Endobronchial Ultrasound 

Background

Endobronchial ultrasound (EBUS) is a technique that uses ultrasound along with bronchoscope to visualize airway wall and structures adjacent to it. The clinical application and diagnostic benefit of EBUS have been established in many studies. EBUS has been incorporated into routine practice in many centers because of its high diagnostic informative value and low risk. It may replace more invasive methods for staging lung cancer or for evaluating mediastinal lymphadenopathy and lesions in the future. EBUS and guided sampling is gaining popularity rapidly.

Two types of EBUS exist: radial probe EBUS (RP-EBUS) and convex probe EBUS (CP-EBUS). Radial probe EBUS was commercially available in 1992, which increased the yield of TBNA of mediastinal lymph nodes. The first CP-EBUS bronchoscope with "Echo camera" and "Aloka" ultrasonic probe was introduced in 1992. Another CP-EBUS device (Olympus XBF-UC40P) was introduced in 2002, but Olympus BF-UC160F-OL8 is the currently available CP-EBUS bronchoscope in the United States.

Physicians should have knowledge of mediastinal lymph node stations and sonographic anatomy of airway wall. The endobronchial ultrasound image visualize distinct layers of the bronchial wall with mucosa, submucosa, endochondrium, cartilage, perichondrium, connective tissue and adventitia. Mucosa, endochondrium, perichondrial layer, adventitia are hyperechoic while submucosa, cartilage and connective tissue appear hypoechoic.

Indications

Staging of non-small cell lung cancer (NSCLC)

EBUS-guided transbronchial needle aspiration (TBNA) has higher diagnostic yield than conventional TBNA in all lymph node stations except subcarinal lymph nodes in determining the lymph node involvement in NSCLC.^[1] Its ability to precisely visualize the airway wall invasion helps to categorize the tumor (T) component of staging and surgical resection planning.^[2] It can be combined with endoscopic ultrasound-guided fine-needle aspiration to near complete sampling of mediastinum using a single endobronchial ultrasound bronchoscope.^[3] It can also be used to restage the lung cancer in mediastinum.^[4]

Evaluation of mediastinal lesions, intrapulmonary pulmonary nodules, and endobronchial lesions

EBUS can visualize and allow physicians to sample and diagnose various mediastinal abnormalities,^[5] including sarcoidosis^{[6, 7]} and mediastinal lymphoma.^{[8, 9]} It can characterize the intraparenchymal and endobronchial lesions and help to determine the likelihood of malignancy based on appearance. EBUS-TBNA can visualize and allow sampling of pulmonary nodules that are not visualized by fluoroscopy and may avert the need for surgical procedures.^[10] RP-EBUS is relatively accurate tool in the investigation of peripheral pulmonary lesions.^[11]

Guidance of endobronchial therapy

EBUS provides useful additional information during various interventions including resection of endobronchial lesion, stricture dilatation, stenting, laser therapy, and argon plasma coagulation.^[12]

Contraindications

Contraindications to endobronchial ultrasound (EBUS) are similar to contraindications to flexible bronchoscopy and include following:

• Life-threatening cardiac arrhythmias
• Current or recent myocardial ischemia
• Poorly controlled heart failure
• Severe hypoxemia
• Uncooperative patient

Additional contraindications to EBUS-TBNA are related to bleeding risk and include following:

• Current anti-platelet agents^[13]
• Current anticoagulant therapy
• Coagulopathy
• Thrombocytopenia
• Elevated blood urea nitrogen or serum creatinine

Preparation

Anesthesia

EBUS is usually performed under procedural sedation and local anesthesia. Local anesthesia on airways is done by nebulizing 1% or 2% lidocaine and spraying lidocaine spray in the posterior pharynx. A 1-2 mL of 1% to 2% lidocaine can be installed through the working channel of bronchoscope during insertion and procedure, if needed. EBUS can be done in general anesthesia. The use of a laryngeal mask airway allows access to upper paratracheal nodes, which may not be accessible with endotracheal tube in place. The size of endotracheal tube should be at least No. 8 or larger, to accommodate the CP-EBUS bronchoscope. Patient should be NPO for at least 6 hours.

