The Skeptics Guide to Emergency Medicine

Date: August 18th, 2020 Guest Skeptic: Dr. Corey Heitz is an emergency physician in Roanoke, Virginia. He is also the CME editor for Academic Emergency Medicine. Reference: Carpenter et al. Diagnosing COVID-19 in the Emergency Department: A Scoping Review of Clinical Exam, Labs, Imaging Accuracy and Biases. AEM August 2020 Case: You are working in the emergency department during the COVID-19 outbreak, and you see a patient with oxygen saturations of 75% on room air, a fever, and a cough. Upon review of systems, you learn that she lost her sense of taste about two days ago. Your hospital performs COVID reverse transcriptase polymerase chain reaction (rt-PCR) nasal swabs on suspected patients, so you order this test and await the results.  Background: In early 2020, a pandemic broke out with origins thought to be in the Wuhan region of China. A novel coronavirus, SARS-Co-V-2, commonly called COVID-19, rapidly spread around the world, overwhelming hospitals and medical systems, causing significant morbidity and mortality. The speed with which the outbreak occurred made identification of cases difficult, as the disease exhibited a variety of symptoms, and testing lagged spread. The US Federal Drug Administration (FDA) allowed for emergency development and use of rt-PCR assays, and dozens of companies released assay kits. Mask4All Debate I consciously have tried to avoid contributing to the COVID-19 information overload. However, I did do a CAEP Town Hall on therapeutics (SGEM Xtra: Be Skeptical) with Dr. Sean Moore and a friendly debate on mandatory universal masking in public with Dr. Joe Vipond (SGEM Xtra: Masks4All). This review discusses the diagnostic accuracy of rt-PCR for COVID-19, as well as signs, symptoms, imaging, and other laboratory tests. Clinical Question: What is the diagnostic accuracy of history, clinical examination, routine labs, rt-PCR, immunology tests and imaging tests for the emergency department diagnosis for COVID19?  Reference: Carpenter et al. Diagnosing COVID-19 in the Emergency Department: A Scoping Review of Clinical Exam, Labs, Imaging Accuracy and Biases. AEM August 2020 Population: Original research studies describing the frequency of history, physical findings, or diagnostic accuracy of history/physical findings, lab test, or imaging tests for COVID-19 Intervention: None Comparison: None Outcome: Diagnostic accuracy (sensitivity, specificity, and likelihood ratios) Dr. Chris Carpenter This is an SGEMHOP episode which means we have the lead author on the show.  Dr. Chris Carpenter is Professor of Emergency Medicine at Washington University in St. Louis and a member of their Emergency Medicine Research Core. He is a member of the SAEM Board of Directors and the former Chair of the SAEM EBM Interest Group and ACEP Geriatric Section. He is Deputy Editor-in-Chief of Academic Emergency Medicine where he is leading the development of the "Guidelines for Reasonable and Appropriate Emergency Care" (GRACE) project. He is also Associate Editor of Annals of Internal Medicine’s ACP Journal Club and the Journal of the American Geriatrics Society, and he serves on the American College of Emergency Physician's (ACEP) Clinical Policy Committee. Dr. Carpenter also wrote the book on diagnostic testing and clinical decision rules. Authors’ Conclusions: “With the exception of fever and disorders of smell/taste, history and physical exam findings are unhelpful to distinguish COVID-19 from other infectious conditions that mimic SARS-CoV-2 like influenza. Routine labs are also non-diagnostic, although lymphopenia is a common finding and other abnormalities may predict severe disease. Although rRT-PCR is the current criterion standard, more inclusive consensus-based criteria will likely emerge because of the high false-negative rate of polymerase chain reaction tests. The role of serology and CT in ED assessments remains undefined.”

