18 Cardiac Arrhythmias
18.1 Antiarrhythmic Drugs
Antiarrhythmic drugs play a central role in the treatment of cardiac arrhythmias in childhood. But their use must be weighed critically. There are numerous studies in adults showing that class I antiarrhythmic drugs do not reduce mortality, but even increase it in patients with ventricular tachycardia and myocardial ischemia. It is unclear, however, whether these results can be transferred to children, since coronary perfusion problems are not usually present in children. In addition, all antiarrhythmic drugs themselves have proarrhythmogenic effects. Furthermore, the majority of the antiarrhythmic drugs have a negative inotropic effect. Adverse effects on the central nervous system are not uncommon.
Antiarrhythmic drugs are classified according to their mechanism of action and influence on the action potential. They act by influencing the ion channels (Na, K, Ca) and beta receptors. Table 18.1 presents an overview of indications and properties and dosages are summarized in Table 18.2.
2–10 mg/kg every 3–6 h (IV treatment not recommended)
15–60 mg/kg/d in 4–5 single doses (sulfate formulation). Test dose before starting treatment 2 mg/kg
Infants: 10–30 mg/kg/d
Toddlers: 10–20 mg/kg/d
Children: 10–15 mg/kg/d
Adolescents: 6–15 mg/kg/d
In 4 single doses (standard formulation) or 2 single doses (retard formulation)
1 mg/kg as bolus (can be repeated twice at 5-min intervals), then continuous infusion with 20–50 μg/kg/min
3 mg/kg for 15 min, then continuous infusion with 1 mg/kg/h
5–15 mg/kg/d in 3 single doses
4–7 mg/kg/d in 3 single doses, can be increased to 15–20 mg/kg/d
Initially 1–3 mg/kg/d in 3 single doses, gradually increase to 3–8 mg/kg/d in 3 single doses
0.01–0.1 mg/kg for 10 min, the same dose can be repeated every 6–8 h (start with a 0.01 mg/kg single dose for neonates), maximum 1 mg for toddlers and 3 mg for older children
Begin with 0.5–1 mg/kg/d (0.25 mg/kg/d for neonates) in 3–4 single doses, gradually increase up to the usual maintenance dosage of 2–6 mg/kg/d in 3–4 single doses
0.1 mg/kg as slow bolus
1–2 mg/kg 2 to 4 times daily
200 μg/kg as slow bolus, then continuous infusion with 50–200 μg/kg/min
Saturation dose: 5 mg/kg as a rapid bolus in VT without pulse or ventricular fibrillation and for 30–60 min for hemodynamically stable patients (total of 2 to 3 times a week), then continuous infusion with 10 (to 20) mg/kg/d (dissolved in 5% glucose)
Saturation dose: toddlers 10–20 mg/kg/d in 2 single doses for 5–14 days, children and adolescents 10 mg/kg/d in 2 single doses for 5–14 days
Maintenance dosage: 5–7 mg/kg/d in 1 single dose, gradually reduce to the lowest effective dosage
80–200 mg/m2 BSA/d (equivalent to approx. 4 mg/kg/d) in 3 single doses (toddlers) and 2 single doses (older children), 30 min before meals, do not take with milk
0.1–0.2–0.3 mg/kg for 2 min (max. 5 mg), if unsuccessful, can be repeated after 30 min
4–8 mg/kg/d in 3 single doses (standard formulation) or 1 single dose (retard formulation)
0.01–0.03 mg/kg as bolus, 0.1 μg/kg/min as continuous infusion
0.5–1 mg/kg/d in 4–6 single doses
0.02–0.04 mg/kg as bolus (minimum dose 0.1 mg, maximum dose 1 mg)
0.1 mg/kg (max. 6 mg) as rapid bolus, then flush quickly with NaCl 0.9%, repeat with 0.2 (to 0.3–0.5) mg/kg (max. 18 mg) if necessary
Begin with 0.3–0.5 mmol/kg for 30–60 min, can be repeated if necessary
Class I Antiarrhythmic Drugs (Sodium Channel Blockers)
Class I antiarrhythmic drugs impair sodium transport into the cell. They are subdivided into the subclasses a, b, and c depending on their effect on the action potential:
Class Ia prolongs the action potential: quinidine, procainamide
Class Ib shortens the action potential: lidocaine, mexiletine
Class Ic has no effect on the duration of the action potential: propafenone, flecainide
Class Ia antiarrhythmic drugs
After administration of class Ia antiarrhythmic drugs, the sodium channels reactivate slowly. Accordingly, the QRS duration is prolonged. In addition, these antiarrhythmic drugs prolong the QTc interval. It is also important to note that they have a parasympatholytic (anticholinergic) effect on the sinus and AV nodes. The heart rate is increased and AV conduction is accelerated. Due to the shortened AV conduction, ventricular tachycardia may be induced in patients with atrial flutter. Class Ia antiarrhythmic drugs are rarely used in children.
Class Ib antiarrhythmic drugs
Class Ib antiarrhythmic drugs act primarily on the ventricles. The effect on the atrial and AV node is low. The negative inotropic properties are not very pronounced. Lidocaine is administered only intravenously; mexiletine is administered orally. These antiarrhythmic drugs are rarely used in children.
Class Ic antiarrhythmic drugs
Class Ic antiarrhythmic drugs cause a reduction of the atrial and ventricular rates. They also act on the conduction system. There is a decrease in the frequency of the sinus node as well as a conduction delay in the AV node and ventricles. In the ECG, the duration of the QRS complex increases. If QRS widening is 130% or more of the initial value, the dose should be reduced. These antiarrhythmic drugs are often used in children.
Class II Antiarrhythmic Drugs (Beta Blockers)
Examples of beta blockers are propranolol, metoprolol, and esmolol. They reduce the sympatico-adrenergic stimulation of the heart. Beta blockers have the following effects on the heart:
Negative bathmotropic effect: reduce the excitability of the heart
Negative chronotropic effect: reduce the heart rate
Negative dromotropic effect: reduce the conduction speed
Negative inotropic effect: reduce cardiac contractility
Typical indications for beta blockers are sinus tachycardia, supraventricular re-entrant tachycardia, long QT syndromes, symptomatic supraventricular extrasystoles, ventricular extrasystoles, and bursts. The use of beta blockers is limited by the deterioration of ventricular function, bradycardia, the risk of AV block, and exacerbation of bronchospasm, as well as the induction of hypoglycemia.
