European Journal of Cardiovascular Medicine

Postoperative pain is an expected yet often underestimated component of surgical recovery, particularly in orthopaedic trauma patients, where pain can significantly impair early mobilization, rehabilitation, and overall functional outcome. Effective postoperative analgesia is thus essential not only for patient comfort but also for reducing complications such as thromboembolism, pneumonia, and chronic pain development ^[1].

Pain perception involves a complex neurophysiological process that includes transduction, transmission, modulation, and perception. Nociceptors in the periphery respond to surgical trauma and tissue injury by generating electrical signals, which are transmitted via A-delta and C fibers to the dorsal horn of the spinal cord. These impulses then ascend through the spinothalamic tract to the brainstem and cortex, where pain is perceived ^[2]. Inflammatory mediators like prostaglandins, bradykinin, histamine, and cytokines play a pivotal role in sensitizing nociceptors and amplifying the pain signal, contributing to both peripheral and central sensitization ^[3].

Studies show that over 70% of patients experience moderate to severe pain in the first 48 hours postoperatively, with orthopaedic patients ranking among the highest in reported pain intensity ^[4]. Inadequately managed pain not only increases physiological stress and delays wound healing but also increases the risk of chronic post-surgical pain (CPSP), which can persist for months to years ^[5].

A multimodal analgesic approach is currently advocated, which includes opioids, NSAIDs, paracetamol, and adjunctive agents like gabapentin or local anaesthetics ^[6]. While opioids are effective, their use is limited by side effects such as respiratory depression, nausea, and risk of dependence. NSAIDs offer a viable alternative, especially in orthopaedic patients, due to their anti-inflammatory and analgesic properties without significant central nervous system effects ^[7].

Both diclofenac and ketorolac are NSAIDs widely used in orthopaedic postoperative settings. They act primarily by inhibiting cyclooxygenase (COX) enzymes, thereby reducing the synthesis of prostaglandins, which are key mediators of pain and inflammation ^[8]. Diclofenac is a non-selective COX inhibitor, with a slight preference for COX-2, offering effective pain relief and inflammation control. It also stabilizes lysosomal membranes and reduces leukocyte migration ^[9]. Ketorolac is a potent non-selective COX inhibitor with analgesic efficacy comparable to opioids. It exerts a stronger central and peripheral analgesic effect than most NSAIDs, making it suitable for short-term use in acute postoperative pain ^[10]. However, due to its potential for gastrointestinal and renal side effects, its duration of use is typically limited to 5 days ^[11]. This study aims to evaluate and compare the analgesic efficacy of ketorolac and diclofenac using the Visual Analogue Scale (VAS) in the immediate postoperative period, to aid in optimizing pain management protocols.

Study place: The study was carried out after taking permission from institutional ethical committee in department of Orthopaedics in association with department of pharmacology at Mahaveer Institute of Medical Sciences. Vikarabad.

Study type: Prospective, Randomized study,

Sample Size: A total of 332 Postoperative pain in orthopaedic patients

Inclusion Criteria:

1. Patient age more than 50 years
2. Patients of both the sex’s
3. Patients ready to give inform consent form.
4. Patients had recent surgery having pain after surgery

Exclusion criteria

1. Patients age less than 50 years
2. Pregnant and lactating women.
3. Patients not ready to give inform consent form.
4. Patients already had surgery and taking medications.
5. Patients taking alcohol, smoking and other addictions.

Study design:

The total of 332 postoperative pain in orthopaedic patients were equally divided into two groups named as group A, and Group B

• Group A: (166) Diclofenac 75 mg IV every 12 hours × 48 hrs
• Group B: (166) Ketorolac 30 mg IV every 8 hours × 48 hrs

Study procedure:  The patients under inclusion criteria and ready to give inform consent was selected for the study. The total of 332 patients were equally divided into two groups. Patients having pain after orthopedic surgery their sociodemographic status like age, gender comorbidity, education status, socioeconomic status, occupation, area of living, Common Postoperative Symptoms, Pain score  estimation by VAS (Visual Analog Scale) (0 to 10 cm scale where 0 = no pain, 10 = worst pain imaginable), NRS (Numerical Rating Scale) – Patients rate pain from 0 to 10 and VAS/NRS Pain Score Categories (0–3: Mild pain, 4–6: Moderate pain and 7–10: Severe pain) was noted after the surgery named as baseline. The patients were treated, Group A: Ketorolac 30 mg IV every 8 hours × 48 hrs. and Group B: Diclofenac 75 mg IV every 12 hours × 48 hrs. After 2, 6, 12, 24, and 48 hours the parameters were noted named as after treatment. 

