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Palliative Medicine Doctors’ Meeting____________________________HKSPM Newsletter 2007 Dec Issue 3 p 16
Management of Excessive Respiratory Secretions:
A Sharing of Two Patients’ Stories
Dr Lam Wai Man, Haven of Hope Hospital.
Correspondence: [email protected]
Case histories contributed by Dr Ng Sheung
Ching and Dr Ma Chi Ming
The Story of Madam C
Madam C, a 72-year old retired farmer, had
been suffering from right biliary papillomatosis
since 2003 with extended right hepatectomy
performed. Extensive liver metastases were
noted
since
2006
and
metastatic
adenocarcinoma to left lung was detected in
2003. She refused chemotherapy and accepted
palliative care.
She complained of cough with profuse whitish
mucoid sputum which had increased to over 300
ml per day. Oral hyoscine methobromide had
been tried with initial improvement. However, the
disease progressed and the sputum volume
increased to around one liter per day causing
dyspnea even at rest. A clinical diagnosis of
bronchorrhea was made.
Various
medications
including
oral
erythromycin 500 mg twice daily and oral
indomethacin 50 mg twice daily were tried with no
improvement in bronchorrhea but were
complicated by nausea with erythromycin and
impaired renal function with indomethacin.
Continuous subcutaneous infusion of hyoscine
hydrobromide up to 1.6 mg per day was given
with no improvement in sputum volume but
resulted in excessive drowsiness. Continuous
subcutaneous infusion of fentanyl and
midazolam was needed to control her dyspnea
and restlessness.
Subsequently, continuous subcutaneous
infusion of octreotide was given at a dose of
200-300 micrograms per day. There was
significant improvement in the volume of
respiratory
secretions,
dyspnea,
and
restlessness. Subcutaneous hyoscine and
midazolam infusions were stopped due to
improvement in symptoms. Her alertness also
improved. She subsequently died 10 days after
commencement of octreotide infusion.
The Story of Madam S
Madam Sin, aged 48, was previously a trainer
in a cosmetic and fitness center. She had a
second marriage. She was diagnosed to have
polymyositis in 1997 presenting with weakness.
Multiple immunosuppressive therapies had been
tried including glucocorticoids, azathioprine,
cyclophosphamide, cyclosporin, intravenous
immunoglobulins, mycophenolate mofetil, and
rituximab, but her disease progressed. She had
an episode of severe pneumonia requiring
intubation and subsequent tracheostomy. She
was then transferred to the rehabilitation ward for
convalescence.
Upon admission, she was totally dependent in
her daily living, and she needed non-oral feeding
due to dysphagia. She was just able to move her
eyes and fingers. Her main physical symptoms
were excessive saliva and sputum affecting her
speech and eating, sense of suffocation due to
secretions, pain and numbness over pressure
points, and pain in multiple joints.
Concerning her psychological state, she had a
strong sense of helplessness due to repeated
treatment failures and loss of independence, fear
of dying from suffocation, sense of loneliness due
to infrequent visits from her family, and anger and
frustration about her physical needs not being
promptly addressed by staff. She frequently
called for help with dramatic gestures and
repeated call bells ringing.
The multidisciplinary team attempted to
address her multiple needs. The physiotherapist
performed vigorous chest physiotherapy and
hand function enhancement exercises; the
occupational therapist designed a special chair
and a foot platform to facilitate her sitting out; the
speech therapist provided speech training; the
clinical psychologist enhanced her self
expression by drawing; the chaplain and some
volunteers provided religious, spiritual and social
support; and the social worker assisted her in
hiring a maid to take care of her in the
Palliative Medicine Doctors’ Meeting____________________________HKSPM Newsletter 2007 Dec Issue 3 p 17
and the nurses educated her on performing self
suction of saliva. The doctor tried many
medications to manage her saliva secretions
including oral promethazine, oral amitriptyline,
and inhaled ipratropium, but they were not
effective.
