Legally prescribed opioids play a significant role in the U.S. opioid epidemic as a major source of opioids available in the community for diversion and nonmedical use.1,2 Contributing to this supply are opioids prescribed after surgery, because more than half of these opioids go unused.3–6 Cesarean birth is the most common major surgical procedure in the United States, with 1.3 million procedures performed each year.7 On average, 10–15 prescription opioid tablets per person are unused, which is estimated to result in 13–19.5 million unused tablets generated annually from cesarean deliveries alone.8,9
Despite growing awareness of overprescribing,10 little guidance exists regarding how to prescribe opioids after discharge.11,12 The Interagency Guideline on Prescribing Opioids for Pain offers the most comprehensive recommendations, including multimodal therapy, tapering opioids after discharge, and targeted patient education about risks of opioids. However, these guidelines do not address how to determine the quantity of tablets prescribed or how to tailor prescribing methods to individual need.12 Recent studies confirm that most health care providers use a “one-size-fits-all” approach, giving a uniform quantity of opioids regardless of patient characteristics.9,10
We questioned whether individualized prescribing might reduce unused opioids after cesarean birth. Prior research found that inpatient opioid use was highly associated with discharge opioid use.9 Therefore, we undertook this study to examine whether individualizing discharge opioid prescribing derived from inpatient use reduces unused opioids after cesarean birth compared with standard prescribing. We also examined whether individualized opioid prescribing is associated with worse patient-reported pain outcomes.
MATERIALS AND METHODS
We performed a randomized, controlled trial at Vanderbilt University Medical Center with approval from the institutional review board. Women who underwent cesarean birth and were age 18 years of age or older were included. We excluded women who experienced a complicated cesarean birth, defined as hysterectomy during or after the cesarean birth, bowel or bladder injury during the cesarean birth, need for reoperation, or immediate wound complication. Women with a diagnosis of an opioid use disorder or who reported opioid use for greater than 14 days during the current pregnancy were excluded, as were women who spoke languages other than English or Spanish.
Trained research staff approached eligible women and obtained informed, written consent on postoperative day 1 in the postpartum unit. Enrolled participants completed Survey 1 (Appendix 1, available online at http://links.lww.com/AOG/B127), which queried them about surgical and opioid history as well as their perceived pain experience during hospitalization. Randomization was performed centrally using REDCap13 and occurred before discharge using random, permuted blocks of four to eight. Participants were assigned in a 1:1 ratio to either a standard discharge prescription (30 tablets) or an individualized prescription (variable number of tablets) of 5 mg oxycodone. The standard prescription represents the most common number of tablets (30) provided at discharge from our institution. The quantity of tablets for the individualized prescriptions was derived from prior research data correlating inpatient opioid use with postdischarge opioid use. The formula used (predicted opioid use after discharge=48.8+[1.77×IP24–47]) derives from a linear regression of those data, in which discharge opioid use is the dependent variable and IP24–47 (inpatient use from 24 to 47 hours) is the independent variable.9 Reasons for the selected time period were twofold. First, most women undergoing cesarean birth receive long-acting spinal morphine, which reduces oral opioid demand during the first 24 hours after cesarean birth. Second, half of our population is discharged starting at 48 hours after cesarean birth, precluding the use of inpatient opioid use data beyond 48 hours in the postdischarge prescription prediction formula. During their inpatient stay, all patients are generally prescribed oxycodone or hydrocodone and acetaminophen every 6 hours as needed as well as 600 mg ibuprofen every 6 hours as needed. Prescriptions were filled by the outpatient pharmacy and delivered to participants' hospital rooms before discharge, which is typical at our institution. All participants were also prescribed 600 mg ibuprofen at discharge, to be taken every 6 hours, which is customary at our institution.
