Download Toxic Bradycardia and Hypotension

Toxic Bradycardia
and Hypotension
Alyssa Reed, R1
Thanks to Dr Mark Yarema
CASE
 It is 330 am when the paramedics patch to tell you they are
on scene with a man who has a pulse of 45 and SBP of 80
 What medical conditions could cause this?
Medical Causes of Bradycardia
 MI
 Sick Sinus Syndrome
 Hyperkalemia
 Hypothermia
 Increased ICP
 Vasovagal
 Physiologic (athletes)
CASE CONTINUED…
 The patient arrives. Vitals are unchanged after 2L N/S and
2 mg of atropine. He is obtunded but breathing
spontaneously. His wife says he has a history or atrial
fibrillation, angina, hypertension and depression. The
paramedics found a lot of pill bottles beside him and
suspect an overdose. They left the bottles behind.
 What medications cause bradycardia?
TOXIC BRADYCARDIA
 Beta Blockers
 Calcium Channel Blockers
 Cardiac glycosides (digoxin)
 Cholinergic agents
 Clonidine/Imidazolines (alpha2 agonists)
 Opioids/Sedative Hypnotics
 Phenylpropanolamine (alpha1 agonists)
 Sodium channel blockers
Can we eliminate any of these based on clinical presentation?
TOXIC BRADYCARDIA
 Beta Blockers
 Calcium Channel Blockers
 Cardiac glycosides (digoxin)
 Cholinergic agents
 Clonidine/Imidazolines (alpha2 agonists)
 Opioids/Sedative Hypnotics
 Phenylpropanolamine (alpha1 agonists)
 Sodium channel blockers
THE “BIG FOUR”
 Beta Blockers
 Calcium Channel Blockers
 Cardiac Glycosides
 Sodium Channel Blockers
Introduction
 Maybe put in some physiology and table 17.11 page 393 of
lilly
CASE
 40M brought by EMS after an OD. Drug unknown. Pulse is
50 and SBP is 90.
 Which of the four do you think is most likely responsible?
Na Channel Blockers
 Class IA Antiarrhythmics
 TCAs
• Quinidine
 Diltiazem/Verapamil
• Procainamide
 Propranolol
• Disopyramide
 Carbamazepine
 Class IC Antiarrhythmics
• Flecainide
• Propafenone
 Cocaine
Presentation
 QRS widening
 Hypotension
 Seizures
 Altered Mental Status
 Membrane Stabilizing Activity
 Decreased perfusion
Management
 Sodium Bicarbonate
 50ml = 50mEq = 1ampule
 Indications
QRS > 100ms
2 Persistent hypotension despite adequate fluid resus
3 Dysrhythmias
 Dosing
• Bolus 3 amps
• 3 amps in a bag of D5W and infuse and 2-3x
maintenance
1
 Hypertonic Saline
CASE
 A 55M is brought in by the paramedics with a pulse of 40
and SBP of 78. His BG is 18. He is AOx3.
 He has a history of “heart problems” and no other medical
history
 K 4.0
 Which of the “big four” is likely responsible? (see next ECG to
help eliminate)
 Put in ECG that is slow and narrow
Beta Blockers
Calcium Channel Blockers
Vitals
Hypotensive
Bradycardic
Hypotensive
Bradycardic
Tachycardic
Mental Status
Depressed
Preserved
Blood Glucose
Low-Normal
High
Calcium Channel Blockers
 All block L-type calcium channels
 Heart*
Contractile Tissue
• Pacemaker cells
Vascular Smooth Muscle*
Endocrine (including beta pancreatic cells)
Retina
Skeletal muscle
•




1) Myocyte depolzn
triggers opening of
LTCC
 Put in a pic of the channels and depolarization
2) Causes release
of stored Ca from
SR
3) Contract
Calcium Channel Blockers
2 Major Clasess
 Dihydropyridines
• Preferentially block L-type calcium channels in the
vasculature
• Potent vasodilators with little negative effect upon
cardiac contractillity or conduction
 Non-dihydropyridines
• Preferentially block L-type calcium channels in the
myocardium
• Negative inotropic effects and decrease AV node
conduction
Q: Why is brady not listed as complication of the dihydropyridines?
CCB OD Presentation
 Hypotension
 Bradydysrhythmias (or reflex tachycardia)
 Normal mental status
 Hyperglycemia
 disruption of fatty acid metabolism creating relative insulin
resistance and decreased release of insulin from β panc cells
 Pulmonary Edema
 Heart failure + vasodilation and extravasation
 Ileus
 Decreased smooth muscle function in bowel
CCB OD Dx
 No urine or serum test readily available
 ECG
 CXR
 Lytes (including Ca, Mg)
 Blood Glucose
 ABG
What are some of the ECG findings/rhythms in CCB OD?
