Clinical trial NCT03860974: Serratus Plane Versus Paravertebral Nerve Blocks for Breast Surgery
Official title: A Randomized, Subject-Masked, Active-Controlled, Parallel-Arm Clinical Trial Comparing Serratus Plane and Paravertebral Nerve Blocks
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Breast Surgery
Keywords: regional anesthesia
paravertebral
erector spinae
nerve block
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2019-03-04
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Following painful surgical procedures of the breast, postoperative analgesia is often provided with a paravertebral nerve block (PVB). For intense, but shorter-duration acute pain, a single-injection of local anesthetic is used with a duration of approximately 12 hours. Recently an alternative block has been reported: the serratus plane block.2 The theoretical benefits include ease of administration since it is a plane superficial to the PVB and therefore easier to identify and target with ultrasound (therefore increasing success rate); and an increased safety margin as there are fewer anatomic structures in the immediate area which could be injured with the needle; and, the target plane is much further from the intrathecal/epidural space relative to the PVB, therefore leakage of cerebrospinal fluid or injury to the spinal cord are less likely with the serratus compared to the PVB.3 There are, therefore, multiple theoretical reasons to prefer the serratus over the PVB. Unfortunately, it remains unknown if the analgesia provided by this new technique is comparable to that provided with the PVB.4 The investigators therefore propose to compare these two techniques with a randomized, subject-masked, active-controlled, parallel-arm clinical trial.

Detailed description: This investigation will be a randomized, subject-masked, active-controlled parallel-arm, human subjects clinical trial. Of note, the investigators will be using standard-of-care local anesthetic under an FDA-approved purpose and do not plan to research a possible change of indication or use of these medications as part of this research project. The treatments in both groups are currently used at our institution and there is true clinical equipoise at this time. The only difference in treatment between subjects who enroll versus those not enrolled in this study will be those who enroll will have the decision between which anatomic block location determined randomly, as opposed to the physician simply choosing him/herself.

Enrollment. Consenting adults undergoing breast surgery with a planned single-injection regional analgesic will be offered enrollment. Patients undergoing breast surgery with a planned perineural catheter regional analgesic will be excluded. Study inclusion will be proposed to eligible patients prior to surgery. If a patient desires study participation, written, informed consent will be obtained using a current UCSD IRB-approved ICF. Selection for inclusion will not be based on gender, race, or socioeconomic status. The study population of interest includes men and women of all races and socioeconomic status.

Preoperative Procedures. Following written, informed consent, the investigators will collect baseline anthropomorphic information (e.g., age, sex, height, and weight). All subjects will have a peripheral intravenous (IV) catheter inserted, standard noninvasive monitors applied, supplemental oxygen administered via a nasal cannula or face mask, and placed in the sitting position. Midazolam and fentanyl (IV) will be titrated for patient comfort, while ensuring that patients remain responsive to verbal cues. Both possible block locations will be viewed with ultrasound. If one or both of the locations is unacceptable for block placement in the clinician's opinion, the subject will not be randomized and will not proceed further with the study.

Subjects will then be randomized using a computer-generated list and opaque, sealed envelopes to one of two treatment groups: (blocks of 4, stratified for unilateral vs. bilateral surgery): (1) serratus plane or (2) paravertebral block. All blocks will be placed by a regional anesthesia fellow or resident under the direct supervision and guidance of a regional anesthesia attending (or by the attending themselves).

The area of needle insertion will be cleaned with chlorhexidine gluconate and isopropyl alcohol. All blocks will be placed using standard UCSD ultrasound-guided techniques as previously described.

Ropivacaine 0.5% (20 mL for unilateral surgery; 16 mL each side for bilateral surgery) will be administered via the needle into the target plane(s). For PVBs without axillary involvement, this will be at the T3 and T5 levels. For PVBs with axillary involvement, this will be at the T2 and T4 levels. For unilateral PVBs, 10 mL of local anesthetic will be injected per level. For bilateral PVBs, 8 mL of local anesthetic will be injected per level.

