Continuing Education Activity
Ketorolac is a medication used in the management and treatment of acute moderate to severe pain. It is in the nonsteroidal anti-inflammatory drug class. This activity outlines the indications, actions, and contraindications for ketorolac as a valuable agent in treating acute pain. It will also highlight the mechanism of action, adverse event profile, and other key factors (e.g., contraindications, monitoring, toxicity) pertinent for members of the interprofessional team in treating patients with acute moderate to severe pain.
- Review the indications and appropriate dosing for ketorolac.
- Identify the most common adverse effects of ketorolac.
- Summarize the contraindications for ketorolac.
- Outline the importance of collaboration and coordination among the interprofessional team to enhance patient care when dosing, monitoring, and selecting appropriate patients for the use of ketorolac to improve outcomes for patients with acute moderate to severe pain.
Ketorolac is an FDA-approved medication used in the treatment of moderate to severe acute onset pain. It is in the nonsteroidal anti-inflammatory drug (NSAID) drug class. Ketorolac is versatile, as it is available in multiple-dose forms: oral, nasal spray, IV, or IM. It is commonly used postoperatively for pain management. In combination with opioids, Ketorolac results in a significant decrease in opioid requirement and lowers the incidence of adverse effects such as vomiting and decreased gastrointestinal motility. In children, ketorolac is as effective as major opioid analgesics. Thus, it is a great pain management alternative or adjunct for pediatric (off-label for acute moderate to severe pain) or adult individuals for whom there is concern regarding opioid dependence. In the emergency department setting, it is successful in treating musculoskeletal pain, migraines, and sickle cell crisis. Lastly, NSAIDs such as ketorolac are effective for pain associated with cancer that has metastasized to bones.
Mechanism of Action
The exact mechanism for ketorolac is not known. Ketorolac, like other NSAIDs, blocks cyclooxygenases (COX), which are enzymes that convert arachidonic acid into prostaglandins, prostacyclin, and thromboxane. The inhibition of these substances decreases pain, fever, and inflammation. Ketorolac does so by inhibiting both cyclooxygenase-1 and cyclooxygenase-2. It has higher demonstrated potency than most other NSAIDs.
The administration of ketorolac is via oral, nasal spray, IV, or IM routes. The oral version should be administered only following IV or IM ketorolac. Ketorolac administration should not be for longer than five days given an increased risk of cardiac thrombotic events, renal failure, peptic ulcers, and increased risk of bleeding beyond this point.
IV and IM dosing for adults are recommended at 30 mg single dose or 30 mg every 6 hours, not exceeding 120 mg in 24 hours.
The recommendation for oral dosing in adults is a 20 mg single dose after IV or IM therapy, then 10 mg every 4 to 6 hours, not exceeding 40 mg in 24 hours.
Half-life: 5.6 hours for a single 30 mg IM or single 10 mg oral dose
Pediatric Dosing (off label for acute moderate to severe pain; ketorolac has no approval for use under the age of 17)
Less than 2 years:
2 to 16 years:
- Single-dose: 0.5 mg/kg IV/IM once; not to exceed 15 mg
- Multiple-dose: 0.5 mg/kg IV/IM q6h; not to exceed 5 days
Over 16 years, less than 50kg:
- IV: 15 mg in a single dose or 15 mg every 6 hours; do not exceed 60 mg/day
- IM: 30 mg in a single dose or 15 mg every 6 hours; do not exceed 60 mg/day
- PO: 10 mg once after IV/IM therapy, then 10mg every 6 hours; do not exceed 40 mg/day
Over 16 years, greater than 50 kg:
- Adult dosing as described above
Like other NSAIDs, ketorolac shows correlations with significant gastrointestinal (GI), renal, and cardiovascular risks. In the GI system, it can cause peptic ulcers and/or perforations of the stomach or intestines. In an extensive pooled data set, all NSAIDs, including COX2 inhibitors, were shown to increase the relative risk for peptic ulcers, with ketorolac having the highest RR at 11.5. Because of its antiplatelet properties, ketorolac increases the risk of GI bleeding. It also increases postoperative bleeding risk when compared with opioids.
