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Pharmacotherapy In
Cardiopulmonary
Resuscitation (CPR)
Dr Abdollahi
www.ssu.ac.ir
3 May 2017
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Cardiac arrest is defined as cessation of cardiac
mechanical activity. Cardiopulmonary resuscitation
(CPR) is an attempt to restore spontaneous circulation
through several maneuvers and techniques.
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Aims
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Hypoxemia correction
Acidosis correction
Increases perfusion pressure
Increases myocardial contractility
Increase HR
Arrhythmia control
Pain management and pulmonary
edema treatment
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DRUG THERAPY
During cardiac arrest, drug therapy is secondary
to more fundamental intervention.
Chest compressions, defibrillation (if appropriate),
and ventilation should take precedence over
medications. Establishing IV access and
administering drugs, although important,
should not interrupt sustained chest
compressions and ventilation.
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Oxygen
Patients in cardiac arrest or low cardiac
output states should receive 100% oxygen as
soon as possible.
Oxygen will increase arterial oxygen tension
and hemoglobin saturation if ventilation is
supported and improve tissue oxygenation
when circulation is supported.
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Of the drugs used during CPR, only
vasopressors are acknowledged to
help restore spontaneous circulation.
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Vasopressor agents given during cardiac arrest
aim to improve aortic diastolic pressure.
Consequently, increases in coronary and cerebral
perfusion pressures enhance both myocardial and
cerebral blood flow and improve survival .
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Vasopressor Agents
Mechanism of Action
Epinephrine has been used in
resuscitation since the 1890s and has
been the vasopressor of choice in
modern CPR.
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Epinephrine
Epinephrine is a combined direct (α and βreceptor agonist.
When epinephrine is administered during CPR,
peripheral asoconstriction results in higher
aortic pressure causing an increase in
coronary and cerebral perfusion pressures
and myocardial and brain blood Flows .
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Epinephrine
When added to chest compressions,
epinephrine helps to develop the critical
coronary perfusion pressure necessary
to provide enough myocardial blood flow
for restoration of spontaneous
circulation.
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Flow to other organs either does not improve
or diminishes further when epinephrine is
given, despite the increase in aortic
pressure.
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If invasive monitoring is present during CPR,
an arterial diastolic pressure of 40 mm Hg
or coronary perfusion pressure of 20 mm
Hg must be obtained with good chest
compression technique and/or epinephrine
therapy.
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Current recommendations are to give
intravenous epinephrine, 1 mg in the
adult or 0.01 mg/kg in children, every
3–5 minutes. Higher doses may be
indicated in specific circumstances, or
if treatment has been delayed and
the standard dose seems ineffective.
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The 4H:
1. Hypoxia
2. Hypovolemia
3. Hyper/hypokalemia, hypocalcemia
and acidemia
4. Hypothermia
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The 4T:
1. Tension pneumothorax
2. Cardiac tamponade
3. Thromboembolic or mechanical
obstruction (e.g.pulmonary
embolism)
4. Toxic or therapeutic substances in
overdose
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Nonadrenergic vasopressors
Vasopressin
The newest addition to the pharmacologic
armamentarium in CPR is arginine
vasopressin. It is currently recommended as
an alternative to either the first or second
dose of epinephrine in a dose of 40 units
intravenously. If additional vasopressor
doses are needed, epinephrine should be
used.
The half-life in the intact circulation is 10–20
minutes, and longer than epinephrine during
CPR.
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It has several advantages over adrenaline
in CPR :
 Due to lack of the beta effect and
impact of acidosis on its efficacy
 Lower incidence of post resuscitation
myocardial dysfunction.
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According to the current CPR guidelines, use of
vasopressin as an alternative to adrenaline for
shock refractory ventricular fibrillation is
recommended as a Class IIb . Use of
vasopressin in patients with asystole or pulseless
electrical activity (PEA) or in infants and children
is recommended as Class indeterminate.
It is not established whether a second dose of
vasopressin is required or not .
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Overall, evidence currently suggests
that, like other potent vasopressors,
vasopressin is equivalent to, but not
better than, epinephrine for use
during CPR.
