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. 2024 Dec 2;36(12):1503–1508. doi: 10.1016/j.sdentj.2024.12.004

Oral surgery considerations in patients at high-risk of complications related to drug intake: A systematic review

D Morgado-Sevillano a, J Rodríguez-Molinero a,b, C García-Bravo c, JF Peña-Cardelles a, JA Ruiz-Roca d, I García-Guerrero a,⁎, R Gómez-de Diego a
PMCID: PMC11976089  PMID: 40952869

Abstract

Purpose

This study aims to identify and comprehend the management of the most frequent complications in oral surgery that arise from the consumption of multiple drugs.

Materials and Methods

A comprehensive review of 23 articles was conducted, focusing on the complications that arise from the consumption of drugs in patients undergoing oral surgery treatment, in addition to the strategies for prevention and treatment.

Results

All the reviewed articles offered insightful knowledge into preventing complications through well-defined protocols that encompass both pre- and post-operative measures. These measures include local interventions such as periodontal treatments, dental prophylaxis, and hygiene instructions, as well as systemic approaches like antibiotic prophylaxis and post-surgical antibiotic coverage. Additionally, specific measures like monitoring prothrombin time with the International Normalized Ratio in patients with coagulation disorders, and implementing hemostatic techniques, were also discussed.

Conclusion

The most prevalent complications in oral surgery are hemorrhage in anticoagulated patients, infections in immunosuppressed patients, and osteonecrosis in patients who take antiresorptive drugs. Edema, pain, and inflammation are also common post-operative concerns. When managing high-risk patients pharmacologically, it is crucial to provide effective antibiotic coverage both pre- and post-procedure and to utilize minimally invasive dental procedures with local hemostatic measures.

Keywords: Polypharmacy, Multi-pharmacotherapy, Implantology, Oral surgery, Dental implant

1. Introduction

The significant increase in life expectancy today is largely due to notable advancements in medicine and pharmacology. Because of this, the development of new therapies for chronic diseases has led to a growing number of patients, especially older adults, seeking dental care while on one or more medications. This situation heightens the risk of complications in daily clinical practice, particularly during oral surgical procedures (Fretwurst and Nelson, 2021, Guillot et al., 2022, Bryant, 2022).

Osteoporosis is especially prevalent among postmenopausal women, affecting an estimated 25 % around the age of 50, and increasing to 40 % among women aged 70 to 79. In comparison, 11.3 % of men within the same age group suffer from it (Fretwurst and Nelson, 2021, Guillot et al., 2022, Bryant, 2022, Nakamura et al., 2021). Furthermore, conditions such as thyroid disorders, hematological diseases, and various autoimmune disorders − including rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, psoriasis, and systemic sclerosis − affect over 5 % of the population. These conditions may also exhibit symptoms in the oral cavity (Fretwurst and Nelson, 2021, Bryant, 2022, Nakamura et al., 2021).

Pharmacological treatments for these diseases can result in side effects and oral complications, such as osteonecrosis and hemorrhage −- these are among the most frequently observed issues (Fretwurst and Nelson, 2021, Guillot et al., 2022, Bryant, 2022, Nakamura et al., 2021). Rollason and Vogt (2003) delineate three types of polypharmacy: appropriate polypharmacy, where all prescribed medications have a clear clinical indication; inappropriate polypharmacy, where unneeded medications are included; and pseudopolypharmacy, where more medications are listed than the patient actually takes (Fretwurst and Nelson, 2021, Guillot et al., 2022, Bryant, 2022, Nakamura et al., 2021, Rollason and Vogt, 2003). Among patients on multiple medications, two main patterns are evident in dental practice: one involves individuals with conditions necessitating numerous drugs; the other mainly includes elderly patients with multiple comorbidities, each treated with one or more medications (Fretwurst and Nelson, 2021, Guillot et al., 2022, Bryant, 2022, Nakamura et al., 2021, Rollason and Vogt, 2003, López-Álvarez et al., 2013).

