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Endovascular Closure of a Patent Foramen Ovale in the Fat Embolism Syndrome
Changes in the Embolic Patterns as Detected by Transcranial Doppler
Alejandro M. Forteza, MD;
Alejandro Rabinstein, MD;
Sebastian Koch, MD;
Gregory Zych, DO;
Jay Chandar, MD;
Jose G. Romano, MD;
Iszet Campo Bustillo, MD
Arch Neurol. 2002;59:455-459.
ABSTRACT
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Background The posttraumatic fat embolism syndrome (FES) is characterized by petechiae
and pulmonary and cerebral dysfunction. A patent foramen ovale (PFO) could
worsen the prognosis of FES by allowing larger emboli to reach the systemic
circulation. Transcranial Doppler ultrasonography can be used to diagnose
and monitor cerebral microembolism in FES.
Objective To describe a case of successful percutaneous closure of PFO in a patient
with posttraumatic FES with excellent clinical outcome.
Patient and Methods A 17-year-old girl presented with a posttraumatic long-bone fracture
complicated by typical severe FES. Transcranial Doppler disclosed multiple
microembolic signals over both middle cerebral and basilar arteries. A large
PFO was diagnosed by transesophageal echocardiogram. A brain magnetic resonance
image with diffusion-weighted sequences showed multiple bilateral areas of
abnormal diffusion in watershed territories. Percutaneous PFO closure with
a buttoned device was successfully performed.
Results Closure of PFO was associated with marked reduction in the number and
intensity of microembolic signals. Subsequent surgical repair of the fracture
with the patient under transcranial Doppler monitoring was uneventful. There
was excellent correlation between clinical course and microembolic signal
load by transcranial Doppler.
Conclusions Cerebral fat embolism after long-bone fractures can be detected in vivo
and monitored over time with the use of transcranial Doppler techniques. If
a PFO is present, its closure before surgical manipulation of the fracture
is feasible and could have important protective effects against massive systemic
embolization.
INTRODUCTION
THE POSTTRAUMATIC fat embolism syndrome (FES) is a multisystem disorder
characterized by the clinical triad of petechial rash, dyspnea, and signs
of cerebral dysfunction.1-2 Pathological
studies of patients who died after having FES typically show widespread microvascular
occlusion by fat emboli, particularly within the lungs and brain.3-4 The presence of a patent foramen ovale
(PFO) has been suggested to worsen the prognosis of FES by allowing a larger
embolic load to reach the systemic circulation,4-6
and it has been shown that during bone surgery large fat globules may cross
a PFO, causing severe cerebral complications, including death.4
Our group recently reported that cerebral microembolism in patients
with FES can be diagnosed and monitored in real time with transcranial Doppler
(TCD).6 Two years ago, we began a prospective
study in which patients with long bone fractures were monitored with TCD within
24 hours of trauma. Our preliminary results, presented elsewhere,7 suggest that the presence of a PFO is a risk factor
for developing more severe manifestations of FES. If this holds true, it may
be helpful to occlude the right-to-left shunt before a critical embolic load
has caused irreversible or significant damage.
We describe a patient with severe posttraumatic FES and a PFO who successfully
underwent percutaneous closure of the intracardiac shunt followed by excellent
clinical recovery.
REPORT OF A CASE
A 17-year-old girl had a car crash and was brought to our Trauma Emergency
Room. No loss of consciousness or head trauma occurred. Her Glasgow Coma Scale
score was 15 at the scene of the accident and on arrival to the hospital.
Initial evaluation showed a fully alert patient in no significant distress
who complained only of left thigh pain. Vital signs showed a regular tachycardia
of 100 beats per minute, a blood pressure of 120/80 mm Hg, and a respiratory
frequency of 16/min. The left thigh was swollen and deformed, but there was
no disruption of the skin continuity.
A radiologic survey was performed, including a computerized tomographic
scan of the brain, with normal results. An x-ray film of the left femur showed
a comminuted, transverse fracture at the junction of the proximal and middle
thirds of the shaft, with lateral and posterior displacement of the distal
fragment. Routine blood work showed leukocytosis (white blood cell count,
22.7 x103/µL) and mild anemia (hemoglobin level, 11.9
g/dL; hematocrit, 37%). Prothrombin time was 14 seconds, and activated thromboplastin
time, 24 seconds. Initial blood gas values while the patient was breathing
room air were as follows: pH 7.41, PCO2, 34 mm Hg; PO2,
61 mm Hg; bicarbonate, 21 mEq/L; and arterial oxygen saturation, 92%. The
patient was placed in skeletal traction and received nonopiate pain medication.
