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Double-blinded, Placebo-controlled, Prospective Randomized Trial Evaluating the Efficacy of Paravertebral Block with and Without Continuous Paravertebral Block Analgesia in Outpatient Breast Cancer Surgery

Chester C. Buckenmaier III MD, Kyung H. Kwon CRNP, Robin S. Howard MA, Geselle M. McKnight CRNA, Craig D. Shriver MD, William T. Fritz MD, Gerard A. Garguilo MD, Kristin H. Joltes PA-C, Alexander Stojadinovic MD
DOI: http://dx.doi.org/10.1111/j.1526-4637.2010.00842.x 790-799 First published online: 1 May 2010

Abstract

Background. Paravertebral block (PVB) is an effective alternative to general anesthesia for breast cancer surgery. Continuous paravertebral block (CPVB) anesthesia may extend postoperative analgesia at home and improve quality of early postoperative recovery of breast cancer patients.

Purpose. This double-blinded randomized trial was conducted to compare degree of pain, nausea, mood, level of symptom distress, and time to return to normal daily activity between PVB and PVB + CPVB in patients undergoing outpatient breast cancer surgery.

Patients and Methods. Between July 2003 and April 2008 we randomly assigned 94 (73 evaluable) patients in a 1:1:1 ratio with early breast cancer to single injection PVB followed by CPVB infusion of 0.1% or 0.2% ropivacaine vs placebo (saline) for 48 hours postoperatively for unilateral breast cancer surgery without reconstruction. The primary study endpoint was the degree of pain, nausea, mood state, level of symptom distress, and recovery time.

Results. Of the 468 patients assessed for eligibility, 94 consented and 21 with incomplete data or follow-up were excluded, leaving 73 subjects for analysis. There was no clinically significant difference in degree of postoperative pain, nausea, mood state, level of symptom distress, or return to normal activity among the three study groups.

Conclusion. The current study does not support the routine use of continuous paravertebral catheter anesthesia in patients undergoing operative treatment for breast cancer.

  • Regional Anesthesia
  • Paravertebral Nerve Block
  • Continuous Peripheral Nerve Block
  • Outcomes

Introduction

The transition of care from the inpatient to ambulatory and office-based setting has engendered interest in techniques that facilitate early discharge and return to activities of daily living (ADL). Thoracic (T1–T6) paravertebral block (PVB) has permitted ambulatory surgical management of breast cancer with excellent patient satisfaction and minimal side effects, and has demonstrated potential for significant cost savings [1]. When compared with general anesthesia, PVB has proven safe and effective, as it has been shown to provide significant reduction in complications of nausea, vomiting, and early postoperative pain, and to facilitate earlier return to normal activities in patients undergoing breast surgery [2–4].

Improvements in continuous peripheral nerve block catheter technology and the development of disposable infusion pumps led to investigations of continuous paravertebral block (CPVB) anesthesia as a means to prolong perioperative analgesia into the early postoperative recovery period in patients undergoing breast cancer surgery, while still preserving the benefits of early hospital discharge [5,6]. Earlier studies have shown the feasibility and safety of continuous local anesthetic infusions at home following surgery for breast cancer, and have correlated high patient satisfaction with prolonged pain control [7,8]. This two-institution, double-blinded, placebo-controlled, prospective randomized clinical trial was undertaken to determine if the addition of outpatient continuous paravertebral catheter anesthesia to single injection paravertebral block can improve postoperative pain, mood, level of symptom distress, and time to return to normal daily activity in patients undergoing unilateral breast cancer surgery without immediate reconstruction.

Methods

This report complies with the reporting standards established by the revised Consolidated Standards of Reporting Trials consensus statement [9].

