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Impact of pectoral nerve block on postoperative pain and quality of recovery in patients undergoing breast cancer surgery

A randomised controlled trial

Kamiya, Yoshinori; Hasegawa, Miki; Yoshida, Takayuki; Takamatsu, Misako; Koyama, Yu

European Journal of Anaesthesiology (EJA): March 2018 - Volume 35 - Issue 3 - p 215–223
doi: 10.1097/EJA.0000000000000762
Loco-regional anaesthesia

BACKGROUND In recent years, thoracic wall nerve blocks, such as the pectoral nerve (PECS) block and the serratus plane block have become popular for peri-operative pain control in patients undergoing breast cancer surgery. The effect of PECS block on quality of recovery (QoR) after breast cancer surgery has not been evaluated.

OBJECTIVES To evaluate the ability of PECS block to decrease postoperative pain and anaesthesia and analgesia requirements and to improve postoperative QoR in patients undergoing breast cancer surgery.

DESIGN Randomised controlled study.

SETTING A tertiary hospital.

PATIENTS Sixty women undergoing breast cancer surgery between April 2014 and February 2015.

INTERVENTIONS The patients were randomised to receive a PECS block consisting of 30 ml of levobupivacaine 0.25% after induction of anaesthesia (PECS group) or a saline mock block (control group). The patients answered a 40-item QoR questionnaire (QoR-40) before and 1 day after breast cancer surgery.

MAIN OUTCOME MEASURES Numeric Rating Scale score for postoperative pain, requirement for intra-operative propofol and remifentanil, and QoR-40 score on postoperative day 1.

RESULTS PECS block combined with propofol–remifentanil anaesthesia significantly improved the median [interquartile range] pain score at 6 h postoperatively (PECS group 1 [0 to 2] vs. Control group 1 [0.25 to 2.75]; P = 0.018]. PECS block also reduced propofol mean (± SD) estimated target blood concentration to maintain bispectral index (BIS) between 40 and 50 (PECS group 2.65 (± 0.52) vs. Control group 3.08 (± 0.41) μg ml−1; P < 0.001) but not remifentanil consumption (PECS group 10.5 (± 4.28) vs. Control group 10.4 (± 4.68) μg kg−1 h−1; P = 0.95). PECS block did not improve the QoR-40 score on postoperative day 1 (PECS group 182 [176 to 189] vs. Control group 174.5 [157.75 to 175]).

CONCLUSION In patients undergoing breast cancer surgery, PECS block combined with general anaesthesia reduced the requirement for propofol but not that for remifentanil, due to the inability of the PECS block to reach the internal mammary area. Further, PECS block improved postoperative pain but not the postoperative QoR-40 score due to the factors that cannot be measured by analgesia immediately after surgery, such as rebound pain.

TRIAL REGISTRATION This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000013435).

From the Division of Anesthesiology (YK, TY, MT), Division of Digestive and General Surgery (MH), Department of Anesthesiology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital (YK), Department of Breast Surgery, Niigata Cancer Center Hospital, Niigata (MH), Department of Anesthesiology, Kansai Medical University Hospital, Osaka (TY) and Department of Nursing, Niigata University Graduate School of Health Sciences, Niigata, Japan (YK)

Correspondence to Yoshinori Kamiya, MD, PhD, Division of Anesthesiology, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Chuo ward, Niigata, Niigata 951-8510, Japan Tel: +81 25 227 2328; fax: +81 25 227 0790; e-mail:

Published online 8 December 2017

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Despite the recent shift towards less invasive procedures, breast cancer surgery is still associated with moderate to severe postoperative pain that can impede recovery after surgery. Regional anaesthesia techniques with or without general anaesthesia have been reported to provide better acute pain control.1–5 Thoracic paravertebral block (TPVB) combined with general anaesthesia has been shown to improve quality of recovery (QoR), a patient-oriented outcome measure evaluated using a multidimensional QoR assessment tool.1,6–9 However, TPVB has the potential risks of pneumothorax and spread of local anaesthetic into the spinal canal, even under ultrasound guidance.10,11 In recent years, thoracic wall nerve blocks, such as the pectoral nerve (PECS) block12,13 and the serratus plane block,14 have become popular for peri-operative pain control in patients undergoing breast cancer surgery.15–18 Earlier clinical trials have shown that a PECS block combined with general anaesthesia achieves superior outcomes with regard to postoperative pain control, duration of hospital stay and incidence of postoperative nausea and vomiting (PONV) when compared with general anaesthesia only16 or TPVB with general anaesthesia.17 However, the effect of PECS block on QoR in patients undergoing breast cancer surgery has still not been elucidated.

