Hemoptysis

Hemoptysis

I. Problem/Condition.

Hemoptysis, which literally means “spitting up blood”, is clinically used to describe expectoration of bloody sputum.

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

Hemoptysis is associated with a myriad of pulmonary conditions including infection, malignancy, vascular abnormalities, injury, and vasculitis. Infections include bacterial pneumonia, fungal infections, tuberculosis, and lung abscess. Malignancies may be primary or metastatic. Vascular abnormalities include aneurysms, thoracic aortic dissection, pulmonary embolism both thrombotic and septic, as well as arterial fistulas.

The differential diagnosis also includes inflammatory conditions (e.g., chronic bronchitis or bronchiectasis), vasculitis (particularly granulomatosis with polyangiitis [formerly known as Wegener’s granulomatosis]), and autoimmune diseases (e.g., Goodpasture syndrome and systemic lupus erythematosus). Lung injury, whether it be external from pulmonary contusion, status post-biopsy, or inhalant injury from an aspirated foreign body or cocaine (i.e., “crack lung”) can also lead to hemoptysis.

In addition, pulmonary hypertension, severe mitral stenosis, and decompensated congestive left heart failure can lead to hemoptysis. In younger patients, the differential diagnosis should be expanded to include cystic fibrosis and idiopathic pulmonary hemosiderosis.

B. Describe a diagnostic approach/method to the patient with this problem

First, remain calm. Although popular media portrays even mild hemoptysis as having high acute mortality, the literature does not support this. This perception however increases the anxiety of both patients and providers.

It is often difficult to quantify the amount of blood expectorated, and a clearly defined limit for massive hemorrhage has not been agreed upon, although volumes in the range of 200-500 mL have been considered. Risk factors for massive hemoptysis include alcoholism, cancer, aspergillosis, pulmonary artery involvement, and mechanical ventilation.

Based on the history, hemoptysis can often be differentiated from hematemesis (vomiting of blood) or oropharyngeal bleeding. Attempt to obtain duration, quantity, and the trigger for bloody cough. Obtaining associated symptoms related to specific disease states may help narrow the differential diagnosis.

1. Historical information important in the diagnosis of this problem.

The natural history of the sputum is important to understand. Frothy bloody sputum is associated with pulmonary edema and hence congestive heart failure and pulmonary embolism. Purulent (i.e., yellow or green) sputum, either preceding or associated with hemoptysis, is more indicative of infectious etiology. Consider asking your patient the following questions:

“How long have you been coughing up blood?”

“What does it look like?”

“Is there mucus?”

“Did it come before the blood or did the blood start all at once?”

“How much blood do you think there was – just a little, like foam, or a lot more than that?”

“What size container did you fill or could you have filled?”

Sometimes the patient will have already started to fill an emesis basin or other bedside container, and a volume rate can be estimated from how rapidly they have filled that container. Always remember to elicit a history of smoking or inhalation of other (acute) caustic and (remote) carcinogenic substances.

Seek out associated symptoms, such as chest pain, i.e., pleuritic pain associated with pulmonary infection or pulmonary embolism, versus pain radiating to the back associated with thoracic aortic dissection.

A review of systems sensitive for risk factors of pulmonary embolism should increase clinical suspicion for the presence of a clot. If considering septic emboli, elicit a history of intravenous drug use or recent vascular access by central line, pacemaker, or defibrillator.

For infection consider asking: “Have you had any fever, chills, shakes, night sweats, malaise, fatigue, or decreased appetite?” For tuberculosis, questions regarding immune suppression, HIV exposure, foreign travel, or incarceration will be important.

When considering malignancy review smoking history, asbestos exposure, recurrent pneumonia, unintentional weight loss, family history, and more chronic hemoptysis.

If vasculitis is suspected (particularly when considering granulomatosis with polyangiitis), be sure to pursue urinary symptoms, particularly hematuria: “Has your urine changed color or looked bloody?” If systemic lupus erythematosus is suspected, history of myalgia, fatigue, fever, rash, and weight-change may be present.

