Adult periodontitis treated with a new device for subgingival lavage-a randomized controlled clinical trial using a split-mouth design

Objectives : To evaluate in patients with untreated adult periodontitis, the effect of treatment with a novel pocket irrigator/evacuator device (IED) compared to conventional subgingival debridement (CPT), both provided during the initial phase of active periodontal therapy. Methods : This study was an examiner-blind, randomized controlled clinical trial using a split-mouth design. Systemically healthy patients with adult periodontitis were selected. Full-mouth probing pocket depth (PPD), gingival bleeding on pocket probing scores (BOPP), gingival recession (REC) and dental plaque (PI) were assessed at base-line. All participants received oral hygiene instructions and supragingival prophylaxis including polishing. In 2 randomly assigned contra-lateral quadrants, approximal sites were irrigated


| INTRODUC TI ON
Periodontitis is one of the most common chronic inflammatory diseases in humans, characterized by gingival inflammation and periodontal tissue breakdown.Loss of alveolar bone support ultimately results in loss of teeth. 1 The most important risk factor for periodontitis is the accumulation of a plaque biofilm at and below the gingival margin within which dysbiosis develops and which is associated with an inappropriate and destructive host inflammatory immune response. 2Periodontitis is a ubiquitous disease affecting over 50% of the world's adult population, the occurrence of which increases with age. 3 Severe periodontitis is the sixth most prevalent human disease, with a standardized prevalence of 11.2% 4 according to the 2010 global burden of diseases study, and a major cause of tooth loss.It has a negative impact on oral health, quality of life, speech, nutrition, confidence and overall well-being and is independently associated with several systemic chronic inflammatory diseases.Periodontitis, therefore, represents a significant public health concern. 2 The goals of periodontal therapy are to preserve, improve and maintain the natural dentition.The majority of patients can retain their dentition over their lifetime with appropriate treatment, selfperformed dental plaque control and continue maintenance care. 5riodontal therapy consists of the elimination of the biofilm by supra-and subgingival cleaning, and if necessary the reduction in the residual deep periodontal pockets by surgical treatment.Subgingival instrumentation of the teeth is performed with curettes or with an ultrasonic device.Ultrasonic scalers are operated with a water flow that serves several purposes, including the reduction in frictional heating of the scaler tip.A documented benefit of the flowing water is the generation of biophysical forces-namely cavitation and microstreaming. 6Meticulous subgingival debridement is an inherently time-consuming and difficult procedure, and it requires a great deal of stamina on the part of the operator as well as the patient.Success is highly dependent on the skill of the clinician and the attention to detail in instrumentation. 7merous studies from the past decade address the impact of subgingival irrigation on clinical and microbiologic parameters. 8vestigations using subgingival irrigation as a monotherapy and in combination with root planing provided a perspective on the benefits and limitations of this treatment method. 9The biological rationale for subgingival irrigation is a non-specific action of flushing the pocket contents and thereby effectively altering the quality and quantity of unattached subgingival plaque. 10The pocket penetration by powered oral irrigation devices was found to be 71% for shallow sites, 44% for moderately deep sites and 68% for deep sites, with a maximum pocket penetration of 4-5 mm.Using specially designed subgingival irrigation tips placed 1 mm below the gingival margin, irrigants can access 90% of the depth of 6 mm pockets and 64% of the depth of pockets exceeding 7 mm. 11The American Academy of Periodontology (AAP) 12 concludes that there is insufficient evidence to support one-time, professionally provided subgingival irrigation even as a supplemental procedure to augment the effects of scaling and root planing.The aim of this study was to evaluate in patients with adult periodontitis, the effect of this novel pocket irrigator/evacuator device without subgingival instrumentation, compared to conventional periodontal treatment using a combination of subgingival ultrasonic and hand instrumentation, both provided during the initial phase of active periodontal therapy.

| MATERIAL AND ME THODS
The recommendations for strengthening the reporting procedure were followed as suggested by the guideline Consolidated Standards of Reporting Trials (CONSORT) and the checklist Template for Intervention Description (TIDieR), as retrieved from the EQUATOR Network (available at: https://www.equator-network/org/reporting-guidelines).

