DR.

HOWARD CHO (Orcid ID : 0000-0001-8603-3425)

Accepted Article
Article type : Review Article (non-solicited)

Post-operative interventions to reduce inflammatory complications after

third molar surgery: Review of the current evidence.

Authors

• Dr Howard Cho, BDS, MBBS – MPhil Candidate, School of Medicine, The

University of Queensland, Brisbane, Australia

• A/Prof Anthony J. Lynham, BDSc, BMed(Hons), FRACDS(OMS), FRCS Ed –

Research Supervisor, School of Medicine, The University of Queensland, Brisbane,

Australia

• Dr Edward Hsu, BDSc(Hons), MBBS, FRACDS(OMS) – Consultant, Maxillofacial

Unit, Royal Brisbane and Women’s Hospital, Brisbane, Australia

Correspondence

Dr Howard Cho

Maxillofacial Registrar

Townsville Hospital

100 Angus Smith Drive

Douglas
This article has been accepted for publication and undergone full peer review but has
not been through the copyediting, typesetting, pagination and proofreading process,
which may lead to differences between this version and the Version of Record. Please
cite this article as doi: 10.1111/adj.12526

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 Queensland 4814
Accepted Article
Australia

Tel: +61 7 4433 1111

E-mail: h.cho@uq.edu.au

Sources of support

Nil

Abstract

Background: Inflammatory complications such as pain, swelling, trismus, infection

and alveolar osteitis, have an adverse affect on the quality of life of patients after third

molar removal. This review presents the current evidence on post-operative strategies

to reduce these complications.

Methods: A literature search was performed to identify articles published in English

between 2000 to 2016 using the following key words: third molar(s), wisdom

tooth/teeth, pain, swelling, trismus, infection, alveolar osteitis, and dry socket.

Results: In total, 221 papers were reviewed. Methods published included analgesics,

antibiotics, corticosteroids, mouthwashes, topical gels, cryotherapy, and ozone

therapy. This review highlights the variability in evidence available and summarises

the findings from best quality evidence.

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 Conclusions: Paracetamol and ibuprofen are efficacious in managing post-operative
Accepted Article pain. Corticosteroids and antibiotics should only be used in selected cases.

Chlorhexidine reduces alveolar osteitis. The benefits of cryotherapy, post-operative

irrigation and ozone gel are yet to be established.

Introduction

Surgical removal of third molars can result in post-operative complications. The most

commonly researched are those relating to inflammation, which result in discomfort and

significant morbidity. These problems include pain, swelling, trismus, surgical site infection

and alveolar osteitis (dry socket)1. Many patients report a negative impact on lifestyle and

oral function after third molar surgery2, 3. Therefore, clinicians have a great interest in

minimising these complications, to improve patient satisfaction and reduce additional

follow-up visits.

The aim of this study is to evaluate the current literature on interventions performed after

third molar surgery. This includes oral medications, topical agents as well as newer

technologies such as ozone gel. Recently, additional randomised control trials and meta-

analyses have been published that contribute to the overall body of evidence. An

understanding of the potential risks and benefits of each modality is essential, to effectively

reduce complication rates post-operatively.

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 Methods
Accepted Article
A literature search was conducted using four databases searched systematically: PubMed,

Cochrane Library, ScienceDirect and Google Scholar. Strings of MeSH and text search terms

(“molar, third” OR “wisdom teeth”) AND (“post-operative” OR “post-op”) AND

(“complications”) were used in searching the databases. In addition specific post-operative

complication keywords were searched: pain, swelling, oedema, trismus, infection, alveolar

osteitis and dry socket. The review was limited to studies published from 2000 – 2016. From

the search results, articles were selected for review based on their relevance to the research

question. Only post-operative interventions employed after patients’ discharge were

included. Abstracts were assessed and a full copy of the articles that met inclusion criteria

was obtained. Reference sections of accepted articles were screened to identify further

articles that may be relevant.

Results

A total of 221 papers have been included in this literature review. During the past 16 years,

interventions used post-operatively for the management of inflammatory complications

include analgesics, corticosteroids, antibiotics, chlorhexidine mouthwash, topical gels,

irrigation, and cryotherapy. Findings from meta-analyses, systematic reviews and

randomised control trials were synthesised. The National Health and Medical Research

Council4 (NHMRC, Australian Government) body of evidence matrix and evidence hierarchy

were applied to determine the grades of recommendations and levels of evidence

respectively. The results are summarised in tables 1 to 3.

