INTRODUCTION — The primary drugs used for pediatric resuscitation are reviewed here.

Pediatric basic life support, pediatric advanced life support, and the use of naloxone in children with opioid intoxication are discussed separately:

●(See "Pediatric basic life support (BLS) for health care providers".)

●(See "Pediatric advanced life support (PALS)".)

●(See "Opioid intoxication in children and adolescents", section on 'Naloxone'.)

DRUG THERAPY BY CLINICAL CONDITION — The primary drugs used in pediatric advanced life support (PALS) and pediatric resuscitation according to clinical presentation are as follows (table 1) [1] (see "Pediatric advanced life support (PALS)"):

●Hypoxemia – Oxygen

●Hypoglycemia – Glucose

●Asystole or pulseless electrical activity – Oxygen, epinephrine (algorithm 1)

●Pulseless with a shockable rhythm (VF, pulseless ventricular tachycardia [pVT], or torsades de pointes [TdP]) – Oxygen, epinephrine, and, for VF and pVT, lidocaine or amiodarone, and for TdP, magnesium sulfate as adjuncts to high quality cardiopulmonary resuscitation and defibrillation (algorithm 1)

●Uncomplicated supraventricular tachycardia (SVT) – Oxygen, adenosine (algorithm 2)

●Possible ventricular tachycardia or aberrant SVT – Oxygen, adenosine, amiodarone, procainamide (algorithm 2)

●Hypomagnesemia or TdP – Magnesium sulfate

●Bradycardia – Oxygen, epinephrine, atropine (algorithm 3)

●Severe metabolic acidosis associated with prolonged cardiac arrest or shock – Sodium bicarbonate

●Hypocalcemia, hypermagnesemia, hyperkalemia or calcium channel blocker overdose – Calcium chloride

The use of naloxone for children with suspected opioid intoxication and clinical findings of coma, depressed respirations, and/or miosis is discussed separately. (See "Opioid intoxication in children and adolescents", section on 'Naloxone'.)

In children undergoing pediatric advanced life support (PALS), medications are of secondary importance to the prompt treatment of hypoxemia and respiratory impairment, initiation of high quality cardiopulmonary resuscitation in pulseless patients, and early defibrillation in patients with ventricular arrhythmias (ventricular fibrillation [VF], pulseless ventricular tachycardia [pVT], or pulseless torsade de pointes [TdP]). (See "Pediatric basic life support (BLS) for health care providers", section on 'Basic life support approach' and "Pediatric advanced life support (PALS)".)

SUBSTRATE DELIVERY

Oxygen — The fundamental goal of basic and advanced life support is to support cerebral, myocardial, and systemic oxygenation before irreversible injury occurs. Because respiratory compromise is the leading cause of cardiac arrests in children, 100 percent oxygen should be administered, to any child who is suspected of being hypoxemic using an appropriate delivery device. The potential negative effects of high concentrations of oxygen are not a consideration in the setting of cardiopulmonary arrest. (See "Continuous oxygen delivery systems for the acute care of infants, children, and adults" and "Pulmonary consequences of supplemental oxygen".)

However, in perfusing patients and those who were in arrest but regained spontaneous circulation, oxygen therapy should be titrated to maintain PaO₂ between 60 and 300 mmHg or pulse oximetry of 94 to 99 percent to avoid oxygen toxicity. (See "Pediatric advanced life support (PALS)", section on 'Avoid low and high arterial oxygen'.)

Dextrose (glucose) — Hypoglycemia may accompany trauma, respiratory failure, shock, sepsis, and many other illnesses that result in cardiopulmonary arrest. Small infants are particularly prone to developing hypoglycemia because of inadequate glycogen stores. In addition, acute illness may have caused decreased caloric intake or excessive losses (eg, from diarrhea and vomiting).

A rapid bedside glucose test should be performed in all pediatric patients who are clinically unstable because the clinical signs of hypoglycemia and hypoxemia are similar (eg, altered mental status, poor perfusion, tachycardia, and hypotension). (See "Approach to hypoglycemia in infants and children".)

●Mechanisms – Glucose is the primary metabolic substrate for the neonatal myocardium, and hypoglycemia may contribute to myocardial dysfunction [2]. Glucose also is a significant energy source in older infants and children during periods of ischemia [2]. Whether glucose administration improves cardiac function or survival in hypoglycemic children with cardiac arrest is not known [2].

●Indications and contraindications – During pediatric resuscitation, patients with a low bedside glucose (<60 mg/dL [3.3 mmol/L]) warrant treatment, but routine administration of glucose without evaluation of the serum glucose is not recommended [2]. Empiric treatment with glucose may be appropriate if bedside glucose determination is not available and the infant or child has symptoms of severe hypoglycemia or is at risk for developing hypoglycemia. Symptomatic patients with a bedside glucose between 60 and 70 mg/dL [3.89 mmol/L] may also warrant treatment especially if they have a condition such as diabetes mellitus which has led to habituation to a higher than normal baseline blood glucose. (See "Approach to hypoglycemia in infants and children".)

