Abstract 抽象
Background 背景
Ludwig's angina is a potentially deadly condition that must not be missed in the emergency department (ED).
路德維希氏心絞痛是一種可能致命的疾病，在急診科 （ED） 一定不能錯過。
Objective 目的
The purpose of this narrative review article is to provide a summary of the epidemiology, pathophysiology, diagnosis, and management of Ludwig's angina with a focus on emergency clinicians.
本敘述性綜述文章的目的是總結路德維希氏心絞痛的流行病學、病理生理學、診斷和管理，重點是急診臨床醫生。
Discussion 討論
Ludwig's angina is a rapidly spreading infection that involves the floor of the mouth. It occurs more commonly in those with poor dentition or immunosuppression. Patients may have a woody or indurated floor of the mouth with submandibular swelling. Trismus is a late finding. Computed tomography of the neck soft tissue with contrast is preferred if the patient is able to safely leave the ED and can tolerate lying supine. Point-of-care ultrasound can be a useful adjunct, particularly in those who cannot tolerate lying supine. Due to the threat of rapid airway compromise, emergent consultation to anesthesia and otolaryngology, if available, may be helpful if a definitive airway is required. The first line approach for airway intervention in the ED is flexible intubating endoscopy with preparation for a surgical airway. Broad spectrum antibiotics and surgical source control are keys in treating the infection. These patients should then be admitted to the intensive care unit for close airway observation.
路德維希氏心絞痛是一種迅速擴散的感染，累及口腔底部。它更常見於牙列不良或免疫抑制的患者。患者可能有木質或硬化的口腔底部，伴有下頜下腫脹。牙關緊閉是晚期發現。如果患者能夠安全地離開急診室並且可以忍受仰臥，則首選頸部軟組織造影劑計算機斷層掃描。床旁超聲可能是一種有用的輔助手段，特別是對於不能耐受仰臥位的患者。由於存在快速氣道受損的威脅，如果需要確定氣道，緊急會診麻醉和耳鼻喉科（如果有）可能會有所説明。急診科氣道干預的一線方法是軟插管內窺鏡檢查，為手術氣道做準備。廣譜抗生素和手術感染源控制是治療感染的關鍵。然後，這些患者應收入重症監護病房進行密切氣道觀察。
Conclusion 結論
Ludwig's angina is a life-threatening condition that all emergency clinicians need to consider. It is important for clinicians to be aware of the current evidence regarding the diagnosis, management, and disposition of these patients.
路德維希氏心絞痛是一種危及生命的疾病，所有急診醫生都需要考慮。臨床醫生瞭解有關這些患者的診斷、管理和處置的當前證據非常重要。
1
Introduction 介紹
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 [ ]. Airway compromise is the leading cause of death in these patients [ ].
路德維希氏心絞痛 （LA） 是一種涉及口腔底部的快速擴散感染。它以 1836 年的卡爾·弗裡德里希·威廉·馮·路德維希 （Karl Friedrich Wilhelm von Ludwig） 的名字命名，他首先描述了致命且快速進展的感染 [ ]。氣道受損是這些患者死亡的主要原因 [ ]。
There are numerous etiologies and risk factors associated with LA ( Table 1 ). Odontogenic infection accounts for 70% of LA cases [ ]. 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 [ ]. 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 [ ]. 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 [ , , ]. Therefore, it is important for emergency clinicians to be aware of this condition.