Participants

A two-center, double-blinded, placebo-controlled, prospective randomized clinical trial was conducted by the Defense and Veterans Pain Management Initiative (DVPMI; http://www.DVPMI.org). This study was approved by the Department of Clinical Investigation, Human Use Committee (Institutional Review Board), Walter Reed Army Medical Center, Washington, DC, and Conemaugh Memorial Medical Center, Johnstown, PA. This study was conducted from July 2003 to April 2008 at the Walter Reed Army Medical Center and Conemaugh Memorial Medical Center. Written (signed) informed consent was obtained from each study subject. Participants were enrolled by the research coordinator and assigned to their group by the Investigational Pharmacy team member.

During the study period, 468 patients were assessed for study eligibility and 94 patients enrolled and provided informed consent. Once eligibility was confirmed, study subjects were assigned randomly to undergo single injection paravertebral block (PVB) at thoracic level 3 (T3 with T1 and T6 supplementation) followed by continuous infusion of either saline, 0.1% or 0.2% ropivacaine at 10 mL/h via a paravertebral catheter placed prior to operation at T3. Treatment groups are summarized in Table 1.

View this table:
Table 1

Postoperative continuous paravertebral block (CPVB) study treatment group, volume of infusion, and infusion rate

TreatmentVolume of infusion (mL)CPVB infusion rate over 72 hours after operation
0.9% sodium chloride solution750 mL10 mL/h
0.1% ropivacaine750 mL10 mL/h
0.2% ropivacaine750 mL10 mL/h

Eligible patients were nonpregnant, military health care beneficiaries older than 18 years of age, capable of providing informed consent. Eligible patients presented with nonpainful, nonlocally advanced, biopsy-proven infiltrating carcinoma of the breast scheduled to undergo one of the following procedures: modified radical mastectomy, simple mastectomy, lumpectomy with axillary lymphadenectomy, and lumpectomy with sentinel lymph node mapping and biopsy. Patients with active antibiotic-requiring infection, morbid obesity (body mass index >40 kg/m2), serious uncontrolled nonmalignant illness, competing clinical trial involvement, coagulopathy (international normalized ratio [INR] > 1.5), and allergy to local anesthetics were ineligible for study. Twenty-one of the 94 study subjects enrolled were excluded from study, leaving 73 evaluable subjects. The randomization flow diagram is in Figure 1.

Figure 1

Randomization flow diagram. f/u = follow-up.

Study Drugs and Blinding

The placebo (0.9% sodium chloride solution) and study drugs (0.1% and 0.2% ropivacaine) were prepared by the Investigational Pharmacy and packaged and labeled identically. All study drugs were in the form of a clear liquid prepared in two intravenous bags (one 250 mL bag while in the hospital and one 500 mL bag for outpatient use) to a total volume of 750 mL. The placebo (normal saline) was prepared identically. The placebo preparation was indistinguishable from the study drug preparations upon gross inspection. The paravertebral catheter was placed in the preoperative holding area prior to operation and the drug or placebo infusion begun during the operative procedure. All infusions were maintained at 10 mL/h. Both the study drugs and placebo were infused continuously for 72 hours. The disposable infusion pump (ambiT® infusion pump, Sorenson Medical, Salt Lake City, UT) is tamper resistant and set to prevent patient administration of a higher dose. The study subjects were educated on how to easily stop the infusion at any time. The patients were monitored closely and questioned by the study research nurse coordinator every other day for 7 days via phone calls. Additionally, specified follow-up visits were made with patients due to incomplete dosing in the event of patient-directed discontinuation of the drug infusion.

After informed consent, the research coordinator completed and submitted a prescription for “study drug” to the Investigational Pharmacy. Two intravenous “study drugs” are prepared and one is picked up by the study coordinator on the day of surgery and delivered it to the anesthesia provider. The other intravenous “study drug” is picked up by the study coordinator the next day prior to discharge and is delivered to the study nurse. To ensure blinding, normal saline, 0.1%, and 0.2% ropivacaine preparations were placed in the same clear plastic containers by the Investigational Pharmacist. Neither the subject nor the physician performing the PVB and CPVB anesthesia, and the surgeon had any knowledge of the solution contents. A study coordinator, blinded to the type of CPVB catheter preparation, recorded patient's pain, nausea, mood state, and level of symptom distress twice daily on days 1, 3, 5, and 7 following the operation.

