Semin Respir Crit Care Med 2015; 36(06): 835-841
DOI: 10.1055/s-0035-1564733
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Controversies in the Management of Life-Threatening Pulmonary Embolism

Peter S. Marshall
1   Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, Connecticut
,
Victor Tapson
2   Division of Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles, California
,
David Jiménez
3   Respiratory Department, Ramón y Cajal Hospital, IRYCIS, Alcala de Henares University, Madrid, Spain
› Author Affiliations
Further Information

Publication History

Publication Date:
23 November 2015 (online)

Abstract

Patients with life-threatening pulmonary embolism (PE) offer clinicians a unique opportunity to intervene effectively on the patient's behalf. Hemodynamic status remains the most important short-term prognostic factor for patients with acute PE. Although the evidence is limited, the use of thrombolytic therapy is recommended for patients with acute symptomatic PE and associated hypotension or shock (i.e., high-risk PE) because these patients have a high short-term mortality risk (i.e., >15%) even when receiving anticoagulant treatment. In this setting, the hemodynamic benefits of thrombolytic treatment far outweigh its bleeding risk. For hemodynamically stable patients with PE, the identification of a subgroup of patients with a risk of PE-related complications similar to patients with PE and cardiovascular instability (i.e., intermediate-risk group) may assist with decision making regarding therapy. Given the lack of clear mortality benefit and increased bleeding risk, guidelines do not recommend routine use of systemic thrombolysis for this subgroup of patients. Careful monitoring and rescue fibrinolysis for intermediate-risk PE patients who experience hemodynamic compromise or deterioration while receiving standard anticoagulant therapy can minimize deaths from PE. For patients with life-threatening PE at high risk of bleeding, clinicians might consider the use of low-dose thrombolytic therapy, catheter-directed thrombolysis, or surgical embolectomy, if they have access to the required expertise and resources. The evidence does not support the use of inferior vena cava filters in patients with life-threatening PE unless there is a contraindication to anticoagulation. Since various medical and surgical specialties offer different perspectives and expertise, a multidisciplinary approach to patients with intermediate- and high-risk PE might improve patient outcomes.

