Drugs available for cardiac resuscitation and cardiac dysrhythmia management are also described in chapters 19 and 20. This section will cover those drugs specifically used for resuscitation from cardiac arrest to ROSC. Drugs are an adjunct in the management of cardiac arrest patients. Good CPR, ventilation, and early defibrillation are the cornerstones of management of cardiac arrest. The effectiveness of standard resuscitative drugs on ROSC and survival to hospital discharge has not been well demonstrated.16–18 However, consensus documents recommend the standard resuscitative drugs described below with the presumptive rationale that drugs help "restart" the heart and preserve coronary and cerebral circulation.
Epinephrine (adrenaline) is an endogenous catecholamine. It has an important role in cardiac arrest, although the evidence base for improved outcomes in humans is weak.19 Epinephrine seems to improve ROSC and short-term survival20, but does not appear to improve survival to hospital discharge, or neurologic outcome.21,22 The primary beneficial effect appears to be peripheral vasoconstriction, which improves cerebral and coronary blood flow. Potential adverse effects include an increase in myocardial oxygen consumption and an increase in pulmonary shunting. The most common adverse reaction is tachycardia. Epinephrine may worsen myocardial ischemia and induce ventricular ectopy and VT. Epinephrine is used mainly to treat cardiac arrest from VF or pulseless VT unresponsive to the initial shock, asystole, PEA, and profoundly symptomatic bradycardia. The 2015 updates provide a class IIb recommendation, stating standard dose epinephrine may be reasonable for patients with cardiac arrest. The standard dose in cardiac arrest is 1.0 milligram diluted to 10 mL (10 mL of 1:10,000) given IV. Repeat if needed at 3- to 5-minute intervals. There is no maximum dose. Escalating doses at 2 to 5 milligrams IV every 3 to 5 minutes (high-dose epinephrine) have not resulted in increased long-term survival.19 For IV infusion in patients with cardiogenic shock or symptomatic bradycardia, the dose is 1 milligram in 500 mL normal saline beginning at 2 to 10 micrograms/min, escalating as needed at 3- to 5-minute intervals. Do not add epinephrine to infusions that contain alkaline solutions because epinephrine has ineffective clinical activity in alkaline solutions.
Amiodarone is generally considered a Class III antiarrhythmic drug, but it possesses electrophysiologic characteristics of all four Vaughn-Williams classes. It causes coronary and peripheral artery vasodilation. Its main use in cardiac arrest is for persistent VT or VF after defibrillation and epinephrine. While the 2015 ACLS guidelines recommend amiodarone for refractory VF, a 2016 large multi-center trial failed to demonstrate a difference in survival to hospital discharge for shock-refractory VF or pulseless VT with amiodarone or lidocaine compared to placebo.23
Amiodarone can also be used for hemodynamically stable VT, hemodynamically stable polymorphic VT, and hemodynamically stable wide-complex tachycardia of uncertain origin. It is also used for the pharmacologic conversion of atrial fibrillation, control of rapid ventricular rate in preexcitation supraventricular dysrhythmias, and as an adjunct to electrical cardioversion of refractory paroxysmal supraventricular tachycardia/atrial tachycardia. For pulseless VT or VF, the dose is a bolus of 300 milligrams IV followed by a 20-mL flush with 5% dextrose in water or saline. Give another 150-milligram bolus if there is no response to the first dose. For stable ventricular and supraventricular dysrhythmias, administer amiodarone IV 150 milligrams over 10 to 15 minutes (not to exceed 30 milligrams/min), followed by a maintenance infusion of 1 milligram/min for 6 hours and then 0.5 milligrams/min for the next 18 hours. Infusions exceeding 2 hours should be administered in glass or polyolefin bottles because the drug precipitates in plastic tubing. Hypotension and bradycardia are the most common unwanted effects. These may be addressed by slowing the infusion rate, giving an IV fluid challenge, or using pressors or positive chronotropic agents. Occasionally, temporary pacing for refractory bradycardia from amiodarone may be required, especially if other measures are ineffective.
Recent literature suggests no improvement in survival or favorable neurologic outcome in patients with OHCA due to initial shock-refractory VF or pulseless VT with antiarrhythmic medications such as amiodarone or lidocaine.23 Patients with in-hospital cardiac arrest may receive some benefit when given steroids, vasopressin, and epinephrine as a bundle, though routine use is not recommended.24
Lidocaine (lignocaine) (see also chapter 12, Approach to Shock) is a Class I antiarrhythmic drug. It reduces automaticity, suppresses ventricular ectopy, and may be used for hemodynamically stable VT and refractory VF/pulseless VT. In the 2010 recommendations, lidocaine was the second-choice drug after amiodarone, or was used if amiodarone was not available. However, a 2016 multicenter study suggests no improvement in survival or neurologic outcome with use of lidocaine (or amiodarone or placebo) for OHCA from VF or pulseless VT.23 In the 2010 guidelines for cardiac arrest, the dose was an IV bolus of 1 to 1.5 milligrams/kg body weight. A second bolus of 0.5 to 0.75 milligrams/kg was provided if the rhythm persisted. The 2015 algorithm no longer contains lidocaine, and guidelines state the routine use of lidocaine after ROSC is not recommended, though it may be considered in patients with ROSC after VF or pulseless VT. Upon restoration of spontaneous circulation, lidocaine may be given as an infusion at a rate of 1 to 4 milligrams/min.
