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Postsurgical pain is commonly associated with dental and oral surgery, and the use of analgesics has been investigated in the management of postoperative pain. This systematic review summarizes available evidence on analgesics used to manage dental implant surgery postoperative pain, to identify best therapeutic protocols and knowledge gap. A comprehensive search was conducted including MEDLINE/Pubmed, EMBASE, SCOPUS, clinicaltrials.gov, and the Cochrane Database of Systematic Reviews through May 2020. Only randomized controlled trials were included. PRISMA guidelines were followed, and risk of bias was appraised using Cochrane RoB2 tool. Eleven trials (762 patients overall) were included. Some aspects limited the feasibility of a meaningful meta-analysis; thus, a narrative synthesis was conducted. Risk of bias was low in four studies and high in two studies, while five studies raised some concerns due to the randomization process. Analgesic use seemed to be associated with improved postoperative outcomes (pain, patient’s satisfaction, and need for rescue medication) when compared to placebo. Overall, this review suggests that the administration of analgesics may provide some advantages in the management of postoperative outcomes after dental implant placement, while indications about the best analgesics cannot be provided.
Dental implant therapy has been a revolution in dentistry. Today, oral rehabilitation of single or multiple edentulism with dental implants is a very common procedure, and its use has steadily increased in recent decades (
After dental implant placement surgery, patients may present different degrees of postoperative discomfort. Pain and swelling are common consequences of the surgical trauma, induced by the release of inflammatory mediators (
Pain is usually mild or moderate, although some patients may experience severe pain (
This systematic review aims to summarize available evidence on analgesics in the management of postoperative pain after dental implant placement.
This is a systematic review of randomized controlled trials (RCTs) evaluating analgesic drugs in the management of postoperative pain after dental implant placement. The review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (
To identify relevant studies, we systematically searched MEDLINE/PubMed, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov. The search strategy was carried out without language restrictions from database inception until June 2019. Two investigators (MM and AF) independently reviewed the search results and screened the titles and abstracts. We obtained the full texts of all potentially eligible studies. In PubMed, the following search strategy was used: “((((“dental implants”[MeSH Terms] OR (“dental”[All Fields] AND “implants”[All Fields])) OR “dental implants”[All Fields]) OR (“dental”[All Fields] AND “implant”[All Fields])) OR “dental implant”[All Fields]) AND ((((((“analgesic s”[All Fields] OR “analgesically”[All Fields]) OR “analgesics” [Pharmacological Action]) OR “analgesics”[MeSH Terms]) OR “analgesics”[All Fields]) OR “analgesic”[All Fields]) OR (((“analgesia”[MeSH Terms] OR “analgesia”[All Fields]) OR “analgesias”[All Fields]))).” This search strategy was adapted to suit the other electronic sources. We also hand-searched the reference lists of retrieved articles to identify additional studies of interest. Any inconsistencies were resolved by consensus with a third investigator (MP).
Study design: parallel and crossover RCTs.
Population: adult patients (aged 16 or more) undergoing single or multiple dental implant surgeries.
Intervention: any analgesic drugs, defined as compounds capable of relieving pain without the loss of consciousness.
Comparator: any analgesic drugs or placebo.
Outcome: intensity of postoperative pain, swelling, patient’s satisfaction, need for rescue medication, and adverse events.
Time: postoperative.
Studies not including human subjects were excluded. No language restrictions were applied.
Two investigators (FC and MP) independently extracted key data from the included articles. The inter-rater agreement was assessed using Cohen’s kappa statistics. For each article, we extracted study features (i.e., study design, year of publication, country, number, and age of enrolled patients), type of intervention, and outcomes measures. A third investigator (GZ) checked the extracted data.
Two investigators (FC and MP) independently appraised the risk of bias of the included studies by using the Cochrane revised tool to assess risk of bias in randomized trials (RoB 2.0) (
A narrative synthesis of included studies was conducted, because some aspects limited the feasibility of a meaningful meta-analysis. Such aspects included the large number of type analgesic drugs that were evaluated, the heterogeneous outcome measures, and the heterogeneous timing of assessment. The findings from each study were summarized in tables using a narrative approach rather than a quantitative approach, to improve clarity and readability for the readers.
The search yielded 319 non-duplicated articles. After excluding 303 articles based on title/abstract, 16 articles were retrieved for full-text review. Of these, five were excluded due to different interventions (three studies) or unavailability of results (two ongoing studies). No additional articles were identified
PRISMA flow diagram.
The analysis included 10 parallel RCTs [
Characteristics of included studies.