Class III Antiarrhythmic Drugs (Potassium Channel Blockers)
The class III antiarrhythmic drugs include sotalol and amiodarone. They block the rapid potassium efflux from the cell, but additionally also block the sodium and the calcium channels and the beta receptors. The action potential duration is prolonged. Class III antiarrhythmic drugs affect all cell types in the heart from the sinus node to the ventricular myocardium and are among the most potent antiarrhythmic drugs, especially amiodarone. They have both a supraventricular and a ventricular effect. The negative inotropic properties of amiodarone are also less pronounced, so it can be used even with a poor ventricular function if proper precautions are taken. However, application is limited by numerous serious side effects including corneal deposits, photosensitivity (sun screen is necessary while staying in the sun), thyroid dysfunction (high iodine content in amiodarone), and irreversible lung fibrosis (rare). Regular eye examinations and tests of the thyroid and lung function parameters are therefore required. Class III antiarrhythmic drugs have a very long half-life of 2 to 7 weeks. After oral administration, the onset of its effect begins after 4 to 10 days; following intravenous bolus injection, the onset of effect begins within minutes.
Furthermore, class III antiarrhythmic drugs prolong the QTc interval in the ECG, sometimes considerably, and thus carry the risk of torsades de pointes tachycardia. Regular ECG monitoring is required.
Class IV Antiarrhythmic Drugs (Calcium Channel Blockers)
Class IV antiarrhythmic drugs include verapamil and diltiazem. Of all calcium antagonists, only verapamil has an antiarrhythmic effect. The effect of class IV antiarrhythmic drugs is mediated through inhibition of the slow calcium influx. They act in the heart especially at the sinus and AV nodes.
Calcium channel blockers should not be used in patients with accessory pathways because they facilitate conduction via the accessory pathway and can thus lead to unchecked conduction to the ventricles (triggering ventricular fibrillation) in patients with atrial flutter or fibrillation. Moreover, the intravenous bolus administration in neonates and infants is contraindicated because of the negative inotropic effect, which is especially pronounced in this age group.
Other Antiarrhythmic Drugs
Adenosine (purine nucleoside)
Adenosine causes a complete short-term blockage of AV conduction. It also has a negative chronotropic effect on the sinus node. It has an extremely short half-life (< 10 seconds), requiring rapid intravenous bolus administration. Adenosine is used mainly in supraventricular re-entrant tachycardia, where it can interrupt the re-entrant circuit by an AV block. It is also used diagnostically in supraventricular tachycardia to facilitate the classification of the tachycardia and in ambiguous cases to distinguish between supraventricular and ventricular tachycardia, for example. Ventricular tachycardias are not affected by adenosine. A relevant extracardiac side effect is the induction of bronchospasms.
Atropine acts through a competitive inhibition of acetylcholine. In the heart, it increases the sinus node rate and promotes AV conduction.
Orciprenaline increases the sinus node rate and impulse conduction in the atrium, the AV node, and the His–Purkinje system. It has a positive inotropic and a vasodilative effect. It also increases the excitability of heterotopic automaticity centers and increases myocardial oxygen consumption.
Digoxin inhibits Na-K-ATPase. It acts on the cardiac rhythm by decreasing the sinus rate and inhibiting AV conduction. At the same time, it also increases the excitability of the atrial and ventricular myocardium and leads to an increase of ectopic impulse formation (risk of arrhythmias). In patients with accessory pathways, digoxin probably facilitates conduction via the accessory pathway. In patients with atrial flutter or fibrillation and an accessory pathway, there may be unchecked conduction of the atrial impulses into the ventricles that trigger ventricular fibrillation.
Magnesium is a physiological calcium antagonist. As an antiarrhythmic agent, it is the drug of choice for torsades de pointes tachycardia.
Antiarrhythmic combination treatment
Because of the risk of additive adverse effects, antiarrhythmic drugs may not be combined with those of the same class or subclass.
In addition, the following may not be combined or may be used together only if special precautions are taken (Table 18.3):
+, possible; –, not possible or possible only if special precautionary measures are taken; n/a, no references available.
Class Ia and class III antiarrhythmic drugs: additive prolongation of the QTc interval
Class Ia and class Ic antiarrhythmic drugs: additive prolongation of the QRS duration
Class Ia antiarrhythmic drugs and calcium antagonists: additive negative inotropic and vasodilative effects
Beta blockers and calcium antagonists: risk of sinus bradycardia and AV block
Beta blockers and class III antiarrhythmic drugs: both amiodarone and sotalol have a beta-sympatholytic effect.
Amiodarone and calcium antagonists: additive vasodilative effect
Suitable combinations (Table 18.3):
Class Ia and Ib antiarrhythmic drugs
Class Ic and Ib antiarrhythmic drugs
Class I and II antiarrhythmic drugs
Class Ib and III antiarrhythmic drugs
Class Ic and III antiarrhythmic drugs
18.1.2 Pacemaker Therapy
A pacemaker is a system for primary electrical treatment of bradycardia arrhythmias. It consists of a generator unit and an electrode system. The generator unit generates the impulse that is conducted by the electrodes to the endocardium, myocardium, or epicardium and leads to depolarization of the myocardial cells.
Parameters of the pacing impulse are the amplitude (expressed in volts or milliamps) and pulse width (expressed in milliseconds; Fig. 18.1).
The amplitude required for effective stimulation is usually between 1 and 5 V with a pulse width of 0.2 to 0.6 ms. As amplitude and pulse width increase, energy consumption increases and the life of the battery decreases. Pacemaker batteries last an average of about 5 to 6 years.
The threshold is the minimum electrical stimulus that is required to stimulate the heart. Of particular importance is that the threshold increases significantly within the first days after pacemaker implantation as a result of inflammatory processes in the area of the electrodes. Over the next few weeks, the threshold decreases again and usually nearly approaches the baseline after 3 to 4 months. Modern electrodes that continually release steroids to the surrounding area can lower the threshold.
The rheobase is defined as the smallest amplitude that can cause just one stimulation in an infinitely long pulse width. In practice, instead of an “infinitely long” pulse width, a pulse width of 1 ms is usually used to determine the rheobase.
