Contributor: Travis Barlock MD Educational Pearls: Thrombolytic therapy (tPA or TNK) is often used in the ED for strokes Use of anticoagulants with INR > 1.7 or  PT >15 Warfarin will reliably increase the INR Current use of Direct thrombin inhibitor or Factor Xa inhibitor  aPTT/PT/INR are insufficient to assess the degree of anticoagulant effect of Factor Xa inhibitors like apixaban (Eliquis) and rivaroxaban (Xarelto)  Intracranial or intraspinal surgery in the last 3 months Intracranial neoplasms or arteriovenous malformations also increase the risk of bleeding Current intracranial or subarachnoid hemorrhage History of intracranial hemorrhage from thrombolytic therapy also contraindicates tPA/TNK Recent (within 21 days) or active gastrointestinal bleed Hypertension BP >185 systolic or >110 diastolic Administer labetalol before thrombolytics to lower blood pressure Timing of symptoms Onset > 4.5 hours contraindicates tPA Platelet count BGL Potential alternative explanation for stroke-like symptoms obviating need for thrombolytics References 1. Fugate JE, Rabinstein AA. Absolute and Relative Contraindications to IV rt-PA for Acute Ischemic Stroke. The Neurohospitalist. 2015;5(3):110-121. doi:10.1177/1941874415578532 2. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients with Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke a Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Vol 50.; 2019. doi:10.1161/STR.0000000000000211 Summarized by Jorge Chalit, OMSII | Edited by Jorge Chalit

Contributor: Ricky Dhaliwal, MD Educational Pearls: Takotsubo cardiomyopathy, also known as "broken heart syndrome,” is a temporary heart condition that can mimic the symptoms of a heart attack, including troponin elevations and mimic STEMI on ECG. The exact cause is not fully understood, but it is often triggered by severe emotional or physical stress. The stress can lead to a surge of catecholamines which affects the heart (multivessel spasm/paralysed myocardium). The name "Takotsubo" comes from the Japanese term for a type of octopus trap, as the left ventricle takes on a distinctive shape resembling this trap during systole. The LV is dilated and part of the wall becomes akenetic. These changes can be seen on ultrasound. The population most at risk for Takotsubo are post-menopausal women. Coronary angiography is one of the only ways to differentiate Takotsubo from other acute coronary syndromes. Most people with Takotsubo cardiomyopathy recover fully. References Amin, H. Z., Amin, L. Z., & Pradipta, A. (2020). Takotsubo Cardiomyopathy: A Brief Review. Journal of medicine and life, 13(1), 3–7. https://doi.org/10.25122/jml-2018-0067 Bossone, E., Savarese, G., Ferrara, F., Citro, R., Mosca, S., Musella, F., Limongelli, G., Manfredini, R., Cittadini, A., & Perrone Filardi, P. (2013). Takotsubo cardiomyopathy: overview. Heart failure clinics, 9(2), 249–x. https://doi.org/10.1016/j.hfc.2012.12.015 Dawson D. K. (2018). Acute stress-induced (takotsubo) cardiomyopathy. Heart (British Cardiac Society), 104(2), 96–102. https://doi.org/10.1136/heartjnl-2017-311579 Kida, K., Akashi, Y. J., Fazio, G., & Novo, S. (2010). Takotsubo cardiomyopathy. Current pharmaceutical design, 16(26), 2910–2917. https://doi.org/10.2174/138161210793176509 Summarized by Jeffrey Olson MS2 | Edited by Jorge Chalit, OMSII