Single-injection blocks will be considered successful if, within 30 minutes, the subject experiences decreased sensation to cold temperature with an alcohol pad over the approximate level of the ipsilateral 4th thoracic dermatome. Misplaced blocks will be replaced successfully, or the patient excluded from further study participation. For subjects undergoing bilateral surgical procedures, a block using the same protocol will be administered on the contralateral side.

Intraoperatively, all subjects will receive a general anesthetic using inhaled and intravenous anesthetic and oxygen. Intravenous fentanyl will be administered for cardiovascular responsiveness to noxious stimuli at the discretion of the anesthesia provider.

Postop: Subjects will be discharged with a prescription for oxycodone 5 mg tablets for supplementary analgesia and instructed to record the time at which they take their first opioid tablet as well as the time at which they believe the block starts to wear off.

Outcome measurements (end points). Pain scores will be recorded using the NRS. Within the recovery room, pain scores, opioid requirements, and antiemetic administration will be recorded by nursing staff masked to treatment group. The morning following surgery, all subjects will be contacted by phone or in person \[if hospitalized\] to record lowest, average, highest, and current pain scores; sleep disturbances, and nausea using a 0-10 Likert scale (0 = no nausea; 10 = vomiting). For outpatients, opioid requirements will be recorded while inpatients will have opioid requirements extracted from the electronic medical record. In addition, the investigators will extract antiemetic use from the electronic record. They will collect the times at which subjects felt their block resolve and they consumed their first opioid analgesic pills following recovery room discharge.

Hypothesis 1: Following breast surgery, analgesia will be non-inferior in the recovery room with a serratus plane block compared with a paravertebral block as measured with the Numeric Rating Scale.

Hypothesis 2: For breast surgery, opioid consumption will be non-inferior in the operating and recovery rooms with a serratus plane block compared with a paravertebral block (primary: cumulative intravenous morphine equivalents).

Primary end point: In order to claim that serratus plane blocks are non-inferior to paravertebral blocks, both Hypotheses 1 and 2 must be at least non-inferior.

Statistical methods. Descriptive statistics will be provided by arm and in aggregate. Baseline characteristics of arms will be compared using the Wilcoxon-Mann-Whitney and Fisher's Exact tests. Key characteristics that are significantly different (p\<0.05) will be included as covariates in the analysis models.

Primary aim. The investigators will test the noninferiority of the serratus nerve block compared to the paravertebral nerve block. The 95% confidence interval (CI) associated with the Wilcoxon-Mann-Whitney test will be derived for the group difference (paravertebral minus serratus) in median pain scores within the recovery room. If the lower limit of the 95% CI is greater than -1.25, the investigators will conclude noninferiority. If there are significant differences between the groups in any key characteristics, these characteristics will be included as covariates in a linear model. The same noninferiority margin (-1.25) will be applied to the 95% CI for the covariate adjusted group difference in mean pain derived from the linear model.

The noninferiority of the serratus nerve block with regard to total opioid consumption within the operating and recovery rooms will be tested in the same manner as pain, i.e. comparing the limits of a 95% CI associated with the Wilcoxon-Mann-Whitney test to a predefined noninferiority margin (in this case 2 mg). Covariate adjusted linear models will again be applied in the event that key characteristics are significantly different between the groups.

Sample size justification. Power for the Wilcoxon-Mann-Whitney derived noninferiority testing is based on 10,000 simulated trials. The investigators simulated pain scores from a discrete distribution with median (interquartile range) 3 (2-5). Between the quartiles, the probability of each score was assumed constant. The distribution for each group was assumed to be the same. The sample size of n=50 per group provides 82% power to detect noninferiority in pain with a margin of 1.25. Similarly, opioid consumption was assumed to follow a truncated normal distribution with mean 2.5 mg and standard deviation 2 mg, and minimum value 0 mg. The sample size of n = 50 per group provides at least 95% power to detect noninferiority with margin 2 mg. Therefore, the investigators will enroll 50 subjects for each of two treatments with primary end point values for a total enrollment of 100 subjects with a primary end point. To allow for dropouts, the investigators will request a maximum enrollment of 120 subjects. Noninferiority in pain is tested first, and if significant, noninferiority in opioid consumption is tested. Under this hierarchical testing framework, no adjustment in alpha is necessary to control Type 1 error.