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 Discussion
Accepted Article
Analgesics

Various analgesics have been used to control post-operative pain and swelling following

surgical removal of impacted molar teeth. Paracetamol and non-steroidal anti-inflammatory

drugs (NSAIDs) are widely used and are considered mainstay for many practitioners. This

may be in combination with opioids5 or corticosteroids6. Their efficacy has been

demonstrated repeatedly and are routinely prescribed7.

Weil et al.8 conducted a systematic review of 21 high quality trials. They concluded that

paracetamol was a safe and effective drug for the treatment of post-operative pain following

third molar removal. In a Cochrane review of 2241 patients, Bailey et al.9 found that

ibuprofen provided better post-operative analgesia than paracetamol. In addition, the

combination of ibuprofen and paracetamol appeared to be more effective than the drugs

taken singly when measured at six hours after surgery. Participants taking the combined

drug also had a smaller chance of requiring rescue medication. This mirrors the review of the

Cochrane database by Moore et al.10 They compared 21 over the counter analgesics and

found the combination of paracetamol (1000mg) and ibuprofen (400mg) more effective than

either alone.

Current research also supports the addition of opioids to control pain after third molar

extraction. Au et al.5 performed a meta-analysis of 10 analgesic combinations with a total of

3521 subjects. They found that oxycodone combined with ibuprofen had superior analgesic

efficacy compared to other combinations. In contrast, the efficacy of weaker opioid

combinations such as paracetamol/codeine remains contentious. Evidence suggests that this

combination is less effective than paracetamol/ibuprofen11. Smith et al.12 approached the

issue with a systematic review in 2001. They found only two high quality trials with 77

patients in unbalanced groups that could skew results. Macleod et al.13 compared

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 paracetamol to paracetamol/codeine and found significantly less pain in patients taking the
Accepted Article combination drug at 12 hours post removal of third molars. The current body of evidence for

paracetamol/codeine use post-operatively is not as strong as that for

paracetamol/ibuprofen.

It is important to consider the side effects associated with the use of analgesic medications.

For opioids this primarily relates to nausea, constipation5 and the risk of drug abuse14.

NSAID users should be aware of drug interactions, potential toxicity and gastrointestinal,

hematologic, and renal disorders15. These adverse reactions must be considered when

prescribing analgesics post-operatively.

Corticosteroids

Corticosteroids have long been used after surgery. Their primary role is to reduce

inflammation but also have the benefit of decreasing post-operative nausea and vomiting16,
17
. A number of studies have been published on the effect of corticosteroids in the peri-

operative management of dentoalveolar surgery18. While multiple reviews have

demonstrated steroids to be safe when used as a short course19, 20, the case for routine use

to prevent inflammatory complications has not been substantiated.

Alexander et al.18 performed a literature review documenting the effects of corticosteroid

therapy. The authors confirmed the utility of intravenous, intramuscular and oral routes in

reducing inflammatory complications. They recommended that steroids, if used, should be

started before surgery, given at higher doses and continue for the first and second post-

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 operative days. The authors also discussed potential side effects including adrenal
Accepted Article suppression, gastrointestinal upset, exacerbation of psychosis, infection and interference

with the immune system. For these reasons, steroids should only be used in selected cases.

Markiwicz et al.21 conducted a review and meta-analysis on the subject. Their research

focused on whether peri-operative steroid administration reduced pain, trismus and

oedema after third molar surgery. Twelve papers met their inclusion criteria. They found

that steroids helped to reduce oedema and trismus in the early (1-3 days) and late (>3days)

post-operative phases. However, they could not determine any effect on pain, as most

studies focused on analgesic dosage rather than a visual analogue scale. It is important to

note that for oedema and trismus, reductions of 0.6mm and 4.1mm respectively were found

in those who used corticosteroids. Although these results were statistically significant, it is

questionable whether such small reductions are of clinical significance. The authors also

highlighted the variability of study designs and the need for further large-scale studies to

determine the optimal drug, timing and dose of corticosteroid administration.

A systemic review by Herrera-Briones et al.22 in 2013 provided another update of trials

published. A total 28 research articles were assessed including both pre-operative and post-

operative dosing. The authors concluded that corticosteroids statistically decrease

inflammation and trismus. They also found the parental route, prior to surgery the most

favourable in terms of reducing inflammation. A major limitation of this study was that a full

meta-analysis was not able to be performed due the heterogeneity of the trials23. The

authors also drew conclusions regarding timing and route of administration from selected

trials rather than summarising findings as a whole.

