Pain is common following surgical and non-surgical dental extraction and has been managed by both opioid and non-opioid analgesics. Here in the UK non-steroidal anti-inflammatory (NSAID) drugs are commonly used while opioid prescribing is far more common in the USA where there are public health and safety concerns over the level of opioid use.
The aim of this review and network meta-analysis (NMA) was to assess the comparative effectiveness of pharmacological treatments for the management of pain subsequent to simple and surgical tooth extraction, as well as pain associated with pulpitis or its complications.
Methods
Searches were conducted in the Medline, Embase and CENTRAL databases and the US Clinical Trials registry for randomised clinical trials (RCTs) of pain relief medication in patients aged 12 and above undergoing simple or surgical tooth extraction. The focus was on 10 interventions commonly used in the USA including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and combinations against one another or placebo. Only peer-reviewed articles a published in English were considered. Following training and calibration pairs of reviewers independently screened and selected studies, extracted data, and assessed risk of bias using the Cochrane risk of Bias tool (RoB2). Discrepancies were resolved using a third reviewer.
Outcomes included pain relief at 6 h, total pain relief (TOTPAR) at 6h, summed pain intensity difference (SPID) at 6h, global efficacy rating at 6h, proportion of patients receiving rescue analgesia at 6h and adverse effects. Continuous outcomes were summarised using mean difference (MD) and 95% confidence interval (CI) and dichotomous outcomes using odds ratios (ORs) and risk differences (RDs) and 95% CIs. Frequentist NMAs were undertaken for outcomes with enough data and certainty of evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for NMAs.
Results
- 85 RCTs reported in 82 publications were included.
- 75% of the included RCTs were conducted in the USA.
- All 85 RCTs involved surgical tooth extraction.
- Only 9 RCTs were considered to be at low risk of bias.
- 56 RCTs (9,095 patients) contributed to a NMA for pain relief using scale from 0 to 4, where higher scores represent more pain relief. With reference to placebo the most effective interventions are shown in descending order in the table below
| Intervention | MD (95%CI) | GRADE certainty |
| Ibuprofen 200 to 400mg plus acetaminophen 500 to 1,000mg | 1.68 (1.06 to 2.31) | Moderate |
| Acetaminophen 650 mg plus oxycodone 10 mg | 1.19 (0.85 to 1.54) | Moderate |
- There was no convincing evidence that any of the other interventions were different from placebo for the outcome pain relief.
- 44 RCTs (7,282 patients) were included in the NMA for TOTPAR using a scale of 0 to 24, where higher scores represent more total pain relief. With reference to placebo the most effective interventions are shown in descending order in the table below
| Intervention | MD (95%CI) | GRADE certainty |
| Ibuprofen 200 to 400mg plus acetaminophen 500 to 1,000mg | 11.07 (8.23 to 13.9) | Moderate |
| Acetaminophen 650 mg plus oxycodone 10 mg | 7.91 (6.49 to 9.32) | Moderate |
| Ibuprofen 400 mg (fast acting or acid) | 8.65 (7.82 to 9.48) | Moderate |
| Naproxen 400 to 440mg | 8.47 (6.15 to 10.79) | Moderate |
| Acetaminophen 500 to 1,000mg | 4.20 (3.30 to 5.09) | Moderate |
| Acetaminophen 600 to 650mg plus codeine 60mg | 5.03 (4.04 to 6.03) | Moderate |
- Oxycodone 5 mg and codeine 60 mg was not more effective than placebo.
- 31 RCTs (6,721 patients) were included in the NMA for SPID using an 18-point scale, where higher scores represent better outcomes. With reference to placebo the most effective interventions are shown in descending order in the table below
| Intervention | MD (95%CI) | GRADE certainty |
| Acetaminophen 650mg plus oxycodone 10mg | 5.54 (5.26 to 6.02) | Moderate |
| Ibuprofen 400mg (fast acting or acid) | 5.58 (4.85 to 6.31) | Moderate |
| Acetaminophen 500 to 1,000mg | 2.95 (2.31 to 3.60) | Moderate |
| Acetaminophen 600 to 650mg plus codeine 60mg | 2.92 (2.32 to 3.53) | Moderate |
| Naproxen 400 to 440mg | 5.27 (3.50 to 7.03) | Moderate |
| Ibuprofen 200 to 400 mg plus acetaminophen 500 to 1,000 mg | 4.41(5.78 to 3.04) | Low |
- Oxycodone 5 mg and codeine 60 mg was not more effective than placebo.
- For adverse effects most interventions were considered to be no more harmful than placebo (low and very low certainty evidence).
Conclusions
The authors concluded: –
Based on moderate- and high-certainty evidence, in individuals undergoing surgical tooth extractions, the interventions classified as the most effective for pain relief were ibuprofen 200 to 400 mg plus acetaminophen 500 to 1,000 mg, acetaminophen 650mg plus oxycodone 10mg, ibuprofen 400mg, and naproxen 400–440 mg.
Oxycodone 5 mg or codeine 60 mg and tramadol 37.5mg plus acetaminophen 325mg were no better than placebo.
The results for TOTPAR, SPID, global efficacy rating, and rescue analgesia were similar to pain relief. Based on low- and very low-certainty evidence, most interventions were classified as no more harmful than placebo for most adverse effects
Comments
This review was undertaken to inform a forthcoming guideline for the American Dental Association (ADA) on the management of acute pain. The review was reported in line with the referred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a PRISMA checklist is included in the extensive 76-page supplementary appendix which is open access as is the main publication. Searches were conducted in 3 major databases and the US Clinical Trials registry. However, only English language studies published in peer-reviewed journals were included and only 10 interventions commonly used in the USA considered. This needs to be taken into consideration when interpreting the findings and may have implications for applicability, a point noted by the authors. The authors also note other systematic reviews in this area highlighting points that may contribute to differing conclusions. As this review was to inform forthcoming guidance it will be interesting to see how these findings contribute to the guideline recommendations.
Links
Primary Paper
Miroshnychenko A, Ibrahim S, Azab M, Roldan Y, Martinez JPD, Tamilselvan D, He L, Little JW, Urquhart O, Tampi M, Polk DE, Moore PA, Hersh EV, Claytor B, Carrasco-Labra A, Brignardello-Petersen R. Acute Postoperative Pain Due to Dental Extraction in the Adult Population: A Systematic Review and Network Meta-analysis. J Dent Res. 2023 Apr;102(4):391-401. doi: 10.1177/00220345221139230. Epub 2023 Jan 11. PMID: 36631957.
Other references
ADA Clinical Practice Guidelines
Dental Elf – 18th Jan 2023
Dental Elf – 5th Aug 2019
COX-2 inhibitors for pain management after third molar removal
Dental Elf – 21st Jan 2014
Ibuprofen more effective than paracetamol for postoperative pain following third molar removal
Picture Credits
Photo by Volodymyr Hryshchenko on Unsplash
