Impact of Erector Spinae Plane Block on Chronic Postsurgical Pain in Breast Cancer Patients

Study Overview
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Brief Summary
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Chronic postsurgical pain (CPSP) has an incidence of 46% in patients after breast cancer surgery, which seriously affects patients' physiological and psychological function, as well as quality of life. Acute pain is an independent risk factor for persistent pain after surgery. Erector spinae plane block (ESPB) provided excellent perioperative analgesia in patients undergoing breast surgery. Dexmedetomidine as an adjuvant of local anesthetics prolongs the duration of peripheral nerve block and decreases the requirements of postoperative analgesia. The investigators hypothesize that, for breast cancer patients undergoing mastectomy, ESPB (with a combination of 0.5% ropivacaine 35 ml and dexmedetomidine 1 microgram/kg) can reduce the occurrence of CPSP. The purpose of this randomized controlled trial is to investigate the impact of ESPB with adjuvant dexmedetomidine on the incidence of CPSP in breast cancer patients after mastectomy. We will also observe the impact of ESPB on long-term survival in these patients.

Detailed Description
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Chronic postsurgical pain (CPSP), defined as pain persisting or recurring for longer than three months after surgery, has an incidence of 46% in patients after breast cancer surgery. It seriously affects patients' physiological and psychological function, as well as quality of life. Acute pain is an independent risk factor for persistent pain after surgery. As a core technique in multimodal analgesia, peripheral nerve block plays an important role in controlling acute postoperative pain in breast cancer patients; it may also prevent the occurrence of CPSP. In our previous trial, use of paravertebral block reduced CPSP at six months after breast cancer surgery; the effect was more prominent in the subgroup of patients following mastectomy. But conclusions can not be achieved until now. Regional anesthesia is also supposed to produce favorable effects on long-term oncological outcomes, possibly by relieving surgery-related stress response and immunosuppression. But, again, available evidences are conflicting regarding regional block and long-term cancer outcomes. The erector spinae plane block (ESPB) was first described by Forero in 2016 and provides excellent perioperative analgesia with minimal side effect in patients undergoing thoracic, breast, and spinal surgeries. As one of the interfacial plane block techniques, the ESPB targets dorsal and ventral rami of the spinal nerves from T2-T7; it may produce effect by diffusing into the paravertebral and intercostal spaces and spreading in both cephalic and caudal directions. Dexmedetomidine is a highly selective α2-adrenoceptor agonist with sedative, analgesic and anti-anxiety properties. When used as an adjuvant to local anesthetics, dexmedetomidine prolongs the duration nerve block and decreased the requirement of postoperative analgesia. The investigators hypothesize that, for breast cancer patients undergoing mastectomy, ESPB (with 0.5% ropivacaine 35 ml combined with dexmedetomidine 1 microgram/kg) can reduce the occurrence of CPSP. The purpose of this randomized controlled trial is to investigate the impact of ESPB with adjuvant dexmedetomidine on the incidence of CPSP in breast cancer patients after mastectomy. We will also observe the effect of ESPB on long-term prognosis in this patient population.

Official Title
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Impact of Erector Spinae Plane Block With Adjuvant Dexmedetomidine on Chronic Postsurgical Pain in Breast Cancer Patients: a Two-center Randomized Controlled Trial

Conditions
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Breast Neoplasms, Mastectomy, Nerve Block, Dexmedetomidine, Pain, Postoperative, Chronic Pain, Prognosis

