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inotropes vasopressors
INOTROPES
VASOPRESSORS
R A T I O N A L E O F C H O I C E
SANEESH P JSultan Qaboos University Hospital Muscat
inotropes vasopressors
INOTROPES
VASOPRESSORS
SHOCK
SEPSIS
CARDIAC FAILURE
VASST
NOREPINEPHRINE
DOBUTAMINE
DOPAMINE
RENAL DOSE
HYPOVOLEMIA
RECEPTORS
LEVOSIMENDAN
CATECHOLAMINES
PHENYLEPHRINE
VASOPRESSIN
inotropes vasopressors
INOTROPES amp VASOPRESSORSBasics
Patient ndash clinical features
Pathophysiology
Monitoring
Equipments
Drugs
Shock
CO SV
SVR
Preload
Afterload
inotropes vasopressors
Fundamentals
Volume status
One drugMany receptors
Dose responsecurve
Direct Vs Reflex
actions
inotropes vasopressors
Hemodynamics in Shock
Hypotension
Low SVR(arteriolar tone)
Low CO
inotropes vasopressors
Hemodynamics in Shock
bull Inadequate CObull Comp vasoconstrictionbull Elevated SVR
COLD SHOCK
bull Inadequate SVRbull Pathologic vasodilatationbull Comp elevated CO
WARM SHOCK
Fluid resuscitation
Myocardial dysfunction
inotropes vasopressors
Planning your strategy
inotropes vasopressors
Adrenergic receptors and vasoactive agents
α βα =β
EpinephrinePhenylephrine Norepinephrine
Dopamine
IsoproterenolDobutamine
EpinephrinePhenylephrine
Norepinephrine
DopamineIsoproterenol
Dobutamine
High dose Low dose
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
Inoconstrictors
NorepinephrineEpinephrineDopamine
Inodilators
DobutamineMilrinone
Vasoconstrictors
PhenylephrineVasopressin
Vasodilators
NitroglycerineNitroprusside
Nesiritide
inotropes vasopressors
Vasoconstriction
Vasodilation
PositiveInotropy
Vasopressin
PhenylephrineNorepinephrine
LD EpinephrineDopamine
Dobutamine
HD Dopamine
HD Epinephrine
Nitroprusside
inotropes vasopressors
inotropes vasopressors
HOW DO I MAKE MY CHOICE
inotropes vasopressors
Rationale of choice
EFFECTSAGENTS
inotropes vasopressors
Rationale of choice
Vasopressor Rx
Restoration of adequate BP
BP does NOT always equate to blood flow
inotropes vasopressors
Rationale of choice
Inotrope Rx
IncreaseCardiac Output
To determine whether CO is adequate in patients with shock is a thorny problem
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
INOTROPES
VASOPRESSORS
SHOCK
SEPSIS
CARDIAC FAILURE
VASST
NOREPINEPHRINE
DOBUTAMINE
DOPAMINE
RENAL DOSE
HYPOVOLEMIA
RECEPTORS
LEVOSIMENDAN
CATECHOLAMINES
PHENYLEPHRINE
VASOPRESSIN
inotropes vasopressors
INOTROPES amp VASOPRESSORSBasics
Patient ndash clinical features
Pathophysiology
Monitoring
Equipments
Drugs
Shock
CO SV
SVR
Preload
Afterload
inotropes vasopressors
Fundamentals
Volume status
One drugMany receptors
Dose responsecurve
Direct Vs Reflex
actions
inotropes vasopressors
Hemodynamics in Shock
Hypotension
Low SVR(arteriolar tone)
Low CO
inotropes vasopressors
Hemodynamics in Shock
bull Inadequate CObull Comp vasoconstrictionbull Elevated SVR
COLD SHOCK
bull Inadequate SVRbull Pathologic vasodilatationbull Comp elevated CO
WARM SHOCK
Fluid resuscitation
Myocardial dysfunction
inotropes vasopressors
Planning your strategy
inotropes vasopressors
Adrenergic receptors and vasoactive agents
α βα =β
EpinephrinePhenylephrine Norepinephrine
Dopamine
IsoproterenolDobutamine
EpinephrinePhenylephrine
Norepinephrine
DopamineIsoproterenol
Dobutamine
High dose Low dose
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
Inoconstrictors
NorepinephrineEpinephrineDopamine
Inodilators
DobutamineMilrinone
Vasoconstrictors
PhenylephrineVasopressin
Vasodilators
NitroglycerineNitroprusside
Nesiritide
inotropes vasopressors
Vasoconstriction
Vasodilation
PositiveInotropy
Vasopressin
PhenylephrineNorepinephrine
LD EpinephrineDopamine
Dobutamine
HD Dopamine
HD Epinephrine
Nitroprusside
inotropes vasopressors
inotropes vasopressors
HOW DO I MAKE MY CHOICE
inotropes vasopressors
Rationale of choice
EFFECTSAGENTS
inotropes vasopressors
Rationale of choice
Vasopressor Rx
Restoration of adequate BP
BP does NOT always equate to blood flow
inotropes vasopressors
Rationale of choice
Inotrope Rx