We hypothesised that the PECS block would not only reduce pain during and after breast cancer surgery but also improve QoR. We conducted this prospective, randomised, placebo-controlled, double-blind study to examine this hypothesis. We also compared the postoperative food intake between the two groups because food intake may reflect not only the severity of PONV but also QoR.

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Design and patients

The current clinical trial was approved by the institutional review board at Niigata University Medical and Dental Hospital (accession number 1856; date of approval by the ethics committee 5 March 2014) and is registered at the University Hospital Medical Information Network Clinical Trials Registry [UMIN000013435 (]. After obtaining written informed patient consent, we enrolled women aged 20 to 80 years with American Society of Anesthesiologists physical status I to II who were scheduled for unilateral breast tumour resection. The surgical procedures included partial mastectomy, partial mastectomy with sentinel lymph node biopsy, simple mastectomy, mastectomy with sentinel lymph node biopsy and mastectomy with axillary lymph node dissection. The exclusion criteria included the following: refusal to participate, inability to understand Japanese, history of allergy to the study medication, contraindications to regional anaesthesia (including coagulopathy and infection at the injection site), BMI more than 30 kg m−2, body weight less than 40 kg, hepatic and/or renal failure, pre-existing abnormal sensation affecting the thoracic trunk and history of treatment for chronic pain and/or a psychiatric disorder.

Patients were randomly allocated to a PECS group that received a PECS block and general anaesthesia or a control group that received a mock block with normal saline and general anaesthesia. An investigator not involved in patient care or postoperative assessment performed the randomisation using a computer-generated randomisation sequence ( that was concealed using sealed prenumbered opaque envelopes.

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Anaesthetic procedure

The patients were not premedicated before surgery, but all received 8 mg of intravenous dexamethasone sodium phosphate before induction of anaesthesia as prophylaxis for nausea. General anaesthesia was induced by a target-controlled infusion of propofol (target blood concentration 4.0 μg ml−1), a continuous infusion of remifentanil (0.5 μg kg−1 min−1) and a bolus injection of rocuronium 0.6 mg kg−1 to facilitate insertion of the ProSeal Laryngeal Mask Airway (PLMA; Teleflex Medical Japan, Tokyo, Japan). Anaesthesia was maintained by target-controlled infusion of propofol, and the target site concentration was adjusted so that the value of BIS was within the range of 40 to 50 before starting surgery. The rate of remifentanil infusion was adjusted in the range of 0.05 to 0.5 μg kg−1 min−1 and the heart rate and blood pressure were maintained within 20% of the baseline values. Muscle relaxation was maintained by intermittent boluses of rocuronium as needed. After general anaesthesia was established, a PECS block was performed using 0.25% levobupivacaine (PECS group) or normal saline (control group) with S-Nerve ultrasound apparatus (SonoSite Inc, Bothell, Washington, USA) and a 6 to 13-MHz linear transducer (HFL 38×; SonoSite Inc) as described elsewhere.13 Briefly, the transducer was placed on the outer third of the clavicle and then moved laterally to identify the pectoralis major and minor muscles just above the second rib under sterile conditions. The needle (22-G, 80-mm Uniever for epidural anaesthesia; Unisis Corp., Tokyo, Japan) was inserted in plane with the transducer into the fascial plane between the pectoralis muscles and 10 ml of levobupivacaine 0.25% was injected. The transducer was then moved towards the axilla until the serratus anterior muscle was identified above the third and fourth ribs; the needle was then reinserted until the tip of the needle was in contact with the surface of the fourth rib. Then, 20 ml of 0.25% levobupivacaine was injected beneath the serratus anterior muscle at the fourth rib in increments of 5 ml after confirming negative aspiration. Anaesthetists blinded to study group allocation performed the block procedure. After resection of the tumour and axillary clearance (if applicable), 1 g of acetaminophen and 100 mg of tramadol hydrochloride were administered intravenously for transitional analgesia. After completion of surgery, propofol and remifentanil were discontinued and 4 mg kg−1 of sugammadex was administered for reversal of neuromuscular blockade. After confirming that the patient responded promptly to a verbal command, the PLMA mask was removed. The patients were returned to a ward after 20 min of observation in the operating theatre.