Given the significant number of elderly patients requiring dental care, understanding how to manage those on medications posing high risks during surgical procedures is essential. Such drugs include those affecting homeostasis like antiplatelet agents and anticoagulants, medications that suppress or modulate the immune system such as immunosuppressants and immunomodulators, as well as antiresorptive drugs like bisphosphonates and monoclonal antibodies targeting bone tissue resorption (Bryant, 2022, Nakamura et al., 2021, Rollason and Vogt, 2003, López-Álvarez et al., 2013).

This study aims to provide a current overview of the primary medications impacting oral surgery and to propose strategies for handling the most common complications resulting from their use.

2. Material and methods

A thorough bibliographic search was conducted in the MEDLINE (PubMed), Web of Science (WoS), and Scopus databases using MeSH (Medical Subject Headings) terms combined with appropriate Boolean operators. The terms included: “Polypharmacy,” “Polymedicated,” “Drugs,” “Systemic pathology,” and “Maxillofacial surgery,” as well as “Dentistry,” “Odontology,” “Dental implant,” “Implantology,” and “Oral surgery.”.

This systematic review strictly adhered to the guidelines set forth by the Cochrane Handbook for Systematic Reviews of Interventions and followed the framework of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), using its four-phase flowchart. The review protocol was registered in the PROSPERO (International Prospective Register of Systematic Reviews) with the code CRD42023432268 (Page et al., 2021).

The main objective was to answer the following “PICO” (P = patient/problem/population; I = intervention; C = comparison; O = outcome) question (Table 1).

Table 1.

PICO question.

Research question Does knowing the interactions and knowing how to manage the complications derived from drugs in polymedicated patients influence the success of oral surgery or implantology treatments?
PICO
 P I C O
Polymedicated patients undergoing oral surgery surgical treatments. Complications and pharmacological interactions derived from drugs. Management of the patient based on his medication to perform a surgical procedure in the oral cavity. Success or not of oral surgery depending on the management of the patient based on the drugs he consumes.
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The inclusion criteria were: (a) Randomized clinical trials (RCTs), (b) prospective and retrospective clinical studies, (c) human studies, (d) articles published in English, Portuguese, and Spanish, (e) case reports, and (f) studies published between 2004 and 2022, addressing the management of poly-medicated or high pharmacological risk patients in oral surgery.

The exclusion criteria were: (a) systematic reviews, (b) meta-analyses, (c) literature reviews, (d) non-comparative studies, (e) articles published before 2001, and (f) animal and in vitro studies.

The data extracted from each publication included: sample size, study objectives, study design details, randomization and blinding methods, inclusion and exclusion criteria, medications examined, complications and interactions associated with these drugs, and surgical outcomes.

The methodological quality of the selected studies was evaluated using the Jadad scale (Jadad et al., 1996). This scale comprises five items, and the total score ranges from 0 to 5 points. Studies with scores below 3 points were categorized as having low methodological quality, whereas those with scores of 3 or higher were deemed to exhibit acceptable, good, or excellent quality. Moreover, the level of evidence and recommendation grade for the included studies were ascertained with the Oxford Centre for Evidence-Based Medicine Scale, classifying evidence levels according to the most suitable design for each clinical scenario (Jadad et al., 1996).

3. Results

A total of 260 publications were initially identified, of which 45 were found to be duplicates and thus discarded, leaving 215 unique results. After applying the inclusion and exclusion criteria, the tally of publications shrank to 57. Upon analyzing the titles and abstracts, 23 articles met the parameters for inclusion in this review. These are displayed in the flowchart (Fig. 1).

Fig. 1.

Fig. 1

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Flowchart.

Supplementary material 1 provides comprehensive information about the selected studies, including their design, objectives, methodology, follow-up period, and sample size.

The drugs most frequently encountered that may affect oral surgery outcomes are antiplatelet/anticoagulant, immunosuppressant/immunomodulator, and antiresorptive drugs.