Fourteen hours after admission, she suddenly became confused and agitated.
Tachycardia and tachypnea worsened and pulse oximetry showed that the arterial
oxygen saturation had dropped to 85% while the patient was breathing room
air, improving to 98% when 4 L of oxygen by nasal cannula was administered.
Repeated blood gas measurement showed a pH of 7.42, PCO2 of 35
mm Hg, PO2 of 45 mm Hg, bicarbonate level of 22 mEq/L, and arterial
oxygen saturation of 83%. The patient was transferred to the intensive care
unit and intubated orally. At that time, she was stuporous, responding with
eye opening, grimacing, and withdrawing limbs to painful stimuli. Bilateral
Babinski signs and bilateral subconjunctival petechiae were noted.
A TCD examination disclosed multiple microembolic signals (MES) over
both middle cerebral arteries (MCAs) and the basilar artery (Figure 1A-B shows MES over left MCA). Two seconds after the injection
of agitated isotonic sodium chloride solution in an antecubital vein, numerous
MES appeared over both MCAs and the basilar artery, indicating the presence
of a right-to-left shunt (Figure 1C-E).
A venous duplex scan of the lower extremities and a ventilation-perfusion
nuclear scan of the lungs obtained during the following 12 hours were unremarkable.
A transesophageal echocardiogram performed during the third hospital day showed
a redundant interatrial septum, confirmed the presence of a PFO, and showed
spontaneous passage of aerated microbubbles across the septum (Figure 2A-B). A brain magnetic resonance image with diffusion-weighted
images obtained that same day showed multiple areas of abnormal diffusion
on diffusion-weighted images, some with high T2 and fluid-attenuated inversion
recovery signal intensity, located in the subcortical and periventricular
white matter of both cerebral hemispheres in the distribution of the watershed
territories (Figure 3).
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Figure 1. Microembolic signal (MES) characteristics.
A, Large MES with an intensity greater than 12 dB (arrowhead) detected in
the left middle cerebral artery. B, Small MES of less than 12 dB (long arrow)
detected in the left middle cerebral artery. C-E, Multiple MES over the right
middle cerebral artery observed within seconds of intravenous injection of
aerated, agitated isotonic sodium chloride solution.
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Figure 2. Transesophageal view of redundant
interatrial septum and patent foramen ovale (A) with spontaneous passage of
contrast (aerated isotonic sodium chloride solution) from right atrium (RA)
to left atrium (LA) (B). After deployment of the occluding device, there is
no further passage of contrast from right to left (C and D). T indicates transverse
axis; L, longitudinal axis; RV, right ventricle; and LV, left ventricle.
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Figure 3. Brain magnetic resonance images
showing fluid-attenuated inversion recovery signal changes in the deep anterior
and posterior watershed areas (A and B) and abnormal diffusion on diffusion-weighted
images (C and D).
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On the fourth day of admission, after informed consent was signed by
proxy, a transcatheter device closure of the PFO was successfully performed
with the patient under general anesthesia and transesophageal echocardiographic
control (Figure 2C-D). A 40-mm buttoned
device (Custom Medical Devices, Amarillo, Tex) was placed in the left atrium
with the use of a 10F sheath from the femoral vein. The right-to-left shunt
was eliminated by adding a 25-mm inverted counter occluder in the right atrium.
Treatment with clopidogrel bisulfate and enoxaparin sodium was started.
During the next 36 hours, the patient exhibited progressive improvement,
eventually recovering normal mental status. An echocardiogram performed 5
days after the catheterization confirmed that the device remained in place
with no passage of microbubbles from right to left. On the 10th day of admission,
the patient underwent surgical repair of her femoral fracture without complications.
Continuous TCD monitoring was performed during surgery. Close clinical follow-up
did not show any suggestion that the surgery worsened the patient's mental
status. On the contrary, during the days after the surgery, she continued
to improve and was discharged home while receiving warfarin sodium on the
16th hospital day.
