Breast resection with associated lymph node biopsy was performed in 21 (70%) patients in the PVB group and 22 (73%) patients in the sham group, and thus, mastectomy was performed at the primary operation in 9 (30%) patients in the PVB group and 8 (27%) patients in the sham group (P = 0.774). Lymph node involvement requiring axillary dissection was diagnosed in 12 patients in the PVB group and 11 patients in the sham group (P = 0.79). Five patients in the PVB and 3 in the sham group (P = 0.45) had axillary dissection in a second operation 2–4 wk later. Mastectomy was performed in 3 patients in the PVB group and in 2 in the sham group (P = 0.64) 2–4 wk after the primary operation, which had included axillary dissection in all but 1 patient. One patient in the PVB group had both axillary dissection and mastectomy performed in the second operation. The patients did not receive any regional anesthetic block for the second operation. Patients who had axillary dissection at the primary operation consumed more pain medication during the first 14 postoperative days (Table 3). The study results did not change markedly when all data were recalculated without the patients who had more than one operation.
Chemotherapy was given to 15 (50%) patients in the PVB group and 13 (43%) patients in the sham group (P = 0.49), whereas radiotherapy was given to 24 (80%) patients in the PVB group and 22 (73%) in the sham group (P = 0.41). Chemotherapy was given to the 22 (71%) patients who required axillary dissection and to 6 (21%) who did not (P < 0.01), whereas radiotherapy was given to 28 (90%) patients who required axillary dissection and to 18 (62%) who did not (P < 0.05). Chemotherapy started 1–4 mo (median, 2 mo) after surgery and continued until 4–7 mo (median, 6 mo) after surgery. Most of the patients who did not require axillary dissection or chemotherapy had completed their radiotherapy before the 6-mo interview, whereas 21 of 22 patients who required axillary dissection, chemotherapy, and radiotherapy received their radiotherapy after the 6-mo interview.
Logistic regression was used to analyze the relationship between known and suspected risk factors (2,4) and the pain symptoms 12 mo after surgery (Table 4). The independent variables used in the logistic regression analysis were PVB, axillary dissection, pain (VAS) in the postanesthesia care unit, pain (VAS) on hospital ward, pain (VAS) at home (14-day), motion restriction (VAS) (14-day), occurrence of breast pain (14-day), occurrence of axillary pain (14-day), occurrence of arm pain (14-day), use of rescue analgesics (14-day), depression (1 mo), pain symptoms (1 mo), chemotherapy, and radiotherapy. The most interesting results in the logistic regression analyses were that PVB prevented motion-related pain and chronic pain symptoms, that the consumption of rescue opioid during the first 14 postoperative days correlated with pain at rest, with axillary pain, and with neuropathic pain, and that radiotherapy correlated with pain at rest.
A group-blinded anesthesiologist phoned all patients who had reported pain symptoms in the telephone interviews: 12 in the PVB group and 23 in the sham group (P = 0.004). Common causes of pain were skin inflammation during radiotherapy (11 patients), musculoskeletal pain (8 patients), and fluid sequestration in the wound (5 patients). Ten of these patients were seen at the pain clinic (3 from the PVB group and 7 from the SHAM group; P = 0.211) on average 6–7 mo after the operation in both groups. We diagnosed neuropathic pain in two patients of the PVB group and in three of the sham group. Of the five patients diagnosed with neuropathic pain during the follow-up, one patient in both groups had tumor resection with axillary dissection, one patient in both groups had tumor resection without axillary dissection, and one patient in the sham group had radical mastectomy with axillary dissection. Musculoskeletal pain was diagnosed in the other five patients seen at the pain clinic. Neuropathic pain was characterized by continuous burning or sharp pain with dynamic and static allodynia, hypersensitivity, or dysesthesia to light tactile and thermal stimuli. The five patients who suffered from neuropathic pain had higher depression scores 1 mo after surgery (12 [9–21] versus 6 [0–25]; scale, 0–32) than the other 55 patients (P = 0.040) and had consumed more rescue analgesics during the first 14 postoperative days than the other 55 patients (Table 3). All five patients with neuropathic pain had received postoperative radiotherapy.
Both groups scored similarly with regard to five aspects (depression, anxiety, hostility, fatigue, and confusion) in the POMS questionnaire during the entire 12-mo follow-up period. However, the PVB group had significantly higher scores for vigor at all measurement points, including the preanesthesia visit, except at 6 mo after the operation, when the scores were similar. The depression score 1 mo after surgery was higher (10 [0–23] versus 5 [0–25]; P = 0.016) in the patients who required axillary dissection during or after the primary operation.
