Download Massive pulmonary embolism

Vascular Medicine 2002; 7: 181–185
Massive pulmonary embolism: a remarkable case and
review of treatment
Joshua M Cooper and Joshua A Beckman
Abstract: Although the clinical syndrome following pulmonary embolism (PE) may be subtle,
in the case of massive PE the severity of the clinical presentation typically makes the picture
more obvious. If more than two lobar pulmonary arteries become obstructed, the hemodynamic
and respiratory consequences are severe, and may be life threatening. We present an unusual
case where a patient experienced transient hemodynamic collapse during valsalva, and a massive saddle pulmonary embolus was discovered incidentally. Current treatment options for
massive PE are then discussed.
Key words: pulmonary embolism; thrombectomy/embolectomy; thrombolysis
Case report
A 68-year-old man presented to the emergency department
because of a syncopal episode. At a health club with
friends, just after using the leg press machine, he suddenly
lost consciousness for 30 seconds. He reported no symptoms either before or after the syncopal episode. His friends
took him out for dinner, and then brought him to the emergency department, where he began to experience mild chest
pains which radiated to his upper back.
His past medical history was signiŽ cant for prostate cancer, treated with radical prostatectomy four years previously. He had no history of cardiovascular or pulmonary
disease. He took no medications, did not smoke, and exercised daily without symptoms.
In the emergency department, his pulse was 95 beats per
minute, blood pressure was 112/64 mmHg, and respirations
were 14 breaths per minute, with 98% oxygen saturation
on room air. SigniŽ cant physical Ž ndings included a jugular
venous pressure of 8 cm water, symmetric pulses and blood
pressures, a normal lung exam, a normal cardiac exam, no
edema or cyanosis, and intact radial and pedal pulses.
His electrocardiogram revealed normal sinus rhythm,
normal axis, normal intervals, and an occasional premature
ventricular contraction with fusion. Laboratory values were
remarkable as follows: creatinine 1.5 mg/dl, creatine kinase
695 U/l with ,1% MB fraction, and troponin I 1.1 ng/ml
(normal 0–0.08).
Because of the concern for aortic dissection as an explanation for intrascapular pain and syncope, a spiral CT scan
with intravenous contrast was obtained. The CT scan
revealed a massive saddle pulmonary embolus (Figure 1).
In addition, the abdominal images demonstrated a 9.3 3
7.6 cm mass in the left kidney, with thrombus seen Ž lling
a left renal vein, extending to the midline and into the
Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Address for correspondence: Joshua A Beckman, Brigham and Women’s
Hospital, 75 Francis Street, Boston, MA 02115, USA. Tel: +1 617 732
6186; Fax: +1 617 232 2749; E-mail: [email protected]
Ó Arnold 2002
suprarenal inferior vena cava (Figure 2). Urgent echocardiography revealed normal left ventricular size and function
with an ejection fraction of 50%. The interventricular septum was mildly  attened and there was hypokinesis of the
anterior free wall of the right ventricle, suggestive of right
ventricular (RV) pressure overload. There was mild tricuspid regurgitation with a peak velocity of 3.5 m/s, indicative
of a RV systolic pressure of 49 mmHg plus right atrial
pressure.
Because of the location and size of the embolus, surgical
removal was felt to be the best treatment strategy. In the
operating room, transesophageal echocardiography conŽ rmed the presence of a massive saddle pulmonary
embolus, extending into and nearly obstructing both the
right and left main pulmonary arteries (Figure 3). Mild RV
strain was noted. The patient underwent pulmonary embolectomy with complete removal of central venous thrombus,
as well as left radical nephrectomy an inferior vena cava
thromboectomy.
Pathological evaluation of the renal mass revealed renal
cell carcinoma, and the embolus contained a mixture of
renal cell carcinoma and Ž brin. Surgical resection margins
revealed neither local invasion nor tumor-laden lymph
nodes. The patient recovered and was discharged 6 days
postoperatively on warfarin. He remained asymptomatic
with no clinical evidence of tumor recurrence until 15
months later, when he was found to have hepatic and pulmonary metastases.
Discussion
PE remains a clinically challenging diagnosis, more often
missed than found, with no decline in its incidental discovery at autopsy over the past 30 years.1 The 3-month
mortality after PE is as high as 17%,2 and outcomes are
closely linked to the degree of pulmonary vascular obstruction and resulting RV strain.3 As the extent of obstruction
approaches 75%, the right ventricle must generate a systolic
pressure in excess of 50 mmHg to preserve perfusion, a
task that a normal right ventricle cannot accomplish
acutely.4 When pulmonary artery obstruction overwhelms
10.1191/1358863x02vm441cr
182 JM Cooper and JA Beckman
Figure 1 Computed tomography scan of the chest demonstrating a ‘saddle’ pulmonary embolus extending into the right and left
main pulmonary arteries.
