|Year : 2019 | Volume
| Issue : 3 | Page : 131-135
Risk factors analysis for development of chronic postsurgical pain after modified radical mastectomy: A single-centered, prospective, observational study
Vidya Bhagat, Sweta Salgaonkar, Priti Devalkar, Jayshree Gite
Department of Anaesthesia, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
|Date of Submission||12-Jun-2019|
|Date of Decision||05-Aug-2019|
|Date of Acceptance||23-Aug-2019|
|Date of Web Publication||5-Dec-2019|
Dr. Sweta Salgaonkar
Department of Anaesthesia, Seth GS Medical College and KEM Hospital, Parel, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: The “chronic post-surgical pain” (CPSP) is defined as pain of at least 2 months duration which has developed after a surgical procedure when other causes such as disease recurrence or preexisting pain syndromes are ruled out. The incidence of CPSP is found maximum after amputation surgeries (50%–85%), followed by thoracotomy (30%–50%) and mastectomy. The aim of our study is to analyze the risk factors such as preoperative pain, anxiety, and specific surgical techniques for development of CPSP after modified radical mastectomy (MRM). Materials and Methods: A total of thirty patients undergoing MRM satisfying inclusion criteria were enrolled out, of which one patient died during the study period of 1 year. Preoperative pain evaluation was done with Visual Analog Scale, and for measuring preoperative anxiety, Hamilton Anxiety Rating Scale was used. Medical and surgical records were studied for evaluation of some postoperative parameters. Appropriate statistical tests were used to evaluate the relationship of different risk factors for development of CPSP. Results: Incidence proportion of CPSP in our study was approximately 24%. All the risk factors we analyzed, i.e. preoperative pain and anxiety, surgical techniques like preservation of intercostobrachialis nerve, type of surgical incision, and duration of surgery were found to be statistically insignificant for development of CPSP. Conclusion: In conclusion, one should be very cautious to identify women who are at risk of developing CPSP or who have already developed CPSP. Establishing a prediction model based on known risk factors to identify susceptible patients and applying protective measures are important steps toward preventive, personalized health care.
Keywords: Chronic postsurgical pain, Hamilton Anxiety Rating Scale, intercostobrachialis nerve, modified radical mastectomy, Visual Analog Scale
|How to cite this article:|
Bhagat V, Salgaonkar S, Devalkar P, Gite J. Risk factors analysis for development of chronic postsurgical pain after modified radical mastectomy: A single-centered, prospective, observational study. Indian J Pain 2019;33:131-5
|How to cite this URL:|
Bhagat V, Salgaonkar S, Devalkar P, Gite J. Risk factors analysis for development of chronic postsurgical pain after modified radical mastectomy: A single-centered, prospective, observational study. Indian J Pain [serial online] 2019 [cited 2022 May 23];33:131-5. Available from: https://www.indianjpain.org/text.asp?2019/33/3/131/272380
| Introduction|| |
Chronic postsurgical pain (CPSP) is a common problem that can occur after any type of surgery., The prevalence of moderate-to-severe CPSP varies between 10% and 60%.,, Pain is one of the most prevalent complications in postoperative patients. The “Chronic or persistent postsurgical pain” is defined as pain of at least 2 months duration which has developed after a surgical procedure, whereas other causes such as disease recurrence or preexisting pain syndromes have been excluded.
The nature and properties of persistent surgical pain are poorly characterized. It is not clear whether there is a distinct transition between acute and chronic pain or whether the chronic pain is merely an extension of perioperative pain. The incidence of CPSP can vary anywhere from 0.5% to 85% depending on the type of surgery. The incidence of CPSP in post Mastectomy patients is 20%-50% and that in post modified radical mastectomy patients is 11%-57%. The most well-established risk factor for CPSP is type of surgery with higher incidence following significant nerve or tissue injury. Maximum incidence of CPSP is found in amputation surgeries (50%–85%), followed by thoracotomy (30%–50%) and mastectomy.