CCB OD and the ECG
 Bradysrhythmias
• AV block of all degrees
• Sinus arrest
• AV dissociation
• Junctional rhythm
• Asystole
 Reflex Sinus Tach
• Nifedipine OD
OD General Approach
1. ABCs
2. GI Decontamination
•
•
•
Activated charcoal (50G in adult, 1g/kg in peds)
Gastric Lavage
Whole Bowel Irrigation (polyethylene glycol 2L/hr
adults, 500cc/hr peds)
3. Enhanced Elimination
•
Hemodialysis
4. Antidotes
5. Supportive care
CCB OD Mx
 HYPOTENSION
 BRADYCARDIA
• Fluids
• Atropine
• Calcium
• Calcium
• Glucagon
• Glucagon
• Pressors
• Pacer
Atropine
 Given routinely to symptomatic bradycardic
patients
 Often ineffective
 Adults: 0.5-1 mg IV Q3min to a max of 3mg
 Peds: 0.02mg/kg IV with a min dose of 0.1mg
and a max of 1mg
Calcium
 CALCIUM CHLORIDE
 CALCIUM GLUCONATE
• 10% solution
• 10% solution
• 1g/10ml
• 1g/10ml
• 1g = 13.6 mEq
• 1g = 4.5 mEq
• Central line
• Peripheral line
• Dose: 1g over 10 min
• Dose: 3g (30cc) over
(10cc) Q15 to a max
of 6 g and can infuse
1-2g/hr if responsive
10 min
Glucagon
 Increases intracellular levels of cAMP
• Opens Ca channels
 Animal models
• increase in heart rate
• Little effect on MAP
 Bolus: 5mg over 1-2 min, to max of 15mg (this is diluted in
10cc N/S)
 Maintenance: infusion of response dose mg/hr
 Vomiting and aspiration risk
 Phenol toxicity
Glucagon
Catecholamine
pressors
Glucagon
Gs
Amrinone
ATP
cAMP
Phosphodiesterase
AMP
Pressors
Q: What would be the ideal properties of a pressor in CCB tox?
A: Direct-acting agent with +chronotropy, inotropy, and
vasoconstrictive effects
Q: What would you use?
A: Norepinenphrine is initial choice
Dopamine not because indirect effects and little alpha
Can increase pulmonary edema and ischemic vascular dz
and renal failure
Insulin and Glucose
 CJEM 2006 Prediger and Yarema
 Systematic review of 13 papers
 20 cases of CCB OD (17 adult, 3 pediatric)
 Most effective at treating hypotension (n=15)
 3 patients converted to sinus from AV block
 Dosing and length of treatment varied widely
 AE: asymptomatic hypoglycemia
(n=8),hypokalemia (n=4)
 Conclusion: HDIG is safe and effective treatment of
CCB overdose
Insulin and Glucose
 The heart usually metabolizes free fatty acids but in shock
state it needs glucose
 In CCB OD cardiac glucose uptake is impaired b/c
Decreased insulin release (calcium mediated)
2. CCB toxicity induces a state of insulin resistance
(myocardium and rest of body)
3. Acidosis and low perfusion limits glycolysis and carbohydrte
delivery to the heart
1.
 Insulin acts as a pressor

Improved glucose delivery and uptake to the heart and
improving cardiac performance
Insulin and Glucose
 Disrupt state of carbohydrate dependence and insulin
resistance
 Animal models
• Improved survival with hyperinsulinemia/euglycemia
compared to calcium, pressors and glucagon
• Positive inotropic effects
 Bolus: 0.1U/kg IV of regular insulin
 Infusion: 0.2-0.5 U/kg/hr
 Glucose: 25-50 g of dextrose at beginning or can infuse at
0.5 g/kg/hr
Other Therapies
 Phosphodiesterase Inhibitors
• Amrinone , milrinone
• Increase cAMP by preventing degradation of it by
phosphodiesterase enzyme
• May exacerbate hypotension
• ICU setting with pulmonary artery catheter
 Sodium Bicarbonate
• Prolonged QRS or lactic acidosis
• 1amp= 50mEq
• Put 3 amps in 1L D5W and infuse and two times
maintenance
Invasive Mx
 Transvenous pacing
• Does not counteract negative inotropic
effects
• Successful capture may not correct
hypotension
 Intraaortic balloon pump
 Cardiopulmonary bypass
Summary
 Block L-type channels
• Vascular smooth muscle
• Cardiac muscle cells and pacemaker cells
 Hypotension, brady or tachy, preserved mental status,
hyperglycemic
 Mx
• Early WBI
• Fluids/atropine
• Calcium
• Glucagon
• Pressors
• Insulin and glucose
CASE
 50F brought in by EMS. Patient is altered. T= 37, P= 50,
RR= 12, SBP= 74, O2=90%RA, BG 3.5
 Hx of “heart problems” and hypertension
 Which of the big four do you suspect?