IncreaseCardiac Output
To determine whether CO is adequate in patients with shock is a thorny problem
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
INOTROPES amp VASOPRESSORSBasics
Patient ndash clinical features
Pathophysiology
Monitoring
Equipments
Drugs
Shock
CO SV
SVR
Preload
Afterload
inotropes vasopressors
Fundamentals
Volume status
One drugMany receptors
Dose responsecurve
Direct Vs Reflex
actions
inotropes vasopressors
Hemodynamics in Shock
Hypotension
Low SVR(arteriolar tone)
Low CO
inotropes vasopressors
Hemodynamics in Shock
bull Inadequate CObull Comp vasoconstrictionbull Elevated SVR
COLD SHOCK
bull Inadequate SVRbull Pathologic vasodilatationbull Comp elevated CO
WARM SHOCK
Fluid resuscitation
Myocardial dysfunction
inotropes vasopressors
Planning your strategy
inotropes vasopressors
Adrenergic receptors and vasoactive agents
α βα =β
EpinephrinePhenylephrine Norepinephrine
Dopamine
IsoproterenolDobutamine
EpinephrinePhenylephrine
Norepinephrine
DopamineIsoproterenol
Dobutamine
High dose Low dose
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
Inoconstrictors
NorepinephrineEpinephrineDopamine
Inodilators
DobutamineMilrinone
Vasoconstrictors
PhenylephrineVasopressin
Vasodilators
NitroglycerineNitroprusside
Nesiritide
inotropes vasopressors
Vasoconstriction
Vasodilation
PositiveInotropy
Vasopressin
PhenylephrineNorepinephrine
LD EpinephrineDopamine
Dobutamine
HD Dopamine
HD Epinephrine
Nitroprusside
inotropes vasopressors
inotropes vasopressors
HOW DO I MAKE MY CHOICE
inotropes vasopressors
Rationale of choice
EFFECTSAGENTS
inotropes vasopressors
Rationale of choice
Vasopressor Rx
Restoration of adequate BP
BP does NOT always equate to blood flow
inotropes vasopressors
Rationale of choice
Inotrope Rx
IncreaseCardiac Output
To determine whether CO is adequate in patients with shock is a thorny problem
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
Fundamentals
Volume status
One drugMany receptors
Dose responsecurve
Direct Vs Reflex
actions
inotropes vasopressors
Hemodynamics in Shock
Hypotension
Low SVR(arteriolar tone)
Low CO
inotropes vasopressors
Hemodynamics in Shock
bull Inadequate CObull Comp vasoconstrictionbull Elevated SVR
COLD SHOCK
bull Inadequate SVRbull Pathologic vasodilatationbull Comp elevated CO
WARM SHOCK
Fluid resuscitation
Myocardial dysfunction
inotropes vasopressors
Planning your strategy
inotropes vasopressors
Adrenergic receptors and vasoactive agents
α βα =β
EpinephrinePhenylephrine Norepinephrine
Dopamine
IsoproterenolDobutamine
EpinephrinePhenylephrine
Norepinephrine
DopamineIsoproterenol
Dobutamine
High dose Low dose
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
Inoconstrictors
NorepinephrineEpinephrineDopamine
Inodilators
DobutamineMilrinone
Vasoconstrictors
PhenylephrineVasopressin
Vasodilators
NitroglycerineNitroprusside
Nesiritide
inotropes vasopressors
Vasoconstriction
Vasodilation
PositiveInotropy
Vasopressin
PhenylephrineNorepinephrine
LD EpinephrineDopamine
Dobutamine
HD Dopamine
HD Epinephrine
Nitroprusside
inotropes vasopressors
inotropes vasopressors
HOW DO I MAKE MY CHOICE
inotropes vasopressors
Rationale of choice
EFFECTSAGENTS
inotropes vasopressors
Rationale of choice
Vasopressor Rx
Restoration of adequate BP
BP does NOT always equate to blood flow
inotropes vasopressors
Rationale of choice
Inotrope Rx
IncreaseCardiac Output
To determine whether CO is adequate in patients with shock is a thorny problem
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
Hemodynamics in Shock
Hypotension
Low SVR(arteriolar tone)
Low CO
inotropes vasopressors
Hemodynamics in Shock
bull Inadequate CObull Comp vasoconstrictionbull Elevated SVR
COLD SHOCK
bull Inadequate SVRbull Pathologic vasodilatationbull Comp elevated CO
WARM SHOCK
Fluid resuscitation
Myocardial dysfunction
inotropes vasopressors
Planning your strategy
inotropes vasopressors
Adrenergic receptors and vasoactive agents
α βα =β
EpinephrinePhenylephrine Norepinephrine
Dopamine
