severe acute postoperative pain affects nearly 60% of breast surgery patients, potentially triggering adverse physiological and psychological responses, increased chronic pain incidence, and elevated healthcare costs. Effective perioperative pain management reduces chronic pain occurrence, improves recovery quality, and enables early hospital discharge, thus reducing overall healthcare expenses. Various analgesic strategies exist, ranging from regional techniques to opioid-based approaches. Combining multimodal analgesia with regional anesthesia offers superior pain control and enhances recovery quality. The chest wall and breast skin receive innervation from intercostal nerves, with branches providing sensory input to different areas. Understanding this innervation pattern is crucial for optimizing analgesic approaches in breast surgery and ensuring comprehensive pain relief across all affected regions.

Regional analgesic techniques offer several advantages over traditional parenteral opioid therapy, including enhanced pain relief, reduced opioid consumption and related side effects, quicker PACU discharge, and lower chronic pain occurrence. Paravertebral analgesia is particularly effective for breast surgery but presents drawbacks that limit its popularity, such as variable sensory distribution, potential epidural spread, failure rates, and serious risks like total spinal anesthesia or pneumothorax. Interfascial block techniques, aided by ultrasound, have gained traction in regional anesthesia. These techniques involve injecting local anesthetic into neuro-fascial planes adjacent to muscles or between muscle layers, facilitating its distribution to nerves. Interfascial blocks offer advantages like ease of performance, increased safety by avoiding direct nerve targeting, fewer injections, and superficial application, reducing risks associated with deeper nerve blocks. Given these benefits and a thorough understanding of thoracic wall anatomy, several interfascial blocks have been developed as alternatives to paravertebral blocks, aiming for equal efficacy with fewer risks, particularly important in the context of day case breast surgeries.

The serratus block for breast surgery:

The Serratus Plane Block, introduced by Blanco in 2013, involves injecting local anesthetic beneath the serratus anterior muscle to target intercostal nerve branches. However, our recent anatomical study revealed that a single midaxillary line injection inadequately covers the entire breast, prompting additional parasternal injections for comprehensive sensory coverage. Despite this refinement, no randomized controlled trial has yet assessed the efficacy of combined serratus and parasternal infrapectoral blocks in breast surgery analgesia.

Questions and Hypothesis:

1. Primary Question:

   Does the addition of serratus block and parasternal infrapectoral nerve block to patients undergoing breast surgery result in improved perioperative patient care resulting in early hospital discharge (breast reduction mammoplasty and simple mastectomy) compared to patients getting wound infiltration with local anesthetic infiltration by surgeon for analgesia?
2. Secondary Questions:

Does the addition of these blocks to general anesthesia result in other benefits such as:

I. Decreased chronic postoperative pain after 3 months, as assessed at 6 month post-surgery follow-up meeting.

II. less acute post-operative pain. III. less intraoperative opioid consumption. IV. less postoperative opioid consumption. V. less incidence of opioid-related side effects such as nausea, vomitus and pruritus.

VI. greater patient satisfaction with their pain relief improved. VII. greater quality of recovery after anesthesia. VIII. shorter phase I (PACU) and phase II (surgical day care, SDC) recovery times).

Trial Design:

This will be a prospective, double-blinded, randomized and controlled trial conducted at St. Joseph's Hospital, London, Ontario. The study will enroll 133 participants undergoing unilateral simple mastectomy or oncoplastic reduction mammoplasty surgery under general anesthesia. After obtaining written informed consent from eligible patients, study participants will be randomly assigned to one of two groups:

1. Study Group:

   Participants will receive preoperative ultrasound-guided unilateral serratus block with 20 ml of 0.5% ropivacaine on each injection at anterior axillary line at 4th rib and unilateral ultrasound guided parasternal infrapectoral block at the level of 4th with 20ml of 0.5% ropivacaine on each injection, at the surgical site, 15 minutes prior to receiving general anesthesia for the surgery. Patients in the study group will also receive sham injection of saline as infiltration by the surgeon near the conclusion of surgery (40 ml of saline).
2. Control group:

Before general anesthesia, participants will receive a preoperative "placebo injection" of 40 mls of saline instead of ropivacaine for unilateral serratus and parasternal infrapectoral nerve block on the surgical site. Patients will then receive 40 ml of 0.5% ropivacaine as injected by the surgeon as infiltration near the conclusion of surgery.

