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(Chest. 2001;120:120-125.)
© 2001 American College of Chest Physicians

Thrombolysis or Heparin Therapy in Massive Pulmonary Embolism With Right Ventricular Dilation*

Results From a 128-Patient Monocenter Registry

Emmanuel Hamel, MD; Gérard Pacouret, MD; Dominique Vincentelli, MD; Jean François Forissier, MD; Patrick Peycher, MD; Jean Marie Pottier, MD and Bernard Charbonnier, MD

* From the Intensive Care Unit and Cardiology D Department (Drs. Hamel, Pacouret, Vincentelli, Forissier, Peycher, and Charbonnier), and Nuclear Medicine Department (Dr. Pottier), Trousseau University Hospital, Tours, France.

Correspondence to: Gérard Pacouret, MD, Intensive Care Unit and Cardiology D Department, Trousseau University Hospital, Tours, France; e-mail: drpacouret{at}online.fr


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Study objectives: To assess the potential benefit of thrombolysis in patients with massive pulmonary embolism (PE) with stable hemodynamics and right ventricular dysfunction.

Design: Retrospective, cohort study.

Setting: University-based, tertiary referral medical center.

Patients: One hundred fifty-three consecutive patients with massive PE from January 1992 to December 1997 treated with heparin or thrombolysis.

Measurements and results: Massive PE was confirmed by perfusion lung scan or pulmonary angiography. Right ventricular dysfunction was assessed by echocardiography (right ventricular/left ventricular [RV/LV] diastolic diameter ratio > 0.6) in all patients. In order to study a homogeneous population, 64 patients treated with thrombolysis (group 1) were matched on baseline RV/LV diameter ratio to 64 patients treated with heparin (group 2). Perfusion lung scan was repeated at day 7 to day 10. Mean relative improvement in perfusion lung scans was higher in group 1 than group 2 (54% vs 42%, respectively). PE recurrences were the same in both groups (4.7%; n = 3). There were no bleeding complications and no deaths in group 2. Conversely, in group 1, 15.6% (n = 10) of patients suffered from bleeding (4.7%; n = 3 with intracranial bleeding) and 6.25% (n = 4) of them died.

Conclusions: The results of this monocenter registry do not support the indication for thrombolysis in patients suffering from massive PE with stable hemodynamics and right ventricular dysfunction. Appropriate therapy in such patients still remains unknown. Further prospective randomized trials should be performed.

Key Words: heparin • low-molecular-weight heparin • massive pulmonary embolism • right ventricular dysfunction • thrombolysis


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Despite many previous studies1 2 3 4 of pulmonary embolism (PE) showing clear improvement of early revascularization with thrombolysis, treatment of massive PE still remains unclear in patients in hemodynamically stable condition. Thrombolysis, if not contraindicated, is the recommended treatment in patients with life-threatening massive PE, with shock or hypotension.5 In the late 1970s, Alpert et al6 showed that the prognosis of massive PE without signs of shock seemed to be equivalent to that of nonmassive PE. More recent studies7 8 9 showed that echocardiographic right ventricular dysfunction could be a prognostic factor in patients in stable condition with massive PE, leading authors to recommend thrombolysis in such patients. The aims of this study were to compare in-hospital lung scan defect evolution, PE recurrences, bleeding complications, and death in patients in hemodynamically stable condition suffering from massive PE with echocardiographic right ventricular dysfunction, who were treated either with thrombolysis or heparin.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusion
 References
 
Patients
From January 1992 to December 1997, 153 consecutive patients with massive PE were admitted to the ICU of the cardiology department and were treated either with thrombolysis (n = 80) or heparin (n = 73).

Inclusion Criteria: Inclusion criteria included (1) PE confirmed by a high-probability perfusion lung scan based on revised Prospective Investigation of Pulmonary Embolism Diagnosis criteria,10 coupled with a positive leg ultrasound test result or by pulmonary angiography in all other cases; (2) Miller index of 20/34 on pulmonary angiogram,1 and/or pulmonary vascular obstruction score > 40% on perfusion lung scan; and (3) echocardiographic right ventricular dilation, ie, right ventricular/left ventricular diameter (RV/LV) ratio > 0.6 from left parasternal or subcostal view in supine position, and end-diastole, in the absence of left ventricular or mitral valve disease.

