Winter Meeting - Pearls February 29, 2020 EM Pearls - New, Old, - - PowerPoint PPT Presentation

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

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

Something old for a new indication

Chronic marijuana use, typically over years Relief with hot showers = pertinent finding

Cannabinoid Hyperemesis Syndrome (CHS)

Two commonly used treatments in our ED include

Treatment of CHS

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

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

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

Indication for VPA treatment? Supportive care, Activated charcoal, Levocarnitine, Hemodialysis Tincture of time Won’t address all sequelae of VPA toxicity

Limitations

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

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)

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

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 triphosphate cGMP ‐ cyclic guanosine monophosphate sGC ‐ soluble guanylate cyclase

“Indications”: sepsis, post‐cardiac bypass, anaphylaxis, IHD‐induced hypoTN Contraindications

• Concurrent ‘serotonergic’ meds
• G6PD deficiency
• Pregnancy

Customary to hum a song with ‘blue’ in the title ‐ many, many to choose from 

Something Blue

SUGGESTIONS

Blue ‐ Eiffel 65 Blue Monday ‐ New Order Behind Blue Eyes ‐ The Who Blue Bayou ‐ Linda Ronstadt Counting Blue Cars ‐ Dishwalla Blue Suede Shoes ‐ Elvis Presley Blue Christmas ‐ Elvis Presley (seasonal) Blue Eyes Crying in the Rain ‐ Willie Nelson

“Indications”: sepsis, post‐cardiac bypass, anaphylaxis, IHD‐induced hypoTN & Ifosfamide‐induced encephalopathy Monitoring

• O2 saturations upon administration
• Hemodynamic resolution
• Methemoglobin

Alternative medication for vasoplegia?

Something Blue

• 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

• verdoses 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

• verdoses 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

• verdoses 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

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

• f the following, EXCEPT:
• A. Pregnancy
• B. glucose-6-phosphate dehydrogenase (G6PD) deficiency
• C. Serotonergic medication use
• D. Yellow food dye intolerance

Test Questions

• 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

• 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
• verdose 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