Acute Postoperative Pain Due to Dental Extraction in the Adult Population: A Systematic Review and Network Meta-analysis

Abstract

This study compares the effectiveness of pharmacological treatments to develop guidelines for the management of acute pain after tooth extraction. We searched Medline, EMBASE, CENTRAL, and US Clinical Trials registry on November 21, 2020. We included randomized clinical trials (RCTs) of participants undergoing dental extractions comparing 10 interventions, including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and combinations to placebo. After duplicate screening and data abstraction, we conducted a frequentist network meta-analysis for each outcome at 6 h (i.e., pain relief, total pain relief [TOTPAR], summed pain intensity difference [SPID], global efficacy rating, rescue analgesia, and adverse effects). We assessed the risk of bias using a modified Cochrane RoB 2.0 tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We implemented the analyses in RStudio version 3.5.3 and classified interventions from most to least beneficial or harmful. We included 82 RCTs. Fifty-six RCTs enrolling 9,095 participants found moderate- and high-certainty evidence that ibuprofen 200 to 400 mg plus acetaminophen 500 to 1,000 mg (mean difference compared to placebo [MDp], 1.68; 95% confidence interval [CI], 1.06–2.31), acetaminophen 650 mg plus oxycodone 10 mg (MDp, 1.19; 95% CI, 0.85–1.54), ibuprofen 400 mg (MDp, 1.31; 95% CI, 1.17–1.45), and naproxen 400–440 mg (MDp, 1.44; 95% CI, 1.07–1.80) were most effective for pain relief on a 0 to 4 scale. Oxycodone 5 mg, codeine 60 mg, and tramadol 37.5 mg plus acetaminophen 325 mg were no better than placebo. The results for TOTPAR, SPID, global efficacy rating, and rescue analgesia were similar. Based on low- and very low-certainty evidence, most interventions were classified as no more harmful than placebo for most adverse effects. Based on moderate- and high-certainty evidence, NSAIDs with or without acetaminophen result in better pain-related outcomes than opioids with or without acetaminophen (except acetaminophen 650 mg plus oxycodone 10 mg) or placebo.

A guide and pragmatic considerations for applying GRADE to network meta-analysis

“…To date, we have assessed the certainty of evidence for the original version and the four updates of the living systematic review and NMA of randomised trials investigating the treatment of covid-19, which included more than 4000 comparisons in the latest version 9. Although the approach has not been formally tested yet, it has been successfully implemented in other systematic reviews with NMA 12131415…”

“…We then developed a spreadsheet (supplementary file 1) that allowed automation of some steps and made modifications based on informal feedback from eight reviewers in charge of assessing the certainty of evidence in the living systematic review and NMA of randomised trials looking at the prophylaxis and treatment of covid-19. The approach was then successfully implemented in other four systematic reviews with NMA 12131415. This article describes practical strategies, including rule setting and automation that can facilitate implementation of the GRADE approach for NMA.…”

Pain management following dental trauma and surgical procedures

“…A 2023 systematic review and network meta‐analysis of acute postoperative pain secondary to surgical tooth extraction by Miroshnychenko et al, concluded that the most effective oral pain management therapies were as follows: IBU 200 mg–400 mg plus APAP 500 mg–1000 mg; APAP 650 mg plus oxycodone 10 mg; and IBU 400 mg plus NAP 400 mg–440 mg. Oxycodone 5 mg, codeine 60 mg, or tramadol 37.5 mg plus APAP 325 mg, were no better than placebo. Opioids and their combinations were associated with higher rates of acute adverse events 48 …”

“…The most valuable advantage for combining ibuprofen and APAP is the potential to improve analgesic efficacy without increasing the incidence of adverse drug reactions 48,57 …”

“…The most valuable advantage for combining ibuprofen and APAP is the potential to improve analgesic efficacy without increasing the incidence of adverse drug reactions. 48,57 For severe-pain, IBU 400-600 mg with APAP 650 mg with hydrocodone 10 mg every 6 h in a fixed interval for 24-48 h, followed by IBU 400-600 mg with APAP 500 mg every 6 h prn pain.…”