Fibrinolysis Treatment for Loculated Parapneumonic Pleural Effusion Secondary to

Proc. West. Pharmacol. Soc. 52: 11-13 (2009)
Fibrinolysis Treatment for Loculated Parapneumonic Pleural Effusion Secondary to
Right Lower Lobe Pneumonia
Lourdes G. Merlo, Saba Ansari, Bhupinder Singh, Fikerte F. Teferedgin, Kelly L. Cervellione
Jonas Gintautas and Mohammad A. Babury
Department of Clinical Research, Jamaica Hospital Medical Center, 8900 Van Wyck Expressway, Jamaica, NY 11418
*Email: [email protected]
The administration of fibrinolytic agents in the pleural cavity is an alternative treatment for the management of
loculated empyemas in patients who are poor candidates for surgery and/or do not respond to more standard
treatments (e.g., chest tube placement, pleurodesis). Unfortunately, in practice it is not frequently offered as an
alternative treatment approach. Here we present the case of a 79-year-old male with right lower lobe pneumonia
complicated by a parapneumonic pleural effusion that showed minimal improvement after chest tube placement
and broad-spectrum antibiotic treatment. Intrapleural tissue plasminogen activator (tPA) was administered daily for
three consecutive days, which resulted in the breakdown of intrapleural loculations and facilitation of drainage,
followed by significant clinical and radiologic improvement. tPA was successful in the treatment of parapneumonic
pleural effusions in a patient who was not a candidate for surgical intervention and who failed to respond to
standard treatments.
In most patients with symptomatic pleural effusion
secondary to the progression of empyemas, the
insertion of a chest tube is the first step in disease
management. However, some patients experience an
evolution of illness from the exudative stage (i.e. freeflowing pleural fluid) to an organized stage,
characterized by fibrin strands bridging the pleural
membrane. This causes development of a loculated
pleural effusion that rarely responds to chest tube
placement. In addition, in many cases, these patients
are poor candidates for surgical treatment like
thoracoscopic debridements or open thoracotomy,
leaving palliative care as the best option for care.
Intrapleural fibrinolytic (IPF) agents, however, can be
used in these patients to break down the fibrin strands
of intrapleuritic collection while circumventing the need
for surgical drainage.
In a recent article by the American College of Chest
Physicians, it was concluded that fibrinolytic therapy
and surgical drainage techniques represent competing
options, but that appropriate patient selection and the
relative timing of the procedures remain uncertain [1].
In the case we present, a 79-year-old male who was a
poor surgical candidate was successfully treated for
parapneumonic pleural effusion with intrapleural tissue
plasminogen activator (tPA) after more standard
treatments failed. This case illustrates the important
role that tPA can have in the treatment of this and
similar conditions.
Case Report
A 79-year-old black male presented to the emergency
department with one week of progressive shortness of
breath with associated left pleuritic chest pain and lowgrade fever. No dizziness, palpitation, perspiration,
cough, peripheral edema, nausea or vomiting were
present. He had moved to New York from the West
Indies five years earlier. Past medical history included
hypertension, chronic heart failure (EF: 15 %), chronic
atrial fibrillation, chronic renal failure, chronic anemia,
osteoarthritis and seizures. He was noncompliant with
medications, including anticoagulants. He reported no
surgical history and an unknown family history.
During the initial evaluation, the patient was alert and
oriented, hemodynamically stable and had no labored
breathing. Electrocardiogram showed atrial fibrillation
with rapid ventricular response. Chest x-ray (CXR)
revealed cardiomegaly; the mediastinum was
unremarkable, lungs were clear, and osseous structure
was intact. After nitroglycerin patch placement,
metoprolol (50 mg PO) and diltiazen (25 mg IV) were
administered. Blood pressure dropped from 130/82 to
80/65 mmHg. The patient became poorly responsive,
hypoxemic (02 Sat 88% in non-rebreathalble mask) and
was intubated. Ventilation/perfusion scan had
borderline suspicion for pulmonary embolism.
Anticoagulation was initiated.
During first week of admission, the patient was
diagnosed with non-ST elevation myocardial infarction.
All blood and urine cultures were negative. The patient
Proc. West. Pharmacol. Soc. 52: 11-13 (2009)
remained on ventilator. CXR showed a new, small, right
infrahilar infiltrate. He was started on moxifloxacin. On
day 9, the patient was extubated. Over the following
two weeks, the patient had persistent, productive
cough with yellowish sputum. There was progressive
dispnea and persistently elevated white cell counts.
