Diagnosis and management of Ludwig's angina: An evidence-based review  RSS  下载PDF
路德維希氏蜂窩組織炎的診斷與管理：基於證據的綜述

1.1

Epidemiology  流行病學

Ludwig's angina (LA) is a rapidly spreading infection involving the floor of the mouth. It was named after Karl Friedrich Wilhelm von Ludwig in 1836, who first described the fatal and rapidly progressive infection [ 1 ]. Airway compromise is the leading cause of death in these patients [ 2 ].
路德維氏顎下蜂窩組織炎（LA）是一種迅速擴散的口底感染。此病於 1836 年由卡爾·弗里德里希·威廉·馮·路德維首次描述，為致命且迅速進展的感染[1]。氣道阻塞是這些患者死亡的主要原因[2]。

There are numerous etiologies and risk factors associated with LA ( Table 1 ). Odontogenic infection accounts for 70% of LA cases [ 3 ]. In adults, periapical abscesses between the mandibular molars (teeth # 19 and #30) are the most common etiology, while upper respiratory infections account for most cases of LA in children [ 3 ]. Of note, patients with IgG hypogammaglobulinemia are at particularly high risk for severe complications, as hypogammaglobulinemia has been associated with severity of illness in sepsis, especially in patients without other obvious comorbidities. However, of all IgG immunodeficiencies, only IgG1 levels are independently associated with mortality, with one case reporting severe LA with a prolonged course in a patient with IgG1 deficiency [ 4 5 6 ]. Mortality is most often from airway compromise and is as high as 50% in untreated LA patients, although it is closer to 8% among those who receive adequate treatment [ 1 , 7 , 8 ]. Therefore, it is important for emergency clinicians to be aware of this condition.
與路德維希氏蜂窩組織炎（LA）相關的病因和危險因素眾多（見表 1）。牙源性感染佔 LA 病例的 70%[3]。在成人中，下頜臼齒（牙齒編號 19 和 30）間的根尖膿腫是最常見的病因，而上呼吸道感染則是兒童 LA 病例的主要原因[3]。值得注意的是，IgG 低丙種球蛋白血症患者特別容易出現嚴重併發症，因為低丙種球蛋白血症與敗血症的病情嚴重程度有關，尤其是在沒有其他明顯合併症的患者中。然而，在所有 IgG 免疫缺陷中，只有 IgG1 水平與死亡率獨立相關，曾有一例報告指出 IgG1 缺乏患者出現嚴重且病程延長的 LA[4 5 6]。死亡原因多為氣道阻塞，未治療的 LA 患者死亡率高達 50%，而接受適當治療者則約為 8%[1, 7, 8]。因此，急診醫師需對此病症保持警覺。

3.1

Pathophysiology and microbiology
病理生理學與微生物學

It is important to review the anatomy of the oropharynx in order to understand the rapid progression and eventual airway occlusion that can occur from LA [ 14 ]. The mylohyoid muscle subdivides the submandibular space into the sublingual space and the submylohyoid space. The roots of the mandibular teeth are located below the mylohyoid mandibular attachments, allowing infection to enter the submylohyoid space. The infection then spreads posteriorly and superiorly, tracking to the sublingual and submandibular spaces [ 1 , 14 ]. Involvement of these spaces may result in tongue enlargement by a factor of 2–3 and elevation against the hypopharynx, eventually leading to airway occlusion if no intervention is performed. The infection may also result in edema involving the epiglottitis, true and false vocal cords, and aryepiglottic folds [ 14 ]. Edema of the airway structures may progress rapidly, occurring within 30–45 min of initial presentation [ 14 ]. The infection can also spread via the styloglossus muscle into the parapharyngeal space, retropharyngeal space, and finally into the superior mediastinum [ 14 , 15 ].
了解口咽部的解剖結構對於理解路德維希氏蜂窩組織炎（LA）快速進展及最終氣道阻塞的發生非常重要[14]。頦舌肌將下頜下間隙分為舌下間隙和頦舌肌下間隙。下頜牙齒的根部位於頦舌肌下頜附著點之下，使感染能進入頦舌肌下間隙。感染隨後向後及向上擴散，追蹤至舌下間隙和下頜下間隙[1, 14]。這些間隙的受累可能導致舌頭腫大 2 至 3 倍，並向下咽部抬升，若未及時介入，最終會導致氣道阻塞。感染也可能引起會厭、真聲帶與假聲帶及會厭聲帶襞的水腫[14]。氣道結構的水腫可能迅速進展，於初次就診後 30 至 45 分鐘內發生[14]。感染亦可經由舌骨舌肌擴散至咽旁間隙、咽後間隙，最終進入上縱隔[14, 15]。

