Emergency Medical Minute

In the past two weeks, warnings, questions, and misinformation concerning COVID-19 and NSAID use have been spreading...no pun intended..virally. The pace of this evolving pandemic and the equally quick pace of the news and social media news cycle have meant that information and misinformation travel equally fast. Today we bring to you the story of how a letter in The Lancet led to a world of confusion. Host: Elizabeth Esty, MD Research By: Elizabeth Esty & Nathan Novotny Sound Editing By: Stephen Bahmani Time Stamps: 0:00 - COVID-19 Statistics 2:55 - The Lancet Letter: What Started the Rumor 4:10 - ACE Inhibitors & ARB's 5:00 - What The Lancet Letter Got Wrong 6:25 - Treatment of HTN and DM in China vs. the U.S. 9:13 - Do ACE Inhibitors Actually Increase ACE-2 Expression? 11:00 - The French Ministry of Health and Their Warning About NSAIDs 14:09 - Misinformation in the Age of COVID-19 15:09 - Potential Harms of Tylenol Use 16:11 - The Need for High-Quality Science to Overcome COVID-19 References: Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? The Lancet Respiratory Medicine. March 2020:S2213260020301168. doi:10.1016/S2213-2600(20)30116-8 Kane S. Ibuprofen - Drug Usage Statistics, ClinCalc DrugStats Database. ClinCalc DrugStats Database. https://clincalc.com/DrugStats/Drugs/Ibuprofen. Published December 23, 2019. Accessed March 30, 2020. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. March 2020. doi:10.1016/j.cell.2020.02.052 Lu J, Lu Y, Wang X, et al. Prevalence, awareness, treatment, and control of hypertension in China: data from 1·7 million adults in a population-based screening study (China PEACE Million Persons Project). The Lancet. 2017;390(10112):2549-2558. doi:10.1016/S0140-6736(17)32478-9 Wang Zengwu, Chen Zuo, Zhang Linfeng, et al. Status of Hypertension in China. Circulation. 2018;137(22):2344-2356. doi:10.1161/CIRCULATIONAHA.117.032380 Hu C, Jia W. Diabetes in China: Epidemiology and Genetic Risk Factors and Their Clinical Utility in Personalized Medication. Diabetes. 2018;67(1):3-11. doi:10.2337/dbi17-0013 Yuan H, Li X, Wan G, et al. Type 2 diabetes epidemic in East Asia: a 35-year systematic trend analysis. Oncotarget. 2018;9(6). doi:10.18632/oncotarget.22961 Woo KS, Nicholls MG. High prevalence of persistent cough with angiotensin converting enzyme inhibitors in Chinese. Br J Clin Pharmacol. 1995;40(2):141-144. Chen X, Hu W, Ling J, et al. Hypertension and Diabetes Delay the Viral Clearance in COVID-19 Patients. medRxiv. March 2020:2020.03.22.20040774. doi:10.1101/2020.03.22.20040774 Perico L, Benigni A, Remuzzi G. Should COVID-19 Concern Nephrologists? Why and to What Extent? The Emerging Impasse of Angiotensin Blockade. NEF. March 2020:1-9. doi:10.1159/000507305 Qiao Y, Shin J-I, Chen TK, et al. Association Between Renin-Angiotensin System Blockade Discontinuation and All-Cause Mortality Among Persons With Low Estimated Glomerular Filtration Rate. JAMA Intern Med. March 2020. doi:10.1001/jamainternmed.2020.0193 The Local. UPDATE - Coronavirus: French health minister and WHO issue warning over taking anti-inflammatories. https://www.thelocal.fr/20200314/coronavirus-french-health-minister-issues-warning-over-anti-flammatories. Published March 14, 2020. Accessed March 30, 2020. ScienceAlert. Updated: WHO Now Doesn't Recommend Avoiding Ibuprofen For COVID-19 Symptoms. https://www.sciencealert.com/who-recommends-to-avoid-taking-ibuprofen-for-covid-19-symptoms. Accessed March 30, 2020. European Medicines Agency. Coronavirus disease (COVID-19). https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19#advice-on-using-non-steroidal-anti-inflammatory-medicines-such-as-ibuprofen--section. Published March 18, 2020. U.S. Food and Drug Administration. FDA advises patients on use of non-steroidal anti-inflammatory drugs (NSAIDs) for COVID-19. https://www.fda.gov/drugs/drug-safety-and-availability/fda-advises-patients-use-non-steroidal-anti-inflammatory-drugs-nsaids-covid-19. Published March 19, 2020. BBC Reality Check team and BBC Monitoring. Coronavirus and ibuprofen: Separating fact from fiction. BBC News. https://www.bbc.com/news/51929628. Published March 17, 2020. Mosbergen D. Tylenol Overdose Risk Is Staggering; Acetaminophen Safeguards Remain Insufficient: Report. HuffPost. https://www.huffpost.com/entry/tylenol-overdose_n_3976991. Published September 24, 2013.

