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R E V I E W
Alveolar osteitis: a critical review of the aetiology
and management
B. Veale
Oral and Maxillofacial Surgery, Charles Clifford Dental Hospital, Sheffield Teaching Hospitals, South Yorkshire, UK
Key words: complication, dental, pain, surgery, wound healing
Correspondence to: Mr B Veale Oral and Maxillofacial Surgery Charles Clifford Dental Hospital Sheffield Teaching Hospitals South Yorkshire UK Tel.: +0114 271 7800 Fax: +0114 271 7836 email: [email protected]
Accepted: 29 August 2014
doi:10.1111/ors.
Abstract
Alveolar osteitis (dry socket; AO) is a well-recognised complication follow- ing tooth extraction where accelerated breakdown of the clot within the socket results in increased localised inflammation and severe discomfort for the patient. Conventional treatment is quick and simple, with different medicated packing available for topical treatment. Recent literature on the subject advises against some approaches to treatment, and strengthened evidence that appropriate perioperative management may significantly reduce the incidence of AO. It is the purpose of this article to review these findings and summarise what current evidence suggests to be the best approach for treatment and prevention of AO, as well as identifying key risk factors.
Clinical relevance
Scientific rationale for study
The use of antibiotics, and chlorhexidine, in the prac- tice of dentistry are both topical subjects in the UK due to increasing concern over antibiotic-resistance and chlorhexidine anaphylaxis. The aim of this article is to provide a detailed background to the subject, and present the most up-to-date interpretation of appro- priate perioperative care with regard to AO.
Principal findings
Antibiotics are not indicated in the management of AO. When used appropriately, chlorhexidine can be an effective and cost-efficient preventative measure and treatment option.
Practical implications
Routine use of perioperative chlorhexidine mouth rinses is recommended.
Introduction
Alveolar osteitis (AO), also known as dry socket, is one of the most common post-operative complications fol- lowing removal of permanent teeth, resulting in severe pain and discomfort for the patient. Definitions vary, but centre around the total or partial loss/breakdown of the blood clot from the socket, resulting in a localised inflammatory response^1 and intense pain radiating to the auricular and temporal regions2,3. This typically occurs within 2–4 days post-extraction4–9. It has been given a variety of different terms in the surrounding literature: localised osteitis, post-operative alveolitis, alveolalgia, alveolitis sicca dolorosa, septic socket, necrotic socket, localised osteomyelitis and fibrinolytic alveolitis^5. AO has an overall incidence of around 3–5% for all extractions10–12. However, it is reported to have a much greater incidence following extraction of mandibular teeth^13. Mandibular third molars are reported to have a varied rate of incidence of AO, anywhere as high as 47%4,5,7–9,14–19, but stronger studies suggest 25–30%5,20,21. There are many factors influencing the occurrence of
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68 Oral Surgery 8 (2015) 68–77.
post-extraction complications, which can have a sig- nificant effect on the outcome. In addition to this, a diagnosis of dry socket is based upon the judgement of the clinician, which can vary greatly between dentists.
Pathogenesis
The onset of AO is typically around 2–4 days post- extraction. Blum explains how it is unlikely to occur before the first 24 h due to the presence of antiplasmin (plasmin inhibitor) which delays fibrinolysis; and it is only once levels of antiplasmin have been reduced that breakdown of the clot occurs^5. Its duration varies, but is speculated to range between 5 and 10 days. Birn’s fibrinolytic theory^2 explains that marked or prolonged trauma during an extraction, or indeed infection of the socket, causes increased localised inflammation within the bone which triggers the local release of plasminogen activators. These facilitate the conversion of plasminogen to plasmin, which breaks down fibrin and leads to lysis of the blood clot. Plasmin also plays an active role in the production of kinins^22. Kinins not only propagate the process of inflammation by stimulating the release of inflammatory mediators, but also play a major part in the sensitisation and stimulation of pain receptors^23. All of these factors tie in with the main features of AO, which are breakdown of the clot and intense pain. Evidence linking AO with poor oral hygiene, peri- odontal disease and pericoronitis24–26^ has prompted an expanded theory, incorporating an entirely extrinsic aetiological factor. There is evidence to suggest that certain bacteria demonstrate fibrinolytic activity inde- pendent of the host response, and act directly on the blood clot. Nitzan et al. demonstrated fibrinolytic activity in Treponema denticola which produced its own fibrinolytic enzyme: fibrinolysin^27. In the same study, the authors also commented on how Prevotella oralis releases proteases that convert plasminogen into plasmin, and so further increases fibrinolysis. With both of these bacteria being linked to periodontal disease28,29, this strengthens links between periodontal disease and AO, but should be considered carefully in cases of periodontal disease with a smoking habit that could present an element of confounding.
