Is Toradol (ketorolac) safe to use for acute chest wall pain in a patient with liver failure and ascites, with normal renal function?

Toradol (Ketorolac) Should Not Be Given to This Patient

Toradol is contraindicated in patients with cirrhosis and ascites, regardless of renal function, due to high risk of acute renal failure, hyponatremia, and diuretic resistance. 1

Why NSAIDs Are Contraindicated in Liver Failure with Ascites

The European Association for the Study of the Liver (EASL) explicitly states that NSAIDs—including ketorolac (Toradol), ibuprofen, aspirin, and indomethacin—should not be used in patients with cirrhosis and ascites. 1 The mechanism of harm is inhibition of renal prostaglandin synthesis, which leads to:

• Acute renal failure due to reduced renal perfusion 1
• Hyponatremia from impaired free water excretion 1
• Diuretic resistance, making ascites management more difficult 1

The Korean Association for the Study of the Liver reinforces this, recommending discontinuation of NSAIDs as first-line treatment for all grades of ascites. 1

The eGFR of 89 Does Not Make NSAIDs Safe

While the patient's current eGFR is normal, this does not protect against NSAID-induced acute kidney injury in the setting of cirrhosis with ascites. Cirrhotic patients have:

• Baseline renal hypoperfusion from splanchnic vasodilation and effective arterial underfilling 1
• Dependence on prostaglandins to maintain renal blood flow 1
• High susceptibility to rapid deterioration when prostaglandin synthesis is blocked 1

The FDA label for ketorolac confirms it should be used with caution in hepatic impairment, noting risks of severe hepatic reactions including fulminant hepatitis and hepatic failure. 2

Safe Alternatives for Acute Chest Wall Pain

First-Line: Acetaminophen (Paracetamol)

• Acetaminophen at reduced doses (2 grams daily maximum) is the preferred analgesic in patients with liver disease and ascites 3, 4
• It avoids the platelet impairment, gastrointestinal toxicity, and nephrotoxicity associated with NSAIDs 3
• Short-term use at therapeutic doses does not deplete glutathione stores to critical levels in chronic liver disease 3
• The half-life may be prolonged, but cytochrome P-450 activity is not increased at recommended doses 3

Second-Line: Opioids (with caution)

If acetaminophen is insufficient:

• Fentanyl, sufentanil, or remifentanil have pharmacokinetics that appear unaffected in hepatic disease 4, 5
• Buprenorphine exhibits a safe pharmacological profile in hepatic impairment 5
• Morphine, hydromorphone, or oxycodone can be used but require dose reduction and longer dosing intervals due to increased oral bioavailability and decreased clearance 4
• Avoid codeine and tramadol, as they rely on hepatic biotransformation to active metabolites, which may be impaired 4
• Avoid pethidine (meperidine), as toxic metabolites accumulate 4

Critical Monitoring with Opioids

All opioids can precipitate or aggravate hepatic encephalopathy in severe liver disease, requiring cautious use and careful monitoring. 4

Common Pitfalls to Avoid

• Do not assume normal renal function protects against NSAID toxicity in cirrhosis with ascites—the risk is driven by altered renal hemodynamics, not baseline GFR 1
• Do not use selective COX-2 inhibitors as an alternative—while preliminary data suggested they might be safer, further studies are needed to confirm safety 1
• Do not use aspirin, even at low doses, as it carries the same risks as other NSAIDs in this population 1
• Do not use compound analgesics containing aspirin or NSAIDs with acetaminophen 5

Clinical Algorithm for Pain Management

1. Start with acetaminophen 500-650 mg every 6-8 hours (maximum 2 grams daily) 3, 4
2. If inadequate pain control, add a short-acting opioid (fentanyl or buprenorphine preferred) at reduced doses 4, 5
3. Monitor closely for hepatic encephalopathy with any opioid use 4
4. Avoid all NSAIDs including ketorolac regardless of renal function 1