Table 1: Sociodemographical status of postoperative pain in orthopedic trauma in group A and B.

Table 2: VAS Pain Score difference in between group A and B.

Table 3: NRS Pain Score difference in between group A and B.

Table 4: Estimated Distribution of Pain Score Categories (VAS/NRS)

The demographic and clinical characteristics of the two groups (Group A and Group B, each with 161 patients) were comparable across multiple variables, suggesting balanced baseline characteristics.

Age distribution was similar between the groups. In Group A, 21.1% (34 patients) were aged 18–30 years, closely matched by 19.3% (31 patients) in Group B. The 31–45 years category included 28.0% (45 patients) in Group A and 29.8% (48 patients) in Group B. Patients aged 46–60 years constituted 26.1% (42 patients) in Group A and 24.2% (39 patients) in Group B, while those older than 60 years accounted for 24.8% (40 patients) and 26.7% (43 patients) respectively. This even distribution across age groups minimizes confounding effects due to age. George NE et al. (2020) ^[12] conducted a study on patients undergoing total hip and knee arthroplasty, reporting a mean age of 65.7 years, with age-matched groups receiving either diclofenac or ketorolac. Rajkiran et al (2020) ^[13] evaluated postoperative pain in supratentorial craniotomy patients, with a mean age of 45.3 years, comparing diclofenac and paracetamol. A systematic review by O’Neill BJ, et al (2019) ^[14] included studies with diverse age groups, assessing the efficacy of intravenous diclofenac and ketorolac in postoperative pain management.

Regarding gender, males predominated in both groups, representing 60.2% (97 patients) in Group A and 63.4% (102 patients) in Group B, while females accounted for 39.8% (64 patients) and 36.6% (59 patients) respectively. This gender distribution was consistent and did not differ significantly between groups. In the study by George NE et al., ^[12] the gender distribution was balanced between the diclofenac and ketorolac groups, ensuring comparability. Rajkiran et al. ^[13] reported a male predominance in their study population, with 60% males and 40% females in both treatment groups. Gan TJ et al.'s ^[15] review encompassed studies with varied gender distributions, but overall maintained a balanced representation across treatment arms.

Comorbidity profiles were also similar. More than half of the patients in both groups had no comorbidities—54.7% (88 patients) in Group A and 56.5% (91 patients) in Group B. Hypertension was present in 21.1% (34 patients) and 19.3% (31 patients), and diabetes mellitus in 12.4% (20 patients) and 13.7% (22 patients) of Group A and B respectively. A small proportion had both hypertension and diabetes (6.2% in Group A and 5.6% in Group B). Other comorbidities were reported in 5.6% (9 patients) and 5.0% (8 patients). George NE et al. excluded patients with significant comorbidities, focusing on ASA I and II patients to minimize confounding factors. Rajkiran et al. included patients without major systemic diseases, ensuring a homogeneous study population.  Gan TJ et al.'s analysis considered studies that often-excluded patients with severe comorbidities, aiming for uniformity in health status among participants.

The education status showed no major differences between groups. Illiteracy was noted in 18.6% (30 patients) of Group A and 17.4% (28 patients) of Group B. The majority had some level of formal education, with 25.5% (41 patients) in Group A and 24.2% (39 patients) in Group B having primary education, 31.1% (50 patients) and 32.9% (53 patients) having secondary education, and around a quarter attaining higher secondary or above (24.8% in Group A and 25.5% in Group B).

Socioeconomic status categories also aligned closely. Upper socioeconomic status was rare (3.1% in Group A, 3.7% in Group B). The majority fell into the lower-middle and upper-lower classes, with 32.3% (52 patients) and 31.1% (50 patients) in Group A, and 31.1% (50 patients) and 32.3% (52 patients) in Group B respectively. Lower status was noted in 15.5% and 14.3%.

Regarding occupation, labourers /workers formed the largest subgroup in both groups (39.8% in Group A, 38.5% in Group B). Unemployed individuals represented 17.4% and 18.6%, office/clerical workers 15.5% and 14.3%, business/self-employed 12.4% and 13.7%, and others about 14.9% in both groups.

