Complications and treatment errors in periodontal therapy in medically compromised patients

Patients who are medically compromised may be at an increased risk of complications and treatment errors following periodontal therapy. A review of the evidence on the topic is presented, in relation to the type of complication reported, of periodontal treatment, and of patients' medical status. Further, a framework for risk assessment and appropriate treatment modifications is introduced, with the aim of facilitating the management of patients with existing comorbidities and reducing the incidence of treatment complications.

6][7] In addition, the type of medical problems patients present with can differ significantly depending upon the facility where periodontal care is provided. 8Findings from a retrospective analysis demonstrated a lower prevalence of medically compromised patients with periodontitis who attended a private dental practice (28%) compared with those attending a dental school or hospital clinic (46% and 74%, respectively). 8Differences between participants in terms of age, socioeconomic status, or health awareness could explain these findings. 87][8][9][10] As a direct consequence of medical comorbidities, a substantial number of patients will be taking multiple medications, which may also have an impact on their periodontal management.
Radfar and Suresh 11 observed that of 1041 patients treated in their dental school, 360 (35%) were taking antihypertensives, 202 (19%) painkillers, 181 (17%) antidepressants, 107 (10%) antidyslipidemic agents, and 95 (9%) antiplatelet drugs.This highlights an additional consideration in terms of the potential pharmacologic interactions with anesthetics or other medications that we might need to prescribe for these patients after certain periodontal procedures.
In addition to the systemic pathology inherent to age and polypharmacy, the increased survival of patients with certain congenital diseases with periodontal manifestations has created a growing demand for periodontal treatment.These congenital disorders include diseases with a considerable prevalence such as Down syndrome 12 and around 14% of rare disorders with a low prevalence. 13The provision of dental treatment for these patients is not exempt from some potential complications, because the etiopathogenic mechanisms of these diseases include hemorrhagic diatheses, immunodeficiencies, and alterations in the metabolism of vitamins, minerals, and trace elements. 13eatment of periodontitis is part of routine care of patients attending dental practices, but it may be associated with complications, particularly when invasive/surgical approaches are required.
The aim of this narrative review is to provide a comprehensive overview of the potential complications and treatment errors that can occur in medically compromised patients undergoing both nonsurgical and surgical treatment of periodontitis.Specific risk reduction strategies for these patients are also discussed.

| E VIDEN CE S E ARCH ME THODOLOGY
To gather all the evidence published in relation to complications after periodontal treatment in medically compromised patients, a systematic search in Medline OvidSP was carried out from 1946 to 10 July 2020.Three key searchable concepts were identified: "Periodontal Diseases", "Surgical and Non-Surgical Periodontal Therapies", and "Systemic Diseases".Given the broad scope of the concept "Medically Compromised Patients", a list of all diseases to be included in the review was compiled at the protocol stage and search strategies were created for each disease to be appended to a search including the first two concepts.
We conducted searches for each concept using text word terms and medical subject headings wherever these were available.When we carried out text word searches, synonyms, related terms, and singular/plural forms for each concept were used.This strategy ensured that we retrieved studies where surgical and nonsurgical periodontal therapies for periodontal diseases (including dental extractions as part of the periodontal treatment) were discussed along with each systemic disease of interest.We exported the results for each search to the reference management software Endnote X9, which we used to manage our references.We applied no language or date restrictions and used the high-sensitivity animal filter for Medline OvidSP (exp animals/not humans.sh),which we combined with our search strategy with the use of the Boolean operator NOT to exclude animal studies.No restriction was made in terms of study design (ie, from case reports to randomized clinical trials).
The total number of records retrieved by the electronic database was 9294, and one additional article was obtained via a manual search.After removing duplicates, we screened 6599 titles/abstracts and selected 112 articles for full-text screening.Finally, we chose 20 articles to be included in this narrative review.

| Bleeding-related complications
Four different groups of patients could be identified when prolonged gingival bleeding was reported as a complication after periodontal treatment: in patients with bleeding disorders, drug-induced gingival overgrowth, those taking antithrombotic medications, and patients with hypertension.

| Bleeding disorders
Bleeding disorders can be congenital or acquired (Table 2).0 Bleeding complications from the palatal donor site when performing mucogingival surgery have been reported. 22,31Mitigating procedures reported to stop the bleeding include one from Shapiro, 31 described as a ligation of lesser palatine artery with 4/0 silk suture, and this procedure was repeated two more times after surgery together with the use of 11 units of fresh frozen plasma.In the case reported by Blanco-Carrion et al, 22 a combination of 2500 units of factor VIII concentrate twice a day during 1 week with prophylactic factor VIII concentrate (2500 units once every 2 days for two more weeks) was used to manage the same complication.Further, data from 63 consecutive patients with von Willebrand disease receiving dental extractions and surgical periodontal procedures were retrospectively analyzed.Results

Intervention
showed that the complication rate of severe gingival bleeding was 3.1% and this was managed through local application of fibrin glue in the bleeding area. 37However, some case series did not find any bleeding episodes in patients with von Willebrand disease after either nonsurgical 42 or surgical periodontal therapy. 43Likewise, a low incidence of gingival bleeding in patients with HIV was reported in a cross-sectional study where different periodontal procedures were carried out. 35When other inherited bleeding conditions such as plasminogen activator deficiency or hereditary hemorrhagic telangiectasia were evaluated, the risk of bleeding was minimal, 30 if any at all. 44

| Drug-induced gingival overgrowth
Gingival overgrowth may occur in patients taking anticonvulsants (eg, phenobarbital, sodium valproate, and phenytoin) (Figure 1), immunosuppressants (eg, ciclosporin), or calcium channel blocker antihypertensive drugs (eg, nifedipine and amlodipine). 45Severe cases may require surgical excision of the enlarged gingiva.While a few case reports showed prolonged intraoperative and postoperative bleeding after gingivectomy, 29,32,33 others did not find any bleeding episodes after gingival tissues were treated with both nonsurgical and surgical approaches. 46,47Jones et al 34 performed 39 gingivectomies in patients with cerebral palsy who presented gingival overgrowth resulting from diphenylhydantoin use and, although they did not observe any bleeding problems, two out of 12 patients had slow resumption of adequate oral food intake.

