Comparative Study of Functional Outcome and Pain Control with Non-steroidal Anti-inflammatory Drugs (NSAIDs) and Non-NSAIDs in Early Post-operative Period in Total Knee Arthroplasty

Abstract

Introduction:

Primary aim – To evaluate the pain control with non-steroidal anti-inflammatory drugs (NSAIDs) and non-NSAIDs in early post-operative period during hospital stays in total knee arthroplasty (TKA) and compare them. Secondary aim – To evaluate the functional outcome with NSAIDs and non-NSAIDs in early post-operative period after 28 days, 3 months, and 6 months in TKA and compare them.

Objectives:

The objectives are as follows: (1) To assess the effectiveness of NSAIDs and non-NSAIDs in pain control during early post-operative period after TKA, using Visual Analog Scale (VAS) during hospital stay-every 4 hourly. (2) To compare the VAS pain scores in NSAIDs and non-NSAID patients during hospital stays. (3) To assess the functional outcome in NSAIDs and non-NSAIDs patients using Oxford Knee Score (OKS) and knee society score (KSS) after 28 days, 3 months, and 6 months. (4) To compare the functional outcome obtained by OKS and KSS in NSAIDs and non-NSAIDs patients after 28 days, 3 months, and 6 months.

Materials and Methods:

Study duration: This study was 12 months (April 1st, 2023–March 31st, 2024).

Study design:

This was a comparative prospective study.

Conclusion:

Evaluation of Oxford KSSs for pain management post-surgery for long duration showed statistically significant 44 difference in the OKS score at 1 month and 3-months (p = 0.05) between the two groups. Thus, at 6 months, the NSAID and non-NSAID group patients report similar pain scores with minimal or no pain.

Learning Point of the Article:

Careful attention to pain management in TKA especially the selection of analgesic becomes crucial in achieving good functional outcome early post-operative period.

Introduction

Total knee joint arthroplasty represents a cornerstone of orthopedic surgery with an aging population and an increasing prevalence of obesity. Total knee arthroplasty (TKA) is an effective and widely used method for restoring knee joint function, reducing pain, correcting deformity, and improving the quality of life. TKA is recommended for patients who have severe knee pain or stiffness that limits daily activities, namely, walking, sitting, and climbing stairs [1]. In Moderate or severe knee pain at rest [2] and/or knee deformities the most common cause of chronic knee pain and disability is arthritis in the form of osteoarthritis, rheumatoid arthritis, or post-traumatic arthritis in Kellgren and Lawrence Stage III or IV [3].

The goal of TKA surgery is to resurface the parts of the knee joint that have been damaged and to relieve knee pain that failed to respond to conservative management, either medical, including intra-articular injections, oral analgesics, or physiotherapy. Following TKA, most patients can start using their knees a few hours following surgery. Appropriate acute pain control after surgery is essential to improve early mobilization and start physiotherapy sessions. Post-operative pain or inadequate analgesia following TKA that is not well controlled may hamper patients from early rehabilitation which might lead to venous thromboembolism; delayed recovery apart from other complications such as lung atelectasis and prolonged hospital stay. Severe post-operative pain influences perioperative blood loss through various mechanisms such as sympathetic stimulation and increased arterial blood pressure [4]. The excruciating post-operating pain might also increase stress on the cardiovascular system and be related to ischemic cardiac events and myocardial insufficiency [5].

Different techniques and drugs are utilized, namely, central and peripheral nerve block, epidural anesthesia, opioids, non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, local anesthetics, glucocorticoids, and gabapentinoids. A single class of analgesic is seldom adequate. A combination of analgesic drugs is often utilized because some drugs have some limitations such as ceiling effect, contraindication at high dosage, respiratory insufficiency, and liver damage, risk of upper gastrointestinal complications or renal insufficiency [2].

The concept of multimodal contest-sensitive analgesia is now well accepted for the treatment of post-operative pain. It is still not known which NSAIDs and centrally acting analgesic are the most effective in terms of pain management and preventing side effects [6]. Accordingly, there are no fixed or appropriate guidelines. It has been demonstrated that different classes of analgesics are more effective than a single drug due to different mechanisms of action, and they can be used at low doses, reducing the incidence of side effects and increasing the quality of perceived analgesia [7].

