Pulmonary Embolism without Cardiogenic Shock - Thrombolytic Therapy

2/22/2005

Question:  What is the effectiveness and safety of thrombolytic therapy, for hemodynamically stable patients with PE, or patients having PE without cardiogenic shock?

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16264048.ui or 16127178.ui or 16246981.ui or 16246980.ui or 15997693.ui or 15721504.ui or 15383479.ui or 15262836.ui or 12583371.ui or 11245113.ui or 11129828.ui or 10728526.ui or 9749233.ui or 9737225.ui or 9367474.ui

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16264048[PMID] OR 16127178[PMID] OR 16246981[PMID] OR 16246980[PMID] OR 15997693[PMID] OR 15721504[PMID] OR 15383479[PMID] OR 15262836[PMID] OR 12583371[PMID] OR 11245113[PMID] OR 11129828[PMID] OR 10728526[PMID] OR 9749233[PMID] OR 9737225[PMID] OR 9367474[PMID]

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<1>

Unique Identifier [PMID]: 16264048

Authors: Capstick T. Henry MT.

Institution: Dept of Respiratory Medicine, Leeds General Infirmary, Great George St., Leeds LS1 3EX, UK.

Title: Efficacy of thrombolytic agents in the treatment of pulmonary embolism. [Review] [39 refs]

Source: European Respiratory Journal. 26(5):864-74, 2005 Nov.

Abstract: Recent guidelines recommend bolus-dose alteplase for treating massive pulmonary embolism (PE). However, the safest and most effective treatment is as yet unknown. In the present study, a meta-analysis of published studies of alteplase infusion, bolus-dose alteplase and streptokinase was performed. The outcome measures were as follows: objective assessment of thrombolysis; all-cause mortality; deaths due to initial PE, major bleeding episodes and recurrent PE; and morbidity. In total, 26 studies were identified; however, only two comparative studies of alteplase infusion versus either bolus-dose alteplase or streptokinase were found. Meta-analysis revealed no significant difference between the three regimens, but was compromised by a paucity of data. Crude analysis of summated data on thrombolytic efficacy from all studies revealed that alteplase infusion was more effective than bolus-dose alteplase (relative risk (RR): 1.95; 95% confidence interval (CI): 1.19-3.2), whereas streptokinase was more effective than alteplase infusion (RR: 1.27; 95% CI: 1.09-1.47). Alteplase infusion had a lower mortality due to the initial PE than both bolus-dose alteplase and streptokinase (RR: 0.16; 95% CI: 0.05-0.59 and RR: 0.13; 95% CI: 0.04-0.46, respectively). In conclusion, this evidence suggests that the three thrombolytic agents may vary in efficacy. However, large-scale randomised controlled trials are needed to confirm these results. [References: 39]

Publication Type: Journal Article. Meta-Analysis. Review.

<2>

Unique Identifier [PMID]: 16127178

Authors: Sakuma M. Nakamura M. Nakanishi N. Miyahara Y. Tanabe N. Yamada N. Kuriyama T. Kunieda T. Sugimoto T. Nakano T. Shirato K.

Institution: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sandai, Japan.

Title: Clinical characteristics, diagnosis and management of patients with pulmonary thromboembolism who are not diagnosed in the acute phase and not classified as chronic thromboembolic pulmonary hypertension.

Source: Circulation Journal. 69(9):1009-15, 2005 Sep.