Regional Anesthesia and Primary Outcome Assessment

Dose and duration of opioid/non-opioid analgesic use (through twice daily interviews and a patient maintained pain and analgesic diary), time to regular diet and return to ADL and full employment, serial pain and nausea/vomiting scores, mood state and mood state or level of symptom distress measures, 1- to 2-week and 30-day operative morbidity data were recorded for each study subject in this trial. Study participants that had provided informed consent to participate in this clinical trial were asked to report the degree of pain, nausea, mood state, and symptom distress they were experiencing prior to operation by completing a standardized 10-point Likert scale (0 no pain to 10 worst pain), Wong-Baker FACES Pain Rating Scale, McGill Pain Questionnaire [10], shortened version of the Profile of Mood States (POMS-SV) checklist [11], and McCorkle Symptom Distress Scale (SDS) [12].

Prior to surgery, subjects were given instructions regarding postoperative care of the paravertebral catheter, surgical drain, and associated skin entry sites by a study nurse. Subjects were admitted to the hospital through the ambulatory surgery center on the day of surgery. Prior to their operation, all participants received paravertebral nerve block [13] at levels T1 and T6 (5 mL of 1% ropivacaine and epinephrine 1:400,000 at both levels) followed by a single injection PVB with placement of a T3 paravertebral catheter [5] (18 gauge, 9 cm Tuohy needle access followed by 20 gauge open tip, single orifice epidural catheter advanced 2 cm into the paravertebral space) in the hospital regional anesthesia section. During catheter placement, a surgical block was instituted with 0.3 mL/kg, 0.5% ropivacaine with epinephrine 1:400,000 to a maximum of 25 mL of local anesthetic. A standard regional anesthesia negative test dose of the catheter with 3 mL of 1% lidocaine with epinephrine 1:200,000 was performed prior to catheter use. PVB and catheter placement was performed by an attending anesthesiologist experienced in regional anesthetic techniques, using standard patient monitoring and intravenous sedation (titrated midazolam and fentanyl) in accordance with institutional standards of practice.

All CPVB infusions were started in the operating room. Sedation was achieved during the operation with propofol 50–150 mg/kg/min and titrated to effect. Increases in baseline mean arterial pressure or heart rate greater the 20% above baseline were used as criteria for inadequate PVB and necessitated supplemental anesthesia. Conversion to general anesthesia was possible at any time during the operation at the discretion of the attending provider. Following operation, all patients were transferred to the overnight care unit. CPVB infusions begun in the operating room at 10 mL/h continued for 72 hours into the recovery period. Neither the patient, investigator, nor study personnel were aware of which investigational treatment the subject was receiving. Subjects were prescribed acetaminophen 325 mg by mouth three times daily and patient controlled analgesia morphine as needed using institutional standard dosing guidelines while in the hospital.

Prior to discharge from the hospital on the first postoperative day, subjects were provided one disposable infusion pump to continue their CPVB infusion for the remaining time required to complete 72 hours of study drug. The subjects were provided detailed written and oral instructions on issues related to the pump, including care of the pump, indications to seek medical treatment, and instructions on removing the catheters at the completion of the infusion. Participants were provided a folder to take home containing all study follow-up questionnaires, drug dosing, and pain diaries in order to facilitate telephone interviews during the first week following operation. Prior to discharge home, the day after operation, subjects and their chaperones were educated as to the symptoms of systemic local anesthetic toxicity and instructed to turn off the CPVB infusion in the unlikely event of experiencing toxicity symptoms. Following hospital discharge, subjects were prescribed naproxen 500 mg by mouth twice a day for 4 days and acetaminophen 300 mg/codeine phosphate 30 mg 1–2 tablets by mouth every 4 hours as needed or acetaminophen 325 mg/oxycodone 5 mg, if allergic to codeine, 1–2 tablets every 4 hours as needed. Concomitant prescription and over-the-counter pharmacotherapy administered was recorded by the subject in pain diaries and by the clinical trial nurse during study-specified telephone and clinical follow-up.

