A “Hot Topic Video” by Editor-in-Chief Rod J. Rohrich, M.D., accompanies this article. Go to PRSJournal.com and click on “Plastic Surgery Hot Topics” in the “Videos” tab to watch.” On the iPad, tap on the Hot Topics icon.
In recent years, opioid prescribing has faced intense scrutiny. From 2000 to 2009, the number of prescriptions written for opioid analgesics increased by 35 percent.1 The United States consumes the highest total number of opioid prescriptions in the world, and prescription opioids contribute to more overdose deaths than cocaine and heroin combined.2–6 The adverse health effects of chronic opioid use are well documented, and include increased risks of falls, fractures, myocardial infarctions, respiratory distress, and bowel obstruction.7–9
Nonetheless, opioid analgesics are the mainstay of inpatient and outpatient postoperative pain control, and are highly effective in managing acute pain following surgical procedures.10,11 To date, consensus guidelines to direct perioperative opioid prescription are sparse, and the majority of recommendations are focused on opioid prescribing in the setting of chronic pain. Despite their efficacy, opioid analgesics may pose an important risk of dependency and prolonged use, particularly when opioids are prescribed immediately after surgery.12 Moreover, chronic opioid use is associated with important effects that may complicate perioperative management, including hyperalgesia, respiratory and central nervous system depression, and ileus. Patients who use opioids are significantly more likely to require hospitalization than patients receiving other forms of pain control, and have increased health care use and morbidity following surgical procedures.8,13,14
Cancer patients are particularly susceptible to opioid dependence, and recent studies suggest that rates of opioid dependence may be underestimated.15 Therefore, identifying the provocative and protective factors for prolonged opioid use following common surgical procedures in the preoperatively opioid-naive patient is critical to minimize the excess morbidity and mortality associated with chronic opioid use. Breast reconstruction represents the most common cancer reconstruction performed, with over 100,000 procedures each year, and opioids are commonly used to manage postoperative pain.16 In this context, we sought to examine (1) the use patterns of outpatient prescription opioids among women undergoing postmastectomy reconstruction, and (2) the factors that may influence prolonged (defined as >90 days after surgery) opioid use following breast reconstruction.
PATIENTS AND METHODS
Data Source and Study Cohort
We examined employer-based health care claims data drawn from the Truven Health MarketScan Research Databases, including the MarketScan Commercial Claims and Encounters Database and the Medicare Supplemental and Coordination of Benefits Database. These sources host health use records, including service use, and payment and enrollment data for approximately 50 million active employees, early retirees, Medicare-eligible retirees with employer-provided Medicare Supplemental plans, and their dependents for each year. These databases cover inpatient, outpatient, and prescription drug services.
We analyzed outpatient pharmaceutical claims from 4113 women, aged 18 years and older, who underwent breast reconstruction immediately following mastectomy from January 1, 2010, to August 31, 2014. We included only women who were “opioid-naive,” defined as the lack of any prescription fills for opioid medications in the prescription 365 to 31 days before surgery, assuming that prescriptions obtained in the 30 days before surgery were given in anticipation of surgery. The International Classification of Diseases, Ninth Revision, diagnosis codes and Current Procedural Terminology codes were used to determine the indication and procedure descriptions, respectively. (See Appendix, Supplemental Digital Content 1, which shows the codes for immediate breast reconstruction. ICD-9, International Classification of Diseases, Ninth Revision; CPT, Current Procedural Terminology; TRAM, transverse rectus abdominis myocutaneous; DIEP, deep inferior epigastric perforator; SIEA, superficial inferior epigastric artery; GAP, gluteal artery perforator; ADM, acellular dermal matrix, http://links.lww.com/PRS/C426.) Insurance claims data were used to identify all women undergoing these procedures unilaterally or bilaterally, for both therapeutic and prophylactic indications. We specified that patients included in this study had continuous enrollment in their insurance plan from the year before surgery, from which preoperative medication fills and comorbidities were obtained, through 120 days after, during which time all postoperative outcomes were obtained. All patient data were deidentified before being queried, and this study was deemed exempt from review by the University of Michigan Institutional Review Board.
