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VasopressorsVasopressors
Judith Hellman, M.D.Judith Hellman, M.D.Associate
ProfessorAssociate Professor
Anesthesia and Perioperative CareAnesthesia and Perioperative
CareUniversity of California, San FranciscoUniversity of
California, San Francisco
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OverviewOverview Define shock statesDefine shock states Review
drugs commonly used to treat hypotensionReview drugs commonly used
to treat hypotension Overview of drug management of shock
statesOverview of drug management of shock states Describe recent
studies on pharmacologic management Describe recent studies on
pharmacologic management
of hypotension in septic shockof hypotension in septic shock
VASST VASST -- Vasopressin versus Vasopressin versus Norepinephrine
Norepinephrine for septic for septic
shockshock European study European study -- Epinephrine
Epinephrine vs Norepinephrine vs Norepinephrine + +
dobutaminedobutamine Portuguese Study Portuguese Study --
Dopamine versus Dopamine versus NorepinephrineNorepinephrine
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Shock StatesShock States CardiogenicCardiogenic Hypovolemic
Hypovolemic Obstructive Obstructive -- Impairment of
normalImpairment of normal flow of bloodflow of blood
Obstruction of outflow Obstruction of outflow -- PE, pulmonary
HTN, severe ASPE, pulmonary HTN, severe AS Obstruction of inflow
Obstruction of inflow -- Cardiac Cardiac tamponadetamponade, ,
pneumothoraxpneumothorax
Medication effectsMedication effects Neuraxial Neuraxial local
anestheticslocal anesthetics Systemically active drugsSystemically
active drugs
DistributiveDistributive -- Low vascular tone, increased
vascular Low vascular tone, increased vascular
capacitancecapacitance Sepsis and other systemic inflammatory
processesSepsis and other systemic inflammatory processes Acute
adrenal insufficiencyAcute adrenal insufficiency Neurogenic
Neurogenic shockshock
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Drugs Commonly Used to TreatDrugs Commonly Used to TreatShock in
ICUsShock in ICUs
Adrenergic AgentsAdrenergic Agents
PhenylephrinePhenylephrine NorepinephrineNorepinephrine
EpinephrineEpinephrine DopamineDopamine DobutamineDobutamine
IsoproterenolIsoproterenol
VasopressinVasopressin
1 2+++ +++ ++ +
+++ +++ ++
++ ++ +
+ +++ +
+++ +++
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PhenylephrinePhenylephrine Receptors: Receptors: Vascular
effects: Vascular effects: Potent vasoconstrictorPotent
vasoconstrictor Cardiac effectsCardiac effects -- ReflexReflex
BradycardiaBradycardia Decreased cardiac outputDecreased cardiac
output
UsesUses Epidural and spinal anesthesia/analgesiaEpidural and
spinal anesthesia/analgesia Vasodilation Vasodilation (autonomic
instability,(autonomic instability, vasodilators)vasodilators) To
temporize while awaiting access forTo temporize while awaiting
access for other agentsother agents When agents with When agents
with --adrenergic activity cause tachycardiaadrenergic activity
cause tachycardia
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NorepinephrineNorepinephrine Receptors: Receptors: and and 1, 1,
minimal minimal 2 2 -- > > Vascular effects: Vascular
effects: Potent vasoconstrictorPotent vasoconstrictor Cardiac
effectsCardiac effects Increased contractilityIncreased
contractility Increased heart rate/tachycardia (variable)Increased
heart rate/tachycardia (variable)
UsesUses Combined Combined vasodilation vasodilation and
myocardial dysfunctionand myocardial dysfunction
Sepsis/SIRSSepsis/SIRS
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EpinephrineEpinephrine Receptors: Receptors: and and -- = =
Vascular effects: Vascular effects: Potent vasoconstrictorPotent