# | Study | Country | Study design | Enrolled participants, no | Participant age, years | Implants | Types of analgesic drugs | Timing of administration of analgesic drugs | Outcome measures of interest |
---|---|---|---|---|---|---|---|---|---|
1 |
|
Brazil | Parallel RCT | 54 | 37–74 | Single | Ibuprofen vs. placebo | 1 h before surgery | Postop pain (VAS), need for rescue medication, adverse events |
2 |
|
India | Parallel RCT | 40 | 16–40 | Single | Piroxicam vs. placebo | 1 h before surgery | Postop pain (VAS), swelling (using the distance between the lateral corner of the eye and the angle of the mandible and the distance between the tragus of the ear and the outer corner of the mouth) |
3 |
|
United States | Parallel RCT | 69 | ≥18 | Full-arch | Standard care + liposomal bupivacaine vs. standard care | At the end of surgery | Postop pain (0–10 scale), patient’s satisfaction (1–5 scale), need for rescue medication, adverse events |
4 |
|
Spain | Parallel RCT | 100 | ≥18 | Single | Dexketoprofen trometamol vs. placebo | 15 min before surgery | Postop pain (VAS), adverse events |
5 |
|
Kingdom of Saudi Arabia | Parallel RCT | 117 | ≥18 | Single | Ibuprofen vs. dexamethasone vs. Placebo | 1 h before surgery + 6 h after the first dose | Post pain (VAS, NR101), patient’s satisfaction (VRS-4), need for rescue medication, adverse events |
6 |
|
Argentina | Parallel RCT | 30 | 40–85 | Multiple | Ketorolac vs. ketorolac + betamethasone | Within 2 h before surgery | Postop pain (VAS) |
7 |
|
Iran | Parallel RCT | 80 | 35–55 | Single | Caffeine vs. Codeine | 1 h before surgery + every 6 h until 48 h | Postop pain (VAS), swelling (based on VAS) |
8 |
|
India | Crossover RCT | 20 | 30–65 | Single | Diclofenac diethylamine transdermal patches vs. Oral diclofenac sodium | After surgery for 72 h | Postop pain (NRS, VRS, PRS), patient’s satisfaction (preferred treatment), adverse events |
9 |
|
China | Parallel RCT | 60 | 19–60 | Multiple | Midazolam + fentanyl vs. dexmedetomidine + fentanyl | Peri-operative | Postop pain (VAS) |
10 |
|
Turkey | Parallel RCT | 92 | 18–65 | Single/multiple | Lornoxicam vs. Placebo | After surgery | Postop pain (0–3 scale), patient’s satisfaction (1–7 scale), need for rescue medication, adverse events |
11 |
|
Turkey | Parallel RCT | 100 | Mean 53 | Multiple | Meloxicam vs. teloxicam | 1 day before surgery + 1 h before surgery + for 2 days after surgery | Postop pain (VAS), need for rescue medication |
In
The risk of bias is reported in
Summary of risk of bias.
All eleven studies investigated postoperative pain as reported by patients using visual analogue scale (VAS) [
Postoperative pain (narrative synthesis).
# | Study | Postoperative pain |
---|---|---|
1 |
|
Lower with ibuprofen vs. placebo (1–24 h postop) |
2 |
|
Lower with piroxicam vs. placebo (6 h–5 days postop) |
3 |
|
Lower with standard care + liposomal bupivacaine vs. standard care (0–7 days postop) |
4 |
|
Lower with dexketoprofen trometamol vs. placebo (immediate postop) |
5 |
|
Lower with ibuprofen or dexamethasone vs. placebo, but no statistically significant difference between ibuprofen and dexamethasone (1–3 days postop) |
6 |
|
No statistically significant difference between ketorolac vs. ketorolac + betamethasone (3–14 days postop) |
7 |
|
Lower with codeine vs. caffeine (3–6–12 h postop) |
8 |
|
Inconclusive results |
9 |
|
Lower with dexmedetomidine + fentanyl vs. midazolam + fentanyl (2–4 h postop) |
10 |
|
Lower with lornoxicam vs. placebo (0.5–4 h postop) |
11 |
|
No statistically significant difference between meloxicam vs. teloxicam (1–7 days postop) |
Two studies (
Swelling (narrative synthesis).
# | Study | Swelling |
---|---|---|
2 |
|
Lower with piroxicam vs. placebo (1–5 days postop) |
7 |
|
Lower with caffeine vs. codeine (1–3 days postop) |
Four studies [
Patient’s satisfaction (narrative synthesis).