Blood cultures remained negative. CXR showed large,
loculated right pleural effusion in the right hemithorax.
Pleural tap confirmed empyema and a chest tube was
placed. A course of broad-spectrum antibiotics was
begun. In the following days, there was minimal
drainage and there was no improvement on CXR’s (Fig
1). The patient experienced respiratory failure,
hypotension, and worsening renal failure. Endotracheal
intubation, vasopressor support, and hemodialysis were
required. Video-assisted thoracoscopic surgery (VATS)
with decortications was ruled out as a treatment option
due to the multiple co-morbid conditions and high risk
for mortality.
improvement was detected in the following 3-5 days
with evident improvement in chest tube drainage (Fig.
2). The patient was successfully intubated. He remained
stable, afebrile, and had spontaneous ventilation. He
was subsequently discharged with no adverse events
related to this hospitalization over the next 3 months.
He had no reoccurrence of loculated parapneumonic
pleural effusion.
Figure 2. CT scan pre- (left) and post- (right) tPA
administration shows significant improvement.
Figure 1. Chest x-ray pre- (left) and post- (right) chest
tube placement shows minimal drainage.
Due to the limited treatment options, IPT was started
with tPA 10 mg in 50ml NS via right chest tube daily for
three days. The chest tube was clamped after each daily
dose of tPA and was unclamped every 12 hours to
inspect drainage. The patient’s position was changed
every 2 hours. A markedly clinical and radiological
It is well known that there are high morbidity and
mortality rates related to the development of empyema
and complicated parapneumonic effusion, with an
estimated case-fatality rate of 15% [2]. Since the mid1900’s, IPFT has been known and accepted as a
therapeutic option for the management of complicated
parapneumonic effusion secondary to pneumonia,
clotted hemothorax, or malignancy. Since unpurified
fibrinolytic agents were initially used, significant
systemic side effects were observed, thus lessening its
attractiveness as a treatment option. Three decades
later, the development of a purified form of
Proc. West. Pharmacol. Soc. 52: 11-13 (2009)
streptokinase improved effectiveness, consequently
increasing its use as a therapeutic alternative for the
management of complicated parapneumonic effusions.
Since then, numerous studies have demonstrated the
safety and effectiveness with the use of IPFT [3].
instillation, improving clinical status by favoring the
apposition of the pleural surfaces and the expansion of
lung parenchyma. The majority of these patients go
later for pleurodesis with satisfactory resolution of the
Open thoracotomy and VATS are effective procedures
in the management of complicated loculated
parapneumonic effusions. VATS initiates a breakdown
of adhesions, making drainage of the collection
possible. It has an efficacy rate greater than 80% (4).
Though VATS is a preferred treatment option, it carries
a high risk of significant morbidity secondary to
complications (e.g. prolonged air leak, gas embolism,
dysrhythmia, respiratory failure, bleeding, infection,
and lung perforation). It is absolutely contraindicated in
patients with severe bullous lung disease or pulmonary
hypertension. In addition, it is not always available in
health centers and is very costly [4]. IPFT with
streptokinase, urokinase, and t-PA is a widely-available
and effective alternative to surgical management [5].
Some complications associated with intrapleural
fibrinolisis are allergic reactions, bronchopleural fistula
and pleural hemorrhage (more frequently seen with the
use of streptokinase). Urokinase is a safer option than
streptokinase, however, since it is made from human
cells, there is an unpredictable risk for the development
of infections after its use [6]. t-PA is made using
recombinant DNA technology; side effects like allergic
reactions and infections are thus less likely. Though the
technique of administration of IPT is not yet
standardized and there is a considerable lack of
experience of its use for this type of indication, risks and
benefits must be weighed on a case by case basis [3].
Based on our positive experience of successful
treatment of IPF with tPA, we recommend considering
parapneumonic effusion secondary to pneumonia who
respond poorly to antibiotic therapy and chest tube
placement, especially in patients for which surgical
management is not an option or is not available. IPFT is
widely available and may be an effective therapeutic
option in patients where the benefits overweigh the
risks [8]. More extensive training of the use of IPT for
situations such as that described here will improve
patient care by widening the range of potential
treatment options.
Progression of empyema is characterized by the
development of fibrinous adhesions (fibrothorax) and
loculations, which makes drainage very difficult and in
many cases even impossible to achieve. A second chest
tube may not a good alternative when the initial tube
thoracostomy is insufficient. IPFT clearly increases the
rate of drainage after intrapleuritic treatment
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