The infection is typically polymicrobial, primarily including oral cavity flora. Viridans group streptococci are found in over 40% of cases, followed by Staphylococcus aureus (27%) and Staphylococcus epidermidis (23%) [ 16 , 17 ]. Other commonly involved bacteria include Enterococcus species, E. coli , Fusobacterium , Streptococcus species, S. aureus , Klebsiella pneumonia , and Actinomyces species [ 18 19 20 ]. Klebsiella may be present in over half of cases involving diabetics [ 14 ]. Streptococcus anginosus is a virulent strain of viridans group streptococci that may result in a more rapidly progressive disease compared to other bacteria [ 4 ]. Disease originating from dental abscesses often includes oral anaerobes such as Actinomyces, Peptostreptococcus, Fusobacterium, and Bacteroides [ 4 , 19 20 21 ]. Immunocompromised patients are at high risk of Gram-negative aerobic infection as well as methicillin-resistant Staphylococcus aureus (MRSA) [ 21 22 23 ]. Risk factors for MRSA include diabetes, injection drug use, hemodialysis, hospitalization in the preceding year, or resident of a long-term care facility [ 24 ].
感染通常為多重菌種感染，主要包括口腔菌群。綠膿桿菌群鏈球菌在超過 40%的病例中被發現，其次是金黃色葡萄球菌（27%）和表皮葡萄球菌（23%）[16, 17]。其他常見的細菌包括腸球菌屬、大腸桿菌、梭狀芽孢桿菌、鏈球菌屬、金黃色葡萄球菌、肺炎克雷伯菌和放線菌屬[18 19 20]。在糖尿病患者中，肺炎克雷伯菌可能出現在超過一半的病例中[14]。鏈球菌屬中的致病菌鏈球菌 anginosus 是一種綠膿桿菌群鏈球菌，可能導致比其他細菌更快速進展的疾病[4]。起源於牙齒膿腫的疾病通常包括口腔厭氧菌，如放線菌、厭氧鏈球菌、梭狀芽孢桿菌和擬桿菌屬[4, 19 20 21]。免疫功能低下的患者高風險感染革蘭氏陰性需氧菌以及耐甲氧西林金黃色葡萄球菌（MRSA）[21 22 23]。MRSA 的風險因素包括糖尿病、注射藥物使用、血液透析、過去一年內住院史或長期照護機構居民[24]。

3.2

History and physical examination
病史與身體檢查

While LA initially begins as an oral infection, patients often present with fever, malaise, chills, and generalized weakness. More advanced symptoms, such as trismus, meningismus, drooling, dysphagia, and tripod positioning suggest airway involvement, which may occur later in the clinical course as severe obstruction worsens and there is risk of impending airway loss. As symptoms worsen, patients may lean forward in the tripoding position in order to maximize their airway diameter [ 25 ]. Respiratory distress and failure are marked by difficulty breathing, stridor, cyanosis, and mental status changes. Trismus suggests extension to the parapharyngeal space, while meningismus suggests involvement of the retropharyngeal space.
雖然路德維希氏蜂窩組織炎（LA）最初始於口腔感染，患者常表現出發燒、全身不適、寒顫及全身無力。較嚴重的症狀如張口困難、腦膜刺激徵象、流口水、吞嚥困難及三腳架姿勢，提示氣道受累，這可能在臨床過程後期出現，當嚴重阻塞加劇且有氣道即將喪失的風險時。隨著症狀惡化，患者可能會採取前傾的三腳架姿勢以最大化氣道直徑[25]。呼吸困難及呼吸衰竭的表現包括呼吸困難、喘鳴、發紺及意識狀態改變。張口困難提示感染擴散至咽旁間隙，而腦膜刺激徵象則提示後咽間隙受累。