| Design
The experiment used a split-mouth model in which contra-lateral quadrants were randomly assigned to the test treatment of irrigation or the conventional mechanical periodontal therapy as control. 13All measurements were performed under identical conditions by one and the same clinical examiner (MAL) who was blinded to the assigned treatment.Randomization was performed using true random numbers, which were generated by sampling and processing a source of atmospheric noise (available at: https://www.random.org).
The randomization code was kept in a sealed envelope in the investigator site file and was only accessible to the coordinator (LJvD), who was therefore responsible for allocation concealment.Records of earlier examinations were not available to the examiner at the time of re-examination To further conceal the intervention from the examiner, the participants were instructed not to reveal their assignment in any way.Professional instructions and instrumentation took place in an area separate from that of the examiner (Figure 1).

| Participants
Consecutive patients with adult periodontitis who had been referred in the period of October 2010 up to June 2012 by general dentists to the Clinic for Periodontology Groningen (The Netherlands) were verbally invited to participate.Upon receiving a positive response, written detailed information about the outline, purpose and duration of the study was provided.Participants were asked to read this information carefully and if willing to participate they were requested to sign the informed consent.Those who consented were scheduled for a baseline clinical assessment.
Eligible participants were defined by the following criteria: 1. antibiotic medication within 3 months preceding the start of the study;

use of other medication (such as anti-inflammatory medication)
that might affect the outcome of the study;

| Conventional subgingival debridement (CPT)
The ultrasonic scaler (Piezo Master 400, EMS ® ) with metal EMS tips (P, PS, PL3) was used underwater irrigation according to the manufacturer's instructions.At the decision of the dental hygienist, this was followed by the use of an assortment of manual periodontal curettes (Gracey, SG # 11/12, 13/14, Hu-Friedy Ins.Co.).The curettes were sharpened as the operator deemed necessary.Conventional subgingival debridement was finished when the operator felt the surface to be smooth.Local anaesthesia was used according to the patients' needs (Septanest N 40 mg/ml, Septodont ® , Saint-Maur-Des-Fossés, France).

| Novel pocket irrigator/evacuator device (IED)
Introducing an irrigation fluid into the periodontal pockets results in a positive pressure towards the base of the pocket, which likely prevents the fluid from reaching the entire subgingival area.With this novel irrigation device, a light negative pressure of 0.35 mm Hg is applied with the nozzle at the entrance of a periodontal pocket thus removing subgingival fluid from the pocket (see Figure 2A).Alternatingly, irrigation fluid is applied by a thin hose which is located in the centre of the nozzle (see Figure 2B).In this study, demineralized water was used as the irrigation fluid.The negative pressure alternating with the application of fluid was repeated at a high frequency of 250 milliseconds per cycle.

| Clinical measurements
The primary clinical outcome measured was a change in probing pocket depth.Bleeding upon probing and recession were considered as secondary outcomes.As the treatment effect is known to be dependent on the level of oral hygiene, 14 dental plaque was scored as a surrogate parameter providing an indication of the participants' compliance with instructions in daily oral self-care.
The following clinical measurements were performed at baseline before the initial therapy and at the 3-month evaluation visit.Six sites around each tooth were scored (mesio-buccal, buccal, disto-buccal, mesio-palatal, palatal and disto-palatal).The PPD, BOPP and REC were measured using a periodontal probe with William's markings (PQW, Hu-Friedy Ins.Co.).Pocket probe readings were rounded off to the nearest millimetre.All measurements were performed by one examiner (MAL) who was blinded to the assigned treatment.