| Antithrombotics
Patients taking antithrombotic medications may present with extensive bleeding episodes after periodontal therapy.Most of these patients take anticoagulants (eg, warfarin, dabigatran, apixaban, and

Idiopathic
• Disseminated intravascular coagulation rivaroxaban) or antiplatelet (eg, aspirin and clopidogrel) drugs, which makes them more prone to experience bleeding problems in the dental setting.A cross-sectional study of 45 patients who received cardiac valve surgery and were under oral anticoagulation therapy reported a low incidence (<5%) of bleeding independent of using a neodymium-doped yttrium aluminum garnet laser for periodontal surgery. 36Uncontrolled severe gingival bleeding was also found after delivering scaling and root surface debridement on a patient who was taking aspirin and clopidogrel. 25

| Hypertension
Knapp and Fiori 26 described a case of prolonged postoperative bleeding and hypertensive crisis associated with resective periodontal surgery.In this case report, a patient diagnosed with hypertension (180/120 mm Hg) underwent periodontal treatment consisting of an initial phase on nonsurgical periodontal therapy followed by two apically repositioned flaps with osseous surgery.
Two days after the second surgery, the patient began to bleed spontaneously from the surgical site and was unable to control the local hemorrhage.When the patient attended the emergency room, the amount of blood he had lost was approximately 100 mL/h and at that time the blood pressure was 210/140 mm Hg.He was given his normal dose of clonidine to stop the hypertensive crisis, but no apparent effect was noted.Immediately, a sodium nitroprusside drip was started in the intensive care unit, where his blood pressure dropped to 130/88 mm Hg.Once the blood pressure was stabilized, oral bleeding stopped and healing of the periodontal surgical site was uneventful.

| Other complications
Soft tissue complications after mucogingival surgery have been described in two case reports. 21,22The first case consisted of a patient diagnosed with Crohn's disease (a type of inflammatory bowel disease) who presented with multiple Miller's class I gingival recessions.Three different mucogingival surgeries with a 4-week interval difference were carried out using a coronally advanced flap technique and an enamel matrix derivative was used before coronally repositioning the flap in the last two procedures.Two of the three surgeries (one with and another without the use of amelogenins) showed incomplete healing, with a red and swollen appearance of the surgical area that lasted up to 6 weeks.To manage these complications, chlorhexidine gluconate gel and mouthwash were administered.Another study reported a case of a patient with hemophilia and HIV requiring a root coverage procedure of single Miller's class II gingival recession that was carried out by applying a subepithelial connective tissue graft technique.At 1 week postsurgery, the palate (donor site) showed secondary intention healing associated with the necrotic area. 22Conversely, another case report describes a patient with HIV who received the lateral sliding flap technique and experienced uneventful healing over 8 months. 48In a case series of 21 patients with HIV, the same authors found no complications (ie, delayed healing or infection) after crown lengthening had been undertaken. 49layed healing could be expected after periodontal procedures in patients experiencing dystrophic epidermolysis bullosa, as described in two case reports.These cases detail one patient who underwent mucogingival procedures to cover exposed roots by means of a coronally positioned flap combined with a subepithelial connective tissue graft, 50 and another who received an acellular dermal matrix allograft to increase the width of the attached gingiva. 51Neither patient developed any complications either during or after surgery.
Diabetes mellitus is also known to be associated with impaired wound healing, and patients are more likely to develop infections.Mattson et al 27 treated an intrabony defect with guided tissue regeneration from a patient with type II diabetes mellitus. 25sorbable collagen membrane exposure was noticed after 1 week of healing. 27The membrane was not removed but was irrigated with chlorhexidine and diluted salt water until the soft tissue had healed. 27Similarly, Mullally et al 28 also reported membrane exposure after a guided tissue regeneration procedure in a patient with diabetes mellitus.Moreover, a fungal infection by Candida albicans was diagnosed clinically and confirmed histologically afterwards. 28 this case, the membrane was removed, the tooth extracted, and antifungal medication was prescribed. 28Conversely, in a patient with type I diabetes mellitus, the formation of "liver clots" (without clot retraction for up to 10 days) resulting from poor healing 1 week after modified Widman surgery and the extraction of hopeless teeth was observed. 23However, this finding is not common and results from a recent randomized controlled clinical trial including patients with type II diabetes mellitus and moderate-tosevere periodontitis showed a low incidence of complications after periodontal treatment.D'Aiuto et al 39 did not find any statistically significant differences in terms of oral and systemic complications when intensive periodontal therapy (including subgingival Gingival overgrowth and bleeding tendency secondary to the administration of valproate in a patient with severe epilepsy. debridement and modified Widman flap surgery) was compared with a control treatment (only supragingival scaling) over a period of follow-up lasting 1 year.
There are some medications such as antiresorptives and antiangiogenics that could also interfere in both soft and hard tissue healing.A case has been published reporting osteonecrosis of the jaw after nonsurgical periodontal therapy on a patient who was receiving subcutaneous injections of denosumab every 6 months (Figure 2). 24e complication was managed by means of administration of chlorhexidine mouthwash and systemic antibiotics (doxycycline) together with removal of the affected teeth, sequestrectomy, and surgical debridement of necrotic bone.

