The change in incidence and severity of odontogenic infections: an analysis and cross-sectional study one decade apart Dr Benjamin Fu BDSc (HONS), MD

A thesis submitted for the degree of Master of Philosophy at The University of Queensland in 2019 School of Medicine Abstract Background Odontogenic infections are usually treated by general dentists in the community. However, when the infection spreads beyond the confines of the bony maxilla or mandible, it has the potential to result in life-threatening complications. The diagnosis and treatment of these odontogenic infections that warrant in-hospital treatment remains a significant burden to the health care system.

Aims 1. To determine if there have been any changes to the demographics and presentation of patients being treated for odontogenic infections at a tertiary hospital in Brisbane, Australia. 2. To determine if there are any clinical or biochemical predictors of Intensive Care Unit (ICU) admission. 3. To determine if pre-operative imaging, namely Computed Tomography (CT) scans are being appropriately used in the management of these odontogenic infections.

Methods A retrospective chart review was conducted after ethics and site-specific approval. All patients taken to theatre with odontogenic infections between 2003 to 2004 and 2013 to 2014 at Royal Brisbane and Women’s Hospital were identified and included in the study. Hospital records were individually reviewed and data de-identified and recorded. A standardised data collection sheet was used to collect details on patient demographics, presentation, prior history, antimicrobial therapy, imaging and treatment outcome. Descriptive statistics were utilised for each recorded attribute, and a chi-square analysis was used to compare the data for the two cohorts. A multiple regression model was used to analyse predictors of ICU admission.

Results There was no significant difference in patient demographics between the two cohorts. 101 patients were identified in the earlier cohort, compared to 191 identified in the later cohort. The 2013/14 cohort had a two-fold increase in presentation of lower third-molar related infections (p=0.000), 50% increase in trismus presentation (p=0.000) and 20% increase in submandibular swelling (p=0.010). The percentage of patients admitted to ICU increased by 3.5-fold in the 2013/14 cohort (p=0.000). The overall length of stay increased from 1.7 to 3.5 days (p=0.004). The most significant predictors of ICU admission were lower third molar involvement (p=0.026), dysphagia (p=0.02) and CRP levels exceeding 150mg/L (p=0.039). Preoperative CT scanning increased from 6% in the earlier cohort to 79% in the later cohort.

Conclusion The presentation of odontogenic infection has increased in the decade from 2003/04 to 2013/14. Measures of disease severity have increased, while demographics of the patients remained constant. The utilisation of ICU and the length of hospital stay have increased. There needs to be improved effort in primary preventative measures and early interventions are needed to alleviate the burden of severe odontogenic infections on the public health system. Further research is required to assess whether judicious use of CT scanning, combined with prompt surgical intervention, can lead to improvement in treatment outcomes. Declaration by author

This thesis is composed of my original work, and contains no material previously published or written by another person except where due reference has been made in the text. I have clearly stated the contribution by others to jointly-authored works that I have included in my thesis.

I have clearly stated the contribution of others to my thesis as a whole, including statistical assistance, survey design, data analysis, significant technical procedures, professional editorial advice, financial support and any other original research work used or reported in my thesis. The content of my thesis is the result of work I have carried out since the commencement of my higher degree by research candidature and does not include a substantial part of work that has been submitted to qualify for the award of any other degree or diploma in any university or other tertiary institution. I have clearly stated which parts of my thesis, if any, have been submitted to qualify for another award.

I acknowledge that an electronic copy of my thesis must be lodged with the University Library and, subject to the policy and procedures of The University of Queensland, the thesis be made available for research and study in accordance with the Copyright Act 1968 unless a period of embargo has been approved by the Dean of the Graduate School.

I acknowledge that copyright of all material contained in my thesis resides with the copyright holder(s) of that material. Where appropriate I have obtained copyright permission from the copyright holder to reproduce material in this thesis and have sought permission from co-authors for any jointly authored works included in the thesis.

Publications included in this thesis

Peer-Reviewed Journal Articles Fu B, McGowan K, Sun H, Batstone M. Increasing use of intensive care unit for odontogenic infection over one decade: Incidence and predictors. Journal of Oral and Maxillofacial Surgery. 2018 Nov 1;76(11):2340-7.

Accepted Peer-Reviewed Journal Articles Fu B, McGowan K, Sun H, Batstone M. Increasing frequency and severity of odontogenic infection requiring hospital admission and surgical management. British Journal of Oral and Maxillofacial Surgery. Accepted for Publication 2019

Presentations of research from this thesis

Cervico-facial Infections. Head & Neck Surgery Grand Rounds. 2nd of August 2017. Gold Coast University Hospital, Gold Coast, Australia.

Antibiotic overuse in Dentistry and Oral and Maxillofacial Surgery. National Antimicrobial Resistance (AMR) Forum. 8th of November 2019. Royal Brisbane and Women’s Hospital, Brisbane, Australia. Publications included in this thesis

Fu B, McGowan K, Sun H, Batstone M. Increasing use of intensive care unit for odontogenic infection over one decade: Incidence and predictors. Journal of Oral and Maxillofacial Surgery. 2018 Nov 1;76(11):2340-7. Contributor Statement of Contribution Dr Benjamin Fu Data Collection, 100%; Wrote and edited paper, 100% Dr Kelly McGowan Statistical analysis, 50%, reviewed and edited paper 50% Dr Hansen Sun Statistical analysis, 50% A/Prof Martin Batstone Original idea and design 100%, reviewed and edited paper 50%

Fu B, McGowan K, Sun H, Batstone M. Increasing frequency and severity of odontogenic infection requiring hospital admission and surgical management. British Journal of Oral and Maxillofacial Surgery. Accepted for Publication 2019 Contributor Statement of Contribution Dr Benjamin Fu Data Collection 100%, Wrote and edited paper, 100% Dr Kelly McGowan Statistical analysis, 50%, reviewed and edited paper 50% Dr Hansen Sun Statistical analysis, 50% A/Prof Martin Batstone Original idea and design 100%, reviewed and edited paper 50%

Contributions by others to the thesis Dr Kelly McGowan, University of Queensland, provided assistance with statistical analysis and editing of published manuscripts Dr Hansen Sun, Queensland University of Technology, provided assistance with statistical analysis

Statement of parts of the thesis submitted to qualify for the award of another degree No works submitted towards another degree have been included in this thesis.

Research Involving Human or Animal Subjects No animal or human subjects were involved in this research.

Acknowledgements I would like to acknowledge my supervisors for their support and guidance throughout my studies; and wife Sophia for her love and support.

Financial support No financial support was provided to fund this research.

Keywords Odontogenic infections, surgical management, ICU admission Australian and New Zealand Standard Research Classifications (ANZSRC) ANZSRC Code: 110323, Clinical Sciences – Surgery, 100%

Fields of Research (FoR) Classification FoR code: 1103, Clinical Sciences – Surgery, 100%

Table of Contents • Chapter 1: Literature review of odontogenic infections • Chapter 2: Increasing frequency and severity of odontogenic infection requiring hospital admission and surgical management • Chapter 3: Increasing use of intensive care unit for odontogenic infections over one decade: incidence and predictors • Chapter 4: Thesis conclusion • References

List of Figures & Tables

Table 2.1. Demographic information Table 2.2. Clinical presentation Table 2.3. Vitals and investigations Table 2.4. Antimicrobial therapy Table 3.1. Treatment outcomes Table 3.2. Demographics of patients admitted to ICU Table 3.3. Clinical presentation of patients admitted to ICU Table 3.4. Multiple logistic regression modelling of predictors of ICU admission Table 4.1. Key recommendations for prevention of odontogenic infections Figure 4.1. Patients with facial swellings in the dental practice: Common misconceptions Figure 4.2. Treatment algorithm for patients presenting with dental pain to the emergency department

List of Abbreviations Used in the Thesis

ATSI = Aboriginal & Torres Strait Islander CCI = Charlson Comorbidity Index CRP = C-Reactive Protein CT = Computed Tomography ED = Emergency Department GCS = Glasgow Coma Scale ICU = Intensive Care Unit LOS = Length of Stay MRI = Magnetic Resonance Imaging RBWH = Royal Brisbane & Women’s Hospital SIRS = Systemic Inflammatory Response Syndrome WCC = White Cell Count

Chapter 1: Literature Review of Odontogenic Infections

Introduction Odontogenic infections continue to be one of the most commonly managed pathologies by maxillofacial surgeons and remain a significant burden on the health system. According the Australian Institute of Health and Welfare, in 2010-11, there were 60,590 hospitalisations across Australia due to dental conditions that could have been avoided if timely and adequate non-hospital care had been provided. This literature review provides an overview of odontogenic infections, including the anatomy and how infection spreads, potential complications, diagnostic imaging, and predictors of severe disease course. It also considers the economic burden of odontogenic infections and identifies need for further research.