| Study outline
The flow of the treatment as provided is presented in Figure 3.At the baseline assessment, the clinical situation was assessed by the examiner (MAL), and appointments for active periodontal therapy were made.Treatment was provided by a dental hygienist with 3 appointments over the course of 3 consecutive weeks.These visits included repeated oral hygiene instructions as well as supragingival scaling and polishing.Two contra-lateral quadrants (one in the upper and one in the lower jaw; either 1st and 3rd or 2nd and 4th) were treated subgingivally in the conventional mechanical way using both ultrasonic and hand instruments and served as control sides (CPT).
In the opposing contra-lateral quadrants, the subgingival pocket areas were irrigated by the dental hygienist with the novel irrigation device (IED).The irrigation nozzle was applied for 10 seconds at each interproximal site and approached both from the buccal and palatal aspect.Treatment was provided twice a week for a period of 3 consecutive weeks.
During an intermediate appointment with the dental hygienist, 1 month prior to the final evaluation of the full-mouth dentition was scaled and polished supragingivally.Assessment of the periodontal condition was performed 3 months after the last treatment by the same examiner (MAL).

| Power calculation
Recent data indicate that the intra-individual standard deviation in mean PPD measurements is 0.48. 17

| Statistical analysis
With the irrigation nozzle primarily applied at the interdental aspect, the data of 4 sites were used for the purpose of this study, namely the interproximal sites (mesio-buccal, disto-buccal, mesio-lingual and disto-lingual).Four repeated outcomes were calculated from the multiple repeated measures on all of the teeth, by taking either an average (for the numerical and ordinal outcomes) or a sum (for binary outcomes).They were calculated per treatment for each follow-up time (baseline and one follow-up).For numerical (PPD and REC) and ordinal values (plaque scores), a linear mixed effects model was applied, while for binary outcomes (bleeding score), a generalized linear mixed model was applied.Restricted maximum-likelihood estimation was used for the linear mixed effects model, and generalized estimating equations (GEE) were selected for the generalized linear mixed model.Each of the 4 results has a mean which may be differently affected by smoking (0 = participants who had not smoked for at least 1 year, 1 = smokers who smoke 1-10 cigarettes a day, 2 = smokers who smoke more than 10 cigarettes a day).To address correlation between the repeated values, an unstructured variancecovariance matrix was applied to follow-up time with an additional correlation coefficient for the treatments in case of numerical values.An exchangeable working correlation matrix with the empirical estimator was applied with GEE for the analysis of binary variables, using a binomial distribution with logit link function.Based on the fitted model, appropriate contrast statements were created to determine the effect of treatment with respect to the baseline results as well as whether the effect size between the 2 treatments was different.Effect sizes with a P-value smaller than .05were considered significant.Analysis was performed per protocol.

| Ethics approval
The study followed instructions based on the Helsinki principles (2008).The protocol was independently reviewed and approved by the Medical Ethics Committee of the University Medical Centre Groningen under the number NL31743.042.10.

| RE SULTS
Of the 28 patients with adult periodontitis who were enrolled in the study, the data of 3 were excluded because they were prescribed antibiotics during the course of the study, thus leaving 25 patients for the study, consisting of 12 females and 13 males with a mean age of 46 years (range 34-67).Of these patients, 15 were non-smokers, 4 were light smokers and 6 were heavy smokers.
The plaque score data are presented in Table 1 and show that the level of oral hygiene at baseline for the control and test quadrants was comparable (P = .286).Self-performed oral hygiene improved = sub-gingival debridement with mechanical instruments.The assigned quadrants were divided into several segments which wee treated separately over the three sessions.
= sub-gingival lavage with irrigator/evacuator device of all approximal sites in the assigned quadrants and repeated in the five consecuƟve sessions.significantly in both sets of contra-lateral quadrants (P < .001).The incremental difference between treatments was −0.029 and not significantly different (P = .571).

