Enhanced Recovery Strategies in Elective Breast Surgery

Opioid Use Clinical Trial

Official title:

Evaluating the Use of Enhanced Recovery Strategies and Paravertebral Block in Elective Breast Reduction and Breast Augmentation

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT03187080
• Other study ID #: 2016-1388
• Secondary ID: A539730SMPH\SURG
• Status: Suspended
• Phase: Phase 4
• Start date: April 2024
• Est. completion date: April 2026

Study information

• Verified date: September 2023
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Postoperative pain, nausea, and vomiting are frustrating sequelae of elective breast surgery. Poorly managed postoperative pain can lead to increased opioid use, increased postoperative nausea and vomiting (PONV), delayed return to work and usual activities, unplanned hospital admissions, surgical complications, and patient dissatisfaction. In light of the growing opioid epidemic in the United States, any intervention that potentially minimizes opioid use may have meaningful individual and societal impact. In patients undergoing breast reduction and breast augmentation surgery, multiple techniques for managing postoperative pain are used commonly. One such technique is the use of a paravertebral block (PVB), which is a method of injecting local anesthesia into the area surrounding the spinal nerves in order to decrease sensation and pain in the chests and breasts in the setting of breast surgery. PVB is generally used concomitantly with standard multimodal perioperative pain management including cool compress, non-steroidal anti-inflammatories (NSAIDs), acetaminophen, and opioids. All of these pain management strategies are used at the University of Wisconsin and are considered standard of care for breast surgery nationwide.

The overall purpose of this study is to evaluate interventions that aim to optimize pain control, minimize the risk of PONV, and improve recovery after elective breast surgery. We will do this by (1) Comparing PVB with standard pain management strategies in patients undergoing planned breast reduction and breast augmentation, and (2) Comparing "enhanced recovery after surgery" (ERAS) strategies to standard of care for patients undergoing planned breast reduction and breast augmentation. This will be studied using pain assessments, validated surveys, medication logs, and review of medical records.

Description:

Bilateral breast reduction and bilateral breast augmentation are both routine plastic surgery procedures commonly performed on an outpatient basis. While patient satisfaction following these procedures is high, postoperative pain management can be challenging, resulting in decreased patient satisfaction, delayed recovery including delayed return to work and daily activities, increased opioid pain medication requirements and occasionally unplanned hospital admissions, surgical complications, and increased cost of care [Davis].

PVB is a common procedure used for analgesia in breast surgery in combination with multimodal perioperative pain regimens, though its use has not been formally studied in a prospective fashion. Our Division recently retrospectively studied the use of PVB in breast reduction, finding that postoperative pain scores and rates of PONV were decreased with the use of PVB. To date, no prospective, randomized, blinded study has been performed to evaluate the efficacy of PVB on perioperative pain management in this patient population. Multiple studies performed in patients undergoing post-mastectomy breast reconstruction have demonstrated the safety and efficacy of PVB as an adjunctive pain control modality. In a prospective study evaluating patients undergoing post-mastectomy autologous breast reconstruction, Parikh and colleagues found that patients who received PVB had significant improvement in postoperative pain, shorter time to oral-only opioid usage and decreased length of hospital stay compared to patients who received standard postoperative pain control [Parikh]. A meta-analysis conducted by Schnabel and colleagues studied 15 randomized controlled trials evaluating PVB in addition to general anesthesia for patients undergoing breast surgery found significant decrease in postoperative pain scores with low risk ratio for adverse events [Schnabel].

The concept of "enhanced recovery" or "fast track" surgery was borne out of several prospective studies in the gastrointestinal surgery literature, and has been shown in multiple types of operations and across specialties to be beneficial for patients as well as economically advantageous [Anderson, Bonde, Adamina]. The concept of using an integrative, multimodal, multidisciplinary approach for minimizing the physiologic stress response in attempt to improve recovery after surgery was first described in 1997 [Kehlet]. Throughout the past several years there has been increasing focus on applying such principles to breast surgery, though to date the literature has focused on operations primarily performed for breast cancer, including mastectomy and breast reconstruction [Arsalani, Bonde]. The goal of "enhanced recovery after surgery" (or "ERAS") protocols is to identify and employ a set of pre-, peri- and postoperative strategies to improve patient outcomes and the recovery process after surgery. Such interventions have the goal of minimizing perioperative physiologic stressors (e.g. pain, fatigue, anxiety, nausea and vomiting) that can lead to morbidity. Categories related to "enhanced recovery after breast surgery" (ERABS) include standardized preadmission counseling, preoperative fasting, preanesthetic anxiolytics, anesthetic protocols, intraoperative warming, pain control, prevention of nausea and vomiting, mobilization, and postdischarge support [Arsalani].