Exclusion Criteria: Exclusion criteria included (1) arterial hypotension (defined as systolic BP < 90 mm Hg) with or without peripheral signs of hypoperfusion, (2) syncope prior to hospitalization, (3) usual contraindications to thrombolysis, and (4) necessity of IV inotropic support.

In order to have two comparable groups, patients treated with thrombolytic therapy were matched to those treated with heparin therapy, on baseline echocardiographic RV/LV ratio (according to the chronologic order of hospital admission). Therefore, 64 patients treated with thrombolysis (group 1) were compared to 64 patients treated with heparin (group 2).

Medication
Thrombolysis in group 1 was IV: 100-mg infusion (10 mg of which was injected as a bolus) or 0.6 mg/kg of alteplase over a 2-h period (n = 33), 15,000 IU/kg/20-min of urokinase (n = 20) or 80-mg/1 h infusion of saruplase, 10 mg of which was injected as a bolus (n = 11). IV unfractionated heparin (UFH) was administered at the end of thrombolytic drug perfusion, and was adjusted to keep the activated partial thromboplastin time at two to three times the normal value. In group 2, heparin treatment was as follows: UFH (n = 6), low-molecular-weight-heparin (LMWH, n = 56), and both UFH and LMWH in two cases (n = 2). LMWHs were administered subcutaneously twice daily in the following fixed doses: 100 antifactor Xa/kg units injection of dalteparin (n = 43); 92 antifactor Xa/kg units injection of nadroparin (n = 13); and once-daily 175 antifactor Xa units injection of tinzaparin (n = 2). All patients were treated with oral anticoagulant, warfarin, from day 3 to day 4 on average, adjusted to an international normalized ratio of 2 to 3.

Study Design
For each patient, baseline evaluation included a clinical examination, ECG, transthoracic echocardiography, perfusion lung scan, and conventional pulmonary angiography if needed. Clinical examination and perfusion lung scans were repeated at day 7 to day 10, and earlier in case of clinically suspected recurrence. Efficacy was evaluated on clinical criteria and on perfusion lung scan evolution. Safety was evaluated by bleeding complications. Severe bleedings were defined as intracranial hemorrhage (confirmed by CT), a decrease in hemoglobin level (at least 4 g/100 mL) and bleeding that required surgery or blood transfusion of >= 2 U.

Echocardiographic Doppler data were obtained on patients in the supine position by one of three physicians. The diameters of the right and left ventricles were taken in relation to a line perpendicular to left ventricular long axis, at the end of the diastole (beginning of the QRS complex), in parasternal and subcostal views. Right ventricular dysfunction was appreciated with RV/LV ratio; 0.6 was considered as a significant right ventricular overload. Pulmonary artery systolic pressure was calculated as the sum of estimates of the maximum pressure difference between the right ventricle and right atrium (on tricuspid regurgitation Doppler echocardiographic signal) and the estimate of mean right atrial pressure.

Statistical Analysis
The characteristics of the patients in the two groups were compared using the Pearson test for the qualitative variables and Student’s t test for the quantitative variables. Quantitative values are expressed as mean ± SD. The data were analyzed with SPSS software (release 5.0; SPSS; Chicago, IL).11


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusion
 References
 
The baseline characteristics of the two groups of patients were similar, as shown in Table 1 . The mean age of the patients was 72 ± 12 years. Approximately 15% of them had a previous PE history. Pulmonary arterial systolic pressure was 56 ± 12 mm Hg, and mean RV/LV ratios were 0.80 and 0.81, respectively. Lung scan defect was higher in group 1 (thrombolysis; 46 ± 10%) than in group 2 (heparin; 43 ± 11%) but without significant difference.


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  		Table 1.. Baseline Characteristics of the 128 Selected Patients*

 
Mean relative improvement in perfusion lung scan defect was significantly higher in group 1 (54%) vs group 2 (42%; p = 0.01). At day 7, perfusion lung scan defect was 21 ± 12% in group 1 vs 23 ± 12% in group 2 (Fig 1 ). A relative improvement of perfusion lung scan defect > 50% was seen in 57% of patients in group 1 vs 37% in group 2 (Fig 2 ).



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  		Figure 1.. Perfusion lung scan follow-up (absolute values).

 


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  		Figure 2.. Relative perfusion lung scan defect improvement from day 1 to days 7 to 10 in group 1 (thrombolysis) and group 2 (heparin).