Date: July 20th, 2020 Guest Skeptic: Professor Simon Carley is Creator, Webmaster, owner and Editor in Chief of the St. Emlyn’s blog and podcast. He is Professor of Emergency Medicine at Manchester Metropolitan University and a Consultant in adult and paediatric Emergency Medicine at Manchester Foundation Trust. Dr. Carley is even verified on twitter as @EMManchester. Reference: Carley et al. Evidence-based medicine and COVID-19: what to believe and when to change. BMJ_EMJ July 2020 This is an SGEM Xtra episode. It was great to have one of the giants of the FOAMed world back on the SGEM. The last time Dr. Carely was on was on SGEM#148. The bottom line from that episode on skin glue for peripheral intravenous lines was: "Skin glue does appear to decrease the failure rate of IVs in patients admitted to hospital from the ED at 48 hours. We do not know if this is a good idea for all ED patients and we do not know the true effect size, but for high stakes cannulas that we really want to stay in this intervention should be considered.”  This SGEM Xtra is based on a wonderful article by Simon Carley, Daniel Horner, Rick Body, and Kevin Mackway-Jones published in the BMJ-Emergency Medicine Journal. The article was titled: Evidence-based medicine and COVID-19: what to believe and when to change. Simon and I discussed the what inspired him to write this article. It was great that it started with a definition of evidence-based medicine (EBM). They used the one proposed by Dr. David Sackett in 1996: “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients" We gave a shout out to our friends Dr. Justin Morgenstern (First10EM) and Dr. Casey Parker (Broome Doc) on their recent podcast called EBM 2.0 with guest Dr. Senthi. It is important to remember the literature is just one of three pillars of EBM. There are many problems and limitations with medical research. This includes the dreaded p-value (dichotomization), biases (something that systematically moves us away from the "truth"), and the replication crisis. However, the other two pillars of EBM are equally as important. That includes the clinician’s judgment and the patient’s values and preferences. The first section of the article was about knowledge translation (KT) during the COVID19 pandemic. Listeners know the the SGEM is trying to cut the KT window down from over 10 years to less than one year using the power of social media. There is a study that quantify the KT gap being 17 years for 14% of high-quality, clinically relevant information to reach the patient (Morris, Wooding and Grant JRSM 2011). We then went on to talk about the precipitous decisions that are being made during COVID19 and give some examples. This is not a unique situation to a pandemic. There is something called intervention bias. This is the desire by the "medical community to intervene, whether it is with drugs, diagnostic tests, non-invasive procedures, or surgeries, when not intervening would be a reasonable alternative." Dr. Jerome Hoffman The concept of intervention bias reminds me of one of my favourite ideas I learned from the Legend of EM, Dr. Jerry Hoffman, "don’t just do something, stand there". There is a great fantastic article on this idea by Keijzers et al 2018. Many of us have been asked many questions during the pandemic. Some probably have been asked "what would you want if you got COVID19" or "what's the harm in trying" something to treat this terrible new infectious deadly disease? We talked about some of these questions and Simon listed some of the potential harms of just trying without good evidence including: distraction, false hope, suboptimal use of resources, misunderstanding of patient trajectory and loss of equipoise. It is also known that harms are systematically underreported in research studies (Saini et al BMJ 2014). Four Strategies As A Way Forward

Date: July 13th, 2020 Guest Skeptic: Dr. Justin Morgenstern is an emergency physician and the creator of the excellent #FOAMed project called First10EM.com. He has a great new blog post about increasing diversity in medicine using something called the BSAP approach and an interesting Broome Doc podcast with Dr. Casey Parker called EBM 2.0.   Reference: Ebell et al. Accuracy of Signs and Symptoms for the Diagnosis of Community‐acquired Pneumonia: A Meta‐analysis. AEM July 2020 Case: A 67-year-old woman with no previous health problems presents with fever, cough, and myalgias. You are working with a medical student on their very first rotation, and you want to spend some time teaching them about the history and physical exam. However, being an evidence-based medicine enthusiast, you wonder what aspects of the patient’s presentation are going to be truly helpful in making a diagnosis.  Background: Depending on the time of year, fever and cough can be one of the most common presentations seen in the emergency department. It is important not to miss pneumonia in the sea of viral illnesses. We have covered various aspects of this issue a number of times on the SGEM: SGEM#287: Difficult to Breathe – It Could Be Pneumonia SGEM#286: Behind the Mask – Does it need to be an N95 mask? SGEM#263: Please Stop, Prescribing – Antibiotics for Viral Acute Respiratory Infections SGEM#216: Pump It Up – Corticosteroids for Patients with Pneumonia Admitted to Hospital SGEM#120: One Thing or Two for Community Acquired Pneumonia? Antibiotic overuse is a significant problem, and ordering chest x-rays (CXR) on everyone is inefficient, expensive, and adds potentially unnecessary risk from radiation. Thus, it is important to know how accurate the history and physical exam is for identifying patients with pneumonia. A prior meta-analysis demonstrated that the combination of normal vital signs and normal lung exam effectively rules out pneumonia (Marchellow eat al JABFM 2019), and that a physician’s overall clinical impression is moderately accurate (Dale et al BrJGP 2019). However, there has not been a meta-analysis looking at the evidence for individual signs and symptoms for pneumonia in the last decade. Clinical Question: What is the accuracy of individual signs and symptoms for diagnosing community acquired pneumonia? Reference: Ebell et al. Accuracy of Signs and Symptoms for the Diagnosis of Community‐acquired Pneumonia: A Meta‐analysis. AEM July 2020 Population: Adolescents and adults presenting with symptoms of respiratory infection or clinically suspected pneumonia in the outpatient setting Intervention: Any clinical sign or symptom (including vital signs) for pneumonia Comparison: Outcome: Radiologically confirmed pneumonia (using CXR as the gold standard) Dr. Mark Ebell This is an SGEMHOP episode which means we have the lead author on the show.  Dr. Mark Ebell is a Family Physician and Professor at the University of Georgia in Athens. He is a co-founder of POEMs, editor-in-chief of Essential Evidence, deputy editor of American Family Physician, and co-host of the podcast Primary Care Update and POEM of the Week.   Authors’ Conclusions: “While most individual signs and symptoms were unhelpful, selected individual signs and symptoms are of value for diagnosing CAP. Teaching and performing these high value elements of the physical examination should be prioritized, with the goal of better targeting chest radiographs and ultimately antibiotics. Quality Checklist for Systematic Review Diagnostic Studies: The diagnostic question is clinically relevant with an established criterion standard. Unsure. The search for studies was detailed and exhaustive. Yes The methodological quality of primary studies were assessed for common forms of diagnostic research bias. Yes The assessment of studies were reproducible. Yes There was low heterogeneity for estimates of sensitivit...

Date: June 30th, 2020 Guest Skeptic: Professor Daniel Fatovich is an emergency physician and clinical researcher based at Royal Perth Hospital, Western Australia. He is Head of the Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research; Professor of Emergency Medicine, University of Western Australia; and Director of Research for Royal Perth Hospital. Reference: Alper et al. Thrombolysis with alteplase 3–4.5 hours after acute ischaemic stroke: trial reanalysis adjusted for baseline imbalances. BMJ Evidence Based Medicine 2020 Case: A 65-year-old man arrives from home to the emergency department by EMS with right-sided weakness beginning three hours prior. Advance neuroimaging demonstrates he does not qualify for endovascular clot retrieval. He has an NIHSS score of 11 and no contra-indications for systemic thrombolysis. Background: Thrombolysis for acute ischemic stroke has to be one of, if not the most, controversial subjects of my career. The debate dates back to the classic NINDS paper published in the NEJM in 1995. We reviewed that publication with Dr. Anand Swaminathan on SGEM#70. Some people might argue that it’s less relevant now because of endovascular clot retrieval, but it’s a living example of issues with research methodology, critical appraisal, bias, conflicts of interest, etc. These elements are continuously present in medicine – look at all the COVID-19 literature – made worse by the preprint archives of non-peer reviewed papers. Thrombolysis in acute ischaemic stroke. The Lancet 2012 Truth, thinking and thrombolysis. EMA 2016 Response from Prof. Fatovich to Stroke thrombolysis: Leaving the past, understanding the present and moving forward. EMA 2013 The “Fragility” of Stroke Thrombolysis. TMJ 2020 Believing is seeing: Stroke thrombolysis remains unproven after the third international stroke trial (IST-3). EMA 2012 Don't Just Do Something, Stand There! The Value and Art of Deliberate Clinical Inertia. EMA 2018 Dr. Jerome Hoffman It was Dr. Jerome Hoffman that introduced me to this issue and was a basis of my skepticism. I used to think if the study was published in a high-impact journal it must be true. His mentorship and teaching are why I consider Dr. Hoffman a legend of emergency medicine. We have covered the issue of thrombolysis for acute ischemic stroke a number of times on the SGEM. I have also published a review on the topic of thrombolytics for stroke beyond three hours (Carpenter et al JEM 2011). More recently, I published a pro/con debate on the subject with Dr. Eddy Lange looking at the evidence (Milne et al CJEM 2020). SGEM#29: Stroke Me, Stroke Me SGEM Xtra: Walk of Life SGEM Xtra: No Retreat, No Surrender SGEM#269: Pre-Hospital Nitroglycerin for Acute Stroke Patients? SGEM#290: Neurologist Led Stroke Teams – Working 9 to 5 There has been a lot of skepticism around thrombolysis in acute ischemic stroke since the beginning. A reanalysis of the NINDS data by Dr. Hoffman and Dr. Schriger was published in Annals of Emergency Medicine in 2009. At least one other reanalysis has questioned the 2009 reanalysis (Saver et al Ann Emerg Med 2010).  Thus, there is a degree of uncertainty in the NINDS-II results. The major takeaway from this reanalysis was that the baseline imbalance in stroke severity led to the difference in outcomes. If tPA really works, we should see a bigger change in the NIHSS score in the tPA group vs. the placebo group. Yet the difference was 0.0. People can forget that a clinical trial has internal validity if and only if the imbalance between groups, bias in the assessment of outcome, and chance, have been excluded as possible explanations for the difference in outcomes. Baseline imbalance is a recurring theme. So, replication studies are hugely important. It was the NINDS trial that changed guidelines and practices to provide thrombolysis in patients with stroke symptoms less ...