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Antiarrythmic agents
The use of antiarrythmic drugs has been recommended
to aid electrical defibrillation, to prevent the
reoccurrence of ventricular fibrillation and to
terminate serious electrical arrhythmias .
Antiarrythmic drugs should increase the likelihood
of successful defibrillation by suppressing a variety
of potentially malignant arrhythmias .
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Amiodarone
Amiodarone should be considered as a
Class IIb,following adrenaline, to
treat shock refractory VF/VT as early
as after three shocks are provided .
Amiodarone improves survival to
hospital admission but not to hospital
discharge because of the side effects
such as hypotension and bradycardia
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Amiodarone does prevent ventricular arrhythmias and
animal studies demonstrated that it could reduce the
defibrillation threshold . In an experimental model of
persistant VF, animals receiving amiodarone alone had
significantly lower resuscitation generated aortic (systolic
and diastolic), right atrial systolic and coronary perfusion
pressures than did either adrenaline alone or the
combination of amiodarone and adrenaline. This study
suggested that for optimal hemodynamic support during
ongoing CPR adrenaline or other vasoconstrictive agents
should be given in combination with, or precede, the
administration of amiodarone .
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Amiodarone has many different hemodynamic effects.
It blocks potassium channels leading to prolongation in
the duration of the action potential. It also causes block in
sodium and calcium channels and alpha and beta
adrenergic receptors. As a result of its direct effect on
smooth muscle, and its ability to block calcium channels
and alpha adrenergic receptors, amiodarone dilates
coronary arteries. It also dilates peripheral arteries
leading to vasodilatation and reduction in afterload and
systemic blood pressure. Hypotension complicates its use
particularly in the setting of a rapid infusion. Therefore,
amiodarone is effective in treating most ventricular and
supraventricular tachyarrythmias .
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The recommended dose of amiodarone is 300 mg
diluted in 20 ml 5% dextrose as an iv bolus via a
peripheral vein when there is no central venous route .
It should be given after the third shock without allowing
delay in the delivery of the fourth shock . A further
dose of 150 mg amiodarone may be required in
refractory cases followed by an infusion of 1 mg min-1 for
6 h and then 0.5 mg/min to a maximum of 2 g in 24 h.
However, according to European datasheet maximum
dose of amiodarone is 1.2 g in 24 h .
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Atropine
Atropine sulfate enhances sinus node
automaticity and atrioventricular conduction
by its vagolytic effects. Atropine is
indicated when bradycardia coexists with
hypotension, ventricular ectopy, or
symptoms associated with myocardial
ischemia.
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Because atropine has few adverse effects, it can be tried
in arrest refractory to epinephrine and oxygenation.
The recommended dose for bradycardia in adults is
0.5 mg IV every 3–5 minutes to a total dose of 3.0
mg. The pediatric dose for treating bradycardia is
0.02 mg/kg with a minimum dose of 0.1 mg and a
maximum total dose of 1.0 mg in a child and 3.0 mg
in an adolescent. The dose may be repeated every 3–
5 minutes.
Atropine is no longer recommended for use in pulseless
arrest in children.
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Calcium Salts
With normal cardiovascular physiology,
calcium increases myocardial
contractility and enhances ventricular
automaticity. Consequently, calcium
salts have been administered during
attempted resuscitation of asystole
and EMD for many years.
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However, multiple clinical studies have found
that calcium is no better than placebo in
promoting resuscitation and survival from
asystole or EMD. Calcium is not indicated for
use during cardiac arrest in adults or
children. It may be useful for treatment of
hyperkalemia, ionized hypocalcemia,
hypermagnesemia or calcium channel
blocker toxicity.
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If calcium is administrated the chloride
salt (2–4 mg/kg) is recommended
because it produces higher and more
consistent levels of ionized calcium
than other salts.
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Sodium Bicarbonate
Although sodium bicarbonate was used commonly during
CPR in the past, there is little evidence to support its
efficacy. Its use during resuscitation was predicated
on the adverse cardiovascular consequences of
acidosis, including impaired myocardial function,
decreased catecholamine responsiveness, and
peripheral vasodilatation.
However, most studies have been unable to demonstrate
improvement in success of defibrillation or
resuscitation with the use of bicarbonate.
