Abstract
Although the reported clinical outcomes of total hip arthroplasty (THA) for hip osteoarthritis are satisfactory, not all patients are completely satisfied. Thus, there is interest in predicting postoperative satisfaction before surgery. The influence of comorbidities and preoperative medications on the incidence of complications and duration of hospitalization following THA has become apparent. However, studies about the associations of preoperative medication with clinical outcomes of THA are limited. Therefore, this study aimed to clarify the relationship between preoperative medications and postoperative patient-reported outcomes. This retrospective cross-sectional multicenter study enrolled post-THA patients (79 patients, 90 hips) who were examined from February to March 2019 in eight general hospitals. Outcome measures included patient-reported outcome as Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) score. Preoperative medications were investigated from medical records. Medications were categorized, and analgesics were categorized into non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, pregabalin, duloxetine, neurotropin (an extract from inflammatory rabbit skin inoculated by vaccinia virus), and opioid. To identify the factors associated with JHEQ score, the patients were divided into lower (<55 score) and higher (≥55) JHEQ score groups. Spearman rank correlation coefficient (r) showed significant difference between the total number of preoperative medications and postoperative JHEQ movement subscale (r = −0.37, p < 0.01), mental subscale (r = −0.29, p < 0.01), and JHEQ (r = −0.30, p < 0.01) scores. In the multiple logistic regression analysis, only the total number of preoperative medications was identified as a risk factor for lower JHEQ score (p < 0.01). This study clarified an inverse correlation between the total preoperative medication count and postoperative outcomes and found that larger total count of preoperative medications is a risk factor of poor postoperative patient-reported outcomes of THA.
Keywords: Total hip arthroplasty, Patient-reported outcomes, Comorbidities
1. Introduction
The reported clinical outcomes of total hip arthroplasty (THA) are very satisfactory; however, not all patients are completely satisfied. The main drugs for hip OA remains non-steroidal anti-inflammatory drugs (NSAIDs). Other analgesics are also available, including opioids and non-opioid analgesics.1,2 Although the number of analgesics increases before THA,2 there are few reports about the preoperative medications for hip OA.
In addition, most of the hip OA patients are older and often have several comorbidities. Such patients require different daily medications. Previous studies have shown that comorbidity has a positive correlation with the length of hospital stay3 and that the increasing number of preoperative medications is associated with longer length of hospital stay.4, 5, 6 Furthermore, it is also associated with an increased postoperative complication rate.7
In recent years, patient-reported outcomes have been attracting increasing attention as a decent tool to evaluate clinical outcomes of various operations including THA. Some reports indicated that the postoperative patient-reported outcome of THA is related to the degree of preoperative pain and dysfunction.8 Therefore, we hypothesized that the number of analgesics and other medications used before surgery may be related to the postoperative clinical outcomes.
The Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) is one of the patient-reported outcome evaluation tools for hip joint disease and is reported to have high reliability.9 However, to our knowledge, no study has reported about the associations of preoperative THA medication with JHEQ score. Therefore, this study aimed to clarify the relationship between preoperative medications and postoperative patient-reported outcomes as JHEQ score.
2. Methods
This retrospective cross-sectional multicenter study enrolled post-THA who were examined from February to March 2019 in eight general hospitals. In this study, the inclusion criteria were primary THA for terminal stage hip OA due to primary or developmental dysplasia of the hip. Unilateral hip OA cases where the contralateral hip joint was asymptomatic and bilateral ones where both hips were operated were included. Patients who had undergone surgery on only one side in the context of bilateral hip OA, revision surgery, or THA for a femur neck fracture or had < 1-year follow-up were excluded, leaving 79 patients (90 hips) for analyses (Fig. 1). Operations were performed by an experienced surgeon at each facility, and the surgical approach and implant were decided by the surgeon. No patients had collagen disease, medical histories of surgery for the spine, knee diseases or postoperative deep venous thrombosis, hip dislocation, surgical site infection, and revision hip surgery.
