intensive care cardiovascular pharmacology
DESCRIPTION
Toni Petrillo-Albarano, MD Director, Pediatric Transport Division of Critical Care Medicine. Intensive Care Cardiovascular Pharmacology. Catecholamines Naturally occurring, biologically active amines Sympathomimetic Mimics stimulation of the sympathetic nervous system. - PowerPoint PPT PresentationTRANSCRIPT
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Toni Petrillo-Albarano, MDDirector, Pediatric Transport
Division of Critical Care Medicine
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"F igh t o r F lig h t "
S ym pa the tic
"S no o ze an d L o ose"
P a ra sym pa the tic
A u to n om ic S ys tem S o m a tic S ys tem
P e rip he ra l N e rv ou s system C e ntra l N erv ou s S ys tem
N e rvo us S ys tem
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Catecholamines Naturally occurring, biologically active
amines Sympathomimetic
Mimics stimulation of the sympathetic nervous system
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Adrenergic Refers to the sympathetic nervous system
Cholinergic Refers to the parasympathetic nervous
system Dopaminergic
Dopamine receptors in renal, visceral, coronary, and cerebral areas
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Inotropic Influencing the force of contraction
Chronotropic Influencing the rate of contraction
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Six receptor subtypes: alpha 1 (post-synaptic)
alpha 2 (pre-synaptic)
beta 1 (cardiac)
beta 2 (vascular/bronchial smooth muscle)
DA 1 (post-synaptic)
DA 2 (pre-synaptic)
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ALPHA 1: Vasoconstriction Mydriasis Uterine contraction Bladder contraction Insulin inhibition Glucagon inhibition
ALPHA 2: Inhibition of
norepinephrine release
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BETA 1: Inotropy Chronotropy Lipolysis
BETA 2: Vasodilation Bronchodilation Uterine relaxation Bladder relaxation Insulin release Glucagon release
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Desensitization: 2o to Chronic exposure
Mechanisms Uncoupling Down-regulation Sequestration
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BaroreceptorsBaroreceptors
Peripheral Peripheral vascular vascular resistanceresistance
Parasympathetic Parasympathetic autonomic autonomic
nervous nervous systemsystem
Heart Heart raterate
VASOMOTOR CENTERVASOMOTOR CENTER
Sympathetic Sympathetic autonomic autonomic
nervous nervous systemsystem
Contractile Contractile forceforce
Venous Venous tonetone
Blood Blood volumevolume
VenousVenousreturnreturn
StrokeStrokevolumevolume
CardiacCardiac outputoutput
Meanarterial
pressure
Renal blood Renal blood flow/pressureflow/pressure
ReninRenin AngiotensinAngiotensinAldosteroneAldosterone
Hor
mon
al
feed
bac
k lo
opA
uto
nom
ic
feed
bac
k lo
op
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C.O.=Heart Rate x Stroke Volume Heart rate Stroke volume:
Preload- volume of blood in ventricle Afterload- resistance to contraction Contractility- force applied
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PreloadPreloadAfterloadAfterloadContractiliContractilityty
ResistancResistancee
Cardiac Cardiac OutputOutput
Stroke Stroke VolumeVolume
Heart RateHeart Rate
Arterial Arterial PressurePressure
OO22 Delivery Delivery
OO22 Content Content
x
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Inadequate tissue perfusion to meet the tissue demands a result of inadequate blood flow and/or
inadequate oxygen delivery.
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Fluid
Pump
Vessels
Flow
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H ig h o rN o r m a lF u n c tio n
M ald is tr ib u tedB lood F low
D ecreased S V R
C om p en sa ted
D em in ish edT issue
P erfu s ion
L owC ard iacO u tp ut
R ed u cedS y sto lic F in c t ion
U n com p en sa ted
M y ocard ia lD y sfun ct ion
M y ocard ia lD am age
R ed u cedV en tr icu lar
F illin g
P er icard ia lT am p on ade
R ed u cedP re load
H em m orrh age
Septic (Distributive) Cardiogenic Obstructive Hypovolemic
SHOCKSHOCK
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Inadequate Fluid Volume (decreased preload) Fluid depletion
internal external
Hemorrhage internal external
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Pump Malfunction (decreased contractility) Electrical Failure Mechanical Failure
cardiomyopathy metabolic anatomic hypoxia/ischemia
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Abnormal Vessel Tone (decreased afterload) Sepsis Anaphylaxis Neurogenesis (spinal) Drug intoxication (TCA, calcium channel
blocker)
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OBSTRUCTED FLOW
Pericardial tamponade
Pulmonary embolism
Pulmonary hypertension
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Type of Shock
Preload
Afterload
Contractility
Cardiac Output
Cardiogenic
Hypovolemic
Septic
Early
Late
Obstructive
Distributive
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DopamineDopamine
EpinephrineEpinephrineNorepinephrine
Norepinephrine Dobutamine
Dobutamine
Isopro
ternol
Isopro
ternol
Neosynephrine
Neosynephrine
ßß
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Usage: activates multiple receptors
DA1, DA2, beta, alpha
receptors activated in dose related manner
shown to increase at low doses: glomerular filtration rate renal plasma flow urinary Na+ excretion
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Pharmacodynamics: 0.5 - 2.0 mcg/kg/min - dopaminergic 2.0 - 5.0 mcg/kg/min - beta 1 5.0 - 20 mcg/kg/min - alpha
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Indications: Low cardiac output Hypotension with SVR Risk of renal ischemia
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In healthy humans and animal models, RDD augments: RBF, GFR, and natriuresis
In experimental models of ischemia and nephrotoxic ARF, RDD augments: RBF, GFR, and natriuresis
Denton et al, Kidney Int. 49:4-14,1996Denton et al, Kidney Int. 49:4-14,1996
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Most human studies failed to demonstrate: RDD prevents ARF in high risk patients improves renal function or effects outcome in
established ARF The “dark side”
cardiovascular and metabolic complications
Denton et al, Kidney Int. 49:4-14,1996Denton et al, Kidney Int. 49:4-14,1996
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Complications: activity with NE depletion PA pressure pulmonary vascular resistance Dysrhythmias Renal vasoconstriction Tissue necrosis
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Is Dopamine the Devil?
