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Clinical Audit of Two Standard Surgical Site Treatments Following Dental Extractions and The Impact on Incidence of Alveolar Osteitis Within a Specialist Dental Clinic

Alveolar osteitis is a painful condition following dental extraction associated with absence of blood clot and consequent exposure of underlying alveolar bone. It is a condition whose exact aetiology is unresolved and a known complication in up to 30-40% of dental extractions. The following report details a retrospective evaluation of two approved, long-standing wound care treatments used, post-extraction, within our clinic to assess for relationship with alveolar osteitis incidence.


Abstract
Background Alveolar osteitis is a painful condition following dental extraction associated with absence of blood clot and consequent exposure of underlying alveolar bone. It is a condition whose exact aetiology is unresolved and a known complication in up to 30-40% of dental extractions. The following report details a retrospective evaluation of two approved, long-standing wound care treatments used, post-extraction, within our clinic to assess for relationship with alveolar osteitis incidence.

Methods
Patients undergoing non-acute dental extraction at a dental out-patient clinic in the UK had received two different standard treatments for a period from 2000 to 2014. The treatments were mouth rinse with physiologic saline or surgical site irrigation and mouth rinse with physiologic saline-low dose aqueous chlorine used in wound and burn-site care. Retrospective, post-operative outcome analysis suggested improved outcomes with one of the standard treatments versus the other. A full retrospective audit of consecutive treatment outcomes was implemented to test the hypothesis. The audit data-collection was blinded to the treatment administered and to the identity of the treating clinician. Statistical analysis was carried out independently and blinded to the treatment modality.

Results
All patients were routinely reviewed within seven days and a determination of un-complicated healing vs alveolar osteitis (requiring further intervention) was made. Our results show that treatment with of aqueous chlorine in physiological saline signi cantly reduced the incidence of alveolar osteitis versus the control group who received physiologic saline without socket irrigation and chlorhexidine oral rinse homecare. (Odds Ratio 0.0146 Relative Risk 0.029 (95%CI 0.0093 to 0.0928) signi cance (p<0.001).

Conclusions
This is the rst report to show an extremely signi cant reduction in the incidence of alveolar osteitis following treatment with low dose aqueous chlorine in physiological saline compared with those receiving the physiologic saline and saline mouth rinse or Corsodyl mouth rinse. This shows an approach to surgical site care is superior to the most common, reported, standard of care treatment. The impact of this has led to improved antibiotic stewardship within the clinic for dental extraction or elective oral surgery, including third molars. addressing the potential to disinfect contaminated surgical or wound sites without producing adverse effects [12,13,14,16].
The clinical use of very low level hypochlorite has been extensively reported for over 70 years [12,13,14,16]. In addition to the long standing evidence of clinical utility there are multiple reports and reviews of pre-clinical investigations which address safe concentration and e cacy as an antimicrobial [7,12,16].
Furthermore, the endogenous production of hypochlorite by neutrophils as a derivative of myeloperoxidase produced hypochlorous acid is described by investigators of neutrophil function [15,17]. Indeed, a review of the biochemistry of endogenous myeloperoxidase function calculates a highest level of concentration of the endogenous hypochlorous acid-hypochlorite blend in in ammatory foci as between 25-50nM (equivalent to 1300 -2600 ppm) [15]. The same review of the function of this endogenously produced very low dose hypochlorous acid-hypochlorite compound blend examines the reactions of the compounds with multiple key biologically important structural and messenger molecules and compounds including proteins, fatty acids, cholesterol-derived hormones and nucleic acids [15]. The implication of these analyses suggests that a concentration and formulation close to that found endogenously can be produced by a dilution of approved formulations. If such a biomimetic formulation were produced it should be possible to maintain wound or surgical sites with a low level of microbial contamination without resorting to antibiotics. Within this clinical evaluation, the formulation of the combination of hypochlorite, hypochlorous acid and saline was used as a surgical site and wound wash and this was derived from approved compounds.
One of the most common and painful conditions following dental extraction is alveolar osteitis or "dry socket" which is often linked to repeated visits to the dental surgery or the hospital and an increased burden, nancially, physically and psychologically on the patient.
As a result this condition has been linked with a number of contributing factors and so consequently a large range of treatments are offered including rinsing of the socket with chlorhexidine or saline or placement of speci c dressing. Whilst true infection and osteomyelitis is rare following dental extraction and oral surgery, alveolar osteitis has been reported as a known complication following as many as 30 -40% elective oral surgical procedures [1][2][3][4][5]. Antibiotic use following dental extraction is common. In 2012 both Tolstunov [4] and Yengopal [5] reported on alveolar osteitis and current methods used to reduce its incidence. Neither found evidence of effectiveness using chlorhexidine (0.2% solution or gel) or isotonic (normal) saline surgical site irrigation [4,5]. Indeed, the most startling nding was that doing nothing was preferable to using any surgical site treatment [4].
In a recent investigation of a concentrated growth factor administered to dental extraction surgical sites reported a reduction in the incidence of alveolar osteitis versus a control group, where antibiotics were also routinely administered prospectively [6].
However there have been growing concerns about the increased use of antibiotics and with this in mind we were aware that component oxidizing agents present in unbuffered dilute sodium hypochlorite in saline solutions have previously been shown to have antibacterial properties [7]. Such approaches have been used over many years principally in the eld of burns care and in the care of gunshot trauma and treatment of non-healing leg ulcers [7,13,14]. Moreover such solutions have also been suggested to assist wound repair through their ability to induce the proliferation of keratinocytes [8-10].
Within the reporting specialist dental clinic the standard physiologic saline with low dose aqueous chlorine was used from 2000 to 2014 in addition to the more commonly reported approach of no socket irrigation and rinse with saline and or chlorhexidine mouth-rinse. Because it was perceived that outcomes following dental extraction surgery had improved a full retrospective audit of clinical outcomes was performed. The primary objective of the retrospective audit was to record outcomes and, in particular, incidence of alveolar osteitis following surgical dental extraction. The audit was performed via analysis of data reporting consecutive dental extraction surgeries.

