Management of Shock

Role of Inotropic & Vasoactive drugs

Dr. Waheed A. Radwan

Professor of Critical Care Medicine
Cairo University
 Glossary of terms
• Inotropes: agents that improve myocardial
contractility and enhance stroke volume
• Pressors: agents that increase systemic
vascular resistance and increase blood pressure
• Chronotropic: Increase heart rate
• Lusotropic: improve relaxation during diastole
and decrease EDP in the ventricles
 Determinants of Cardiac Output

CONTRACTILITY HEART RATE

CARDIAC
OUTPUT
L/Min

(CI=CO/m²)

PRELOAD AFTERLOAD
 CARDIOVASCULAR
MEDICATIONS
• From ICU standpoint, can be divided into
two main groups:
– Cardiac arrest medications
– Cardiac medications via continuous infusions
• Many of the meds used during a cardiac
arrest may also be given as continuous
infusions.
 CARDIOVASCULAR
MEDICATIONS
• Main actions of most of the following
cardiovascular medications will be
determined by the adrenergic effects of the
medications.
• Can either be:
– alpha-adrenergic
– beta-adrenergic
– dopaminergic
 ALPHA-ADRENERGIC
MEDICATIONS
• Can be divided into:
– Alpha1-adrenergic effects:
• Vascular smooth muscle contraction
– Alpha2-adrenergic effects:
• Vascular smooth muscle relaxation--this is a very
mild effect only at low doses of an alpha-adrenergic
agent like epinephrine.
 BETA-ADRENERGIC
MEDICATIONS
• Can be divided into:
– Beta1-adrenergic effects:
• Direct cardiac effects
– Inotropy (improved cardiac contractility)
– Chronotropy (increased heart rate)
– Beta2-adrenergic effects:
• Vasodilation
• Bronchodilation
 CARDIAC MEDS VIA
CONTINUOUS INFUSION
• Epinephrine
• Norepinephrine
• Dopamine
• Dobutamine
• Milrinone/Amrinone
• Sodium Nitroprusside
• Nitroglycerin
• Isoproterenol
 EPINEPHRINE
• Both an alpha- and beta-adrenergic agent
• Therefore, indications for its use as a
continuous infusion are:
– low cardiac output state
• beta effects will improve cardiac function
• alpha effects may increase afterload and decrease
cardiac output
– septic shock
• useful for both inotropy and vasoconstriction
 EPINEPHRINE
• Actions are dose dependent (mcg/kg/min):
– 0.02-0.08 = mostly beta1 and beta2 stimulation.
• increased cardiac output
• mild vasodilation
– 0.1-2.0 = mix of beta1 and alpha1
• increase cardiac output
• increase SVR = vasoconstriction
– > 2.0 = mostly alpha1
• increase SVR, and may decrease CO by increasing
afterload
 EPINEPHRINE
• Side effects include:
• Anxiety, tremors,palpitations
• Tachycardia and tachyarrhythmias
• Increased myocardial oxygen requirements and
potential to cause ischemia
• Decreased splanchnic and hepatic circulation
(elevation of AST and ALT)
• Anti-Insulin effects: lactic acidosis, hyperglycemia
 NOREPINEPHRINE
• Employed primarily for its alpha agonist
effect - increases SVR (and B.P.) without
significantly increasing C.O.
• Used in cases of low SVR and hypotension
such as profound “warm shock” with a
normal or high C.O. state
• Infusion rates titrated between 0.05 to 1
mcg/kg/min
 NOREPINEPHRINE
• In general, norepinephrine differs from
epinephrine in that at doses used in clinical
practice, the vasoconstriction outweighs any
increase in cardiac output.