IsoproterenolDobutamine
EpinephrinePhenylephrine
Norepinephrine
DopamineIsoproterenol
Dobutamine
High dose Low dose
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
Inoconstrictors
NorepinephrineEpinephrineDopamine
Inodilators
DobutamineMilrinone
Vasoconstrictors
PhenylephrineVasopressin
Vasodilators
NitroglycerineNitroprusside
Nesiritide
inotropes vasopressors
Vasoconstriction
Vasodilation
PositiveInotropy
Vasopressin
PhenylephrineNorepinephrine
LD EpinephrineDopamine
Dobutamine
HD Dopamine
HD Epinephrine
Nitroprusside
inotropes vasopressors
inotropes vasopressors
HOW DO I MAKE MY CHOICE
inotropes vasopressors
Rationale of choice
EFFECTSAGENTS
inotropes vasopressors
Rationale of choice
Vasopressor Rx
Restoration of adequate BP
BP does NOT always equate to blood flow
inotropes vasopressors
Rationale of choice
Inotrope Rx
IncreaseCardiac Output
To determine whether CO is adequate in patients with shock is a thorny problem
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
Hemodynamics in Shock
bull Inadequate CObull Comp vasoconstrictionbull Elevated SVR
COLD SHOCK
bull Inadequate SVRbull Pathologic vasodilatationbull Comp elevated CO
WARM SHOCK
Fluid resuscitation
Myocardial dysfunction
inotropes vasopressors
Planning your strategy
inotropes vasopressors
Adrenergic receptors and vasoactive agents
α βα =β
EpinephrinePhenylephrine Norepinephrine
Dopamine
IsoproterenolDobutamine
EpinephrinePhenylephrine
Norepinephrine
DopamineIsoproterenol
Dobutamine
High dose Low dose
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
Inoconstrictors
NorepinephrineEpinephrineDopamine
Inodilators
DobutamineMilrinone
Vasoconstrictors
PhenylephrineVasopressin
Vasodilators
NitroglycerineNitroprusside
Nesiritide
inotropes vasopressors
Vasoconstriction
Vasodilation
PositiveInotropy
Vasopressin
PhenylephrineNorepinephrine
LD EpinephrineDopamine
Dobutamine
HD Dopamine
HD Epinephrine
Nitroprusside
inotropes vasopressors
inotropes vasopressors
HOW DO I MAKE MY CHOICE
inotropes vasopressors
Rationale of choice
EFFECTSAGENTS
inotropes vasopressors
Rationale of choice
Vasopressor Rx
Restoration of adequate BP
BP does NOT always equate to blood flow
inotropes vasopressors
Rationale of choice
Inotrope Rx
IncreaseCardiac Output
To determine whether CO is adequate in patients with shock is a thorny problem
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
Planning your strategy
inotropes vasopressors
Adrenergic receptors and vasoactive agents
α βα =β
EpinephrinePhenylephrine Norepinephrine
Dopamine
IsoproterenolDobutamine
EpinephrinePhenylephrine
Norepinephrine
DopamineIsoproterenol
Dobutamine
High dose Low dose
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
Inoconstrictors
NorepinephrineEpinephrineDopamine
Inodilators
DobutamineMilrinone
Vasoconstrictors
PhenylephrineVasopressin
Vasodilators
NitroglycerineNitroprusside
Nesiritide
inotropes vasopressors
Vasoconstriction
Vasodilation
PositiveInotropy
Vasopressin
PhenylephrineNorepinephrine
LD EpinephrineDopamine
Dobutamine
HD Dopamine
HD Epinephrine
Nitroprusside
inotropes vasopressors
inotropes vasopressors
HOW DO I MAKE MY CHOICE
inotropes vasopressors
Rationale of choice
EFFECTSAGENTS
inotropes vasopressors
Rationale of choice
Vasopressor Rx
Restoration of adequate BP
BP does NOT always equate to blood flow
inotropes vasopressors
Rationale of choice
Inotrope Rx
IncreaseCardiac Output
To determine whether CO is adequate in patients with shock is a thorny problem
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
Adrenergic receptors and vasoactive agents
α βα =β
EpinephrinePhenylephrine Norepinephrine
Dopamine
IsoproterenolDobutamine
EpinephrinePhenylephrine
Norepinephrine
DopamineIsoproterenol
Dobutamine
High dose Low dose
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
Inoconstrictors
NorepinephrineEpinephrineDopamine
Inodilators
DobutamineMilrinone
Vasoconstrictors
PhenylephrineVasopressin
Vasodilators
NitroglycerineNitroprusside
Nesiritide
inotropes vasopressors
