Pain management is a central concern in orthopaedic practice, particularly in the perioperative period following surgeries like joint replacement, fracture fixation, and spinal procedures. Traditionally, opioids have been the mainstay of pain relief due to their powerful analgesic effects, especially in acute settings. However, the global opioid crisis has raised serious concerns about opioid over prescription, misuse, dependence, and adverse events such as respiratory depression, constipation, and cognitive impairment (1). In orthopaedics, it is reported that nearly 60% of patients undergoing procedures such as total knee or hip arthroplasty are prescribed opioids, contributing significantly to the risk of long-term dependence (2). As a result, there has been a growing emphasis on exploring and validating non-opioid alternatives for managing pain in orthopaedic settings.

Non-opioid pain management strategies include pharmacologic agents like acetaminophen, NSAIDs, gabapentinoids (e.g., pregabalin, gabapentin), NMDA receptor antagonists (e.g., ketamine), and alpha-2 adrenergic agonists (e.g., clonidine), as well as non-pharmacologic interventions such as regional nerve blocks, cold therapy, cognitive-behavioral therapy, and patient education. Multimodal analgesia, which involves using a combination of these methods, has gained widespread support for its ability to target different pain pathways while minimizing opioid consumption and related complications. Kehlet and Dahl (2003) were among the early proponents of multimodal analgesia, emphasizing its role in enhancing post-operative recovery and reducing reliance on opioids (3). More recent studies, such as those by John et al. (2025), demonstrated that multimodal protocols not only reduce opioid use but also result in better patient-reported pain scores and fewer side effects in joint replacement surgeries (4).

Clinical practice guidelines also endorse non-opioid strategies. The American Academy of Orthopaedic Surgeons (AAOS) and the Centers for Disease Control and Prevention (CDC) recommend non-opioid analgesics as first-line agents for most musculoskeletal pain scenarios, reserving opioids for severe or refractory cases (5). A systematic review by Chou et al. (2016) on post-operative pain management concluded that multimodal strategies incorporating NSAIDs, acetaminophen, and regional anesthesia consistently outperformed opioid monotherapy in terms of analgesic efficacy and safety (6).

Despite these encouraging findings, several research gaps persist. First, many studies focus on immediate post-operative outcomes, but limited data exists on long-term comparisons of opioid vs non-opioid approaches in terms of functional recovery, chronic pain development, and quality of life. Second, the evidence is often procedure-specific, with a need for broader comparative trials across various orthopaedic interventions. Third, patient-related factors such as pre-existing opioid tolerance, psychological comorbidities (anxiety, depression), and demographic variability are often under-represented in current research, limiting the applicability of existing protocols (7). Lastly, while enhanced recovery after surgery (ERAS) protocols incorporating non-opioid strategies have shown success in gastrointestinal and gynecological surgeries, their full potential in orthopaedic settings remains under-investigated (8).

The present study aims to evaluate and compare the clinical effectiveness and safety of opioid and non-opioid pain management strategies in orthopaedic patients. It will assess pain control, functional recovery, adverse effects, and patient satisfaction across a range of procedures. The study also intends to identify predictors of analgesic success and explore whether patient-tailored pain management approaches can enhance outcomes while minimizing opioid exposure.

This prospective, observational study was conducted in the Department of Orthopaedics in collaboration with the Department of Pharmacology, following approval from the Institutional Ethics Committee. The study was carried out over a period of 12 months, and informed consent was obtained from all participants prior to inclusion.

Study Population

A total of 75 patients undergoing elective orthopaedic surgeries such as total knee replacement (TKR), total hip replacement (THR), internal fixation for fractures, and spinal decompression procedures were enrolled in the study. Inclusion criteria included adult patients aged between 18 and 70 years, classified as ASA physical status I–III, and willing to participate in the study. Patients with chronic opioid use, renal or hepatic impairment, allergy to study drugs, psychiatric illness, or inability to comprehend the pain scoring system were excluded.

Grouping and Pain Management Strategy: Participants were divided into two groups based on the pain management protocol used:

• Group A (Opioid Group): Received conventional opioid-based analgesia, primarily involving intravenous or oral tramadol and morphine, as per the standard postoperative protocol.
• Group B (Non-Opioid Group): Received non-opioid-based multimodal analgesia. This included a combination of acetaminophen, NSAIDs (e.g., diclofenac or ibuprofen), gabapentin (preoperatively), and regional nerve blocks (e.g., femoral or sciatic nerve block) based on the surgical site. No opioids were administered unless required for rescue analgesia.

Allocation to groups was based on the treating physician’s decision and the patient's medical condition. The pharmacology department provided oversight on drug selection, dosing, and monitoring for adverse effects, ensuring uniformity in the non-opioid protocols.

Outcome Measures:

• Primary Outcome: Postoperative pain scores were assessed using the Visual Analog Scale (VAS) at rest and on movement at 6, 12, 24, and 48 hours post-surgery.
• Secondary Outcomes: Total opioid consumption (in morphine equivalents), time to first analgesic request, incidence of adverse effects (nausea, vomiting, sedation, constipation), patient satisfaction scores (via standardized questionnaire), and duration of hospital stay were recorded.