The routine administration of glucose during pediatric resuscitation is not recommended because of the absence of data demonstrating benefit and the potential harm of hyperglycemia. Large volumes of dextrose-containing fluids should not be given to normoglycemic children during resuscitation because they can cause hyperglycemia, which can induce osmotic diuresis, produce or aggravate hypokalemia, or worsen ischemic brain injury [2-5]. Evidence for the harm of empiric glucose administration is less convincing for neonates. As an example, in a newborn animal model, administration of glucose improved survival in hypoxic rat pups and did not increase the extent of hypoxic-ischemic brain damage [6].

●Dose and administration – The dose of intravenous dextrose (glucose) for symptomatic hypoglycemia is 0.5 to 1 g/kg per American Heart Association Pediatric Life Support recommendations [2]. However, other experts have suggested a lower dose of 0.2 to 0.25 g/kg to avoid unintentional osmotic diuresis. (See "Approach to hypoglycemia in infants and children", section on 'Treatment'.)

It should be administered via intravenous (IV) or intraosseous (IO) infusion. The maximum concentration of dextrose that can be administered through a peripheral vein is 25 percent dextrose in water (D25W); higher concentrations cause sclerosis of peripheral veins. Thus, 50 percent solutions of dextrose in water (D50W) must be diluted 1:1 with sterile water before peripheral administration in children. However, in infants and children younger than five years of age, 10 percent dextrose in water is typically used.

The volume of solution necessary to achieve the desired dose varies depending upon the dextrose concentration of the solution. Each of the following alternatives provides 0.5 to 1 g/kg of dextrose [2]:

•2 to 4 mL/kg of D25W

•5 to 10 mL/kg of 10 percent dextrose in water (D10W)

•A bolus of 10 to 20 mL/kg of 5 percent dextrose in normal saline or Lactated Ringer solution

Children with hypoglycemia due to a sulfonylurea overdose may especially warrant this higher initial dose of glucose. (See "Sulfonylurea agent poisoning", section on 'Hypoglycemia'.)

After the initial dextrose infusion, the unconscious child should receive additional intravenous dextrose at an infusion rate that will maintain glucose levels (5 to 6 mg/kg per minute in infants and 2 to 3 mg/kg per minute in children) and undergo frequent measurement of blood glucose. (See "Approach to hypoglycemia in infants and children", section on 'Treatment'.)

CARDIAC ARREST (ASYSTOLE OR PULSELESS ELECTRICAL ACTIVITY)

Epinephrine — Administration of epinephrine is the intervention most likely to be of benefit when basic life support and volume resuscitation do not restore effective circulation (algorithm 1 and table 1) [7,8].

●Mechanisms – The actions of epinephrine include both alpha- and beta-adrenergic stimulation.

The alpha-mediated peripheral arterial vasoconstriction is the beneficial action of epinephrine in cardiac arrest. Peripheral arterial vasoconstriction elevates systemic vascular resistance, thereby increasing the aortic-right atrial pressure gradient during the decompression phase of cardiopulmonary resuscitation (CPR). This gradient, also called the coronary perfusion pressure, correlates directly with myocardial blood flow in animal models, and is a good predictor of return of spontaneous circulation (ROSC) in animals and humans [9-11].

In addition, increased systemic vascular tone raises the arterial pressure during the compression phase of CPR, thereby raising the cerebral perfusion pressure [12].

Thus, the administration of epinephrine increases blood flow to both the heart and the brain. Additional alpha-adrenergic vasoconstrictor effects of epinephrine include reduced blood flow to the splanchnic, renal, mucosal, and dermal vascular beds [2].

Beta-adrenergic stimulation increases myocardial contractility and heart rate and relaxes smooth muscle in the coronary arteries, cerebral arteries, skeletal muscle vascular beds, and bronchi [2,13]. Other effects of epinephrine include stimulation of spontaneous cardiac contraction in asystole and enhanced ability to terminate ventricular fibrillation by electrical defibrillation [14].

●Indications and contraindications – Epinephrine is indicated for the treatment of cardiac arrest, symptomatic bradycardia not responsive to oxygen and ventilation, and hypotension not responsive to fluid administration [2]. Asystole and bradyarrhythmias are the most common rhythms in pediatric cardiac arrests [2]. The administration of epinephrine to children with these rhythms may generate a perfusing pressure [15]. In addition, the use of epinephrine in children with ventricular fibrillation, an uncommon rhythm in pediatric arrest, may render the rhythm more susceptible to electrical defibrillation [9].

Contraindications to the use of epinephrine are rare in children and consist of:

•Hypersensitivity to epinephrine or one of its components – Although evidence is lacking for its use as the initial drug for pediatric arrest, vasopressin is a possible alternative to epinephrine in patients with cardiac arrest. Children with bradycardia and hemodynamic compromise can be given atropine and, if necessary, undergo transthoracic or transvenous pacing.

•Narrow angle glaucoma – The risk of worsening narrow angle glaucoma will rarely outweigh the benefit for children in cardiac arrest with this uncommon condition. The clinician should weigh the harm of worsening narrow angle glaucoma with the benefit of epinephrine administration in children with cardiac arrest, in those rare instances in which a patient is known to carry this diagnosis. For children with bradycardia and cardiac compromise, atropine and, if necessary, transthoracic or intravenous pacing may attempted rather than giving epinephrine.

