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.

July 16, 2020

Background: The cornerstones of sepsis management continues to include early identification, early appropriate empiric antibiotics, definitive source control, and vasopressors to support end organ perfusion. There have been multiple studies looking at the co-administration of hydrocortisone, ascorbic acid, and thiamine (known as HAT therapy or the metabolic cocktail) to help reduce mortality and reverse shock. Despite the original Marik study showing an association between HAT therapy and a 31.9% overall decrease in mortality and a 3-fold decrease in time to vasopressor discontinuation in patients presenting with severe sepsis and septic shock, the mortality benefit has not been reproduced in subsequent randomized clinical trials.  Studies focused specifically on the use of corticosteroids have demonstrated reduced time on vasopressors in patients in septic shock.  The bigger question is does vitamin C and thiamine add anything additional to help improve mortality (The ORANGES Trial)?

July 9, 2020

Background: Acute atrial fibrillation (AF) is one of the most common dysrhythmias seen in the emergency department (ED). There has been extensive discussion and debate about the best way to manage acute AF centered around rate and rhythm control.  However, there is little data to guide the optimal approach to rhythm control once this option is selected. As a result of the absence of good evidence, there is significant variation in management. Better data is integral to establishing best practices. The RAFF2 randomized trial attempted to provide more data on this debate of electrical vs pharmacological cardioversion in patients with acute atrial fibrillation/flutter.

July 6, 2020

Background: Hydroxychloroquine (HCQ) is an antimalarial and immunomodulatory drug that is postulated to exert an antiviral effect by increasing intracellular pH resulting in decreased viral binding at the ACE2 receptor. Azithromycin is a macrolide antibiotic that also has anti-inflammatory and immunomodulatory properties which could help decrease viral replication and viral binding. Both of these medications have been used to treat COVID patients based on in vitro findings. However, in vitro studies often do not extrapolate to patient oriented outcomes. In June 2020 the US FDA revoked the prior emergency use authorization to HCQ and chloroquine (CQ) in patients with COVID-19. We now have yet another retrospective observational trial of HCQ, azithromycin, and the drugs in combination.

July 2, 2020

Background: In patients presenting to the ED with acute coronary syndrome (ACS), dual antiplatelet therapy is the current standard treatment.  This typically consists of aspirin and an adenosine diphosphate receptor antagonist.  It is fairly well understood that prasugrel and ticagrelor provide greater, and more rapid platelet inhibition than clopidogrel (i.e. Plavix) [5][6]. Both ticagrelor and prasurgel have a class I recommendation for use in ACS with or without ST-segment elevation. The loading strategies of these two medications are different: ticagrelor is administered as a pre-treatment medication prior to diagnostic angiography while prasugrel is given after coronary anatomy has been assessed by angiography (No advantage has been observed when prasugrel is used as pretreatment) [7].  The authors of this trial (ISAR-REACT 5) looked to compare ticagrelor vs prasugrel in patients with ACS to evaluate efficacy and safety.