Contributor: Dylan Luyten, MD Educational Pearls: After you diagnose a pulmonary embolism (PE) via CT or VQ scan, we need to categorize the PE as massive, sub-massive, or just PE to dictate treatment. Massive PE: shock with hypotension due to an embolism, and the treatment of choice is thrombolysis with IV tPA with anticoagulation after lysis. Catheter thrombolysis is not used in the hemodynamically unstable patient but can be done after they are stable. Sub-massive: signs of right heart strain/failure but hemodynamically stable. This can be EKG changes, positive biomarkers, or imaging findings. These patients can be treated with IV heparin as there may benefit from catheter directed thrombolysis which has been shown to lead to better functional outcomes. Everything else can be stratified to determine whether inpatient even outpatient treatment is necessary Pulmonary Embolism Severity Index (PESI) or Hestia criteria and can help determine if the patient is better suited for in or outpatient management. Non massive or sub-massive PEs are treated with heparin/Lovenox bridged to Warfarin, a factor Xa inhibitor (ex. Xarelto), or direct oral anticoagulants (DOAC). Editor's note: intravenous heparin is preferable to other anticoagulants when considering interventional radiology as it can be shut off and/or reversed if necessary prior to procedure References 1. Sista, A. et al. Stratification, Imaging, and Management of Acute Massive and Submassive Pulmonary Embolism. 2017 Jul;284(1):5-24 2. Aujesky D, Obrosky DS, Stone RA, Auble TE, Perrier A, Cornuz J, Roy PM, Fine MJ. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005 Oct 15;172(8):1041-6 3. Jimenez, D. et al. Risk stratification of patients with acute symptomatic pulmonary embolism. Intern Emerg Med. 2016 Feb;11(1):11-8. Summarized by Jackson Roos, MS3 | Edited by Erik Verzemnieks, MD

Host: Elizabeth Esty, MD Research By: Elizabeth Esty and Nathan Novotny References: Osumi M. Questions raised over COVID-19 reinfection after Japanese woman develops illness again. The Japan Times. https://www.japantimes.co.jp/news/2020/02/28/national/coronavirus-reinfection/#.Xn4coZNKhQI. Published February 28, 2020. Bao L, Deng W, Gao H, et al. Reinfection could not occur in SARS-CoV-2 infected rhesus macaques. bioRxiv. March 2020:2020.03.13.990226. doi:10.1101/2020.03.13.990226 Steinbuch Y. Doctor asks recovered coronavirus patients to be tested for antibodies. New York Post. https://nypost.com/2020/03/26/doctor-asks-recovered-coronavirus-patients-to-be-tested-for-antibodies/. Published March 26, 2020. Casadevall A. How a Boy's Blood Stopped an Outbreak. The Wall Street Journal. https://www.wsj.com/articles/how-a-boys-blood-stopped-an-outbreak-11582847330. Published February 27, 2020. U.S. Food and Drug Administration. Investigational COVID-19 Convalescent Plasma - Emergency INDs.https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/investigational-covid-19-convalescent-plasma-emergency-inds. Published March 24, 2020. Carmichael T. Takeda Pharmaceutical Announces a Plasma-Derived Coronavirus Therapy. Nasdaq. https://www.nasdaq.com/articles/takeda-pharmaceutical-announces-a-plasma-derived-coronavirus-therapy-2020-03-04. Published March 4, 2020. Maxmen A. How blood from coronavirus survivors might save lives. Nature. March 2020. https://www.nature.com/articles/d41586-020-00895-8. Amanat F, Nguyen T, Chromikova V, et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. medRxiv. March 2020:2020.03.17.20037713. doi:10.1101/2020.03.17.20037713 Steinbuch Y. Mount Sinai researchers develop test for coronavirus antibodies. New York Post. https://nypost.com/2020/03/24/mount-sinai-researchers-develop-test-for-coronavirus-antibodies/. Published March 24, 2020.

Recorded 3/26/20

The circumstances surrounding the COVID-19 virus are quickly evolving and that means that EMM will have to as well. For the foreseeable future, EMM will be releasing COVID-19 updates. In this series, we will report the most recent statistics, summarize the newest literature and answer YOUR burning questions. Submit your questions through comments on this post or through private messages on any of our social media platforms. Host: Elizabeth Esty, MD Research By: Elizabeth Esty, Jackson Roos, Nathan Novotny & Mason Tuttle Time Stamps: 0:00 - COVID-19 by the numbers 2:50 - Hydroxychloroquine and Azithromycin 6:05 - Ongoing Anti-Viral Therapy Research 7:47 - Anosmia 9:31 - Viability of COVID-19 Aerosolized vs. on Surfaces 10:49 - Listener Questions References: [1] The Center for Systems Science and Engineering (CSSE) at Johns Hopkins University Interactive Map [2] Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of COVID‐19: results of an open‐label nonrandomized clinical trial. International Journal of Antimicrobial Agents – In Press 17 March 2020 –DOI : 10.1016/j.ijantimicag.2020.105949 [3] Belhadi D, Peiffer-Smadja N, Yazdanpanah Y, Mentré F, Laouénan C. A brief review of antiviral drugs evaluated in registered clinical trials for COVID-19. medRxiv. March 2020:2020.03.18.20038190.doi:10.1101/2020.03.18.20038190 [4] Hopkins C, Kumar N, ENT UK at The Royal College of Surgeons of England. Loss of sense of smell as marker of COVID-19 infection. https://www.entuk.org/sites/default/files/files/Loss%20of%20sense%20of%20smell%20as%20marker%20of%20COVID.pdf.