●Dose and administration – The dose of epinephrine varies depending on the route of administration. Although it can be given endotracheally, the intravenous (IV) or intraosseous (IO) route is preferred [1]. Epinephrine should be administered through a secure intravascular line because infiltration into the tissues may cause local ischemia, which may lead to tissue injury and ulceration [15]. Epinephrine is inactivated by alkaline solutions and should not be added to solutions containing sodium bicarbonate. To help prevent medication errors, ratio expressions have been removed from epinephrine labels in the United States [16]. Ampules, vials, and syringes of epinephrine with ratio expressions may, however, remain in inventory until replaced by products with revised labeling. Therefore, the 0.1 mg/mL concentration of epinephrine may be labeled as 1:10,000 and the 1 mg/mL concentration may be labeled as 1:1000.

•Parenteral – The IV or IO dose of epinephrine is 0.01 mg/kg given as 0.1 mL/kg of the 0.1 mg/mL solution. Repeated doses may be given every three to five minutes as needed [1].

•Endotracheal – The recommended dose of epinephrine when given by the endotracheal route is 0.1 mg/kg given as 0.1 mL/kg of the 1 mg/mL solution, which can also be repeated every three to five minutes as needed [1]. The endotracheal dosing of epinephrine in neonates is discussed separately. (See "Neonatal resuscitation in the delivery room", section on 'Epinephrine'.)

Higher doses of epinephrine are required for endotracheal administration because peak levels achieved via this route are less than 10 percent of those achieved with IV administration [17]. In addition, studies in animals using endotracheal epinephrine at doses of 0.01 to 0.02 mg/kg demonstrated no discernible effect on systolic or diastolic blood pressure [18].

Optimal endotracheal drug absorption depends upon delivery of the drug as deeply as possible into the airway [19]. Administration of medications endotracheally is discussed below. (See 'Endotracheal drug administration' below.)

•High-dose epinephrine – High-dose epinephrine (HDE) is no longer recommended for use in pediatric resuscitation [1].

HDE (0.1 to 0.2 mg/kg) had been previously recommended for second and subsequent doses for infants and children with unresponsive asystole or pulseless electrical activity (PEA) on the basis of animal and adult studies that demonstrated improved cerebral and cardiac perfusion with higher doses of epinephrine [15,20-22]. In addition, several studies reported an increase in return of spontaneous circulation in children who received HDE after failing to respond to two standard doses (SDE) [10,23].

However, subsequent large, multi-institutional, adult trials, well controlled animal outcome studies, and retrospective pediatric reviews failed to show any benefit of HDE in terms of survival to discharge and neurologic outcome [24-28]. Finally, a controlled trial evaluated children with in-hospital cardiac arrest who were randomly assigned to receive HDE or SDE after failure of an initial dose of SDE [29]. Although return of spontaneous circulation was similar in both groups, HDE was associated with increased risk of death (adjusted odds ratio [OR] 7.9, 95% CI 0.9-72.5).

HDE is also not indicated for symptomatic bradycardia unresponsive to oxygen and ventilation and/or hypotension unresponsive to fluid therapy [2,13,19]. In these situations, a continuous epinephrine infusion should be administered. (See "Systemic inflammatory response syndrome (SIRS) and sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis" and "Hypovolemic shock in children: Initial evaluation and management", section on 'Fluid resuscitation'.)

Despite the recognized benefits of increasing coronary and cerebral perfusion pressures, evidence has shown a negative safety profile of epinephrine, due to its ability to increase myocardial workload, decrease subendocardial perfusion, and induce ventricular arrhythmias [30]. Most of the evidence on the toxicity of epinephrine has been described in hemodynamically intact animals and adults. Whether these results can be applied to the low flow state present during cardiac arrest is not clear [10,19]. Very high doses of epinephrine have been associated with a pattern of myocardial injury called "contraction band necrosis" [31]. Damage to the arterial vascular endothelium also may occur [32]. One study found that adult patients receiving more than 15 mg cumulative-dose epinephrine had an increased mortality rate at 24 hours after arrest compared with patients receiving less than 15 mg [33].

●Vasopressin versus epinephrine for pulseless arrest – Vasopressin, a nonadrenergic endogenous peptide that induces peripheral, coronary, and renal vasoconstriction via stimulation of Vasopression1 receptors, lacks the adverse effects of epinephrine and has gained much attention as a replacement vasopressor [34]. Another possible advantage of vasopressin is that Vasopressin2 receptor stimulation induces vasodilation and may lessen the end-organ hypoperfusion thought to occur with epinephrine [35].

Small pediatric case series suggest that vasopressin, or its long-acting analog, terlipressin, may be effective in refractory cardiac arrest when standard therapy fails [36-38]. These reports include patients with prolonged return of spontaneous circulation (ROSC) and intact neurologic survival. However, a large National Registry of Cardiopulmonary Resuscitation (NRCPR) retrospective observational study found that vasopressin was associated with a lower frequency of ROSC, and a trend toward lower 24-hour and discharge survival [39]. Thus, vasopressin is not included in the consensus pediatric cardiac arrest algorithm (algorithm 1).

The use of vasopressin in adult resuscitation is discussed separately. (See "Supportive data for advanced cardiac life support in adults with sudden cardiac arrest", section on 'Vasopressin'.)

TACHYARRHYTHMIAS AND CARDIAC ARREST (SHOCKABLE RHYTHM)

Adenosine — Adenosine is the drug of choice for uncomplicated supraventricular tachycardia (SVT) in children (table 1).

