Saved by the pump: Two successful resuscitations utilising emergency department-initiated extracorporeal cardiopulmonary resuscitation in South Africa.

Extracorporeal life support is the utilisation of advanced techniques to sustain circulatory and/or ventilatory functions in critically ill patients when standard therapies fail. It is well established in developed countries. There is increasing literature supporting its application in refractory cardiac arrest with a potential reversible cause, a procedure also known as extracorporeal cardiopulmonary resuscitation (eCPR). Two cases where eCPR was successfully utilised in a busy (>30 000 visits per year) private South African emergency department are described here, the first such cases to be reported on the African continent. The first patient had a life-threatening cardiac arrhythmia due to toxin ingestion, and the second a refractory ventricular fibrillation due to acute myocardial infarction. In both these cases the cardiac arrest was witnessed, occurred in the emergency department, and failed to respond to standard advanced resuscitative measures. Both the patients were discharged neurologically intact. Although it is effective, the benefit of this advanced method of resuscitation in a low- to middle-income country is debated.

Safety of Outpatient Initiation of Disopyramide for Obstructive Hypertrophic Cardiomyopathy Patients.

BACKGROUND: Disopyramide is effective in ameliorating symptoms in patients with hypertrophic cardiomyopathy; however, its potential for proarrhythmic effect has raised concerns about its use in the ambulatory setting. The risk of initiating disopyramide in this manner has never been evaluated. METHODS AND RESULTS: All charts of patients seen in the outpatient hypertrophic cardiomyopathy clinic between 2010 and 2014 were screened for initiation of disopyramide and data were extracted. Disopyramide in our clinic is usually initiated at a dose of 300 mg daily and titrated during follow-up. A total of 2015 patients were seen in the clinic, including 168 who were started on disopyramide. There were no cardiac events within 3 months of disopyramide initiation. During long-term follow-up (255 patient-years; mean, 447 days; interquartile range, 201-779), only 2 patients developed cardiac events (syncope of unknown cause in both). Thirty-eight patients (23%) developed side effects of disopyramide and 18 (11%) stopped the drug because of these side effects. Of the patients continuing disopyramide long term, 63% remained free of septal reduction interventions at end of follow-up. Disopyramide at a dose of 300 mg prolonged the mean QTc interval by 19±23 ms; however, increasing the dose to 600 mg had no further significant effect. CONCLUSIONS: Initiation of disopyramide in the outpatient setting is safe and the risk of subsequent sudden cardiac death is low. Because of its QT-prolonging effect, precautions may be necessary in patients at higher risk of torsades de pointes.

Beers criteria for potentially inappropriate medication use in older adults.

Nurses can decrease the risk of adverse drug problems with medication review and prompt interventions. The Beers Criteria lists medications to avoid using among elderly clients. The origin of the Beers Criteria, its 2002 modification, and application in acute care settings are explained.

Disopyramide-induced hypoglycemia in a non-diabetic hemodialysis patient: a case report and review of the literature.

Disopyramide, an antiarrhythmic drug, has been reported to cause hypoglycemia; however, its mechanism of action remains unclear. Pre-existing factors that increase the concentration of the drug in the blood increase the risk of hypoglycemia. Furthermore, other factors can also increase the risk of hypoglycemia even when disopyramide levels are in the therapeutic range. It has been proposed that disopyramide-induced hypoglycemia is caused by stimulation of insulin secretion due to the inhibition of the pancreatic beta-cell ATP-sensitive K+ channels. We report a case of severe disopyramide-induced hypoglycemia in a nondiabetic 72-year-old woman on hemodialysis. Concentrations of counter-regulatory hormones, serum insulin, and C-peptide were measured. From these data, it appears that disopyramide-induced hypoglycemia results from sustained endogenous insulin secretion, with a concomitant inadequate counter-regulatory response. Although hypoglycemia occurs infrequently in patients treated with disopyramide, this adverse effect is clinically important and potentially life-threatening. Evidence suggests that disopyramide-induced hypoglycemia results from endogenous insulin secretion and can occur in patients with therapeutic blood concentrations of the drug. Patients at risk include those with renal impairment, advanced age, and malnutrition, and blood glucose levels should be monitored carefully in such patients.

Torsades de Pointes induced by a combination of garenoxacin and disopyramide and other cytochrome P450, family 3, subfamily A polypeptide-4-influencing drugs during hypokalemia due to licorice.

We report an 82-year-old man who developed ventricular tachycardia and Torsades de Pointes (TdP) after oral administration of garenoxacin, a novel quinolone antibiotic agent that differs from the third-generation quinolones, for pneumonia. He had hypokalemia (K 2.3 mmol/L) induced by licorice and also had received disopyramide for arrhythmia, bicalutamide for prostate cancer, and silodosin for prostate hypertrophy. After taking him off all drugs and administering spironolactone supplemented with potassium, his low serum potassium level was ameliorated. Therefore, although garenoxacin reportedly causes fewer adverse reactions for cardiac rhythms than third-generation quinolone antibiotics, one must be cautious of the interference of other drugs during hypokalemia in order to prevent TdP.

