Influence of Frailty Status on the Efficacy of Epidural Steroid Injections in Elderly Patients With Degenerative Lumbar Spinal Disease

Background: The global increase in the elderly population has led to a higher prevalence of degenerative lumbar spinal diseases. Epidural steroid injection (ESI) is a widely used procedure for managing lower back pain. This study investigated the association of preprocedural frailty status with the efficacy of ESI in elderly patients diagnosed with degenerative lumbar spinal diseases. Methods: This retrospective observational study included patients aged 65 years and older who underwent lumbar ESI. Frailty status (robust, prefrail, and frail) assessed via the Frailty Phenotype Questionnaire was collected along with demographic and clinical parameters. Good analgesia was defined as a ≥ 50% reduction in pain score at 4-week follow-up evaluation. Multivariable logistic regression analyses were performed to identify factors associated with poor analgesia. Results: We included 289 patients in this study. Frailty status correlated with analgesic outcomes, with worsening frailty status correlating with increasingly poor analgesia after the injection (robust = 34.5%, prefrail = 40.8%, and frail = 60.0%, p=0.003), predominantly in female patients. After adjusting for demographic and clinical factors, frail patients demonstrated much higher odds of poor analgesia than robust individuals (adjusted odds ratio [aOR] = 2.673, 95% confidence interval [CI] = 1.338–5.342, p=0.005). Conversely, prefrail patients did not show a significant association with analgesic outcome (aOR = 1.293, 95% CI = 0.736–2.272, p=0.372). Conclusions: Frailty, but not prefrailty, appeared to be an independent factor associated with poor analgesic efficacy of ESI in elderly patients with symptomatic degenerative lumbar spinal disease receiving conservative care.


Introduction
Te global elderly population is experiencing rapid growth, driven by socioeconomic progress and signifcant medical advancements [1].Tis demographic shift contributes to an increased prevalence of chronic low back pain [2], with degenerative lumbar spinal diseases constituting a signifcant portion of radiographic pathologies in this population [3].Among the numerous treatment options for relieving pain in older individuals experiencing chronic low back pain, epidural steroid injection (ESI) is one of the most frequently performed procedures [4,5].Several prognostic factors have been proposed to predict pain relief following ESI, including the grade of nerve root compression by magnetic resonance imaging (MRI), interferon-gamma levels from epidural lavage fuid, and epidural contrast dispersal patterns during the procedure [6,7].Additionally, a prior investigation [8] revealed that reduced handgrip strength (HGS), a key diagnostic factor for sarcopenia [9], was independently associated with poor analgesic efcacy of ESI in elderly patients with low back pain.
Frailty is characterized by a deterioration in functioning across various physiological systems, coupled with a heightened susceptibility to stressors [10,11].Frailty is a signifcant risk factor for mortality in elderly people and is associated with a diverse array of outcomes, including falls, disability, worsening mobility, fractures, depression, cognitive decline, and hospitalization [11].Additionally, across diferent spinal surgery populations, frailty has been reported as a predictor of adverse events, mortality within various timespans, hospital length of stay, and discharge disposition [12,13].However, no previous study has explored the relationship between frailty status and the analgesic efects of ESI in elderly individuals with degenerative lumbar spinal disease.
Terefore, our objective in this study was to assess the association between preprocedural frailty status and the analgesic efcacy of ESI in elderly patients with degenerative lumbar spinal disease.Additionally, we aimed to determine whether frailty status would be independently associated with the analgesic efcacy of ESI in this population.

Study Population.
Tis study was approved by the Institutional Review Board of Yonsei University Health System in Seoul, Republic of Korea (no.4-2023-1346).Given the retrospective observational design of this study, the requirement for obtaining informed consent from patients was waived.Te study's fowchart is depicted in Figure 1.Among patients aged 65 years and older who visited our pain clinic between March 2022 and February 2023, we included those who presented with degenerative lumbar spinal disease and received a lumbar ESI.Patients who did not undergo an MRI examination and those who did not receive ESI or underwent procedures other than ESI were excluded.Additionally, patients with no follow-up or incomplete electronic medical records and patients with artifcial shadows on their MRI images due to surgical instruments were also excluded from this study.

