A 23 y/o otherwise healthy patient is admitted to the ICU with multiple fractures and injuries due to a motorcycle accident. After several surgeries, all his fractures are set and healing. After several days of opioids to control his pain, he develops significant constipation from the opiates. The team decides to switch him to injectable ketorolac q6h, which provides adequate relief of his post-op pain. Three days later, the patient, recovering nicely, is transferred to the ward. The intern wants to continue his ketorolac orally (10mg po TID) for the duration of his hospital stay, expected to be another 5-7 days.

Do you concur or not? Why or why not?
 

No.

I don't mean to insult anyone's intelligence with this Pearl. I thought it was time to refresh everyone's memory regarding all the "black box" warnings for ketorolac [Toradol®]. The reason it's come to mind is we had an adverse drug reaction reported where a patient with a GI bleed received ketorolac for pain control. Let's go over, briefly, the contraindications and precautions for using ketorolac.

CONTRAindications include:

- Hypersensitivity (no explanation needed)
- Complete or partial syndrome of nasal polyps, angioedema, and bronchospastic reactivity to aspirin or other anti-inflammatory agents (triad predisposes to severe allergic reactions)
- History of or active peptic ulcer disease, gastrointestinal bleeding, or perforations (significant bleeding risk based on anti-platelet actions and direct toxicity to GI mucosa. All NSAIDs (except maybe the COX2 agents) confer a greater risk of GI ulceration and bleeding compared to placebo)
- Advanced renal impairment (ALL NSAIDs are nephrotoxic due to inhibition of vasodilatory prostaglandins in the kidney)
- Risk for renal failure due to volume depletion (see above)
- Labor/delivery (greater risk of bleeding)
- Nursing women (excreted in breast milk. Prostanglandin inhibition can have adverse effects in the infant.)
- Preoperatively or intraoperatively for analgesia (increased risk of bleeding)
- Patients receiving aspirin or other nonsteroidal anti-inflammatory agents (additive risk of GI toxicity)
- Epidural or intrathecal route of administration
- Concurrent use with probenecid (inhibits the tubular secretion of organic acids. Increases the half-life and AUC or ketorolac 2-3 times when given in combination)
- Suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, and patients at high risk of bleeding (see above)
- Total duration of parenteral and/or oral therapy should not exceed 5 days

Precautions include:

Hypertension or cardiac conditions aggravated by fluid retention and edema
History of coagulation defects
Therapeutic doses of anticoagulants
Impaired liver function or history of liver disease
Impaired renal function, dehydration, diuretic therapy
Bleeding of ocular tissues, including hyphemas, after ocular surgery (ophthalmic ketorolac)
Potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, other

Dosing:

Injectable: The intramuscular dose for patients less than 65 years of age is 30 milligrams (mg) every 6 hours; the maximum daily dose is 120 mg. The dose for patients 65 years of age and older, renally impaired, or weighing less than 50 kilograms is 15 mg every 6 hours; the maximum daily dose is 60 mg.
The safety and efficacy of parenteral and oral ketorolac has NOT been established in patients less than 16 years old.

Oral: For patients less than 65 years of age, the first oral dose is 20 milligrams if the patient received a single 60 milligram intramuscular dose, a single 30 milligram intravenous dose or multiple 30 milligram doses. This is followed by ketorolac 10 milligrams every 4 to 6 hours as needed. The oral dose should not exceed 40 milligrams per day. In patients greater than 65 years, renally impaired patients or patients weighing less than 50 kilograms, the first and subsequent doses are 10 milligrams every 4 to 6 hours, not to exceed 40 milligrams per day. Again, combined use of ketorolac parenteral and oral should not exceed 5 days.

Ketorolac is a good non-opioid analgesic but it comes with it's own concerns. Choose patients carefully and limit the total use (injectable and oral) to a total of 5 days total therapy to minimize the risk of adverse events.