CPCR - DRUGS
Pharmacotherapy In Cardiopulmonary Resuscitation (CPR)
Dr Abdollahiwww.ssu.ac.ir
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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
Hypoxemia correctionAcidosis correctionIncreases perfusion
pressureIncreases myocardial contractility Increase HRArrhythmia
control Pain management and pulmonary edema treatment
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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.
DRUG THERAPY
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Oxygen
Patients in cardiac arrest or low cardiacoutput 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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Epinephrine has been used in resuscitation since the 1890s and
has been the vasopressor of choice in modern CPR.
Vasopressor AgentsMechanism of Action
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Epinephrine
Epinephrine is a combined direct ( and -receptor 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
criticalcoronary perfusion pressure necessaryto 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 35 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. Hypoxia2. Hypovolemia3. Hyper/hypokalemia, hypocalcemia and
acidemia4. Hypothermia
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The 4T:
1. Tension pneumothorax2. Cardiac tamponade3. 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 1020 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 efficacyLower
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 andanimal
studies demonstrated that it could reduce thedefibrillation
threshold . In an experimental model ofpersistant VF, animals
receiving amiodarone alone hadsignificantly lower resuscitation
generated aortic (systolicand diastolic), right atrial systolic and
coronary perfusionpressures than did either adrenaline alone or
thecombination of amiodarone and adrenaline. This studysuggested
that for optimal hemodynamic support duringongoing CPR adrenaline
or other vasoconstrictive agentsshould be given in combination
with, or precede, theadministration of amiodarone .
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Amiodarone has many different hemodynamic effects.It blocks
potassium channels leading to prolongation inthe duration of the
action potential. It also causes block insodium and calcium
channels and alpha and betaadrenergic receptors. As a result of its
direct effect onsmooth muscle, and its ability to block calcium
channelsand alpha adrenergic receptors, amiodarone dilatescoronary
arteries. It also dilates peripheral arteriesleading to
vasodilatation and reduction in afterload andsystemic blood
pressure. Hypotension complicates its useparticularly in the
setting of a rapid infusion. Therefore,amiodarone is effective in
treating most ventricular andsupraventricular tachyarrythmias
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The recommended dose of amiodarone is 300 mgdiluted in 20 ml 5%
dextrose as an iv bolus via aperipheral vein when there is no
central venous route .It should be given after the third shock
without allowingdelay in the delivery of the fourth shock . A
furtherdose of 150 mg amiodarone may be required inrefractory cases
followed by an infusion of 1 mg min-1 for6 h and then 0.5 mg/min to
a maximum of 2 g in 24 h.However, according to European datasheet
maximumdose of amiodarone is 1.2 g in 24 h .
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Atropine
Atropine sulfate enhances sinus nodeautomaticity 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 35 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 35 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 (24 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
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 3mg/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 mediatedby the activation
of membrane sodium-potassiumadenosine triphosphatase and blocking
of slow calciumchannels . Magnesium is universally accepted for
thetherapy of torsades de pointes . 1-2 g (4-8 mmol) ofmagnesium
sulphate diluted in 100 ml of 5% dextrose isrecommended to be given
over 30-60 min followed by aninfusion of 0.5 -1 g/h . Its use is
recommended forshock refractory VF when hypomagnesemia is
suspectede.g patients on potassium losing diuretics,
becausemagnesium mirrors the action of extracellular potassiumin
stabilizing myocardial cell membrane .
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Drug therapy during cardiopulmonary resuscitation
IndicationsdoseOxygenAll cardiac arrests 100%EpinephrineAll cardiac arrests0.5-1 mg IV (10 g.kg-1 in children)1 mg in 10 ml through TTRepeat every 5 minutes consider higher doses in refractory cardiac arrestSodium bicarbonateNot recommended except in selected patients (hyperkalemia) Adequate alveolar ventilation is the most important factor in management of hypoxic lactic acidosis1 mEq.kg-1 IV initially; 0.5 mEq.kh-1 IV every 10 minutes of continued CPR or as dictated by PH LidocaineRecurrent ventricular fibrillation or ventricular fibrillation or ventricular tachycardia1 mg.kg-1 IV or TT 1-4 mg.min-1IV (adult) BretyliumWhen lidocaine is not effective 5 mg.kg-1IV every 5 minutes; not to exceed 30 mg.kg-1 in an adultIsoproterenolAsystole when atropine is not effective0.30-0.3 g.kg-1 .min-1 IV (2-20 g.min-1 IV in adults)AdenostineParoxysmal atrial tachycardia6-12 mg IV (may repeat once in 1-2 min)Dopamine 5-20 g.kg-1 .min-1 IV
Calcium chlorideNot recommended except in selectedpatients for treatment of hypocalcemia or hyperkalemia
Conclusion
Survival following cardiac arrest mostly depends onthe interval
between collapse to initiation of CPR andcollapse to
defibrillation. Although no drug has beenreliably proven to
increase survival to hospital dischargeafter cardiac arrest, basic
cardiac medication drugs usedduring ACLS were reviewed. For
example; vasopressinhas been recommended in case of fibrillatory
arrest, theuse 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 out-of-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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