Thus, the overarching goal of this study is to evaluate the safety and efficacy of PVB alone, as well as in conjunction with a global set of perioperative enhanced recovery strategies in elective breast surgery. We hypothesize that the use of such strategies will improve the patient experience of breast reduction and augmentation beyond the current standard of care.

We are conducting this study because, to our knowledge, no previous study has prospectively evaluated the use of PVB (with or without additional ERAS strategies) in groups comprised only of patients undergoing non-oncologic breast surgery. We hypothesize that the use of PVB in breast reduction and breast augmentation may be as beneficial as it has been shown to be in patients undergoing lumpectomy or mastectomy and subsequent reconstruction. In addition, no other study, to our knowledge, has prospectively studied enhanced recovery strategies (with PVB) in elective breast surgery (including reduction and augmentation). Due to the physical and psychosocial differences in patients undergoing elective breast surgery (compared to oncologic breast surgery), we wish to study elective breast surgery to better understand the effects of ERABS strategies on postoperative pain, nausea, and overall patient recovery.

There are four serial aims of this study. The overarching goal of the study is to prospectively assess the use of PVB as an adjunct for postoperative pain control both alone and in the setting of related ERABS strategies in elective breast surgery (both breast reduction and breast augmentation, two of the most common non-oncologic breast operations performed in an ambulatory setting). The methodologies used to assess postoperative pain, the set of collective ERABS strategies, the potential risks and benefits of study participation, and the inclusion/exclusion criteria will be the same in the groups studying breast reduction and those studying breast augmentation. As both operations are performed on a regular basis in the PI's practice, we feel it essential to evaluate both operations.

Following completion of all 4 groups, we will be able to assess the impact of PVB alone as well as the impact of ERABS strategies in both breast reduction and breast augmentation. We hope that this will help inform clinical conversations with patients and also guide clinical decision-making with respect to postoperative pain management and overall optimization of recovery in elective breast surgery. We feel it important that the four distinct groups be included under the single protocol.

The primary aim in all four groups in this study is to evaluate postoperative pain scores in patients receiving either paravertebral block or ERABS strategies compared to patients who do not receive these interventions. Additional outcomes include use of analgesic and antiemetic medication, development of PONV, time to discharge, patients' assessment of quality of recovery as determined by a validated survey and overall patient satisfaction.

Group 1: To prospectively determine the effect of PVB on perioperative pain and postoperative recovery following breast reduction. We will use patient-reported pain assessments (including a numeric rating scale) to evaluate our primary endpoint (pain scores on postoperative day 1 (POD1)) as well as additional outcome measures of pain scores in recovery and at 1 week post-surgery. To determine the effect of PVB on secondary endpoints of this study, we will calculate analgesic and antiemetic medication use, compare average time (minutes) spent in the PACU, average time (minutes) spent in Phase 2, total time (minutes) between the end of the operation and discharge to home, and evaluate the occurrence of unplanned hospital admission, PONV, overall satisfaction, patients' assessment of quality of recovery as determined by a validated survey [Gornall, Myles], and complications. This data will be obtained through review of medical records, surveys, and postoperative diaries.

Patients electing to undergo breast reduction will be invited to participate in the study at their preoperative visit. All patients choosing to take part in the study will be consented prior to their procedure. The study participants will be randomized to one of two arms within each Group using block randomization. Details of the allocated group will be written on a piece of paper and placed inside sealed, opaque, and sequentially numbered, envelopes. Block randomization will be performed using a computer-generated number list and an Excel spreadsheet template. Block randomization will ensure equal numbers of subjects in each group. Either the anesthesiologist or the surgical team will open the envelope when the patient presents to UW Transformations Surgery Center or Madison Surgery Center (MSC) the day of surgery. The subject will be randomized to receive either (a) standard postoperative nausea and pain control as well as a sham superficial injection of normal saline or (b) PVB in addition to standard postoperative nausea and pain control. PVB and sham superficial injections of normal saline will be performed by a trained anesthesiology provider and will be performed in the routine manner. Surgery will take place in the usual fashion and participants will receive standard of care for pain and nausea control.

