Is coadministration of preemptive medications an effective strategy for reducing inflammatory clinical events and the need for rescue medication after mandibular third molar surgery? A systematic review of randomized clinical trials

Abstract

This study aimed to evaluate the scientific evidence on the effect of preemptive drug coadministration (PDC) for relieving inflammatory events (pain, swelling, and trismus) in mandibular third molar surgery. A PROSPERO-registered systematic review (CRD42022314546) was conducted according to the PRISMA guide. The searches were carried out in six primary databases and the gray literature. Studies not written in languages with the Latin alphabet (Roman) were excluded. Potential randomized controlled trials (RCTs) were screened for eligibility. Cochrane’s Risk of Bias-2.0 (RoB) tool was assessed. A synthesis without meta-analysis (SWiM) based on a vote counting and an effect direction plot. Nine studies (low RoB) fulfilled the eligibility criteria and were included for data analysis, with a total of 484 patients. PDC mostly involved corticosteroids (Cort) and non-steroidal anti-inflammatory drugs (NSAIDs). PDC of Cort and other drugs mainly reduced pain scores (6 and 12 h postoperatively) and swelling (48 h postoperatively). PDC of NSAIDs and other drugs mainly reduced pain scores at 6, 8, and 24 h follow-up; swelling and trismus intensity ameliorated at 48 h postoperatively. The most frequently prescribed rescue medication was paracetamol, dipyrone, and paracetamol plus codeine. Results from individual studies have shown reduced consumption of ingested rescue analgesics. In summary, the available evidence from clinical trials included in this SWiM suggests that PDC may provide benefits in reducing the severity of inflammatory outcomes related to mandibular third molar surgery, especially the pain scores in the first hours after surgery, and the rescue analgesic consumption during the postoperative period.

Appendices

Appendix

Appendix A. Search terms specific

Electronic database

Search strategy used

Keywords

Molar, Third; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents; Analgesics; Premedication; Drgu Therapy; Dexamethasone; Glucocorticoids; Therapeutics; Drug Therapy, Combination; Anti-Anxiety Agents "Molar, Third"[Mesh] = "Third Molar" OR "Third Molars" OR "Wisdom Tooth" OR "Wisdom Teeth" "Anti-Inflammatory Agents, Non-Steroidal"[Mesh] = "NSAIDs" OR "Non-Steroidal Anti-Inflammatory Agents" OR "Non Steroidal Anti Inflammatory Agents" OR "Nonsteroidal Anti-Inflammatory Agents" OR "Nonsteroidal Anti Inflammatory Agents" OR "Nonsteroidal Antiinflammatory Agents" OR "Anti-Inflammatory Analgesics" OR "Aspirin-Like Agents" OR "Aspirin Like Agents" OR "Analgesia" OR "Analgesias" OR "Preoperative Period" OR "Pain Management" OR "Pain Managements" OR "preemptive" OR "pre-emptive" "Anti-Inflammatory Agents"[Mesh] = “Agents, Anti-Inflammator” OR “Agents, Antiinflammatory” OR “Anti-Inflammatories” OR “Anti-Inflammatory Agent” OR “Antiinflammatories” OR “Antiinflammatory Agent” OR “Antiinflammatory Agents” "Analgesics"[Mesh] = “Analgesic” OR “Analgesic Agents” OR “Analgesic Drugs” OR “Anodynes” OR “Antinociceptive Agents” “Premedication” [Mesh] “Drug Therapy” [Mesh] = “Chemotherapy” OR “Pharmacotherapy” OR “Therapy, Drug” “Dexamethasone” [Mesh] = “Decaject” OR “Decaject-L.A.” OR “Decameth” OR “Decaspray” OR “Dexasone” OR “Dexpak” OR “Hexadecadrol” OR “Hexadrol” OR “Maxidex” OR “Methylfluorprednisolone” OR “Millicorten” OR “Oradexon” “Glucocorticoids” [Mesh] = “Glucocorticoid” OR “Glucocorticoid Effect” OR “Glucorticoid Effects” "Therapeutics"[Mesh] = “Therapy” OR “Treatment” "Drug Therapy, Combination"[Mesh] = “Chemotherapy, Combination” OR “Combination Chemotherapy” OR “Combination Drug Therapy” OR “Drug Polytherapy” OR “Polychemotherapy” OR “Therapy, Combination Drug” "Anti-Anxiety Agents"[Mesh] = “Anti-Anxiety Agent” OR “Anti-Anxiety Drug” OR “Anti-Anxiety Drugs” OR “Anti-Anxiety Effect” OR “Anti-Anxiety Effects” OR “Antianxiety Effect” OR “Antianxiety Effects” OR “Anxiolytic” OR “Anxiolytic Agent” OR “Anxiolytic Agents” OR “Anxiolytic Effect” OR “Anxiolytic Effects” OR “Anxiolytics” OR “Tranquilizing Agents, Minor” OR “Tranquillizing Agents, Minor”