Vasoconstriction
Vasodilation
PositiveInotropy
Vasopressin
PhenylephrineNorepinephrine
LD EpinephrineDopamine
Dobutamine
HD Dopamine
HD Epinephrine
Nitroprusside
inotropes vasopressors
inotropes vasopressors
HOW DO I MAKE MY CHOICE
inotropes vasopressors
Rationale of choice
EFFECTSAGENTS
inotropes vasopressors
Rationale of choice
Vasopressor Rx
Restoration of adequate BP
BP does NOT always equate to blood flow
inotropes vasopressors
Rationale of choice
Inotrope Rx
IncreaseCardiac Output
To determine whether CO is adequate in patients with shock is a thorny problem
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
Inoconstrictors
NorepinephrineEpinephrineDopamine
Inodilators
DobutamineMilrinone
Vasoconstrictors
PhenylephrineVasopressin
Vasodilators
NitroglycerineNitroprusside
Nesiritide
inotropes vasopressors
Vasoconstriction
Vasodilation
PositiveInotropy
Vasopressin
PhenylephrineNorepinephrine
LD EpinephrineDopamine
Dobutamine
HD Dopamine
HD Epinephrine
Nitroprusside
inotropes vasopressors
inotropes vasopressors
HOW DO I MAKE MY CHOICE
inotropes vasopressors
Rationale of choice
EFFECTSAGENTS
inotropes vasopressors
Rationale of choice
Vasopressor Rx
Restoration of adequate BP
BP does NOT always equate to blood flow
inotropes vasopressors
Rationale of choice
Inotrope Rx
IncreaseCardiac Output
To determine whether CO is adequate in patients with shock is a thorny problem
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
Direct inotropic effectsPe
riphe
ral v
ascu
lar e
ffect
sYESNO
Vaso
dila
tatio
nVa
soco
nstri
ctio
n
INOTROPES
VAS
OP
RE
SS
OR
S
Inoconstrictors
NorepinephrineEpinephrineDopamine
Inodilators
DobutamineMilrinone
Vasoconstrictors
PhenylephrineVasopressin
Vasodilators
NitroglycerineNitroprusside
Nesiritide
inotropes vasopressors
Vasoconstriction
Vasodilation
PositiveInotropy
Vasopressin
PhenylephrineNorepinephrine
LD EpinephrineDopamine
Dobutamine
HD Dopamine
HD Epinephrine
Nitroprusside
inotropes vasopressors
inotropes vasopressors
HOW DO I MAKE MY CHOICE
inotropes vasopressors
Rationale of choice
EFFECTSAGENTS
inotropes vasopressors
Rationale of choice
Vasopressor Rx
Restoration of adequate BP
BP does NOT always equate to blood flow
inotropes vasopressors
Rationale of choice
Inotrope Rx
IncreaseCardiac Output
To determine whether CO is adequate in patients with shock is a thorny problem
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
Vasoconstriction
Vasodilation
PositiveInotropy
Vasopressin
PhenylephrineNorepinephrine
LD EpinephrineDopamine
Dobutamine
HD Dopamine
HD Epinephrine
Nitroprusside
inotropes vasopressors
inotropes vasopressors
HOW DO I MAKE MY CHOICE
inotropes vasopressors
Rationale of choice
EFFECTSAGENTS
inotropes vasopressors
Rationale of choice
Vasopressor Rx
Restoration of adequate BP
BP does NOT always equate to blood flow
inotropes vasopressors
Rationale of choice
Inotrope Rx
IncreaseCardiac Output
To determine whether CO is adequate in patients with shock is a thorny problem
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
inotropes vasopressors
HOW DO I MAKE MY CHOICE
inotropes vasopressors
Rationale of choice
EFFECTSAGENTS
inotropes vasopressors
Rationale of choice
Vasopressor Rx
Restoration of adequate BP
BP does NOT always equate to blood flow
inotropes vasopressors
Rationale of choice
Inotrope Rx
IncreaseCardiac Output
To determine whether CO is adequate in patients with shock is a thorny problem
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
HOW DO I MAKE MY CHOICE
inotropes vasopressors
Rationale of choice
EFFECTSAGENTS
inotropes vasopressors
Rationale of choice
Vasopressor Rx
Restoration of adequate BP
BP does NOT always equate to blood flow
inotropes vasopressors
Rationale of choice
Inotrope Rx
IncreaseCardiac Output
To determine whether CO is adequate in patients with shock is a thorny problem
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
Rationale of choice
EFFECTSAGENTS
inotropes vasopressors
Rationale of choice
Vasopressor Rx