有許多與 LA 相關的病因和危險因素 （ 表 1 ）。牙源性感染佔 LA 病例的 70% [ ]。在成人中，下頜磨牙之間的根尖周膿腫（牙齒 # 19 和 #30）是最常見的病因，而上呼吸道感染是兒童 LA 病例的大多數 [ ].值得注意的是，IgG 低丙種球蛋白血症患者發生嚴重併發症的風險特別高，因為低丙種球蛋白血症與膿毒症疾病的嚴重程度有關，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 水準與死亡率獨立相關，一例報告了 IgG1 缺陷患者病情延長的嚴重 LA [ <按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0025” data-refid=“bb0025” class=“j-inline-reference inline-reference u-els-color-linkblue”> 5<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0030” data-refid=“bb0030” class=“j-inline-reference inline-reference u-els-color-linkblue”> 6 ]. 死亡率通常是由於氣道受損造成的，在未經治療的 LA 患者中高達 50%，但在接受充分治療的患者中接近 8% [ ， ， ].因此，急診臨床醫生瞭解這種情況很重要。
路德維希氏心絞痛的危險因素 [ , ]
| Medical 醫療 | Recent dental infection 近期牙齒感染 |
| Oral piercings 口腔穿孔 | |
| Immunosuppression 免疫抑制 | |
| Malnutrition 營養不良 | |
| Diabetes mellitus 糖尿病 | |
| Oral or dental trauma 口腔或牙齒外傷 | |
| Lifestyle 生活方式 | Injection drug use 注射吸毒 |
| Chronic alcohol use 長期飲酒 | |
| Recent tongue piercing 近期舌頭穿孔 |
2
Methods 方法
Authors searched PubMed and Google Scholar for articles using the keywords “Ludwig's angina” and “deep space neck infection”. The literature search was restricted to studies published in English. Authors evaluated case reports and series, retrospective and prospective studies, systematic reviews and meta-analyses, and other narrative reviews. Authors also reviewed guidelines and supporting citations of included articles. The literature search focused on emergency medicine and critical care literature. Authors decided which studies to include for the review by consensus. When available, systematic reviews and meta-analyses were preferentially selected. Three authors selected a total of 61 articles for inclusion from 467 resources found on literature search, with majority voting to resolve any disagreement.
作者在 PubMed 和 Google Scholar 上檢索了使用關鍵詞 “Ludwig's angina” 和 “deep space neck infection” 的文章。文獻檢索僅限於以英文發表的研究。作者評價了病例報告和系列、回顧性和前瞻性研究、系統評價和薈萃分析以及其他敘述性評價。作者還審查了納入文章的指南和支援引用。文獻檢索側重於急診醫學和重症監護文獻。作者通過協商一致決定納入哪些研究。如果可用，優先選擇系統評價和薈萃分析。三位作者從文獻檢索中找到的 467 個資源中共選擇了 61 篇文章納入，大多數人投票解決任何分歧。
3
Discussion 討論
3.1
Pathophysiology and microbiology
病理生理學和微生物學
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 [ ]. 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 [ , ]. 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 [ ]. Edema of the airway structures may progress rapidly, occurring within 30–45 min of initial presentation [ ]. The infection can also spread via the styloglossus muscle into the parapharyngeal space, retropharyngeal space, and finally into the superior mediastinum [ , ].
回顧口咽部的解剖結構以瞭解 LA 可能發生的快速進展和最終氣道閉塞非常重要 [ ].髓舌骨肌將下頜下間隙細分為舌下間隙和髓舌骨下間隙。下頜牙的根部位於髓舌骨下頜附著物下方，使感染進入髓舌骨下腔。然後感染向後和上部擴散，追蹤到舌下和下頜下間隙 [ ， ].這些空間的受累可能導致舌頭擴大 2-3 倍並抬高下咽部，如果不進行干預，最終導致氣道阻塞。感染還可能導致水腫，涉及會厭炎、真假聲帶和杓會厭皺襞 [ ]。 氣道結構水腫可能會迅速發展，發生在初次出現后 30-45 分鐘內 [ ]。感染還可以通過莖突舌肌擴散到咽旁間隙、咽後間隙，最後擴散到上縱隔 [ ， ].
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%) [ , ]. Other commonly involved bacteria include Enterococcus species, E. coli , Fusobacterium , Streptococcus species, S. aureus , Klebsiella pneumonia , and Actinomyces species [ ]. Klebsiella may be present in over half of cases involving diabetics [ ]. Streptococcus anginosus is a virulent strain of viridans group streptococci that may result in a more rapidly progressive disease compared to other bacteria [ ]. Disease originating from dental abscesses often includes oral anaerobes such as Actinomyces, Peptostreptococcus, Fusobacterium, and Bacteroides [ , ]. Immunocompromised patients are at high risk of Gram-negative aerobic infection as well as methicillin-resistant Staphylococcus aureus (MRSA) [ ]. Risk factors for MRSA include diabetes, injection drug use, hemodialysis, hospitalization in the preceding year, or resident of a long-term care facility [ ].