| RIS K A SS E SS MENT FR AME WORK AND APPROPRIATE TRE ATMENT MODIFIC ATIONS
When planning treatment for periodontal therapy in patients who are medically compromised, it is important to consider additional factors to provide holistic care.In addition to clinical and radiographic examination, a thorough medical, social, and dental history will enable a comprehensive risk assessment (Table 3).This will ensure that appropriate modifications can be implemented prior to commencement of periodontal therapy, thereby reducing complications and treatment errors.The ACCESS mnemonic 52,53 is a systematic approach to treatment modification, considering six domains that address different aspects of care:  4).

| PRE VENTION AND MANAG EMENT OF COMPLI C ATI ON S AND TRE ATMENT ERROR S IN PERI ODONTAL THER APY
Complications and treatment errors may occur when providing periodontal therapy in patients who are medically compromised.These will be presented in relation to pain control, bleeding, infection, and wound healing.

| Analgesia and pain control
Effective pain control is essential for delivery of invasive periodontal procedures.Adaptations may be required in relation to certain medical conditions, operator skills, and availability of equipment, for instance, a computer-controlled local anesthetic delivery system.
The type, dose, and technique for local anesthetic administration may need consideration.For example, patients may have resistance to local anesthetic, as in the case for the hypermobile type of Ehlers Danlos Syndrome.These patients require a systematic approach to the type of local anesthetic selected. 54It may be administered in order of potency 55 or in combination, for instance lidocaine could be administered first, followed by articaine and then bupivacaine.
A retrospective survey of 980 people with Ehlers Danlos Syndrome reported the highest success rate of 30% with articaine, followed by bupivacaine at 25%. 56 When it is not possible to achieve adequate local anesthesia, alternative anesthetic modalities should be considered.
Allergy to local anesthetic and its constituents is rare, and is estimated to have an incidence of less than 1%. 57,58Further information should be sought to determine the nature of the reported allergy, and, where appropriate, the patient should be referred for formal allergy testing. 59The most commonly reported reaction to local anesthetics is vasovagal syncope, which the patient may report as an allergy. 60e dose of local anesthetic solution may need to be administered with caution in patients with a severe cardiac condition.Good pain control is essential to minimize stress on the myocardium secondary to pain sensation.The local anesthetic should be administered slowly with an aspirating syringe to assess the physiological response and reduce the risk of cardiovascular toxicity. 58There is insufficient evidence to suggest that local anesthetic with or without adrenaline as a vasoconstrictor poses a risk to patients with hypertension or other cardiomyopathies. 61However, anesthetics with adrenaline should be avoided in patients with severe hypertension and it is not recommended to use more than two anesthetic cartridges with adrenaline at 1:100 000 (0.04 mg) in patients with certain cardiac conditions, such as those with coronary stents or those with a history of myocardial infarction. 58I G U R E 2 Medication-related osteonecrosis of the jaw after nonsurgical periodontal therapy on a patient under antiangiogenics (denosumab).
Patients with long-term use of opioids, for instance, because of chronic pain syndrome, may present with increased tolerance to local anesthetic.Studies on nondental procedures showed that a higher dose of local anesthetic solution was required to achieve the same efficacy. 62An increased amount of local anesthetic solution may be required for dental procedures.
Modification of the technique used to deliver local anesthetic may be required in relation to the underlying medical condition.For example, patients with severe bleeding disorders require careful assessment if inferior alveolar nerve blocks or lingual infiltrations are planned, as hematological support (eg, coagulation factor replacement) will be needed. 63The risks of proceeding without this in place are significant and include hematoma formation and potential risk to the airway.Buccal infiltration has been reported as a safe technique in patients with differing severity of hemophilia, without the need for additional factor cover. 64 Preoperative tests may be required for patients on anticoagulants such as warfarin for whom inferior alveolar nerve blocks are required.The clinician should confirm that the patient's international normalized ratio readings are generally stable.
For patients with unstable international normalized ratio profiles, it has been proposed that the international normalized ratio should be checked preoperatively if block injections are planned and given cautiously with a self-aspirating syringe. 65,66 patients with trismus, alternative techniques to the conventional inferior alveolar nerve block may be indicated.[69] These may be considered in patients with trismus or when the conventional technique fails.Both alternative techniques should be used with caution, and each carries a higher risk of complications. 67traligamentary and intraosseous anesthesic injection techniques may be used as alternatives to mandibular nerve blocks. 70mputer-controlled local anesthetic delivery systems can be utilized in patients with needle phobia, especially if there are additional medical comorbidities that contraindicate alternative anesthetic modalities. 71,72The technique can be used in children and adults, and has been found to reduce the perceived pain on administration, and to achieve greater efficacy compared with the conventional local anesthetic technique. 71,73It has been suggested that a computer-controlled intraosseous anesthesia system may be useful for root planing procedures because it reduces the pain of the injection and provides a larger area of anesthesia with a single puncture. 74In a randomized split-mouth study in patients with chronic periodontitis who underwent open-flap debridement on premolars and molars, the authors reported substantial relief from injection pain with a computer-controlled anesthetic delivery system compared with a conventional local anesthetic technique. 75 aspirating local anesthetic syringe should always be used. 58e local anesthetic solution should be delivered in areas without localized inflammation and/or infection, as the presence of inflammation may affect the success of local anesthesia.Block techniques are useful adjuncts in these instances, as the local anesthetic solution is deposited at a site away from inflammation and infection. 76 patients with fragile mucosa surfaces, as in the case of epidermolysis bullosa, the technique may need to be altered.Depending on the severity, the local anesthetic solution should be deposited slowly and deeply in the tissues to avoid mechanical separation of the mucosal layer and the formation of blisters. 77If iatrogenic blisters appear as a result of the injection of local anesthesia, they must be drained to prevent the lesion from expanding (puncturing with a needle or cutting the blister with scissors). 78Postoperatively, patients should also be instructed to take extra care to avoid traumatizing the mucosa. 77 adequate local anesthesia is not achievable, alternative anesthetic modalities may need to be considered, such as conscious sedation and general anesthesia.In patients who are medically compromised, preoperative anesthetic assessment may be required to assess their suitability. 52Postoperative pain is common among patients undergoing periodontal treatment, and it has been suggested that it is conditioned by variables such as age, the degree of patient anxiety, and the type of procedure performed. 79Scaling and root planing can cause considerable pain in terms of intensity and duration, 80 although the magnitude of pain is generally greater after surgical periodontal treatment. 16Acetaminophen (paracetamol) and nonsteroidal anti-inflammatory drugs are the agents of choice to tackle postoperative pain in dentistry, 81 but they are not exempt from adverse effects and should be administered with caution in patients with certain systemic diseases. 82The interval between acetaminophen intakes should be adjusted in patients with chronic kidney disease and the total daily dose should be limited in patients with liver disease. 83Most nonselective cyclooxygenase-1 and cyclooxygenase-2 inhibitor nonsteroidal anti-inflammatory drugs should be avoided in patients with a history of peptic ulcer or gastroesophageal bleeding, in patients receiving anticoagulants, lithium, or methotrexate, with uncontrolled hypertension and chronic kidney disease, or with severe liver failure. 84Nonsteroidal anti-inflammatory drugs that act as preferential cyclooxygenase-2 inhibitors have also been used to control postoperative pain after periodontal procedures. 85,86Cyclooxygenase-2 inhibitors reduce the incidence of gastrointestinal side effects and have little or no effect on platelet function, so the risk of bleeding is minimal.
However, most selective cyclooxygenase-2 inhibitors have been withdrawn from the market because of the risk of serious cardiovascular events, 87 and nimesulide is also not marketed in some countries because of the risk of acute hepatotoxicity and should not be administered to patients with liver failure.TA B L E 4 (Continued)