If dysrhythmia reappears during the infusion of lidocaine, give a bolus of 0.5 milligrams/kg and increase the infusion rate to 4 milligrams/min. Toxicity may occur with doses exceeding 3 milligrams/kg body weight bolus or in patients with liver disease, since the drug is hepatically metabolized. Symptoms include neurologic changes such as drowsiness, disorientation, reduced hearing ability, perioral paresthesia, muscle tremors, and seizures. Myocardial depression and circulatory depression are also features of toxicity, and these may be illustrated by widening QRS complexes and falling blood pressures. In patients with known impaired liver function or patients >70 years old, give the same recommended bolus doses, but decrease the normal infusion rate by 50%.
In animal studies, β-blockers can reduce myocardial oxygen requirements, decrease the number of shocks needed for defibrillation, and can prolong survival from VF/pulseless VT. Successful use in humans is based primarily upon case reports. However, one retrospective series of patients with refractory VF or VT who received at least 3 defibrillation attempts, 300 mg of amiodarone, and 3 mg of adrenalin, without success, reported that esmolol given during resuscitation improved rate of ROSC, ICU admission, survival to hospital discharge, and favorable neurologic outcome.25 Further study is required.
Magnesium is a cofactor in numerous enzymatic reactions. It is essential for the function of the Na-K-ATPase pump. Magnesium deficiency may be associated with cardiac arrhythmias, sudden death, and precipitation of VF. Magnesium is used to treat hypomagnesemia, with or without dysrhythmias.
Magnesium is initial treatment for torsades de pointes and dysrhythmias secondary to hypomagnesemia, cardiac arrest from QTc prolongation, or cardiac glycoside toxicity.16,26 For patients in VF or pulseless VT due to the above conditions, give 1 to 2 grams in 10mL 5% dextrose in water IV over 1 minute. Magnesium provides no benefit for routine use in cardiac arrest. For patients with a pulse, the dose is 1 to 4 grams in 50 mL 5% dextrose in water over 60 minutes. Adverse reactions include flushing, sweating, mild bradycardia, hypotension, asystole with circulatory collapse (with too rapid administration), and respiratory depression. Hypermagnesemia may produce depressed reflexes, flaccid paralysis, diarrhea, respiratory depression, and circulatory collapse.
OTHER DRUGS IN CARDIAC ARREST
Atropine is a parasympatholytic agent that enhances sinus node automaticity and atrioventricular conduction by direct vagolytic action. It is not recommended for PEA or for treatment of cardiac arrest. It is indicated for symptomatic bradycardia. The dose is 0.5 or 0.6 milligrams IV (dose depends on formulation in country of use) and may be repeated at 5- to 10-minute intervals up to a maximum of 0.04 milligrams/kg body weight. Atropine may induce tachycardia or premature ventricular contractions and cause worsening of myocardial ischemia. Symptoms of overdosage include tachycardia, delirium, coma, flushed and hot skin, ataxia, and blurred vision. Administration of low doses less than 0.5 milligrams IV may produce paradoxical bradycardia and precipitate VF.
Calcium is given during resuscitation only for cardiac arrest from hyperkalemia, hypocalcemia, or calcium channel blocker overdose. Calcium is not recommended for routine administration for VF/pulseless VT or PEA.16,27 The dose of calcium chloride is 0.2 mL/kg of 10% calcium chloride, given as a slow IV bolus.
The use of sodium bicarbonate during cardiac arrest was advocated in the past to treat presumptive acidosis, because severe acidosis decreases myocardial contractility.28 However, routine use during cardiac arrest is no longer recommended due to a number of potential adverse effects. Sodium bicarbonate causes hypernatremia, hyperosmolality, and alkalosis (which in turn induces a left shift of the oxyhemoglobin dissociation curve), and IV sodium bicarbonate produces carbon dioxide, resulting in hypercarbia unless ventilation is increased. It does not appear to improve defibrillation success. It may be given in cardiac arrest from hyperkalemia or cyclic antidepressant overdose. It is also acceptable and possibly helpful for intubated patients with a long arrest interval until ROSC and with persistent severe metabolic acidosis. The dose is 1 to 1.5 mEq/kg IV bolus, followed by 0.75 mEq/kg every 10 to 15 minutes as needed. If continuous infusion of sodium bicarbonate is used, check pH to guide therapy.
Vasopressin, also called antidiuretic hormone, is a naturally occurring neurohypophysial peptide hormone synthesized in the hypothalamus and stored in the pituitary gland. It increases water absorption in the nephron and increases peripheral vascular resistance. Vasopressin levels elevate during cardiac arrest, and this observation led to investigation of its role in resuscitation. Vasopressin has a longer duration of action and, in laboratory studies, maintains coronary perfusion pressure, myocardial blood flow, and cerebral blood flow better than epinephrine. However, most studies do not show superiority of vasopressin over epinephrine.19,27 Vasopressin as a first-line agent in cardiac arrest (40-unit dose) does not improve long-term survival when compared to epinephrine,29 although vasopressin might improve short-term survival in patients with prolonged cardiac arrest.29 Combining vasopressin (40 units) with epinephrine does not appear to improve outcomes.19 The 2015 updates remove vasopressin from all algorithms. A combination of vasopressin, epinephrine, and steroids is not recommended at this time for routine use, due to low quality of evidence.