Case Report
Cerebral Gas Embolism Caused by Pleural
Fibrinolytic Treatment
Manuel Menéndez-González, MD; Pedro Oliva-Nacarino, MD; Almudena Álvarez-Cofiño, MD
Background and Purpose—Intrapleural fibrinolytic therapy is a technique used to treat empyemas and parapneumonic
effusions. Cerebral air embolism is an unusual potentially severe complication of this technique.
Summary of Case—A patient with parapneumonic pleural effusion underwent pleural lavage with streptokinase when he
suddenly demonstrated focal neurological signs and seizures. The CT revealed multiple air-isodense spots in right
hemisphere of the brain, suggesting cerebral air embolism. As a result of early diagnosis and emergency hyperbaric
oxygenation, the patient recovered without delayed sequelae.
Conclusions—Air embolism is a potentially severe complication which can occur during fibrinolytic pleural lavage, and
clinicians should be aware of this risk. In this context, the onset of acute focal neurological signs or seizures should
suggest the possibility of air embolism and lead to the transfer of the patient close to a hyperbaric facility within a few
hours. (Stroke. 2007;38:2602-2604.)
Key Words: air embolism 䡲 fibrinolytic therapy 䡲 hyperbaric oxygenation 䡲 stroke

P

arapneumonic effusions and empyema may complicate
lower respiratory tract infections. In this condition, loculation of fluid is a major problem, and therapeutic options
include conventional surgical drainage, video-assisted thoracoscopic surgery and the use of intrapleural fibrinolytic
agents (urokinase and streptokinase) to break down fibrin
bands that may cause loculation.1– 4 Although many physicians use fibrinolytic agents, the technique of instillation has
not yet been standardized.5 A Cochrane Systematic Review6
evaluated the benefit of adding intrapleural fibrinolytic therapy to intercostal tube drainage in the treatment of complicated parapneumonic effusions and empyema. Controlled
trials conducted up to 2003 were reviewed, concluding that
intrapleural fibrinolytic therapy conferred significant benefits
when compared with normal saline control. However, the
routine use of fibrinolytic therapy cannot be recommended
because the trial numbers were too small. A recent meta-analysis raised the same conclusions.7 Remarkably, complications
attributable to therapy were not observed at all in these trials,
although several case reports of cerebral air embolism have
been published.8 –10 Herein we report a new case.

Case Reports
A 50-year-old male patient, with a previous history of intestinal
adenocarcinoma and resection of colorectal liver metastases
developed a right purulent pleural effusion (Figure, A). He was
admitted to hospital for daily pleural lavages with saline associated with streptokinase and for antibiotic treatment. During the

third lavage he suddenly developed a generalized tonic-clonic
seizure. Neurological examination showed a drowsy patient,
with a conjugated gaze deviation toward the right, lower left
facial paralysis, left hemiplegia and left Babinski sign. He
immediately underwent a CT scan of the brain which revealed
multiple air-isodense spots in the right hemisphere suggesting
cerebral air embolisms (Figure, B). He received hyperbaric oxygen
therapy (a 135-minute session at 2.8 ATA, followed by 70
minutes at 2.3 ATA) with a favorable outcome within 24 hours.

Discussion
Gas embolism is a known complication of various invasive
procedures. Air bubbles circulating in the blood stream obstruct
the blood flow, causing tissue ischemia. There are 2 broad
categories of gas embolism, venous and arterial, which may be
differentiated by the mechanism of gas entry and the site where
the emboli ultimately lodge. In venous gas embolism, the air is
transported to the lungs through the pulmonary arteries, causing
interference with gas exchange, cardiac arrhythmias, pulmonary
hypertension, right ventricular strain, and, eventually, cardiac
failure. Furthermore, retrograde cerebral venous gas embolism
(CVGE) is possible.11 Arterial gas embolism is caused by the
entry of gas into the pulmonary veins or directly into the arteries
of the systemic circulation. The systemic passage of air from the
pleura is possible by different theoretical mechanisms. A direct
communication between the pulmonary vasculature and either
the pleural cavity (pleurovascular fistula) or the bronchial tree
(bronchovascular fistula) is necessary. An accidental lesion of