Examination may reveal a tender, symmetric, tense, woody, and indurated submandibular area [ 26 ]. Lingual swelling may keep the mouth held open, while the floor of the mouth can be erythematous, tender, and elevated. The outer neck may appear erythematous and edematous. Sublingual, submental, and cervical lymphadenopathy may also be present, although their absence should not exclude the diagnosis [ 25 ].
檢查可能顯示下頜下區域觸痛、對稱、緊繃、硬木狀且硬化[26]。舌頭腫脹可能使口腔保持張開狀態，而口底可能呈現紅斑、觸痛及隆起。外頸部可能出現紅斑和水腫。舌下、頦下及頸部淋巴結腫大也可能存在，但其缺失不應排除診斷[25]。

3.3

Laboratory testing  實驗室檢測

Laboratory testing has limited utility in these patients. Culture of the involved area, either through needle aspiration or swab is not recommended as the diagnostic yield is low, it has a high rate of contaminants, and it can trigger worsening airway obstruction. Blood cultures should be obtained.
實驗室檢測在這些患者中效用有限。不建議對受影響區域進行針吸或拭子培養，因為診斷率低，污染率高，且可能引發氣道阻塞惡化。應取得血液培養。

3.4

Imaging  影像學檢查

While the diagnosis of LA is clinical, further imaging can be helpful to better diagnose or exclude this condition in early or unclear cases. Computed tomography (CT) of the neck with intravenous (IV) contrast is the imaging modality of choice, as it can assist in determining the location and extent of infection [ 27 ]. Findings on CT can include soft tissue thickening, increased attenuation of the subcutaneous fat, loss of fat planes in the submandibular space, soft tissue gas, focal fluid collections, and muscle edema ( Fig. 1 ) [ 26 ].
雖然路德維希氏蜂窩組織炎（LA）的診斷主要依靠臨床表現，但在早期或不明確病例中，進一步的影像學檢查有助於更好地診斷或排除此病症。頸部電腦斷層掃描（CT）搭配靜脈注射（IV）對比劑是首選的影像檢查方式，因其能協助判定感染的位置及範圍[27]。CT 影像可能顯示軟組織增厚、皮下脂肪密度增加、下頜下間隙脂肪平面消失、軟組織氣體、局部液體積聚及肌肉水腫（圖 1）[26]。

 查看原图打开原图

Sagittal slice of a CT neck with contrast demonstrating sublingual, submental, and submandibular enhancing regions with fluid collection (arrow) characteristic of LA. Case courtesy of Dr. Yair Glick, Radiopaedia.org , rID: 51942.
帶造影劑的頸部 CT 矢狀面切片顯示舌下、頦下及下頷下增強區域伴有液體積聚（箭頭），為路德維希氏蜂窩組織炎的特徵。病例由 Dr. Yair Glick 提供，來源：Radiopaedia.org，rID: 51942。

CT demonstrates a sensitivity of 95% and a specificity of 53% for LA [ 28 ]. However, one study found that when the CT was combined with clinical examination, the specificity increased to 80% while the sensitivity remained at 95% [ 28 ]. Magnetic resonance imaging can also be used for diagnosis, but due to the time required to obtain the test, it is not typically feasible in the ED setting. If imaging is pursued, the provider must first ensure the patient is appropriate to leave the ED for testing. As the patient will be laying supine during imaging, the provider must also ensure the patient can lay supine in an area with resuscitation equipment prior to imaging. Point-of-care ultrasound can also be used to detect LA by evaluating for hypoechoic lesions within the face and neck by utilizing a curvilinear or linear array transducer in a submandibular view [ 29 30 31 ]. Ultrasound can also reliably assess for airway involvement and estimate the subglottic airway diameter, especially in those who cannot tolerate a supine position [ 29 , 32 33 34 35 36 37 ].
CT 對於路德維氏蜂窩組織炎（LA）的敏感度為 95%，特異性為 53%[28]。然而，一項研究發現，當 CT 與臨床檢查結合時，特異性提高至 80%，而敏感度仍維持在 95%[28]。磁振造影（MRI）也可用於診斷，但由於檢查所需時間較長，通常在急診室環境中不可行。如果進行影像檢查，醫護人員必須先確保患者適合離開急診室接受檢查。由於患者在影像檢查時需仰臥，醫護人員還必須確保患者能在有復甦設備的區域仰臥。床邊超音波也可用於檢測 LA，透過使用曲線或線性陣列探頭在下頜下視角評估臉部及頸部的低回聲病灶[29 30 31]。超音波還能可靠地評估氣道受累情況並估計聲門下氣道直徑，特別適用於無法耐受仰臥姿勢的患者[29, 32 33 34 35 36 37]。