Abstract: BACKGROUND: There have been many cases of pulmonary thromboembolism (PTE) that were not diagnosed in the acute phase and not classified as chronic thromboembolic pulmonary hypertension (CTEPH). The aim of the present study was clarify the clinical characteristics of chronic PTE. METHODS AND RESULTS: The study subjects were 601 patients (chronic PTE = 92, acute PTE = 456, CTEPH = 53) who were clinically diagnosed before their death. Dyspnea and chest pain, which are frequently found in acute PTE, were found less frequently in chronic PTE. The diagnosis of chronic PTE is often delayed in cases of mild to moderate severity with atypical onset. Chronic heart failure and chronic respiratory failure were most frequent in chronic PTE, and cerebrovascular disease was present in approximately 15% of the cases of chronic PTE. Pulmonary angiography and ventilation lung scan were used least frequently in acute PTE. Heparin and thrombolysis were used most frequently in acute PTE. CONCLUSIONS: Besides the atypical onset and reduced severity, the presence of preexisting diseases may be one of the reasons why the diagnosis for chronic PTE is delayed. The diagnostic and management techniques differ according to the type of PTE.

Publication Type: Journal Article.

<3>

Unique Identifier [PMID]: 16246981

Authors: Thabut G. Logeart D.

Institution: Service de Pneumologie et Reanimation Respiratoire, Hopital Beaujon, Clichy, France. gabriel.thabut@bjn.ap-hop-paris.fr

Title: Thrombolysis for pulmonary embolism in patients with right ventricular dysfunction: con.[comment]. [Review] [39 refs]

Comments Comment on: Arch Intern Med. 2005 Oct 24;165(19):2197-9; discussion 2204-5; PMID: 16246980

Source: Archives of Internal Medicine. 165(19):2200-3; discussion 2204-5, 2005 Oct 24.

Publication Type: Comment. Journal Article. Review.

<4>

Unique Identifier [PMID]: 16246980

Authors: Goldhaber SZ.

Institution: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02115, USA. sgoldhaber@partners.org

Title: Thrombolytic therapy for patients with pulmonary embolism who are hemodynamically stable but have right ventricular dysfunction: pro.[see comment]. [Review] [17 refs]

Comments Comment in: Arch Intern Med. 2005 Oct 24;165(19):2200-3; discussion 2204-5; PMID: 16246981

Source: Archives of Internal Medicine. 165(19):2197-9; discussion 2204-5, 2005 Oct 24.

Publication Type: Journal Article. Review.

<5>

Unique Identifier [PMID]: 15997693

Authors: Kamphuisen PW. Heijdra YF. van Die CE. van Dijk AP. Bredie SJ.

Institution: Universitair Medisch Centrum St Radboud, Nijmegen. kamphuisen.botermans@planet.nl

Title: [Therapeutic dilemmas in patients with a centrally-located pulmonary embolism confirmed by spiral CT-scan but with no cardiogenic shock].[see comment]. [Dutch]

Comments Comment in: Ned Tijdschr Geneeskd. 2005 Jun 18;149(25):1373-5; PMID: 15997688, Comment in: Ned Tijdschr Geneeskd. 2005 Oct 8;149(41):2310; author reply 2310; PMID: 16245399

Source: Nederlands Tijdschrift voor Geneeskunde. 149(25):1400-5, 2005 Jun 18.

Abstract: 3 patients, 2 women aged 64 and 44 and 1 man aged 67, had severe dyspnoea and a large centrally-located pulmonary embolism (PE) without any accompanying arterial hypotension. They were all given conventional anticoagulation therapy, although thrombolytic therapy was also considered. The women recovered but the man eventually died of a second massive embolism. PE is a disease with a potentially high mortality. Patients with cardiogenic shock due to PE are candidates for thrombolytic therapy. A subset of patients with right-ventricular dysfunction (submassive PE) also have a poorer prognosis despite the absence ofarterial hypotension or shock. Spiral CT-scan is becoming the first-line imaging test of preference in patients with suspected PE. Spiral CT enables the accurate visualization ofthrombi. The value of risk management using cardial biomarkers, spiral CT and echocardiography is not yet clear. There is no evidence that thrombolytic therapy is beneficial in patients with acute PE and right-ventricular dysfunction without overt shock.

Publication Type: Case Reports. Journal Article.

<6>

Unique Identifier [PMID]: 15721504

Authors: Nakamura M. Nakanishi N. Yamada N. Sakuma M. Miyahara Y. Okada O. Tanabe N. Kuriyama T. Kunieda T. Shirato K. Sugimoto T. Nakano T.

