Higher efficacy of direct hemoperfusion using coated activated-charcoal column for disopyramide poisoning: A case report.

RATIONALE: Cases of severe disopyramide poisoning are rare and few have been reported. We report a case in which activated-charcoal column hemoperfusion was dramatically effective for life-threatening disopyramide poisoning. PATIENT CONCERNS: A teenage girl who had overdosed on disopyramide (total dose, 4950 mg) was brought to our hospital. She was resuscitated from short period cardiopulmonary arrest and subsequently showed severe cardiogenic shock and ventricular arrhythmia. DIAGNOSES: Disopyramide poisoning (self-evident). INTERVENTIONS: As hemodynamics remained unstable after providing percutaneous cardiopulmonary support and intra-aortic balloon pumping, we attempted direct hemoperfusion using a coated activated-charcoal hemoperfusion column. OUTCOMES: Hemodynamics including electrocardiography and serum disopyramide concentration were dramatically improved, and the patient was ambulatory by hospital day 14. LESSONS: Because disopyramide has low molecular weight and a small distribution volume, blood purification is considered to be the most effective therapy. We selected direct hemoperfusion for relatively high protein-binding rate. In fact, clinical status was dramatically improved, and the calculated half-life of the direct hemoperfusion phase was the shortest of all phases. In cases of severe or life-threatening disopyramide poisoning, blood purification therapy including direct hemoperfusion using a coated activated-charcoal column should be performed.

Disopyramide and mianserin intoxication: a unique fatal case--review of the literature.

Lethal occurrence is exceptional after disopyramide or mianserin poisoning. A case of intentional lethal intoxication with these drugs was reported, as well as a review of the literature. Pre- and postmortem blood concentrations of disopyramide or mianserin were assessed in a woman who died from acute cardiac failure after ingestion. The premortem blood concentration of disopyramide alone was considered lethal, and a toxic premortem concentration of mianserin was observed that may have increased cardiovascular failure induced by disopyramide because the metabolism of both drugs is mediated via cytochrome P450. Moreover, it was shown that the postmortem redistribution of disopyramide was limited, as pre- and postmortem concentrations were 48 and 65 mg/L, respectively. As regards mianserin, redistribution was observed after death with pre- and portmortem concentrations at 0.23 and 0.79 mg/L, respectively. This case illustrates that if postmortem blood concentration of disopyramide is known, the premortem concentration can be deduced.

[A patient with disopyramide intoxication rescued by percutaneous cardiopulmonary support].

A 28-year-old man was admitted to our hospital in a hypotensive state 2 hours after taking 8,400 mg disopyramide. Infusion of catecholamine and gastric lavage restored normal blood pressure. However, 8 hours after taking the disopyramide he became hypotensive again and electrocardiographic findings revealed bizarre ventricular complexes resulting in ventricular flutter. Although standard cardiopulmonary resuscitation was not effective, his circulatory status was maintained by percutaneous cardiopulmonary support (PCPS). After 36 hours electrocardiography showed sinus rhythm, and his cardiac function became normal. Patients with severe cardiac dysfunction or cardiac arrest caused by disopyramide intoxication can be supported by PCPS until cardiac function is restored.

An overdose fatality in a child involving disopyramide and sulindac.

The results of an accidental overdose fatality in a child involving disopyramide and sulindac are reported in this paper. Quantitation of disopyramide was performed by gas chromatography using codeine as the internal standard. Sulindac was assayed by high- performance liquid chromatography using ketoprofen as the internal standard. The postmortem blood concentrations of disopyramide and sulindac were 41.3 and 12.2 mg/L, respectively. The concentrations of disopyramide and sulindac were also quantitated in the liver, in bile, and in urine.

Prolonged cardiopulmonary resuscitation during acute disopyramide poisoning.

A case is reported of sustained electromechanical dissociation due to deliberate disopyramide over-dosage in a young healthy girl. Circulatory recovery was achieved with standard resuscitative measures, including prolonged cardiac massage and isoproterenol infusion plus high dose calcium chloride. Neurological recovery was complete.

Poisoning due to class IA antiarrhythmic drugs. Quinidine, procainamide and disopyramide.

