CASE REPORT

The Effect of Nebulized Glycopyrrolate on Posterior Drooling in
Patients with Brain Injury
Two Cases of Different Brain Lesions
Zee-Ihn Lee, MD, PhD, Kwang Jae Yu, MD, Dae Hee Lee, MD, Seong Kyung Hong, MD, Seung Beom Woo, MD,
Jong Min Kim, MD, and Donghwi Park, MD
Abstract: Posterior drooling, which can lead to substantial respiratory morbidity, including unexplained lung diseases and recurrent pneumonia, is an important issue in the rehabilitation unit. There are various treatment options for posterior drooling, including pharmacologic therapy, oral motor or behavioral therapy, biofeedback, local glandular injection of botulinum toxin, irradiation, and surgery.
Among them, nebulized glycopyrrolate has the following advantages: It is noninvasive and is relatively free of central adverse effects
because it does not cross the blood-brain barrier unlike other anticholinergics. Although there has been one case report regarding the
effectiveness of nebulized glycopyrrolate for drooling in a motor neuron patient, there have not been any reports on its effectiveness
for posterior drooling. Herein, we report two cases (an 82-year-old male bilateral hemiplegic stroke patient and a 1-year-old female cerebral
palsy infant with bilaterally spastic hemiplegia of posterior drooling treated with nebulized glycopyrrolate) and identify salivary aspiration and the effect of nebulized glycopyrrolate using radionuclide salivagram. Considering its advantages and effectiveness, nebulized
glycopyrrolate should be considered as one of the reliable methods to manage posterior drooling in patients with impaired cognition or
swallowing difficulties, such as severe brain injury.
Key Words: Posterior Drooling, Salivagram, Glycopyrrolate, Salivary Aspiration, Dysphagia
(Am J Phys Med Rehabil 2017;00:00–00)

rooling is the unintentional loss of saliva from the mouth,
D
known as anterior drooling. However, it is important to
distinguish anterior drooling from posterior drooling. The lat1

ter refers to saliva that is spilled over the tongue through the
faucial isthmus.1 Posterior drooling can lead to substantial respiratory morbidity, including unexplained lung diseases and
recurrent pneumonia. Hence, it is an important issue in the rehabilitation unit.2,3 In particular, patients with neurologic diseases who have been in a bedridden state for an extended
period of time can be at greater risk for the development of
chronic salivary aspiration and pulmonary complications.4,5
Continuous secretion of saliva and aspiration, in contrast to aspiration only during swallowing, is difficult to manage, even
with modifications to food consistencies or complete cessation
of oral feeding altogether.5
From the Department of Rehabilitation Medicine, Daegu Fatima Hospital, Daegu,
South Korea.
All correspondence and requests for reprints should be addressed to: Donghwi Park,
MD, Department of Rehabilitation Medicine, Daegu Fatima Hospital, 99 Ayang-ro,
Dong-gui, Daegu 41199, South Korea.
No commercial party having a direct financial interest in the results of the research
supporting this article has or will confer a benefit on the authors or on any
organization with which the authors are associated.
Financial disclosure statements have been obtained, and no conflicts of interest have
been reported by the authors or by any individuals in control of the content of
this article.
Supplemental digital content is available for this article. Direct URL citations appear
in the printed text and are provided in the HTML and PDF versions of this article
on the journal’s Web site (www.ajpmr.com).
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 0894-9115
DOI: 10.1097/PHM.0000000000000669

There are various treatment options for posterior drooling,
including anticholinergics or patches, oral motor or behavioral
therapy, biofeedback, local glandular injection of botulinum
toxin, irradiation, and surgery.6 Recently, botulinum toxin injection was introduced as the one of the treatment options for
posterior drooling.1,5 However, it is an invasive procedure that
has been associated with rare complications, such as swallowing difficulty and pain at the injection site. Although anticholinergic medication has been the primary drug of choice, its
inability to restrict antimuscarinic activities has limited its
use.7 Moreover, the applicability of oral anticholinergic agents
in patients with swallowing difficulty is also a limitation. To overcome these limitations, noninvasive and parenteral anticholinergics, such as transdermal and nebulized anticholinergics, have
been investigated for applicability in patients with drooling.8,9
Among them, nebulized glycopyrrolate (glycopyrronium
bromide) has been shown to be advantageous owing to its
noninvasiveness and relative freedom from central adverse effects, as there is no crossing of the blood-brain barrier, unlike
other anticholinergics, such as scopolamine and atropine.8,10
Although there has been one previous case report regarding
the effectiveness of nebulized glycopyrrolate for drooling in
a motor neuron patient,8 there have not been any reports, to
the best of our knowledge, about its effectiveness for posterior
drooling via a radionuclide salivagram.
In the following two cases, glycopyrrolate was administered via a nebulizer to patients with posterior drooling. We detected salivary aspiration and evaluated the effect of nebulized
glycopyrrolate using radionuclide salivagram. These cases

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Volume 00, Number 00, Month 2017

Lee et al.

were approved by the institutional review board at our institution, and all authors have read and approved the paper. In
addition, this study conforms to all CARE guidelines and reports the required information accordingly (Supplementary
Checklist, http://links.lww.com/PHM/A365).