3.1. Antiaggregants and anticoagulants

Of the five chosen studies, four (Lillis et al., 2011, Girotra et al., 2014, Clemm et al., 2016, Schmitt et al., 2020) concentrated on managing patients undergoing tooth extractions or dental implant placement while receiving anticoagulant or antiplatelet therapy. The remaining study (Napeñas et al., 2009) investigated the frequency of bleeding complications in patients with hemostatic disorders undergoing invasive dental procedures.

Lillis et al. (2011) and Girotra et al. (2014) observed that patients on dual therapy (aspirin and clopidogrel) had a higher risk of bleeding during minor surgical procedures. However, all bleeding episodes were effectively managed using local hemostatic techniques. In contrast, Napeñas et al. (2009) found no statistically significant difference in bleeding complications between patients on dual therapy and those on single therapy. Similarly, Clemm et al. (2016) and Schmitt et al. (2020) noted an increased risk of thromboembolic events in patients treated with vitamin K antagonists (warfarin and acenocoumarol). Despite this, any bleeding events were successfully managed using local hemostatic measures. Overall, the studies concluded that discontinuing these medications is not a recommended approach, as the risks associated with oral complications are significantly lower than those linked to thromboembolic or cardiovascular events.

3.2. Immunosuppressants and immunomodulators

Four studies were selected that addressed this category of medications. One study by Montebugnoli et al. (2015) evaluated the peri-implant response in immunocompromised patients one year after prosthesis loading. The remaining three studies (Heckmann et al., 2004, Gu et al., 2011, Gu and Yu, 2011) investigated implant treatments in immunosuppressed patients and the complications associated with them.

Montebugnoli et al. (2015) reported the use of antibiotic prophylaxis but did not specify the type or dosage. In contrast, other studies (Heckmann et al., 2004, Gu et al., 2011, Gu and Yu, 2011) did not administer antibiotic prophylaxis before implant placement. Nevertheless, all studies provided post-surgical antibiotic coverage to patients, as detailed in Supplementary Material 2. During post-operative follow-ups, all authors (Montebugnoli et al., 2015, Heckmann et al., 2004, Gu et al., 2011, Gu and Yu, 2011) monitored inflammatory responses with a focus on bone and periodontal parameters and reported no complications.

3.3. Antiresorptive drugs

3.3.1. Monoclonal antibodies

Among the eight selected studies, all involved patients undergoing treatment with monoclonal antibodies, focusing on the risk of jaw osteonecrosis. Seven studies evaluated this risk following tooth extractions (Hoefert and Eufinger, 2010, Neuprez et al., 2014, Preidl et al., 2014, Aghaloo et al., 2014, Cassoni et al., 2016, Kaczoruk-Wieremczuk et al., 2021, Viviano et al., 2017). One study assessed the risk after dental implant placement (Fleissig et al., 2012).

In every instance, medication-related osteonecrosis of the jaw (MRONJ) was reported (Hoefert and Eufinger, 2010, Neuprez et al., 2014, Preidl et al., 2014, Aghaloo et al., 2014, Cassoni et al., 2016, Viviano et al., 2017, Fleissig et al., 2012). To lessen or prevent MRONJ-associated complications, Kaczoruk-Wieremczuk et al. (2021) suggested a protocol that covers pre-extraction, intraoperative, and post-operative care.

3.3.2. Bisphosphonates

Among the six selected studies, two (Grant et al., 2008, Lazarovici et al., 2010) investigated MRONJ-associated with dental implant placement, while another two (Lodi et al., 2010, Mozzati et al., 2013) focused on MRONJ following tooth extractions. The remaining studies (Zahid et al., 2011, Shabestari et al., 2010) examined implant failure rates and peri-implant bone loss in patients treated with bisphosphonates.

Mozzati et al. (2013) and Lodi et al. (2010) introduced a protocol that combines mechanical, antibiotic, and antibacterial strategies. In the study by Lodi et al., only one patient developed a minute area of exposed bone. This issue resolved spontaneously within 2 months and was not classified as MRONJ.