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Sodium bicarbonate use during CPR
should be restricted not only because
of its lack of efficacy but because of
the documented complications from
excessive use, including
hyperosmolality, hypernatremia,
metabolic alkalosis and hypercapnia
from CO2 liberation.
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Lidocaine
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LA
Ventricular arrhythmia
Increases VF threshold
Dosage (bolus & infusion)
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Lidocaine is a second choice after amiodarone
and procainamid. It is acceptable for use in
pVT after defibrillation, hemodynamically
unstable ventricular premature contractions
and hemodynamically stable VT.
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The recommended dose is 1-1.5 mg/kg
iv bolus and is repeated in the dose of
0.5-0.75 mg/kg not exceeding 3
mg/kg/h. Continuous infusion of 1-4
mg/min is started only if spontaneous
circulation returns during CPR.
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Toxicity
 Decrease CO and cardiovascular
depression
 CNS irritability (agitation – confusion
–auditory – convulsion )
 Treatment ( holding – airway –
diazepam or barbiturate )
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Procainamide
It is an other alternative to amiodarone but
the necessity for relatively slow rate of
infusion (30 mg min-1 to a total of 17
mg/kg) makes it a less favorable option.
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Magnesium
The antiarrhythmic action of magnesium is mediated
by the activation of membrane sodium-potassium
adenosine triphosphatase and blocking of slow calcium
channels . Magnesium is universally accepted for the
therapy of torsades de pointes . 1-2 g (4-8 mmol) of
magnesium sulphate diluted in 100 ml of 5% dextrose is
recommended to be given over 30-60 min followed by an
infusion of 0.5 -1 g/h . Its use is recommended for
shock refractory VF when hypomagnesemia is suspected
e.g patients on potassium losing diuretics, because
magnesium mirrors the action of extracellular potassium
in stabilizing myocardial cell membrane .
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Drug therapy during cardiopulmonary
resuscitation
Indications
dose
Oxygen
All cardiac arrests
100%
Epinephrine
All cardiac arrests
0.5-1 mg IV (10 μg.kg-1 in
children)
1 mg in 10 ml through TT
Repeat every 5 minutes
consider higher doses in
refractory cardiac arrest
Sodium bicarbonate
Not recommended except in
selected patients
(hyperkalemia)
Adequate alveolar ventilation
is the most important factor in
management of hypoxic lactic
acidosis
1 mEq.kg-1 IV initially; 0.5
mEq.kh-1 IV every 10 minutes
of continued CPR or as dictated
by PH
Lidocaine
Recurrent ventricular
fibrillation or ventricular
fibrillation or ventricular
tachycardia
1 mg.kg-1 IV or TT 1-4 mg.min1IV (adult)
Bretylium
When lidocaine is not effective
5 mg.kg-1IV every 5 minutes;
not to exceed 30 mg.kg-1 in an
adult
Isoproterenol
Asystole when atropine is not
effective
0.30-0.3 μg.kg-1 .min-1 IV (2-20
μg.min-1 IV in adults)
Adenostine
Paroxysmal atrial tachycardia
6-12 mg IV (may repeat once in
1-2 min)
-1
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Conclusion
Survival following cardiac arrest mostly depends on
the interval between collapse to initiation of CPR and
collapse to defibrillation. Although no drug has been
reliably proven to increase survival to hospital discharge
after cardiac arrest, basic cardiac medication drugs used
during ACLS were reviewed. For example; vasopressin
has been recommended in case of fibrillatory arrest, the
use of lidocaine in refractory ventricular fibrillation remains
contentious, whereas amiodarone is recommended after
defibrillation and adrenaline.
Lidocaine and procainamide are alternatives if amiodarone is
not available.
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Amiodarone may improve short term survival after outof-hospital ventricular fibrillation cardiac arrest.
Magnesium therapy is recommended especially for
torsades de pointes and shock resistant ventricular
fibrillation associated with hypomagnesemia.
Atropine is the drug of choice in PEA associated with
bradycardia and asystole. Sodium bicarbonate and
calcium indications are restricted. It is still difficult to
say whether drugs used during ACLS are really
effective unless further prospective randomized
human studies are completed.
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