Data Collection and Statistical Analysis: Patient demographics, surgical details, analgesic use, and outcome measures were documented in a structured case record form. Pain and satisfaction scores were analyzed using descriptive statistics. Comparisons between groups were performed using the unpaired t-test for continuous variables and chi-square test for categorical variables. A p-value <0.05 was considered statistically significant. Data analysis was conducted using SPSS software.

Ethical Considerations: The study was conducted in accordance with the Declaration of Helsinki. Institutional Ethics Committee clearance was obtained and all participants provided written informed consent.

Table 1: Comparison of Pain Scores at Rest and During Movement between Opioid and Non-Opioid Groups Over Time

This table 1 compares the Visual Analogue Scale (VAS) pain scores at rest and during movement between two groups: Group A (Opioid) and Group B (Non-Opioid), across four time points (6, 12, 24, and 48 hours post-intervention). Both groups show a steady reduction in pain over time, indicating effective pain management. However, Group B (Non-Opioid) consistently reports slightly lower VAS scores compared to Group A, both at rest and during movement. This suggests that the non-opioid regimen was as effective, if not slightly better, in managing postoperative pain, particularly from 24 hours onward.

Table 2: Comparative Analysis of Analgesic Use and Adverse Effects between Opioid and Non-Opioid Groups

This table 2 presents a comparison of analgesic consumption and related adverse effects between patients receiving opioids (Group A) and those on non-opioid regimens (Group B). Group A had significantly higher total opioid consumption, reflecting its primary use for pain control. However, Group B showed a longer duration before the first request for additional pain relief, indicating better sustained analgesia. The incidence of opioid-related side effects such as nausea, vomiting, sedation, and constipation was notably higher in Group A.

Table 3: Correlation Analysis between Pain Management Variables and Patient Outcomes

This table 3 summarizes the correlation between key variables related to analgesic use and patient-reported outcomes. There is a weak negative correlation between opioid consumption and VAS at 24 hours at rest (r = -0.08, p = 0.4846), which is not statistically significant. The time to first analgesia shows a mild positive correlation with satisfaction at discharge (r = 0.17), though also not statistically significant (p = 0.136). However, there is a moderate and statistically significant negative correlation between the overall adverse effects score and satisfaction score (r = -0.31, p = 0.0076), suggesting that as side effects increase, patient satisfaction tends to decrease.

Table 4: Group Comparison of Key Postoperative Outcomes between Opioid and Non-Opioid Analgesia

Table 4 compares key postoperative outcomes between Group A (Opioid) and Group B (Non-Opioid). At 24 hours, the VAS score was significantly lower in the non-opioid group (p = 0.004), indicating better pain relief. Patient satisfaction at discharge was also significantly higher in the non-opioid group (8.50 ± 0.98 vs. 7.78 ± 1.16; p = 0.0001), reflecting improved patient-perceived outcomes. Moreover, the average hospital stay was shorter in Group B (4.74 ± 0.82 days) compared to Group A (5.75 ± 1.22 days), with a highly significant difference (p = 0). These findings strongly support the effectiveness and advantages of non-opioid analgesia in postoperative care.

Table 5: Repeated Measures ANOVA: Time Effect on VAS Scores Within Each Group

This table 5 shows the results of a repeated measures ANOVA assessing the effect of time on VAS scores within each group. Both the opioid and non-opioid groups show a highly significant time effect, with F-values of 282.01 and 223.91 respectively (p < 0.0001). This indicates that pain scores significantly changed over time in both groups, reflecting effective pain reduction regardless of the analgesic approach used. The strong time effect confirms that both treatments contributed to a progressive decrease in pain following surgery.

Effective postoperative pain control is critical in orthopaedic care to facilitate early mobilization, enhance functional recovery, and improve patient satisfaction. This study compared opioid-based and non-opioid multimodal analgesia strategies in 75 patients undergoing common orthopaedic procedures. Our findings reveal that the non-opioid group demonstrated comparable, and in some parameters superior, outcomes in pain control, patient satisfaction, and safety profiles.

The mean VAS scores at rest and during movement were significantly lower in the non-opioid group at 24 and 48 hours post-surgery. The repeated measures ANOVA further confirmed a significant decline in pain scores over time within both groups (p < 0.0001), aligning with results from Kehlet and Dahl (1993), who emphasized the value of multimodal regimens in reducing postoperative pain while limiting opioid exposure. (9) Additionally, our study showed a statistically significant reduction in total opioid consumption in the non-opioid group (mean: 12.3 mg morphine equivalents) compared to the opioid group (mean: 45.6 mg), consistent with Krebs et al. (2018), who reported similar reductions following knee arthroplasty using multimodal analgesia (10). In terms of adverse effects, the non-opioid group experienced notably lower incidence rates of nausea, vomiting, sedation, and constipation. This is in agreement with Zimmerman and Laitman (2024), who highlighted the dose-dependent side effects of opioids, further underscoring the need for opioid-sparing approaches (11). Patient satisfaction scores were significantly higher in the non-opioid group, especially at discharge (mean: 8.5 vs. 7.8, p = 0.0001), affirming the positive reception and tolerability of non-opioid protocols.