Date: June 27th, 2020 I had the pleasure of presenting at the Northern Constellation Faculty Development Conference 2020 on May 8th. This was the 9th annual conference put on by the Northern School of Medicine (NOSM). Dr. Sarah McIsaac was kind enough to invite me to present at the Northern Constellation Conference. She is an anesthesiologist/intensivist at Health Sciences North, Assistant Professor and Medical Director of Faculty Development for NOSM. This presentation is available to watch on the SGEM YouTube Channel or listened to on the SGEM podcast. All of the slides can also be downloaded from this link. I was asked to give a presentation about evidence-based medicine (EBM), critical appraisal and relate it back to COVID. Certainly there has been a lot of information coming out on the topic and it can seem like you are drinking from a fire hose at times. The presentation was broken down into three parts: Evidence-Based Medicine (EBM), critical appraisal and the Peltzman Effect (risk compensation): Part I: Evidence-Based Medicine (EBM) It is always good to define terms at the beginning of any discussion. I used the original definition of EBM given by Dr. David Sackett: “The conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.”  (Sackett et al BMJ 1996) There are three pillars to EBM than can be represented in a Venn diagram. People often make the mistake of thinking that EBM is just about the scientific literature. This is not true. The evidence informs and guides our care but it does not dictate our care. EBM also needs your clinical judgement based on your experience. We also need to engage with patients and ask them about their preferences and values. These three components make up EBM: The literature, our judgement and the patients values.  There is a hierarchy to the evidence and we want to use the best evidence so patients get the best care.  The hierarch is usually described as a pyramid with the lowest form of evidence being expert opinion and the highest level being a systematic review. This is an over simplification of the levels of evidence. A good randomized control trial (RCT) can be more informative than a systematic review (SR) that only includes low quality study (GIGO - garbage in, garbage out). There are arguments against EBM and it does have limitations. One that is often pointed out is that it would be unethical to do an RCT on harm. The 2003 Smith and Pell parachute trial is usually pointed to as an example (BMJ 2003). This could be considered a straw man argument because most medical practices are not parachutes (Hayes et al CMAJ 2018). In addition, a randomized control trial has been done assessing the efficacy of parachutes to prevent gravitationally related morbidity and mortality and was reviewed on SGEM#284. Five alternatives to EBM were discussed (Adapted from Isaacs and Fitzgerald BMJ 1999) : Eminence-Based Medicine (EmBM): The more senior the colleague, the less importance he or she placed on the need for anything as mundane as evidence. Experience, it seems, is worth any amount of evidence. These colleagues have a touching faith in clinical experience, which has been defined as ‘‘making the same mistakes with increasing confidence over an impressive number of years.” The eminent physician’s white hair and balding pate are called the “halo” effect. Vehemence-Based Medicine (VBM): The substitution of volume for evidence is an effective technique for brow beating your more timorous colleagues and for convincing relatives of your ability. Eloquence-Based Medicine (ElBM): The year round suntan, silk tie, Armani suit, and tongue should all be equally smooth. Sartorial elegance and verbal eloquence are powerful substitutes for evidence. Nervousness-Based Medicine (NBM): Fear of litigation is a powerful stimulus to over investigation and over trea...