Figure 2 Computed tomography scan of the abdomen demonstrating a left renal mass and thrombus in the left renal vein
(arrows). (IVC, inferior vena cava.)
the ability of the right ventricle to maintain cardiac output
and adequate left ventricular Ž lling, hemodynamic collapse
rapidly occurs; 85% of deaths from massive PE occur
within the Ž rst 6 hours.4
The goal of therapy in massive PE is an improvement in
forward  ow and a reduction in RV afterload to avoid right
Vascular Medicine 2002; 7: 181–185
ventricular failure. By reducing the degree of occlusion in
the pulmonary vasculature and minimizing the humoral
vasoconstrictors that emanate from intravascular thrombus,
pulmonary vascular resistance and pulmonary artery pressure fall. Increasing the patent pulmonary artery cross-sectional area is the goal of every treatment strategy in massive
Massive pulmonary embolism 183
Figure 3 Intraoperative echocardiogram. The ultrasound transducer is placed directly on the pulmonary artery at its main
bifurcation. The thrombus almost completely occludes both the right and left main pulmonary arteries.
PE. The three main modalities of reducing obstruction
include thrombolysis, clot fragmentation, and clot removal.
Treatment selection depends on several factors, including
risk of bleeding, stability of the patient, resource availability, and the speciŽ c characteristics of the thrombus burden.
Thrombolysis
Thrombolytic agents activate plasminogen to form plasmin
on the surface of Ž brin clots, resulting in Ž brinolysis. This
Ž brin degradation occurs at the blood-thrombus interface
and causes dissolution of the clot on its exposed surfaces.
As the thrombus shrinks and fragments, it embolizes distally in the pulmonary arterial tree, while Ž brinolysis continues. Thrombolytic therapy has been demonstrated to
reduce clot burden in patients with PE more rapidly than
heparin alone.5 There is no evidence that infusion of a
thrombolytic agent into the pulmonary artery has any
advantage over intravenous administration.6 The Food and
Drug Administration has approved the use of urokinase
(4400 IU/kg intravenously over 10 minutes, then 4400
IU/kg per hour for 12 hours), streptokinase (250 000 IU
intravenously over 30 minutes, then 100 000 IU/hour for
24 hours), and tissue plasminogen activator (100 mg intravenously over 2 hours) for the treatment of PE. Systemic
anticoagulation should be instituted after thrombolytic
administration when the partial thromboplastin time is
twice normal. The American Heart Association has issued
a scientiŽ c statement that recommends the consideration of
thrombolysis for major PE in the setting of syncope, hypotension, severe hypoxemia, or heart failure.7
The data that demonstrate a mortality reduction from PE
thrombolysis are quite sparse.8 There is only one randomized trial that studied patients with massive PE and
hemodynamic collapse.9 It showed a strong life-saving
effect of thrombolysis in this population, and was stopped
after only eight patients were enrolled. In hemodynamically
Vascular Medicine 2002; 7: 181–185
stable patients with major PE and RV dysfunction, thrombolysis has been retrospectively demonstrated to reduce 30day mortality.1 0 The beneŽ t in this population is thought to
be due to rapid improvement in lung perfusion demonstrated via improved RV function after thrombolysis,
shown echocardiographically.1 1 This improvement in mortality, however, has not been universally reported,1 2 so
thrombolysis for PE in hemodynamically stable patients
with RV dysfunction remains controversial.
Major hemorrhage remains the main risk of thrombolytic
agents. The risk of intracranial hemorrhage has varied from
1.5% to 3% in various trials and registries.8 Major bleeding
was seen in 22% of patients after thrombolysis in a large
international PE registry.1 3 Because of the lack of randomized control trial data, the decision to use a thrombolytic agent for massive PE needs to be made on an individual case basis, with attention paid to risk factors for
hemorrhage.
