Postoperative Analgesic Effects of Ibuprofen Versus Ketorolac in Patients Undergoing in Orthopedic Surgery
Condition: Intravenous Drug Usage; Ibuprofen; Ketorolac; Knee Arthroscopy; Postoperative Pain
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Objectives: To compare the postoperative analgesic effects of ibuprofen versus ketorolac in
      patients undergoing orthopedic surgery at Combined Military Hospital, Rawalpindi.

      Study design: Randomized controlled trial Setting: Department of Anasthesiology, Combined
      military Hospital, Rawalpindi Duration of study:6 months (01st August 2021 to 31st January
      2022) Material and methods: After ethical approval, 100 patients in randomly divided two
      equal groups (A and B) were selected. In group A, 800 mg IV ibuprofen while in group B, 30 mg
      IV ketorolac was given within 30 min of skin closure after orthopedic surgery. The pain was
      assessed via visual analogue scale postoperatively. The SPSS version 25 was used for analysis
      of data. P value ≤ 0.05 was considered as significant.
    

Detailed description: 
      INTRODUCTION Healthcare seeks to decrease postoperative pain to ensure better and faster
      postoperative mobilization.1 Postoperative pain pathways identify populations at risk for
      30-day readmissions and emergency department visits that are not due to post discharge
      complications.2 Chronic pain is acknowledged as a disease per se, and addressing pain control
      expectations before discharge could reduce surgical readmissions.3 However, despite advances
      in perioperative protocols, pain remains a very frequent clinical symptom seen by orthopedic
      surgeons and a major reason for patients to seek medical assistance. Moreover, pain
      management after orthopedic procedures remains suboptimal for many patients.4 For instance,
      37% of orthopedic patients reported their pain to be severe at its highest intensity, where
      postoperative pain remains a problem that requires consensus and joint efforts.5 Several
      modalities are available to alleviate the postoperative period, which range from nerve blocks
      to the use of various classes of drugs. Opioids have been widely used for pain relief.
      However, this class of drug is associated with a wide range of side effects, including a
      potential for developing drug dependence and addiction. On the other hand, non-steroidal
      anti-inflammatory drugs (NSAIDs), have been used widely for pain relief. NSAIDs are widely
      available as compared to opioids. NSAIDs also have several side effects, but a study has
      proven NSAIDs to be safe for controlling acute postoperative pain if they are used
      appropriately.6 Several studies have compared the different drugs belonging to the NSAID
      class in terms of their efficacy as postoperative analgesia. A study found no difference in
      pain and satisfaction between two groups of patients receiving either IV ketorolac or IV
      Ibuprofen as part of postoperative analgesia following urogynecological surgeries.7 However,
      patients who underwent laparotomies had less pain with Keterolac.8 In another study carried
      out on patients undergoing knee arthroscopies, preemptive use of Ibuprofen 800 mg was
      associated with less postoperative pain.9 Uribe et al. compared the postoperative analgesic
      effects of ibuprofen and ketorolac and discovered a difference in rescue analgesic use (55%
      vs. 83.9%), time to first rescue analgesic use (77.62 ± 33.03 vs. 55.78 ± 35.37 hours), and
      analgesic requirement in PACU (5.53 ± 5.89 vs. 19.92 ± 15.63 mg, p value 0.05).10
      Postoperative pain is one of the principal concerns of surgeons and anesthesiologists, which
      leads to prolonged hospitalization and an increased analgesic requirement. Both factors
      expose the patient to hospital acquired infection and the untoward side effects of
      analgesics. As a result, a balanced or multimodal analgesia with adjuvant medications is
      required. It is important that, as anesthesiologists, we understand the effective method for
      pain suppression during orthopedic procedures. Therefore, this study is aimed at filling this
      knowledge gap. Data from this study would add information and serve as a baseline for the
      development of management guidelines for pain management.