The management of bronchorrhea includes
general supportive measures to promote comfort,
maintenance of fluid and electrolyte balance, and
measures to reduce bronchial secretion
production. The following seven entities have
been tried in reducing bronchial secretions:
Local injection of Botulinum toxin (Botox) 15
Units into each submandibular gland, was
performed under ultrasound guidance. It was
effective in reducing the volume of saliva
secretions by about 70% at one week after
injection. The tracheostomy was successfully
weaned off. She became less anxious, more
talkative and expressive. She survived for six
more months after Botox injection with no
recurrence of excessive salivation, and she died
of acute myocardial infarction and hospital
acquired pneumonia.
1.
2.
3.
4.
5.
6.
7.
The Management of Bronchorrhea
Bronchorrhea is arbitrarily defined as watery
sputum production of over 100 ml per day.1 Up to
9 Liters per day has been reported.2 It can be
caused by primary lung malignancy especially of
bronchioloalveolar cell type and metastases to
lung especially from cells of glandular origin (e.g.
adenocarcinoma of cervix, colonic adenocarcinoma, and pancreatic cancer). 3, 4, 5 It can
also be caused by non-malignant conditions like
chronic bronchitis, asthma, and endobronchial
tuberculosis.
There are three postulated pathophysiological
mechanisms for bronchorrhea:
1.
Hyper-secretion of mucus-glycoprotein and
other glandular products from mucusglycoprotein producing cells – neutrophils
accumulating in airway mucosa may
stimulate goblet cells secretion.
2.
Increased transepithelial chloride secretionthis can be mediated by receptors for
prostaglandins (PGE2, PEF2α) or secretin in
the bronchial epithelium.
3.
Excessive transudation of plasma products
into the airway. 6
Bronchorrhea has negative impact on both
survival and quality of life. It can cause excessive
cough, sleep disturbance and dyspnea. When
severe, it may lead to respiratory failure,
dehydration and electrolyte disturbance.
Radiotherapy and traditional chemotherapy
Anticholinergic agents
Macrolides
Pulsed methylprednisolone
Inhaled indomethacin
Gefitinib (EGFR-TKI)
Octreotide
The responses of bronchorrhea to radiotherapy,
traditional
chemotherapy,
and
anticholinergic drugs are variable. Macrolides act
by affecting neutrophil migration and activities in
the lung and inhibiting the synthesis and
secretion of a mucus secretogogue from
pulmonary macrophages.7 There were case
reports of using oral clarithromycin combined
with inhaled beclomethasone in managing
bronchorrhea in alveolar cell carcinoma,8 pulsed
methylprednisolone in a patient with bronchioloalveolar carcinoma (BAC),9 and inhaled
indomethacin in patients with chronic airway
diseases like chronic bronchitis, diffuse
panbronchiolitis and bronchiectasis, presumably
by reducing the levels of prostaglandins and its
metabolites in sputum.10. Nebulised indomethacin was successful in two patients with
BAC suffering from bronchorrhea in reducing the
sputum volume, improving the quality of life, and
possibly prolonging the survival. 11
Two more recent weapons in treating
bronchorrhea are Gefitinib and Octreotide.
Gefitinib, an Epidermal Growth Factor Tyrosine
Kinase Inhibitor, is thought to reduce
bronchorrhea by inhibiting the expression of a
major mucin in BAC cells, the MUC5AC mucin,
based on findings from animal study and
laboratory setting. 12, 13 There were case reports
of its successful reduction of sputum volume in
BAC patients.14, 15 As the onset of improvement
occurred within 24 hours of use, it is likely that its
inhibitory action on mucin production is
independent of its anti-proliferative effect.
Octreotide, a somatostatin analogue, has
been reported to significantly reduce the volume
of secretions in a lady with the acinar type of
Palliative Medicine Doctors’ Meeting____________________________HKSPM Newsletter 2007 Dec Issue 3 p 18
adenocarcinoma of lung at a dose 300-500
micrograms daily.16 It is postulated to have an
inhibitory action on the secretin receptors in the
bronchial tree. The patient we presented above
further substantiates its potential role in
bronchorrhea.
Surgical techniques are limited by its
irreversibility and patients’ fitness for surgery.
