Pulmonary Hemorrhage

Etiology

The usual source of massive pulmonary hemorrhage is the bronchial vasculature. This high-pressure system is responsible for up to 90% of massive hemoptysis.[2] Other sources include aortobronchial fistulas, ruptured aneurysms, nonbronchial sources (5%), and pulmonary vessels (5%).

Based on the results from a retrospective cohort study of 1087 patients at a single tertiary hospital in France, the most common causes of massive pulmonary hemorrhage are:

• Tuberculosis (25%; with active responsible for 12% and sequelae 13%)
• Bronchiectasis (20%)
• Mycetomas (6%)
• Cryptogenic hemoptysis (18%)
• Bronchogenic carcinomas (17%) [4][1]
• Other sources: Trauma and iatrogenic

Results from a more recent prospective Italian study of 606 patients from 5 Italian hospitals showed the most common causes to be:

• Lung cancer (19.1%)
• Pneumonia/lung abscess (18.6%)
• Bronchiectasis (14.9%)
• Acute bronchitis (13.7%)
• Tubercluosis (5%; active [3.3%] and sequelae [1.7%]) [5]

In a Greek study, results showed that bronchiectasis and neoplasms are the leading cause of moderate-to-severe pulmonary hemorrhage (moderate defined as 20-500 mL in 24 hours; severe defined as more significant than 500 mL in 24 hrs).[6]

Epidemiology

Hemoptysis, coughing up blood from the respiratory tract, presents varied epidemiological patterns influenced by underlying conditions and geographic factors. A symptom rather than a disease is commonly associated with respiratory infections, chronic lung diseases, and malignancies. Hemoptysis generally involves minimal bleeding, often linked to inflammatory or infectious causes, usually amounting to less than 100 mL of blood over 24 hours. Although massive hemoptysis is rare, accounting for 5% to 15% of cases, it is a life-threatening condition that requires immediate and effective assessment and management. The definition of massive hemoptysis varies widely in the literature, with previous descriptions ranging from more than 200 mL to over 1000 mL of blood within 24 hours.[7]

The prevalence and incidence of hemoptysis vary widely across different regions and populations, with higher rates often observed in areas with a high burden of tuberculosis (TB), bronchiectasis, and lung cancer. In developed countries, chronic bronchitis and bronchiectasis significantly contribute to hemoptysis, whereas TB remains a prominent cause in developing regions. Epidemiological studies indicate a bimodal distribution, with peaks in younger adults due to infections like TB and in older adults due to malignancies such as lung cancer. In a single-center French study, the median age was 54; 71% of the patients were men, and a smoking history was present in 71% of the patients. The study by Mondoni et al showed a median age of 67, 66.7% of the patients were men, and a smoking history was present in 54% of the patients.[5] 

Pathophysiology

The pathophysiology of various conditions is described below: 

• Tuberculosis
  • During active TB, bleeding is usually a result of ulcerations with subsequent necrosis of adjacent vessels.[8] In patients with a history of TB, it is often a consequence of the erosion of a calcified lymph node into a vessel and trachea, bronchiectasis secondary to the prior infection, or fungal infection in a cavity left from an earlier infection.[9] While the offending vessel is usually one of the bronchial arteries, a rupture of a Rasmussen aneurysm may occasionally come off the pulmonary artery circulation.[10]
• Bronchiectasis
  • This includes rupture of the tortuous vessels and hypertrophy due to chronic inflammation in the bronchial arterial system and blood vessels in the peribronchial and submucosal plexus.
• Mycetomas
  • The most common organism responsible for this condition is Aspergillus fumigatus (50%-90%), which is known to cause vascular and parenchymal changes in infection.[8]
• Smoking
  • Cryptogenic bleeding tends to occur in smokers.[11][12]
• Carcinoma
  • Squamous cell carcinoma and other centrally located malignancies are either vascular sources themselves or erode into nearby vessels.[2]
• Pneumonia
  • Staphylococcus aureus is among the most common pathogens. The production of Panton-Valentine Leukocidin (PVL) toxin in methicillin-susceptible Staphylococcus aureus and methicillin-resistant Staphylococcus aureus strains is linked to heightened bacterial virulence.[13] Pathogenicity of the PVL exotoxin is thought to be due to binding via a G protein-coupled membrane-bound receptor that causes neutrophil adhesion to endothelial cells, capillary dilation, leukocyte migration, and vascular necrosis.