Risk factors
Operative technique
The fibrinolytic theory of AO stems from trauma or infection leading to increased fibrinolysis. It is well recorded in the literature that prolonged, or particu-
larly traumatic extractions, have a greater incidence of AO2,6,30,31. Additionally, there has been noted to be a positive correlation between operator inexperience and increased incidence of AO32–35, which could be due to many factors, including prolonged operating time and increased trauma. Interestingly, some studies link flap design to inci- dence of dry socket in removal of third molars, and discuss how incidence of AO was reduced using the modified triangular flap, compared with the envelope flap 36,37; however, no statistically significant difference was yielded from either of the studies. Similarly, Waite and Cherala studied the outcomes of using a suture-less technique, allowing just passive repositioning of the flap, and reported that AO occurred in only 8.7% of third molars^38. The conclusions drawn from this study are not entirely reliable due to the lack of control group for comparison. Piezotomes are reported to have a lower risk of post-operative complications, including AO, due to the reduced trauma to the tissues, but do have a increased operating time due to a slower cutting rate 39–41.
Mechanical disruption of blood clot It would make sense that if the blood clot is prema- turely lost from the socket, then this leave the bone exposed to bacterial ingress and subsequent inflam- mation leading to AO, but no evidence could be found to support this theory. Specifically, the negative pres- sure created intra-orally when using straws is often said to disrupt the clot which has formed and subsequently lead to the development of AO, but this action has been suggested to have no impact on the incidence of AO^42.
Smoking Smoking has long been associated with post-operative complications, including AO, but the surrounding lit- erature is divided as to whether or not it has any impact on the incidence of AO specifically. Although some studies do demonstrate a positive correlation43–46, many others show only minor trends, but with no statistically significant results11,47,48, and some show no link49,50. However, many of these studies classify the effects of smoking by whether or not a patient smokes, as opposed to whether or not a patient smoked within the 24 h following the extraction. If routine post-operative instructions are given, this would include temporary smoking cessation, typically for at least 24 h. The studies do not take into account whether or not these
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or other debris, reducing bacterial presence, and con- sequentially reduces inflammation5,16. However, Tolstunov reflects on the results of his study to put forward that it may be the action of irrigating that dis- rupts the clotting process and thus promoting AO^62. The effect of immediate post-operative lavage on AO incidence is unclear, and research is lacking in this area.
Prevention
Chlorhexidine
There are mixed opinions regarding chlorhexidine as an effective preventative measure63–65, but there is a greater quantity of stronger evidence demonstrating its efficacy. A recent Cochrane review^66 discussed how there was some evidence to show peri-operative chlorhexidine rinses (0.12% and 0.2%), as well as immediate post-operative intra-alveolar placement of chlorhexidine gel (0.2%), both help reduce incidence of AO. There is some evidence to show that the effect is greater with 1% chlorhexidine in comparison with 0.2% 67 , but evidence showing difference between 0.12% and 0.2% is limited^64. In addition, it appears to have no impact whether chlorhexidine application is pre-, intra- or post-operative, or if in liquid or gel form 64 , although significant reduction in AO incidence has been observed when using the gel68,69. Multiple peri-operative rinses (continued for several days post- extraction) with chlorhexidine have been shown to be more effective than a single rinse on the day of surgery 70. In recent years, there has been growing concern within the profession regarding the incidence of chlorhexidine allergy and its impact on dentistry, fol- lowing reports of two deaths resulting from anaphy- laxis^71. Hypersensitivity to chlorhexidine is not a new issue^72 , and cases have more commonly involved intra-urethral catheters^71. Nevertheless, the risk of hypersensitivity is present no matter what the applica- tion, and should be considered in the dental setting whenever chlorhexidine may be indicated. This could be more important if considering intra-alveolar irriga- tion as oppose to oral rinses alone due to the increased direct contact with the bloodstream^71. However, clini- cians should not be deterred from using chlorhexidine where it is indicated, as long as the allergy status of the patient is negative. With such widespread use within medicine and surgery, rare cases of anaphylaxis will occur, but with such a long history of being a safe and effective antimicrobial, it should not be avoided unnecessarily.
Systemic antibiotics Several antibiotics have been investigated over the years, both for the prevention and treatment of AO. The main focus has been on penicillins, macrolides, clindamycin and metronidazole, which have all been shown to be effective50,73–77, although this is contested78,79. Studies into metronidazole have indi- cated that high preoperative doses (1000 mg and 1600 mg) are not effective in preventing AO, and suggest that regular post-operative doses may be more successful80,81. A Cochrane review, carried out by Lodi et al. in 2012, looked at studies surrounding the topic of the efficacy of antibiotics in reducing post-operative complications following removal of mandibular third molars^82. It concluded that although there is evidence to show that prophylactic antibiotics reduce the risk of AO, among other complications, it may not be indicated in fit and healthy patients, given the increasing prevalence of bacterial resistance. This concern is echoed in many other papers5,9,16,17,63,79. In addition, guidance from the SDCEP does not indicate prescription of antibiotics for this purpose^83.