Beta Receptors
Beta 1
 Primarily in the heart
 Increase 1) heart rate, 2) contractility, and 3) AV
conduction
 Decrease AV node refractoriness
Beta 2
 Primarily in bronchial and peripheral smooth muscle
 Also in liver, uterus, heart
 Vasodilation, bronchodilation, gluconeogenesis,
glycogenolysis
Beta 3
 Adipose tissue and heart
 Thermogenesis
Beta Blockers
 Structurally resemble isoproterenol (pure β agonist)
 Competitively inhibit endogenous catecholamines
(ex. Epinephrine) at the B-receptor
 These catecholamines normally bind to the receptor
and result in activation of adenyl cyclase, resulting in
cAMP
 cAMP augments:
Inotropy (myocardial contraction)
2. Dromotropy (cardiac conduction)
3. Chronotropy (heart rate)
1.
How would you expect the patient to
present?
Clinical Presentation
 Bradycardia
 Seizures (esp.
 Hypotension
propranolol)
 Symptomatic
Bronchospasm
 VT or VF
 Mild hyperK
 Unconsciousness
 Respiratory arrest
or insufficiency
 Hypoglycemia
(uncommon in
adults)
Rosen’s Table 150-8
βB Properties
1. Membrane-Stabilizing Activity (MSA)
•
•
Inhibition of myocardial fast sodium channels
Can result in wide QRS and other dysrhythmias
2. Lipophilicity
•
•
High lipid solubility= rapidly cross BBB
Cause altered LOC (independent of hypoperfusion)
3. Intrinsic Sympathomimetic Activity (ISA)



Partial agonist effect at beta receptor site
Cause less bradycardia and hypotension
DO NOT completely protect
Noncardioselective βB
MSA
Lipophilic
ISA
½ life (hr)
Comments
Propranolol
++
+
-
4
Most deaths
Nadolol
-
-
-
10-20
Dialyzable
Labetalol
+
-
-
4-6
α blocker too
Sotalol
-
+
-
7-18
Class III/II
Rosen’s Table 150-3
Cardioselective βB
MSE
Lipohilic
ISA
½ life (hr)
Metoprolol
-
+
-
3-4
Atenolol
-
-
-
5-8
Esmolol
-
-
-
0.13
Acebutolol
++
+
+
2-4
Rosen’s Table 150-3
Comments
Dialyzable
QT long
βB OD and the ECG
 Increased PR from decreased conduction
velocity down AV node
 Bradycardia from decreased automaticity
within SA node
 Ventricular tachydysrhythmias with MSA βB
 Wide QRS with MSA βB
 QT prolongation with sotalol OD
Which beta blocker might cause
this dysrhythmia?
βB OD Mx
 HYPOTENSION
 BRADYCARDIA*
• Fluids
• Atropine
• Glucagon
• Glucagon
• Epinephrine
• Pacemaker
• Isoproterenol
• Epinephrine
• Isoproterenol
* Only tx if third degree block or symptomatic
Atropine
 Symptomatic bradycardia only
 Adults: O.5-1mg IV to a max of 3mg
 Peds: 0.02mg/kg with a min of 0.1mg and max of
1mg
 Poor effect on improving bradycardia and
hypotension
Glucagon
 Remember glucagon activates adenylate cyclase at a
site independent from beta-adrenergic sites
• Increases cAMP= increases intracellular Ca=
increasing contractility
 Considered first line (“antidotal”)
 Dose
• 2-5mg (50mcg/kg in peds) diluted in 10cc N/S over 1-
2 min to a max of 15mg
• Maintenance: response dose in mg/hr
Beta blocker “antidotes”
Catecholamine
pressors
Glucagon
Gs
Amrinone
ATP
cAMP
Phosphodiesterase
AMP
Insulin
 Animal models show promise
• Improved cardio and hemodynamic parameters
and decreased mortality
 No definite dosing regimen
• Regular insulin infusion starting at 0.1U/kg/hr
combined with glucose at 1g/kg/hr
• Check glucose levels every 30-60min
• Less than in CCB OD (0.2-0.5U/kg/hr after a bolus)
Others
 Calcium
• Shown to reverse hypotension in animal and human
models
• Dosing: see CCB OD section (Calcium chloride vs.