There are previous studies available depicting the risk factors for development of CPSP. However, none of them had done actual analysis of these risk factors of CPSP for a specific surgery. Furthermore, there is a vast difference between the incidence variability, thus leading to the fact that the data about the risk factors that lead to postoperative pain are not thoroughly studied. Considering a developing country like India where majority of patients undergo chemotherapy and surgery for breast cancer, lack of prediction models for CPSP made this management very painful and miserable. Hence, we are conducting a pilot study of analysis of different risk factors for development of CPSP in patients undergoing MRM in a tertiary care hospital of India.
Aims and objectives
The main aims of the study were: (1) to know the incidence of CPSP in post-MRM patients, (2) effect of preoperative pain level on incidence of CPSP, (3) effect of preoperative anxiety on incidence of CPSP, and (4) effect of surgical techniques including incision type, duration, and sparing of nerve on incidence of CPSP.
| Materials and Methods|| |
This was a prospective, observational study, in which we enrolled patients confirmed of having breast cancer, who were posted for MRM. The number of patients was decided by complete enumeration method or census method, i.e. all the patients fulfilling the inclusion criteria, who get admitted during the study duration of 1 year. The study was approved by institutional clinical ethics committee. Women were approached individually at one of the tertiary care hospital in Western India. The inclusion criteria were sequentially approached from April 2016 to March 2017. Informed consent was obtained from the interested women at the time of clinic visits. Disease and treatment information were obtained from medical records. Specific data regarding surgical techniques and postoperative complications were extracted separately from medical records by one of two trained reviewers. Patients having breast cancer posted for MRM and are willing to comply with study follow-up requirements were included in the study. Patients refusal, inability to understand the study methodology, change of address, and patients with organ metastases were excluded.
A preoperative evaluation was done of patients diagnosed to have MRM and those who gave consent for the study which included collection of demographic data including age, sex, address, type and stage of tumor, fine-needle aspiration cytology reports, preexisting chronic pain, associated comorbidities, hematological reports, X-ray chest, details of radio or chemotherapy with the number of cycles and drug used, type of operation suggested, and preoperative Hamilton Anxiety Rating Scale. All preoperative pain was evaluated by Visual Analog Scale (VAS) score. The patients were evaluated postoperatively for the type of operation, the technique used, the sparing of intercostobrachialis nerve (ICBN), type of anesthesia, use of perioperative analgesics, and immediate postoperative pain management. The pain was be evaluated by VAS score. These patients were followed up on 30th, 60th, 90th, and 180th postoperative day. The follow-up was done at KEM hospital or by telephonic conversation.
Results of the study were filled in Microsoft Excel sheet analyzed statistically with Chi-square test, Fisher's exact test, and Mann–Whitney test with α = 0.05. P < 0.05 were considered statistically significant.
| Results|| |
In total, thirty patients made through the inclusion criteria during the study period. Mean age was 49.5 years and median age was 50.69 years. One of them died during the course of study. Out of 29 patients, 28 received general anesthesia only and one received epidural analgesia in addition to general anesthesia.
Preoperative and postoperative pain measurement was done by using VAS. Mean and standard deviation of preoperative VAS was 1.37 and 1.84, respectively. The VAS of postsurgical chronic pain on day 90 was 0.667 with standard deviation of 1.21, and at day 180, it was 0.593 with standard deviation of 1.12 [Table 1].
|Table 1: Mean and standard deviation in postoperative Visual Analog Scale at day 90 and 180|
Click here to view
The incidence proportion of CPSP in our study was found to be approximately 24%, i.e., seven patients out of 29 developed CPSP at postoperative day 180. [Table 2] showed effect of preoperative pain on incidence of postsurgical chronic pain was found to be statistically insignificant as P = 0.66. Hamilton Anxiety Rating Scale was used to assess preoperative anxiety in all enrolled patients. They were divided into three groups; mild, moderate, and severe depending on the Hamilton anxiety rating score [Table 3]. Out of 29, 8 patients had mild anxiety, 9 patients had moderate, and 12 patients had severe anxiety. [Table 3] showed effect of preoperative anxiety on the incidence of postsurgical chronic pain was found to be statistically insignificant with P = 0.067.
