The ‘Ceiling’ Effect of NSAIDs

Today’s pearl is about the dose ceiling effect of NSAIDs (the idea that increasing doses does not lead to further pain relief)

Are we giving to much without benefit?
More isn’t always better.

For acute pain, parenteral ketorolac was historically administered as 30 mg IV or 60 mg IM. And, what about ibuprofen doses > 400 mg? Dr. Chris Bond wrote about the ‘ceiling effect’ of NSAIDS highlighting previous studies (many in the dental field). The question is: Are we using too much ketorolac and ibuprofen without getting additional pain benefit?

Two ED RCTs investigated this question and report some interesting results:

  1. Ketorolac (Motov 2017) – There was no difference in pain scores at 30 minutes between 10 mg, 15, mg, and 30 mg doses
  2. Ibuprofen (Motov 2019) – There was no difference in pain scores at 60 minutes between 400 mg, 600 mg, and 800 mg doses

Implications for Clinical Practice

  • Ketorolac doses of 10 mg or 15 mg may be just as effective as 30 mg (or 60 mg) and should be used preferentially over higher doses in the ED (Motov 2017, Reuben 1998, Staquet 1989, Minotti 1998, Brown 1990)
  • Ibuprofen doses of 400 mg may be just as effective as 600 mg (or 800 mg) for pain relief at 60 minutes in the ED (Motov 2019)
  • Higher NSAID doses may be indicated in some situations, particularly when inflammation is involved

In-depth discussion of dose-response: Dr. Andrew Stolbach, EM physician and medical toxicologist at Johns Hopkins, deep-dives the ceiling effect concept on The Dantastic Mr. Tox & Howard podcast and highlights that there may be some more nuance to it.

For acute pain, parenteral ketorolac was historically administered as 30 mg IV or 60 mg IM. And, what about ibuprofen doses > 400 mg? Dr. Chris Bond wrote about the ‘ceiling effect’ of NSAIDS highlighting previous studies (many in the dental field). The question is: are we using too much ketorolac and ibuprofen without getting additional pain benefit?

Two ED RCTs investigated this question and report some interesting results:

  1. Ketorolac (Motov 2017) – There was no difference in pain scores at 30 minutes between 10 mg, 15, mg, and 30 mg doses
  2. Ibuprofen (Motov 2019) – There was no difference in pain scores at 60 minutes between 400 mg, 600 mg, and 800 mg doses

Implications for Clinical Practice

  • Ketorolac doses of 10 mg or 15 mg may be just as effective as 30 mg (or 60 mg) and should be used preferentially over higher doses in the ED (Motov 2017Reuben 1998Staquet 1989Minotti 1998Brown 1990)
  • Ibuprofen doses of 400 mg may be just as effective as 600 mg (or 800 mg) for pain relief at 60 minutes in the ED (Motov 2019)
  • Higher NSAID doses may be indicated in some situations, particularly when inflammation is involved

In-depth discussion of dose-response: Dr. Andrew Stolbach, EM physician and medical toxicologist at Johns Hopkins, deep-dives the ceiling effect concept on The Dantastic Mr. Tox & Howard podcast and highlights that there may be some more nuance to it.

#17

Author: Bryan D. Hayes, PharmD

Attending Pharmacist, Emergency Medicine and Toxicology, Massachusetts General Hospital; Assistant Professor of EM, Harvard Medical School

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