●Mechanisms – Adenosine interacts with Adenosine1 receptors on the surface of cardiac cells; the resulting effects include slowing of the sinus rate and an increase in the atrioventricular node conduction delay. These actions interrupt the reentrant circuit of tachycardias that require the atrioventricular node for reentry, which account for the great majority of cases of SVT in children. While adenosine is effective in terminating SVT associated with atrioventricular (AV) node reentry, AV reentry tachycardia associated with an accessory pathway, sinus node reentry, and automatic atrial tachycardia, it is not effective for atrial flutter, atrial fibrillation, or tachycardias that are not caused by reentry at the AV node. (See "Management of supraventricular tachycardia in children", section on 'First-line therapy (adenosine)'.)

●Indication and contraindications – Adenosine is the drug of choice for the acute medical conversion of SVT unresponsive to vagal maneuvers (algorithm 2 and table 2 and waveform 1). However, in children with Wolff-Parkinson-White syndrome, adenosine administration for SVT can cause atrial fibrillation with progression to ventricular fibrillation. As a result, caution should be used when giving adenosine if WPW is a possible mechanism; emergency resuscitation equipment should be available and when possible, a pediatric cardiologist should be consulted before treatment. (See "Management of supraventricular tachycardia in children", section on 'Supraventricular tachycardia refractory to vagal maneuvers'.)

Adenosine is also contraindicated in patients with pre-existing second or third degree heart block or sinus node disease. (See "Management of supraventricular tachycardia in children", section on 'First-line therapy (adenosine)'.)

Although adenosine is considered to be the drug of choice for conversion of uncomplicated SVT in children, there are some children with frequently recurrent or refractory SVT who are poorly responsive to adenosine. These patients commonly have impaired ventricular function or are recovering from surgery for congenital heart disease [40]. Procainamide or amiodarone are suggested agents for such patients if they do not respond to adenosine. (See 'Procainamide' below and 'Amiodarone' below.)

●Dose and administration – The usual initial dose of adenosine for SVT is 0.1 mg/kg rapid IV push (maximum first dose 6 mg) followed immediately with a 5 mL saline flush to promote drug entry into the systemic circulation. Dosing is discussed in greater detail separately. (See "Management of supraventricular tachycardia in children", section on 'First-line therapy (adenosine)'.)

Because the elimination half-life of adenosine is 10 seconds, it should be given in an intravenous line as close to the heart as possible. If adenosine is given too slowly or with an inadequate saline flush, then less of the drug may reach the heart and decrease efficacy. The use of two syringes (one with adenosine and the other with normal saline flush) connected to a T-connector or a stopcock is a useful way of ensuring rapid and effective drug delivery.

A systematic review of five case series (232 infants and children) suggests that an adenosine dose of 0.1 mg/kg will successfully reverse SVT in 20 to 65 percent of patients [41]. Subsequent doses may be increased by 0.1 mg/kg to a maximum single dose of 0.3 mg/kg (maximum total single dose 12 mg). In children >50 kg, the initial adult dose of 6 mg should be given with subsequent doses being the maximum single dose of 12 mg. (See "Management of supraventricular tachycardia in children", section on 'First-line therapy (adenosine)'.)

The most common side effects reported after adenosine administration are flushing, chest discomfort, nausea, and headache. Transient sinus bradycardia or heart block may occur, usually lasting between 10 and 40 seconds. Bronchospasm has been reported in patients with asthma who receive adenosine. (See "Management of supraventricular tachycardia in children", section on 'First-line therapy (adenosine)'.)

Amiodarone — Amiodarone may be used for the treatment of pulseless ventricular arrhythmias and is also potentially useful for supraventricular and stable ventricular arrhythmias (table 1).

●Mechanisms – Amiodarone is a class III antiarrhythmic agent that slows atrioventricular (AV) node conduction, prolongs the AV node refractory period and QT interval, and slows ventricular conduction (widens the QRS). These actions are mediated through effects on sodium, potassium, and calcium channels as well as blocking alpha- and beta-adrenergic receptors. (See "Amiodarone: Clinical uses", section on 'Pharmacokinetics'.)

●Indications and contraindications – Amiodarone is effective in treating both ventricular and supraventricular arrhythmias that are resistant to other therapies.

In children, amiodarone is suggested for the treatment of pulseless ventricular arrhythmias or stable ventricular tachycardia (VT) (algorithm 2). Based upon the pediatric cardiac arrest algorithm (algorithm 1), amiodarone is not preferred over lidocaine for the treatment of shock-refractory ventricular fibrillation or pulseless ventricular tachycardia [42-45].

Amiodarone is also used for supraventricular tachycardia that is refractory to adenosine. However, procainamide may be more effective in this situation. (See 'Procainamide' below and 'Adenosine' above and "Management of supraventricular tachycardia in children", section on 'Supraventricular tachycardia refractory to adenosine'.)

Amiodarone should not be administered together with another drug that causes QT prolongation, such as procainamide, without expert consultation [1]. It is contraindicated in patients with congenital prolonged QT syndrome because it can exacerbate ventricular arrhythmias [46].

In a small pediatric case series of 40 children who did not respond to standard therapy, 80 percent had successful cessation of critical tachyarrhythmias (eg, atrial or ventricular tachyarrhythmias, junctional ectopic tachycardia) after receiving intravenous amiodarone [47]. Most of these patients developed these arrhythmias after cardiac surgery.

