It was another fine morning. We were finishing our first scheduled laparoscopic urologic surgery case when I received a Stat page to the operating room (OR). As I was reaching the OR, I could hear our famous urologist roaring at my resident. Apparently, my patient-compassionate resident had used ketorolac (Toradol; 30 mg IV) for postoperative pain control, and our surgical friend firmly believed that it would lead to renal failure or post-surgical bleed. I tried dodging his logic of so-called experience with my shield of scientific data leading to more noise pollution in the OR. The end result of our battle for Middle Earth was the formulation of the Eleventh Commandment by our respected colleague: “NO TORADOL for any of my patients EVER.” Currently, ketorolac is perhaps one of the leading causes of tense anesthesiologist-surgeon relationships, and it is briefly discussed in this chapter.

Ketorolac tromethamine (commercially available as Toradol) is a member of the pyrrole-pyrrole group of nonsteroidal anti-inflammatory drugs (NSAIDs). It is available for intravenous (IV) or intramuscular (IM) administration as 15 mg in 1 mL and 30 mg in 1 mL (60 mg in 2 mL) solution. It is also available in tablets of 10 mg for oral use. It is a peripherally acting analgesic agent that inhibits prostaglandin synthesis. The drug possesses no sedative properties, making it a good agent in the perioperative setting. The bioavailability with oral, IM, or IV use is 100%, with peak analgesic activity time of 2 to 3 hours via oral route and 1 to 2 hours when used parenterally. Ketorolac is highly protein bound; metabolized in the liver via hydroxylation and conjugation, and eliminated by the kidneys (60% metabolites, 40% parent drug). It has a half-life of about 5 to 6 hours. The drug half-life is prolonged and unpredictable in the elderly and in the presence of renal impairment, having poor correlation with creatinine clearance values. Its pharmacokinetics are relatively unchanged in the presence of mild to moderate hepatic dysfunction. Thirty milligrams of IV ketorolac provide similar
analgesic results as 4 mg of IV morphine, but a similar dose via IM route is equivalent to 6 to 8 mg of IM morphine. When used with opioids for postoperative pain management, ketorolac reduces opioid requirements, lowering their potential side effects.

Currently, ketorolac is indicated for short-term (≤5 days) management of moderately severe pain in the postoperative setting. It may be given as a single or multiple dose on a regular or as needed schedule up to a maximum of 5 days. Its frequently used dose profile is depicted in Table 165.1. IV injection is recommended to be given over at least 15 seconds, while the IM dose must be given slowly and deeply into the muscle. The time of onset of ketorolac is roughly 30 minutes. Peak effects are seen in 1 to 2 hours via either route, and clinical effects last for 4 to 6 hours. Mixing parenteral formulations with morphine, meperidine, promethazine, or hydroxyzine in the same syringe leads to precipitation and should be avoided.

Despite these desirable attributes, use of ketorolac comes with its own set of problems. Its relevant side effects and absolute contraindications are described in Table 165.2. Prostaglandins play a positive role in maintenance of platelet function and renal perfusion. The potent inhibitory effects of ketorolac on prostaglandin synthesis might jeopardize either of these vital phenomenons. Ketorolac use should be avoided in patients on therapeutic doses of anticoagulants, including prophylactic low-dose heparin therapy. It should also be avoided preoperatively, in any major surgical case, or when hemostasis is critical. It should be kept in mind that ketorolac-induced increased risk of bleeding cannot be detected on routine testing, via platelet count, prothrombin time, or activated partial thromboplastin time. It should also be used with extreme caution, if at all, in patients with impaired renal function. Ketorolac may cause dose-dependent reduction in renal prostaglandin formation and may precipitate acute renal failure. This is more likely to occur in patients with impaired hepatic or renal functions, dehydration, heart failure, concomitant use of diuretics, and advanced age. It is, therefore, not surprising that our surgical colleagues get really nervous with ketorolac use.