Emergency Medical Minute

Contributor: Aaron Lessen MD Educational Pearls: Opioid overdoses that are reversed with naloxone (Narcan), a mu-opioid antagonist, can precipitate acute withdrawal in some patients Treatment of opioid use disorder with buprenorphine can also precipitate withdrawal Opioid withdrawal symptoms include nausea, vomiting, diarrhea, and agitation Buprenorphine works as a partial agonist at mu-opioid receptors, which may alleviate withdrawal symptoms The preferred dose of buprenorphine is 16 mg Treatment of buprenorphine-induced opioid withdrawal is additional buprenorphine Adjunctive treatments may be used for other opioid withdrawal symptoms Nausea with ondansetron Diarrhea with loperamide Agitation with hydroxyzine References 1. Quattlebaum THN, Kiyokawa M, Murata KA. A case of buprenorphine-precipitated withdrawal managed with high-dose buprenorphine. Fam Pract. 2022;39(2):292-294. doi:10.1093/fampra/cmab073 2. Spadaro A, Long B, Koyfman A, Perrone J. Buprenorphine precipitated opioid withdrawal: Prevention and management in the ED setting. Am J Emerg Med. 2022;58:22-26. doi:10.1016/j.ajem.2022.05.013 Summarized by Jorge Chalit, OMSII | Edited by Meg Joyce & Jorge Chalit

Contributor: Travis Barlock MD Educational Pearls: How do you differentiate between compensated and decompensated cirrhosis? Use the acronym VIBE to look for signs of being decompensated. V-Volume Cirrhosis can cause volume overload through a variety of mechanisms such as by increasing pressure in the portal vein system and the decreased production of albumin. Look for pulmonary edema (dyspnea, orthopnea, wheezing/crackles, coughing up frothy pink sputum, etc.) or a tense abdomen. I-Infection The ascitic fluid can become infected with bacteria, a complication called Spontaneous Bacterial Peritonitis (SBP). Look for abdominal pain, fever, hypotension, and tachycardia. Diagnosis is made with ascitic fluid cell analyses (polymorphonuclear neutrophils >250/mm3) B-Bleeding Another consequence of increased portal pressure is that blood backs up into smaller blood vessels, including those in the esophagus. Over time, this increased pressure can result in the development of dilated, fragile veins called esophageal varices, which are prone to bleeding. Look for hematemesis, melena, lightheadedness, and pale skin. E-Encephalopathy A failing liver also does not clear toxins which can affect the brain. Look for asterixis (flapping motion of the hands when you tell the patient to hold their hands up like they are going to stop a bus) Other complications to look out for. Hepatorenal syndrome Hepatopulmonary syndrome References Engelmann, C., Clària, J., Szabo, G., Bosch, J., & Bernardi, M. (2021). Pathophysiology of decompensated cirrhosis: Portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction. Journal of hepatology, 75 Suppl 1(Suppl 1), S49–S66. https://doi.org/10.1016/j.jhep.2021.01.002 Enomoto, H., Inoue, S., Matsuhisa, A., & Nishiguchi, S. (2014). Diagnosis of spontaneous bacterial peritonitis and an in situ hybridization approach to detect an "unidentified" pathogen. International journal of hepatology, 2014, 634617. https://doi.org/10.1155/2014/634617 Mansour, D., & McPherson, S. (2018). Management of decompensated cirrhosis. Clinical medicine (London, England), 18(Suppl 2), s60–s65. https://doi.org/10.7861/clinmedicine.18-2-s60 Summarized by Jeffrey Olson MS2 | Edited by Meg Joyce & Jorge Chalit, OMS II

Contributor: Aaron Lessen MD Educational Pearls: Lorazepam (Ativan) is dosed at 0.1 mg/kg up to a maximum of 4 mg in status epilepticus Some ED protocols only give 2 mg initially The maximum recommended dose of levetiracetam (Keppra) is 60 mg/kg or 4.5 g In one retrospective study, only 50% of patients received the correct dose of lorazepam For levetiracetam, it was only 35% of patients Underdosing leads to complications Higher rates of intubations More likely to progress to refractory status epilepticus References 1. Cetnarowski A, Cunningham B, Mullen C, Fowler M. Evaluation of intravenous lorazepam dosing strategies and the incidence of refractory status epilepticus. Epilepsy Res. 2023;190(November 2022):107067. doi:10.1016/j.eplepsyres.2022.107067 2. Sathe AG, Tillman H, Coles LD, et al. Underdosing of Benzodiazepines in Patients With Status Epilepticus Enrolled in Established Status Epilepticus Treatment Trial. Acad Emerg Med. 2019;26(8):940-943. doi:10.1111/acem.13811 Summarized by Jorge Chalit, OMSII | Edited by Meg Joyce & Jorge Chalit

Dr. Travis Barlock discusses ketamine dosing in the emergency department. Highlights include pain relief at 0.3 mg/kg, induction for intubation at 1 mg/kg, and IM for acute agitation at 3 mg/kg. Quick ketamine administration can cause laryngospasm. Avoid recreational doses for unpleasant hallucinations.

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