Eugenol: A Definitive Solution for Dry Socket, Therapeutic Controversies Regarding the Iatrogenic Effects of Iodoform, and Implications for Implants

Due to the controversies arising from the heterogeneity of proposed treatments for dry socket and their dissent, there is no standard protocol, leading to confusion among dental professionals. We present a rare case of the introduction and compaction of iodine-based cement into a post-extraction dental alveolus with a dry socket refractory to iatrogenic treatment, followed by restoration with a dental implant.
The formulations used for the treatment of dry sockets containing iodoform could impair tissue healing. Therefore, the cement inserted was excised and the alveolar cavity was cleaned. Basic therapy with eugenolated gauze, exchanged periodically for 40 days, was administered to an extreme case of alveolitis refractory to iodoform treatment, which delayed the healing of soft tissues and alveolar bone three times longer than usual. A dental implant was inserted three months later into this healed bone with very low density using a 15% reduced final surgical drill protocol. However, the success of bone healing and peri-implant tissue health was confirmed by clinical and radiographic follow-up of the dental crown on the implant subjected to masticatory loading for 18 months.
The comprehensive treatment of DS to standardize a safe protocol remains a pending task for our scientific community. Nevertheless, we propose continuing specific lines of research on eugenolated gauze because it relieves pain in the first session and in less than two minutes, does not require complementary analgesic or anti-inflammatory medication, and does not interfere with or delay normal tissue healing, allowing for successful dental implant treatment, even in extremely refractory cases. Furthermore, because it is a classic medication, its availability, immediate availability, and affordability are guaranteed in all dental offices worldwide. However, clinical trials and comparative studies should be conducted in the future to validate this protocol.

Introduction

Alveolar osteitis or dry socket (DS) is an unusual complication of tooth extraction surgery that most commonly affects mandibular molars. It is associated with severe pain developing 2 to 3 days postoperatively with or without halitosis, a socket that may be partially or completely devoid of a blood clot and increased postoperative visits [1]. Following tooth extraction, SD may develop when the clot within the post-extraction socket disintegrates and dissolves prematurely, leaving the bone unprotected and exposed to the oral environment. Both bacteria and food may then fill the socket, and their degradation products are thought to lead to further dissolution [2]. In addition to severe pain, premature loss of the fibrin clot delays the biological processes of alveolar bone formation that should start within 7 days [3] and leads to prolonged endoplasmic reticulum stress on osteoblasts, causing cell apoptosis, reduced expression of osteogenic markers, and decreased osteogenic capacity [4], [5]. However, rapid wound healing after tooth extraction is essential to preserve alveolar ridge height for dental implant rehabilitation [6].

When treating a dry socket lesion, the goal is to optimize the lesion so that the alveolus is able to optimally form a durable epithelial layer covering the exposed bone within the alveolus and around the occlusal perimeter of the alveolus [7].

The diversity and quantity of scientific publications on SD therapeutics can be overwhelming. Treatments with medicated gauze and/or dressings, mouthwashes, cements, biological products, foods, plants, gases, radiation, vitamins, oils, and commercial products have all been proposed for the treatment and prevention of SD with varying therapeutic results. Hundreds of dissimilar scientific works have been published proposing countless treatments for DS, the main therapeutic categories include natural products, chemical compounds, physical methods, anesthetics, bioactive substances and commercial preparations [7]–[25] (Table I) which has caused great confusion in the therapies applied by dentists and controversies in the scientific field.

Table I. Main Therapeutic Categories Used in the Treatment of Dry Socket

Natural products	Chemical compounds	Physical methods	Anesthetics	Bioactive substances	Commercial preparations
Eugenol	Iodoform	Low laser terapy	Lidocaína hydrochloride	Hyaluronic acid	Alvogyl®
Propolis	Zinc Oxide	Ozone gas	Tetracaina hydrochloride	Platelet rich fibrin	Neocone®
Honey	Chlorhexidine gel	Magnetotherapy	Benzocaine	Concentrated growth factor	Alveodont®
Nigella sativa oil	Quaternary ammonium	Photobiomodulation	Prilocaine	Chitosan-pectin	Alvofar®
Turmeric	Oxytetracycline-hydrocortisone,	Multifrequency laser		Fibrin	Alveolex®
Gelatin	chitosan/carboxymethyl			Nanovitamin C	Alveogyl®
Sunflower oil	Alginate sponges			Nanovitamin E	SaliCept patch®
Olive oil					Alveospad®

Treatment with iodoform pastes/cements alone or in combination with other materials has been widely used in dry socket treatment for its antiseptic properties and granulation stimulation in bone healing by secondary intention, with varying results [26], [27].

This study aims to test whether a standardized eugenolated gauze protocol used in a series of 37 dry socket cases performed by our team is more effective for dry socket management, provides rapid pain relief, does not interfere with healing, and promotes successful dental implant placement in a complex case of dry socket compared to iodoform treatments.

