Received: 26 April 2022 | Accepted: 26 May 2022

DOI: 10.1111/prd.12444

REVIEW ARTICLE

Complications and treatment errors in periodontal therapy in

medically compromised patients

Yago Leira1,2,3 | Hana Cho4 | Debora Marletta5 | Marco Orlandi1 | Pedro Diz6 |
Navdeep Kumar4 | Francesco D’Aiuto1
1
Periodontology Unit, UCL Eastman Dental Institute & NIHR UCLH Biomedical Research Centre, University College London, London, UK
2
Periodontology Unit, Faculty of Odontology, University of Santiago de Compostela & Medical-­Surgical Dentistry Research Group, Health Research Institute of
Santiago de Compostela (IDIS), Santiago de Compostela, Spain
3
Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
4
Special Care Dentistry Unit, ENT & Eastman Dental Hospital, UCLH NHS Foundation Trust, London, UK
5
UCL Library Services, University College London, London, UK
6
Special Care Dentistry Unit, Faculty of Odontology, University of Santiago de Compostela & Medical-­Surgical Dentistry Research Group, Health Research
Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain

Correspondence
Francesco D’Aiuto, Periodontology Unit, UCL Eastman Dental Institute, 21 University Street, London WC1E 6DE, UK.
Email: [email protected]

Funding information
National Institute for Health Research; UCL Biomedical Research Centre, Grant/Award Number: NIHR-­INF-­0387

1 | I NTRO D U C TI O N participants in terms of age, socioeconomic status, or health aware-

ness could explain these findings.8 The most frequently reported
In 2019, worldwide life expectancy was estimated at approximately medical problems in the dental office are allergies to medications
72 years of age. This has improved dramatically over decades, and is followed by cardiovascular diseases (including hypertension) and en-
mirrored in childhood survival rates.1 As a consequence, the number docrine disorders (including diabetes mellitus).5-­10
of people presenting with long-­term conditions is increasing rapidly, As a direct consequence of medical comorbidities, a sub-
as it is closely related to aging. 2 Multimorbidity in this aging popu- stantial number of patients will be taking multiple medications,
lation is common and it has been rising in prevalence over recent which may also have an impact on their periodontal management.
years, with one in three adults living with more than one chronic Radfar and Suresh11 observed that of 1041 patients treated in
disease.3,4 their dental school, 360 (35%) were taking antihypertensives, 202
Evidence on the prevalence of systemic diseases in patients pre- (19%) painkillers, 181 (17%) antidepressants, 107 (10%) antidys-
senting for periodontal care suggests that between 40% and 52% lipidemic agents, and 95 (9%) antiplatelet drugs. This highlights an
of patients have more than one systemic condition, and these es- additional consideration in terms of the potential pharmacologic
5-­7
timates increase with age. In addition, the type of medical prob- interactions with anesthetics or other medications that we might
lems patients present with can differ significantly depending upon need to prescribe for these patients after certain periodontal
the facility where periodontal care is provided.8 Findings from a ret- procedures.
rospective analysis demonstrated a lower prevalence of medically In addition to the systemic pathology inherent to age and poly-
compromised patients with periodontitis who attended a private pharmacy, the increased survival of patients with certain congenital
dental practice (28%) compared with those attending a dental school diseases with periodontal manifestations has created a growing de-
or hospital clinic (46% and 74%, respectively).8 Differences between mand for periodontal treatment. These congenital disorders include

Yago Leira contributed equally to the manuscript.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2022 The Authors. Periodontology 2000 published by John Wiley & Sons Ltd.

Periodontology 2000. 2023;92:197–219.  wileyonlinelibrary.com/journal/prd | 197

198 | LEIRA et al.

diseases with a considerable prevalence such as Down syndrome12 we carried out text word searches, synonyms, related terms, and
13
and around 14% of rare disorders with a low prevalence. The provi- singular/plural forms for each concept were used. This strategy
sion of dental treatment for these patients is not exempt from some ensured that we retrieved studies where surgical and nonsurgical
potential complications, because the etiopathogenic mechanisms of periodontal therapies for periodontal diseases (including dental ex-
these diseases include hemorrhagic diatheses, immunodeficiencies, tractions as part of the periodontal treatment) were discussed along
and alterations in the metabolism of vitamins, minerals, and trace with each systemic disease of interest. We exported the results for
elements.13 each search to the reference management software Endnote X9,
Treatment of periodontitis is part of routine care of patients which we used to manage our references. We applied no language
attending dental practices, but it may be associated with complica- or date restrictions and used the high-­sensitivity animal filter for
tions, particularly when invasive/surgical approaches are required. Medline OvidSP (exp animals/not humans.sh), which we combined
Although the overall incidence of these complications is low, it in- with our search strategy with the use of the Boolean operator NOT
cludes prolonged bleeding (1%-­8%),14-­17 infection (1%-­4%),14-­16,18-­20 to exclude animal studies. No restriction was made in terms of study
swelling (1%-­60%),14-­16 pain (4%-­49%),14-­17 and delayed wound heal- design (ie, from case reports to randomized clinical trials).
14
ing (2.5%). In some lower number of cases, complications linked to The total number of records retrieved by the electronic data-
specific surgical procedures may occur, such as membrane barrier base was 9294, and one additional article was obtained via a manual
exposure, flap dehiscence, or graft (soft or hard tissue-­derived) ne- search. After removing duplicates, we screened 6599 titles/ab-
crosis.14 The variability of complication rates is strictly dependent stracts and selected 112 articles for full-­text screening. Finally, we
14,16 14
upon the periodontal procedure performed. Askar et al retro- chose 20 articles to be included in this narrative review.
spectively evaluated complication rates of different periodontal pro-
cedures and found that patients who received osseous surgery more
frequently developed some type of complication (in 25% of cases), 3 | CO M PLI C ATI O N S A F TE R
followed by free gingival graft technique (20%), crown lengthen- PE R I O D O NTA L TH E R A PY I N PATI E NT S
ing (16%), guided tissue regeneration (13%), open flap debridement W ITH CO M O R B I D ITI E S
(12%), and connective tissue graft procedures (10%). Gingivectomy
appeared to be the surgical periodontal technique with the lowest Most studies reported different complications following nonsur-
14
rate of complications (5%). gical and surgical periodontal procedures in medically compro-
The presence of any long-­term condition may increase the risk mised patients (Table 1). Most of the studies included were case
of having a complication during or after treatment of periodontitis, reports. 21-­32 Two publications were case series,33,34 four studies
14
as evidenced by Askar et al, who reported that patients diagnosed had a cross-­sectional design,35-­38 and only two were randomized
with diabetes mellitus were six and 25 times more likely to experi- controlled clinical trials.39,40 The type of complication reported
enced delayed wound healing after an open flap debridement proce- was related to the modality of periodontal treatment and the pa-
dure and mucogingival surgery, respectively. tient's systemic condition. In most of the studies, a low complication
The aim of this narrative review is to provide a comprehensive rate was observed (≈5%). The most frequently reported complica-
overview of the potential complications and treatment errors that tion was bleeding in more than half of the studies included in this
can occur in medically compromised patients undergoing both non- review. 22,23,25,26,29-­33,35-­38,40 Other less common oral complications
surgical and surgical treatment of periodontitis. Specific risk reduc- include delayed wound healing, 21,22 barrier membrane exposure, 27,28
tion strategies for these patients are also discussed. infection, 28,39 and medication-­related osteonecrosis of the jaw. 24

2 | E V I D E N C E S E A RC H M E TH O D O LO G Y 3.1 | Bleeding-­related complications

To gather all the evidence published in relation to complications Four different groups of patients could be identified when pro-
after periodontal treatment in medically compromised patients, a longed gingival bleeding was reported as a complication after peri-
systematic search in Medline OvidSP was carried out from 1946 odontal treatment: in patients with bleeding disorders, drug-­induced
to 10 July 2020. Three key searchable concepts were identified: gingival overgrowth, those taking antithrombotic medications, and
“Periodontal Diseases”, “Surgical and Non-­Surgical Periodontal patients with hypertension.
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 3.1.1 | Bleeding disorders
search strategies were created for each disease to be appended to a
search including the first two concepts. Bleeding disorders can be congenital or acquired (Table 2). An in-­
We conducted searches for each concept using text word terms depth review of their relationship with periodontics has been previ-
and medical subject headings wherever these were available. When ously published and it is not within the scope of the current review.41
TA B L E 1 Summary of publications reporting on complications related to periodontal therapy in medically compromised patients

Authors (year) Country Study design Systemic condition Intervention Complication Complication rate Complication management
LEIRA et al.