Lumbar epidural analgesia is a common modality for pain relief following hip and knee replacement surgeries. A recently conducted systematic review reported that, in the first 4–6 h after surgery, patients receiving epidural analgesia had less pain at rest, based on visual analog scale (VAS) scores, than patients receiving systemic analgesia (SMD −0.77; 95% CI −1.24–−0.31). This effect was not statistically significant by 18–24 h (SMD −0.29; 95% CI −0.73–0.16). The choice of epidural agents may also influence the extent to which epidural analgesia differs from systemic analgesia.

Epidural analgesia and systemic analgesia have similar frequency of respiratory depression, nausea, and vomiting. Sedation occurred less frequently with epidural analgesia (OR 0.30; 95% CI 0.09–0.97) with a number-needed-to-harm of 7.7 (95% CI 3.5–42.0) patients for the systemic analgesia group. Retention of urine, itching, and low blood pressure were more frequent with epidural than systemic analgesia. There were insufficient numbers to draw conclusions on the epidural analgesia compared to systemic analgesia [8].

Although studies are available on the management of post-operative pain management in TKA, there is sparse literature comparing the NSAIDs and non-NSAIDS in TKA postoperatively, especially in India and Maharashtra. Hence, this study was attempted.

Materials and Methods

Study area

This was Apollo Hospital, CBD Belapur, Navi Mumbai, Maharashtra, India.

Study population

All patients with knee osteoarthritis admitted for TKA in the Department of Orthopedics at Apollo Hospital, Navi Mumbai, Maharashtra, India. Based on the detailed history collected from the study participants, they were allocated into two groups Group 1 having patients on NSAIDs (Control group) and Group 2 having patients on non – NSAIDs. The participants were blinded and not aware of the analgesic drugs given for post-operative pain management.

Sample size

Based on pain reduction by NSAIDs and pregabalin in a study by Tamilselvan and Kalaivani [9], mean VAS score in NSAID group 5.18 ± 0.59 and in pregabalin group was 3.97 ± 0.46.

Where σ = S.D

µ1 and µ2 are the mean values Z1-α/2 = 1.96 at 95% confidence

Z1-β = 0.84 at 80% power

µ1 = Mean VAS score in NSAID group = 5.18±0.59

µ2 = Mean VAS score in non-NSAID group = 3.97±0.46 Here (µ1 – µ2)2 = (5.18 – 3.97)2 = (1.21)2 = 1.4641

σ2 = (0.59)2 + (0.46)2 / 2 = 0.2798

N = 2 × 0.2798 (1.96 + 0.84)2/1.4641

=4.37315/1.4641

=2.9931

N = 3

N = Minimum sample size = 3

In this study, we considered Group 1 = 30 patients on NSAIDs

Group 2 = 30 patients on non-NSAIDs.

Sampling technique

Systematic random sampling was used to divide the study participants into two groups. As the patients got admitted, those who had odd admission number were included in Group 1 and those with even admission number were included in Group 2. For example, 1st patient since the commencement of the study was allocated in Group 1 and 2nd patient in Group 2 and likewise, until the required sample size was met.

Inclusion criteria

1. Patients of any gender aged 38 years and above

2. Patients in stage 3 osteoarthritis and/or more severe disease

3. Patients undergoing one side primary TKA

4. Patients having varus OR valgus deformity of <30°

5. Patients who are medically fit to undergo surgical intervention

6. Patients who consented for TKA surgery and take part in study.

Exclusion criteria

1. Revision of TKA

2. Patients with varus and valgus deformity more than 30°

3. Inability to understand the requirements of the study or be unwilling to provide written informed consent

4. Bilateral primary TKA.

Study duration

This study duration was 12 months (April 1st, 2023–March 31st, 2024).

Study design

This was comparative prospective study.

Study intervention

Comparing effectiveness of NSAIDs and non-NSAIDs in pain control and functional outcome in early post-operative period.

Study methodology

We conducted a prospective investigation into patients diagnosed with arthritis of the knee and underwent primary unilateral TKA. The study was performed on patients undergoing TKA and satisfied inclusion criteria. Informed, verbal, and written consent was taken before starting the study. All patients after detailed history were examined clinically and radiologically. All pre-operative routine investigations were done as per standard protocol. The patients were divided into two groups. (1) NSAIDs group: (control group) who received parenteral NSAID injection diclofenac sodium, inj. tramadol hydrochloride, and inj. paracetamol during hospital stay and after discharge oral analgesic agents, namely, NSAIDS (Selective and non-selective COX2 inhibitor) for 2 weeks; (2) non-NSAIDs group: who did not receive parenteral NSAID (Diclofenac) during post-operative period due to contraindication, having had diagnosis of chronic kidney disease or more or perioperative serum creatinine >1.3, allergy to NSAIDs, previous history of peptic ulceration, and bronchial asthma. Injection tramadol and injection paracetamol were given in ward and after discharge from hospital, tablet tramadol hydrochloride and tablet paracetamol given for 2 weeks. Parenteral medication injection tramadol, injection paracetamol, and epidural were common modality for managing pain in both groups during hospital stays.

Pre-operative process

The investigations included blood (complete hemogram, blood urea, serum creatinine, serum electrolytes, blood grouping and Rh typing, urine routine, random blood sugar, coagulation profile, HIV and HBsAg, and HCV), Electrocardiogram, 2D echo, etc. Radiological Examination: Chest X-ray, X-ray both knees AP (Standing) and lateral view and both lower limbs standing (AP), a radiograph of both lower limbs (scannogram) was obtained. All patients have undergone routine pre-anesthetic checkup and physician fitness. The surgery was performed under spinal plus epidural anesthesia. All patients operated in supine position.

Surgical technique

All of the surgical procedures were performed by a single surgeon using a similar pre-operative protocol and technique. Aspirin therapy was discontinued at least 5 days before surgery. All procedures were carried out under regional anesthesia with bupivacaine. A standard medial parapatellar arthrotomy with approximately 10 cm of skin incision was performed with tourniquet control at 300 mmHg. The bone cut was done using conventional instruments with intra-medullary and extra-medullary guides for reference in the distal femur and the proximal tibia. The opened femoral medullary canal was occluded with a bone plug after femur preparation. The patellar arthroplasty was done for all cases. A PAI was performed in all cases with 20 mL 0.5% bupivacaine that was diluted with normal saline solution. Cemented posterior-stabilized knee prostheses were used in all patients. Topical tranexamic acid was poured into the knee joint before the arthrotomy closure. A compressive dressing was also applied and subsequently removed 24 h after the surgery.

1. Spinal + Epidural (Ropivacaine 1% or bupivacaine 0.5%) anesthesia given

2. Under all aseptic precautions, parts scrubbed, painted, and draped

3. Anterior midline incision taken; medial parapatellar arthrotomy done

4. ACL, PCL, MM, and LM cut-cruciate sacrificing, posterior stabilized TKA planned

5. Medial tibial soft-tissue release; standard tibial cut taken with extramedullary zig

6. Femur distal valgus cut taken with intramedullary zig

7. Extension gap balancing done; femur-anterior, posterior, and chamfer and box cut taken

8. Flexon gap balancing done

9. Patella cut taken for arthroplasty. Trial done according to size

10. Joint reduced and joint stability checked on all ROM; patella tracking checked; tourniquet raised; pulse lavage given with 3 L normal saline

11. Appropriate size cemented prosthesis inserted on tibia, femur, and patella

12. Torniquet pressure released

13. Hemostasis achieved

14. Closure in layer

15. No drain used

16. Sterile dressing done

17. Distal pulsation checked and confirmed.

Post-operative process

Similar post-operative care was utilized for all patients. A similar post-operative physio protocol was followed, CPM device was applied, and progress recorded daily. Chemoprophylaxis for deep vein thrombosis (DVT), consisting of low-molecular-weight heparin injection and bridging oral Ecosprin 75 mg for 2 weeks, was administered for all patients.

On day 0, pain management was done using analgesics as per the group (NSAIDs/non NSAIDs). All the patients were assessed based on a Visual Analog Scale 4 hourly during hospital stay. On post-operative day 1, physiotherapy started. Patient mobilized out of bed with walker. On post-operative day 2, epidural and Foley catheters were discarded. Discharge given on Day 4 for group 1 with tab etodolac ER400 mg, tab tramadol sodium, and paracetamol and 2nd group with oral tramadol sodium and paracetamol and 1st follow-up was taken after 14 days from date of surgery for suture removal and to evaluate the patient.