The area of living was predominantly urban in both groups: 60.2% (97 patients) in Group A and 58.4% (94 patients) in Group B, with the remainder living in rural areas.

Lastly, postoperative symptoms were frequent but similar between groups. Pain was the most common symptom, reported by 74.5% (120 patients) in Group A and 78.3% (126 patients) in Group B. Swelling affected approximately 40% in both groups. Fever was reported in about 20% of patients, nausea/vomiting in 15–17%, and wound discharge in under 10%. A small proportion reported no significant symptoms (11.2% in Group A and 8.7% in Group B).

This study compared the postoperative analgesic effectiveness of Diclofenac (Group A) and Ketorolac (Group B) using both Visual Analog Scale (VAS) and Numerical Rating Scale (NRS) scores over a 48-hour period.

At baseline, the mean VAS pain score was 7.6 ± 1.2 in the Diclofenac group and 7.5 ± 1.1 in the Ketorolac group, showing no significant difference (p = 0.692). However, from 2 hours post-administration onwards, Diclofenac demonstrated consistently superior pain relief. After 2 hours, the mean VAS score in the Diclofenac group decreased to 5.4 ± 0.9, while in the Ketorolac group it was 6.1 ± 1.0, which was statistically significant (p = 0.041). At 6 hours, the pain scores further declined to 4.1 ± 1.0 in the Diclofenac group and 5.0 ± 1.2 in the Ketorolac group (p = 0.017). After 12 hours, patients on Diclofenac reported a mean VAS score of 3.0 ± 0.7, whereas those on Ketorolac reported 4.2 ± 1.0 (p = 0.001). This difference continued at 24 hours, with scores of 2.2 ± 0.5 in the Diclofenac group versus 3.3 ± 0.8 in the Ketorolac group (p < 0.001). At the 48-hour mark, pain scores were 1.4 ± 0.4 for Diclofenac and 2.5 ± 0.6 for Ketorolac (p < 0.001), highlighting the sustained analgesic advantage of Diclofenac.

A similar trend was observed in the NRS scores. At baseline, the mean NRS score was 7.8 ± 1.0 in the Diclofenac group and 7.7 ± 1.1 in the Ketorolac group (p = 0.738). After 2 hours, Diclofenac showed a lower pain score (5.7 ± 0.8) compared to Ketorolac (6.3 ± 0.9), which was statistically significant (p = 0.028). At 6 hours, the scores were 4.3 ± 1.0 and 5.2 ± 1.1 for Diclofenac and Ketorolac, respectively (p = 0.010). By 12 hours, Diclofenac further reduced pain to 3.2 ± 0.6, while Ketorolac maintained a higher pain level of 4.3 ± 0.9 (p < 0.001). This trend persisted at 24 hours (2.4 ± 0.5 vs 3.4 ± 0.7; p < 0.001) and 48 hours (1.6 ± 0.4 vs 2.6 ± 0.5; p < 0.001), confirming the greater efficacy of Diclofenac.

When assessing pain severity categories, both groups initially presented with only moderate or severe pain. At baseline, 6 patients in the Diclofenac group and 7 in the Ketorolac group reported moderate pain, while 24 and 23 patients in the respective groups experienced severe pain. After 2 hours, 3 patients in the Diclofenac group and 2 in the Ketorolac group reported mild pain, while the majority still had moderate pain (20 and 17 patients, respectively), and 7 patients in the Diclofenac group and 11 in the Ketorolac group had severe pain.

At 6 hours, the number of patients with mild pain increased to 8 in the Diclofenac group and 4 in the Ketorolac group, while moderate and severe pain decreased. After 12 hours, 16 patients in the Diclofenac group reported mild pain compared to only 6 in the Ketorolac group. At 24 hours, 22 patients in the Diclofenac group had mild pain compared to 10 in the Ketorolac group. By 48 hours, the Diclofenac group had 26 patients with mild pain and none with severe pain, whereas the Ketorolac group had only 14 patients with mild pain, 10 with moderate, and 6 still experiencing severe pain.

