Age and postoperative opioid use in women undergoing pelvic organ prolapse surgery

Abstract

Introduction

Our objective was to explore the relation between patient age and postoperative opioid use up to 24 hours following pelvic organ prolapse (POP) surgery.

Material and methods

We conducted a prospective cohort study following 335 women ranging in age from 26 to 82 years who underwent surgery for multi‐compartment POP at a tertiary center in Alberta, Canada. Patient characteristics were measured using baseline questionnaires. Perioperative data were collected from medical chart review during and up to 24 hours following surgery. We used logistic regression to analyze the odds of being opioid‐free and linear regression to analyze mean differences in opioid dose, measured as total morphine equivalent daily dose, exploring for a potential non‐linear effect of age. Adjusted models controlled for preoperative pain, surgical characteristics and patient health factors.

Results

Overall, age was positively associated with greater odds of being opioid‐free in the first 24 hours after surgery (adjusted odds ratio per increasing year of age = 1.07, 95% confidence interval [CI] 1.04–1.09, n = 332 women). Among opioid users, age was inversely associated with total opioid dose (adjusted mean difference per increasing year of age = 0.71 mg morphine equivalent daily dose, 95% CI −0.99 to −0.44, n = 204 women). There was no evidence of a non‐linear relation between age and postoperative opioid use or dose.

Conclusions

In the context of POP surgery, we found that younger women were more likely to use opioids after surgery and to use a higher dose in the first 24 hours when compared with older women. These findings support physicians to consider age when counseling POP patients regarding pain management after surgery, and to direct resources aimed at opioid‐free pain control towards younger patients.

Age was inversely associated with opioid use in the first 24 hours after pelvic organ prolapse surgery; younger patients were less likely to be opioid‐free and used a higher opioid dose. Findings can help tailor strategies aimed at postoperative opioid reduction.

Abbreviations

CI

confidence interval

ERAS

enhanced recovery after surgery

HUPPS Study

Hysterectomy vs Uterine Preservation for Pelvic organ prolapse Surgery Study

MD

mean difference

MEDD

morphine equivalent daily dose

OR

odds ratio

POP

pelvic organ prolapse

STOBE

Strengthening the Reporting of Observational Studies in Epidemiology

Key message.

Age was inversely associated with opioid use in the first 24 hours after POP surgery; younger patients were less likely to be opioid‐free and used a higher opioid dose. Findings can help tailor strategies aimed at postoperative opioid reduction.

1. INTRODUCTION

Gynecologic surgery is frequently associated with postoperative pain, with a patient‐reported pain intensity known to exceed that of procedures from other surgical specialties (eg orthopedics). ¹ , ² Contemporary best practices for enhanced recovery after surgery (ERAS) in gynecology therefore recommend that opioids such as fentanyl, morphine and hydrocodone be prescribed to patients judiciously and as needed to manage postoperative pain. ³ However, optimal management of postoperative pain is an ongoing clinical issue with important implications for health expenditures and outcomes. On one hand, inadequate postoperative pain management is associated with delayed hospital discharge and greater use of health services following surgery, as well as increased risk of patient morbidity (eg postoperative delirium), psychological distress, functional impairments and the development of chronic pain. ⁴ , ⁵ On the other hand, excessive postoperative pain management carries the serious risk of opioid misuse and dependency6, 7 an estimated 1 in 65 patients experienced prolonged opioid use following minor gynecologic surgery with higher prescribed opioid doses as a major contributor. ⁸

Substantial efforts have been directed towards understanding predisposing factors for opioid use following gynecologic surgery so that pain management practices can be tailored to individual patients undergoing specific surgical procedures. ³ , ⁹ However, few studies to date have specifically focused on predisposing factors following surgical treatment for pelvic organ prolapse (POP), which has unique perioperative considerations. Reconstructive elements that are exclusive to POP procedures, such as suspension of the vagina or uterus and vaginal wall repair, could result in a distinct pain profile compared with other gynecologic procedures. The risk of patient constipation following opioid use, even in small and brief doses, may also compromise the likelihood of POP cure by causing increased Valsalva pressures and pelvic strain, adding to the potential harms of opioid use and overuse for POP patients. ¹⁰ , ¹¹ Although it has been suggested that young age is a predictor of postoperative pain and opioid use more broadly, studies attempting to verify this risk factor in a POP patient population have unnecessarily dichotomized age, not reported the actual range of ages represented in the sample, and incompletely accounted for the potential confounding role of preoperative pelvic pain and mental health. ¹² , ¹³ , ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹

Elucidating the role of patient age as a predisposing factor for postoperative opioid use following POP surgery is important for tailoring physician counseling and pain management strategies in line with ERAS guidelines. Specifically, if younger patients indeed use higher doses of postoperative opioids, physicians will be better informed of the need for awareness of pain management complications in the postoperative period for this patient population, which could potentially be addressed through proactive management of pain expectations, as well as incorporation of, and advocacy for, non‐narcotic pain management strategies following surgery. We therefore explored the relation between patient age and postoperative opioid use up to 24 hours following surgery for multi‐compartment POP repair procedures.

