Clinical trial NCT05711030: Thoracic Paravertebral Block Anesthesia for Breast Cancer Surgery
Official title: Thoracic Paravertebral Block Anesthesia for Breast Cancer Surgery: Single-Injection Versus Multiple Injections. A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Neoplasms
Breast Neoplasm Female
Cancer, Breast
Breast Cancer
Lead sponsor: Ciusss de L'Est de l'Île de Montréal
Sponsor class: OTHER
First posted: 2023-02-02
Enrollment: 68
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background:

Mastectomies are traditionally performed under general anesthesia (GA), often with the addition of regional anesthesia for post-operative pain relief. Thoracic paravertebral blocks (TPVB) had previously been described in the literature to be sufficient for intra-operative anesthesia as an alternative to GA. A 2021 literature review by Cochrane Library comparing paravertebral anesthesia (with or without sedation) to general anesthesia for patients undergoing oncologic breast surgery showed that TPVB could reduce post-operative nausea and vomiting (PONV), hospital stay, postoperative pain and time to ambulation. It also resulted in greater patient satisfaction compared to GA.

The aim of this study is to demonstrate the efficacy of single-injection TPVB done under ultrasound guidance for patients undergoing breast cancer surgery without axillary node dissection.

Hypothesis: Single-injection thoracic paravertebral block is non-inferior to multiple (3) injections for oncologic unilateral breast surgery anesthesia.

Methods: The current study is a prospective randomized controlled trial of patients undergoing oncologic breast surgery without axillary node dissection or immediate reconstruction. Patients will be randomized into two groups; thoracic paravertebral block (TPVB) single-injection or TPVB multiple (three) injections.

Significance/Importance: Oncologic breast surgery performed under TPVB and sedation lowers the risks of post-operative nausea and vomiting, decreases peri-operative use of narcotics, decreases pain scores at rest and on mobilization and leads to better overall patient satisfaction when compared to GA. It also leads to shorter hospital stays. Most studies use multiple injections to perform the block. Even though the risks associated with TPVB are low (3.6 per 1000 surgeries), the single-injection technique could reduce the risks even more. One injection is also easier to perform and of shorter duration, leading to greater patient tolerance and less side effects related to blocks performance duration such as vaso-vagal reactions or general discomfort. To date, no studies have compared the efficacy of single-injection paravertebral block and multiple injection techniques as the main modality of anesthesia for breast cancer surgery.

Detailed description: Breast cancer is the most common cancer among women representing around 25% of new cancer cases worldwide. Surgery is the mainstay of treatment. Mastectomies are usually performed under general anesthesia (GA), often with the addition of regional anesthesia for post-operative pain relief. TPVB have previously been described in the literature to be sufficient for intra-operative anesthesia as an alternative to GA. This technique was first developed by Sellheim in 1905, and was popularized by Eason and Wyatt in 1978. In recent years, there has been a regain of interest for this technique with the easier access to high-performance ultrasound. The thoracic paravertebral space is a wedged shaped space adjacent to the spine bilaterally. It is a continuous space filled with adipose tissue that communicates cranially and caudally. TPVB produce unilateral, segmental, sympathetic and somatic blockade of the chest. Landmark-based techniques were first described, but in recent years ultrasound-guided techniques have been shown to improve the success rate of the block. They can be performed through multiple injections at different thoracic levels or with a single injection. Mutiple injections offer many advantages including coverage for each dermatome associated to the blocked level. Whereas blockade of multiple contiguous levels when performing a single injection implies relying on the spread of local anesthetic (LA) to caudal and cranial levels to block more dermatomes. Some studies have demonstrated that single-injection paravertebral blocks at the level of T3-T4 could be a suitable alternative to general anesthesia, but the blocks were not done under ultrasound guidance and they did not compare the single-injection technique to the multiple injection technique. Thus, a randomized controlled trial comparing the single-injection TPVB technique to the multiple injection technique done under ultrasound guidance for breast cancer surgery anesthesia is needed. The single-injection technique would allow us to offer the TPVB benefits to our patients while decreasing the time to perform the block, the complication rate and therefore potentially improve patient satisfaction.

Our hypothesis is that the TPVB performed as a single injection is non inferior to multiple (three) injections for unilateral oncologic breast surgery without axillary intervention.

The current study is a prospective randomized controlled trial of patients undergoing oncologic breast surgery without axillary node dissection or immediate reconstruction. Patients will be randomized into two groups; thoracic paravertebral block (TPVB) single-injection or TPVB multiple (three) injections. Sedation and analgesia will be standardized for both groups. The block will be performed preemptively by a blinded anesthesiologist at least 20 minutes before surgical incision. 30 milliliters (ml) of ropivacaine 0.5% will be injected on the operating side (maximum 3 milligrams per kilograms (mg/kg)) either as a single injection or fractionated into three injections at three different paravertebral levels.