感染通常是多種微生物感染，主要包括口腔菌群。在超過 40% 的病例中發現了草綠色鏈球菌，其次是金黃色葡萄球菌 （27%） 和表皮葡萄球菌 （23%） [ ， ].其他常見的涉及細菌包括腸球菌屬、大 腸桿菌屬、 梭桿菌屬 、 鏈球菌屬、 金黃色葡萄球菌屬、 肺炎克雷伯菌屬和放線菌屬 [ <按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0095” data-refid=“bb0095” class=“j-inline-reference inline-reference u-els-color-linkblue”> 19<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0100” data-refid=“bb0100” class=“j-inline-reference inline-reference u-els-color-linkblue”> 20 ].克雷伯氏菌可能存在於超過一半的涉及糖尿病患者的病例中 [ ]。 鏈球菌 心絞痛鏈球菌是一種毒力強的草綠色鏈球菌菌株，與其他細菌相比，它可能導致疾病進展得更快 [ ]。由牙膿腫引起的疾病通常包括口腔厭氧菌，如放線菌、消化鏈球菌、梭桿菌和擬桿菌 [ ，<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0095” data-refid=“bb0095” class=“j-inline-reference inline-reference u-els-color-linkblue”> 19<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0100” data-refid=“bb0100” class=“j-inline-reference inline-reference u-els-color-linkblue”> 20 ]. 免疫功能低下的患者患革蘭氏陰性需氧感染以及耐甲氧西林金黃色葡萄球菌 （MRSA） 的風險很高 [ <按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0110” data-refid=“bb0110” class=“j-inline-reference inline-reference u-els-color-linkblue”> 22<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0115” data-refid=“bb0115” class=“j-inline-reference inline-reference u-els-color-linkblue”> 23].MRSA 的危險因素包括糖尿病、注射吸毒、血液透析、前一年住院治療或長期護理機構的居民 [ ]。
3.2
History and physical examination
病史和體格檢查
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 [ ]. 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 LA 最初以口腔感染開始，但患者通常表現為發熱、不適、寒戰和全身無力。更晚期的癥狀，如牙關緊閉、假性腦膜炎、流涎、吞咽困難和三腳架姿勢提示氣道受累，這可能在臨床病程後期發生，因為嚴重梗阻惡化，有即將發生氣道丟失的風險。隨著癥狀的惡化，患者可能會以三腳架姿勢向前傾，以最大化他們的氣道直徑 [ ]。呼吸窘迫和衰竭的特點是呼吸困難、喘鳴、發紺和精神狀態改變。牙關緊閉提示延伸至咽旁間隙，而假性腦膜炎提示受累於咽後間隙。
Examination may reveal a tender, symmetric, tense, woody, and indurated submandibular area [ ]. 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 [ ].
檢查可能顯示壓痛、對稱、緊張、木質和硬化的下頜下區域 [ ]。舌腫脹可能會使嘴巴張開，而口腔底部可能呈紅斑、壓痛和隆起。頸部外側可能出現紅斑和水腫。也可能存在舌下、颏下和頸部淋巴結腫大，但不存在不應排除診斷 [ ]。
3.3
Laboratory testing 實驗室檢查
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.
實驗室檢查在這些患者中的效用有限。不建議通過針吸或拭子對受累區域進行培養，因為診斷率低，污染物率高，並且可能引發氣道阻塞惡化。應進行血培養。
3.4
Imaging 成像
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 [ ]. 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 ) [ ].