2. MATERIAL AND METHODS

2.1. Study design and setting

We analyzed data from the Hysterectomy vs Uterine Preservation for Pelvic organ prolapse Surgery (HUPPS) Study, an ongoing prospective cohort study of patients undergoing their first surgery for multi‐compartment POP in Calgary, Alberta. Since July 2020, female patients have been recruited at the time of their initial surgical consultation (baseline) from a single tertiary care center that receives the majority of POP referrals in Calgary and surrounding rural areas, with a population of approximately 2.2 million residents. At this center, perioperative ERAS protocols have been universally implemented; this includes preoperative administration of 1000 mg acetaminophen and 400 mg ibuprofen; phenazopyridine 200 mg was administered by mouth 1 hour prior to surgery to facilitate visualization of ureteric jets at time of intraoperative cystoscopy; as well as around‐the‐clock dosing of postoperative acetaminophen and non‐steroidal anti‐inflammatory drugs. ³ Opioids after surgery are prescribed for all patients through standardized ERAS postoperative order sets which specify available dose, route and intervals. Opioids are only dispensed by postoperative nursing based on patient‐reported need for additional pain control beyond the postoperative acetaminophen and non‐steroidal anti‐inflammatory drugs. Surgeries were performed on the same day as admission to the hospital, followed by an overnight stay and anticipated next‐day discharge. Overnight admission is generally required for an individual to complete a standardized trial of void before discharge, as postoperative urinary retention (POUR) is common after multi‐compartment POP surgery; during this time, patients with POUR will typically be taught how to self‐catheterize intermittently at home until residual urine volumes diminish. ²⁰

Data on patient demographic characteristics, birth history, pelvic floor symptoms and physical and mental health were collected using standardized patient questionnaires at baseline. Data on clinical severity of POP, surgical characteristics and postoperative opioid use were collected using medical chart review and extraction at baseline and during the surgical hospitalization encounter. Patient questionnaires and clinical follow‐up continued over the course of the year following surgery for POP symptoms and objective findings.

For this analysis, we used questionnaire and medical chart data from baseline and the surgical encounter to maintain a focus on postoperative opioid use that occurs in a supervised hospital setting and is thus amenable to clinical intervention. We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. ²¹

2.2. Patient involvement

Patient partners who advise the HUPPS Study team indicated that research on pain expectations following surgery were a patient priority topic, given the common experience of feeling unprepared and under‐informed about postoperative pain intensity and management.

2.3. Participants

Patients were eligible for the HUPPS Study if they: (1) had diagnosed multi‐compartment POP of stage ≥2 using the globally recognized Pelvic Organ Prolapse‐Quantification System ²² ; (2) elected surgical management of POP; (3) demonstrated presence of apical prolapse on clinical examination deemed to require either a hysterectomy and concomitant vaginal vault suspension or uterine suspension to properly address their POP during surgical correction; (4) had no previous hysterectomy; (5) did not desire further pregnancy; (6) could communicate in English, and (7) were ≥18 years in age. ²³ For this analysis, we included patients enrolled in HUPPS who underwent surgery by March 7, 2023.

2.4. Exposure

Age in years was measured at the time of surgery. Age was analyzed as a continuous exposure and not arbitrarily dichotomized as in previous studies to limit information loss, maximize statistical efficiency and permit flexible modeling of the true relation between age and our outcomes of interest. ²⁴

2.5. Outcomes

Our primary outcome was proportion of patients who were opioid‐free in the first 24 hours; that is, their medical chart indicated that no opioids were dispensed in this period. Our secondary outcome was the opioid dose in the first 24 hours after surgery among patients who used post‐operative opioids, measured by accounting for and standardizing use of all oral and intravenous opioid medications recorded in the medical chart into the morphine equivalent daily dose (MEDD mg).