All the patients were assessed clinically at regular intervals of 4 weeks, 3 months, and 6 months for Knee Society Score (KSS) and Oxford Knee Score (OKS).

Data collection method

• By History: Name, age, sex, weight, and comorbidities

• Using VAS for pain over the period of a hospital stay of up to 3–5 days

• By follow-up will be 28 days, 3 months, and 6 months after surgery for KSS, OKS.

• By clinical examination by case papers.

Any complications that occurred were recorded.

Outcome measure

1. VAS for pain during a hospital stay every 4 hourly starting postoperatively

2. Functional outcome of patients will be evaluated by clinical examination, KSS, and OKS after 28 days, 3 months, and 6 months.

Assessment

Post-operative pain level was assessed with a 10-cm VAS at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, and 80 h after surgery. VAS is used for post-operative pain evaluation during a hospital stay-4 hourly.

Functional outcome is assessed by OKS and KSS during postoperatively follow-up at, 28 days and 3 months, 6 months.

Pre-operative, intraoperative, and post-operative factors were taken into consideration to assess their influence on functional outcome.

Statistical analysis

Data collected were entered in Microsoft Excel spreadsheet and double checked for errors. Data analysis was done using Microsoft Excel and SPSS version 24. Results are expressed in terms of mean ± SD for continuous variables and percentages for categorical variables. Association between categorical variables were analyzed using Chi-square test. Association between two continuous variables were analyzed using Student “T” test for parametric data and Mann–Whitney U-test for non-parametric data. P < 0.05 is considered statistically significant.

Ethical clearance

The Institutional Ethics Committee clearance taken. Informed consent will be taken from all the participants after explaining to them in detail the nature of the study in understandable language and they will be assured that their identity will be kept anonymous. Confidentiality will be maintained at all times. All information provided by the patient and all data and information generated as part of the study (patient’s medical records) will be kept confidential. The data and information will not be used by the investigator for any purpose other than for research.

Observation and Results

In the present study, patient demographics for 60 patients and knees were determined. There were two groups made as,

• Group 1: NSAIDs group (control group)

• Group 2: Non-NSAIDs group

Majority of the study participants in Group 1 and Group 2 were in 60–70 years age group, 21 (70.0%) and 17 (56.7%), respectively. In Group 1, 5 (16.7%) belonged to <60 years age group and 4 (1.3%) to >70 years age group. In Group 2, 5 (16.7%) were below 60 years age and 8 (2.6%) were >70 years. Mean age of study participants was 64.10 ± 8.18 years in Group 1 and 66.57 ± 5.32 years in Group 2. There was no significant difference in the age distribution of participants in Group 1 and Group 2 (t = −1.384, P = 0.172). Hence, they are comparable.

Both the Group 1 and Group 2 had 15 (50.0%) males and 15 (50.0%) females each. There was no significant difference in the distribution of study participants based on gender (Table 1).

Table 1.

Age gender distribution of study participants.

The average age of males in NSAID group was 67.13 ± 5.64 years and females was 61.07 ± 9.33, while in Non-NSAID group, average age of males was 68.93 ± 5.23 years and females was 64.2 ± 4.41 years (Table 2).

Table 2.

Age and gender distribution of patients.

In the NSAIDs group, there were 15 males with an average weight of 76.9 ± 6.34 kg and 15 females with an average age of 68.6 ± 7.75 kg. In non-NSAIDs group, there were 15 males with an average weight of 74.6 ± 6.91 kg and 15 females with an average weight of 69.5 ± 7.10 kg (Table 3).

Table 3.

Distribution of patients according to weight.

Among the study participants, 50% from the NSAIDs group and 50% from the non-NSAIDs group got their right knee operated, 50% from NSAID and 50% from non-NSAID group had their left knee operated.

The VAS scores were significantly higher in non-NSAID group compared to NSAID group at 24 h (P = 0.001), 48 h (P = 0.000), and 72 h (P = 0.000) (Table 4).

Table 4.

Visual analog scores analyzed during hospital stay over 80 h of time (Compared using Mann–Whitney U-test for non-parametric data).