Method

Case Report

A healthy 30-year-old female patient with no comorbidities presented for consultation. The patient presented with severe pain due to iatrogenic DS treatment performed a week earlier, resulting in complete cementum impaction with iodoform in the post-extraction alveolus. The cementum was completely removed at the first appointment, thoroughly flushing the cavity with 10 vol [3%] hydrogen peroxide to remove any cementum residue adhering to the alveolar walls.

Eugenolated Gauze Protocol

A gauze pad, cut to approximately 80% of the volume of the socket to be filled, soaked in 100% pure Farmadental® USP-grade eugenol (4-Allyl-2-methoxyphenol)-C10H12O2-(MW: 164.2), was placed and exchanged every 24 hours during the first week. The patient reported complete pain relief 98 seconds after applying the gauze at the first appointment. The eugenolated gauze pad was inserted with cotton tweezers without applying excessive pressure into the dental socket, taking care not to touch the surrounding soft tissues. Gauze exchanges were spaced 48 hours apart during the second week, after which the usual epithelialization of the socket was not observed. From the third week onwards, the gauze size was reduced by 50% and exchanges were performed every 72 hours until soft tissue healing, which took 40 days during which the patient did not perceive pain. Our study on 37 patients with dry alveolitis who were treated with lavage with 3% hydrogen peroxide and filling the cavity with pure eugenol achieved permanent pain elimination in less than 2 minutes after starting the protocol, and soft tissue healing was achieved in a maximum of 2 weeks. In addition, it reduced the need for complementary analgesic or anti-inflammatory medication and did not delay normal healing of hard and soft tissues [28]. At the first appointment (Fig. 1), the dental alveolus was verified by X-ray to be completely filled with iodine-formed cementum (a), previously observed as yellow during the clinical inspection (b). The cementum excision was performed manually with curettes without using rotary instruments despite the strong compaction to preserve the vitality of the bone tissue (c). The extracted cementum fragments are observed in (d) and the empty dental alveolus with cementum remains penetrating its palatal cortex in (e). Finally, a control X-ray was taken to verify that 80% of the alveolar volume had been filled with eugenolated gauze (f).

Fig. 1. Clinical and radiographic sequence of cementum excision.

Wound Healing

The patient reported immediate relief of pain from the first session, which continued until the final eugenolated gauze exchange after the wound healing was complete at 40 days. Intra-alveolar epithelialization took 6 weeks, three times longer than our series of 37 cases, where healing was achieved in 2 weeks. The treatment sequence can be seen in Fig. 2. The first eugenolated gauze change was performed at 24 hours (a), and at 48 hours, initial epithelialization was observed at the distal edge of the alveolus (b). During the 9 days, complete epithelialization of the alveolar contour occurred; however, a delay in intra-alveolar epithelialization was observed (c), and the healing follow-up at 55 days (d). After 3 months of healing, volume loss of the alveolar vestibular wall and ischemia of the palatal mucosa anesthetized before surgery were observed (e).

Fig. 2. Three-month follow-up of healing.

Implant Surgery

Three months after starting treatment, normal soft tissue healing was observed clinically, with a reduction in the width of the alveolar ridge at the expense of the buccal bone wall. After confirming bone healing using radiovisiography, low-density bone was observed in the alveolar bed area (Fig. 3a). Nevertheless, it was decided to perform surgery to insert the dental implant. When drilling with a lance drill, (Fig. 3b) minimal pressure was required to prepare the implant bed, which tactilely confirmed low-density Misch type 4 dental implant bone [29]. Due to this situation, instead of performing the protocol step of the final drill with a 3.25 mm diameter, minimal drilling was performed with a final 2.75 mm drill (a 15% reduction in the standardized diameter) to insert a 4.0 mm diameter implant with good initial anchorage to the cortical bone of the maxillary sinus floor (Fig. 3c).

Fig. 3. Radiographic sequence of dental implant insertion.

Results

Prosthetic Rehabilitation

After 4 months of osseointegration of the dental implant (conventional load-free protocol), the width of the alveolar ridge was visualized. After anesthesia, the implant connection was discovered, verifying its osseointegration by percussion and the absence of mobility (Fig. 4a). The healing abutment was connected for 14 days for initial soft tissue healing (Fig. 4b). A silicone impression was then taken using an indirect technique with transfer (Fig. 4c) to fabricate a screw-retained metal-ceramic crown with an access hole for the prosthetic screw (Fig. 4d), which was filled with 3M® Dentin Z350 nanoparticle composite. In addition, a 2 mm loss of bone thickness was observed in the mucosal contour at the expense of the vestibular wall (Fig. 4e). Finally, radiovisiography was performed to control the fit of the implant/dental crown connection (Fig. 4f) and the clinical visualization of the soft tissue integrity and the achieved aesthetics (Fig. 4g).

