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

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

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.

Study Overview

• Status: Unknown
• Conditions: Pain; Pain, Postoperative
• Intervention / Treatment: Drug: Ketorolac Tromethamine; Drug: Ketorolac Tromethamine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Recruiting
      • Foothills Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 15 mg ketorolac IV	Drug: Ketorolac Tromethamine; 15 mg ketorolac IV as a bolus 30 minutes before closure of surgery.; Other Names: Toradol; Drug: Ketorolac Tromethamine; 30 mg ketorolac IV as a bolus 30 minutes before closure of surgery.; Other Names: Toradol
Active Comparator: 30 mg ketorolac IV	Drug: Ketorolac Tromethamine; 15 mg ketorolac IV as a bolus 30 minutes before closure of surgery.; Other Names: Toradol; Drug: Ketorolac Tromethamine; 30 mg ketorolac IV as a bolus 30 minutes before closure of surgery.; Other Names: Toradol

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Calgary
• Investigators: Principal Investigator: Kaylene Duttchen, MD, University of Calgary - Department of Anesthesia; Principal Investigator: Melinda Davis, MD, University of Calgary - Department of Anesthesia

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Anticipated): September 1, 2011
• Study Completion (Anticipated): September 1, 2011

Study Registration Dates

• First Submitted: October 27, 2010
• First Submitted That Met QC Criteria: October 27, 2010
• First Posted (Estimate): October 29, 2010

Study Record Updates

• Last Update Posted (Estimate): October 29, 2010
• Last Update Submitted That Met QC Criteria: October 27, 2010
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Keywords: Anti-Inflammatory Agents, Non-Steroidal; Ketorolac; Pain, Postoperative; Intraoperative Care
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ketorolac; Ketorolac Tromethamine
• Other Study ID Numbers: 23237