– i.e. norepinephrine usually increases blood

pressure and SVR, often without increasing
cardiac output.
 NOREPINEPHRINE
• Side Effects:
• Similar to those of Epinephrine
• Can compromise perfusion in extremities and
may need to be combined with a vasodilator
e.g. Dobutamine or Nipride
• More profound effect on sphlancnic
circulation and myocardial oxygen
consumption
 DOPAMINE
• Intermediate product in the enzymatic
pathway leading to the production of
norepinephrine; thus, it indirectly acts by
releasing norepinephrine.
• Directly has alpha, beta and dopaminergic
actions which are dose-dependent.
• Indications are based on the adrenergic
actions desired.
 DOPAMINE
• Improve renal perfusion 2-5 mcg/kg/min
• Improve C.O. in mild to moderate
Cardiogenic or Distributive Shock 5-
10mcg/kg/min
• Post-resuscitation stabilization in patients
with hypotension (in conjuction with fluid
therapy) 10-20mcg/kg/min
 DOBUTAMINE
• Synthetic catecholamine with inotropic
effect (increases stroke volume) and
peripheral vasodilation (decreases afterload)
• Positive chronotropic effect (increases HR)
• Some lusotropic effect
• Overall, improves Cardiac Output by above
beta-agonist acitivity
 DOBUTAMINE
• Major metabolite is 3-O-methyldobutamine,
a potent inhibitor of alpha-adrenoceptors.
– Therefore, vasodilation is possible secondary to
this metabolite.
• Usual starting infusion rate is
5 mcg/kg/min, with the dose being titrated
to effect up to 20 mcg/kg/min.
 DOBUTAMINE
• Used in low C.O. states and CHF e.g.
myocarditis, cardiomyopathy, myocardial
infarction
• If BP adequate, can be combined with
afterload reducer (Nipride or ACE inhibitor)
• In combination with Epi/Norepi in profound
shock states to improve Cardiac Output and
provide some peripheral vasodilatation
 MILRINONE/AMRINONE
• Belong to new class of agents “Bipyridines”
• Non-receptor mediated activity based on
selective inhibition of Phosphodiesterase Type
III enzyme resulting in cAMP accumulation in
myocardium
• cAMP increases force of contraction and rate
and extent of relaxation of myocardium
• Inotropic, vasodilator and lusotropic effect
 AMRINONE
• First generation agent - limited use now
• Long half-life (4.4 hours) with potential for
prolonged hypotension after loading dose
• Associated with thrombocytopenia
• Dosage: Load with 0.75 mg/kg with
infusion rate of 5-10 mcg/kg/min
• Milrinone is preferred drug from this group
 MILRINONE
• Increases CO by improving contractility,
decreased SVR, PVR (?), lusotropic effect;
decreased preload due to vasodilatation
• Unique in beneficial effects on RV function
• Half-life is 1-2 hours
• Load with 50 mcg/kg over 30 mins followed by
0.3 to 0.75 mcg/kg/min
• No increase in myocardial O2 requirement
 VASODILATORS
• Classified by site of action
• Venodilators: reduce preload - Nitroglycerin
• Arteriolar dilators: reduce afterload
Minoxidil and Hydralazine
• Combined: act on both arterial and venous
beds and reduce both pre- and afterload
Sodium Nitroprusside (Nipride)
 NITROPRUSSIDE
• Vasodilator that acts directly on arterial and
venous vascular smooth muscle.
• Indicated in hypertension and low cardiac
output states with increased SVR.
• Also used in post-operative cardiac surgery to
decrease afterload on an injured heart.
• Action is immediate; half-life is short;
titratable action.
 NITROPRUSSIDE
• Toxicity is with cyanide, one of the
metabolites of the breakdown of nipride.
• Severe, unexplained metabolic acidosis
might suggest cyanide toxicity.
• Dose starts at 0.5 mcg/kg/min and titrate to 5
mcg/kg/min to desired effect. May go higher
(up to 10 mcg/kg/min) for short periods of
time.
 NITROGLYCERIN
• Direct vasodilator as well, but the major effect
is as a venodilator with lesser effect on
arterioles.
• Not as effective as nitroprusside in lowering
blood pressure.
• Another potential benefit is relaxation of the
coronary arteries, thus improving myocardial
regional blood flow and myocardial oxygen
demand.
 NITROGLYCERIN
• Used to improve myocardial perfusion
following cardiac surgery
• Dose ranges from 0.5 to 8 mcg/kg/min.
Typical dose is 2 mcg/kg/min for 24 to 48
hours post-operatively
• Methemoglobinemia is potential side effect
 ISOPROTERENOL
• Synthetic catecholamine
• Non-specific beta agonist with minimal alpha-
adrenergic effects.
• Causes inotropy, chronotropy, and systemic
and pulmonary vasodilatation.
• Indications: bradycardia, decreased cardiac
output, bronchospasm (bronchodilator).
• No longer available in some markets
 ISOPROTERENOL

• Occasionally used to maintain heart rate

following heart transplantation.
• Dose starts at 0.01 mcg/kg/min and is
increased to 1.0 mcg/kg/min for desired
effect.
 INHALED NITRIC OXIDE
• Selective Pulmonary vasodilator
• Dilates only pulmonary capillaries to
alveoli participating in gas exchange
• Decreases intrapulmonary shunt and
improves V/Q matching
• Rapidly inactivated by Hgb in pulm. cap. so
no systemic side effects (eg hypotension)
 INHALED NITRIC OXIDE
• Potential for use in ARDS and Pulmonary
Hypertension
• Currently only approved for use in neonatal
Pulmonary Hypertension
• Expensive
• Special monitoring equipment required
• Dose: Concentration of 0.5-60 ppm in inhaled
gas
 Additional considerations
• Mechanical ventilation and oxygen therapy (to
conserve CO)
• Analgesia, anxiolysis and sedation
• Electrolyte homeostasis esp Ca and Mg
• Nutrition - avoid hypoglycemia
• Anemia is an “unconstitutional surcharge”
• Last but not the least: Maintain appropriate
intravascular volume
 Selecting inotropic and vasopressor agents for specific hemodynamic disturbances in children
Blood pressure or SVR

Hemodynamic pattern Normal Deceased Elevated

Septic Shock
Stroke index High None or dopamine Norepinephrine None
Stroke Index low to N Dobutamine or dopamine Dopamine or epinephrine Dobutamine
(or dobutamine plus plus
norephinephrine) nitroprusside