Chronaxie is the term for the pulse width that can trigger effective stimulation when the rheobase amplitude is doubled. With these two values, modern pacemakers can independently calculate a chronaxie–rheobase curve (Fig. 18.2). A combination of amplitude and pulse width located above the curve results in effective stimulation. For safety reasons, the stimulation amplitude is usually selected twice as high as the threshold in the range of the chronaxie. The pulse width is then selected to be approximately as long as the chronaxie. Another possibility is to prolong the pulse width by three to four times.
To ensure that even in intrinsic cardiac activity, the heart’s signals are detected by the pacemaker, the sensing threshold of the electrode must be determined. This value describes which amplitude of intrinsic cardiac activity can be just detected by the electrode. A high value indicates a high threshold, thus low sensitivity. The more sensitive the detection threshold setting, the greater is the risk that noise signals such as muscle potentials will be incorrectly classified as cardiac activity (oversensing) and pacemaker stimulation will be suppressed. On the other hand, if the sensing threshold is too insensitive, the pacemaker will not recognize intrinsic cardiac activity and there will be interference between the cardiac activity and the pacemaker impulses (undersensing, pacemaker is asynchronous).
A distinction is made between unipolar and bipolar electrodes (Fig. 18.3). In unipolar electrodes, the electrode tip is the cathode and the pacemaker box is the anode. In bipolar electrodes, both the anode and the cathode are located in the electrode tip. The main characteristics of the electrodes are as follows:
Low energy consumption
Significant pacemaker spikes in the surface ECG (readily assessable)
Small electrode thickness, good handling during transvenous implantation
Susceptible to interference from muscle potentials
Rarely cause muscle or diaphragmatic twitching
Better sensing behavior
Only small pacemaker spikes in the surface ECG (often difficult to assess pacemaker activity in the surface ECG)
Pacemakers are classified according to the stimulation site and sensing of intrinsic activity. A maximum five-character code describes the operation of the pacemaker (Table 18.4).
Pacemaker response to sensed event
0 = None
V = Ventricle
A = Atrium
D = Dual (A + V)
S = Single
0 = None
V = Ventricle
A = Atrium
D = Dual (A + V)
S = Single
I = Inhibited
T = Triggered
D = Dual (I + T)
0 = None
R = Rate modulation
0 = None
V = Ventricle
A = Atrium
D = Dual (A + V)
The response of the pacemaker to sensed intrinsic activity of the heart can be inhibition or triggering. In inhibition, the pacemaker is inhibited by sensed activity and emits no electrical stimulus. In triggering, a pacing impulse is triggered by a sensed event.
Rate modulation systems can adapt the pacing frequency to physical stress. To assess physical activity, there are various sensors that measure factors such as muscle activity, QT interval, and temperature and respiratory excursions. This system is useful for sinus node dysfunction, for example, when the heart does not respond under stress with a corresponding increase in heart rate (chronotropic incompetence).
The fifth position in the pacemaker code is for the stimulation of a third ventricle, for example, in a biventricular pacemaker system.
The most common pacemaker systems used in children are explained below:
The pacemaker stimulates the atrium when the intrinsic heart rate falls below the programmed intervention rate. Intrinsic activity inhibits the pacemaker. A prerequisite for implanting such a system is that AV conduction is not disturbed. Typical indication is sinus node dysfunction. For chronotropic incompetence, a system with rate modulation (AAIR) should be selected.
The pacemaker stimulates the ventricle when the ventricle’s intrinsic frequency falls below the programmed intervention rate. A disadvantage of this system is that contraction of the atria and ventricles is uncoordinated because the pacemaker does not take atrial activity into account. In childhood, this type is still sometimes implanted in neonates, as very small generator units are available. Rate modulation (VVIR) is usually also possible in these systems.
This is a dual chamber system that stimulates the atrium and the ventricle in physiological sequence (AV sequential) when the intrinsic frequency falls below the programmed intervention rate. The atrial pacemaker impulse is suppressed if there is intrinsic atrial activity. If the atrial rate is lower than the programmed intervention rate, the atrium is stimulated. If the conduction of atrial activity to the ventricles is prevented by an AV block, the ventricle is stimulated according to a programmed AV interval (Fig. 18.4). DDD systems are used in AV blocks. A great advantage is that the coordinates of the atria and the ventricles are preserved. DDD systems require an atrial and a ventricular electrode. The atrial electrode may be particularly difficult to anchor in young children. If necessary, reprogramming can allow a switch to an AAI or VVI system. A DDDR system is used for chronotropic incompetence.
Excursus: Additional technical terms for pacemaker technology
In the absence of intrinsic activity, if the heart rate falls below the intervention rate, the pacemaker begins stimulation.
Maximum rate limit
The maximum achievable rate in a dual chamber system. If this rate is exceeded, the pacemaker switches to a 2:1 conduction from the atrium to the ventricle.
The period between the last intrinsic action and the first pacemaker stimulus.
Hysteresis (Greek for “lag”)
If a pacemaker senses intrinsic activity, the escape interval is prolonged until the next pacemaker impulse, so that the heart “has more time” to create new intrinsic activity before the next pacemaker impulse is delivered.
To avoid over-pacing, the pacemaker is therefore “allowed” to stimulate only when the heart rate falls below the programmed intervention rate (e.g., intervention rate 60 bpm, hysteresis 50 bpm).
That means that the pacemaker stimulates at a frequency of 60 bpm when the patient’s intrinsic rate drops below 50 bpm. Accordingly, some heart rates are lower than the programmed intervention rate. This prevents unnecessary intervention and encourages intrinsic activity of the heart.
The time interval between atrial and ventricular stimulation or between sensing intrinsic activity in the atrium and ventricle stimulation.
The time interval after stimulation or sensing in which neither stimulation nor sensing is possible.
Postventricular atrial refractory period (PVARP)
The period following a ventricular pacemaker action at the atrial level when neither stimulation nor sensing is possible.
An atrial stimulus is mistakenly sensed by the ventricle electrode to be a ventricular signal. Because of the misperception, the pacemaker gives no ventricular stimulus. The other possibility is that a ventricular impulse is mistakenly sensed by the atrial electrode to be atrial activity.
The period in which all signals in the respective ventricle or atrium are ignored by the pacemaker. This is done to blank all signals coming from another ventricle or atrium. The blanking time is to prevent “cross talk.” Thus, for example, if the atrial blanking period is sufficient, a ventricular R wave detected in the atrium is not misinterpreted as atrial activity.
Automatic change of stimulation mode when atrial tachyarrhythmia occurs, for example, switching from DDD(R) to DDI(R) or VDI(R). This prevents atrial tachycardia from being conducted 1:1 to the ventricle and inducing ventricular tachycardia.