|Table 2: Effect of preoperative pain on the incidence of postsurgical chronic pain|
Click here to view
|Table 3: Effect of preoperative anxiety on the incidence of chronic or persistent postsurgical pain|
Click here to view
As per previous studies, different surgical techniques of MRM had effect on the outcome of treatment. We studied the effect of type of incision taken for MRM, duration of MRM surgery, and preservation of intercostobrachialis nerve during MRM on incidence of development of CPSP. [Table 4] showed the effect of type of incision taken during MRM over the incidence of CPSP and was found to be statistically insignificant (P = 0.557 and 0.75). Mean duration of MRM surgery was 2.77 h and does not affect incidence of post surgical chronic pain significantly (P = 0.941) as shown in [Table 5]. Out of 29 patients, intercostobrachialis nerve was preserved in 11 patients (37.93%). From [Table 6], it was seen that there was no significant difference whether nerve was preserved or not on chronic postsurgical pain, as P = 0.94 at day 90 and P = 0.71 at day 180.
|Table 4: Effect of type of incision taken during modified radical mastectomy on the incidence of chronic or persistent postsurgical pain|
Click here to view
|Table 5: Effect of duration of surgery over the incidence of chronic or persistent postsurgical pain|
Click here to view
|Table 6: Effect of preservation of nerve on the incidence of chronic or persistent postsurgical pain|
Click here to view
| Discussion|| |
In this study, we conducted prospective risk factors analysis for CPSP after MRM of 29 patients. Out of which, 24% of patients (7 of 29) developed CPSP over the period of 180 days after surgery. There are many factors affecting the incidence of CPSP. First and foremost is the type of surgery patient undergoing. There is variability in the incidence of CPSP with regard to different operative procedures in different studies. Reports of postoperative chronic pain incidences following different operations such as mastectomy, cesarean section, amputation, cardiac surgery, hernia repair, cholecystectomy, hip prosthesis surgery, and thoracotomy have been studied in the USA and England. This prospective observational study highlighted the incidence proportion of 24% which were in accordance with Tyalan Akkaya et al., who found the same to be 20%–50% after mastectomy and maximum of 50%–85% after amputation surgery.
We tried to analyze the presence of risk factors for development of CPSP in post-MRM patients and found that the presence or absence of risk factors previously identified in the clinical literature does not uniformly predict whether a certain individual will develop CPSP or not. Knowledge of demographic information, disease status, and plan of surgery may be of limited value in accurately identifying those who actually develop CPSP.
First risk factor we analyzed was presence of preoperative pain. As per the previous literature, preoperative pain has been identified as a well-established risk factor for development of CPSP. However, we encountered nil statistical significance between the presence of preoperative pain with development of CPSP. These results are in accordance with Peters et al., who found less CPSP after general surgery in patients with preoperative pain (odds ratio: 0.32; 95% confidence interval: 0.17–0.60). However, this study did not specify the type of surgery and defined CPSP as merely an increase of pain after surgery. Pain in the breast is far more frequent in benign diseases of the breast and is therefore often overlooked in the context of a malignant disease. However, a study comparing benign and malignant breast disease found that 16% of patients diagnosed with breast cancer presented with pain at initial contact, and it should thus be registered in future studies to clarify its role as a risk factor. But again, there are many references available showing the positivity of preoperative pain as a risk factor after surgeries other than MRM.,, Six months after gastrointestinal surgery, 35% and 29% of patients with surgical site and/or remotely located preoperative pain reported CPSP compared with only 3% of patients without preoperative pain. Regarding hysterectomy, preoperative abdominopelvic pain tripled the odds of chronic persistent pain. In a study by Nikolajsen et al., they suggested that preamputation pain increased the risk of stump and phantom pain. While a similar relation was stated between mastalgia and phantom breast pain, this correlation was not established in total hip arthroplasty operations.
