Solid organ transplant patient management undergoing oral surgery: a review of literature

Introduction

A relationship between various specialties and adverse effects of post-transplant treatments gives rise to a permanent search for ways to reduce these complications. In the last ten years, the number of transplants has been increasing, and the world transplant organization reported 146,840 transplants worldwide, with a 6% increase from previous year [1].
In Europe, the 2019 data included 11,325 transplants, with an increase of 5% as compared with previous year. In this sense, Spain was reported to perform the highest number of transplants in Europe and in the world, and continues to report the uppermost data. In 2019, Spain has registered 5,326 transplants, demonstrating 6% of the worldwide and 20% of European data. This is highly relevant, considering 9.1% in Spanish population at the European level, and 0.6% at the global level [1].
Regarding transplant types performed in Spain, kidney transplants were the most prevalent with 3,423 transplants in 2019, followed by 1,227 of liver transplantation, 300 of heart transplants, 419 of lung transplantation, 76 of pancreas transplants, and 4 cases of intestinal transplantation [1].
Regarding logistics, the National Transplant Organization (ONT) provides guidelines for organs’ transplantation, including distribution of organs, organization of transport, management of waiting lists, statistics, and general and specialized information as well as any action that can help improving donation and transplant process.
All the above-mentioned are based on the continued success rates in solid organ transplants as well as the importance of dentists in the control of oral health of these patients, both prior to and after transplantations [2].
Pre-transplant dental treatment has positive effects on the success of transplant by reducing the possibility of infection. Dental care prior to transplant involves elimi­nating possible sources of oral infection, such as dental caries and periodontal disease, which could lead to systemic infection after transplantation or transplant failure [3-5]. Post-transplant dental care generally consists of prevention of oral infections, treatment of dental caries, and prosthetic rehabilitation. Drug-induced immunosuppression can predispose solid organ transplant patients to different complications, including chronic infections and oral lesions [6]. Furthermore, prosthetic rehabilitation allows patients’ good oral intake and better nutrition [7].
The prevention and treatment of oral infections usually require oral surgery or periodontics treatments, such as tooth extraction, biopsies, and scaling and root planing. The management of these patients before or after transplantation is of high importance in order to reduce complications of oral surgery treatments.
The present review aimed to assess and analyze the current published clinical guidelines and the observed effects in transplant patients undergoing oral surgery. The main objective of the review was to determine the current evidence on the use of antibiotic prophylaxis in transplant patients undergoing oral surgery treatments. The secondary objective was to determine the medication administered to prevent post-operative complications of oral surgery.

Material and methods

To assess the objectives of the review, a research question was raised: “What are the guidelines described in the literature for oral surgery treatments in transplanted patients?”. A systematic review of the literature following PRISMA guidelines based on an electronic search was carried out in the National Library of American Medicine (Medline), PubMed, Web of Science, and Scopus databases, using a combination of the following terms: “Oral Surgery” AND “Solid Organ Transplanted Patient” OR “Organ Transplanted”, with filters, such as year since 1990, studies on humans, and full-text available.
The following inclusion criteria were applied: articles published since 1990, written in English or Spanish, patients who received a solid organ transplant or were planning to undergo transplantation and who needed any oral surgery procedures, articles with complete information about solid organ transplant, oral surgery procedure, and antibiotic treatment or other care applied to prevent complication, in accordance with the objectives of this review.
Exclusion criteria were articles published prior to 1990, written in language other than Spanish or English, animals studies, duplicates, and papers not related to the main objectives of this review.
Database search was carried out by two independent researchers (LS and DR) and in case of disagreement, a third researcher (LMS) determined the criteria for paper identification and inclusion. <

Results

A total of 160 studies were identified using electronic search, complemented by a manual search that identified two more articles. From the 162 initially identified studies, 156 were excluded after title and abstract screening, and finally, 6 studies met the inclusion criteria after full-text assessment (Figure 1). These 6 studies (clinical trials) were included in the review. A total of 784 patients were included. The characteristics of patients of the studies included are shown in Tables 1 and 2.
Tables 1 and 2 present visible heterogeneity, consi­dering the clinical measurements performed and the type of transplant. There were five clinical trials and one case report. Their main objectives were considerations and management of transplanted patients with solid organs undergoing surgical dental treatments, such as extractions, biopsies, and scaling and root planning. Liver transplantation was the most commonly reported transplant type. A total of 784 patients were included, aged between 18 and 80 years, with a history of liver, heart, kidney, or pancreas transplants, to whom, depending on the study, different medications were administered, among which antibiotic prophylaxis was the most common, in addition to other substances for the managements of post-operative complications.

