One of your surgeons writes an order for a continuous IV infusion of ketorolac for a post-op orthopedic patient. He wants a 30mg IV 'bolus', followed by a continuous infusion of 2-4 mg/hour. The patient is a 32 y/o AD member s/p arthroscopic knee surgery (ACL repair). He's in good health, on no other chronic medications, and has no significant medical history. While an inpatient, he's also receiving cefazolin 1gm IVPB q8h x 2 doses and morphine sulfate 2-5 mg IM q3-4h as needed for pain. The physician states this infusion will provide some 'opiate sparing' effects.

      Do you fill the order? Is this an appropriate dose and route of administration for ketorolac?

Probably yes, BUT there is very limited published data regarding this drug via this route and at this dose. Ketorolac is the only currently available injectable nonsteroidal anti-inflammatory drug (NSAID). It is also available as a 10mg oral tablet for SHORT-TERM use as continuation therapy after the IV/IM product (NTE 5 days total therapy). Ketorolac has a number of serious side effects and prominent warnings in its' package insert. They are summarized below:

KETOROLAC is CONTRAINDICATED:

- as prophylactic analgesic before any major surgery

- intraoperatively when hemostasis is critical because of the increased risk of bleeding.

- for intrathecal or epidural administration due to its alcohol content

- in labor and delivery because it may adversely affect fetal circulation and inhibit uterine contractions and in nursing mothers because of the potential adverse effects of prostaglandin-inhibiting drugs on neonates.

- in patients with active peptic ulcer disease, recent gastrointestinal bleeding or perforation, or with a history of peptic ulcer disease or gastrointestinal bleeding.

- in patients with advanced renal impairment or at risk for renal failure due to volume depletion.

- in patients with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis or those at high risk of bleeding.

- in patients with previously demonstrated hypersensitivity to ketorolac tromethamine or allergic manifestations to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs).

- in patients with currently receiving ASA or other NSAIDs because of the cumulative risk of inducing serious NSAID-related side effects.

KETOROLAC ORAL is indicated only as continuation therapy to KETOROLAC IV/IM and the combined duration of use of KETOROLAC IV/IM and KETOROLAC ORAL is not to exceed 5 days because of the increased risk of serious adverse events.

KETOROLAC, a nonsteroidal anti-inflammatory drug (NSAID), is indicated for the short-term (up to 5 days) management of moderately severe acute pain that requires analgesia at the opioid level. It is NOT indicated for minor or chronic painful conditions.

The recommended total daily dose of KETOROLAC ORAL (maximum 40 mg) is significantly lower than for KETOROLAC IV/IM (maximum 120 mg). Dosage should be adjusted for patients 65 years or older, for patients under 50 kg (110 lbs) of body weight (see DOSAGE AND ADMINISTRATION ) and for patients with moderately elevated serum creatinine. Doses of KETOROLAC IV/IM are not to exceed 60 mg (total dose per day) in these patients.

All NSAIDs may cause gastrointestinal irritation, dyspepsia, nephrotoxicity, decreased platelet function, prolonged bleeding, etc. Histamine 2 receptor blockers (ex. ranitidine) may help with the dyspepsia but do NOT prevent NSAID-induced erosions or bleeding. In general, H2RAs will heal NSAID-induced ulcers once they occur. Misoprostol is approved for prevention of NSAID-induced ulcers. Limited short term studies conclude proton pump inhibitors may also be effective but longer term studies need to be done. PPIs do not have the indication for prevention of NSAID-induced ulcers.

From MICROmedex:

Post-surgical pain:

In a comparison of ketorolac and morphine for patient-controlled analgesia (PC) after surgery, ketorolac-treated patients required more morphine rescue (5 to 10 milligrams (mg) intramuscularly) than did PCA morphine patients. All patients were given PCA devices that delivered bolus doses of 1 milliliter (mL) with a lockout interval of 8 minutes. PCA cartridges held 30 mL of drug. There were 3 treatment groups: an intravenous loading dose of ketorolac 30 mg, plus continuous infusion of ketorolac 2.5 mg/hour and the PCA device with ketorolac 2 mg/mL (KI, na); a loading dose of ketorolac 30 mg, continuous infusion of placebo, and the PCA device with ketorolac 4 Mg/mL (K, nc); or, a loading dose of morphine 4 mg, continuous infusion of placebo, and the PCA device with morphine 1 mg/mL (M, ng). The study ended 24 hours after the loading dose or when the PCA cartridge was empty, whichever occurred first. There were no statistically significant differences among groups for pain intensity. Pain relief scores were better for KI and M than for K. Sedation was greater in the M group at baseline and at 2 hours, but there were no significant differences at later times. Ketorolac had a morphine-sparing effect, in that total average intake was 6.0 and 6.2 mg for the KI and K groups and 33.3 mg for the M group. The median time using the PCA devices was shorter in the KI and K groups (8.5 and 9.4 hours) than in the M group (14.0 hours). It was speculated that the slow onset of ketorolac relative to that of morphine caused patients to activate their PAC devices more often in an attempt to achieve pain relief; a more suitable lockout time might have been 20 minutes (O'Hara et al, 1997).

Cancer pain: