Yonago Acta medica 2010;53:17–24

Local Thrombolysis for Acute Massive Pulmonary Embolism
using a Pulse-Infusion-Thrombolysis Catheter
Yujiro Ina*†, Katsuhiro Kondo*, Masashi Iwabuchi*, Masakiyo Nobuyoshi*, Toshio
Kaminou† and Toshihide Ogawa†*Clinic of Cardiology, Kokura Memorial Hospital, Kitakyushu 802-8555 and †Division of Radiology, Department of Pathophysiological Therapeutic Science, School of Medicine, Tottori University
Faculty of Medicine, Yonago 683-8504, Japan

Acute massive pulmonary embolism (PE) is a common life-threatening condition requiring
emergent and suitable treatment. The aim of this study is to assess the efficacy and safetyof local thrombolysis with a pulse-infusion-thrombolysis (PIT) catheter in the managementof acute massive PE. Thirty-nine patients with PE were treated with catheter directedintervention (CDI). CDI involves suction embolectomy and local thrombolysis with a PIT
catheter. Procedural success was achieved in all patients (100%). After the CDI, a significant increase of mean systemic blood pressure was observed (93.8 ± 22.0 mmHg versus
100.8 ± 22.9 mmHg, P = 0.02), and pulmonary perfusion on the basis of Miller score was
improved (19.6 ± 7.6 versus 16.3 ± 7.1, P = 0.04). Clinical success was achieved in 36 of 39
patients (92.3%). Two patients died of PE after CDI despite a successful recanalization,and 1 patient died of disseminated intravascular coagulation after the CDI. No majorcomplication occurred in the remaining 36 patients and minor complications developed in
3 patients (7.7%). Local thrombolysis using a PIT catheter for massive PE is safe and effective treatment with minimal complication.
Key words: catheter; pulmonary embolism; thrombolysis; tissue plasminogen activator

Acute massive pulmonary embolism (PE) is defined as a life-threatening condition with high mortality (Goldhaber et al., 1999; Kucher et al., 2006;
Tapson, 2008). Especially, patients with massive
PE are at serious risk of death due to right ventricular failure and the presence of hemodynamic
instability within the first hour of onset (Adam etal., 2008). Survival depends on rapid recanalization of the pulmonary arterial occlusion and reduction of the right ventricular afterload. The standard
medical management for patients with massive PEis systemic thrombolysis using a tissue plasminogen activator (t-PA) or a novel modified t-PA, monteplase (Buller et al., 2004). This treatment is as-sociated with hemorrhagic risks, and some patientscannot receive systemic thrombolysis due to contraindications. Catheter directed intervention (CDI)
is an alternative therapy for patients with massive
PE with contraindications to systemic thrombolysis, and this method is considered to be much lessinvasive than the open surgery. CDI includes several interventional techniques, for example, suction
embolectomy and local thrombolysis (Blaustein
et al., 2004; Kuo et al., 2009). CDI with local administration of a thrombolytic agent, urokinase
and t-PA has been used by several investigators(Verstraete et al., 1988; Gonzales-Juanatey et al.,
1992; Kucher, 2007). A recent study (Yamamoto

Abbreviations: CDI, catheter directed intervention; PAP, pulmonary artery pressure; PE, pulmonary embolism; PIT, pulse
infusion thrombolysis; RVD, right ventricular dysfunction; SBP, systolic blood pressure; t-PA, tissue plasminogen activator17

Y. Ina et al.

et al, 2009) showed that CDI with monteplase was
effective for major PE; however, the safety and efficacy of local thrombolysis by CDI still remains
controversial. Pulse infusion thrombolysis (PIT)
is available for thrombotic diseases such as deep
venous thrombosis, because of forceful delivery ofthrombolytic agent in a spray-like fashion throughmultiple side holes (Hokimoto et al., 2008). This
technique was first applied to peripheral arteryand shunt thrombotic occlusion by Bookstein et al.
(1989). In the present study, we used a PIT catheter(Senko Medical Instrument, Tokyo, Japan) for local
thrombolysis of PE, and evaluated the safety andefficacy of CDI, and also demonstrated the earlyand late outcomes.