Preemptive postoperative analgesia plan:

• Each patient will receive standard preemptive postoperative analgesic medication comprising of oral acetaminophen 1 gram (g) preoperatively

Preemptive postoperative nausea and vomiting prevention plan:

• Each patient will receive standard preemptive postoperative nausea and vomiting prevention medication comprising of dexamethasone 4 mg intravenous (IV) at the beginning of the procedure and ondansetron 4 mg IV at the end of the procedure.

Patients will be offered midazolam 1-2 mg IV as needed (PRN) and fentanyl 25-50 mcg IV PRN before performing the TPVB.

All patients will be monitored using 5-lead electrocardiogram, non-invasive blood pressure, pulse oximetry and end-tidal carbon dioxide monitoring. A NOL index (NOL trademark (™), Medasense Biometrics Ltd, Ramat Gan, Israel) as well as a bispectral index device (BIS, Covidien, USA) to allow anesthesia nociception and depth monitoring respectively.

Procedural sedation will be maintained with propofol using BIS monitoring for a target range of 60-80. All patients will receive oxygen (O2) through nasal cannula with end-tidal carbon dioxide (EtCO2) monitoring.

A NOL index monitor will be used to guide analgesic dosage intra-operatively. A NOL \> 25 for 1 minute suggests a high nociceptive response. The anesthesiologist will be allowed to give fentanyl in 25 mcg increments every 3 minutes for a maximum of 2 mcg/kg of adjusted body weight. If the maximum dose of fentanyl has been reached, ketamine 0.25 mg/kg can be given and repeated after 10 minutes. If the patient cannot tolerate the surgical procedure after both doses of ketamine have been given, the anesthesiologist will convert to GA by the method of his/her choice.

The total dose of IV fentanyl and ketamine given intraoperatively will be recorded as primary outcomes. Total dose of IV propofol used for sedation will also be recorded.

For the total duration of the anesthesia, monitoring data will be collected electronically via a computer connected to the monitors as well as on the Drager ventilator system. A logbook will be created to allow standardized data collection regarding the primary and secondary endpoints. Total intraoperative fentanyl and ketamine dosages and total postoperative hydromorphone consumption will be recorded. Postoperative hydromorphone will be given in the post-anesthesia care unit (PACU) if the Visual Analog Score (VAS) is \> 4/10. Time to meet discharge criteria (Aldrete score \> 9) and the incidence of PONV will also be noted.

Eligibility criteria: Inclusion Criteria:

• Patients \> 18 years old with American Society of Anaesthesiologists (ASA) status I-III, BMI\<35, undergoing partial or total mastectomies without axillary lymph node dissection

Exclusion Criteria:

* \< 18 years old
* Body mass index (BMI) \> 35
* Body weight under 50 kg
* Obstructive sleep apnea (moderate to severe)
* Unable to communicate with the investigators
* Receiving anticoagulation or experiencing any bleeding disorder
* Known allergy to local anesthetics, fentanyl or hydromorphone
* Active infection at injection sites
* Preexisting neurological deficit or psychiatric illness
* Severe cardiovascular disease
* Liver failure
* Renal failure (estimated glomerular filtration rate \<15 mL/ min/1.73 m2)
* Pregnancy
* Arrhythmia (NOL monitoring cannot be used reliably)
* Technical inability to proceed with the blocks
* History of chronic pain with daily opioid use during the 3 months before surgery
* Patient refusal

Primary outcomes:
measure: Total perioperative fentanyl (mcg) consumption
timeFrame: Intraoperative, about 30 minutes
measure: Total perioperative ketamine (mg) consumption
timeFrame: Intraoperative, about 30 minutes
Secondary outcomes:
measure: Total dose of propofol (mg) required for sedation
timeFrame: Intraoperative, about 30 minutes
measure: Adverse events
timeFrame: Intraoperative and postoperative, about 3 hours
measure: Level of the block using ice test preoperatively
timeFrame: Intraoperative, about 30 minutes
measure: Postoperative pain at rest and on movement (VAS) in PACU and day surgery unit
timeFrame: Postoperative, about 2 hours
measure: Postoperative total analgesic dose of hydromorphone (mg)
timeFrame: Postoperative, about 2 hours
measure: PONV (Post Operative Nausea and Vomiting) in PACU and day surgery unit
timeFrame: Postoperative, about 2 hours
measure: Readiness for hospital discharge (following regular institution criteria)
timeFrame: Postoperative, about 2 hours
measure: Conversion rate to General Anesthesia (GA)
timeFrame: Intraoperative, about 30 minutes
measure: Block failure rate requiring General Anesthesia (GA) to commence surgery
timeFrame: Intraoperative, about 30 minutes
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: CIUSSS de l'Est de l'Île de Montréal
state: Quebec
Study officials:
affiliation: Ciusss de L'Est de l'Île de Montréal
name: Ariane Clairoux, MD
role: PRINCIPAL_INVESTIGATOR
References: