Causes and management of massive hemoptysis in adults David H Ingbar, MD UpToDate performs a continuous review of over 350 journals

and other resources. Updates are added as important new information is published. The literature review for version 14.1 is current through December 2005; this topic was last changed on November 29, 2004. The next version of UpToDate (14.2) will be released in June 2006. INTRODUCTION Massive hemoptysis is variably defined as expectoration of blood exceeding 100 to 600 mL over a 24-hour period. Its significance is derived from two features: it is often a sign of an important underlying disease, and the hemoptysis itself may be life-threatening due to asphyxiation. While only five percent of hemoptysis is massive, some studies report a mortality rate of up to 80 percent. The causes and the general management of massive hemoptysis will be discussed here, while the diagnostic approach to this problem is covered elsewhere. (See "Diagnostic approach to massive hemoptysis in adults"). Causes and evaluation of hemoptysis that is not massive are also considered separately. (See "Etiology and evaluation of hemoptysis in adults"). Several comprehensive reviews are available for those seeking additional information [1-3], but there are virtually no large series of patients with massive hemoptysis. The only exceptions are two retrospective modern series of 120 patients with massive hemoptysis reported from South Africa [4] and 29 patients from Israel [5]. CAUSES OF MASSIVE HEMOPTYSIS Before assuming a lower respiratory source of the bleeding, it is important to consider whether the blood may be coming from a non-pulmonary source, such as the upper airway or the gastrointestinal tract. This may be a difficult distinction that requires careful examination by an otolaryngology and/or gastrointestinal subspecialist, respectively. As an example, blood from the upper gastrointestinal tract can be aspirated and coughed up, or blood from the lungs can be swallowed and be present in the stomach. Alkaline pH, foaminess, or the presence of pus may sometimes suggest the lungs as the primary source of bleeding rather than the stomach. There are numerous causes of massive hemoptysis originating from the lower respiratory tract, the most common and important of which will be discussed here (show table 1).

The literature from the 1940s through the 1960s supports three major etiologies accounting for 90 percent of cases: tuberculosis (TB); bronchiectasis; and lung abscess. Most of these reports were from municipal hospitals that cared for patients at higher risk of infectious lung diseases due to their living conditions and underlying illnesses. Most experts believe that the frequency of each of these etiologies has decreased significantly over the past thirty years. Two modern studies of predominantly nonmassive hemoptysis demonstrated that TB and bronchiectasis presently account for fewer cases of hemoptysis than in the past [6,7]. TB accounted for six and seven percent of cases and bronchiectasis for only one percent in these outpatient retrospective studies. Bronchitis was the attributed cause of hemoptysis in 23 and 37 percent of patients, including 27 percent of cases of massive hemoptysis in one series [7]. However, since computed tomography (CT) of the chest was rarely done

in these patients, it is likely that many of the patients with bronchitis also had bronchiectasis. One series reported information about 22 patients with massive hemoptysis (defined as more than 200 mL over 24 hours): six patients had bronchitis and four had TB, while no other etiology accounted for more than one case [7].

In the United States, invasive medical procedures and the increased number of patients with immuno-compromising neutropenia or thrombocytopenia probably contribute significantly to present cases of massive hemoptysis. In addition, the survival of more patients with cystic fibrosis into adulthood has made this a more common etiology of massive hemoptysis [8]. Similarly, early recognition and treatment of arteriovenous malformations (AVM) have increased the survival of patients with hereditary hemorrhagic telangiectasia (HHT), and now more than eight percent of these patients have episodes of massive pulmonary bleeding [9]. (See "Pulmonary AVMs, including hereditary hemorrhagic telangiectasia: Etiology and clinical features"). A summary of the frequency of etiologies of massive hemoptysis as reported in several series is presented in Table 2 (show table 2) [4,5,10].

Tuberculosis TB can cause massive hemoptysis through multiple mechanisms: Active cavitary or noncavitary lung disease can cause small or large amounts of bleeding. Most of these patients have sputum smears that stain positively for acid-fast bacilli. Active disease can cause sudden rupture of a Rasmussen's aneurysm [11]. This is an aneurysm of the pulmonary artery that slowly expands into an adjacent cavity because of inflammatory erosion of the external vessel wall until it bursts. There is some uncertainty about whether these aneurysms also can arise from bronchial arteries. Inactive TB can cause bleeding due to residual bronchiectasis, erosion of a broncholith through a vessel and into an airway, or by leaving a cavity that subsequently acquires a mycetoma. Rarely, scar carcinomas form in areas of old tuberculous pneumonitis and may cause hemoptysis. In the South African series, patients usually had bronchiectasis or cavitation, but approximately one third had noncavitary active disease [4].

