CVS_Drug_Poisoning-Dr Jang - Jacobi Emergency Medicine
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Transcript CVS_Drug_Poisoning-Dr Jang - Jacobi Emergency Medicine
New York University
Department of Emergency
Medicine/Medical Toxicology
Antidotes for cardiovascular drug
poisoning
David H. Jang
Assistant Professor
Masters of Science Degree in Clinical Investigation (K30)
Clinical and Translational Science Institute (CTSI)
*Funded by the American Academy of Clinical Toxicology Junior Investigator Research Grant and also
supported in part by grant 1UL1RR029893 from the National Center for Research Resources,
National Institutes of Health.
Case
44 year-old man
presents with a
“overdose” after an
argument with his
mother
Patient obtained these
medications from his
mother who he still
lives with in her
basement
Case
Vitals on presentation:
Blood pressure: 140/90
mmHG
Heart rate: 90 BPM
Respiratory rate: 12
Temperature: 98.6
Oxygen saturation:
100% RA
Case
6 hours later…
Case
Repeat Vitals:
Blood pressure: 85/40
mmHG
Heart rate: 40 BPM
Respiratory rate: 20
Temperature: 98.6
Oxygen saturation:
100% RA
Case
Intubated
Hemodynamic support
On norepinephrine
On dopamine
On epinephrine
Still hypotensive…
Options?
Antidotes for cardiovascular
drug poisoning
Cardiovascular drug class
Antihypertensives
Imidazolines
Beta-blockers
Calcium channel
blockers
ACE-Is and ARBs
Cardioactive steroids
Digoxin
Antidysrhythmics
Flecainide
Cardiovascular drug class
Antihypertensives
Imidazolines
Beta-blockers
Calcium channel
blockers
ACE-Is and ARBs
Cardioactive steroids
Digoxin
Antidysrhythmics
Flecainide
Not all things are created
equal…
Beta-blockers
Non-selective
B1-selective
Carvedilol
Atenolol
Esmolol
Intrinsic
sympathomimetic
Pindolol
Beta-blockers
Potassium channel
blockers
Sotalol
Membrane-stabilizing
Propanolol
Calcium channel blockers
Phenylalkylamine
Benzothiazepine
Verapamil
Diltiazem
Dihydropyridines
Nifedipine
Amlodipine
Nicardipine
Epidemiology
Epidemiology
Epidemiology
Epidemiology
Beta and calcium channel
blocker poisoning
Clinical Features
Bradycardia
Hypotension
Management
Isotonic fluids
Glucagon
Inotropes/Pressors
High-insulin
Lipid emulsion
Beta and calcium channel
blocker poisoning
Clinical Features
Bradycardia
Hypotension
Management
Isotonic fluids
Glucagon
Inotropes/Pressors
High-insulin
Lipid emulsion
Beta and calcium channel
blocker poisoning
Clinical Features
Bradycardia
Hypotension
Management
Isotonic fluids
Glucagon
Inotropes/Pressors
High-insulin
Lipid emulsion
High insulin-euglycemic
therapy (HIE)
Historical use
Glucose-insulinpotassium (GIK)
Acute myocardial
infarction
Heart failure
Myocardium
Background
Hallmark of BB and
CCB poisoning
Bradycardia
Vasodilation
Decreased contractility
Background
Altered myocardial
physiology
Hyperglycemia
(pancreas/liver)
Altered myocardial
substrate use
Inhibition of lactate
oxidation
Mechanism of action
Alters ions
homeostasis
(potassium/calcium/so
dium)
Metabolic support
Increase lactate uptake
Epi and glucagon
promote FFA use
(increase energy)
Experimental evidence
Experimental evidence
Groups
1. Control: (0/6)
2. Epi: (4/6)(2/4)
3. HIE: (6/6)(6/6)
4. Glucagon: (3/6)(0/3)
Experimental evidence
Groups
1. Control: (0/6)
2. Epi: (4/6)(2/4)
3. HIE: (6/6)(6/6)
4. Glucagon: (3/6)(0/3)
Clinical experience
Clinical experience
Adverse events
Hypoglycemia
Hypokalemia
Treatment guidelines
Intralipid
Background
Triglycerides and
phospholipids
Primary triglycerides
composed of linoleic,
linolenic, and stearic
acid
pH 8, isotonic, various
concentrations
availiable (20% is
primarily used)
Mechanism of action
1. Modulation of
intracellular
metabolism
2. Lipid sink
3. Activation of ion
channels
Experimental evidence
Experimental evidence
Clinical experience
Adverse events
Adverse events
Treatment guidelines
www.lipidrescue.org
Treatment guidelines
Summary
Consider HIE early for
suspected CCB
poisoning
Consider lipid emulsion
when a patient is
perimortem with
suspected lipid-soluble
medication
Methylene blue (MB)
Methylene blue
Sentinel node
detection
Acquired
methemoglobinemia
Vasodilatory shock
Anaphylaxis
Sepsis
Nitric oxide synthase
Physiology of vascular
tone
The evidence for MB
Mechanism of action
Vasodilatory shock from
overdose?
Why calcium channel
blockers?
Why calcium channel
blockers?
Mechanism of action
So to test this…
Methods
Design:
Controlled, blinded
animal design
Subjects:
Adult Sprague-Dawley
rats (300-600 grams)
Preparation
(Instrumentation/sedation)
Protocol:
Phase 1: Dose-finding
Phase 2: Methylene
blue
Protocol summary and
timeline
Phase 1: Amlodipine dose determination
4 mg/kg: Incrementally increase dose 50% and decrease 50%
(5 rats per group – 1, 2, 4, 6, 8 mg/kg)
End-point: Decrease of mean arterial pressure
to10% of baseline
Amlodipine dose
Protocol summary and
timeline
Group 1: AmlodipineNormal saline (Control group)
Group 2: AmlodipineMethylene Blue (Treatment group)
Protocol summary and
timeline
Group 1: AmlodipineNormal saline (Control group)
Group 2: AmlodipineMethylene Blue (Treatment group)
Phase 2: Methylene blue treatment
Baseline Amlodipine
15 min
MB (2 mg/kg)
or saline
3-hours or until death
5 min
0 mins
180 mins
Results
Methylene blue-Pending
Normal Saline-Pending
Questions?