Study subject demographic data, comorbid conditions, past surgical history, stage of breast cancer, American Society of Anesthesiologists classification, operative time, estimated blood loss, volume of fluid received, intra-operative medications administered and operative complications, total inpatient and outpatient analgesic (narcotic and non-narcotic) consumption, time to tolerated regular diet, return to normal activity level (daily household work and physical activity) and full employment, and early (<30 days) surgical morbidity were recorded and entered into a computerized, relational database (Filemaker Pro, Santa Clara, CA).

During the week following surgery, primary outcome data regarding pain, nausea, mood state, and level of symptom distress were recorded. Subjects maintained a diary to record pain and all medications taken during the first postoperative week. A study coordinator and clinical trial nurse blinded to study group assignment telephoned each study subject twice daily every other day for 7 days following operation. At each phone interview, the following surveys were conducted: Wong-Baker FACES Pain Rating Scale, McGill Pain Questionnaire, POMS-SV checklist, and McCorkle SDS, which included nausea and vomiting. Perioperative complications were recorded. One month following surgery, patients were questioned regarding time to return to normal daily activity and employment.

Patients had printed copies of the questionnaires to refer to during the telephone interview. The Wong-Baker FACES Pain Rating Scale is a well established and validated pain assessment instrument currently utilized at participating study sites. The McGill Pain Questionnaire consists of sensory, affective, and evaluative descriptors characterizing the patient's subjective appraisal of pain as well as an intensity scale providing quantitative measures of pain, which can be analyzed statistically. In this scoring system, the word in each subclass implying the least pain is given a value of 1, the next word given a value of 2, and so on. The values of the words chosen by the patient are then added to obtain a total score or “Pain Rating Intensity” for all subclasses comprising the questionnaire. Scores for the McGill Questionnaire used in this study can range from 0 to a maximum of 78. The POMS consists of 65 items based on a 5-point Likert scale ranging from 0 (not at all) to 4 (extremely) describing six mood states: tension-anxiety (T), depression-dejection (D), anger-hostility (A), vigor-activity (V), fatigue-inertia (F), and confusion-bewilderment (C). A shortened version of the POMS-SV, previously validated in cancer patients, was utilized in this study. The McCorkle SDS is a 10-item scale that measures degree of distress with 10 common symptoms, including: nausea, mood, appetite, insomnia, pain, mobility, fatigue, bowel pattern, concentration, and appearance.

Objective

The principal aim of this study was to determine if the addition of CPVB anesthesia to PVB could improve postoperative pain, mood, level of symptom distress, and time to return to normal daily activity in patients undergoing outpatient unilateral breast cancer surgery. The null hypothesis tested (Ho) was: there is no difference in the degree of pain, mood state, level of symptom distress, or time to return to normal activity between continuous paravertebral block and single injection paravertebral block for breast cancer surgery, vs (H1) there is a difference in the degree of pain or mood state or level of symptom distress, or time to return to normal activity between continuous paravertebral block and single injection paravertebral block for breast cancer surgery.

Outcomes

The primary study endpoint was patient-reported pain, nausea, mood, level of symptom distress, and time to return to normal daily activities following breast cancer surgery performed under PVB or PVB + CPVB anesthesia using the Wong-Baker FACES Pain Rating Scale, McGill Pain Questionnaire, POMS-SV checklist, and McCorkle SDS.

