13hellman- vasopressors
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13Hellman- VasopressorsTRANSCRIPT
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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