However, in a multicenter observational study of inpatient treatment of pulseless ventricular tachycardia and ventricular fibrillation in 889 patients younger than 18 years of age, administration of amiodarone (171 patients; 82 who also received lidocaine) was not associated with return of spontaneous circulation (ROSC), 24 hour survival, or survival to discharge [48]. Lidocaine administration (295 patients) was associated with significantly improved ROSC (adjusted odds ratio [OR] 2.0) and 24 hour survival (adjusted OR 1.7) but not survival to discharge. Thus, either amiodarone or lidocaine is an appropriate medication for the initial treatment of ventricular arrhythmias in children.

●Dose and administration – Amiodarone may be given via rapid intravenous or intraosseous bolus in a dose of 5 mg/kg (maximum single dose: 300 mg). The 5 mg/kg dose may be repeated up to a maximum daily dose of 15 mg/kg (maximum recommended daily dose 2.2 g) [49]. Alternatively, based upon a small case series, a 10 mg/kg per day continuous infusion appears safe and effective and may be started if there is a response to the initial bolus [50].

Amiodarone should not be administered through an endotracheal tube.

Procainamide — Procainamide is a class IA antiarrhythmic that is an alternative to amiodarone for the treatment of supraventricular tachycardia (SVT) refractory to adenosine or stable ventricular tachycardia (table 1).

●Mechanisms – Procainamide is a sodium channel blocker that prolongs the refractory period of both the atria and ventricles and slows conduction velocity. Unlike adenosine, procainamide does not block reentry at the atrioventricular node and can be safely used in patients with Wolff-Parkinson-White syndrome. (See "Management of supraventricular tachycardia in children", section on 'Supraventricular tachycardia refractory to adenosine'.)

●Indications and contraindications – Procainamide is suggested for the treatment SVT that is unresponsive to adenosine or stable ventricular tachycardia (algorithm 2). Procainamide may be more effective than amiodarone in patients with refractory supraventricular arrhythmias. As an example, in an observational study of 37 pediatric patients (24 with congenital heart disease), procainamide was significantly more effective than amiodarone in terminating refractory supraventricular tachycardia (50 versus 15 percent) without an observed difference in adverse effects [40].

Procainamide should be avoided in patients who have received amiodarone. It is contraindicated for patients with allergy to procainamide or related drugs (eg, procaine penicillin), heart block (eg, complete or second degree heart block), or torsades de pointes.

●Dose and administration – Consultation with a pediatric cardiologist is advised. The intravenous (IV) loading dose depends upon patient age:

•Neonates: 7 to 10 mg/kg [51,52]

•Older infants and children: 15 mg/kg (maximum dose, 1 g) [52,53]

To avoid transient hypotension caused by rapid administration, give the loading dose slowly over 30 to 60 minutes. During loading, ensure frequent BP measurements and continuous electrocardiogram (ECG) monitoring.

For stable patients in normal sinus rhythm who are receiving procainamide, stop administration if the QRS interval increases >50 percent from baseline or an arrhythmia develops [52].

After the loading dose, start a continuous IV infusion at 20 mcg/kg per minute and titrate up to a maximum dose of 80 mcg/kg per minute as needed for rhythm control (maximum daily dose, 2 g over 24 hours). Measure plasma levels (procainamide and N-acetyl procainamide) four hours after completion of the loading dose [51,52].

Adverse effects of procainamide include heart block, negative inotropic effects, and prolongation of the QRS and QT intervals (which will predispose to ventricular arrhythmias and torsade de pointes) [52,54].

Use lower doses in patients with renal impairment to avoid supratherapeutic levels [51,52].

Lidocaine — Lidocaine may be used as an alternative to amiodarone for the treatment of pulseless ventricular arrhythmias (table 1).

●Mechanisms – Lidocaine is a class IB antiarrhythmic that blocks sodium channels in cardiac conductive tissue when they are in the inactivated state at the end of depolarization and during early repolarization. This action results in inhibition of electrical conduction and automaticity, particularly in ischemic tissue [1].

●Indication and contraindications – Lidocaine is suggested for the treatment of pulseless ventricular arrhythmias that are refractory to high quality cardiopulmonary resuscitation, defibrillation, and epinephrine. Based upon the pediatric cardiac arrest algorithm (algorithm 1), amiodarone is not preferred over lidocaine for this indication.

In one multicenter observational study of 889 children younger than 18 years of age with inpatient treatment of pulseless ventricular tachycardia and ventricular fibrillation, lidocaine administration (295 patients) was associated with improved return of spontaneous circulation and 24 hour survival, but not survival to discharge. Thus, lidocaine or amiodarone are suggested for the treatment of shock-resistant ventricular arrhythmias. Further study is needed to the reproducibility of these results and whether or not they are generalizable to out-of-hospital settings. (See 'Amiodarone' above.)

Lidocaine is contraindicated in patients with Wolff-Parkinson-White syndrome and those who are allergic to amide-type local anesthetics (table 3). It may also cause seizures and myocardial and circulatory depression, especially in children with poor cardiac output and those with renal or liver failure [1]. (See "Major side effects of class I antiarrhythmic drugs", section on 'Lidocaine (intravenous)'.)