Our follow-up showed that preoperative PVB reduced the prevalence and severity of pain up to one year after breast cancer surgery. The prospective fashion of the study and the excellent patient compliance strengthen the validity of our results. There have been no reports on the long-term effects of PVB on chronic pain after breast surgery for cancer (16,17). Interestingly, the application of EMLA® (lidocaine and prilocaine) cream on the breast and the axilla, started before surgery and continued for four days, has been reported to reduce the incidence of chronic pain in the area of surgery three months after surgery (18).
The intensity of postoperative pain and the increased requirement of analgesics during the first days after surgery may play a role in the development of chronic postoperative pain (3,4,11,12,18). We found that a preincisional PVB with bupivacaine provided significant immediate postoperative analgesia, reducing the consumption of IV opioid by 40% in the postanesthesia care unit (8). The correlation between the consumption of the rescue analgesics during the first 14 postoperative days and pain at rest, and any pain in the axilla 12 months after surgery is in accordance with the concept that significant early postoperative pain predisposes to chronic pain symptoms (4).
The benefits of PVB were evident at every interview, with increasing benefits culminating at the 12-month interview when the PVB group had less motion-related pain and less pain at rest. Radiotherapy about 6 months after surgery may have aggravated the pain symptoms recorded at 12 months after surgery, but even in such cases, PVB seems to have had a positive effect.
The patients in the PVB group had fewer pain symptoms 6 and 12 months after surgery. One month after surgery, the many pain symptoms seen in both groups were probably the result of new acute postoperative pain after the secondary axillary dissection/mastectomy that had to be performed in 12 patients (20% of patients) 2–4 weeks after surgery.
Chronic pain is reportedly more common after breast-conserving surgery than after radical surgery (3). The patients in the PVB group had less pain 12 months after the operation regardless of whether the axilla had been dissected (52% of patients). In our hospital, after the studies by Tasmuth et al. (4,19) on chronic pain in breast cancer patients, the surgeons have paid special attention to sparing the intercostobrachial and other nerves during axillary clearance, at least when there is no metastatic involvement of the axillary lymph nodes. After 12 months, the incidence of pain in the arm was very low, i.e., 3% in both study groups. Sparing of the intercostobrachial and other nerves together with breast-conserving surgery (70% breast resections) are probably the reasons for the absence of phantom pain in our study.
An influence of PVB on the incidence and severity of symptoms related to chemotherapy and radiotherapy, such as fatigue, nausea and vomiting, and inflammation of the skin (20), could not be demonstrated because in the one-year interview, the prevalence of these symptoms was already low. PVB seemed to prevent the aggravation of pain in the breast area occurring after radiotherapy in patients who did not need axillary dissection. In almost all of the patients (21 of 22) who had axillary dissection and chemotherapy and radiotherapy, the latter was commenced after the 6-month interview. Therefore, the impact of radiotherapy on their symptoms could not be evaluated until the 12-month interview.
The prevalence of chronic pain symptoms (Table 2) is comparable to that reported earlier in our hospital (1,3). Importantly, however, the incidence of neuropathic pain (8.3%) in our patients was less frequent than in several earlier studies (17%–50%) (1–3,11), and the favorable results, independent of the PVB, may be ascribed to the nerve-sparing surgical technique of axillary dissection (3,11,19).
The development of chronic pain in patients undergoing surgery for breast cancer is associated with depression (11). However, in our study, we did not detect any difference in the POMS scores for depression or anxiety between the PVB and sham groups during the 12-month study period. However, higher depression scores had been detected one month after surgery in patients who required axillary dissection and in the five patients who developed neuropathic pain approximately six months after surgery. Several studies have, in fact, confirmed that the presence of depression predisposes to the development of chronic pain (21,22).
Preincisional PVB was found to reduce motion-related pain and chronic pain symptoms 12 months after surgery independently of whether or not axillary dissection had been performed (Tables 1, 2, and 4). Radiotherapy was related to pain at rest 12 months after surgery (Table 4), and in addition, all five patients who were diagnosed with neuropathic pain received radiotherapy. This confirms radiotherapy as a predisposing factor for chronic pain (4). Pain (VAS) at home (1–14 days) was related to motion-related pain and chronic pain symptoms 12 months after surgery (Table 4). The consumption of acetaminophen + codeine in addition to standard ibuprofen and acetaminophen alone during the first 14 days was related to axillary pain, pain at rest, and neuropathic pain 12 months after surgery. The patients, with or without axillary dissection, who experience prolonged acute postoperative pain and require opioids in addition to ibuprofen during the first 14 postoperative days are predisposed to development of chronic pain and require special attention to prevent chronic postoperative pain (4).
In addition to providing good acute postoperative pain relief, preoperative PVB prevented pain conditions for up to one year after breast cancer surgery. These extended benefits should encourage the use of PVB in connection with breast cancer surgery. However, it is also important for the surgeon to spare the intercostobrachial nerves in the axillary dissection.
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© 2006 International Anesthesia Research Society
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