Cardiogenic shock Dobutamine or amrinone Epinephrine or dopamine --

or dopamine

Myocardial dysfunction Dobutamine or dopamine Epinephrine or dopamine Dobutamine

(complicating critical or amrinone (or dobutamine plus plus
illness) norepinephrine) nitroprusside

CHF Dobutamine or dopamine -- Dobutamine

or amrinone plus
nitroprusside

Bradycardia None Isoproterenol None

 CARDIAC ARREST
MEDICATIONS

• Epinephrine
• Atropine
• Sodium Bicarbonate
• Calcium (Chloride or Gluconate)
• Lidocaine
 EPINEPHRINE
• Both an alpha- and beta-adrenergic agent
• During cardiac arrest, most think it has the
greatest benefit by alpha-adrenergic actions,
increasing afterload and thus diastolic blood
pressure, leading to improved coronary
artery perfusion.
 EPINEPHRINE
• Indications:
– Cardiac arrest
– Severe bronchospasm
– Anaphylactic reactions
• Route of Administration
– IV or IO
– SQ or IM (for bronchospasm)
– ET (cardiac arrest without IV or IO access)
 EPINEPHRINE
• Dosage:
– initial (low) dose: 0.01 mg/kg
= 0.1 cc/kg of 1:10,000

– subsequent (high) doses: 0.1 mg/kg

= (0.1 cc/kg of 1:1,000)
 ATROPINE
• Parasympathetic (not an alpha- or beta-
adrenergic) agent--acts by blocking
cholinergic stimulation of the muscarinic
receptors of the heart.
• Results in an increase in the sinus rate of the
heart.
• Little effect on systemic vascular resistance
or myocardial contractility.
 ATROPINE
• Indications:
– Bradycardia
– Second or third degree heart block
– Asystole
– Pulseless electrical activity (electrical
mechanical dissociation)
• Route of Administration
– IV, IO, ET, SQ, IM, nebulization
 ATROPINE
• Dosage:
– 10 to 20 mcg/kg
– minimum dose is 0.1 mg--smaller doses may
cause reflex bradycardia (central stimulatory
effect on the medullary vagal nuclei)
– maximum (adult) dose is 2 mg
 SODIUM BICARBONATE
• Use during CPR remains a controversial issue
due to lack of evidence showing benefit from
receiving bicarbonate.
• Elevates blood pH by binding with hydrogen
to form water and CO2
• HCO-3 + H+ => H2CO3 => H2O + CO2
• Must have adequate ventilation to remove CO2
or respiratory acidosis will worsen
 SODIUM BICARBONATE
• Adverse effects of acidosis:
– Cardiac
• Decrease contractility
• Lower threshold for ventricular fibrillation
• Decrease responsiveness to catecholamines
– Vascular
• Decrease systemic vascular resistance
• Decrease systemic vascular responsiveness to
catecholamines
• Increase pulmonary vascular resistance
 SODIUM BICARBONATE
• Indications:
– Pre-existing acidosis
– Prolonged CPR (after 10 minutes)
– Pulmonary hypertensive crisis
– Hyperkalemia
• Route of administration:
– IV, IO
• Dosage
– 1-2 meq/kg/dose (1 meq/cc or 0.5 meq/cc)
 CALCIUM
• Current recommendations for the use of
calcium during CPR are restricted to a few
specific situations.
• Intracellular calcium plays an important
role in the process of cell death, but no
studies have shown that transient
hypercalcemia worsens outcome after
cardiac arrest.
 CALCIUM
• Adverse Effects of Hypocalcemia
– Decreased myocardial contractility
– Decreased systemic vascular resistance
– Decreased catecholamine release
– Decreased cardiovascular response to
catecholamines
 CALCIUM
• Indications:
– Hypocalcemia
• Ionized hypocalcemia may result from severe
alkalosis or after large transfusions of citrated blood
products.
– Hyperkalemia
– Hypermagnesemia
– Calcium channel blocker overdose
 CALCIUM
• Route of administration:
– IV, IO only
– Calcium chloride--central venous line
– Calcium gluconate--peripheral venous line
• Dosage:
– Calcium chloride = 10-20 mg/kg
– Calcium gluconate = 100-200 mg/kg
 LIDOCAINE
• Class 1B antiarrhythmic
• Decreases automaticity threshold and
ventricular fibrillation threshold.
• Effective in terminating PVCs.
• Rarely used in pediatric arrests as
ventricular tachycardia and ventricular
fibrillation are not commonplace.
 LIDOCAINE
• Indications:
– Ventricular Tachycardia
– Ventricular Fibrillation
– Frequent PVCs
• Route of Administration:
– IV, IO, ET
• Dosage:
– 1 mg/kg/dose (may need up to 2.5 mg/kg ET)
 ENDOTRACHEAL
MEDICATIONS
• LEAN
– Lidocaine
– Epinephrine
– Atropine
– Naloxone (Narcan)