What is the efficacy and safety of administering intravenous (IV) acetaminophen and intravenous (IV) ketorolac together?

From the Guidelines

Combining IV acetaminophen and IV ketorolac is both effective and generally safe for multimodal pain management, as evidenced by the most recent and highest quality study available 1. This combination leverages complementary mechanisms of action—acetaminophen works centrally while ketorolac acts peripherally as an NSAID—providing superior pain relief compared to either medication alone. Some key points to consider when using this combination include:

• Typical dosing is acetaminophen 1000 mg IV every 6 hours (maximum 4000 mg/day) and ketorolac 30 mg IV initially, then 15-30 mg every 6 hours (not exceeding 5 days of use) 1.
• This combination is particularly valuable for post-surgical pain, reducing opioid requirements and associated side effects.
• Certain precautions are necessary: ketorolac should be avoided in patients with renal impairment, bleeding disorders, or history of GI bleeding, and used cautiously in the elderly (reduced dose of 15 mg recommended) 1.
• Acetaminophen dosing should be reduced in patients with hepatic impairment.
• Monitor for potential side effects including renal dysfunction, bleeding, and hepatotoxicity, especially in high-risk patients or with prolonged use. The use of this combination is supported by various studies, including one that found the combination of NSAIDs with acetaminophen improves the quality of pain relief compared to the appointment of each of the drugs separately 1. Additionally, a study found that perioperative administration of Ibuprofen IV 800 mg every 6 h decreased morphine requirements and pain score and it has been found safe and well tolerated 1. However, it is essential to consider the potential risks and benefits of this combination, particularly in patients with certain comorbidities or taking other medications. Overall, the combination of IV acetaminophen and IV ketorolac can be a valuable component of balanced analgesia strategies when used appropriately with attention to patient-specific risk factors.

From the Research

Efficacy of IV Acetaminophen and IV Ketorolac

• The study 2 compared the effectiveness of intravenous acetaminophen with that of ketorolac in pre-hospital pain control and found no statistically significant differences between the two groups in terms of delta pain score (pain reduction).
• Another study 3 reviewed the literature on intravenous acetaminophen and intravenous ketorolac for management of pediatric surgical pain and found that both medications can be used as part of a multimodal approach to pain management.

Safety of IV Acetaminophen and IV Ketorolac

• The study 4 noted that acetaminophen is well tolerated, but lower doses should be used in patients with advanced hepatic disease, malnutrition, or severe alcohol use disorder.
• The same study 4 also noted that nonsteroidal anti-inflammatory drugs (NSAIDs), such as ketorolac, should be used with caution in patients with a history of gastrointestinal bleeding, cardiovascular disease, or chronic renal disease.
• The study 2 found that both ketorolac and acetaminophen could be administered for pain management in prehospital settings, but contraindications should be considered.

Combination Therapy

• The study 5 discussed the use of intravenous acetaminophen as part of a multimodal pain therapy strategy, including combination with other agents such as opioids.
• The study 3 also discussed the use of intravenous acetaminophen and ketorolac as part of a multimodal approach to pain management in pediatric surgical patients.
• The study 4 noted that adjunctive medications, such as muscle relaxants, may be added as appropriate for specific conditions if the recommended dose and schedule of first-line agents are inadequate.