Date: June 14th, 2020 Guest Skeptic: Dr. Dennis Ren is a Pediatric Emergency Medicine fellow at Children’s National Hospital in Washington, DC. Reference: Kuppermann et al. A Clinical Prediction Rule to Identify Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial Infections. JAMA Pediatr. 2019. Case: A 5-week-old full term female presents to the Emergency Department (ED) for fever with rectal temp of 100.6F (38.1C). Her mother states that she has been fussier today. She also seems “congested” and is not feeding as well. She continues to have the usual number of wet diapers. The mother is worried about her sick baby. She wants to know if they will need a spinal tap, be placed on antibiotics or will need to be admitted to the hospital? Background: Fever without source in infants less than three months old represents a significant diagnostic dilemma for clinicians. Several criteria have been developed previously, including the Rochester (Jaskiewicz et al 1994), Boston (Baskin et al 1992) and Philadelphia (Baker et al 1993) criteria to help clinicians stratify the risk of serious bacterial infections (SBI). Febrile infants commonly present to the emergency department. It is estimated 8-13% may have SBI that may include urinary tract infections, bacteremia, and bacterial meningitis. It is difficult to identify which infants have SBI by clinical examination alone. There are serious consequences from missed SBI. Workup for SBI may include lumbar puncture, antibiotics, and hospitalization. These criteria (Rochester, Boston and Philadelphia) could be considered out of date in our current era of vaccinations. We covered a new protocol called the Step-by-Step approach on SGEM#171. The “Step-by-Step”rule combined both clinical factors and laboratory factors in febrile infants aged 22 to 90 days. It had a sensitivity of 98.9% to detect all SBIs. The SGEM Bottom Line #171: “If you have availability of serum procalcitonin measurement in a clinically-relevant time frame, the Step-by-Step approach to fever without source in infants 90 days old or younger is better than using the Rochester criteria or Lab-score methods. With the caveat that you should be careful with infants between 22-28 days old or those who present within two hours of fever onset.” It is important to balance the consequences of missing an SBI with performing unnecessary procedures (lumbar punctures), exposing infants to antibiotics, and prolonging hospital stay. The new study proposes a novel way of identifying low risk febrile infants 29-60 days based on three objective lab criteria. Clinical Question: Can a clinical prediction rule (tool) using laboratory data identify febrile infants under 60 days of age who are at low risk for serious bacterial infection (urinary tract infection, bacteremia, and bacterial meningitis) and reduce unnecessary lumbar punctures, antibiotic exposure, and hospitalization? Reference: Kuppermann et al. A Clinical Prediction Rule to Identify Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial Infections. JAMA Pediatr. 2019. Population: Febrile infants <60 days of age who look good and whose blood cultures were obtained to rule out SBI (fever was a rectal temperature of at least 38C) Excluded: Infants who looked critically ill, had antibiotics in the previous 48 hours, history of prematurity (≤36 weeks’ gestation), pre-existing medical conditions, indwelling devices or soft tissue infections. Intervention: Derivation and validation of accurate clinical prediction rule (tool) for infants at low risk of SBI using a negative urinalysis, ANC <4,090/uL, and procalcitonin 1.71 ng/ml or less Comparison: Pre-existing algorithms combining subjective clinical findings and lab markers Outcome: Accuracy of the prediction rule to identify infants at low risk for SBI (sensitivity, specificity, negative prediction value and negative likelihood ratio).