Anatomy and Pathway of Spread of Infection Odontogenic infection has been shown to be the most common cause of deep neck infections in the adult population1, 2. Studies have also consistently demonstrated that mandibular molars are the most frequent source of odontogenic infections requiring hospital admission2-6. In terms of fascial space involvement, the submandibular space is considered to be the most commonly affected site2-7. Understanding the anatomy of, and the relationship and communication between various neck spaces helps to explain these epidemiological trends.

Odontogenic infections are usually confined by the bony cortex of the maxilla or mandible8. The infective process originates from the apex of the tooth and spreads via the pathway of least resistance, eroding through the bony cortex of the maxilla or mandible prior to reaching facial planes8, 9. Maxillary infections tend to spread through the thin buccal cortex to reach the buccal or canine space, while mandibular infections can spread either buccally or lingually depending on the location of the root apex in relation to the mandibular cortex8, 9. CT studies have shown mandibular molars, especially third molars, are more frequently situated lingually in the mandible with thinner cortical thickness9. This allows infection to perforate the mandible more easily on the lingual aspect and is congruent with the clinical observation that mandibular third molar infections are more likely to involve lingual or submandibular spaces9, 10.

Once the infection perforates the mandible, the spread of infection from mandibular teeth closely relates to their relationship with the mylohyoid muscle8, 9, 11. The mylohyoid muscle represents the anatomical floor of the mouth and extends transversely from the medial aspect of the mandible to meet at the midline10, 12. Above the mylohyoid is the sublingual space, and below it is the submandibular space10, 12. Posteriorly, the mylohyoid has a free edge that extends approximately to the level of the second and third molar, allowing free communication between the sublingual and submandibular space10, 12. Therefore, infections originating in posterior teeth tend to perforate the lingual cortices below the mylohyoid line and can gain direct access to the submandibular space8, 9, 11. On the other hand, anterior teeth perforate the lingual cortices above the mylohyoid line and are initially confined in the sublingual space8, 9, 11. As the infection progresses, it can spread through the mylohyoid muscle into the submandibular space, or gain entry via the posterior free edge11. Oshima et al9 observed that regardless of position of the mandibular molar apices in relation to the mylohyoid muscle, most infections consequently involve the submandibular space.

Another frequently involved space in odontogenic infection is the masticatory space8. The masticator space encompasses the posterior body of the mandible, ramus and condyle, as well as associated masticatory muscles10, 12. Involvement of these muscles explains the characteristic symptom of trismus in these patients9, 11. Odontogenic infections that initially involve the masticatory space frequently extend medially into the submandibular space directly from the masseter or from the medial pterygoid muscles through the investing layers of the deep cervical fascia11.

Ariji et al11 summarised the spread of odontogenic infection to the submandibular space via three main pathways: 1) through the mylohyoid muscle or sublingual space; 2) through the bony structures of the mandible or; 3) from the masticatory space. The multitude of pathways available explains why the submandibular space has been demonstrated to be the most frequently involved fascial space in multiple studies.

Further Complications Aggressive infection of the floor of the mouth can rapidly extend across midline and down into deeper cervical spaces, known as Ludwig’s angina10. Ludwig’s angina is a clinical diagnosis given to large, firm and rapidly spreading cellulitis simultaneously affecting bilateral sublingual, submental and submandibular spaces13. 70-85% of Ludwig’s angina cases are due to odontogenic infection of the second or third mandibular molars13, 14. Progressive swelling of the soft tissue, and elevation and posterior displacement of the tongue can be observed clinically14. Since there are no distinct fascial barriers, infection frequently spreads from the submandibular space to the parapharyngeal space9, 11. Involvement of the parapharyngeal space often results in dysphagia or dyspnoea, and can precede rapid and critical airway obstruction11.

Further spread of infection into deep cervical spaces can progress through the prevertebral space and retropharyngeal space into the anterior and posterior parts of the mediastinum respectively15. Even with antibiotics and surgical treatment, mediastinitis has a fatality rate ranging from 35-65%13, 15. Necrotizing fasciitis, pericarditis, pleural emphysema and arterial erosion have all been reported to stem from descending odontogenic infections originating from the mandible2, 8, 16.

Life threatening infections are not limited to mandibular teeth alone. The extensive communication between intracranial and extracranial veins can allow retrograde spread of infection of maxillary teeth17. This can result in dangerous complications such as orbital abscess, cavernous sinus thrombosis and cerebral abscess17-19. Cavernous sinus thrombosis, the spread of infection via emissary veins, classically presents with signs of sepsis, chemosis, periorbital oedema and proptosis; impaired extraocular motility and vision impairment can occur, and subsequent intracranial extension may result in meningitis, encephalitis, brain abscess, possible coma and death20. Prompt surgical intervention is critical in containing the spread of infection.

Antibiotic Use and Resistance The use of antibiotics is an important adjunct in the treatment of odontogenic infection. However, antibiotic resistance is an increasing problem globally, and in terms of odontogenic infections, the use and misuse of antibiotics by general dental and medical practitioners are contributing to this problem21.

Amoxycillin is the most commonly prescribed antibiotic by general dentists in Australia (64.3% in 2016); this is followed by metronidazole (13.9%), broad-spectrum amoxicillin/clavulanic acid (10.4%) and clindamycin (5%); the authors raised concern over the increased use of amoxicillin/clavulanic acid which is not first line treatment of odontogenic infections22. A recent South Australian study reported overall antibiotic resistance rate of 17.8%, and those patients who demonstrated antibiotic resistance exhibited a poorer response to primary surgical therapy, requiring longer length of stay and return to theatre23.

There needs to be a continued effort to ensure appropriate antibiotic prescription according to the therapeutic guidelines at the primary care level. Prompt surgical drainage still remains the primary goal in the management of odontogenic infections.

Diagnostic Imaging Although visual inspection and palpation of the head and neck is relatively easy under normal circumstances, more severe odontogenic infections can significantly affect mobility of the mandible and limit adequate clinical assessment10. Under these circumstances, evaluation by imaging is often helpful, especially if there is concern with deep neck space involvement and encroachment of the airway.

The radiographic techniques available to assess deep maxillofacial infections include lateral cervical radiography, ultrasonography, magnetic resonance imaging (MRI), and computed tomography (CT).

Lateral cervical x-ray is the most convenient technique for cases with suspicion of retropharyngeal or prevertebral space involvement. Lateral cervical films can measure the distance from the anterior aspect of the vertebral body to the air column of the posterior pharyngeal wall24. However, a false negative rate of 33% has been reported and clinical judgment is paramount in determining the need for further imaging24.

Ultrasound has been used to detect neck abscesses but it is operator dependent and lacks anatomical detail for accurate diagnosis15. It is usually reserved for evaluation of more superficial infections10.

MRI can provide detailed images of anatomic structures and define otherwise obscure infections15. However, several disadvantages prevent its routine use, including high cost, time for image processing, and the cooperation required from the patient15, 24.

Contrast-enhanced CT is currently considered to be the radiologic evaluation method of choice for deep neck infections2. The immediate availability, high quality of anatomical detail, and ability to create multidimensional reformatted images, make it the optimal modality for imaging deep neck space infections in the emergency setting10. Characteristic findings of infection include the loss of definition between contiguous anatomic spaces of the neck, thickened muscles with hazy contours, and stranding of the subcutaneous fat planes10, 15. When contrast material is used, the existence of an abscess can be observed by the higher attenuation in the periphery and a central zone of lesser density10, 15. If a hypodense lesion is seen with no peripheral wall or rim-effect, it is usually interpreted as cellulitis2, 10, 15.

Differentiating between an abscess and cellulitis in deep neck infection on imaging is of clinical importance as it influences management. Traditionally, only infections that have progressed to abscess have required surgical intervention25, while infections in the cellulitis stage may, at times, be successfully treated with source control and antibiotics24. It is therefore important to accurately identify an abscess with discrete collection of pus suitable for drainage, and several studies have examined the diagnostic accuracy between preoperative CT and operative findings. Rosenthal et al24 reported preoperative diagnosis of either abscess or cellulitis on CT was confirmed in surgery in 80.6% of cases. Smith et al25 found a positive predictive value of 75% where pus was successfully drained. Most authors agree there is a 20-25% negative exploration rate when an abscess is predicted on CT, and the management must not rely on imaging findings alone, but take into consideration the overall clinical picture2, 15, 24-26. Identification of variables associated with more severe disease course would therefore be helpful in clinical practice.