Sample size

Sample size estimation was based on the assumption that the difference in mean pain scores would be 2.2 (on a scale from 0 to 10, corresponding to means of 3.2 and 1.0) and the common within-group standard deviation would be 2.4. These estimates were based on data obtained from our outcomes database. Controlling for the probability of a Type I error at alpha = 0.025 (the alpha level was reduced using a Bonferroni correction, 0.05/2 = 0.025, to allow for comparisons of both dose groups with the saline group), a sample of 24 subjects per group would have 80% power to detect a similar difference on the 10-point Likert pain scale. Sample size calculation was based on expected accrual of 10 patients per month who were expected to meet eligibility criteria. To allow for anticipated dropouts (∼10%), a total recruitment of up to 80 subjects was planned.

Randomization

This trial was planned as a double-blinded, placebo-controlled prospective randomized study. Subjects were randomized in a 1:1:1 ratio to undergo either normal saline, 0.1%, or 0.2% ropivacaine continuous infusion at 10 mL/h for 48 hours via a paravertebral catheter placed prior to breast surgery. Randomization was achieved through a computerized randomization system based on random number generation at the Department of Clinical Investigation, Division of Biostatistics, Walter Reed Army Medical Center. The randomization sequence was concealed until the treatment group was assigned. The allocation sequence was generated by the study biostatistician. Both study participants as well as those administering the study drugs were blinded to group assignment, which was unblinded after the last study subject was enrolled and completed study procedures.

Statistical Methods

Baseline characteristics of subjects in each group were compared using analysis of variance for continuous/scale variables and Fisher's exact test or χ2 test for categorical variables. Continuous/scale outcomes measured over the study period were analyzed using repeated measures analysis of variance and changes between two time points were examined using the paired t-test. The standardized pain, mood, and symptom distress scales utilized in this study have been validated and are utilized routinely in clinical practice. Time to event comparisons between groups were examined using Kaplan–Meier survival analysis (Breslow test). Statistical analysis was performed using SPSS for Windows software (version 17, SPSS, Inc., Chicago, IL). Data are expressed as the mean ± standard deviation and a P value <0.05 was considered significant.

Role of the Sponsors

All funding for the study was obtained from an intra-mural program at the DVPMI located at Walter Reed Army Medical Center supported through the John P. Murtha Neuroscience and Pain Institute (Johnstown, PA). The corresponding author had full access to all of the data and the final responsibility to submit for publication.

Results

Patients

During the period from July 2003 to April 2009, 468 patients were assessed for eligibility (Figure 1). Among the patients who met the study criteria, 94 were consented, of which 16 subjects declined to participate in the study post-consent. The remaining 78 participants were randomized into one of three study groups: placebo or normal saline group (n = 24), 0.1% ropivacaine (n = 27), 0.2% ropivacaine (n = 27) (Figure 1). Assignment to the three groups was stratified by surgery class so as to obtain a comparable composition within the three groups (breast conservation, simple mastectomy, and modified radical mastectomy). Five subjects were excluded from the study post-randomization for the following reasons: one subject refused operation after enrollment, one subject became ineligible after induction chemotherapy, one subject sought care at another facility, one subject's CPVB had to be discontinued, and one subject had incomplete and unreliable data. This left 73 subjects for final analysis (Figure 1). Baseline demographic characteristics of the study participants are reported in Table 2. Subjects were on average 56 years old, predominately of white ethnic origin (88%), and female (with one male exception). Statistical tests indicated no unbalanced distribution of these characteristics across the three study groups.