2.6. Covariates

Covariates were selected a priori based on literature review. Patient characteristics were self‐reported at baseline and included body mass index as a continuous variable (in kg/m²), ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁵ race/ethnicity (white; black, indigenous, or person of color), ¹³ , ¹⁶ , ¹⁷ , ¹⁸ , ²⁶ parity (number of births), ¹⁷ , ²⁶ preexisting daily pelvic pain (no, yes), ¹⁵ smoking status (never, ever) ¹⁶ , ¹⁷ , ²⁵ and anxiety and depressive symptoms measured using the EQ‐5D‐5L anxiety/depression dimension ²⁷ (no, yes). ¹⁷ , ¹⁹ Perioperative factors were extracted from medical records and included surgical route (laparoscopic, vaginal), ¹⁴ , ¹⁵ , ¹⁶ , ²⁶ total time in the operating room (in minutes), ¹⁷ , ¹⁸ , ¹⁹ , ²⁶ complications during surgery (eg bladder perforation, blood transfusion), ²⁸ , ²⁹ placement of a mid‐urethral sling (no, yes), vaginal prolapse repair (none, anterior colporrhaphy, posterior colporrhaphy) and type of apical prolapse repair (hysterectomy, uterine preservation). ¹³ , ¹⁴ , ¹⁵ , ¹⁸ , ¹⁹

Missing self‐reported covariate data were recovered, where possible, from medical charts and were therefore minimal (<1%).

2.7. Statistical analyses

We described sample characteristics in women who did and did not use opioids in the first 24 hours following surgery using frequencies and proportions for categorical data and means and standard deviations for continuous data. Among the full sample, we used logistic regression to model the relation between age and opioid‐free status with odds ratios (OR) and 95% confidence intervals (CI). Among women who use opioids, we used linear regression to model the relation between age and total MEDD with mean differences (MD) and 95% CI. Potential non‐linear effects of age on the outcomes of interest were explored by comparing models with age as a restricted cubic spline with four knots (ie differing effects across age values) to models with age as a linear term (ie uniform effects per year increase of age). The final model was selected based on the lowest Bayesian Information Criterion and confirmed through visual inspection of Lowess curves. Adjusted models controlled for all prespecified covariates. We conducted one sensitivity analysis removing large opioid dose outliers from the linear regression model to explore whether results were influenced by extreme values. All data were cleaned and analyzed using STATA V17.0.

2.8. Ethics statement

The HUPPS Study was approved by the Conjoint Health Research Ethics Board at the University of Calgary (#REB19‐2134) on March 12, 2020, and required all women to provide informed written or electronic consent upon enrollment.

3. RESULTS

3.1. Sample characteristics

Data from 335 patients undergoing surgery by March 7, 2023 were analyzed. The mean age of the sample was 55.8 ± 13.2 years, ranging from 26 to 82 years. Table 1 describes sample characteristics in women who did and did not use opioids in the first 24 hours after surgery. Women who used opioids were more likely to be younger, report preexisting daily pelvic pain, report mental health symptoms, and smoke, and more often experienced a longer time in the operating room, a concomitant surgery and a hysterectomy‐based prolapse repair.

TABLE 1.

Sample characteristics of women who underwent pelvic organ prolapse surgery according to postoperative opioid use in the first 24 hours (n = 335).

	Opioid‐free (n = 129)		Used opioids (n = 206)
	N (%)
Age, mean ± SD	61.5 ± 11.0		52.2 ± 13.2
Body mass index, mean ± SD	26.3 ± 4.8		27.3 ± 5.2
Self‐identified race/ethnicity
White	113	87.6	175	84.7
BIPOC	16	12.4	31	15.1
Preoperative pelvic pain	37	28.7	97	47.1
Anxiety or depressive symptoms	63	48.8	134	65.1
Smoking status
Never	98	76.0	142	68.9
Ever	31	24.0	64	31.1
Parity, median (interquartile range)	2 (2–3)		2 (2–3)
Time in operating room, mean ± SD	128.2 ± 67.2		141.4 ± 35.7
Surgical route
Laparoscopic	83	64.3	142	68.9
Vaginal	46	35.7	64	31.1
Surgical complications	9	7.00	20	9.7
Concomitant procedures
Mid‐urethral sling	26	20.2	73	35.4
Vaginal prolapse repair
Anterior colporrhaphy	110	88.0	171	85.9
Posterior colporrhaphy	15	12.0	28	14.1
Type of apical prolapse repair
Hysterectomy	58	45.0	114	55.3
Uterine preservation	71	55.0	92	44.7

Note: Totals may vary due to missing data for race/ethnicity (n = 1) or time in operating room (n = 2).

Abbreviations: BIPOC: black, indigenous, or person of color. SD: standard deviation.