Catheter fragmentation
There are many different catheter designs that have been
invented to attempt percutaneous fragmentation of a massive central pulmonary artery clot burden.1 4 The rationale of
fragmentation involves clot embolization further into the
pulmonary tree, where the total cross-sectional area of the
vasculature is larger.1 4 It has also been pointed out, however, that the total obstructive cross-sectional area of the
fragmented clot would potentially become much greater,
which could more than offset the purported beneŽ t of distal
embolization.1 5 In fact, reports of pure clot fragmentation
typically record either an unchanged or an increased pulmonary artery pressure immediately following the procedure.1 6 ,1 7
Most studies of mechanical disruption, however, have
used adjunctive thrombolytic therapy. This combination
treatment seems to be effective in restoring clinical and
hemodynamic parameters in acutely ill patients with mas-
184 JM Cooper and JA Beckman
sive PE.1 8 ,1 9 Theoretically, thrombolysis should proceed at
a faster rate with the larger exposed surface area of fragmented thrombus. Technical problems with various fragmentation devices have included vascular wall damage, difŽ culty with device positioning, and the inability to
adequately disrupt large or old thrombi. There are no randomized trials to clarify whether mechanical fragmentation
is a useful component of acute therapy, whether or not
thrombolytics are used.
Catheter thrombectomy
Thrombectomy is the ultimate goal of therapy for massive
PE. The Ž rst device to percutaneously extract intact thrombi
used a metal suction cup, introduced either from the leg or
the neck.2 0 Although a number of patients had successful
clot extractions with this device and immediate hemodynamic improvement,2 1 this procedure has limitations. It
requires a venous cutdown, can be complicated by reembolization of the clot being extracted or inability to
access certain branches of the pulmonary artery, and there
may be difŽ culty in removing old thrombus.
Devices have also been designed that use Venturi jets to
pulverize and aspirate thrombus material from the pulmonary arteries.2 2 ,2 3 While these catheters have been successfully used to remove a small percentage of thrombus
material from fresh pulmonary artery emboli, the small
catheter size (5 French) limits their ability to treat large
central thrombi adequately. In addition, there can be a signiŽ cant amount of blood aspiration with a prolonged procedure, and clots that have already formed stable Ž brin
crosslinks are not amenable to disruption by this method.
Surgical embolectomy
While surgical removal of a massive central pulmonary
arterial embolus is the most deŽ nitive treatment, it is also
the most invasive. The decision to proceed to the operating
room is dependent on the prompt availability of surgical
resources, and it requires the surgeon to accept the signiŽ cant possibility of a poor outcome. It is because of these
issues that randomized trials have not been done and that
the reported case series are necessarily affected by selection bias.
Surgical embolectomy is typically reserved for the hemodynamically unstable patient, sometimes after failed thrombolysis. In one non-randomized case series of patients with
massive PE complicated by shock, surgical therapy yielded
a slightly lower mortality when compared with thrombolysis.2 4 The main predictor of mortality in patients
undergoing surgical pulmonary embolectomy is pre-operative cardiac arrest requiring resuscitation. Patients with hemodynamic collapse prior to surgery have an operative mortality ranging from 43% to 84%.2 5 More recently, Aklog
and colleagues reported the results of 29 consecutive
patients with massive proximal PE, RV dysfunction, but
preserved hemodynamics.2 6 In this setting, 89% of the
patients were alive more than 1 month after surgery. Use
of cardiopulmonary bypass may also improve survival.2 7
Conclusion
Massive PE requires urgent therapy to restore pulmonary
arterial  ow. In the absence of treatment, mortality from
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PE remains high.2 8 Anticoagulation is the standard of care
for PE, with the addition of thrombolysis or surgical embolectomy when the clot burden and clinical presentation warrant more aggressive treatment. Catheter-based treatments
have not shown any additional therapeutic beneŽ t. The optimal strategy for treating tumor-containing massive PE is
unknown. In this case, we felt surgical removal of the
saddle PE was most appropriate. The patient was hemodynamically stable, reducing the likelihood of intraoperative
mortality. The PE was likely to be partially composed of
carcinoma, making the prediction of the efŽ cacy of thrombolysis or the consequence of promoting distal embolization of tumor-containing material impossible. Lastly,
there was the theoretical possibility of precipitating sudden
death by converting a subtotal occlusion to a complete
occlusion if the central clot were to be manipulated medically or mechanically without deŽ nitive removal. The
patient is alive 24 months after presentation.
References
1 Stein PD, Henry JW. Prevalence of acute pulmonary embolism among
patients in a general hospital and at autopsy. Chest 1995; 108: 978–81.
2 Goldhaber SZ. Treatment of pulmonary thromboembolism. Intern Med
1999; 38: 620–25.
3 GriŽ oni S, Olivotto I, Cecchini P et al. Short-term clinical outcome
of patients with acute pulmonary embolism, normal blood pressure,
and echocardiographic right ventricular dysfunction. Circulation 2000;
101: 2817–22.
4 Tapson VF, Witty LA. Massive pulmonary embolism: diagnostic and
therapeutic strategies. Clin Chest Med 1995; 16: 329–40.