Contributor: Ricky Dhaliwal MD Educational Pearls: Primary adrenal insufficiency (most common risk factor for adrenal crises) An autoimmune condition commonly known as Addison's Disease Defects in the cells of the adrenal glomerulosa and fasciculata result in deficient glucocorticoids and mineralocorticoids Mineralocorticoid deficiency leads to hyponatremia and hypovolemia Lack of aldosterone downregulates Endothelial Sodium Channels (ENaCs) at the renal tubules Water follows sodium and generates a hypovolemic state Glucocorticoid deficiency contributes further to hypotension and hyponatremia Decreased vascular responsiveness to angiotensin II Increased secretion of vasopressin (ADH) from the posterior pituitary An adrenal crisis is defined as a sudden worsening of adrenal insufficiency Presents with non-specific symptoms including nausea, vomiting, fatigue, confusion, and fevers Fevers may be the result of underlying infection Work-up in the ED includes labs looking for infection and adding cortisol + ACTH levels Emergent treatment is required 100 mg hydrocortisone bolus followed by 50 mg every 6 hours Immediate IV fluid repletion with 1L normal saline The most common cause of an adrenal crisis is an acute infection in patients with baseline adrenal insufficiency Often due to a gastrointestinal infection References 1. Bancos I, Hahner S, Tomlinson J, Arlt W. Diagnosis and management of adrenal insufficiency. Lancet Diabetes Endocrinol. 2015;3(3):216-226. doi:10.1016/S2213-8587(14)70142-1 2. Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(2):364-389. doi:10.1210/jc.2015-1710 3. Cronin CC, Callaghan N, Kearney PJ, Murnaghan DJ, Shanahan F. Addison disease in patients treated with glucocorticoid therapy. Arch Intern Med. 1997;157(4):456-458. 4. Feldman RD, Gros R. Vascular effects of aldosterone: sorting out the receptors and the ligands. Clin Exp Pharmacol Physiol. 2013;40(12):916-921. doi:10.1111/1440-1681.12157 5. Hahner S, Loeffler M, Bleicken B, et al. Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol. 2010;162(3):597-602. doi:10.1530/EJE-09-0884  Summarized by Jorge Chalit, OMSII | Edited by Meg Joyce & Jorge Chalit  

Contributor: Travis Barlock, MD Educational Pearls: Cancer-related emergencies can be sorted into a few buckets: Infection Cancer itself and the treatments (chemotherapy/radiation) can be immunosuppressive. Look out for conditions such as sepsis and neutropenic fever. Obstruction Cancer causes a hypercoagulable state. Look out for blood clots which can cause emergencies such as a pulmonary embolism, stroke, superior vena cava (SVC) syndrome, and cardiac tamponade. Metabolic Cancer can affect the metabolic system in a variety of ways. For example, certain cancers like bone cancers can stimulate the bones to release large amounts of calcium leading to hypercalcemia. Tumor lysis syndrome is another consideration in which either spontaneously or due to treatment, tumor cells will release large amounts of electrolytes into the bloodstream causing hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. Medication side effect Immunomodulators can have strange side effects. A common one to know is Keytruda (pembrolizumab), which can cause inflammation in any organ. So if you have a cancer patient on immunomodulators with any inflammatory changes (cystitis, colitis, pneumonitis, etc), talk to oncology about whether steroids are indicated. Chemotherapy can cause tumor lysis syndrome (see above), and multiple chemotherapeutics are known to cause heart failure (doxorubicin, trastuzumab), kidney failure (cisplatin), and pulmonary toxicity (bleomycin). References Campello, E., Ilich, A., Simioni, P., & Key, N. S. (2019). The relationship between pancreatic cancer and hypercoagulability: a comprehensive review on epidemiological and biological issues. British journal of cancer, 121(5), 359–371. https://doi.org/10.1038/s41416-019-0510-x Gyamfi, J., Kim, J., & Choi, J. (2022). Cancer as a Metabolic Disorder. International journal of molecular sciences, 23(3), 1155. https://doi.org/10.3390/ijms23031155 Kwok, G., Yau, T. C., Chiu, J. W., Tse, E., & Kwong, Y. L. (2016). Pembrolizumab (Keytruda). Human vaccines & immunotherapeutics, 12(11), 2777–2789. https://doi.org/10.1080/21645515.2016.1199310 Wang, S. J., Dougan, S. K., & Dougan, M. (2023). Immune mechanisms of toxicity from checkpoint inhibitors. Trends in cancer, 9(7), 543–553. https://doi.org/10.1016/j.trecan.2023.04.002 Zimmer, A. J., & Freifeld, A. G. (2019). Optimal Management of Neutropenic Fever in Patients With Cancer. Journal of oncology practice, 15(1), 19–24. https://doi.org/10.1200/JOP.18.00269 Summarized by Jeffrey Olson MS2 | Edited by Meg Joyce & Jorge Chalit, OMSII  

Contributor: Travis Barlock MD Educational Pearls: There are three indications for IV albumin in the ED Spontaneous bacterial peritonitis (SBP) Patients with SBP develop renal failure from volume depletion Albumin repletes volume stores and reduces renal impairment Albumin binds inflammatory cytokines and expands plasma volume Reduced all-cause mortality if IV albumin is given with antibiotics Hepatorenal syndrome Cirrhosis of the liver causes the release of endogenous vasodilators The renin-angiotensin-aldosterone system (RAAS) fails systemically but maintains vasoconstriction at the kidneys, leading to decreased renal perfusion IV albumin expands plasma volume and prevents failure of the RAAS Large volume paracentesis Large-volume removal may lead to circulatory dysfunction IV albumin is associated with a reduced risk of paracentesis-associated circulatory dysfunction There are many other FDA-approved conditions for which to use exogenous albumin but the data are conflicted about the benefits on mortality References 1. Arroyo V, Fernandez J. Pathophysiological basis of albumin use in cirrhosis. Ann Hepatol. 2011;10(SUPPL. 1):S6-S14. doi:10.1016/s1665-2681(19)31600-x 2. Bai Z, Wang L, Wang R, et al. Use of human albumin infusion in cirrhotic patients: a systematic review and meta-analysis of randomized controlled trials. Hepatol Int. 2022;16(6):1468-1483. doi:10.1007/s12072-022-10374-z 3. Batool S, Waheed MD, Vuthaluru K, et al. Efficacy of Intravenous Albumin for Spontaneous Bacterial Peritonitis Infection Among Patients With Cirrhosis: A Meta-Analysis of Randomized Control Trials. Cureus. 2022;14(12). doi:10.7759/cureus.33124 4. Kwok CS, Krupa L, Mahtani A, et al. Albumin reduces paracentesis-induced circulatory dysfunction and reduces death and renal impairment among patients with cirrhosis and infection: A systematic review and meta-analysis. Biomed Res Int. 2013;2013. doi:10.1155/2013/295153 5. Sort P, Navasa M, Arroyo V, et al. Effect of Intravenous Albumin on Renal Impairment and Mortality in Patients with Cirrhosis and Spontaneous Bacterial Peritonitis. N Engl J Med. 1999;341(6):403-409. Summarized by Jorge Chalit, OMSII | Edited by Meg Joyce & Jorge Chalit  

Contributor: Ricky Dhaliwal, MD Educational Pearls: What are DKA and HHS? DKA (Diabetic Ketoacidosis) and HHS (Hyperosmolar Hyperglycemic State) are both acute hyperglycemic states. DKA More common in type 1 diabetes. Triggered by decreased circulating insulin. The body needs energy but cannot use glucose because it can’t get it into the cells. This leads to increased metabolism of free fatty acids and the increased production of ketones. The buildup of ketones causes acidosis. The kidneys attempt to compensate for the acidosis by increasing diuresis. These patients present as dry and altered, with sweet-smelling breath and Kussmaul (fast and deep) respirations. HSS More common in type 2 diabetes. In this condition there is still enough circulating insulin to avoid the breakdown of fats for energy but not enough insulin to prevent hyperglycemia. Serum glucose levels are very high – around 600 to 1200 mg/dl. Also