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Dexamethasone

Mark Donaldson, PharmD, and Jason H. Goodchild, DMD

November 2019 Issue - Expires Wednesday, November 30th, 2022

Inside Dentistry

Abstract

The current epidemic of opioid abuse in the United States has forced oral healthcare practitioners to assess their roles and reevaluate their prescribing practices for pain medication following dental procedures. A combination of ibuprofen and acetaminophen taken every 6 hours during the 24-hour period following procedures has been recognized as the postoperative prescription of choice for acute nociceptive orofacial pain. This article discusses how the addition of the glucocorticoid dexamethasone, either as a preemptive or postoperative oral administration or a single intraoperative injection administered submucosally and adjacent to the area of treatment, can improve pain control and patient comfort during the procedure as well as reduce the need for narcotic medication afterward.

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High rates of opioid pre-scribing have been linked to the growing epidemic of opioid abuse in the United States, which is a significant public health concern.1-4 Unfortunately, oral healthcare practitioners are more likely to prescribe opioids than primary care physicians, and areas with a higher number of dentists per capita are associated with increased opioid prescribing rates.5,6 In fact, dentists are responsible for 6.4% of all outpatient immediate-release opioid prescriptions in the United States.6,7 An article published more than 7 years ago in the Journal of the American Dental Association identified, even at that time, that "the appropriate use of opioids requires dentists to follow responsible and tailored prescribing practices to provide adequate pain control while limiting opportunities for abuse and diversion."8 Since then, many publications have come forward with additional statistics to highlight this issue, but very few of these have been directional in helping the frontline prescribing oral healthcare practitioners choose better alternatives to manage their patients' pain.9-15

Postoperative Analgesia

In a 2010 publication, "Appropriate analgesic prescribing for the general dentist,"  the mnemonic "2-4-24" was introduced to help practitioners remember the postoperative prescription of choice for acute nociceptive orofacial pain.16 This memory aid refers to, "2 drugs, in 4 doses, for 24 hours," which indicates a combination of ibuprofen 600 mg and acetaminophen 650 mg to be administered every 6 hours for 24 hours. This dosing mnemonic is especially useful because it is both effective and safe. For the treatment of acute pain, the maximum recommended dose that should not be exceeded during a 24-hour period is 2,400 mg for ibuprofen and 3,000 mg for acetaminophen. The combination of a nonsteroidal anti-inflammatory drug (NSAID), such as ibuprofen, and acetaminophen administered every 6 hours for at least 24 hours has been recognized and validated by both individual studies and meta-analyses as the postoperative prescription of choice for acute nociceptive orofacial pain.16-19 An understanding of the inflammatory process, the pharmacokinetics of these medications, and routine dosing (as opposed to prn or "as needed" dosing) during the initial 24-hour postoperative period is required to ensure success. In a majority of cases, if the patient is compliant with these four doses of two different medications, he or she may not require any further analgesic medication beyond the first 24 hours. These doses can be administered every 6 hours, either together or in a staggered fashion, based on dentist and patient preference (eg, 650 mg of acetaminophen now, then 600 mg of ibuprofen 3 hours later, then 650 mg of acetaminophen 3 hours after that, and so on for the first 24-hour postoperative period). The staggered approach is sometimes valuable for patients known as "clock watchers" for whom more frequent medication administration may be more psychologically beneficial following dental surgery. These two medications work by different mechanisms of action, and compliance is the key to the success of this analgesic regimen, which may require that patients set alarms so that they do not miss the prescribed doses during the initial 24-hour postoperative period. After the initial 24-hour postoperative period, patients can reduce their regimen to a prn administration of either drug by itself or in combination. However, if patients still require routine pain medication after the initial 48-hour period following the dental procedure despite excellent compliance, reexamination by the dental practitioner should be considered to rule out confounders such as wound disturbances or infection.

Although dexamethasone was approved by the US Food & Drug Administration in 1958 under the brand name Decadron®, the first published reference discussing glucocorticoid use in dentistry utilized other corticosteroids, such as cortisone and prednisolone.20,21 The first recorded use of dexamethasone for endodontic procedures was not until 1968, and its use continues to be an important pain control modality today.22 Dexamethasone comes in both oral and injectable formulations. The oral formulation is especially useful for postoperative analgesia and is more commonly recognized as a 6-, 10-, or 13-day tapered regimen (eg, Dexpak®).23 These tapered regimens are not required to prevent adrenal insufficiency because it typically takes 14 days of supraphysiological doses of exogenous glucocorticoids to suppress the hypopituitary axis. As was demonstrated in a recent systematic review, a simpler strategy would be to consider prescribing 4 to 8 mg of oral dexamethasone to be taken twice a day for up to 48 hours after dental surgery.24 Alternatively, dexamethasone has also been successfully used as a postoperative intramuscular injection for the control of pain, swelling, and trismus after third molar surgery, which was demonstrated in a systematic review and meta-analysis by Fernandes and colleagues.25

