What is the risk of delirium and hallucinations associated with ketorolac (Toradol) compared to opioids?

From the Guidelines

Ketorolac has a significantly lower risk of causing delirium and hallucinations compared to opioid medications, as evidenced by a multicenter, randomized controlled trial showing more patients in the opioid group reported adverse drug events, including serious ones, compared to those receiving ketorolac 1. When considering the management of acute pain, the risk of delirium and hallucinations is a critical factor, particularly in vulnerable populations such as the elderly or those with underlying cognitive impairment.

• The mechanism of action of ketorolac, which primarily involves peripheral inhibition of prostaglandin synthesis with minimal central nervous system penetration, contributes to its lower neuropsychiatric risk profile compared to opioids.
• Opioids, on the other hand, can cause delirium through their effects on multiple neurotransmitter systems, particularly their action on mu-opioid receptors and interaction with dopamine pathways.
• A study by Innes et al, as referenced in 1, demonstrated that patients receiving opioids had a higher incidence of adverse drug events, including serious ones, compared to those receiving ketorolac, highlighting the increased risk associated with opioid use.
• While ketorolac may be preferred for managing acute pain in certain populations due to its lower risk of delirium and hallucinations, it is essential to carefully consider its own significant risks, including gastrointestinal bleeding, renal impairment, and cardiovascular effects, particularly in elderly patients or those with comorbidities.
• The typical dosing of ketorolac, usually 15-30mg IV/IM every 6 hours with a 5-day maximum duration, should be adhered to, and patients should be closely monitored for any adverse effects.

From the Research

Risk of Delirium and Hallucinations

• The risk of delirium and hallucinations from ketorolac vs opioid is not directly compared in the provided studies.
• However, the studies suggest that ketorolac has a different side effect profile compared to opioids, with a lower risk of respiratory depression, constipation, and addiction 2, 3, 4.
• Ketorolac has been associated with gastrointestinal bleeding, platelet inhibition, and renal impairment, but the incidence of these adverse events is generally lower than with opioids 2, 5.
• There is no mention of delirium and hallucinations as a common side effect of ketorolac in the provided studies.
• Opioids, on the other hand, are known to have a higher risk of delirium and hallucinations, especially in elderly patients or those with a history of substance abuse 3, 4.

Comparison of Ketorolac and Opioids

• Ketorolac has been shown to have similar analgesic efficacy to opioids, such as meperidine and morphine, in some studies 3, 6.
• However, ketorolac may have a slower onset of action and a higher risk of gastrointestinal side effects compared to opioids 3, 6.
• The choice between ketorolac and opioids should be based on individual patient factors, such as medical history, current medications, and potential side effects 2, 5, 4.

Clinical Implications

• Ketorolac may be a useful alternative to opioids for patients with acute pain who are at risk of opioid-related side effects or addiction 2, 3, 4.
• However, ketorolac should be used with caution in patients with a history of gastrointestinal bleeding, renal impairment, or platelet inhibition 2, 5.
• Further studies are needed to fully compare the risks and benefits of ketorolac and opioids in different patient populations 6, 4.