Fig. 1.
Patient selection from our registry.
In addition to patient demographics, preoperative comorbidities and medications were investigated from medical records. Comorbidities were evaluated by Charlson comorbidity index, and medications were categorized as analgesics, antihypertensives, anticoagulants, antiplatelets, diabetes drugs, steroids, antidepressants, and other drugs. Other drugs include dyslipidemia medications, gastrointestinal medications, sleeping drugs, and osteoporosis medications, and none of the patients used antibacterial, antithyroid, antirheumatic, immunosuppressive, antiepileptic, diuretic, cardiovascular agonist, or antiarrhythmic drugs.
Analgesics were categorized as NSAIDs, acetaminophen, pregabalin, duloxetine, neurotropin (an extract from inflammatory rabbit skin inoculated by vaccinia virus), and opioid. We counted the kinds of analgesics and kinds of oral medications used by patients.
Outcome measures included patient-reported outcome as JHEQ score at the last follow-up. The JHEQ is a self-administered questionnaire that consists of pain (28 points), movement (28 points), and mental (28 points) subscales, with higher scores indicating a better outcome. Each item is scored between 0 and 4 points, and the maximum total score is 84 points. Furthermore, JHEQ can evaluate dissatisfaction with the current condition and hip joint pain on each side; pain was assessed as a mark on a visual analog scale (VAS) from 0 (complete satisfaction or no pain at all) to 100 mm (complete dissatisfaction or maximum pain).10,11 Patient demographics and clinical results are shown in Table 1. Among patients, the mean JHEQ score was 54.0. Therefore, to identify the factors associated with JHEQ score, we divided the patients into two groups based on the JHEQ score, i.e., <55 score as “lower JHEQ score group” and ≥55 score as “higher JHEQ score group.”
Table 1.
Demographic characteristics of the patients.
| Demographics | Patients (%) |
|---|---|
| Number/hip | 79/90 |
| Age, years | 67.9 ± 10.7 |
| Sex, male:female, n (%) | 15 (19.0):64 (81.0) |
| Diagnosis, primary OA:DDH (%) | 44 (48.9):46 (51.1) |
| Follow-up time, months | 35.2 ± 23.2 |
| Bilateral operation, n (%) | 17 (21.5) |
| Charlson comorbidity index | 0.1 ± 0.4 |
| 0:1:2:>3 (%) | 66 (83.5):12 (15.2):1 (1.3):0 |
| JHEQ total score | 54.1 ± 17.9 |
| -Pain | 23.0 ± 6.0 |
| -Movement | 12.5 ± 7.1 |
| -Mental | 18.6 ± 8.0 |
| VAS | 22.1 ± 27.4 |
| Number of preoperative analgesics | 1.0 ± 1.0 |
| Total number of preoperative medications | 4.2 ± 2.8 |
Values are expressed as number of patients or mean ± standard deviation with ranges; DDH, developmental dysplasia of the hip; JHEQ, Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire; OA, osteoarthritis; VAS, visual analog scale.
The study protocol was reviewed and approved by the institutional review boards of the participating institutions. The data used to support the findings of this study are available from the corresponding author upon request.
2.1. Statistical analysis
The primary variables were the total number of preoperative medications, including preoperative analgesics and use of medications in each category. All continuous variables were expressed as means ± standard deviations (SD). Student's t-tests and Chi-squared (χ2) tests were used to compare characteristics between the two groups.
Spearman's rank correlation coefficient was used to investigate the correlation of medications, JHEQ score, and VAS score. A multiple logistic regression analysis was used to identify factors associated with postoperative JHEQ score. Results were verified using R version 3.5.1 (R Foundation for Statistical Computing, Vienna, Austria). A p-value less than 0.05 was considered statistically significant.
