Antidysrhythmic Drugs Research Articles

Safety and Effectiveness of Antidysrhythmic Drugs for Pharmacologic Cardioversion of Recent-Onset Atrial Fibrillation: a Systematic Review and Bayesian Network Meta-analysis.

The available evidence to determine which antidysrhythmic drug is superior for pharmacologic cardioversion of recent-onset (onset within 48h) atrial fibrillation (AF) is uncertain. We aimed to identify the safest and most effective agent for pharmacologic cardioversion of recent-onset AF in the emergency department. We searched MEDLINE, Embase, and Web of Science from inception to February 21, 2023 (PROSPERO: CRD42018083781). Eligible studies were randomized controlled trials that enrolled adult participants with AF ≤ 48h, compared a guideline-recommended antidysrhythmic drug with another antidysrhythmic drug or a different formulation of the same drug or placebo and reported specific adverse events. The primary outcome was immediate, serious adverse event - cardiac arrest, sustained ventricular tachydysrhythmia, atrial flutter 1:1 atrioventricular conduction, hypotension, and bradycardia. Additional analyses included the outcomes of conversion to sinus rhythm within 4h and 24h. We extracted data according to PRISMA-NMA and appraised trials using Cochrane RoB 2. We performed Bayesian network meta-analysis (NMA) using a Markov Chain Monte Carlo method with random-effect model and vague prior distribution to calculate odds ratios with 95% credible intervals. We assessed confidence using CINeMA. We used surface under the cumulative ranking curve (SUCRA) to rank agent(s). The systematic review initially identified 5545 studies. Twenty-five studies met eligibility criteria, and 22 studies (n = 3082) provided data for NMA, which demonstrated that vernakalant (SUCRA = 70.9%) is most likely to be safest. Additional effectiveness NMA demonstrated that flecainide (SUCRA = 89.0%) is most likely to be superior for conversion within 4h (27 studies; n = 2681), and ranolazine-amiodarone IV (SUCRA 93.7%) is most likely to be superior for conversion within 24h (24 studies; n = 3213). Confidence in the NMA estimates is variable and limited mostly by within-study bias and imprecision. Among guideline-recommended antidysrhythmic drugs, the combination of digoxin IV and amiodarone IV is definitely among the least safe for cardioversion of recent onset AF; flecainide, vernakalant, ibutilide, propafenone, and amiodarone IV are definitely among the most effective for cardioversion within 4h; flecainide is definitely among the most effective for cardioversion within 24h. Further, randomized controlled trials with predetermined and strictly defined, hemodynamic adverse event outcomes are recommended.

Metabolic Activation and Cytotoxicity of Propafenone Mediated by CYP2D6.

Propafenone (PPF) is a class IC antidysrhythmic drug, which is commonly used for the treatment of atrial fibrillation and other supraventricular arrhythmias. It is also a β-adrenoceptor antagonist that can cause bradycardia and bronchospasm. Hepatotoxicity is one of the adverse reactions reported, with clinical manifestations including acute cholestasis and hepatocyte necrosis. However, the mechanism of PPF-induced hepatotoxicity remains unclear. The present study was conducted to identify reactive metabolite(s) to determine related metabolic pathways and define the possible association of the bioactivation with PPF cytotoxicity. An O-demethylation phase I metabolite (M1), a further position C5 hydroxylation (para-position of the benzene ring) metabolite (M2), glutathione (GSH) conjugates (M3 and M4), and N-acetylcysteine (NAC) conjugates (M5 and M6) were detected in rat liver microsomal incubations containing PPF and GSH or NAC as trapping agents. The corresponding GSH conjugates and NAC conjugates were found in the bile and urine of rats after PPF administration, respectively. The observed GSH and NAC conjugates indicate that a quinone metabolite was generated in vitro and in vivo. Recombinant P450 enzyme incubations showed that CYP2D6 was the principal enzyme catalyzing this metabolic activation. Quinidine, a selective inhibitor of CYP2D6, attenuated the susceptibility of hepatocytes to the cytotoxicity of PPF. The results suggest that PPF was metabolized to a p-quinone intermediate which may be involved in PPF-induced hepatotoxicity.