TCD EXAMINATIONS
Embolus detection monitoring was performed on admission, intraoperatively,
and daily until a 1-hour monitoring period failed to identify MES. All studies
were performed with a TCD unit (Pioneer TC 4040; Nicolet Biomedical Inc, Madison,
Wis) equipped with microembolus detection software, version 2.31, 256-point
fast Fourier transform with a sample volume of 10 mm. Each study lasted 1
hour. A 2-MHz probe was used to insonate the right and left MCAs and the basilar
artery through temporal and transforaminal windows. All studies were performed
at a depth of insonation between 5 and 5.6 cm for the MCAs and between 8 and
9 cm for the basilar artery. A headband was used to immobilize the probe against
the temporal window. Two experienced technicians (including I.C.B.) performed
all studies, and any suspicious signals were saved manually. Two independent
blinded observers (A.M.F. and S.K.) reviewed all studies.
The initial study on the day after trauma showed 14 MES per hour, with
only 2 MES smaller than 12 dB. Daily studies during the next 2 days demonstrated
a similar pattern, with more than 80% of all emboli having an intensity of
12 dB or more. Percutaneous closure of the PFO eliminated all large emboli
and decreased the embolic load, so that on day 8 only 1 MES per hour was detected.
An increase in the number of emboli to 16 MES per hour was noted during femur
surgery, of which 75% were smaller than 12 dB. Postoperative monitoring was
continued for 72 hours, when only 1 MES per hour was found (Figure 4).
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Figure 4. Daily embolus detection monitoring
demonstrating large emboli from the day of injury until patent foramen ovale
(PFO) closure, with a small increase the day of femur surgery. Gray bars indicate
emboli of 12 dB or more; black bars, emboli less than 12 dB. MES indicates
microembolic signals.
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DETECTION OF RIGHT-TO-LEFT SHUNT
Nine milliliters of isotonic sodium chloride solution was vigorously
mixed with 1 mL of air and injected into an antecubital vein, while 1 MCA
was monitored. A second injection was performed with the patient performing
a Valsalva maneuver 5 seconds after the injection. The study was considered
positive with the appearance of embolic signals within 60 seconds of the injection
(Figure 1C-E).
COMMENT
The clinical spectrum of the FES ranges from asymptomatic to fulminant
cases.2, 8 The incidence of FES
after single long-bone fractures is estimated to be between 0.5% and 3%, even
though fat globules can be detected in the venous blood of almost every patient
with these fractures.9 The factors that determine
the development and severity of FES remain incompletely understood.
The occurrence of fat microembolism has been solidly documented in vivo,1, 6, 10 and the prevailing
theory in posttraumatic cases of FES proposes that damaged intramedullary
veins allow the intravasation and subsequent embolism of marrow fat.11 Fat emboli are suspected to be able to modify their
shape to reach the systemic circulation either through pulmonary precapillary
shunts or directly across the pulmonary-capillary bed.12-14
However, presence of a PFO has been shown to be responsible for the occurrence
of paradoxic embolism in some patients with FES,4-6
and it may be associated with a worse outcome. By blocking the lumen of pulmonary
capillaries, fat emboli could lead to an increase in right ventricular filling
pressures, thereby favoring right-to-left shunting in patients with PFO.
Our patient presented with a typical clinical picture of posttraumatic
FES. The elements of the diagnostic clinical triad were present: acute respiratory
distress, petechiae, and signs of cerebral dysfunction. Embolus monitoring
showed the presence of numerous MES in the absence of any evidence of deep
venous thrombosis in the lower extremities. Magnetic resonance imaging of
the brain showed multiple areas of abnormal diffusion suggesting acute ischemia
distributed throughout watershed regions. This pattern of magnetic resonance
imaging findings has been previously reported in patients with FES.6, 15-16
The embolic load and the intensity of the emboli as assessed by TCD
were significantly reduced after our patient underwent successful percutaneous
closure of her PFO, but the emboli did not disappear immediately, rising again
during the surgical repair of the fracture (Figure 4). Our results suggest that the endovascular closure of
the PFO stopped large emboli from being shunted through the heart, but small
emboli continued to reach the brain (although in smaller numbers) for several
days, possibly crossing through intrapulmonary shunts.12-13
Progressive clinical improvement followed this procedure, and subsequent surgical
repair of her femoral fracture did not alter this favorable course.
