Study of Whether 15 mg Dose of Ketorolac IV is as Effective as a 30 mg Dose.

Study Overview
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Brief Summary
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The primary aim of this study is to show the non-inferiority of 15 mg intraoperative dose of ketorolac as compared to the standard 30 mg ketorolac by looking at the VAS scores 4 hours after an adult spine surgery.

Detailed Description
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Opioids have traditionally been the cornerstone of acute postoperative pain management. Problematic side effects such as nausea, vomiting, ileus, urinary retention, excess sedation, and respiratory depression are significant disadvantages with the use of opioids. Alternative treatments have been sought. The concept of adding a nonsedating non opioid analgesic agent is appealing and has been validated by previous studies. Nonsteroidal anti-inflammatory drugs (NSAID) are nonsedating and combine analgesic and anti-inflammatory properties ideal for pain after surgery. Ketorolac is a potent intravenous nonsteroidal anti-inflammatory drug (NSAID), and a non selective cyclooxygenase inhibitor which mediates pain, inflammation and fever. It has been evaluated and used for treatment of moderate to severe pain including postoperative pain. Although intravenous route is not approved by Health Canada, its use is supported in medical literature and clinical practice. Previous studies have demonstrated the effectiveness of standard 30 mg intravenous ketorolac as an adjunct to opioids for postoperative pain relief. Standard parenteral dose recommended by manufacturer for healthy non elderly population is 30 mg based on a number clinical trials. Alberta Health Services (AHS) Pharmacy formulary has approved the intravenous use of ketorolac in the dosage range of 10-30 mg depending the patient's weight and medical comorbidities. NSAIDs, including ketorolac, have an analgesic ceiling effect in which higher doses do not provide any additional pain relief but may increase the likelihood of side effects. Single dose IM ketorolac have been studied in the past showing no difference in analgesia with the 30 and 90 mg dose. Because of risk of drug toxicity and unwanted side effects, patients should be given the lowest effective ketorolac dose. Low dose ketorolac was studied in the adolescents undergoing spine surgery and showed that dose of 0.2mg/kg (11mg) provides supplemental analgesia postoperatively. However, there were no previous studies found on review of the literature using medline search that look at parallel comparison between intraoperative doses of ketorolac in terms of efficacy and safety profile.

Official Title
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Intraoperative Ketorolac Dose of 15 mg Versus the Standard 30 mg on Early Postoperative Pain After Spine Surgery: A Randomised, Blinded, Non-Inferiority Trial

Conditions
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Pain, Pain, Postoperative

Intervention / Treatment
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* Drug: Ketorolac Tromethamine
* Drug: Ketorolac Tromethamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients booked for 1-2 level spine laminectomies and/or decompression Adult 18 - 65 years Weight of 50 - 110 kg Exclusion Criteria: Previous lumbar laminectomy Current anticoagulant use with INR > 1.2 Narcotic use > 4 weeks Known allergy or sensitivity to NSAID or morphine Renal insufficiency with creatinine >100 umol/L Known liver disease History of gastrointestinal bleeding Pregnancy, history of bronchial asthma NSAID use 2 days before surgery.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 15 mg ketorolac IV<br> | Drug: Ketorolac Tromethamine<br>* 15 mg ketorolac IV as a bolus 30 minutes before closure of surgery.<br>* Other names: Toradol;|
| Active Comparator: 30 mg ketorolac IV<br> | Drug: Ketorolac Tromethamine<br>* 30 mg ketorolac IV as a bolus 30 minutes before closure of surgery.<br>* Other names: Toradol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Score | To show the non-inferiority of 15 mg intraoperative dose of ketorolac as compared to the standard 30 mg ketorolac by looking at the VAS scores 4 hours after an adult spine surgery. Minimum clinically significant decrease in VAS pain score is 18 mm. | Four hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morphine Usage After Surgery | A 10 mg decrease in morphine use in 24 hours is considered clinically significant. | 8 hours and 24 hours after surgery | 
| Morphine Adverse Effects | Presence of morphine-related adverse effects such as sedation, nausea, vomiting, respiratory depression, and pruritus. | First 24 hours | 
| Postoperative Bleeding | Hemoglobin levels will be measured before surgery and 24 hours surgery. | 24 hours after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Postoperative, Ketorolac, Anti-Inflammatory Agents, Non-Steroidal, Intraoperative Care