“Hey there”, say the enthusiastic emergency department registrar, “I’m glad I caught you. I’ve just seen this 51 year old lady who came in to the department with pleuritic left sided chest pain and feeling a bit short of breath. She flew in from Buenos Aires 3 days ago. She, s a bit tachycardic (105bpm), tachypnoeic (24bpm) and her SpO2 is 93% on room air before putting her on a Venturi mask at an FiO2 of 0.4.
The CXR was clear, so I got a CTPA and it shows a fairly big left main pulmonary artery. I’ve read some data on this and so I’ve done a bedside ECHO and she has a marginally dilated RV and an estimated RVsP of about 38mmHg. Ad her BNP is 120.
I’m planning on giving her a fibrinolytic, so do you have a bed for her for afterwards?”
This ED registrar is clearly talking about fibrinolysis for a submassive PE. The evidence for this intervention is fairly controversial and causes some heated debates. What is your position?
There is no set answer to this question. You are being asked to take a position and defend it. There is a growing push to give tPA for submassive PEs. There is no hard evidence of a mortality benefit for this practice but the outcome that generates the most debate is whether or not giving the fibrinolytic reduces the incidence of subsequent significant RV dysfunction with resultant cardiorespiratory compromise.
Here are a few resources that might help you decide what you would do and why:
1) A talk by Dr. Jeff Kline, who has published a number of papers on this topic – Fibrinolysis in submassive acute PE.
- Fibrinolysis for massive acute PE is supported by good data and both European Society of Cardiology guidelines and
- Fibrinolysis for submassive acute PE makes the patient feel better and look better
- Fibrinolysis for submassive acute PE has not been shown to improve mortality
- Fibrinolysis for submassive acute PE appears to double the overall risk of bleeding compared to heparin alone from 5% to 10%
- Fibrinolysis for submassive acute PE appears to roughly double the risk of intracranial haemorrhage compared to heparin alone from 0.3% to 0.5%.
- Fibrinolysis for submassive acute PE appears to result in an improved RVsP at 6 months follow up on ECHO compared to an apparent increase in RVsP in those who recieved only IV Heparin. (Don’t know what happens beyond this window. Do they ultimately equilibrate at 9, 12 or 24 months?)
- It is worth considering the patient’s premorbid exercise function prior to deciding to give a fibrinolytic for submassive acute PE with hypoxia, labile BP, elevated BNP or evidence of isolated increased RVsP.
- There is debate over whether the tPA, if given at all, should be administered by a loading dose followed by an infusion or simply by a single intravenous bolus
2) Here are some other often quoted papers examining the use of fibrinolytics for submassive acute PE:
- The MAPPET trial: Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002; 347: 1143–1150. – n=256, placebo controlled RCT. Reduction in primary outcome of in-hospital mortality and clinical deterioration (need for CPR, IPPV, catecholamine therapy, open-label rescue fibrinolysis, mechanical embolectomy).
- Kline JA, Steuerwald MT, Marchick MR, Hernandez-Nino J, Rose GA. Prospective evaluation of right ventricular function and functional status 6 months after acute submassive pulmonary embolism: frequency of persistent or subsequent elevation in estimated pulmonary artery pressure. Chest. 2009; 136: 1202–1210. n=200 with CT proven PE and baseline ECHO. RVsP adn symptom burden lower at 6 months in patients who had tPA + Heparin versus Heparin alone.
- The PEITHO trial: A planned n=1000 prospective MC-DB-RCT across 12 countries assessing tenectaplase + heparin versus placebo + heparin for combined all-cause mortality and haemodynamic colllapse within 7 days, with safety outcomes and 180-day clinical and echocardiographic follow-up as secondary end-points. Results expected this year (2013).
- The ICOPER Registry: Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999; 353: 1386–1389. – The incidence of ICH in fibrinolysis for submassive PE may be as high as 3%.
- Gregory Piazza, MD; Samuel Z. Goldhaber, MD. Clinician Update: Management of Submassive Pulmonary Embolism. Circulation. 2010; 122: 1124-1129
3) Here are some online resources that focus on acute submassive PE management: