THE CODE STROKE THAT WASN’T

1. THE CODE STROKE THAT WASN’T Amy Gutman MD Director of Emergency Medicine

2. OBJECTIVES • Case presentation • Protocol review • Assessment & management

3. CASE PRESENTATION • 911 call for “Stroke” at local SNF • 85 yo female, last seen well at breakfast 3 hours earlier • Normally with dementia, but otherwise neurologically intact • Now with AMS, slurred speech

4. PMH / SOCIAL • PMH • Alzheimer's • Hypertension • Hypercholesterolemia • Social • 40+ PYH, quit x 20 years, (-) ETOH / drugs • Full Code

5. MEDICATIONS • Haloperidol 5mg po prn • Metoprolol XL 50mg po BID • Atorvastatin 40mg po qDay • Aspirin 81mg po qDay

6. INITIAL ASSESSMENT • Elderly female, drooling, minimally responsive but maintaining airway • ABC • Maintaining airway, adequate respirations, diminished distal pulses • Vitals • HR 28 RR 10 BP 60/P Sat 92% ra

7. EMS AMS PROTOCOL

8. SECONDARY SURVEY • Stroke Scale • Face symmetrical • Speech slurred • Both arms weak • Glucose 58

9. EKG

10. ON SCENE • Problems identified • AMS • Bradycardia • Hypotension • Treatments initiated • 1 IV & 200cc NS • 1 amp dextrose • 4mg naloxone • Cardiac monitor • Medical control – called to notify of “Code Stroke 5 minutes out” • At EMS arrival patient remained altered, hypotensive & bradycardic • Let’s discuss…

11. AMS, BRADYCARDIA, HYPOTENSION • What is the priority? • Once bradycardia & hypotension identified, it’s difficult but important to address both simultaneously • Equally important to start putting together a differential diagnosis as the shock is not going to kill this patient…it’s what’s CAUSING the shock that’s going to kill the patient!

12. AMS MNEMONIC – AEIOU TIPS • A Alcohol, acidosis, arrythmia • E Encephalopathy, electrolytes, endocrine, environmental • I Insulin • O Opiates, oxygen (hypoxia) • U Uremia • T Trauma, toxins • I Infection, increased ICP • P Psychosis, poisoning (CO, cyanide), porphyria • S Stroke, shock, seizure • But…What Causes AMS, Bradycardia & Hypotension? • CVA w/ increased ICP • Infection • Cardiogenic shock • Potassium • Toxin

13. AMS, BRADYCARDIA, HYPOTENSION DDX

14. BRADYCARDIA MANAGEMENT https://www.aclsmedicaltraining.com/adult-bradycardia-algorithm/

15. HYPOTENSION CAUSES https://www.cvphysiology.com/Blood%20Pressure/BP030

16. MANAGEMENT: VOLUME, RATE OR PUMP? https://accessemergencymedicine.mhmedical.com/content.aspx?sectionid=41069038&bookid=521

17. VASOPRESSORS & INOTROPES • Inotropy • Myocardial contractility • Chronotropy • Heat rate • Inotropic agents primary increase heart rate • Vasopressor agents (to varying degrees) increase HR, SVR & CO https://umem.org/educational_pearls/2506/

18. VASOPRESSORS & INOTROPES • Alpha-1 • Increase arterial tone / MAP & venous tone • Augment cardiac preload  • Beta-1  • Increase inotropy, chronotropy & arterial tone / SVR • Beta-2 & Dopamine • Vasodilation increases increases perfusion to cardiac, renal & GI tissues • V1 • Increase arterial vasoconstriction /  MAP https://umem.org/educational_pearls/2506/

19. IN THE ED • Patient had seizure then intubated for airway protection • Radiology: • Optic nerve sheath US normal • eFAST normal • Head CT normal • CXR CHF, cardiomegaly • Cardiac US: • Poor EF, right atrial collapse, global wall motion abnormality https://www.grepmed.com/images/1632; http://www.sonomojo.org/keeping-an-eye-on-intracranial-pressure-detecting-elevated-icp-using-ocular-ultrasound/