Date: June 9th, 2020 Guest Skeptic: Dr. Chris Bond is an Emergency Medicine Physician and Assistant Professor at the University of Calgary. He is also an avid FOAM supporter/producer through various online outlets including TheSGEM. Reference: Westafer et al. Provider Perspectives on the Use of Evidence-based Risk Stratification Tools in the Evaluation of Pulmonary Embolism: A Qualitative Study. AEM June 2020. Case: A 63-year-old female presents to the emergency department (ED) with chest pain for the past eight hours. It is pleuritic, worse with certain movements and associated with some shortness of breath. Her vital signs are within normal limits and oxygen saturation is 95% on room air. An ECG, chest x-ray and troponin are all within normal limits and she has no calf swelling or tenderness. She does have a previous history of DVT/PE 12 years ago after returning from a transatlantic flight. She has also been doing more work around the house and lifting the past few weeks because of COVID and has some mild chest wall tenderness on palpation. The remainder of her Wells’ criteria are unremarkable. How do you proceed in evaluating this patient for pulmonary embolism (PE)? Background: Pulmonary embolism is a common ED diagnosis with an estimated 1-2% of all patients presenting to United States EDs undergoing CT for suspected PE (1). However, less than 10% of these scans show PE (2-4). We have covered the topic of PE frequently on the SGEM. SGEM#51: Home (Discharging Patients with Acute Pulmonary Emboli Home from the Emergency Department) SGEM#118: I Hope you Had a Negative D-dimer (ADJUST PE Study) SGEM#126: Take me to the Rivaroxaban – Outpatient treatment of VTE SGEM#163: Shuffle off to Buffalo to Talk Thrombolysis for Acute Pulmonary Embolism SGEM#219: Shout, Shout, PERC Rule Them Out SGEM#277: In the Pregnant YEARS – Diagnosing Pulmonary Embolism SGEM#282: It’s All ‘bout that Bayes, ‘Bout that Bayes- No Trouble – In Diagnosing Pulmonary Embolism There are multiple validated risk stratification tools to evaluate for PE and reduce inappropriate testing, including the Pulmonary Embolism Rule Out Criteria (PERC), Wells’score, YEARS algorithm and D-Dimer testing (5-7). There have also been more recent adjustments to D-Dimer threshold based on clinical probability as calculated by a trichotomized Wells score (8). Unfortunately, clinician uptake of these validated tools has been incomplete, with some ED studies finding 25% of patients who warranted no laboratory or imaging studies still received testing (4, 9-12.) Low-value testing increases costs, ED length of stay and subjects patients to unnecessary ionizing radiation and risk of anaphylaxis from intravenous contrast dye (13-14).  Moreover, false positives CT scans are common and estimated to be between 10-26%, resulting in unnecessary anti-coagulation and risk to patients (15-17). This can ultimately lead to over-testing, over-diagnosing and over-treating. The American Board of Internal Medicine (ABIM) started the project called Choosing Wisely to try and mitigate this problem. The SGEM looked at this imitative on an SGEM Xtra. The American College of Emergency Physicians (ACEP) is part of the Choosing Wisely program and has a number of recommendations. One of the recommendations is on CT scans for ruling out PE. They have encouraged physicians to” “Avoid CT pulmonary angiography in emergency department patients with a low-pretest probability of pulmonary embolism and either a negative Pulmonary Embolism Rule-Out Criteria (PERC) or a negative D-dimer.” ACEP 2014 The Right Care Alliance (RCA) was established in 2015. Certainly, patients at times need less care but they also at times need more care. This group’s goal is to advocate for the goldilocks zone of care, not too much but also not too little (SGEM Xtra). Clinical Question: What are the barriers and facilitators to the uptake of evidence-based practice in the ED ev...

Date: June 2nd, 2020 Reference: Permpikul et al. Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER): A Randomized Trial. Respir Crit Care Med 2019. Guest Skeptic: Dr. Max Hockstein trained as an Emergency Medicine physician at University of Texas Southwestern and is finishing his Intensive Care fellowship at Emory. Max is then going to Georgetown to be an attending in both EM and ICU. Case: It’s another day in your emergency department (ED).  Six hours into your shift, you finish dispo’ing the “really quick sign-out” from the night before.  The triage nurse places a 61 year-old-man with fever, hypotension, cough into the smallest room in the ED.  You scan through the EMR and see the blood pressure is 60/40.  Being an astute emergency physician, you surmise that this value is one number column short of normal.  