CASE 1
An 82-year-old male bilateral hemiplegic patient with subarachnoid hemorrhage and subsequent several cerebral infarctions had been having recurrent saliva aspiration and recurrent
pneumonia for 9 months, nasogastric tube feeding. He showed
poor cooperation and had a tracheostomy tube. Moreover, he
did not have any episode of esophageal peristalsis alteration,
such as gastroesophageal reflux and vomiting. Radionuclide
salivagram was conducted to detect salivary aspiration. A drop
of saline solution (0.1 mL), containing 1.0 mCi of technetium
99m sulfur colloid (Techne; Fujifilm RI pharma Co, Japan),
was placed on the tongue of the patient while he was in supine position.11 Sequential images were obtained after 1 and
5 minutes, and then at 10-minute intervals thereafter for a total
duration of 60 minutes. Pulmonary aspiration of saliva, determined by the presence of radiotracer activity in the trachea or
both bronchi, was evaluated.3 On the initial salivagram,
abnormal radionuclide uptake was observed in the trachea and
bilateral bronchial tree (Fig. 1A) After diagnosis of pulmonary
aspiration of saliva, nebulized glycopyrrolate (0.2 mg/mL
ampoules; Tabinul, Hana Pharm, Seoul, South Korea) was
started to manage saliva aspiration. Nebulized glycopyrrolate
was started with a dose of 0.2 mg once daily. Two days after
the application of nebulized glycopyrrolate, the dose of
glycopyrrolate was increased to 0.2 mg twice per day. Four

days after the application of nebulized glycopyrrolate, the
dose of glycopyrrolate was increased to 0.4 mg twice per
day. After the treatment with nebulized glycopyrrolate, the
numbers of suction (from 10 to 12/day to 2 to 3/day) was significantly decreased. Moreover, a visual analog scale (VAS) of
caregiver for the amount of drooling was also decreased
from 9 to 1.5 (Table 1). Two weeks after the application of
nebulized glycopyrrolate, the frequency and severity, as indicated by the drooling scoring system, improved from profuse,
constant drooling to mild, occasional drooling.12 Moreover, he
experienced no urinary problems or any other anticholinergic
adverse effects. A follow-up salivagram, which was performed
3 weeks after the treatment, showed no extraesophageal
uptake of radiotracer for saliva aspiration. The increased
uptake of radiotracer on both bonchi had disappeared in
the follow-up salivagram compared with the initial study
(Fig. 1B). In addition, VAS and the number of suctions per
day were maintained the same as 2 weeks after treatment.

CASE 2
A 1-year-old female cerebral palsy infant with bilaterally
spastic hemiplegia had salivary aspiration and recurrent pneumonia. She was born at 37 weeks and 3 days, and her body
weight at birth was 1950 g. Magnetic resonance imaging (MRI)
of the brain at birth showed hypoxic ischemic encephalopathy due to perinatal asphyxia. She had difficulty turning over
by herself and had percutaneous endoscopic jejunostomy
feeding and tracheostomy, and her Gross Motor Function
Classification System (GMFCS) score was 5. She had
drooling and frequent tracheal suction, which occurred more
than 15 times on average during the day and 10 times on

FIGURE 1. Sequential images of a radionuclide salivagram throughout a period of 1 hour. A, Initial radionuclide salivagram of case 1. Presence of
radioactivity in the esophageal area, as well as the bilateral bronchi and trachea, demonstrating positivity for posterior drooling on the salivagram
(arrow). B, Follow-up radionuclide salivagram of case 1. There was no extraesophageal uptake of radiotracer on the follow-up salivagram after the
application of nebulized glycopyrrolate.

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Volume 00, Number 00, Month 2017

Effect of Glycopyrrolate on Posterior Drooling

TABLE 1. Changes in VAS and the number of suctions
between before-treatment and 2 weeks follow-up after treatment
in case 1 and 2 patients
Before Treatment
Patient 1
Patient 2

After Treatment

VAS

No. Suctions

VAS

No. Suctions

9
10

10–12/day
25/day

1.5
2

2–3/day
1–2/day

average during the night, which severely interfered with
her sleep.
In the initial radionuclide salivagram (Fig. 2) using the
aforementioned method, we observed radioactivity in the
esophageal area as well as the trachea and bilateral bronchial
tree, which indicated aspiration of saliva. After the diagnosis
of pulmonary aspiration of saliva, she was given a nebulized
glycopyrrolate (Tabinul, 0.2 mg/1-mL ampoules) treatment
with a dose of 0.1 mg once per night. At the start of the treatment, her body weight was 10.0 kg. After the treatment, the
frequency of suction had decreased remarkably during her
sleep, at most, only once or twice per night. Two weeks after
the application of nebulized glycopyrrolate, the frequency
and severity, as indicated by the drooling scoring system,
improved from profuse, constant drooling to mild, occasional
drooling.12 The VAS of caregiver for drooling also decreased
from 10 to 2 (Table 1). She also experienced no urinary problems or any other anticholinergic adverse effects. However, a
follow-up salivagram was not performed because her parents
did not consent to any additional radionuclide salivagram.