Decompensated heart failure might be elicited with, “Are you using more pillows to sleep comfortably at night? Has your weight increased? Do you have worsened swelling of the legs?” Severe mitral stenosis may also present with congestive heart failure-like symptoms.

Presumably, in adult patients, cystic fibrosis and idiopathic pulmonary hemosiderosis would be part of their known past medical history.

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

Thorough examination of the oropharynx and nasopharynx with a strong light source and tongue blade may yield diagnostic clues for vasculitis and help to confirm the source of bleeding as being oropharyngeal rather than pulmonary.

Although nonspecific, crackles may localize bleeding to the left or right lung. A murmur may increase suspicion for mitral stenosis. Jugular venous distention may increase suspicion for decompensated heart failure or pulmonary hypertension.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Routine diagnostic work-up includes:

Complete blood count (CBC)

Comprehensive metabolic panel (CMP) – elevated BUN may be indicative of consumed blood; abnormal liver function tests may be indicative of coagulopathy secondary to liver disease; decreased total protein and albumin or hypercalcemia may be indicative of pulmonary malignancy.

Prothrombin time /international normalized ration (PT/INR)

Partial thromboplastin time (PTT)

Chest X-ray, preferably posterior-anterior and lateral views.

Other diagnostic testing that may be useful by suspected etiology:

Sputum and blood cultures in suspected infectious causes with acid fast bacteria cultures of sputum and blood in suspected tuberculosis. In younger patients consider HIV testing. Consider a “Pneumonia Panel” which includes serum, urine, and nasal wash antigen and/or serology testing for Legionella, Pneumococcus, Mycoplasma, and viral studies.

D-dimer if low to intermediate pre-test probability; if positive, pursue CT pulmonary embolism protocol or ventilation perfusion scan with or without lower extremity venous Doppler. Remember that D-dimer may be elevated in any type of clotting even that of recurrent pulmonary bleeding. With low to intermediate pre-test probability, a negative D-dimer rules out pulmonary embolism as well as thoracic aorta dissection.

Cardiac markers, brain natriuretic peptide (BNP) and electrocardiogram (ECG) are necessary to confirm decompensated congestive heart failure if suspected by history and physical examination.

If granulomatosis with polyangiitis is suspected, ANCA and urine analysis are appropriate. In addition, ANA, C3 and C4, cryoglobulins, hepatitis serology, and HIV screen may be important to rule out other etiologies.

Consider transthoracic echocardiography as the first line test if you suspect pulmonary hypertension, mitral stenosis, or infective endocarditis leading to septic pulmonary emboli. Transesophageal echocardiography may still be warranted if the initial echocardiogram is inconclusive.

Urine toxicology may be of benefit in suspected “crack lung” if patient is unable to provide history.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

Chronic bronchitis is defined as cough productive of sputum for at least three months per year in two consecutive years. It is considered a type of chronic obstructive pulmonary disease.

Pneumonia is clinically defined as radiographic evidence of infiltrate, with or without microbiological data, and the associated clinical symptoms of fever, cough, sputum production and/or pleuritic chest pain.

Tuberculosis can be ruled out when three consecutive acid fast bacilli cultures are negative.

Bronchiectasis is diagnosed by high resolution computed tomography (CT) and pulmonary function testing.

Malignancies and abscess will have a characteristic radiographic appearance but may be confused with one another. They both require tissue biopsy either by bronchoscopy, radiologically guided needle biopsy, or thoracoscopy to confirm diagnosis. Gram stain may also be helpful.

Vascular abnormalities including aneurysms, thoracic aortic dissection and pulmonary embolism, are computed tomographic angiography (CTA) diagnoses. Some arterial fistulas may be radiographically apparent but others may require bronchoscopic visualization. Infective endocarditis is defined by modified Duke criteria.

Granulomatosis with polyangiitis, whether the ANCA is positive or negative, requires a tissue diagnosis of either lung or renal lesions, but not both. Systemic lupus erythematosus has specific diagnostic criteria written by the American College of Rheumatology.

Pulmonary hypertension, mitral stenosis, and left systolic heart failure are characterized by specific echocardiographic criteria.

Lung injury, whether trauma or inhalant in origin, can be diagnosed by history and clinical examination. Radiography may be of adjunctive help.