3.2. Non‐linear effects

For both the primary and secondary outcomes, comparison of model fit using Bayesian Information Criterion suggested that the spline model and linear model were comparable and provided no evidence of non‐linear effects. This was confirmed by visual inspection of the Lowess curves. Accordingly, age was modeled with a linear term.

3.3. Age and opioid‐free status

Overall, 38.5% of women were opioid‐free in the first 24 hours after surgery. The crude model indicated that age was positively and significantly associated with opioid‐free status. Each year increase in age was associated with a 6% increase in the relative odds of being opioid‐free (95% CI 1.04–1.08). Results from the adjusted model were similar (adjusted OR = 1.07, 95% CI 1.04–1.09, n = 332 women).

3.4. Age and opioid dose

Among opioid users, the mean opioid dose was 26.6 ± 23.3 mg MEDD in the first 24 hours after surgery. A scatterplot of opioid dose by patient age is depicted in Figure 1. The crude model indicated that age was inversely and significantly associated with opioid dose. Each year increase in age was associated with a −0.65 mg MEDD mean reduction in postoperative opioid dose (95% CI −0.87 to −0.42). Results from the adjusted model were similar (adjusted MD = −0.71, 95% CI −0.99 to −0.44, n = 204 women) and were robust to sensitivity analysis with removal of large opioid dose outliers exceeding 100 mg MEDD (adjusted MD = 0.62, 95% CI −0.84 to −0.39, n = 200 women).

FIGURE 1.

Scatterplot and unadjusted linear association between patient age and opioid dose. Dots represent individual participant data. Line demonstrates the line of best fit for the relation between opioid dose used and participant age.

4. DISCUSSION

In this prospective cohort study of women undergoing their first multi‐compartment POP procedure, younger women were less likely to be opioid‐free and used a significantly larger dose of opioids during the first 24 hours after surgery. We also found that age was inversely and linearly associated with postoperative opioid use during this period after controlling for confounding from patient and surgical factors. Findings from this work emphasize the importance of considering patient age when designing pain management strategies following reconstructive surgery for POP.

Prior studies have suggested an association between younger age and increased pain or opioid following pelvic reconstructive surgery, specifically in a POP population. ¹² , ¹³ , ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ Notably, many of these studies dichotomized age at different and arbitrary cut‐points, resulting in a loss of statistical efficiency and inability to characterize opioid use fully across the spectrum of patient ages (such as exploring for the presence of a parabola or plateau effect). ¹² , ¹³ , ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ¹⁹ , ²⁴ For example, Willis‐Gray (2019) analyzed 183 US patients who underwent POP or stress incontinence surgery and reported that women aged 65 and younger were more likely to be given opioids and received higher amounts of opioids while in post‐anesthesia care than were women older than 65 years, after controlling for surgical factors, depression and body mass index. Additionally, potential confounding due to preoperative pain and patient factors, such as mental health, known to be related to patient age and associated with postoperative pain and opioid use, has been incompletely accounted for to date. For example, Shatkin‐Margolis et al. analyzed 364 US patients who underwent vaginal reconstructive surgery for POP and reported a crude inverse association between patient age and pain intensity on postoperative day 1 measured with a visual analogue scale. Willis‐Gray et al. (2020), analyzed 217 460 US patients who underwent POP or stress incontinence surgery recorded in a commercial insurance database and reported that age (in 10‐year bands) was inversely associated with filling a perioperative opioid prescription, defined as 30 days before to 7 days after surgery, after controlling only for surgical factors and region. Leach et al. analyzed 1830 US patients who underwent POP surgery and reported a crude inverse trend between patient age and pain and opioid dose at discharge as well as opioid refills up to 30 days post‐discharge.

Our study adds to the literature by investigating age as a continuous variable in relation to postoperative opioid use in the first 24 hours, exploring for non‐linear effects and controlling for a fulsome set of patient factors including mental health symptoms, preexisting pelvic pain, body mass index and smoking. Our findings aligned with previous studies indicating greater opioid use in younger POP patients, but further demonstrated that each additional year in patient age confers increasingly higher odds of being opioid‐free and a lower overall opioid dose in the first 24 hours following surgery. Importantly, our findings show that this inverse association between patient and postoperative opioid use persists in a sample with broad age representation (26–82 years) and in a care setting with contemporary ERAS practices.