Predictors of Outcome Studies looking into length of stay (LOS) and intensive care unit (ICU) admission in patients admitted and treated for odontogenic infections have identified a number of variables. Several papers found a correlation between older age, elevated temperatures and systemic comorbidities such as diabetes mellitus with increased LOS3-5. A study by Christensen et al27 found that increased number of fascial spaces involved higher peak WBC count, peak blood sugar and peak temperature are associated with increased LOS. Surprisingly the authors found ICU admission, increased WBC count, and bilateral infection was associated with decreased LOS27. They speculate that the clinicians may have consciously or subconsciously recognized these cases as more severe and treated them earlier, with more aggressive management and monitoring, leading to a decrease in LOS27.

Efforts have been made to establish predictors for ICU use in odontogenic infection in the literature. Ylijoki et al16 in 2001 found a particularly high CRP level on admission was associated with a more severe disease course requiring ICU admission; however the authors failed to identify any additional predictors. Christensen et al27 found operating room time, number of spaces involved and peak blood sugar were significantly associated with an increased likelihood of ICU admission. However, the authors conceded there was still a large proportion of variation (60%) still unexplained, and further research is required into odontogenic infection and ICU use27.

Cost Impact of Odontogenic Infections Despite being largely preventable, odontogenic infections continue to be one of the most commonly managed pathologies by oral and maxillofacial surgeons7. Severe infections requiring hospital admission or ICU use can lead to significant economic burden on the health system. Jundt et al3 in 2012 estimates the hospitalization cost for one day per patient to be $17842 USD. Christensen et al7 in 2013 found a very similar figure of $17053 per patient per day. In view of these staggering high costs, clinicians must be vigilant about the decision to admit, take to the OR, and admit to ICU. Cost efficiency, although important, should be secondary to quality patient care.

Chapter 2:

Increasing frequency and severity of odontogenic infection requiring hospital admission and surgical management

British Journal of Oral and Maxillofacial Surgery (2019) - Accepted

Introduction Odontogenic infections were the fourth leading cause of death according to the London Bills of Mortality in the early 1600's28, and were associated with a death rate between 10- 40% in the pre-antibiotic era29. Access to improved dental care and broad-spectrum antibiotics have significantly decreased the morbidity and mortality of dental infections30; however, it remains a significant burden to the public health system.

Data from developed countries suggest that the rate and severity of odontogenic infections presenting to hospital emergency departments (ED) are increasing29, 31-34. A proportion of these patients have late-stage spreading odontogenic infections that require surgical management and potential intensive care unit (ICU) admission. Another proportion have early odontogenic infection, but seek emergency medical care, instead of outpatient dental care, due to complex barriers to dental treatment35.

Odontogenic infections that spread beyond the confines of the jawbone pose a serious threat to the airway and have the propensity to cause deep neck infections36. Severe complications of odontogenic infections have been recorded in the literature including cerebral abscess37, descending mediastinitis38, toxic shock syndrome39, necrotising faciitis40, foetal distress requiring urgent delivery in a pregnant patient41, and development of MRSA while in ICU29. These adverse outcomes could have been avoided if the patient had sought and received early dental treatment at the onset of symptoms.

There is currently limited Australian data available on the number and characteristics of patients presenting to tertiary facilities with odontogenic infections, and therefore this study aims to: (i) determine if the number of patients admitted to a major tertiary hospital in Australia with odontogenic infections has increased over the last decade, and (ii) describe the changes in the presentation, clinical management, and outcomes over that period.

Materials & Methods: Ethical approval for the project was obtained from the RBWH Human Research Ethics Committee (ID: EC00172, HREC/14/QRBW/351). A retrospective review was conducted comparing all patients taken to theatre with odontogenic infections by the RBWH Maxillofacial Surgery Department between January 2003-December 2004, and January 2013- December 2014. 101 patients were identified in the earlier cohort, compared to 191 identified in the later cohort. This department is the largest tertiary referral centre in Queensland, servicing approximately 20% of the state’s population, which grew by approximately 22% between the two study periods42, 43. Patients were identified using the hospital operation record database, and only inpatients who underwent surgical procedures for incision and drainage of an odontogenic infection were eligible for inclusion. Elective procedures with a previous history of infection were excluded.

All patient records were assigned codes and de-identified to preserve anonymity during the analysis. Data on five key clinical areas were collated: 1. Demographics: age, gender, Aboriginal & Torres Strait Islander (ATSI) status, smoking history, diabetic status, immunosuppression, chronic kidney disease, and Charlson comorbidity index score.

2. Clinical Presentation: site of infection, number of days from onset of symptoms to hospital presentation, clinical findings (trismus, dysphagia, dyspnoea, stridor, tongue elevation, submandibular swelling), preceding dental consultation, and preceding antibiotic prescription.

3. Vitals and Investigations: systemic inflammatory response syndrome (SIRS) criteria (fever, tachycardia, elevated white cell count and increased respiratory rate), hypotension, reduced Glasgow Coma Scale (GCS) score, C-reactive protein (CRP) levels, and blood culture results.

4. Antimicrobial therapy: pre-operative antibiotics prescription, known antibiotic allergies, empiric susceptibility, adherence to the Therapeutic Guidelines, antibiotic spectrum broadening, and post-operative antibiotics prescription on discharge.

5. Treatment outcomes: time from ED presentation to theatre, number of ICU admissions, length of stay in Intensive Care Unit (ICU), any returns to theatre, and overall length of stay.

The collected data was entered into Excel spreadsheets (Microsoft, Redmond, USA). The statistical analyses were conducted using IBM SPSS Statistics, Version 24.0.0 (IBM Corporation, Aarmonk, USA). Descriptive statistics were run for each recorded attribute, and a chi-square analysis was used to compare the data for the two cohorts. Independent samples t-tests were used to compare age, time to theatre, and duration of stay. The level of statistical significance was set at a value of p<0.05, and the hypothesis tests were two- sided.

Results: Demographics: In the earlier cohort, 101 patients were taken to theatre with odontogenic infections, compared to 191 in later cohort. The demographics of the two cohorts were similar; there were no statistically significant differences in age, gender or ATSI status, nor patient comorbidities as outlined in Table 1. The later cohort had a lower proportion of smokers (57.6% compared to 70.7%), but this did not reach statistical significance (p=0.053). Amongst both cohorts, 57% were male, 6.2% were ATSI, and the mean age at presentation was 36.14 ±14.7 years old.

Table 2.1. Demographic information 2003-04 (n = 101) 2013-14 (n = 191) c2 p N (%) N (%) Age Under 30 45 (44.6) 79 (41.4) 0.28 0.600 Over 30 56 (55.4) 112 (58.6) Gender Male 59 (58.4) 108 (56.5) 0.09 0.759 Female 42 (41.6) 83 (43.5) ATSI status ATSI 5 (5.0) 13 (6.8) 0.39 0.531 Non-ATSI 96 (95.0) 178 (93.2) Smoking status Non-smoker 22 (29.3) 72 (42.4) 3.73 0.053 Smoker 53 (70.7) 98 (57.6) Diabetic status Non-diabetic 97 (97.0) 174 (91.1) 3.57 0.059 Diabetic (Type I or II) 3 (3.0) 17 (8.9) Immune status Normal 100 (99.0) 187 (97.9) 0.48 0.489 Immunosuppressed 1 (1.0) 4 (2.1) Renal status CKD stage 1 or 2, GFR >60 101 (100.0) 190 (99.5) 0.53 0.466 CKD stage 3 or worse, GFR <60 0 (0.0) 1 (0.5) Charlson Comorbidity Index None (score 0) 89 (88.1) 167 (87.4) 2.75 0.432 Mild (score 1-2) 10 (9.9) 19 (9.9) Moderate (score 3-4) 1 (1.0) 5 (2.6) Severe (score 5+) 1 (1.0) 0 (0.0) Demographic characteristics of the two cohorts were similar. Percentages are calculated based on the number of valid cases. Therefore due to missing data, percentages may not correlate with cohort total. Abbreviations: A&TSI, Aboriginal & Torres Strait Islander; CKD, chronic kidney disease; GFR, glomerular filtration rate.

Clinical Presentation: The later cohort had a higher percentage of odontogenic infections resulting from mandibular teeth (p=0.002), and in particular, lower third molars (p=0.000) (see Table 2). The percentage of patients who had preceding dental consultations was similar in both groups (41.6% and 44.5% respectively), as was the percentage of patients who were prescribed antibiotics prior to hospital presentation (57.4% and 62.8% respectively). While comparable proportions presented with dysphagia, dyspnoea, stridor and tongue elevation, the percentage of patients presenting with trismus (p=0.000) and palpable submandibular swellings (p=0.010) was higher in the later cohort.