presents similarly to DKA with the patient being dry and altered. Important labs to monitor Serum glucose Potassium Phosphorus Magnesium Anion gap (Na - Cl - HCO3) Renal function (Creatinine and BUN) ABG/VBG for pH Urinalysis and urine ketones by dipstick Treatment Identify the cause, i.e. Has the patient stopped taking their insulin? Aggressive hydration with isotonic fluids. Normal Saline (NS) vs Lactated Ringers (LR)? LR might resolve the DKA/HHS faster with less risk of hypernatremia. Should you bolus with insulin? No, just start a drip. 0.1-0.14 units per kg of insulin. Make sure you have your potassium back before starting insulin as the insulin can shift the potassium into the cells and lead to dangerous hypokalemia. Should you treat hyponatremia? Make sure to correct for hyperglycemia before treating. This artificially depresses the sodium. Should you give bicarb? Replace if the pH Don’t intubate, if the patient is breathing fast it is because they are compensating for their acidosis. References Andrade-Castellanos, C. A., Colunga-Lozano, L. E., Delgado-Figueroa, N., & Gonzalez-Padilla, D. A. (2016). Subcutaneous rapid-acting insulin analogues for diabetic ketoacidosis. The Cochrane database of systematic reviews, 2016(1), CD011281. https://doi.org/10.1002/14651858.CD011281.pub2 Chaithongdi, N., Subauste, J. S., Koch, C. A., & Geraci, S. A. (2011). Diagnosis and management of hyperglycemic emergencies. Hormones (Athens, Greece), 10(4), 250–260. https://doi.org/10.14310/horm.2002.1316 Dhatariya, K. K., Glaser, N. S., Codner, E., & Umpierrez, G. E. (2020). Diabetic ketoacidosis. Nature reviews. Disease primers, 6(1), 40. https://doi.org/10.1038/s41572-020-0165-1 Duhon, B., Attridge, R. L., Franco-Martinez, A. C., Maxwell, P. R., & Hughes, D. W. (2013). Intravenous sodium bicarbonate therapy in severely acidotic diabetic ketoacidosis. The Annals of pharmacotherapy, 47(7-8), 970–975. https://doi.org/10.1345/aph.1S014 Modi, A., Agrawal, A., & Morgan, F. (2017). Euglycemic Diabetic Ketoacidosis: A Review. Current diabetes reviews, 13(3), 315–321. https://doi.org/10.2174/1573399812666160421121307 Self, W. H., Evans, C. S., Jenkins, C. A., Brown, R. M., Casey, J. D., Collins, S. P., Coston, T. D., Felbinger, M., Flemmons, L. N., Hellervik, S. M., Lindsell, C. J., Liu, D., McCoin, N. S., Niswender, K. D., Slovis, C. M., Stollings, J. L., Wang, L., Rice, T. W., Semler, M. W., & Pragmatic Critical Care Research Group (2020). Clinical Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis: A Subgroup Analysis of Cluster Randomized Clinical Trials. JAMA network open, 3(11), e2024596. https://doi.org/10.1001/jamanetworkopen.2020.24596 Summarized by Jeffrey Olson MS2 | Edited by Meg Joyce & Jorge Chalit, OMSII

Contributor: Aaron Lessen MD Educational Pearls: Button batteries cause alkaline corrosion and erosion of the esophagus when swallowed Children swallow button batteries, which create a medical emergency as they can perforate the esophagus A recent study compared various home remedies as first-aid therapy for button battery ingestion Honey, jam, normal saline, Coca-Cola, orange juice, milk, and yogurt The study used a porcine esophageal model to assess resistance to alkalinization with the different home remedies Honey and jam demonstrated a significantly lower esophageal tissue pH compared with normal saline Histologic changes in the tissue samples appeared 60 minutes later with honey and jam compared with normal saline These treatments do not preclude medical intervention and battery removal References 1. Chiew AL, Lin CS, Nguyen DT, Sinclair FAW, Chan BS, Solinas A. Home Therapies to Neutralize Button Battery Injury in a Porcine Esophageal Model. Ann Emerg Med. 2023:1-9. doi:10.1016/j.annemergmed.2023.08.018 Summarized by Jorge Chalit, OMSII | Edited by Meg Joyce & Jorge Chalit  