Apart from the Rasmussen's aneurysm, the source of bleeding in each of these causes is usually the bronchial arterial circulation. Bronchiectasis Chronic airway inflammation in bronchiectasis causes hypertrophy and tortuosity of the bronchial arteries that accompany the regional bronchial trees, with expansion of the submucosal and peribronchial plexus of vessels. This circulation is under systemic blood pressure, so that rupture of either the tortuous vessels or the capillary plexus causes rapid bleeding. Bronchiectasis may result from prior bacterial or viral infection, cystic fibrosis, TB, host immune defects, or impairment of the mucociliary clearance apparatus (ciliary dyskinesia, which in the primary form may be associated with Kartagener's syndrome, and Young's syndrome). (See "Clinical manifestations and diagnosis of bronchiectasis" and see "Primary ciliary dyskinesia (Immotile-cilia syndrome)"). Fungal infections Fungal infections are increasing in frequency, especially in immunocompromised patients or those with preexisting cavitary disease. Hemoptysis occurs in 50 to 90 percent of patients with aspergilloma and may be massive, but the exact cause of bleeding is uncertain. Invasive parenchymal fungal infections also frequently cause hemoptysis, particularly the angioinvasive fungi Aspergillus and Mucor. The accompanying lung infarction probably augments the likelihood of bleeding from necrotizing infection. Bleeding may be somewhat more likely when bone marrow production of neutrophils is returning, since local inflammation may increase [12]. (See "Aspergilloma", see "Clinical features and diagnosis of invasive aspergillosis", and see "Mucormycosis (Zygomycosis)"). Other lung infections Other lung infections, particularly lung abscess, can cause massive hemoptysis. Bleeding may occur acutely from necrosis of lung tissue or from rupture of hypertrophied bronchial arteries in the setting of chronic inflammation. In

other countries, parasitic infections are very common etiologies of hemoptysis, particularly paragonimiasis in Southeast Asia. Severe leptospirosis may be complicated by massive alveolar bleeding and hemoptysis [13]. Bronchogenic carcinoma Bronchogenic carcinoma is an infrequent cause of massive bleeding, although it commonly causes nonmassive hemoptysis. Hemoptysis occurs at presentation in seven to 10 percent and sometime during the course in approximately 20 percent of patients with lung cancer. In one large series, three percent of lung cancer patients had massive, terminal hemoptysis [14]. Most patients with hemoptysis had small, sentinel bleeding episodes in the prior weeks, but in 20 percent the initial episode of hemoptysis was massive. The patients with massive hemoptysis typically had large, centrally located tumors, especially squamous cell carcinoma. Hemoptysis is also common in patients with bronchial carcinoid tumors, and the amount of bleeding is quite variable. Chemotherapy and bone marrow transplantation Patients undergoing chemotherapy for leukemia or those who have received a bone marrow transplant may have sudden and massive pulmonary hemorrhage that is frequently fatal. (See "Pulmonary complications after autologous hematopoietic cell transplantation"). The etiology is uncertain, but postmortem pathology suggests that it is due to diffuse lung injury, presumably from a combination of drugs, radiation, and/or thrombocytopenia. There may also be contributions from underlying fungal or viral infection. These patients are at risk for developing diffuse alveolar hemorrhage and respiratory failure even in the absence of hemoptysis. Usual treatment includes highdose glucocorticoids, and platelet transfusion if thrombocytopenia is present. The optimal dose and duration of steroid therapy is not clearly defined in this setting. Immunologic lung diseases A number of diffuse parenchymal lung diseases with an immunologic basis may cause massive bleeding. Specific etiologies include Goodpasture's syndrome, Wegener's granulomatosis, systemic lupus erythematosus (SLE), and idiopathic pulmonary hemosiderosis. Pathologically, many of these diseases have components of pulmonary capillaritis, particularly SLE, Wegener's granulomatosis, and microscopic polyangiitis. The causes and features of diffuse alveolar hemorrhage are summarized in Table 3 (show table 3A-3B) [15,16].

Surprisingly, the degree of hemoptysis may be much less than the amount of bleeding, since the alveolar location of the bleeding may not stimulate the cough reflex to the same degree that occurs with other, predominantly larger airway locations of bleeding. However, recognizing diffuse alveolar hemorrhage and diagnosing its underlying etiology is important because of the necessity of early treatment with steroids, possibly cytotoxic drugs, and/or plasmapheresis. (See "Treatment of anti-GBM antibody disease (Goodpasture's syndrome)", see "Initial and maintenance therapy of Wegener's granulomatosis and microscopic polyangiitis", and see "Pulmonary manifestations of systemic lupus erythematosus in adults"). Cardiac and vascular disease Cardiovascular etiologies infrequently cause massive hemoptysis. Pulmonary arteriovenous malformations may bleed, whether they are single or multiple and whether or not they are part of hereditary hemorrhagic telangiectasia (HHT or Osler-Weber-Rendu syndrome) [9,17].