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

Due to the perceived association between hemoptysis and acute mortality, patients with hemoptysis are often placed at a higher level of care than needed. They are also subjected to tests that are of minimal benefit. Diagnostic testing should be based on a differential diagnosis developed from a sound history and physical. Due to the wide number of etiological processes, a stepwise approach to diagnostic testing is preferred.

Strongly consider PA and lateral views for chest radiography rather than simply portable films for greater diagnostic yield.

CT will often be necessary but not essential for work-up, thus starting with plain chest radiography is appropriate. If CT is deemed necessary consider whether or not the diagnosis requires contrast and if so, what phase contrast will be most diagnostic.

CTA of the arterial phase examines abnormalities in systemic arterial contrast, e.g., aortic dissection, aortic fistula, while venous phase examines abnormalities in pulmonary arterial contrast, e.g., pulmonary embolism. Thus knowing what you are looking for will determine when, after the contrast bolus, the images will be acquired.

Bronchoscopy has decreased yield, and is presumably not indicated in patients who are below 40 years old, non-smokers, with less than 1 week of hemoptysis, and who have a normal chest X-ray.

III. Management while the Diagnostic Process is Proceeding

A. Management of hemoptysis.

The first clinical decision must be whether to intubate the patient for airway protection. A patient will need intubation if they are unable to clear blood or other secretions, in extremis, failing non-invasive positive pressure support ventilation, or if they have worsening hemodynamics, or a decline in mentation despite interventions.

If it is possible to localize the bleed, it may be necessary to perform intubation of main left or right bronchus to isolate bleeding and protect the other lung. Patients requiring intubation may need more urgent bronchoscopy or arteriography to isolate bleeding.

If you suspect tuberculosis, airborne isolation should be ordered empirically to protect other patients and providers.

Continuous positive pressure ventilation may, theoretically, play a role by applying positive pressure (i.e., tamponade) to allow clotting to occur.

Initial work-up:

Continuous pulse oximetry

Arterial blood gas (ABG)

CBC with differential

CMP

PT/INR

PTT

D-dimer (if low to intermediate modified Geneva criteria, if high go immediately to pulmonary embolism imaging)

Type and screen

Chest X-ray (posterior-anterior and lateral), portable (anterior-posterior) chest X-ray if patient unable to stand or hemodynamically unstable

Request old records (with particular attention to previous pulmonary function testing, CT, and pulmonary function testing)

Decrease cough (i.e., by decreasing pulmonary “trauma” from cough, clot can organize and bleeding stops):

Dextromethorphan 10-20mg every 4 hours PO as needed

Benzonatate 100mg every 4 hours PO as needed

Codeine 10-20mg every 4-6 hours PO as needed

Morphine 1-2mg every 2-4 hours IV/IM as needed

(Guaifenesin is an expectorant and would not be of benefit)

Correct coagulopathy:

Depending on the nature of the patient’s anticoagulation type and reason, vitamin K, fresh frozen plasma, platelets, protamine, and/or prothrombin complex concentrate may be required.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem

Focusing on the blood that the patient is expectorating rather than the cause of the hemoptysis is the primary pitfall of management. In order to avoid this pitfall, an accurate history must be obtained, but this may be difficult with the panic that frank blood can cause in the patient, family, and ancillary providers.

If the patient cannot provide a history an important distinction needs to be made rapidly. Either the patient is hypoxemic due to hemorrhage into the lungs, which should lower the threshold for intubation, or they are anxious due to the visceral impact of hemoptysis and require reassurance with symptom control. If administration of an antitussive and correction of coagulopathy is enough to halt or slow the hemoptysis, do this first and then re-approach the patient.

To the patient and nursing staff, any amount of blood forcibly ejected from the mouth is too much. Thus, repeated bedside assessment to gauge whether the hemoptysis is improving or worsening is important. If hemoptysis is improving due to the interventions above, then you have increased the time to engage in diagnostic inquiry. If hemoptysis is worsening, particularly with increasing respiratory and heart rate, the threshold for intubation should decrease.