Our case brings out issues with both clinical and pathophysiologic implications.
Several aspects of the case reaffirm the concept of FES as a microembolic
state.3 Microembolic signals were clearly demonstrated
throughout the course of the disease and were maximal at the time of worst
clinical status. Their clinical relevance was further supported by the appearance
in the magnetic resonance image of the brain of multiple areas of abnormal
diffusion along the watershed distribution. Furthermore, after closure of
the PFO, the reduction of MES reaching the systemic circulation was associated
with a clear and persistent clinical improvement.
Presence of a PFO has previously been implicated as a poor prognostic
factor in patients with FES.4-6
The severity of the clinical presentation in our case and the improvement
after correction of the intracardiac shunt add further credence to this notion.
The presence of a PFO allows the passage of larger and therefore more dangerous
fat particles, as suggested by the MES detected before and after PFO closure
in Figure 4. In fact, our decision
to close the PFO in this case was based on the experience with a previous
patient with FES and PFO who ultimately developed severe neurologic sequelae.6
This case also illustrates the value of TCD monitoring and magnetic
resonance imaging with diffusion-weighted images in the evaluation of patients
with long-bone fractures and early neurologic symptoms. We believe that the
presence of numerous and particularly of large MES as well as the evidence
of areas of abnormal diffusion should prompt the search for a correctable
intracardiac shunt, such as a PFO. This is especially important, since intraoperative
monitoring with transesophageal echocardiography may detect fat embolism in
approximately 40% of patients undergoing major orthopedic procedures,17 and intraoperative transesophageal echocardiography
has been proposed as a useful diagnostic tool to monitor these patients.4
The periprocedural complication rates of percutaneous PFO closure vary
with the method and device used, and they have ranged between 0% and 10%.18-20 Complications may
include damage to the peripheral vessels with ensuing retroperitoneal hematoma,
perforation of the right atrium with pericardial tamponade, intraprocedural
stroke presumably due to air embolism, and embolization of the device.18 Success rates as defined by trivial or no residual
shunt seen on echocardiography have ranged between 86% and 98%.18-19
Follow-up for up to 5 years showed an incidence of recurrent thromboembolic
events of 3.2% to 3.4%,18-19 and
these events were more frequent in cases of suboptimal closure. How this transcatheter
percutaneous technique compares with surgical closure remains to be determined.21-22
In summary, we present a provocative case of severe posttraumatic FES
in a patient with PFO who was successfully treated by percutaneous closure
of the intracardiac shunt. This case reaffirms that cerebral fat embolism
after long-bone fractures can be detected in vivo and monitored over time
with the use of TCD. If a PFO is present, its closure before the surgical
manipulation of the fracture could have important protective effects against
massive systemic embolization.
AUTHOR INFORMATION
Accepted for publication October 29, 2001.
Author contributions: Study
concept and design (Drs Forteza, Rabinstein, and Koch); acquisition of data (Drs Forteza, Rabinstein, Koch, Zych, Chandar,
and Campo Bustillo); analysis and interpretation of data (Drs Forteza, Rabinstein, Koch, Romano, and Campo Bustillo); drafting of the manuscript (Drs Forteza and Rabinstein); critical revision of the manuscript for important intellectual
content (Drs Forteza, Koch, Zych, Chandar, and Romano); obtaining funding (Dr Forteza); administrative, technical,
or material support (Drs Forteza, Chandar, and Campo Bustillo); study supervision (Drs Forteza and Zych).
Corresponding author and reprints: Alejandro M. Forteza, MD, Professional
Arts Center, 1150 NW 14th St, Suite 304, Miami, FL 33136 (e-mail: aforteza{at}med.miami.edu).
From the Division of Cerebrovascular Diseases, Department of Neurology
(Drs Forteza, Rabinstein, Koch, Romano, and Campo Bustillo), Department of
Orthopedic Surgery (Dr Zych), and Division of Pediatric Cardiology, Department
of Pediatrics (Dr Chandar), University of Miami School of Medicine, Miami,
Fla.
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