vasoconstrictor Cardiac effectsCardiac effects
More potent effect on contractility than More potent effect on
contractility than norepinephrinenorepinephrine Increased heart
rate/tachycardiaIncreased heart rate/tachycardia
UsesUses When severe myocardial dysfunction is contributing to
shockWhen severe myocardial dysfunction is contributing to shock
Cardiac arrest Cardiac arrest -- Can be givenCan be given
intraintra--tracheallytracheally AnaphylaxisAnaphylaxis
Potential ProblemsPotential Problems Reduced Reduced splanchnic
splanchnic blood flowblood flow Increased myocardial work load
Increased myocardial work load ischemia, heart failureischemia,
heart failure
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DopamineDopamine Receptors: Receptors: , , 1>2, 1>2,
dopaminergicdopaminergic Vascular effects: Vascular effects:
Vasoconstricts Vasoconstricts at higher dosesat higher doses
Cardiac effects Cardiac effects -- Lower dosesLower doses
Increased cardiac outputIncreased cardiac output Increased heart
rateIncreased heart rate
UsesUses Shock from sepsis or other systemic inflammatory
processesShock from sepsis or other systemic inflammatory processes
To increase urine output (low dose, To increase urine output (low
dose, dopaminergic dopaminergic effect)effect)
Potential problemsPotential problems Dysrhythmias Dysrhythmias
-- Atrial Atrial fibrillation,fibrillation, STST Not a potent
vasoconstrictor Not a potent vasoconstrictor -- oftenoften needneed
additional additional pressorspressors
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DobutamineDobutamine Receptors: Receptors: 1> 1> 22
CardiacCardiac effects: effects: 11
Increased cardiac output Increased cardiac output -- Strong
Strong inotropeinotrope Increased heart rateIncreased heart
rate
Vascular effects: Vascular effects: 2, 2,
VasodilationVasodilation Effect on BP variableEffect on BP variable
UsesUses
Cardiogenic Cardiogenic shockshock Refractory shock from sepsis
or other systemic inflammatory Refractory shock from sepsis or
other systemic inflammatory
processprocess Potential problemsPotential problems
TachydysrhythmiasTachydysrhythmias Hypotension can occur
2Hypotension can occur 2 toto 2 effects2 effects
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VasopressinVasopressin Hormone with many effects: vascular,
renal, endocrineHormone with many effects: vascular, renal,
endocrine VascularVascular
Important role in BP regulationImportant role in BP regulation
Variable vasoconstriction and Variable vasoconstriction and
vasodilation vasodilation of vascular bedsof vascular beds
Vasopressin levels are decreased in sepsisVasopressin levels are
decreased in sepsis UsesUses
Shock from sepsis and other inflammatory processes Shock from
sepsis and other inflammatory processes -- Low dose Low dose
PeriPeri--cardiopulmonary cardiopulmonary bypassbypass Instead
ofInstead of epinephrine during epinephrine during
cardiorespiratory cardiorespiratory arrestarrest Hypotension due to
ACE inhibitorHypotension due to ACE inhibitor
Potential problemsPotential problems Reduced GI blood flow, even
atReduced GI blood flow, even at low doselow dose Cardiac
ischemiaCardiac ischemia
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Vasoactive Vasoactive Drug Management Drug Management of Shock
Statesof Shock States
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Cardiogenic Cardiogenic ShockShock
Dobutamine Dobutamine NorephinephrineNorephinephrine
EpinephrineEpinephrine Phosphdiesterase Phosphdiesterase inhibitors
inhibitors -- Amrinone/milrinoneAmrinone/milrinone
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Hypovolemic Hypovolemic ShockShock
Fluid resuscitation!!Fluid resuscitation!!