Following surgery, patients will be assessed for postoperative pain, nausea and vomiting. Assessment for postoperative pain will consist of a validated pain score survey administered prior to transfer to phase II postoperatively, on POD1, and at their one-week postoperative visit. Participants will also be asked to record, using a postoperative diary/log, when they take postoperative analgesics and antiemetics, which medications are taken, and quantity of medication taken. This will also be reviewed both in the medical record and upon discussion with the participant at the postoperative visits. Assessment of the time spent in the recovery room, time spent in Phase 2 of recovery, and time to discharge from the hospital (total time between the end of surgery to discharge from hospital), will be obtained via review of the medical record. At the first postoperative visit, participants will undergo a routine interview that includes discussion of their pain control, analgesic and antiemetic use, recovery process, and overall satisfaction. The medical record will be reviewed for any unplanned postoperative hospital readmissions related to the surgery.

Group 2: To prospectively determine the effect of PVB on perioperative pain and postoperative recovery following breast augmentation. We will use patient-reported pain assessments (including a numeric rating scale) to evaluate our primary endpoint (pain scores on postoperative day 1 (POD1)) as well as additional outcome measures of pain scores in recovery and at 1 week post-surgery. To determine the effect of PVB on secondary endpoints of this study, we will calculate analgesic and antiemetic medication use, compare average time (minutes) spent in the PACU, average time (minutes) spent in Phase 2, total time (minutes) between the end of the operation and discharge to home, and evaluate the occurrence of unplanned hospital admission, PONV, overall satisfaction, patients' assessment of quality of recovery as determined by a validated survey, and complications. This data will be obtained through review of medical records, surveys, and postoperative diaries.

The procedures will be the same as those described for Group 1, except patients will be undergoing planned breast augmentation.

Groups 3 and 4: To prospectively compare the standard of care for ambulatory breast surgery to "fast track" (also known as "enhanced recovery") strategies for breast surgery by assessing pain scores, pain medication and antiemetic use, development of nausea/vomiting, time to discharge, and patient satisfaction.

For the third serial Group in the study, patients electing to undergo breast reduction surgery will be invited to participate in the study at their preoperative visit. For the fourth Group in the study, all procedures will be the same as described in this section, but the patients will be undergoing breast augmentation surgery (not breast reduction). All patients choosing to take part in the study will be consented prior to their procedure. The study participants will be randomized, using block randomization, a computer-generated randomization template, and sealed, numbered, and opaque envelopes, to either receive (a) perioperative pain, nausea, and recovery strategies as part of our Enhanced Recovery after Breast Surgery (ERABS) protocol, or (b) perioperative instructions, anesthesia and medications as per our institution's current standard of care for elective breast reduction or breast augmentation.

We will use validated pain assessments to evaluate our primary endpoint (pain scores on postoperative day 1 (POD1)) as well as additional outcome measures of pain scores in recovery and at 1 week post-surgery. To determine the effect of PVB on secondary endpoints of this study, we will calculate analgesic and antiemetic medication use, compare average time (minutes) spent in the PACU, average time (minutes) spent in Phase 2, total time (minutes) between the end of the operation and discharge to home, and evaluate the occurrence of unplanned hospital admission, occurrence of PONV, assessment of recovery, overall satisfaction, and complications. This data will be obtained through review of medical records, questionnaires, and postoperative diaries.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 296
• Est. completion date: April 2026
• Est. primary completion date: April 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age equal to and greater than 18 years.

• Medically cleared to undergo elective breast surgery (including associated anesthesia) at UW Transformations Surgery Center or Madison Surgery Center (MSC).

• Undergoing bilateral breast augmentation or bilateral breast reduction by the PI (Dr. Venkat Rao).

Exclusion Criteria:

• Minors or under the age of 18

• Pregnant or breast feeding women

• Incarcerated women

• Males

• Individuals unable to give consent due to another condition such as impaired decision-making capacity.

• Women who take opioid pain medications on a regular basis prior to surgery.

• Women with a history of opioid abuse and/or dependence.

• Women who, based on anesthesiologist discretion, are not candidates for paravertebral block.

