Treatment of Massive Acute Pulmonary Embolism: The Use of Low Doses of Intrapulmonary Arterial Streptokinase Combined with Full Doses of Systemic Heparin

doi:10.1378/chest.93.2.234

Chest

Volume 93, Issue 2, February 1988, Pages 234-240

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The efficacy of low-dose, locally administered streptokinase (SK) combined with full therapeutic systemic doses of heparin was investigated. Seven patients with angiographically proven massive acute pulmonary embolism were treated. Streptokinase, 10,000-20,000 units/hour, was administered directly into the left or right pulmonary artery for 9 to 24 hours. Heparin was administered concurrently. The number of unperfused segments of the infused lung shown on the lung scan decreased from 5 ± 2 to 2 ± 1 after 12-24 hours (p<.01). No change was shown in the contralateral lung. The angiographic index of severity score in the infused lung decreased from 16 ± 1 to 9 ± 4 (p<.01). The partial pressure of oxygen in arterial blood improved within four hours. In spite of the low doses of streptokinase, however, two major bleeding episodes occurred that required blood transfusion. In conclusion, low dose intrapulmonary streptokinase, combined with intravenous heparin, may provide a therapeutic option in patients with life-threatening massive acute pulmonary embolism in whom full dose lytic therapy may be hazardous, although even low dose lytic therapy was associated with risk.

Section snippets

MATERIALS AND METHODS

Seven consecutive patients with angiogrpahically proven massive acute pulmonary embolism were evaluated. Massive pulmonary embolism was defined as obstruction of two or more lobar arteries.¹ Hemodynamically stable, as well as unstable patients, were included in this study, provided that surgical interventions, such as inferior vena cava interruption or pulmonary embolectomy, were not contemplated.

Patients with previously defined contraindications to thrombolytic therapy were excluded.⁴ However,

RESULTS

The control perfusion scans in all patients demonstrated significant defects classified as high probability for pulmonary embolism. All of the patients showed improvement as evidenced by a reduction in the number of unperfused segments on the side of the infusion. The number of segmental defects on the perfusion scan of the lung in which streptokinase was infused decreased from five ± two segments to two ± one segments (mean ± SD) (p<.01) within 12 to 24 hours following treatment (Figure 1,

DISCUSSION

The rationale for low-dose streptokinase at 1/10 to 1/20 of the conventional systemic dose is to deliver the drug locally in close proximity to the clot. Hopefully, a locally high concentration would significantly lyse clots without the development of an excessive systemic fibrinolytic state. Heparin administration in conjunction with streptokinase presumably inhibits further fibrin deposition,⁶ and protects against further propagation of the clot and recurrent embolization.

The rate of

CONCLUSION

The local infusion of low-dose streptokinase in conjunction with heparin therapy resulted in clot lysis in the treated lung within 12 to 24 hours in five of seven patients with massive acute pulmonary embolism. The local infusion of streptokinase in low doses in combination with systemic heparin seems efficacious in the lysis of massive pulmonary emboli on the infused side. This was a preliminary study with only seven patients. Our experience suggests that this approach may be of potential

ACKNOWLEDGMENT

The authors thank Ms. Ida Borum for secretarial assistance.

REFERENCES (9)

IR Edwards et al.
Low-dose urokinase in major pulmonary embolism
Lancet
(1973)
AS Gallus et al.
Thrombolysis with a combination of small doses of streptokinase and full doses of heparin
Seminars in Thrombosis and Hemostasis
(1975)
I Vujic et al.
Massive pulmonary embolism: Treatment with full heparinization and topical low-dose streptokinase
Radiology
(1983)
Urokinase-streptokinase Embolism Trial
Phase 2 results. JAMA
(1974)

There are more references available in the full text version of this article.