Additional diagnostic testing, as stated above, will usually, but not always, include CT of the chest. Clinical suspicion of the underlying etiology should drive the decision as to whether the imaging is necessary, and if so what type of scan should be obtained.

• Pneumonia or malignancy will often be seen on a CT chest without contrast. However, lesions are better characterized with contrast than without, or by using high resolution CT of chest. Contrast administration carries a risk of renal injury and high resolution scans involve increased resolution, thus the clinical benefits of diagnosis must be weighed against these risks.

• CTA of chest (arterial phase) is best suited for suspected aneurysms, thoracic aorta dissections, and arterial fistulas.

• If pulmonary embolism is suspected as the cause, obtain a CTA of chest (venous phase, i.e., “CT PE protocol”). If the patient is dye intolerant due to allergy or renal impairment, consider using ventilation perfusion scan with or without lower extremity venous Dopplers.

• CTA of chest both phases can be used in cases where the cause is unclear and the benefits of diagnosis outweigh harms from radiation and contrast.

• Bronchial artery embolism (BAE) or surgical intervention may be necessary in the case of massive hemoptysis or recurrent hemoptysis.

• Pulmonary function testing may be useful to diagnose obstructive or restrictive lung disease that could cause hemoptysis. It is unlikely that this will be useful or obtainable acutely but may be indicated in follow-up if the underlying cause of the hemoptysis is still unclear.

Further diagnostic testing will also be driven by clinical suspicion. A suspected etiology should be hypothesized based on the history, pertinent exam findings, and available diagnostic data. This diagnosis and any pertinent differentials should be pursued. Blanket testing in the form of diagnostic testing and radiology is not recommended.

Suspected infectious cause:

Repeat blood cultures (x3 if suspecting infectious endocarditis)

Sputum culture and sensitivity

“Pneumonia panel” (see above)

Human immunodeficiency virus (HIV) screen

If suspecting tuberculosis:

Airborne isolation

Acid-fast bacilli blood culture

Sputum acid fast bacilli daily x3

Suspected cardiac cause:

ECG

Brain natriuretic peptide (BNP)

Repeat cardiac markers

Telemetry

Transthoracic echocardiogram

Transesophageal echocardiogram

Suspected inflammatory cause:

Anti-neutrophil cytoplasmic antibody (ANCA)

Urine analysis

Antinuclear antibody (ANA)

C3 and C4

Cryoglobulins

Hepatitis serology

HIV screen

Respiratory therapy:

Room air

Supplemental oxygen

Nasal cannula (NC)

Ventimask (VM)

Non-rebreather (NRB)

Continuous positive pressure ventilation (CPAP)

Antitussives:

Dextromethorphan 10-20mg every 4 hours PO as needed

Benzonatate 100mg every 4 hours PO as needed

Codeine 10-20mg every 4-6 hours PO as needed

Morphine 1-2mg every 2-4 hours IV/IM as needed

What's the evidence?

Ramírez Mejía, AR, Méndez Montero, JV, Vásquez-Caicedo, ML, Bustos García de Castro, A. “Radiological Evaluation and Endovascular Treatment of Hemoptysis”. Curr Probl Diagn Radiol. vol. 45. 2016. pp. 215-24. (This review discusses the pathophysiology of hemoptysis in relation to the blood supply of the lungs. It also breaks down the different imaging modalities and emphasizes which modality may be best to identify the exact location of the bleed. It highlights the role of bronchoscopy and CT angiography and how the information obtained from these studies is used in bronchial artery embolization or surgical interventions.)

Yendamuri, S. “Massive Airway Hemorrhage”. Thoracic Surgery Clinics. vol. 25. 2015. pp. 255-260. (This review focuses on the management of patients with massive hemoptysis. It provides a clear outline to approaching such patients in the clinical setting.)

Larici, AR, Franchi, P, Occhipinti, M, Contegiacomo, A. “Diagnosis and management of hemoptysis”. Diagn Interv Radiol. vol. 20. 2014. pp. 299-309. (This article was also written in the context of review lung anatomy and ways to localize the source of the bleeding in a patient presenting with hemoptysis. The authors present management algorithms for both massive and non-massive hemoptysis.)

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