Prescription Opioid Pharmacy Claims
We examined pharmaceutical claims data to determine the type of opioid prescribed, dose, duration of prescription in days, and number of refills. Prescription medications were identified using generic names. We then evaluated each prescription dose in terms of oral morphine equivalents using publicly available morphine equivalents–per-milligram conversion factors.17,18
We restricted our analysis to opioid-naive women who received a perioperative opioid prescription (a prescription filled 30 days preoperatively to 30 days postoperatively), to better understand the impact of perioperative opioid fills on long-term outcomes. We examined the following outcomes among women undergoing breast reconstruction: (1) average daily oral morphine equivalents (the number of oral morphine equivalents given divided by the total days supplied, all within the perioperative period), and (2) prolonged fills (the percentage of women who filled an opioid prescription within the perioperative period and continued to refill between postoperative days 90 and 120). We excluded all women who underwent procedures requiring anesthesia in the postoperative period to minimize confounding from opiate prescriptions filled for secondary operations (Fig. 1).
We included the following sociodemographic factors in this analysis: age (18 to 34 years, 35 to 44 years, 45 to 54 years, 55 to 64 years, and 65 years and older), median local household income, and insurance plan type. Median household income was determined by using a patient’s metropolitan statistical area, a geographic grouping that contains a high-density urban center and the neighboring communities that share similar social and economic features. Patient metropolitan statistical area was compared with financial data from the 2010 census to approximate the median household income for each patient’s region of residence.19 Each patient was then assigned to an income grouping based on this information. Insurance type was divided into five groups: (1) comprehensive health insurance, (2) health maintenance organization, (3) preferred provider organization, (4) point-of-service plan, and (5) other.
Preoperative comorbidities were identified by International Classification of Diseases, Ninth Revision, codes from the year before surgery, using the Elixhauser index,20 and psychiatric diagnoses of anxiety, depression, and substance use disorders from the past year were obtained and included separately. (See Appendix, Supplemental Digital Content 2, which shows the codes for mental health diagnoses. ICD-9, International Classification of Diseases, Ninth Revision; CPT, Current Procedural Terminology, http://links.lww.com/PRS/C427.) Finally, we included the receipt of neoadjuvant chemotherapy in the 6 months before diagnosis as a proxy for locally advanced disease.
Reconstructive procedure was identified by Current Procedural Terminology code (see Appendix, Supplemental Digital Content 1, http://links.lww.com/PRS/C426) and then stratified into the following four categories: (1) prosthesis, with implant or tissue expansion; (2) autologous pedicled muscle or myocutaneous flap coverage with either implant or expander; (3) autologous pedicled muscle or myocutaneous reconstruction without prosthesis placement; and (4) autologous free flap reconstruction requiring microsurgery. To account for the postoperative course, the following complications data were obtained by means of Current Procedural Terminology/International Classification of Diseases, Ninth Revision, diagnosis codes from the first 120 days after surgery and included as a cofactor in our modeling: presence of infection, wound complication, hematoma development, mechanical complication, capsule contracture, fat necrosis, and venous congestion. (See Appendix, Supplemental Digital Content 3, which shows the codes for complications/failures. ICD-9, International Classification of Diseases, Ninth Revision; CPT, Current Procedural Terminology, http://links.lww.com/PRS/C428.)
We generated descriptive statistics to illustrate the characteristics of the study cohort and the patterns of opioid prescriptions provided. Multivariable logistic regression was used to determine the associations between the aforementioned independent variables and prolonged opioid fills. We used multivariable linear regression to calculate adjusted daily oral morphine equivalents within 90 days postoperatively, adjusted for all of the aforementioned independent variables. Two-sided significance tests were used with a p-value threshold of alpha = 0.05. All analyses were performed using SAS v9.4 (SAS Institute, Inc., Cary, N.C.).
We identified 4113 opioid-naive women who underwent immediate breast reconstruction following total mastectomy (Table 1). The majority of patients [3691 (90 percent)] filled an opioid prescription in the perioperative period, and 10 percent of those patients continued to fill an opioid prescription after 90 days after surgery. In comparison, 74 percent of chronic opioid users (n = 327) continued to fill opioid prescriptions following surgery, with an average daily intake of 89 mg oral morphine equivalents. Reconstruction by prosthesis was the most common procedure type (76 percent). The majority of patients were aged 45 years and older. Most patients had a preferred provider organization insurance plan and more than two comorbidities, and the median income for each metropolitan statistical area was between $50,000 and $60,000. Of the patients in our analysis, 17 percent had a psychiatric diagnosis; the most common diagnosis was anxiety (9 percent). In this cohort, 20 percent of patients experienced complications following surgery, most commonly infection (9.5 percent of patients).