There are several possible explanations and hypotheses for this association. Neurologically, older individuals tend to have increased pain thresholds and reduced pain sensitivity, ³⁰ which may result in a lower need for opioids. González‐Róldan and colleagues sought to explain this theory through neurologic changes in the aging brain; older adults have an irregular hyperconnectivity in the primary and secondary somatosensory cortices along with the dorsolateral prefrontal cortices and anterior cingulate cortex, which are various brain regions related to pain sensation. ³¹ Physiologically, aging results in slower metabolism and consequently a lower dose of medication is needed to attain the desired effects. ³² Pharmacologic studies have shown that older patients tend to have a longer elimination half‐life and slower plasma clearance of opioids ³³ and required an estimated 50% lower opioid dose due to increased brain sensitivity. ³⁴ Patients’ medical complexity is also important to consider. Older adults are more likely to experience polypharmacy and comorbidities and consequently an increased risk of adverse events following opioid use, ³⁵ which may make physicians more hesitant to prescribe opioids to older individuals or make older patients more hesitant to accept them. Moreover, older adults may remain stoic or minimize their pain due to societal perceptions, self‐doubt and reluctance to label the sensation as pain. ³⁶ , ³⁷ They also tend to have their pain under‐recognized and untreated compared with younger adults, potentially due to ageist beliefs and treatment from healthcare professionals. ³⁸ , ³⁹ It is possible that intersections between these biological and psychosocial factors in aging play a role in the associations we observed.

Our study is not without limitations. We lacked data on postoperative pain scores in the first 24 hours following surgery, which precluded accounting for underlying pain in our analysis. The HUPPS Study is set in a tertiary center with a high volume of gynecologic surgeries and an associated ERAS program, and thus our findings may be less applicable to centers that are smaller, have a lower volume of gynecologic surgeries or lack standardized postoperative pain policies. Owing to a very low prevalence of preoperative opioid use (only three patients reporting intermittent acetaminophen and codeine combination products used on an infrequent, as‐needed basis), preoperative opioid use was not included as a covariate. As such, our findings may not apply to people undergoing POP surgery who use opioids regularly as part of their medical care. Additionally, these findings cannot be generalized to patients who have previously undergone surgery for prolapse, as this was not included in our analysis.

Our findings have important clinical implications. In the field of Urogynecology, the patient population tends to be older and previous studies have found that physicians tend to prescribe more narcotics than patients either require or use. ⁴⁰ Physicians offering POP surgery should tailor patient counseling about pain expectations and co‐design a pain management plan according to the patient's age. This tailored approach can help to normalize intense pain experiences for younger patients and realign expectations that may have been informed heuristically based on information from older family or friends. ⁴¹ Such an approach can also stimulate proactive discussion about non‐narcotic strategies for managing pain after surgery, to limit the use and downstream risks of opioid use in younger patients and appropriately allocate finite resources, such as ancillary pain services, towards higher‐risk younger patients. Examples of strategies include psychological interventions focused on relaxation, psychoeducation and behavioral modification therapy, as well as the use of mindfulness through meditation and music therapy. ⁴² Additionally, future research to‐ build on our results should explore longer‐term opioid use outcomes, such as prescription filling in the community after discharge, to determine whether this inverse age association persists or changes over time.

5. CONCLUSION

This cohort study demonstrated that patient age was linearly and inversely associated with postoperative opioid use following the first multi‐compartment POP surgery. Younger women were less likely to be opioid‐free and used a higher overall opioid dose compared with older women within the first 24 hours following surgery. Findings underscore the importance of preoperative counseling and expectation setting tailored to patient age, and indicate th‐at younger POP patients may benefit from additional strategies and supports aimed at reducing immediate postoperative opioid use. Nevertheless, all patients could benefit from additional pain management support.

AUTHOR CONTRIBUTIONS

EAB and NVS conceptualized the HUPPS Study, secured study funding, and oversaw study operations. SC and EAB designed and conducted data analysis for this paper. SC, NVS, EAB interpreted the data and co‐wrote and wrote the draft. All authors approved the final version of the article.

ACKNOWLEDGMENTS

The authors would like to acknowledge the roles of Dr. Allison Edwards, Dr. Alison Carter Ramirez, Dr. Jena Hall and Dr. Shunaha Kim‐Fine for their contributions to participant enrollment and data collection.

FUNDING INFORMATION

This work is supported by a grant from the MSI Foundation, as well as an Early Career Investigator Grant in Maternal, Reproductive, Child & Youth Health (#442148) and Operating Grant: Women's Health Clinical Mentorship (#433250) from the Canadian Institutes of Health Research. NVS is supported by a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research.

CONFLICT OF INTEREST STATEMENT

The authors have stated explicitly that there are no conflicts of interest in connection with this article.

Cummings S, Scime NV, Brennand EA. Age and postoperative opioid use in women undergoing pelvic organ prolapse surgery. Acta Obstet Gynecol Scand. 2023;102:1371‐1377. doi: 10.1111/aogs.14638