The Incidence and Risk Factors of Persistent Opioid Use After Surgery

A retrospective secondary data analysis

Background: The risk of persistent postoperative opioid use (PPOU) and its association with the type of surgery are still unclear in Germany.

Methods: We conducted a nationwide retrospective cohort study on the basis of claims data from BARMER, a statutory health insurance carrier in Germany. Opioid-naive adults who did not have cancer and who underwent inpatient surgery in 2018 were included in the study. The operations were divided into 103 categories. PPOU was defined as the prescribing of opioids between postoperative days 1 and 90 and also between postoperative days 91 and 180 after hospital discharge. Patient-associated risk factors in the 12 months before surgery were investigated.

Results: 203 327 patients were included. 1.4% had PPOU (95% confidence interval [1.4; 1.5]). There were major differences between operation groups: major amputations and orthopedic procedures carried the greatest risk for the development of PPOU. The type of surgery had a larger effect on the risk of PPOU than pre-existing risk factors (explained variance 22.3% vs. 14.3%). Among such factors, alcohol abuse and pre-existing treatment with antidepressant drugs were associated with the highest risk for PPOU (odds ratios [OR] 1.515 [1.277; 1.797] and 2.131 [1.943; 2.336]).

Conclusion: The incidence of PPOU in Germany is low (1.4%). The type of surgery plays an important role in its development.

Opioid misuse in the United States is still a major problem and leads to high rates of overdose-related deaths (24.2/100 000 population per year between 2018 and 2021) (1). Prescription after surgery is often the patient’s first exposure (2, 3) and may trigger medically non-indicated prolonged postoperative opioid use (PPOU) (4). Knowledge of the influence of type of surgery is limited as most studies included only a single type of surgery or single surgical specialty (5, 6, 7). The few studies with a mixed surgical sample focused only on a narrow set of 8–13 pre-selected operations or used a coarse classification by organ system or surgical site (8, 9, 10, 11). Therefore, two recent systematic reviews were not able to draw definitive conclusions on the importance of type of surgery for the development of PPOU (5, 7).

Comparisons of incidence of PPOU across countries are challenging, due to different health care systems and to the wide variation in study methodology, especially regarding the many different definitions of PPOU that have been used (6). The only single-center study on PPOU in Germany found that the rate of opioid use 6 months after surgery was four to seven times higher for joint and back surgery than for urological surgery (12).

Therefore, the aims of our study were (a) to assess the incidence of PPOU in a large, population-based sample in Germany and (b) to investigate differences in the risk for PPOU among a large variety of surgical procedures.

Materials and methods

Study design

We conducted a retrospective cohort study based on German administrative health care claims data. Opioid-naïve, adult patients without cancer who underwent inpatient surgery in 2018 were selected for analysis. The year 2018 was chosen so that a follow-up for up to 12 months was completed before the start of the COVID-19 pandemic, which led to severe restrictions on surgery and aftercare. The influence of both pre-existing patient-related factors and type of surgery on PPOU was assessed descriptively and by regression analysis. The study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of the Jena University Hospital (approval number 2020–1952-Daten) in October 2020. As the claims data were anonymous, informed consent was not required. The description of the study follows the Reporting of studies Conducted using Observational Routinely-collected Data (RECORD) guidelines (13).

Data source

The study is based on anonymized health claims data provided by the statutory medical health insurer BARMER GEK, the second largest German health insurance fund with approximately 9 million members, 10% of the total German population. The data were provided via the BARMER scientific data warehouse and were assessed using controlled remote data processing.

Patient cohort

Adult BARMER insurance holders who received an inpatient surgical procedure (coded according to the German operation and procedure classification system [OPS], chapter 5) in 2018 were included. In the event of multiple hospital stays for surgery, the first stay in 2018 was chosen as the index hospitalization. Opioid naivety was defined as not having received an opioid prescription in the year prior to the index hospitalization. Patients with a cancer diagnosis (ICD-10 code C00-C97) at any time during the period from 12 months before to 12 months after the surgery were excluded, as they might have received opioids primarily due to cancer-related pain. Patients had to be continuously insured with BARMER throughout the observation period (see eMethods for further details).

Variables

Our primary outcome was PPOU, defined as prescriptions of opioids during days 1–90 and days 91–180 after discharge (8). To define type of surgery in the index stay, we adapted a previously reported classification of surgical procedures for use with claims data, which resulted in 103 distinct surgical groups (14). Pre-existing risk factors were defined based on claims data from the 12 months prior to the index stay. Details are presented in the eMethods.

Statistical analysis

The incidence of PPOU was calculated for the complete sample and for each surgical group with 95% Wilson Score confidence interval (CI). Pre-existing risk factors were compared between cases with and without PPOU. To assess the importance of type of surgery in comparison with pre-existing risk factors for the risk of PPOU, we calculated a random intercept-only logistic regression model including surgical group as random intercept and risk factors as fixed effects. The total contribution of patient history risk factors and the total contribution of type of surgery to prediction of PPOU were estimated based on variance components and residual intraclass correlation (ICC) (15). To assess whether adjustment for pre-existing risk factors causes large changes to the ranking of the surgical procedures with regard to risk of PPOU, we calculated the random intercepts per surgical group both from the model including risk factors and from the model not including risk factors and calculated the Pearson correlation between the two (see eMethods). All statistical analyses were performed using the statistical freeware R (16). Tests were conducted on significance level 0.05.