 
In-hospital results are shown in Table 2 . The PE recurrence rate was the same in the two groups (4.7%). All patients survived in group 2, but four patients died in group 1 (6.5%): one patient died on day 3 from shock that occurred after thrombolysis, one patient died from PE recurrence with shock on day 3, and two patients died from cerebral bleeding on day 1 and day 5, respectively. Bleedings were significantly lower in group 2 (heparin; no bleeding) vs 15.6% (n = 10) in group 1 (p = 0.001). The bleeding events in group 1 were as follows: three puncture site bleedings, one epistaxis, three intracranial bleedings (two of which were fatal), two GI bleedings, and one occult bleeding leading to RBC transfusion. The difference in severe bleeding rates, as previously defined, was also statistically significant between the two groups: 0% in group 2 and 9.4% in group 1 (p = 0.028). The results of each thrombolytic drug are detailed in Table 3 .


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  		Table 2.. In-hospital Results*

 

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  		Table 3.. Results of Each Thrombolytic Drug Treatment*

 
The first patient suffering from intracranial bleeding was a 91-year-old woman without any history of hypertension, who was treated with urokinase infusion. Four hours later, she had high systolic BP; intracranial hemorrhage was noticed on CT scan 8 h after the beginning of the infusion, and the patient died 2 h later. The second patient was an 85-year-old woman without any history of hypertension, who was treated with alteplase infusion (0.6 mg/kg/2 h). Systolic hypertension was noticed at day 1, immediately followed by an occipital hemorrhage. She was discharged with visual sequelae. The third patient was a 58-year-old man with prior moderate hypertension, who was treated with alteplase infusion (100 mg/2 h). BP was 160/100 mm Hg on hospital admission. An occipital hemorrhage occurred 13 h after the beginning of infusion, and the patient died on day 5.

The baseline characteristics and hospitalization data of the 25 excluded patients are listed in Table 4 . The mean age of the excluded patients was comparable to the mean age of the study group, but the RV/LV ratio was higher, especially in the 15 patients treated with thrombolysis; overall mortality rate was 12% as compared to 3% in the study group.


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  		Table 4.. Baseline Characteristics and Hospitalization Data of the 25 Excluded Patients*

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusion
 References
 
Doppler echocardiography is particularly useful for detection of right ventricular dysfunction in severe or massive PE.12 13 RV/LV end-diastolic diameter ratio, though not commonly used in North America, has been validated in various studies as a very sensitive criterion for the diagnosis of PE severity. Come14 showed a good correlation between the RV/LV end-diastolic diameter ratio measured in parasternal view and the percentage of vascular obstruction. Fournier et al15 showed, in a series of 50 patients with a group of massive PE and a group of nonmassive PE (according to pulmonary angiography results), that an RV/LV ratio > 0.6 was observed in 97% of patients with massive PE vs 39% of patients with nonmassive PE. Chapoutot et al16 showed that the RV/LV diameter ratio was also a good criterion of treatment efficacy in a series of patients with severe massive PE (pulmonary vascular obstruction of 67 ± 10%) treated with thrombolysis, with a decrease from 0.87 ± 0.3 prior to treatment to 0.60 ± 0.16 a few hours later (p < 0.001). Patients with right ventricular overload have an increase of relative risk of death from 5 to 7% to about 8 to 14%.8 17 According to some authors,18 thrombolysis should be used in such patients despite clinical stability and increased bleeding risk. Thus, Konstantinides et al9 found that overall 30-day mortality was significantly lower in the group of patients treated with thrombolysis than in the group of those treated with IV UFH alone (4.7% vs 11.1%, respectively), but these results were observed in a registry of heterogeneous patients. Many of them had signs of clinical severity: > 40% of patients had arterial hypotension and 25% had syncope. Besides, there were more patients with prior chronic pulmonary disease in the heparin-treated group.