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Obstructive Forms of ShockObstructive Forms of Shock
Outflow problems Outflow problems -- PE,PE, Aortic Aortic
coarctationcoarctation, Aortic , Aortic stenosisstenosis, pulmonary
HTN, pulmonary HTN Judicious fluidsJudicious fluids Inotropes
Inotropes or mixed or mixed inotrope/vasoconstrictor
inotrope/vasoconstrictor -- dobutaminedobutamine, ,
norepinephrinenorepinephrine Inflow problems Inflow problems --
Cardiac Cardiac tamponadetamponade, , pneumothoraxpneumothorax
FluidsFluids Relieve sourceRelieve source
((pericardiocentesispericardiocentesis, chest tube), chest
tube)
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MedicationMedication--Induced ShockInduced Shock
PathophysiologyPathophysiology VasodilationVasodilation Cardiac
dysfunctionCardiac dysfunction
Neuraxial Neuraxial blockade blockade --
PhenylephrinePhenylephrine Systemic vasodilators Systemic
vasodilators -- Phenylephrine Phenylephrine or or
norepinephrine norepinephrine (depending on additional
factors)(depending on additional factors) Cardiac
depressantsCardiac depressants
Inotrope Inotrope such as such as dobutaminedobutamine Consider
Consider norepinephrine norepinephrine if suspect concomitant if
suspect concomitant vasodilationvasodilation
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Shock Associated with Systemic Shock Associated with Systemic
Inflammatory ProcessInflammatory Process
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Shock Associated with InflammationShock Associated with
Inflammation
Agents used routinely to treat hypotension due to sepsis Agents
used routinely to treat hypotension due to sepsis and other
systemic inflammatory processes:and other systemic inflammatory
processes: NorephinephrineNorephinephrine DopamineDopamine
VasopressinVasopressin PhenylephrinePhenylephrine
DobutamineDobutamine EpinephrineEpinephrine
Physiology ofPhysiology of hypotension in systemic inflammatory
hypotension in systemic inflammatory processesprocesses Decreased
vascular tone Decreased vascular tone increased vascular
capacitanceincreased vascular capacitance Decreased myocardial
contractilityDecreased myocardial contractility
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VASST Trial: VASST Trial: Vasopressin versus Vasopressin versus
NorepinephrineNorepinephrine
Hypothesis: Low dose vasopressin Hypothesis: Low dose
vasopressin decrease mortality decrease mortality vs norepinephrine
vs norepinephrine (NE) in septic shock(NE) in septic shock
Inclusion criteriaInclusion criteria SIRS SIRS w/documented
w/documented or suspected infectionor suspected infection NE at NE
at 5 5 g/ming/min New organ dysfunctionNew organ dysfunction
Interventions Interventions Vasopressin 0.01Vasopressin
0.01--0.03U/min 0.03U/min vs vs NE at 5NE at 5--15 15 g/ming/min
Titrate other Titrate other pressorpressor(s) to(s) to achieve BP
goalsachieve BP goals
Primary Endpoint: 28 day mortalityPrimary Endpoint: 28 day
mortalityNEJM 2008; 28;358(9):877NEJM 2008; 28;358(9):877--8787
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VASST: ResultsVASST: Results
Subjects Subjects -- 778 patients randomized778 patients
randomized VasopressinVasopressin 396396 NE 382 NE 382
OutcomeOutcome Overall no reduction in 28d (Primary endpoint,
P0.26) or 90d Overall no reduction in 28d (Primary endpoint, P0.26)
or 90d
mortality (P 0.11)mortality (P 0.11) NoNo significant
differences in serious adverse eventssignificant differences in
serious adverse events Subgroups Subgroups
More severe More severe NE > 15mcg/min NE > 15mcg/min
Higher mortality in Higher mortality in vasopressin
groupvasopressin group
Less severe Less severe NE 5NE 5--15 mcg/min 15 mcg/min -- Lower
mortality at 28d Lower mortality at 28d (P 0.05)(P 0.05)
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Recommendations about Vasopressin Recommendations about
Vasopressin Based on Available DataBased on Available Data
Consider using vasopressin in: Consider using vasopressin in:
Patients with septic shock that are on a midPatients with septic
shock that are on a mid--range dose of range dose of
NE (5NE (5--15 mcg/min)15 mcg/min) Patients that develop
Patients that develop tachydysrhythmias tachydysrhythmias on NEon
NE Patients that are extremely Patients that are extremely acidemic
acidemic so wonso wont respond as well t respond as well