Results

Study cohort

A total of 203 327 opioid-naive patients without cancer were included in at least one of the 103 defined surgery groups (Figure 1). Of these, 193 392‬ were allocated to only one surgical group, while 9935 were allocated to more than one group, which shows that the defined groups were largely distinct from each other. The baseline characteristics of the patients are shown in Table 1. Females were overrepresented in the sample (63.4%), reflecting the demographic structure of BARMER’s policy holders. Cocaine abuse occurred very rarely in the study sample (0.1%) and was therefore not included in the prediction model.

Figure 1

Study flow chart

Table 1

Demographics and pre-existing comorbidity/medication of the study sample

Incidence of prolonged postoperative opioid use

The overall incidence of cases with PPOU was 1.4% (95% CI [1.4; 1.5]). Presence of any single pre-existing risk factor was associated with only modest increases in risk (e.g. from 1.06% without to 3.59% with previous prescription of antidepressants, eTable 4). Figure 2 presents PPOU for the 33 surgery groups with n > 50 cases and risk of PPOU ≥ 1% (results for all surgery groups are presented in eTable 5). In general, we found that orthopedic and trauma surgery and vascular surgery were associated with higher risk of PPOU. The highest incidence was found in patients with major amputation (transfemoral amputation: 21.7% [14.5; 31.2], transtibial amputation: 15.3% [8.8; 25.3]) followed by orthopedic interventions (partial shoulder joint replacement: 8.0% [4.0; 15.7], spine surgery: 6.7% [6.2; 7.2], revision of knee joint replacement: 5.3% [3.8; 7.3]). Toe amputation was associated with a risk of 4.1% [3.1; 5.4]. In a post-hoc analysis, we found that the majority of amputations were due to ischemia (81.7%), while only 1.4% were due to trauma (see eMethods, eResults, eTable 6).

Figure 2

Incidence of PPOU with 95% confidence intervals (CI) by surgical group. Presented are groups with n > 50 cases and incidence of PPOU of at least 1% (see eTable 5 for presentation of all surgical groups).

eTable 4

Risk of PPOU according to presence of risk factors

eTable 6

Subgroups of amputations according to etiology

Influence of type of surgery and pre-existing risk factors on prolonged postsurgical opioid use

Table 2 gives the results of the random-intercept logistic regression model with pre-existing risk factors. Explained variance is a measure of what proportion of the risk of PPOU is predicted by the statistical model. Overall, the model explained 36.65% of the variance of risk of PPOU. Patient history factors explained 14.33%, while the remaining 22.32% was explained by the surgical groups (statistical details given in eTable 7). This indicates that type of surgery might be more important than the considered risk factors for development of PPOU. The ranking of surgical procedures in risk of PPOU was not changed to a relevant extent by controlling for differences in pre-existing risk factors (r = 0.97 between random intercepts from the model not including risk factors and the adjusted random intercepts from the model including risk factors). Prescription of antidepressants, abuse of alcohol, prescription of non-opioid analgesics, and a chronic pain diagnosis were the strongest predictors of PPOU among pre-existing risk factors when controlling for type of surgery and all other risk factors in model (Table 2).

Table 2

Predictors of prolonged postoperative opioid use

eTable 7

Random effects of the random-intercept logistic regression model

Discussion

We conducted a retrospective cohort study using German administrative claims data to investigate the incidence of PPOU across a wide range of surgical procedures. In a sample of opioid-naive patients without cancer undergoing inpatient surgery, the overall incidence of PPOU was 1.4%. There was wide variation among the surgical groups studied, with the risk of PPOU being more than ten times higher for procedures identified as high-risk. Special attention should be paid to amputations and spine surgery. The importance of the type of surgery is underlined by the finding that it explained 22.3% of the variance in PPOU, while only 14.3% was explained by pre-existing risk factors.

Only a small number of studies on PPOU have been conducted outside the USA and Canada (7, 17), and only one single-center study has been performed in Germany (12). Due to large differences in the operations included, samples, and definitions of PPOU, two recent meta-analyses reached no definitive conclusions regarding country-specific risks (7, 17). Compared with a risk of 1.4% in our sample, population-based mixed-procedure studies from Canada and the USA found substantially higher incidence of PPOU, between 3.5% and 6.5%, using definitions similar to that in our study (6, 8, 10). Therefore, our study provides some evidence that PPOU in general is less of a problem in Germany.