Contributor: Ricky Dhaliwal, MD Educational Pearls: What can you do to control bleeding in a penetrating wound? Apply direct pinpoint pressure on the wound as well as proximal to the wound. Build a compression dressing. How do you build a compression dressing? Think about building an upside-down pyramid with the gauze. Consider coagulation agents such as an absorbent gelatin sponge material, microporous polysaccharide hemispheres, oxidized cellulose, fibrin sealants, topical thrombin, or tranexamic acid. What are the indications to use a tourniquet? The Stop The Bleed campaign recommends looking for the following features of “life-threatening” bleeding. Pulsatile bleeding. Blood is pooling on the ground. The overlying clothes are soaked. Bandages are ineffective. Partial or full amputation. And if the patient is in shock. How do you put on a tourniquet? If using a Combat Application Tourniquet (C-A-T) tourniquet, apply it proximal to the wound, then rotate the plastic rod until the bleeding stops. Then secure the plastic rod with a clip and make sure the Velcro is in place. Mark the time - generally, there is a spot on the tourniquet to write. Have a plan for the next steps. Does the patient need emergent surgery? Do they need to be transfered? How long can you leave a tourniquet on? Less than 90 minutes. What are the risks? Nerve injury. Ischemia. References Latina R, Iacorossi L, Fauci AJ, Biffi A, Castellini G, Coclite D, D'Angelo D, Gianola S, Mari V, Napoletano A, Porcu G, Ruggeri M, Iannone P, Chiara O, On Behalf Of Inih-Major Trauma. Effectiveness of Pre-Hospital Tourniquet in Emergency Patients with Major Trauma and Uncontrolled Haemorrhage: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2021 Dec 6;18(23):12861. doi: 10.3390/ijerph182312861. PMID: 34886586; PMCID: PMC8657739. Martinson J, Park H, Butler FK Jr, Hammesfahr R, DuBose JJ, Scalea TM. Tourniquets USA: A Review of the Current Literature for Commercially Available Alternative Tourniquets for Use in the Prehospital Civilian Environment. J Spec Oper Med. 2020 Summer;20(2):116-122. doi: 10.55460/CT9D-TMZE. PMID: 32573747. Resources poster booklet. (n.d.). Stop the Bleed. https://www.stopthebleed.org/resources-poster-booklet/ Summarized by Jeffrey Olson MS2 | Edited by Meg Joyce & Jorge Chalit, OMSII  

Contributors: Kali Olson PharmD, Travis Barlock MD, Jeffrey Olson MS2 Summary: In this episode of Pharmacy Phriday, Dr. Kali Olson joins Dr. Travis Barlock and Jeffrey Olson in studio to discuss a variety of interesting topics in the form of a segment show. Dr. Kali Olson earned her Doctorate of Pharmacy from the University of Colorado, Skaggs School of Pharmacy and completed a PGY1 residency at Detroit Receiving Hospital and a PGY2 residency in Emergency Medicine at Denver Health. She now works as an Emergency Medicine Pharmacist at Denver Health.  In segment one of the show, Kali and Travis answer the Get-To-Know-You questionnaire. In segment two, they work together to answer a series of pharmacy-based riddles. In segment three they play a “Balderdash” like game in which they guess the definitions of medical jargon. In segment four they play the Number Needed to Treat game, invented by the AFP podcast. And in segment five they work together to answer a question about a far-out scenario involving medications and time travel!   