Winter Meeting - Pearls February 29, 2020
EM Pearls - New, Old, Borrowed & Blue Cole Sloan Pharm.D., BCPS, BCGP Emergency Medicine Pharmacist Program Director, PGY2 EM Pharmacy University of Utah Health
Disclosure Instructions: No relevant relationships or conflicts of interest, financial or otherwise, to disclose We will discuss off-label use(s) of medications
Learning Objectives At the conclusion of this activity, pharmacists should be able to successfully: 1. Identify medications for atypical indications used in Emergency Medicine 2. Assess appropriateness of an order where limited literature exists
Learning Objectives At the conclusion of this activity, pharmacy technicians should be able to successfully: 1. Recognize a medication order possibly for an atypical indication 2. Determine when an atypical order may need to be expedited
Something old for a new indication 26 yoM presents to your ED with intractable N/V PMH unremarkable, CBC/BMP/UA WNL Reports “occasional” alcohol, marijuana use NKDA, No rx/OTC meds reported
Cannabinoid Hyperemesis Syndrome (CHS) Chronic marijuana use, typically over years Relief with hot showers = pertinent finding
Treatment of CHS Two commonly used treatments in our ED include
Safety of Droperidol BBW for Torsades de Pointes (TdP) Original FDA warning does not apply to doses below 2.5 mg (as those are not labeled doses) Be mindful of existing risk factors for prolonged QT, even at lower doses Akathisia, anxiety also common ADRs
Administration of Capsaicin MOA of capsaicin For capsaicin – HCPs should use gloves when applying topically to abdominal area Caution patients of impending burning sensation, if intolerable can try milk, lidocaine but the best “reversal agent” anecdotally is mayonnaise
Something Borrowed Important Drug-Drug Interaction: carbapenems severely reduce serum levels of valproic acid (VPA) Case report when DDI does NOT occur Drug Interaction We can ‘borrow’ this DDI for use in VPA overdose Spriet. Ann Pharmacother 2011;45(9):1167 ‐ 8
Limitations Indication for VPA treatment? Supportive care, Activated charcoal, Levocarnitine, Hemodialysis Tincture of time Won’t address all sequelae of VPA toxicity
Which Carbapenem? All available carbapenems associated with DDI ◦ Availability / Formulary ◦ Pharmacokinetics ◦ Duration of therapy? ◦ ‘Antidote Stewardship’ Imipenem ‐ Cilastatin, greater risk of seizures? ◦ Imipenem (7/1124) vs meropenem (4/1116) ◦ Odds Ratio 1.48 (0.54, 4.04) ◦ Population had no seizure hx (or VPA use) Cannon. J Antimicrob Chemother. 2014;69(8):2043 ‐ 55
Pearl #3 Vasoplegia ‘uncontrolled vasodilation’ seen in advanced shock states Hemodynamic definitions vary ‐ Mean Arterial Pressure (MAP) ‐ Minimal effect of vasopressors ‐ Systemic Vascular Resistance (SVR) ‐ Cardiac Index (CI)
Something Blue Ensure adequate resuscitation prior to ‘rescue’ therapies Identify/treat etiology Assess fluids/electrolytes Vasopressor(s) Adjunct therapies Corticosteroids Vitamins Pt close to the edge? Consider…
Something Blue Mechanism of Methylene Blue (MB) in treating vasoplegia Dosing 1 ‐ 2 mg/kg IVP 5 minutes CI 0.5 – 2 mg/kg/h Most ADRs noted when cumulative eNOS ‐ endothelial nitric oxide synthase NO ‐ Nitric Oxide iNOS ‐ inducible nitric oxide synthase GTP ‐ guanosine triphosphate dose exceeds 7 mg/kg cGMP ‐ cyclic guanosine monophosphate sGC ‐ soluble guanylate cyclase Severe hemolysis, hyperbilirubinemia, death single doses > 20 mg/kg
Something Blue “Indications”: sepsis, post ‐ cardiac bypass, anaphylaxis, IHD ‐ induced hypoTN SUGGESTIONS Blue ‐ Eiffel 65 Blue Monday ‐ New Order Contraindications Behind Blue Eyes ‐ The Who Concurrent ‘serotonergic’ meds Blue Bayou ‐ Linda Ronstadt G6PD deficiency Counting Blue Cars ‐ Dishwalla Blue Suede Shoes ‐ Elvis Presley Pregnancy Blue Christmas ‐ Elvis Presley (seasonal) Blue Eyes Crying in the Rain ‐ Willie Nelson Customary to hum a song with ‘blue’ in the title ‐ many, many to choose from
Something Blue “Indications”: sepsis, post ‐ cardiac bypass, anaphylaxis, IHD ‐ induced hypoTN & Ifosfamide ‐ induced encephalopathy Monitoring O2 saturations upon administration Hemodynamic resolution Methemoglobin Alternative medication for vasoplegia?