View this table:
Table 2

Study population characteristics

CharacteristicNormal Saline0.1% Ropivacaine0.2% RopivacainePTotal patients
N = 21N = 26N = 26N = 73
No.%No.%No.%No.%
Patient age (years)
  Mean ± SD58.4 ± 9.854.3 ± 11.454.8 ± 10.30.3755.6 ± 10.6
Body mass index (kg/m2)
  Mean ± SD27.2 ± 4.327.0 ± 4.226.0 ± 3.90.5722.6 ± 4.1
Gender
  Female2095.226100261000.297298.6
Race/Ethnicity
  White1885.72284.62492.30.376487.7
  Black29.5415.413.879.5
  Hispanic/Latino000013.811.4
  Asian/Pacific Islander14.8000011.4
Surgery class
  Breast conservation1466.71869.21765.40.824967.1
  Simple mastectomy419.0623.1415.41419.2
  MRM314.327.7519.21013.7
ASA levels
  II1990.52388.52284.60.916487.7
  III29.5311.5415.4912.3
OR time (minutes)
  Mean ± SD116.7 ± 48.0120.9 ± 35.1140.7 ± 65.40.22126.7 ± 51.6
Conversion from RA to general
  Yes419.027.7311.50.61912.3
  No1781.02492.32388.56487.7
AJCC stage 6th edition
  O00.000.0311.50.2634.1
  I1361.92076.91350.04663.0
  II628.6519.2726.91824.7
  III14.813.8311.556.8
  IV14.800.000.011.4
  • SD = standard deviation; MRM = modified radical mastectomy; ASA = American Society of Anesthesiologists; OR = operating room; RA = regional anesthesia; AJCC = American Joint Committee on Cancer.

Surgical and Regional Anesthetic Morbidity

There were no intra-operative complications. Thirty-day surgical morbidity was 9%. Seven patients had surgical complications (wound seroma, N = 2; lymphedema, N = 2; superficial surgical site infection, N = 1; urinary tract infection, N = 1; retained magnetic resonance imaging [MRI] guide wire requiring removal, N = 1). Two patients (3%) had regional anesthesia complications, one with Horner's Syndrome, and one with mild numbness in the left arm, both self-limited, resolving within 1 week of surgery.

Patient Pain Ratings

Pain ratings were assessed at baseline prior to surgery and on days 1, 3, 5, and 7 postoperatively. Mean preoperative pain scores were similar across all study groups, and mean pain scores were relatively low for the study population during the postoperative period (mean score <3 on a scale of 0–10). Overall postoperative pain scores were marginally increased above baseline preoperative pain ratings (Figure 2). During the first postoperative week, mean pain scores decreased in the placebo group (−1.0 ± 1.9, mean ± standard deviation, P = 0.033) and in the 0.2% ropivacaine group (−1.1 ± 1.3, P < 0.0005), and did not significantly change in the 0.1% ropivacaine group (0.3 ± 1.5, P = 0.35). The difference in the decrease in mean pain scores between the placebo and 0.2% ropivacaine groups was 0.1 (95% confidence interval: −1.1 to 0.9). There was no significant difference in maximum pain on day 1 between the subjects having breast conservation (2.6 ± 2.4), simple mastectomy (3.2 ± 2.1), and radical mastectomy (2.4 ± 1.0), P = 0.99.

Figure 2

Perioperative profile of mood state (POMS-SV), symptom distress score (McCorkle SDS), pain score (McGill Pain Questionnaire), and nausea/vomiting scores.

Another outcome variable complementary to pain rating is the total parental morphine equivalent dosage, which measures the sum of all narcotics given in the perioperative and 7 days postoperative period. A comparison of this narcotic analgesic intake measure among the three groups did not yield significant differences (Table 3, P = 0.58). On average, only four acetaminophen 300 mg and codeine phosphate 30 mg tablets were used during the 7 days follow-up period among all three groups.

