What are the risks and side effects of frequent Toradol (ketorolac) injections, especially in patients with a history of peptic ulcer disease, renal disease, or bleeding disorders, and in those over 65 years old or with cardiovascular disease?

Risks and Side Effects of Frequent Toradol (Ketorolac) Injections

Frequent Toradol injections carry substantial risks of gastrointestinal bleeding, acute renal failure, and operative site hemorrhage, with these risks escalating dramatically when used beyond 5 days, at doses exceeding 60 mg/day, or in patients over 65 years old—making it contraindicated in patients with peptic ulcer disease, renal impairment, or bleeding disorders. 1

Critical Duration and Dosing Limitations

• Ketorolac should never be used for more than 5 days due to dose-dependent increases in serious adverse events, particularly gastrointestinal bleeding and renal toxicity 1, 2
• The FDA label explicitly warns that prolonged therapy beyond 5 days markedly increases the risk of serious complications 1
• Dosages exceeding 60 mg/day are associated with significantly higher rates of clinically serious gastrointestinal bleeding, especially in elderly patients 1

Gastrointestinal Risks: The Most Common Serious Complication

• In patients without prior peptic ulcer disease (PUB) who are under 65 years old, the risk of serious GI bleeding is 0.4% at ≤60 mg/day but jumps to 4.6% at doses >120 mg/day 1
• For patients ≥65 years without PUB history, the risk increases from 1.2% at ≤60 mg/day to 7.7% at doses >120 mg/day 1
• Patients with a history of peptic ulcer disease face catastrophic risks: 25% incidence of serious GI bleeding in those ≥65 years receiving >120 mg/day 1
• Gastric ulcer perforation can occur within just 4 days of treatment, even in patients with no previous history of peptic ulcer disease 3
• Ketorolac is absolutely contraindicated in patients with active peptic ulcer disease or history of gastrointestinal bleeding 4, 5

Renal Toxicity: Reversible but Potentially Severe

• Acute renal failure is a well-documented complication of ketorolac use, though usually reversible after drug discontinuation 1, 2, 6
• Patients with pre-existing renal impairment, volume depletion, heart failure, or cirrhosis are at particularly high risk because they depend on prostaglandin-mediated renal perfusion 4, 7
• Hyperkalemia can develop alongside acute renal failure in susceptible patients 6
• The American Geriatrics Society explicitly states NSAIDs like ketorolac should be avoided in persons with renal disease due to risk of decreased renal perfusion, volume-dependent renal failure, interstitial nephritis, and nephrotic syndrome 7
• Approximately 2% of all patients taking NSAIDs discontinue them due to renal complications, with higher rates in those with pre-existing renal disease 7

Bleeding and Hematologic Complications

• Ketorolac inhibits platelet function and can cause postoperative wound hemorrhage, sometimes requiring blood transfusion 1
• The combination of ketorolac with anticoagulants (warfarin, heparin), antiplatelets, or SSRIs/SNRIs significantly increases hemorrhagic complications 4, 8
• Rare but serious hematologic effects include agranulocytosis, aplastic anemia, and hemolytic anemia 1
• Ketorolac is contraindicated in patients with compromised hemostasis or bleeding disorders 2

Cardiovascular Risks

• NSAIDs including ketorolac can cause or worsen hypertension and precipitate heart failure 4
• Patients with cardiovascular disease or at risk for cardiovascular complications should avoid ketorolac 4
• The drug should be discontinued if hypertension develops or worsens during treatment 4

Special Population Risks

Elderly Patients (≥65 years)

• The elderly face dramatically elevated risks across all adverse event categories, particularly GI bleeding 1
• Even with apparently normal serum creatinine, patients over 75 years require dose reduction due to increased risk of adverse events 8
• The American Geriatrics Society 2019 Beers Criteria recommends avoiding ketorolac in older adults due to increased risk of GI bleeding and acute kidney injury 4

Patients with Cardiovascular Disease

• Ketorolac can worsen heart failure and should be avoided in patients with HFrEF 4
• The drug impairs blood pressure control and can cause nephrotoxicity and hyperkalemia 4

Patients on Anticoagulation or Antiplatelet Therapy

• Combination with anticoagulants, antiplatelets, thrombolytics, other NSAIDs, SSRIs, or SNRIs is explicitly contraindicated 4, 8
• This combination creates unacceptably high bleeding risk 4

Life-Threatening Reactions

• Anaphylactic and anaphylactoid reactions can occur, potentially fatal 1, 9
• Ketorolac may trigger allergic or hypersensitivity reactions, similar to other NSAIDs 2
• The drug is contraindicated in patients with hypersensitivity to aspirin or other NSAIDs 2

Hepatic Toxicity

• Liver failure has been reported, though less common than GI or renal complications 1
• Liver function studies should be monitored, and ketorolac discontinued if values increase 3 times the upper limit of normal 4

Safer Alternatives for High-Risk Patients

• Acetaminophen up to 3 grams daily is the preferred first-line alternative in elderly patients or those with renal impairment, peptic ulcer disease, or bleeding disorders 5, 7, 8
• Topical NSAIDs provide localized pain relief with minimal systemic absorption and negligible renal or GI effects 7, 8
• If systemic NSAID use is unavoidable, ketorolac should be prescribed at the lowest effective dose for the shortest duration possible (maximum 5 days) 1, 2

Essential Monitoring Requirements

• Baseline and periodic monitoring should include: blood pressure, BUN, creatinine, liver function studies, CBC, and fecal occult blood 4
• For patients requiring NSAID therapy, monitoring should occur weekly for the first 3 weeks, then monthly 7
• Patients should be educated to recognize signs of bleeding, renal dysfunction, and other serious adverse effects 4