 
  • References

  • 1 Laporte S, Mismetti P, Décousus H , et al; RIETE Investigators. Clinical predictors for fatal pulmonary embolism in 15,520 patients with venous thromboembolism: findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) Registry. Circulation 2008; 117 (13) 1711-1716
  • 2 Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999; 353 (9162) 1386-1389
  • 3 Konstantinides SV, Torbicki A, Agnelli G , et al; Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014; 35 (43) 3033-3069 , 3069a–3069k
  • 4 Jaff MR, McMurtry MS, Archer SL , et al; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; American Heart Association Council on Peripheral Vascular Disease; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011; 123: 1788-1830
  • 5 Kasper W, Konstantinides S, Geibel A , et al. Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol 1997; 30 (5) 1165-1171
  • 6 Jiménez D. Point: should systemic lytic therapy be used for submassive pulmonary embolism? Yes. Chest 2013; 143 (2) 296-299
  • 7 Sanchez O, Trinquart L, Colombet I , et al. Prognostic value of right ventricular dysfunction in patients with haemodynamically stable pulmonary embolism: a systematic review. Eur Heart J 2008; 29 (12) 1569-1577
  • 8 Schoepf UJ, Kucher N, Kipfmueller F, Quiroz R, Costello P, Goldhaber SZ. Right ventricular enlargement on chest computed tomography: a predictor of early death in acute pulmonary embolism. Circulation 2004; 110 (20) 3276-3280
  • 9 Kang DK, Thilo C, Schoepf UJ , et al. CT signs of right ventricular dysfunction: prognostic role in acute pulmonary embolism. JACC Cardiovasc Imaging 2011; 4 (8) 841-849
  • 10 Stein PD, Beemath A, Matta F , et al. Enlarged right ventricle without shock in acute pulmonary embolism: prognosis. Am J Med 2008; 121 (1) 34-42
  • 11 Trujillo-Santos J, den Exter PL, Gómez V , et al. Computed tomography-assessed right ventricular dysfunction and risk stratification of patients with acute non-massive pulmonary embolism: systematic review and meta-analysis. J Thromb Haemost 2013; 11 (10) 1823-1832
  • 12 Becattini C, Vedovati MC, Agnelli G. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation 2007; 116 (4) 427-433
  • 13 Jiménez D, Aujesky D, Yusen RD. Risk stratification of normotensive patients with acute symptomatic pulmonary embolism. Br J Haematol 2010; 151 (5) 415-424
  • 14 Kearon C, Akl EA, Comerota AJ , et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141: e419S-e494S
  • 15 Jiménez D, Aujesky D, Moores L , et al. Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolism. Thorax 2011; 66 (1) 75-81
  • 16 Sanchez O, Trinquart L, Planquette B , et al. Echocardiography and pulmonary embolism severity index have independent prognostic roles in pulmonary embolism. Eur Respir J 2013; 42 (3) 681-688
  • 17 Jiménez D, Kopecna D, Tapson V , et al; On Behalf Of The Protect Investigators. Derivation and validation of multimarker prognostication for normotensive patients with acute symptomatic pulmonary embolism. Am J Respir Crit Care Med 2014; 189 (6) 718-726
  • 18 Jiménez D, Aujesky D, Moores L , et al; RIETE Investigators. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med 2010; 170 (15) 1383-1389
  • 19 Bova C, Sanchez O, Prandoni P , et al. Identification of intermediate-risk patients with acute symptomatic pulmonary embolism. Eur Respir J 2014; 44 (3) 694-703
  • 20 Fernández C, Bova C, Sanchez O , et al. Validation of a model for identification of patients at intermediate to high risk for complications associated with acute symptomatic pulmonary embolism. Chest 2015; 148 (1) 211-218
  • 21 Goldhaber SZ, Haire WD, Feldstein ML , et al. Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion. Lancet 1993; 341 (8844) 507-511
  • 22 Dalla-Volta S, Palla A, Santolicandro A , et al. PAIMS 2: alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolism. Plasminogen activator Italian multicenter study 2. J Am Coll Cardiol 1992; 20 (3) 520-526
  • 23 Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W ; Management Strategies and Prognosis of Pulmonary Embolism-3 Trial Investigators. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med 2002; 347 (15) 1143-1150
  • 24 Meyer G, Vicaut E, Danays T , et al; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 2014; 370 (15) 1402-1411
  • 25 Kline JA, Nordenholz KE, Courtney DM , et al. Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double-blind, placebo-controlled randomized trial. J Thromb Haemost 2014; 12 (4) 459-468
  • 26 Chatterjee S, Chakraborty A, Weinberg I , et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA 2014; 311 (23) 2414-2421
  • 27 Kucher N, Boekstegers P, Müller OJ , et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation 2014; 129 (4) 479-486
  • 28 Wang TF, Squizzato A, Dentali F, Ageno W. The role of thrombolytic therapy in pulmonary embolism. Blood 2015; 125 (14) 2191-2199
  • 29 Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M ; “MOPETT” Investigators. Moderate pulmonary embolism treated with thrombolytics (from the ‘MOPETT’ trial). Am J Cardiol 2013; 111: 273-277
  • 30 Engelberger RP, Kucher N. Ultrasound-assisted thrombolysis for acute pulmonary embolism: a systematic review. Eur Heart J 2014; 35 (12) 758-764
  • 31 Stein PD, Matta F, Keyes DC, Willyerd GL. Impact of vena cava filters on in-hospital case fatality rate from pulmonary embolism. Am J Med 2012; 125 (5) 478-484
  • 32 Mismetti P. Randomized trial assessing the efficacy of the partial interruption of the inferior vena cava by an optional vena caval filter in the prevention of the recurrence of pulmonary embolism. PREPIC 2 trial: prevention of embolic recurrences by caval interruption (prospective, multicentric, randomised, open trial) [in French]. Rev Pneumol Clin 2008; 64 (6) 328-331
  • 33 Mismetti P, Laporte S, Pellerin O , et al; PREPIC2 Study Group. Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism: a randomized clinical trial. JAMA 2015; 313 (16) 1627-1635
  • 34 Muriel A, Jiménez D, Aujesky D , et al; RIETE Investigators. Survival effects of inferior vena cava filter in patients with acute symptomatic venous thromboembolism and a significant bleeding risk. J Am Coll Cardiol 2014; 63 (16) 1675-1683
  • 35 Kuo WT, Gould MK, Louie JD, Rosenberg JK, Sze DY, Hofmann LV. Catheter-directed therapy for the treatment of massive pulmonary embolism: systematic review and meta-analysis of modern techniques. J Vasc Interv Radiol 2009; 20 (11) 1431-1440
  • 36 Goldhaber SZ, Agnelli G, Levine MN ; The Bolus Alteplase Pulmonary Embolism Group. Reduced dose bolus alteplase vs conventional alteplase infusion for pulmonary embolism thrombolysis. An international multicenter randomized trial. Chest 1994; 106 (3) 718-724
  • 37 Aujesky D, Obrosky DS, Stone RA , et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med 2005; 172 (8) 1041-1046
  • 38 Mikkola KM, Patel SR, Parker JA, Grodstein F, Goldhaber SZ. Increasing age is a major risk factor for hemorrhagic complications after pulmonary embolism thrombolysis. Am Heart J 1997; 134 (1) 69-72
  • 39 Kabrhel C, Jaff MR, Channick RN, Baker JN, Rosenfield K. A multidisciplinary pulmonary embolism response team. Chest 2013; 144 (5) 1738-1739
  • 40 Provias T, Dudzinski DM, Jaff MR , et al. The Massachusetts General Hospital Pulmonary Embolism Response Team (MGH PERT): creation of a multidisciplinary program to improve care of patients with massive and submassive pulmonary embolism. Hosp Pract (1995) 2014; 42 (1) 31-37
  • 41 Klok FA, Mos IC, Huisman MV. Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism: a systematic review and meta-analysis. Am J Respir Crit Care Med 2008; 178 (4) 425-430
  • 42 Jiménez D, Aujesky D, Díaz G , et al; RIETE Investigators. Prognostic significance of deep vein thrombosis in patients presenting with acute symptomatic pulmonary embolism. Am J Respir Crit Care Med 2010; 181 (9) 983-991
  • 43 Lobo JL, Zorrilla V, Aizpuru F , et al; RIETE Investigators. D-dimer levels and 15-day outcome in acute pulmonary embolism. Findings from the RIETE Registry. J Thromb Haemost 2009; 7 (11) 1795-1801
  • 44 van der Meer RW, Pattynama PM, van Strijen MJ , et al. Right ventricular dysfunction and pulmonary obstruction index at helical CT: prediction of clinical outcome during 3-month follow-up in patients with acute pulmonary embolism. Radiology 2005; 235 (3) 798-803
  • 45 Lankeit M, Jiménez D, Kostrubiec M , et al. Predictive value of the high-sensitivity troponin T assay and the simplified Pulmonary Embolism Severity Index in hemodynamically stable patients with acute pulmonary embolism: a prospective validation study. Circulation 2011; 124 (24) 2716-2724
  • 46 Dellas C, Puls M, Lankeit M , et al. Elevated heart-type fatty acid-binding protein levels on admission predict an adverse outcome in normotensive patients with acute pulmonary embolism. J Am Coll Cardiol 2010; 55 (19) 2150-2157