Next risk factor we followed for analysis was presence of preoperative anxiety. We were unable to establish a statistically positive relationship of preoperative anxiety with development of CPSP, even though anxiety was one the major risk factor as per previous literature. This could be due to the smaller sample size we analyzed in limited period of time at only one tertiary care center. Anxiety of a person will be one of the effects (outward expression of one's emotion) of his/her psychological condition at that point. The relationship between pain and psychological morbidity is well established. Psychological factors known to influence pain perception include depression, anxiety, and fear of pain. In the literature we reviewed, many studies included some form of assessment of psychosocial functioning. Tasmuth et al. found a positive correlation between level of anxiety and depression and symptoms in the breast region. Kudel et al., found a correlation between presurgical pain, i.e. pain other than that related to the surgery, as well as scar pain and higher depression and anxiety scores. However, Poleshuck et al., found no correlation between chronic pain and emotional functioning. The evidence available infers that there is a concomitant occurrence of pain and psychosocial comorbidity among these patients. The relationship of causality is not clear because of the lack of sufficiently designed prospective studies. Hence, our study was just a small step toward identifying human pain as one of its emotion. Thus, there is a need for a standardized procedure-specific instrument to measure the relationship between psychosocial factors, especially anxiety with development of CPSP.
Some specific surgical techniques were known to reduce the chances of development of CPSP. We studied the effect of preservation of intercostobrachialis nerve during MRM, the type of incision, and the duration of surgery. As per our study, none of the above factor had statistically significant effect over development of CPSP. The intercostobrachialis nerve (ICBN) arises from the lateral cutaneous branch of the second intercostal nerve (T2). It enters the axilla, perforating the C2 and the serratus anterior in the midaxillary line, and passes through with considerable variability to the posteromedial border of the upper arm. Thus, the ICBN is vulnerable during axillary surgery. As the sentinel node is often placed in proximity to the ICBN, sentinel lymph node biopsy may theoretically also damage this nerve. The clinical relevance of preserving the intercostobrachialis nerve has been an issue of discussion and is practiced differently from center to center. As nerve damage is a prerequisite for neuropathic pain, it is hypothesized that preservation of ICBN during axillary surgery may reduce the development of CPSP. Even if preservation is attempted, this may be challenging, and a complete or part sectioning may happen inadvertently. The majority of previous studies showed a higher frequency of sensory disturbances after ICBN transection. In the study by Torresan et al., patients randomized to preservation, in which the nerve was inadvertently sectioned, were excluded, and a new patient included. Pain was evaluated in terms of anesthesia, hypoesthesia, and hyperesthesia as compared to no complaints, which was rather vague. Salmon et al., reported any symptoms in the arm in only 4.5% in the preservation group, and 6.4% in the section group, which is much lower than reported in other studies. Hence, a larger, more detailed, observational study with consideration of only one parameter of ICBN to clarify the precise role of ICBN injury for the development of CPSP is needed. Findings from this study suggest that the risk factors mentioned in previous clinical literature may not uniformly predict the development of CPSP in a specific patient.
The negative relationship between risk factors and development of CPSP could be due to very small sample size in only one tertiary care center. To develop a reliable prediction model to estimate an individual's susceptibility to CPSP, many such prospective multicenter studies with huge sample size over longer period of time in a more standardized way need to be conducted. An important step in the development and validation of a prediction model of CPSP is to conduct logistic regression models to obtain hierarchy in the importance of established risk factors.
| Conclusion|| |
Caution should be exercised when attempting to identify women who are at risk for developing CPSP or who have already developed CPSP. Establishing a prediction model based on known risk factors to identify susceptible patients and applying protective measures is an important step toward preventive, personalized health care. The probable risk factors we studied for developing CPSP were the level of preoperative pain and anxiety, specific surgical techniques like incision type, duration and sparing of nerve, that were found statistically insignificant and reason behind it is already explained in limitation of study. It can be recommended to screen all operated breast cancer patients for development of CPSP. Such widespread screening is needed to identify those suffering from CPSP so that pain management strategies can be instituted in a timely fashion.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: Risk factors and prevention. Lancet 2006;367:1618-25.
Hoofwijk DM, Fiddelers AA, Emans PJ, Joosten EA, Gramke HF, Marcus MA, et al.