| Bleeding
There are congenital and acquired bleeding conditions that may increase the risk of bleeding perioperatively and postoperatively (Table 2).Treatment modifications will be explored to reduce the risk of bleeding resulting from periodontal therapy.
The dental setting should be selected based on the risk of bleeding in relation to the medical condition, dental procedure, and experience of the operator. 89The clinician should establish whether the patient is under the care of a medical team and consult with them to confirm the severity of their condition and management plan.This will aid in determining the level of risk of bleeding as a complication and/or treatment error in periodontal therapy.For instance, patients who are undergoing chemotherapy for the management of malignant conditions can receive different types of agents.Some agents will predispose the individuals to chemotherapy-induced thrombocytopenia, and others will impact platelets to a lesser degree. 90Patients with severe risk of bleeding who require onsite medical support for invasive periodontal therapy are more appropriately managed in a secondary care setting. 91 the planned periodontal therapy has an increased risk of bleeding, the appointment should be timed earlier in the day and the week, so that postoperative complications can be managed accordingly. 66The timing of appointments should be in line with the medical management of each patient's condition.For instance, patients who are taking direct oral anticoagulants should provide information about the time of the scheduled dose so as to minimize interruption to the drug regime. 66The risk of thrombosis outweighs the potential risks of postoperative bleeding from dental procedures. 66Similarly, single or dual therapy antiplatelets should not be interrupted for dental procedures, 92 including periodontal therapy. 66However, in patients with a high risk of bleeding and dual therapy, some guidelines have recommended suspending one of the antiplatelet agents before the procedure (5 days in the case of clopidogrel), generally maintaining the administration of aspirin. 93For patients with hemophilia who have regular prophylactic factor replacement, the dental procedure should be timed as close to the time of administration to avoid the need for additional factor replacement, and thus maximizing therapeutic effects, and reducing risks and overall treatment costs. 63,89,94,95Patients undergoing renal dialysis should not be seen on the dialysis day because of fatigue and an increased risk of bleeding secondary to heparin and abnormal platelet function. 96pending on the underlying cause of the increased bleeding risk, special investigations may be indicated.Appropriate blood tests such as full blood counts, clotting screen, and liver function tests should be arranged as part of the preoperative assessment depending on the medical condition and its stability 91 (Figure 3).The timing of the blood test needs to reflect the underlying medical condition and its treatment regime.For example, it is acceptable to use a 72hour international normalized ratio test on patients on warfarin who are stable, but for those with an unstable international normalized ratio, it should be undertaken within 24 hours. 65,66Point-of-care tests for international normalized ratio are available and can be used in the dental setting.The international normalized ratio should be <4 to undertake periodontal therapy. 65,66Morimoto et al 97 undertook a retrospective study on periodontal therapy in patients taking warfarin.They confirmed that nonsurgical periodontal therapy can be safely performed when the international normalized ratio is <4, and that surgical periodontal therapy surgery can be safely performed when the international normalized ratio is <3.These international normalized ratio values are applicable in patients without other concomitant factors that may favor bleeding, such as liver failure or uncontrolled hypertension. 58rthermore, for patients having pharmacotherapy that affects their blood counts, they may require a blood test on the day of the procedure or within the last 24-48 hours to account for more frequent fluctuations in blood counts. 98It may also be necessary to liaise with the laboratories regarding specific requirements and timely reporting of the investigation results.
Additional hematological support may be required in patients with thrombocytopenia.This will be dependent on the planned periodontal procedure, as well as a preoperative blood test and liaison with the medical team to determine the requirements for platelet transfusions.The most accepted threshold for platelet counts is ≥50 × 10 9 /L for invasive dental procedures, which includes periodontal surgery or tooth extractions.Patients with platelet counts of <50 × 10 9 /L are at an increased risk of experiencing perioperative and postoperative bleeding. 99Platelet transfusion may be indicated preoperatively, perioperatively, and/or postoperatively.