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 The review by Kim et al.19 included nine studies on the effect of corticosteroids after removal
Accepted Article of bilateral impacted third molars. Eight of these demonstrated subjects taking

corticosteroids had significantly less swelling than controls. It is important to note there was

significant inter-study variability in the routes and timing of steroid administration, as well as

the method of assessing facial swelling. The authors concluded that steroids, when given,

should be at a dose that is equivalent to 300mg cortisol (e.g. 60mg prednisone) and continue

for 3-5 days for maximum benefit. This is because swelling peaks 48-72 hours after surgery,

whereas most steroids do not exert their effect beyond 24 hours when given as a single

dose. The authors also recommend that steroids be reserved for complex oral surgical

procedures in which trauma is categorised as moderate to severe.

In general, the research shows that corticosteroids can bring about a statistical reduction in

swelling and trismus after third molar surgery. However, it is important to note that the

volumetric reduction in many studies was relatively small and may not be of clinical

significance. It’s efficacy in reducing post-operative nausea and vomiting has been well

documented. Corticosteroids can be useful in selected cases when significant surgical

trauma is anticipated or the patient is at risk of excessive oedema. Its use must be balanced

against potential risks and side effects.

Antibiotics

Another method of reducing inflammatory complications is the use of antibiotics peri-

operatively. Antibiotic prophylaxis has a well-established place for specific surgical

procedures such as joint replacement and prevention of infective endocarditis24. However,

their role in routine third molar surgery is not so clear.

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 There are a multitude of studies both for and against antibiotic use. They vary in design as
Accepted Article well as type and route of antibiotic administered, making critical appraisal difficult. In 2007,

Ren and Malmstrom25 published a meta-analysis of 16 clinical trials with a total of 2932

patients. They concluded that pre-operative antibiotics reduced alveolar osteitis by 6.1% and

wound infection by 4% with a number needed to treat of 25 to avoid one such complication.

Susarla et al.26 found a similar benefit and recommended antibiotic administration pre-

operatively and post-operatively for 2 to 7 days.

A Cochrane review by Lodi et al.27 in 2012 analysed 18 clinical trials with a total of 2456

subjects. All trials included healthy patients undergoing extraction of impacted third molars.

They found that antibiotics given prior or just after surgery reduced the rate of infection and

alveolar osteitis by 70% and 38% respectively. This translates to 12 patients receiving

antibiotics to prevent one case of infection and 38 patients needing to take antibiotics to

prevent one case of alveolar osteitis. It is also important to note that for every 21 people

who receive antibiotics, a minor adverse reaction to antibiotics is likely. From this, the

authors’ could not support routine prescription of antibiotics for healthy people undergoing

extraction of third molars. The main reasons were the low risk of infection after tooth

extraction in healthy young adults, the significant increase risk of experience adverse effects

from antibiotics and the potential development of resistant bacteria,

The most recent meta-analysis by Ramos et al.28 demonstrates a benefit to prescribing

antibiotics. Their review included 22 papers with an overall NNT (number needed to treat) of

14 to prevent one episode of infection. However, the study included all regimes, most of

which included antibiotics administered one hour prior to surgery. Only one trial used post-

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 operative antibiotics exclusively29. This study found amoxicillin/clavulanate efficacious in
Accepted Article reducing the incidence of inflammatory complications following third molar extraction but

its use should be limited to select cases.

The literature demonstrates that antibiotics given at the time of or prior to third molar

surgery can reduce alveolar osteitis and infection. However, the majority of infective

complications after third molar surgery are relatively minor and the benefit of antibiotics

must be weighed against potential microbial resistance, adverse reactions, and cost.

Furthermore, there is a lack of evidence to support prescription of antibiotics post-

operatively in healthy patients undergoing routine removal of third molars.

Antibacterial mouthwashes

Mouthwashes have the benefit of acting locally at the surgical site as well as providing

mechanical debridement. In general, they are cheap and have fewer side effects.

Mouthwashes don't require a script and no return to clinic is necessary, meaning less cost

for both the patient and clinician. One disadvantage is the need for patient adherence to the

mouth washing protocol.

A variety of different types of commercial mouthwashes have been reviewed in the

literature. Commonly available mouthwashes include benzadymine hydrochloride, essential

oils, cetylpyridinium chloride, sodium benzoate, triclosan, oxygenating agents, povodine-

iodine, peroxidase, and fluoride30. While all of these have antimicrobial activity, the gold

standard is considered to be chlorhexidine for its ability to reduce plaque31, broad spectrum

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 of activity against oral aerobes and anaerobes, general tolerability, and lack of bacterial
Accepted Article resistance32. The use of warm saline has also been reported. The theory is that the

hypertonic solution is believed to be bacteriostatic and promote healing by causing

vasodilation to the extraction site33. However objective studies into its efficacy are lacking

and multiple studies have demonstrated chlorhexidine to be the more effective than saline

controls34, 35.