Appendix B. Search terms specific for each database and truncations

Electronic database	Search strategy used	Items found
PubMed	("Molar, Third"[Mesh]) AND ((((((((((((((("Anti-Inflammatory Agents, Non-Steroidal"[Mesh]) OR "Analgesia"[Mesh]) OR "Preoperative Period"[Mesh]) OR preemptive) OR pre-emptive) OR "Pain Management"[Mesh]) OR "Anti-Inflammatory Agents"[Mesh]) OR "Analgesics"[Mesh]) OR “Premedication”[Mesh]) OR “Drug Therapy”[Mesh]) OR “Dexamethasone”[Mesh]) OR “Glucocorticoids”[Mesh]) OR "Therapeutics"[Mesh]) OR "Drug Therapy, Combination"[Mesh]) OR "Anti-Anxiety Agents"[Mesh])	1462
Scopus	TITLE-ABS-KEY ("Third Molar" OR "Third Molars" OR "Wisdom Tooth" OR "Wisdom Teeth") AND TITLE-ABS-KEY ( "NSAIDs" OR "Non-Steroidal Anti-Inflammatory Agents" OR "Non Steroidal Anti Inflammatory Agents" OR "Nonsteroidal Anti-Inflammatory Agents" OR "Nonsteroidal Anti Inflammatory Agents" OR "Nonsteroidal Antiinflammatory Agents" OR "Anti-Inflammatory Analgesics" OR "Aspirin-Like Agents" OR "Aspirin Like Agents" OR "Analgesia" OR "Analgesias" OR "Preoperative Period" OR "Pain Management" OR "Pain Managements" OR "preemptive" OR "pre-emptive" OR "Anti-Inflammatory Agents" OR “Agents, Anti-Inflammator” OR “Agents, Antiinflammatory” OR “Anti-Inflammatories” OR “Anti-Inflammatory Agent” OR “Antiinflammatories” OR “Antiinflammatory Agent” OR “Antiinflammatory Agents” OR "Analgesics" OR “Analgesic” OR “Analgesic Agents” OR “Analgesic Drugs” OR “Anodynes” OR “Antinociceptive Agents” OR “Premedication” OR “Drug Therapy” OR “Chemotherapy” OR “Pharmacotherapy” OR “Therapy, Drug” OR “Dexamethasone” OR “Decaject” OR “Decaject-L.A.” OR “Decameth” OR “Decaspray” OR “Dexasone” OR “Dexpak” OR “Hexadecadrol” OR “Hexadrol” OR “Maxidex” OR “Methylfluorprednisolone” OR “Millicorten” OR “Oradexon” OR “Glucocorticoids” OR “Glucocorticoid” OR “Glucocorticoid Effect” OR “Glucorticoid Effects” OR "Therapeutics" OR “Therapy” OR “Treatment” OR "Drug Therapy, Combination" OR “Chemotherapy, Combination” OR “Combination Chemotherapy” OR “Combination Drug Therapy” OR “Drug Polytherapy” OR “Polychemotherapy” OR “Therapy, Combination Drug” OR "Anti-Anxiety Agents" OR “Anti-Anxiety Agent” OR “Anti-Anxiety Drug” OR “Anti-Anxiety Drugs” OR “Anti-Anxiety Effect” OR “Anti-Anxiety Effects” OR “Antianxiety Effect” OR “Antianxiety Effects” OR “Anxiolytic” OR “Anxiolytic Agent” OR “Anxiolytic Agents” OR “Anxiolytic Effect” OR “Anxiolytic Effects” OR “Anxiolytics” OR “Tranquilizing Agents, Minor” OR “Tranquillizing Agents, Minor”)	1790