Screening for Frailty.
As a frailty screen, the Frailty Phenotype Questionnaire [14] was administered during the initial outpatient clinic visit.Tis questionnaire consists of fve components: fatigue, resistance, ambulation, inactivity, and weight loss.According to the Fried frailty phenotype criteria, participants scoring "0" on the Frailty Phenotype Questionnaire were categorized as robust, those with a score of 1 or 2 were designated as prefrail, and individuals with a score of 3 or more were identifed as frail.
2.3.Fluoroscopy-Guided Lumbar ESI.All procedures were conducted by two practitioners with similar clinical experience.Patients were positioned in the prone posture and sterilely draped for the procedure.Local anesthesia with 1% lidocaine was applied to the skin and soft tissue in the targeted needle entry area.For the interlaminar approach, a 20-gauge, 10-cm Tuohy needle was inserted into the target interlaminar space with anteroposterior fuoroscopic guidance.Te loss of resistance technique was employed to navigate the needle tip accurately to the epidural space.Upon achieving loss of resistance, a lateral view was taken to ensure the precise placement of the needle tip.In the transforaminal approach, under an oblique view, a 22-gauge, 10-cm Quincke tip needle was inserted and cautiously advanced just caudad to the inferior margin of the pedicle.With a lateral view, the needle was further progressed into the neural foramen, immediately superior, lateral, and anterior to the exiting nerve root, until it encountered the anterior epidural space [15].In the caudal approach, a 22gauge, 8-cm Quincke tip needle was inserted just below the sacral hiatus at a 45 °angle, reaching the bone.After a slight withdrawal and repositioning parallel to the skin, it was advanced into the sacral canal.Confrmation of the needle's placement in the caudal epidural space was done using a lateral fuoroscopic view.In all injections, to ensure appropriate epidural spread, 1-2 mL of contrast medium was administered during each injection.For the interlaminar approach, 5 mL of 0.5% lidocaine mixed with 5 mg of dexamethasone and 1500 IU of hyaluronidase was injected.For each level of the transforaminal approach, 2 mL of 0.5% lidocaine mixed with 5 mg of dexamethasone and 1500 IU of hyaluronidase was administered.Te caudal approach involved injecting 15 mL of 0.2% lidocaine mixed with 5 mg of dexamethasone and 1500 IU of hyaluronidase.

Patient Demographics and Clinical Data Measurements.
Demographic and clinical data were extracted through a review of electronic medical records.HGS was measured according to the standard protocol during the initial visit [8].Te collected patient characteristics included age, sex, body mass index (BMI), diagnosed comorbidities with current 2 Pain Research and Management medications (hypertension, diabetes mellitus, and cardiovascular disease), history of cancer, psychological disease, osteopenia/osteoporosis, and prior spinal surgery.Painrelated factors included the duration of pain, baseline numeric rating scale, opioid usage for at least 1 month before ESI, and the presence of sleep disturbance.MRI fndings were collected to assess the presence of a herniated disc, graded foraminal stenosis, or central stenosis [16,17], compression fracture, and spondylolisthesis.Te method of epidural injection-interlaminar, transforaminal, or caudal-was identifed in the study population.Additionally, patients progressing to surgery within 1 year after ESI were investigated.For this study, good analgesia was defned as a ≥ 50% decrease in pain score at 4 weeks after the procedure without an increase in analgesic medication [18].Conversely, poor analgesia was defned as a < 50% decrease in pain score at 4 weeks after the procedure.Pain Research and Management the regression model was evaluated using variance infation factors.Multivariable logistic regression analyses using backward elimination with likelihood ratio tests were conducted to identify predictors of poor analgesia following lumbar ESI, resulting in adjusted odds ratios (aORs) and corresponding 95% confdence intervals (CIs).A p value less than 0.05 was considered statistically signifcant.