Some aspects of pharmacological support with antidysrhythmic drugs

A high level of morbidity and mortality from cardiovascular diseases remains prevalent in the Russian Federation, despite a decreasing trend that emerged in recent years. Rhythm and conduction disorders play an essential role in the thanatogenesis of cardiovascular pathology, which determines the medical and social significance of their pharmacotherapy. This is indicated by the stable demand for antidysrhythmic drugs from both the state and the population. This is evidenced by high levels of public procurements and retail sales of drugs for the treatment of cardiovascular diseases, since patients take this drug group for a long time and often permanently. Our marketing analysis of the antidysrhythmic drugs market used current open data from the State Register of Medicines and the State Register of Maximum Selling Prices and available analytical data. It showed that from 54.5% (metoprolol drugs) to 100% (procainamide drugs) of the market share is occupied by generic drugs made in Russia. The presented analysis confirms the assumption of a significant increase in the share of generic drugs in public procurements. This is associated with the implementation of the drug safety program for vital and essential drugs and the optimization of costs by the state. A priority of the state drug policy in Russia is to monitor the effectiveness and safety throughout its entire life cycle. Moreover, particular importance should be given to the issue of interchangeability, which is regulated by Federal Law No. 1360 dated September 5, 2020, On the Procedure for Determining the Interchangeability of Medicines for Medical Use. The annual increase in the share of generic domestic antidysrhythmic drugs on the market poses the problem of selecting the most efficient and safe approach to pharmacotherapy for practicing specialists. The solution may be to develop and implement open automated information systems for the safety profiles of the original and generic antidysrhythmic drugs.

Pharmacologic cardioversion of recent-onset atrial fibrillation: a systematic review and network meta-analysis.

We sought to identify the most effective antidysrhythmic drug for pharmacologic cardioversion of recent-onset atrial fibrillation (AF). We searched MEDLINE, Embase, and Web of Science from inception to March 2019, limited to human subjects and English language. We also searched for unpublished data. We limited studies to randomized controlled trials that enrolled adult patients with AF ≤ 48 h and compared antidysrhythmic agents, placebo, or control. We determined these outcomes prior to data extraction: (i) rate of conversion to sinus rhythm within 24 h, (ii) time to cardioversion to sinus rhythm, (iii) rate of significant adverse events, and (iv) rate of thromboembolism within 30 days. We extracted data according to PRISMA-NMA and appraised selected trials using the Cochrane review handbook. The systematic review initially identified 640 studies; 30 met inclusion criteria. Twenty-one trials that randomized 2785 patients provided efficacy data for the conversion rate outcome. Bayesian network meta-analysis using a random-effects model demonstrated that ranolazine + amiodarone intravenous (IV) [odds ratio (OR) 39.8, 95% credible interval (CrI) 8.3-203.1], vernakalant (OR 22.9, 95% CrI 3.7-146.3), flecainide (OR 16.9, 95% CrI 4.1-73.3), amiodarone oral (OR 10.2, 95% CrI 3.1-36.0), ibutilide (OR 7.9, 95% CrI 1.2-52.5), amiodarone IV (OR 5.4, 95% CrI 2.1-14.6), and propafenone (OR 4.1, 95% CrI 1.7-10.5) were associated with significantly increased likelihood of conversion within 24 h when compared to placebo/control. Overall quality was low, and the network exhibited inconsistency. Probabilistic analysis ranked vernakalant and flecainide high and propafenone and amiodarone IV low. For pharmacologic cardioversion of recent-onset AF within 24 h, there is insufficient evidence to determine which treatment is superior. Vernakalant and flecainide may be relatively more efficacious agents. Propafenone and IV amiodarone may be relatively less efficacious. Further high-quality study is necessary.

PharmABCology: an initiative to create logical mnemonics systems for learning drug names

