The Ceiling Effect of IV Ketorolac

For acute pain in the ED, parenteral ketorolac is generally administered as 30 mg IV or 60 mg IM. Dr. Chris Bond (@socbmobem) has written about the ‘ceiling effect’ of NSAIDS. The question is: are we using too much ketorolac without getting additional pain benefit?

Hot-off-the-press is a new randomized, double-blind trial from Dr. Sergey Motov’s group (@painfreeED) that addresses this exact question.

What they did

240 patients with acute pain in a 711-bed urban community teaching hospital ED were randomized to receive 10 mg, 15 mg, or 30 mg of IV ketorolac as a single-dose.

• Age 18 to 65 years
• Acute flank, abdominal, musculoskeletal, or headache pain with an intensity of 5 or greater on a standard 0 to 10 numeric rating scale
• Patients who would routinely be treated with IV ketorolac
• Pain scores, vital signs, and adverse effects were recorded at baseline and 15, 30, 60, 90, and 120 minutes
• Subjects still desiring pain medication 30 min after study drug administration were offered IV morphine 0.1 mg/kg as a rescue

Outcome

The primary outcome was reduction in numeric rating scale pain score at 30 minutes from medication administration.

What they found

1. There was no difference in reduction of pain scores between the groups
   • 10 mg – 7.7 to 5.2
   • 15 mg – 7.5 to 5.1
   • 30 mg – 7.8 to 4.8
2. There were no differences between the groups with respect to use of rescue morphine analgesia at any time
3. There were no clinically concerning changes in vital signs and no clinically significant adverse effects related to the study medication at any dose

There was no placebo group and the box plot (Figure 2) revealed wide variability in all of the treatment arms.

Implications for Clinical Practice

This is a well-conducted study demonstrating no difference in pain score reduction for various doses of IV ketorolac. Doses of 10 mg or 15 mg are just as effective as 30 mg and should be used preferentially over higher doses. Higher doses can cause more adverse effects, especially if more than one dose is administered.

Reference

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 2016. [Article in press link] 

Author: Bryan D. Hayes, PharmD

Attending Pharmacist, Emergency Medicine and Toxicology, Massachusetts General Hospital; Assistant Professor of EM, Harvard Medical School View all posts by Bryan D. Hayes, PharmD