Received January 28, 2007; final revision received March 25, 2007; accepted March 28, 2007.
From the Neurology Unit (M.M.G.), Hospital Álvarez-Buylla, Mieres, Oviedo, Spain; the Neurology Department (P.O.N.), Hospital Universitario
Central de Asturias, Celestino Villamil, Asturias, Oviedo, Spain; and the Radiology Department (A.A.C.), Hospital Universitario Central de Asturias,
Celestino Villamil, Asturias, Oviedo, Spain.
Correspondence to Manuel Menéndez González, Unidad de Neurologı́a, Hospital Álvarez-Buylla, Mieres, Oviedo, 33616, Spain. E-mail
manuelmenendez@gmail.com
© 2007 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org

DOI: 10.1161/STROKEAHA.106.477752

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Menéndez-González et al

Cerebral Gas Embolism

2603

A, A chest radiograph at admission showed a
right pleural effusion. B, Air densities were demonstrated along the right hemisphere on a CT
performed 1 hour after the onset of embolism.

the pulmonary tissue can also be caused by chest drain, which
may have led to a breach, as happens in lung trauma or in
iatrogenic pneumothorax. In this case it would be expected that
the symptoms occur during the first lavages, or at least that the
patient refers from the beginning some symptom of discomfort
such as coughing. Whatever the source of air, the fibrinolytic
agent might dissolve fibrin membranes of the visceral pleura and
vasculature and thereby open a passage for air, especially in the
presence of a favorable pressure gradient. Although obstruction
is possible in any artery, obstruction of arteries of the brain
(CAGE) is especially serious and may be fatal because of the
vulnerability of the brain to short periods of hypoxia. In CAGE,
the cerebral distribution of bubbles will depend on the corporal
position. When the patient is laid on the left side most bubbles
will lead to the right hemisphere.12
Although the hypothesis of an enzyme-induced fistula to
explain gas embolism by pleural fibrinolytic treatment is very
attractive, a perforation caused by the tools used during the
procedure cannot be excluded. Nevertheless, this patient had
undergone 2 previous lavages without complications, which
makes the enzyme-induced mechanism more plausible. This
procedure is usually performed in our hospital, and no similar
complications had ever occurred. Other complications of this
procedure have previously been reported, such as cardiac arrest
of secondary distress respiratory syndrome6 but no signs or
symptoms suggesting embolisms in different organs were observed in this patient.
The temporal relationship between this procedure and the
onset of acute focal neurological signs is the most important clue
for diagnosing cerebral gas embolism. CT scan and MRI of the
brain are usually confirmatory tests. In CAGE, CT demonstrates
intraarterial air in 1 or both cerebral hemispheres,13,14 but only
macroscopic bubbles (1.3-mm radius) are identifiable and only if
the CT slices, usually at 1-cm intervals, coincidentally intersect
the appropriate level.15 Therefore, absence of air on CT scan
does not exclude the diagnosis. MRI provides a higher sensitivity.16 In CVGE, brain CT is diagnostic only if obtained immediately because air is rapidly resorbed from the brain arterioles.
Diffusion-weighted MRI shows multiple areas of restricted
diffusion in a gyriform pattern affecting predominantly cortical
areas in both hemispheres.17
Oxygen should be administered at as high a concentration as
possible.13 Administration of oxygen is important not only to

treat hypoxia and hypoxemia but also to eliminate the gas in the
bubbles by establishing a diffusion gradient that favors the
egress of gas from the bubbles. In patients requiring mechanical
ventilation, ventilatory pressures and volumes should be kept as
low as possible to maintain adequate oxygenation and to limit a
pressure gradient which would favor gas entry in the pulmonary
circulation.18 The improvements in the oxygen-carrying capacity
of plasma and in the delivery of oxygen to tissues offset the
embolic insult to the microvasculature. Several CAGE published
cases8,19,20 have also reported very good outcomes when treated
with hyperbaric oxygenation.

Acknowledgments
We thank Dr Sergio Calleja for his critical review of this manuscript.

Disclosures
None.

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Cerebral Gas Embolism Caused by Pleural Fibrinolytic Treatment
Manuel Menéndez-González, Pedro Oliva-Nacarino and Almudena Álvarez-Cofiño
Stroke. 2007;38:2602-2604; originally published online August 2, 2007;
doi: 10.1161/STROKEAHA.106.477752
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2007 American Heart Association, Inc. All rights reserved.
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