Objectives Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line analgesics following third molar extraction, but some patients require supplemental opioids for pain management. The objective of this study was to identify demographic and clinical factors that predicted supplemental opioid use following third molar extraction in patients treated with an evidence-based analgesic regimen.

Methods Healthy adults underwent surgical extraction of partial or full bony impacted mandibular third molar. When pain intensity was ≥4/10, participants were given ibuprofen 400 mg (N=59) or placebo (N=26) in a randomized, double-blind design. After 4h, all participants transitioned to open-label ibuprofen 400 mg + acetaminophen 500 mg, with oxycodone 5 mg available for breakthrough pain. Analgesic use was documented for the first week after extraction. Predictors of supplemental opioid use in addition to ibuprofen + acetaminophen were evaluated by logistic regression.

Results Ibuprofen + acetaminophen provided adequate analgesia in most of the 85 participants, with 17 participants (20%) using supplemental oxycodone in the first week after extraction. Female sex (OR: 6.770; 95% CI: 1.657-35.57; p=0.013) and higher body mass index (BMI) (OR: 1.253; 95% CI: 1.052-1.525; p=0.016) were associated with increased odds of supplemental opioid use, while higher difficulty index (Pederson score) slightly decreased the odds of supplemental opioid use (OR: 0.852; 95% CI: 0.724-0.993; p=0.043). Adding pre-surgery neutrophil counts improved model fit, with higher neutrophil counts associated with lower odds of supplemental opioid use (OR: 0.435; 95% CI: 0.212-0.775; p=0.011).

Conclusions Female sex, higher BMI, and pre-surgery neutrophil counts were predictors of supplemental opioid use in patients treated with an evidence-based analgesic regimen. Greater surgical difficulty of third molar extraction does not increase the likelihood of supplemental opioid use.

The authors have declared no competing interest.

NCT03893175

This work was supported by funds from the Penn Center for Precision Medicine, an Oral and Maxillofacial Surgery Foundation Clinical Research Grant, and funding from the National Institute of Oral and Craniofacial Research (R01DE033405) and the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR001878). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication.

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The study protocol was approved by the University of Pennsylvania Institutional Review Board (IRB#832417), and all participants provided informed consent.

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Funding Sources: Penn Center for Precision Medicine, Oral and Maxillofacial Surgery Foundation, the National Institute of Dental and Craniofacial Research (R01DE033405), and the National Center for Advancing Translational Sciences (UL1TR001878)

All data produced in the present study are available upon reasonable request to the authors