Intrinsic activity is not detected by the pacemaker. ECG: pacemaker stimulation is independent of the P wave or the QRS complex. Cause: electrode defect or dislocation, sensing threshold too high.
Erroneous assessment of extracardiac signals (e.g., muscle potentials) or intracardiac signals as intrinsic cardiac activity (e.g., perception of the R wave in the atrium). ECG: no stimulation by the pacemaker. In DDD systems, rapid stimulation of the ventricle is also possible if rapid inappropriate signals are sensed in the atrium. Cause: almost exclusively in unipolar electrodes (poorer sensing properties), insulation defects, sensing threshold too low.
Ineffective stimulation of the heart by the pacemaker impulse. ECG: pacemaker spike without subsequent QRS complex or without subsequent P wave. Cause: increased threshold, battery exhaustion, defective electrodes. Caution: risk of bradycardia or asystole.
Permanent pacemaker therapy in childhood is most frequently needed in children with AV block after surgery for a congenital heart defect or for a congenital complete AV block, which occurs mainly in the context of a maternal autoimmune disease in about 1 in 15,000 neonates. Up to 5% of all cardiac surgeries result in a postoperative complete AV block that persists in about half the cases. Typical operations with a risk for the occurrence of an AV block are interventions in the vicinity of the AV node in the cranial part of the ventricular septum (VSD closure, AV canal correction, aortic valve surgery, correction of Ebstein anomaly, etc.).
Sinus node dysfunction that develops in children and adolescents, especially in the long term after surgery in the atrium area (e.g., atrial baffle or Fontan operation), is another significant indication for permanent pacemaker therapy.
The detailed indications according to current guidelines are summarized in Table 18.5. The most important are:
Symptomatic congenital complete AV block
Complete AV block that persists longer than 7 to 14 days after cardiac surgery
Sinus node dysfunction with symptomatic bradycardia
Table 18.5 Indications for permanent pacemaker therapy in childhood (according to ACC, AHA, NASPE 2002 recommendations)
Class I (general agreement that pacemaker implantation is indicated)
Higher degree and complete AV block with symptomatic bradycardia, progressive ventricular enlargement, heart failure, or reduced cardiac output
Sinus node dysfunction with inadequate-for-age symptomatic bradycardia
High degree or complete AV block after cardiac surgery, considered irreversible or persisting at least 7 days
Congenital complete AV block with an escape rhythm with widened ventricular complexes, complex ventricular ectopy, or ventricular dysfunction
Congenital complete AV block in a neonate with a structurally normal heart and a ventricular rate of less than 50–55 bpm or in conjunction with a congenital heart defect and a ventricular rate of less than 70 bpm (averaged over 7 beats)
Persistent, bradycardia-induced ventricular tachycardia (with or without QT prolongation) with proven benefit of pacemaker therapy
Class IIa (conflicting opinions but tendency in favor of usefulness of pacemaker implantation)
Bradycardia–tachycardia syndrome with concomitant antiarrhythmic therapy except digoxin
Congenital complete AV block after age 1 year with an mean ventricular rate of less than 50 bpm or sudden asystole of more than two to three times the basic cycle duration or symptomatic chronotropic incompetence.
Long QT syndrome with 2:1 AV block or complete AV block
Asymptomatic sinus bradycardia in a child with a complex congenital heart defect and a ventricular rate of less than 35 bpm at rest or asystole of more than 3 s
Class IIb (conflicting opinions, less evidence of the efficacy of a pacemaker implantation)
Temporary complete postoperative AV block with restitution of sinus rhythm with residual bi-fascicular block
Congenital complete AV block in an asymptomatic neonate, child or adolescent with an acceptable ventricular rate, a narrow QRS complex, and normal left ventricular function
Asymptomatic sinus bradycardia in an adolescent with congenital heart disease and a ventricular rate at rest below 40 bpm or asystole of more than 3 s.
Neuromuscular disease with all grades of AV blocks (including 1st degree) with or without symptoms due to the incalculable risk of progression of functional impairment of the specific conduction tissue
Class III (general agreement that pacemaker implantation is not indicated)
Temporary postoperative complete AV block with restitution of sinus rhythm
Asymptomatic child with a postoperative bi-fascicular block with or without 1st degree AV block
Asymptomatic 2nd degree AV block type I (Wenckebach)
Asymptomatic sinus bradycardia in an adolescent with a minimum ventricular rate of about 40 bpm or asystole of less than 3 s.
Transvenous endocardial access
In the usual procedure, the electrodes are advanced into the right atrium or the right ventricle under fluoroscopic guidance via the subclavian or jugular vein. The electrodes are then anchored in the atrium or ventricle with a screw or anchor mechanism. The pacemaker generator unit is implanted under the pectoral muscle or subcutaneously below the clavicle.
The transvenous access is usually possible in children weighing more than 10 kg. It is not possible in patients after Fontan surgery in whom the atrium or the ventricle cannot be accessed transvenously.
Subxiphoid access and epimyocardial electrodes
In neonates or infants, epimyocardial electrodes are usually used that are placed directly on the atrium or ventricle. The pacemaker generator unit is then usually implanted in the preperitoneal region under the abdominal muscles.
Air embolism in transvenous implantation of the pacemaker
Infection of the pacemaker pocket or of the system
Vascular or myocardial perforation, pericardial effusion
Specific pacemaker complications
Probe dysfunction (dislocation, insulation failures, broken probe; in the ECG: exit block, undersensing, or oversensing)
Incorrect sensing of muscle potentials
Increased thresholds with stimulation loss (“exit block”), especially during the healing phase
Failure of the pacemaker unit or the battery
Phantom programming through external interference frequencies (e.g., MRI, defibrillator)
Venous thrombosis or vascular occlusion during the transvenous implantation
18.1.3 Special Pacemaker Applications
Temporary pacemakers are used mainly in children after cardiac surgery associated with an increased risk of an AV block or arrhythmia, where a benefit from pacemaker therapy (e.g., JET, sinus bradycardia) is expected. Epimyocardial electrodes are applied intraoperatively and are led outward through the skin. The stimulation comes from an external pacemaker generator unit. The electrodes can later be easily removed by simply pulling them out or possibly cutting them off just below the skin level.
Temporary pacemaker electrodes can also be advanced into the right atrium or right ventricle via a sheath through the femoral vein, the subclavian vein, or the internal jugular vein.