Patient enrollment and consent:

Patients will be approached for participation in this study when they present for their surgical consultation in the Breast Surgical Clinic or at the surgeon's clinic by the surgical team. They will be provided with information regarding the study (Introduction Letter and Letter of Information and Consent Form) and if they provide consent to be contacted for further information and eligibility assessment. One of study team members will then contact the patient after a week by telephone and review the study with them. They will have all questions addressed by telephone and if they wish to participate, they will bring their consent form with them on the surgery day (to avoid unnecessary visits to hospital during pandemic) and sign consent with a witness prior to any study intervention. They will have a further opportunity to have any questions answered at this time as well and can decline to participate in the study at any time. The signed consent form will be photocopied and they will be provided with a signed copy of their consent form for their records.

Randomization and Blinding:

Patients will be randomized to one of two groups by a computer-generated sequence. Investigators and participants will both be blinded to patient assignment at the time of randomization as well as throughout treatment and assessment. Randomization information will be kept in sealed individual envelopes that are opaque to light and sequentially numbered. Each envelope will only be opened after informed consent is given, and immediately prior to the commencement of the block procedure. The individual who generates the randomization schedule will not have contact with study patients. Patients who are randomized to the control group will receive equivalent volume of normal saline solutions for the bilateral blocks procedure in contrast to the patients in the intervention group who receive four injections of 20mls of 0.5% Ropivaciane for each injection. This is meant to maintain patient and investigator blinding. The anesthetist(s) performing the block will be blinded to the intervention along with the anesthetists performing the general anesthesia and the surgical team. Importantly, the intraoperative and postoperative opioids will be administered by anesthetists and nurses, respectively, who are blinded to group allocation. Furthermore, the research coordinator collecting all outcome data will also be blinded.

Surgical Interventions:

1. Simple Mastectomy:

   Patients undergoing simple mastectomy (removal of breast gland and skin envelope) without immediate reconstruction are typically booked as same day surgeries, meaning they go home after their surgery on the same day. The skin is incised and elevated off the breast gland at the subcutaneous plane, leaving only enough skin for primary wound closure. The breast gland is elevated off the pectoralis fascia which contributes to the majority of postoperative pain. A drain is typically left into the subcutaneous plane and managed by homecare until the drainage is less than 30 cc/24 hour period (most drains are in place for 5-7 days).
2. Oncoplastic reduction mammoplasty:

Oncoplastic breast reduction mammoplasty is another surgical technique meant as a breast conserving alternative to mastectomy in patients with larger, ptotic breasts in whom up to 60% of the breast is affected by disease and needs to be removed. In these procedures, the area of affected breast gland to be removed is excised while sparing the breast skin envelope, and the remaining gland is elevated off the pectoralis fascia and rotated to fill the defect, creating essentially a breast reduction pattern, upon which the breast skin is then redraped, creating a smaller breast without defect.

Preoperative Management:

Standard monitoring (ECG, blood pressure and oxygen saturation monitoring) will be applied, an intravenous access will be established and participants will receive midazolam 1-2 mg IV for anxiolysis as required. They will be positioned supine for the block performance. The skin overlying the chest wall will be disinfected using a chlorhexidine solution and a high-frequency linear ultrasound transducer (6-13 MHz, Sonosite M-Turbo) will be covered with a sterile plastic sheath. The block will be performed under strictly aseptic conditions by a staff regional anesthetist, by two regional anesthesiologists specialized to perform this nerve block.