5 The Urokinase Pulmonary Embolism Trial. A national cooperative
study. Circulation 1973; 47 (2 suppl): II, 1–108.
6 Verstraete M, Miller GAH, Bounameaux H et al. Intravenous and
intrapulmonary recombinant tissue-type plasminogen activator in the
treatment of acute massive pulmonary embolism. Circulation 1988;
77: 353–60.
7 Hirsh J, Hoak J. Management of deep vein thrombosis and pulmonary
embolism: a statement for healthcare professionals from the council
on thrombosis (in consultation with the council on cardiovascular
radiology), American Heart Association. Circulation 1996; 93:
2212–45.
8 Goldhaber SZ. Thrombolysis in pulmonary embolism: a debatable
indication. Thromb Haemost 2001; 86: 444–51.
9 Jerjes-Sanchez C, Ramirez-Rivera A, de Lourdes Garcia M et al.
Streptokinase and heparin versus heparin alone in massive pulmonary
embolism: a randomized controlled trial. J Thromb Thrombolysis
1995; 2: 227–29.
10 Konstantinides S, Geibel A, Olschewski M et al. Association between
thrombolytic treatment and the prognosis of hemodynamically stable
patients with major pulmonary embolism: results of a multicenter
registry. Circulation 1997; 96: 882–88.
11 Nass N, McConnell MV, Goldhaber SZ, Chyu S, Solomon SD. Recovery of regional right ventricular function after thrombolysis for pulmonary embolism. Am J Cardiol 1999; 83: 804–806.
12 Hamel E, Pacouret G, Veincentelli D et al. Thrombolysis or heparin
therapy in massive pulmonary embolism with right ventricular
dilation: results from a 128-patient monocenter registry. Chest 2001;
120: 120–25.
13 Goldhaber SZ, Visani L, De Rosa M, for ICOPER. Acute pulmonary
embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999; 353: 1386–89.
14 U acker R. Interventional therapy for pulmonary embolism. J Vasc
Interv Radiol 2001; 12: 147–64.
15 Girard P, Simonneau G. Catheter fragmentation of pulmonary emboli.
Chest 1999; 115: 1759.
Massive pulmonary embolism 185
16 U acker R, Strange C, Vujic I. Massive pulmonary embolism: preliminary results of treatment with the amplatz thrombectomy device. J
Vasc Interv Radiol 1996; 7: 519–28.
17 Schmitz-Rode T, Janssens U, Schild HH, Basche S, Hanrath P,
Gunther RW. Fragmentation of massive pulmonary embolism using a
pigtail rotation catheter. Chest 1998; 114: 1427–36.
18 Fava M, Loyola S, Flores P, Huete I. Mechanical fragmentation and
pharmacologic thrombolysis in massive pulmonary embolism. J Vasc
Interv Radiol 1997; 8: 261–66.
19 Essop MR, Middlemost S, Skoularigis J, Sareli P. Simultaneous mechanical clot fragmentation and pharmacologic thrombolysis in acute
massive pulmonary embolism. Am J Cardiol 1992; 69: 427–30.
20 GreenŽ eld LJ, Kimmell GO, McCurdy WC. Transvenous removal of
pulmonary emboli by vacuum-cup catheter technique. J Surg Res
1969; 9: 347–52.
21 GreenŽ eld LJ, Proctor MC, Williams DM, WakeŽ eld TW. Long-term
experience with transvenous catheter pulmonary embolectomy. J Vasc
Surg 1993; 18: 450–58.
Vascular Medicine 2002; 7: 181–185
22 Koning R, Cribier A, Gerber L et al. A new treatment for severe pulmonary embolism: percutaneous rheolytic thrombectomy. Circulation
1997; 96: 2498–500.
23 Voigtlander T, Rupprecht H-J, Nowak B et al. Clinical application of
a new rheolytic thrombectomy catheter system for massive pulmonary
embolism. Catheter Cardiovasc Interv 1999; 47: 91–96.
24 Gulba DC, Schmid C, Borst H-G, Lichtlen P, Dietz R, Luft FC. Medical compared with surgical treatment for massive pulmonary embolism. Lancet 1994; 343: 576–77.
25 Riedel M. Acute pulmonary embolism 2: treatment. Heart 2001; 85:
351–60.
26 Aklog L, Williams CS, Byrne JG, Goldhaber SZ. Acute pulmonary
embolectomy: a contemporary approach. Circulation 2002; 105:
1416–19.
27 Del Campo C. Pulmonary embolectomy: a review. Can J Surg 1985;
28: 111–13.
28 Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. Lancet 1960; 1i: 1309–12.