Karasneh et al 100  In relation to patient education and the risk of bleeding, patients should be informed of possible minor bleeding related to the planned periodontal therapy.There is a tendency for patients with bleeding conditions to use soft toothbrushes, which may not effectively remove plaque deposits.In addition, patients may have been advised by their doctors to avoid brushing their teeth or to undertake interdental cleaning measures when they have thrombocytopenia.There is a lack of evidence to suggest the benefits of such an approach. 104study conducted by Padrón et al 105 concluded that patients under anticoagulation therapy had greater accumulations of dental plaque, more gingival bleeding, and deeper periodontal pockets than healthy controls, and approximately 17% of them never brushed their teeth compared with 3% of the control group.It has been suggested that fear of gingival bleeding could induce patients using anticoagulants to brush their teeth less. 105A lack of good oral hygiene measures may predispose the patient to dental disease, and possibly progress to infection, which may compromise their medical health.Dental professionals should consider the risk of bleeding before advising on the most appropriate oral hygiene measure.
For all types of procedures, general precautions should be followed, including gentle handling of the oral mucosa, instruments, and equipment. 106For pain and anxiety control, appropriate selection of local anesthetic solution and technique is required.Factor replacement may be required for patients with hemophilia in relation to the local anesthetic technique and proposed procedure. 91The site of surgery helps to determine an appropriate local anesthetic technique for treatment.In patients with hemophilia and other severe bleeding conditions, inferior alveolar nerve blocks and lingual infiltrations pose a risk of airway obstruction, caused by hemorrhage into musculature and the formation of hematomas in retromolar and pterygoid spaces. 107Factor replacement decreases the risk of bleeding. 94On the contrary, infiltrations (with the exception of lingual), as well as intraligamentary, intraosseous, and intrapulpal injections, do not require factor replacement. 108Articaine infiltrations may be used in the mandible to avoid block techniques 109,110 and eliminate the need for factor cover. 111 Low-risk procedures for bleeding include nonsurgical periodontal therapy. 112No additional hematological cover is necessary, provided local anesthesia principles are followed. 113Although routine scaling is unlikely to cause significant bleeding, the overall periodontal condition must be assessed, as hematological support may be indicated in selected cases. 89High-risk procedures consist of extractions and periodontal surgery. 112The degree of prophylaxis cover is determined by the hematologist.Local hemostatic measures should be followed, including closure of surgical sites and the use of hemostatic agents. 114The use of a surgical splint has been suggested to protect the surgical site. 94itially, the treatment area should be limited and staged to assess the bleeding risk, and reassessed before proceeding. 66Surgical trauma should be minimized where possible, with closure of the wound.At the end of the procedure, the procedural site should be observed for an extended period of time to ensure that there is hemostasis.If there is evidence of bleeding, the site should be compressed with a damp gauze dressing for 10-15 minutes.Consider the use of topical coagulating agents such as oxidized cellulose and gelatin foam to aid hemostasis. 66,115Rubino et al 115 undertook a retrospective analysis of patients who had invasive periodontal therapy and were on antithrombotic medications (antiplatelets and anticoagulants).The drug regime was not interrupted for most participants (99.6%), and local hemostatic measures were followed.
Postoperative bleeding was only observed in three out of 867 procedures (0.35%).
A prescription for tranexamic acid 5% mouthwash, an antifibrinolytic agent, may be considered for use up to four times a day as required.This is a nonformulary preparation and therefore may not be readily accessible in primary care dental services.Successful use of a 2-day course of tranexamic acid 4.8% mouthwash in the management of postoperative bleeding was reported for patients taking warfarin who received tooth extractions because of severe periodontal disease and the results were similar to those obtained for a 5-day course. 116To manage the bleeding, participants were initially asked to use compression with a gauze pad for 20 minutes, and if the bleeding persisted, the tranexamic acid mouthwash was applied via a gauze pad for a further 20 minutes.Systematic reviews of the evidence on the use of topical tranexamic acid for dental procedures showed successful hemostasis for patients on vitamin K antagonists, 117 and inconclusive evidence for congenital bleeding disorders. 118If local measures are insufficient to achieve adequate local hemostasis, the appropriate medical team should be contacted to assess the need for systemic agents.
Postoperatively, the dental practitioner should ensure that patients have access to dental emergency services to minimize distress for the patient and facilitate timely access if required. 66escription should be administered with caution.Nonselective cyclooxygenase-1 and cyclooxygenase-2 inhibitor nonsteroidal antiinflammatory drugs for pain control should be avoided in patients at risk of bleeding, as this may exacerbate the risk of bleeding. 66,119etaminophen is the preferred analgesic.

