An Ultrasound-Guided Injection of Therapeutic Drugs into Human Salivary Glands

Overview

The video demonstrates an ultrasound-guided injection technique for administering therapeutic drugs into the salivary glands of a human patient.

Protocol

All procedures involving human participants have been performed in compliance with the institutional, national, and international guidelines for human welfare and have been reviewed by the local institutional review board.

1. Procedure​

1. BoNT-A preparation NOTE: The abobotulinumtoxinA is a botulinum toxin type A of the Clostridium botulinum complex-hemagglutinin. It is a powder for solution for intramuscular or subcutaneous injection.
   1. For the treatment of sialorrhea in adults, reconstitute 500 IU abobotulinumtoxinA with 2 mL of 0.9% sodium chloride solution for injection in order to obtain a solution containing 250 IU/mL of abobotulinumtoxinA.
   2. Administer a total of 250 IU of abobotulinumtoxinA per patient as follows: 50 IU in each submandibular gland and 75 IU in each parotid gland. In this way treat two patients with a single vial to avoid drug wastage.
2. Patients' preparation​
   1. After an adequate explanation of the procedure and of the potential risks and benefits of the treatment, obtain written informed consent from the patient.
   2. Place the patient on the ultrasound table in the supine position and possibly with the neck extended.
      NOTE: Consider that not all neurological conditions leading to sialorrhea allow for the complete extension of the neck.
   3. Disinfect the skin in the area over the parotid and the submandibular glands with an antiseptic. Anesthetize each skin access site with ethylene chloride spray.
3. Ultrasound guidance
   ​NOTE: An ultrasound-guided procedure with a linear transducer (5 - 10 MHz) is used for gland localization in order to obtain real-time visualization of muscles, glands, bigger vessels or salivary ducts, and other surrounding structures, as well as of the correct needle position within the glandular tissue.
   1. Turn on the ultrasound system and press the "Start-end" button to begin the exam.
   2. Press the "Probe" button to select the high frequency probe (5 - 10 MHz).
   3. Press the "Patient" button and insert the patient's name and surname.
   4. Press the "Protocol" button to select the appropriate protocol and sub-protocol (i.e., protocol: "small tissues", sub-protocol: "general").
   5. Press the "Depth" button and specify the depth of view to 5 cm.
   6. Press the "Focus" button to select the maximum detail of 2 cm.
   7. Place the transducer under the mandible, between the anterior and posterior bellies of the digastric muscle, to visualize the submandibular gland, which appears as a hypoechoic area with homogeneous echotexture compared to the surrounding tissues.
      NOTE: Consider the submandibular gland ideally divided into two quadrants, one cranial and one caudal. Identify the widest gland diameter for the lateral needle access.
   8. Place the transducer below the external acoustic meatus to visualize the parotid gland, which appears as a hypoechoic area with homogeneous echotexture compared to the surrounding tissues.
      NOTE: Consider the parotid gland ideally divided into four quadrants, two cranial and two caudal. Identify the two access sites for injection midway between the external auditory canal and the mandible angle, one in the cranial part and one in the caudal part of the gland (Figure 1).

2. BoNT-A injection

NOTE: Use a 22 G needle for injections, with needle penetration at least 0.5 cm from the transducer. The transducer must be oriented longitudinally to the needle so that the needle is visible as a bright echoic line. In this way, the penetration of the needle into the soft tissues can be monitored during the procedure as the needle tip proceeds towards the target, preventing injuries to neurovascular structures.

1. Use a lateral short-access approach at the widest gland diameter to access the submandibular gland.
2. Inject 25 IU BoNT-A into the upper submandibular quadrant. After the injection, slightly retract the needle and change the direction of the needle tip towards the lower submandibular quadrant, injecting 25 IU BoNT-A for a total of 50 IU to each submandibular gland.
   NOTE: In this way, two submandibular areas (cranial and caudal) are injected, providing a widespread diffusion of the drug within the glandular tissue.
3. Use two access sites for the parotid gland injection. Identify the two accesses midway between the external auditory canal and the mandible angle, one in the cranial part of the gland and one in the caudal part of the gland.
4. Using the upper access (in the cranial part of the gland), inject 18 - 19 IU BoNT-A into the medial-cranial quadrant. After the injection, slightly retract the needle, without leaving the site of the cranial part of the gland, and change the direction of the needle tip towards the lateral-cranial quadrant; inject 18 - 19 IU BoNT-A.
5. Using the lower access (in the caudal part of the gland), inject 18 - 19 BoNT-A IU into the medial-caudal quadrant. After the injection, slightly retract the needle, without leaving the site of the caudal part of the gland, and change the direction of the needle tip towards the lateral-caudal quadrant; inject 18 - 19 IU BoNT-A.
   NOTE: In this way, four parotid areas (medial-cranial, lateral-cranial, medial-caudal and lateral-caudal) are injected with a total of 75 IU BoNT-A, providing a widespread diffusion of the drug within the glandular tissue.
6. After each injection, dab any bleeding with sterile gauze for 1 - 2 min. Re-evaluate the patient after one hour for any potential adverse events. Administer a nonsteroidal anti-inflammatory drug in case of persisting pain. Schedule a follow-up examination after 1 month.

Representative Results

Figure 1: Representation of the Ideal Injection Sites. A) Schematic division of the parotid gland into four quadrants, two cranial and two caudal, for correct injection into four different glandular sites. B) Schematic division of the submandibular gland into one cranial and one caudal quadrant for correct injection into two different glandular sites.

Materials

Name	Company	Catalog Number	Comments
abobotulinumtoxinA (Dysport)	IpsenBiopharm, Wrexham, UK		Delivered drug
MyLab Twice	Esaote		Ultraonograph
LA523 5–10 MHz	Esaote		Linear transducer