雖然 LA 的診斷是臨床診斷，但進一步的影像學檢查可能有助於在早期或不明確的病例中更好地診斷或排除這種情況。靜脈注射 （IV） 造影劑的頸部計算機斷層掃描 （CT） 是首選的成像方式，因為它可以幫助確定感染的位置和程度 [ ].CT 檢查結果包括軟組織增厚、皮下脂肪衰減增加、下頜下間隙脂肪平面減少、軟組織氣體、局灶性積液和肌肉水腫（ 圖 1）[ <按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0130” data-refid=“bb0130” class=“j-inline-reference inline-reference u-els-color-linkblue”> 26 ]。
頸部 CT 矢狀面切片與造影劑顯示舌下、颏下和下頜下增強區域，伴有 LA 特徵的積液（箭頭）。案例由 Yair Glick 博士提供， Radiopaedia.org，rID ：51942。
CT demonstrates a sensitivity of 95% and a specificity of 53% for LA [ ]. However, one study found that when the CT was combined with clinical examination, the specificity increased to 80% while the sensitivity remained at 95% [ ]. 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 [ ]. Ultrasound can also reliably assess for airway involvement and estimate the subglottic airway diameter, especially in those who cannot tolerate a supine position [ , ].
CT 顯示對 LA 的敏感性為 95%，特異性為 53% [ ]。然而，一項研究發現，當 CT 與臨床檢查相結合時，特異性增加到 80%，而敏感性保持在 95% [ ].磁共振成像也可用於診斷，但由於進行檢查所需的時間，在 ED 環境中通常不可行。如果進行影像學檢查，醫務人員必須首先確保患者適合離開急診室進行檢測。由於患者在成像過程中將仰臥，因此提供者還必須確保患者在成像前可以仰臥在裝有復甦設備的區域。 床旁超聲也可用於檢測 LA，通過在下頜下視圖中使用曲線或線性陣列換能器來評估面部和頸部內的低回聲病變 [ <按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0150” data-refid=“bb0150” class=“j-inline-reference inline-reference u-els-color-linkblue”> 30<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0155” data-refid=“bb0155” class=“j-inline-reference inline-reference u-els-color-linkblue”> 31 ]. 超聲還可以可靠地評估氣道受累情況並估計聲門下氣道直徑，尤其是在那些不能忍受仰臥位的人 [ ，<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0160” data-refid=“bb0160” class=“j-inline-reference inline-reference u-els-color-linkblue”> 32<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0165” data-refid=“bb0165” class=“j-inline-reference inline-reference u-els-color-linkblue”> 33<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0170” data-refid=“bb0170” class=“j-inline-reference inline-reference u-els-color-linkblue”> 34<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0175” data-refid=“bb0175” class=“j-inline-reference inline-reference u-els-color-linkblue”> 35 ].
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 [ , , ]. 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 [ , , ]. 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 [ ]. Supraglottic airway devices should also be avoided because they can be displaced as the swelling progresses [ ]. 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) [ ]. Awake intubation should incorporate lidocaine (atomized, topical, and viscous) with consideration of a sedative agent ( Table 2 ) [ ]. 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 [ , ]. Awake tracheotomy may be necessary in patients with LA who have severe edema [ , ].