3.5

Treatment  治療

Management focuses on serial assessments of the patient's airway and hemodynamic status. Many cases may be initially managed with antibiotics and close observation in an intensive care setting, but patients with significant airway swelling, dyspnea, stridor, cyanosis, or worsening airway symptoms require airway intervention [ 27 , 38 , 39 ]. Emergent consultation with otolaryngology and anesthesia is recommended if available, as these patients are best managed in the operating room if they can be safely transported there [ 27 , 38 , 40 41 42 ]. Patients should be started on supplemental oxygen if hypoxic. Mask ventilation will likely be difficult due to neck swelling, so it is important to pre‑oxygenate these patients using whichever approach works best. Blind oral or nasotracheal intubation in which an endotracheal tube is passed without a laryngoscope or visualization of the larynx can result in airway trauma leading to worsening edema and even severe laryngospasm; therefore, this approach is not recommended [ 26 ]. Supraglottic airway devices should also be avoided because they can be displaced as the swelling progresses [ 14 ]. If possible, patients should be nasotracheally intubated in the seated position with a flexible intubating endoscope using an awake intubation technique with preparation for a surgical airway (i.e., cricothyrotomy) [ 42 ]. Awake intubation should incorporate lidocaine (atomized, topical, and viscous) with consideration of a sedative agent ( Table 2 ) [ 38 ]. While clinicians should prepare for a surgical airway, cricothyrotomy may be particularly challenging in these patients due to the distortion of the anterior neck in cases of extensive infection [ 38 , 39 ]. Awake tracheotomy may be necessary in patients with LA who have severe edema [ 14 , 27 ].
管理重點在於對患者的氣道和血流動力學狀態進行連續評估。許多病例最初可透過抗生素治療和在加護病房密切觀察來管理，但若患者出現明顯的氣道腫脹、呼吸困難、喘鳴、發紺或氣道症狀惡化，則需進行氣道介入[27, 38, 39]。若有條件，建議緊急諮詢耳鼻喉科和麻醉科，因為這些患者若能安全轉送至手術室，則在手術室中管理效果最佳[27, 38, 40, 41, 42]。若患者缺氧，應開始給予補充氧氣。由於頸部腫脹，面罩通氣可能困難，因此重要的是使用最適合的方法對患者進行預氧合。盲目口腔或鼻氣管插管，即在未使用喉鏡或未視覺化喉部的情況下插入氣管內管，可能導致氣道損傷，進而加重水腫甚至引發嚴重喉痙攣，因此不建議採用此方法[26]。也應避免使用喉上氣道裝置，因為隨著腫脹進展，這些裝置可能會移位[14]。 如果可能，應讓患者在坐姿下使用柔性插管內視鏡進行鼻氣管插管，採用清醒插管技術，並準備外科氣道（即環甲膜切開術）[42]。清醒插管應結合利多卡因（霧化、局部和黏稠劑型），並考慮使用鎮靜劑（表 2）[38]。雖然臨床醫師應準備外科氣道，但由於廣泛感染導致前頸部變形，環甲膜切開術在這些患者中可能特別具有挑戰性[38, 39]。對於有嚴重水腫的路德維希氏腺炎患者，可能需要進行清醒氣管切開術[14, 27]。

Broad-spectrum antibiotics covering anaerobic, aerobic, and oral flora are recommended. Table 3 depicts antibiotic regimens for LA. Of note, clindamycin alone is not recommended, as resistance rates approach over 30% for streptococcal species and MRSA.
建議使用涵蓋厭氧菌、好氧菌及口腔菌群的廣效抗生素。表 3 顯示了路德維氏蜂窩組織炎的抗生素治療方案。值得注意的是，不建議單獨使用克林黴素，因為鏈球菌和耐甲氧西林金黃色葡萄球菌（MRSA）的抗藥率接近 30%以上。