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Table 3

Perioperative pain scores and opioid use

Normal Saline0.1% Ropivacaine0.2% RopivacainePTotal Patients
N = 21N = 26N = 26N = 73
Pre-op pain (visual analog scale: 0–10)
  Mean ± SD0.3 ± 0.80.3 ± 1.20.7 ± 1.70.550.5 ± 1.3
Worst post-op pain (visual analog scale: 0–10)
  Post-op day 12.8 ± 2.22.7 ± 2.52.5 ± 1.80.0422.7 ± 2.2
  Post-op day 31.8 ± 2.42.4 ± 2.52.2 ± 2.02.1 ± 2.3
  Post-op day 51.7 ± 1.72.5 ± 2.21.8 ± 1.82.0 ± 2.0
  Post-op day 71.9 ± 1.92.7 ± 2.51.2 ± 1.21.9 ± 2.0
Total opioid use (morphine equivalents: mg/MSO4)
  Mean ± SD36.2 ± 18.343.7 ± 31.541.4 ± 21.30.5840.7 ± 24.6
  • SD = standard deviation.

Quality of Life During Recovery

Patient-reported nausea, mood, and level of symptom distress following breast cancer surgery performed under PVB or PVB + CPVB anesthesia was assessed using the Wong-Baker FACES Pain Rating Scale, McGill Pain Questionnaire, POMS-SV checklist, and McCorkle SDS. There was no statistically significant difference in degree of postoperative nausea (P = 0.68), mood state (P = 0.54), or symptom distress (P = 0.45) among the three study groups (Figure 2). Interestingly, all study groups reported the highest mood state score (alteration in mood) prior to operation.

There were no significant differences between study groups in terms of time to return to regular diet (P = 0.63), ADL (P = 0.59), or full employment (P = 0.68). All subjects resumed regular diet within a day of surgery, and most returned to ADL by postoperative day 3. All but four of the subjects returned to full employment within the 30 days follow-up period (Figure 3).

Figure 3

Time to return to regular diet, activities of daily living (ADL), and full employment.

Discussion

This prospective, double-blinded, placebo-controlled trial is the first to our knowledge, which evaluates the effectiveness of outpatient CPVB in the management of pain following breast cancer surgery. Patients receiving 0.2% ropivacaine via their CPVB catheters did report a significant relative decrease in pain scores during the first postoperative week though total opioid use remained constant among all three treatment groups. Interestingly, postoperative pain scores were low overall (<3 on a 0–10 visual analog scale) and patients consumed on average only four acetaminophen 300 mg and codeine phosphate 30 mg tablets during the first postoperative week. The low pain scores noted in this study compare favorably with other studies demonstrating superior postoperative analgesia following paravertebral block when compared with general anesthesia [3,4]. This study did not reveal any additional clinically meaningful benefit from the use of local anesthetic administered via CPVB infusions in terms of nausea, mood, or symptom distress following breast surgery. Additionally, no advantage in times to resumption of regular diet, ADL, or return to full employment was seen in the local anesthetic infusion groups compared with controls.

Advances in peripheral nerve block catheters and infusion pump technology have brought about a proliferation of different continuous peripheral nerve block (CPNB) use in the outpatient surgical setting. Improved postoperative analgesia, quality of life, patient satisfaction, and reduced overall opioid requirements have all been cited as advantages of CPNB when administered in the home setting [14]. This investigation represents the first large series describing the use of CPVB in the outpatient setting. Complications with this analgesic technique were very infrequent, self-limited, and did not directly involve problems with outpatient catheter management. This study adds to the growing body of literature supporting the safe and routine use of CPNB catheters in outpatients for non-opioid-based analgesia that can be extended for days in the early postoperative period. Notwithstanding the advantages of outpatient CPNB, all CPNB techniques expose the patient to potential complications of the procedure itself or related anesthetic infusion. The use of CPNB techniques in the management of postoperative pain must be further evaluated in prospective random assignment trials against standard of practice before general adoption can be recommended. In this respect, negative trials are vital if evidence-based medical practice, rather than provider preference, will guide therapy. Despite the mild improvement in analgesic scores seen in the present study with postoperative 0.2% ropivacaine infusion via CPVB catheter, it would be difficult to recommend the routine use of CPVB in patients undergoing the type of breast cancer operations evaluated in this study (modified radical mastectomy, simple mastectomy, lumpectomy with axillary staging, or lymphadenectomy procedures) based on the generally low overall pain scores and universal lack of difference in quality-of-life measures seen in this population.