3. Results
The mean age was 67.9 years (SD 10.7), and majority of the patients (81.0%) were women. The mean follow-up duration was 35.2 months (SD 23.2), and 21.5% of the patients had undergone surgery for bilateral hips. In most of the cases, the Charlson comorbidity index was 0 (83.5%) and no case had an index higher than 3. The mean JHEQ score and VAS score were 54.1 (SD 17.9) and 22.1 (27.4), respectively. The mean number of preoperative analgesics was 1.0 (SD 1.0), and total number of preoperative medications was 4.2 (SD 2.8) (Table 1).
NSAIDs were the most frequently used analgesics (41.1%), followed by acetaminophen (17.8%), opioids (14.4%), and pregabalin (14.4%). Opioids only included tramadol and did not include other opioids. Among patients using analgesics, 30.0% used one kind of analgesic, 18.9% used two kinds, 7.8% used three kinds, and 1.1% used four kinds. In the drug category, antihypertensive drugs were most used (37.7%). However, 42.2% of the cases did not use preoperative medication (Table 2). Table 3 shows the Spearman rank correlation coefficient (r) of the postoperative total JHEQ score, each subscale, and VAS score according to patient age, Charlson comorbidity index, number of preoperative analgesics, and total number of medications. Postoperative JHEQ movement subscale (r = −0.37, p < 0.01), mental subscale (r = −0.29, p < 0.01), and JHEQ (r = −0.30, p < 0.01) scores had a significant negative correlation with the total number of preoperative medications. Table 4 shows the demographics of patients between the two groups. No significant differences were found in age, sex, preoperative diagnosis, Charlson comorbidity index, or number of preoperative analgesics used. However, the total number of preoperative medications was high in the lower JHEQ score group (5.06 vs 3.37, p < 0.01).
Table 2.
Medication usage profile among the patients.
| Medication | Patients (%) |
|---|---|
| NSAIDs | 37 (41.1) |
| Acetaminophen | 16 (17.8) |
| Pregabalin | 13 (14.4) |
| Duloxetine | 3 (3.3) |
| Neurotropin | 6 (6.7) |
| Opioid | 13 (14.4) |
| Number of using analgesics drugs | |
| 0 | 38 (42.2) |
| 1 | 27 (30.0) |
| 2 | 17 (18.9) |
| 3 | 7 (7.8) |
| 4 | 1 (1.1) |
| Antihypertensive drugs | 34 (37.7) |
| Anticoagulant | 5 (5.5) |
| Antiplatelet | 3 (3.3) |
| Diabetes medication | 6 (6.7) |
| Steroid | 1 (1.1) |
| Antidepressant | 1 (1.1) |
| No preoperative medications | 38 (42.2) |
NSAIDs, non-steroidal anti-inflammatory drugs.
Table 3.
Spearman's rank correlation coefficients of the postoperative JHEQ score and VAS score.
| Variables | Number of preoperative analgesics |
Total number of preoperative medications |
||
|---|---|---|---|---|
| r | p value | r | p value | |
| JHEQ total score |
−0.0150 | 0.8884 | −0.3044 | 0.0037∗ |
| -Pain | −0.1147 | 0.2843 | −0.1108 | 0.3010 |
| -Movement | 0.0729 | 0.4970 | −0.3747 | 0.0002∗ |
| -Mental | −0.1035 | 0.3344 | −0.2868 | 0.0064∗ |
| VAS | 0.0709 | 0.5085 | 0.1230 | 0.2505 |
* Indicates significant finding; JHEQ, Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire; r, correlation coefficient; VAS, visual analog scale.
Table 4.