Supraventricular tachycardias including atrial flutter may possibly be terminated by overdrive stimulation (high atrial stimulation rate, e.g., 300–500 bpm). Transesophageal overdrive stimulation can also be carried out due to the close anatomical proximity of the left atrium and the esophagus.
In an emergency, external stimulation via large adhesive electrodes is possible. Most modern defibrillators provide this feature today. However, external stimulation is painful and should be performed only on unconscious or deeply sedated patients.
Temporary transesophageal pacemaker stimulation is also possible in emergencies using special electrodes that are advanced into the esophagus.
The programming and the first test of the pacemaker are performed in the operating room. The next checkup is performed a few days after surgery because of the initially rising threshold, then usually after 1 and 3 months. Biannual checkups are sufficient later. When battery exhaustion is imminent, checkups should be more frequent, of course.
At each pacemaker checkup, the programmed parameters are monitored telemetrically. This monitoring includes the intervention rate, electrical amplitude, and width. Threshold tests are also performed and, if necessary, the parameters are adjusted. In children and adolescents, the probe location is also regularly monitored (e.g., annually) by chest X-ray. A pacemaker ID card is issued to all pacemaker patients, containing information on the generator unit, the electrodes, and the current settings.
18.1.5 Behavior in Everyday Life
Most electronic devices are safe for pacemaker patients. Unproblematic devices include radios, televisions, computers, infrared remote controls, wireless headphones, microwaves, ceramic hobs, airbags, landline telephones including wireless devices, ultrasonic devices (due to possible thermal effects a distance of 10 cm from the implant should be maintained), and X-ray equipment.
Mobile phone users should keep a distance of not less than 15 to 20 cm between phone and pacemaker generator unit (hold the cell phone to the ear on the opposite side and never carry it in the breast pocket over the device). Anti-theft systems in department stores should be passed quickly. When using a drill, avoid holding it close to the chest. Using electrical welding equipment is risky and being in the vicinity of transformer stations is strictly prohibited.
The vicinity of very large loudspeakers (disco, concert) should be avoided due to the strong magnetic field. In addition, bass vibration can cause rate modulation.
MRI is contraindicated. If an MRI is urgently indicated, supervision by a physician experienced in dealing with pacemakers is absolutely necessary. There are MRI compatable defibrillators available now (1,5 tesla, not 3 tesla), these devices however make MRI investigation of the chest impossible due to significant artifacts. Pacemaker wearers should be encouraged to engage in physical activity unless contraindicated by a heart defect. Recreational sports are unproblematic. Contact sports and horseback riding are not recommended. Martial arts, gymnastics on the uneven bars, platform diving, and scuba diving are absolutely prohibited.
18.1.6 Antitachycardia Pacemakers and Implantable Cardioverter Defibrillators
Antitachycardia pacemakers can detect supraventricular and ventricular tachycardias and terminate them through overstimulation.
Implantable cardioverter defibrillators
Implantable cardioverter defibrillators (ICDs) are now available for children with malignant arrhythmias. The ICD can be implanted subpectorally like a pacemaker generator unit and the shock electrodes are inserted transvenously. These systems usually make it possible to terminate ventricular tachycardia through over-stimulation, cardioversion, or defibrillation. They also usually have the possibility of antibradycardia stimulation. The most common indications for implantation of an ICD in childhood are prior cardiac arrhythmias that necessitated resuscitation, ventricular tachycardia that cannot be controlled by other measures such as antiarrhythmic drugs or catheter ablation, cardiomyopathy, or long QT syndrome.
18.2 Sinus Arrhythmia
In a sinus arrhythmia there are phasic fluctuations in the heart rate. The electrical excitation originates in the sinus node, which is regulated by the autonomic nervous system. In childhood, a sinus arrhythmia is physiological. A loss of this heart rate variability in children is pathological and can be found in the context of neuropathy, for example.
In childhood, a sinus arrhythmia is physiological and diminishes with increasing age. The most common cause by far is respiratory arrhythmia.
In respiratory arrhythmia, there is an increase of the heart rate during inspiration and a decrease during expiration. The cause is probably an increased vagal tone during expiration.
18.2.2 Diagnostic Measures
A sinus arrhythmia is almost always asymptomatic. Palpitations occur very rarely.
Significant symptoms such as dizziness or syncopes cannot be explained by respiratory arrhythmia.
In the ECG, there are variations of the RR intervals and possibly discrete changes in the P wave morphology (Fig. 18.5). A phasic increase in heart rate during inspiration and a decrease during expiration are typical findings (mnemonic tip: Inspiration → Increase in heart rate).
Second degree sinoatrial (SA) block type II (Mobitz): In a 2nd degree SA block type II (Mobitz), there is an abrupt change of the PP intervals. The PP intervals in the SA block are a multiple of the normal PP intervals.
No further diagnostic procedures such as echocardiography, electrophysiology study, or laboratory tests are required for a sinus arrhythmia.
No treatment is necessary.
This condition is not pathological.
18.3 Sinus Bradycardia
Sinus bradycardia is present when the heart rate of a sinus rhythm falls below the normal level for the age for a prolonged period (indicative values: in neonates < 100 bpm, in older children < 80 bpm, in adolescents < 60 bpm).
Sinus bradycardia occurs frequently and can be considered physiological in many cases (e.g., physically fit athletes).
Physiological and pathological causes of a sinus bradycardia must be distinguished. Sinus bradycardia is physiological in physically fit older children and adolescents (high vagal tone) and during sleep.
Vasovagal reactions (vasovagal syncopes, severe anxiety/fright reactions)
Premature birth (typical apnea and bradycardia syndrome in premature infants)
Hypoxia (e.g., hypoxic neonates)
Increased intracranial pressure
Mechanical vagus nerve stimulation (Valsalva maneuver, bulbar pressure)
Drugs (e.g., beta blockers, digoxin, antidepressants)
Sinus node dysfunction
Sinus bradycardia is caused by slowed impulse formation in the sinus node.
18.3.2 Diagnostic Measures
Sinus bradycardia is usually asymptomatic. Dizziness, palpitations, or syncope occur rarely. If, in severe cases, the heart rate is no longer sufficient to produce adequate cardiac output, symptoms of heart failure may develop. In pathological bradycardia, the heart rate does not increase sufficiently during exercise.