In 2005, Caso et al.34 published a meta-analysis review of prevention of alveolar osteitis with

chlorhexidine after lower third molar extractions. They compared pre-operative rinsing, pre-

operative and post-operative rinsing together to a third control group. Overall, the studies

investigated have possible cofounders and vary in design. However, there is strong evidence

for the use of chlorhexidine in the form of a rinse following third molar removal. The authors

concluded that the use of chlorhexidine mouth rinse on the day of surgery alone was not

statistically significant. However, when this is combined with chlorhexidine mouthwash used

for 7 days post-operatively, it produced a significant reduction in alveolar osteitis.

Hedstrom and Sjogren36 systematically reviewed 32 randomised control trials on prevention

of alveolar osteitis. They concluded that 0.12% chlorhexidine rinsing pre-operatively and 7

days post-operatively, seemed to have significant and clinically relevant preventive effects

on alveolar osteitis, following surgical removal of lower third molars.

This is supported by a Cochrane review by Daly et al.37 Their systematic review included 21

trials with 2570 participants. Most of the included studies were involved extractions

undertaken by experienced oral surgeons in hospital or military minor oral surgery clinics.

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 The authors found that chlorhexidine mouthwash (0.12% and 0.2%) both before and after
Accepted Article extraction prevented approximately 42% of dry sockets. The number of patients needed-to-

be-treated with chlorhexidine rinse to prevent one patient having dry socket (NNT) was 232,

47 and 8 for control prevalences of dry socket of 1%, 5% and 30% respectively.

It is also important to note that chlorhexidine has side effects although these are generally

minimal. These can include staining of teeth, increased calculus formation, mucosal

irritation, and taste alterations38. However, more severe hypersensitivity reactions have

been reported in the literature. These reactions range from lip and mucosal swelling to

severe anaphylaxis39. In light of this, it is important for practitioners to be aware of such

reactions.

Topical gels

Topical gels contain antimicrobial agents that are directly applied to a post-operative surgical

site. A topical gel may be more effective than mouthwash because the positioning of the gel

can prolong release of medication, generating more direct action on the alveolus, and also

allow more bioavailability. Additionally, the gel can be applied immediately after tooth

extraction whereas mouthwashes are typically avoided in the first 24 hours due to risk of

clot dissolution40.

Hita-Iglesias et al.41 conducted a randomised control trial comparing the efficacy of

chlorhexidine gel versus chlorhexidine mouthwash. The participants used a twice daily, 7-

day post-operative protocol. The study reported a significant decrease (30%) in the

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 incidence of post-operative alveolar osteitis in the topical chlorhexidine gel group, which had
Accepted Article an incidence of only 7.5%. This is compared to an incidence of alveolar osteitis of 25% in the

chlorhexidine rinse group. The authors concluded that the reduced incidence in the gel

group was because of the prolonged release of chlorhexidine from the daily gel application.

Minguez-Serra et al.40 performed a meta-analysis of chlorhexidine mouthwash and gels.

Their paper included 12 different trials, which used different concentrations and dosing

regimes. The authors found that the application of a 0.2% chlorhexidine gel every 12 hours

for 1 week after third molar surgery was the most effective in decreasing the incidence of

alveolar osteitis. In contrast, the meta-analysis by Zhou et al.42 found no significant

difference between chlorhexidine mouthwash and gel. However, they did confirm the

efficacy of chlorhexidine gel compared to no treatment and placebo. The authors concluded

that on average, 0.2% chlorhexidine gel reduced the risk of alveolar osteitis by 62% following

mandibular third molar extraction.

More recently, ozone gel has been purported as having a beneficial effect after third molar

surgery. Ozone is a strong oxidant and has broad anti-microbial properties. It is also known

to enhance oxygen metabolism, induce enzymes and activate the immune response43. This

has the effect of reducing the possibility of post-operative infection, improve tissue

regeneration and speed up wound healing44.

It has been shown that ozone gel applied to the surgical site can reduce post-operative

inflammatory complications. Sivalingam et al.45 conducted a randomised control trial of 66

patients comparing ozone gel (Aqua Ozone, Akaroa, New Zealand) to systemic antibiotics.

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 They found a significant reduction in pain, swelling and trismus in patients using ozone gel,
Accepted Article with no significant adverse effects.

The literature supports the use of chlorhexidine gel to reduce alveolar osteitis post-

operatively. The use of ozone containing gels shows promise but more high quality,

randomised control trials are needed to confirm its efficacy. Practitioners must also bear in

mind the higher cost associated with gels compared with traditional mouth rinse.