Institution: The First Department of Internal Medicine, Mie University, Edobashi 2-147, Tsu 514-8507, Japan. mashio@clin.mie-u.ac.jp

Title: Effectiveness and safety of the thrombolytic therapy for acute pulmonary thromboembolism: results of a multicenter registry in the Japanese Society of Pulmonary Embolism Research.

Source: International Journal of Cardiology. 99(1):83-9, 2005 Mar 10.

Abstract: OBJECTIVE: To assess the effectiveness and safety of thrombolytic treatment for acute pulmonary thromboembolism (APTE), especially in the hemodynamically stable patients with right ventricular afterload stress. METHODS AND RESULTS: In a total of 221 patients with APTE, the association between thrombolytic treatment and the clinical outcomes were investigated. Thrombolysis was given to 121 patients (Thrombolytic Group), and the remaining 100 patients were treated with anticoagulation alone (Anticoagulation Group). In both patients with prolonged shock and patients who were hemodynamically stable without right ventricular afterload stress, the rate of death and recurrence of APTE in Anticoagulation Group were similar to those in Thrombolytic Group. In patients with right ventricular afterload stress, better outcomes were observed in Thrombolytic Group than in Anticoagulation Group, although the difference did not reach statistical significance. There was no significant difference in the rate of major bleeding episode between these two groups. CONCLUSION: Our results suggested that performing thrombolytic treatment in APTE patients with right ventricular afterload stress should be considered even in Japan.

Publication Type: Journal Article. Multicenter Study.

<7>

Unique Identifier [PMID]: 15383479

Authors: Buller HR. Agnelli G. Hull RD. Hyers TM. Prins MH. Raskob GE.

Institution: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Title: Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.[see comment][erratum appears in Chest. 2005 Jan;127(1):416]. [Review] [196 refs]

Comments Comment in: Chest. 2005 Sep;128(3):1888-9; PMID: 16162804

Source: Chest. 126(3 Suppl):401S-428S, 2004 Sep.

Abstract: This chapter about antithrombotic therapy for venous thromboembolic disease is part of the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following: for patients with objectively confirmed deep vein thrombosis (DVT), we recommend short-term treatment with subcutaneous (SC) low molecular weight heparin (LMWH) or, alternatively, IV unfractionated heparin (UFH) [both Grade 1A]. For patients with a high clinical suspicion of DVT, we recommend treatment with anticoagulants while awaiting the outcome of diagnostic tests (Grade 1C+). In acute DVT, we recommend initial treatment with LMWH or UFH for at least 5 days (Grade 1C), initiation of vitamin K antagonist (VKA) together with LMWH or UFH on the first treatment day, and discontinuation of heparin when the international normalized ratio (INR) is stable and > 2.0 (Grade 1A). For the duration and intensity of treatment for acute DVT of the leg, the recommendations include the following: for patients with a first episode of DVT secondary to a transient (reversible) risk factor, we recommend long-term treatment with a VKA for 3 months over treatment for shorter periods (Grade 1A). For patients with a first episode of idiopathic DVT, we recommend treatment with a VKA for at least 6 to 12 months (Grade 1A). We recommend that the dose of VKA be adjusted to maintain a target INR of 2.5 (INR range, 2.0 to 3.0) for all treatment durations (Grade 1A). We recommend against high-intensity VKA therapy (INR range, 3.1 to 4.0) [Grade 1A] and against low-intensity therapy (INR range, 1.5 to 1.9) compared to INR range of 2.0 to 3.0 (Grade 1A). For the prevention of the postthrombotic syndrome, we recommend the use of an elastic compression stocking (Grade 1A). For patients with objectively confirmed nonmassive PE, we recommend acute treatment with SC LMWH or, alternatively, IV UFH (both Grade 1A). For most patients with pulmonary embolism (PE), we recommend clinicians not use systemic thrombolytic therapy (Grade 1A). For the duration and intensity of treatment for PE, the recommendations are similar to those for DVT. [References: 196]

Publication Type: Guideline. Journal Article. Practice Guideline. Review.