more criteria right ventricular dysfunction (RVD)
without hypotension. We enrolled 39 patients for
CDI using the PIT catheter, except 4 patients who
had contraindication for thrombolysis.
The clinical definition of massive PE was established in the presence of cardiogenic shock or
hypotension, the latter defined as systemic systolicblood pressure (SBP) < 90 mmHg, or a pressure
drop > 40 mmHg for > 15 min not caused by arrhythmia, hypovolemia or sepsis (Adam et al.,2008). In all patients, RVD was confirmed by transthoracic echocardiography before angiography.
The criteria applied for the diagnosis of RVD werea diastolic diameter of the right ventricle > 30 mm,
a right ventricular diastolic diameter/left ventricular diastolic diameter ratio > 1, paradoxical septal
movement, hypokinesia of the right ventricular
free wall, loss of inspiratory collapse of the inferior
vena cava, and tricuspid regurgitation at a velocity> 2.5 m/s in the absence of inspiratory collapse of
the inferior vena cava or > 2.8 m/s (Wood, 2002).
Written informed consent for CDI and thepotential use of the PIT was obtained in the earlyphase of admission. The study protocol was inagreement with the guidelines of Human Ethics
Committee of the institution. If a patient was unconscious and receiving respiratory therapy at thetime of inclusion in the study, the ethics committee
was notified of the inclusion, and consent was initially obtained from the family.
Baseline characteristics of patients are described in Table 1. There were 15 men and 24
women with mean age of 67.9 ± 13.7 years. The
most frequent risk factor was deep vein thrombosis(67%). Twelve were high-risk patients for PE withsystemic SBP < 90 mmHg or shock index > 0.9.
Two patients were in the state of cardiopulmonaryarrest. RVD was observed in 26 patients (66.7%)
by transthoracic echocardiology before procedure.
Three patients became cardiopulmonary arrest andunderwent cardiopulmonary resuscitation. Before
local thrombolytics, 27 patients (69.2%) with deep
venous thrombosis were implanted inferior vena
cava filter to inhibit the recurrence of PE.

Materials and Methods
Subjects
Between January 2006 and August 2009, 113 consecutive patients referred to our department for suspected of acute PE, of whom 43 patients met criteria for acute massive PE confirmed by contrastenhanced computerized tomography and one orTable 1. Patients’ baseline characteristics
Patientn (%)
Male/female ratio
Age (year)
Prior deep venous thrombosis
CancerTime after major surgery (< 15 days)
Smoking
ObesityHigh risk pulmonary embolism
Cardiopulmonary arrest
Right ventricular dysfunction
Inferior vena cava filter
Treatment time (min)15/24
67.9 ± 13.7
26 (66.7)
3 ( 7.7)
4 (10.3)
7 (17.9)
11 (28.1)
12 (30.8)
2 ( 5.1)
26 (66.7)
27 (69.2)
89.2 ± 24.6

Data are number (n) and percentage of patients; except age
and treatment time shown in mean ± SD, and male/female
ratio.
Total number of patients, 39.

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Local thrombolysis for pulmonary embolism

Fig. 1. Hand pulse-infusion-thrombolysis (PIT) system. The powered pump is attached to a 2.5-mL syringe. The Tshaped, one-way valve allows forceful propulsion of the thrombolytic drug and also aspiration of emboli through the PIT
catheter.

a PIT catheter (Fig. 2). The side holes of the PIT
catheter are placed into the thrombus and the hand
PIT pump allows forcefully directed delivery ofthrombolytic agent into the thrombus. This system
makes it possible to increase the drug contact surface and to accelerate the thrombolytic process.