Patient Factors and Daily Opioid Dosages
Table 2 details the multivariate analysis examining the patient characteristics associated with differences in average daily opioid prescribed (oral morphine equivalents). We observed that patients with a diagnosis of depression were more likely to fill prescriptions of higher daily doses (74.2 mg versus 58.3 mg; p = 0.003), as were patients who underwent bilateral reconstruction procedures (74.5 mg versus 55.2 mg; p = 0.02). Notably, compared with those undergoing repair by prosthesis, patients undergoing autologous pedicled reconstructions (51.4 mg versus 61.8 mg) or free tissue transfer (49.1 mg versus 61.8 mg; p = 0.002) filled prescriptions of significantly lower average daily oral morphine equivalents. Patients aged 55 to 64 years filled prescriptions of lower oral morphine equivalents compared with younger patients (53.6 mg versus 66.9 mg; p = 0.029). Preoperative radiation therapy did not significantly affect oral morphine equivalents (p = 0.718).
Predictors of Prolonged Opioid Fills
Table 3 describes the patient factors that are associated with continuing to fill a prescription between 90 and 120 days after surgery. We observed that patients with a diagnosis of anxiety were more likely to continue to fill an opioid prescriptions for a prolonged period after surgery (13.4 percent versus 9.1 percent; p = 0.007). Patients who experienced postoperative complications were also more likely to fill opioid prescriptions beyond 90 days postoperatively (12.8 percent versus 8.9 percent; p < 0.001). In addition, we observed that patients who received neoadjuvant chemotherapy were less likely (6 percent versus 10 percent; p = 0.025) to fill an opioid prescription for a prolonged period after surgery. Finally, patients undergoing free flap reconstruction were significantly less likely to continue to fill prescriptions than those undergoing a prosthesis procedure (5.9 percent versus 10.2 percent; p = 0.008).
In this national sample of patients undergoing breast reconstruction, the majority of patients fill opioid prescriptions following surgery, and 10 percent of patients continue to fill prescriptions up to 4 months postoperatively. Patients with coexisting mood disorders were more likely to fill greater quantities of opioid prescriptions and go on to prolonged use following surgery. We observed differences in prolonged opioid use by surgical technique, and patients who underwent prosthesis-based reconstruction were more likely to fill prescriptions of higher daily doses, and develop new persistent use. Considered together, our findings suggest that a substantial number of women continue to fill prescriptions for an extended time after surgery, and that autologous reconstruction is associated with lower rates of prolonged opioid use.
Our findings are congruent with prior studies that have demonstrated that approximately 80 percent of patients fill opioid prescriptions following low-risk surgical procedures, and roughly 5 to 15 percent of opioid-naive patients continue to use opioids regardless of major or minor procedures.12,21–27 The reasons why patients continue to fill opioid prescriptions following surgery are multifactorial, and include patient, procedural, and disease factors. In our cohort, similar to other national estimates, the majority of women underwent prosthesis-based reconstruction. Immediate implant placement is possible for some women, but many require tissue expansion and an extended period of device fills, which may cause substantial discomfort and could contribute to the increased need for opioid analgesics.28–30 Autologous reconstruction and free tissue transfer typically require longer procedures, with donor-site morbidity and longer hospitalizations, and it is often assumed that patients may have greater pain following surgery.31 Today, the advent of perforator-based, muscle-sparing techniques may offer a smoother recovery, resulting in decreased postoperative pain and morphine requirements compared with prosthesis-based reconstruction.32 Finally, in our cohort, neoadjuvant chemotherapy was associated with lower rates of prolonged fills. Neoadjuvant chemotherapy regimens are often associated with pain and neurotoxicity from regimens, and it is possible that these patients may have initiated opioids before surgery and were excluded from our cohort. Patients who remained may have different coping strategies or more experience with opioid alternatives, yielding a protective effect in the postoperative period.33–37
Consistent with prior studies, we also observed that mental health conditions—specifically, depression and anxiety—correlate with opioid use following surgery.12,21,22,38–42 For example, recent evidence suggests that depression is an independent risk factor for opioid misuse.43 Patients with depression are more likely to experience centralized pain that is less responsive to opioid analgesics, and may be better managed by centrally acting agents such as gabapentinoids or serotonin-norepinephrine reuptake inhibitors.44 Although depression and anxiety are often grouped together, and are commonly treated with similar serotonergic agents, they influence postoperative opioid use differently. Stress disorders including anxiety arise from dysregulation of reward pathways in the brain, and may predispose patients to addiction and dependence.45 Benzodiazepines in particular are commonly prescribed for patients with anxiety disorders, and have been associated with chronic opioid use and increase the risk of concomitant use because of respiratory depression.46,47 In the context of surgery, clinicians should be aware of coexisting mental health diagnoses that may influence the perception of pain and use of opioids. Close consultation with providers in primary care, psychiatry, and pain management during the postoperative period can provide more coordinated care with opioid alternatives for these complex and potentially vulnerable patients.