●Dose and administration – Lidocaine should be initially given as a single intravenous (IV) or intraosseous (IO) bolus dose of 1 mg/kg followed by an infusion of 20 to 50 mcg/kg/minute. If the start of the infusion will be delayed longer than 15 minutes, then a second IV or IO bolus dose of 1 mg/kg is suggested.

The initial bolus dose of lidocaine can be given endotracheally although IV or IO administration is strongly preferred. The suggested endotracheal dose is 2 to 3 mg/kg. The technique for endotracheal medication administration is discussed below. Studies evaluating the absorption of lidocaine by the endotracheal route are lacking. (See 'Endotracheal drug administration' below.)

Magnesium sulfate — Magnesium sulfate is the primary agent recommended for the treatment of torsades de pointes (table 1).

●Mechanisms – Magnesium is a crucial cofactor in the sodium-potassium-ATPase enzyme system. It stabilizes the motor membrane by reducing the sensitivity of the motor end plate to acetylcholine. A decreased intracellular magnesium level promotes myocardial excitability but, even in the absence of a low magnesium level, a bolus of IV magnesium will suppress ectopic ventricular beats. At high levels, magnesium acts as a calcium channel blocker and can produce bradycardia with atrioventricular block and cardiac arrest. (See "Hypermagnesemia: Causes, symptoms, and treatment", section on 'Cardiovascular effects'.)

●Indications and contraindications – Magnesium sulfate is indicated in the treatment of torsades de pointes (polymorphic VT with long QT interval) or documented hypomagnesemia. Patients with hypokalemia and arrhythmias frequently have associated hypomagnesemia. (See "Supportive data for advanced cardiac life support in adults with sudden cardiac arrest", section on 'Magnesium sulfate' and "Hypomagnesemia: Clinical manifestations of magnesium depletion", section on 'Hypokalemia'.)

Patients who receive magnesium sulfate require monitoring of serum magnesium concentrations. Magnesium should be administered with caution to patients with myasthenia gravis or other neuromuscular disease and patients with renal impairment.

●Dose and administration – For torsades de pointes, magnesium sulfate should be diluted in 5 percent dextrose (D5W) to a 20 percent solution or less and given as an intravenous or intraosseous infusion at a dose of 25 to 50 mg/kg (maximum dose: 2 g). The rate of infusion depends upon the clinical situation:

•Patients with pulseless arrest – Infuse over one to two minutes.

•Perfusing patients – Infuse over 15 minutes because rapid infusion is associated with hypotension and asystole.

LIMITED INDICATIONS

Atropine — Atropine is primarily indicated for vasovagal-induced bradycardia or the treatment of primary atrioventricular block (table 1).

●Mechanisms – Atropine is a parasympatholytic drug that increases heart rate by accelerating the sinus and atrial pacemaker and improving conduction through the AV node. Although the dominant cardiac response is tachycardia, the heart rate may decrease transiently when small doses are administered [55]. This decrease is thought to occur because atropine, at low doses, blocks the M1 muscarinic postganglionic receptors that provide feedback inhibition for synaptic acetylcholine release [56]; the resulting increase in acetylcholine inhibits spontaneous impulse generation in the SA node.

●Indications and contraindications – Atropine is recommended for children with bradycardia caused by increased vagal tone or primary atrioventricular block or unresponsive to oxygen, airway support, and administration of epinephrine (algorithm 3).

Atropine is no longer routinely recommended in children undergoing endotracheal intubation and is not recommended for pediatric patients with cardiac arrest (algorithm 1). However, it is suggested as a pre-treatment for rapid sequence intubation (RSI) in patients with septic or late stage hypovolemic shock, children ≤5 years of age receiving succinylcholine, and children >5 years of age requiring a second dose of succinylcholine. Furthermore, it is frequently used during RSI in infants <1 year of age to counteract vagally-induced bradycardia. (See "Rapid sequence intubation (RSI) outside the operating room in children: Approach", section on 'Pretreatment'.)

Sinus tachycardia may occur after administration of atropine but it usually is well tolerated in children. The development of hypoxia-induced bradycardia may be masked if atropine is given to block vagal-induced bradycardia during intubation. In these cases, the use of pulse oximetry is recommended to monitor oxygenation. (See "Rapid sequence intubation (RSI) outside the operating room in children: Approach", section on 'Pretreatment'.)

Fixed and dilated pupils should not be attributed to atropine because atropine causes dilation of the pupils but does not eliminate the pupil constrictive response to light [57].

When not being used in a resuscitation situation, atropine is contraindicated in patients with obstructive gastrointestinal or genitourinary conditions (eg, surgical abdomen, paralytic ileus, posterior urethral valves), and myasthenia gravis (unless treating side effects of acetylcholinesterase inhibition) because it may exacerbate the underlying condition [58]. Atropine may cause additional tachycardia in patients with thyrotoxicosis and mucous plugging in patients with asthma. It should also be used with caution in patients with hyperthermia and delirium because of its central anticholinergic effects. (See "Anticholinergic poisoning".)

●Dose and administration – The dose of atropine varies depending on the route of administration. Although it can be given endotracheally, administration by the intravenous (IV) or the intraosseous route (IO) is preferred [1].

•IV/IO route – The recommended IV or IO dose of atropine is 0.02 mg/kg. The maximum single dose is 1 mg. The dose may be repeated once, if needed [1]. Higher doses probably are not routinely necessary because a total dose of 2 mg is sufficient to produce full vagal blockade in an adult [59].