gluconate)
 Pressors
• Epinephrine and norepinephrine have both been used
• Poor outcomes
 Isoproterenol
• Should be ideal because B1 and B2 agonist effects
• However, can worsen hypotension
Others
 Phosphodiesterase Inhibitors
• Inhibit breakdown of cAMP by phosphodiesterases
• Case reports only
• Use only after other therapies have failed
 Sodium Bicarbonate
• Safe adjunct
• Use if QRS wide
• 1-2mEq/kg IV push
 Magnesium
• Ventricular arrhythmias
• Sotalol OD
Others
 Intravenous pacing
• Profound bradycardia
• Frequently cannot capture
• Can increase heart rate without a corresponding increase in
perfusion
 Intraaortic balloon pump
• Successful case reports in failed pharmacological tx of
propranolol and atenolol OD
 Hemodialysis
• Nadolol, sotalol, atenolol
Summary
BETA BLOCKER OD
1. GI Decontamination
2. Atropine/Fluids
3. Glucagon
4. Calcium
5. Insulin/Glucose
6. Pressors (with caution)
7. Phosphodiesterase
inhibitors
8. Invasive tx
CCB OD
1. GI decontamination
2. Atropine/Fluids
3. Calcium
4. Glucagon
5. Insulin/glucose
6. Pressors (with caution)
7. Invasive tx
CASE
 55M brought in by EMS. Pulse is 45, SBP is 95. Patient
complaint of nausea and vomiting for several days and
difficulty seeing for the last day.
 Hx: HTN, Afib
Vomiting and PVCs
What did he likely take?
Cardiac Glycosides
Na-K ATPase Inhhibitors
 Digoxin, Digitoxin, Ouabain, Foxglove, Lilly of the
valley, oleander
 2 desired effects of Digoxin
1. Improve the contractility of the failing heart
•
By blocking the Na-K ATPase pump and
ultimately increasing intracellular Ca which
increases the force of contraction
2. Prolong the refractory period of the AV node in pts with
SVT
• By enhancing vagal tone and reducing
sympathetic activity
Clinical Presentation
 ACUTE
 Few initial signs and
symptoms
 Cardiac instability
 HyperK
* Usually preserve BP and not
significantly hypotensive like βB
and CCBs
 CHRONIC
 Fatigue
 Vision
• Blurred vision
• Color disturbances
 GI
• Abdo pain
• Diarrhea
• Nausea/Vomiting
 CNS
• Headache
• Dizziness
• Confusion
Diagnosis
 ECG
 Electrolytes
 Serum digoxin level
 Measure at least 6 hrs after last dose (time needed to
reach steady state)
 False + elevated levels (no SSx)
• Pregnant women
• Chronic renal failure or hepatobiliary dz
 False – normal levels (sig SSx)
• Foxglove or oleander ingestion
Digoxin and the ECG
Increased
vagal tone.
What are common digoxin toxic arrhythmias?
Increased
automaticity
Dig Tox and the ECG
 NONSPECIFIC
 PVCs
 1st, 2nd (type 1), 3rd




degree AV block
Sinus bradycardia
Sinus tachycardia
Sinoatrial block or
arrest
Afib with slow
ventricular response
 Junctional escape




rhythm
AV dissociation
Ventricular bigeminy
and trigeminy
VTach/VFib
Torsades de pointes
Dig Tox and the ECG
 MORE SPECIFIC
 Afib with slow, regular ventricular rate (AV
dissociation)
 Nonparoxysmal junctional tachycardia (70-130
bpm)
 Atrial tachycardia with block (150-200 bpm)
 Bidirectional VTach
Dig Tox and the ECG
 Very rarely see
 Mobitz Type II block
 Afib or Aflutter with rapid ventricular
response
 Unimorphic Vtach
AFIB with Slow Ventricular
Response
Nonparoxysmal Junctional
Tachycardia
Bidirectional VT
Potassium and Dig Toxicity
 Acute Toxicity
• Correlates with hyperkalemia
• K level determines prognosis and treatment
 Chronic Toxicity
• K normal or low
• Slow rise over time allows kidneys to balance
• Patients often also on diuretic which reduce the K
level
Potassium and acute digoxin toxicity
8
K<5.0, 0% mortality
K 5-5.5, 50% mortality
K>5.5 100% mortality
7
6
5
4
3
Died
Survived
Bismuth, C., et al. Hyperkalemia in acute digitalis poisoning: prognostic
significance and therapeutic implications. Clin Toxicol 1973; 6:153.