Preemptive Analgesia

Medications such as acetaminophen and ibuprofen can also be given preoperatively to mitigate postoperative pain and analgesic medication requirements.26,27 A cyclooxygenase-2 (COX-2) selective NSAID, such as celecoxib, is ideally suited for this strategy. When compared with traditional nonselective NSAIDs, celecoxib can preemptively ameliorate the inflammatory response without causing increased bleeding or delayed wound healing postoperatively.28-30 A 400 mg dose of celecoxib administered orally 30 minutes prior to the dental procedure can maximize this potential benefit. For those patients who are currently on an anticoagulant (eg, warfarin, dabigatran, rivaroxaban, apixaban, betrixaban, edoxaban), a COX-2 inhibitor such as celecoxib could further be used to replace the previously described postoperative ibuprofen prescription (ie, 200 mg given every 12 hours for the initial 24-hour postoperative period).

Preemptive analgesia with 4 to 8 mg of a glucocorticoid, such as dexamethasone, taken orally 30 minutes prior to the procedure has also been shown to be an excellent strategy, either alone or in addition to celecoxib.31,32

Intraoperative Analgesia

Intraoperative analgesia is at least a 70-year-old concept in dentistry; lidocaine entered its seventh decade as a part of the United States Pharmacopeia in 2018.33 The opioid epidemic has renewed interest in intraoperative analgesics because they not only help with immediate pain management but also decrease a patient's typical requirement for postoperative narcotics.

A single intraoperative injection of 4 to 8 mg of dexamethasone administered submucosally adjacent to the area of treatment is an excellent addition to the pain control strategies discussed thus far.16,34 Dan and colleagues had already shown in an earlier meta-analysis that an intraoperative injection of methylprednisolone significantly reduced edema and pain following oral surgery without an increased risk of infection or other adverse effects35; then, in a more recent meta-analysis, Chen and colleagues found that a single intraoperative injection of up to 10 mg of dexamethasone reduced not only early and late edema but also early trismus and pain following third molar extractions.34 Particularly helpful for practitioners is that a single intraoperative injection of dexamethasone can provide analgesia for up to 6 days when compared with oral administration, which provides an approximate 2-day duration of action.36 Many endodontists have been using this strategy successfully for years, but the new evidence helps to support the more routine use of a single intraoperative injection of dexamethasone following other types of dental surgeries. This submucosal injection, which is similar to a typical infiltration approach, is easily administered and should be delivered into a location of the mouth that has already been anesthetized to improve the patient's comfort (Figure 1).

Because patient safety is always the foremost concern, an additional benefit of this single intraoperative injection of dexamethasone is that it is accompanied by very few contraindications. Although it is not recommended for patients who are pregnant or lactating or who have uncontrolled diabetes, the chance of experiencing a life-threatening reaction to a single intraoperative dose of dexamethasone is highly unlikely. In their systematic review, Chen and colleagues found that none of the included studies addressed the safety of dexamethasone; however, none of the studies reported any severe complications either.34

Conclusion

Recent data reveal that oral healthcare practitioners contribute to the overprescription and overutilization of immediate-release opioid analgesics to manage pain. Although there is a dearth of reports and data, few research articles make suggestions for effective alternative strategies to include drugs, doses, and durations. The combination of 600 mg of an NSAID (eg, ibuprofen) and 650 mg of acetaminophen administered every 6 hours for at least 24 hours has been recognized and validated by individual studies and meta-analyses alike as the postoperative prescription of choice for acute nociceptive orofacial pain. The addition of 4 to 8 mg of oral dexamethasone for preemptive analgesia or 4 to 8 mg of oral dexamethasone twice daily for up to 48 hours after dental surgery also have demonstrated high levels of effectiveness in a recent systematic review on this subject. Finally, a single intraoperative submucosal injection of dexamethasone has been shown to further improve the pain, edema, and trismus that are experienced after dental procedures. Although each of these strategies, either alone or in combination, has greatly aided the clinical management of orofacial pain, all offer the additional benefit of being non-opioid solutions that can be administered to some of the most difficult to manage patients.

Authors' note: The views expressed in this article are those of the authors and do not necessarily reflect those of Premier Dental Products Company, the Creighton University School of Dentistry, the Rutgers School of Dental Medicine, or Vizient, Inc.