Table 2.2. Clinical Presentation

2003-04 (n = 101) 2013-14 (n = 191) c2 p N (%) N (%) Location Maxilla 27 (26.7) 23 (12.0) 10.05 0.002 Mandible 74 (73.3) 168 (88.0) Lower third molar No 77 (76.2) 100 (52.4) 15.79 0.000 Yes 24 (23.8) 91 (47.6) Time from onset to presentation Within 48 hours 32 (32.0) 51 (27.0) 0.80 0.370 3+ days 68 (68.0) 138 (73.0) Attended dentist prior to presentation No 59 (58.4) 106 (55.5) 0.23 0.632 Yes 42 (41.6) 85 (44.5) Received antibiotics prior to presentation No 43 (42.6) 71 (37.2) 0.81 0.368 Yes 58 (57.4) 120 (62.8) Clinical findings Trismus 46 (47.9) 135 (71.8%) 15.70 0.000 Dysphagia 33 (32.7) 83 (43.5) 3.21 0.073 Dyspnoea 5 (5.0) 5 (2.6) 1.09 0.297 Stridor 1 (1.0) 1 (0.5) 0.21 0.646 Tongue elevation 25 (24.8) 60 (31.4) 1.42 0.233 Submandibular swelling 71 (70.3) 159 (83.2) 6.62 0.010 Significantly more patients in the later cohort presented with mandibular infections, and in particular lower third molar infections. Percentages are calculated based on the number of valid cases. Therefore due to missing data, percentages may not correlate with cohort total.

Vitals and Investigations: There were no statistically significant differences in the number of patients presenting with fever, tachycardia, elevated WCC, or increased respiratory rates between the cohorts (see Table 3). Positive blood cultures were rare in both cohorts (one patient in each, p=0.673), and no patients in either group presented with a reduced GCS score. However, more patients in the later cohort recorded C-reactive protein levels above 150mg/L.

Table 2.3. Vitals and Investigations 2003-04 (n = 101) 2013-14 (n = 191) c2 p N (%) N (%) SIRS criteria Fever 20 (19.8) 28 (14.7) 1.27 0.259 Tachycardia 10 (9.9) 33 (17.3) 2.86 0.091 Elevated WCC (>12) 32 (42.1) 94 (54.3) 3.16 0.075 Increased respiratory rate 2 (2.0) 8 (4.2) 0.97 0.324 Blood culture result Negative 19 (18.8) 40 (20.9) 1.54 0.673 Positive 1 (1.0) 1 (0.5) N/A – no culture ordered 81 (80.2) 150 (78.6) Hypotension No (SBP >100mmHg) 75 (97.4) 153 (95.0) 0.73 0.394 Yes (SBP <100mmHg 2 (2.6) 8 (5.0) Reduced GCS GCS > 14 77 (100.0) 161 (100.0) - - GCS < 14 0 (0.0) 0 (0.0) C-reactive protein level 0-150 7 (100.0) 25 (62.5) 3.86 0.050 151+ 0 (0.0) 15 (37.5) Vitals and the results of clinical investigations were similar between the cohorts, with the exception of CRP results. Percentages are calculated based on the number of valid cases. Therefore due to missing data, percentages may not correlate with cohort total. Abbreviations: WCC, white cell count; SBP, systolic blood pressure; GCS, Glasgow Coma Scale

Antimicrobial Therapy: The Therapeutic Guidelines for prescribing antibiotics were followed in 90.8% and 96.7% of cases respectively (p=0.036). However, the number of cases where broadening of antibiotics was required increased from 2% to 10.5% (p=0.009). The most common antibiotic regimen prescribed was amoxicillin plus metronidazole (82.5%), in accordance with the Therapeutic Guidelines. Piperacillin with tazobactam was the most common agent used when antibiotic coverage was broadened. Chi-square analysis of factors pertaining to antimicrobial therapy are presented in Table 4.

Table 2.4. Antimicrobial therapy 2003-04 (n = 101) 2013-14 (n = 191) c2 p N (%) N (%) Antibiotic allergy Known allergy 12 (11.9) 24 (12.6) 0.03 0.866 No known allergy 89 (88.1) 167 (87.4) Therapeutic Guidelines followed Yes 89 (90.8) 177 (96.7) 4.40 0.036 No 9 (9.2) 6 (3.3) Microbiology testing sent Yes 72 (71.3) 151 (79.5) 2.47 0.116 No 29 (28.7) 39 (20.5) Susceptible to empiric prescription Yes 60 (92.3) 134 (98.5) 5.07 0.024 No 5 (7.7) 2 (1.5) Broadening of antibiotics required Yes 2 (2.0) 20 (10.5) 6.84 0.009 No 99 (98.0) 171 (89.5) Discharged on oral antibiotics Yes 96 (95.0) 182 (95.8) 0.09 0.771 No 5 (5.0) 8 (4.2) More patients in the later cohort required broadening of antibiotic therapy. Percentages are calculated based on the number of valid cases. Therefore due to missing data, percentages may not correlate with cohort total.

Treatment Outcomes: No patient deaths were recorded in either group. The time from ED presentation to theatre increased significantly from a mean of 11.0 hours to 15.4 hours (p=0.018). The overall length of stay increased from 3.33±2.0 days to 4.13±4 days (p=0.024). ICU admission also increased from 6.9% to 23.8% (p=0.000). Patients admitted to ICU in the later cohort also remained in intensive care for significantly longer durations (p=0.019).

Discussion: At the RBWH, the number of hospital admissions for surgical management of odontogenic infection nearly doubled over the course of a decade. In the 2013-2014 cohort, the percentage of patients presenting with mandibular infections increased by 20%, and infections involving the lower third molar doubled. This correlates with an increased presentation of trismus and submandibular swelling (50% and 30% respectively); no other clinical parameters were significantly different. Consequently, the percentage of patients requiring ICU admission and the overall length of hospital stay increased in the later cohort.

Odontogenic infections are a preventable disease, but remains a significant burden on the healthcare system. The increased number of admissions for odontogenic infections identified in this study cannot be explained by population growth alone. Queensland had an estimated population growth of 22% from 3.88 to 4.72 million between 2004 to 201442, 43. In contrast, the number of admissions increased by nearly 90%. This suggests problems with current primary prevention strategies and pre-hospital management of odontogenic infections.

Studies from the USA and the UK temporally correlate an increase in ED presentations of odontogenic infections to changes in government policy that restricted access to preventative dental care31, 32. In Australia, accessibility to dental care arguably increased with the Medicare Chronic Dental Disease Scheme (CDDS) funding approximately 5 million dental services between November 2007 to December 201244. However, the majority of patients in this study were systemically healthy, and thus presumably ineligible for CDDS benefits. This indicates a lack of primary prevention strategies targeted to younger and systemically healthy populations. Other potential barriers to dental treatment include fear, cost, mental illness, substance abuse, poor health literacy and perceptions that oral disease is of low importance35.

Despite the increase in incidence, the demographic characteristics of the patient populations have remained largely consistent. There was a slight male predominance and most patients were in their mid-30s with few medical comorbidities. These findings are consistent with previously published data from other Australian states29, 30, 36, 45 and internationally5, 32, 34, 46. The rate of cigarette smoking in both cohorts (70.7% and 57.6% respectively) are much higher than the smoking rate of the general population. According to the Australian Bureau of Statistics, 22.4% of the Australian population smoked in 2001, and the rate dropped to 14.5% in 201447. The higher prevalence of cigarette smoking seen in patients presenting with odontogenic infections is a potential reflection of general health neglect amongst this population48. The number of days from onset of symptoms to hospital presentation remained similar between the two cohorts and the percentage of patients who sought dental treatment prior to hospital presentation remained alarmingly high (41.6% and 44.5% respectively). Nearly two-thirds of patients were prescribed oral antibiotics by either their dentist or general medical practitioner before they presented to hospital (57.4% and 62.8% respectively). Two previous studies of odontogenic infections presenting to major Australian hospitals have identified sub-optimal management of patients by dentists and general medical practitioners as a contributing factor29, 36; some clinicians failed to recognise the need to promptly establish surgical drainage and there was an over-reliance on antimicrobials as the primary mode of management. In a national audit of patients in the UK, 66% of the patients who visited a general dental practitioner prior to their admission received antibiotics only49. A number of patients in this study reported that they were prescribed antibiotics and had their appointments rescheduled because the dentist advised them the acute swelling would render local anaesthetics ineffective, and therefore management involved preliminary use of antibiotics to reduce swelling. This common misconception fundamentally contradicts the principle of establishing early surgical drainage.