Irrigation

Irrigation in surgery involves delivery of a stream of fluid for the purpose of washing or

debridement. In third molar surgery it is used in the post-operative phase for the

management of alveolar osteitis. It has been postulated that removal of any necrotic debris

or food particles can help to eliminate a potential source of inflammation and pain46.

Patients with alveolar osteitis are usually given a plastic syringe with a curved tip, for home

irrigation with chlorhexidine or saline and instructed to keep the socket clean until the

socket no longer collects debris. The benefit of this lacks scientific evidence, although the

reasoning appeals to common sense. Daly et al.37 confirmed this in a Cochrane review, which

concluded that there was insufficient evidence to support any existing treatments for dry

socket.

In 2016, Ghaeminia et al.47 published the first paper on the use of post-operative irrigation

by patients after discharge. They compared tap water irrigation with a Monoject syringe

(Tyco/healthcare-Kendall, Mansfield, MA, USA) to no intervention using 333 third molar

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 sites. A significant reduction in inflammatory complications including alveolar osteitis was
Accepted Article found in the group that used irrigation. However, in this study a large number of patients

(42%) failed to use the irrigation. Also, no comparison was made to rinsing alone.

Nevertheless, it presents an interesting case for a cost effective and readily accessible

intervention to reduce inflammatory complications after third molar surgery.

Cryotherapy

The application of ice to the extra-oral site of surgery is simple and favoured by many

clinicians. The theory is that reduced temperatures cause vasoconstriction and reduces post-

operative swelling. It can also reduce nerve fibre conduction velocity resulting in an

analgesic effect48. Several authors have demonstrated a good efficacy in reducing post-

operative swelling and pain48-51.

In the treatment of impacted third molars, the use of ice in the literature remains

controversial. Van der Westhuijzen et al.52 state that there is no scientific evidence to

support the use of an icepack in oral and maxillofacial surgery and report that a slight, but

not significant, difference in swelling was observed in patients in whom ice was applied

continuously for 24 hours after extraction of third molars compared to untreated controls.

Similarly, Zandi et al.53 could not demonstrate any significant difference in post-operative

inflammatory complications in their split mouth study. Greenstein’s54 review was also

inconclusive with respect to the clinical benefits of cryotherapy.

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 Although ice applied to the mandibular angle produces rapid cooling in the cutaneous layer,
Accepted Article the effect is significantly reduced 2-3cm beyond the skin surface48. This means anatomic

variation can have a significant impact of the effectiveness of cryotherapy. The application of

ice for too long can also be harmful. Tissue death can result due to prolonged

vasoconstriction, ischemia and capillary thrombosis55. Other factors to consider include type

of cryotherapy (crushed ice, ice pack, frozen peas, Hilotherm, or chemical gel pack), as well

as duration, and amount of compression used. This multitude of factors is likely contributory

to the variability in study results.

Based on physiologic principles, the application of cold after third molar removal should

produce a favourable response. However, the current evidence base for this is inconsistent.

Much like the management of dry socket, clinical anecdotes and techniques often come

before science. Further clinical trials and meta-analyses are needed to provide scientific

validation to use of cryotherapy after third molar surgery.

Conclusion

This review has presented the different modalities to reduce inflammatory complications

after third molar removal. There is strong evidence for the use of paracetamol and ibuprofen

to manage post-operative pain. Corticosteroids reduce swelling and trismus after surgery

however, should only be used in selected cases. Antibiotics reduce infection when used as

surgical prophylaxis but should not be used post-operatively in healthy patients undergoing

routine third molar removal. Chlorhexidine mouthwash and gels are proven to be efficacious

in reducing alveolar osteitis. There is conflicting evidence with regards to cryotherapy.

Further research is required to confirm the benefits of post-operative irrigation and ozone

gel.

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 References
Accepted Article
1. Chuang SK, Perrott DH, Susarla SM, Dodson TB. Risk factors for inflammatory

complications following third molar surgery in adults. J Oral Maxillofac Surg 2008;66:2213-

2218.

2. Shugars DA, Gentile MA, Ahmad N, et al. Assessment of oral health-related quality of

life before and after third molar surgery. J Oral Maxillofac Surg 2006;64:1721-1730.

3. Slade GD, Foy SP, Shugars DA, Phillips C, White RP, Jr. The impact of third molar

symptoms, pain, and swelling on oral health-related quality of life. J Oral Maxillofac Surg

2004;62:1118-1124.

4. National Health and Medical Research Council. NHMRC additional levels of evidence

and grades for recommendations for developers of guidelines. Australian Government, 2009.