Andersen et al. Norway Case report Crohn's disease Mucogingival surgery Altered and delayed —­ 0.2% clorhexidine
(2003)21 (coronally advanced flap healing mouthwash + 1%
with or without enamel clorhexidine gel (once/d
matrix derivative) for 3 wk)
Blanco-­C arrion Spain Case report Moderate hemophilia Mucogingival surgery Area of necrosis at donor —­ Factor VIII concentrate (2500
et al. (2004)22 A, HIV infection (B2 (subepithelial palatal site with units twice/d, during
stage), and chronic connective tissue graft) spontaneous bleeding 1 wk) + prophylactic Factor
hepatitis C 1 wk after procedure VIII concentrate (2500
units once/2 d, for 2 more
wk)
Campo et al. Spain Cross-­sectional HIV infection a. Dental prophylaxis a. None a. 0.0% (0/45) Not reported
(2007)35 (n = 33) b. Prolonged gingival b. 5.8% (1/17)
b. Scaling and root planing bleeding c. 0.0% (0/4)
(n = 8) c. None
c. Surgical therapy (n = 3)
Cutler et al. USA Case report Type 1 diabetes mellitus Nonsurgical periodontal Liver clots without clot —­ Not reported
(1991)23 treatment (scaling and retraction for up to
root planing) + dental 10 d postextractions
extractions
D’Aiuto et al. UK Randomized Type 2 diabetes mellitus a. Intensive periodontal a. Oral: tooth pain, a. Dental pain (4%), sensitivity Not reported
(2018)39 controlled therapy (scaling and tooth sensitivity, (3.1%), infection (2.5%),
clinical trial root planing + re-­ tooth infection, fracture (1.1%), restoration
(intensive instrumentation or tooth fracture, tooth (0.8%), gum swelling (1.1%),
periodontal modified Widman flap restoration and gum chest infection (1.2%),
therapy technique) (n = 133) swelling headache (0.8%), influenza
vs control b. Control periodontal b. Systemic: chest (0.7%), throat infection
periodontal therapy (supragingival infection, headache, (0.4%), foot infection
therapy) scaling and polishing) influenza, throat (0.5%), fainting (0.3%),
(n = 131) infection, foot infection, dizziness (0.4%) and back
fainting, dizziness, and pain (0.3%)
back pain b. Dental pain (3.0%),
sensitivity (0.9%), infection
(2.6%), fracture (1.6%),
restoration (1.1%), gum
swelling (0.8%), chest
infection (1.0%), headache
(0.4%), influenza (0.7%),
throat infection (0.5%), foot
infection (0.6%), fainting
(0.3%), dizziness (0.4%) and
back pain (0.5%)
|
199

(Continues)
TA B L E 1 (Continued)
200
|

Authors (year) Country Study design Systemic condition Intervention Complication Complication rate Complication management

Diniz-­Freitas Spain Case report Osteoporosis treated Nonsurgical periodontal Medication-­related —­ Extraction of teeth
et al. (2018)24 with biannual treatment (scaling and osteonecrosis of the involved in the
subcutaneous root planing) jaw (stage I) sequestration + complete
injections of 60 mg surgical debridement
of denosumab of necrotic bone + 0.2%
chlorhexidine mouthwash
(2/d) and doxycycline
(200 mg/d) from the 7 d
prior to surgery until 3 wk
postsurgery
Deppe et al. Germany Cross-­sectional Prosthetic heart valve a. Periodontal surgery Gingival bleeding within 24 a. 3.7% (2/53) Local hemostasis with
(2013)36 surgery (modified Widman flap h after postoperative b. 4.5% (2/44) either Nd:YAG laser or
Relevant medication: technique) with the use hemostasis conventional methods
anticoagulant of Nd:YAG laser + dental
coumarin drug extractions (n = 24)
b. Periodontal surgery
(modified Widman flap
technique) without
the use of Nd:YAG
laser + dental extractions
(n = 21)
Elad et al. Israel Case report Coronary angioplasty Nonsurgical periodontal Severe gingival —­ 4/0 vicril suture + local
(2008)25 and subsequent treatment (scaling and bleeding >10 h pressure with gauze
drug-­eluting stent root planing) after postoperative soaked with tranexamic
because of ischemic hemostasis acid solution in the
heart disease and bleeding area
acute myocardial
infarct
Relevant medication:
aspirin 100 mg and
clopidrogrel 75 mg
Federici et al. Italy Cross-­sectional von Willebrand disease Resective periodontal Severe gingival 3.1% (2/63) Local application of fibrin glue
(2000)37 surgery + dental bleeding 6-­8 h in the bleeding area
extractions (n = 63) after postoperative
hemostasis
Franchini et al. Italy Cross-­sectional Severe hemophilia A a. Nonsurgical periodontal Severe gingival a. 0.7% (1/133) Factor VIII 2000 + 1500 IU
(2005)38 treatment (scaling and bleeding 48 h after b. 0.0% (0/19) after 12 h
root planing) (n = 133) postoperative
b. Periodontal surgery hemostasis
(n = 19)
LEIRA et al.
TA B L E 1 (Continued)

Authors (year) Country Study design Systemic condition Intervention Complication Complication rate Complication management
LEIRA et al.

Gregoriou et al. USA Case series Cerebral palsy with Gingivectomy (n = 2) Severe gingival —­ Transfusion of 250 cc of
(1996)33 gingival overgrowth bleeding 2-­3 h cross-­matched O+ blood
Relevant medication: after postoperative and 1255 cc plasmanate
phenobarbital hemostasis (case 1)
6000 units of topical
application of hemostatic
agent thrombin powder
(case 2)
Jones et al. USA Case series Cerebral palsy with Gingivectomy (n = 24) Slow to start adequate oral 8.3% (2/24) Not reported
(1988)34 gingival overgrowth food intake
Relevant medication:
dyphenylhydantoin
Knapp and Fiori USA Case report Hypertension Resective periodontal Prolonged gingival —­ a. Gingival bleeding: not
(1984)26 surgery bleeding + hypertensive reported
crisis b. Hypertensive crisis: sodium
nitroprusside drip
Lee et al. UK Randomized Hemophilia A or B Nonsurgical periodontal Prolonged gingival 61.5% (8/13) Not reported
(2005) 40 controlled treatment (dental bleeding
clinical trial scaling) (n = 13)
(active 5%
tranexamic
acid
mouthwash vs
placebo)
Mattson et al. USA Case report Type 2 diabetes mellitus Regenerative periodontal Membrane exposure —­ Irrigation of surgical site with
(1998)27 surgery (guided tissue 0.12% clorhexidine and
regeneration using a diluted salt water
collagen resorbable
membrane)
Mullally et al. UK Case report Type 1 diabetes mellitus Regenerative periodontal Membrane —­ 100 000 units of Nystatin
(1993)28 surgery (guided tissue exposure + candida pastilles (4 times/d
regeneration using infection for 1 wk) + membrane
a nonresorbable removal + tooth extraction
membrane)
|
201

(Continues)
TA B L E 1 (Continued)
202
|

Authors (year) Country Study design Systemic condition Intervention Complication Complication rate Complication management

Nishide et al. Japan Case report Chronic renal failure Gingivectomy + periodontal Extensive intraoperative —­ Acrylic splints containing
(2005)29 (under hemodialysis) surgery (modified gingival bleeding thrombin powder to cover
with gingival Widman flap surgical area + 4 units of
overgrowth technique) + dental concentrated red blood
Relevant medication: extractions cells transfusion + regional
amlodipine anticoagulation
hemodialysis with
nafamostat-­mesilate
Scheitler et al. USA Case report Plasminogen activator Nonsurgical periodontal Minimal intraoperative —­ Direct pressure with gauzes
(1988)30 deficiency treatment (scaling and gingival bleeding
root planing) + dental
extractions
Shapiro (1993)31 USA Case report Hemophilia C Mucogingival surgery (free Bleeding from the —­ Ligation of lesser palatine
gingival graft) palatal donor site 5 d artery with 4/0 silk suture
postsurgery and this was repeated
on day 8 and 10 after
surgery + 11 units of fresh
frozen plasma
Thomason et al. UK Case report Renal transplant with Gingivectomy Bleeding 40 min after —­ Local hemostasis by means of
(1997)32 gingival overgrowth postoperative pressure and infiltration
Relevant medication: hemostasis of anesthetic with
cyclosporine adrenaline + 6 units of
450 mg/d, platelets
azathioprine 75 mg/d,
amlodipine 10 mg/d,
and aspirin 150 mg/d

Abbreviations: IU, International unit; Nd:YAG, neodymium-­doped yttrium aluminum garnet.