• Women with BMI >35

• Women with a diagnosis of obstructive sleep apnea who are noncompliant with their treatment (e.g. CPAP use).

• Women with a history of bleeding disorders precluding safe paravertebral block.

• Women on anticoagulation therapy who have not held their anticoagulation as recommended by their surgeon or anesthesiologist.

• Women with a history of infection at the site of paravertebral block.

• Women not medically cleared for surgery at Transformations or MSC and thus would not be undergoing surgery at Transformations or MSC. This would include women with sepsis/bacteremia, significant valvular disorders or heart conditions.

Related Conditions & MeSH terms

• Acute Pain
• Nausea
• Opioid Use
• Pain, Acute
• Postoperative Nausea and Vomiting
• Satisfaction
• Vomiting
• Vomiting, Postoperative

Intervention

Procedure:
• Paravertebral block procedure using either local anesthetic (0.25% bupivacaine) or sterile saline
Paravertebral block (PVB) will be performed in the standard fashion using an out-of-plane ultrasound approach by an anesthesiologist with appropriate training in regional anesthesia. Landmarks on the patient will be identified. The skin will be sterilized. The intended target (paravertebral space) will be located using an ultrasound. A Pajunk UniPlex NanoLine needle will be inserted. A syringe filled with sterile saline (used for hydrodissection) connected to a syringe of 0.25% bupivacaine with 2.5 mcg/mL of epinephrine will be connected to the Pajunk needle and used for injection. The needle will be advanced toward and through the superior costotransverse ligament or internal intercostal membrane. Once through the ligament, the pleura will be seen deflecting anteriorly with the hydrodissection. Negative aspiration will be confirmed, and the local anesthetic will be injected into the paravertebral space.

Other:
• Enhanced recovery after breast surgery (ERABS) strategies
For comparing ERABS strategies to our current standard of care, we will utilize the following perioperative strategies [Arsalani]: Standardized written information given preoperatively. Allow clear liquids for up to 2 hours prior to arrival at the surgery center. Use paravertebral block to augment postoperative pain control. Standardized multimodal analgesic regimen Antiemetics Easily accessible call-in or walk-in postop care/support The proposed strategies differ from standard of care in the following ways: PVB is less commonly used in elective surgery. Patients do not eat or drink after midnight. There is no standardized preoperative information packet. Anesthetic/intraoperative analgesic and antiemetic regimen varies between providers.

Procedure:
• Sham paravertebral block using saline
Paravertebral block (PVB) will be performed in the standard fashion using an out-of-plane ultrasound approach by an anesthesiologist with appropriate training in regional anesthesia. Landmarks on the patient will be identified. The skin will be sterilized. The intended target (paravertebral space) will be located using an ultrasound. A Pajunk UniPlex NanoLine needle will be inserted. A syringe filled with sterile saline (used for hydrodissection) connected to a syringe of sterile saline will be connected to the Pajunk needle and used for injection. The needle will be advanced toward and through the superior costotransverse ligament or internal intercostal membrane. Once through the ligament, the pleura will be seen deflecting anteriorly with the hydrodissection. Negative aspiration will be confirmed, and the local anesthetic will be injected into the paravertebral space.

Drug:
• Paravertebral block using local anesthetic
Use of local anesthetic (0.25% bupivacaine) that is *NOT* an experimental drug but will be used as part of the paravertebral block to provide local anesthetic. This will not be given to those in the sham block groups.

Locations

Country	Name	City	State
United States	University of Wisconsin Madison	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
University of Wisconsin, Madison

Country where clinical trial is conducted

United States, 

References & Publications (13)

Adamina M, Kehlet H, Tomlinson GA, Senagore AJ, Delaney CP. Enhanced recovery pathways optimize health outcomes and resource utilization: a meta-analysis of randomized controlled trials in colorectal surgery. Surgery. 2011 Jun;149(6):830-40. doi: 10.1016/j.surg.2010.11.003. Epub 2011 Jan 14. — View Citation

Anderson AD, McNaught CE, MacFie J, Tring I, Barker P, Mitchell CJ. Randomized clinical trial of multimodal optimization and standard perioperative surgical care. Br J Surg. 2003 Dec;90(12):1497-504. doi: 10.1002/bjs.4371. — View Citation