Anticholinergic drugs and antidepressants are
limited by their side effects. Radiation to salivary
glands may be complicated by development of
head and neck malignancies in the long run.
The Management of Sialorrhea
There are case reports of the usefulness of
local botulinum toxin injection into salivary glands
in patients with head and neck cancer,
neurodegenerative disorders, and stroke with no
reported side effects. 18, 19 Randomized controlled
studies have also proven its efficacy. (Table 2)20
Normal adults produce 750 to 1500 ml of
saliva per day. Unlike bronchorrhea which is
usually the result of excessive secretion,
sialorrhea is usually due to oropharyngeal
dysphagia and impaired cough effort caused by
various neurological diseases, or esophageal
dysphagia caused by mechanical obstruction or
esophageal dysmotility. Sialorrhea may affect
feeding, interfere with speech, lead to social
embarrassment, induce sense of suffocation with
resultant fear, and increase susceptibility to
aspiration pneumonia.
The clinical aspects of botulinum toxin
injection have also been reviewed.20 It can be
injected into parotid glands, submandibular
glands, or both. The injections can be guided by
anatomical landmarks or ultrasound localization
of the salivary glands. Use of ultrasound leads to
a higher success rate and fewer side effects, and
the dose used can be lower. However, it requires
The management of excessive oropharyngeal
certain expertise. The dosages reported varied
secretions comprises of physical modalities,
from 5-75 U into each parotid gland and 5-30 U
medications, irradiation to salivary glands and
into each submandibular gland. Usually one to
various surgical maneuvers.17 (Table 1)
1.5 milliliters of drugs is injected into each gland,
and the effect is achieved by diffusion. The
17
onset of reduced saliva production can be
Table 1: Management of excessive oropharyngeal secretions
rapid within 1-2 weeks, and the effect can
Physical
Manual suction
last from a few weeks to several months.
modalities
Various respiratory physical therapy techniques:
The potential side effects are dry mouth,
Postural drainage / Percussion and vibration /
dysphagia, jaw weakness and jaw
Incentive spirometry / Glossopharyngeal breathing /
dislocation. Caution must be exercised in
frog breathing / Active cycle of breathing /
Forced expiratory maneuvers / Cough assist
patients with neuromuscular and muscular
disease. Its potential indications in
Medications Anticholinergic dugs
palliative care lie in the management of
Tricyclic antidepressants
Botulinum toxin
saliva aspiration and drooling in patients
with neurological disorders affecting
Radiation
To salivary glands
swallowing, surgery involving upper
Surgery
On salivary glands
aerodigestive tract, laryngeal and upper
On neural innervation of saliva production
Table 2: Randomized studies on the use of botulinum toxin in sialorrhea 20
Researcher
Patient group
N
Type of study
Outcome
Mancini 2003
20
Lipp22 2003
Parkinson’s disease
Multiple system atrophy
Sialorrhea
Double blind placebo
controlled
Dose finding study
Ondo23 2004
Parkinson’s disease
16
Jongerius 24 2004
Cerebral palsy
45
Improvement shown at 1 week
and 3 months
Effect achieved with 75 U into
each parotid gland
Improved VAS, drooling score and
global score
Similar effects; fewer side effects
Lagalla 25 2006
Parkinison’s disease
32
21
32
Double blind placebo
controlled
Compared with transdermal
scopolamine
Double blind placebo
controlled
Less frequent drooling; less saliva production
& improved family and social functioning
Palliative Medicine Doctors’ Meeting____________________________HKSPM Newsletter 2007 Dec Issue 3 p 19
aerodigestive tract tumors, as well as patients
with saliva fistula after parotid gland surgery,
laryngectomy or pharyngectomy.
Conclusion
We have reported the usefulness of
subcutaneous octreotide infusion and local
botulinum toxin injection into submandibular
glands in the management of bronchorrhea and
sialorrhea respectively, and in both patients, a
better symptom control and better quality of life
had been achieved. Though these two
medications are expensive, its use in selected
cases should be carefully considered.
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