Intraoperative Management:

All subjects will receive a standardized general anesthesia with a laryngeal mask airway or endotracheal intubation depending on the anesthesiologist looking after the participant for their surgery. They will receive intravenous induction using standard doses of fentanyl 1-2 mcg/kg, propofol 2-4 mg/kg and rocuronium 0.6mg/kg if needed. Anesthesia will be maintained with desflurane/sevoflurane (end-tidal concentration corresponding to 1-1.3 MAC, age-corrected) in a mixture of room air (50%) and oxygen (50%). Positive pressure ventilation will only be initiated when spontaneous ventilation cannot be maintained (e.g. when muscle relaxant is used). Positive pressure support will be titrated to maintain an end-tidal CO2 value of 30-40 mmHg. As per routine practice, fentanyl 1 mcg/kg, morphine 0.05 - 0.1 mg/kg or hydromorphone 0.0075 - 0.015 mg/kg will be administered to treat hemodynamic increases of more than 25% above pre-induction baseline values. As per routine antiemetic prophylaxis, dexamethasone 0.1mg/kg at the beginning of surgery and ondansetron 4 mg IV will be given 30 min before the anticipated end of surgery and dimenhydrinate (gravol) 0.5 mg/kg will only be reserved as a last-line therapy in PACU for otherwise not controllable PONV.

Postoperative pain management:

As per routine practice, morphine 2 mg IV or hydromorphone 0.4 mg IV every 5 min as needed will be administered to all participants with pain on a Numeric Rating Scale (NRS) ≥ 4 or after participant request. As soon as oral intake is started, participants will also have access to oxycodone 5 mg PO when needed. Upon discharge from hospital, participants will receive a prescription for Tylenol #3 (acetaminophen 300 mg/codeine 30 mg per tablet) 1-2 tablets every 4 h as needed or Percocet® (acetaminophen 325 mg/oxycodone HCl 5 mg per tablet) if intolerant to codeine. Participants will be contacted over the phone the following day inquiring about their quality of recovery based on the (QoR-15) questionnaire and will also be asked about their level of pain based on numerical analogue score, total and cumulative oral analgesic consumed since discharge from the hospital, opioid-related side effects, block-related side effects, and satisfaction with postoperative analgesia at postoperative days one.

Eligibility criteria: Inclusion Criteria:

* women aged 18-80 years
* ASA I to III (American Society of Anesthesiologists Physical Status Classification System)
* Undergoing unilateral oncoplastic breast reduction mammoplasty, simple mastectomy surgery, or lumpectomy at St. Joseph's Hospital.
* Day surgery procedures

Exclusion Criteria:

* Inability to understand or to provide consent
* Inability or unwillingness to comply with required follow-up assessments
* Psychiatric disorder affecting patient assessment
* Contraindication to regional anesthesia, e.g. coagulopathy
* Allergy to local anesthetic
* Chronic pain and/or chronic use of opioids with a daily use of over 30 mg oxycodone or equivalent per day
* Contraindication to a component of multimodal analgesia
* Preexisting neuropathy with motor or sensory deficits in the area of the anterolateral chest wall
* Infection near injection site
* Pregnancy
* BMI\>40
* Complication or adverse events unrelated to the study intervention that precludes evaluation of the primary and secondary outcomes.

Primary outcomes:
measure: Time to hospital discharge.
timeFrame: 24 hours postoperative period
Secondary outcomes:
measure: post operative pain score
timeFrame: 48 hours
measure: Cumulative Opioid consumption (in Intravenous Morphine equivalent).
timeFrame: 48 hours
measure: Duration of Hospital stay in minutes.
timeFrame: 24 hours
measure: Opioid-related side effects requiring treatment.
timeFrame: 48 hours
measure: Presence/absence of block-related side effects.
timeFrame: 48 hours
measure: Quality of recovery score (QoR) after anesthesia (at discharge and on Post Operative Day 1)
timeFrame: 48 hours
Other outcomes:
Locations:
city: London
country: Canada
facility: St. Joseph's Hospital
state: Ontario
Study officials:
affiliation: London Health Sciences Center, Western University, London. Ontario. Canada
name: Abhijit Biswas, MD
role: PRINCIPAL_INVESTIGATOR
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