Data from a non-randomised study have hinted that in patients with acute pulmonary embolism (PE), thrombolysis followed by heparin more rapidly reverses right-ventricular dysfunction and restores pulmonary tissue perfusion than does heparin alone. We have pursued this idea in a randomised protocol. 46 haemodynamically stable patients were randomised to recombinant tissue plasminogen activator (alteplase, rt-PA) 100 mg over 2 h followed by intravenous heparin and 55 to heparin alone. Right-ventricular wall motion was assessed qualitatively, and right-ventricular end diastolic area was estimated by planimetry from echocardiograms at baseline and at 3 and 24 hours. Pulmonary perfusion scans were obtained at baseline and 24 hours. In 39% of rt-PA patients but in only 17% of heparin alone patients right-ventricular wall motion at 24 hours had improved from baseline and in 2% and 17%, respectively, it worsened (p = 0.005). rt-PA patients also had a significant decrease in right-ventricular end-diastolic area during the 24 hours after randomisation and a significant absolute improvement in pulmonary perfusion (14.6% vs 1.5%). No clinical episodes of recurrent PE were noted among rt-PA patients, but there were 2 fatal and 3 non-fatal clinically suspected recurrent PEs within 14 days in patients randomised to heparin alone. rt-PA rapidly improves right-ventricular function and pulmonary perfusion among patients with PE and may lead to a lower rate of adverse clinical outcomes.

We update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics.We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence.For VTE and no cancer, as long-term anticoagulant therapy, we suggest dabigatran (Grade 2B), rivaroxaban (Grade 2B), apixaban (Grade 2B), or edoxaban (Grade 2B) over vitamin K antagonist (VKA) therapy, and suggest VKA therapy over low-molecular-weight heparin (LMWH; Grade 2C). For VTE and cancer, we suggest LMWH over VKA (Grade 2B), dabigatran (Grade 2C), rivaroxaban (Grade 2C), apixaban (Grade 2C), or edoxaban (Grade 2C). We have not changed recommendations for who should stop anticoagulation at 3 months or receive extended therapy. For VTE treated with anticoagulants, we recommend against an inferior vena cava filter (Grade 1B). For DVT, we suggest not using compression stockings routinely to prevent PTS (Grade 2B). For subsegmental pulmonary embolism and no proximal DVT, we suggest clinical surveillance over anticoagulation with a low risk of recurrent VTE (Grade 2C), and anticoagulation over clinical surveillance with a high risk (Grade 2C). We suggest thrombolytic therapy for pulmonary embolism with hypotension (Grade 2B), and systemic therapy over catheter-directed thrombolysis (Grade 2C). For recurrent VTE on a non-LMWH anticoagulant, we suggest LMWH (Grade 2C); for recurrent VTE on LMWH, we suggest increasing the LMWH dose (Grade 2C).Of 54 recommendations included in the 30 statements, 20 were strong and none was based on high-quality evidence, highlighting the need for further research.Copyright © 2016 American College of Chest Physicians. All rights reserved.

Thrombolytic therapy may be beneficial in the treatment of some patients with pulmonary embolism. To date, no analysis has had adequate statistical power to determine whether thrombolytic therapy is associated with improved survival, compared with conventional anticoagulation.To determine mortality benefits and bleeding risks associated with thrombolytic therapy compared with anticoagulation in acute pulmonary embolism, including the subset of hemodynamically stable patients with right ventricular dysfunction (intermediate-risk pulmonary embolism).PubMed, the Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from inception through April 10, 2014.Eligible studies were randomized clinical trials comparing thrombolytic therapy vs anticoagulant therapy in pulmonary embolism patients. Sixteen trials comprising 2115 individuals were identified. Eight trials comprising 1775 patients specified inclusion of patients with intermediate-risk pulmonary embolism.Two reviewers independently extracted trial-level data including number of patients, patient characteristics, duration of follow-up, and outcomes.The primary outcomes were all-cause mortality and major bleeding. Secondary outcomes were risk of recurrent embolism and intracranial hemorrhage (ICH). Peto odds ratio (OR) estimates and associated 95% CIs were calculated using a fixed-effects model.Use of thrombolytics was associated with lower all-cause mortality (OR, 0.53; 95% CI, 0.32-0.88; 2.17% [23/1061] vs 3.89% [41/1054] with anticoagulants; number needed to treat [NNT] = 59) and greater risks of major bleeding (OR, 2.73; 95% CI, 1.91-3.91; 9.24% [98/1061] vs 3.42% [36/1054]; number needed to harm [NNH] = 18) and ICH (OR, 4.63; 95% CI, 1.78-12.04; 1.46% [15/1024] vs 0.19% [2/1019]; NNH = 78). Major bleeding was not significantly increased in patients 65 years and younger (OR, 1.25; 95% CI, 0.50-3.14). Thrombolysis was associated with a lower risk of recurrent pulmonary embolism (OR, 0.40; 95% CI, 0.22-0.74; 1.17% [12/1024] vs 3.04% [31/1019]; NNT = 54). In intermediate-risk pulmonary embolism trials, thrombolysis was associated with lower mortality (OR, 0.48; 95% CI, 0.25-0.92) and more major bleeding events (OR, 3.19; 95% CI, 2.07-4.92).Among patients with pulmonary embolism, including those who were hemodynamically stable with right ventricular dysfunction, thrombolytic therapy was associated with lower rates of all-cause mortality and increased risks of major bleeding and ICH. However, findings may not apply to patients with pulmonary embolism who are hemodynamically stable without right ventricular dysfunction.