Patients with poisoning from cholinesterase inhibiting agents may require much higher doses of atropine to dry bronchial secretions. (See "Organophosphate and carbamate poisoning", section on 'Atropine'.)

A minimum parenteral dose of 0.1 mg has been suggested based upon a study that showed that very low doses of atropine (0.0036 mg/kg) were associated with a mild slowing of heart rate [55]. This low dose effect was most evident in school-aged children. However, in neonates who weigh less than 5 kg, this minimum dose can lead to anticholinergic toxicity [60,61]. In the 2015 update, the American Heart Association Emergency Care Committee supports a weight-based dose of 0.02 mg/kg with no minimum dose when atropine is given prior to endotracheal intubation [7,8,60].

•Endotracheal route – Studies evaluating the absorption of atropine by the endotracheal route are lacking. The recommended dose for endotracheal administration is 0.04 to 0.06 mg/kg, which may also be repeated once [1]. The technique for endotracheal medication administration is provided below. (See 'Endotracheal drug administration' below.)

Sodium bicarbonate — The routine use of sodium bicarbonate is not recommended because of lack of convincing evidence of beneficial effects and potential adverse effects [15].

A combined respiratory and metabolic acidosis develops during cardiopulmonary arrest. Hypoxia-induced anaerobic metabolism generates lactic acid, and ventilatory failure causes carbon dioxide retention. In addition, during shock or cardiac arrest, metabolic acid excretion is diminished because renal perfusion is inadequate. The severity of the acidosis worsens as the arrested state continues [62].

The most effective means of correcting the acidosis in cardiac arrest is to provide adequate oxygenation, ventilation, and tissue perfusion. Because most pediatric cardiac arrests are caused by respiratory failure, support of ventilation through early intubation is the primary treatment, followed by support of the circulation with fluids and inotropic agents [2,62].

●Mechanisms – Sodium bicarbonate increases blood pH by buffering excess blood hydrogen ion as long as the patient has adequate ventilation to excrete carbon dioxide.

●Indications and contraindications – The American Heart Association (AHA) recommends that sodium bicarbonate be considered only in children with prolonged cardiac arrest and documented severe metabolic acidosis who fail to respond to oxygenation, ventilation, fluids, and chest compressions combined with epinephrine in recommended doses [7,8,15]. Sodium bicarbonate also may be considered when shock is associated with documented metabolic acidosis. (See "Systemic inflammatory response syndrome (SIRS) and sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis" and "Hypovolemic shock in children: Initial evaluation and management", section on 'Fluid resuscitation'.)

In children without cardiac arrest or shock, metabolic acidosis typically resolves with adequate volume replacement and ventilatory support. Additional indications for the administration of sodium bicarbonate include hyperkalemia, hypermagnesemia, tricyclic antidepressant overdose, or overdose from other sodium channel blocking agents [2,15,63,64]. (See "Treatment and prevention of hyperkalemia in adults" and "Tricyclic antidepressant poisoning".)

Sodium bicarbonate administration should not be given to children with inadequate ventilation because inadequate respiratory excretion of carbon dioxide will lead to retention and worsening respiratory acidosis [15].

Excess administration of sodium bicarbonate during resuscitation has been associated with the following effects and should be avoided:

•Hypertonicity

•Worsening of intracellular acidosis with impairment of myocardial contractility

•Extreme metabolic alkalosis with reduced oxygen delivery to the tissues, hypokalemia, and decreased plasma ionized calcium concentration; all of these adverse effects increase the risk for cardiac arrhythmias

●Dose and administration – Sodium bicarbonate is administered by the intravenous (IV) or intraosseous (IO) route. It should not be given endotracheally because it is irritating to the airways, destroys lung surfactant, and can produce massive atelectasis [13].

The initial dose of sodium bicarbonate is 1 mEq/kg (1 mL/kg of 8.4 percent solution or 2 mL/kg of 4.2 percent solution [recommended for children younger than six months of age]). The usual maximum single dose of sodium bicarbonate is 50 mEq for a child to 100 mEq for an adult patient.

During prolonged arrests, subsequent doses of 0.5 mEq/kg each may be given every 10 minutes by slow (one to two minutes) infusion or based upon blood gas analysis [1,2]. However, arterial blood gas analysis taken during cardiac arrest or severe shock may overestimate tissue and venous pH. Thus, central venous blood gas measurements, if possible, are advised to accurately assess acid-base status during resuscitation [65,66].

IV/IO tubing must be irrigated with normal saline before and after giving infusions of sodium bicarbonate to prevent inactivation of administered epinephrine or, in hypocalcemic or hyperkalemic patients, precipitation with calcium chloride. (See 'Epinephrine' above and 'Calcium' below.)

Repeated doses of sodium bicarbonate can also produce symptomatic hypernatremia and hyperosmolarity [67,68]. Compared with plasma, the standard 8.4 percent sodium bicarbonate solution is hyperosmolar (2000 versus 289 mOsm/L) [2]. Use of hypertonic solutions in premature infants has been associated with an increased risk of developing periventricular-intraventricular hemorrhage [69]. For this reason, a more dilute solution (4.2 percent) should be used in infants younger than six months of age [2,13,62].