LEIRA et al.
LEIRA et al. | 203

TA B L E 2 Examples of inherited and acquired bleeding disorders

episode, 2 days after subgingival instrumentation that was treated
Examples of medical with factor VIII concentrate.38 A pilot, randomized, double-­
Classification Body system conditions blind, placebo-­controlled clinical trial testing the use of active 5%
Congenital Hematological A Vascular disorders tranexamic acid mouthwash before dental scaling in patients with
• Hereditary hemophilia A/B reported that 38.5% of those who completed the
hemorrhagic
study did not show any sign of gingival bleeding.40 Bleeding compli-
telangiectasia
B Platelet disorders cations from the palatal donor site when performing mucogingival
• Bernard Soulier disease surgery have been reported. 22,31 Mitigating procedures reported to
• Idiopathic stop the bleeding include one from Shapiro,31 described as a ligation
thrombocytopenic
of lesser palatine artery with 4/0 silk suture, and this procedure was
purpura
C Coagulopathies repeated two more times after surgery together with the use of 11
• Von Willebrand disease units of fresh frozen plasma. In the case reported by Blanco-­C arrion
• Hemophilia et al, 22 a combination of 2500 units of factor VIII concentrate twice
D Fibrinolytic disorders
a day during 1 week with prophylactic factor VIII concentrate (2500
• Plasminogen activator
deficiency units once every 2 days for two more weeks) was used to manage
the same complication. Further, data from 63 consecutive patients
Cardiac • Cyanotic congenital heart
disease with von Willebrand disease receiving dental extractions and surgi-

Connective tissue • Ehlers Danlos Syndrome cal periodontal procedures were retrospectively analyzed. Results
showed that the complication rate of severe gingival bleeding was
Acquired Liver disease • Liver cirrhosis
• Liver malignancy 3.1% and this was managed through local application of fibrin glue
Renal • Chronic kidney disease in the bleeding area.37 However, some case series did not find any

Hematological • Aplastic anemia

bleeding episodes in patients with von Willebrand disease after ei-
-­pancytopenia ther nonsurgical42 or surgical periodontal therapy.43 Likewise, a low
Immune • Systemic lupus incidence of gingival bleeding in patients with HIV was reported
erythematous in a cross-­sectional study where different periodontal procedures
• Antiphospholipid were carried out.35 When other inherited bleeding conditions such
syndrome
as plasminogen activator deficiency or hereditary hemorrhagic tel-
• HIV
• Immune angiectasia were evaluated, the risk of bleeding was minimal, 30 if
thrombocytopenia any at all.44
purpura
Malignancy A Hematological
malignancies 3.1.2 | Drug-­induced gingival overgrowth
• Leukemia
• Lymphoma
• Multiple myeloma Gingival overgrowth may occur in patients taking anticonvulsants
• Myelodysplasia (eg, phenobarbital, sodium valproate, and phenytoin) (Figure 1), im-
B Nonhematological munosuppressants (eg, ciclosporin), or calcium channel blocker an-
malignancies:
tihypertensive drugs (eg, nifedipine and amlodipine).45 Severe cases
• Patients undergoing
chemotherapy may require surgical excision of the enlarged gingiva. While a few

Drugs • Alcohol case reports showed prolonged intraoperative and postoperative

• Antiplatelets bleeding after gingivectomy, 29,32,33 others did not find any bleeding
• Anticoagulants episodes after gingival tissues were treated with both nonsurgical
• Nonsteroidal anti-­
and surgical approaches.46,47 Jones et al34 performed 39 gingivec-
inflammatory drugs
• Corticosteroids
tomies in patients with cerebral palsy who presented gingival over-
• Chemotherapy growth resulting from diphenylhydantoin use and, although they did
Idiopathic • Disseminated not observe any bleeding problems, two out of 12 patients had slow
intravascular coagulation resumption of adequate oral food intake.

A multicenter retrospective analysis of 247 patients with different 3.1.3 | Antithrombotics

bleeding disorders who received a total of 543 dental procedures
presented an incidence of 1.9% of bleeding complications. Of those Patients taking antithrombotic medications may present with ex-
undergoing periodontal procedures (n = 152), only one participant tensive bleeding episodes after periodontal therapy. Most of these
diagnosed with severe hemophilia A experienced a hemorrhagic patients take anticoagulants (eg, warfarin, dabigatran, apixaban, and
204 | LEIRA et al.

diagnosed with Crohn's disease (a type of inflammatory bowel dis-

ease) who presented with multiple Miller's class I gingival reces-
sions. Three different mucogingival surgeries with a 4-­week interval
difference were carried out using a coronally advanced flap tech-
nique 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 compli-
cations, chlorhexidine gluconate gel and mouthwash were adminis-
tered. 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
F I G U R E 1 Gingival overgrowth and bleeding tendency connective tissue graft technique. At 1 week postsurgery, the pal-
secondary to the administration of valproate in a patient with ate (donor site) showed secondary intention healing associated with
severe epilepsy.
the necrotic area. 22 Conversely, another case report describes a pa-
tient with HIV who received the lateral sliding flap technique and
rivaroxaban) or antiplatelet (eg, aspirin and clopidogrel) drugs, which experienced uneventful healing over 8 months.48 In a case series
makes them more prone to experience bleeding problems in the of 21 patients with HIV, the same authors found no complications
dental setting. A cross-­sectional study of 45 patients who received (ie, delayed healing or infection) after crown lengthening had been
cardiac valve surgery and were under oral anticoagulation therapy undertaken.49
reported a low incidence (<5%) of bleeding independent of using Delayed healing could be expected after periodontal proce-
a neodymium-­doped yttrium aluminum garnet laser for periodon- dures in patients experiencing dystrophic epidermolysis bullosa, as
tal surgery.36 Uncontrolled severe gingival bleeding was also found described in two case reports. These cases detail one patient who
after delivering scaling and root surface debridement on a patient underwent mucogingival procedures to cover exposed roots by
25
who was taking aspirin and clopidogrel. 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 gin-
3.1.4 | Hypertension giva. 51 Neither patient developed any complications either during
or after surgery.
Knapp and Fiori26 described a case of prolonged postoperative Diabetes mellitus is also known to be associated with impaired
bleeding and hypertensive crisis associated with resective peri- wound healing, and patients are more likely to develop infec-
odontal surgery. In this case report, a patient diagnosed with hy- tions. Mattson et al27 treated an intrabony defect with guided tis-
pertension (180/120 mm Hg) underwent periodontal treatment sue regeneration from a patient with type II diabetes mellitus. 25
consisting of an initial phase on nonsurgical periodontal therapy Resorbable collagen membrane exposure was noticed after 1 week
followed by two apically repositioned flaps with osseous surgery. of healing. 27 The membrane was not removed but was irrigated
Two days after the second surgery, the patient began to bleed spon- with chlorhexidine and diluted salt water until the soft tissue had
taneously from the surgical site and was unable to control the local healed. 27 Similarly, Mullally et al28 also reported membrane expo-
hemorrhage. When the patient attended the emergency room, the sure after a guided tissue regeneration procedure in a patient with
amount of blood he had lost was approximately 100 mL/h and at diabetes mellitus. Moreover, a fungal infection by Candida albicans
that time the blood pressure was 210/140 mm Hg. He was given was diagnosed clinically and confirmed histologically afterwards. 28
his normal dose of clonidine to stop the hypertensive crisis, but no In this case, the membrane was removed, the tooth extracted, and
apparent effect was noted. Immediately, a sodium nitroprusside antifungal medication was prescribed. 28 Conversely, in a patient
drip was started in the intensive care unit, where his blood pressure with type I diabetes mellitus, the formation of “liver clots” (with-
dropped to 130/88 mm Hg. Once the blood pressure was stabilized, out clot retraction for up to 10 days) resulting from poor healing 1
oral bleeding stopped and healing of the periodontal surgical site week after modified Widman surgery and the extraction of hope-
was uneventful. less teeth was observed. 23 However, this finding is not common
and results from a recent randomized controlled clinical trial in-
cluding patients with type II diabetes mellitus and moderate-­to-­
3.2 | Other complications severe periodontitis showed a low incidence of complications after
periodontal treatment. D'Aiuto et al39 did not find any statistically
Soft tissue complications after mucogingival surgery have been de- significant differences in terms of oral and systemic complica-
scribed in two case reports. 21,22 The first case consisted of a patient tions when intensive periodontal therapy (including subgingival
LEIRA et al. | 205