20. FURTHER STABILIZATION • Central line placed • Norepinephrine drip • 2 liters lactated ringers • Foley – good UOP • ABG • Combined respiratory alkalosis & metabolic acidosis • Bradycardia resistant to medications • Atropine, glucagon, insulin, glucose had little effect • Transvenous pacemaker placed in ED http://www.tamingthesru.com/blog/procedural-education/transvenous-pacemaker-placement-part-1-the-walkthrough

21. THE “OH…BY THE WAY” • SNF nurse called the ED 2 hours later with the “Oh…by the way…the patient likely also took her room-mates medications when she got up from the breakfast table. Actually…they sit together at breakfast a lot…..” • Her room-mate’s medications? • Metoprolol XL 100mg • Metformin 500mg • Warfarin 10mg po

22. SO…NOT A CODE STROKE!

23. METOPROLOL • Selective β1receptor blocker • Decreases slope of phase 4 action potential • Reduces Na+ uptake & prolongs phase 3 repolarization slowing down K+ release • Lipophilic • No sympathomimetic activity • Weak membrane stabilizing activity • Decreases HR, CO, BP & contractility https://commons.wikimedia.org/wiki/File:Cardiac_action_potential.png

24. BETA RECEPTORS • B1 • Cardiac, renal, adipose • B2 • Smooth muscle (lungs, peripheral vasculature), cardiac • Vasodilation, bronchodilation • B3 • Adipose, cardiac • Thermogenesis, decrease contractility

25. CLINICAL SIGNS & SYMPTOMS • Usually within 2 hours, but 95% within 6 hours of Ingestion • Hypotension • Bradycardia • Arrythmias • Seizures • AMS • Bronchospasm • Hypoglycemia

26. SSX OF BETA BLOCKER OD • Primary organ system affected is cardiovascular • Hallmark of severe toxicity is bradycardia & shock • Selectivity lost in large overdoses

27. WHY HYPOGLYCEMIA? • Normally heart uses free fatty acids as primary energy source • Switches to carbohydrates / glucose when “stressed” • Glycogenolysis & gluconeogenesis inhibition reduce glucose availability • In addition…this woman took her room-mate’s metformin!

28. WHY SEIZURES? • Beta-blockers with sodium channel antagonism can cause a wide-complex bradycardia • Wide-complex bradycardia contributes to seizure development • In this patient, likely prolonged QT + hypoglycemia = seizure

29. POLYPHARMACY • Haloperidol • Metabolized by CYP450 • Worsens AMS • Increases metoprolol effects • Glyburide • Prolonged hypoglycemia • Metformin • Prolonged hypoglycemia • Lactic acidosis • Atorvastatin • CYP450 inducer • Worsens metoprolol effects • Aspirin • Cardioprotective – a positive for this patient • Warfarin • Vitamin K antagonist – made the central line interesting

30. POLYPHARMACY CONCERNS • Majority of patient’s medications utilize CYP450 system • She was on 2 medications that amplified the effects, increased the duration of action & decreased the elimination of metoprolol • Haloperidol & atorvastatin • Add in her room-mate’s medications (warfarin, glyburide, more metoprolol), & this is a recipe for disaster

31. BETA BLOCKER OD + POLYPHARMACY MANAGEMENT • Airway stabilization • IVF boluses • Glucagon • Calcium salts • Vasopressors • Insulin + glucose • Lipid emulsion therapy • Sodium bicarbonate + magnesium (occasionally)

32. SIMULTANEOUS ASSESSMENT & MANAGEMENT • History is incredibly important • Screening labs • ABCs • Intubated & mechanically ventilated • Then address: • Hypotension & bradycardia • Hypoglycemia • Seizures

33. GLUCAGON • Activates adenylyl cyclase  increases CAMP  increased Ca++ available for muscle contraction • (+) Inotropic & chronotropic effects • Side effects: • Nausea & vomiting from esophageal sphincter relaxation • IV 0.05-0.15 mg/kg (3-10mg) bolus • Effects of IV bolus within 1-2 minutes • Duration of action 10-20 mins requires continuous infusion 1-10 mg/hr

34. INSULIN THERAPY • Insulin facilitates cardiac utilization of glucose • “Stress” substrate • Glucagon, epinephrine & calcium all promote free fatty acid utilization • 1 unit/kg IV bolus then 0.5-1.0 unit/kg/h continuous infusion