Hand PIT system
The hand PIT system consists of a hand PIT pump
and a PIT catheter (Fig. 1). The hand PIT pump allows intermittent spray-like drug delivery throughProcedureIn this study, CDI involves suction embolectomy
and local thrombolysis with the hand PIT system.
We used monteplase or urokinase as a thrombolytic
agent on the basis of the severity of patient condition. Monteplase was used when the hemodynamic
improvement of the patient was needed as soon as
possible because of instable condition, otherwise
urokinase was used (Sors et al., 1994). CDI was
performed by a 6- to 8-Gauge French short sheath
introduced into the femoral vein or internal jugularvein. When the transfemoral access was consid-

Fig. 2. Pulse-infusion-thrombolysis catheter. This catheter has spirally placed side-holes that make it possible toinject thrombolytic agent in a spray-like fashion.

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Y. Ina et al.

ered to be contraindicated in case of iliocaval or
ipsilateral femoral venous thrombus, we selected
the transjugular route. If deep venous thrombosis
was confirmed by venous ultrasound or contrastenhanced computerized tomographic images, aninferior vena cava filter was inserted through thedelivering catheter and implanted below the levelof the renal vein.
Immediately after the diagnosis of PE, intravenous unfractionated heparin was started witha bolus dose of 5,000 IU, followed by continuous
infusion with 10,000 to 15,000 IU/day. Pulmonary
artery pressure (PAP) was measured by SwanGanz-catheter (Baxter Healthcare, Irvine, CA) inthe pulmonary artery trunk just before and immediately after CDI. After hemodynamic measurement had been taken, pulmonary angiography was
performed in all patients using a combination ofdigital subtraction angiography and conventionalfilm angiography through a 6- to 8-Gauge French
Judkins right guide-catheter (Terumo, Tokyo,
Japan) using iopromide 240 mgI/mL as a contrast
medium. Angiography was performed with thecatheter placed in the pulmonary trunk and selectively in the right and left main pulmonary arteries. We assessed the extent of thrombus formation
by a scoring system of Miller et al. (1971). In thismethod, the right and left main pulmonary arteries are considered to have nine and seven major
branches, respectively, and an embolus in any ofthese branches is scored as 1 point. The maximum
possible score for involvement is 16 points. In addition, the effect of embolism on pulmonary arteryflow is scored as follows: each lung is considered toA

B

Fig. 3. Pulmonary angiograms in a 65-year-old woman
with massive pulmonary embolism.
A: Pretreatment image shows emboli in the left lower
lobe artery (arrowhead). The pulmonary arterypressure (PAP) was 33/19 mmHg (mean, 25 mmHg),
and the Miller score was 14.
B: Local thrombolysis was performed using the pulse
infusion thrombolysis catheter.
C: Posttreatment image shows complete recanalizationof pulmonary artery occlusion. The PAP was 30/10
mmHg (mean, 18 mmHg), and the Miller score was
10.

C
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Local thrombolysis for pulmonary embolism
SBP which is an indicator of acute critical illness(Rady et al., 1994). Other variables analyzed toevaluate the effect of the therapy were mean PAP,
mean SBP and RVD on transthoracic echocardiography before and after treatment. Clinical success
was defined as the stabilization of hemodynamic
parameter, the resolution of shock, the complete
weaning off ventilatory and inotropic support andsurvival until discharge from the hospital. Midterm outcomes were defined as most recent patient’s condition after discharge including analysis
of occurrence of cardiovascular death, recurrent PE
and RVD on transthoracic echocardiography (Liuet al., 2003).