Other adjunctive treatments include steroids and nebulized epinephrine. Steroids may reduce facial swelling and airway edema, as well as improve antibiotic penetration [ 1 , 27 , 44 45 46 ]. The most common steroid utilized is dexamethasone (10 mg IV). Nebulized epinephrine (1 mL of 1:1000 diluted to 5 mL in 0.9% normal saline) may also reduce airway obstruction, but the evidence is limited [ 47 ].
其他輔助治療包括類固醇和霧化腎上腺素。類固醇可能減少面部腫脹和氣道水腫，並改善抗生素的滲透性[1, 27, 44 45 46]。最常使用的類固醇是地塞米松（10 毫克靜脈注射）。霧化腎上腺素（1 毫升 1:1000 稀釋至 5 毫升 0.9%生理鹽水）也可能減少氣道阻塞，但證據有限[47]。

While the evidence is controversial, early surgical intervention may improve airway status [ 27 , 48 49 50 51 52 53 54 55 ]. Therefore, otolaryngology should be consulted, as well as oromaxillofacial surgery, depending upon the institution and resources available [ 39 ]. One study of 55 patients found that those undergoing surgical intervention had lower rates of airway compromise (2.9%) compared with those undergoing medical therapy alone (26.3%) [ 56 ]. Surgical intervention typically includes debriding necrotic tissue and draining all pathologic fluid collections. Indications for surgery include patients who fail to improve with antibiotics, if fluctuance is detected on examination, or if there are visible abscesses on imaging [ 27 ]. If otolaryngology and/or anesthesia consultation is not available, the emergency clinician should focus on early airway management if there is concern for airway compromise, appropriate antibiotic administration, and rapid transfer to a higher level of care with consultants who can acquire operative source control.
雖然證據存在爭議，早期外科介入可能改善氣道狀況[27, 48 49 50 51 52 53 54 55]。因此，應根據機構和可用資源，諮詢耳鼻喉科以及口腔顎面外科[39]。一項針對 55 名患者的研究發現，接受外科介入的患者氣道受損率較低（2.9%），而僅接受藥物治療者為 26.3%[56]。外科介入通常包括清除壞死組織和引流所有病理性液體積聚。手術指徵包括抗生素治療無效、檢查時發現波動感，或影像學顯示有明顯膿腫[27]。若無法取得耳鼻喉科及/或麻醉科諮詢，急診醫師應專注於早期氣道管理（若懷疑氣道受損）、適當使用抗生素，並迅速轉送至具備可進行手術源頭控制的專科醫師的更高層級醫療機構。

3.6

Complications  併發症

Although the mortality rate has decreased, ranging from 10% if expediently treated to 50% in those not receiving appropriate management, several complications can occur, with descending mediastinitis comprising one of the most severe complications [ 57 , 58 ]. Others include necrotizing fasciitis of the neck and chest, pericarditis, carotid artery rupture, jugular vein thrombosis, pleural empyema, pneumonia, and acute respiratory distress syndrome [ 59 , 60 ]. Complications may occur in over one quarter of patients [ 61 ].
儘管死亡率已有所下降，若及時治療則約為 10%，未接受適當治療者則高達 50%，但仍可能發生多種併發症，其中下降性縱隔炎是最嚴重的併發症之一[57, 58]。其他併發症包括頸部及胸部的壞死性筋膜炎、心包炎、頸動脈破裂、頸靜脈血栓、胸膜膿胸、肺炎及急性呼吸窘迫症候群[59, 60]。超過四分之一的患者可能會出現併發症[61]。

3.7

Disposition  處置

Due to the risk of airway compromise and severe complications, patients with LA should be admitted to the intensive care setting. Close observation of the patient's airway is necessary. Patients with the highest risk for mortality and complication include those with age greater than 65 years, diabetes, alcohol use, and immunocompromise.
由於氣道阻塞及嚴重併發症的風險，患有路德維希氏蜂窩組織炎（LA）的患者應入住加護病房。必須密切觀察患者的氣道狀況。死亡率及併發症風險最高的患者包括年齡超過 65 歲、糖尿病、酗酒及免疫功能低下者。