Dopamine administration can reduce the release of a number of hormones from the anterior pituitary gland, including prolactin which can have important immunoprotective effects
Dopamine administration was associated with ICU and hospital mortality rates 20% higher than in patients with shock who did not receive dopamine
Critical Care Medicine - Volume 34, Issue 3 (March 2006)
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Synthetic catecholamine Direct beta1 weak alpha Indications:
Low cardiac output in patients at risk for: Myocardial ischemia Pulmonary hypertension LV dysfunction (cardiomyopathy)
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Dosemcg/kg/min
0.5-2.5 5 7.5-10
Receptor beta 1 beta 1 beta 1
MajorEffects
VariablyCI (15%)
CI (15%) BP (5%)HR (no change)SVRPVR
CI (30%) BP (15%) HR (5%)SVRPVR
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Major indication bradycardia
Pure beta Potent pulmonary/ bronchial vasodilator Increased cardiac output Widened pulse pressure Increased flow to non-critical tissue beds
(skeletal muscle)
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Tachycardia Dysrhythmias Peripheral vasodilation Increased myocardial consumption
CPK indicating myocardial necrosis Decreased coronary O2 delivery “Splanchnic steal” by skeletal muscle
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Pressor of choice post-arrest Shock
with bradycardia unresponsiveness to other
vasopressors anaphylaxis
Low cardiac output syndrome
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Limited data available in children Plasma concentration varies linearly with
infusion rate Clearance
15.6-79.2 m/kg/min
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Most potent catecholamine Direct acting
no catecholamine stores needed Prominent alpha and beta
effects Increased diastolic pressures
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Dosemcg/kg/min
0.02-0.08 0.2-0.8 0.8-2.0 >2.0
Population Adultspost CVsurgery
Newbornanimals
Newbornanimals
Newbornanimals
Receptor beta1,beta2
beta1,beta2
beta1, alpha1 alpha1
Majoreffects
CI HR BP SVR PVR
CI HR BP SVR PVR
CI SVR PVR
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Complications Renal ischemia Dysrhythmias Severe hypertension Myocardial necrosis Hyperglycemia Hypokalemia
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Leave ‘em Dead!Leave ‘em Dead!
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Indications Sepsis with vasodilation unresponsive
to volume expansion Hypotension unresponsive to therapy
Dose: 0.05 - 1 mcg/kg/min
t 1/2 = 2 - 2.5 min
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Potent peripheral alpha agonist Little beta 1 effects
Minimal to no beta 2
Produces vasoconstriction SVR, PVR increases systolic, MAP, diastolic BP
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Renal vasoconstriction may be decreased with dopamine
Possible cardiac function due to increased afterload
Dysrhythmias Tissue necrosis
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Mechanism of action Phosphodiesterase III inhibitor
Pharmacodynamics: Almost pure inotrope
CI Potent vasodilator
SVR PVR
Bolus: 50 mcg/kg Infusion: 0.375 - 0.75 mcg/kg/min
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Pharmacokinetics: t 1/2 = 90 min
Side effects: Hypotension Thrombocytopenia
Advantages: No precipitation Short t 1/2
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ADH Analog Increases cyclic adenosine monophosphate (cAMP)
which increases water permeability at the renal tubule resulting in decreased urine volume and increased osmolality
direct vasoconstrictor (primarily of capillaries and small arterioles) through the V1 vascular receptors
directly stimulates receptors in pituitary gland resulting in increased ACTH production; may restore catecholamine sensitivity
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Vasodilatory shock with hypotension unresponsive to fluid resuscitation and exogenous catecholamines 0.0003-0.002 units/kg/minute (0.018-0.12
units/kg/hour); titrate to effect
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A Rational Approach to Pressor A Rational Approach to Pressor Use in the PICUUse in the PICU
Shock / HypotensionShock / Hypotension
Volume ResuscitationVolume Resuscitation
Signs of adequate circulationSigns of adequate circulation
Adequate MAPAdequate MAP
NONO
NO NO pressorspressors
YesYes
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A Rational Approach to Pressor A Rational Approach to Pressor Use in the PICUUse in the PICU
NONO
Dopamine?? Or Dopamine?? Or perhaps now NEperhaps now NE
Inadequate MAPInadequate MAP
NorepiNorepi
Signs of adequate circulationSigns of adequate circulation
Adequate MAPAdequate MAP
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A Rational Approach to Pressor A Rational Approach to Pressor Use in the PICUUse in the PICU
norepinephrinenorepinephrine
Inadequate MAPInadequate MAP
low C.O.low C.O.
epinephrineepinephrine
adequate adequate MAPMAP
Milrinone or Milrinone or dobutaminedobutamine
Good C.OGood C.O
VasopressinVasopressin
COCO
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Questions ???Questions ???