Lazarovici et al. (2010) included 27 patients in their study, 11 of whom were taking oral bisphosphonates while 16 were receiving intravenous treatment. All patients developed MRONJ, with six cases surfacing within 6 months, and 16 requiring implant removal. The study deduced that MRONJ related to implant placement is a late complication, not directly connected to oral surgery. In contrast, Grant et al., 2008, Shabestari et al., 2010, and Zahid et al. (2011) reported very high implant success rates. However, patients on oral bisphosphonates demonstrated a heightened risk of peri-implant bone loss.

4. Discussion

Poly-medicated individuals account for a considerable portion of patients visiting dental clinics (Candotto et al., 2019, Radoï et al., 2019). Among oral surgery and implantology procedures, third molar extractions display the highest complication rates, which include edema, pain, dry or suppurative alveolitis, bleeding, and post-operative infections like osteomyelitis (Candotto et al., 2019). Surgeries that involve large flaps also exhibit a high incidence of complications.

All reviewed studies concur that the primary concern for dentists managing patients on antiplatelet or anticoagulant therapy is the increased risk of bleeding during or after procedures (Lillis et al., 2011, Girotra et al., 2014, Clemm et al., 2016, Schmitt et al., 2020, Napeñas et al., 2009). Patients on Direct Oral Anticoagulants (DOACs) or vitamin K inhibitors such as warfarin or acenocoumarol exceeding 100 mg should engage with their hematologist at least 3 days before surgery to assess the need for any medication adjustments (Clemm et al., 2016, Schmitt et al., 2020, Gaballah and Hassan, 2022, Radoï et al., 2019). For those consuming vitamin K inhibitors, it is vital to get the International Normalized Ratio (INR) evaluated on the day of the procedure, confirming it is below 4 to safely proceed (Clemm et al., 2016, Schmitt et al., 2020, Gaballah and Hassan, 2022, Radoï et al., 2019).

Patients receiving dual therapy with clopidogrel and acetylsalicylic acid (ASA) exhibit more significant bleeding compared to those on single therapy (either ASA or clopidogrel). In instances where the tooth due for extraction is affected by pericoronitis (common in third molars) or periodontitis, the risk of bleeding escalates due to the weakened blood vessels caused by acute tissue inflammation (Lillis et al., 2011, Girotra et al., 2014). Articaine or lidocaine with epinephrine as a vasoconstrictor were the preferred anesthetics for enhancing hemostatic effects (Lillis et al., 2011, Girotra et al., 2014, Clemm et al., 2016, Schmitt et al., 2020).

To minimize bleeding risks, several authors emphasize the importance of an effective hemostatic protocol (Lillis et al., 2011, Girotra et al., 2014, Clemm et al., 2016, Schmitt et al., 2020). They recommend performing surgical procedures in the morning (Lillis et al., 2011). Post-operative care should include the placement of a hemostatic sponge (such as collagen, fibrin, or oxidized cellulose) in the wound, applying pressure with a gauze soaked in tranexamic acid for 30 min, and suturing the site (Lillis et al., 2011, Clemm et al., 2016, Schmitt et al., 2020, Gaballah and Hassan, 2022, Radoï et al., 2019).

Additionally, Schmitt et al. (2020) recommend avoiding removable dentures for 2 weeks. Both Schmitt et al. (2020) and Clemm et al. (2016) suggest additional post-operative measures such as maintaining a soft diet for 10 days, brushing twice daily with the exclusion of the surgical area, rinsing with 0.2 % chlorhexidine twice a day for one week, and applying cold compresses for 2 days following surgery.