Methods
This audit was designed to compare the outcomes of the two, standard, wound-care treatments used in the clinic over the period examined; where treatment of surgical sites was either no socket irrigation and saline mouth rinse or irrigation of the dental extraction socket with low dose aqueous chlorine in physiological saline. The study was carried out as a consequence of the observation that outcomes seemed to be improved when the dental extraction sites were irrigated with physiologic saline with low dose aqueous chlorine and the same composition used as a mouth rinse. The study was conducted at a dental practise in Melbourne Cambridgeshire between July 2000 and May 2014 and was carried out in accordance with the ICH Guidance for Industry E6 Good Clinical Practice (ICH-GCP) and the Declaration of Helsinki (52nd WMA General Assembly, Edinburgh, October 2000, with clari cation on Paragraph 29 by 53rd WMA General Assembly, Washington, October 2000) and conducted by scienti cally and medically quali ed persons. As per standard procedure, all patients consented to dental extraction.
The audit was of consecutive dental extractions within the specialist dental practice where the dental extraction was performed by one of the two clinicians. Both clinicians had similar levels of training, experience and competence in performing the oral surgery procedures. No pre-or post-operative antibiotics were prescribed unless indicated at the post-surgical review. The individuals represented a normal cross-section of this patient population and included people with concomitant co-morbidities including diabetes, post-splenectomy, hypertension and coronary heart disease. No patients who were t enough for a dental extraction under local anaesthetic where excluded. Only patients requiring general anaesthesia were excluded.
Patients attended via routine, out-patient appointment following a consultation. They had not been starved and had taken any routine medications as prescribed by their general medical practitioner. Anaesthesia / analgesia was achieved via standard approaches using standard local anaesthetic solutions licensed in the UK (lignocaine hydrochloride 2% with 1 in 80,000 adrenaline) and the dental extractions were carried out using standard techniques. Haemostasis was achieved via local pressure over the socket with cotton wool rolls and biting pressure. Occasionally, 3/0 braided silk sutures were required.
Within the physiologic saline & aqueous chlorine group, once the tooth was extracted the area was irrigated with aqueous chlorine (9.6 mM / 500ppm) in physiological saline as a wash using up to 10-20ml of the solution in 3ml aliquots. Dental cotton rolls were soaked in the same solution and the patient applied biting pressure onto the wound via the soaked cotton rolls. Home-care instructions were given that the patient should rinse four times a day with 10mls of this solution for ve days.
Within the physiologic saline group all protocols were identical except the wound was not irrigated at all and the cotton rolls were either dry or soaked in saline solution. Home-care instructions were given that instructed the patient to rinse four times a day with warm salt-water mouth-rinse or 0.2% chlorhexidine anti-microbial solution (Corsodyl -GSK UK) mouth-rinse for ve days. The post-surgery rinse protocol is currently the most frequently recommended standard treatment.
Once the procedure was completed and haemostasis achieved the patient was discharged home with care instructions. All of the study group were reviewed a week after the surgical procedure to assess pain and the success of healing. Additionally, if a patient returned within 14 days with increasing pain and/or un-successful healing and/or infection it was classi ed as alveolar osteitis.