debridement and modified Widman flap surgery) was compared These domains will be explored further throughout this review
with a control treatment (only supragingival scaling) over a period with specific examples (Table 4).
of follow-­up lasting 1 year.
There are some medications such as antiresorptives and antian-
giogenics that could also interfere in both soft and hard tissue heal- 5 | PR E V E NTI O N A N D M A N AG E M E NT
ing. A case has been published reporting osteonecrosis of the jaw O F CO M PLI C ATI O N S A N D TR E ATM E NT
after nonsurgical periodontal therapy on a patient who was receiving E R RO R S I N PE R I O D O NTA L TH E R A PY
subcutaneous injections of denosumab every 6 months (Figure 2). 24
The complication was managed by means of administration of chlor- Complications and treatment errors may occur when providing peri-
hexidine mouthwash and systemic antibiotics (doxycycline) together odontal therapy in patients who are medically compromised. These
with removal of the affected teeth, sequestrectomy, and surgical de- will be presented in relation to pain control, bleeding, infection, and
bridement of necrotic bone. wound healing.

4 | R I S K A S S E S S M E NT FR A M E WO R K 5.1 | Analgesia and pain control

A N D A PPRO PR I ATE TR E ATM E NT
M O D I FI C ATI O N S Effective pain control is essential for delivery of invasive periodon-
tal procedures. Adaptations may be required in relation to certain
When planning treatment for periodontal therapy in patients who medical conditions, operator skills, and availability of equipment, for
are medically compromised, it is important to consider additional instance, a computer-­controlled local anesthetic delivery system.
factors to provide holistic care. In addition to clinical and radio- The type, dose, and technique for local anesthetic administration
graphic examination, a thorough medical, social, and dental history may need consideration. For example, patients may have resistance
will enable a comprehensive risk assessment (Table 3). This will en- to local anesthetic, as in the case for the hypermobile type of Ehlers
sure that appropriate modifications can be implemented prior to Danlos Syndrome. These patients require a systematic approach to
commencement of periodontal therapy, thereby reducing complica- the type of local anesthetic selected. 54 It may be administered in
tions and treatment errors. The ACCESS mnemonic52,53 is a system- order of potency55 or in combination, for instance lidocaine could
atic approach to treatment modification, considering six domains be administered first, followed by articaine and then bupivacaine.
that address different aspects of care: A retrospective survey of 980 people with Ehlers Danlos Syndrome
reported the highest success rate of 30% with articaine, followed
1. Access by bupivacaine at 25%. 56 When it is not possible to achieve ade-
2. Communication quate local anesthesia, alternative anesthetic modalities should be
3. Consent considered.
4. Education Allergy to local anesthetic and its constituents is rare, and is esti-
5. Surgery mated to have an incidence of less than 1%.57,58 Further information
6. Spread of infection should be sought to determine the nature of the reported allergy,
and, where appropriate, the patient should be referred for formal
allergy testing.59 The most commonly reported reaction to local an-
esthetics is vasovagal syncope, which the patient may report as an
allergy.60
The dose of local anesthetic solution may need to be adminis-
tered with caution in patients with a severe cardiac condition. Good
pain control is essential to minimize stress on the myocardium sec-
ondary to pain sensation. The local anesthetic should be adminis-
tered slowly with an aspirating syringe to assess the physiological
response and reduce the risk of cardiovascular toxicity.58 There is
insufficient evidence to suggest that local anesthetic with or with-
out adrenaline as a vasoconstrictor poses a risk to patients with hy-
pertension or other cardiomyopathies.61 However, anesthetics with
adrenaline should be avoided in patients with severe hypertension
and it is not recommended to use more than two anesthetic car-

F I G U R E 2 Medication-­related osteonecrosis of the jaw after tridges with adrenaline at 1:100 000 (0.04 mg) in patients with cer-
nonsurgical periodontal therapy on a patient under antiangiogenics tain cardiac conditions, such as those with coronary stents or those
(denosumab). with a history of myocardial infarction.58
206 | LEIRA et al.

TA B L E 3 Examples of potential
Category Potential risks
medical, social, and dental risks
Medical Aspiration
Bleeding
Delayed healing
Local infection
Infective endocarditis
Hypoglycemia
Trismus
Social Ability to attend appointments
Timing of appointments
Communication aids
Lack of capacity to consent to periodontal therapy
Reduced mobility
Dental Periodontal disease
Reduced cooperation
Reduced manual dexterity

Patients with long-­term use of opioids, for instance, because administration, and to achieve greater efficacy compared with the
of chronic pain syndrome, may present with increased tolerance to conventional local anesthetic technique.71,73 It has been suggested
local anesthetic. Studies on nondental procedures showed that a that a computer-­controlled intraosseous anesthesia system may be
higher dose of local anesthetic solution was required to achieve the useful for root planing procedures because it reduces the pain of the
same efficacy.62 An increased amount of local anesthetic solution injection and provides a larger area of anesthesia with a single punc-
may be required for dental procedures. ture.74 In a randomized split-­mouth study in patients with chronic
Modification of the technique used to deliver local anesthetic periodontitis who underwent open-­flap debridement on premolars
may be required in relation to the underlying medical condition. For and molars, the authors reported substantial relief from injection
example, patients with severe bleeding disorders require careful as- pain with a computer-­controlled anesthetic delivery system com-
sessment if inferior alveolar nerve blocks or lingual infiltrations are pared with a conventional local anesthetic technique.75
planned, as hematological support (eg, coagulation factor replace- An aspirating local anesthetic syringe should always be used.58
63
ment) will be needed. The risks of proceeding without this in place The local anesthetic solution should be delivered in areas without lo-
are significant and include hematoma formation and potential risk to calized inflammation and/or infection, as the presence of inflamma-
the airway. Buccal infiltration has been reported as a safe technique tion may affect the success of local anesthesia. Block techniques are
in patients with differing severity of hemophilia, without the need useful adjuncts in these instances, as the local anesthetic solution is
for additional factor cover.64 Preoperative tests may be required for deposited at a site away from inflammation and infection.76
patients on anticoagulants such as warfarin for whom inferior alve- In patients with fragile mucosa surfaces, as in the case of epider-
olar nerve blocks are required. The clinician should confirm that the molysis bullosa, the technique may need to be altered. Depending
patient's international normalized ratio readings are generally stable. on the severity, the local anesthetic solution should be deposited
For patients with unstable international normalized ratio profiles, it slowly and deeply in the tissues to avoid mechanical separation
has been proposed that the international normalized ratio should of the mucosal layer and the formation of blisters.77 If iatrogenic
be checked preoperatively if block injections are planned and given blisters appear as a result of the injection of local anesthesia, they
cautiously with a self-­aspirating syringe.65,66 must be drained to prevent the lesion from expanding (puncturing
In patients with trismus, alternative techniques to the conven- with a needle or cutting the blister with scissors).78 Postoperatively,
tional inferior alveolar nerve block may be indicated. Gow-­Gates and patients should also be instructed to take extra care to avoid trau-
Akinosi techniques deliver the local anesthetic solution higher than matizing the mucosa.77
67-­69
the conventional technique and have similar anesthetic efficacy. If adequate local anesthesia is not achievable, alternative an-
These may be considered in patients with trismus or when the con- esthetic modalities may need to be considered, such as conscious
ventional technique fails. Both alternative techniques should be sedation and general anesthesia. In patients who are medically com-
67
used with caution, and each carries a higher risk of complications. promised, preoperative anesthetic assessment may be required to
Intraligamentary and intraosseous anesthesic injection techniques assess their suitability. 52 Postoperative pain is common among pa-
70
may be used as alternatives to mandibular nerve blocks. tients undergoing periodontal treatment, and it has been suggested
Computer-­controlled local anesthetic delivery systems can be that it is conditioned by variables such as age, the degree of patient
utilized in patients with needle phobia, especially if there are ad- anxiety, and the type of procedure performed.79 Scaling and root
ditional medical comorbidities that contraindicate alternative an- planing can cause considerable pain in terms of intensity and du-
esthetic modalities.71,72 The technique can be used in children ration, 80 although the magnitude of pain is generally greater after
and adults, and has been found to reduce the perceived pain on surgical periodontal treatment.16 Acetaminophen (paracetamol) and
LEIRA et al. | 207