Fig. 4. Clinical sequence and X-ray verification of the prosthetic rehabilitation.

Follow-Up

The patient has no harmful habits, is in excellent general health, and maintains regular dental hygiene. Quarterly checkups were performed during the first year after the crown was placed on the implant. The 18-month follow-up revealed healthy peri-implant soft tissues without inflammation (Fig. 5a), and radiovisiography showed the maintenance of the bone crest height and the stability of the implant-crown connection (Fig. 5b).

Fig. 5. Clinical-radiographic follow-up 18 months after the installation of the dental crown on the implant.

Discussion

The multiple treatments proposed for post-tooth extraction dry socket lead to confusion among dental professionals. The choice of the ideal treatment is still controversial in the scientific field due to the diversity of therapies proposed in the literature, as well as the actual etiology, pathophysiology, and the best prevention and treatment methods [30]. Systematic reviews focused on the prevention of dry socket through the use of chlorhexidine and platelet-rich plasma present a low level of evidence [2], [9] and should not be considered as a preventive protocol. The same is true for most of the proposed treatments developed in the preceding introduction. Although there is a wide range of reported data on dry socket, to date there is no standard prevention or treatment [31].

There are records of iatrogenic treatments with impacted cementum in SD. Its use remains controversial and has been linked to some side effects such as neuritis, foreign body reactions, and myospherulosis. One case mimicked trigeminal neuralgia for 3 years and resulted in chronic maxillary osteomyelitis and a foreign body reaction. This long-term complication was successfully controlled by complete removal of the foreign body and curettage of the affected area [32]. In direct relation to the delayed healing in our clinical case, a recent experimental study in Wistar rats found that the addition of iodoform hindered tissue repair and delayed collagen fiber maturation [33]. This could explain why intra-alveolar epithelialization took 6 weeks, three times longer than our series of 37 cases, where healing was achieved in 2 weeks. Furthermore, the low bone density found during drilling of the dental implant site could play a role in the delay in intra-alveolar bone maturation and regeneration, which is expected due to the decrease in osteogenic activity in DS [4], [5]. However, the effect could have been aggravated by the residual action of iodoform, as it has been shown to be effective in chemical debridement by facilitating collagen fibrinolysis [34]. For this reason, we considered underpreparing the implant bed with a drill 15% smaller than the standardized diameter in surgical protocols to achieve optimal initial anchorage.

The beneficial role of eugenol-based paste in preventing alveolar osteitis and promoting improved wound healing was reported in a study involving 270 patients undergoing third molar extraction [35]. Furthermore, eugenol mitigates chronic inflammation by decreasing the expression of various inflammatory mediators (TNF-α, NF-κB, COX-2, IL-1β, IL-4, IL-5, IL-6, iNOS, and NO) in both in vitro and in vivo models and also, those associated with an increase in antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase, and glutathione peroxidase) [36], A systematic review addressed the effects of eugenol on arachidonic acid (AA) derived inflammatory mediators and reported the inhibitory effect of eugenol on prostaglandin and leukotriene production and reduction of edema formation in several animal models of inflammation. Furthermore, in human platelets, eugenol inhibited AA- and platelet-activating factor (PAF-)-induced aggregation. Eugenol and sodium eugenol acetate have also been shown to inhibit AA-induced thromboxane B2 and PGE2 formation in a concentration-dependent manner, as well as oxidative stress (mainly of mitochondrial origin) [37]. Eugenol also achieved pain reduction by inhibiting periapical/interdental innervation activity [38]. Although our study successfully resolved alveolar pathology and achieved dental implant rehabilitation with an 18-month follow-up, due to the limitations of the single case, controlled studies are suggested for future research.

Conclusion

Formulations containing iodoform for the treatment of dry socket may impair tissue healing. We present a basic treatment with eugenolated gauze for an extreme case of dry socket refractory to iatrogenic iodoform treatment, which delayed soft tissue and alveolar bone healing three times longer than usual. A dental implant was inserted into this healed bone with very low density using a 15% reduced final surgical drill protocol. However, the success of bone healing achieved with the proposed treatment for SD was confirmed by monitoring the dental crown on the implant subjected to masticatory loads for 18 months.

The comprehensive treatment of SD to standardize a safe protocol remains a pending task for our scientific community. Even so, we propose pursuing specific lines of research on eugenolated gauze because it relieves pain in the first session and in less than two minutes, does not require complementary analgesic or anti-inflammatory medication, and does not interfere with or delay normal tissue healing, allowing for successful dental implant treatment, even in extremely refractory cases. Furthermore, because it is a conventional medication, its availability, immediate availability, and affordability are guaranteed in all dental offices worldwide. However, clinical trials and comparative studies will need to be conducted in the future to validate this protocol.