35. INSULIN THERAPY • Adverse effects include hypoglycemia & hypokalemia • Always give 0.5 gram/kg glucose when initial glucose <400 mg/dL • Q30 minute monitoring of glucose & potassium • Potassium drops precipitously when insulin pushes it into the cell

36. ADRENERGIC RECEPTOR AGONISTS • Beta-adrenergic receptor agonists improve hypotension • Norepinephrine, dopamine, epinephrine, isoproterenol • Most effective is norepinephrine • Works primarily on Beta 1 receptors • Increases HR & BP

37. CALCIUM SALTS • In refractory shock to increase inotropy • Calcium chloride has 3 x more elemental calcium than calcium gluconate • 10% gluconate 0.6 mL/kg over 5-10 mins • Then 0.6-1.5 mL/kg/h • 10% chloride 0.2 mL/kg over 5-10 minutes • Then 0.2-0.5 mL/kg/h https://scholarblogs.emory.edu/curbsideconsult/2014/05/09/case-of-the-month-beta-blocker-overdose/

38. SODIUM BICARBONATE • QRS interval >120 MS • Dose 2-3 mEq/kg of 8.4% NaHCO3 • May repeat boluses

39. TRANSVENOUS PACING • Electrical capture & restoration of blood pressure https://emedtravel.wordpress.com/2012/04/13/%E2%99%A5-understanding-pacemakers-part-5-of-5/

40. PHOSPHODIESTERASE INHIBITORS (MILRINONE)? • Limited data • Inhibits breakdown of cAMP by PDE • Maintains intracellular calcium levels • (+) Inotropic effects • No increase in myocardial oxygen demand or HR • Continuous IV infusion of 0.5 micrograms/kg/min

41. NOT HELPFUL • Atropine • Muscarinic blocker • Unlikely to help or harm • GI decontamination • Activated charcoal of limited benefit within 1-2 hours after ingestion • Whole-bowel irrigation +/- benefit

42. LAST DITCH OPTIONS • Hemodialysis not an option for metoprolol • Lipid-bound • Intralipid emulsion therapy • Promising, but not standard of care • For intractable hypotension / cardiogenic shock: • ECMO • Intra-aortic balloon pump

43. REFERENCES • Wax PM et al. beta-blocker ingestion: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila) 2005; 43:131 • Lyden AE, Cooper C, Park E. Beta-Blocker Overdose Treated with Extended Duration High Dose Insulin Therapy. J PharmacolClinToxicol 2014; 2:1015. http://www.jscimedcentral.com/Pharmacology/pharmacology-2-1015.pdf (Accessed on June 16, 2014). • Shepherd et, al. “Treatment of poisoning caused by B-adrenergic and calcium-channel blockers”. Am J Health Syst. Pharm- Vol 63. Oct 1 2006. • Bronstein AC, Spyker DA, Cantilena LR Jr, et al. 2006 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS). Clin Toxicol (Phila) 2007; 45:815. • Bailey B. Glucagon in beta blocker and calcium channel blocker overdoses: a systematic review. Journal of Clinical Toxicology. 2003; 41 (5); 595-602. • Love JN, Howell JM, Litovitz TL, Klein-Schwartz W. Acute beta blocker overdose: factors associated with the development of cardiovascular morbidity. J Toxicol Clin Toxicol 2000; 38:275. • Leppikangas, et al. Levosimendan as a rescue drug in experimental propanolol-induced myocardial depression: a randomized study. Ann Emerg Med. 2009 Dec; 54(6): 811-817. • Vucinić S, Joksović D, Jovanović D, et al. Factors influencing the degree and outcome of acute beta-blockers poisoning. Vojnosanit Pregl 2000; 57:619. • Taboulet P, Cariou A, Berdeaux A, Bismuth C. Pathophysiology and management of self-poisoning with beta-blockers. J Toxicol Clin Toxicol 1993; 31:531.

44. SUMMARYprehospitalmd@gmail.com / PreparedRescuer.com • When patient can’t give history, rely on what you see with your own eyes • Start resuscitation in the field – if you cannot, notify medical control • Don’t dismiss clinical clues because they do not “fit” your differential • Beware polypharmacy – what you are seeing may be primary or secondary effects of a medical problem or a drug-interaction