Key Takeaways Cannabinoid Hyperemesis Syndrome is becoming more prevalent, while abstaining from marijuana is key, acute treatments include droperidol and capsaicin topical. Both carry pertinent ADRs pharmacists need to know Valproic acid levels will precipitously drop when administering a carbapenem antibiotic; even if pharmacists are not involved with VPA overdoses this is an essential DDI to identify and manage Methylene blue is a medication with many uses, including refractory vasoplegia. Pharmacists involvement is encouraged when identifying contraindication and monitoring effect of therapy
Key Takeaways Cannabinoid Hyperemesis Syndrome is becoming more prevalent, while abstaining from marijuana is key, acute treatments include droperidol and capsaicin topical. Both carry pertinent ADRs pharmacists need to know Valproic acid levels will precipitously drop when administering a carbapenem antibiotic; even if pharmacists are not involved with VPA overdoses this is an essential DDI to identify and manage Methylene blue is a medication with many uses, including refractory vasoplegia. Pharmacists involvement is encouraged when identifying contraindication and monitoring effect of therapy
Key Takeaways Cannabinoid Hyperemesis Syndrome is becoming more prevalent, while abstaining from marijuana is key, acute treatments include droperidol and capsaicin topical. Both carry pertinent ADRs pharmacists need to know Valproic acid levels will precipitously drop when administering a carbapenem antibiotic; even if pharmacists are not involved with VPA overdoses this is an essential DDI to identify and manage Methylene blue is a medication with many uses, including refractory vasoplegia. Pharmacists involvement is encouraged when identifying contraindication and monitoring effect of therapy
Test Questions T/F : Capsaicin topically applied to the face is an effective treatment for ethanol- induced hyperemesis syndrome. A. True B. False
Test Questions MC: Which of the following antibiotics will cause a precipitous lowering of serum levels of valproic acid in the subsequent days? A. Linezolid B. Tigecycline C. Ertapenem D. Amikacin
Test Questions MC: Absolute or relative contraindications to methylene blue treatment include all of the following, EXCEPT: A. Pregnancy B. glucose-6-phosphate dehydrogenase (G6PD) deficiency C. Serotonergic medication use D. Yellow food dye intolerance
References 1/2 Rappaport BA. FDA Response to Droperidol Black Box Warning Editorials. Anesthesia & Analgesia 2008;106(5):1585–1. PMID 18420886 Horowitz BZ, Bizovi K, Moreno R. Droperidol–behind the black box warning. Acad Emerg Med. 2002;9:615 ‐ 8. PMID 1205077 Perkins J, Ho JD, Vilke GM, DeMers G. American Academy of Emergency Medicine Position Statement: Safety of Droperidol Use in the Emergency Department. J Emerg Med. 2015 Jul;49(1):91 ‐ 7. PMID 25837231 Cai Y, et al. The use of intravenous hydroxocobalamin as a rescue in methylene blue ‐ resistant vasoplegic syndrome in cardiac surgery. Ann Card Anaesth 2017 Oct ‐ Dec; 20(4):462 ‐ 464. PMID: 28994688 Cannon, et al. The risk of seizures among the carbapenems: a meta ‐ analysis. J Antimicrob Chemother. 2014;69(8):2043 ‐ 55. PMID: 24744302 Dreucean D, Beres K, McNierney ‐ Moore A, Gravino D. Use of meropenem to treat valproic acid overdose. Am J Emerg Med. 2019 Nov;37(11):2120.e5 ‐ 2120.e7. PMID 31500925 Fudio, et al. Epileptic seizures caused by low valproic acid levels from an interaction with meropenem. J Clin Pharm Ther. 2006;31(4):393 ‐ 6. PMID: 16882111 Haroutiunian, et al. Valproic acid plasma concentration decreases in a dose ‐ independent manner following administration of meropenem: a retrospective study. J Clin Pharmacol. 2009;49(11):1363 ‐ 9. PMID: 19773524 Khobrani MA, Dudley SW, Huckleberry YC, Kopp BJ, et al. Intentional use of carbapenem antibiotics for valproic acid toxicity: A case report. J Clin Pharm Ther. 2018 Oct;43(5):723 ‐ 725. PMID 29733112
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