Participants were contacted starting 14 days after cesarean birth by phone or email to ascertain total number of opioid tablets used and unused. When able, they were asked to locate the tablet container and count the remaining tablets. Participants who could not provide a numeric estimate of tablets used or remaining were designated “unable to confirm unused opioids.” Participants were also administered Survey 2 (Appendix 2, available online at http://links.lww.com/AOG/B128), which queried perceived pain control and activities of daily living since discharge, whether they felt they received a sufficient quantity of opioids at discharge, reasons for using opioids, and disposal of remaining opioids after they finished. Participants were contacted at least three times by telephone, email, or text until they were designated as lost to followup; those still taking opioids at the time of initial contact were then called weekly until they had completed opioid use. The electronic health record was accessed to determine whether surgical complications had occurred after discharge, and participants were also queried in Survey 2 in the event that they sought care at another facility. The Tennessee Controlled Substance Monitoring Database was accessed to determine whether additional opioid prescriptions had been prescribed in Tennessee or the surrounding states.
The primary outcome was total number of unused 5-mg oxycodone tablets prescribed after cesarean birth. Secondary outcomes included total tablets used, frequency of using all or no opioid tablets, frequency of obtaining additional opioid prescriptions after discharge, inpatient and outpatient pain scores, and patient-reported pain outcomes. We examined how many (zero to five) of the five questions relating to analgesic adequacy each patient responded to in a negative way and the proportion of these responses was presented graphically. Demographic, delivery, anesthetic, and in-hospital opioid use patterns were extracted from the electronic health record.
All statistical analyses were performed using SAS 9.4 and data were collected and managed using REDCap, a secure online electronic database hosted at Vanderbilt University. Trained research assistants entered all data. χ2 or Fisher exact tests were used to analyze categorical variables and Student t test, Mann-Whitney U, and Spearman correlation coefficient were used as appropriate to analyze continuous variables. Relative risks and 95% CIs were calculated when applicable. Based on our prior data, the mean unused number of 5-mg oxycodone tablets was 17 (SD±12). With an α of 5% and a β of 80%, we estimated that 160 participants would be required to detect a 30% reduction in unused opioid tablets with individualized prescribing. We anticipated a lost to follow-up rate of 20% and therefore inflated our target sample size to 200 participants.
Between June 14, 2017, and August 26, 2017, 323 potential participants were assessed for eligibility and 172 enrolled and analyzed (Fig. 1). Baseline characteristics were similar between groups (Table 1) as were inpatient pain scores (standard 4.6±2.9 and individualized 4.9±2.5, P=.52). Of women who used all their opioid tablets, most reported using them to treat pain, but 30% (13/44) reported an interpretation that they were to use all tablets until completion and one stated that she took all opioids to help with sleep.
Participants who received an individualized prescription were discharged with half the number of prescribed opioid tablets compared with women in the standard prescription group (14 [interquartile range 12–16] vs 30 [interquartile range 30–30], P<.001). They also had 50% fewer unused opioid tablets 2 weeks after discharge compared with those in the standard prescription group (5 [interquartile range 1–8] vs 10 [interquartile range 0–22] tablets, P<.001), which is represented graphically in Figure 2. The individualized prescription group participants used, on average, approximately 50% fewer oxycodone tablets after discharge (8 [interquartile range 4–14] vs 15 [interquartile range 6–30], P<.001). Participants in both groups used the same proportion of their prescribed opioid tablets (60% [interquartile range 23–100] vs 61% [interquartile range 29–89], P=.93). Furthermore, the proportions of women using no postdischarge opioids and all prescribed opioids were similar in both groups. We found no significant differences between groups in the total quantity of opioid and nonopioid analgesics used while inpatients. Seven participants sought and obtained additional opioid prescriptions with no significant differences between groups (Table 2).
There were no significant differences in pain measures between groups (Table 2). Figure 3 represents the distribution of negative pain responses by representing the total number of negative responses (inadequate pain control) from 0 to 5 to the five pain-related questions. Most women had either no responses indicating inadequate pain control or responded negatively to only one question. Finally, we compared predicted with actual opioid use. Overall, predicted use was moderately correlated with actual use (r=0.53), which improved with individualized prescribing (r=0.65) and worsened with standard prescribing (r=0.44).