Conversely, in our study, whose clinical efficacy results are not in favor of thrombolysis, the two groups of patients were comparable according to prior history of cardiac or pulmonary disease, right ventricular dysfunction, and perfusion lung scan defect, and all patients were free of clinical signs of severity. Treatment was heterogeneous in group 1, but all thrombolytic regimens were European-approved regimens except for saruplase. Saruplase efficacy and safety have been validated in myocardial infarction,19 20 and the same dosage (80 mg over 1 h) has been tested successfully in a series of 20 patients suffering from acute massive PE.21 Most of the patients of group 2 were treated with LMWHs, the efficacy and safety of which have been validated in the treatment of symptomatic proximal deep venous thrombosis,22 23 a situation in which silent PE, sometimes massive, is frequently associated. In two recent trials, LMWHs were compared to IV UFH to treat symptomatic PE: in the study by Simonneau et al,24 tinzaparin (175 antifactor Xa U/kg subcutaneously qd), and reviparin (twice-daily weight adapted) in the Columbus Investigators study.25 In the study by Simonneau et al,24 28% of patients had severe PE, and 41% of them had lung scan defect > 50%. Efficacy and safety of tinzaparin vs heparin were comparable, with a low severe bleeding rate (0.9% and 1.6%, respectively). In the Columbus Investigators study,25 about one third of patients (271 patients) had symptomatic PE and there was no difference between the two treatment groups over the 3 months of follow-up with respect to the major clinical outcomes. Also, in opposition to the results of Konstantinides et al,9 Ribeiro et al,26 in patients in stable condition suffering from severe PE and treated either with thrombolysis or heparin, found the same in-hospital mortality rate of 8.6% in the two groups.

The only advantage of thrombolysis over heparin found in our study was a higher 1-week perfusion lung scan improvement, as previously observed in the Urokinase Pulmonary Embolism Trial.2 The in-hospital PE recurrence rate was equivalent in our two treatment groups, as also observed in the Urokinase Pulmonary Embolism Trial.2

Severe bleeding rate was higher in the thrombolysis group, and the difference reached statistical significance despite more stringent criteria of definition than in previously published studies. It has to be noted that two deaths out of four in our study resulted from cerebral bleeding in the group of patients treated with thrombolysis. Unfortunately, cerebral bleedings are not exceptional (1.9%) with thrombolysis, as it was reported in a 1997 overview.18 Our safety data are consistent with the results of this overview. Nevertheless, we have to point out that all cerebral bleedings occurred in high-risk patients (ie, elderly, hypertensive). In 1993, Meneveau et al,27 following the results of a study comparing thrombolysis between elderly and nonelderly patients suffering from massive PE, concluded that this therapy was as effective and safe in elderly patients as in younger ones. Nevertheless, their population size was probably too limited (36 patients > 70 years old) to assess the bleeding risk with accuracy. Also in 1993, Simoons et al28 compared the data of 150 patients with documented intracranial hemorrhage following thrombolysis for myocardial infarction to 294 matched control subjects. They concluded that age > 65 years, systemic hypertension on hospital admission, body weight < 70 kg, and administration of alteplase were independent predictors of cerebral bleeding. A recently published study29 of thrombolysis in 7,864 patients with myocardial infarction suggests that this therapy is not efficient in patients > 75 years old and may be harmful with a stroke rate of 2.7%, as compared to 1.4% in younger patients. Therefore, thrombolysis should be considered as contraindicated in high-bleeding-risk patients without life-threatening massive PE unless a clear clinical benefit is demonstrated in a prospective randomized trial.

Several limitations have to be considered regarding our study. It is a retrospective study, and the number of included patients is relatively small. But our population is homogeneous with patients matched together on baseline echocardiographic findings. Echocardiography is an obvious and important noninvasive procedure to assess right ventricular dysfunction, but its accurate quantification remains uncertain; it may be that its threshold of severity needs better definition. Finally, to compare the results of these two treatments with hard end points (death, severe bleedings, etc) would require a prospective randomized trial with > 1,000 patients; such a trial would be mandatory to answer the question and would be difficult to perform.


   Conclusion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
References
 
Despite several limitations regarding its retrospective design and the small number of included patients, the results of this case-controlled study do not favor thrombolysis in patients suffering from massive PE with stable hemodynamics and right ventricular dysfunction. To demonstrate which treatment, thrombolysis or heparin, has the best efficacy/safety profile will require a large-scale, prospective randomized trial.


   Acknowledgements
 
We thank Samuel Goldhaber for his help and his technical assistance in preparing this article.