TA B L E 4 The ACCESS risk assessment and treatment modification framework

Examples of conditions that

Domain Considerations may require adaptations Examples of treatment modification

Access Appropriate Bleeding Low platelets (eg, secondary Patients requiring platelet support should
dental to chemotherapy, platelet ideally be seen in a hospital setting
setting disorders)
Access to the Timing of Antithrombotic medications Appointments early in the day and week for
dental appointment (eg, oral anticoagulants, invasive dental procedures
surgery antiplatelets)
Chronic kidney disease and Appointment the day after dialysis
dialysis
History of myocardial infarction Avoid elective dental procedures within 6 mo
of myocardial infarction
Escort Learning disability, dementia Depending on severity, may require family
member and/or carer to accompany the
patient
Transport Frailty, physical disability Hospital transport
Wheelchair access Wheelchair user Wheelchair recliner if unable to transfer to
the dental chair
Access to the Aspiration Dysphagia Semisupine or upright position in the dental
patient's chair
mouth Involuntary Movement disorders (eg, Vacuum cushion and/or clinical holding to
movement Parkinson's disease) support the head and neck to minimize
trauma
Temporomandibular Ehlers Danlos Syndrome Mouth prop, frequent breaks, and shorter
dysfunction appointments
Trismus Head and neck cancer therapy Pediatric handpieces, mouth prop
Fragile oral mucosa Epidermolysis bullosa Lubrication and careful handling of soft
tissues
Altered anatomic Obesity, previous surgery to the Alternative technique to deliver local
landmarks head and neck anesthetic may be required
Communication With the medical team Immunosuppression (eg, The ideal timing for elective periodontal
transplant) therapy should be consulted with the
medical team
With the laboratory Low neutrophils (eg, secondary Timely reporting of urgent blood tests prior
to chemotherapy) to invasive periodontal therapy
With social care professionals Learning disability, mental Assistance in organizing appointments for
health conditions patients who require additional social
support
With patients Nonverbal communication (eg, Communication aids (eg, Makaton, pictures,
stroke, learning disability) and easy read patient information
leaflets)
Consent Capacity to consent Learning disability, mental Undertake capacity assessment, if
health conditions, dementia lacks capacity to consent to specific
periodontal therapy, involve family and/
or carers in the decision-­making process
Fatigue Fatigue related to the medical Undertake capacity assessment, avoid early
condition morning appointments
Implications in relation to medical Infection risk in patients who Extraction of teeth with infection risk
health are immunocompromised because of the potential impact on their
(eg, cancer) systemic condition
Long-­term implications Neurodegenerative conditions Discuss the patient's ability to maintain oral
(eg, dementia, Parkinson's hygiene as the condition progresses
disease)

(Continues)
208 | LEIRA et al.

TA B L E 4 (Continued)

Examples of conditions that

Domain Considerations may require adaptations Examples of treatment modification

Education Relationship between medical Diabetes mellitus Patient informed of the bidirectional
conditions and dental disease relationship between periodontal
disease and diabetes mellitus, and
the importance of managing good
periodontal health
Education of family and/or carers Learning disability, Oral hygiene instructions to the family and/
neurodegenerative or carers for patients who are partly or
conditions (eg, dementia, fully dependent on others for activities
Parkinson's disease) of daily living
Reduced manual dexterity Cerebral palsy, multiple Adaptation of oral hygiene tools (eg,
sclerosis toothbrush handle holder, and long-­
handled interdental brushes)
Dental team Unstable asthma, angina, Medical emergency training
epilepsy
Surgery Preoperative Blood test Low neutrophils (eg, Full blood count may be required within 24 h
chemotherapy) prior to invasive periodontal therapy
Blood test Warfarin INR test within 24 h (or 72 h if stable) prior to
invasive periodontal therapy
Antibiotics Special consideration group Antibiotic cover 1 h before invasive
for infective endocarditis periodontal therapy may be required
(eg, prosthetic heart after consulting the patient and their
valve, previous infective cardiologist
endocarditis)
Perioperative Local anesthesia Resistance to local anesthesia Select the most appropriate local anesthetic
(eg, Ehlers Danlos agent
Syndrome)
Monitoring vital Moderate to severe respiratory Monitoring of vital signs
signs condition
Oxygen At risk of hypoxia (eg, sickle cell Supplemental oxygen via nasal cannula
disease) during invasive periodontal therapy
Postoperative Prescription Patients on warfarin Avoid prescribing metronidazole because of
drug interactions
Follow-­up At risk of osteoradionecrosis Review 8 wk after invasive periodontal
(eg, head and neck cancer) therapy
Emergency access Bleeding disorders Details of emergency services for patients at
higher risk of bleeding
Spread of Patients who are immunocompromised Patients undergoing May require prophylactic antibiotics; consult
infection chemotherapy the medical team

Abbreviation: INR, international normalized ratio.

nonsteroidal anti-­inflammatory drugs are the agents of choice to chronic kidney disease, or with severe liver failure.84 Nonsteroidal
81
tackle postoperative pain in dentistry, but they are not exempt anti-­inflammatory drugs that act as preferential cyclooxygenase-­2
from adverse effects and should be administered with caution in inhibitors have also been used to control postoperative pain after
patients with certain systemic diseases.82 The interval between periodontal procedures.85,86 Cyclooxygenase-­2 inhibitors reduce
acetaminophen intakes should be adjusted in patients with chronic the incidence of gastrointestinal side effects and have little or
kidney disease and the total daily dose should be limited in pa- no effect on platelet function, so the risk of bleeding is minimal.
tients with liver disease.83 Most nonselective cyclooxygenase-­1 However, most selective cyclooxygenase-­2 inhibitors have been
and cyclooxygenase-­2 inhibitor nonsteroidal anti-­inflammatory withdrawn from the market because of the risk of serious cardiovas-
drugs should be avoided in patients with a history of peptic ulcer cular events,87 and nimesulide is also not marketed in some coun-
or gastroesophageal bleeding, in patients receiving anticoagu- tries because of the risk of acute hepatotoxicity and should not be
lants, lithium, or methotrexate, with uncontrolled hypertension and administered to patients with liver failure.88
LEIRA et al. | 209

5.2 | 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 bleed-
ing in relation to the medical condition, dental procedure, and expe-
rience of the operator.89 The 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 F I G U R E 3 Multiple hematomas following scaling and root
conditions can receive different types of agents. Some agents will planing in a patient with liver cirrhosis.