With a handful of comprehensive pharmacology textbooks on the market, students in any healthcare discipline are likely able to find at least one book that suits their individual needs. The more challenging part for students, however, is to become better acquainted with drug names. Textbooks seldom provide meaningful ways to help readers remember drug names and/or their mechanisms. Existing mnemonics, not widely used among students in general, may lack in providing the learner with an intuitive or logical approach to mentally connect with the drug names. For example, names of persons, objects or action verbs were chosen by random to represent a particular drug class or therapeutic drug use. The pharmABCology project was conceived with the final aim of creating logical mnemonics systems for drugs that students will commonly encounter in their studies. In this pilot presentation, two approaches, one based on the alphabet system and the other based on pharmacological mechanisms, were demonstrated in the mnemonics for four classes of drugs: 1) anti‐dyslipidaemics, 2) anti‐dysrhythmics, 3) anti‐hypertensives and 4) anti‐ischaemic drugs. For the alphabetical approach, the names, drug classes or mechanisms of anti‐dyslipidaemics and anti‐hypertensives are listed in alphabetical order. The other approach takes advantage of the spellings of anti‐dyslipidaemic and anti‐dysrhythmic drug names in formulating a meaningful sentence or phrase that is readily associated with the mechanisms of actions of these drugs. Some of the mnemonics systems above had been used in a sample (n = 30) of students in undergraduate MBChB tutorials, and the feedback was overwhelmingly satisfactory based on a 5‐point Likert scale. Of the 22 respondents (73 % response rate), 10 (45 %) and 9 (41 %), respectively, strongly agreed and somewhat agreed that pharmABCology mnemonics system helped with the learning of drug names. In light of the early promising results, similar approaches will be used to develop mnemonics for other drug classes with the intention of publicising this learning tool to the pharmacy, nursing and students in other healthcare‐related disciplines.Support or Funding InformationNilThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Comprehensive review of cardiovascular toxicity of drugs and related agents.

Cardiovascular diseases are a leading cause of morbidity and mortality in most developed countries of the world. Pharmaceuticals, illicit drugs, and toxins can significantly contribute to the overall cardiovascular burden and thus deserve attention. The present article is a systematic overview of drugs that may induce distinct cardiovascular toxicity. The compounds are classified into agents that have significant effects on the heart, blood vessels, or both. The mechanism(s) of toxic action are discussed and treatment modalities are briefly mentioned in relevant cases. Due to the large number of clinically relevant compounds discussed, this article could be of interest to a broad audience including pharmacologists and toxicologists, pharmacists, physicians, and medicinal chemists. Particular emphasis is given to clinically relevant topics including the cardiovascular toxicity of illicit sympathomimetic drugs (e.g., cocaine, amphetamines, cathinones), drugs that prolong the QT interval, antidysrhythmic drugs, digoxin and other cardioactive steroids, beta‐blockers, calcium channel blockers, female hormones, nonsteroidal anti‐inflammatory, and anticancer compounds encompassing anthracyclines and novel targeted therapy interfering with the HER2 or the vascular endothelial growth factor pathway.

The protective effect of grape seed and Ginkgo biloba against hepatotoxicity induced by the antidysrhythmic drug “amiodarone” in male albino rats

Amiodarone was an orally effective antiarrhythmic drug widely used throughout the world, had long-term administration side effects such as hepatotoxicity. The actions of two antioxidants; grape seed and Ginkgo biloba on the extent of tissue damage in amiodarone-induced hepatotoxicity were elucidated in this study. We equally divided thirty-six albino rats into six groups given doses by gastric tube daily for 8 weeks as follow; the 1st group (G1) served as an untreated control group under the same laboratory conditions and was given distilled water, the 2nd group (G2) grape seed-treated group that received (100 mg/kg/day), the 3rd group (G3)Ginkgo biloba-treated group that received (100 mg/kg/day), the 4th group (G4) amiodarone-treated group that received (40 mg/kg/day), the 5th group (G5) received amiodarone parallel with grape seed at the same time and the 6th group (G6) received amiodarone parallel with Ginkgo biloba at the same time. The current histological study revealed that amiodarone caused marked change in the liver including degeneration, proliferation of bile duct, inflammatory cells infiltration and fatty changes of hepatocytes in addition to deposition of collagen fibers in the hepatic tissue moreover, ultra-structural observations in the liver including vacuolation, fibrosis and pyknotic nuclei. In addition, histochemical study revealed depletion of glycogen and comet assay revealed marked of DNA damage.Treatment with the two used antioxidants reduced the extent of liver damage induced by amiodarone as indicated by decreased Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) activities. These antioxidants ameliorated the histopathological, histochemical and ultrastructure alternations of the liver tissue. In conclusion, grape seed was markedly effective than Ginkgo biloba in protecting rats against amiodarone.

