Erector Spinae Versus Paravertebral Nerve Blocks for Breast Surgery

Breast Surgery Clinical Trial

Official title:

A Randomized, Subject-Masked, Active-Controlled, Parallel-Arm Clinical Trial Comparing Erector Spinae and Paravertebral Nerve Blocks

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03549234
• Other study ID #: Erector Spinae vs PVB
• Status: Completed
• Phase: Phase 4
• Start date: July 12, 2018
• Est. completion date: May 8, 2019

Study information

• Verified date: July 2020
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. The PVB has several limitations: it can decrease blood pressure, and very rare—but serious—complications have occurred, including neuraxial injection, neuraxial hematoma, and pleural puncture. An alternative block has been described: the erector spinae plane block. 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: there are few 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. Lastly, the plane may be easier to catheterize for continuous peripheral nerve blocks relative to the relatively-small volume PVB.

There are therefore multiple theoretical reasons to prefer the erector spinae plane block. Unfortunately, it remains unknown if the analgesia provided by this new technique is comparable to that provided with the PVB. The investigators therefore propose to compare these two techniques with a randomized, subject-masked, active-controlled, parallel-arm, human subjects clinical trial.

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 the study 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 University of California San Diego (UCSD) Institutional Review Board (IRB)-approved Informed Consent Form (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. Inclusion and exclusion criteria are listed in another section.

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) erector spinae 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 him/herself).

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.

Ropivacaine 0.5% (with epinephrine 1:200,000-400,000) will be administered via the needle into the target plane. For erector spinae plane blocks, this will be at the T3 level for surgery involving the axilla and the T4 level for surgery not involving the axilla (20 mL of local anesthetic for unilateral surgery; 16 mL of local anesthetic each side for bilateral surgery). For PVBs without axillary work, this will be at the T3 and T5 levels. For PVBs with axillary work, 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 subjects take their first opioid tablet as well as the time at which subjects believe the block starts to wear off.

Outcome measurements (end points). Pain scores will be recorded using the Numeric Rating Scale (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. The investigators will collect the times at which subjects felt their block resolve and subjects 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 an erector spinae 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 an erector spinae plane block compared with a paravertebral block (primary: cumulative intravenous morphine equivalents).

Primary end point: In order to claim that erector spinae 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 erector spinae 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 erector spinae) 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 erector spinae 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) [Kairaluoma, 2004]. 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 a total enrollment of 100 subjects. 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 [Mascha, et al 2012].

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: May 8, 2019
• Est. primary completion date: May 8, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Surgery

Intervention

Drug:
• Erector Spinae (single injection)
Ropivacaine 0.5% (with epinephrine 1:200,000-400,000) will be administered via the needle into the target plane.
• Paravertebral (single injection)
Ropivacaine 0.5% (with epinephrine 1:200,000-400,000) will be administered via the needle into the target plane.

Locations

Country	Name	City	State
United States	UCSD Medical Center (Hillcrest and Thornton)	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

Country where clinical trial is conducted

United States, 

References & Publications (7)

Finneran JJ 4th, Gabriel RA, Khatibi B. Erector Spinae Plane Blocks Provide Analgesia for Breast and Axillary Surgery: A Series of 3 Cases. Reg Anesth Pain Med. 2018 Jan;43(1):101-102. doi: 10.1097/AAP.0000000000000695. — View Citation

Forero M, Adhikary SD, Lopez H, Tsui C, Chin KJ. The Erector Spinae Plane Block: A Novel Analgesic Technique in Thoracic Neuropathic Pain. Reg Anesth Pain Med. 2016 Sep-Oct;41(5):621-7. doi: 10.1097/AAP.0000000000000451. — View Citation

Forero M, Rajarathinam M, Adhikary S, Chin KJ. Continuous Erector Spinae Plane Block for Rescue Analgesia in Thoracotomy After Epidural Failure: A Case Report. A A Case Rep. 2017 May 15;8(10):254-256. doi: 10.1213/XAA.0000000000000478. — View Citation

Ilfeld BM, Madison SJ, Suresh PJ, Sandhu NS, Kormylo NJ, Malhotra N, Loland VJ, Wallace MS, Proudfoot JA, Morgan AC, Wen CH, Wallace AM. Treatment of postmastectomy pain with ambulatory continuous paravertebral nerve blocks: a randomized, triple-masked, placebo-controlled study. Reg Anesth Pain Med. 2014 Mar-Apr;39(2):89-96. doi: 10.1097/AAP.0000000000000035. — View Citation

Kairaluoma PM, Bachmann MS, Korpinen AK, Rosenberg PH, Pere PJ. Single-injection paravertebral block before general anesthesia enhances analgesia after breast cancer surgery with and without associated lymph node biopsy. Anesth Analg. 2004 Dec;99(6):1837-43, table of contents. — View Citation

Mascha EJ, Turan A. Joint hypothesis testing and gatekeeping procedures for studies with multiple endpoints. Anesth Analg. 2012 Jun;114(6):1304-17. doi: 10.1213/ANE.0b013e3182504435. Epub 2012 May 3. — View Citation

Naja Z, Lönnqvist PA. Somatic paravertebral nerve blockade. Incidence of failed block and complications. Anaesthesia. 2001 Dec;56(12):1184-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Nausea and Vomiting	Nausea and vomiting was recorded using a 0-10 Likert scale (0 = no nausea; 10 = vomiting) on postoperative day 1. Higher scores represent a worse outcome.	postoperative day 1
Other	Sleep Disturbances		postoperative day 1
Other	Time of Block Resolution	This was recorded as the time at which a participant subjectively noticed that the nerve block was wearing off and sensation was returning.	postoperative day 1
Other	Opioid Consumption	Number of oxycodone tablets (in mg) taken by the participant after discharge from the recovery room was recorded during follow-up on postoperative day 1.	postoperative day 1
Primary	Numeric Rating Scale Pain Scores	Range scale minimum 0, maximum 10. Lower pain scores are considered a better outcome, higher pain scores are considered a worse outcome.	1 day (PACU pain scores)
Primary	OR and PACU Opioid Consumption	This outcome measure reflects the total amount of opioid administered in the operating room and recovery room perioperatively. Specific time points are not applicable since operating room and recovery room times differ among subjects.	up to 1 day, in the OR and PACU