Results
Troughout the study duration, 469 patients older than 65 years were diagnosed with degenerative lumbar spinal disease and underwent ESI.Among them, 289 patients were included in the study after excluding those who met the exclusion criteria (Figure 1).Table 1 compares patient characteristics and clinical data between individuals who experienced good analgesia and those with poor analgesia after ESI.No signifcant diferences were observed between the groups in terms of age, sex, BMI, and medical comorbidities (hypertension, diabetes mellitus, cardiovascular disease, cancer, psychological disease, osteoporosis/osteopenia, and prior lumbar surgery).Te two groups had similarities in their pain-related data: pain duration, baseline pain score, opioid use history, and sleep disturbance.Te MRI fndings before the procedure revealed no signifcant diferences between the groups.However, the HGS in the good analgesic group was signifcantly higher than the HGS in the poor analgesic group (24.96 ± 10.29 vs. 21.11± 8.53, p � 0.001).Additionally, a notable diference was observed between groups categorized based on frailty status.Te percentage of patients experiencing poor analgesia 4 weeks post-ESI increased signifcantly with worsening frailty status (robust � 34.5%, prefrail � 40.8%, and frail � 60.0%, p � 0.003) (Figure 2).
Table 2 compares the frailty status of patients between the good and poor analgesia groups according to sex.Among male patients, the deterioration of frailty status had some correlation with an increase in the number of individuals experiencing poor analgesia following ESI; however, no signifcant diference was observed among the three groups (robust � 35.1%, prefrail � 42.2%, and frail � 57.7%, p � 0.083).In contrast, among female patients, the number of individuals with poor analgesic efects rose substantially as frailty status worsened (robust � 34.0%, prefrail � 40.2%, and frail � 61.8%, p � 0.016).