| Infection
Infection may occur following periodontal therapy in patients who are medically compromised.This will be discussed in relation to immunosuppression, infective endocarditis, aspiration pneumonia, blood-borne viruses, and wound healing.

| Immunosuppression
Patients who have immunosuppression are at an increased risk of infection after invasive periodontal therapy.The causes of immunosuppression can be categorized into congenital and acquired (Table 5).
The timing of the dental appointment should be made taking into consideration the cause, severity, and the likely duration of the immunosuppression.For example, nonurgent periodontal therapy should be postponed for patients undergoing active chemotherapy. 98,120,121Patients may have bone marrow suppression, and resultant low white cell count and neutrophils, which predisposes them to infections.Acute periodontal infection should be treated in a timely manner as it poses a risk of bacteremia and sepsis in patients with neutropenia. 122The ideal treatment window period should be determined after consultation with the oncology team, 98 for instance between chemotherapy cycles.
Another group of patients for which the timing of dental treatment is important consists of those who have had solid organ transplantation.This cohort receive long-term immunosuppressants, with a lower maintenance dose after approximately 6 months.Therefore, elective periodontal therapy should be delayed for 3-6 months after the transplant. 123,124Georgakopoulou et al 123 reported an increased level of risk of severe oral infections in patients who have undergone renal transplantation.The recommendation for routine periodontal therapy 6 months posttransplant is that scaling can be undertaken in a staged manner, with a small number of teeth cleaned at a time.
Invasive periodontal therapy may require further preoperative investigations and close liaison with the patient's physician.To minimize the risk of infection when patients are immunosuppressed, a pretransplant dental assessment should be undertaken. 124,125Periodontal health should be stabilized, and the source of infection eliminated. 124r patients who require regular blood transfusions (eg, thalassemia major) or red cell exchange transfusions (eg, sickle cell anemia), the dental visit should be scheduled soon after their routine transfusions. 126,127Treatment on the same day should be avoided as the patients are fatigued. 127In addition, patients with hemoglobinopathies (eg, thalassemia, sickle cell disease) may have either nonfunctional or absence of spleen.This predisposes individuals to infections, and potential sources of periodontal infection should be managed in a timely manner. 127,128eoperative investigations may be required to determine the severity of immunosuppression including complete blood count with differential, coagulation assessment and liver and kidney function tests, to evaluate whether the procedure should be delayed, if it can be done in an outpatient setting, the need for antibiotic prophylaxis, the risk of bleeding, and the dosage of prescriptions.For example, for patients at risk of neutropenia, a preoperative full blood count should be undertaken prior to invasive periodontal procedures.If the neutrophil count is <1 × 10 9 /L, periodontal probing and elective invasive periodontal therapy should be postponed because of an increased risk of infection. 104In an observational study, 10 out of 116 patients (8.6%) with mild (1.00-1.50× 10 9 /L), moderate (0.50-0.99 × 10 9 /L), and severe (<0.0-0.49× 10 9 /L) neutropenia who had extractions presented with one or more complications. 129The most common complication was delayed healing, 7 followed by postoperative pain 6 and surgical site infection. 3The likelihood of complications was not associated with the severity of neutropenia.The preoperative management was variable, with some participants receiving preoperative, perioperative, and/or postoperative antibiotics and granulocyte colony-stimulating factor to increase neutrophil levels.
Prophylactic administration of antibiotics may be indicated in patients who are immunosuppressed. 130For example, in patients who have had a splenectomy (eg, thalassemia and sickle cell disease), antibiotic cover should be considered for invasive dental procedures. 127,131,132Those who are on immunosuppressive therapy constitute another cohort of patients.The American Association of Pediatric Dentistry advises that antibiotic coverage may be required for patients with a neutrophil count of <2 × 10 9 /L, and should be discussed with the medical team. 133The suggested antibiotic regime is that used for infective endocarditis, 134 although in some cases it is necessary to consult with the medical team (eg, patients with severe immunosuppression, solid organ transplant recipients, or those who have received multiple antibiotic regimens).
The risk of developing systemic infection from a dental source has been reported to be associated with the presence of preexisting infection. 130A timely and more aggressive antibiotic regime may reduce the risk of infection and its impact on the general health of patients who are immunosuppressed. 130,133 the contrary, the British Society for Antimicrobial Chemotherapy do not routine use of prophylactic antibiotics for dental procedures in patients who are immunosuppressed. 135This is supported by the antimicrobial dental guidelines for immunocompromised patients, including diabetes mellitus, HIV, chemotherapy, solid organ transplants, and hematological malignancies. 136The case-specific decision is advised by consulting with the medical team, as there may be additional medical factors that indicate the use of antibiotics (Figure 4).

Corticosteroids can cause immunosuppression, predisposing an
individual to infections.Patients on a higher dosage of corticosteroids and who have Addison's disease are at an increased risk of adrenal crisis when exposed to stress.A literature review found that adrenal crisis related to dental procedures is rare. 137The risk is increased in the presence of pain and infection, in addition to invasive procedures, and treatment under general anesthesia.Steroid cover is indicated for patients taking ≥7.5 to 10 mg prednisolone for longer than 3 months and undergoing invasive periodontal therapy and/or treatment under general anesthesia. 138,139If the patient is on other corticosteroids, the equivalent dose to prednisolone should be calculated, and advice followed accordingly.Patients taking above 50 mg prednisolone are close to the innate maximum cortisol level seen in patients when stressed and may not require further supplementation. 139 recent years there have been great advances in targeted anticancer therapies, including monoclonal antibodies, fusion proteins, tyrosine kinase inhibitors, and mammalian target of rapamycin inhibitors, among others. 140The indications for biologic response modifiers, and in particular monoclonal antibodies, have been extended to numerous cardiovascular and inflammatory diseases (eg, rheumatoid arthritis, psoriasis, or Crohn's disease), transplant rejection, multiple sclerosis, and viral infections. 82In addition to the immunosuppressive effect, these molecules can cause thrombocytopenia, wound delayed healing, and medication-related osteonecrosis of the jaw. 140