Provokable left ventricular outflow tract obstruction in a patient without hypertrophy.

BACKGROUND: A 61-year-old man presented with shortness of breath and chest pain on exertion. He had been diagnosed as having hiatus hernia 2 years previously and was taking proton-pump inhibitors as necessary. He had a family history of ischemic heart disease and subarachnoid hemorrhage. INVESTIGATIONS: Physical examination, electrocardiography, echocardiography, cardiopulmonary exercise testing, coronary angiography, transoesophageal echocardiography, stress echocardiography. DIAGNOSIS: Provokable left ventricular outflow tract obstruction without electrocardiographic abnormalities or left ventricular hypertrophy on echocardiography. MANAGEMENT: Pharmacological therapy (atenolol 50 mg daily, disopyramide 250 mg twice daily), dual-chamber pacemaker implantation.

Mechanism of disopyramide-induced hypoglycaemia in a patient with Type 2 diabetes.

BACKGROUND: Disopyramide, an antiarrhythmia drug, has been reported to cause hypoglycaemia. Pre-existing factors that increase the concentration of the drug in the blood increase the risk of hypoglycaemia. Furthermore, other factors can also increase the risk of hypoglycaemia even when disopyramide levels are in the therapeutic range. It has been proposed that disopyramide-induced hypoglycaemia is caused by inhibition of the pancreatic B-cell K(ATP) channels. CASE REPORT: We report a case of severe disopyramide-induced hypoglycaemia in a 62-year-old woman with Type 2 diabetes taking low-dose glimepiride treatment. She had not experienced hypoglycaemia prior to the start of disopyramide therapy. No further hypoglycaemic episodes occurred following withdrawal of disopyramide therapy. FUNCTIONAL STUDY: Current recordings of K(ATP) channels expressed in Xenopus oocytes showed that at their estimated therapeutic concentrations, disopyramide and glimepiride inhibited K(ATP) channels by about 50-60%. However, when both drugs were applied together, K(ATP) channels were almost completely closed (approximately 95%). Such dramatic inhibition of K(ATP) channels is sufficient to cause B-cell membrane depolarization and stimulate insulin secretion. CONCLUSIONS: Disopyramide therapy is not recommended for patients treated with K(ATP) channel inhibitors.

Severe respiratory failure and torsades de pointes induced by disopyramide in a patient with myasthenia gravis.

Class 1a anti-arrhythmic drugs are often used for the treatment of atrial fibrillation (AF), but it is not well known that myasthenia gravis (MG)-like symptoms can be generated by their anti-cholinergic effects. We had a patient with MG who developed symptomatic MG aggravation after AF treatment with disopyramide. Symptomatic MG aggravation was followed by Takotsubo-shaped cardiomyopathy, QT prolongation, and torsades de pointes. We suggest that the anti-cholinergic effects of disopyramide can induce MG crisis and should therefore be carefully considered when disopyramide is used to treat AF in patients with MG.

Effects of serum concentrations of disopyramide and its metabolite mono-N-dealkyldisopyramide on the anticholinergic side effects associated with disopyramide.

The aim of this study was to evaluate the relationship between the anticholinergic side effects associated with disopyramide (DP) and serum DP or mono-N-dealkyldisopyramide (MND) concentrations and the safety range of DP or MND for prevention of anticholinergic side effects in 141 inpatients. The serum DP and MND concentrations were determined by high-performance liquid chromatography. No correlation was observed between creatinine clearance (Ccr) and the ratio of the serum concentration to the dose (C/D) of DP, but a significant inverse correlation was observed between Ccr and the C/D of MND. It was observed that the ratio of MND concentration to DP concentration in the group, whose Ccr was below 20 ml/min, was higher than that of the other groups. Although no significant difference was observed in the DP concentration between the patients without (Group 1) or with (Group 2) anticholinergic side effects, significant differences were observed in the MND concentration, Ccr, and the ratio of MND/DP. The DP concentrations of both Groups 1 and 2 were distributed from 0.13 to about 5 microg/ml. On the other hand, although the MND concentrations of Group 1 were below about 1 microg/ml, the MND concentrations of Group 2 were above about 1 microg/ml. These results suggest that not only DP concentration but also MND concentration should be monitored in patients whose renal function is decreased to prevent anticholinergic side effects associated with DP, and that when serum MND concentration was over approximately 1 microg/ml, the dose should be decreased or discontinued.

Atrial pacing failure following termination of atrial fibrillation by acute administration of disopyramide phosphate.

Atrial pacing failure occurred after termination of atrial fibrillation by acute administration of disopyramide phosphate in a 71-year-old woman implanted with an AAI pacemaker for sick sinus syndrome. The atrial pacing threshold showed an 810% increase; however, the serum concentration of disopyramide corresponded to therapeutic level. Infusion of the same dose of disopyramide phosphate used during the period of atrial pacing rhythm did not increase the atrial pacing threshold. In the present patient, we supposed that atrial pacing failure did not occur by the effect of disopyramide alone, but rather was a reciprocal action in response to atrial fibrillation.