Brugada Pattern Caused by a Flecainide Overdose

BackgroundBrugada pattern can be found on the electrocardiogram (ECG) of patients with altered mental status, usually with fever or drug intoxication. Diagnosis remains challenging, because the ECG changes are dynamic and variable. In addition, triggers are not always clearly identified. In patients with atrial fibrillation (AF), the use of class IC antidysrhythmic drugs can unmask a Brugada pattern on the ECG, especially if combined with other medications acting on sodium channels. Case ReportA 62-year-old man with a medical history of AF was admitted to our emergency department for altered mental status. The ECG at the time of admission showed a Brugada pattern, triggered by a flecainide overdose (about 1 g), in association with an unknown dose of lamotrigine and quetiapine. After discontinuation of all medications, the Brugada pattern disappeared and his ECG showed no abnormalities. Why Should an Emergency Physician be Aware of This?In patients with AF, the use of class IC antidysrhythmic drugs, if overdosed, can trigger a Brugada ECG pattern, and therefore it can increase the risk for malignant dysrhythmias. It is important to provide, to all patients with a Brugada ECG pattern, a list of drugs to avoid, and to underline the synergistic interplay between drugs, taking into consideration all patients' comorbidities.

Amiodarone-related thyroid dysfunction.

Nowadays, amiodarone is the most commonly used antidysrhythmic drug in clinical practice. It is highly effective in the management of recurrent ventricular dysrhythmias, paroxysmal supraventricular dysrhythmias, including atrial fibrillation and flutter, and in the maintenance of sinus rhythm after electrical cardioversion of atrial fibrillation. Moreover, it has the added benefit of being well tolerated in patients with both normal and impaired left ventricular systolic function. Despite amiodarone's potent antidysrhythmic actions, its use is hampered by numerous adverse effects on various organs, including the thyroid. Adverse effects are becoming more prevalent given the increasing incidence of dysrhythmias and wider amiodarone use. Thus, physicians and patients should both be aware of the potential thyroid-specific sequelae. However, amiodarone is likely to remain a significant problem for endocrinologists as concerns exist over the use of the new alternative antiarrhythmic agent, dronedarone, especially in patients with heart failure and left ventricular dysfunction because of the risk of hepatic injury and increased mortality. The final diagnostic and therapeutic approaches must be discussed among the patient, the general practitioner, the cardiologist, and the endocrinologist.

A Study of the Efficacy of Cardiac Antidysrhythmic Drugs in Attenuating Haemodynamic Responses to Laryngoscopy and Endotracheal Intubation in the Black Population

Background: Laryngeal, tracheal and bronchial receptors are stimulated by mechanical and chemical irritants during laryngoscopy and endotracheal intubation. That almost always triggers powerful cardiovascular responses. Various attempts have been made to attenuate these responses. The aim of this study was to compare the efficacy and safety of cardiac antidysrhythmic drugs lidocaine, diltiazem and esmolol in the attenuation of cardiovascular responses to endotracheal intubation in the Black normotensive population. Patients and Methods: A randomized controlled trial was conducted in 160 adult patients of ASA physical status I or II undergoing various elective surgeries. The patients were randomly divided into four groups of 40 patients in each group - C, L, D, and E. Group - “C” received no drug (control) as placebo, group -“L” received 1.5 mg kg-1 preservative free lidocaine, group -“D” received 0.2 mg kg-1 diltiazem, and group-“E” received 2mg kg-1 esmolol IV. Group “C”, “D” and “E”, “L” one and two minutes before intubation. Changes in heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured and then compared within and between groups. Rate pressure product (RPP) was calculated and evaluated as well. Patients were also observed for any complications. Result: There was a significant increase in SBP, DBP, HR, MAP and RPP from the base line in control group “C” at 1 minute with onward decreases at 3 and 5 minutes respectively after intubation. Percentage change in haemodynamic variables in groups C, L, D and E at 1 minute are as follows: SBP= 23.58%, 11.84%, 9.64% and 9.9%, DBP= 18.73%, 18.89%, 11.93% and 10.40%, HR= 30.45%, 26.00%, 7.01% and 1.50%; MAP= 20.80%, 15.89%, 10.90 and 10.20%; RPP= 61.44%, 40.86%, 17.26% and 11.68% respectively. Only patients receiving placebo had increased SBP, DBP, HR, MAP and RPP values after intubation compared with baseline values (p < 0.05). Conclusions: Given the difference in the pharmacological mechanisms of these drugs, the prophylactic therapy with 2mg kg-1 esmolol is significantly more effective and safe for attenuating haemodynamic changes to laryngoscopy and tracheal intubation, without producing increased risk of hypertension in the Black population.