DISCUSSION
Radionuclide salivagram has been used to detect passive
aspiration of saliva, especially in patients with oral feeding

difficulties or poor cooperation.13 After sublingual instillation
of a small amount of radiolabeled colloid, serial images are
evaluated for the presence of radiotracer uptake in the tracheobronchial tree, which suggests aspiration.3 For these
reasons, salivagram can be used in patients with recurrent
aspiration pneumonia, despite parenteral feeding.
The safety of inhaled glycopyrrolate has been supported
extensively in previous clinical studies.8,14 Glycopyrrolate is a
long-acting muscarinic antagonist with a slow receptor dissociation time; it is kinetically selective for M1 and M3 receptors.15
The effect of glycopyrrolate is exerted by blocking the anticholinergic muscarinic receptors on the salivary glands.10
Unlike other anticholinergic drugs used for sialorrhea, such
as atropine, scopolamine, biperiden, and amitriptyline, the
quaternary structure of glycopyrrolate prevents it from passing through the blood-brain barrier.8,10 This characteristic of
glycopyrrolate may have advantages in minimizing the central
adverse effects, such as preservation of cognitive function.16 In
addition, the slow dissociation property of glycopyrrolate contributes to the long-lasting effect on the salivary glands.17,18
Moreover, its ability to rapidly be absorbed also contributes to
its efficacy on treating posterior drooling. In a previous study,
the mean delivery time for nebulized glycopyrrolate was shown
to be less than 2 minutes, and nebulized glycopyrrolate was
rapidly absorbed with the peak plasma concentration of 15 to
30 minutes.17 Nebulized glycopyrrolate may have been rapidly
effective because (1) the nebulizer allowed for a rapid absorption of the drug in a given area with rich blood supply and lymphatic vessels, like the buccal area and (2) glycopyrrolate had a
direct effect on the salivary glands. In a previous report about
nebulized glycopyrrolate in patients with anterior drooling, a
dose of 0.4 mg twice daily was applied. Although there was
no recommended maximum dose for nebulized glycopyrrolate
in children, most clinical studies and case series published to
date have used intravenous or intramuscular glycopyrrolate in

FIGURE 2. Sequential images of a radionuclide salivagram throughout a period of 1 hour. Initial radionuclide salivagram of case 2. Presence
of radioactivity in the esophageal area, as well as the bilateral bronchi and trachea, demonstrating positivity for posterior drooling on the
salivagram (arrows).
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Lee et al.

a range of 4.0 to 6.0 μg/kg, and some authors have even used
a dose as high as 10.0 μg/kg in children.19 In our case,
100 μg of nebulized glycopyrrolate was used in a child
weighing 10.0 kg. Considering that 8.0 μg/kg of intramuscular glycopyrrolate raises the peak plasma concentration to as
high as 3.47 ± 1.48 μg/mL in children20 and 100 μg of nebulized glycopyrrolate raises the peak plasma concentration
to as high as 0.162 ± 0.082 μg/mL,17 we determined that
100 μg of nebulized glycopyrrolate would be safe for our
1-year-old infant weighing 10.0 kg. No adverse effects were
observed in both of our cases during the nebulized
glycopyrrolate treatment. Although a previous study reported
that the half-life of 0.1 mg (1/2 ampoule), 0.2 mg (1 ampoule),
and 0.4 mg (2 ampoules) of nebulized glycopyrrolate was
3.3 ± 1.2 hours, 3.4 ± 1.3 hours, and 4.8 ± 3.0 hours,17 respectively, further studies may be necessary to estimate the longterm effects of nebulized glycopyrrolate on posterior drooling.
In both of our cases, nebulized glycopyrrolate was well
tolerated, and the caregivers noticed an improvement in symptoms within 30 minutes of application. Moreover, the effects
lasted almost an entire day. Although a follow-up radionuclide
salivagram was not performed in the second case, the effectiveness of nebulized glycopyrrolate on posterior drooling in
patients with severe brain injury was observed, as both cases
resulted in the improvement of posterior drooling symptoms. Considering its advantages and effectiveness, nebulized glycopyrrolate should be considered as one of the
reliable methods for the management of posterior drooling
in patients with impaired cognition or swallowing difficulties, such as severe brain injury.
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