After surgery, a 25-mg diclofenac sodium suppository and 15 mg of intramuscular pentazocine were provided as first-line and second-line rescue analgesics, respectively, for breakthrough pain. After starting oral intake of food, loxoprofen 60 mg and acetaminophen 500 mg were provided when the Numeric Rating Scale (NRS) score (0 = no pain, 10 = worst pain) for postoperative pain was more than 4 or additional analgesics were required. Intravenous opioids were not used during the postoperative period in this study to minimise the risk of PONV, which was treated with intravenous metoclopramide 10 mg as needed. Patients were permitted to drink water 4 h after surgery and to eat food on postoperative day (POD) 1.

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The ward nursing staff, blinded to each patient's treatment allocation, recorded postoperative pain at rest at 1, 3, 6, 24 and 48 h after surgery using the NRS and recorded the presence of PONV at any time after surgery. The nursing staff also recorded the amount of food intake at breakfast, lunch and supper (0, 25, 33, 50, 66, 75, 80 and 100% of the total quantity served). Patients could be discharged 24 h after surgery if they met all the discharge criteria (no drainage from the surgical site, no active bleeding, no intractable pain that could not be controlled by the oral medication described above and absence of PONV).

The quality of postoperative functional recovery was assessed using the Japanese version of the 40-item QoR questionnaire (QoR-40), which assesses five dimensions of recovery, comprising physical comfort (12 items), emotional state (nine items), physical independence (five items), psychological support (seven items) and pain (seven items).19 Each item is rated on a five-point Likert scale, that is none of the time, some of the time, usually, most of the time, and all of the time. The total score on the QoR-40 ranges from 40 (poorest QoR) to 200 (best QoR). The QoR-40 was administered on the day before surgery, POD 1 (between 6 and 9 p.m.), and 1 month after surgery. At the 1-month assessment, the patients answered the QoR questionnaire before receiving an explanation of their condition at the outpatient breast surgery clinic.

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The primary outcome was the severity of postoperative pain on the NRS at 6 h after surgery. The secondary outcomes were differences in doses of propofol and remifentanil, QoR-40 score on POD 1 between the two groups, the incidence and severity of PONV, incidence of adverse events and the amount of food intake after surgery. The QoR-40 score 1 month after surgery was also recorded to evaluate the long-term effects of PECS block on QoR after surgery. We also evaluated the relationship between QoR score and patient age.

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Statistical analysis

Our sample size calculation was based on the assumption that the difference in NRS scores for pain at 6 h after surgery would be significant if there was at least one point of difference between patients who received a PECS block before breast cancer surgery and those who received a mock block, as in a previous study.16 According to our preliminary study, the variability (SD) of NRS scores for pain at 6 h after breast cancer surgery was 1.25. Thus, a power analysis using a type I error estimate of 5% and a power of 80% indicated that a sample size of 25 patients per group was needed to detect this difference. Considering dropout, we planned to enrol 60 patients.

The Shapiro–Wilk test was used to check the normality of the data. Categorical data (presented as frequencies) were compared using Fisher's exact test. Ordinal data and nonnormally distributed continuous data (presented as the median and interquartile range) were compared between the groups using the Mann–Whitney U test. Normally distributed data (presented as the mean and SD) were compared between the groups using the two sample-independent t tests. For evaluation of postoperative NRS scores and percentage of food intake, we used the Mann–Whitney U test for pairwise comparisons at each time point. We also used Pearson's test to evaluate the relationship between several parameters and QoR scores.

A power analysis was performed using G*power version 3.1.9 for Macintosh and other statistical analyses were performed using Microsoft Excel 2011 for Macintosh (Microsoft, Redmond, Washington, USA) with a statistical macro (XLSTAT version 2013.6.01; Addinsoft, New York, New York, USA). A P value less than 0.05 was considered to be statistically significant.

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Basic information

We assessed 79 patients for eligibility to participate in the study. Ten patients did not meet the inclusion criteria, nine declined enrolment and the remaining 60 patients consented to participate. Thirty patients were allocated to the PECS group and 30 to the control group. One patient in the PECS group was excluded because of an incomplete QoR questionnaire, leaving 29 patients in the PECS group and 30 in the control group for analysis. At the time of the QoR survey 1 month after surgery, five and nine patients in the PECS group and control group, respectively, were excluded from the analysis because of an incomplete QoR questionnaire or loss to follow-up (Fig. 1).

Fig. 1

Fig. 1

The groups were comparable with respect to age, height, weight, BMI, American Society of Anesthesiologists physical status and the surgical procedures performed (Table 1).

