Thrombolysis for PE

July 2010

Thrombolysis for PE

Search Strategy: .Cochrane Database of Systematic Reviews published a review in 2006 in which 35 articles were identified. 27 of these articles were excluded, leaving eight articles included in the review. Pubmed Clinical Query “pulmonary embolism thrombolysis” narrow/specific search reveals 28 articles, but nothing that was not included in the Cochrane review (see http://tinyurl.com/38goodq and http://tinyurl.com/34k76ax).

You are working an overnight EM2 shift. In between pelvic exams you dart into room 27 to see Mr. S. He is a 65 year old male with a history of hypertension, coronary artery disease s/p LAD stent in 1998, and osteoarthritis. Two-weeks ago he had a right knee replacement. Today he was sent from outpatient rehab complaining of sudden onset shortness of breath and chest heaviness that began suddenly while being put through range of motion exercises two-hours prior to arrival.

Physical Exam:

  • Vitals: T 37.5 HR 112, BP 110/63, RR 22, SpO2 90% on room air (96% on 2 liters oxygen by NC).
  • General: Well-nourished male with mild tachypnea, but not in acute distress
  • Pulmonary: Lungs clear & symmetric
  • Cardiac: Tachycardia, regular rhythm, no murmurs/rubs/gallops
  • Skin: Warm, dry, pink with good capillary refill

An EKG reveals sinus tachycardia with a right bundle branch block which is new compared with his pre-op EKG three-weeks prior. Lab work is unremarkable and CXR is clear. PE protocol CT reveals a large saddle pulmonary embolism at the bifurcation of the pulmonary artery. As the patient is hemodynamically stable and in no distress, you provide an intravenous bolus of heparin followed by a heparin drip and admit the patient to the Medicine service on telemetry. At the end of your shift, while driving home, your mind goes back to Mr. S, and you begin to wonder whether lytics would have been a good idea. What are the indications for thrombolysis in pulmonary embolism? You arrive home and being evidence-based medicine savvy, go to your computer and begin searching the 3 major medical databases (Google, Yahoo, and Hotbot). Finding little help there, you turn instead to the Cochrane Database, Pubmed, and EMBase, and start finding some answers.


PICO Question

Population: Hemodynamically stable ED patients with acute pulmonary embolism and evidence of right ventricular dysfunction

Intervention: Thrombolysis plus IV heparin

Comparison: IV Heparin alone

Outcome: Mortality, major bleeding, minor bleeding, escalation of treatment, recurrent PE


Years

First years: Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion, Lancet 1993; 341: 507-511. (http://pmid.us/8094768)

Second years: Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism, N Engl J Med 2002; 347: 1143-1150. (http://pmid.us/12374874)

Third years: Thrombolysis compared with heparin for the initial treatment of pulmonary embolism: A meta-analysis of the randomized controlled trials. Circulation 2004; 110: 744-749. (http://pmid.us/15262836)

Fourth years: Thrombolytic therapy for pulmonary embolism, Cochrane Database Syst Rev 2006, Issue 2, Art No.: CD004437. DOI: 10.1002/14651858.CD004437.pub2. (http://pmid.us/16625603)


Articles

Article 1: Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion Lancet 1993; 341:501-511
ANSWER KEY

Article 2: Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism, NEJM 2002; 347:1143-1150
ANSWER KEY

Article 3: Thrombolysis Compared With Heparin for the Initial Treatment of Pulmonary Embolism: A Meta-Analysis of the Randomized Controlled Trials Circ 2004; 110:744-749
ANSWER KEY

Article 4: Thrombolytic therapy for pulmonary embolism, Cochrane Database Syst Review 2006; Issue 2. Art No.: CD004437. DOI: 10.1002/14651858. CD004437 pub 2
ANSWER KEY


Bottom Line

Two meta-analyses offered similar conclusions. There is insufficient evidence to support thrombolysis in addition to heparin for unselected PE patients. However, hemodynamically unstable PE patients have a significant benefit with thrombolysis with a NNT = 10 to prevent recurrent PE or death at 30-days. Further research is needed to better understand the NNH for massive PE thrombolysis and the potential role of thrombolytics in well-defined submassive PE since some trials have demonstrated improved outcomes. Two of those trials are briefly reviewed in the next paragraph (from the PGY I & PGY II articles).

In select PE patients (see multiple exclusion criteria below), rt-PA [100mg over 2h administered up to 1.5 days after heparin is initiated] can significantly decrease 24-hour RV wall motion deterioration (NNT = 7) compared with heparin alone. The subset with RV wall motion abnormalities at baseline may benefit the most from thrombolysis and should be the focus of future investigations. However, future trials need to assess patient-oriented outcomes. The other trial demonstrated that select hemodynamically stable PE patients with (formal echocardiographer-defined) RV dysfunction or pulmonary hypertension, alteplase plus heparin improves outcomes compared with heparin alone by reducing the need for secondary thrombolysis up to 30-days after presentation (NNT =8). The external validity of these findings must be tested in EDs without ready access to echocardiography around-the-clock.

Exclusion criteria

  • Major internal bleeding in the previous 6-months
  • Intracranial or intraspinal disease
  • Operation or biopsy in the preceding 10-days
  • Occult blood in stool
  • Hct < 28%
  • Platelet < 100,000/µL
  • Systolic BP > 200 or diastolic BP > 110 mmHg
  • Severely impaired hepatic function
  • Pregnancy
  • Endocarditis
  • Hemorrhagic retinopathy
  • Any concurrent condition considered to limit survival to less than 1 month
  • Age > 80-years (in one-trial)
  • Already on anti-coagulation therapy

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