3-mo
The data for approximal sites only are presented in Table 2 with a subanalysis for pockets initially measuring 4-5 mm and ≥5 mm.At baseline, the mean approximal PPD was 4.37 and 4.46 mm for the control and test treatment sites, respectively, which was not significantly different (P = .425).At 3 months, a significant reduction was observed in both sets of contra-lateral quadrants as a result of treatment (P < .001).The incremental difference between both sets of contra-lateral quadrants of 0.19 mm was significantly different (P = .009)in favour of the control treatment.
The bleeding upon probing data are presented in Table 3.At baseline, the mean BOPP was 72% and 69% for the control and test treatment sites, respectively, which shows that the level of periodontal inflammation at baseline was not comparable (P = .033)with a slightly higher number of bleeding sites in the control group.As a result of treatment, bleeding scores improved significantly in both sets of contra-lateral quadrants (P < .001).
The data with respect to visible gingival recession are presented in Table 4 and show that the position of the gingival margin at baseline was comparable (P = .106)for the control and test treatments.
As a result of treatment, REC increased significantly in both sets of contra-lateral quadrants (P = .031and P = .006for the control and test treatments, respectively) but the incremental difference of 0.031 mm between treatments was not significant (P = .533).
The subanalysis by smoking status revealed that the incremental difference between the control and test treatments for plaque scores The incremental difference between contra-lateral sides was, however, significant for the decrease in PPD and BOPP scores in favour of the CPT (Table 2).The absence of a difference in REC indicates that the reduction in PPD is probably the result of a gain in clinical attachment level.The results were likely not influenced by the level of self-care because incremental differences in plaque scores were comparable in both sets of contra-lateral quadrants.Optimal supragingival plaque control was secured through individual oral hygiene instruction as is evident from the plaque scores, which dropped in both the control and test quadrants with 70%.In addition, all participants in the present study were subjected to supragingival scaling.
The mean reduction in PPD for the control treatment, which represented conventional active periodontal therapy, in pockets of ≥5 mm was 1.71 mm.This compares favourably with the estimated mean outcome of subgingival debridement as estimated in a metaanalysis by Van der Weijden & Timmerman. 18These authors calculated that in pockets≥ 5 mm, a mean decrease of 1.18 mm in probing pocket depth may be expected.The mean results for the control treatment can also be considered comparable to those reported by Cobb. 19Based on various clinical studies published over several decades, he calculated the mean reduction in PPD for pockets initially measuring 4-6 mm to be 1.29 and 2.16 mm for pockets of ≥7 mm.
Also for the test treatment, the mean reduction of 1.27 mm in pockets of ≥5 mm is comparable to above-mentioned average outcomes.
Rinsing alone has been found to be an ineffective means of penetrating into periodontal pockets.Subgingival irrigation devices are suggested to improve access to pockets. 20The intentional irrigation of a gingival crevice or pocket, with the point of delivery directed below the gingival margin, aims at disrupting bacterial colonization and growth.Lainson et al 21 suggest that improved gingival health after oral irrigation may be the result of altered microbial viability, while Hagiware et al 22 show that pocket irrigation by distilled water is potentially effective in eliminating subgingival plaque.The 2 approaches for the application of subgingival irrigation are either daily irrigation by the patient as part of a home-based oral hygiene programme and periodic, professionally administered application of irrigation. 23e present study evaluated subgingival irrigation/evacuation as a monotherapy in the treatment of periodontitis for which there is a paucity of data available.When aimed perpendicular to the tooth long axis, an irrigation device creates 2 zones of hydrokinetic activity which aid in the removal of plaque and debris.The first zone is due to the initial direct impact of spray against the tooth.A second zone is created by the deflection of spray from the tooth surface and results in a flushing action.The turbulence is further heightened as a portion of the stream impacting on the specimen bounces back into the emerging stream. 24As irrigation does not routinely project fluid into deep pockets, devices usually provide a pulsating stream of water that incorporates a compression and interpulse decompression phase.The decompression phase is included to facilitate the displacement of debris and bacteria.A continuous flow of water would cause constant tissue compression and impede the escape of contaminants. 25The novel IED in the present study goes beyond a decompression phase and utilizes a high-frequency change in evacuation and irrigation to cause a hydrokinetics turbulence with the intention to flush out the subgingival biofilm.
Smoking is also implicated as a factor that reduces the effectiveness of treatment.It appears that smokers may respond to non-surgical periodontal therapy less favourably than non-smokers, especially in terms of probing depth and bone level.When the effect of the level of cigarette consumption is considered, it seems that the response to periodontal therapy is related to the amount of cigarettes smoked. 26In agreement with this, the present study showed that the largest incremental difference in PPD was observed in nonsmokers.At baseline, there was no significant difference between the BOPP scores of smokers and non-smokers.This observation is in agreement with Van der Weijden et al, 27 who also found no statistically significant differences between smokers and non-smokers regarding the mean percentage of sites that bled upon probing in untreated periodontitis patients.Recently, Ramseier et al 28 observed in patients enrolled in supportive periodontal therapy for at least 5 years that, concomitantly with an increased prevalence of residual pockets, smokers demonstrate a lower mean BOPP.In the present study, no significant incremental difference in treatment response between smokers and non-smokers was observed.