to NE (vasopressin not inactivated by low pH)to NE (vasopressin
not inactivated by low pH) Patients on extremely high doses of
NEPatients on extremely high doses of NE ACLS ACLS as an
alternative to epinephrineas an alternative to epinephrine
PeriPeri--CPBCPB
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European Trial: Epinephrine versus European Trial: Epinephrine
versus Norepinephrine Norepinephrine + + DobutamineDobutamine
Hypothesis:Hypothesis: Epi Epi may be better than NE + may be
better than NE + Dobutamine Dobutamine based based on more on more
activityactivity
Study Design:Study Design: RandomizedRandomized trial of
patients with septic shocktrial of patients with septic shock
Subjects:Subjects: 330 patients randomized330 patients
randomized
Epinephrine 161Epinephrine 161 NE + NE + Dobutamine Dobutamine
169 169
OutcomeOutcome Overall no reduction in 28d mortality (Primary
endpoint, P Overall no reduction in 28d mortality (Primary
endpoint, P
0.31) or other secondary endpoints0.31) or other secondary
endpoints NoNo significant differences in serious adverse
eventssignificant differences in serious adverse events
ConclusionsConclusions No significant differenceNo significant
difference
Lancet. 2007 Aug 25;370(9588):676-84
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Dopamine: Dopamine: Sepsis Occurrence in Acutely Ill Patients
(SOAP) Study
Hypothesis: Hypothesis: DA worsens outcome in shock Study
Design: Observational study in 198 ICUsStudy Design: Observational
study in 198 ICUs Subjects: 1058 patients with shock; 462 patients
with Subjects: 1058 patients with shock; 462 patients with
septic shockseptic shock NE: 80.2%; 31.8% received only NENE:
80.2%; 31.8% received only NE DA: 35.4%; 8.8%%; 8.8% received only
DAreceived only DA Epi: 23.3%; 4.5% only Epi: 23.3%; 4.5% only
epiepi Dobutamine Dobutamine + + catecholamines catecholamines
33.9%33.9%
OutcomeOutcome DA and epinephrine used more in nonDA and
epinephrine used more in non--survivorssurvivors DADA an
independent risk factor for mortality in patients with an
independent risk factor for mortality in patients with
shock, and in the subcategory of patients with septic
shockshock, and in the subcategory of patients with septic
shockCrit Care Med. 2006;34(3):589-97
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Portuguese Portuguese Community AcquiredSepsis Study :: Dopamine
(DA) Dopamine (DA) vs vs NENE
Hypothesis:Hypothesis: Study Design:Study Design:
MulticenterMulticenter, observational study of patients with ,
observational study of patients with
communitycommunity--acquired sepsis in 17 ICUsacquired sepsis in
17 ICUs Subjects:Subjects: 458 patients with septic shock458
patients with septic shock
73% received NE73% received NE 50.5% received DA50.5% received
DA
OutcomeOutcome NE associated with worse outcomeNE associated
with worse outcome NE independent risk factor for ICU mortality in
septic shockNE independent risk factor for ICU mortality in septic
shock
Crit Care Med. 2009;37(2):410-6
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Surviving Sepsis Campaign:Surviving Sepsis Campaign:2008
Guidelines2008 Guidelines
Vasopressors NE and DA are the initial vasopressors of choice
Epinephrine, phenylephrine, or vasopressin should not be
administered as the initial vasopressor in septic shock
Vasopressin 0.03 units/min may be subsequently added to
NE Use epinephrine as the first alternative agent in septic
shock
when blood pressure is poorly responsive to NE or DA. Do not use
low-dose dopamine for renal protection
Inotropic therapy Use dobutamine in patients with myocardial
dysfunction
Crit Care Med. 2008 Jan;36(1):296-327
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Thank You!!
Gram-negativeBacteria
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TerlipressinTerlipressin
Vasopressin analogueVasopressin analogue Longer acting than
vasopressin (halfLonger acting than vasopressin (half--life ~ 6
hours versus 6 life ~ 6 hours versus 6
minutes)minutes) Widely used inWidely used in EuropeEurope
UndergoingUndergoing trials in UStrials in US
UsesUses Shock associated with sepsis and other systemic
inflammatory Shock associated with sepsis and other systemic
inflammatory
processesprocesses
Potential problemsPotential problems Decreased cardiac
outputDecreased cardiac output