About the Authors

Mark Donaldson, PharmD
Fellow
American Society of Health-System Pharmacists
Fellow
American College of Healthcare Executives
Associate Principal
Vizient Pharmacy Advisory Solutions
Irving, Texas
Clinical Professor
University of Montana
School of Pharmacy
Missoula, Montana

Jason H. Goodchild, DMD
Vice President, Clinical Affairs
Premier Dental Products Company
Plymouth Meeting, Pennsylvania
Associate Clinical Professor
Department of Oral and Maxillofacial Surgery
Creighton University
School of Dentistry
Omaha, Nebraska
Adjunct Assistant Professor
Division of Oral Diagnosis
Department of Diagnostic Sciences
Rutgers University
School of Dental Medicine
Newark, New Jersey

References

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2. U.S. Department of Health & Human Services. HHS acting secretary declares public health emergency to address national opioid crisis. U.S. Department of Health & Human Services website. https://www.hhs.gov/about/news/2017/10/26/hhs-acting-secretary-declares-public-health-emergency-address-national-opioid-crisis.html. Published October 26, 2017. Accessed April 12, 2019.

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25. Fernandes IA, de Souza GM, Pinheiro MLP, et al. Intramuscular injection of dexamethasone for the control of pain, swelling, and trismus after third molar surgery: a systematic review and meta-analysis. Int J Oral Maxillofac Surg. 2019;48(5):659-668.

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28. Boonriong T, Tangtrakulwanich B, Glabglay P, Nimmaanrat S. Comparing etoricoxib and celecoxib for preemptive analgesia for acute postoperative pain in patients undergoing arthroscopic anterior cruciate ligament reconstruction: A randomized controlled trial. BMC Musculoskelet Disord. 2010;11:246. doi: 10.1186/1471-2474-11-246.

29. Al-Sukhun J, Al-Sukhun S, Penttilä H, et al. Preemptive analgesic effect of low doses of celecoxib is superior to low doses of traditional nonsteroidal anti-inflammatory drugs. J Craniofac Surg. 2012;23(2):526-529.

30. Munteanu AM, Cionac Florescu S, Anastase DM, et al. Is there any analgesic benefit from preoperative vs. postoperative administration of etoricoxib in total knee arthroplasty under spinal anaesthesia?: A randomised double-blind placebo-controlled trial. Eur J Anaesthesiol. 2016;33(11):840-845.

31. Falci SGM, Lima TC, Martins CC, et al. Preemptive effect of dexamethasone in third-molar surgery: a meta-analysis. Anesth Prog. 2017;64(3):136-143.

32. Alcântara CE, Falci SG, Oliveira-Ferreira F, et al. Pre-emptive effect of dexamethasone and methylprednisolone on pain, swelling, and trismus after third molar surgery: a split-mouth randomized triple-blind clinical trial. Int J Oral Maxillofac Surg. 2014;43(1):93-98.

33. Donaldson M, Goodchild JG. Lidocaine turns 70: the evolution of dental local anesthesia. Gen Dent. 2018;66(3):6-9.

34. Chen Q, Chen J, Hu B, et al. Submucosal injection of dexamethasone reduces postoperative discomfort after third-molar extraction: a systematic review and meta-analysis. J Am Dent Assoc. 2017;148(2):81-91.

35. Dan AE, Thygesen TH, Pinholt EM. Corticosteroid administration in oral and orthognathic surgery: a systematic review of the literature and meta-analysis. J Oral Maxillofac Surg. 2010;68(9):2207-2220.

36. Dwyer Schull P. Dexamethasone. In: Johnson CA, Pancotti R, eds. Nurse's Drug Handbook. 7th ed. Plano, TX: McGraw-Hill Company, Inc; 2013:351.

(1.) Intraoral view of 4 mg of dexamethasone being injected submucosally via an infiltration technique following root canal therapy for tooth No. 5.

Figure 1

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PROVIDER: AEGIS Publications, LLC
SOURCE: Inside Dentistry | November 2019

Learning Objectives:

  • Discuss the importance of adjusting prescribing practices for narcotic pain medication in the wake of the US opioid epidemic.
  • Describe the postoperative pain management prescription of choice involving ibuprofen and acetaminophen.
  • Explain how oral dexamethasone can be used to enhance analgesia preemptively as well as postoperatively.
  • Explain how an intraoperative submucosal injection of dexamethasone can enhance analgesia and patient comfort.

Author Qualifications:

Mark Donaldson, PharmD Fellow, American Society of Health-System Pharmacists, Fellow, American College of Healthcare Executives, Associate Principal, Vizient Pharmacy Advisory Solutions, Irving, Texas, Clinical Professor, University of Montana School of Pharmacy, Missoula, Montana Jason H. Goodchild, DMD Vice President, Clinical Affairs, Premier Dental Products Company, Plymouth Meeting, Pennsylvania, Associate Clinical Professor, Department of Oral and Maxillofacial Surgery, Creighton University, School of Dentistry, Omaha, Nebraska, Adjunct Assistant Professor, Division of Oral Diagnosis, Department of Diagnostic Sciences, Rutgers University, School of Dental Medicine, Newark, New Jersey

Disclosures:

The author reports no conflicts of interest associated with this work.

Queries for the author may be directed to justin.romano@broadcastmed.com.