Previous studies investigated only individual surgical procedures or small sets of preselected interventions using very diverse samples and methods, which biases meta-analytic comparisons across studies. In their meta-analysis of 31 studies, Lawal et al. (7) found no difference between major and minor operations but also reported difficulty in making comparisons due to the methodological heterogeneity of the studies. Likewise, in their systematic review Kent et al. (5) were unable to identify any specific surgeries with an increased risk of PPOU and assumed that surgical characteristics may play only a minor role in assessment of risk. In contrast, based on more than 100 major and minor surgery groups, we found that 22.3% of the variance in the risk of PPOU was explained by the type of surgery. Although we included the significant risk factors identified in previous research (7, 18, 19, 20, 22, 23), these explained only the smaller part of the risk variation (14.3%). Therefore, type of surgery plays a major role in risk assessment for PPOU. We found that especially orthopedic and trauma surgery, vascular surgery, and minor and major amputation are associated with increased risk of PPOU. Regarding the association of individual pre-existing risk factors with PPOU, we replicated previous findings from international studies showing an increased risk for female sex, antidepressants, pain medication, chronic pain, alcohol or drug abuse, other psychological comorbidity, and total comorbidity (7, 18, 19, 20, 21, 22) (see eDiscussion for further details).

This study presents comprehensive data on the incidence of PPOU in Germany. One of its strengths is that it is based on a large national sample that is fairly representative of the adult population of Germany, although women are slightly overrepresented (24). It is also the first study worldwide to investigate the risk for PPOU across a broad spectrum of more than 100 surgical procedures. The analysis using a random-intercept logistic regression model allowed the effects of type of surgery on the development of PPOU to be distinguished from the effects of patient history.

However, the study also has some limitations. BARMER patients differ from the German population in that a slightly higher proportion are female and they are slightly younger (24). While this plays a minor role when comparing individual operations, it may bias the estimate of overall risk for PPOU. Claims data contain limited clinically relevant information. Opioid use could be assessed only on the basis of prescriptions, not actual consumption – a limitation shared by other international claims-based studies on PPOU (8, 9, 10, 11). Claims data are designed for purposes of billing and health care administration; they do not fully reflect clinical reality and may be affected by information biases, particularly regarding ICD coding (25, 26, 27). Based on incorrect assignment of ICD codes, estimates of effects of some pre-existing risk factors may be biased. On the other hand, as both surgery coding and opioid prescribing are relevant for reimbursement, we consider both to be highly trustworthy. A major limitation shared with all previous studies is the lack of a common definition of PPOU, which makes it difficult to compare incidence across studies (5, 6). Therefore, we chose the definition that yielded the best international comparability (6, 7, 8, 10), although this does not allow differentiation between indicated PPOU and misuse. However, this will not affect the relative differences in PPOU between the surgical interventions.

Conclusions

At 1.4%, the overall incidence of PPOU in Germany seems to be relatively low compared with North America, although direct comparison is difficult because of differences in studied populations and definitions of PPOU. On the other hand, PPOU may pose a relevant problem for a subgroup of these patients, as well as for the German health care system. Especially patients undergoing any of the identified high-risk interventions may deserve more attention to avoidance of the side effects of long-term opioid use or misuse. All clinicians should be aware that initially indicated opioid use may later develop into non-indicated use. Patients with a surgery which has a high risk of PPOU, or with at least one of the identified risk factors should be closely monitored for pain and appropriate postoperative analgesic management, e.g., through post-discharge screening programs, pain specialists, and transitional pain services (28). The national and international guidelines offer helpful practical tools, with numerous recommendations for postoperative pain therapy and long-term opioid treatment (29, 30). Further research is needed to characterize the transition from perioperative to long-term opioid use and to explain the differences in the incidence of PPOU among health systems worldwide.

Funding

The LOPSTER project on which this publication is based was funded by the Innovation Committee of the German Federal Joint Committee (G-BA), Berlin, Germany under grant number 01VSF19019.

Conflict of interest statement

WM has received research grants for his institution from the European Commission, Gemeinsamer Bundesausschuss (G-BA), Medtronic, Pfizer, Mundipharma, Grünenthal, Vertanical and personal honoraria from Merck, Sanofi, MSD, Tafalgie, Kyowa, Mundipharma, Grünenthal and Ethypharm. T.V. reports research grants from Sedana medical, Ratiopharm, Saarland, Pfizer, Infecto Pharm, and Cyto Sorbents Europe GmbH (all paid to the institution) and personal lecture fees from Pajunk and CSL Behring. TV is past president of The European Society of Regional Anaesthesia & Pain Therapy. HLR receives research funding from the DFG, the BMBF and the G-BA. She was honored for lectures by Grünenthal and received consulting fees from Orion.

The remaining authors declare that no conflict of interest exists.

Received on 2 May 2024, revised version accepted on 25 September 2024

Corresponding author

PD Dr. phil./med. habil. Daniel Schwarzkopf

Klinik für Anästhesiologie und Intensivmedizin

Friedrich-Schiller-Universität Jena

Universitätsklinikum Jena

Am Klinikum 1

07747 Jena, Germany

Cite this as
Dreiling J, Rose N, Arnold C, Baumbach P, Fleischmann-Struzek C, Kubulus C, Komann M, Marschall U, Rittner HL, Volk T, Meißner W, Schwarzkopf D: The incidence and risk factors of persistent opioid use after surgery—a retrospective secondary data analysis. Dtsch Arztebl Int 2024; 121: 757–63. DOI: 10.3238/arztebl.m2024.0200

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