<8>

Unique Identifier [PMID]: 15262836

Authors: Wan S. Quinlan DJ. Agnelli G. Eikelboom JW.

Institution: School of Medicine and Pharmacology, University of Western Australia, Perth, West Australia.

Title: Thrombolysis compared with heparin for the initial treatment of pulmonary embolism: a meta-analysis of the randomized controlled trials.[see comment].

Comments Comment in: Evid Based Nurs. 2005 Apr;8(2):52; PMID: 15830425

Source: Circulation. 110(6):744-9, 2004 Aug 10.

Abstract: BACKGROUND: Randomized trials and meta-analyses have reached conflicting conclusions about the role of thrombolytic therapy for the treatment of acute pulmonary embolism. METHODS AND RESULTS: We performed a meta-analysis of all randomized trials comparing thrombolytic therapy with heparin in patients with acute pulmonary embolism. Eleven trials, involving 748 patients, were included. Compared with heparin, thrombolytic therapy was associated with a nonsignificant reduction in recurrent pulmonary embolism or death (6.7% versus 9.6%; OR 0.67, 95% CI 0.40 to 1.12, P for heterogeneity=0.48), a nonsignificant increase in major bleeding (9.1% versus 6.1%; OR 1.42, 95% CI 0.81 to 2.46), and a significant increase in nonmajor bleeding (22.7% versus 10.0%; OR 2.63, 95% CI 1.53 to 4.54; number needed to harm=8). Thrombolytic therapy compared with heparin was associated with a significant reduction in recurrent pulmonary embolism or death in trials that also enrolled patients with major (hemodynamically unstable) pulmonary embolism (9.4% versus 19.0%; OR 0.45, 95% CI 0.22 to 0.92; number needed to treat=10) but not in trials that excluded these patients (5.3% versus 4.8%; OR 1.07, 95% CI 0.50 to 2.30), with significant heterogeneity between these 2 groups of trials (P=0.10). CONCLUSIONS: Currently available data provide no evidence for a benefit of thrombolytic therapy compared with heparin for the initial treatment of unselected patients with acute pulmonary embolism. A benefit is suggested in those at highest risk of recurrence or death. The number of patients enrolled in randomized trials to date is modest, and further evaluation of the efficacy and safety of thrombolytic therapy for the treatment of high-risk patients with acute pulmonary embolism appears warranted.

Publication Type: Journal Article. Meta-Analysis.

<9>

Unique Identifier [PMID]: 12583371

Authors: Wood KE.

Institution: University of Wisconsin Hospital and Clinics, Section of Pulmonary and Critical Care Medicine, Madison 53792-9988, USA. kew@medicine.wisc.edu

Title: The presence of shock defines the threshold to initiate thrombolytic therapy in patients with pulmonary embolism.[see comment]. [Review] [56 refs]

Comments Comment in: Intensive Care Med. 2002 Nov;28(11):1547-51; PMID: 12583373

Source: Intensive Care Medicine. 28(11):1537-46, 2002 Nov.

Publication Type: Journal Article. Review.

<10>

Unique Identifier [PMID]: 11245113

Authors: Civelek AC. Wang EA. Barr L. Urban BA. Eng J.

Institution: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins Medical Institutions, Out Patient Center, Baltimore, Maryland 21287-0817, USA. ccivelek@jhmi.edu

Title: Asymptomatic large main pulmonary artery thromboembolism with a low-probability ventilation-perfusion lung scan.

Source: Clinical Nuclear Medicine. 26(3):216-20, 2001 Mar.

Abstract: The incidence of the interpretation of low-probability lung scans in asymptomatic patients with large central pulmonary embolisms and the prognostic implication of the ventilation-perfusion scan appearance in this clinical setting is not documented.

Publication Type: Case Reports. Journal Article.

