I. The status and confusion of pharmacological treatment of arrhythmias Although current pharmacological treatment cannot cure arrhythmias and does not significantly reduce the overall mortality rate of patients, in the acute phase of arrhythmias, especially for tachyarrhythmias, the first step is to terminate the attack and relieve the symptoms before subsequent device therapy can be administered, and the rapid effectiveness of pharmacological treatment is crucial at this time. Amiodarone by slow intravenous infusion is the “ace” of tachyarrhythmia pharmacotherapy and is strongly recommended by various guidelines. However, there is no substitute for the role of medication in rhythm reversal and recurrence prevention, and the high benefit and simplicity of pharmacological treatment should be given sufficient clinical attention. For the treatment of tachyarrhythmia with organic heart disease, cardiac insufficiency, acute coronary syndrome and rapid ventricular rate atrial fibrillation, amiodarone is preferred by the guidelines, which is effective and safe. The onset and progression of arrhythmias are influenced by a variety of factors. Pharmacological treatment needs to be considered comprehensively in the context of the patient’s underlying disease to develop the best individualized treatment plan. However, due to the different experiences and strategies of different domestic and foreign experts in the use of arrhythmia drugs, the problem of over-specification of drugs is serious, which leads to confusion among clinicians about the standardized use of arrhythmia drugs. The main points and principles of antiarrhythmic drug application The treatment process of acute and chronic arrhythmias is different, and the principles and points of treatment are also significantly different. First, for acute arrhythmias, the hemodynamic status should be considered. If the arrhythmia has caused severe hemodynamic disturbance, the guidelines strongly recommend electrical resuscitation to urgently terminate the hemodynamically unstable arrhythmia, and at this time, the diagnosis and differential diagnosis are not demanding; for patients with stable hemodynamics, drugs can be used. Second, the management of acute arrhythmias should balance the relationship between underlying cardiovascular disease and arrhythmia treatment, and the combination of organic heart disease (especially myocardial ischemia and cardiac insufficiency) is a consideration that should not be overlooked. 2013 Expert Consensus on the Emergency Management of Arrhythmias recommends that antiarrhythmic drugs should be selected based on underlying disease, cardiac functional status, and the nature of the arrhythmia. When the efficacy of an intravenous drug is unsatisfactory, the first step is to review whether the medication is standardized and whether the dose is up to standard. It is generally not recommended to replace or combine another intravenous antiarrhythmic drug within a short period of time, and it is advisable to consider non-pharmacological methods, such as electrical resuscitation or esophageal atrial pacing. Sequential or combined intravenous medications are prone to adverse drug reactions and proarrhythmic effects; therefore, they should be considered only when ventricular tachycardia, ventricular fibrillation storms persist or other intractable arrhythmias are present for management. The main goal of chronic arrhythmia treatment is to prevent the recurrence of atrial fibrillation, ventricular tachycardia, and ventricular fibrillation. Depending on the nature of the patient’s disease, the underlying disease status, and individual differences in response to treatment, individualized treatment should be emphasized within the framework of guideline recommendations. For patients on long-term drug therapy, in addition to the arrhythmia treatment effect, attention should be paid to the safety of drugs and regular follow-up, so as to avoid unnecessary discontinuation and timely detection of adverse reactions. Amiodarone has been used clinically for 45 years, the first 15 years as a treatment for angina pectoris in coronary heart disease. 1985, Amiodarone changed its status to an antiarrhythmic drug. Its 30 years of clinical application as an antiarrhythmic drug has been a mainstay in the treatment of cardiac arrhythmias. There are many points in the standardized application of this drug, and ten points are briefly described. （In the past 20 years, all arrhythmia-related guidelines have strongly recommended the use of amiodarone, making it widely used in the treatment of various tachyarrhythmias (supraventricular and ventricular). In Europe and the United States, its application accounts for 1/3 of the total prescription of antiarrhythmic drugs and about 70% in Latin American countries, while in China it accounts for only 15%. This suggests that the application of amiodarone in China is not popular, or the range of medication is too narrow, or the applied dose is not sufficient. Except for a few contraindications, amiodarone can be applied in almost all tachyarrhythmias of supraventricular and ventricular origin. In some cases, amiodarone is recommended in Class I and in some cases in Class II, not because it is less effective, but because these arrhythmias are relatively “mild” and amiodarone is used when other drugs are not effective. The few conditions in which amiodarone is contraindicated include bradycardia (sinus disease, severe atrioventricular block), prolonged QT interval, thyroid dysfunction, and significant liver function abnormalities. Caution or relative contraindication during pregnancy and lactation. (2) Long time to reach steady state and half-life in vivo The effective volume of amiodarone distribution in vivo reaches 5000L, while the average blood volume in vivo is 4-6L, so its distribution volume outside the blood vessels is large and its concentration is high. Amiodarone is a highly fat-soluble drug with high fat and protein binding rate, which determines the application characteristics of amiodarone: 1. long time to reach steady-state blood concentration, about 2-4 weeks or longer when taken orally; 2. long clearance half-life, one half-life is about 2 months after stopping the drug; 3. administration should pay attention to individualization, obese people have large lipid pool, high body weight people have large fat and protein content, and the saturation amount is also increased. (3) Calculation of the total amount of medication when mixing oral and intravenous administration Many tachyarrhythmias are accompanied by hemodynamic instability and require the application of intravenous amiodarone, which often requires subsequent oral amiodarone maintenance after the onset of effect, such as tachyarrhythmias and atrial fibrillation with rapid ventricular rate. At this point, the physician is faced with the calculation of the total amount of medication. The bioavailability of oral