Intervention / Treatment
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* Procedure: Erector spinae plane block
* Procedure: Control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of 18 years or over, but less than 85 years; Scheduled to undergo mastectomy for primary unilateral breast cancer. Exclusion Criteria: Previous breast cancer surgery with an incision of >2 cm; Chronic opioid dependence or long-term intake of analgesic medicines (>3 months); Any contraindication to erector spinae plane block, including intrathoracic infection, infection at the puncture site, cancer invasion of the puncture site, severe spinal deformity, history of spinal surgery, and severe coagulopathy; Inability to communicate in the preoperative period because of profound dementia, deafness, language barriers, or end-stage disease; History of malignant tumor in other organs, or a current combination of malignant tumor of other organs; History of coronary heart disease (diagnosed coronary stenosis, previous myocardial infarction, previous percutaneous coronary intervention or coronary artery bypass grafting); preoperative hepatic or renal impairment (alanine transaminase and/or aspartate transaminase ≥2 times of upper limit of normal, or serum creatinine>133 µmol/L); history of peptic ulcer or hemorrhage; ASA classification IV or above; Allergy to ropivacaine.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erector spinae plane block group<br>Prior to general anesthesia, ultrasound guided erector spinae plane block (ESPB; performed with 0.5% ropivacaine 35 ml with dexmedetomidine 1microgram/kg) is performed at T2 level (15 ml) and T4 level (20 ml). | Procedure: Erector spinae plane block<br>* Prior to general anesthesia, ultrasound guided erector spinae plane block (ESPB; performed with 0.5% ropivacaine 35 ml with dexmedetomidine 1 microgram/kg) is performed at T2 level (15 ml) and T4 level (20 ml).<br>|
| Sham Comparator: Control group<br>General anesthesia alone. | Procedure: Control group<br>* General anesthesia alone.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of chronic postsurgical pain (CPSP) at 6 months after surgery | CPSP is defined as pain persisting for at least three months after surgery that was not present before surgery or that had different characteristics, and other possible causes of pain were excluded (e.g., cancer recurrence, infection). | At 6 months after surgery | 
| Progression-free survival (long-term outcomes) | Progression-free survival is defined as the time from randomization to disease progression (recurrence or metastasis) or death from any cause. | Up to 3 years after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of chronic postsurgical pain (CPSP) at 3 and 12 months after surgery | CPSP is defined as pain persisting for at least three months after surgery that was not present before surgery or that had different characteristics, and other possible causes of pain were excluded (e.g., cancer recurrence, infection). | At 3 and 12 months after surgery | 
| Incidence of neuropathic pain at 3, 6, and 12 months after surgery | Neuropathic pain is defined as a score at or above 0 on the Neuropathic Pain Questionnaire Short-form. The questionnaire contains three items, i.e., tingling pain, numbness, and increased pain due to touch. Each item is scored from 0 (no pain) to 100 (worst pain imaginable), and multiplied by a discriminant function coefficient (tingling: 0.017, numbness: 0.015, increased pain to touch: 0.011). The total sum of these is added to a constant value (-1.302) to yield a final score ranging from -1.302 to 2.998, with a cutoff of ≥0 suggesting neuropathic pain. | At 3, 6 and 12 months after surgery | 
| Overall survival (long-term outcome) | Overall survival is defined as the time from randomization to death from any cause. | Up to 3 years after surgery | 
| Event-free survival (long-term outcome) | Event-free survival is defined as the time from randomization to tumor recurrence/metastasis, re-hospitalization for any reason, or death from any cause. | Up to 3 years after surgery | 
| Quality of life (long-term outcome) | Quality of life is assessed with the breast cancer-specific Quality of Life Questionnaire (EORTC QLQ-BR53). It consists of EORTC-C30 [a 30-item questionnaire that provides assessments of functional dimensions (physical, role, cognitive, emotional, social, fatigue, pain, nausea/vomiting, a global health), the total score ranges from 0 to 100, with higher score indicating better function] and EORTC-BR23 [a 23-item questionnaire that provides assessments of symptom dimensions (systemic therapy side effects, arm symptoms, breast symptoms, body image, sexual functioning, sexual enjoyment, feeling of upset due to hair loss, and future perspective), the total score ranges from 0 to 100,with higher score indicating worse symptom]. | At 1 year, 2 years, and 3 years after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Mastectomy, Erector spinae plane block, Dexmedetomidine, Postoperative pain, Chronic postsurgical pain, Long-term prognosis