<11>

Unique Identifier [PMID]: 11129828

Authors: Katchan BM.

Institution: Department of Medicine, North York General Hospital, 4001 Leslie St., Toronto, ON M2K 1E1. bkatch@hotmail.com

Title: Thrombolytic therapy for pulmonary embolism. [Review] [29 refs]

Source: Canadian Journal of Surgery. 43(6):411-6, 2000 Dec.

Abstract: Consensus regarding the use of thrombolysis to treat acute pulmonary embolism has not yet been reached. There is good evidence that thrombolytic agents dissolve clot more rapidly than heparin. However, proving that this benefit reduces the death rate from pulmonary embolism has been difficult. Each of the 3 thrombolytic agents (tissue type-plasminogen activator, streptokinase and urokinase) is equally efficacious at dissolving clot, but all are associated with an increased risk of major hemorrhage when compared with heparin. One evolving position is that, in addition to patients presenting in circulatory collapse, for whom thrombolysis has been demonstrated to be life-saving, a subgroup of patients may be identified by echocardiography, through its ability to assess right ventricular dysfunction, who should also be considered for thrombolytic therapy. It remains to be seen whether this approach can reduce the death rate associated with pulmonary embolism. [References: 29]

Publication Type: Journal Article. Review.

<12>

Unique Identifier [PMID]: 10728526

Authors: Onuigbo M. Cuffy-Hallam M. Mangano A. Schwartz M. Alikhan M.

Institution: Department of Internal Medicine, Greater Baltimore Medical Center, MD 21204, USA.

Title: Successful thrombolytic therapy for massive pulmonary embolism.

Source: Southern Medical Journal. 93(3):327-9, 2000 Mar.

Abstract: The use and scope of thrombolytic therapy in the management of pulmonary embolism (PE) continues to evolve. The results of small studies suggest that thrombolytic therapy might have an impact on survival in massive PE with cardiogenic shock; however, no large studies to further this notion exist. Furthermore, the expanded application of thrombolytic therapy to patients with PE and right ventricular dysfunction (RVD) but without overt hemodynamic collapse remains controversial. We report successful use of the thrombolytic agent tissue plasminogen activator (tPA) in the management of life-threatening PE with RVD without overt cardiovascular collapse. We present evidence for the meritorious use of thrombolytic therapy in this category of PE patients. We believe that a broadened application of thrombolytic therapy to patients with PE and RVD but without cardiogenic shock, especially in younger patients, is beneficial and worth the risk.

Publication Type: Case Reports. Journal Article.

<13>

Unique Identifier [PMID]: 9749233

Authors: Hamel E. Pacouret G. Casset-Senon D. Dessenne X. Bertrand P. Pottier JM. Charbonnier B.

Institution: Service de cardiologie D, CHU Trousseau, Tours.

Title: [Comparative efficacy and risks of low molecular weight heparins and thrombolysis in massive pulmonary embolism without cardiogenic shock]. [French]

Source: Archives des Maladies du Coeur et des Vaisseaux. 91(3):295-9, 1998 Mar.

Abstract: The aim of this retrospective study was to assess pulmonary reperfusion by scintigraphy, the risks of recurrent embolism and of bleeding complications at the 7th day and 3rd month in 2 groups of patients admitted to hospital for massive pulmonary embolism without cardiogenic shock treated by intravenous thrombolysis (Group I) and by subcutaneous low molecular weight heparin (Group II) paired by Miller's index. The basal characteristics of the two groups, each comprising 31 patients, were comparable with respect to the severity of the pulmonary embolism with an average global scintigraphic defect of 40.6 +/- 13.5% in Group I and 39 +/- 13.7% in Group II. The scintigraphic changes at the 7th day were comparable with a relative improvement of 55 and 51% respectively and at 3 months of 74% in both groups. There was no significant difference in terms of recurrence of embolism (3 versus 0% at the 7th day and 3% in each group at 3 months) or of bleeding complications (13 and 10% at the 7th day and 10 and 6% at 3 months respectively). Low molecular weight heparin seems to be as effective as intravenous thrombolysis for the treatment of massive pulmonary embolism without shock. This result requires confirmation by a large scale prospective randomised trial.