Prevalence and predictive factors of chronic postsurgical pain and global surgical recovery 1 year after outpatient knee arthroscopy: A prospective cohort study. Med (Baltimore) 2015;94:e2017.
Perkins FM, Kehlet H. Chronic pain as an outcome of surgery. A review of predictive factors. Anesthesiolo 2000;93:1123-33.
Fletcher D. Epidemiology of chronic postsurgical pain. In: Chronic Postsurgical Pain. Mick G, Guastella V, editors. Switzerland: Springer International Publishing; 2014. p. 13-20.
Akkaya T, Ozkan D. Chronic post-surgical pain. Agri 2009;21:1-9.
Gärtner R, Jensen MB, Nielsen J, Ewertz M, Kroman N, Kehlet H, et al.
Prevalence of and factors associated with persistent pain following breast cancer surgery. JAMA 2009;302:1985-92.
Macrae WA. Chronic post-surgical pain: 10 years on. Br J Anaesth 2008;101:77-86.
Peters ML, Sommer M, de Rijke JM, Kessels F, Heineman E, Patijn J, et al.
Somatic and psychologic predictors of long-term unfavorable outcome after surgical intervention. Ann Surg 2007;245:487-94.
Macdonald L, Bruce J, Scott NW, Smith WC, Chambers WA. Long-term follow-up of breast cancer survivors with post-mastectomy pain syndrome. Br J Cancer 2005;92:225-30.
VanDenKerkhof EG, Hopman WM, Reitsma ML, Goldstein DH, Wilson RA, Belliveau P, et al.
Chronic pain, healthcare utilization, and quality of life following gastrointestinal surgery. Can J Anaesth 2012;59:670-80.
VanDenKerkhof EG, Hopman WM, Goldstein DH, Wilson RA, Towheed TE, Lam M, et al.
Impact of perioperative pain intensity, pain qualities, and opioid use on chronic pain after surgery: A prospective cohort study. Reg Anesth Pain Med 2012;37:19-27.
Pinto PR, McIntyre T, Nogueira-Silva C, Almeida A, Araújo-Soares V. Risk factors for persistent postsurgical pain in women undergoing hysterectomy due to benign causes: A prospective predictive study. J Pain 2012;13:1045-57.
Nikolajsen L, Ilkjaer S, Krøner K, Christensen JH, Jensen TS. The influence of preamputation pain on postamputation stump and phantom pain. Pain 1997;72:393-405.
Katz J, Poleshuck EL, Andrus CH, Hogan LA, Jung BF, Kulick DI, et al.
Risk factors for acute pain and its persistence following breast cancer surgery. Pain 2005;119:16-25.
Tasmuth T, Estlanderb AM, Kalso E. Effect of present pain and mood on the memory of past postoperative pain in women treated surgically for breast cancer. Pain 1996;68:343-7.
Kudel I, Edwards RR, Kozachik S, Block BM, Agarwal S, Heinberg LJ, et al.
Predictors and consequences of multiple persistent postmastectomy pains. J Pain Symptom Manage 2007;34:619-27.
Poleshuck EL, Katz J, Andrus CH, Hogan LA, Jung BF, Kulick DI, et al.
Risk factors for chronic pain following breast cancer surgery: A prospective study. J Pain 2006;7:626-34.
Loukas M, Hullett J, Louis RG Jr., Holdman S, Holdman D. The gross anatomy of the extrathoracic course of the intercostobrachial nerve. Clin Anat 2006;19:106-11.
Pecha V, Kolarik D, Kozevnikova R, Hovorkova K, Hrabetova P, Halaska M, et al.
Sentinel lymph node biopsy in breast cancer patients treated with neoadjuvant chemotherapy. Cancer 2011;117:4606-16.
Torresan RZ, Cabello C, Conde DM, Brenelli HB. Impact of the preservation of the intercostobrachial nerve in axillary lymphadenectomy due to breast cancer. Breast J 2003;9:389-92.
Salmon RJ, Ansquer Y, Asselain B. Preservation versus section of intercostal-brachial nerve (IBN) in axillary dissection for breast cancer – A prospective randomized trial. Eur J Surg Oncol 1998;24:158-61.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]