   Footnotes
 
Abbreviations: LMWH = low-molecular-weight heparin; PE = pulmonary embolism; RV/LV = right ventricular/left ventricular; UFH = unfractionated heparin

Received for publication March 8, 2000. Accepted for publication February 12, 2001.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 

  1. Miller, GH, Sutton, GC, Kerr, IH, et al (1971) Comparison of streptokinase and heparin in treatment of isolated acute massive pulmonary embolism. BMJ 2,681-684
  2. The Urokinase Pulmonary Embolism Trial: a national cooperative study. Circulation 1973; 47(suppl II):II1–II108
  3. Levine, M, Hirsh, J, Weitz, J, et al (1990) A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism. Chest 98,1473-1479[Abstract/Free Full Text]
  4. Dalla-Volta, S, Palla, A, Santolicandro, AM, et al (1992) Alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolism: Plasminogen Activator Italian Multicenter Study 2. J Am Coll Cardiol 20,520-526[Abstract]
  5. Hyers, TM, Agnelli, G, Hull, RD, et al (1998) Antithrombotic therapy for venous thromboembolic disease: Fifth ACCP Consensus Conference of Antithrombotic Therapy. Chest 114,561S-578S[ISI][Medline]
  6. Alpert, JS, Smith, R, Carlson, J, et al (1976) Mortality in patients treated for pulmonary embolism. JAMA 236,1477-1480[Abstract]
  7. Goldhaber, SZ, Haire, WD, Feldstein, ML, et al (1993) Alteplase versus heparin in acute pulmonary embolism: randomized trial assessing right-ventricular function and pulmonary perfusion. Lancet 341,507-511[CrossRef][ISI][Medline]
  8. Kasper, W, Konstantanides, S, Geibel, A, et al (1997) Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol 30,1165-1171[Abstract]
  9. Konstantinides, S, Geibel, A, Olschewski, M, et al (1997) Association between thrombolytic treatment and the prognosis of hemodynamically stable patients with major pulmonary embolism: results of a multicenter registry. Circulation 96,882-888[Abstract/Free Full Text]
  10. Stein, PD, Terrin, ML, Gottschalk, A, et al (1992) Value of ventilation/perfusion scans versus perfusion scans alone in acute pulmonary embolism. Am J Cardiol 69,1239-1241[CrossRef][ISI][Medline]
  11. Norussis MJ. SPSS for Windows base system user’s guide, release 5.O. Chicago, IL: SPSS, 1992
  12. Kasper, W, Meinertz, T, Henkel, B, et al (1986) Echocardiographic findings in patients with proved pulmonary embolism. Am Heart J 112,1284-1290[CrossRef][ISI][Medline]
  13. Jardin, F, Dubourg, O, Bourdarias, J-P (1997) Echocardiographic pattern of acute cor pulmonale. Chest 111,209-217[Free Full Text]
  14. Come, PC (1992) Echocardiographic evaluation of pulmonary embolism and its response to therapeutic interventions. Chest 101,151S-162S[Abstract/Free Full Text]
  15. Fournier, P, Gerard, F, Pottier, JM, et al (1993) The role of ultrasonography in the diagnosis of moderate to severe pulmonary embolism. Ann Cardiol Angeiol 42,447-451
  16. Chapoutot, L, Metz, D, Chabert, JP, et al (1991) Doppler echocardiographic evaluation of the efficacy of fibrinolytic treatment of pulmonary embolism. Arch Mal Coeur Vaiss 84,179-183[ISI][Medline]
  17. Ribeiro, A, Lindmarker, P, Juhlin-Dannfelt, A, et al (1997) Echocardiography Doppler in pulmonary embolism: right ventricular dysfunction as a predictor of mortality rate. Am Heart J 134,479-487[CrossRef][ISI][Medline]
  18. Kanter, DS, Mikkola, KM, Patel, SR, et al (1997) Thrombolytic therapy for pulmonary embolism: frequency of intracranial hemorrhage and associated risk factors. Chest 111,1241-1245[Abstract/Free Full Text]
  19. Tebbe, U, Michels, R, Adgey, J, et al (1998) Randomized, double-blind study comparing saruplase with streptokinase therapy in acute myocardial infarction: the COMPASS Equivalence Trial; Comparison Trial of Saruplase and Streptokinase (COMASS) Investigators. J Am Coll Cardiol 31,487-493[Abstract/Free Full Text]
  20. Vermeer, F, Bosl, I, Meyer, J, et al (1999) Saruplase is a safe and effective thrombolytic agent; observations in 1,698 patients: results of the PASS study. J Thromb Thrombol 8,143-150[CrossRef][ISI][Medline]
  21. Pacouret, G, Barnes, SJ, Hopkins, G, et al (1998) Rapid hemodynamic improvement following saruplase in recent massive pulmonary embolism. Thromb Haemost 79,264-267[ISI][Medline]
  22. Leizorovicz, A, Simmoneau, G, Decousus, H, et al (1994) Comparison of efficacy and safety of low molecular weight heparins and unfractionated heparin in initial treatment of deep venous thrombosis: a meta-analysis. BMJ 309,299-304[Abstract/Free Full Text]
  23. Hirsh, J, Siragusa, S, Cosmi, B, et al (1995) Low molecular weight heparins (LMWH) in the treatment of patients with acute venous thromboembolism. Thromb Haemost 74,360-363[ISI][Medline]
  24. Simonneau, G, Sors, H, Charbonnier, B, et al (1997) A comparison of low molecular weight heparin with unfractionated heparin for acute pulmonary embolism. N Engl J Med 337,663-669[Abstract/Free Full Text]
  25. . The Columbus Investigators. (1997) Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 337,657-662[Abstract/Free Full Text]
  26. Ribeiro, A, Lindmarker, P, Johnsson, H, et al (1999) Pulmonary embolism: one-year follow-up with echocardiography Dopp- ler and five-year survival analysis. Circulation 99,1325-1330[Abstract/Free Full Text]
  27. Meneveau, N, Bassand, JP, Schiele, F, et al (1993) Safety of thrombolytic therapy in elderly patients with massive pulmonary embolism: a comparison with nonelderly patients. J Am Coll Cardiol 22,1075-1079[Abstract]
  28. Simoons, ML, Maggioni, AP, Knatterud, G, et al (1993) Individual risk assessment for intracranial hemorrhage during thrombolytic therapy. Lancet 342,1523-1528[CrossRef][ISI][Medline]
  29. Thiemann, DR, Coresh, J, Schulman, SP, et al (2000) Lack of benefit for intravenous thrombolysis in patients with myocardial infarction who are older than 75 years. Circulation 101,2239-2246[Abstract/Free Full Text]