In this randomized controlled trial, women randomized to receive individualized opioid prescriptions based on inpatient use reported having 50% fewer unused oxycodone tablets compared with women who received a standard prescription (30 tablets, 5 mg oxycodone) after discharge for cesarean birth. In addition, individualized opioid prescribing was associated with less opioid use, specifically a 50% reduction in use compared with women receiving a standard prescription. Although variation in opioid use was great, both groups used, on average, 60% of their total prescribed tablets and both groups had near identical proportions of women who used no opioids (13–14%) or all opioids (24–27%). These findings occurred without statistically significant differences in reported pain outcomes.
Several studies have examined interventions to reduce unused opioids. In a trial of patients undergoing dental surgery (n=79), adults randomized to education about proper opioid disposal after surgery were more likely to dispose or intend to dispose of opioids after surgery; however, the results were not statistically significant.14 In a nonrandomized intervention study by Prabhu et al,15 women (n=50) participating in a shared decision-making intervention—education about opioids and patient selection of discharge opioid tablet number—used 50% fewer opioids after discharge compared with usual prescribing at that institution. Patient satisfaction with outpatient pain management was high (90%) and few required additional prescriptions. Although the reduction in opioid use we observed was substantial, we suspect a further reduction with interventions targeted at improving knowledge about multimodal therapy, how to taper opioids, and education about potential side effects for both the mother and infant. For example, almost one third of women who used all opioids did so not to manage their pain, but because they incorrectly thought that they were following directions to take until finished.
Unexpectedly, women who received individualized prescriptions not only had fewer unused opioid tablets, but took less opioid medication as well. Consistent with this, the proportion of women who used all prescribed opioids was similar in both groups. In fact, the mean proportion of opioids used relative to that prescribed was the same (60%) in both groups. If pain were the only determinant of opioid use, randomization should yield similar opioid use in both study groups. These findings suggest that factors other than pain influence opioid use patterns. Our results are consistent with those of Bateman et al16 who reported greater opioid use among patients after cesarean birth who were discharged home with greater than 30 tablets compared with those prescribed 30 tablets or less (relative risk 1.35 [1.10–1.65] and relative risk 2.01 [1.48–2.75]). The investigators proposed that simply prescribing less may be a reasonable strategy to reduce opioid consumption. Our pain outcome differences (survey questions related to pain and satisfaction and composite pain score), although not statistically different, suggest potential for inferior pain control among women in the individualized group. This finding makes us hesitant to endorse the conclusion of Batemen et al without further research.
A larger sample size is needed to have sufficient power to estimate whether a uniform opioid restriction strategy might have the unintended consequence of undertreating pain in some patients. Furthermore, opioid prescriptions in most states, including ours, require a physician assessment and a paper prescription, precluding e-prescribing or phone prescriptions. The requirement to travel to visit a health care provider to obtain a refill for inadequate postoperative analgesia presents a significant barrier for mothers caring for newborns. Efforts to achieve the public health goal of reducing unused opioids available for diversion and misuse must carefully consider potential suffering from undertreatment of postcesarean birth pain.
Finally, we acknowledge limitations with our selected model for individualizing opioid prescribing. We chose to begin with a single variable—inpatient opioid use—which we previously found to be most associated with outpatient use. When comparing predicted with actual use, individualized prescribing improved this correlation compared with standard prescribing; however, the correlation was moderate at best. We propose that a more complex model might better predict outpatient use and, thus, might also reduce patient-reported pain outcomes indicative of worse pain control.
In conclusion, individualized opioid prescriptions based on inpatient use substantially reduced both the amount of opioid used and unused after discharge for cesarean birth compared with standard prescribing. Annualized for our institution's total cesarean birth rate, individualized prescribing would result in 12,960 fewer opioid tablets unused after cesarean birth per year. Given that cesarean birth is the most common major surgery in the United States, the public health implications of our findings are significant. Further research is warranted to examine the relative contributions of patient education, expectations, and behavioral factors influencing opioid use and patient-reported pain outcomes after cesarean birth.
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