5. Au AH, Choi SW, Cheung CW, Leung YY. The Efficacy and Clinical Safety of Various

Analgesic Combinations for Post-Operative Pain after Third Molar Surgery: A Systematic

Review and Meta-Analysis. PLoS ONE 2015;10:e0127611.

6. Bamgbose BO, Akinwande JA, Adeyemo WL, Ladeinde AL, Arotiba GT, Ogunlewe

MO. Effects of co-administered dexamethasone and diclofenac potassium on pain, swelling

and trismus following third molar surgery. Head Face Med 2005;1:11.

7. Oral and Dental Expert Group. Therapeutic guidelines: oral and dental. 2 edn.

Melbourne: Therapeutic Guidelines Limited, 2012:Pages 145-155.

8. Weil K, Hooper L, Afzal Z, et al. Paracetamol for pain relief after surgical removal of

lower wisdom teeth. Cochrane Database Syst Rev 2007:CD004487.

9. Bailey E, Worthington H, Coulthard P. Ibuprofen and/or paracetamol

(acetaminophen) for pain relief after surgical removal of lower wisdom teeth, a Cochrane

This article is protected by copyright. All rights reserved.

 systematic review. Br Dent J 2014;216:451-455.
Accepted Article
10. Moore RA, Wiffen PJ, Derry S, Maguire T, Roy YM, Tyrrell L. Non-prescription (OTC)

oral analgesics for acute pain - an overview of Cochrane reviews. Cochrane Database Syst

Rev 2015:CD010794.

11. Moore PA, Hersh EV. Combining ibuprofen and acetaminophen for acute pain

management after third-molar extractions: translating clinical research to dental practice. J

Am Dent Assoc 2013;144:898-908.

12. Smith LA, Moore RA, McQuay HJ, Gavaghan D. Using evidence from different

sources: an example using paracetamol 1000 mg plus codeine 60 mg. BMC Med Res

Methodol 2001;1.

13. Macleod AG, Ashford B, Voltz M, et al. Paracetamol versus paracetamol-codeine in

the treatment of post-operative dental pain: a randomized, double-blind, prospective trial.

Aust Dent J 2002;47:147-151.

14. Mutlu I, Abubaker AO, Laskin DM. Narcotic prescribing habits and other methods of

pain control by oral and maxillofacial surgeons after impacted third molar removal. J Oral

Maxillofac Surg 2013;71:1500-1503.

15. Ong KS, Seymour RA. Maximizing the safety of nonsteroidal anti-inflammatory drug

use for postoperative dental pain: an evidence-based approach. Anesth Progress

2003;50:62-74.

16. Fujii Y, Nakayama M, Nakano M. Propofol alone and combined with dexamethasone

for the prevention of postoperative nausea and vomiting in adult Japanese patients having

third molars extracted. Br J Oral Maxillofac Surg 2008;46:207-210.

17. Sekhavat L, Davar R, Behdad S. Efficacy of prophylactic dexamethasone in prevention

This article is protected by copyright. All rights reserved.

 of postoperative nausea and vomiting. J Epidemiol Glob Health 2015;5:175-179.
Accepted Article
18. Alexander RE, Throndson RR. A review of perioperative corticosteroid use in

dentoalveolar surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:406-415.

19. Kim K, Brar P, Jakubowski J, Kaltman S, Lopez E. The use of corticosteroids and

nonsteroidal antiinflammatory medication for the management of pain and inflammation

after third molar surgery: a review of the literature. Oral Surg Oral Med Oral Pathol Oral

Radiol Endod 2009;107:630-640.

20. Ngeow WC, Lim D. Do Corticosteroids Still Have a Role in the Management of Third

Molar Surgery? Adv Ther 2016;33:1105-1139.

21. Markiewicz MR, Brady MF, Ding EL, Dodson TB. Corticosteroids reduce postoperative

morbidity after third molar surgery: a systematic review and meta-analysis. J Oral Maxillofac

Surg 2008;66:1881-1894.

22. Herrera-Briones FJ, Prados Sanchez E, Reyes Botella C, Vallecillo Capilla M. Update

on the use of corticosteroids in third molar surgery: systematic review of the literature. Oral

Surg Oral Med Oral Pathol Oral Radiol 2013;116:e342-351.

23. Beirne OR. Corticosteroids decrease pain, swelling and trismus. Evid Based Dent

2013;14:111.

24. Fenton DA, Piecuch JF. Perioperative strategies for third molar surgery. Atlas Oral

Maxillofac Surg Clin North Am 2012;20:225-232.

25. Ren YF, Malmstrom HS. Effectiveness of antibiotic prophylaxis in third molar surgery:

a meta-analysis of randomized controlled clinical trials. J Oral Maxillofac Surg 2007;65:1909-

1921.