Mitral stenosis used to be common, but now is rare. There is calcification and increased resistance in the pulmonary veins, accompanied by reversal of blood flow from the pulmonary capillaries into the bronchial veins. The resulting submucosal bronchial varices may rupture, causing "cardiac apoplexy." Cardiopulmonary bypass can markedly reduce such bleeding when it is life-threatening. Hemoptysis from pulmonary emboli is usually scant in volume, but may become massive after anticoagulation or the use of thrombolytic agents. Pulmonary artery catheterization can result in iatrogenic pulmonary artery perforation. Septic pulmonary emboli from right-sided infective endocarditis occasionally may result in massive bleeding. Congenital heart disease or severe pulmonary hypertension can also cause significant hemoptysis. Aortic aneurysm can present with either submassive or massive hemoptysis.

ACUTE MANAGEMENT The acute and general management of patients with massive hemoptysis is difficult for several reasons: There are a multitude of potential etiologies. The course of bleeding is unpredictable. As an example, sometimes a small, sentinel bleed heralds a massive, asphyxiating bleed. It is frightening to see patients dying from asphyxiation, even in spite of intubation. There is no consensus regarding the optimal management of these patients, and there are no large series of patients studied.

Initial priorities are insuring adequate airway protection, ventilation, and cardiovascular function [18]. Patients with poor gas exchange, rapid ongoing hemoptysis, hemodynamic instability, or severe shortness of breath should be orally intubated with a large bore endotracheal tube (size 8.0 or greater). Coagulation disorders should be rapidly reversed. Early consultation with pulmonary medicine and thoracic surgery should be obtained, possibly supplemented by invasive radiology. Once the patient is stabilized, early bronchoscopy should be performed. The clinician's judgment about whether there is blood accumulating in the lungs, the patient's current physiologic status, and the patient's underlying pulmonary reserve all influence the need for aggressive intervention. Patients who are clinically stable, have adequate gas exchange and hemodynamics, and have intermittent or slowing hemoptysis can be evaluated with a detailed history and physical examination followed by a more considered diagnostic evaluation. (See "Diagnostic approach to massive hemoptysis in adults").

Protection of the nonbleeding lung Protection of the nonbleeding lung is a major priority in the acute management of ongoing hemoptysis. Spillage of blood into the non-bleeding lung can either block the airway with clot or fill the alveoli and prevent gas exchange. Unfortunately, protection of the nonbleeding lung requires identification of the likely site of bleeding, which may not be readily apparent. If the location or side of bleeding is known, placing the bleeding lung in a dependent position may prevent blood spillage into the nonbleeding lung. An alternative strategy involves placement of a typical, single lumen endotracheal tube into either the right or left mainstem bronchus. This is easier to achieve with bleeding from the left lung, when one wants to selectively intubate the right mainstem bronchus. However, a potential problem is that right mainstem bronchial intubation often blocks the right upper lobe bronchus. The approach of selective intubation is less practical when the right lung is bleeding, because selective intubation of the left mainstem bronchus may be quite difficult. A third alternative is the placement of a double lumen endotracheal tube specially designed for selective intubation of the right or left mainstem bronchi [19]. In general, selective intubation of the left lung is preferable, since there is little risk of obstructing the right upper lobe bronchus with the bronchial cuff. While double lumen tubes are conceptually appealing, there are a number of practical problems with their use: They may be difficult to place, even by experienced anesthesiologists, especially when patients are bleeding rapidly. Insuring proper placement is difficult, and a tube that was properly positioned may move when the patient's position changes. When the tube moves, either blood spillage or bronchial obstruction may result. Consequently, patients with double lumen tubes usually should be paralyzed and should not be moved unless absolutely necessary. The individual lumen size often is small and may prohibit passage of a bronchoscope and necessitate a tube change for diagnostic procedures. Individuals caring for the patient must be knowledgeable about determining whether or not the tube is properly positioned. The small endotracheal tube lumen may predispose to intra-tube clot and airway obstruction.