| Limitation
-Penetration into deep pockets may have been easier than into moderate pockets because of the more advanced tissue inflammation in the former. 29However, the results of this study did not show a predictable factor in enhanced penetration of the irrigation fluid to the bottom of the pocket.The major difference between the control and test treatments was found in pockets of ≥5 mm, which include deep pockets (Table 5).
-Application of the irrigator/evacuator was combined with supragingival scaling and polishing which may also have impacted the subgingival biofilm. 30ith conventional active periodontal therapy, the supragingival and subgingival biofilm and the calculus are mechanically removed by scaling and root planing. 31Possibly, the lack of calculus removal negatively affected the outcome of irrigator/evacuator therapy.On the other hand, Listgarten & Ellegaard 32 show that epithelial adhesion in principle can take place on calculus.The root cementum of periodontitis involved teeth has been shown to contain cytotoxic products of bacterial origin, that is endotoxins, which have been suggested to prevent proper healing following periodontal therapy. 33With the irrigator/evacuator, no diseased cementum was removed.However, endotoxin is lightly bound to the root surface and therefore may be easily removed by a turbulence streaming phenomenon. 34

| Future research considerations
Where the present study did not support the irrigator/evacuator as monotherapy over CPT, subgingival lavage may be of value when

A
novel irrigator/evacuator device (IED) has been developed to improve the flushing of the subgingival area.A nozzle placed on the interdental papillae, covering the entrance of the interdental pockets is connected with a vacuum pump which causes a negative pressure in the pockets.This is alternated by the application of a rinsing fluid (demineralized water) through a small hose in the centre of the nozzle.A frequent change in evacuation and irrigation causes a hydrokinetics turbulence intended to flush out the subgingival biofilm.

1 . 3 . 4 .
Diagnosed with untreated adult periodontitis 2. ≥10% of sites with pockets of ≥5 mm Pockets comparably divided over the 4 quadrants in the mouth Systemically healthy as assessed by the medical questionnaire Exclusion criteria were as follows:

1 . 2 .
Probing pocket depth (PPD) as measured from the bottom of the pocket to the gingival margin.Visible gingival recession (REC) as measured from the cementoenamel junction to the gingival margin 3. Bleeding on pocket probing (BOPP) according to the criteria described by Lie et al.

4 .
Plaque score (PI) according to the criteria of the modified Plaque Index of Silness & Loё16 "A priori" power calculations revealed that a study with 23 pairs would be able to detect a difference of 0.28 (α = .05;β = .20).For the purpose of this study, 28 subjects were enrolled to anticipate for potential dropouts.F I G U R E 2 (A) Nozzle in situ.(B) Nozzle with fluid tube nozzle in situ nozzle with fluid tube

=
Flow of the clinical assessment during the 3-mo study period and the time points of the assigned interventions Oral hygiene instrucƟon and reinforcement supra-gingival cleaning and polishing TA B L E 1 Mean plaque score and range [min-max] for control and test treatments for all patients.The results reported at the 2 time points are estimated means from the fitted model a 0 = no plaque present, 1 = thin film of plaque visible by disclosing fluid or using a probe, 2 = moderate accumulation of plaque.b Statistical analysis between baseline and end scores.
TA B L E 2 Mean probing pocket depth and range [min-max] in mm for control and test treatments for all patients.Results reported are estimated means from the fitted model.The number of sites represents the data per participant Mean bleeding score and range [min-max] for control and test treatments for all patients (results reported are estimated proportions from the fitted model.The effect size for difference in proportions is reported as odds ratio) a Based on the 4 approximal sites per tooth.bStatistical analysis between baseline and end scores.TA B L E 3 b Statistical analysis between baseline and end scores.