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The analysis has been reported in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines [16]. We found 62 studies across all specified categories with 1848 patients and 1872 CDTs [17–78]. We could ascertain the haemodynamic significance of PE in 35 studies.
We sought to estimate the efficacy and safety outcomes of catheter-directed treatment (CDT) for patients with acute pulmonary embolism (PE).
We searched SCOPUS for studies reporting outcomes after CDT for acute PE. Studies were categorized in three groups for analyses due to heterogeneity in the classification of acute PE: 1) patients with PE causing right ventricular dysfunction and haemodynamic instability: unstable haemodynamic status, 2) patients with PE causing right ventricular dysfunction where study outcomes were not stratified by haemodynamic status: stable and unstable haemodynamic status, and 3) patients with PE causing right ventricular dysfunction who remained haemodynamically stable: stable haemodynamic status. Efficacy and safety outcomes were estimated and presented as point estimates with 95% confidence intervals.
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We provide descriptive measures of efficacy and safety for patients who underwent CDT for acute PE.
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Some clinicians elect to simply continue heparin through the thrombolytic infusion. Although thrombolytics have been administered as local intrapulmonary arterial infusions, standard systemic intravenous therapy appears adequate in most cases.30–34 Thrombolytic therapy is contraindicated in patients at high risk for bleeding (Table 3).
Early and Long-Term Clinical Results of AngioJet Rheolytic Thrombectomy in Patients With Acute Pulmonary Embolism
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In addition, a sizable portion of patients is ineligible for fibrinolysis.1 Selective infusion of the fibrinolytic agent in a small series of patients with massive PE yielded promising results,10 but other studies did not find any difference between selective and systemic thrombolyses,11 and surgical thrombectomy is traditionally reserved to very selected cases.1 As in coronary revascularization, percutaneous means of thrombus removal hold the promise of effective locoregional treatment of pulmonary thromboembolism, potentially with a wider therapeutic window, thanks to minimization of bleeding complications.
Anticoagulant and thrombolytic therapies are a mainstay in the management of acute pulmonary embolism (PE), especially when hemodynamic compromise is present. However, systemic drugs cannot achieve timely and effective treatment of acute PE in all patients. In such a setting, mechanical removal of thrombus from the pulmonary circulation holds the promise of significant clinical benefits, although it remains untested. We report early and long-term outcome of patients with massive or submassive acute PE treated with rheolytic thrombectomy by means of the 6Fr Xpeedior AngioJet device at our institution. Three main groups were defined pre hoc: subjects with severe (i.e., shock), moderate, or mild hemodynamic compromise. Technical and procedural successes, obstruction, perfusion and Miller indexes, and clinical events were appraised. In total 25 patients were treated with thrombectomy (8 in severe, 12 in moderate, and 5 in mild hemodynamic compromise). Technical and procedural successes were obtained in all patients, as confirmed by the significant improvement in obstruction, perfusion and Miller indexes overall, and in each subgroup (all p values <0.001). Improvement in obstruction, perfusion, and Miller indexes at the end of the procedure could also be confirmed in patients (n = 8) treated with local fibrinolysis and in the absence of concomitant thrombolysis (n = 17, p <0.05). Four patients died in hospital, all other patients but 1 were safely discharged after an appropriate hospital stay, and all were alive at long-term follow-up (median 61 months). In conclusion, this study supports at early and long-term follow-up the effectiveness and safety of rheolytic thrombectomy for PE.
Pulmonary Embolism
2008, Critical Care Medicine: Principles of Diagnosis and Management in the Adult
Impact of morphologic characteristics of central pulmonary thromboemboli in massive pulmonary embolism
2002, Chest