As this was a retrospective study, there are some limitations when interpreting the results: missing data, coding errors, inaccessible patient records, and the inability to control potential confounders. Nevertheless, the results indicate that the number of patients presenting with mandibular infections, especially lower third molar infections, has increased significantly over the decade of the study. The percentage of patients who presented with trismus and/or a palpable submandibular swelling also increased. More patients in the later cohort required ICU admission, with an associated increase in overall length of hospital admission. The NICE guideline in 2000 advocated against prophylactic removal of asymptomatic and disease free third molars50, and this could potentially contribute to the increased rate of infection seen in the later cohort. Another reason for the increase in mandibular and third molar infections could be that general dentists may be becoming less confident to perform minor oral surgery. A 2016 survey published in the British Dental Journal51 reported that 64% of dental graduates felt their undergraduate training did not adequately prepare them to perform oral surgery in clinical practice, reporting a lack of support and lack of equipment. Another potential contributing factor, although not reported in literature, is that accommodating and treating patients promptly when they present with an acute infection to a busy general dental practice can be difficult. Dental extractions can be unpredictable and challenging, especially lower third molar extractions, and clinicians may feel tempted to place patients on antibiotics, defer treatment to a later date when more time is allocated, or refer the patient to a specialist for management. This delay in treatment can lead to a more severe course of disease, especially in mandibular infections where there is a potential for development of trismus and the swelling may threaten the airway. As a result, these patients must be managed more cautiously, often requiring invasive intubation techniques such as awake fibre-optic intubation and post-operative ICU support for airway protection. This results in longer hospital stays and ultimately augments the burden on the healthcare system.

The data collected on antibiotic use showed an increase in adherence to the Therapeutic Guidelines for antimicrobial therapy post-admission in the 2013/2014 cohort. There was also a significant increase in the number of cases where broadening of antibiotic therapy was required; this is likely a reflection of the more clinically severe presentations in the later cohort. However, it cannot be emphasised strongly enough that antibiotics are only an adjunct and the key to successfully treating odontogenic infections is prompt surgical drainage. Ongoing effort is required to increase the number of patients being definitively managed by dentists before hospitalisation is required.

The increasing incidence shown in the study outlines that odontogenic infection continues be a significant financial burden on the public health care system. Most of the available data on the financial cost of managing dental infections comes from the United States, and while this does not directly translate to Australian hospitals, it does paint a bleak picture of the monetary burden of late-stage odontogenic disease. The estimated cost per patient for a hospital admission for odontogenic infection in the United States is between $13,590 and $20,2903, 52-54, and another study reported 403,149 ED presentations related to pulpal and peri-apical disease in 2006, resulting in 5721 hospital admissions and costing $160 million55. While an exact figure for odontogenic infections in Australia is not available, it is estimated that a one-night stay in ICU at RBWH costs $450056; therefore the 170 days in ICU required by patients in this study translates to $765,000 in ICU costs alone. Given that hospital admissions for odontogenic infections are avoidable through primary prevention and early intervention, there needs to be a continued effort to improve outpatient management in the early stages of the disease process. This can include improvements to undergraduate training, and continuing education for practicing dentists in the appropriate triage and management of odontogenic infections.

Conclusion: The number of patients admitted to RBWH for surgical management of odontogenic infections has increased in the decade from 2003/2004 to 2013/2014. The severity of symptoms and the number of admissions related to lower wisdom teeth has also increased, as has the average length of stay and the number of patients requiring ICU admission. Despite the change in measures of disease severity, patient demographics remain constant. Both a concerted effort to address the barriers to dental care, and the improved training of medical and dental practitioners in the management of odontogenic infections, are required to alleviate the growing burden of preventable odontogenic diseases on the public health system. Chapter 3: Increasing use of intensive care unit for odontogenic infections over one decade: incidence and predictors

Journal of Oral and Maxillofacial Surgery (2018)

Introduction Odontogenic infections have the potential to result in significant morbidity and mortality37, 57. Early stages of disease are generally well-localised to the affected tooth and respond well to surgical interventions, such as elimination of the source of infection via extraction or root canal therapy58. However, without early surgical intervention, the inflammatory process can erode through the bony cortex of the maxilla or mandible, and spread via direct extension along fascial planes36. Antibiotics alone without surgical drainage is ineffective at altering the course of the disease process59, and as the infection progresses, soft tissues in the face and neck region are displaced to accommodate the accumulating pus and inflammatory exudate58.

The path of spread of odontogenic infection is well documented8. In the maxilla, extension into the canine, buccal and masticator spaces is common60. Although they rarely pose a threat to the airway8, they do have the potential to cause serious complications such as orbital abscess61, cavernous sinus thrombosis17 and cerebral abscess18. In the mandible, the thin lingual cortex in the posterior molar region allows for rapid spread of odontogenic infection into the sublingual, submandibular and parapharyngeal spaces11. Acute upper airway obstruction can occur due to the mass effect of a deep neck infection62, while further spread of the infection via fascial planes can lead to necrotising fasciitis63 and mediastinitis64. In the most severe cases, odontogenic infection can be fatal, usually due to upper airway obstruction or multi-organ failure65. The intensive care unit (ICU) therefore plays a critical role in airway protection and perioperative support for severe cases of odontogenic infections.

The number of patients presenting to emergency departments (EDs) with odontogenic infections is increasing29, 30, 32-34, which is likely due to a number of factors including cost, fear, mental illness, substance abuse, low health literacy and perceptions that oral disease is of low importance35, 66. While some of these patients can be discharged safely from ED for treatment in outpatient clinics, others will require inpatient admission for more urgent incision and drainage. Severity scoring systems have been published to aid clinical decision making in the emergency department, focusing on ‘red flag’ symptoms such as trismus, dysphagia, sepsis and airway compromise67. A percentage of patients with severe odontogenic infections will also require ICU support in the immediate post-operative period following surgical drainage.

The rate of ICU admission for odontogenic infection differs widely amongst literature. Jundt et al reported an ICU admission rate of 14%3, while Ylijoki reported 18%16. A recent retrospective review published by Gams reported 45% of their cohort required ICU admission following surgery68. The difference in reported rates is likely due to different patient populations and local hospital policies, and as the intensive care unit is not standardised across different hospitals, it would be useful to investigate the pattern of ICU use in one institution over a period of time. This paper aims to investigate the pattern of ICU use for odontogenic infections over one decade in a major Australian tertiary hospital and determine: 1) whether utilisation of ICU for patients surgically managed for odontogenic infection has changed over the course of the decade, 2) whether the demographics and clinical presentation of patients admitted to ICU have changed, and 3) whether certain clinical features could be used as predictors for ICU admission.

Materials & Methods: Ethical approval for the project was obtained from the Royal Brisbane and Women’s Hospital Human Research Ethics Committee (ID: EC00172, HREC/14/QRBW/351). A retrospective review was conducted at the Maxillofacial Surgery Department of Royal Brisbane & Women’s Hospital comparing the 24-month period from January 2003 to December 2004 with admission data from January 2013 to December 2014. Patients were identified using the hospital operation record database. Patients who were admitted as an inpatient and underwent a surgical procedure for incision and drainage of an odontogenic infection were eligible for inclusion. RBWH is an adult hospital, and therefore the study population does not include any paediatric patients. Charts were individually reviewed and those admitted to ICU for postoperative support were manually identified.

The following data was de-identified and recorded into an Excel spreadsheet (Microsoft, Redmond, WA, USA) for analysis: 1. Patient outcomes: number of ICU admissions for odontogenic infections, number of days in ICU, overall length of stay. 2. Demographic information: gender, age, Aboriginal & Torres Strait Islander (ATSI) status, smoking status. 3. Comorbidities: diabetes, chronic renal disease, immunosuppression (HIV, leukaemia, lymphoma, neutropenia, organ transplant, current malignancy, corticosteroids for 4 or more weeks at >20mg) and Charlson Comorbidity Index (CCI) score69. 4. Clinical presentation: site of infection, third molar involvement, trismus, dysphagia, dyspnoea, tongue elevation, submandibular swelling, whether antibiotics were prescribed prior to admission, and whether the patient had sought dental treatment for their infection. 5. Vitals and investigations: fever (>38.oC), tachycardia (heart rate >90bpm), altered

respiratory rate (>20 breaths per minute or PaCO2<4.3kPa), peak white cell count (WCC), and C-reactive protein (CRP) level. 6. Medical imaging: use of pre-operative OPG and CT scans, and patterns of imaging requests by clinicians.

The statistical analyses were conducted using IBM SPSS Statistics, Version 24.0.0 (IBM Corporation 2012 ©, Aarmonk, NY, USA). Chi-square analysis was conducted to compare the demographics, admission data, and clinical management of patients in the earlier cohort (2003-2004) with those admitted in the later cohort (2013-2014). Independent samples t-test was used to determine if there was a significant difference in the age, days spent in ICU, or overall length of stay.

