Is it safe to give Toradol (ketorolac) to a patient with elevated serum creatinine indicating impaired renal function?

Toradol (Ketorolac) Should Be Avoided in Patients with Elevated Creatinine

Ketorolac is contraindicated in patients with elevated serum creatinine indicating advanced renal impairment and should be used with extreme caution, if at all, in patients with any degree of renal dysfunction. 1

FDA Contraindications and Warnings

• Ketorolac is absolutely contraindicated in patients with serum creatinine concentrations indicating advanced renal impairment. 1

• The FDA label explicitly states that ketorolac should be used with caution in patients with impaired renal function or a history of kidney disease because it is a potent inhibitor of prostaglandin synthesis. 1

• Patients with underlying renal insufficiency are at increased risk of developing acute renal decompensation or failure, and the risks and benefits must be assessed prior to administration. 1

• Ketorolac and its metabolites are eliminated primarily by the kidneys, and patients with reduced creatinine clearance will have diminished drug clearance, leading to accumulation and increased toxicity risk. 1

Guideline Recommendations Against NSAIDs in Renal Impairment

• The European Society of Cardiology guidelines explicitly state that NSAIDs or COX-2 inhibitors are not recommended in patients with heart failure or renal dysfunction, as they increase the risk of worsening renal function and hospitalization. 2

• NSAIDs should be avoided in people with chronic kidney disease (CKD) with GFR <30 mL/min/1.73 m², and prolonged therapy is not recommended even in patients with GFR <60 mL/min/1.73 m². 2

• The KDOQI guidelines emphasize avoiding NSAIDs in patients taking RAAS blocking agents (ACE inhibitors, ARBs) due to compounded renal risk. 2

Clinical Evidence of Ketorolac-Induced Renal Failure

• Acute renal failure has been documented after even a single intramuscular dose of ketorolac in patients with compromised renal perfusion. 3

• A large retrospective cohort study of over 10,000 patients found that ketorolac use for more than 5 days was associated with a doubled risk of acute renal failure compared to opioids (rate ratio 2.08,95% CI 1.08-4.00). 4

• Multiple case reports document reversible oliguric renal insufficiency with short-term ketorolac administration, with serum creatinine increasing from baseline mean of 106 μmol/L to peak values of 256 μmol/L. 5

• Irreversible renal failure has been reported in vulnerable populations, particularly in patients with conditions causing compromised renal perfusion. 6

Mechanism of Renal Toxicity

• Ketorolac inhibits prostaglandin synthesis, which is critical for maintaining renal blood flow in states of decreased renal perfusion. 1

• In patients with impaired renal function, renal prostaglandins play a compensatory role in maintaining renal perfusion; NSAID administration causes dose-dependent reduction in prostaglandin formation and secondary reduction in renal blood flow, precipitating overt renal decompensation. 1

• Acute renal failure, interstitial nephritis, and nephrotic syndrome have all been reported with ketorolac use. 1

Safer Alternative Analgesics for Renal Impairment

• For patients requiring strong analgesia with renal insufficiency (GFR <30 mL/min/1.73 m²), opioids with no active metabolites are preferred: fentanyl, sufentanil, and methadone. 2, 7

• Avoid meperidine, codeine, morphine, tramadol, and tapentadol in renal impairment due to accumulation of active metabolites and increased toxicity risk. 2, 7

• Hydrocodone, oxycodone, and hydromorphone may be used with caution and dose adjustment in renal insufficiency. 2

High-Risk Patient Populations

Patients at greatest risk for ketorolac-induced renal failure include those with: 1

• Pre-existing impaired renal function
• Heart failure
• Liver dysfunction
• Concurrent diuretic use
• Concurrent ACE inhibitor or ARB use
• Advanced age (elderly patients)
• Volume depletion or dehydration

Practical Clinical Approach

Before considering ketorolac in any patient with elevated creatinine:

1. Calculate the estimated glomerular filtration rate (eGFR) to accurately assess renal function beyond just the creatinine value. 7 A creatinine of 0.52 mg/dL may indicate mild impairment depending on age, gender, and muscle mass.

2. If eGFR is <60 mL/min/1.73 m², avoid ketorolac entirely and choose alternative analgesics. 2, 7

3. If eGFR is <30 mL/min/1.73 m², ketorolac is absolutely contraindicated. 2, 1

4. Even with normal baseline renal function, limit ketorolac duration to ≤5 days maximum, as risk of acute renal failure increases significantly beyond this timeframe. 4

Common Pitfalls to Avoid

• Do not rely solely on serum creatinine values, especially in elderly patients or those with low muscle mass, as creatinine underestimates renal dysfunction in these populations. 2

• Do not assume that short-term use is always safe—acute renal failure has occurred after a single dose in high-risk patients. 3

• Do not combine ketorolac with other nephrotoxic agents, diuretics, or RAAS inhibitors without extreme caution and close monitoring. 2, 1

• Do not continue ketorolac if any increase in creatinine is observed during therapy—discontinue immediately and monitor for recovery. 1, 5