Web of Science	TÓPICO: ((("Third Molar" OR "Third Molars") OR "Wisdom Tooth") OR "Wisdom Teeth") AND TÓPICO: ((((((((((((((((((((((((((((((((((((((((((((((((((("NSAIDs" OR "Non-Steroidal Anti-Inflammatory Agents") OR "Non Steroidal Anti Inflammatory Agents") OR "Nonsteroidal Anti-Inflammatory Agents") OR "Nonsteroidal Anti Inflammatory Agents") OR "Nonsteroidal Antiinflammatory Agents") OR "Anti-Inflammatory Analgesics") OR "Aspirin-Like Agents") OR "Aspirin Like Agents") OR "Analgesia") OR "analgesics") OR "Preoperative Period") OR "Pain Management") OR "Pain Managements") OR "preemptive") OR "pre-emptive") OR "Anti-Inflammatory Agents") OR “Agents, Anti-Inflammator”) OR “Agents, Antiinflammatory”) OR “Anti-Inflammatories”) OR “Anti-Inflammatory Agent”) OR “Antiinflammatories”) OR “Antiinflammatory Agent”) OR “Antiinflammatory Agents”) OR "Analgesics") OR “Analgesic”) OR “Analgesic Agents”) OR “Analgesic Drugs”) OR “Anodynes”) OR “Antinociceptive Agents”) OR “Premedication”) OR “Drug Therapy”) OR “Chemotherapy”) OR “Pharmacotherapy”) OR “Therapy, Drug”) OR “Dexamethasone”) OR “Decaject”) OR “Decaject-L.A.”) OR “Decameth”) OR “Decaspray”) OR “Dexasone”) OR “Dexpak”) OR “Hexadecadrol”) OR “Hexadrol”) OR “Maxidex”) OR “Methylfluorprednisolone”) OR “Millicorten”) OR “Oradexon”) OR “Glucocorticoids”) OR “Glucocorticoid”) OR “Glucocorticoid Effect”) OR “Glucorticoid Effects”))	851
COCHRANE	ID Search Hits #1 "Third Molar" OR "Third Molars" OR "Wisdom Tooth" OR "Wisdom Teeth":ti,ab,kw (Word variations have been searched) #2 "NSAIDs" OR "Non-Steroidal Anti-Inflammatory Agents" OR "Non Steroidal Anti Inflammatory Agents" OR "Nonsteroidal Anti-Inflammatory Agents" OR "Nonsteroidal Anti Inflammatory Agents" OR "Nonsteroidal Antiinflammatory Agents" OR "Anti-Inflammatory Analgesics" OR "Aspirin-Like Agents" OR "Aspirin Like Agents" OR "Analgesia" OR "Analgesias" OR "Preoperative Period" OR "Pain Management" OR "Pain Managements" OR "preemptive" OR "pre-emptive" OR "Anti-Inflammatory Agents" OR “Agents, Anti-Inflammator” OR “Agents, Antiinflammatory” OR “Anti-Inflammatories” OR “Anti-Inflammatory Agent” OR “Antiinflammatories” OR “Antiinflammatory Agent” OR “Antiinflammatory Agents” OR "Analgesics" OR “Analgesic” OR “Analgesic Agents” OR “Analgesic Drugs” OR “Anodynes” OR “Antinociceptive Agents” OR “Premedication” OR “Drug Therapy” OR “Chemotherapy” OR “Pharmacotherapy” OR “Therapy, Drug” OR “Dexamethasone” OR “Decaject” OR “Decaject-L.A.” OR “Decameth” OR “Decaspray” OR “Dexasone” OR “Dexpak” OR “Hexadecadrol” OR “Hexadrol” OR “Maxidex” OR “Methylfluorprednisolone” OR “Millicorten” OR “Oradexon” OR “Glucocorticoids” OR “Glucocorticoid” OR “Glucocorticoid Effect” OR “Glucorticoid Effects":ti,ab,kw (Word variations have been searched) #3 #1 and #2	675
LILACS	(tw:("Third Molar" OR "Third Molars" OR "Wisdom Tooth" OR "Wisdom Teeth")) AND (tw:( "NSAIDs" OR "Non-Steroidal Anti-Inflammatory Agents" OR "Non Steroidal Anti Inflammatory Agents" OR "Nonsteroidal Anti-Inflammatory Agents" OR "Nonsteroidal Anti Inflammatory Agents" OR "Nonsteroidal Antiinflammatory Agents" OR "Anti-Inflammatory Analgesics" OR "Aspirin-Like Agents" OR "Aspirin Like Agents" OR "Analgesia" OR "Analgesias" OR "Preoperative Period" OR "Pain Management" OR "Pain Managements" OR "preemptive" OR "pre-emptive" OR "Anti-Inflammatory Agents" OR “Agents, Anti-Inflammator” OR “Agents, Antiinflammatory” OR “Anti-Inflammatories” OR “Anti-Inflammatory Agent” OR “Antiinflammatories” OR “Antiinflammatory Agent” OR “Antiinflammatory Agents” OR "Analgesics" OR “Analgesic” OR “Analgesic Agents” OR “Analgesic Drugs” OR “Anodynes” OR “Antinociceptive Agents” OR “Premedication” OR “Drug Therapy” OR “Chemotherapy” OR “Pharmacotherapy” OR “Therapy, Drug” OR “Dexamethasone” OR “Decaject” OR “Decaject-L.A.” OR “Decameth” OR “Decaspray” OR “Dexasone” OR “Dexpak” OR “Hexadecadrol” OR “Hexadrol” OR “Maxidex” OR “Methylfluorprednisolone” OR “Millicorten” OR “Oradexon” OR “Glucocorticoids” OR “Glucocorticoid” OR “Glucocorticoid Effect” OR “Glucorticoid Effects”))	44
DOSS	( "Third Molar" OR "Third Molars" OR "Wisdom Tooth" OR "Wisdom Teeth") AND ("NSAIDs" OR "Non-Steroidal Anti-Inflammatory Agents" OR "Non Steroidal Anti Inflammatory Agents" OR "Nonsteroidal Anti-Inflammatory Agents" OR "Nonsteroidal Anti Inflammatory Agents" OR "Nonsteroidal Antiinflammatory Agents" OR "Anti-Inflammatory Analgesics" OR "Aspirin-Like Agents" OR "Aspirin Like Agents" OR "Analgesia" OR "Analgesias" OR "Preoperative Period" OR "Pain Management" OR "Pain Managements" OR "preemptive" OR "pre-emptive" OR "Anti-Inflammatory Agents" OR “Agents, Anti-Inflammator” OR “Agents, Antiinflammatory” OR “Anti-Inflammatories” OR “Anti-Inflammatory Agent” OR “Antiinflammatories” OR “Antiinflammatory Agent” OR “Antiinflammatory Agents” OR "Analgesics" OR “Analgesic” OR “Analgesic Agents” OR “Analgesic Drugs” OR “Anodynes” OR “Antinociceptive Agents” OR “Premedication” OR “Drug Therapy” OR “Chemotherapy” OR “Pharmacotherapy” OR “Therapy, Drug” OR “Dexamethasone” OR “Decaject” OR “Decaject-L.A.” OR “Decameth” OR “Decaspray” OR “Dexasone” OR “Dexpak” OR “Hexadecadrol” OR “Hexadrol” OR “Maxidex” OR “Methylfluorprednisolone” OR “Millicorten” OR “Oradexon” OR “Glucocorticoids” OR “Glucocorticoid” OR “Glucocorticoid Effect” OR “Glucorticoid Effects”)	437
Grey literature
Google Scholar	Busca #1. allintitle: third molar (total 26) Busca #2. allintitle: Non-Steroidal Anti-Inflammatory Agents (total 9) Busca #3. allintitle: preemptive (total 1) Busca #4. allintitle: Anti-Inflammatory Agents (total 7) Busca #5. allintitle: Premedication (total 4) Busca #6. allintitle: Glucocorticoids (total 13)	60
ProQuest	noft(Third Molar OR Third Molars OR Wisdom Tooth OR Wisdom Teeth) AND noft(NSAIDs OR Non-Steroidal Anti-Inflammatory Agents OR Non Steroidal Anti Inflammatory Agents OR Nonsteroidal Anti-Inflammatory Agents OR Nonsteroidal Anti Inflammatory Agents OR Nonsteroidal Antiinflammatory Agents OR Anti-Inflammatory Analgesics OR Aspirin-Like Agents OR Aspirin Like Agents OR Analgesia OR Analgesias OR Preoperative Period OR Pain Management OR Pain Managements OR preemptive OR pre-emptive)	65
OpenGrey	Third molar	33
Total		5417