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Winter Meeting - PearlsFebruary 29, 2020
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EM Pearls - New, Old, Borrowed & Blue
Cole Sloan Pharm.D., BCPS, BCGPEmergency Medicine Pharmacist
Program Director, PGY2 EM PharmacyUniversity of Utah Health
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Disclosure
Instructions: No relevant relationships or conflicts of interest, financial or otherwise, to disclose
We will discuss off-label use(s) of medications
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Learning Objectives
At the conclusion of this activity, pharmacists should be able to successfully:
1. Identify medications for atypical indications used in Emergency Medicine2. Assess appropriateness of an order where limited literature exists
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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
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26 yoM presents to your ED with intractable N/V PMH unremarkable, CBC/BMP/UA WNLReports “occasional” alcohol, marijuana useNKDA, No rx/OTC meds reported
Something old for a new indication
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Chronic marijuana use, typically over years
Relief with hot showers = pertinent finding
Cannabinoid Hyperemesis Syndrome (CHS)
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Two commonly used treatments in our ED include
Treatment of CHS
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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
Safety of Droperidol
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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
Administration of Capsaicin
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Important Drug-Drug Interaction: carbapenems severely reduce serum levels of valproic acid (VPA)
Case report when DDI does NOT occur
We can ‘borrow’ this DDI for use in VPA overdose
Something Borrowed
Drug Interaction
Spriet. Ann Pharmacother 2011;45(9):1167‐8
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Indication for VPA treatment?
Supportive care, Activated charcoal,Levocarnitine, HemodialysisTincture of time
Won’t address all sequelae of VPA toxicity
Limitations
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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)
Which Carbapenem?
Cannon. J Antimicrob Chemother. 2014;69(8):2043‐55
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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)
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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
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Mechanism of Methylene Blue (MB) in treating vasoplegia
Dosing 1‐2 mg/kg IVP 5 minutesCI 0.5 – 2 mg/kg/h
Most ADRs noted when cumulative dose exceeds 7 mg/kg Severe hemolysis, hyperbilirubinemia, death single doses > 20 mg/kg
Something Blue
eNOS ‐ endothelial nitric oxide synthase NO ‐ Nitric Oxide iNOS ‐ inducible nitric oxide synthase GTP ‐ guanosine triphosphatecGMP ‐ cyclic guanosine monophosphate sGC ‐ soluble guanylate cyclase
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“Indications”: sepsis, post‐cardiac bypass, anaphylaxis, IHD‐induced hypoTN
ContraindicationsConcurrent ‘serotonergic’ medsG6PD deficiencyPregnancy
Customary to hum a song with ‘blue’ in the title ‐many, many to choose from
Something Blue
SUGGESTIONSBlue ‐ Eiffel 65
Blue Monday ‐ New OrderBehind Blue Eyes ‐ The WhoBlue Bayou ‐ Linda RonstadtCounting Blue Cars ‐ DishwallaBlue Suede Shoes ‐ Elvis Presley
Blue Christmas ‐ Elvis Presley (seasonal)Blue Eyes Crying in the Rain ‐Willie Nelson
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“Indications”: sepsis, post‐cardiac bypass, anaphylaxis, IHD‐induced hypoTN & Ifosfamide‐induced encephalopathy
MonitoringO2 saturations upon administrationHemodynamic resolutionMethemoglobin
Alternative medication for vasoplegia?
Something Blue
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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
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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
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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
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T/F: Capsaicin topically applied to the face is an effective treatment for ethanol-induced hyperemesis syndrome.
A. True
B. False
Test Questions
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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
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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
Test Questions
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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
References 1/2
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Levy B, et al. Vasoplegia treatments: the past, the present, and the future. Crit Care 2018; 22(1):52. PMID: 29486781
Lambden S, et al. Definitions and pathophysiology of vasoplegic shock. Crit Care. 2018; 22(1):174. PMID: 29980217
Jentzer JC, et al. Management of Refractory Vasodilatory Shock. Chest 2018; pii: S0012‐3692(18)30072‐2. PMID: 29329694
Mancl, et al. The effect of carbapenem antibiotics on plasma concentrations of valproic acid. Ann Pharmacother. 2009;43(12):2082‐7. PMID: 19934386
Spriet, et al. No interaction between valproate and meropenem in a cirrhotic patient. Ann Pharmacother. 2011;45(9):1167‐8. PMID: 21811003
Spriet, et al. Interaction between valproate and meropenem: a retrospective study. Ann Pharmacother. 2007;41(7):1130‐6. PMID: 17609232
Spriet, et al. Meropenem ‐valproic acid interaction in patients with cefepime‐associated status epilepticus. Am J Health Syst Pharm. 2007;64(1):54‐8. PMID: 17189580
Thomas C, Priano J, Smith TL. Meropenem as an antidote for intentional valproic acid overdose: A case report. Am J Emerg Med. 2020 Jan 8. pii: S0735‐6757(19)30621‐7. PMID 31980292
Zosel, et al. Novel use of ertapenem to intentionally decease serum valproate concentration after an intentional overdose of valproate resulting in toxicity. NACCT 2015 Poster #106. Link
Stawicki SP, et al. Methylene blue and vasoplegia: who, when, and how? Mini Rev Med Chem. 2008 May;8(5):472‐90. PMID 18473936
References 2/2