predispose the individuals to chemotherapy-­induced thrombocyto-

penia, and others will impact platelets to a lesser degree.90 Patients in the dental setting. The international normalized ratio should be <4
with severe risk of bleeding who require onsite medical support for to undertake periodontal therapy.65,66 Morimoto et al97 undertook a
invasive periodontal therapy are more appropriately managed in a retrospective study on periodontal therapy in patients taking war-
secondary care setting.91 farin. They confirmed that nonsurgical periodontal therapy can be
If the planned periodontal therapy has an increased risk of safely performed when the international normalized ratio is <4, and
bleeding, the appointment should be timed earlier in the day and the that surgical periodontal therapy surgery can be safely performed
week, so that postoperative complications can be managed accord- when the international normalized ratio is <3. These international
ingly.66 The timing of appointments should be in line with the med- normalized ratio values are applicable in patients without other con-
ical management of each patient’s condition. For instance, patients comitant factors that may favor bleeding, such as liver failure or un-
who are taking direct oral anticoagulants should provide information controlled hypertension.58
about the time of the scheduled dose so as to minimize interruption Furthermore, for patients having pharmacotherapy that affects
to the drug regime.66 The risk of thrombosis outweighs the potential their blood counts, they may require a blood test on the day of the
risks of postoperative bleeding from dental procedures.66 Similarly, procedure or within the last 24-­48 hours to account for more fre-
single or dual therapy antiplatelets should not be interrupted for quent fluctuations in blood counts.98 It may also be necessary to li-
92 66
dental procedures, including periodontal therapy. However, in aise with the laboratories regarding specific requirements and timely
patients with a high risk of bleeding and dual therapy, some guide- reporting of the investigation results.
lines have recommended suspending one of the antiplatelet agents Additional hematological support may be required in patients
before the procedure (5 days in the case of clopidogrel), generally with thrombocytopenia. This will be dependent on the planned peri-
maintaining the administration of aspirin.93 For patients with hemo- odontal procedure, as well as a preoperative blood test and liaison
philia who have regular prophylactic factor replacement, the dental with the medical team to determine the requirements for platelet
procedure should be timed as close to the time of administration transfusions. The most accepted threshold for platelet counts is
to avoid the need for additional factor replacement, and thus maxi- ≥50 × 109/L for invasive dental procedures, which includes peri-
mizing therapeutic effects, and reducing risks and overall treatment odontal surgery or tooth extractions. Patients with platelet counts
costs.63,89,94,95 Patients undergoing renal dialysis should not be seen of <50 × 109/L are at an increased risk of experiencing periopera-
on the dialysis day because of fatigue and an increased risk of bleed- tive and postoperative bleeding.99 Platelet transfusion may be in-
ing secondary to heparin and abnormal platelet function.96 dicated preoperatively, perioperatively, and/or postoperatively.
Depending on the underlying cause of the increased bleeding Karasneh et al100 systematically reviewed the evidence on a platelet
risk, special investigations may be indicated. Appropriate blood tests count threshold of <50 × 109/L for platelet transfusions for invasive
such as full blood counts, clotting screen, and liver function tests dental procedures. Two out of nine studies included patients with
should be arranged as part of the preoperative assessment depend- thrombocytopenia who underwent scaling. One of these studies
ing on the medical condition and its stability 91 (Figure 3). The timing had a lower threshold of ≤30 × 109/L for prophylactic platelet trans-
of the blood test needs to reflect the underlying medical condition fusion for three patients who required scaling. Overall, there was
and its treatment regime. For example, it is acceptable to use a 72-­ insufficient evidence to suggest that a platelet count of ≥50 × 109/L
hour international normalized ratio test on patients on warfarin who or prophylactic platelet transfusions prevented significant post-
are stable, but for those with an unstable international normalized operative bleeding. Local measures were sufficient in managing
ratio, it should be undertaken within 24 hours.65,66 Point-­of-­care bleeding. The studies included in the review were small cohort stud-
tests for international normalized ratio are available and can be used ies that were heterogenous. Another retrospective cohort study
210 | LEIRA et al.

investigated bleeding complications in patients with mild to severe Low-­risk procedures for bleeding include nonsurgical periodon-
101
thrombocytopenia after extractions. Over half of the patients tal therapy.112 No additional hematological cover is necessary, pro-
displayed evidence of chronic periodontitis, although the reasons vided local anesthesia principles are followed.113 Although routine
for the extractions were not specified. Only four out of 89 (4.4%) scaling is unlikely to cause significant bleeding, the overall peri-
patients experienced postoperative bleeding. Prophylactic platelet odontal condition must be assessed, as hematological support may
transfusions did not reduce the risk of bleeding. Inherited qualitative be indicated in selected cases.89 High-­risk procedures consist of
platelet disorders are a broad spectrum of diseases characterized by extractions and periodontal surgery.112 The degree of prophylaxis
platelet dysfunction in the early phases of hemostasis (eg, Bernard-­ cover is determined by the hematologist. Local hemostatic measures
Soulier syndrome or Glanzmann's thrombasthenia). Traditionally, should be followed, including closure of surgical sites and the use of
the treatment of these patients has been carried out under platelet hemostatic agents.114 The use of a surgical splint has been suggested
102
transfusion. However, based on the high rate of alloimmunization to protect the surgical site.94
to platelet surface antigens and human leukocyte antigens, recent Initially, the treatment area should be limited and staged to as-
guidelines recommend the use of tranexamic acid and desmopres- sess the bleeding risk, and reassessed before proceeding.66 Surgical
sin, avoiding prophylactic platelet transfusions, and restricting their trauma should be minimized where possible, with closure of the
therapeutic administration only for severe inherited functional wound. At the end of the procedure, the procedural site should
platelet disorders and unresponsive cases.103 be observed for an extended period of time to ensure that there
In relation to patient education and the risk of bleeding, patients is hemostasis. If there is evidence of bleeding, the site should be
should be informed of possible minor bleeding related to the planned compressed with a damp gauze dressing for 10-­15 minutes. Consider
periodontal therapy. There is a tendency for patients with bleeding the use of topical coagulating agents such as oxidized cellulose
conditions to use soft toothbrushes, which may not effectively re- and gelatin foam to aid hemostasis.66,115 Rubino et al115 undertook
move plaque deposits. In addition, patients may have been advised a retrospective analysis of patients who had invasive periodon-
by their doctors to avoid brushing their teeth or to undertake inter- tal therapy and were on antithrombotic medications (antiplatelets
dental cleaning measures when they have thrombocytopenia. There and anticoagulants). The drug regime was not interrupted for most
is a lack of evidence to suggest the benefits of such an approach.104 participants (99.6%), and local hemostatic measures were followed.
A study conducted by Padrón et al105 concluded that patients under Postoperative bleeding was only observed in three out of 867 pro-
anticoagulation therapy had greater accumulations of dental plaque, cedures (0.35%).
more gingival bleeding, and deeper periodontal pockets than healthy A prescription for tranexamic acid 5% mouthwash, an antifi-
controls, and approximately 17% of them never brushed their teeth brinolytic agent, may be considered for use up to four times a day
compared with 3% of the control group. It has been suggested that as required. This is a nonformulary preparation and therefore may
fear of gingival bleeding could induce patients using anticoagulants not be readily accessible in primary care dental services. Successful
to brush their teeth less.105 A lack of good oral hygiene measures use of a 2-­day course of tranexamic acid 4.8% mouthwash in the
may predispose the patient to dental disease, and possibly progress management of postoperative bleeding was reported for patients
to infection, which may compromise their medical health. Dental taking warfarin who received tooth extractions because of severe
professionals should consider the risk of bleeding before advising on periodontal disease and the results were similar to those obtained
the most appropriate oral hygiene measure. for a 5-­day course.116 To manage the bleeding, participants were
For all types of procedures, general precautions should be fol- initially asked to use compression with a gauze pad for 20 minutes,
lowed, including gentle handling of the oral mucosa, instruments, and if the bleeding persisted, the tranexamic acid mouthwash was
106
and equipment. For pain and anxiety control, appropriate selec- applied via a gauze pad for a further 20 minutes. Systematic reviews
tion of local anesthetic solution and technique is required. Factor of the evidence on the use of topical tranexamic acid for dental
replacement may be required for patients with hemophilia in relation procedures showed successful hemostasis for patients on vitamin
to the local anesthetic technique and proposed procedure.91 The K antagonists,117 and inconclusive evidence for congenital bleeding
site of surgery helps to determine an appropriate local anesthetic disorders.118 If local measures are insufficient to achieve adequate
technique for treatment. In patients with hemophilia and other se- local hemostasis, the appropriate medical team should be contacted
vere bleeding conditions, inferior alveolar nerve blocks and lingual to assess the need for systemic agents.
infiltrations pose a risk of airway obstruction, caused by hemorrhage Postoperatively, the dental practitioner should ensure that
into musculature and the formation of hematomas in retromolar and patients have access to dental emergency services to minimize
pterygoid spaces.107 Factor replacement decreases the risk of bleed- distress for the patient and facilitate timely access if required.66
94
ing. On the contrary, infiltrations (with the exception of lingual), Prescription should be administered with caution. Nonselective cy-
as well as intraligamentary, intraosseous, and intrapulpal injections, clooxygenase-­1 and cyclooxygenase-­2 inhibitor nonsteroidal anti-­
108
do not require factor replacement. Articaine infiltrations may be inflammatory drugs for pain control should be avoided in patients
used in the mandible to avoid block techniques109,110 and eliminate at risk of bleeding, as this may exacerbate the risk of bleeding.66,119
111
the need for factor cover. Acetaminophen is the preferred analgesic.
LEIRA et al. | 211