Restoration of adequate BP
BP does NOT always equate to blood flow
inotropes vasopressors
Rationale of choice
Inotrope Rx
IncreaseCardiac Output
To determine whether CO is adequate in patients with shock is a thorny problem
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
Rationale of choice
Vasopressor Rx
Restoration of adequate BP
BP does NOT always equate to blood flow
inotropes vasopressors
Rationale of choice
Inotrope Rx
IncreaseCardiac Output
To determine whether CO is adequate in patients with shock is a thorny problem
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
Rationale of choice
Inotrope Rx
IncreaseCardiac Output
To determine whether CO is adequate in patients with shock is a thorny problem
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
Hypotension ndash reduced perfusion pressure
Abnormal shunting of blood flow within organs
Cellular alterations ndash inability to use delivered substrates
Down-regulation of adrenergic receptors
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
Volume status
Vasopressors Inotropes
Monitors
bull Restore effective tissue perfusionbull Normalise cellular metabolism
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
Decision makingbull Which one worksbull Sequencebull Mechanism of action == goals of therapybull Consider the best available clinical evidence
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
1CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
INOTROPESVASOPRESSORS
Ventricular arrhythmiasContraction- band necrosisInfarct expansion
Compromised myocardial perfusionElevated LV filling pressuresIncreased myocardial O2 reqrmtFurther reduction in CPP
Criticalhypotension
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP 70-100mmHgNo SS of Shock SS of Shock +
DOBUTAMINE DOPAMINE
Moderate doses of these agents maximize inotropy and avoid excessive 1113090α1-adrenergic stimulation that can result in end-organ ischemia
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
+ antithrombotic effects
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
SBP lt70 mmHgInadequate response to medium dose DOPAMINE or DOPAMINEDOBUT
Promote thrombosis in coronary vasculatureExacerbate lactic acidosis
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION
NOREPINEPHRINE-resistant vasodilatory shock
Improve MAP Cardiac indexLV stroke workReduce NorEpi doseImprove Coronary blood flow (catecholamine sparing)
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
2NEUROCRITICAL CARE
TRAUMATIC BRAIN INJURY
ACUTE NEUROLOGIC INJURY
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
Although high-quality clinical data are scarce the available evidence
suggests that NOREPINEPHRINE should be considered as the
vasopressor of choice when BP elevation is indicated in patients with
acute neurologic injury
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
September 2008 - Volume 36 - Issue 9 - pp 2641-2650doi 101097CCM0b013e3181847af3
After 2hrs of resuscitation of TBI phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure gt70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure gt12 mm Hg plus glucose to maintain normoglycemia
Vasopressin Phenylephrine
ICP
Brain tissue PO2
Peripheral tissue PO2
+10mmHg
+6mmHg
+10
AFTER 6 HRS
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
3SEVERE SEPSIS SHOCK
Surviving Sepsis Campaign International guidelines for management of severe sepsis and septic shock Intensive Care Med 2013 39(2) 165-228 and Crit Care Med 2013 41(2) 580- 637
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
SEVERE SEPSIS SHOCK
Vasopressor therapy initially to target MAP 65mmHg
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Improves systemic blood pressure bull Does not substantially worsen end-organ ischemia in
most studies of crystalloid-resuscitated septic shock patients
bull Equivalent efficacy in increasing mean arterial pressure oxygen consumption and oxygen delivery