It’s uncomfortably low – is it time to start a norepinephrine infusion? Background: I think we have covered sepsis more often than any other topic on the SGEM. It was the landmark paper published 19 years ago by Dr. Emanuel Rivers on early goal directed therapy in the treatment of severe sepsis and septic shock that sensitized the medical community (Rivers et al NEJM 2001). SGEM#44: Pause (Etomidate and Rapid Sequence Intubation in Sepsis) SGEM#69: Cry Me A River (Early Goal Directed Therapy) ProCESS Trial SGEM#90: Hunting High and Low (Best MAP for Sepsis Patients) SGEM#92: ARISE Up, ARISE Up (EGDT vs. Usual Care for Sepsis) SGEM#113: EGDT – ProMISe(s) ProMISe(s) SGEM#174: Don’t Believe the Hype – Vitamin C Cocktail for Sepsis SGEM#207: Ahh (Don’t) Push It – Pre-Hospital IV Antibiotics for Sepsis. One of the goals of the early treatment of septic shock is to restore end-organ perfusion.  Significant effort has been placed on the administration of IV crystalloids to address concerns for hypovolemia in septic shock.  However, it has become evident that patients are often over-resuscitated with IV fluids which adversely impacts outcome.  As such, the idea of the early norepinephrine administration to restore end-organ perfusion in septic shock has been suggested. Monitor-Oriented Outcomes (MOOs) Trials that examine outcomes in shock, historically, have examined two types of outcomes: patient-oriented outcomes (POOs) and monitor-oriented outcomes (MOOs).  POOs focus on occurrences that matter to patients while MOOs do not.  Many trials examining vasoactive infusions use MOOs as an endpoint(s) targeted to the medication’s intended use (i.e. increase in MAP).  Much like titrating a therapy to an outcome, MOOs are frequently easier to monitor (ex: blood pressure, heart rate, mean arterial pressure, oxygen saturation, etc). An old adage in resuscitating the hypotensive patient “first, fill the tank” has gone largely unchallenged over the past several years.  Oddly enough, however, shortening the duration of shock time-to-shock-resolution hasn’t translated to any measurably better outcomes. Clinical Question: Does starting norepinephrine earlier in septic shock lead to earlier shock control? Reference: Permpikul et al.Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER): A Randomized Trial. Respir Crit Care Med 2019. Population: Adult patients (18 year of age and older) presenting to the ED with a mean arterial pressure (MAP) < 65 mmHg. Infection needed to be the suspected cause of the hypotension. Patients also had to meet 2012 surviving sepsis diagnostic criteria. Exclusions: Acute cardiac and cerebral conditions, pulmonary edema, status asthmaticus, gastrointestinal bleeding, pregnancy, burn, drug overdose, trauma, need immediate surgery and cancer. Intervention: Early norepinephrine adjusted to 0.05ug/kg/min for 24hrs plus usual care Comparison: Placebo plus usual care (intravenous fluids, appropriate antibiotics, source control and organ support as directed by the attending physician) Outcome:

Date: May 29th, 2020 Reference: Erramouspe et al. Mortality and Complication Rates in Adult Trauma Patients Receiving Tranexamic Acid: A Single-center Experience in the Post–CRASH-2 Era. AEM May 2020 Guest Skeptic: Dr. Corey Heitz is an emergency physician in Roanoke, Virginia. He is also the CME editor for Academic Emergency Medicine. Case: A 44-year-old male presents to your level 1 trauma center by EMS after a motor vehicle collision. He is hypotensive and tachycardic. You suspect abdomen and pelvic trauma and calculate his injury severity score (ISS) to be 22. Your hospital protocol is to give tranexamic acid (TXA) 1g IV over 10 minutes followed by a 1g infusion over eight hours. You wonder what his over-all chance of dying or developing a thromboembolic event when treated with TXA. Background: TXA is synthetic derivative of lysine that controls bleeding by inhibiting fibrinolysis and thus stabilizing clots that are formed.  We have covered TXA as a treatment modality a number of times on the SGEM. The evidence for TXA providing a patient-oriented outcome (POO) has been mixed. It seems to work for epistaxis (SGEM#53 and SGEM#210), failed to demonstrate a decrease in all-cause mortality in post-partum hemorrhage (SGEM#214), and did not result in an improved neurologic outcome in hemorrhagic strokes (SGEM#236). REBEL EM has looked at using TXA for those conditions plus a few others (we will include a table in the show notes). It is unclear if it provides a benefit for gastrointestinal bleeds (GIB). Nebulized TXA shows promise for both post-tonsillectomy bleeding and hemoptysis. However, better studies are needed to confirm these observations. Dr. Anand Swaminathan and I covered the classic CRASH-2 Trial (SGEM#80). This study published in 2010 showed an absolute mortality reduction of 1.5% in adult trauma patients giving a number needed to treat to prevent one death of 67 (Shakur et al. Lancet 2010) CRASH-3 was a well-designed, large, multi-centred randomized placebo controlled trial published in October 2019 (The Lancet). It asked if TXA had a mortality benefit in patients with isolated head trauma (SGEM#270)? While there was a suggestion of benefit in a secondary subgroup analysis, the primary outcome demonstrated no statistical difference in head-injury related mortality with TXA compared to placebo (18.5% TXA vs. 19.8% placebo, RR 0.94 [95% CI 0.86 to 1.02]). One of the limitations to both CRASH-2 and CRASH-3 was the external validity. The majority of sites involved were in middle to low income countries. CRASH-3 had one Canadian site and the USA had no participating centres. Transfusion practices and identification of adverse events may differ in developing countries compared to the USA. Clinical Question: What is the mortality and thromboembolic events in adult trauma patients receiving TXA an American Level 1 Trauma Center? Reference: Erramouspe et al. Mortality and Complication Rates in Adult Trauma Patients Receiving Tranexamic Acid: A Single-center Experience in the Post–CRASH-2 Era. AEM May 2020 Population: Adults (18 years or older) who received TXA after an acute traumatic injury Excluded: Patients who received oral TXA, received it for elective surgery or nontrauma indications, received TXA 8 hours or longer after the injury, and patients with cardiac arrest at time of ED arrival. Intervention: TXA 1g IV over 10 minutes and maintenance infusion of 1g IV over 8 hours Comparison: None Outcome: Primary Outcome: In-hospital mortality Safety Outcome: Thromboembolic event within 28 day Dr. Erramousepe This is an SGEMHOP episode and we are pleased to have both the lead author and senior author on the episode. Dr. Joaquin Erramouspe is a medical doctor, who finished medical school in Uruguay, moved to the USA for further training and research, and now, is working as a researcher at Queensland University of Technology while obtaining his mas...

Date: May 19th, 2020 Reference: Yang P et al. Endovascular thrombectomy with or without intravenous alteplase in acute stroke. NJEM 2020. Guest Skeptic: Dr. Anand Swaminathan is an Assistant Professor of Emergency Medicine at St. Joseph’s Regional Medical Center in Paterson, NJ. Managing editor of EM:RAP and Associate Editor at REBEL EM. Case: A 53-year-old previously healthy man presents with 1.5 hours of right sided weakness as well as slurred speech. A rapid bedside assessment gives you a National Institute of Health Stroke Score/Scale (NIHSS) of 9 and you are concerned about a large vessel occlusion (LVO) based on the high NIHSS as well as the presence of both an upper extremity drift and the speech abnormality. A non-contrast CT shows no evidence of intracranial hemorrhage. A CT angiogram plus CT perfusion demonstrate a clot in the left proximal middle cerebral artery (MCA) with a small infarcted area and a large penumbra. Based on your institution’s current guidelines, the patient is a candidate for endovascular therapy, but they are also within the current window for the administration of alteplase. You wonder if you should give the alteplase while waiting for your neurointerventional team? Background: The issue of thrombolytics for stroke has been debated since at least 1995. This is the year that the famous NINDS trial was published. We cover this as an SGEM classic that all EM physicians should know about on SGEM#70. Our bottom line was that we were skeptical thrombolysis has a net patient-oriented benefit for acute ischemic strokes. We have covered this issue of thrombolysis for acute ischemic stroke a number of times on the SGEM SGEM#29: Stroke Me, Stroke Me SGEM Xtra:Thrombolysis for Acute Stroke SGEM#290: Neurologist Led Stroke Teams – Working 9 to 5 You also had the Legend of Emergency Medicine, Dr. Jerome Hoffman on to reflect upon the last 25 years and the thrombolysis for acute ischemic stroke debate (No Retreat, No Surrender) I also invited my EBM friend, Dr. Eddy Lang onto the SGEM to discuss his perspective on the issue (SGEM Xtra). This led to a pro/con publication in the Canadian Journal of Emergency Medicine (CJEM) tPA should be the initial treatment in eligible patients presenting with an acute ischemic stroke (Milne et al CJEM April 2020). 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 LVOpresenting within sixhours 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 the below workflow: 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 thrombolytics plus endovascular therapy (Phan 2017, Rai 2018). There is a clear need for further research into systemic thrombolytics dosing and use. Clinical Question: Is endovascular therapy alone non-inferior to endovascular therapy plus systemic thrombolytics in the treatment of patients with large vessel occlusion strokes presenting within 4.5 hours of onset? Reference: Yang P et al. Endovascular thrombectomy with or without intravenous alteplase in acute stroke. NJEM 2020. Population: Adult patients (18 years of age or older) presenting within 4.5 hours of ischemic stroke symptom onset and with cerebral vascular occlusion on CT angiography of the intracrania...