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Grand Rounds: Is It Time to Reconsider Ketorolac?

Grand Rounds is a monthly blog series developed by EMS World and FlightBridgeED that will feature top EMS medical directors exploring the intricacies of critical care in EMS practice. In this installment FlightBridgeED Chief Medical Officer Jeffrey Jarvis, MD, PM, reviews the drug ketorolac.

Unless you’ve been very committed to keeping your head in the sand, you’ve probably noticed we’re in the midst of an opioid epidemic. Though there is little evidence that the one or two doses of IV opioid medications EMS might give for acute pain contribute to opioid misuse, there are other reasons to have multiple analgesia options in our toolbox. Perhaps patients don’t want an opioid because they are in recovery or fear addiction. Maybe a patient had adverse reactions to opioids in the past, or perhaps other types of medications just work better for them. Regardless, it might be time to consider adding an IV nonopioid medication to our protocols.

Ketorolac (Toradol) is a nonsteroidal anti-inflammatory drug that works through the inhibition of cyclooxygenase.1 It is an effective analgesic by itself and an opioid-sparing analgesic when used in combination with narcotics.2–5 It is as effective as opioids for renal colic6–8 and migraines.2,9,10

As an NSAID, it can have adverse effects. The primary ones are platelet inhibition, bone remodeling, and worsening of renal failure.11 There is some debate about the extent of such effects, particularly on renal failure.12

Because of these adverse effects, there has been a reluctance to add ketorolac to EMS protocols. In recognition of the opioid epidemic—and the understandable desire of some patients to avoid opioids—it might be time to reconsider.

Renal Colic, Other Uses

While ketorolac has been used for various painful conditions, the evidence is probably most substantial for flank pain felt to be from renal colic (where it is perhaps most effective). It is also useful for musculoskeletal pain felt unlikely to be from a fracture (sprains and contusions come to mind) and atraumatic headaches with a low probability of involving bleeding. Let’s talk a bit about how to evaluate these complaints.

Renal colic occurs as a stone moves from the renal pelvis down to the bladder. The sharp edges cause bleeding (hence the hematuria) and lead to spasm of the smooth muscle surrounding the proximal ureters. These patients often have had stones before. Patients who can tell you their pain feels exactly like their prior episodes are often good diagnosticians, and we probably should consider what they have to say. They classically report a sudden onset of sharp, stabbing pain that may radiate from their flank to their groin (basically along the path of the ureter). The pain usually comes in waves, coming on intensely and then ebbing into an ache before returning with a vengeance. Patients are often up, pacing, and unable to find a comfortable position. They may or may not have noticed blood in their urine. Nausea and even vomiting are not uncommon, likely from pain. Kidney stones by themselves should not cause fever.

Sprains, strains, and contusions can sometimes be challenging to differentiate from fractures. A decent way to tell is by looking at weight-bearing. If they can put their full weight on the injury, it is less likely to be broken. That’s not perfect, but it’s a general rule of thumb. However, the opposite is not true: People who can’t put any weight on an injury often end up without a fracture at all. Fortunately, while prolonged use of NSAIDS may (the jury is still out) inhibit bone regrowth, I’ve never seen convincing evidence that a single dose of ketorolac will be problematic if we inadvertently give it in a fracture situation. This doesn’t, of course, mean we won’t get yelled at by an orthopedic surgeon.

Headaches are another good candidate for ketorolac use, provided we think there is a low likelihood of intracranial bleeding. In the absence of trauma (avoid ketorolac for those with significant head trauma), most intracranial bleeds occur from subarachnoid hemorrhages. The textbook description of a subarachnoid headache is one that comes on rapidly—i.e., a “thunderclap” headache. This means it reaches its maximal intensity within a few minutes. Patients should have a normal neurologic exam and, obviously, no altered mental status. Older patients and those on blood thinners are more at risk of spontaneous bleeding. Young patients with a long history of similar headaches are a good choice for ketorolac.

Some patients should not receive ketorolac. These include those with major trauma, any patient with concern for bleeding of any kind, and patients with peptic or gastric ulcer disease (because of the bleeding).