5.3 | Infection infections. Acute periodontal infection should be treated in a timely

manner as it poses a risk of bacteremia and sepsis in patients with
Infection may occur following periodontal therapy in patients who neutropenia.122 The ideal treatment window period should be de-
are medically compromised. This will be discussed in relation to im- termined after consultation with the oncology team,98 for instance
munosuppression, infective endocarditis, aspiration pneumonia, between chemotherapy cycles.
blood-­borne viruses, and wound healing. Another group of patients for which the timing of dental treat-
ment is important consists of those who have had solid organ trans-
plantation. This cohort receive long-­term immunosuppressants, with
5.3.1 | Immunosuppression a lower maintenance dose after approximately 6 months. Therefore,
elective periodontal therapy should be delayed for 3-­6 months after
Patients who have immunosuppression are at an increased risk of the transplant.123,124 Georgakopoulou et al123 reported an increased
infection after invasive periodontal therapy. The causes of immu- level of risk of severe oral infections in patients who have undergone
nosuppression can be categorized into congenital and acquired renal transplantation. The recommendation for routine periodontal
(Table 5). therapy 6 months posttransplant is that scaling can be undertaken
The timing of the dental appointment should be made taking in a staged manner, with a small number of teeth cleaned at a time.
into consideration the cause, severity, and the likely duration of the Invasive periodontal therapy may require further preoperative inves-
immunosuppression. For example, nonurgent periodontal therapy tigations and close liaison with the patient's physician. To minimize the
should be postponed for patients undergoing active chemother- risk of infection when patients are immunosuppressed, a pretrans-
apy.98,120,121 Patients may have bone marrow suppression, and resul- plant dental assessment should be undertaken.124,125 Periodontal
tant low white cell count and neutrophils, which predisposes them to health should be stabilized, and the source of infection eliminated.124
For patients who require regular blood transfusions (eg, thalas-
TA B L E 5 Examples of congenital and acquired
semia major) or red cell exchange transfusions (eg, sickle cell ane-
immunosuppressive disorders
mia), the dental visit should be scheduled soon after their routine
Classification Body system Example of conditions transfusions.126,127 Treatment on the same day should be avoided
Congenital Syndromes • Down syndrome as the patients are fatigued.127 In addition, patients with hemoglo-

• Kostmann syndrome binopathies (eg, thalassemia, sickle cell disease) may have either
nonfunctional or absence of spleen. This predisposes individuals to
• Chediak Higashi syndrome
infections, and potential sources of periodontal infection should be
Metabolic • Glucose-­6 phosphate
dehydrogenase deficiency managed in a timely manner.127,128

Acquired Endocrine • Diabetes mellitus Preoperative investigations may be required to determine the
• Addison's disease severity of immunosuppression including complete blood count with
Liver disease • Liver cirrhosis differential, coagulation assessment and liver and kidney function

Renal • Chronic kidney disease tests, to evaluate whether the procedure should be delayed, if it can
be done in an outpatient setting, the need for antibiotic prophylaxis,
Hematological • Aplastic anemia
• Thalassemia the risk of bleeding, and the dosage of prescriptions. For example,
• Sickle cell disease for patients at risk of neutropenia, a preoperative full blood count
Immune • HIV should be undertaken prior to invasive periodontal procedures. If
• Rheumatoid arthritis the neutrophil count is <1 × 109/L, periodontal probing and elective
• Systemic lupus
invasive periodontal therapy should be postponed because of an
erythematous
increased risk of infection.104 In an observational study, 10 out of
Malignancy • Hematological (secondary
116 patients (8.6%) with mild (1.00-­1.50 × 109/L), moderate (0.50-­
to the malignancy
and treatment; eg, 0.99 × 109/L), and severe (<0.0-­0.49 × 109/L) neutropenia who had
chemotherapy, extractions presented with one or more complications.129 The most
radiotherapy, transplant) common complication was delayed healing,7 followed by postopera-
• Nonhematological tive pain6 and surgical site infection.3 The likelihood of complications
(secondary to treatment;
was not associated with the severity of neutropenia. The preoper-
eg, chemotherapy,
radiotherapy, transplant) ative management was variable, with some participants receiving
preoperative, perioperative, and/or postoperative antibiotics and
Drugs • Corticosteroids
granulocyte colony-­stimulating factor to increase neutrophil levels.
• Immunosuppressants
(calcineurin inhibitors, Prophylactic administration of antibiotics may be indicated in
antimetabolite agents, patients who are immunosuppressed.130 For example, in patients
polyclonal and monoclonal who have had a splenectomy (eg, thalassemia and sickle cell dis-
antibodies, mTOR inhibitors)
ease), antibiotic cover should be considered for invasive dental
212 | LEIRA et al.

procedures.127,131,132 Those who are on immunosuppressive therapy followed accordingly. Patients taking above 50 mg prednisolone are
constitute another cohort of patients. The American Association of close to the innate maximum cortisol level seen in patients when
Pediatric Dentistry advises that antibiotic coverage may be required stressed and may not require further supplementation.139
9
for patients with a neutrophil count of <2 × 10 /L, and should be dis- In recent years there have been great advances in targeted anti-
cussed with the medical team.133 The suggested antibiotic regime is cancer therapies, including monoclonal antibodies, fusion proteins,
that used for infective endocarditis,134 although in some cases it is tyrosine kinase inhibitors, and mammalian target of rapamycin inhib-
necessary to consult with the medical team (eg, patients with severe itors, among others.140 The indications for biologic response modifi-
immunosuppression, solid organ transplant recipients, or those who ers, and in particular monoclonal antibodies, have been extended to
have received multiple antibiotic regimens). numerous cardiovascular and inflammatory diseases (eg, rheumatoid
The risk of developing systemic infection from a dental source arthritis, psoriasis, or Crohn's disease), transplant rejection, multiple
has been reported to be associated with the presence of preexist- sclerosis, and viral infections.82 In addition to the immunosuppres-
130
ing infection. A timely and more aggressive antibiotic regime may sive effect, these molecules can cause thrombocytopenia, wound
reduce the risk of infection and its impact on the general health of delayed healing, and medication-­related osteonecrosis of the jaw.140
patients who are immunosuppressed.130,133
On the contrary, the British Society for Antimicrobial
Chemotherapy do not recommend routine use of prophylactic 5.3.2 | Infective endocarditis
antibiotics for dental procedures in patients who are immunosup-
pressed.135 This is supported by the antimicrobial dental guidelines Patients with susceptible cardiac conditions are at an increased risk
for immunocompromised patients, including diabetes mellitus, HIV, of infective endocarditis following invasive dental procedures. Oral
chemotherapy, solid organ transplants, and hematological malignan- pathogens have been implicated in infective endocarditis, namely,
cies.136 The case-­specific decision is advised by consulting with the viridans streptococci.141-­143 Periodontal bacterial species such as
medical team, as there may be additional medical factors that indi- Aggregatibacter actinomycetemcomitans have been detected in
cate the use of antibiotics (Figure 4). specimens from damaged heart valves and aortic aneurysm walls.144
Corticosteroids can cause immunosuppression, predisposing an Dhotre et al142 reported, in a series of confirmed cases of infective
individual to infections. Patients on a higher dosage of corticosteroids endocarditis undergoing dental extractions, that more than 40% had
and who have Addison's disease are at an increased risk of adrenal periodontitis, suggesting that periodontal disease enhances viridans
crisis when exposed to stress. A literature review found that adrenal streptococcal bacteremia. The prevalence of bacteremia resulting
crisis related to dental procedures is rare.137 The risk is increased in from periodontal pathogens is probably underestimated because of
the presence of pain and infection, in addition to invasive procedures, the limitations of microbiologic detection techniques.145
and treatment under general anesthesia. Steroid cover is indicated for Bacteremia may result from noninvasive dental procedures.
patients taking ≥7.5 to 10 mg prednisolone for longer than 3 months Toothbrushing has been reported as a potential risk factor for in-
and undergoing invasive periodontal therapy and/or treatment under fective endocarditis.146,147 A randomized controlled trial reported a
138,139
general anesthesia. If the patient is on other corticosteroids, lower incidence of infective endocarditis with toothbrushing com-
the equivalent dose to prednisolone should be calculated, and advice pared with extractions.148 However, 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.143
Invasive periodontal treatment can cause bacteremia leading to
the development of endocarditis, although the relationship between
dental treatment and infective endocarditis remains a controversial
issue.150 Transient bacteremia following dental procedures depends
on the state of oral health and the treatment modality, estimating after
scaling and root planing in 25%-­61%.151 The 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 prophy-
laxis is not routinely recommended by the National Institute for Health
F I G U R E 4 Patient with severe primary immunodeficiency
and Care Excellence (UK) guidelines.141 There are patient cohorts that
who has received several antibiotic regimens. Before carrying
out periodontal treatment, the medical team was consulted, who are more susceptible to infective endocarditis, requiring special con-
recommended microbiologic and antimicrobial susceptibility sideration.149 In these patients, European and American expert com-
testing. mittees agree that when high-­risk heart conditions are specified in
LEIRA et al. | 213