Depending on the weight of the study participants, drugs were administered as above based on the group they belonged, NSAID and non-NSAID group. Injections were administered during the first 3 post-operative days, followed by oral medication subsequently for 2 week’s duration initially and longer in case, it was required (Table 5).

Table 5.

Weight-dependent dosage of NSAIDs and non-NSAIDs in patients.

The mean of total duration of medication was 19.63 ± 3.26 days in the NSAID group and 24.24 ± 4.13 days in the non-NSAID group. The difference was statistically significant (P < 0.0001) (Table 6).

Table 6.

Knee society score analysis of NSAID and non-NSAID group of patients (t test).

KSS evaluates the clinical profile with respect to pain-intensity, range of motion and stability, flexion deformities, and poor alignment. Evaluation of clinical KSS and functional score (fs) showed that patients treated with NSAIDs (Diclofenac Sodium +paracetamol+ tramadol hydrochloride) had better clinical KSS than non-NSAID (Tramadol hydrochloride + paracetamol) patients 1 month from surgery, and the difference is statistically significant (P < 0.05). In the later stage at 3 months and 6 months, the difference in the mean scores of two groups is not significant (P > 0.05).

Analysis of fs showed no significant difference at all 3 times (1, 3, and 6 months) (Table 7). OKS is based on the questionnaire given to patients and their response.

Table 7.

Oxford knee score analysis of NSAID treated and non-NSAID treated patients.

Thus, it is a subjective response to measure pain and function activities. Evaluation of Oxford KSSs for pain management post-surgery for long duration showed statistically significant difference in the OKS score at 1 month and 3 months (P < 0.05), while at 6 months, the values showed no significant difference (P > 0.05) between the two groups. Thus, at 6 months, the NSAID and non-NSAID group patients report similar pain scores with minimal or no pain. There were no complications noted in the present study, in both the groups.

Discussion

Before every TKA, the optimal and the most suitable analgesic method should be selected based on the updated guidelines and meta- analyses, the pain team’s experience, and specific patient conditions and characteristics [10].The present study aimed at delineating the effect of NSAIDs in comparison to non-NSAIDs on pain management in post-TKA. A total of 60 patients were included, 30 in Group 1 were treated with NSAIDs, diclofenac sodium, tramadol hydrochloride, and paracetamol, while the other 30 in Group 2 were not given any NSAID drugs and treated with tramadol and paracetamol for pain management. The pain profile was monitored from the day of surgery up to 6 months using knee society system (KSS), the OKS, and VAS.

In the present study, majority of the study participants in Group 1 and Group 2 were in 60-70 years age group, 21 (70.0%) and 17 (56.7%), respectively. In Group 1, 5 (16.7%) belonged to <60 years age group and 4 (1.3%) to >70 years age group. In Group 2, 8 (2.6%) were >70 years and 5 (16.7%) were below 60 years age. Mean age of study participants was 64.10 ± 8.18 years in Group 1 and 66.57 ± 5.32 years in Group 2. There was no significant difference in the age distribution of participants in Group 1 and Group 2 (t = −1.384, P = 0.172). Hence, they are comparable. One of the studies has shown that the morphine consumption, pain score 6 h postoperatively, 24 h post-operative at rest and at movement, post-operative nausea and vomiting, and pruritus were comparatively lower in NSAIDs group [11].

In a study by Ban et al. [12], the mean age was 63 ± 11 years in the non-NSAID group, very close to the present study. Similarly, in a study by Laoruengthana et al. [13], the mean age was 66.32 ± 8.16 years in the NSAID group and 68.09 ± 7.74 years in the non-NSAID group, with no statistically significant difference (P = 0.210) in age distribution of two groups..

There was no significant difference in the distribution of study participants based on gender, with both the Group 1 and Group 2 having 15 (50.0%) males and 15 (50.0%) females each in the present study. However, Laoruengthana et al. [13] found that 75% were females and only 25% males in NSAID group and 92.6% females and 7.4% males in non-NSAID group. They found that females were significantly more in both the groups with p 0.011.