A Study of the Efficacy of Cardiac Antidysrhythmic Drugs in Attenuating Haemodynamic Responses to Laryngoscopy and Endotracheal Intubation in the Black Population

Background: Laryngeal, tracheal and bronchial receptors are stimulated by mechanical and chemical irritants during laryngoscopy and endotracheal intubation. That almost always triggers powerful cardiovascular responses. Various attempts have been made to attenuate these responses. The aim of this study was to compare the efficacy and safety of cardiac antidysrhythmic drugs lidocaine, diltiazem and esmolol in the attenuation of cardiovascular responses to endotracheal intubation in the Black normotensive population. Patients and Methods: A randomized controlled trial was conducted in 160 adult patients of ASA physical status I or II undergoing various elective surgeries. The patients were randomly divided into four groups of 40 patients in each group - C, L, D, and E. Group - “C” received no drug (control) as placebo, group -“L” received 1.5 mg kg-1 preservative free lidocaine, group -“D” received 0.2 mg kg-1 diltiazem, and group-“E” received 2mg kg-1 esmolol IV. Group “C”, “D” and “E”, “L” one and two minutes before intubation. Changes in Heart Rate (HR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Mean Arterial Pressure (MAP) were measured and then compared within and between groups. Rate Pressure Product (RPP) was calculated and evaluated as well. Patients were also observed for any complications. Result: There was a significant increase in SBP, DBP, HR, MAP and RPP from the base line in control group “C” at 1 minute with onward decreases at 3 and 5 minutes respectively after intubation. Percentage change in haemodynamic variables in groups C, L, D and E at 1 minute are as follows: SBP=23.58%, 11.84%, 9.64% and 9.9%, DBP=18.73%, 18.89%, 11.93% and 10.40%, HR=30.45%, 26.00%, 7.01% and 1.50%, MAP=20.80%, 15.89%, 10.90 and 10.20%; RPP=61.44%, 40.86%, 17.26% and 11.68% respectively. Only patients receiving placebo had increased SBP, DBP, HR, MAP and RPP values after intubation compared with baseline values (p<0.05). Conclusions: Given the difference in the pharmacological mechanisms of these drugs, the prophylactic therapy with 2 mg kg-1 esmolol is significantly more effective and safe for attenuating haemodynamic changes to laryngoscopy and tracheal intubation, without producing increased risk of hypertension in the Black population.

Cardiac safety, drug‐induced QT prolongation and torsade de pointes (TdP)

Torquere is Latin for ‘to twist’ and gave rise to ‘torque’ in English and, in French, to ‘torsade’ a ‘twisted fringe, cord or ribbon’. Torsade de pointes (TdP) is a ballet sequence in which the dancer twists around her ‘pointes’ (dancing en pointe means ‘on the tip’ and is a classical ballet technique, usually performed using special shoes called pointes). Dessertenne used this phrase to describe a distinctive form of ventricular tachycardia in an elderly woman, because the electrical axis of the ventricular complexes varied cyclically giving the electrocardiogram (ECG) a twisted appearance (Figure 1) [1]. Similar polymorphic ventricular tachycardia had previously been identified as the cause of loss of consciousness during quinidine therapy (‘quinidine syncope’) [2]. TdP can be fatal and occurs in several clinical settings associated with prolongation of the ventricular action potential, notably drug treatment and inherited abnormalities of cardiac ion channels [3]. Prolongation of the ventricular action potential is recognized non-invasively by QT segment prolongation on the ECG (a useful but tricky surrogate end-point for risk of clinically important TdP – see below).We have commented previously on druginduced QT prolongation and its importance in drug development [4–7]. Several antidysrhythmic drugs, for example disopyramide and procainamide, as well as quinidine, cause TdP including some (flecainide, encainide and D-sotalol) that have increased mortality in randomized controlled trials [8, 9].Several non-cardiac drugs can also, albeit less frequently cause TdP. These include domperidone (in high dose intravenously – see below), methadone, arsenic trioxide, and several antihistamines, antipsychotic drugs and antiinfective drugs [3]. Not only do drugs differ in their potential to cause TdP, but several patient factors also strongly influence the risk [3]. One of the strongest of these is female sex [10] perhaps because testosterone, which shortens QT interval [11], is lower in women than in men. Several other susceptibility factors can be understood in terms of their influence on cardiac repolarization. These include poor left ventricular function, hypokalaemia, severe hypomagnesaemia and genetic polymorphisms in cardiac ion channels associated with inherited long QT syndromes (LQTS). Drug–drug interactions are clinically important, notably the interaction between ketoconazole (a potent inhibitor of CYP3A) and terfenadine [12], which contributed to the withdrawal of terfenadine from the market after several years of use, including over the counter sales. Diet (especially fruit juice consumption) also influences drug disposition in complex ways [13] underscoring the difficulties for regulators concerned about the potential for low frequency but severe drug harms.

