A comparison of Ketoprofen and Diclofenac for acute musculoskeletal pain relief: a prospective randomised clinical trial

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1 Hong Kong Journal of Emergency Medicine A comparison of Ketoprofen and Diclofenac for acute musculoskeletal pain relief: a prospective randomised clinical trial P Ng, CW Kam, HH Yau Objectives: To compare the efficacy and adverse effects of Ketoprofen and Diclofenac in the treatment of acute musculoskeletal pain. Methods: In a prospective randomised clinical trial, patients admitted to an emergency department with acute musculoskeletal injuries requiring intramuscular (IM) injection for pain treatment were enrolled. The target study patients were Chinese adults who suffered from any musculoskeletal injuries of less than 12 hours. They received either 100 mg of Ketoprofen or 75 mg of Diclofenac. Pain was assessed by a 10-point visual analog score (VAS) and evaluations were performed at 30-minute intervals from treatment. Rescue analgesic was given if insufficient analgesia was achieved by one hour. The outcomes and the adverse effects were recorded. Results: We recruited 77 cases in the Diclofenac group and 74 cases in the Ketoprofen group. The demographic data with regards to age, sex and patterns of injury were comparable in both groups. Following the administration of treatment, both groups showed highly statistically significant (P<0.001) reduction in pain level at 30-minute and 60-minute intervals. Comparing the mean decrease of pain level, there was no statistically significant difference between the two groups at 30-minute interval (P=0.6) and 60-minute interval (P=0.5). In each group, there was one patient experiencing skin rash after treatment. Four patients in the Ketoprofen group and one in Diclofenac group required rescue medicine. With respect to the number of admission following treatment, there was no statistically significant difference between the two groups. Conclusions: Ketoprofen and Diclofenac are equally effective and safe in the treatment of acute musculoskeletal pain in Hong Kong Chinese population. (Hong Kong j.emerg.med. 2001;8:73-77) Keywords: Diclofenac, injury, Ketoprofen, musculoskelekal, pain relief Background In the emergency department, we often encounter patients with acute musculoskeletal injuries. The choice of parenteral Non-Steroidal Anti- Inflammatory Drugs (NSAIDs) depends on their analgesic potencies, the adverse effect profile, and their cost. NSAIDs inhibit the enzyme cyclooxygenase thereby decreasing prostaglandin synthesis. The prostaglandins are released from the Correspondence to: Paulin Ng, MBChB(CUHK), FRCSEd Tuen Mun Hospital, Accident and Emergency Department, Tsing Chung Koon Road, Tuen Mun, N.T., Hong Kong ngp1262@netvigator.com Kam Chak Wah, MRCP, FRCSEd, FRCSG Yau Hon Hung, MBBS, FRCSEd, FHKCEM injured tissues and are known as pain modulating factors. As we know, different NSAIDs have different efficacy in specific clinical settings. Yalcin and colleagues 1 had demonstrated that diflunisal was superior to dipyrone in treatment of moderate to severe cancer pain. Meloxicam had better results regarding pain on movement and global efficacy in the treatment of osteoarthritis of knee when compared to diclofenac. 2 Diclofenac was better than ketoprofen to relieve pain after maxillofacial surgery. 3 Concerning the treatment of dental pain, ketoprofen group had a lower median pain score than the diclofenac group. 4 However, there were other studies showing similar efficacy of different NSAIDs. 5-7 Owning to these conflicting results, a study was carried out to look into the relative efficacies of the two commonly used NSAIDs, ketoprofen and diclofenac, in our emergency department.

2 74 Hong Kong j. emerg. med. n Vol. 8(2) n Apr 2001 Methods The Ethics Committee of Tuen Mun Hospital approved this single-blinded randomised clinical trial. Patients who suffered from acute musculoskeletal injuries requiring intramuscular (IM) NSAIDs for pain relief were recruited. The inclusion criteria were Chinese adult patients (age ³18), who sustained acute musculoskeletal injuries (<12 hours) and were mentally fit for consent and pain score assessment. The nature of injury included fracture, contusion, sprain and soft tissue injuries. The exclusion criteria were noted as follows: 1) known allergic history to any NSAIDs, 2) medical illness such as proven peptic ulcer, asthma and renal failure, 3) patients who were taking anticoagulants, 4) pregnant and lactating mothers, and 5) any other contraindications to NSAIDs. In addition, patients who required immediate admission were excluded to avoid delay in any definitive treatment. After detailed explanation of the study to the patients, the doctor was responsible for obtaining a written consent and making an initial assessment of pain severity by the 10-point visual analog score (VAS). 8,9 Subsequently, the patient was randomly allocated to the two treatment regimes according to their enrolled case numbers. The patients received either 100 mg of ketoprofen or 75 mg of diclofenac by random allocation and they were blinded to the choice. In order to standardise the injection technique, all patients received a deep intragluteal injection into the upper outer quadrant of the buttock by an experienced nurse using a 23G one-inch long needle. Some patients would proceed to other treatment modalities, such as close reduction of fractures, suturing, and wound management. Most patients were kept in the observation ward for an hour. They were requested to report their pain intensity scores at 30-minute intervals till discharge. Rescue analgesics, such as doloxene, pethidine, or morphine, were offered if insufficient analgesia was achieved by one hour. The outcomes of the patients were also noted for further analysis. The patient flows were summarised in Figure 1. Any adverse reaction to treatment was noted. Statistical analysis was performed with the SPSS software and the paired t test was performed to assess the relative efficacy of the two NSAIDs. Results We had recruited 154 patients in this study and all of them suffered from blunt trauma. Three cases in the ketoprofen group were excluded from statistical analysis because of inadequate data. As a result, there were 77 cases in the diclofenac group and 74 cases in the ketoprofen group. The groups were similar with respect to age, sex, and patterns of injury. (Table 1) The types of musculoskeletal injuries of both groups in this study were noted. (Table 2) Following the administration of parental NSAIDs, both groups showed reductions in pain intensity at 30-minute and 60-minute interval. (Table 3) Table 1. Demographics of Ketoprofen versus Diclofenac groups. Ketoprofen Diclofenac (Orudis ) (Voltaren ) (n=74) (n=77) Demographic data Age, year (SD) 44.0 (16.6) 39.5 (13.7) Male: Female 49:25 48:29 Nature of injury Fracture 8 8 Sprain injury Contusion Table 2. The exact nature of injuries. Nature of injury Ketoprofen Diclofenac Total (Voltaren ) (Orudis ) Fractures Hand & foot Forearm & wrist Shoulder Other fractures Sprain injury Ankle & foot Back Neck Others Contusion Hand & foot Knee Arm & forearm Others Total