# | Study | Patient’s satisfaction |
---|---|---|
3 |
|
Higher with standard care + liposomal bupivacaine vs. standard care (days 0–1) |
5 |
|
Higher with ibuprofen or dexamethasone vs. placebo, but no statistically significant difference between ibuprofen and dexamethasone (1–2 days postop) |
8 |
|
18/20 patients preferred transdermal diclofenac diethylamine over oral diclofenac sodium |
10 |
|
Higher with lornoxicam vs. placebo (12 h postop) |
Six studies [
Need for rescue medication (narrative synthesis).
# | Study | Need for rescue medication |
---|---|---|
1 |
|
Lower with ibuprofen vs. placebo |
3 |
|
No statistically significant difference between standard care + liposomal bupivacaine vs. standard care |
5 |
|
Lower with ibuprofen or dexamethasone vs. placebo, but no statistically significant different between ibuprofen and dexamethasone |
8 |
|
0/20 transdermal diclofenac diethylamine vs. unclear in oral diclofenac sodium |
10 |
|
Lower with lornoxicam vs. placebo |
11 |
|
No statistically significant difference between meloxicam vs. teloxicam |
Six studies [
Adverse events (narrative synthesis).
# | Study | Adverse events |
---|---|---|
1 |
|
None |
3 |
|
No statistically significant difference between standard care + liposomal bupivacaine vs. standard care |
4 |
|
More bleeding with dexketoprofen trometamol vs. placebo |
5 |
|
None |
8 |
|
No statistically significant difference between transdermal diclofenac diethylamine vs. oral diclofenac sodium |
10 |
|
None |
Overall, this review suggested that analgesic use in dental implant placement could be associated with improved postoperative outcomes (including pain, patient’s satisfaction, and need for rescue medication), whereas indications about the best analgesics could not be provided.
To our knowledge, this is the first systematic review about analgesics in dental implant surgery.
Postoperative pain and patient’s discomfort are common consequences of such surgical procedures, and their postoperative management has gathered the attention of several researchers (
Overall, several analgesics (ibuprofen, piroxicam, dexketoprofen trometamol, dexamethasone, and lornoxicam) were superior in reducing postoperative pain when compared to placebo. (
However, NSAIDs have a well-known effect in reducing pain (
Corticosteroids are usually administered to reduce the inflammatory response after oral surgery (
Opioids (such as codeine and fentanyl) have well-known analgesic effects, but other aspects (side effects, abuse, and dependency) should be considered when administered for postsurgical pain. They should be prescribed only when an alternative therapy is not possible or effective, and only for a short period of time (
Liposomal bupivacaine is a local anesthetic formulation consisting of bupivacaine hydrochloride encapsulated within multiple nonconcentric lipid bilayers, in order to offer sustained-release analgesia (
Dexmedetomidine is an α2-adrenoreceptor agonist with sedative, anxiolytic, sympatholytic, and analgesic-sparing effects, and minimal depression of respiratory function. Analgesic effects of α2-agonists are thought to be mediated by α2-receptor binding on central and spinal cord α2-receptors. Pain transmission is suppressed by hyperpolarization of interneurons and reduction of the release of pronociceptive transmitters such as substance P and glutamate (
Midazolam is a benzodiazepine characterized by rapid onset of clinical effects and short duration of action; like other benzodiazepines, its pharmacological action includes sedation, sleep induction, anxiolysis, and amnesia (
The use of caffeine (>100 mg) as an adjunct to common analgesics has been reported to provide a small but important increase (5–10%) in the proportion of patients who experience pain relief (
Patients usually report high satisfaction about dental implants, with some influence of pre-operatory anxiety and prosthetic complications over time (
Rescue medication includes drugs that may be administered to the patient when the efficacy of the investigational medical product is not satisfactory (
No adverse events occurred when using ibuprofen, dexamethasone, and lornoxicam (
The findings of this review should be interpreted within its limitations. First, the heterogeneity in analgesic drugs and timing of assessment precluded the pooling of the results, thus limiting the summary of the findings to a narrative synthesis. Second, the mixed quality of the included studies and the small number of studies investigating each outcome prevented from drawing strong conclusions.
Nonetheless, this review suggests that the administration of analgesics may provide some advantages in the management of postoperative pain after dental implant placement, but further research is warranted. While the available literature offers some analgesic protocols for dental pain based on anticipated postprocedural pain level (
The original contributions presented in the study are included in the article/Supplementary Material, and further inquiries can be directed to the corresponding author.
Conception or design of the work: all authors. Acquisition of data: MM, AF, and GZ. Analysis and interpretation of data: FC and MP. Draft of the work: MM, AF, and FC. Revision of the manuscript for important intellectual content: MP and GZ. All authors approved the submitted version and agreed to be accountable for the submitted work.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.