July 27, 2020

Background: The scientific process in medicine is complicated. Obtaining high-quality data to guide management requires hypothesis formulation, data to support the hypothesis and study replication. Time and again beneficial findings in therapeutic studies fail to be replicated in subsequent studies. A single positive trial may cause some to feel it unethical to assign patients to a standard therapy that could potentially deprive them of benefit. Alternatively, pharmaceutical companies have little impetus to attempt or support collecting additional data that may jeopardize their product. In research, repetition is the pillar on which clinical trials results should be founded on. As this may not be feasible, complete transparency of all aspects of a trial are essential. One of the most hotly debated topics in emergency medicine is the use of systemic thrombolysis in acute ischemic stroke.  There are only two randomized clinical trials that demonstrate benefit in neurologic outcomes: NINDS-II and ECASS-III (see table below).  Methodological experts, however, have raised concerns that both studies had baseline imbalances in stroke severity that may have biased the trials final results. Both studies have undergone re-analysis taking these baseline differences into account.

May 14, 2020

Background: The publication of the MR CLEAN trial in January 2015 changed the face of ischemic stroke care. This was the first study demonstrating a benefit to endovascular treatment of a specific subset of ischemic stroke patients: those with a large vessel occlusion (LVO) presenting within 6 hours of symptom onset. MR CLEAN was followed by a flurry of publications seeking to replicate and refine treatment as well as expand the window for treatment. The REBEL EM team reviewed this literature back in 2018 and, with the help of Dr. Evie Marcolini, created a workflow (shown below).

One major component of LVO management is the use of systemic thrombolytics in patients presenting within the current thrombolytic treatment window prior to endovascular intervention. However, it’s unclear if systemic thrombolytic administration results in better outcomes or if it simply exposes the patient to increased risks at a higher cost. Limited evidence questions the utility of the current approach with lytics + endovascular therapy (Phan 2017, Rai 2018). There is a clear need for further research into systemic thrombolytics dosing and use.

September 24, 2015

Background: When evaluating therapeutic options for PE, there are three categories in my mind: Subsegmental, Submassive, and Massive. For simplicity sake lets just say subsegmental PEs get treated with anticoagulation and massive PEs get treated with thrombolysis. The submassive category is a bit trickier. For example the PEITHO trial looked at full dose systemic fibrinolysis, tenecteplace in intermediate-risk pulmonary embolism and found a reduced risk of death or cardiovascular collapse by 56% but this was offset by an almost 5-fold increased risk of major bleeding and 10-fold increased risk of intracranial hemorrhage compared to anticoagulation alone. The MOPETT Trial on the other hand, looked at half dose systemic tPA for submassive PE and found that there was a significant reduction in pulmonary artery systolic pressures at 28 months vs usual care, with no increase in intracranial hemorrhage but failed to show any statistical mortality benefit compared to anticoagulation alone. Maybe a more simple answer to the submassive PE group would be to do catheter directed thrombolysis at lower doses than given with systemic fibrinolysis.
0