治療的重點是對患者的氣道和血流動力學狀態進行連續評估。許多病例最初可以通過抗生素治療並在重症監護環境中進行密切觀察，但有明顯氣道腫脹、呼吸困難、喘鳴、發紺或氣道癥狀惡化的患者需要氣道干預 [ ，<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0190” data-refid=“bb0190” class=“j-inline-reference inline-reference u-els-color-linkblue”> 38 ， <按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0195” data-refid=“bb0195” class=“j-inline-reference inline-reference u-els-color-linkblue”> 39 ]. 如果有條件，建議緊急會診耳鼻喉科和麻醉科，因為如果可以安全地運送這些患者，最好在手術室進行管理 [ ，<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0190” data-refid=“bb0190” class=“j-inline-reference inline-reference u-els-color-linkblue”> 38 ， <按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0200” data-refid=“bb0200” class=“j-inline-reference inline-reference u-els-color-linkblue”> 40<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0205” data-refid=“bb0205” class=“j-inline-reference inline-reference u-els-color-linkblue”> 41<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0210” data-refid=“bb0210” class=“j-inline-reference inline-reference u-els-color-linkblue”> 42].如果缺氧，患者應開始補充氧氣。由於頸部腫脹，面罩通氣可能會很困難，因此使用最有效的方法為這些患者預充氧非常重要。 盲目經口或鼻氣管插管，在沒有喉鏡或喉部觀察的情況下通過氣管插管，可導致氣道創傷，導致水腫惡化，甚至嚴重的喉痙攣;因此，不建議使用這種方法 [ ]。還應避免使用聲門上氣道裝置，因為它們可能會隨著腫脹的進展而移位 [ ]。如果可能，應使用清醒插管技術，在坐位用柔性插管內窺鏡對患者進行鼻氣管插管，併為手術氣道（即環甲膜切開術）做準備 [ ].清醒插管應加入利多卡因（霧化、局部和粘稠）並考慮使用鎮靜劑（ 表 2 ） [ ]。 雖然臨床醫生應該為手術氣道做準備，但環甲膜切開術在這些患者中可能特別具有挑戰性，因為在廣泛感染的情況下，前頸會變形 [ ， ]。對於患有嚴重水腫的 LA 患者，可能需要清醒氣管切開術 [ ， ]。
清醒插管程式
| Steps for awake intubation 清醒插管的步驟 | |
|---|---|
| Preparation 製備 |
|
| Intubation 插管 |
|
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群、需氧菌群和口腔菌群的廣譜抗生素。 表 3 描述了 LA 的抗生素方案。值得注意的是，不推薦單獨使用克林黴素，因為鏈球菌和 MRSA 的耐葯率接近 30% 以上。
LA 的抗生素建議 [ ]
| Patient population 患者群體 | Recommended medication 推薦藥物 |
|---|---|
| Immunocompetent 免疫功能正常 | Ampicillin-sulbactam 3 g IV every 6 h 氨苄西林 - 舒巴坦 3 g IV 每 6 小時 or 或 Ceftriaxone 2 g IV every 12 h plus metronidazole 500 mg IV every 8 h 頭孢曲松 2 g IV 每 12 小時一次加甲硝唑 500 mg IV 每 8 小時 or 或 Clindamycin 600 mg IV every 6–8 h plus levofloxacin 750 mg IV every 24 h 克林黴素 600 mg 靜脈注射，每 6-8 小時一次，加上左氧氟沙星 750 mg 靜脈注射，每 24 小時一次 |
| Immunocompromised 免疫功能低下 | Cefepime 2 g IV every 8 h plus metronidazole 500 mg IV every 8 h 頭孢吡肟 2 g IV 每 8 小時加甲硝唑 500 mg IV 每 8 小時 or 或 Imipenem 1 g IV every 6–8 h 亞胺培南 1 g IV 每 6-8 小時 or 或 Meropenem 2 g IV every 8 h 美羅培南 2 g IV 每 8 小時 or 或 Piperacillin-tazobactam 4.5 g IV every 6 h 哌拉西林-他唑巴坦 4.5 g IV 每 6 小時一次 |
| MRSA Coverage MRSA 覆蓋範圍 | To the above coverage, add: 在上述覆蓋範圍中，添加： Vancomycin 20 mg/kg IV 萬古黴素 20 mg/kg IV or 或 Linezolid 600 mg IV every 12 h 利奈唑胺 600 mg IV 每 12 小時 |
Other adjunctive treatments include steroids and nebulized epinephrine. Steroids may reduce facial swelling and airway edema, as well as improve antibiotic penetration [ , , ]. 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 [ ].
其他輔助治療包括類固醇和霧化腎上腺素。類固醇可以減少面部腫脹和氣道水腫，並提高抗生素滲透率 [ ，<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0135” data-refid=“bb0135” class=“j-inline-reference inline-reference u-els-color-linkblue”> 27 ， <按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0220” data-refid=“bb0220” class=“j-inline-reference inline-reference u-els-color-linkblue”> 44<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0225” data-refid=“bb0225” class=“j-inline-reference inline-reference u-els-color-linkblue”> 45<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0230” data-refid=“bb0230” class=“j-inline-reference inline-reference u-els-color-linkblue”> 46].最常用的類固醇是地塞米松（10 mg IV）。霧化吸入腎上腺素（1 mL 1：1000 稀釋至 5 mL，溶於 0.9% 生理鹽水中）也可減輕氣道阻塞，但證據有限 [ ]。
While the evidence is controversial, early surgical intervention may improve airway status [ , ]. Therefore, otolaryngology should be consulted, as well as oromaxillofacial surgery, depending upon the institution and resources available [ ]. 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%) [ ]. 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 [ ]. 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，但早期手術干預可能會改善氣道狀態 [ ，<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0240” data-refid=“bb0240” class=“j-inline-reference inline-reference u-els-color-linkblue”> 48 <按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0245” data-refid=“bb0245” class=“j-inline-reference inline-reference u-els-color-linkblue”> 49<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0250” data-refid=“bb0250” class=“j-inline-reference inline-reference u-els-color-linkblue”> 50<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0255” data-refid=“bb0255” class=“j-inline-reference inline-reference u-els-color-linkblue”> 51<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0260” data-refid=“bb0260” class=“j-inline-reference inline-reference u-els-color-linkblue”> 52<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0265” data-refid=“bb0265” class=“j-inline-reference inline-reference u-els-color-linkblue”> 53<按鈕 data-immersive-translate-walked=“548edf44-71fa-44cf-a850-66b523c623c3” id=“refInSitubb0275” data-refid=“bb0275” class=“j-inline-reference inline-reference u-els-color-linkblue”> 55 ]. 因此，應諮詢耳鼻喉科以及口腔頜面外科，具體取決於可用的機構和資源 [ ]。一項針對 55 名患者的研究發現，與單獨接受藥物治療的患者 （26.3%） 相比，接受手術干預的患者氣道受損率 （2.9%） 較低 [ ].手術干預通常包括清創壞死組織和引流所有病理性積液。手術適應症包括抗生素治療未見改善的患者，檢查發現波動，或影像學檢查可見膿腫 [ ].如果無法進行耳鼻喉科和/或麻醉會診，如果擔心氣道受損，急診臨床醫生應專注於早期氣道管理、適當的抗生素給葯，並迅速轉移到更高級別的護理機構，由能夠控制手術感染源的會診醫生。
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 [ , ]. Others include necrotizing fasciitis of the neck and chest, pericarditis, carotid artery rupture, jugular vein thrombosis, pleural empyema, pneumonia, and acute respiratory distress syndrome [ , ]. Complications may occur in over one quarter of patients [ ].
儘管死亡率有所下降，從適當治療的 10% 到未接受適當治療的患者的 50% 不等，但仍可發生多種併發症，其中降性縱隔炎是最嚴重的併發症之一 [ ， ].其他包括頸部和胸部壞死性筋膜炎、心包炎、頸動脈破裂、頸靜脈血栓形成、胸膜積膿、肺炎和急性呼吸窘迫綜合征 [ ， ].超過四分之一的患者可能會出現併發症 [ ]。
3.7
Disposition 配置
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.
由於存在氣道受損和嚴重併發症的風險，LA 患者應收入重症監護病房。有必要密切觀察患者的氣道。死亡和併發症風險最高的患者包括 65 歲以上、糖尿病、酗酒和免疫功能低下的患者。
4
Conclusion 結論
LA is a rapidly progressing infection of the floor of the mouth, which can quickly compromise the patient's airway. It occurs more commonly in those with poor dentition or immunosuppression. Patients may have a woody or indurated mouth floor with submandibular swelling. Trismus is a late and serious finding. CT of the neck soft tissue with intravenous contrast is an accurate imaging modality for diagnosis if the patient is able to safely leave the ED. Point-of-care ultrasound can be a useful adjunct, particularly in those who cannot tolerate lying supine. Due to the threat of rapid airway compromise, emergent consultation to anesthesia and otolaryngology is vital, especially if a definitive airway is required. The first line approach for airway intervention in the ED is flexible intubating endoscopy with preparation for a surgical airway. Broad spectrum antibiotics, such as ampicillin-sulbactam, and surgical source control are key in controlling infection. Emergency clinicians should be aware of this emergent diagnosis, requiring rapid recognition and airway protection.