The administration of sodium bicarbonate may sclerose small veins and produces a chemical burn if extravasated into subcutaneous tissues [2]. Transient vasodilation and hypotension can occur with rapid infusion [70].

Calcium — Calcium has limited uses in pediatric resuscitation which include the treatment of hypocalcemia, hypermagnesemia, hyperkalemia, or calcium channel blocker overdose.

●Mechanisms – Calcium increases cardiac inotropy. Influx and efflux of calcium ions are important for the maintenance of normal conductivity and rhythm.

●Indications and contraindications – Calcium has a very specific indication in cardiac arrests as emergency protection against the arrhythmogenic effects of hypocalcemia, hyperkalemia, hypermagnesemia, or calcium channel blocker overdose [1]. It is otherwise not recommended for pediatric cardiopulmonary arrest because of an observed association with decreased survival and poor neurologic outcomes after pediatric arrests [71].

●Dose and administration – The optimum dose of calcium is based upon extrapolation from adult data and limited pediatric data. Calcium chloride is preferred over calcium gluconate because it provides greater bioavailability of calcium but should only be given if central venous access is available because administration through a peripheral intravenous line is associated with skin necrosis and sloughing [72]. Calcium gluconate is less irritating to the veins and may be administered by peripheral or central venous access.

The recommended dose of elemental calcium is 5 to 7 mg/kg [1]. Dosing in this range can be achieved by giving 0.2 mL/kg of calcium chloride 10 percent which provides 5.4 mg/kg of elemental calcium or 0.6 mL/kg of calcium gluconate 10 percent which provides 5.6 mg/kg of elemental calcium. The maximum single dose is 540 mg of elemental calcium. Calcium chloride or calcium gluconate should be administered by slow intravenous push over 10 to 20 seconds in cardiac arrest and more slowly (eg, over 5 to 10 minutes) in perfusing patients.

Rapid administration may cause bradycardia or asystole. If sodium bicarbonate is being given through the same intravenous line, the tubing must be thoroughly flushed before and after calcium administration. Otherwise an insoluble precipitate can form in the catheter lumen.

ENDOTRACHEAL DRUG ADMINISTRATION — Although lipid soluble drugs, such as lidocaine, epinephrine, atropine, and naloxone ("LEAN") may be administered via an endotracheal tube (ETT), the intravascular route is always preferred [7,8]. Optimal drug dosing via endotracheal tube is unknown for many medications. Unpredictable drug absorption may lead to lower blood levels when compared with the same dose given intravascularly.

Several key actions are needed when giving drugs via an ETT:

●Increase the epinephrine dose 10-fold and the dose of other medications (atropine, lidocaine, naloxone) two- to threefold. (See 'Epinephrine' above and 'Atropine' above and "Opioid intoxication in children and adolescents", section on 'Dosing and administration'.)

●Hold compressions during ETT administration.

●Dilute the medication in normal saline to a volume of 3 to 5 mL and instill into the endotracheal tube or beyond the tip of the endotracheal tube with a suction catheter.

●Follow drug administration with 3 to 5 mL of normal saline.

●Provide five positive pressure ventilations after instilling the drug.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Basic and advanced cardiac life support in children".)

SUMMARY

●The primary drugs used in pediatric advanced life support (PALS), according to clinical presentation, are as follows (table 1) (see 'Drug therapy by clinical condition' above):

•Hypoxemia – Oxygen

•Hypoglycemia – Glucose

•Asystole or pulseless electrical activity – Oxygen, epinephrine (algorithm 1)

•Pulseless with a shockable rhythm (ventricular fibrillation [VF], pulseless ventricular tachycardia [pVT], or torsades de pointes [TdP]) – Oxygen, epinephrine, and, for VF and pVT, lidocaine or amiodarone, and for TdP, magnesium sulfate as adjuncts to high quality cardiopulmonary resuscitation and defibrillation (algorithm 1)

•Uncomplicated supraventricular tachycardia (SVT) – Oxygen, adenosine (algorithm 2)

•Possible ventricular tachycardia or aberrant SVT – Oxygen, adenosine, amiodarone, procainamide (algorithm 2)

•Hypomagnesemia or TdP – Magnesium sulfate

•Bradycardia – Oxygen, epinephrine, atropine (algorithm 3)

•Severe metabolic acidosis associated with prolonged cardiac arrest or shock – Sodium bicarbonate

•Hypocalcemia, hypermagnesemia, hyperkalemia or calcium channel blocker overdose – Calcium chloride

●In addition to these agents, all critically ill children should receive supplemental oxygen. (See 'Oxygen' above.)

●The use of naloxone for children with suspected opioid intoxication and clinical findings of coma, depressed respirations, and/or miosis is discussed separately. (See "Opioid intoxication in children and adolescents", section on 'Naloxone'.)

●In children undergoing pediatric advanced life support (PALS), medications are of secondary importance to the prompt treatment of hypoxemia and respiratory impairment, initiation of high quality compressions during cardiopulmonary resuscitation, and, in pulseless patients with ventricular arrhythmias, early defibrillation. (See 'Drug therapy by clinical condition' above and "Basic airway management in children" and "Pediatric basic life support (BLS) for health care providers" and "Defibrillation and cardioversion in children (including automated external defibrillation)".)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Pamela Bailey, MD, who contributed to an earlier version of this topic review.