Equipment

RP-EBUS probe

• The system has ultrasound processor and balloon catheter that are attached to the probe. The balloon is fixed at the tip of the probe. If overinflation or excessive pressure occurs, the balloon slips from the tip and small amount of water is released from the balloon to prevent balloon rupture. The 20 MHz miniature radial probe is the standard probe. The 30 MHz miniature radial probe provides a more detailed image of the airway wall and surrounding structures. These probes have diameter of 2.5 mm so, a flexible bronchoscope with working channel of 2.8 mm is required to use it. The 20 MHz ultra-miniature radial probe is smaller than either miniature radial probe, so it can be inserted through the 2 mm working channel of a bronchoscope and can extend further into subsegmental bronchi than the miniature radial probe.

CP-EBUS bronchoscope

• Currently available CP-EBUS bronchoscope (Olympus BF-UC160F-0L8) has linear curved array ultrasonic transducer of 7.5 MHz at the distal tip, which has capability of displaying B-mode and color Doppler mode (see the image below). A) Convex endobronchial ultrasound probe B) Convex endobronchial ultrasound probe with balloon.
• The field of view is 80 º, and the direction of view is 35 º forward oblique. The outer diameter of the bronchoscope is 6.2 mm and inner channel diameter is 2 mm. The dedicated 22-gauge needle (NA-201SX-4022 single use) has echogenic dimpled tip to enhance visibility by ultrasound. The maximum extruding stroke is 40 mm with safety mechanism that stop at 20 mm. The needle has internal sheath which prevents contamination of sample by bronchial wall tissue (see the image below). Convex endobronchial ultrasound bronchoscope probe, distal end with needle out.

Positioning

EBUS is usually performed on supine position with operator standing on head end of bed. The bronchoscopist should have clear view of monitor.

Approach The monitoring devices are placed onto the patient, supplemental oxygen is administered by nasal cannula, and intravenous access is established before starting the procedure. Eyes should be covered to prevent splashing the normal saline, secretion, or blood into the eyes.

RP-EBUS

Conventional bronchoscopy with working channel of at least 2.8 mm is required for RP-EBUS. When the bronchoscope is in the airway and around the target lesion, the radial probe is placed in a catheter sheath and inserted through the working channel of the bronchoscope. The probe is positioned at the target level and the balloon is filled with water till it has firm contact with the airway. Complete circular image of airway wall and surrounding structures is obtained when the balloon has firm contact with the airway wall. RP-EBUS gives 360 º image of the airway wall and surrounding structures (see the image below).

If patient does not tolerate complete obstruction of airway, the balloon can be filled partially and applied to the airway wall in semicircular manner.

Sequential TBNA

Sequential TBNA is defined as localization of lesion first and subsequent sampling of the lesion. When the ultrasound identify the target lesion, the radial probe is removed from the working channel of bronchoscope and TBNA needle is introduced through it. TBNA of the lesion is performed using technique similar to conventional TBNA. Sequential TBNA can also be used to localize and sample intraparenchymal lesion. The probe should be introduced using catheter with extended working channel and placed exactly on the lesion. With guide sheath in position, the radial probe is removed and biopsy forceps or brush is used to sample the lesion through the guide sheath. It can also be combined with virtual bronchoscopic navigation system.^[14]

CP-EBUS

A regular fiberoptic bronchoscopy should be done first to determine anatomy and exclude endobronchial lesion. CP-EBUS is usually performed orally, as ultrasound probe in it prevents using nasal route. The image quality is lower to that of a regular bronchoscope. A disposable latex balloon is attached to the ultrasound probe. The tip of the bronchoscope should be positioned more anteriorly while passing through the vocal cords to avoid sticking the EBUS bronchoscope on the posterior part of vocal cords. Once in the airways, a syringe filled with sterile water is attached to the balloon channel of the scope and the balloon is filled with water to achieve contact with the airways. Lymph nodes are identified with its typical sonographic appearance (see the image below).

Lymph nodes should be differentiated from vascular structures, which are also hypoechoic. Doppler accurately differentiates lymph nodes and vascular structures. All mediastinal lymph node stations should be evaluated systematically. Subcarinal lymph node can be visualized either from right main or left main bronchus. The bronchoscopic and ultrasonic views can be toggled alternatively or two-screen display of both views can be used in the monitor. The tip should be flexed up for ultrasound image and down for endoscopic image. The ultrasound image can be frozen, allowing the size of lesions to be measured.

Real-time TBNA

Real-time TBNA is defined as simultaneous sonographic visualization and sampling of the lesion. Once the target lesion is identified, the dedicated 22-gauge needle is inserted through the working channel of the bronchoscope and fastened to it. The tip of bronchoscope should be in neutral position to allow the sheath to come out of the distal end of working channel. The needle should remain within the catheter during passage through the working channel in order to prevent injury to the bronchoscope. Once the catheter emerges out of the bronchoscope, the needle is advanced from the catheter and locked into position. The insertion point of needle is localized and it is then pushed through the bronchial wall into the target lymph node under direct ultrasound visualization (see the image below).