Dosing

Now for dosing. When you look up the dose for ketorolac, you’ll typically see 60 mg when given IM and 30 mg when given IV. An excellent study by New York physician Sergey Motov, MD, looked at three different doses (10, 15, and 30 mg) when given for pain in the ED.13 He found there was no additional short-term (up to three hours) analgesic benefit between the doses.

Conclusion

Ketorolac is a nonopioid NSAID analgesic that can either replace opioids or decrease the amount used to treat pain. It is commonly used in the hospital with good effect. Now might be the time to consider adding it to our analgesic armamentarium.

References

1. Mahmoodi AN, Kim PY. Ketorolac. StatPearls [Internet]; www.ncbi.nlm.nih.gov/books/NBK545172/.

2. Rao AS, Gelaye B, Kurth T, et al. A Randomized Trial of Ketorolac vs. Sumatriptan vs. Placebo Nasal Spray (KSPN) for Acute Migraine. Headache, 2016; 56: 331–40.

3. Hong JY, Won Han S, et al. Fentanyl sparing effects of combined ketorolac and acetaminophen for outpatient inguinal hernia repair in children. J Urol, 2010; 183: 1,551–5.

4. Beiter JL Jr., Simon HK, Chambliss CR, Adamkiewicz K, Sullivan K. Intravenous ketorolac in the emergency department management of sickle cell pain and predictors of its effectiveness. Arch Pediatr Adolesc Med, 2001 Apr; 155(4): 496–500.

5. Power I, Bowler GM, Pugh GC, Chambers WA. Ketorolac as a component of balanced analgesia after thoracotomy. Br J Anaesth, 1994; 72: 224–6.

6. Rezaei B, Salimi R, Kalantari A, Astaraki P. Comparison of efficacy nebulized fentanyl with intravenous ketorolac for renal colic in patients over 12 years old. Am J Emerg Med, 2020 Apr 21; S0735-6757(20)30257-6 [epub ahead of print].

7. Olsen JC, McGrath NA, Schwarz DG, Cutcliffe BJ, Stern JL. A double-blind randomized clinical trial evaluating the analgesic efficacy of ketorolac versus butorphanol for patients with suspected biliary colic in the emergency department. Acad Emerg Med, 2008 Aug; 15(8): 718–22.

8. Henderson SO, Swadron S, Newton E. Comparison of intravenous ketorolac and meperidine in the treatment of biliary colic. J Emerg Med, 2002 Oct; 23(3): 237–41.

9. Davis CP, Torre PR, Williams C, et al. Ketorolac versus meperidine-plus-promethazine treatment of migraine headache: evaluations by patients. Am J Emerg Med, 1995 Mar; 13(2): 146–50.

10. Duarte C, Dunaway F, Turner L, Aldag J, Frederick R. Ketorolac Versus Meperidine and Hydroxyzine in the Treatment of Acute Migraine Headache: A Randomized, Prospective, Double-Blind Trial. Ann Emerg Med, 1992 Sep; 21(9): 1,116–21.

11. Gillis JC, Brogden RN. Ketorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management. Drugs, 1997 Jan; 53(1): 139–88.

12. Feldman HI, Kinman JL, Berlin JA, et al. Parenteral ketorolac: the risk for acute renal failure. Ann Intern Med, 1997 Feb 1; 126(3): 193–9.

13. Motov S, Yasavolian M, Likourezos A, et al. Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med, 2017 Aug; 70(2): 177–84.

Jeffrey L. Jarvis, MD, MS, EMT-P, FACEP, FAEMS, is the chief medical officer for FlightBridgeED, LLC and cohost of the FlightBridgeED EMS Lighthouse Project Podcast. He also serves as an EMS medical director for the Williamson County EMS system and Marble Falls Area EMS and is an emergency physician at Baylor Scott & White Hospital in Round Rock, Tex. He is board-certified in emergency medicine and EMS. He began his career as a paramedic with Williamson County EMS in 1988 and continues to maintain his paramedic license.

 

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