Comparing the demographic characteristics of patients between the two groups.
| Demographics | Lower group (JHEQ<55) (%) | Higher group (JHEQ≧55) (%) | p value |
|---|---|---|---|
| Hip | 45 | 45 | |
| Age, years | 66.7 ± 11.5 | 69.0 ± 9.8 | 0.3030 |
| Sex, male:female (%) | 11 (24.4):34 (75.6) | 7 (15.6):38 (84.4) | 0.2918 |
| Diagnosis, primary OA: DDH (%) | 18 (40.0):27(60.0) | 26 (57.7):19 (42.3) | 0.0916 |
| Follow-up time, months | 37.8 ± 25.3 | 32.6 ± 21.6 | 0.2981 |
| Bilateral operation (%) | 18 (40.0):27 (60.0) | 17 (37.8):28 (62.2) | 0.7241 |
| Charlson comorbidity index | 0.2 ± 0.4 | 0.1 ± 0.3 | 0.2875 |
| 0: 1: 2: >3 (%) | 37 (82.2):7 (15.6): 1 (2.2):0 |
40 (88.9): 5 (11.1):0:0 |
0.4843 |
| JHEQ total score | 38.7 ± 9.3 | 69.8 ± 7.9 | <0.0001* |
| -Pain | 19.6 ± 6.4 | 26.5 ± 2.8 | <0.0001* |
| -Movement | 7.1 ± 3.9 | 18.1 ± 5.1 | <0.0001* |
| -Mental | 12.3 ± 5.8 | 24.95 ± 3.41 | <0.0001* |
| VAS | 36.9 ± 29.9 | 6.9 ± 12.5 | <0.0001* |
| Number of preoperative analgesics | 1.0 ± 1.1 | 0.9 ± 1.0 | 0.6988 |
| Total number of preoperative medications | 5.1 ± 2.9 | 3.4 ± 2.5 | 0.0037* |
Values are expressed as the number of patients or mean ± standard deviation with ranges. * indicates significant finding; DDH, developmental dysplasia of the hip; JHEQ, Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire; OA, osteoarthritis; VAS, visual analog scale.
In the univariate analysis to investigate factors associated with JHEQ, the total number of preoperative medications was identified as a risk factor for lower JHEQ score. On multiple logistic regression analysis, only the total number of preoperative medications was identified as a risk factor for lower JHEQ score (odds ratio: 1.37, p < 0.01) (Table 5).
Table 5.
Univariate and multivariate analyses of factors associated with lower JHEQ score.
| Variables |
Univariate |
Multivariate |
|||||
|---|---|---|---|---|---|---|---|
| OR | 95% CI | p value | OR | 95% CI | p value | ||
| Age | 0.9678 | 0.9232–1.012 | 0.1620 | 0.9668 | 0.9134–1.0213 | 0.2315 | |
| Sex, Female | 1.7187 | 0.5288–5.2055 | 0.3460 | 2.0500 | 0.6053–7.3298 | 0.2535 | |
| Diagnosis- DDH | 2.2569 | 0.9789–5.3311 | 0.0588 | 3.3474 | 0.9715–12.651 | 0.0619 | |
| Bilateral operation | 2.4545 | 0.9227–6.6861 | 0.0731 | 0.4970 | 0.1415–1.6122 | 0.2551 | |
| Charlson comorbidity index | 1.7162 | 0.5203–5.2474 | 0.3440 | 1.2610 | 0.3565–4.8806 | 0.7236 | |
| Number of preoperative analgesics | 1.2643 | 0.8145–1.9520 | 0.2840 | ||||
| Total number of preoperative medications | 1.2450 | 1.0608–1.4894 | 0.0106* | 1.3752 | 1.1247–1.7226 | 0.0031* |
* Indicates significant finding; 95% CI; 95% confidence interval; DDH, developmental dysplasia of the hip; OR, odds ratio.
4. Discussion
In this study, we evaluated the correlation between clinical outcomes of THA and preoperative medications and found an inverse correlation between the total number of preoperative medications and the postoperative patient-reported outcome score. These findings suggest that the number of preoperative medications could be a factor predicting postoperative clinical outcomes following THA.
