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 RR 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 Treatments initiated
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
CAUSE
DIFFERENTIAL
MANAGEMENT
Beta Blocker
Hypoglycemia
Glucagon, Insulin + glucose, pressors
Calcium Channel Blocker
High lactate, hyperglycemia
Calcium, pressors, insulin + glucose
Cardiac glycosides (digitalis)
Ventricular arrythmia, high digoxin level, hyperkalemia
Digibind
Class IC Antiarrhythmic (propafenone)
Wide-complex bradycardia
Inotropes, vasopressors, NaHCO3, pacemaker
Clonidine
Opiod-like symptoms (miosis, bradypnea)
Naloxone
Cyanide
Metabolic acidosis, high lactate
Hydroxocobalamin
Organophosphates
Muscarinic toxidrome
Atropine, 2PAM

14. BRADYCARDIA MANAGEMENT

15. HYPOTENSION CAUSES

16. MANAGEMENT: VOLUME, RATE OR PUMP?

17. VASOPRESSORS & INOTROPES
Inotropy
Myocardial contractility
Chronotropy
Heat rate
Inotropic agents primary increase heart rate
Vasopressor agents (to varying degrees) increase HR, SVR & CO

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

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

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

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 β1 receptor blocker Lipophilic
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

24. BETA RECEPTORS B1 B2 B3 Cardiac, renal, adipose
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
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 mg/kg (3-10mg) bolus
Effects of IV bolus within 1-2 minutes
Duration of action 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 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 mL/kg/h
10% chloride 0.2 mL/kg over 5-10 minutes
Then mL/kg/h

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

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 GI decontamination 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 Pharmacol ClinToxicol 2014; 2: (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
Bronstein AC, Spyker DA, Cantilena LR Jr, et al 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);
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 Dec; 54(6):
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. SUMMARY prehospitalmd@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