Table 1

Table 1

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Postoperative pain and requirement for intra-operative anaesthesia

NRS scores were significantly lower at 6 h after surgery in the PECS group than those in the control group (P = 0.018, Table 2); however, the pain-sparing effect of the PECS block disappeared 24 h after surgery. The requirement for rescue analgesia (nonsteroidal anti-inflammatory drugs, acetaminophen, pentazocine) and the incidence of PONV were not significantly different between the two groups (Table 2). The mean remifentanil dose required were almost identical between the groups, although the mean propofol blood target concentration to maintain BIS between 40 and 50 was significantly higher in the control group than in the PECS group (Table 1).

Table 2

Table 2

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Quality of recovery

The pre-operative global QoR-40 score was similar between the two groups (Table 3). Contrary to our expectation, the PECS block did not improve QoR-40 scores on POD 1 (182 [176 to 189] in the PECS group and 174.5 [157.75 to 175] in the control group; P = 0.143, Table 3). Of the five dimensions of the QoR-40, only the psychological support score was significantly higher in the PECS group when compared with the control group (P = 0.044). We also evaluated the change in QoR score (postoperative QoR score–pre-operative QoR score) in each patient. Our results indicated that neither the global score nor any of the scores for the five dimensions of the QoR-40 were significantly improved in the PECS group when compared with the control group (Table 3). The differences in postoperative pain and QoR-40 scores between the two groups disappeared by 1 month after surgery (Tables 2 and 3).

Table 3

Table 3

We also evaluated the relationship between patient age and QoR scores and found that the global, psychological support and physical independence scores correlated with patient age in the control group. However, these correlations were not observed in the PECS group (Fig. 2).

Fig. 2

Fig. 2

We also evaluated peri-operative food intake. Patients were permitted to resume a normal diet on the morning following the day of surgery. Food intake on POD 1 was higher in the PECS group than in the control group, but the difference was no longer present by POD 2 (Table 4).

Table 4

Table 4

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In this study, we evaluated the effects of PECS block combined with general anaesthesia on postoperative pain as measured by the NRS and intra-operative doses of propofol and remifentanil in a double-blind fashion. We also evaluated the effects of PECS block on QoR using the Japanese version of the QoR-40.19 PECS block could reduce postoperative pain for up to 6 h after surgery as previously reported.15–17 Significantly, PECS block decreased the requirement for propofol (as measured by the mean blood target concentration to maintain BIS between 40 and 50) but not that for remifentanil during surgery. However, contrary to our expectation, PECS block did not improve the total QoR-40 score on POD 1 after breast cancer surgery.

PECS block did not affect the intra-operative requirement for remifentanil despite decreasing postoperative pain and the intra-operative requirement for propofol. A PECS block can block the lateral cutaneous branches of the spinal nerves at T2 to T6, and possibly the anterior cutaneous branches if sufficient local anaesthetic penetrates the external intercostal muscles.13,16,17 The long thoracic nerve can be blocked by local anaesthetic agents entering the axilla.13 However, the anterior cutaneous branch of the spinal nerve may not be blocked if local anaesthetic agents do not penetrate the external intercostal muscles; if this is the case, anaesthesia in the medial part of the chest wall would be inadequate.16 Our results may reflect the anatomic nature of the anterior chest wall. The similar intra-operative requirement for remifentanil in the two groups suggests that the surgical invasion reached the medial part of the chest wall in most patients.

The propofol dose-sparing observed in this study might have been affected by the systemic effects of local anaesthetics. The PECS block is one of the interfascial plane blocks. Several reports have shown that the concentrations of local anaesthetic in the blood after a transversus abdominis plane block, which is also an interfascial plane block, were in the order of sub-μg ml−1 to μg ml−1.20,21 These low concentrations might affect the ability of local anaesthetic agents circulating in the systemic circulation to suppress functioning of the sodium channel in the central nervous system, resulting in sedation.22–24

In addition, the analgesic effect of PECS block did not reflect improvement in the pain dimension of the QoR-40 score, even though the NRS score for postoperative pain in the PECS group was significantly lower than that in the control group in our study. ‘Rebound’ pain may account for this finding. When a PECS block is effective, the duration of analgesia has been reported to be up to 24 h.16 However, several studies, including a meta-analysis, have shown that patients can suffer rebound pain after cessation of a nerve block or peri-articular injection.25–28 In our study, the QoR-40 score on POD 1 was evaluated approximately 24 h after surgery and by then the NRS score was almost the same in the two groups. Postoperative pain strongly affects QoR after surgery,1,29 and this may be a reason why the global and pain dimensions of the QoR-40 scores on POD 1 were not significantly different between the groups.