Discussion

Several oral pathologies can occur in solid organ transplant patients. High-rate of oral diseases resulting from immunosuppressants and their organic circumstances should be prevented or treated [2]. In order to prevent infections, dental care before and after transplantation is crucial. Most common sources of infection come from oral pathology, such as dental caries and periodontal disease, which could lead to systemic infection after transplantation or transplant failure [4-6]. Oral infections can cause abscesses, transplant failure, and life-threatening sepsis.
In case of cyclosporin [9-11] administration as immunosuppressant treatment, this medication produces gingival hypertrophy, a frequent pathology with great implication at the oral level. In patients treated with azathioprine [10] as immunosuppressant, oral stomatitis or opportunistic infections can occur, such as candidiasis and herpes due to their action in immune system. Myco­phenolate [9] as a selective immunosuppressant can cause cold sores and oral stomatitis. Among other pathologies in the oral cavity is xerostomia [10, 11]; this occurs because of prolonged immunosuppressive the­rapy, making patients more susceptible to opportunistic infections, cavities, and other pathologies. Although awareness of the importance of dental treatment in this context has increased, few studies have directly investigated what dental treatments are actually provided to transplanted patients [12-19].
Among the included studies, there were a variety of methodologies utilized for the treatment of patients after transplantation, leading to different conclusions depending on the objective regarding the management of this type of patients after oral surgery.
A study published by Borea et al. [20] aimed to assess the circulatory dynamics in heart transplant patients who underwent dental extraction procedures, concluding that this type of intervention represents a safe procedure in these patients. The differences found in blood pressure and heart rate values before, during, and after the treatment were insignificant compared with the control group. Taking into account both the stress involved in undergoing an invasive dental procedure and the medication used in transplanted patients, these values had slight variations when compared with the controls. Due to transplantation received, denervation of organs lack vagal or sympathetic effects, which determine the response to a high-stress event, and simplify the management of these patients both clinically and pharmacologically. In recent years, much of medical research has focused on investigation and development of new protocols for the application of stem cells in transplant patients. It is important to underline the need of developing alternative therapies capable of improving healing and prognosis [21].
Other studies focused on evaluating the prophylactic antibiotic dose efficacy in transplant patients undergoing oral surgery procedures, such as dental extractions, scaling and root planning, and oral biopsies. Lopes et al. [22] conducted a clinical trial comparing the effects of prophylactic antibiotic dose of 500 mg of amoxicillin prior to oral surgery procedure versus the administration of 500 mg prophylactic antibiotic prior to the procedure and other dose at 8 hours after treatment. The authors reported no differences between both the groups, and no patient infection at the surgical anatomical site. These results were similar to those obtained by Karacaglar et al. [23], where the antibiotic prophylaxis recommendations of the Ameri­can Heart Association of 2017 were employed. The authors emphasized the necessity for further studies, considering high-risk of infections in transplant patients and lack of specific recommendations. Levenson et al. [24] in their case report highlighted the importance of using antibiotic prophylaxis as a tool to prevent infections in transplanted patients, with amoxicillin being the antibiotic of choice, clindamycin and its deri­vatives in cases of allergies to penicillin, and avoidance of macrolides, such as erythromycin or azithromycin due their negative interference with liver metabolism. Furthermore, Garg et al. [25] used antibiotic prophylaxis in all patients consisting of 500 mg amoxicillin in addition to 500 mg of metronidazole administered at 1 hour before the procedure.
On the other hand, some studies have focused on the complications that may occur after performing surgical dental procedures, and their management. Helenius- Hietala et al. [26] and Garg et al. [25] performed surgical treatments in liver transplant patients, and observed that the most common complication was post-operative bleeding, which they recommended treating either compressively with gauze or by applying anti-fibrinolytic substances.
Even though the analyzed studies were very hetero­geneous, and included patients with different types of transplants, the objectives ranged in efficacy of antibiotic prophylaxis evaluation, pharmacological management, and possible complications associated with dental procedures, it was observed that most of the authors employed antibiotic prophylaxis prior to a dental procedure, despite stating that the guidelines in some cases agreed and in others disagreed. These studies insisted on the importance of transplanted patients’ prolonged treatments with immunosuppressants, which can condition patients’ response to healing process, where there is a high-risk of post-operative infection. Considering that, the use of prophylaxis is of utmost importance, and plays a fundamental role in the prevention of post- operative infections. In the same way, an objective comparison between all the studies was not possible due to the heterogeneity of samples, type of transplant, type of antibiotic used, and procedures performed.
As liver transplantation was the most common among all transplantations reported, the studies highlighted the presence of complications after the prescribed surgical dental treatment, which in most cases, corresponded to dental extractions. In order to limit the exposition of patient to radiation dose due to diagnostic examination, other alternatives and no-radiation diagnostic exams, which can improve daily clinical practice should be considered, such as magnetic resonance imaging (MRI) and ultrasound [27].
The complications reported in the analyzed studies were related to post-extraction bleeding due to the altered coagulation status and hemostasis, treated with the use of topical or intravenous application of anti- fibrinolytics, such as tranexamic acid, which was mostly used, and gauze compression.
Most of the studies did not include a detailed description of complications, which may occur after surgical dental treatments in transplanted patients.
Therefore, considering the lack of research, there is a need for an evaluation of complications after dental treatments and oral surgeries as well their prevention, treatment, and evolution.
The current study main weakness was the limited information within the literature review, in which the main electronic search was complemented by means of a manual search. Moreover, the research did not take into account the quality of evidence identified, risk of bias in the included studies, and potential biases in the review process.

Conclusions

Considering the limitations of the present review, it can be concluded that there is a lack of scientific evidence to establish a clear and universal guidelines for the management of solid organ transplant patients. Even though the use of antibiotic prophylaxis was a widespread practice among the analyzed studies, there is no established recommendations regarding its use in transplant patients; still, the use of antibiotics is recommended. Likewise, the use of antibiotics, usually 500 mg of amoxicillin administered at 1 hour prior to the surgery, and the application of anti-fibrinolytic agents, were described as the most common tools for the management of possible post- operative complications in transplanted patients; although a protocol for their prevention has not been determined.
It will be convenient to establish specific and delineated research for investigating this type of patients, considering prior to treatment medication, type of anesthetics used, possible surgical dental complications, and transplanted organ management and evolution.

Disclosures

1. Institutional review board statement: Not applicable.
2. Assistance with the article: None.
3. Financial support and sponsorship: None.
4. Conflicts of interest: The authors declare no potential conflicts of interest concerning the research, authorship, and/or publication of this article.

References