26. Susarla SM, Sharaf B, Dodson TB. Do antibiotics reduce the frequency of surgical site

This article is protected by copyright. All rights reserved.

 infections after impacted mandibular third molar surgery? Oral Maxillofac Surg Clin North
Accepted Article Am 2011;23:541-546, vi.

27. Lodi G, Figini L, Sardella A, Carrassi A, Del Fabbro M, Furness S. Antibiotics to prevent

complications following tooth extractions. Cochrane Database Syst Rev 2012;11:CD003811.

28. Ramos E, Santamaria J, Santamaria G, Barbier L, Arteagoitia I. Do systemic antibiotics

prevent dry socket and infection after third molar extraction? A systematic review and meta-

analysis. Oral Surg Oral Med Oral Pathol Oral Radiol 2016;122:403-425.

29. Arteagoitia I, Diez A, Barbier L, Santamaria G, Santamaria J. Efficacy of

amoxicillin/clavulanic acid in preventing infectious and inflammatory complications following

impacted mandibular third molar extraction. Oral Surg Oral Med Oral Pathol Oral Radiol

Endod 2005;100:e11-18.

30. Farah CS, McIntosh L, McCullough MJ. Mouthwashes. Australian Prescriber

2009;32:162-164.

31. Quintas V, Prada-Lopez I, Donos N, Suarez-Quintanilla D, Tomas I. Antiplaque effect

of essential oils and 0.2% chlorhexidine on an in situ model of oral biofilm growth: a

randomised clinical trial. PLoS ONE 2015;10:e0117177.

32. Hermesch CB, Hilton TJ, Biesbrock AR, et al. Perioperative use of 0.12%

chlorhexidine gluconate for the prevention of alveolar osteitis. Oral Surg Oral Med Oral

Pathol Oral Radiol Endod 1998;85:381-387.

33. Osunde OD, Adebola RA, Adeoye JB, Bassey GO. Comparative study of the effect of

warm saline mouth rinse on complications after dental extractions. Int J Oral Maxillofac Surg

2014;43:649-653.

34. Caso A, Hung LK, Beirne OR. Prevention of alveolar osteitis with chlorhexidine: a

This article is protected by copyright. All rights reserved.

 meta-analytic review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:155-159.
Accepted Article
35. Yengopal V, Mickenautsch S. Chlorhexidine for the prevention of alveolar osteitis. Int

J Oral Maxillofac Surg 2012;41:1253-1264.

36. Hedstrom L, Sjogren P. Effect estimates and methodological quality of randomized

controlled trials about prevention of alveolar osteitis following tooth extraction: a systematic

review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:8-15.

37. Daly B, Sharif MO, Newton T, Jones K, Worthington HV. Local interventions for the

management of alveolar osteitis (dry socket). Cochrane Database Syst Rev

2012;12:CD006968.

38. Silvestri DL, McEnery-Stonelake M. Chlorhexidine: uses and adverse reactions.

Dermatitis 2013;24:112-118.

39. Pemberton MN, Gibson J. Chlorhexidine and hypersensitivity reactions in dentistry.

Br Dent J 2012;213:547-550.

40. Minguez-Serra MP, Salort-Llorca C, Silvestre-Donat FJ. Chlorhexidine in the

prevention of dry socket: effectiveness of different dosage forms and regimens. Med Oral

Patol Oral Cir Bucal 2009;14:e445-449.

41. Hita-Iglesias P, Torres-Lagares D, Flores-Ruiz R, Magallanes-Abad N, Basallote-

Gonzalez M, Gutierrez-Perez JL. Effectiveness of chlorhexidine gel versus chlorhexidine rinse

in reducing alveolar osteitis in mandibular third molar surgery. J Oral Maxillofac Surg

2008;66:441-445.

42. Zhou J, Hu B, Liu Y, Yang Z, Song J. The efficacy of intra-alveolar 0.2% chlorhexidine

gel on alveolar osteitis: a meta-analysis. Oral Dis 2016.

43. Filipovic-Zore I, Divic Z, Duski R, Gnjatovic N, Galic N, Prebeg D. Impact of ozone on

This article is protected by copyright. All rights reserved.

 healing after alveolectomy of impacted lower third molars. Saudi Med J 2011;32:642-644.
Accepted Article
44. Nogales CG, Ferrari PA, Kantorovich EO, Lage-Marques JL. Ozone Therapy in

Medicine and Dentistry. J Contemp Dent Pract 2008;9:075-084.