Disparities in management of new-onset atrial fibrillation in the emergency department despite adherence to the current guidelines: data from a large metropolitan area

Atrial Fibrillation management is still a matter for debate. Past research has largely been based on the outpatient setting in which patients are followed during ambulatory visits. Very little data exist on the optimal management of AF in the Emergency Department (ED). This study investigated which factors drive different AF treatments in the ED, describing their use in different hospitals. Finally, the efficacy of different strategies in terms of cardioversion in the ED was analyzed. Charts of patients treated for atrial fibrillation (AF) were collected in 6 EDs in a large metropolitan area over a 24-consecutive month period and were reviewed and analysed. Demographics, comorbidities, treatment strategy and ED outcome were collected. Inclusion criteria were symptom onset <3 weeks and stable hemodynamic conditions at presentation. A propensity score was used to adjust for baseline clinical characteristics and to compare the efficacy of different treatments. 3,085 patients were included in the analysis. Variables associated with a rhythm control strategy were onset of symptoms <48 h, age, dyspnea, palpitations, renal failure and the presence of a mechanical valve. Different EDs applied different strategies in terms of drugs used and the electrocardioversion rate, showing heterogeneity in AF management. Adjusting for the propensity score, electrocardioversion and antidysrhythmic drugs of class Ic were more effective than a wait-and-watch strategy in the ED. Despite international guidelines being respected, AF management is heterogeneous in different ED settings. A rhythm control strategy with electrocardioversion and Class Ic drugs is more effective than a wait-and watch approach during the ED visit. Further research, toward an evidence-based approach to the emergent management of AF in the ED, is still needed.

Jugular foramen schwannoma presenting with glossopharyngeal neuralgia syncope syndrome

Jugular foramen schwannomas are rare skull base tumours which typically have a variable clinical presentation. Glossopharyngeal syncope syndrome is an unusual clinical presentation; in the following case report, it was the sole presentation of an extracranial jugular foramen tumour. The presentation of a patient with glossopharyngeal neuralgia syncope syndrome is reviewed and the pathophysiology, clinical features and treatment discussed. A 45-year-old woman presented with unilateral throat pain, bradycardia and hypotension leading to episodes of impaired consciousness when lying on her left side or turning her head to the left. Imaging detected a left-sided extracranial jugular foramen schwannoma. The tumour was excised, and the patient had no more syncopal attacks. Glossopharyngeal neuralgia syncope syndrome can be the sole presentation of a jugular foramen schwannoma. Although this syndrome may be treated with anti-dysrhythmic drugs, cardiac pacing or nerve section, in the presented patient excision of the jugular foramen schwannoma was successful in preventing further episodes of syncope.

Management and survival of patients admitted with an exacerbation of COPD: Comparison of two Danish patient cohorts