| Infective endocarditis
Patients with susceptible cardiac conditions are at an increased risk of infective endocarditis following invasive dental procedures.2][143] Periodontal bacterial species such as Aggregatibacter actinomycetemcomitans have been detected in specimens from damaged heart valves and aortic aneurysm walls. 144otre et al 142 reported, in a series of confirmed cases of infective endocarditis undergoing dental extractions, that more than 40% had periodontitis, suggesting that periodontal disease enhances viridans streptococcal bacteremia.The prevalence of bacteremia resulting from periodontal pathogens is probably underestimated because of the limitations of microbiologic detection techniques. 145cteremia may result from noninvasive dental procedures.
Toothbrushing has been reported as a potential risk factor for infective endocarditis. 146,147A randomized controlled trial reported a lower incidence of infective endocarditis with toothbrushing compared with extractions. 148However, as toothbrushing is performed more frequently on a daily basis, over time it may potentially have a comparable or higher cumulative risk.Patients should be informed of the importance of maintaining good oral hygiene, 149 which will subsequently reduce the incidence of bacteremia as well as the need for invasive dental procedures. 143vasive periodontal treatment can cause bacteremia leading to the development of endocarditis, although the relationship between dental treatment and infective endocarditis remains a controversial issue. 150Transient bacteremia following dental procedures depends on the state of oral health and the treatment modality, estimating after scaling and root planing in 25%-61%. 151The rationale for antibiotic prophylaxis prior to invasive procedures is to reduce the bacteremia and subsequently the presumed reduced risk of infective endocarditis.
For patients requiring invasive dental procedures, antibiotic prophylaxis is not routinely recommended by the National Institute for Health and Care Excellence (UK) guidelines. 141There are patient cohorts that are more susceptible to infective endocarditis, requiring special consideration. 149In these patients, European and American expert committees agree that when high-risk heart conditions are specified in F I G U R E 4 Patient with severe primary immunodeficiency who has received several antibiotic regimens.Before carrying out periodontal treatment, the medical team was consulted, who recommended microbiologic and antimicrobial susceptibility testing. | these patients, it is essential to discuss with them, and eventually their cardiologists and/or surgeons, whether they should receive antibiotic prophylaxis for invasive periodontal procedures, including full periodontal examination, root surface debridement, and surgery. 134,149,152

| Aspiration pneumonia
Dysphagia (or difficulty in eating, drinking, or swallowing) has a prevalence of up to 16% in the general population. 153Patients with dysphagia are at risk of aspiration, which may progress to pneumonia, which carries a significant risk of morbidity and mortality.[155] Periodontitis represents a potential risk factor for the development of aspiration pneumonia in the elderly. 156Dental plaque has been suggested as a risk factor for healthcare-associated pneumonia in patients who are hospitalized, with an increase in dental plaque levels with longer hospital stays. 157Good oral hygiene is one of the most effective interventions in reducing the risk of aspiration pneumonia. 158This includes toothbrushing and denture hygiene, as well as professional cleaning.In relation to toothbrushing, depending on the severity of dysphagia, it should be undertaken in an upright position using a nonfoaming toothpaste. 154,159en delivering periodontal care, there are several strategies that can be implemented to reduce the risk of aspiration.Depending on the severity of dysphagia, patients may need to be kept in an upright or semisupine position of no more than 45° if the airway is compromised. 154,155,159,160The airway may be protected with a gauze trap. 155In addition to frequent breaks during treatment, ultrasonic scalers should be used with caution with high volume suction. 154It is important to note that some patients will be at risk of silent aspiration during procedures, without any signs or symptoms of protective reflexes. 155

| Blood-borne viruses
Patients who received inactivated blood products up to the 1990s may have contracted transfusion-transmitted infections, including HIV and hepatitis. 127,161This risk is increased in patients who are likely to have received transfusions multiple times, including transfusion-dependent thalassemia, sickle cell disease, hemophilia, and hematological malignancies. 162Complications of blood-borne viruses include liver disease and, depending on its severity, will have additional considerations for the management of this cohort. 163,164rrent procedures for blood products with virus deactivation processes have reduced the prevalence of transfusion-related infections. 165The transmission rate of hepatitis viruses to dental professionals is low and is concentrated in developing countries with a higher prevalence of hepatitis-infected individuals, 166 and probably in those who do not have direct access to antiviral agents that cure HIV infection in more than 95% of patients.The risk of HIV transmission in the dental setting is also low, especially when rapid HIV testing of the source patient is available and, if necessary, access to postexposure prophylaxis. 167Standard infection prevention and control procedures, careful history taking, appropriate immunization of the dental team, and sharps injury protocol should be in place to minimize the risk of transmission. 168Applying these measures, periodontal treatment is effective in patients with virologically controlled HIV infection and can be performed safely in the dental clinic. 169The potential complications of dental treatment of patients with viral hepatitis include the potential transmission of the infectious agent and those derived from hepatic dysfunction that favor the appearance of hemorrhages because of coagulation factor deficiency and requires restricting the prescription of hepatic metabolism drugs. 170