To manage pain and inflammation, numerous studies (Lillis et al., 2011, Girotra et al., 2014, Clemm et al., 2016, Schmitt et al., 2020, Napeñas et al., 2009, Gaballah and Hassan, 2022) recommend prescribing either magnesium metamizole (575 mg) or paracetamol (1 g). They advise against the usage of NSAIDs due to their antiplatelet properties and potential gastrointestinal side effects such as ulcers and bleeding. Broad-spectrum antibiotics should be used with caution since they can diminish the production of vitamin K, critical for synthesizing clotting factors (Gaballah and Hassan, 2022). The antibiotic of choice is amoxicillin, either used alone or in combination with clavulanic acid. Clindamycin is an alternative for patients with allergies (Clemm et al., 2016, Schmitt et al., 2020, Gaballah and Hassan, 2022). Antibiotic prophylaxis should be reserved for clinically justified cases and not prescribed routinely, following the American Heart Association’s guidelines (Milic et al., 2021). This involves administering 2 g of amoxicillin or 600 mg of clindamycin (for those allergic to amoxicillin) one hour before the procedure.

Regarding immunosuppressants and immunomodulators affecting the immune system, the reviewed articles (Montebugnoli et al., 2015, Heckmann et al., 2004, Gu et al., 2011, Gu and Yu, 2011, Hoefert and Eufinger, 2010, Neuprez et al., 2014, Preidl et al., 2014, Aghaloo et al., 2014, Cassoni et al., 2016, Kaczoruk-Wieremczuk et al., 2021, Viviano et al., 2017, Fleissig et al., 2012, Grant et al., 2008, Lazarovici et al., 2010) concurs with Gutiérrez et al. (2006) in emphasizing the importance of effective antibiotic therapy for these patients. Immunosuppressed individuals have an increased risk for local and systemic infections, making appropriate antibiotic prophylaxis essential (Montebugnoli et al., 2015, Heckmann et al., 2004). Before beginning treatment, dental prophylaxis and minimally invasive surgical techniques are recommended (Gu et al., 2011, Gu and Yu, 2011). Post-operative care includes oral hygiene instructions (Montebugnoli et al., 2015, Gu et al., 2011), rinsing with chlorhexidine three times daily for one to 3 weeks (Montebugnoli et al., 2015, Gu and Yu, 2011), smoking cessation (Gu & Yu, 2011), and avoiding provisional restorations if implants are placed (Montebugnoli et al., 2015).

Post-operative antibiotic therapy for these patients is compulsory. Heckmann et al. (2004) administered 2 g of intravenous ceftriaxone an hour before surgery, continuing the regimen for 13 days. Gu et al. (2011) prescribed a combination of amoxicillin and clavulanic acid (1 g twice daily for 5 days). They provided moxifloxacin (400 mg once daily for 6 days) as an alternative for those who were allergic. Montebugnoli et al. (2015) chose an 8-day course of amoxicillin, which corresponded with the sutures’ removal.

The recommended waiting period for initiating the second phase of treatment after implant placement is 3 to 6 months. Heckmann et al. (2004) suggest follow-up visits every 6 months following prosthesis placement, while Gu et al. (2011) and Montebugnoli et al. (2015) advocate for annual reviews. Heckmann et al. (2004) and Gu & Yu (2011) associate peri-implantitis more with inadequate plaque control than the impacts of immunosuppression.

Osteonecrosis is another complication associated with the use of monoclonal antibodies (Viviano et al., 2017). Numerous studies have reported cases of osteonecrosis following extractions or implant placements in patients treated with monoclonal antibodies such as Denosumab (Neuprez et al., 2014, Aghaloo et al., 2014), Sunitinib (Hoefert and Eufinger, 2010, Fleissig et al., 2012), Ipilimumab (Owosho et al., 2015), Imatinib (Viviano et al., 2017), and Adalimumab (Preidl et al., 2014, Cassoni et al., 2016). The risk of osteonecrosis is particularly high in patients treated with Denosumab (Neuprez et al., 2014), and this risk is magnified when monoclonal antibodies are partnered with bisphosphonate therapy (Preidl et al., 2014, Aghaloo et al., 2014). Extraction procedures bear the highest risk for osteonecrosis, followed by periodontal surgery and implant placement (Hoefert and Eufinger, 2010, Aghaloo et al., 2014, Owosho et al., 2015).