amiodarone is 50%, which means that after oral administration, during the absorption into the bloodstream through the gastrointestinal tract, a larger proportion is metabolized and excreted through the hepatic and intestinal circulation, and the intravenous dose is equivalent to twice the oral dose. Therefore, the total amount of drug in the body is equal to: oral amount + intravenous amount × 2. (iv) The saturation amount of amiodarone (loading amount) For many years, the relevant guidelines have been recommending that amiodarone should be given in the treatment of atrial fibrillation before reaching the saturation amount, which is the amount of drug required to reach the steady-state blood concentration in the body. Amiodarone is used to treat atrial fibrillation by giving a loading dose of 10 g followed by a maintenance dose. In contrast, 15 g of amiodarone is required to achieve a steady-state blood level in the body. This shows that the guideline recommended loading dose already leaves a margin of safety. The loading dose of oral amiodarone is usually 3-4 tablets/day, and the maintenance dose will be given after reaching 10g. (v) More suitable for arrhythmias associated with heart failure The incidence of clinical heart failure has been increasing year by year, and heart failure is an important cause of arrhythmias, so heart failure combined with arrhythmias is common in clinical practice. Since all antiarrhythmic drugs have negative inotropic effects, there are concerns about deterioration of cardiac function with general antiarrhythmic drugs for the treatment of heart failure with arrhythmias. Therefore, all guidelines recommend treatment with amiodarone or digoxin. The direct pharmacological effects of amiodarone are inhibition of β-receptors and blockade of Ca2+ inward flow, which in turn inhibits myocardial contractility, but amiodarone increases cardiac output in 98% of patients with heart failure. This is due to its ability to dilate peripheral arteries, reduce peripheral vascular resistance, and decrease cardiac load. It also inhibits beta receptors, which have the effect of slowing heart rate and reducing oxygen consumption. Thus, the net effect of the drug is to increase cardiac output in patients with heart failure. (vi) More suitable for arrhythmias associated with coronary artery disease Similar to heart failure, patients with various types of coronary artery disease have a high incidence of combined arrhythmias. Amiodarone has a dual effect of increasing myocardial oxygen supply and reducing cardiac load and oxygen consumption in such patients, therefore, this type of arrhythmia is also a strong indication for the application of amiodarone, which was mainly used for anti-anginal treatment when it was marketed in France in 1968, and it has obvious tube dilation and coronary dilation effects. Therefore, amiodarone is more suitable for the treatment of unstable myocardial ischemia such as acute coronary syndrome and arrhythmias associated with chronic stable myocardial ischemia, which can kill two birds with one stone and treat both myocardial ischemia and arrhythmias. (vii) Application during cardiac electrical storm In the expert consensus on ventricular arrhythmias issued in 2014, electrical storm is defined as a rapid ventricular arrhythmia requiring urgent treatment with three or more spontaneous episodes within 24 hours. Amiodarone has a broad electrophysiological effect and is a multiple ion channel blocker; therefore, the guideline category I recommends the application of intravenous amiodarone in cases of electrical storms. In addition, the pronounced beta-receptor inhibition during intravenous administration of amiodarone has a therapeutic effect on the sympathetic hyperactivation and excitation associated with this condition in vivo. In addition, amiodarone has a beneficial effect on the treatment of “intractable ventricular fibrillation”. The application of intravenous amiodarone in persistent ventricular fibrillation differs from plain in two ways: 1. The dose is large, 300 mg at a time; 2. (viii) Proper management of arrhythmia “rebound” phenomenon The phenomenon of rebound refers to the re-emergence of arrhythmia after long-term amiodarone administration with stable efficacy. The 2014 guidelines recommend an oral maintenance dose of 200 mg/day after conversion to sinus rhythm, and a maintenance dose of 100 mg/day for paroxysmal atrial fibrillation to maintain sinus rhythm. However, for some patients, this maintenance dose may be insufficient. Initially, amiodarone can maintain the blood concentration in 5 half-lives; after a long time, when the effective blood concentration decreases to maintain the efficacy, the arrhythmia will “rebound”. At this time, the physician should “calm” treatment, appropriate to give another “loading dose” or “half loading dose”, after taking a certain period of time and then give maintenance dose. (ix) Do not be overly afraid of extra-cardiac side effects Amiodarone tablets contain more iodine, so they can produce certain extra-cardiac side effects, especially thyroid dysfunction, which can cause hypothyroidism or hyperthyroidism, with a higher incidence of hypothyroidism. However, thyroid dysfunction is associated with high age (>65 years), long duration of medication (>4 months) and a history of thyroid disease or family history. The pathogenesis is: the high amount of iodine contained affects the metabolism of thyroxine; its chemical structure is similar to thyroxine and can interfere with its function. There are four degrees of thyroid dysfunction: 1. mild abnormalities in thyroid function without symptoms, no need to stop medication; 2. abnormal thyroid function with symptoms, appropriate medication reduction; 3. significant abnormalities in thyroid function with significant symptoms, stop medication; 4. severe abnormalities in symptoms and thyroid function, alternative treatment, thyroxine tablets for hypothyroidism, methionine for hyperthyroidism, etc. Therefore, different measures need to be given in the face of different clinical situations. If the patient has a high degree of amiodarone dependence, substitution therapy can be given along with amiodarone. (x) Moderate follow-up visits During amiodarone administration, follow-up visits are very important. However, excessive concern about side effects should be avoided, and serious side effects should be avoided if the interval between follow-up visits is too long. The guidelines recommend follow-up visits every 3 months during the first year of treatment and every 6 months during the second year of treatment. During the follow-up visits, attention should be paid to the medical history, physical examination, laboratory tests such as liver function, hyperthyroidism, lung function, electrolytes, and review of ECG and chest X-ray. In conclusion, amiodarone is broad-spectrum, highly effective and relatively safe in the treatment of arrhythmias.