輔助性局部投予抗菌劑於牙周病維持治療期之成效評估：系統性文獻回顧及網絡統合分析

Abstract

牙周病是一種成人常見的慢性傳染性疾病，其會造成牙周組織發炎、齒槽骨破壞、牙齒動搖、最後導致牙齒的喪失。目前非手術性牙周治療以洗牙暨牙根整平術為首選，然而傳統的機械性清創有其限制，例如在深度破壞的囊袋中或是在牙根分岔處，器械無法有效率的達到徹底的清創，導致在經過治療後仍會有殘餘之牙周囊袋。因此相關的輔助治療陸續被提出來當作治療殘餘囊袋的方法。這些輔助性治療大多利用全身性或局部投予抗菌劑來達到加強清創的功能，其中局部性投予的路徑既可避免抗藥性菌種的產生亦可直接針對病灶處維持高濃度的藥效，因此各式不同的藥劑相繼被研發使用。本研究旨在透過系統性文獻回顧、更新相關的隨機對照臨床實驗，透過網絡統合分析比較不同輔助性局部投予抗菌劑於治療牙周病維持期患者的殘餘囊袋之效益，以提供臨床治療時的決策參考。 本研究經由Embase 、Medline、Pubmed，以及Cochrane資料庫進行系統性文獻回顧，一共有22篇隨機對照臨床試驗納入網絡統合分析，所評估的治療成效有牙周囊袋深度及牙周附連高度的改變量，並依照觀察時間將結果分成短期(小於或等於三個月)、中期(四至六個月)、長期(大於六個月)報導。 研究結果顯示與洗牙暨牙根整平術合併輔助性投予安慰劑與否比較下，輔助性投予氯己定薄片(Chlorhexidine chip, 效應值：0.67毫米(95% Confidence intervals [CI]：0.15~1.19 ) 、輔助性投予四環黴素纖維(Tetracycline fiber, 效應值：0.57毫米(95% CI：0.19~0.95) 、輔助性投予光動力治療(Photodynamic therapy, 效應值：0.44毫米(95% CI：0.12~0.76)於短期牙周囊袋深度減少及牙周附連高度增加有顯著改善。在中期的部分，輔助性投予氯己定薄片(效應值：0.65毫米(95% CI：0.21~1.10)及輔助性投予四環黴素纖維(效應值：0.64毫米(95% CI：0.20~1.08)於牙周囊袋深度下降有顯著改善，而輔助性投予氯己定薄片(效應值：0.60毫米(95% CI：0.18~1.02及輔助性投予去氧氫四環黴素凝膠(Doxycycline gel, 效應值：0.70毫米(95% CI：0.09~1.31)於牙周附連高度增加可以達到顯著的效果。但在長期的部分，沒有一種輔助性局部投予抗菌劑能夠提供顯著的牙周囊袋深度下降或牙周附連高度增加的效果。 基於上述實證醫學的過程，可以證實局部投予輔助性抗菌劑於治療牙周病維持期殘餘囊袋的臨床成效。在牙周囊袋深度減少及牙周附連高度增加的臨床效果上，相對於單純洗牙暨牙根整平術，合併局部投予輔助性抗藥劑可以得到更多的改善，且效果可維持六個月之久，其中輔助性投予氯己定薄片及輔助性投予四環黴素纖維可以達到最顯著的改善。

Background：Chronic periodontitis(CP) is a disease, which is prevalent in adults, with slow to moderate rate of progression. Non-surgical periodontal therapy, comprised of scaling and root planing (SRP) had proven to be the gold standard of periodontal therapy for most patients with CP. Maintenance phase of periodontal therapy is required after SRP to prevent the recurrence of disease progression. However, residual pockets may still exist during maintenance. The residual pocket may be related to difficulty of thorough debridement, such as sites with initial deep probing pocket depth(PPD) or anatomical structures, which may hinder complete removal of calculus. Therefore, several methods have been introduced as adjuncts to SRP in the treatment of residual pocket in maintenance phase. The aim of this study was to conduct a systematic review and network meta-analysis to determine the treatment effect of different antimicrobial agents in residual pockets. Material and Methods： A systematic literature research was conducting using the Medline, EMBASE (via PubMed), Cochrane Library databases and hand search up to and including October 2017. Primary outcomes were changes in probing pocket depth(PPD) and clinical attachment level(CAL) from baseline to follow-up visits of different time points. Treatment outcomes were reported by specific time periods: short (≤ 3 months), medium (4 ~ 6 months), and long (> 7 months) term. Network meta-analysis was carried out using STATA (version 15, StataCorp LP, College Station, TX, USA) Results：A total of 22 studies were included in this review and following data synthesis. In the short-term follow-up, adjunctive use of tetracycline fiber (0.57 mm (95% CI: 0.19~0.95), chlorhexidine chip (0.67 mm (95% CI: 0.15~1.19), and photodynamic therapy (0.44 mm (95% CI: 0.12~0.76) showed statistically significant results than scaling and root planing alone. In the medium-term follow-up, significantly better results can be obtained using adjunctive tetracycline fiber (0.64 mm (95% CI: 0.20~1.08) and chlorhexidine chip (0.65 mm (95% CI: 0.21~1.10) in probing depth reduction. Besides, adjunctive use of doxycycline gel (0.70 mm (95% CI: 0.09~1.31) and chlorhexidine chip (0.60 mm (95% CI: 0.18~1.02) would achieve significantly better results in clinical attachment level gain. No adjunctive antimicrobial agents showed significant advantage in the long-term follow-up. Conclusion：Adjunctive local antimicrobial agents performed better than scaling and root planing alone in the treatment of residual pockets, and the additional benefits cane be maintained for up to six months. The most consistent advantages were obtained with the use of tetracycline fiber and chlorhexidine chip.