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 Am. J. Respir. Crit. Care Med.Home page
A. Vieillard-Baron, S. Prin, K. Chergui, O. Dubourg, and F. Jardin
Echo-Doppler Demonstration of Acute Cor Pulmonale at the Bedside in the Medical Intensive Care Unit
Am. J. Respir. Crit. Care Med., November 15, 2002; 166(10): 1310 - 1319.
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 J Am Coll CardiolHome page
G. Thabut, D. Thabut, R. P. Myers, B. Bernard-Chabert, R. Marrash-Chahla, H. Mal, and M. Fournier
Thrombolytic therapy of pulmonary embolism: A meta-analysis
J. Am. Coll. Cardiol., November 6, 2002; 40(9): 1660 - 1667.
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 NEJMHome page
S. Konstantinides, A. Geibel, G. Heusel, F. Heinrich, W. Kasper, and the Management Strategies and Prognosis of Pulmona
Heparin plus Alteplase Compared with Heparin Alone in Patients with Submassive Pulmonary Embolism
N. Engl. J. Med., October 10, 2002; 347(15): 1143 - 1150.
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 Vasc MedHome page
J. M Cooper and J. A Beckman
Massive pulmonary embolism: a remarkable case and review of treatment
Vascular Medicine, August 1, 2002; 7(3): 181 - 185.
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 CirculationHome page
L. Aklog, C. S. Williams, J. G. Byrne, and S. Z. Goldhaber
Acute Pulmonary Embolectomy: A Contemporary Approach
Circulation, March 26, 2002; 105(12): 1416 - 1419.
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 ChestHome page
K. E. Wood
Major Pulmonary Embolism : Review of a Pathophysiologic Approach to the Golden Hour of Hemodynamically Significant Pulmonary Embolism
Chest, March 1, 2002; 121(3): 877 - 905.
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 CirculationHome page
S. Z. Goldhaber
Thrombolysis in Pulmonary Embolism: A Large-Scale Clinical Trial Is Overdue
Circulation, December 11, 2001; 104(24): 2876 - 2878.
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 JWatch GeneralHome page
Thrombolysis vs. Heparin for Stable Patients with Massive PE
Journal Watch (General), August 10, 2001; 2001(810): 1 - 1.
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We can not generalize the conclutions
Javier Diaz-Castaņon
Chest Online, 16 Jul 2001 [Full text]
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