References ·       American Family Physician Podcast, https://www.aafp.org/pubs/afp/multimedia/podcast.html ·       Gragnolati, A. (2022, May 5). The Yuzpe method of emergency contraception. GoodRx. https://www.goodrx.com/conditions/emergency-contraceptive/yuzpe-method ·       Manikandan S, Vani NI. Holiday reading: Learning medicine through riddles. CMAJ. 2010 Dec 14;182(18):E863-4. doi: 10.1503/cmaj.100466. PMID: 21149530; PMCID: PMC3001539. ·       Riddle Me This: Mixing Medicine, https://peimpact.com/riddle-me-this-mixing-medicine/ ·       https://thennt.com/nnt/corticosteroids-treatment-kawasaki-disease-children/ ·       https://thennt.com/nnt/aspirin-acute-ischemic-stroke/ ·       https://thennt.com/nnt/tranexamic-acid-treatment-epistaxis/ ·       https://thennt.com/nnt/antibiotics-culture%e2%80%90positive-asymptomatic-bacteriuria-pregnant-women/   Produced, Hosted, Edited, and Summarized by Jeffrey Olson MS2 | Additional editing by Jorge Chalit, OMSII  

Contributor: Taylor Lynch MD Educational Pearls Hypothermia is defined as a core body temperature less than 35 degrees Celsius or less than 95 degrees Fahrenheit  Mild Hypothermia: 32-35 degrees Celsius Presentation: alert, shivering, tachycardic, and cold diuresis Management: Passive rewarming i.e. remove wet clothing and cover the patient with blankets or other insulation Moderate Hypothermia: 28-32 degrees Celsius Presentation: Drowsiness, lack of shivering, bradycardia, hypotension Management: Active external rewarming Severe Hypothermia: 24-28 degrees Celsius Presentation: Heart block, cardiogenic shock, no shivering Management: Active external and internal rewarming Less than 24 degrees Celsius Presentation: Pulseless, ventricular arrhythmia Active External Rewarming Warm fluids are insufficient for warming due to a minimal temperature difference (warmed fluids are maintained at 40 degrees vs. a patient at 30 degrees is not a large enough thermodynamic difference) External: Bear hugger, warm blankets Active Internal Rewarming Thoracic lavage (preferably on the patient’s right side) Place 2 chest tubes (anteriorly and posteriorly); infuse warm IVF anteriorly and hook up the posterior tube to a Pleur-evac Warms the patient 3-6 Celsius per hour Bladder lavage Continuous bladder irrigation with 3-way foley or 300 cc warm fluid Less effective than thoracic lavage due to less surface area Pulseless patients ACLS does not work until patients are rewarmed to 30 degrees High-quality CPR until 30 degrees (longest CPR in a hypothermic patient was 6 hours and 30 minutes) Give epinephrine once you reach 35 degrees, spaced out every 6 minutes ECMO is the best way to warm these patients up (10 degrees per hour) Pronouncing death must occur at 32 degrees or must have potassium > 12 References 1. 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care - Part 1: Introduction. Circulation. 2005;112(24 SUPPL.). doi:10.1161/CIRCULATIONAHA.105.166550 2. Brown DJA, Burgger H, Boyd J, Paal P. Accidental Hypothermia. N Engl J Med. 2012;367:1930-1938. doi:10.1136/bmj.2.5543.51-c 3. Dow J, Giesbrecht GG, Danzl DF, et al. Wilderness Medical Society Clinical Practice Guidelines for the Out-of-Hospital Evaluation and Treatment of Accidental Hypothermia: 2019 Update. Wilderness Environ Med. 2019;30(4S):S47-S69. doi:10.1016/j.wem.2019.10.002 4. Kjærgaard B, Bach P. Warming of patients with accidental hypothermia using warm water pleural lavage. Resuscitation. 2006;68(2):203-207. doi:10.1016/j.resuscitation.2005.06.019 5. Lott C, Truhlář A, Alfonzo A, et al. European Resuscitation Council Guidelines 2021: Cardiac arrest in special circumstances. Resuscitation. 2021;161:152-219. doi:10.1016/j.resuscitation.2021.02.011 6. Plaisier BR. Thoracic lavage in accidental hypothermia with cardiac arrest - Report of a case and review of the literature. Resuscitation. 2005;66(1):99-104. doi:10.1016/j.resuscitation.2004.12.024 Summarized by Jorge Chalit, OMSII | Edited by Meg Joyce & Jorge Chalit, OMSII