Non-Cochrane · intervention · PM41578906
Adverse events of oral analgesics after third molar extraction: A network meta-analysis of randomized controlled trials.
Magesty R-A, de-Souza G-M, Fernandes I-A, et al. · Medicina oral, patologia oral y cirugia bucal · 2026 · PubMed · doi:10.4317/medoral.27956
Findings
Population Patients with moderate to severe pain after lower third molar extraction under local anesthesia
10 findings
| Non opioid analgesic | Placebo | Any adverse event related to medication use before discharge Up to hospital discharge · Single-dose oral analgesic after lower third molar surgery under local anesthesia | RR 1.49 [0.87, 2.55] GRADE not reported Studies not reported |
| Non opioid analgesic plus Opioid | Placebo | Any adverse event related to medication use before discharge Up to hospital discharge · Single-dose oral analgesic after lower third molar surgery under local anesthesia | RR 1.71 [1.05, 2.77] Low Studies not reported |
| NSAID plus Non opioid analgesic | Placebo | Any adverse event related to medication use before discharge Up to hospital discharge · Single-dose oral analgesic after lower third molar surgery under local anesthesia | RR 1.06 [0.31, 3.64] GRADE not reported Studies not reported |
| NSAID plus Non opioid analgesic plus Opioid | Placebo | Any adverse event related to medication use before discharge Up to hospital discharge · Single-dose oral analgesic after lower third molar surgery under local anesthesia | RR 2.41 [0.94, 6.17] GRADE not reported Studies not reported |
| NSAIDs | Placebo | Any adverse event related to medication use before discharge Up to hospital discharge · Single-dose oral analgesic after lower third molar surgery under local anesthesia | RR 0.95 [0.69, 1.31] GRADE not reported Studies not reported |
| Opioid analgesic | Placebo | Any adverse event related to medication use before discharge Up to hospital discharge · Single-dose oral analgesic after lower third molar surgery under local anesthesia | RR 1.69 [0.9, 3.17] GRADE not reported Studies not reported |
| Opioid plus NSAID | Placebo | Any adverse event related to medication use before discharge Up to hospital discharge · Single-dose oral analgesic after lower third molar surgery under local anesthesia | RR 1.76 [0.99, 3.15] GRADE not reported Studies not reported |
| NSAIDs | Non opioid analgesic | Any adverse event related to medication use before discharge Up to hospital discharge · Single-dose oral analgesic after lower third molar surgery under local anesthesia | RR 1.82 [1.24, 2.68] Low Studies not reported |
| NSAIDs | Non opioid analgesic plus Opioid | Any adverse event related to medication use before discharge Up to hospital discharge · Single-dose oral analgesic after lower third molar surgery under local anesthesia | RR 1.42 [1.03, 1.96] Low Studies not reported |
| Opioid analgesic | NSAIDs | Any adverse event related to medication use before discharge Up to hospital discharge · Single-dose oral analgesic after lower third molar surgery under local anesthesia | RR 0.61 [0.41, 0.89] Very low Studies not reported |
Included primary studies 39
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Ahlstrom 1993 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Bakshi 1992 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Bakshi 1994 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Breivik 1999 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Clark 1989 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Desjardins 1983 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Frame 1986 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Fricke 2002 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Gay-Escoda 2019 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Goldstein 1994 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Haglund and Bültzingslöwen 2006 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Hill 2001 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Hill 2006 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Jackson 2004 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Jones 1997 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Jung 2004 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Litkowski 2005 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Macleod 2002 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| McQuay 1996 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Moller 2008 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Moore 1998 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Moore 2015 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Olson 1996 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Olson 2001 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Planas 1998 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Puigvert 1990 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Quiding 1993 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Ragot 1993 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Rowe 1985 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Schleier 2007 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Schou 1998 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Sunshine 1983 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Sunshine 1986 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Varner 2009 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Weiser 2017 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Yamashita 2014 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Yeung 2003 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Young 2013 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Zuniga 2010 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Patients with moderate to severe pain after lower third molar extraction under local anesthesia | Patients after third molar surgery (n=5306 surgeries) |
| Intervention | Anti-inflammatory drugs and/or analgesics, any dose, single oral dose | Monotherapies (non opioid analgesic, NSAIDs, opioid) and combinations (non opioid plus opioid, NSAID plus non opioid, NSAID plus non opioid plus opioid, opioid plus NSAID) |
| Comparison | Placebo, other oral medications, or same drug at different single doses | Placebo (n=1078; 23 RCTs) and active comparators |
| Outcomes | Adverse events related to medication use reported up to discharge | Any adverse event before discharge (28 RCTs in network meta-analysis) |
| Study designs | Parallel, cross-over or split-mouth RCTs | RCTs (n=40 included; n=28 in network meta-analysis) |
| Timing | Up to discharge | Up to discharge |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | Partial Yes | Partial Yes | yes |
| 3Choice of study designs explained | No | No | yes |
| 4Comprehensive literature searchcritical | Partial Yes | Partial Yes | yes |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | No | No | yes |
| 8Included studies described in detail | Partial Yes | Partial Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | RCT: Yes · NRSI: N/A | NRSI: N/A · RCT: Yes | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: Yes · NRSI: N/A | NRSI: N/A · RCT: Yes | no |
| 12Impact of risk of bias on the pooled results | No | No | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | No | No | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Critically Low | Critically Low | yes |