Publication Type: Journal Article.

<14>

Unique Identifier [PMID]: 9737225

Authors: Ryu JH. Olson EJ. Pellikka PA.

Institution: Division of Pulmonary and Critical Care Medicine, Mayo Clinic Rochester, Minnesota 55905, USA.

Title: Clinical recognition of pulmonary embolism: problem of unrecognized and asymptomatic cases. [Review] [76 refs]

Source: Mayo Clinic Proceedings. 73(9):873-9, 1998 Sep.

Abstract: Dyspnea, pleuritic chest pain, and tachypnea are widely appreciated as common initial features of pulmonary embolism (PE). This knowledge is derived primarily from prospective studies evaluating diagnostic tests or therapeutic interventions in which the study patients are suspected to have PE based on their initial symptoms. Autopsy studies, however, continue to show that most cases of fatal PE are unrecognized and undiagnosed. Data from studies screening for PE in patients with deep venous thrombosis and in postoperative patients suggest that many patients with PE are asymptomatic and that PE is unrecognized. We believe that the current concepts regarding the initial clinical features of PE are too narrow and biased toward symptomatic cases. High clinical suspicion may be insufficient in recognizing PE. Herein we summarize the available data and explore the implications for clinical practice. [References: 76]

Publication Type: Journal Article. Review.

<15>

Unique Identifier [PMID]: 9367474

Authors: Krivec B. Voga G. Zuran I. Skale R. Pareznik R. Podbregar M. Noc M.

Institution: Department of Intensive Internal Medicine, General Hospital Celje, Slovenia.

Title: Diagnosis and treatment of shock due to massive pulmonary embolism: approach with transesophageal echocardiography and intrapulmonary thrombolysis.[see comment].

Comments Comment in: Chest. 1997 Nov 5;112(5):1158-9; PMID: 9367450

Source: Chest. 112(5):1310-6, 1997 Nov 5.

Abstract: STUDY OBJECTIVES: To evaluate the diagnostic value of transesophageal echocardiography (TEE) as an initial diagnostic tool in shocked patients. The second objective was to study therapeutic impact of intrapulmonary thrombolysis in patients with diagnosed massive pulmonary embolism. DESIGN: Prospective observational study. SETTING: Medical ICU in 800-bed general hospital. PATIENTS: Twenty-four consecutive patients with unexplained shock and distended jugular veins. MEASUREMENTS AND MAIN RESULTS: In 18 patients, right ventricular dilatation with global or segmental hypokinesis was documented. In addition, central pulmonary thromboemboli (12 patients), reduced contrast flow in right pulmonary artery (one patient), and right ventricular free wall akinesis (one patient) were found. No additional echocardiographic findings were apparent in four patients. According to pulmonary scintigraphy or autopsy, sensitivity of TEE for diagnosis of massive pulmonary embolism (MPE) in patients with right ventricular dilatation was 92% and specificity was 100%. In patients without right ventricular dilatation, left ventricular dysfunction (four patients) or cardiac tamponade (two patients) was confirmed. Intrapulmonary thrombolysis was evaluated in 11 of 13 patients with MPE. Two patients died prior to attempted thrombolysis. Three patients received streptokinase and eight received urokinase. Twenty-four hours after beginning of treatment, total pulmonary resistance index significantly decreased for 59% and mean pulmonary artery pressure for 31%. Cardiac index increased for 74%. Nine of 11 patients receiving thrombolysis survived to hospital discharge. CONCLUSION: Bedside TEE is a valuable tool for diagnosis of MPE. It enables immediate intrapulmonary thrombolysis, which seems to be an effective therapeutic alternative in our group of patients with obstructive shock.

Publication Type: Clinical Trial. Journal Article.