have an upper, middle and lower zones, and in eachof these 3 zones, the absence of pulmonary arteryflow is scored as 3 points; severely reduced flow,
2 points; mildly reduced flow, 1 point; and normal
flow; 0 point. The maximum score for reduction
in pulmonary artery flow is therefore 9 points foreach lung (total 18), and the maximum possible
score for flow reduction and involvement of arteries
by embolism is 34 points. Thus the Miller score
ranges from 0 to 34 with higher scores reflecting
greater pulmonary involvement.
After pulmonary angiography, suction embolecomy was performed for each pulmonary
artery with the guide-catheter described above.
Monteplase or urokinase was administered by the
PIT system (Fig. 3). Dose of thrombolytic agent
was adjusted at minimum according to the angiographic findings, hemodynamic status, and bleeding risk. The effectiveness of CDI was assessed byhemodynamic improvement and the Miller score.
Finally, pulmonary angiography was performed formeasurement of the postprocedure Miller score,and PAP was measured again.
After the CDI, all patients were usually sent
to coronary care unit and monitored for the evaluation of complications. After stabilization of thepatient’s general condition, oral warfarin was also
started and was continued for ≥ 6 months, withthe adjustment to maintain the international normalized ratio between 2 and 3. Major procedural
complications by CDI were defined as follows:hemorrhage requiring blood transfusion, cardiac
tamponade, pulmonary artery perforation, cerebral
vascular accident, and/or death. Minor procedural
complications were defined as follows: catheterrelated infection and hematoma at the puncture siteor hemoptysis not requiring transfusion (Kucher,2007).

Statistical analysis
The data were analyzed using the Student t-test forthe comparison of paired samples. A P value < 0.05
was considered to be statistically significant.
Results
Procedure success rate
Procedural success was achieved in all patients(100%). As a thrombolytic agent, urokinase wasused in 12 patients at mean dose of 340,000 ±
177,866 U, and monteplase in 27 patients with
12,836 ± 5619 IU/kg. Mean total procedure timewas 89.2 ± 21.0 min.
Hemodynamic and angiographic parameters
before and after the procedure are shown in Table 2.
After CDI, a significant increase of mean SBP was
observed (93.8 ± 22.0 mmHg versus 100.8 ± 22.9mmHg, P = 0.02), and a significant decrease of theMiller score was observed (19.6 ± 7.6 versus 16.3
± 7.1, P = 0.04). On the other hand, systolic SBP,
mean PAP and shock index were not significantly
different.

Assessment of efficacy
The procedural success was evaluated by theMiller score after the therapy. The hemodynamic
status of the patient was evaluated by the shock index obtained from dividing heart rate by systemic

In-hospital outcome
Clinical success was achieved in 36 of 39 patients(92.3%). Two patients died of PE after CDI despite
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Y. Ina et al.

Table 2. Hemodynamic and angiographic parameters
Systemic SBP (mmHg)
Mean SBP(mmHg)
Mean PAP(mmHg)
Miller score		
Shock index		Before procedure

After procedure

P value131.8 ± 30.1
93.8 ± 22.0
33.4 ± 10.4
19.6 ± 7.6
0.71 ± 0.28

138.9 ± 31.7
100.8 ± 22.9
33.1 ± 9.7
16.3 ± 7.1
0.64 ± 0.29

0.31
0.02
0.19
0.04
0.34

Shown are mean ± SD.
PAP, pulmonary artery pressure; SBP, systolic blood pressure.

of death due to RVD within the first hours of onset(Dalen and Alpert, 1975). Survival depends on
rapid recanalization of the pulmonary arterial occlusion and reduction of the right ventricular afterload. The American College of Chest Physicians
and the European Society of Cardiology have recommended thrombolytic therapy for these patients(Buller et al., 2004).
There are 2 approaches to administrate
thrombolytic agent: systemic and local thrombolysis with CDI, which is controversial. The standard
treatment for massive PE is systemic thrombolysis(Buller et al., 2004); however, some patients cannot
receive systemic thrombolysis due to contraindications. Although some authors reported no difference for prognosis between these approaches,several reports showed that local thrombolysis
improves severe hemodynamic impairment rapidly
and safety in patients with acute PE (Tajima et al.,
2004; Kuo et al., 2009; Yamamoto et al., 2009). In
our series, local thrombolysis was adopted. In ourstudy, 36 patients with acute PE were treated by
CDI with a clinical success rate of 92.3% that ishigher than previous review (Kuo et al., 2009). Inhospital mortality (7.7%) is lower than that reported
by International Cooperative Pulmonary Embolism
Registry investigation (11.4%, 2 weeks) (Goldhaber
et al., 1999).
PIT has previously been described as an effective device for treating deep venous thrombosis or acute myocardial infarction (Hokimoto etal., 2008; Kuo et al., 2009). PIT catheter makes
it possible to lyse thrombus using the synergetic
mechanisms of mechanical maceration by direct