Quinidine, procainamide and disopyramide are antiarrhythmic drugs in the class 1A category. These drugs have a low toxic to therapeutic ratio, and their use is associated with a number of serious adverse effects during long term therapy and life-threatening sequelae following acute overdose. Class 1A agents inhibit the fast inward sodium current and decrease the maximum rate of rise and amplitude of the cardiac action potential. Prolonged Q-T interval and, to a lesser extent, QRS duration may be observed at therapeutic concentrations of quinidine. With increasing plasma concentrations, progressive depression of automaticity and conduction velocity occur. 'Quinidine syncope' (a transient loss of consciousness due to paroxysmal ventricular tachycardia, frequently of the torsade de pointes type) occurs with therapeutic dosing, often in the first few days of therapy. Extracardiac adverse effects of quinidine include potentially intolerable gastrointestinal effects and hypersensitivity reactions such as fever, rash, blood dyscrasias and hepatitis. Procainamide produces electrophysiological changes that are similar to those of quinidine, although Q-T interval prolongation with the former is less pronounced at therapeutic concentrations. Hypersensitivity reactions including fever, rash and (more seriously) agranulocytosis are associated with procainamide, and a frequent adverse effect requiring cessation of therapy is the development of systemic lupus erythematosus. Of the 3 drugs, disopyramide has the most pronounced negative inotropic effects, which are especially significant in patients with pre-existing left ventricular dysfunction. As with quinidine, unexpected 'disopyramide syncope' at therapeutic concentrations has been described. Anticholinergic side effects are common with this drug and may require cessation of therapy. Disopyramide therapy may unpredictably induce severe hypoglycaemia. Severe intoxication with the class 1A agents may result from acute accidental or intentional overdose, or from accumulation of the drugs during long term therapy. Acute overdose can result in severe disturbances of cardiac conduction and hypotension, frequently accompanied by central nervous system toxicity. Decreased renal function can cause significant accumulation of procainamide and its active metabolite acecainide (N-acetyl-procainamide), resulting in severe intoxication. Mild to moderate renal dysfunction is less likely to lead to quinidine or disopyramide intoxication, unless renal failure is severe or concurrent hepatic dysfunction is present. Management of acute intoxication with class 1A drugs includes gut decontamination with provision of respiratory support and treatment of seizures as needed. Hypertonic sodium bicarbonate, by antagonising the inhibitory effect of quinidine on sodium conductance, may reverse many or all manifestations of cardiovascular toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Distribution of lidocaine and disopyramide in human blood and tissue, a case report of death caused by spinal anesthesia.

An 11-year-old girl was anesthetized with hyper-baric solution of lidocaine as spinal anesthesia for an appendectomy in a surgical clinic. Respiratory arrest which occurred soon after the injection, was not discovered for a period of time. Since spontaneous respiration recovered within 2 h of intensive resuscitation, the patient was transferred to a community hospital for intensive care. Ten hours after the spinal anesthesia, she died of cardiac failure. The concentration of lidocaine in the brain was 5-10 times more than that in other tissues. The relationship between the possibility of malpractice of spinal anesthesia and tissue distribution of the drug was discussed. In addition to lidocaine, a toxic amount of disopyramide, an antiarrhythmic drug, was detected in the body. The distribution of disopyramide was also estimated, and the pharmacokinetics of disopyramide in plasma and tissues were studied experimentally in rats.

Fatal disopyramide intoxication from suicidal/accidental overdose.

Disopyramide is an oral antiarrhythmic drug which reduces conduction velocity, prolongs duration of action potential and the effective refractory period, and exerts vagolytic properties. The drug is usually well absorbed orally. The principal use of the drug is to suppress ventricular extrasystoles with usual oral dosage of 100 to 200 mg every 6 h, until blood levels of 2 to 4 micrograms/mL are attained. The use of the drug for suicide is uncommon as it is a prescription drug. Two cases of fatal disopyramide intoxication seen at the Los Angeles County Medical Examiner's Office will be discussed followed by a review of the literature of fatal suicidal disopyramide overdose. Case 1 was a 31-year-old male pharmacist with known history of depression and no history of heart disease. His decomposed remains were found with a suicide note and with several disopyramide tablets. At autopsy the blood level for disopyramide was 146 micrograms/mL. Case 2 is a 40-year-old male with history of alcoholism and prior suicidal attempts who regularly took disopyramide to control ventricular arrhythmias. He apparently ingested 36 100-mg tablets of disopyramide before his final collapse. At autopsy his blood level of disopyramide was 63 micrograms/mL.