45. Sivalingam VP, Panneerselvam E, Raja KV, Gopi G. Does Topical Ozone Therapy

Improve Patient Comfort After Surgical Removal of Impacted Mandibular Third Molar? A

Randomized Controlled Trial. J Oral Maxillofac Surg 2016.

46. Blum IR. Contemporary views on dry socket (alveolar osteitis): a clinical appraisal of

standardization, aetiopathogenesis and management: a critical review. Int J Oral Maxillofac

Surg 2002;31:309-317.

47. Ghaeminia H, Hoppenreijs TJ, Xi T, et al. Postoperative socket irrigation with drinking

tap water reduces the risk of inflammatory complications following surgical removal of third

molars: a multicenter randomized trial. Clin Oral Investig 2016.

48. Gelesko S, Long L, Faulk J, Phillips C, Dicus C, White RP, Jr. Cryotherapy and topical

minocycline as adjunctive measures to control pain after third molar surgery: an exploratory

study. J Oral Maxillofac Surg 2011;69:e324-332.

49. Laureano Filho JR, de Oliveira e Silva ED, Camargo IB, Gouveia FMV. The influence of

cryotherapy on reduction of swelling, pain and trismus after third-molar extraction: a

preliminary study. The Journal of the American Dental Association 2005;136:774-778.

50. Forouzanfar T, Sabelis A, Ausems S, Baart JA, van der Waal I. Effect of ice

compression on pain after mandibular third molar surgery: a single-blind, randomized

controlled trial. Int J Oral Maxillofac Surg 2008;37:824-830.

51. Ibikunle AA, Adeyemo WL. Oral health-related quality of life following third molar

surgery with or without application of ice pack therapy. Oral Maxillofac Surg 2016;20:239-

This article is protected by copyright. All rights reserved.

 247.
Accepted Article
52. van der Westhuijzen AJ, Becker PJ, Morkel J, Roelse JA. A randomized observer blind

comparison of bilateral facial ice pack therapy with no ice therapy following third molar

surgery. Int J Oral Maxillofac Surg 2005;34:281-286.

53. Zandi M, Amini P, Keshavarz A. Effectiveness of cold therapy in reducing pain,

trismus, and oedema after impacted mandibular third molar surgery: a randomized, self-

controlled, observer-blind, split-mouth clinical trial. Int J Oral Maxillofac Surg 2016;45:118-

123.

54. Greenstein G. Therapeutic efficacy of cold therapy after intraoral surgical

procedures: a literature review. J Periodontol 2007;78:790-800.

55. Sortino F, Cicciu M. Strategies used to inhibit postoperative swelling following

removal of impacted lower third molar. Dent Res J (Isfahan) 2011;8:162-171.

Table 1 – Summary of post-operative interventions and strength of evidence

Post-operative Recommendation Grade of Level of

intervention recommendation evidence

Paracetamol 1000mg doses decrease pain. No difference A I

between IR and SR

Ibuprofen 400mg doses decrease pain A I

Codeine 30-60mg doses may decrease pain C I

Oxycodone 5-10mg doses decrease pain B I

Corticosteroids Decrease swelling and trismus. May reduce pain. A I

Drug, route and dosing requires clarification

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 Post-operative antibiotics Do not decrease infection or dry socket A I
Accepted Article Chlorhexidine mouthwash Used on day of surgery and twice daily for 1 week A I

decreases risk of dry socket

Chlorhexidine gel Used twice daily for 1 week decreases risk of dry A I

socket

Ozone gel Used twice daily, for 5 days decreases pain, C II

swelling and trismus

Monoject irrigation Irrigation twice daily, for 1 week decreases dry C II

socket

Cryotherapy Application of cold decreases pain and swelling C II

IR = immediate release; SR = slow release

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 Table 2 – NHMRC grades of recommendations4
Accepted Article
Grade of Description

recommendation

A Body of evidence can be trusted to guide practice

B Body of evidence can be trusted to guide practice in most situations

C Body of evidence provides some support for recommendation(s) but care

should be taken in its application

D Body of evidence is weak and recommendation must be applied with

caution

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 Table 3 – NHMRC evidence hierarchy4
Accepted Article
Level Intervention

I A systematic review of level II studies

II A randomised controlled trial

III-1 A pseudorandomised controlled trial (i.e. alternate allocation or some

other method)

III-2 A comparative study with concurrent controls:

• Non-randomised, experimental trial

• Cohort study

• Case-control study

• Interrupted time series with a control group

III-3 A comparative study without concurrent controls:

• Historical control study

• Two or more single arm study

• Interrupted time series without a parallel control group

IV Case series with either post-test or pre-test/post-test outcomes

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