Statistical analysis of the clinical features associated with ICU admission was also conducted. Chi-square analysis was used to compare the recorded demographic and clinical characteristics of patients who required admission to ICU with patients who did not require ICU admission. Factors that were significant were considered as potential variables for multiple logistic regression. Third molar involvement, dysphagia, dyspnoea, tongue elevation, CRP, and SIRS status were selected as the most clinically relevant predictor variables for the regression model. Trismus and submandibular swelling were omitted as they were a constant in all patients admitted to ICU. Based on previous research, CRP was selected instead of WCC as it reacts faster to acute infection16 and the two parameters could not both be used due to collinearity. SIRS status was used as it incorporates elevated temperature, heart rate, respiratory rate and WCC while maintaining the most parsimonious model. No significant differences in patient demographics were detected in the Chi-square analysis, and were therefore not included as potential confounders. First, the association between each main effect and the outcome were analysed univariably. Next, a multi-variable model was constructed using the process of backward elimination. Collinearity diagnostics were run to confirm tolerance and VIF values were within acceptable limits, then all candidate main effects were entered into the model and non-significant variables were removed sequentially. At each step, the variable removed was the least significant. The final model was selected when all remaining variables were significant at the p<0.05 level.

Results: In the 24 months between January 2003 and December 2004, 101 patients were admitted to RBWH for incision and drainage of an odontogenic infection, and of these 7 were admitted to ICU. Between January 2013 and December 2014, 191 patients were admitted for surgical management of odontogenic infections, of which 45 required ICU admission. Admission details for the two cohorts are compared in Table 1. This increase in ICU utilisation from 7% to 24% was statistically significant (c2=12.74, p=0.000). No deaths were recorded in either group. The mean number of days spent in ICU increased significantly from 1.7±0.5 in 2003-2004 to 3.24±2.5 in 2013-2014 (t=-3.63, p=0.001). Patients in the later cohort also spent significantly more days in hospital overall, increasing from a mean of 1.7±0.5 days in 2003-2004 to 3.5±4.1 in 2013-2014 (t=2.99, p=0.004).

Table 3.1. Treatment Outcomes 2003-04 (n = 101) 2013-14 (n = 191) c2 p N (%) N (%) Time from ED presentation to theatre 0-12hrs 68 (68.0) 102 (53.7) 8.74 0.013 13-24hrs 25 (25.0) 52 (27.4) 25hrs+ 7 (7.0) 36 (18.9) ICU admission Yes 7 (6.9) 45 (23.8) 12.74 0.000 No 94 (93.1) 144 (76.2) Number of days in ICU 1-2 7 (100.0) 24 (53.3) 5.48 0.019 3+ 0 (0.0) 21 (46.7) Patient returned to theatre Yes 3 (3.0) 11 (5.8) 1.16 0.281 No 98 (97.0) 178 (94.2) Overall length of stay 1-2 days 28 (27.7) 36 (18.8) 9.89 0.020 3-4 days 60 (59.4) 118 (61.8) 5-6 days 12 (11.9) 19 (9.9) 7 + days 1 (1.0) 18 (9.4) Patients admitted between 2013-2014 were more often admitted to ICU, and tended to have a longer overall stay then patients admitted in the earlier cohort. Percentages are calculated based on the number of valid cases. Therefore due to missing data, percentages may not correlate with cohort total. Abbreviations: ED, emergency department; ICU, intensive care unit.

The demographics of patients admitted to ICU in both cohorts were similar with regards to gender, ATSI status, smoking habits, diabetes, and immunosuppression, as per Table 2. The mean age of patients in the 2003-2004 cohort was 34.5±13.8, compared to 37.2±14.4 in 2013-2014. However, this difference was not found to be significant (t=1.60, p=0.158). The clinical presentation of patients admitted to ICU in both cohorts was also similar, with no significant differences detected in any of the signs and symptoms recorded in Table 3. In both cohorts, all patients admitted to ICU had odontogenic infections in the lower jaw, palpable submandibular swellings, and trismus. Of the 52 ICU admissions recorded in total, 67% were related to lower third molars.

Table 3.2. Demographics of Patients Admitted to ICU 2003-2004 (n = 7) 2013-2014 (n = 45) c2 p N (%) N (%) Gender Male 6 (85.7) 28 (62.2) 1.47 0.224 Female 1 (14.3) 17 (37.8) A&TSI No 6 (85.7) 42 (93.3) 0.50 0.482 Yes 1 (14.3) 3 (6.7) Smoker No 1 (20.0) 16 (40.0) 0.76 0.384 Yes 4 (80.0) 24 (60.0) Diabetes No 7 (100.0) 42 (93.3) 0.50 0.482 Yes 0 (0.0) 3 (6.7) Immune suppression No 7 (100.0) 43 (95.6) 0.32 0.569 Yes 0 (0.0) 2 (4.4) No significances in patient demographics were found between the two cohorts. Immune suppression was defined as the presence of HIV, leukaemia, lymphoma, neutropenia, organ transplant, current malignancy, prolonged corticosteroids (4 weeks >20mg) or other significant immunosuppression. Abbreviations: ICU, intensive care unit; A&TSI, Aboriginal & Torres Strait Islander Percentages are calculated based on the number of valid cases. Therefore due to missing data, percentages may not correlate with cohort total.

Table 3.3. Clinical Presentation of Patients Admitted to ICU 2003-2004 (n = 7) 2013-2014 (n = 45) c2 p N (%) N (%) Location of infection Maxilla 0 (0.0) 0 (0.0) - - Mandible 7 (100.0) 45 (100.0) Lower 3rd molar infection No 1 (14.3) 16 (35.6) 1.25 0.264 Yes 6 (85.7) 29 (64.4) Post-op complication No 4 (57.1) 29 (64.4) 0.139 0.709 Yes 3 (42.9) 16 (35.6) Submandibular swelling# No 0 (0.0) 0 (0.0) - - Yes 7 (100.0) 43 (100.0) Trismus# No 0 (0.0) 0 (0.0) - - Yes 7 (100.0) 43 (100.0) Dysphagia No 2 (28.6) 9 (20.0) 0.27 0.605 Yes 5 (71.4) 36 (80.0) Dyspnoea No 5 (71.4) 41 (91.1) 2.30 0.129 Yes 2 (28.6) 4 (8.9) Stridor No 6 (85.7) 44 (97.8) 2.38 0.123 Yes 1 (14.3) 1 (2.2) Tongue elevation No 3 (42.9) 18 (40.0) 0.66 0.719 Yes 4 (57.1) 27 (60.0) Fever (>38.0 oC) No 5 (71.4) 30 (66.7) 0.06 0.803 Yes 2 (28.6) 15 (33.3) Tachycardia (HR>90) No 6 (85.7) 31 (68.9) 0.84 0.361 Yes 1 (14.3) 14 (31.1) Hypotensive (SBP <100) No 7 (100.0) 34 (89.5) 0.81 0.368 Yes 0 (0.0) 4 (10.5) RR>22 or PaCO2<32 No 7 (100.0) 39 (86.7) 1.06 0.304 Yes 0 (0.0) 6 (13.3) No significances in clinical presentation were found for patients admitted to ICU between 2003-2004 and 2013-2014. Percentages are calculated based on the number of valid cases. Therefore due to missing data, percentages may not correlate with cohort total. Abbreviations: HR, heart rate; SBP, systolic blood pressure; RR, respiratory rate; PaCO2, partial pressure carbon dioxide # No statistics could be computed for location, trismus and submandibular swelling because these clinical features were constants in all patients admitted to ICU.

Apart from trismus and submandibular swelling, which were recorded in all patients admitted to ICU, the most common clinical sign on presentation was dysphagia (79%), followed by tongue elevation (58%), fever (33%), and tachycardia (29%). Dyspnoea (12%), hypotension (7.7%), and stridor (4%) were uncommon. 37% of patients met the criteria for SIRS. Only one patient returned a positive blood culture, and no patients recorded a reduced GCS score.

The number of patients with CT scans increased significantly from 42.9% in 2003-2004 to 93.3% in 2013-2014 (c2=13.25, p=0.000). As this increase seemed substantial, the dataset was re-examined to determine if this trend was limited only to patients admitted to ICU or whether it was observed in all admissions for odontogenic infections over the study period. The increased uptake of CT scanning was more pronounced when comparing all admissions, with only 6% of patients in 2003-2004 sent for CT scans preoperatively compared to 79% in 2013-2014 (c2=142.08, p=0.000).

A multiple regression model was used to determine which factors were associated with ICU admission, as per Table 4. The demographic data of patients admitted to ICU was compared to those who did not require ICU, and the results of the Chi-square analysis are available as Supplemental Table 1. Based on the results of the preliminary analysis, third molar involvement, dysphagia, dyspnoea, tongue elevation, CRP, SIRS status, and CT scans were selected as the most clinically relevant predictor variables for the regression model. While all variables were found to be significant in the univariate analysis, the results of the multivariable analysis suggest that lower third molar involvement (p=0.026), dysphagia (p=0.020), and CRP levels exceeding 150mg/L(p=0.039) are the most significant clinical predictors of ICU admission (c2 = 16.43, p =0.001), with the final model accounting for 40.4% of the variation in ICU admissions. Patients admitted to ICU were approximately 6.5 times more likely to have lower third molar infections or dysphagia, and 5 times more likely to present with CRP levels over 150mg/L.