a successful recanalization, and 1 patient died ofdisseminated intravascular coagulation 5 days after
the treatment. Overall mortality was 7.7% (3/39
patients). No major complication such as perforation of pulmonary artery occurred in the remaining
36 patients. Minor complications developed in 3
of 39 patients (7.7%) (hematoma at the puncture
site, 1 patient; hemoptysis, 2 patients). Thirty-six
patients survived and remained stable until thedischarge (mean duration 18.1 ± 7.7 days). RVD
was observed in 6 patients (15.4%) at the point ofdischarge, while observed in 24 patients (61.5%) at
admission.
Mid-term outcome
Follow-up information after discharge was obtained from 33 patients (mean follow-up 25.3 ±16.9 months). One patient died during followup period because of gynecological cancer (1/33
patients, 3.0%). Other patients were confirmed to
be alive. Recurrent PE was not observed duringfollow-up period. RVD was observed in 4 patients(11.1%) after discharge.

Discussion
No randomized clinical trials have been undertaken to evaluate the efficacy and safety of local
thrombolysis with the PIT system for massive PE.
Acute massive PE is defined as a life-threatening
condition with high mortality (Goldhaber et al.,1999). Patients with massive PE are at serious risk

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Local thrombolysis for pulmonary embolism
spray-like delivery of thrombolytic agent into thethrombus. Hence, a high concentration of drug isdelivered into the thrombus, resulting in lower doseof the drug. In the present study, the use of a meandose of thrombolytic agent was approximately halfof the recommended dose. We consider that it contributes to reduce the risk of hemorrhage complication in our study.
Regression of right ventricular overload has
been shown in previous studies after CDI, and rapid recovery from RVD is associated with reduced
morbidity and mortality (Adam et al., 2008). In
our study, PAP indicating right ventriclular overload was not significantly different before and immediately after CDI. However, RVD confirmed bytransthoracic echocardiography was significantly
reduced at the discharge.
Reported complications associated with CDI
include right ventricular perforation, significant
bleeding at the puncture site (2%), mechanicalhemolysis, and blood loss (Kucher, 2007; Skaf etal., 2007; Eid-Lidt et al., 2008). There were no major complications related to the catheter procedurein our study. Although disseminated intravascular
coagulation occurred at 5 days after CDI in 1 patient, association with CDI is unclear. As minor
complications, hematoma was documented in 1
patient. No recurrence of PE or cardiovasculardeath was documented in our study during followup. The absence of PE recurrence could probably
be related to the use of inferior vena cava filter andoral warfarin administration in patients confirmed
as with DVT (Adam et al., 2008).
The present study possesses some limitations
regarding non-randomized study, small samples
from a single institution and retrospective design,
which may have introduced variability in the uniformity of data collection. Although prospective
studies are needed to confirm the effectiveness of
this local thrombolysis with the PIT system, we
believe that this treatment should be effective forpatients with massive PE accompanied by unstable
hemodynamics when there is insufficient time toinfuse intravenous thrombolytics.

In conclusion, local thrombolysis using a PIT
catheter for massive PE is safe and effective treatment with minimal complication.
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Received January 12, 2010; accepted January 20, 2010
Corresponding author: Toshihide Ogawa, MD, PhD

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