LA 是一種快速進展的口腔底部感染，可迅速損害患者的氣道。它更常見於牙列不良或免疫抑制的患者。患者可能有木質或硬化的口底，伴有下頜下腫脹。牙關緊閉是晚期的嚴重發現。如果患者能夠安全離開急診室，靜脈注射造影劑的頸部軟組織 CT 是一種準確的影像學診斷方法。床旁超聲可能是一種有用的輔助手段，特別是對於不能耐受仰臥的患者。由於氣道快速受損的威脅，緊急會診麻醉和耳鼻喉科至關重要，尤其是在需要確定氣道的情況下。急診科氣道干預的一線方法是軟插管內窺鏡檢查，為手術氣道做準備。廣譜抗生素（如氨苄西林舒巴坦）和手術感染源控制是控制感染的關鍵。急診醫生應瞭解這種緊急診斷，需要快速識別和氣道保護。
Declaration of Competing Interest
利益爭奪聲明
None. 沒有。
Acknowledgements 確認
BL, RB, AK, and MG conceived the idea for this manuscript and contributed substantially to the writing and editing of the review. This manuscript did not utilize any grants, and it has not been presented in abstract form. This clinical review has not been published, it is not under consideration for publication elsewhere, its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder. This review does not reflect the views or opinions of the U.S. government, Department of Defense, U.S. Army, U.S. Air Force, or SAUSHEC EM Residency Program.
BL、RB、AK 和 MG 構思了這份手稿的想法，併為評論的撰寫和編輯做出了重大貢獻。這份手稿沒有使用任何資助，也沒有以摘要形式呈現。本臨床綜述尚未發表，未考慮在其他地方發表，其發佈已獲得所有作者的批准，並得到開展工作的主管當局的默許或明確批准，並且如果被接受，它將不會以相同的形式以英語或任何其他語言在其他地方發表， 包括未經版權擁有者書面同意的電子方式。本綜述不反映美國政府、國防部、美國陸軍、美國空軍或 SAUSHEC EM 住院醫師計劃的觀點或意見。
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2
Methods
Authors searched PubMed and Google Scholar for articles using the keywords “Ludwig's angina” and “deep space neck infection”. The literature search was restricted to studies published in English. Authors evaluated case reports and series, retrospective and prospective studies, systematic reviews and meta-analyses, and other narrative reviews. Authors also reviewed guidelines and supporting citations of included articles. The literature search focused on emergency medicine and critical care literature. Authors decided which studies to include for the review by consensus. When available, systematic reviews and meta-analyses were preferentially selected. Three authors selected a total of 61 articles for inclusion from 467 resources found on literature search, with majority voting to resolve any disagreement.
3
Discussion
3.1
Pathophysiology and microbiology
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 [ ]. 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 [ , ]. 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 [ ]. Edema of the airway structures may progress rapidly, occurring within 30–45 min of initial presentation [ ]. The infection can also spread via the styloglossus muscle into the parapharyngeal space, retropharyngeal space, and finally into the superior mediastinum [ , ].
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%) [ , ]. Other commonly involved bacteria include Enterococcus species, E. coli , Fusobacterium , Streptococcus species, S. aureus , Klebsiella pneumonia , and Actinomyces species [ ]. Klebsiella may be present in over half of cases involving diabetics [ ]. Streptococcus anginosus is a virulent strain of viridans group streptococci that may result in a more rapidly progressive disease compared to other bacteria [ ]. Disease originating from dental abscesses often includes oral anaerobes such as Actinomyces, Peptostreptococcus, Fusobacterium, and Bacteroides [ , ]. Immunocompromised patients are at high risk of Gram-negative aerobic infection as well as methicillin-resistant Staphylococcus aureus (MRSA) [ ]. Risk factors for MRSA include diabetes, injection drug use, hemodialysis, hospitalization in the preceding year, or resident of a long-term care facility [ ].