With regard to the use of preoperative analgesics, NSAIDs were the most commonly used in this study, similar to the report by Rajamäki et al.3 Moreover, relatively few patients are using opioids, duloxetine, and neurotropin, and we considered that they are used in combination with other analgesics. However, 42.2% of the patients did not use any analgesics. The finding that nearly half of the patients who underwent THA because of pain did not use analgesics is another valuable data of this study. Previous studies clarified that preoperative pain is associated with postoperative pain in THA.10,12 Therefore, we hypothesized that the number of preoperative analgesics may be an index of preoperative pain and could correlate with postoperative JHEQ score. However, our study indicated that the number of preoperative analgesics did not correlate with postoperative JHEQ and VAS scores. In general, analgesic use is increased before and decreased after THA.2,11 Moreover, in this study, the postoperative JHEQ pain subscale score was relatively high (mean 23.0) compared with other subscale scores, indicating that THA is an excellent surgery for pain relief. However, the pain management methods and preoperative waiting periods differ by each facility and case, and no association was found between the number of analgesics taken and postoperative JHEQ score. This is one of the limitations of this study.
In our study, JHEQ score was associated with preoperative medications and were found to be a risk factor for lower JHEQ score. Peter et al. reported that a greater number of preoperative comorbidities were associated with worsening postoperative physical function and patient-reported outcome.13 Lungu et al. conducted a systematic review and reported that preoperative function and comorbidities led to severe postoperative poor functional outcomes.12 These findings suggest that the assessment of patient comorbidities before surgery is useful not only for evaluating the perioperative risk but also for predicting postoperative outcomes. However, no established comorbidity assessment tool could predict postoperative patient-reported outcome. Greene et al. found that the standard comorbidity measures based on the International Classification of Diseases, 10th Revision, do not predict patient-reported outcomes in THA.14 Similarly, studies have described that the American Society of Anesthesiologists classification is not useful in evaluating patients at risk for adverse functional outcomes and that the Charnley classification15 cannot clearly identify specific conditions.13 This is consistent with our results of the absence of correlation between Charlson comorbidity index and JHEQ score. As a tool for assessing comorbidity, the total number of medications is very simple to obtain and considered helpful because it is related to the severity and state of comorbidities.6 Furthermore, Dietrich et al. reported that prehospital medications correlated with poor THA outcomes.5 These previous reports suggest that evaluating the amounts of preoperative drugs can be used to predict THA outcome.6 Therefore, our finding that the number of preoperative medications showed a significant inverse correlation with the postoperative patient-reported outcome and identified as a risk factor of lower JHEQ score is also reasonable and remarkable.
Various factors such as diagnosis, OA stage, disease duration, preoperative function, coexistence of other joint diseases, and preoperative condition of patients, influenced the clinical outcomes of THA. The preoperative medication count may be very useful in the quantitative assessment of the preoperative state of patients. We are convinced that the evaluation of preoperative medication is associated with surgical outcomes. To our knowledge, this is the first study that has investigated the relationship between preoperative medications and postoperative patient-reported outcomes of THA.
Nevertheless, this study has some limitations, including a small sample size; lack of detailed patient demographics, assessment of other joint diseases, preoperative functional evaluation, and a control group; and possible selection bias. Furthermore, we did not investigate postoperative medications. Despite these limitations, the results of this study could provide a useful framework for physicians. However, further studies with larger sample size, prospective investigations, or direct comparison with other comorbidity indexes are required to develop better predictive tools.
In conclusion, this study investigated the relationship between the number of preoperative medication and patient-reported outcomes in THA. Our results clarified that an inverse correlation existed between the total preoperative medication count and postoperative outcomes. This study potentially suggests a new factor in the analysis and prediction of postoperative patient outcome. Moreover, it could contribute to further improvement of postoperative THA outcome by modifying the surgical indication according to the preoperative condition of the patients.
Declaration of competing interest
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Acknowledgements
We would like to thank Editage (www.editage.com) for English language editing.
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