3 Ng et al./ketoprofen and Diclofenac for acute musculoskeletal pain relief 75 * O: Orudis, V: Voltaren ** ( ): number of patients Eligible patients receiving IM analgesia and observed for an hour (O:74, V:77) Pain relieved (O:58, V:56) Pain not relieved (O:16, V:21) Others (O:2, V:4) Request home for other reasons (O:3, V:5) Rescue analgesia (O:4, V:1) Home (O:67, V:66) Admission (O:7, V:11) Figure 1. A flowchart demonstrating the treatment modalities and outcomes of the patients. Table 3. The reduction of pain score in Ketoprofen and Diclofenac groups. Reduction of VAS (C.I.) Time interval Ketoprofen (Orudis ) Diclofenac (Voltaren ) 30-minute 1.84 ( ) 1.73 ( ) n=63 n=64 60-minute 2.89 ( ) 2.78 ( ) n=71 n=72 *paired t test: p<0.001

4 76 Hong Kong j. emerg. med. n Vol. 8(2) n Apr 2001 Four patients in the ketoprofen group and one in diclofenac group required rescue medicine. With respect to the number of admission and number of patients discharged with pain relief, there was no statistically significant difference between the two groups. (Table 4) A summary of the patient outcomes was shown in Figure 1. Concerning the adverse reaction to treatment, each group had one patient experiencing skin rash. Both patients were discharged after a brief period of observation. Discussion Despite the conflicting evidence of the relative potency of different NSAIDs in different clinical settings, 3-6 our study found that ketoprofen and diclofenac were equally effective in the treatment of acute musculoskeletal pain in our Chinese populations. Comparing the mean reduction of pain score, there was no statistically significant difference between the two groups at 30 min interval [-0.1, ( ), p=0.6] and 60 min interval [-0.1, ( ), p=0.5]. So, the choice of drugs would depend on other factors, such as the drug preparation, the cost, personal preference, and the adverse effects profile. Comparing the drug preparations, 75 mg of diclofenac (Voltaren ) had a volume of 3 ml while 100 mg of ketoprofen (Orudis ) had a volume of 2 ml. In order to minimise the local discomfort at the IM injection site and the risk of sciatic nerve injuries, a smaller volume of injection was preferred. The relative cost of different NSAIDs became an increasingly important issue as most emergency departments are operating on a tight drug budget. Owing to the small sample size in each group, the adverse effect profile of both drugs was not adequately studied. There were some limitations to this study. Firstly, it was a single-blinded study due to the limitation of resources. Secondly, there were some missing data of pain assessment score and three cases in the ketoprofen group were excluded. Fifteen percent (11/74) of the patients in the Ketoprofen group and 17% (13/77) of Diclofenac group had no pain score at 30 min interval. The failure to obtain an assessment might be explained by patients engaging in other X-ray investigations or interventions, such as close reduction of fractures. This proportion of missed data might have a significant effect on the internal validity of the study. Other confounding factors included the use of conscious sedation, the application of local anesthetic agents, and procedures relating to fracture manipulation and wound care. Lastly, the profile of adverse effects of both drugs was not adequately looked into as the sample size was too small. Conclusion Ketoprofen and Diclofenac are equally effective and safe in the treatment of acute musculoskeletal pain of less than 12 hours duration in our Chinese adult population. Other factors such as cost, drug preparation, adverse reaction profile, and personal preference are taken into considerations in the choice of treatment regime for these injuries. Table 4. Other outcome parameters in Ketoprofen and Diclofenac groups. Analgesic group Ketoprofen (Orudis ) Diclofenac (Voltaren ) Progress Adverse reaction 1 1 Rescue analgesic 4 1 Final outcome Admission 7 11 Discharged with pain relief Pain persisted but requested home for social reasons 3 5 Others: DAMA, disappeared 2 4

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