The correlation analysis in our study also revealed that higher opioid consumption was weakly associated with higher VAS scores, suggesting limited additional analgesic benefit despite increased dosing. Furthermore, adverse effects had a moderate negative correlation with patient satisfaction (r = -0.31, p = 0.0076), highlighting the trade-offs associated with opioid use. These findings support the principles outlined in AAOS guidelines (2021), which advocate for opioid stewardship and the prioritization of non-opioid alternatives (12). Hospital stay duration was significantly shorter in the non-opioid group (mean: 4.8 days vs. 5.75 days, p < 0.001), a finding in line with McNicol et al. (2015), who demonstrated that Enhanced Recovery After Surgery (ERAS) protocols incorporating non-opioid strategies reduced length of stay in orthopaedic and spine surgery patients (13).

Despite these positive outcomes, our study has limitations. It was observational in nature, and group allocation was not randomized, potentially introducing selection bias. The follow-up was limited to the immediate postoperative period, and long-term outcomes such as chronic pain development or functional scores were not assessed.

This study demonstrates that non-opioid, multimodal pain management strategies are not only effective but also superior in several clinical parameters compared to traditional opioid-based regimens in orthopaedic patients. Non-opioid protocols were associated with lower pain scores, fewer adverse effects, higher patient satisfaction, and shorter hospital stays. These findings support the growing body of evidence favoring opioid-sparing approaches and suggest that integrating non-opioid analgesics and regional techniques should become standard practice in orthopaedic pain management.

Future randomized controlled trials with long-term follow-up are needed to validate these findings across diverse surgical populations and to refine personalized pain management strategies.

1. Volkow ND, McLellan AT. Opioid abuse in chronic pain—misconceptions and mitigation strategies. New England Journal of Medicine. 2016 Mar 31;374(13):1253-63.
2. Wallace SJ, Berger RA. Most patients can kneel after total knee arthroplasty. The Journal of Arthroplasty. 2019 May 1;34(5):898-900.
3. Kehlet H, Dahl JB. Anaesthesia, surgery, and challenges in postoperative recovery. The Lancet. 2003 Dec 6;362(9399):1921-8.
4. John G H 3rd, Joseph Albert A, Chen AF, Ilyas AM. Reducing Opioid Use in Orthopaedic Surgery. Instr Course Lect. 2025;74:313-322.
5. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. Jama. 2016 Apr 19;315(15):1624-45.
6. Chou R, Gordon DB, de Leon-Casasola OA, Rosenberg JM, Bickler S, Brennan T, Carter T, Cassidy CL, Chittenden EH, Degenhardt E, Griffith S. Management of Postoperative Pain: a clinical practice guideline from the American pain society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' committee on regional anesthesia, executive committee, and administrative council. The journal of pain. 2016 Feb 1;17(2):131-57.
7. Schwenk ES, Viscusi ER, Buvanendran A, Hurley RW, Wasan AD, Narouze S, Bhatia A, Davis FN, Hooten WM, Cohen SP. Consensus guidelines on the use of intravenous ketamine infusions for acute pain management from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Regional Anesthesia & Pain Medicine. 2018 Jul 1;43(5):456-66.
8. Wainwright TW, Immins T, Middleton RG. Enhanced recovery after surgery (ERAS) and its applicability for major spine surgery. Best practice & research Clinical anaesthesiology. 2016 Mar 1;30(1):91-102.
9. Kehlet H, Dahl JB. The value of "multimodal" or "balanced analgesia" in postoperative pain treatment. Anesth Analg. 1993;77(5):1048-1056. doi:10.1213/00000539-199311000-00030
10. Krebs EE, Gravely A, Nugent S, et al. Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain: The SPACE Randomized Clinical Trial. JAMA. 2018;319(9):872-882. doi:10.1001/jama.2018.0899
11. Zimmerman A, Laitman A. Safe Management of Adverse Effects Associated with Prescription Opioids in the Palliative Care Population: A Narrative Review. J Clin Med. 2024;13(10):2746. Published 2024 May 7. doi:10.3390/jcm13102746
12. (2021). Pain Relief Toolkit: Opioid Use and Alternatives. American Academy of Orthopaedic Surgeons. Retrieved from https://www.aaos.org/painrelieftoolkit/
13. McNicol ED, Ferguson MC, Hudcova J. Patient controlled opioid analgesia versus non-patient controlled opioid analgesia for postoperative pain. Cochrane Database Syst Rev. 2015;2015(6):CD003348. Published 2015 Jun 2. doi:10.1002/14651858.CD003348.pub3