The aim of this study was to describe the management and prognosis related to a hospital admission for acute exacerbation of chronic obstructive pulmonary disease and to compare results to an earlier study. This is a retrospective study of 300 consecutively discharged patients admitted in 2006-2007 with an exacerbation of chronic obstructive pulmonary disease from three respiratory departments. Data were collected from patient charts and compared with a replicate study done in 2001. The mean age was 72.1years; 61.7% were women. Mean forced expiratory volume in 1s was 37.6% of predicted. On admission, 11.3% were treated with non-invasive ventilation, and 84.3% were given systemic corticosteroids. In-hospital mortality was 4.7%. At discharge, treatment with inhaled corticosteroids or at least one long-acting bronchodilator was given to 86.7% and 89% of patients, respectively, which was significantly higher than for similarly sampled patients in 2001. Mortality in 30days and 1year after discharge was 4.5% and 25.5%, respectively, compared with 5.5% and 30.3% in 2001, the 12-month mortality being significantly lower (P=0.03). Readmission rate in the 12months following discharge was 42.3%. Long-term oxygen treatment, treatment with anti-dysrhythmic drugs and lack of outpatient follow-up were independent predictors of 1-year mortality. Risk of readmission was increased with dependence in self-care activities, previous admissions and treatment with strong analgesics. Over a period of 6years, a significantly higher number of patients are being treated according to guidelines. Survival following discharge increased over the same period.

Prophylactic magnesium sulphate vs. lidocaine during off-pump coronary artery bypass grafting

Prophylactic magnesium sulphate vs. lidocaine during off-pump coronary artery bypass grafting

Cardiac complications following tricyclc antidepressant overdose

Poisoning with tricyclic antidepressant agents (TCA) may cause myocardial depression and ventricular arrhythmias. Treatment of these arrhythmias is based on adequate supportive therapy and administration of sodium bicarbonate. Specific anti-arrhythmic agents are sometimes required but the choice of drug is complicated by the fact that many agents cause myocardial depression and can be proarrhythmogenic. We present a case of TCA overdose with recurrent ventricular fibrillation despite supportive treatment and sodium bicarbonate administration, and discuss the actions of available antidysrhythmic drugs.

Cardiac complications following tricyclc antidepressant overdose

Poisoning with tricyclic antidepressant agents (TCA) may cause myocardial depression and ventricular arrhythmias. Treatment of these arrhythmias is based on adequate supportive therapy and administration of sodium bicarbonate. Specific anti-arrhythmic agents are sometimes required but the choice of drug is complicated by the fact that many agents cause myocardial depression and can be proarrhythmogenic. We present a case of TCA overdose with recurrent ventricular fibrillation despite supportive treatment and sodium bicarbonate administration, and discuss the actions of available antidysrhythmic drugs.

Effects of cibenzoline on cardiac function and metabolism in the rat heart--lung preparation.

Although there is concern that cibenzoline, an antidysrhythmic drug for the treatment of ventricular and supraventricular dysrhythmias, may be associated with dose-dependent inhibition of myocardial contractility there are few reports about the relationship between myocardial metabolism and cardiac function when it is used. The present study was designed to investigate the effects of cibenzoline on cardiac function and metabolism. The effects of cibenzoline on cardiac function and myocardial metabolism were assessed in the isolated rat heart-lung preparation. Thirty-two male Wistar-ST rats were divided into four groups: control, and those to receive cibenzoline, either 300, 900 or 3000 ng mL(-1). The cibenzoline was administered into the perfusate 5 min after the start of perfusion. Heart rates in the 3000 ng mL(-1) group were significantly lower than those in the control group. Cardiac output in the 3000 ng mL(-1) group at 15 and 30 min was significantly lower than in the control group. In all groups, values for %LV dP/dt max (the ratio of values at each time to those at 5 min) at 20, 25, 30 min were significantly higher than at 5 min. Myocardial adenosine triphosphate concentration in the 3000 ng mL(-1) group was significantly lower than in controls. There was no difference between groups in the lactate/pyruvate ratio. The therapeutic range of cibenzoline has few effects on cardiac function and metabolism, although concentrations 10 times greater may cause a deterioration in myocardial metabolism.

A fourth class of anti-dysrhythmic action? Effect of verapamil and ouabain toxicity, on atrial and ventricular intracellular potentials, and on other features of cardiac function.

Anti-dysrhythmic drugs can be classified as having three main classes of action; (1) direct interference with depolarization (local anaesthetic type); (2) anti-sympathetic action, by neurone blockade or transmitter competition; (3) delay of repolarization. Verapamil has recently been reported to be anti-dysrhythmic, but the present analysis of its pharmacological effects has indicated that this property cannot be attributed to any of the above three actions. It is speculated that it may possess a fourth class of action, interference with calcium conductance, with the implication that calcium currents may contribute to abnormal impulse formation.