The Ibuprofen Analgesic Ceiling

Determining how much is just right can prove challenging.

Case Introduction

A 32-year-old male with no past medical history presents to your emergency department complaining of right ankle pain since yesterday evening. The patient thinks he may have strained his ankle while stepping off the curb and crossing the street. He thought he could walk it off and did not try any interventions to relieve the pain. Following a thorough history, minimal swelling and inflammation noted on exam, and no clinical indication to obtain imaging you conclude his symptoms are likely secondary to a musculoskeletal strain.

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After applying an ice pack and recommending he keep his leg elevated, the patient asks for something to help with his continued discomfort. Having a practice habit of always prescribing the same non-steroidal anti-inflammatory (NSAID) Ibuprofen dose due to anecdotal success, you’re about to offer a single dose of 600 mg of Ibuprofen and, he quickly asks, “Can you give me 800 mg since that’ll help take away more of my pain faster?”

Background Information

NSAIDs such as ibuprofen are among the most commonly prescribed oral analgesics in the emergency department.[^1,2] Since these medications can be found over the counter and easily accessible to patients, it’s important to understand the mechanism behind how they work and their potential side effects. Two Cyclooxgenase (COX) enzymes, COX-1 and COX-2, are responsible for the production of prostaglandins that promote pain, fever and inflammation. These prostaglandins, and the enzymes that produce them, are responsible for lining the stomach epithelium and play a role in platelet activation. NSAIDs work by inhibiting these COX enzymes and thus reduce pain and inflammation. An important distinction must be made here, inflammation does not equal pain. It is well researched that lower doses of ibuprofen may be helpful in treating pain, while higher doses may be more beneficial to inflammation.[^3] Another important point to highlight is that the linear kinetic effects of ibuprofen results in longer duration of analgesia with higher doses, but not necessarily more effective pain control.[^4,5]

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How Much is Just Right?

A recent study published in Annals of Emergency Medicine looked at the analgesic effect of three doses of ibuprofen in emergency department (ED) patients with acute pain. In this double-blind control trial, 225 patients had their pain scored and then were randomized to three groups of 75 patients each. They were then given either 400, 600 or 800 mg dose of ibuprofen and then had their pain scored again 60 minutes following administration. The primary outcome of the study looked for a difference in mean pain scores between the three groups. Their secondary outcomes included a comparison of mean pain scores differences in each group from baseline to 60 minutes, rates of adverse events and the need for rescue analgesia.

All three groups were relatively similar in age, sex and initial pain scores. Furthermore, all three groups had similar chief complaints and final diagnoses (i.e. musculoskeletal sprain, strains, fractures, cutaneous rashes, lacerations and abscesses). Interestingly, the study results showed there was no statistically significant difference in the mean pain scores between the three groups with no clinically concerning adverse effects related to the study medications (Table 1).[^6]

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The current literature supports ibuprofen’s analgesic ceiling dose at 400 mg per dose with a maximum of 1200 mg/day.¹ While a limitation of the above study was that the duration of the different ibuprofen doses was not actually measured, this trial helps add to the knowledge we currently have about NSAIDs, specifically in emergency department patients.

As emergency physicians we are over-prescribing this medication at supra-analgesic doses and may be contributing to the potentially serious long-term adverse reactions such as gastrointestinal hemorrhage and ulcer development. Future studies looking at how the dose of NSAIDs affects their duration of effect are still needed, but until then emergency physicians should utilize the most minimally effective dose of 400 mg to treating a patient’s pain.

Case Conclusion

You explain to the patient that several studies have shown an ibuprofen analgesic ceiling dose of 400 mg to be an effective analgesic for acute pain. The patient agrees to take the lower dose you are recommending. Upon reassessment shortly after, he is feeling better and able to ambulate with less pain. Using shared medical decision making, the patient feels comfortable going home with outpatient primary care follow-up and return precautions to the ED should his symptoms worsen.

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REFERENCES:

1. Motov S et al. Comparison of Oral Ibuprofen at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med 2019. PMID: 31383385
2. Seymour RA, Ward-Booth P, Kelly PJ. Evaluation of different doses of soluble ibuprofen and ibuprofen tablets in postoperative dental pain. Br J Oral Maxillofac Surg 1996 PMID: 8645662
3. Motov, S. (2019). Is There a Limit to the Analgesic Effect of Pain Medications? Medscape. Available Here
4. Mazaleuskaya LL, et al. PharmGKB summary: ibuprofen pathways. Pharmacogenet Genomics. 2015 PMID: 25502615
5. Schwartz NA, et Patients’ perceptions of route of nonsteroidal anti-inflammatory drug administration and its effect on analgesia. Acad Emerg Med. Aug 2000. PMID: 10958124
6. Ramzy M, “A Randomized Control Trial Comparing Oral Ibuprofen at Three Single-Dose Regimens for Treating Acute Pain in the ED”, REBEL EM blog, August 5, 2019. Available here.