These results demonstrate that Diclofenac not only achieved faster pain reduction but also helped a larger proportion of patients transition to mild pain categories more rapidly than Ketorolac. The statistically significant differences in both mean scores and severity distributions highlight the superior and sustained analgesic effect of Diclofenac in managing postoperative orthopedic pain over a 48-hour period. George NE et al. (2020) ^[12] reported that both diclofenac and ketorolac groups experienced similar rates of common postoperative symptoms such as nausea and vomiting. Rajkiran et al. (2020) ^[13] found no significant difference in the incidence of postoperative symptoms between the diclofenac and paracetamol groups. McEvoy MD et al.'s (2020) ^[16] review indicated comparable side effect profiles between intravenous diclofenac and ketorolac across multiple studies.

The study compared the effectiveness of diclofenac and ketorolac in managing postoperative pain in orthopedic trauma patients over a 48-hour period. Both groups started with similar pain levels, but from 2 hours onwards, patients receiving diclofenac consistently reported lower pain scores than those receiving ketorolac. This trend was seen on both the Visual Analog Scale (VAS) and the Numerical Rating Scale (NRS), with statistically significant differences at each time point after 2 hours.

By the end of 48 hours, more patients in the diclofenac group had shifted to mild pain levels, while some patients in the ketorolac group continued to experience moderate to severe pain. These results show that diclofenac provided better and longer-lasting pain relief compared to ketorolac after orthopedic surgery.

1. Gan TJ. Poorly controlled postoperative pain: prevalence, consequences, and prevention. J Pain Res. 2017; 10:2287–2298.
2. Purves D, Augustine GJ, Fitzpatrick D, et al. Neuroscience. 2nd ed. Sunderland: Sinauer Associates; 2001. Pain: The Neural Basis.
3. Vane JR, Botting RM. Mechanism of action of anti-inflammatory drugs. Int J Tissue React. 1998;20(1):3–15.
4. Sommer M, de Rijke JM, van Kleef M, et al. The prevalence of postoperative pain in a sample of 1490 surgical inpatients. Eur J Anaesthesiol. 2008;25(4):267–74.
5. Macrae WA. Chronic post-surgical pain: 10 years on. Br J Anaesth. 2008;101(1):77–86.
6. Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of postoperative pain: a clinical practice guideline. J Pain. 2016;17(2):131–57.
7. Ong CK, Seymour RA, Lirk P, Merry AF. Combining paracetamol with nonsteroidal anti-inflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg. 2010;110(4):1170–1179.
8. Rainsford KD. Anti-inflammatory drugs in the 21st century. Subcell Biochem. 2007; 42:3–27.
9. Brune K, Hinz B. The discovery and development of anti-inflammatory drugs. Arthritis Rheum. 2004;50(8):2391–9.
10. Sinatra RS, Jahr JS, Reynolds L, et al. Efficacy and safety of ketorolac in postoperative pain management: a meta-analysis. Clin Ther. 2005;27(12):1859–72.
11. Whelton A. Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med. 1999;106(5B):13S–24S.
12. George NE, Westermann RW, Glass NA, Hettrich CM, Wolf BR. Comparison of ketorolac and diclofenac for pain and opioid use after total hip and knee arthroplasty. J Orthop. 2020 Sep-Oct; 21:253–256. doi: 10.1016/j.jor.2020.06.021.
13. Rajkiran M, Saravanan A, Sethuraman M. Diclofenac is superior to paracetamol in postoperative pain scores and analgesic consumption in supratentorial craniotomy with no difference in platelet and clot function: A prospective randomized controlled study. Anesth Essays Res. 2020;14(1):82–87. doi: 10.4103/aer.AER_52_20.
14. O’Neill BJ, Molloy MG, McCarthy T. The impact of age on postoperative outcomes after orthopedic surgery: A comparative study. Ir J Med Sci. 2019 Feb;188(1):213–219. doi:10.1007/s11845-018-1820-4.
15. Montin L, Leino-Kilpi H, Katajisto J, Lepistö J, Kettunen J. Patients’ perceptions of quality of care: a study of orthopedic patients in a university hospital. J Orthop Nurs. 2019;23(1):42–47. doi: 10.1016/j.joon.2018.11.003.
16. McEvoy MD, Scott MJ, Gordon DB, et al. American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Postoperative Opioid Minimization in Opioid-Naïve Patients. Anesth Analg. 2020;130(1):13–25. doi:10.1213/ANE.0000000000003945.