With the needle in the target lymph node, the internal sheath is removed. This cleans the lumen of the needle system, which usually becomes contaminated with bronchial cells. Suction is applied using a 20-mL syringe, and the catheter is moved back and forth. Suction is released and the needle is pulled back into the flexible catheter. The entire transbronchial needle system is then removed from the bronchoscope in a single, smooth motion. The tissue core is removed from the needle lumen by reinserting the internal sheath.

The number of needle aspirations per site can impact the yield and range from 3-7 depending on the study, but the first pass has the highest yield.^{[15, 16]} If the TBNA is being done for staging of NSCLC, the sampling should be started from N3 followed by N2 and N1 lymph nodes to avoid contamination and upstaging.

Pearls

• Knowledge of mediastinal anatomy and lymph node stations is essential for EBUS and EBUS-TBNA.
• EBUS is generally safe procedure with high diagnostic accuracy.
• It can be performed with local anesthesia and procedural sedation as an outpatient basis.
• EBUS-TBNA of mediastinal and hilar lymph nodes can be performed real-time using CP-EBUS or sequentially using RP-EBUS.
• Transbronchial biopsy of peripheral pulmonary nodules can only be done sequentially using RP-EBUS.
• Clinical application of EBUS-TBNA may avert the use of more invasive interventions for staging and restaging the lung cancer and diagnosis of mediastinal pathology.
• EBUS is gaining popularity rapidly and can be learned through training.

Complications  EBUS and EBUS-TBNA are usually safe procedures. No serious complications were found on a systematic review of effectiveness and safety of CP-EBUS-TBNA of regional lymph nodes.^[17] Reported complications are agitation, cough, hypoxia, laryngeal injury, fever, bacteremia and infection, bleeding, pneumothorax, and broken equipment becoming stuck in the airway. Mediastinal abscess has been reported as a case report. Complications related to upper airway local anesthesia are laryngospasm, laryngeal edema, bronchospasm, methemoglobinemia, and cardiac arrhythmias. Complications attributable to procedural sedation are respiratory depression, cardiovascular instability, vomiting, and aspiration.

Specimen Preparation

Aspirated specimen is smeared onto glass slides and air dried so that an on-site cytopathologist can evaluate the specimen. The use of rapid on-site evaluation significantly improves the diagnostic yield of transbronchial aspiration^[18] , and it is a cost-effective approach.^[19] It leads to avoidance of additional biopsies without loss in diagnostic yield and also reduces the complication rate of bronchoscopy.^[20] Histological cores are fixed with formalin and sent to the pathology department. The samples can be used for molecular analysis.

Monitoring

Continuous monitoring of cardiac rhythm, heart rate, respiratory rate, oxyhemoglobin saturation, and blood pressure is usually done after the procedure until the effects of sedation and upper airway anesthesia have been resolved. Eating and drinking can be resumed once the gag reflex returns. A chest radiograph should be performed following the procedure to evaluate complications, such as pneumothorax. Outpatients must have stable vital signs, be alert and oriented with baseline ambulation status before discharge.

Cleaning the Bronchoscope

The bronchoscope should be disinfected and hung upright to prevent the accumulation of moisture.

EBUS Training

As EBUS-TBNA is a new technique, a large number of pulmonologists need training on this as it can be learned with appropriate training only. Evidence-based protocols for teaching EBUS-guided TBNA are necessary.^[21] No accepted method exists of assessing EBUS technical skill or competency. An EBUS computer simulator can accurately discriminate between operators with different levels of clinical EBUS experience and help in assessing training and evaluating competency.^[22]

Patient Education

You should not eat or drink at least 6 hrs before the procedure. You may be asked to discontinue blood thinning medications several days prior to the procedure. A thin tube called a bronchoscope is placed in the mouth. It is difficult to speak once the bronchoscope is in the airways. You will be monitored closely for two to four hours after the test. Chest x-ray will be performed. You must not drive an automobile on the same day. A family member or friend must be available to drive or accompany you home. You may have a mild sore throat, hoarseness, cough or fever. If the lung is punctured, it can cause an air leak (pneumothorax), which results in lung collapse. If you have increasing chest pain or shortness of breath, or if you cough up more than a few tablespoons of blood, you should contact your doctor. Result of the test may take few days.