| Wound healing
Wound healing after periodontal therapy may be impaired in patients with medical comorbidities.For example, patients with poorly controlled diabetes mellitus are at an increased risk of delayed wound healing because of impaired immunity. 27,28The severity of the condition and related comorbidities should be assessed, and where appropriate by consulting with the medical team.Prior to invasive periodontal therapy, the blood glucose level should be measured using point-of-care tests meters for safe management. 171determination of HbA1c (ie, glycated hemoglobin) performed in the last 3 months provides information on the degree of control of diabetes and indirectly on the risk of postoperative complications.58 There is insufficient evidence to support the use of routine prophylactic antibiotics in patients with diabetes mellitus to reduce the risk of delayed healing and infection.136,172 The procedural site should be limited and healing monitored closely.171 The medical management of conditions may affect wound healing.For example, patients who have had radiotherapy to the head and neck region are at risk of osteoradionecrosis of the jaw.
Schuurhuis et al 173 followed up patients who had dental assessment and treatment prior to radiotherapy for head and neck cancer over a 2-year period.Compromised extraction site healing was observed more frequently in patients who had periodontal pockets of ≥6 mm at the assessment prior to radiotherapy (19%) compared with those who had pockets of <6 mm (4%).However, this was not statistically significant.Another study reported that the presence of severe periodontitis postoperatively had the strongest correlation for development of osteoradionecrosis. 174Patients should have a detailed dental assessment prior to commencing cancer therapy to remove teeth with poor prognosis and severe periodontal involvement. 98intenance of periodontal health postcancer therapy is essential in reducing the risk of compromised healing and the need for invasive procedures.When surgical periodontal procedures are indicated in areas of irradiated bone, these should be undertaken with caution after liaising with the patient's medical team. 175dications can impact wound healing after periodontal therapy.Among patients taking corticosteroids, immunosuppressants, biologic agents, and disease-modifying antirheumatic drugs, there is a lack of delayed wound healing and medication-related osteonecrosis of the jaw. 161An association between medication-related osteonecrosis of the jaw and periodontitis has been described, although neither the direction of this association nor predisposing factors have been definitively clarified. 82Paradoxically, medication-related osteonecrosis of the jaw can occur following periodontal therapy, 24 although it is more commonly associated with dental extractions.Prevention is key in the management of medication-related osteonecrosis of the jaw, and a dental assessment should be undertaken prior to commencement of antiresorptive therapy. 176For established areas of osteonecrosis, it should be managed conservatively, with symptomatic control and management of infections. 176,177The Faculty General Dental Practice (UK) guidelines 136 support the use of antibiotics when there is the presence of secondary infection.For extensive areas, surgery may be indicated. 177,178 all patients who are medically compromised and at risk of delayed wound healing, a strict follow-up protocol should be in place.
For instance, following invasive periodontal procedures, patients at risk of osteoradionecrosis or medication-related osteonecrosis of the jaw should be reviewed to assess the healing. 98,176In addition, a regular recall interval is essential in maintaining their oral health and reducing the risk of complications. 176,178This should be agreed for individual patients. 179

| CON CLUS IONS
A complication in medicine is an unanticipated problem that arises following, and is a result of, a procedure, treatment, or illness.
Complications may adversely affect the prognosis or outcome of a disease.On the other hand, errors are part of our professional lives.
Dentists, as well as physicians, are prone to errors in their profession that can impact on their patients' health and quality of life.The main difference between an adverse event and a complication is that the former is the consequence of a treatment while the latter is a consequence of the disease process.
In this review we have summarized the most common complications reported in patients with systemic comorbidities undergoing periodontal therapy.A framework for risk assessment was provided, including aspects of preoperative planning and intraoperative performance, which we hope will help colleagues prevent and minimize the incidence of treatment complications.

6 .
Spread of infectionThese domains will be explored further throughout this review with specific examples (Table systematically reviewed the evidence on a platelet count threshold of <50 × 10 9 /L for platelet transfusions for invasive dental procedures.Two out of nine studies included patients with thrombocytopenia who underwent scaling.One of these studies had a lower threshold of ≤30 × 10 9 /L for prophylactic platelet transfusion for three patients who required scaling.Overall, there was insufficient evidence to suggest that a platelet count of ≥50 × 10 9 /L or prophylactic platelet transfusions prevented significant postoperative bleeding.Local measures were sufficient in managing bleeding.The studies included in the review were small cohort studies that were heterogenous.Another retrospective cohort study F I G U R E 3 Multiple hematomas following scaling and root planing in a patient with liver cirrhosis.investigated bleeding complications in patients with mild to severe thrombocytopenia after extractions.101Over half of the patients displayed evidence of chronic periodontitis, although the reasons for the extractions were not specified.Only four out of 89 (4.4%) patients experienced postoperative bleeding.Prophylactic platelet transfusions did not reduce the risk of bleeding.Inherited qualitative platelet disorders are a broad spectrum of diseases characterized by platelet dysfunction in the early phases of hemostasis (eg, Bernard-Soulier syndrome or Glanzmann's thrombasthenia).Traditionally, the treatment of these patients has been carried out under platelet transfusion.102However, based on the high rate of alloimmunization to platelet surface antigens and human leukocyte antigens, recent guidelines recommend the use of tranexamic acid and desmopressin, avoiding prophylactic platelet transfusions, and restricting their therapeutic administration only for severe inherited functional platelet disorders and unresponsive cases.103 Leira held a Senior Clinical Research Fellowship supported by the UCL Biomedical Research Centre (NIHR-INF-0387) and a research contract with Fundación Instituto de Investigación Sanitaria de Santiago de Compostela (fIDIS).Marco Orlandi was a NIHR Clinical Lecturer and Hana Cho held an NIHR Academic Clinical Fellowship.All the authors work at UCL/UCLH, which receives funding from the NIHR.FU N D I N G I N FO R M ATI O NThis review was self-funded.

Authors (year) Country Study design Systemic condition Intervention Complication Complication rate Complication management
Examples of inherited and acquired bleeding disorders TA B L E 2 The ACCESS risk assessment and treatment modification framework 88