      METHODS AND MATERIALS After obtaining approval from the Ethical Committee / Institutional
      Review Board (IRB) (document no. 156/05/21), patients undergoing orthopedic surgeries were
      enrolled in the Department of Anesthesiology and Orthopedics at the Combined Military
      Hospital, Rawalpindi. The sample size for this randomized controlled trial (RCT) was 100
      patients (50 patients in each group), which was calculated from a previous study by taking
      the frequencies of rescue analgesic use as (55% vs. 83.9%). 11 The power of the test was 90%
      with a 5% level of significance. The research lasted six months, from August 1, 2021, to
      January 31, 2022. All patients gave their informed written consent. The patients of either
      gender with an age range of 40-80 years and an ASA grade of 2 who were undergoing orthopedic
      surgeries for fractures of the radius, ulna, and wrist were included in the study. Patients
      with a history of adverse reactions to ibuprofen or ketorolac, a history of epilepsy,
      bronchial asthma, coronary artery disease, renal or hepatic impairments, or use of
      antiarrhythmic or analgesic medications in the last seven days were excluded. Age, gender,
      obesity (BMI > 27 kg/m2), history of smoking (10 or more cigarettes per day for at least 5
      years or 5 or more cigarettes per day for at least 10 years), diabetes, and hypertension were
      registered before pre-operative evaluation of the patients to assess their fitness for
      anesthesia. The patients were labeled as diabetics when they were on anti-diabetic medication
      for at least 6 months or when there was lab evidence of HBA1c >6.5%, fasting blood sugar of
      >126 mg/dL, or a random blood sugar level of >200 mg/dL. Patients were classified as
      hypertensive if they had been taking anti-hypertensive medication for at least 6 months or if
      clinical evidence of blood pressure greater than 140/90 was found on at least two separate
      occasions at least two hours apart. All patients were randomly divided into two equal groups
      (A and B) by using the sealed envelope technique. All surgeries were done under standard
      general anesthesia. Patients were induced with propofol (2 mg/kg) and premedicated with
      fentanyl. Endotracheal intubation was facilitated by the muscle relaxant atracurium 0.5
      mg/kg. Anesthesia was maintained with 50% O2, 50% air, 1 MAC isoflurane, and atracurium. The
      patients were mechanically ventilated to keep ETCO2 between 35 and 40 mmHg. In Group A,
      patients received an intravenous injection of 800 mg of Ibuprofen, while intravenous
      ketorolac (30 mg) was given to patients in Group B, approximately 30 minutes before the skin
      closure. All patients were extubated and transferred to the post-anesthesia care unit (PACU).
      The durations of the surgical procedure and anesthesia were documented. Another
      anesthesiologist on duty was deputed for follow-up with the patients. The patients were kept
      blind to the type of analgesic drug they received. The postoperative pain was measured by VAS
      at 3, 6, and 12 hours postoperatively. The VAS ranged from 0 to 10, with 0 representing no
      pain and 10 representing the maximum bearable pain. When the VAS score was > 4, the injection
      Tramadol 30 mg was given intravenously as a rescue analgesic. The frequency of patients
      requiring rescue analgesia, the time to start rescue analgesia, and the total dose of drug
      during the 12-hour postoperative period were noted in each group.

      Statistical analysis: The data was analyzed by IBM, SPSS Version 20 registered for Microsoft
      Windows. The mean, standard deviation, and frequency/percentages were calculated for
      quantitative and qualitative data, respectively. Chi square and independent sample t-tests
      were used to compare postoperative analgesic parameters between both groups. The p value of
      <0.05 was taken as statistically significant.
    

Intervention name(s): Ibuprofen 800 mg; Ketorolac Injection
Intervention type(s): Drug; Drug
Intervention description(s): Intravenous injection of ibuprofen 800 mg; Intravenous injection of Ketorolac 30 mg
Intervention MeSH terms: Ibuprofen; Ketorolac
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized controlled trial
Masking: Single (Participant)
Primary purpose: Treatment