Predisposing Factors
 Advanced age
 Women
 Renal Insufficiency
 Heart Disease
• Congenital Heart Dz
 Electrolyte Imbalance
• Hypo or hyper kalemia
• Hypomagnesemia
• Hypercalcemia
 Sympathomimetic Drugs
 Cardiotoxic Coingestants
• Ischemic heart Dz
• BB
• CHF
• CCB
• Myocarditis
• Tricyclic antidepressants
 Alkalosis
 Hypothyroidism
 Drug Interactions
• Quinidine, amiodarone
• Erythromycin
Management of Dig Toxicity
 GI Decontamination
 Electrolyte Correction
 Bradycardias
 Ventricular Dysrhythmias
 Fab Fragments
GI Decontamination
 Digoxin is absorbed effectively by activated
charcoal
 Within one hour of ingestion
 50g for adults
 1g/kg for peds
 No improvement in outcome has been proven
Electrolyte Correction
 K
 Hypo: in chronic tox want to replace (goals of 3.5 to 4mEq/L)
•
Oral repletion preferred
• Don’t replace in acute
 Hyper: in acute tox want to reduce it
• Insulin glucose
• Beta agonist
• Sodium bicarbonate
• NOT Calcium
 Mg
• Hypomag often reported
• Replace with 2-4g magnesium sulfate
Bradycardias
 Atropine
• Reverses dig induced vagal tone
• More effective than in other cardiac drug
toxicity (acute toxicity)
• 0.5mg-1mg to a max of 3mg Q2-3 min
 Pacing
• If fail atropine treatment
• Catheter may induce ventricular dysrhythmias
• External pacing safer but not as effective
Ventricular Dysrhythmias
 Vagal Maneuvers
• NO!!! Can cause asystole and cardiac arrest
 Phenytoin
• Safe
• May enhance AV conduction
• Load with 10-15mg/kg
Infuse at 25-50mg/min
 Lidocaine
• Safe
• Load with 1-3mg/kg
Infuse at 1-4mg/min
Fab Fragments
 Digibind™
 Purified from sheep
 Rapidly bind to digoxin in the tissues
 Efflux of intracellular digoxin
 Further binding of free digoxin
 Renally excreted
Indications for Digibind™
1. Vetricular dysrhythmias
2. Severe bradycardia unresponsive to atropine
3. Serum K > 5 mEq/L (acute ingestion)
4. Serum digoxin level

>10 mmol/L at any time
 >12.5 mmol/L 6 hours after ingestion
5. Acute Ingestion of > 10mg (4mg peds)
6. Presence of a digoxin-toxic rhythm in the setting of
an elevated digoxin level
Effectiveness of Digibind
Antman, EM, et al. Circulation 1990
 N=150 (cases of life-threatening digitalis tox)
 Results
• 80% complete resolution of all signs and symptoms
• 10% improved
• 10% showed no response
• Median time to initial response was 19 min
• Time to complete response was 88 min
• 54% of cardiac arrest patients survived
hospitalization
Nonresponders to Digibind
1. Underlying heart disease (that causes some of
the manifestations)
2. Too low a dose of Fab
3. Moribund on presentation
4. Co-ingestion of other cardiac toxic drugs
Dosing of Digibind
 Given IV over 30 minutes
 Unless arrested, then give as a bolus
 Vials of Fab= (Dig level ng/ml x Mass kg)/ 100
 Always round up
 Example: how many vials would you need for a 70kg
woman with a digoxin level of 3 and frequent PVCs?
Vials= (3 x 70) / 100 = 2.1 so you would give 3
What if you don’t know the dig level right away???
Dosing of Digibind
 ACUTE
 Stable- 5 vials
 Unstable- 15 vials
 CHRONIC
 Stable- 1 vial
 Unstable- 4 vials
*1 vial costs approx 400$
Summary- Acute vs Chronic
 CHRONIC
 ACUTE
1. Higher mortality
1. Lower mortality
2. K normal or low
2. K normal or high
3. Ventricular dysrhythmias
3. Bradycardia and AV
more common
4. Usually elderly patients
5. Often need Fab fragment
therapy
6. Underlying heart dz
increases morbidity and
mortality
block more common
4. Usually younger patients
5. Often do well without
Fab fragment therapy
6. Absence of heart dz
decreases morbidity and
mortality
Bradycardia and Hypotension
 Sodium channel blockers
 Wide QRS.
 Rx = bicarbonate
 Digoxin
 Blocks, increased automaticity.
 Rx = digibind.
 Calcium channel blockers
 Increased glucose, preserved mental status
 Rx - Calcium, pressors, insulin / glucose
 Beta blockers
 Altered mental status, normal glucose
 Rx - Glucagon, insulin / glucose, pressors