Our study has several notable limitations. Insurance claims data capture only prescription fills and refills, but not patient-reported pain or opioid consumption. In addition, we cannot account for prescriptions that were written but remained unfilled, or the use of medications from past prescriptions or unintended sources. With respect to procedural aspects of care, we were unable to accurately capture technical details such as the use of regional anesthetic, implant location, or type of autologous flap used.48 Timing of reconstruction and the number of procedures needed vary widely, and our findings primarily reflect opioid use in the early postoperative period.30 Our data are also restricted to the patient level, and we cannot comment on the variation in prescribing patterns between providers, or the clustering of high-risk patients within specific practices. As such, it is possible surgeons may vary in prescribing thresholds, irrespective of a patient-reported pain, and long-term opioid use among opioid-naive patients has been linked to receipt of opioids from high-intensity opioid prescribers in other settings.49 Furthermore, our data set did not include granular identifiers for individual socioeconomic status or race, factors that have been shown to affect prescribing patterns.50,51 Lastly, our data set included only patients enrolled in a private insurance plan and did not contain Medicare recipients. Because we restricted our analysis to those with prescription fills, we presume all seniors included in the analysis had adequate Medicare Part D coverage, but our results may not be applicable to those with alternative plans.
Traditionally, opioids have been used liberally among patients with cancer, given the gravity of the diagnoses, pain related to tumor infiltration and treatment-related side effects, and the possibility of disease progression and metastases. Today, recent studies suggest a prevalence of opioid dependence as high as 7 percent in cancer patients.52 In addition, psychosocial distress at the time of diagnosis and surgical treatment for patients with cancer is common, with over 40 percent of patients newly diagnosed with cancer having subclinical or clinical anxiety symptoms, and may play an important role in postoperative opioid consumption.53–56 Among opioid-naive patients undergoing breast reconstruction, 10 percent will continue to fill an opioid prescription 90 days after their procedure. Rates are higher among those with postoperative complications, mental health conditions, and prosthesis-based reconstruction. Going forward, surgeons should counsel patients on the risk of prolonged opioid use, and consider opioid alternatives for postoperative analgesia, such as antiinflammatory agents and regional anesthesia when possible.57–62
Prolonged opioid use is common following surgery, and recent studies suggest that an increasing number of patients are escalating from first-time use to frequent or highly-frequent opioid use.63 Once a patient transitions into chronic opioid use, cessation is rare, with recent reports estimated that over half of patients who used prescription opioids for at least 90 days remained on opioid analgesics 5 years later.64,65 Therefore, in the setting of surgery, it is critical to intervene in the immediate postoperative period to prevent progression to chronic use. In the select few states that have developed and enforced their own guidelines to combat high-risk opioid prescribing, morbidity and mortality related to opioid abuse have decreased markedly.11,64,66 To date, there are no guidelines to direct perioperative opioid prescribing, and future work that prospectively defines the factors correlated with opioid consumption, dependence, and misuse will be critical to fill this gap in knowledge.67
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