compared with other catecholamine pressorsbull Gastric pH has been observed to increase (not
decrease)
First choice vasopressor
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull Epinephrine is added to and potentially substituted for NE when an additional agent is
needed to maintain adequate MAP
bull DOPAMINE is an alternative agent to NE only in highly selected patients (eg patients with low risk of tachyarrhythmias and absolute or
relative bradycardia)
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull NOT recommended in the Rx of shock except
a) NE associated with serious arrhythmias
b) CO is known to be high and BP persistently low
c) As salvage Rx when combined
inotropevasopressor drugs and low dose
vasopressin have failed to achieve MAP target
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
SEVERE SEPSIS SHOCK
bull VP 003Umin can be added to NE with intent of
either raising MAP or decreasing NE dosage
bull Low dose VP is NOT recommended as the single
initial vasopressor
bull VP doses higher than 003-004Umin should be
reserved for salvage Rx
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
bull 778 patients with septic shock randomly assigned to either low dose vasopressin (001 to 003 units per minute) norepinephrine (5 to 15 mcg per minute)
bull similar 28-day and 90-day mortality rates similar incidence of serious adverse events
Vaso
pres
sin
and
Sept
ic S
hock
Tri
al (
VASS
T)
Russell JA Walley KR Singer J Gordon AC Heacutebert PC Cooper DJ Holmes CL Mehta S Granton JT Storms MM Cook DJ Presneill JJ Ayers D VASST Investigators Vasopressin versus norepinephrine infusion in patients with septic shock N Engl J Med 2008358(9)877
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressorsbull Annane et al Lancet 2007 370 676ndash84 330 patients with septic shock in
French ICUrsquosbull Titrated to maintain MAP at 70mmHg Primary outcome 28 day mortality
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
4ANAPHYLACTIC SHOCK
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
ANAPHYLACTIC SHOCK
Drug of choice Potentially lifesaving
Antagonizes the effects of the released mediators
Maintains blood pressure
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Hypotension in anaphylaxis is due to a dramatic shift of intravascular volume
bull Fundamental treatment intervention after epinephrine is aggressive IV fluid administration
bull Vasopressors may also be needed to support blood pressure
bull Intravenous epinephrine (110000 vv preparation) can be administered as a continuous infusion especially when the response to intramuscular epinephrine (11000 vv) is poor
bull Dopamine infusion can also be used
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
ANAPHYLACTIC SHOCK
bull Beta blocked patients or Refractory shock
bull Glucagonbull both inotropic effects and chronotropic effects on the heart by
increasing intracellular levels of cAMP independent of the beta-adrenergic receptors
bull can also reverse bronchospasm
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
Drug Mechanism Action
Enoximone
milrinone
Phosphodiesterase III (PDE III)
inhibitor prevent hydrolysis of
intracellular cyclic AMP augmenting
its effects Many isoenzymes of
phosphodiesterase ndash PDE III is the
target for inotropic actions
Increased cardiac
contractility and stroke
volume vasodilatation
Levosimendan Calcium sensitizer Increases the
sensitivity of myocardial troponin to
intracellular calcium possible
inhibition of PDE III
Increased cardiac
contractility without
increasing myocardial
oxygen demand effect on
mortality unclear
Vasopressin Endogenous hormone also called
antidiuretic hormone V1 receptor
activity in vascular smooth muscle increasing intracellular calcium
Vasoconstriction increasing
systemic vascular
resistance and blood
pressure
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
T
UO
Y
KNA
H
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
inotropes vasopressors
httpswwwfacebookcomsaneeshpj
saneeshpjyahoocom