Discussion
In this study, we aimed to determine whether frailty status would be associated with the analgesic efcacy following ESI in elderly patients with chronic low back pain with or without lumbar radicular pain.Our fndings showed that a signifcant number of frail patients experienced poor analgesia after ESI.Terefore, preprocedural frailty status is an important factor for predicting the analgesic efcacy of ESI in this population.
As the most efective indicator of age-related muscle changes, reduced muscle strength is a crucial factor for diagnosing sarcopenia and is linked to physical disability in completing instrumental activities of daily living and functional limitations [19].Even though the relationship between sarcopenia and frailty has not been fully characterized, these conditions are recognized to share many similar clinical outcomes and a proposed pathophysiology [20].Moreover, the defning criteria of the frailty phenotype and sarcopenia have signifcant overlap [9,21].Tus, sarcopenia is integral to the manifestation of physical frailty, and the coexistence of physical frailty and sarcopenia is evident [10].In a previous study [8], we demonstrated the association between HGS as a measure of sarcopenia and the analgesic efect of ESI.Similarly, the present study found comparable results regarding the association between frailty status, which might be considered a manifestation of sarcopenia, and the analgesic efect of ESI.Tese consistent fndings imply that HGS and frailty status are closely related and that both might serve as important predictive factors for the analgesic efect of ESI.
In previous studies [22][23][24][25], frailty was closely linked to chronic low back pain and unfavorable outcomes related to spinal surgery, such as postoperative pain and complications.Similarly, our study revealed that frail patients are associated with experiencing poorer analgesic outcomes following spine-related procedures compared with their robust elderly counterparts, with the odds almost three times higher.Tus, our fndings underscore the signifcance of considering frailty as a crucial variable in predicting pain outcomes in elderly patients with degenerative spinal disease.
What makes this study intriguing is the observed sex diference in the association between analgesic efcacy after ESI and frailty.Tere is insufcient information about sex diferences in the relationship between frailty and responses to pain interventions.Frailty and its progression result from a combination of multidomain infuences, including biological, social, and behavioral factors [26].A study that used large population data to examine community-dwelling older adults found a higher prevalence of frailty in women than in men [27].Additionally, an earlier report suggested that the infuence of paraspinal fat infltration on the analgesic efectiveness of ESI might be particularly pronounced in elderly female patients [28].Skeletal muscle undergoes age-related changes that involve alterations in its architecture and macronutrient metabolism [29].Notably, the Pain Research and Management decline in resting energy expenditure occurs more rapidly in both skeletal muscle and overall adipose tissue in females than in males [30].Tis diference might contribute, in part, to the higher susceptibility of females to frailty compared with males.Tis sex-specifc variation adds a nuanced layer to the fndings, emphasizing the importance of considering both frailty and sex when evaluating analgesic outcomes.
Recent research has demonstrated that frailty is a dynamic process [31].Across various studies, it was consistently observed that both deterioration and improvement in frailty were prevalent.During a 4.5-year investigation involving 754 community residents aged 70 years and older in the United States, 58% of participants underwent at least one transition related to frailty [32].In a longitudinal study conducted in Ireland, individuals categorized as prefrail exhibited a 32% probability of reversing to a robust state.Additionally, those classifed as frail had an 18% probability of reverting to a prefrail condition [33].Tose fndings have implications for clinical practice.Tey underscore the signifcance of early frailty identifcation and emphasize the need for timely interventions.Furthermore, incorporating  Pain Research and Management regular frailty assessments into routine clinical care for elderly adults is crucial for monitoring frailty changes.Recognizing when an individual reaches a specifc frailty level is essential to trigger evidence-based clinical actions that address their unique needs [11,26,31].In this study, frailty emerged as a reliable factor for predicting ESI outcomes compared with robust elderly individuals, whereas prefrailty did not exhibit the same predictive capacity.Tus, this result implies that the detection, management, and prevention of frailty could positively infuence the efcacy of ESI in this population.
Our study is subject to several limitations.First, its crosssectional nature prevents the establishment of a causal relationship between the efcacy of ESI and frailty.Additionally, as a retrospective study, the presence of selection bias and information bias cannot be ruled out.Moreover, the study's scope is confned to elderly Korean participants recruited from healthcare settings, potentially limiting the generalizability of the fndings to a broader elderly population.Te study's reliance on a real-world clinical practice model, in which physicians determine the timing for ESI or analgesic use, adds an element of variability that could afect the study's conclusions.In addition, even if the pain reduction is less than 50%, it can be considered good analgesia if the use of painkillers has decreased.However, this was not known since the use of painkillers other than opioids was not investigated in this study.Te uniqueness of spinal disease introduces another layer of complexity because the disease itself might signifcantly infuence frailty measures.Symptoms such as difculty ascending stairs, walking challenges, and inactivity, all characteristic of lumbar spinal stenosis, contribute to the diagnosis of frailty [13].ESI might itself serve as an efective intervention for phenotypic frailty by potentially reversing those symptoms.Although currently in the realm of theory, exploring postprocedural clinical data, including changes in frailty, is a concept that merits deeper investigation.

Conclusions
In summary, our study has demonstrated that frailty, but not prefrailty, was signifcantly associated with poor analgesia after ESI in elderly patients with degenerative lumbar spinal disease.Tis fnding underscores the importance of screening for frailty status as one way to predict the analgesic efcacy of ESI and indicates the need for an interventional study to determine whether reverting to a prefrail condition can improve the analgesic efcacy of ESI in frail patients.

Figure 2 :
Figure 2: Te distribution of patients with good (■) and poor (□) analgesia 4 weeks after epidural steroid injection categorized by frailty status.

Table 1 :
Patient characteristics and clinical data of individuals who experienced good analgesia and those who had poor analgesia after an ESI.

Table 2 :
Frailty status in patients with good and poor analgesia following ESI according to sex.
Abbreviations6Pain Research and Management