There is a regular sinus rhythm (each QRS complex is preceded by a P wave, P wave vector between 0 and 90°). The P waves are often flattened (especially visible in lead II, sometimes even negative in lead III). The PQ interval is often prolonged, but usually returns to normal under stress. If vagal tone is high, the T waves, especially in the precordial leads, are often pointed and high (over two-thirds of the amplitude of the QRS complex).
If the sinus rhythm is slow, escape systoles may be detected. In such cases, a secondary center kicks in to replace the pacemaker function of the slow sinus node. Typical junctional escape systoles that arise in the area of the AV node have narrow QRS complexes. The P wave is usually hidden in the QRS complex or is found shortly before or after the complex. If the rate of the escape mechanism is higher than that of the sinus node for a longer period, AV dissociation occurs, that is, the atria and ventricles beat independently of one another. In this case the atrial rate is slightly lower than the ventricular rate.
A 24-hour Holter ECG is sometimes indicated for documenting bradycardia episodes and the correlating them with the symptoms.
In physiological bradycardia, there is an adequate increase of the heart rate under stress, whereas in pathological bradycardia, no increase occurs.
Laboratory tests are only occasionally indicated—for example, if electrolyte disorders, hypothyroidism, jaundice, or drug intoxication are suspected.
Echocardiography may be useful for assessing cardiac function.
The following differential diagnoses are possible:
1st degree SA block (cannot be diagnosed in the surface ECG)
2nd degree SA block type II (Mobitz) with regular conduction
2nd degree AV block type II (Mobitz) with regular conduction: In a 2nd degree AV block, some P waves are not followed by QRS complexes, whereas in sinus bradycardia, each P wave is followed by a QRS complex.
Asymptomatic patients do not require treatment. If there is secondary sinus bradycardia, the underlying cause should be treated first. Intravenous tropine, orciprenaline, isoprenaline, or epinephrine is used for the acute treatment of symptomatic patients. Rarely, a temporary external or internal pacemaker may be needed.
Symptomatic patients are treated with a pacemaker (e.g., AAI or AAI-R system) after a treatable cause is ruled out. In general, these are patients where sinus bradycardia develops in the context of a sinus node dysfunction.
In most cases, sinus bradycardia has no pathological significance. Secondary sinus bradycardia can usually be successfully treated by targeting the underlying cause. The treatment itself is often more difficult if the bradycardia is related to sinus node dysfunction.
18.4 Sinus Tachycardia
In sinus tachycardia, the heart rate is above the normal level for the age for a prolonged period (indicative values: > 180 bpm in neonates and infants, > 160 bpm in toddlers, > 140 bpm in older children). The site of the impulse formation is the SA node, that is, the vector of the P wave is between 0 and 90°. The rate of sinus tachycardia is almost never over 230 bpm.
Sinus tachycardia is usually physiological, brought on by physical or emotional stress. Pathological causes are rare, but must be ruled out if tachycardia persists.
Physiological causes are physical and emotional stress.
Cor pulmonale (e.g., pulmonary embolism)
Orthostatic circulatory regulation disorders, postural orthostatic tachycardia syndrome (POTS)
Drugs (e.g., beta-sympathomimetic drugs, anticholinergic drugs, catecholamines)
Stimulants (e.g., nicotine, caffeine)
The sinus node is stimulated to more rapid depolarization by the autonomic nervous system. The increase in the heart rate sometimes serves as a compensatory mechanism to increase cardiac output (e.g., during exercise or in the context of heart failure).
18.4.2 Diagnostic Measures
Sinus tachycardia is usually asymptomatic and is well tolerated. Some patients complain of palpitations.
The heart rate is higher than normal for the age. Each QRS complex is preceded by a P wave. The vector of the P wave is between 0 and 90°. There are usually high and pointed P waves in leads II, III, and aVF. The PQ interval is shortened. The ST segment may start below the zero line and ascend. The T waves are frequently flattened. Sometimes the T and P waves merge. Unlike re-entrant tachycardia, which begins and ends abruptly, in sinus tachycardia the heart rate increases continuously and decreases gradually.
Sinus node re-entrant tachycardia: The cause of the tachycardia is a re-entrant mechanism in the sinus node or in close proximity to the sinus node. Start and end are abrupt. The heart rate is usually between 150 and 250 bpm.
AV re-entrant tachycardia with or without accessory pathway (AVRT, AVNRT): Abrupt start and end. In AV re-entrant tachycardia, the P waves are hidden in the QRS complex or located immediately after the QRS complex. The P wave is negative in leads II, III, and aVF. The heart rate is usually higher than in sinus tachycardia.
Permanent junctional reciprocating tachycardia (PJRT): Negative P waves in leads II, III, and aVF are typical for PJRT. The P wave follows the QRS complex at a relatively great distance.
Ectopic atrial tachycardia (EAT): In an EAT, the P wave vector is different from the sinus rhythm vector. If the ectopic focus is near the sinus node, the differential diagnosis can be difficult and may require an electrophysiology study.
Chaotic atrial tachycardia (CAT): This form of supraventricular tachycardia is also referred to as a multifocal atrial tachycardia (MAT). Here, many different atrial foci are found as the origin of the electrical excitation. Correspondingly, there are different P wave morphologies and different P wave vectors in the ECG.
Laboratory tests are rarely required. In individual cases, the following tests are useful: serum electrolytes including K, Mg, Ca, possibly CK/CK-MB, troponin I, drug levels, TSH.
Echocardiography is required in isolated cases. It can be used to rule out or detect congenital heart defects and assess cardiac function.
An electrophysiology study is only rarely indicated to narrow down the differential diagnoses such as ectopic atrial tachycardia or sinus nodal re-entrant tachycardia with the option of ablation treatment.
Usually the underlying cause is treated. In some cases, treatment with a beta blocker may be useful.
Most sinus tachycardias are physiological reactions that have no pathological significance. Otherwise, the prognosis depends on the underlying disease.
18.5 Sinus Node Dysfunction
Synonyms: sick sinus syndrome (SSS), tachycardia–bradycardia syndrome
In sinus node dysfunction, the sinus node as the dominant pacemaker of the heart is dysfunctional. Furthermore, regulation of the sinus node by the autonomic nervous system is disrupted and sinoatrial conduction is impaired. This can cause various atrial arrhythmias such as sinus bradycardia, sinoatrial blocks, and atrial fibrillation at the same time. The occurrence of atrial tachycardia and subsequent bradycardia, until a secondary center kicks in with an escape rhythm is reflected in the term “tachycardia–bradycardia syndrome.”