these patients, it is essential to discuss with them, and eventually their transmission in the dental setting is also low, especially when rapid
cardiologists and/or surgeons, whether they should receive antibiotic HIV testing of the source patient is available and, if necessary, access
prophylaxis for invasive periodontal procedures, including full peri- to postexposure prophylaxis.167 Standard infection prevention and
134,149,152
odontal examination, root surface debridement, and surgery. 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.168 Applying these measures, perio-
5.3.3 | Aspiration pneumonia dontal treatment is effective in patients with virologically controlled
HIV infection and can be performed safely in the dental clinic.169 The
Dysphagia (or difficulty in eating, drinking, or swallowing) has a potential complications of dental treatment of patients with viral
153
prevalence of up to 16% in the general population. Patients with hepatitis include the potential transmission of the infectious agent
dysphagia are at risk of aspiration, which may progress to pneumo- and those derived from hepatic dysfunction that favor the appear-
nia, which carries a significant risk of morbidity and mortality. There ance of hemorrhages because of coagulation factor deficiency and
are multiple causes of dysphagia, including cerebral palsy, learning requires restricting the prescription of hepatic metabolism drugs.170
disability, stroke, and previous head and neck cancer therapy.153-­155
Periodontitis represents a potential risk factor for the develop-
ment of aspiration pneumonia in the elderly.156 Dental plaque has 5.4 | Wound healing
been suggested as a risk factor for healthcare-­associated pneumonia
in patients who are hospitalized, with an increase in dental plaque Wound healing after periodontal therapy may be impaired in pa-
levels with longer hospital stays.157 Good oral hygiene is one of the tients with medical comorbidities. For example, patients with
most effective interventions in reducing the risk of aspiration pneu- poorly controlled diabetes mellitus are at an increased risk of de-
monia.158 This includes toothbrushing and denture hygiene, as well layed wound healing because of impaired immunity. 27,28 The sever-
as professional cleaning. In relation to toothbrushing, depending on ity of the condition and related comorbidities should be assessed,
the severity of dysphagia, it should be undertaken in an upright po- and where appropriate by consulting with the medical team. Prior
sition using a nonfoaming toothpaste.154,159 to invasive periodontal therapy, the blood glucose level should be
When delivering periodontal care, there are several strategies measured using point-­of-­care tests meters for safe management.171
that can be implemented to reduce the risk of aspiration. Depending A determination of HbA1c (ie, glycated hemoglobin) performed in
on the severity of dysphagia, patients may need to be kept in an up- the last 3 months provides information on the degree of control of
right or semisupine position of no more than 45° if the airway is com- diabetes and indirectly on the risk of postoperative complications. 58
154,155,159,160
promised. The airway may be protected with a gauze There is insufficient evidence to support the use of routine prophy-
155
trap. In addition to frequent breaks during treatment, ultrasonic lactic antibiotics in patients with diabetes mellitus to reduce the risk
scalers should be used with caution with high volume suction.154 It is of delayed healing and infection.136,172 The procedural site should be
important to note that some patients will be at risk of silent aspira- limited and healing monitored closely.171
tion during procedures, without any signs or symptoms of protective The medical management of conditions may affect wound
155
reflexes. healing. For example, patients who have had radiotherapy to the
head and neck region are at risk of osteoradionecrosis of the jaw.
Schuurhuis et al173 followed up patients who had dental assessment
5.3.4 | Blood-­borne viruses and treatment prior to radiotherapy for head and neck cancer over
a 2-­year period. Compromised extraction site healing was observed
Patients who received inactivated blood products up to the 1990s more frequently in patients who had periodontal pockets of ≥6 mm
may have contracted transfusion-­transmitted infections, includ- at the assessment prior to radiotherapy (19%) compared with those
ing HIV and hepatitis.127,161 This risk is increased in patients who who had pockets of <6 mm (4%). However, this was not statistically
are likely to have received transfusions multiple times, including significant. Another study reported that the presence of severe
transfusion-­dependent thalassemia, sickle cell disease, hemophilia, periodontitis postoperatively had the strongest correlation for de-
and hematological malignancies.162 Complications of blood-­borne velopment of osteoradionecrosis.174 Patients should have a detailed
viruses include liver disease and, depending on its severity, will have dental assessment prior to commencing cancer therapy to remove
163,164
additional considerations for the management of this cohort. teeth with poor prognosis and severe periodontal involvement.98
Current procedures for blood products with virus deactivation Maintenance of periodontal health postcancer therapy is essential in
processes have reduced the prevalence of transfusion-­related in- reducing the risk of compromised healing and the need for invasive
fections.165 The transmission rate of hepatitis viruses to dental pro- procedures. When surgical periodontal procedures are indicated in
fessionals is low and is concentrated in developing countries with areas of irradiated bone, these should be undertaken with caution
a higher prevalence of hepatitis-­infected individuals,166 and prob- after liaising with the patient's medical team.175
ably in those who do not have direct access to antiviral agents that Medications can impact wound healing after periodontal ther-
cure HIV infection in more than 95% of patients. The risk of HIV apy. Among patients taking corticosteroids, immunosuppressants,
214 | LEIRA et al.

biologic agents, and disease-­modifying antirheumatic drugs, there F U N D I N G I N FO R M AT I O N

is a lack of delayed wound healing and medication-­related osteo- This review was self-­funded.
necrosis of the jaw.161 An association between medication-­related
osteonecrosis of the jaw and periodontitis has been described, C O N FL I C T O F I N T E R E S T
although neither the direction of this association nor predis- The authors report no conflict of interest in connection with this
82
posing factors have been definitively clarified. Paradoxically, review.
medication-­related osteonecrosis of the jaw can occur following
periodontal therapy, 24 although it is more commonly associated DATA AVA I L A B I L I T Y S TAT E M E N T
with dental extractions. Prevention is key in the management of The data that support the findings of this study are available on re-
medication-­related osteonecrosis of the jaw, and a dental assess- quest from the corresponding author. The data are not publicly avail-
ment should be undertaken prior to commencement of antiresorp- able because of privacy or ethical restrictions.
tive therapy.176 For established areas of osteonecrosis, it should
be managed conservatively, with symptomatic control and man- ORCID
176,177
agement of infections. The Faculty General Dental Practice Yago Leira https://orcid.org/0000-0001-5027-7276
(UK) guidelines136 support the use of antibiotics when there is the
presence of secondary infection. For extensive areas, surgery may
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