Table 3.4. Multiple logistic regression modelling of predictors of ICU admission Parameter Crude OR (95% CI) p value Adjusted OR (95% CI) p value Lower 3rd molar 4.15 (2.19, 7.87) 0.000 6.41 (1.25, 33.33) 0.026 Dysphagia 8.26 (4.02, 16.97) 0.000 6.49 (1.33, 31.25) 0.020 Dyspnoea 7.63 (2.07, 27.77) 0.002 Removed - Tongue elevation 5.15 (2.74, 9.71) 0.000 Removed - SIRS 3.03 (1.56, 5.88) 0.001 Removed - CRP 151+mg/L 4.50 (1.21, 16.67) 0.024 5.00 (1.08, 22.72) 0.039 CT scan 7.35 (3.18, 16.95) 0.000 Removed - c2 = 16.43, p =0.001, R2 = 40.4%

Discussion At RBWH, the percentage of patients admitted to ICU following surgical management of odontogenic infection has increased by 3.4-fold over the course of a decade. Patients admitted to ICU in the later cohort had a longer average stay in ICU, as well as a longer overall hospitalisation. Despite the increase in incidence, there was no statistical difference in terms of patient demographics or clinical presentation comparing the two cohorts. Dysphagia, lower third molar involvement and CRP over 150mg/L were found to be significant predictors for ICU admission.

Rates of ICU admission vary widely in reported literature, ranging from 14% to 45%3, 16, 68. Our most recent ICU admission rate of 24% falls in the middle of this range, but has seen a huge increase from only 7% in the previous decade. A similar study conducted in Helsinki comparing odontogenic infections one decade apart also found a significant increase of ICU admission rate from 11% to 32%5. Their length of stay in ICU was 2 days in 1994-1995, and 3 days in 2004-2005, and although this increase was not statistically significant, it appears this general trend of increased ICU use is not isolated to RBWH.

Population growth may be a potential contributor to the increased ICU admission rate observed. Queensland’s population grew by 22% from 3.88 million to 4.72 million in the 10-year period of our study42, 43. The clinical severity of patients presenting with odontogenic infections to RBWH over the decade of the study also worsened slightly, which may have also contributed to the higher number of ICU admissions. The percentage of patients presenting with mandibular infections increased by 20%, and the percentage of patients presenting with a lower third molar infection doubled. This was associated with an increased percentage of patients presenting with trismus and submandibular swelling. Since mandibular odontogenic infections are more likely to threaten the airway62, this increased incidence could account for some of the increased ICU admissions. However, no other clinical parameters were significantly different amongst the two cohorts; rates of dysphagia, dyspnoea, stridor and tongue elevation were similar between the groups. The demographics of the population in terms of age, gender and medical comorbidities between the two decades was also not significantly different, and therefore the 3.4-fold increase in ICU admission is not adequately explained by population growth and worsened clinical severity alone.

We hypothesise that one potential contributor to the increased rate of ICU use was the significant increase in CT scanning over the decade. CT has gained wide spread use as the imaging modality of choice for deep neck-space infections in an emergency setting, as it overcomes the field of view limitations of ultrasonography, and is less time-consuming and more accessible than MRI70. The overall rate of pre-operative CT scanning for odontogenic infections at the RBWH has increased from 6% in the earlier cohort to 79% in the later cohort, and for 58% of patients admitted between 2013-2014, CT scanning was the initial imaging modality requested in preference to OPG. 91% of these CTs were ordered by ED or referring hospitals, and 89% were ordered prior to clinical review by a maxillofacial surgery registrar. Amongst patients with maxillary infections, 55% had a pre- operative CT ordered in addition to OPG. These figures show a significant change in the way CT scans are being ordered at the RBWH.

Like any imaging modality, CT scans have certain limitations. Multiple studies have examined the positive predictive value of CT scans with intraoperative findings in deep neck space infections. Lazor et al reported CT scans have a positive predictive value of 76% for deep neck space abscesses, with a false positive rate of 13.2%26. Freling et al reported a similar positive predictive value of 82%; however when there is a lack of rim enhancement, or when the collection is smaller, the positive predictive value diminishes71. Smith et al reported a negative exploration rate of 25%, and stressed that although CT can add valuable information, the decision to surgically drain a neck space abscess should be made clinically25. The importance of a thorough clinical history and examination has been validated in literature. A study by Rosenthal et al24 that compared pre-operative CT and surgical findings found that the diagnostic accuracy of maxillofacial surgeons reviewing the CT was higher than the radiologist, likely due to the fact that the surgeons were able to correlate radiological evidence with the findings of the clinical examination, whereas the radiologist relies on imaging alone.

We also hypothesise that the significant increase in pre-operative CT scans can have a flow-on effect in the way clinicians subsequently manage these patients. Deep tissue changes that were previously not visualised are now readily seen on CT scans, and subtle changes in upper airway anatomy seen on imaging have the potential to make clinicians more wary of potential airway difficulties and resort to more invasive intubation techniques. These patients are then more likely to remain intubated and sent to ICU for airway protection. Radiographic demonstration of swelling of the upper airway anatomy in the axial plane can also influence the length of intubation in ICU and lead to an increased length of stay in ICU. We hypothesis that in the earlier cohort, due to the very low rate of CT use, clinicians relied more on physical examination and clinical judgement in order to establish whether a patient can be safely extubated at the end of surgery. It is possible that more patients would have gone to ICU in the earlier cohort if CT scans were being ordered at a similar rate.

CT scans undoubtedly will continue to be an invaluable imaging modality when assessing undifferentiated swelling in the neck. However, we argue that when a patient presents to ED with clear history of dental pain suggestive of odontogenic infection, a clinician with a good understanding of the disease process and fascial spaces should be able to accurately diagnose and triage most cases. OPGs allow for rapid identification of large carious lesions and periapical abscesses62, and should be the first line imaging modality for these patients. Source control should be performed regardless of whether the causative dental pathology is associated cellulitis, or a drainable collection, and early surgical consultation should be sought in order to guide patient management. An efficient pathway in the management of odontogenic infections will prevent deterioration of the condition to the point where ICU admission is required. The cost of one night of ICU stay at RBWH is estimated to be $450056. The estimated cost of ICU stay alone in our study amounts to $765,000. Given that odontogenic infection is a preventable disease, optimisation of primary prevention, pre-hospital care and efficient triage and management of the disease remains a priority.

Conclusion The use of ICU in the management of odontogenic infection has increased significantly at the RBWH over a decade. The demographics and clinical presentation of the patients admitted to ICU remains the same. ICU length of stay and total length of stay have both increased. Third molar infections, dysphagia and elevated CRP are strong predictors of ICU admission. There was a significant increase in CT usage for odontogenic infections over a decade, with the majority of these scans ordered by referring clinicians prior to surgical review. More judicious use of CT scanning, combined with prompt surgical consultation and intervention, may reduce the rate of ICU admissions for odontogenic infections.

Chapter 4 Thesis Conclusion This thesis describes the only cross-sectional study regarding how the presentation and management of odontogenic infection in a tertiary Australian hospital changed over the course of a decade. It highlights the fact that odontogenic infection remains a significant public health issue, and ongoing effort is needed to improve primary care and early intervention in the community. Furthermore, optimisation is required in the tertiary care of these patients, especially with regards to reducing unnecessary imaging and reducing ICU admission.

Key Findings Increasing Prevalence of Odontogenic Infection The data presented in this thesis clearly indicate the burden placed on the public health system by odontogenic infections not only remains significant, but has increased over the last decade. Comparing our two cohorts, the number of hospital admissions for surgical management of odontogenic infections nearly doubled over the course of a decade. This increase cannot be attributed to population growth alone, as Queensland’s population only grew by 22% during the same time period42, 43. Similar trends of increasing hospital presentations for odontogenic infections is seen in the UK and the USA31, 32. Odontogenic infection is a preventable disease and attention needs to be drawn to the fact that our current Australian policies and measures in primary prevention are failing.

Demographics and Clinical Presentation The demographics of patients being treated remains largely consistent: slight male predominance, mostly in their mid-30s, and with few medical comorbidities. This is in keeping with multiple international epidemiology studies done on odontogenic infections5, 32, 34, 46. In the later cohort, there is a higher percentage of patients being treated with mandibular infections, especially third molar infections. There are more patients presenting with trismus and palpable submandibular swellings in the later cohort. This has led to more patients requiring broadening of antibiotics during the course of their hospital admission.

