Authors

1. Tooley, Angela RN, BSN
2. Vickers, Hayley RN, BSN

Abstract

Review question/objective: The objective of this review is to identify if intravenous ketorolac increases the incidence of postoperative hemorrhage and hematoma formation.

The specific review question to be addressed is:

Does intravenous ketorolac 15-30 mg given in the perioperative period to surgical patients 18 and older undergoing general anesthesia cause an increased incidence of postoperative hemorrhage and hematoma formation in the first 24 hours following surgery?

Background: Opioids are powerful analgesic medications that have a narrow therapeutic range.1 Traditionally, opioids have been used to control postoperative pain but can cause unfavorable side effects. Opioids are classically used to manage pain during the perioperative and postoperative periods but can consequently cause respiratory depression, cardiac depression, nausea, vomiting, pruritis, constipation, and sedation.2,3,4,5 Ketorolac has surfaced as an alternative to opioids for postoperative pain control. It avoids the side effects of opioids and has a similar efficacy to that of parenteral opioids.6 It is also available for intramuscular and oral administration.6 Ketorolac tromethamine is a member of the nonsteroidal anti-inflammatory drug (NSAID) group and is indicated for use in the short-term management of mild to moderate pain.6 NSAIDs are a group of drugs that provide analgesic, antipyretic properties. Ketorolac became the first NSAID approved for parenteral administration.2

Ketorolac inhibits the formation of thromboxane A2 and prostaglandins by competitively blocking the cyclo-oxygenase (COX) pathway in a non-selective fashion.6, 7 The metabolism of ketorolac is primarily hepatic and excretion is largely renal.8 The most prominent adverse effects associated with ketorolac include bleeding, altered hemostasis, allergic reactions, and renal damage.7 Increased age, high dose range, and increased duration of administration can escalate the risks for side effects.7 Ketorolac intravenous administration is recommended for no longer than five days and in doses of 10 to 30 mg.7, 8 It is contraindicated in patients with severe renal impairment, an increased risk for bleeding, active peptic ulcer disease, and confirmed cerebrovascular bleeding.7, 8 It is also cautioned to avoid ketorolac administration prior to major surgery, and preceding major surgery where hemostasis is critical.7, 8 Ketorolac can also increase the risks for cardiac thrombotic events.8 Patients with asthma may have sensitivity to NSAIDs that could induce bronchospasm, so it should be avoided in this patient population as well.8 This review will specifically examine the bleeding risks associated with ketorolac but exclusion criteria will be extrapolated from the above contraindications and side effects.

Essentially, ketorolac impedes mechanisms that are vital to the mediation of platelet aggregation, which is a process that is necessary to decrease bleeding during and after surgical procedures. Since platelet aggregation is decreased, ketorolac and other NSAIDs have been associated with an increased risk for postoperative bleeding and hematoma formation.7 Postoperative bleeding can increase the chances of infection, the need for revision of the previous surgical procedures, and the length of hospital stay. This has discouraged some providers from using ketorolac on all surgical patients as a mode of analgesia for postoperative pain control. Bleeding risks should be evaluated on an individual basis to determine whether ketorolac should be included in the medication regimen.

Adverse reactions and side effects aside, ketorolac has numerous benefits for the surgical patient. For major surgery, the optimal use of ketorolac typically involves the use of multiple parenteral doses as part of a multimodal analgesic regimen.3 General anesthesia is a state of sleep generated by medications.9 Nausea and vomiting have been associated with some general anesthesia medications as well. Most of the opioids classically used in surgery affect the mu-opioid receptor and these medications must be titrated appropriately based upon the drug lipid solubility, peak effect time, and duration.1 Appropriate titration is critical when administering opioids to avoid some of the associated side effects. Opioids can actually increase patient sensitivity to pain in certain cases, which makes them inadequate for pain relief as the sole agent.1 Multimodal strategy in the management of perioperative pain is crucial in the care of surgical patients. When ketorolac is used as an adjunct to opioids, there may be a 25-50% reduction in opioid requirements.4 Ketorolac does not produce the effects connected with opioids, which makes it an asset in the postoperative period.2,3,4,5 The opioid-sparing properties of ketorolac could possibly reduce the incidence of adverse effects associated with opioid consumption and decrease the postoperative patient's length of hospital stay.4

The onset of ketorolac is rapid, which is ideal for prompt pain relief. Peak plasma concentrations and peak effect occur approximately 45 minutes after parenteral administration.5 Therefore, ketorolac is most effective when the anesthesia professional administers it near the conclusion of a surgical procedure for pain relief in the immediate postoperative period. Another benefit of ketorolac is that it can be administered parentally, which means it can be given to patients that cannot tolerate oral medication.5 This is an advantage over some of its other NSAID cohorts that are limited to oral administration.

There are articles that report cases of death and hemorrhage associated with ketorolac use, but there are also articles that claim there is no evidence of postoperative bleeding associated with ketorolac administration.6,2,4,5,10 The controversial findings surrounding ketorolac have discouraged some practitioners from using it in the perioperative period for postoperative pain management, which could lead to an increase in opioid use and subsequent increase in opioid-related side effects.4 Other practitioners continue to use ketorolac for postoperative pain management, which could mean an increase in postoperative hemorrhage and hematoma formation in their patients. Most providers base their choice whether to include or omit ketorolac on experience.

This review aims to determine whether the use of perioperative ketorolac 15 to 30 mg intravenously increases the risk for bleeding and hematoma formation during the first 24 hours postoperatively in patients aged 18 years and above undergoing general anesthesia. The articles that meet inclusion criteria will be compiled and reviewed with the appropriate Joanna Briggs Institute Extraction Tools. The data will be analyzed to reveal whether the risks for bleeding after ketorolac administration are truly detrimental to patient recovery. Database searches were conducted through the Cochrane Library, JBI Database of Systematic Reviews and Implementation Reports, and Campbell Library with no reviews related to this topic.