3.2
History and physical examination
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 [ ]. 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.
Examination may reveal a tender, symmetric, tense, woody, and indurated submandibular area [ ]. 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 [ ].
3.3
Laboratory testing
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.
3.4
Imaging
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 [ ]. 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 ) [ ].
CT demonstrates a sensitivity of 95% and a specificity of 53% for LA [ ]. However, one study found that when the CT was combined with clinical examination, the specificity increased to 80% while the sensitivity remained at 95% [ ]. 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 [ ]. Ultrasound can also reliably assess for airway involvement and estimate the subglottic airway diameter, especially in those who cannot tolerate a supine position [ , ].
3.5
Treatment
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 [ , , ]. 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 [ , , ]. 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 [ ]. Supraglottic airway devices should also be avoided because they can be displaced as the swelling progresses [ ]. 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) [ ]. Awake intubation should incorporate lidocaine (atomized, topical, and viscous) with consideration of a sedative agent ( Table 2 ) [ ]. 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 [ , ]. Awake tracheotomy may be necessary in patients with LA who have severe edema [ , ].
| Steps for awake intubation | |
|---|---|
| Preparation |
|
| Intubation |
|
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.
| Patient population | Recommended medication |
|---|---|
| Immunocompetent | Ampicillin-sulbactam 3 g IV every 6 h or Ceftriaxone 2 g IV every 12 h plus metronidazole 500 mg IV every 8 h or Clindamycin 600 mg IV every 6–8 h plus levofloxacin 750 mg IV every 24 h |
| Immunocompromised | Cefepime 2 g IV every 8 h plus metronidazole 500 mg IV every 8 h or Imipenem 1 g IV every 6–8 h or Meropenem 2 g IV every 8 h or Piperacillin-tazobactam 4.5 g IV every 6 h |
| MRSA Coverage | To the above coverage, add: Vancomycin 20 mg/kg IV or Linezolid 600 mg IV every 12 h |
Other adjunctive treatments include steroids and nebulized epinephrine. Steroids may reduce facial swelling and airway edema, as well as improve antibiotic penetration [ , , ]. 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 [ ].
While the evidence is controversial, early surgical intervention may improve airway status [ , ]. Therefore, otolaryngology should be consulted, as well as oromaxillofacial surgery, depending upon the institution and resources available [ ]. 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%) [ ]. 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 [ ]. 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.
3.6
Complications
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 [ , ]. Others include necrotizing fasciitis of the neck and chest, pericarditis, carotid artery rupture, jugular vein thrombosis, pleural empyema, pneumonia, and acute respiratory distress syndrome [ , ]. Complications may occur in over one quarter of patients [ ].
3.7
Disposition
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.
4
Conclusion
LA is a rapidly progressing infection of the floor of the mouth, which can quickly compromise the patient's airway. It occurs more commonly in those with poor dentition or immunosuppression. Patients may have a woody or indurated mouth floor with submandibular swelling. Trismus is a late and serious finding. CT of the neck soft tissue with intravenous contrast is an accurate imaging modality for diagnosis if the patient is able to safely leave the ED. Point-of-care ultrasound can be a useful adjunct, particularly in those who cannot tolerate lying supine. Due to the threat of rapid airway compromise, emergent consultation to anesthesia and otolaryngology is vital, especially if a definitive airway is required. The first line approach for airway intervention in the ED is flexible intubating endoscopy with preparation for a surgical airway. Broad spectrum antibiotics, such as ampicillin-sulbactam, and surgical source control are key in controlling infection. Emergency clinicians should be aware of this emergent diagnosis, requiring rapid recognition and airway protection.
Declaration of Competing Interest
None.
Acknowledgements
BL, RB, AK, and MG conceived the idea for this manuscript and contributed substantially to the writing and editing of the review. This manuscript did not utilize any grants, and it has not been presented in abstract form. This clinical review has not been published, it is not under consideration for publication elsewhere, its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder. This review does not reflect the views or opinions of the U.S. government, Department of Defense, U.S. Army, U.S. Air Force, or SAUSHEC EM Residency Program.