Failure of disopyramide to improve right ventricular outflow tract obstruction after living-donor lobar lung transplantation.

Right ventricular (RV) outflow tract obstruction (RVOTO) is an uncommon complication of lung transplantation in patients with pulmonary hypertension (PH) and both medical management and surgical intervention are required. A 28-year-old female with primary PH was referred and because she did not respond to medical treatment, living-donor lobar lung transplantation was performed. The operation was successful, but dyspnea and exercise intolerance developed during rehabilitation and transthoracic echocardiography revealed RVOTO. Intravenous disopyramide during cardiac catheterization reduced the pressure gradient from 35 mmHg to 16 mmHg without decreasing RV systolic pressure. However, electrical and hemodynamic parameters were adversely affected by disopyramide and thus, after cardiac catheterization, administration of fluid and a low dose of atenolol was started, and her symptoms improved. Transthoracic echocardiography showed improvement in the RVOTO. This case suggests that disopyramide should be avoided for patients with RVOTO following lung transplantation and that other negative inotropic agents, such as beta-blockers, are more effective for relief of RVOTO.

Atrial fibrillation: rate control often better than rhythm control.

(1) The treatment aims in atrial fibrillation are to reduce patients' symptoms and to prevent both embolism and deterioration of any underlying heart disease. Therapy consists of anticoagulant or antiplatelet drugs, treatment of any underlying heart disease, and heart rate control. (2) Digoxin, betablockers, diltiazem and verapamil slow the heart rate but rarely restore sinus rhythm. Amiodarone, disopyramide, flecainide, quinidine and sotalol can be used to prevent relapse of atrial fibrillation after electrical cardioversion, but they all have potentially serious adverse effects. New trials of antiarrhythmic treatments have been published since our last review of this subject. (3) In one trial in 403 patients, amiodarone was more effective than sotalol and propafenone in restoring and maintaining sinus rhythm. After 15 months of follow-up, there were fewer strokes among patients treated with amiodarone, but there was no difference between the three drugs in the overall incidence of cardiovascular events. (4) A clinical trial with 4060 patients compared rhythm control (mainly with amiodarone, sotalol or propafenone; sometimes combined with electrical cardioversion) and rate control (with digoxin, betablocker, diltiazem or verapamil; systematically combined with anticoagulant therapy). The antiarrhythmic treatment restored sinus rhythm in more than half the patients in the long term. But rhythm control did not reduce the risk of death or serious cardiovascular events during a mean follow-up period of 3.5 years. Rhythm control caused more adverse events than rate control; subgroup analyses (weak evidence) suggest that rhythm control may also have caused more deaths among patients over 65 and among patients with coronary heart disease. (5) In another trial, electrical cardioversion followed by antiarrhythmic therapy (mainly sotalol) sustainably restored sinus rhythm in more than one-third of 522 patients. But, compared with rate control treatment plus anticoagulant therapy, rhythm control did not reduce the risk of cardiovascular events, and was associated with a larger number of serious adverse cardiac effects. (6) Other recent trials confirm the risk of serious adverse effects, including severe arrhythmia with sotalol (especially at the start of treatment), and adverse thyroid and pulmonary effects with amiodarone. (7) Combined radiofrequency ablation and cardiac stimulation improved symptoms in some patients with incapacitating atrial fibrillation who had not responded to other treatments. However, this approach carries a risk of serious adverse effects, and its impact on the risk of cardiovascular events and death is not known. (8) In practice, an attempt should be made to restore sinus rhythm with amiodarone and/or electrical cardioversion, in symptomatic, recent or paroxysmal atrial fibrillation in patients under 65 who have no signs or symptoms of coronary heart disease. In other situations, rate control is the first-line option, using digoxin, betablockers (other than sotalol) or calcium channel blockers (diltiazem or verapamil). Whatever the option, treatment must be combined with anticoagulant or antiplatelet therapy, and with treatment of any underlying heart disease.

Disopyramide-induced pneumonitis, diagnosed by lymphocyte stimulation test using bronchoalveolar lavage fluid.

A 72-year-old man was admitted to our hospital with fever and cough. He had been on disopyramide treatment for nine days to control cardiac arrhythmia. On admission, chest X-ray examination revealed reticulonodular opacities in both lungs, and impending respiratory failure was evident. A differential cell count of the bronchoalveolar lavage fluid (BALF) showed a marked increase of lymphocytes. A lymphocyte stimulation test (LST) for disopyramide using BALF was positive, although the test using peripheral blood was negative. This case suggests that LST using BALF is useful for the diagnosis of drug-induced pneumonitis.

Disopyramide: interactions with marcolide antibiotics.

Cases of severe cardiac arrhythmia and major hypoglycaemia have occurred in patients receiving disopyramide simultaneously with some macrolide antibiotics, especially erythromycin and clarithromycin.