Arsalani-Zadeh R, ElFadl D, Yassin N, MacFie J. Evidence-based review of enhancing postoperative recovery after breast surgery. Br J Surg. 2011 Feb;98(2):181-96. doi: 10.1002/bjs.7331. — View Citation

Bonde C, Khorasani H, Eriksen K, Wolthers M, Kehlet H, Elberg J. Introducing the fast track surgery principles can reduce length of stay after autologous breast reconstruction using free flaps: A case control study. J Plast Surg Hand Surg. 2015;49(6):367-71. doi: 10.3109/2000656X.2015.1062387. Epub 2015 Jul 10. — View Citation

Dabbagh A, Elyasi H. The role of paravertebral block in decreasing postoperative pain in elective breast surgeries. Med Sci Monit. 2007 Oct;13(10):CR464-7. — View Citation

Davis GM, Ringler SL, Short K, Sherrick D, Bengtson BP. Reduction mammaplasty: long-term efficacy, morbidity, and patient satisfaction. Plast Reconstr Surg. 1995 Oct;96(5):1106-10. — View Citation

Gornall BF, Myles PS, Smith CL, Burke JA, Leslie K, Pereira MJ, Bost JE, Kluivers KB, Nilsson UG, Tanaka Y, Forbes A. Measurement of quality of recovery using the QoR-40: a quantitative systematic review. Br J Anaesth. 2013 Aug;111(2):161-9. doi: 10.1093/bja/aet014. Epub 2013 Mar 6. — 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):1837-1843. doi: 10.1213/01.ANE.0000136775.15566.87. — View Citation

Kehlet H. Multimodal approach to control postoperative pathophysiology and rehabilitation. Br J Anaesth. 1997 May;78(5):606-17. doi: 10.1093/bja/78.5.606. — View Citation

Klein SM, Bergh A, Steele SM, Georgiade GS, Greengrass RA. Thoracic paravertebral block for breast surgery. Anesth Analg. 2000 Jun;90(6):1402-5. doi: 10.1097/00000539-200006000-00026. — View Citation

Myles PS, Weitkamp B, Jones K, Melick J, Hensen S. Validity and reliability of a postoperative quality of recovery score: the QoR-40. Br J Anaesth. 2000 Jan;84(1):11-5. doi: 10.1093/oxfordjournals.bja.a013366. — View Citation

Parikh RP, Sharma K, Guffey R, Myckatyn TM. Preoperative Paravertebral Block Improves Postoperative Pain Control and Reduces Hospital Length of Stay in Patients Undergoing Autologous Breast Reconstruction after Mastectomy for Breast Cancer. Ann Surg Oncol. 2016 Dec;23(13):4262-4269. doi: 10.1245/s10434-016-5471-1. Epub 2016 Aug 3. — View Citation

Schnabel A, Reichl SU, Kranke P, Pogatzki-Zahn EM, Zahn PK. Efficacy and safety of paravertebral blocks in breast surgery: a meta-analysis of randomized controlled trials. Br J Anaesth. 2010 Dec;105(6):842-52. doi: 10.1093/bja/aeq265. Epub 2010 Oct 14. Erratum In: Br J Anaesth. 2013 Sep;111(3):522. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Numerical Pain Scores, rated by patient on 0-10 scale	Our primary outcome of interest is self-reported pain (0-10 visual analog scale) on post-operative day 1 (POD1).	Postoperative day 1.
Secondary	Numerical Pain Scores, rated by patient on 0-10 scale	Pain scores in PACU/recovery area	Day of surgery
Secondary	Time spent in each phase of care prior to discharge	Time spent in recovery after surgery	Day of surgery
Secondary	Time to discharge to home	Time between conclusion of surgery and discharge from the surgery center	Day of surgery
Secondary	Analgesic requirements (pain medication quantity)	Quantity and frequency of pain medication usage	1 week after surgery
Secondary	Post-operative nausea and vomiting (subjective report)	Occurrence of nausea and vomiting after surgery	1 week after surgery
Secondary	Anti-emetic requirements (anti-nausea medication quantity)	Use of anti-nausea mediation postoperatively	1 week after surgery
Secondary	Patients' assessment of perceived quality of recovery using Modified Quality of Recovery Survey (MQOR-40)	Patients' assessment of quality of recovery using validated 'quality of recovery 40' survey	1 week after surgery