Before starting treatment with these drugs, it is essential to complete all required dental procedures such as prophylaxis, extractions, and reconstructions. During the treatment, any surgical intervention should ideally be avoided; however, if absolutely required, it should be as minimally invasive as possible. Surgical procedures like extractions or implants, when possible, should be spaced across multiple sessions to allow for the regularization of bone peaks and tension-free suturing. Also, it is recommended to use 0.2 % chlorhexidine rinses twice daily for 10 days, along with analgesics and antibiotics before and/or after the procedure. Antibiotics such as amoxicillin, clindamycin, and metronidazole, which can penetrate bone tissue, are the preferred choices (Kaczoruk-Wieremczuk et al., 2021, Milic et al., 2021).

Antibiotic prophylaxis is especially important for these patients to prevent post-surgical infections, following the American Heart Association guidelines (Milic et al., 2021). However, for osteonecrosis cases, antibiotic treatment (for example, amoxicillin) may not be sufficient, and patients should be referred to hospital services for further management (Hoefert and Eufinger, 2010, Neuprez et al., 2014, Cassoni et al., 2016, Viviano et al., 2017).

For patients on bisphosphonates, osteonecrosis remains one of the most prevalent complications (Mozzati et al., 2013, Zahid et al., 2011, Shabestari et al., 2010, Radoï et al., 2019). A protocol that includes mechanical, antibacterial, and antibiotic measures should be established for extractions in patients receiving oral or intravenous bisphosphonates. This protocol should encompass preoperative dental prophylaxis, antibiotic prophylaxis (Lodi et al., 2010), minimally invasive surgical techniques, meticulous curettage of the extraction site, stitches for primary closure, and a 17-day course of antibiotic therapy. Moreover, post-surgical hygiene instructions should be provided, and patients should use pre-surgical 0.2 % chlorhexidine rinses and apply 1 % chlorhexidine gel to the wound for 15 days (Lodi et al., 2010, Mozzati et al., 2013). Dental implant-related osteonecrosis is typically a late complication and is not directly associated with oral surgery, but prolonged follow-up is crucial. To minimize risks, it is suggested that implant placement be performed in two phases, with a waiting period of 3 to 5 months before loading (Grant et al., 2008, Lazarovici et al., 2010, Zahid et al., 2011, Shabestari et al., 2010). When implants are placed, the surgical protocol should comprise antibiotic prophylaxis, careful incision for flap release, stitches for primary wound closure, and a 10-day course of antibiotics (Grant et al., 2008, Lazarovici et al., 2010, Zahid et al., 2011, Shabestari et al., 2010, Stavropoulos et al., 2018).

5. Conclusions

The most common complications in oral surgery include hemorrhage in patients undergoing anticoagulant treatment, infections among immunosuppressed patients, and osteonecrosis in those prescribed antiresorptive drugs, along with edema, pain, and inflammation.

When treating patients with high pharmacological risk, it is essential to ensure appropriate pre- and post-operative antibiotic coverage, perform the procedures in a minimally invasive manner, and implement local hemostatic measures.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Footnotes

Appendix A

Supplementary data to this article can be found online at https://doi.org/10.1016/j.sdentj.2024.12.004.

Contributor Information

J. Rodríguez-Molinero, Email: jesus.rodriguez.molinero@urjc.es.

C. García-Bravo, Email: cristina.bravo@urjc.es.

J.A. Ruiz-Roca, Email: jaruizroca@um.es.

I. García-Guerrero, Email: ivan.garcia@clinica.urjc.es.

R Gómez-de Diego, Email: rafael.gomez.dediego@urjc.es.

Appendix A. Supplementary data

The following are the Supplementary data to this article:

Supplementary Data 1
mmc1.docx (36.3KB, docx)

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