Sinus node dysfunction is often associated with AV conduction disturbances. This is termed a binodal lesion.
In childhood, sinus node dysfunction develops primarily after atrial surgery, especially after an atrial baffle procedure, Fontan procedure, correction of an anomalous pulmonary venous connection, or rarely even after the closure of an atrial septal defect (especially in superior sinus venosus defects). In a structurally unremarkable heart, sinus node dysfunction is very rare.
Operations and procedures in the atrium (atrial baffle procedure, Fontan operation, ASD closure, correction of an anomalous pulmonary venous connection or superior sinus venosus defect)
Inflammatory heart disease (myocarditis)
Myocardial ischemia (coronary anomalies, Kawasaki disease)
Drugs (digoxin, beta blockers, calcium channel blockers, amiodarone)
Hypothyroidism, hypothermia (temporary sinus node dysfunction)
In adults, especially in coronary or hypertensive heart disease
Sinus node dysfunction usually develops as a result of direct or indirect injury or scarring of the sinus node, atrial wall, intranodal or intra-atrial conduction pathways, or the supplying coronary arteries.
18.5.2 Diagnostic Measures
Bradycardia may cause dizziness, syncopes, and symptoms of heart failure. Tachycardia may sometimes cause palpitations, dyspnea, and chest pain. Atrial fibrillation increases the risk of arterial embolism.
Various atrial arrhythmias are found concomitantly or alternately in the ECG. Typical findings are:
Pronounced sinus arrhythmia
Slow escape rhythm (ectopic atrial rhythm, junctional escape rhythm, ventricular escape rhythm)
Bradycardia–tachycardia syndrome (bradycardia alternating with atrial tachycardia, usually in the form of atrial fibrillation or flutter)
In the ECG, special attention should be given to the occurrence of AV blocks (binodal lesion).
The 24-hour Holter ECG is used to document the different arrhythmias that occur concomitantly or alternately and to clarify whether the arrhythmias correlate with symptoms. In this way, the Holter ECG is useful for making a decision whether a pacemaker is required.
In sinus node dysfunction, there is chronotropic incompetence, that is, the increase in the heart rate in the stress ECG is not adequate. The reaction of the sinus node to stimulation by the autonomic nervous system remains insufficient.
In some cases, an electrophysiology study may be useful, for example, when clinical symptoms suggest significant bradycardia that was not documented in the (24-hour Holter) ECG.
A typical finding of sinus node dysfunction is a prolonged sinus node recovery time, namely the time until the sinus rhythm is resumed after previous high-frequency atrial stimulation is prolonged. The SA conduction time can also be determined in the examination.
Useful laboratory tests are serum electrolytes including K, Mg, Ca, and CK/CK-MB, troponin I, drug levels (e.g., digoxin, amiodarone), and TSH on a case-by-case basis.
Echocardiography is used to rule out or detect congenital heart defects and to assess cardiac function. After surgery such as an atrial baffle procedure or Fontan procedure, echocardiography is performed for postoperative followup.
Asymptomatic patients usually do not require treatment.
In patients whose main symptom is bradycardia, medication that reinforces sinus bradycardia (e.g., beta blockers) should be discontinued if tenable.
Patients with severe bradycardia and corresponding symptoms are treated with a permanent pacemaker. The choice of a pacemaker system depends on whether additional chronotropic incompetence or AV conduction disturbances are present and how often tachycardia episodes occur. Often, a DDD mode is selected, because an AV block often develops in patients with sinus node dysfunction and after Fontan or atrial baffle procedures. A frequency-adaptive system that allows for an increase in the heart rate during exercise (“rate-response” function) should also be selected for patients with chronotropic incompetence. Patients with frequent atrial tachycardias can be fitted with a special system with an atrial antitachycardia function that recognizes and attempts to terminate atrial tachycardia by atrial overstimulation.
Patients with tachycardia may require additional antiarrhythmic treatment. Class III antiarrhythmic drugs (sotalol, amiodarone) are usually used; a combination of amiodarone with a beta blocker may be required. Pharmacological lowering of the basic heart rate may require the implantation of a pacemaker for antibradycardia therapy.
The acute treatment of severe bradycardia is intravenous atropine, orciprenaline, isoprenaline, or epinephrine or implantation of a temporary external or transvenous pacemaker.
The prognosis is good for symptomatic patients who have been treated with an appropriate pacemaker system and have good ventricular function. But the prognosis is worse for patients with impaired ventricular function. This applies to quite a few patients after an atrial baffle or Fontan procedure.
18.6 AV Junctional Escape Rhythm
Synonyms: AV escape rhythm, atrioventricular nodal rhythm
If the sinus node fails to function as a pacemaker or there is a higher-grade conduction disturbance between the sinus node and atrium, the AV nodal region can assume the pacemaker function. The heart rate of the AV junctional escape rhythm is usually about two-thirds to three-quarters of the normal age-appropriate heart rate. If there is only one single heart action, it is called AV escape systole.
In sinus bradycardia (e.g., during sleep or in physically fit individuals), a junctional escape rhythm occurs physiologically, even in persons with a healthy heart.
In the following situations, the AV region can assume the pacemaker function:
Sinus bradycardia of various causes (good physical condition, high vagal tone, but also increased intracranial pressure, hypothermia)
Sinus node dysfunction (e.g., postoperatively, especially after operations in the atrium)
Drug intoxication (e.g., digoxin)
18.6.2 Diagnostic Measures
The patients are usually asymptomatic; symptoms of bradycardia such as dizziness or palpitations are rare.
Since the origin of the AV junctional escape rhythm is in the region of the AV node or the bundle of His, atrium excitation is retrograde. The P waves are therefore negative in leads II, III, and aVF. The P wave may precede or follow the QRS complex. Often, the P waves are also “hidden” in the QRS complex and are not visible in the surface ECG. The former classification of upper, middle and lower AV escape rhythm depending on the position of the P wave before, in, or after the QRS complex is incorrect from an electrophysiological standpoint.
Since the excitation of the ventricles originates from a center above the bifurcation of the bundle of His, the QRS complexes are narrow. Unlike supraventricular extrasystoles, which come earlier than the expected sinus beat, the AV escape beats follow the QRS complex later than expected.