The average age of males in NSAID group was 67.13 ± 5.64 years and females was 61.07 ± 9.33, while in Non-NSAID group, average age of males was 68.93 ± 5.23 years and females was 64.2 ± 4.41 years. In the NSAIDs group, there were 15 males with an average weight of 76.9 ± 6.34 kg and 15 females with an average age of 68.6 ± 7.75 kg. In non-NSAIDs group, there were 15 males with an average weight of 74.6 ± 6.91 kg and 15 females with an average weight of 69.5 ± 7.10 kg. Among the study participants, 50% from the NSAIDs group and 50% from the non-NSAIDs group got their right knee operated, 50% from NSAID and 50% from non-NSAID group had their left knee operated.

The present study revealed that, VAS scores were significantly higher in non-NSAID group compared to NSAID group during the post-operative period at 24 h (P = 0.001), 48 h (P = 0.000) and 72 h (P = 0.000). In consistence, Laoruengthana et al. [13] found that the VAS pain scores of the non-NSAIDs group were significantly higher than those of the control group during the entire post-operative period.

The non-NSAIDs group also had significantly higher cumulative opioids analgesic consumption at 24 h (9.01 ± 8.39 mg in NSAID vs. 15.84 ± 10.27 in non-NSAID group) and 48 h (12.6 ± 11.34 mg in NSAID vs. 25.36 ± 16.68 in non-NSAID group) after the surgery than the NSAID group in a study by Laoruengthana et al. [13]. Depending on the weight of the study participants, drugs were administered as above based on the group that they belonged, NSAID and non-NSAID group. Injections were administered during the first 3 post-operative days, followed by oral medication subsequently for a week’s duration initially and longer in case, it was required. The mean of total duration of medication was 19.63 ± 3.26 days in the NSAID group and 24.24 ± 4.13 days in the non-NSAID group. The difference was statistically significant (P < 0.0001).

KSS evaluates the clinical profile with respect to pain-intensity, range of motion and stability, flexion deformities, and poor alignment. Evaluation of clinical KSS and fs showed that patients treated with NSAIDs (Diclofenac Sodium +paracetamol+ tramadol hydrochloride) had better clinical KSS than non-NSAID (Tramadol hydrochloride + paracetamol) patients 1 month from surgery, and the difference is statistically significant (P < 0.05). In the later stage at 3 months and 6 months, the difference in the mean scores of two groups is not significant (P > 0.05). In coherence with the present study, Laoruengthana et al. [13] found that the knee flexion angle of the NSAID group (73.43 ± 18.17) was higher than that of the Non-NSAIDs group (65.26 ± 21.71) and the difference was statistically significant (P = 0.045) at 48 h postoperatively. Analysis of fs showed no significant difference at all 3 times (1, 3, and 6 months).

OKS is based on the questionnaire given to patients and their response. Thus, it is a subjective response to measure pain and function activities. Evaluation of Oxford KSSs for pain management post-surgery for long duration showed statistically significant difference in the OKS score at 1 month and 3 months (P < 0.05), while at 6 months, the values showed no significant difference (P > 0.05) between the two groups. Thus, at 6 months, the NSAID and non-NSAID group patients report similar pain scores with minimal or no pain.

Studies have also shown that, the Non-NSAIDs group had more post-operative nausea vomiting (0.48 ± 1.02% in NSAID group vs. 0.67 ± 1.19% in non-NSAID group) and longer length of stay (5.16 ± 1.08 days in NSAID group vs. 5.58 ± 1.67 days in non-NSAID group) than the NSAID group, though not with statistical significance. The calculated blood loss was 552.52 mL (interquartile range [IQR], 403.83–710.64) for the non-NSAIDs group and 397.65 mL (IQR, 266.72–622.87) for the NSAID group (P = 0.02) [57] and blood transfusion rate was 23.1% and 17.3% (P = 0.63), respectively [13].

A study by Laoruengthana et al. [13] found that the cardiac troponin-T (cTnT) of the non-NSAIDs group was rising during the first 48 hours and significantly higher than that of the control group at 48 h. Each group had two patients with cTnT exceeding 14 ng/L during the first 72 h postoperatively and these patients had no subsequent symptom and sign of cardiovascular event during hospitalization. However, there were no such incidents in the present study.

Similar studies have been conducted by many authors. Studies of paracetamol/non-steroidal anti- inflammatory drugs (NSAID Group) combinations versus paracetamol (Non-NSAID Group) alone have shown the following results: (Table 8)

Table 8.