We evaluated the relationship between change in QoR score (before surgery – POD 1) and patient age, and found a negative correlation in the control group but no correlation in the PECS group. This finding indicates that a PECS block using 30 ml of 0.25% levobupivacaine is somewhat effective for suppressing postsurgical discomfort, including postoperative pain. We speculate that younger patients felt more intense pain after surgery and that this affected the QoR findings in our study. Several studies have indicated that younger patients who undergo breast cancer surgery are more susceptible to persistent postoperative pain.30–32

Postsurgical pain has been known to have a negative impact on not only PONV and general fatigue but also appetite in the early stages of recovery.33 Patients who received a PECS block were more likely to have a preserved appetite on POD 1 to 2 than those in the control group in our study. Our anaesthesia protocol was identical in the two study groups except that 0.25% levobupivacaine was used as the injectate for nerve block in the PECS group. We speculated that the analgesic effect of the PECS block might contribute to preservation of appetite. As indicated above, a patient's appetite might be reduced by postsurgical pain during recovery; thus, reduction of postsurgical pain could preserve appetite. An extensive study is needed to clarify the relationship between postoperative pain and appetite.

There are several limitations to this study. First, we used a multimodal peri-operative analgesic regimen including acetaminophen, tramadol, diclofenac and dexamethasone in both groups. A recent study indicated that dexamethasone had not only antiemetic effects but also strong analgesic effects in patients undergoing breast cancer surgery.34 This might account for why we could not find a large difference in postoperative pain between the two groups. Moreover, steroids, including dexamethasone, may improve QoR after surgery,35,36 and our multimodal analgesia regimen may have influenced the small differences in QoR scores between the groups. We believed that all the participants in the study should receive a standardised peri-operative multimodal analgesic regimen even if it reduced the chances of finding a significant difference between the intervention group and the control group. An essential goal of our study was to demonstrate the benefit of adding a PECS block to a generally accepted analgesic regimen in patients undergoing breast cancer surgery, but we did not find the PECS block to be of great benefit.

Second, we did not confirm the efficacy of the PECS block before surgery, because we believed it to be a compartment block with less risk of nerve injury and felt that performing the block under general anaesthesia would be more comfortable for the patients. Recent studies have indicated that PECS block achieves loss of sensation in the lateral part of the chest wall at the T2 to T6 level,17,18 and our block procedure was almost the same as in those reports.

Third, the efficacy of PECS block could have been potentiated by adding adjuvants to the local anaesthetic agents. There have been some reports of dexamethasone,37 betamethasone38 and alpha-2 agonists39 prolonging the effects of brachial plexus block when mixed with local anaesthetics. However, there are some researches suggesting that even systemically administered dexamethasone can prolong the effects of a peripheral nerve block.40,41 Therefore, we did not mix adjuvants with the local anaesthetic agents used in the current study.

Fourth, the sample size might have been too small to determine the effectiveness of PECS block using improvement in the QoR-40 score. Moreover, we should have anticipated a higher dropout rate in the month after breast cancer surgery when recruiting patients for this study of the effects of PECS block.

As alluded to above, the limited distribution of the PECS block may have been one of the reasons why there was no significant difference in the intra-operative remifentanil requirement between the groups. The ultrasound-guided transversus thoracic muscle plane (TTP) block was recently introduced to block the anterior cutaneous branches of the intercostal nerve.42 A TTP block provides analgesia in the internal mammary area, which cannot be reached by a PECS block. Combination of a PECS block and a TTP block provides analgesia superior to that of a PECS block alone.18 The potential ability of a combination of these two blocks to improve analgesia and QoR after breast cancer surgery warrants further investigation in the future.

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The PECS block was effective for reducing postoperative pain. However, contrary to our expectation, a PECS block combined with propofol–remifentanil anaesthesia did not reduce the intra-operative use of remifentanil or improve the postoperative QoR score when compared with a saline-injected mock block. The absence of a remifentanil-saving effect when using the PECS block might stem from the inability of the PECS block to reach the internal mammary area. Further, the failure of the PECS block to improve the postoperative QoR score might be attributable to factors that cannot be measured by analgesia immediately after surgery, such as rebound pain.

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Acknowledgements relating to this article

Assistance with the study: the authors thank Editage for providing editorial assistance.

Financial support and sponsorship: none.

Conflicts of interest: none.

Presentation: none.

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