Contributor: Don Stader, MD Educational Pearls: PPIs (Proton pump inhibitors) reduce stomach acid levels and are commonly prescribed in patients with GERD or peptic ulcer disease Stopping a PPI after sustained use for a month or longer can lead to withdrawal - causing a rebound indigestion or reflux due to a surge in acid production Long term PPI use has noteworthy side effects including increased incidence of bacterial GI infections and pneumonia Be cautious in prescribing a PPI for over 2 weeks. If continued indigestion control is needed, transition to a H2 blocker or OTC antacids if prolonged treatment is needed. References 1)Haastrup PF, Thompson W, Søndergaard J, Jarbøl DE (2018) Side effects of long-term proton pump inhibitor use: a review. Basic Clin Pharmacol Toxicol 123(2):114–121. https://doi.org/10.1111/bcpt.13023 Review 2) Helgadottir, H.; Bjornsson, E.S. Problems Associated with Deprescribing of Proton Pump Inhibitors. Int. J. Mol. Sci. 2019, 20, 5469. Summarized by Jackson Roos, MS3 | Edited by Erik Verzemnieks, MD

In this special edition of our On the Streets podcast, we discuss COVID-19 as well as what first responders and emergency providers need to know to keep themselves and their patients safe during this pandemic.

Contributor: Sam Killian, MD Educational Pearls: Agitation can be due to a number of causes, but regardless of the cause, sedation often plays a key role in patient and provider safety. But what is the best sedative agent? A study looked at control of agitation with intramuscular medication. Specifically, 5 different IM sedative agents were compared to see which one best provides "adequate" sedation in 15 minutes or less. Haldol 5mg, Haldol 10mg, Versed 5mg, Zyprexa 10mg, and Geodon 20mg were all compared, and by far Versed provided the best sedative results. All medications had approximately the same amount of adverse effects. There are so many sedative options, but time and time again large dose benzodiazepines have demonstrated great effectiveness in treating acute agitation References 1) Klein, Lauren R. et al. Intramuscular Midazolam, Olanzapine, Ziprasidone, or Haloperidol for Treating Acute Agitation in the Emergency Department. Annals of Emergency Medicine. 2018. 72(4), 374 - 385 Summarized by Jackson Roos, MS3 | Edited by Erik Verzemnieks, MD

Contributor: Sam Killian, MD Educational Pearls: Classic dogma teaching that epinephrine should not be used in the fingers, nose, penis, and toes when performing local anesthesia due to concerns for ischemia is wrong This has been well documented in multiple literature reviews A prospective, randomized double-blind study compared lidocaine vs lidocaine with epinephrine for finger injuries and the use of epinephrine was associated with less bleeding and better anesthesia Editor's note: in the lidocaine without epinephrine group, 5 (not 7) needed additional dosing of local anesthesia. The groups were also split 29 for lidocaine alone and 31 for lidocaine with epinephrine but we're in a pandemic so who is noticing anyways References 1. Wilhelmi, B.J., et al. Do not use epinephrine in digital blocks: myth or truth? Plast Reconstr Surg. 2001 Feb;107(2):393-7. 2. Ilicki, J. Safety of Epinephrine in Digital Nerve Blocks: A Literature Review. J Emerg Med. 2015 Nov;49(5):799-809. doi: 10.1016/j.jemermed.2015.05.038. Epub 2015 Aug 4. 3. Walsh, K., Baker, B.G., Iyer, S. Adrenaline Auto-injector injuries to digits; a systematic review and recommendations for emergency management. 2020 Feb 8. pii: S1479-666X(20)30016-0. doi: 10.1016/j.surge.2020.01.005. Summarized by Jackson Roos, MS3 | Edited by Erik Verzemnieks, MD

Part 1 of 2: Dr. Adam Graham dishes out the essentials of identifying concerning neurological deficits on the scene, predicting what they mean and how to best care for patients with neurological deficits in the pre-hospital setting. About Dr. Adam Graham: Adam Graham, MD, is a board-certified neurologist with Blue Sky Neurology in Denver. His professional interests include treatment of diseases of the peripheral nerves and muscles, for example ALS, myasthenia gravis and peripheral neuropathy. He works to make EMG procedures as comfortable as possible for patients. Dr. Graham earned his medical degree from Creighton University. He then completed a residency in neurology and a fellowship in neuromuscular medicine and EMG, both at the University of Colorado.