Studies of paracetamol/non-steroidal anti-inflammatory drugs (NSAID Group) combinations versus paracetamol (non-NSAID group).

In this study, we found that the non-NSAIDs group had significantly higher VAS scores at any time point and consumed significantly more morphine in the first 48 h postoperatively than the NSAID group. These results accord with the meta-analysis conducted by Du and Gu [14] and the RCT by Zhu et al. [15], who reported that postoperatively less opioid use, lower pain scores, and better range of knee motion were observed in patients who were administered parenteral parecoxib.

At present, corticosteroid and acetaminophen are considered as useful supplements for controlling post-TKA pain. Intravenous acetaminophen has been revealed by meta-analysis as an efficacious adjunct to multimodal analgesia after total joint arthroplasty in terms of pain scores and opioid consumption in the first 72 h [16]. Tammachote and Kanitnate [17] also revealed that administration of 0.15 mg/ kg of intravenous dexamethasone can significantly relieve pain between 12 h and 21 h after TKA. Alternatively, additional peripheral nerve block could also be considered as an analgesic supplement to overwhelm the pain after TKA [18-22].

Adequate post-operative pain control in total joint replacement (TJR) during post-operative functional recovery is very important, and a sufficient analgesic effect can help relieve pain, allow patients to get out of bed earlier to exercise, restore joint function, and prevent the formation of DVT [22]. Severe pain also leads to prolonged hospital stays and increased opioid use. For instance, epidural analgesia frequently causes complications, such as nausea, hypotension, and urinary retention. TJR patients often receive anticoagulant drugs to prevent DVT, but these agents increase the risk of operative bleeding [23,24]. The effect of intravenous analgesia is poor, and patients are prone to respiratory depression, nausea, vomiting, itching, and sleepiness [24,25].

The patients who were not candidates for NSAIDs administration had significantly higher pain scores and consumed significantly more morphine/other analgesics after TKA. Studies also show that, they tended to have greater blood loss and the rising of cardiac biomarkers during the first 48 h after the surgery. Hence, these patients may benefit from supplementary analgesia and appropriate perioperative monitoring [13].

The present study proved that the patients treated with NSAID, have better pain control over those treated with non-NSAIDs during hospital stay. The KSS and OKS are used for short-term pain assessment and analysis of functional outcome. It shows that in the first month their scores were better for NSAID treated patients (P < 0.05). However, in this month, the fs between the two groups seems similar. In the 3rd month, the OKS that is mostly determined from patients’ response shows better management in NSAIDs treated patients than non-treated. In the 6th month, the values were similar for all the scores, suggesting no significant difference in pain levels when either of the treatments is given. From the overall study, the use of NSAID postoperatively in TKA patients suggests significantly useful in controlling pain and early mobilization. While in the long run, it does not give much significant difference in the use of NSAIDs, tramadol sodium, paracetamol, or non-NSAIDs (Tramadol sodium and paracetamol) drugs in functional outcome. This will help in deciding on the pain management guidelines in TKA patients.

Limitations

The limitations of this study include the short-term follow-up period and lower sample size, which may limit the generalization of the study findings and its application to other population groups.

Conclusion

The present study proved that the patients treated with NSAID have better pain control over those treated with non-NSAIDs during hospital stay. The KSS and OKS are used for short-term pain assessment and analysis of functional outcome. It shows that in the 1st month, their scores were better for NSAID treated patients (P < 0.05). However, in this month, the fs between the two groups seems similar. In the 3rd month, the OKS that is mostly determined from patients’ response shows better management in NSAIDs treated patients than non-treated. In the 6th month, the values were similar for all the scores, suggesting no significant difference in pain levels when either of the treatments is given. From the overall study, the use of NSAID postoperatively in TKA patients suggests significantly useful in controlling pain and early mobilization. While in the long run, it does not give much significant difference in the use of NSAIDs, tramadol sodium, paracetamol, or non-NSAIDs (Tramadol sodium and paracetamol) drugs in functional outcome. This will help in deciding on the pain management guidelines in TKA patients.

Clinical Message.

The use of NSAID’s significantly reduce’s pain in TKA patients especially in the immediate and early post operative period.

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