Given these difficulties, the use of double lumen endotracheal tubes is not recommended except in patients who are exsanguinating and/or asphyxiating from their bleeding, and when no other approaches are possible. Use of bronchoscopy in acute management A bronchoscopic option for protecting the non-bleeding lung is balloon tamponade of the bleeding site, involving placement of a four French 100 cm Fogarty balloon catheter in the segmental or subsegmental bronchus leading to the bleeding site. The balloon is left inflated for 24 to 48 hours, and the patient is then observed for rebleeding with the balloon deflated for several

hours [3]. There is a potential risk of ischemic mucosal injury and postobstructive pneumonia, but these complications have not been reported. Bronchoscopic techniques used to slow or stop bleeding have included lavage with iced saline and application of topical epinephrine (1:20,000), vasopressin, thrombin, or a fibrinogen-thrombin combination [20]. None of these methods has been tested in controlled trials. Anecdotally and in our experience, topical epinephrine sometimes has seemed to slow or stop bleeding. Issues regarding the use of flexible fiberoptic versus rigid bronchoscopy are discussed elsewhere. (See "Diagnostic approach to massive hemoptysis in adults"). If bronchoscopy visualizes a localized bleeding mucosal lesion, laser therapy or electrocautery may be considered, if available. Both techniques can be used through a flexible or rigid bronchoscope. Since excellent visualization of the bleeding site is required, the rigid bronchoscope may be preferred because of its better suction capability. (See "Bronchoscopic laser resection" and see "Endobronchial electrocautery"). Arteriographic embolization The other option for the patient who continues to bleed is arteriographic embolization, either as "semi-definitive" treatment or as a bridge to elective surgery. In the hands of experienced angiographers, embolization successfully stops bleeding more than 85 percent of the time, especially if the bronchial circulation and the systemic arterial supply are carefully defined [21,22]. Early technical failures account for 5 to 10 percent of the patients who have unsuccessful control of bleeding; this usually results from inability to cannulate the bronchial artery or failure to identify and embolize all collateral systemic feeder vessels. Collateral systemic feeder vessels arising from the gastric, intercostal, internal mammary, renal, and hepatic arteries have been reported [22-26]. Routine post-embolization thoracic aortography may improve detection of bleeding from the systemic circulation. In a prospective series of 76 patients managed at a single center, 14 percent of all bleeding vessels were not seen during initial bronchial artery embolization, but were visible when aortography was performed [27]. These vessels arose most commonly from the intercostal and inferior phrenic arteries. Unfortunately, embolization is only "semi-definitive," because rebleeding occurs in a significant minority (eg, at least 10 to 20 percent) of patients over the next 6 to 12 months [10,28-30]. Late rebleeding may be due to incomplete embolization, revascularization, or recanalization. Acute complications of arteriographic embolization include bronchial wall necrosis and ischemic myelopathy due to inadvertent embolization of a spinal artery [31], but are uncommon when the arteriographers are experienced in this procedure [32]. Surgery Patients with lateralized, uncontrollable bleeding should be assessed early for possible surgery in case the bleeding remains brisk and unresponsive to other measures. This assessment ideally includes pulmonary function tests, but often these patients are too ill for physiologic testing, and historical data are therefore used to estimate the patient's ability to undergo lung resection. Relative contraindications to surgery include severe underlying pulmonary disease, active TB, diffuse underlying lung disease (cystic fibrosis, multiple AVMs, multifocal bronchiectasis), and diffuse alveolar hemorrhage.

Morbidity and mortality are significantly greater with emergent surgery for persistent massive bleeding compared with elective surgery in the nonbleeding patient. In most series of emergent therapy, surgical mortality for treatment of massive hemoptysis is approximately 20 percent, with morbidity occurring in an additional 25 to 50 percent of patients. Common complications include empyema, bronchopleural fistula, postoperative pulmonary hemorrhage, lung infarction, respiratory insufficiency, wound infection, and hemothorax. The first two complications are especially frequent after emergent surgery. (See "Sequelae and complications of pneumonectomy"). RESULTS OF ACUTE TREATMENT Considering arteriographic embolization and all other techniques short of surgery as "medical therapy," several retrospective studies have compared medical and surgical treatment for massive hemoptysis [1]. The older literature clearly favors surgery as having a much lower mortality. However, the highest risk patients in these studies were not considered to be surgical candidates and were managed with medical therapy. Reports from the 1980s suggested that the mortality rates from medical and surgical therapy are approximately comparable in patients who qualified as surgical candidates. However, medically treated patients probably have a higher risk of rebleeding within the first six months. RECOMMENDATIONS Based on the above data, the following is a reasonable approach to the patient with massive hemoptysis: First, stabilize the patient and then perform early bronchoscopy along with other appropriate diagnostic studies. (See "Diagnostic approach to massive hemoptysis in adults"). If the patient continues to bleed aggressively, arteriography is most reasonable for localization and therapy. If bleeding persists despite embolization or if the patient is too ill to go to angiography, then blockade therapy or a double lumen tube should be considered in preparation for rigid bronchoscopy in the operating room with possible lung resection if warranted. While surgery remains the only truly definitive therapy, it should not be used in the acute emergent setting unless it cannot be avoided.