History and Physical

Differentiating between gastric and pulmonary sources of bleeding is essential. Asking the patient whether the bleeding is from vomiting or coughing can sometimes help differentiate. A pertinent history will include the amount of blood loss, onset, fevers, history of TB infection or travel to endemic areas, smoking history, cancer history, night sweats, weight loss, and history of anticoagulation use. Asking about the patient's exertional status (ie, ability to climb stairs or walk distances) before the episode is also pertinent, as it may help determine whether or not the patient can functionally tolerate a lobectomy if indicated.[14]

The patient's initial evaluation includes an assessment of their airway, breathing, and circulation. Evaluate the patency of the airway and check the oropharynx for a proximal bleeding source. The bulk of the physical exam should focus on evaluating stability and ruling out any nonpulmonary source (eg, hematemesis or epistaxis).[2] Capillary refill and skin evaluation can help decide if the patient needs an emergent transfusion of blood products. A lung exam may help determine if there is a unilateral source of the bleeding.

The exact amount of blood loss in hemoptysis varies in the literature, ranging from 100 to 200 mL, making it difficult to measure accurately. Given that the anatomical dead space of an average adult is about 200 mL, a patient presenting with distress, tachypnea, and hypoxia alongside significant hemoptysis should prompt immediate resuscitation efforts. This clinical presentation should guide intervention rather than attempting to measure and quantify the precise amount of blood loss.

Evaluation

A complete blood count with differential should be drawn to evaluate the hemoglobin and hematocrit and assess for thrombocytopenia. A basic metabolic panel, blood type, crossmatch, arterial blood gas, and coagulation panel should also be obtained. A frontal chest x-ray (CXR) should be obtained to find a unilateral source. CXR can determine the site of bleeding 45% to 65% of the time and the cause in 25% to 35%.[15] If the patient is stable, a chest computed tomography (CT) scan can be considered to delineate the source and etiology. CT may be more sensitive than bronchoscopy; some sources consider it the first line in the evaluation.[16][17][18][19][20]

Treatment / Management

Lung Isolation

If the chest radiograph shows a unilateral source of bleeding or a known source is elicited in the history and physical, place the affected side down to isolate bleeding and spare the remaining lung.[15][21] Other simple maneuvers include putting the patient in the Trendelenburg or reverse Trendelenburg position to isolate the bleeding source further.[15](B3)

Intubation

If the decision is made to intubate, it is advisable to use at least an 8 mm endotracheal tube (ETT) to allow subsequent use of bronchoscopy and bronchial blockers. Direct laryngoscopy is generally preferred over video laryngoscopy when there is significant bleeding. Attaching a meconium aspirator to the ETT may help with visualization. If bleeding is uncontrolled, intubating the right main stem may be necessary. If the bleeding originates from the left side of the lung and no bronchoscope is available, place the patient in the right-lateral decubitus position to shift the mediastinum to the right. 

In a study on 25 cadavers, the intubating clinicians were able to select the desired lung by first intubating the patient and then rotating the ETT 90° toward the desired side and advancing until resistance was met. This technique was successful 72.3% of the time for the left lung and 94% for the right lung.[22] Suppose attempts to select the proper lung are unsuccessful. In that case, it may be possible to intubate the right main stem with a 5 mm ETT, allowing either ventilation of the right lung if it is unaffected or isolation of the right lung if it is hemorrhaging. If the right lung is the affected side, the 5 mm ETT should be small enough to allow the placement of another ETT to the left lung for ventilation. Approaches like suction suction-assisted laryngoscopy and airway decontamination (SALAD), and double suction techniques have been developed to properly control the soiled airway.[23]

Anticoagulation Reversal

If the patient is on anticoagulation, reversing any medication is paramount in achieving hemostasis.