While powered to answer the question “is there a difference in the degree of pain, mood state, level of symptom distress, or time to return to normal activity between continuous paravertebral block and single injection paravertebral block for breast cancer surgery?”, this study does have important limitations. Although this study had a protracted period of enrollment, standards of practice at participating institutions remained unchanged during this period of time. During the data collection period for this study, Exadaktylos et al. [15] published an article suggesting that paravertebral anesthesia and analgesia for breast cancer surgery can reduce the incidence of cancer recurrence. They suggested this effect may be due to immune system function preservation through reduced general anesthesia drug requirements and diminished perioperative opioid needs. Unfortunately, the design of the present study, the short-term follow-up and the mobile nature of our health-care beneficiary population, precludes the evaluation of this important oncological variable, disease-free survival.

Patients in this study were managed perioperatively with a multimodal analgesic approach that included a local anesthetic block, a nonsteroidal anti-inflammatory drug, and Tylenol #3 as needed. Additionally, the surgical trauma sustained by patients enrolled in this study may not have been of sufficient magnitude, given the assertive analgesic regimen implemented, to warrant CPVB or uncover its potential benefits. Other authors have noted mean pain scores less than 3 (0–10 visual analog scale) in patients undergoing similar breast cancer operations [16]. Perhaps selection of other patient populations such as mastectomy followed by immediate reconstruction (which is associated with relatively greater tissue trauma and pain) would prove a more suitable population to demonstrate the analgesic and aforementioned immune-modulating benefits of paravertebral CPNB.

The current study does not support the routine use of continuous paravertebral catheter anesthesia in patients undergoing operative treatment for breast cancer. CPVB should not be considered for patients undergoing breast conserving surgery for breast cancer. As previous studies have shown, this study also found the use of CPVB in the outpatient setting to be well tolerated and without complication, further reinforcing the need to evaluate the effectiveness of CPVB following more extensive breast cancer surgery. A rigorous evaluation of the impact of prolonged postoperative analgesia, like that provided by CPVB, on the immune system in relation to cancer recurrence is imperative. Given that one out of every five study subjects assessed for eligibility was enrolled in the present trial, future studies will require multicenter participation in order to realize accrual goals in a timely manner and achieve statistical power to reliably evaluate potential clinical benefit of CPVB.

Copyright Protection

Our team is comprised partly of military service members and employees of the U.S. Government. This work was prepared as part of our official duties. Title 17 U.S.C. 105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 U.S.C. 101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person's official duties.

Disclaimer

The views expressed in this presentation are those of the authors and do not reflect the official policy of the Department of the Army, the Department of Defense, or the U.S. Government.

Conflicts of Interest

The authors declare no conflicts of interest.

Authors' Contributions

Conception and design: A.S., C.C.B.

Acquisition of data: A.S., K.H.K., G.M.M., K.H.J.

Analysis and interpretation of data: A.S., K.H.K., R.S.H.

Drafting of manuscript: A.S., K.H.K., C.C.B.

Critical revision: A.S., C.C.B., C.D.S.

Statistical expertise: R.S.H.

Obtaining funding: C.C.B.

Supervision: A.S., C.C.B., W.T.F., G.A.G.

Acknowledgments

We acknowledge Tiffany Felix for her invaluable assistance supported in part by the Henry M. Jackson Foundation for the Advancement of Military Medicine. We are grateful to the members and staff of the United States Military Cancer Institute and the Clinical Breast Care Project for their consistent support of this collaborative research effort. This clinical research effort was supported by the DVPMI and the John P. Murtha Neuroscience and Pain Institute.

Abbreviations:

PVB
paravertebral block
CPVB
continuous paravertebral block
POMS-SV
Profile of Mood States checklist
SDS
McCorkle Symptom Distress Scale
ADL
activity of daily living

References

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