An additional typical finding of AV junctional escape rhythm is AV dissociation—that is, atria and ventricles beat independently. The atrial rate and the frequency of the AV escape rhythm are approximately equal, so that the P waves of the sinus rhythm oscillate around the QRS complexes of the AV escape rhythm (Fig. 18.6).
An echo beat (re-entrant systole) may also develop: An AV junctional escape beat is transmitted to the ventricles simultaneously with retrograde excitation of the atrium. The ECG has a negative P wave following the QRS complex. In the atrium, the excitation changes direction and runs through the AV node toward the ventricle. If the ventricle is no longer refractory, a second ventricular systole develops. There is thus a negative P wave in the ECG surrounded by two QRS complexes.
A 24-hour Holter ECG is indicated to document the bradycardia episodes and correlate them with symptoms.
In physiological bradycardia, there is an adequate increase of the heart rate under physical exertion. In these cases, the sinus node again takes over the pacemaker function. In some pathological causes (e.g., sinus node dysfunction), the heart rate does not increase.
Laboratory tests are indicated only occasionally, such as in cases of suspected electrolyte disorders, hypothyroidism, or drug intoxication.
Echocardiography is sometimes useful for assessing cardiac function or investigating the causes of bradycardia.
In AV escape beats, supraventricular extrasystoles should be distinguished in the differential diagnosis. Unlike AV escape beats, the supraventricular extrasystoles come earlier than expected after the preceding sinus beat.
The same principles apply to treatment as for sinus bradycardia. Asymptomatic patients do not require treatment. In secondary sinus bradycardia, the underlying cause is treated first.
For the acute treatment of sinus bradycardia, intravenous atropine, orciprenaline, isoprenaline, or epinephrine is administered in symptomatic patients. A temporary pacemaker may also be necessary.
After ruling out a treatable cause, symptomatic patients are treated with a permanent pacemaker (e.g., AAI or AAI-R system).
The prognosis depends on the underlying disease. If an underlying disease is ruled out, an AV junctional escape rhythm is not pathological in asymptomatic patients.
18.7 Wandering Pacemaker
A wandering pacemaker is said to exist when a secondary center in the atrium takes over the pacemaker function if there is a slow sinus node rate. In addition to the shape of the P wave, the PQ interval also changes between beats. These changes are explained by the fact that the pacemaker center “wanders” in the atrium.
A wandering pacemaker is relatively rare.
A wandering pacemaker occurs mainly in connection with sinus bradycardia and is observed with high vagal tone. A wandering pacemaker very rarely develops with sinus node dysfunction.
18.7.2 Diagnostic Measures
Patients are usually asymptomatic. Symptoms of bradycardia such as dizziness and palpitations are rare.
Different morphologies of the P waves can be noted in the ECG. For example, there is an increasing flattening of the P waves. In addition, the PQ interval changes (usually shortened). The rate remains approximately the same.
A 24-hour Holter ECG is occasionally indicated to document the bradycardia episodes and correlate them with the symptoms.
Treatment is usually not indicated. Symptomatic bradycardia or sinus node dysfunction should be treated.
A wandering pacemaker is usually a benign rhythm disorder with no pathological significance in adolescents with increased vagal tone.
18.8 Accelerated Idioventricular Rhythm
In accelerated idioventricular rhythm, an ectopic automaticity center in the ventricular myocardium takes over the pacemaker function instead of the sinus rhythm. The heart rate is only slightly higher than the rate of the sinus rhythm.
The disease is rare in childhood and adolescence.
In children and adolescents, usually no underlying structural or organic disease can be detected. In adults, this arrhythmia often occurs after successful thrombolysis in the reperfusion phase after myocardial infarction. Rare causes include myocarditis or drug intoxication (e.g., digoxin).
The pathogenesis is not fully understood. It is assumed that it is caused by an abnormal automaticity in the ventricular myocardium.
18.8.2 Diagnostic Measures
Those affected are usually asymptomatic; they rarely have palpitations.
The ECG typically has bundle branch block–like widened ventricular complexes that have approximately the rate of the sinus rhythm. The ECG pattern shows the typical findings of a ventricular tachycardia, but the rate is much lower. There is AV dissociation or retrograde conduction from the ventricles into the atria (negative P waves after the QRS complexes).
Due to the similar rate, the sinus rhythm and accelerated idioventricular rhythm compete with each other, so that there is frequently a switch between the two rhythms. Fusion beats sometimes occur during the transition between the rhythms.
A 24-hour Holter ECG can detect which segments are marked by an accelerated idioventricular rhythm and which by a sinus rhythm. Ventricular extrasystoles can often be detected that have the same morphology as the beats of the idioventricular rhythm. Physical or emotional stress and an increase in heart rate can suppress the idioventricular rhythm.
The idioventricular rhythm is typically replaced by a sinus rhythm under exertion.
Laboratory tests are usually not necessary. Sometimes they are indicated to rule out drug intoxication (e.g., digoxin.)
Echocardiography may possibly be indicated to rule out (rare) structural or functional heart disease.
The following differential diagnoses must be ruled out:
Ventricular tachycardia: In ventricular tachycardia, the rate is much higher than in accelerated idioventricular rhythm, which usually has nearly the same rate as the sinus rhythm.
Third degree AV block with a ventricular escape rhythm: The rate in these cases is much slower than the sinus rhythm. The P waves in 3rd degree AV block have no regular relationship to the QRS complex.
Ventricular escape rhythm with sinus arrest: In these cases, the rate is significantly slower than the sinus rhythm.
No treatment is usually necessary. In rare cases where there is an organic or structural disease, this cause should be treated.
In most children and adolescents, the idioventricular rhythm subsides over time (but sometimes after years).
18.9 Supraventricular Extrasystoles
Supraventricular extrasystole(s) (SVES) is defined as an extrasystole with an origin above the bundle of His.
SVES are very common and occur mostly in individuals with healthy hearts.
In most cases, SVES are idiopathic in individuals with healthy hearts and have no pathological significance. SVES can also occur in the following disorders:
Acquired heart disease (e.g., myocarditis, coronary artery disease)
Congenital heart defects with atrial overload
After atrial surgery (e.g., after Mustard or Senning atrial baffle procedures, Fontan procedure)
Electrolyte imbalances (especially hypokalemia, hypomagnesemia, hypercalcemia)
Drugs (e.g., antiarrhythmic drugs [proarrhythmogenic effect], digoxin, sympathomimetics)
Stimulants/drugs: cocaine, caffeine, nicotine, alcohol