Tranexamic Acid 

With the success of the World Maternal Antifibrinolytic (WOMAN) and Clinical Randomisation of an Antifibrinolytic in Significant Hemorrhage 2 (CRASH-2) trials in postpartum hemorrhage and trauma, respectively, there have been some case reports of the use of intravenous tranexamic acid (TXA) or nebulized TXA in pulmonary hemorrhage with some success.[21] Results from a recent randomized controlled trial of 47 patients showed 96% resolution of hemoptysis in 5 days with inhaled TXA 500 mg 3 times a day versus the placebo group with 50%. Patients with hemoptysis greater than 200 mL in 24 hours or with hemodynamic or respiratory instability were excluded.[24](A1)

Double-Lumen Endotracheal Tube

Double-lumen tubes are generally not recommended for many reasons:

• The bronchoscope used to place the double-lumen ETT does not have adequate suction channels to give clear visualization in the face of massive bleeding or the ability to suction out large clots.
• The double-lumen ETT only allows pediatric bronchoscopes and not therapeutic bronchoscopies.
• This ETT does not allow evaluation of the proximal airways.
• Placement of the double-lumen ETT is more time-consuming and requires more expertise; this may be difficult to assemble during a crisis.[14]

Bronchoscopy

Fiberoptic bronchoscopy allows for visualization of the source of bleeding, clearing the airway of bleeding and clots (especially in the nonbleeding lung). Visualizing the bleeding source is essential for later hemostatic techniques such as bronchial blocker placement. In large-scale bleeding, fiberoptic bronchoscopy is often necessary for proper intubation of the nonbleeding lung and can be used to wedge into the bleeding site to create tamponade.

Rigid bronchoscopy allows simultaneous evaluation of the bleeding source and ventilation of the nonbleeding lung. The large channels of this device can accommodate additional suction catheters and fiberoptic bronchoscopy for visualizations. The rigid bronchoscope also allows users to use the full array of intrabronchial therapeutic techniques.

Bronchial Blocker

This device allows for the simultaneous ventilation of clear lungs while tamponading the bleeding side. A bronchial blocker is usually inserted with the assistance of a fiberoptic bronchoscope through an ETT, which enables the placement of a cuffed catheter that can tamponade the bleeding lung. The device is generally inserted into the main stem bronchus or bronchus intermedius, providing temporary hemostasis until further definitive treatment can be administered.[25] When a commercial device is unavailable, some clinicians have described the successful placement of a Fogarty catheter through the channel of a fiberoptic bronchoscope, which can also be introduced alongside the ETT.[21](B3)

Intrabronchial Treatments

These include cold saline lavage, epinephrine injections, spigots, cellulose mesh, and antidiuretic hormone derivatives introduced through a fiberoptic or rigid bronchoscope. If a definitive source of bleeding is present and reachable, electrocautery, cryotherapy, laser, or argon plasma coagulation is also an option.[14]  

Bronchial Artery Embolization

Bronchial artery embolization (BAE) is a definitive treatment for bleeding from the bronchial artery system, which accounts for approximately 90% of cases. BAE is often considered the first line of management in massive pulmonary hemorrhage, with success rates reaching up to 90% in the right patient population.[26][27][28] Active contrast extravasation is observed in only 10% to 15% of cases, so site selection typically relies on radiographic signs such as hypertortuosity, artery hypertrophy, aneurysms, or arteriovenous malformations.[26][27][29] Suspected bleeding sources are embolized using microspheres, gelatin sponges, or coils. However, re-bleeding occurs in about 30% of patients within 30 days, making lobe resection a consideration for appropriate candidates.[27] With current technology, the complication rate for anterior spinal artery embolization is as low as 0% to 1%.[15](B2)

Surgery

Resection is considered the last resort for managing pulmonary hemorrhage due to its high mortality rates. According to a study by Adrejak et al, emergent resections have a mortality rate of 35%, which significantly decreases to 4% in resections scheduled after achieving hemostasis and 0% in planned resections after discharge.[30] Therefore, providing temporary hemostasis, when possible, is prudent to avoid emergency resection. This approach allows for medical optimization of the patient and affords more time to thoroughly evaluate the necessary extent of resection.[14](B2)