Management of cardiac drug overdose.

Although overdoses from cardiac drugs are uncommon, these are compounds with narrow therapeutic indices and they may give rise to serious acute toxicity from accidental, deliberate or even iatrogenic overdosage. Through the National Poisons Information Service for England and the Poisons Unit laboratory, we monitor reports of serious toxicity from this group of drugs and use the information gained to assess our recommendations for treatment. This article reviews the toxicity and the management of overdosage with digoxin and representative drugs from each class of anti-arrhythmic drugs. From these observations, a general plan of management applicable to all cardiac drugs is proposed and its is suggested that this form of monitoring should be continued.

Disopyramide fatality: case report and GC/FID analysis.

This case involves massive ingestion of disopyramide by a 19-year-old male, found dead, not having had the benefit of medical intervention. Quantitation of the drug was accomplished by gas chromatography using a flame ionization detector (GC/FID). Identification of the compound was done by thin layer chromatography (TLC) and ultraviolet spectrophotometry (UVS). The blood concentration of disopyramide was 15 times the usual therapeutic level and was easily detected by FID.

Cardiac drug overdose.

Toxicity from cardiac drugs is a particular management challenge since the manifestations of an acute overdose and the initial indications for the drug are often similar. Plasma drug levels are essential but must be interpreted in light of the clinical picture. Hypotension, due to either vasodilatation or decreased myocardial contractility, and arrhythmias are the principal cardiac manifestations, but noncardiac effects are sometimes more troublesome. An antiarrhythmic agent of the same class should not be used in treating an arrhythmia resulting from an overdose.

[Acute voluntary or accidental disopyramide poisoning. A multicentric study of 106 cases (author's transl)]. / Intoxications aiguës par le disopyramide. Etude multicentrique de 106 observations.

Between 1972 and 1978, 106 case-records of disopyramide poisoning were collected from French anti-poison center. Acute intoxication was voluntary in 90% of the cases and occurred in young adults. Clinical symptoms appeared early and consisted mostly of cardiovascular disorders, which were present in 60 patients: cardiogenic shock (24 cases), circulatory arrest (17 cases), atrio-ventricular block (21 cases), intraventricular block (24 cases) and severe ventricular arrhythmia (12 cases). The toxic dose in otherwise healthy adults was 1,5 g and the mortality rate was high (12,2%). An analysis of therapeutic measures and outcome indicated that the best treatment consists of early gastric lavage, cardiorespiratory manoeuvres, electric heart stimulation, administration of sodium lactate in cases with intraventricular conduction disturbances and isoprenaline in cases with cardiogenic shock.

[Disopyramide poisoning]. / Disopyramidvergiftung.

Acute intoxications with the antiarrhythmic drug disopyramide (Norpace) are often life-threatening. After an almost asymptomatic interval of 1 to 4 hours, cardiogenic shock of sudden onset occurs. The usual methods of cardiac resuscitation such as adrenaline and antiarrhythmic drugs should not be used, and transvenous pacemakers often prove ineffective. To lower the high rate of mortality, early appropriate monitoring and facilities for rapid intervention are necessary. Isoprenaline is the most suitable positive inotropic and chronotropic drug. Hemoperfusion with Amberlite XAD 14 is effective but not always needed.

Acute intoxication with diisopyramide: clinical and experimental study by hemoperfusion an Amberlite XAD 4 resin.

Diisopyramide overdose induces an early and severe cardiogenic shock; hemoperfusion on resin (Amberlite XAD 4) is the most efficient treatment. In vitro, 92% of the drug is adsorbed in 240 min. In dog, the plasmatic epuration is 66% with a mean plasma clearance of 74% plasmatic flow. A woman who had absorbed 4.50 g diisopyramide showed an idioventricular rhythm. The cardiac electrical stimulation and positive inotrope drugs were inefficient. Hemoperfusion on resin Amberlite XAD 4 corrected hemodynamic and ECG disturbances in 4 h. The epuration was proved by the decrease of diisopyramide plasma level: 24.4 micrograms/mL before epuration, 1.9 micrograms/mL after epuration, and a mean plasma clearance of 107.8 mL/min (61% of the plasmatic flow). Hemoperfusion of resin (Amberlite XAD 4) is more efficient than hemodialysis (cuprophan) and hemofiltration (polyacrylonitrile). The system that we have used is well tolerated and of low cost.