Statistical Plan
The audit collated the data sets to test for a difference in the mean proportion of alveolar osteitis between the two groups. The audit analysis powered for superiority of an absolute difference with a power of 95% and a type I error rate of 5%. Estimation of the rate of alveolar osteitis has been reported as 30% in the literature and as this was in keeping with clinical experience this was the expected rate under the null hypothesis. A superiority margin of 5% with a minimum effect of interest of 5% were selected as being likely to be a clinically meaningful improvement. From this we calculated the sample size to be 934 extractions and planned analyses were scheduled for each third of the trial. In April 2009 with extraction numbers running at 206 (treatment arm) and 106 (control), interim data analyses revealed a large bene cial clinical effect in the treatment arm. The control arm of the study was suspended, and a singlearm extension study continued to more fully assess the bene ts and identify any potential adverse effects. The treatment arm continued recruiting until a total of 401 extractions were made.
The odds ratio and relative risk were calculated from the results using the online calculator at https://www.medcalc.org. The data was also analysed using the T test in Excel.

Results
Since some patients had multiple extractions, the data was analysed both on a per extraction outcome and on a per person outcome and this is shown in Table 1. It's clear from this Table that treatment with aqueous chlorine in physiological saline had a dramatic effect on the incidence of alveolar osteitis with a signi cant reduction in the incidence of the condition in those receiving the treatment compared with controls.
Whilst treatment reduced the incidence by a factor of 10 between groups, analysis of the incidence of alveolar osteitis per extraction in the treated and control groups revealed an odds ratio of 0.0191 and analysed per person revealed an odds ratio of 0.0146. Both analyses showed a clear and signi cant association between exposure to the treatment regimen and the subsequent outcome (P<0.0001). The relative risk was calculated per patient at 0.029 (95%CI 0.0093 to 0.0928) showing the results were statistically signi cant (p<0.001) Whilst there was a slight difference in the ratio of males to females in the treated group compared to the control group is seems unlikely that this difference could account for the dramatic difference in the incidence of the condition. Previous studies have linked infection with alveolar osteitis and so we noted the incidence of pre-operative infection which we considered could be a confounding variable in the results. However, our treatment group had a higher pre-operative rate of infection than the control group and so this could be discounted as a contributing factor to the outcome.

Discussion
Alveolar osteitis is a common, painful and debilitating condition where multiple forms of treatment have been tested to alleviate the condition, without success. This is the rst study to show a clear statistically signi cant reduction in the incidence of alveolar osteitis following surgical dental extraction using a low dose solution of aqueous chlorine in physiological saline. Use of low dose aqueous chlorine in physiologic saline protocols have been reported as useful in the treatment of burn sites, where systemic antibiotic use has limitations due to the damage to the capillary bed and resultant poor perfusion [12,13].
A recent systematic review revealed that bacteria may play an important role in the pathogenesis of this condition [11] and whilst the use of antibiotics have been suggested to be used postoperatively concerns have arisen because antimicrobial resistance is universally understood to represent a major threat to the provision of healthcare and, in particular, to the risk of infection following elective surgery.
Antibiotic stewardship requires a reduction in the use of antibiotics and places a responsibility on the clinician to use alternative strategies for preventing surgical site infection. Our treatment using aqueous chlorine in physiological saline used as a routine pharmaceutical wound wash in this series of oral surgical procedures resulted in a signi cant improvement in healing outcomes. Furthermore, this was seen in the absence of any use of antibiotics, which is of great potential value in the development of responsible antibiotic stewardship.
An unexpected bene t was consistently seen in the physiologic saline and aqueous chlorine treated group, where patients reported perceiving no pain or very little pain and furthermore, several patients reported that if any soreness developed, aqueous chlorine in physiological saline as a mouth-rinse eliminated it.
If the results of this study can be replicated in other surgical sites and in prospective use, the novel proprietary aqueous chlorine in physiological saline has great potential for use across a wide range of elective and emergency surgical sites to improve clinical outcomes and antibiotic stewardship.

Conclusion
Aqueous chlorine in physiological saline when used at a low concentration has a signi cant effect on reducing alveolar osteitis in patients following dental extraction. This is important for two reasons; rst, alveolar osteitis is a painful condition which has previous seemed intractable to treatment and second, this has been achieved without the prophylactic use of antibiotics which has great potential to improve clinical outcomes and antibiotic stewardship.

Declarations
Ethics approval and consent to participate Not applicable / waived. The audit reports on treatment outcomes following routine dental extraction surgery that had been carried out at a dental practise in Melbourne Cambridgeshire between July 2000 and May 2014 using one of two standard approaches to dental extraction surgical site management. The study was designed as an audit of treatments already in use and advised on by Professor R Aspinall (translational medicine) on basis that the treatments were existing treatments and already being used within the clinic.

Consent for publication
Not applicable

Availability of data and materials
The datasets generated during the current study are not currently publicly available but are available from the corresponding author on reasonable request.  Tables   Table 1 Study Subjects by gender and outcome following surgery Study Subjects