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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