There are a few hypotheses for the higher percentage of patients being treated with mandibular infections and third molar infections in the later cohort. The NICE guidelines, introduced in the UK in 2000, recommends against prophylactic removal of asymptomatic third molars50. This could have had some follow-on effects in Australia. The other hypothesis is that general dentists are de-skilling in terms of minor oral-surgery. This was reflected in a UK study where new graduate dentists felt underprepared to perform minor oral surgery51. Conducting a similar Australian study would be useful in assessing whether this is applicable to Australian dentists. Given that prompt source control remains the top priority in managing odontogenic infection, one would infer that earlier intervention and treatment provided by a general dentist would result in less inpatient management required at a tertiary hospital level.

The emergence of antibiotic resistance is a salient topic. This study identified that a significant proportion (44.5%) of patients who required surgical management of odontogenic infection sought care from a dentist prior to hospital presentation, and alarmingly, 62.8% were prescribed antibiotics without establishment of surgical drainage. Antibiotics certainly play a role in the management of odontogenic infections, but this should not delay prompt surgical management. Improved education of primary care providers is required to address this issue.

Predictors of ICU Admission Our study has found a significant increase in the utilisation of ICU for the management of odontogenic infections, with a 3.4-fold increase in ICU admissions in the later cohort. The most significant predictors of ICU admission were lower third molar involvement, dysphagia and CRP levels exceeding 150mg/L. CRP has been implicated in other studies to be associated with a more severe disease course16. These clinical predictors can be useful in terms of initial triaging and assessment of patients presenting with odontogenic infection, alerting clinicians to patients that potentially require closer monitoring and prompt surgical intervention.

Increasing Use of CT Imaging There has been a significant increase in the use of CT scans in the management of odontogenic infection at RBWH. The percentage of patients who had a CT scan increased from 6% to 79% in the later cohort. The increasing availability of CT scans has not necessarily resulted in improved treatment outcome, as ‘time to theatre’, ‘ICU admission’ and ‘length of stay’ all worsened in the later cohort. We hypothesise that increased use of CT scans has a flow-on effect in the subsequent management of patients with odontogenic infection. Radiographic changes that otherwise would have not been visualised are potentially causing clinicians to treat patients over-cautiously. This has the potential to contribute to the worsening clinical outcomes in the later cohort. This study has identified a clear need for an improved treatment algorithm for patients presenting to the emergency department. Emphasis needs to be placed on appropriate imaging and prompt surgical consultations from the oral and maxillofacial surgery unit.

Recommendations and Potential Future Strategies The research presented in this thesis and its subsequent analysis allows us to make several recommendations in order to reduce the prevalence of odontogenic infections in Australia. They are summarised in Table 4.1.

Table 4.1 - Key Recommendations for Prevention of Odontogenic Infections Pre-Hospital Care • Improved primary prevention programs that target young, healthy individuals in the community • Improved education in primary prevention and management of acute infection for training dentists at a university level • Emphasis on prompt surgical drainage when patients initially present to the community dentist, either via pulp extirpation or tooth extraction • Improved dentist training in performing minor oral surgery, giving clinicians more confidence to intercept early infections • Improved dentist training in appropriate antibiotics use, with emphasis on its role as adjunct therapy to prompt surgical drainage Post-Hospital Care • Improved education of ED physicians in the assessment and management of odontogenic infections • Implementation of a treatment algorithm for ED triaging • Identify high risk patients more likely to have a severe course of infection – third molar infection, dysphagia, CRP >150mg/L • Reduce unnecessary CT scans – thorough clinical examination and OPG should be first line in most presentations • Appropriate use of empirical antibiotics as per local hospital guidelines, and avoid unnecessary broadening of antibiotics when not indicated

Pre-Hospital Care According to the Australian Bureau of Statistics, in 2013 to 2014, there were 12633 hospitalisations due to dental conditions72. Roughly $10 billion is spent on dental services per year, and many Australians face financial barriers in accessing dental services73. Alarmingly, around one-third of Australians aged over 5 years avoided or delayed visiting a dentist due to cost, and 20% who visited a dentist in the last 12 months were unable to proceed with recommended treatment due to cost73. The current Australian government strategies of primary prevention revolves around water fluoridation and fissure sealants in addressing early childhood caries73. This leaves the key demographic identified in our stu dy vulnerable – healthy individuals in their 30s, with a significant proportion facing financial barriers to dental treatment. Primary prevention schemes targeting this demographic group should be considered. A potential option would be a similar scheme to the Medicare Chronic Disease Dental Scheme (CDDS), with the government providing dental treatment vouchers for Australians turning 30, to be accessed and used within 12 months. This has the potential for early interception of disease, and the cost can be recuperated by avoiding lengthy and expensive hospitalisations.

To our knowledge, there is no literature on the topics of emergency management, and incision and drainage of odontogenic infections targeting primary care dentists. In a 2016 study looking at confidence levels of graduating dentists in Cardiff University, ‘surgical extractions involving flap’ and ‘simple surgical procedures’ ranked lowest amongst all procedures51. Dental students at an undergraduate level may have limited exposure to acute presentations of facial swelling and its management. Coupled with low confidence in carrying out surgical procedures, it is understandable that young graduate dentists may prefer to refer patients into hospital for management. There needs to be an emphasis at an undergraduate teaching level on the assessment and management of odontogenic infections. Students should have real-life exposure at a tertiary hospital, shadowing a maxillofacial registrar and attending emergency department consultations for patients presenting with acute infections. Workshops and seminars dedicated to odontogenic infection, with specific emphasis on the anatomical spread of odontogenic infections, as outlined in Chapter 1 of this thesis, is recommended. Practical skills of incision and drainage of small collections can be taught at hands-on workshops. For dentists in the community, it is important to address some common misconceptions regarding odontogenic infections, emphasising early surgical management, rather than deferral and prescription of oral antibiotics. We have created an information poster, targeting general dentists, addressing these common misconceptions (see Figure 4.1). While it is common for medical practitioners to telephone the hospital switchboard to obtain phone advice, in our experience, it is uncommon to receive similar requests from community dentists. Patients are often sent to the emergency department with or without a referral letter. This lack of communication leads to lengthy wait times for patients in the emergency department, as well as delaying urgent patients that need prompt management. Continuing education courses addressing the practical aspect of emergency management should be offered to community dentists by local maxillofacial surgery units. This can allow referring dentists to meet hospital registrars in person, and facilitate better communication for future referrals.

Figure 4.1 – Patients with facial swelling in dental practice: common misconceptions

Post-Hospital Care A recent Australian study explored the knowledge and confidence of ED physicians managing common dental emergencies, and found 38% failed knowledge tests, and alarmingly 40% answered incorrectly to a question regarding Ludwig’s Angina74. The authors concluded that further training in dental emergencies is warranted amongst ED physicians. Our study has identified a large increase in the use of CT scans in the diagnosis and triaging of odontogenic infections in the emergency department. This could be a reflection of the lack of understanding and confidence in the emergency setting, with a reliance on CT scans for diagnosis. To address this, we propose a treatment algorithm targeting the initial assessment and management of patients presenting with dental pain to the hospital. The emphasis is placed on safe triaging and appropriate investigation for patients in the ED environment. For the vast majority of patients presenting with dental pain, only OPG radiographs are warranted. By following this treatment algorithm, only a small percentage of patients presenting with dental pain will receive a CT scan, and only after discussion with an on-call maxillofacial surgery registrar (see figure 4.2). Hospital emergency departments have a high turnover rate of junior medical doctors. A bi-annual seminar or work-shop on the management of odontogenic infection should be run by the maxillofacial surgery department in order to improve patient care and streamline referrals.

Figure 4.2 – Treatment algorithm for patients presenting with dental pain to the emergency department

Further Research This study has identified the increasing use of CT scan as a potential contributor to the increase in ICU admission and increase in overall length of stay for patients being managed for odontogenic infections. This warrants future prospective research in terms of setting clear clinical indicators for requesting CT scans, and whether reducing CT scan rate will lead to a decrease both in terms of financial and clinical burden for treatment of odontogenic infections. The treatment algorithm proposed in this thesis can serve as a basis for such future prospective studies. A submission for publication of this treatment algorithm in a peer-reviewed emergency medicine journal is being planned. Furthermore, there is a lack of literature targeting community dentists regarding the acute management of odontogenic infection, specifically the anatomy of spread and the practical aspect of incision and drainage. This is a target for future publication, as well as studies assessing dentists’ confidence in management of odontogenic infections following improved efforts in undergraduate education and post-graduate continuing education courses.

Final Thoughts This thesis has demonstrated that odontogenic infections remain a significant public health burden in Australia. The demographics of the patients affected have remained the same, but the prevalence and outcome have worsened. There needs to be a continued effort placed on improving primary care of this preventable disease, and streamlining tertiary care provided to these patients once they are admitted to hospital. The dogma of accurate clinical assessment and prompt surgical drainage remains critical in the management of these patients.

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