Topical antibiotics Topical applications clindamycin, tetracycline and metronidazole all have evidence to show effectiveness in reducing AO incidence18,84–90, but it is tetracycline which appears to have the strongest position as a topical agent5,91. Typically, studies have involved place- ment of a resorbable gelatin sponge ( Gelfoam – Pfizer, Surrey, UK) into the socket, impregnated with a solu- tion of the antibiotic. Alternatively, antibiotics can be available in gel form, notably metronidazole gel which is more commonly used in the treatment of periodontal disease and available in preparations such as Elyzol (Colgate-Palmolive, Surrey, UK). While topical antibi- otics are certainly proven to be effective in AO preven- tion, a clinician must also factor in cost-efficiency, as more readily available agents with better shelf-life may produce a similar result.
Antifibrinolytic agents Tranexamic acid and para-hydroxybenzoic acid (PHBA) are both antifibrinolytic agents, which inhibit both plasmin and plasminogen (PHBA being slightly more potent)^65. Both have been investigated as preventative measures for AO, but with mixed success. Tranexamic has only been shown to have a marginal reduction in AO incidence, with no significant effect demonstrated.
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PHBA was previously available in Apernyl cones ( Speiko® , Munster, Germany) – a resorbable medica- ment originally containing 3 mg PHBA and 32 mg ace- tylsalicylic acid. Many studies into its effect on AO prevention produced favourable results92–94. However, it has been speculated that there may be some element of confounding due to the presence of acetylsalicylic acid, with it having a local anti-inflammatory effect that reduces the inflammatory component of AO5,16. The lit- erature surrounding antifibrinolytic agents in regard to the management of AO seems to reflect a passing trend, and although still available on the market, it would seem that Apernyl no longer contains PHBA.
Pre-emptive packing
There is little mentioned regarding pre-emptive packing within the literature. Bloomer reported success in reducing AO incidence by immediate post-extraction application of gauze treated with a eugenol-containing paste 95. Yet eugenol is said to have an irritant effect, and to delay wound healing5,16,63. Non-eugenol-containing medicaments are available, such as SaliCept (Carrington Laboratories, Iriving, Texas USA) which is a resorbable, freeze-dried product containing Acemannan Hydrogel: a mixture of naturally occurring substances with the primary component being acemannan, a β-(1,4)- acetylated mannan obtained from the clear inner gel of aloe vera L^96. A study in 2002 compared SaliCept with Gelfoam sponge treated with clindamycin with regard to AO prophylaxis, and found that SaliCept was shown to be significantly more effective^96. It is important to note that in Bloomer’s study, the non-resorbable dressing was removed 1 week after placement. Anecdotal evidence exists detailing cases where overzealous packing of non-resorbable dressings have led to localised infection, with one case of severe facial cellulitis due to the retention of the dressing^97. Clinicians should take care when placing non- resorbable dressings by only lightly packing the dress- ing into the socket, allowing exfoliation at a later stage. Appropriate follow-up appointments may be consid- ered if indicated.
Plasma rich in growth factors
In comparison with normal healing sockets, dry sockets with a bacterial presence have been shown to have lower levels of growth factors present within 14 days post-extraction, and a lower density of blood vessels, bone neoformation and connective tissue within 7 days post-extraction^98. Studies have shown that plasma that is rich in growth factor is effective as a preventative
measure and as a treatment for AO by accelerating the healing process and reducing pain intensity99,100. The plasma was prepared by obtaining a blood sample from the patient, running that sample through a centrifuge and drawing off the layer with the highest concentra- tion of growth factors. This is certainly an intriguing concept which has seemingly promising results, but with such complex preparation and specialised equip- ment, this is unlikely to become a realistic treatment modality for AO.
Management/treatment
Eugenol-based medicaments Alveogyl (Septodont, Kent, UK) is a non-resorbable medicament available in the UK and is a very popular choice of treatment for AO. It is composed of Penghawar djambi fibres with Eugenol ( Alveogyl Safety Data Sheet, Septodont, 2011), and is targeted at AO management based on the anaesthetic nature of eugenol. The manufacturers claim that it promotes haemostasis by compression, and can prevent AO, but while the latter may be true, no haemostatic properties of any of the constituents are recorded in the literature. Furthermore, to obtain haemostasis by compression with a non-resorbable dressing that is staying in situ would require firm packing into the socket that may hinder exfoliation of the dressing later on. All previous studies have involved Alvogyl (Septodont), which was discontinued as a registered pharmaceutical in 2012, and replaced with similarly named Alveogyl , for which no studies could be found. There is a difference in the composition, with Alvogyl containing butamben and iodoform, as well as Eugenol ( Alvogyl Material Safety Data Sheet, Septodont, 2011). Research into Alvogyl had shown it to be an effective treatment for AO101,102, although retardation of healing is said to occur101,103. Other eugenol-based treatments are available with proven success9,16,104, but with concerns raised regarding the irritant effect of eugenol on the healing socket, and carrier systems involving lipid-containing materials that can potentially cause myospherulosis5,9,16,63: a localised, inflammatory, granulomatous lesion resulting from the action of lipids of extra-vasated erthrocytes, and pre- senting as a brown/black, tar-like product within the socket 20.
SaliCept SaliCept is shown to be an effective treatment for AO, and comparable with Alvogyl^102. But despite praise in
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