Ketorolac can cause an increased risk of cardiovascular thrombotic events, myocardial infarctions, and hemorrhagic stroke. Heart failure is a significant risk factor for the adverse effects of NSAIDs. A large case-controlled study spanning multiple European countries tested the risk of heart failure for 27 different NSAIDs, including 92,163 hospital admissions for heart failure and 824,6403 control patients. Seven NSAIDs were shown to increase the risk of heart failure, with ketorolac having the highest odds ratio of 1.83 vs. the lowest odds ratio of 1.16 for naproxen. Lastly, ketorolac can cause renal damage and failure. In a population-based case-controlled study conducted in southern Italy, ketorolac was shown to have the highest odds ratio of increasing the cumulative risk for chronic kidney disease (or 2.58 after 0 to 90-day use vs. 1.08 for any NSAID).
Adverse effects increase significantly when used in higher doses, for durations over five days, and in patients who are over 75 years old.
Ketorolac is contraindicated in individuals who have adverse reactions or are allergic to NSAIDs. It is not recommended to be given intraoperatively or preoperatively due to the increased risk for bleeding. It is not recommended during labor and delivery, as it negatively affects fetal circulation and decreases uterine contraction. In patients with renal disease or renal failure, ketorolac is contraindicated because it may increase fluid retention and worsen renal function. GI-related contraindications for ketorolac include patients with active peptic ulcer disease, recent GI bleed, or GI perforations. Extreme caution is necessary when administering ketorolac in the geriatric population.
Due to the increased bleeding risk, patients should be closely monitored for GI bleeding; the recommendation is to obtain a complete blood count (CBC) at baseline and periodically monitored. Since this medication primarily undergoes hepatic metabolism, liver function tests should be checked at baseline and regularly monitored, especially in patients with liver compromise. Renal function assessment is necessary via creatinine and urine output before administering this medication and followed closely, given that ketorolac is excreted renally and can cause renal damage.
High quantities or prolonged use of ketorolac can lead to hepatotoxicity and renal toxicity. Ketorolac can cause multiple skin issues, such as toxic epidermal necrolysis. In combination with lithium, it increases the risk of lithium toxicity, given that lithium also gets excreted renally.
Enhancing Healthcare Team Outcomes
In light of the present opioid epidemic in the United States, it is essential to seek alternative pain reduction methods that either reduce or obviate the need for administering opioids. Higher-risk populations for opioid abuse include young males, individuals with a history of misuse, and individuals with significant mental health histories. Clinicians should make a deliberate effort to identify patients in these populations and, as a whole, decrease their opioid prescribing practices where possible. When examining emergency room prescription practices, the recent general trend shows a decrease in opioid prescriptions, but much room remains for improvement.
Ketorolac has demonstrated effectiveness equal to that of morphine when used postoperatively. It has significant potential to be useful in emergency room settings for moderate to severe pain, for which opioids are often regularly prescribed. When considering opioids for acute pain, a multimodal approach can be beneficial to decrease opioid administration to the extent possible. An interprofessional team can also be helpful to correctly identify individuals who might benefit from alternative pain management medications or interventions and coordinate or assist in implementing these alternate strategies. Given the relatively high toxicity profile of ketorolac and the fact that the oral form is recommended for administration only after IV or IM dosage, highly fluid inter-professional collaboration is ideally maintained to reduce adverse outcomes and ensure the right individuals receive this medication.
Health care providers are first and foremost responsible for identifying individuals who could benefit from non-opioid pain medications, both in the emergency department and in the postoperative setting. Recommendations are to include pharmacists in this process, given their expertise in medication pharmacokinetics and proper dosing. Pharmacists can also ensure that adverse drug-to-drug interactions are decreased and help decide which patients would be ideal candidates for ketorolac. Nurses play a vital role, given that they spend the most amount of time with patients and are the individuals responsible for administrating ketorolac in its oral, IV, and IM forms. They assist in monitoring for toxicity, as well. Nurses can also serve as a liaison between the ordering provider and the patient, informing providers of any adverse effects and advocating for patients who might be appropriate candidates for ketorolac. Both nurses and pharmacists are responsible for reporting any concerns or issues to the rest of the health care team.
Coordination of communication between all the above individuals on the interprofessional team is essential to ensure that the patient receives the proper care regarding this medication, thereby optimizing outcomes with its use. [Level 5]