Differential Diagnosis

The following diagnoses should be considered in cases of pulmonary hemorrhage:

• Aspergilloma
• Alveolar hemorrhage
• Arteriovenous malformations
• Bronchitis
• Bronchiectasis
• Coagulopathy
• Emboli (pulmonary)
• Lung abscess
• Mitral stenosis
• Tuberculosis
• Tumor

Prognosis

The prognosis of pulmonary hemorrhage varies significantly based on the underlying cause, the severity of the bleeding, and the promptness and effectiveness of the treatment. Early recognition and intervention are critical to improving outcomes. Pulmonary hemorrhage, particularly when massive, is associated with high mortality rates, historically reaching up to 70% before the advent of BAE. The prognosis is generally favorable for patients with mild to moderate hemoptysis if the underlying cause can be effectively treated. Conditions like bronchiectasis, tuberculosis, and aspergilloma can be managed with appropriate medical or surgical interventions, leading to improved patient outcomes.

The prognosis is more guarded in cases of massive hemoptysis. Prompt and effective management, including airway protection, hemostasis, and definitive treatment of the bleeding source, is crucial. Techniques such as BAE have significantly improved survival rates, with up to 90% success rates in appropriate patient populations. However, there is still a risk of rebleeding, which occurs in approximately 30% of patients within 30 days, necessitating close follow-up and sometimes further intervention.

Overall, the prognosis of pulmonary hemorrhage depends on several factors, including the rapidity of intervention, the availability of advanced medical and surgical techniques, and the patient's overall health and comorbidities. With advances in medical technology and interdisciplinary care, patient outcomes with pulmonary hemorrhage continue to improve. Developing an interprofessional team to care for patients with hemoptysis is crucial to stratify cases, guide interventions, and determine the need for observation or hospital admission. Implementing such a team would help optimize resource allocation, facilitate timely interventions, and improve patient outcomes by effectively managing the root cause and acute bleeding episodes.[7]

Complications

Complications of pulmonary hemorrhage can be severe and life-threatening, reflecting the critical nature of this condition. Here are the primary complications associated with pulmonary hemorrhage:

• Respiratory failure
  • The most immediate and severe complication is respiratory failure due to the obstruction of airways by blood; this can lead to hypoxia, hypercapnia, and acute respiratory distress syndrome.
• Hemodynamic instability
  • Massive pulmonary hemorrhage can lead to significant blood loss, resulting in hypovolemic shock.
• Infection
  • The presence of blood in the airways and lungs can breed infections, including pneumonia; this risk is increased in patients who require prolonged intubation and mechanical ventilation.
• Rebleeding
  • Even after initial control of hemorrhage, there is a substantial risk of rebleeding, particularly in patients with underlying conditions such as bronchiectasis or arteriovenous malformations.
• Airway complications
  • Intubation and bronchoscopic procedures carry risks, including airway trauma, bronchospasm, and mucosal injury.
  • Improper positioning of endotracheal tubes or bronchial blockers can exacerbate bleeding or fail to control it adequately.
• Complications from interventions
  • Procedures like BAE can lead to complications such as nontarget embolization, which may cause ischemia in nontarget areas, including the spinal cord, leading to paraplegia.
  • The risk is low but significant, necessitating careful procedural planning and execution.
• Cardiovascular complications
  • Severe pulmonary hemorrhage can lead to right ventricular strain or failure due to increased pulmonary vascular resistance. 
• Neurological complications
  • Severe hypoxia due to respiratory failure can lead to neurological damage, including hypoxic brain injury. 
• Mortality
  • Despite advances in management, massive pulmonary hemorrhage remains associated with high mortality rates. 
  • The mortality rate is low for patients with mild (2.5%) and moderate (6%) hemoptysis but high (38%) for those with massive hemoptysis.
  • Patients with lung cancer or bleeding diathesis experience higher mortality rates compared to the rest of the group.[31]

Managing pulmonary hemorrhage requires a multidisciplinary approach involving pulmonologists, intensivists, interventional radiologists, and thoracic surgeons to address these complications effectively and improve patient outcomes.