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In our study, pulmonary artery catheterization was performed to study whether the type of central thromboemboli had an influence on thrombolytic efficiency and to optimize volume, inotropic therapy, and vasopressor therapy. The pulmonary artery catheter can simultaneously be used for local thrombolytic therapy, which is thought to be accompanied by more rapid and/or more complete clot lysis.20 However, a randomized study comparing intrapulmonary or systemic rt-PA in a dose of 50 mg administered over > 2 h showed no difference in improvement in pulmonary artery pressure and pulmonary perfusion.21
To assess the impact of morphologically different central pulmonary artery thromboemboli in patients with massive pulmonary emboli (MPEs) on short-term outcome.
A prospective registry of consecutive patients.
An 11-bed closed medical ICU at a 860-bed community general hospital
Forty-seven patients with shock or hypotension due to MPE and central pulmonary thromboemboli detected by transesophageal echocardiography who were treated with thrombolysis between January 1994 and April 2000.
Patients were divided into two groups according to the following characteristics of the detected thromboemboli: group 1, thrombi with one or more long, mobile parts; and group 2, immobile thrombi. Right heart catheterization was performed.
The incidence of both types of thromboemboli was comparable. Groups 1 and 2 showed no differences in demographic data, risk factors for pulmonary embolism, length of preceding clinical symptoms, percentage of patients in shock, hemodynamic variables, serum lactate levels on hospital admission, and treatment. Seven fatal cases due to obstructive shock and right heart failure were present in group 2, but none were present in group 1 (7 of 23 patients vs 0 of 24 patients, respectively; p < 0.05). At 12 h, the cardiac index was lower in group 2 than in group 1 (2.6 ± 1.0 vs 3.1 ± 0.9 L/min/m², respectively; p < 0.05), and the central venous pressure (15.0 ± 6.2 vs 12.5 ± 3.7 mm Hg, respectively; p < 0.05) and total pulmonary resistance (12.9 ± 5.9 vs 8.6 ± 2.7 mm Hg/L/min/m², respectively; p < 0.001) were higher in group 2 compared to group 1. On hospital admission, inclusion in group 2 (p < 0.03; hazard ratio, 9.53; 95% confidence interval [CI], 1.19 to 76.47) and preexisting chronic medical or neurologic disease (p < 0.01; hazard ratio, 16.4; 95% CI, 1.97 to 136.3) were independent predictors of 30-day mortality.
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2002, Journal of Vascular and Interventional Radiology
To assess the efficacy and safety of mechanical fragmentation combined with intrapulmonary thrombolysis in massive pulmonary thromboembolism (PTE) with hemodynamic impairment.
Fifty-nine patients diagnosed with massive PTE with hemodynamic impact were treated. The initial clinical symptoms were shock in 23 patients (38.9%), syncope in eight (13.5%), and dyspnea at rest in 28 (47.4%). Mean 0₂ saturation was 67.8%. Mean pulmonary artery pressure (PAP) was 42.1 mm Hg. During fragmentation, thrombolysis was administered in the form of a urokinase bolus of 200,000–500,000 U in 57 patients and 20 mg of recombinant tissue plasminogen activator (rt-PA) in two patients. The mean urokinase dose used was 2,500,000 IU, whereas the total dose of rt-PA was 100 mg. Heparin sodium infusion was performed to reach activated partial thromboplastin time ratios of 2. The follow-up consisted of clinical assessment, pulmonary scintigraphy, and echocardiography. The patients received treatment with dicoumarin for 6 months after the procedure.
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Supported in part by grant R01-HL23669-07 and contract N01-HR-34008 from the US Public Health Service, National Institutes of Health, National Heart, Lung and Blood Institute, Bethesda.

Manuscript received May 8; revision accepted July 23.

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Chest

Clinical InvestigationsTreatment of Massive Acute Pulmonary Embolism: The Use of Low Doses of Intrapulmonary Arterial Streptokinase Combined with Full Doses of Systemic Heparin

Section snippets

MATERIALS AND METHODS

RESULTS

DISCUSSION

CONCLUSION

ACKNOWLEDGMENT

Lancet

Thrombolysis with a combination of small doses of streptokinase and full doses of heparin

Seminars in Thrombosis and Hemostasis

Massive pulmonary embolism: Treatment with full heparinization and topical low-dose streptokinase

Radiology

Urokinase-streptokinase Embolism Trial

Phase 2 results. JAMA

Clinical Investigations
Treatment of Massive Acute Pulmonary Embolism: The Use of Low Doses of Intrapulmonary Arterial Streptokinase Combined with Full Doses of Systemic Heparin