Eligibility criteria: Inclusion Criteria:

* undergoing unilateral or bilateral breast surgery with at least moderate postoperative pain anticipated
* analgesic plan includes a single-injection peripheral nerve block(s)
* age 18 years or older

Exclusion Criteria:

* morbid obesity as defined by a body mass index \> 40 (BMI=weight in kg / \[height in meters\]2)
* renal insufficiency (preoperative creatinine \> 1.5 mg/dL)
* chronic opioid use (daily use within the 2 weeks prior to surgery and duration of use \> 4 weeks)
* history of opioid abuse
* any comorbidity which results in moderate or severe functional limitation inability to communicate with the investigators or hospital staff
* pregnancy
* planned regional analgesic with perineural catheter placement
* incarceration

Primary outcomes:
measure: Mean/Median Numeric Rating Scale Pain Score Within the Recovery Room
timeFrame: Within the recovery room, averaging approximately 2 hours
measure: Mean/Median Opioid Consumption Within the Recovery Room
timeFrame: Within the recovery room following surgery and prior to recovery room discharge
Secondary outcomes:
measure: Number of Participants Requiring an Anti-emetic Within the Recovery Room
timeFrame: Within the recovery room, averaging approximately 2 hours
measure: Opioid Consumption After Recovery Room Discharge
timeFrame: Between the recovery room discharge to the postoperative day 1 data collection phone call
measure: WORST Pain Measured Using the Numeric Rating Scale Pain Score
timeFrame: Between the recovery room discharge to the postoperative day 1 data collection phone call
measure: Lowest Pain Measured Using the Numeric Rating Scale Pain Score
timeFrame: between the recovery room discharge to the postoperative day 1 data collection phone call
measure: Average Pain Measured Using the Numeric Rating Scale Pain Score
timeFrame: between the recovery room discharge to the postoperative day 1 data collection phone call
measure: Worst RECOVERY ROOM Pain Measured Using the Numeric Rating Scale Pain Score
timeFrame: within the recovery room following surgery and prior to recovery room discharge
measure: Awakenings Due to Pain
timeFrame: the first evening after surgery, averaging approximately 8 hours
measure: LEAST RECOVERY ROOM Pain Measured Using the Numeric Rating Scale Pain Score
timeFrame: within the recovery room following surgery and prior to recovery room discharge
measure: Opioid Consumption Within the Operating Room
timeFrame: Within the operating room, averaging approximately 2 hours
measure: Nausea and Vomiting Following Recovery Room Discharge
timeFrame: between discharge from the recovery room and the data collection phone call on postoperative day 1
measure: Time From Recovery Room Discharge Until First Opioid Use
timeFrame: between discharge from the recovery room and the data collection phone call on postoperative day 1
measure: Time From Recovery Room Discharge Until Block Resolution
timeFrame: between local anesthetic injection completion during the nerve block and the time when block resolution began
measure: WORST Pain Measured DURING NERVE BLOCK Using the Numeric Rating Scale Pain Score
timeFrame: During the placement of the nerve block
measure: Average Pain Measured DURING NERVE BLOCK Using the Numeric Rating Scale Pain Score
timeFrame: During the placement of the nerve block
measure: Time to Perform Nerve Block
timeFrame: The time from initial nerve block needle insertion until nerve block needle withdrawal
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University California San Diego
state: California
Study officials:
affiliation: UCSD Medical Center
name: Brian M Ilfeld, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gabriel RA, Swisher MW, Sztain JF, Curran BP, Said ET, Abramson WB, Khatibi B, Alexander BS, Finneran JJ, Wallace AM, Armani A, Blair S, Dobke M, Suliman A, Reid C, Donohue MC, Ilfeld BM. Serratus anterior plane versus paravertebral nerve blocks for postoperative analgesia after non-mastectomy breast surgery: a randomized controlled non-inferiority trial. Reg Anesth Pain Med. 2021 Sep;46(9):773-778. doi: 10.1136/rapm-2021-102785. Epub 2021 Jun 22.