HPI: A 65 year-old woman presented to the Emergency Department with a 2 day history of unilateral calf swelling and dyspnea after a 10 hour car trip.
PMH: Hypertension and Hperlipidemia
Meds: Atenolol 50 mg and Simvistatin 20 mg
SH: 50 pack-year smoking history
PE: BP 95/60 mmHg, hr- 105 bpm, RR- 24 breaths/min, Oxygenation saturation room air 86 %
Heart: tachycardic, no murmurs, JVP- normal
Extremities: right calf is swollen, erythematous, and tender
ECG: Incomplete RBBB, otherwise normal
CXR: hyper-inflated lungs
Lab studies: Arterial blood gas revealed pH 7.47, Pco2 28 mmHg, and Po2 of 55 mmHg on room air
cTnI: 0.6 ng/ml (99th % 0.04 ng/ml), BNP 650 pg/ml ( reference range < 200 pg/ml).
Treatment: Patient received an IV bolus of 500 cc 0.9 NS and repeat BP was 100/60 and heart rate 100 bpm. Patient was started on oxygen 2 L/min and received IV heparin.
CT scan: Image quality was suboptimal due to patient movement. However, it demonstrated acute pulmonary embolism in the right and left pulmonary arteries with extension into the right upper, right lower, left upper, and left lower segments. Unable to comment on RV strain; RV size appeared at the upper limit of normal.
Tranthoracic Echocardiogram: Technically difficult study. Left ventricle appears to be hyperdynamic, The right ventricle was not well-visualized and unable to estimate the systolic pulmonary artery pressure.
Hospital Course: Patient was admitted to the Intensive Care Unit at 6:00 PM. At 10:00 PM oxygen requirements increased requiring a 50% venti-mask to maintain a saturation > 90%. BP is 95/60 mmHg with heart rate of 110 bpm. The patient had adequate urine output and normal mental status.
The correct answer is: 2. IV thrombolytic therapy
Our answer is #2 (IV thrombolytic therapy), based on borderline hemodynamic status, worsening hypoxia, and elevated biomarkers (TnI, BNP) consistent with significant right ventricular strain. IV thrombolytic therapy (tPA) was administered. Hemodynamic status and oxygenation requirements improved over the next 4 hours.
The use of thrombolytic therapy in the treatment of pulmonary embolism is controversial. As compared to the thousands of patients that have been studied in well-designed placebo controlled trials in acute myocardial infraction, there is a paucity of data involving thrombolyic therapy in the setting of pulmonary embolism (PE). In a recent review there were only 13 randomized studies found comparing thrombolytic therapy to standard anticoagulation therapy in PE.1 This data suggests that there is no mortality benefit in patients with PE who are hemodynamically stable. Unfortunately, thus far there has only been one randomized trial of thrombolytic therapy versus heparin in patients with hemodynamic instability in PE, that included only 8 patients.2 The 4 patients who received streptokinase all survived up to 2 years of follow-up, and all 4 patients who received heparin died during the hospital admission. The American College of Chest Physicians recommend that patients with hemodynamically significant PE defined as systolic BP < 90 mmHg should receive thrombolytic therapy,1 but clearly more data is needed in this area. Embolectomy, either surgical or catheter-based, is recommended to be considered in patients who have contraindications to thrombolytic therapy.
Various tools may assist in the risk-stratification of patients with PE. Echocardiographic evidence for right ventricular dysfunction is associated with higher mortality in PE and some have suggested this finding should be considered in the decision to give thrombolytic therapy. In addition, both the natriuretic peptides (BNP, NT-proBNP) and cardiac troponins (I and T) are associated with higher short-term mortality in PE.4,5 A meta-analysis of 7 studies including a total of 562 patients showed that patients with an elevated BNP were at increased risk of short-term mortality, OR=7.7 (95% CI 2.9-20); similarly a meta analysis of 9 studies including 1,366 patients demonstrated that patients with elevated cardiac troponin ( I or T) were at an increased mortality risk, OR=4.3 (95% CI 2.1- 8.5).5 Whether more aggressive management of patients with elevated cardiac markers will improve outcomes needs to be determined in prospective studies. Importantly, such a trial is underway. The PEITHO trial intends to enroll 1,000 normotensive patients with PE, right ventricular dysfunction as demonstrated by echocardiography or computed tomography, and an elevated cardiac troponin I or T.6 Patients will be randomized to single-bolus tenecteplase plus heparin or heparin alone. This study should help clarify what high-risk patients with PE should receive thrombolytic therapy.
- Kearon, C., 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(2 Suppl):e419S-94S.
- Jerjes-Sanchez, C., et al., Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism: A Randomized Controlled Trial. J Thromb Thrombolysis 1995; 2:227-229.
- Goldhaber, S.Z., Echocardiography in the management of pulmonary embolism. Ann Intern Med 2002; 136:691-700.
- Coutance, G., et al., The prognostic value of markers of right ventricular dysfunction in pulmonary embolism: a meta-analysis. Crit Care 2011; 15: R103.
- Jimenez, D., et al., Troponin-based risk stratification of patients with acute nonmassive pulmonary embolism: systematic review and metaanalysis. Chest 2009; 136:974-82.
- Single-bolus tenecteplase plus heparin compared with heparin alone for normotensive patients with acute pulmonary embolism who have evidence of right ventricular dysfunction and myocardial injury: rationale and design of the Pulmonary Embolism Thrombolysis (PEITHO) trial. Am Heart J 2012; 163:33-38 e1.