One hundred four patients at Brigham and Women's Hospital who received alteplase for acute pulmonary embolism were evaluated. Major bleeding occurred in 20 patients (19.2%). The principal site of bleeding was unknown in 9 (45.0%), gastrointestinal in 6 (30.0%), retroperitoneal in 3 (15.0%), intracranial in 1 (5.0%), and splenic in 1 (5.0%). Independent predictors of major hemorrhage were the administration of catecholamines for systemic arterial hypotension (odds ratio [OR] 115, 95% confidence interval [CI] 9.4 to 1,410.9, p < 0.001), cancer (OR 16.0, 95% CI 3.2 to 80, p = 0.004), diabetes mellitus (OR 9.6, 95% CI 1.7 to 54, p = 0.010), and elevated international normalized ratio before fibrinolysis (OR 5.8, 95% CI 1.5 to 22, p = 0.012).

Bleeding may occur frequently during adult extracorporeal life support; however, there are no detailed investigations of bleeding events, red blood cell transfusion, and their impact on mortality. The purpose of our study was to characterize the incidence of bleeding and red blood cell transfusion during adult extracorporeal life support and examine the impact on mortality.We performed a retrospective analysis of adult extracorporeal life support patients over approximately a 3-year period. The incidence of bleeding events and transfusions were recorded. Unadjusted and adjusted multivariate logistic regression analyses were performed to estimate the odds of inhospital mortality among patients with bleeding and for each red blood cell unit transfused. Ninety-day survival was compared between patients who bled and those who did not.Serious bleeding events occurred in 74 of 132 patients (56.1%), and the rate of bleeding was 10 events per 100 days. The crude odds ratio for inhospital mortality in patients who bled was 2.22 (95% confidence interval [CI]: 1.00 to 4.94, p = 0.05); and for each unit of red blood cells transfused, it was 1.03 (95% CI: 1.01 to 1.04, p = 0.005). The adjusted odds ratios for bleeding and red blood cell transfusions were 0.90 (95% CI: 0.37 to 2.19, p = 0.82) and 1.03 (95% CI: 1.00 to 1.06, p = 0.04). There was a trend toward decreased 90-day survival among patients who bled compared with patients who did not (46.7% versus 64.9%, p = 0.08).Bleeding and red blood cell transfusion occur frequently during adult extracorporeal life support, but only the amount of red blood cell transfusion is associated with inhospital mortality after controlling for confounding variables.Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Extracorporeal membrane oxygenation (ECMO) has been used to stabilize patients with massive pulmonary embolism though few reports describe this approach. We describe the presentation, management and outcomes of patients who received ECMO for massive pulmonary embolism (PE) in our pulmonary embolism response team (PERT) registry.We enrolled a consecutive cohort of patients with confirmed PE for whom PERT was activated and selected patients treated with ECMO. We prospectively captured clinical, therapeutic and outcome data at the time of PERT activation and during the follow-up period for up to 365 days.Thirteen patients who had PERT activation with confirmed PE diagnosis have undergone ECMO since the initiation of our PERT program in 2012. The mean age was 49 ± 19 years. Six (46%) patients were female. All the patients had cardiac arrest, either as an initial presentation or in-hospital cardiac arrest after presentation. All the patients exhibited right ventricular (RV) dilation on echocardiogram with RV hypokinesis. Eight (62%) patients received systemic thrombolysis with intravenous tissue plasminogen activator (tPA) and three (23%) patients underwent catheter-directed thrombolysis therapy using the EKOS system (EKOS Corporation, Bothell, WA, USA). Four (31%) patients underwent surgical embolectomy. Mean ECMO duration was 5.5 days, ranging from 2-18 days. Thirty-day mortality was 31% and one-year mortality was 54%.Patients with massive pulmonary embolism who suffer a cardiac arrest have high morbidity and mortality. ECMO can be used in conjunction with systemic thrombolysis, catheter-directed therapy or as a bridge to surgical embolectomy.

When pulmonary embolism (PE) develops, circulatory collapse and hypoxia are caused at the same time. The rapid and proper use of extracorporeal life support (ECLS) can improve the mortality rate of patients with collapsed massive PE. No study has examined the influence of treatment that involved adding catheter based-intervention to ECLS with massive collapsed PE. Thirty-five patients with massive PE were examined, and 10 of these patients were placed on ECLS. Eight of the 10 patients placed on ECLS for massive PE were female, and the median age was 61 years. Seven patients had in-hospital onset PE and 3 patients out-of-hospital onset PE. Their underlying conditions were a cerebral infarction (3 patients), coronary artery disease (5 patients), collagen disease (one patient), postoperative state (3 patients), and lung disease (2 patients). Pulmonary angiographic findings showed that a filling defect or complete occlusion was observed in all 10 patients in the proximal lobular arteries, 6 of which had large thrombi stretching to the main pulmonary arteries. All patients underwent thrombolysis. Percutaneous catheter embolus fragmentation and/or thrombectomy were undertaken in 7 patients. All patients required red blood cell transfusion for cannulation site bleeding. The mean duration of ECLS bypass was 48 ± 44 hours. The 30 day mortality rate was 30%. The current study clarified the characteristics of patients with massive PE requiring ECLS. These patients have extensive pulmonary thromboemboli, thus, the aggressive use of catheter-based intervention appears to have beneficial effects for massive PE requiring ECLS.