RESUMEN

Anaphylactoid reactions in patients receiving intravenously administered vitamin K have been reported in the literature. To summarize the known data on anaphylactoid reactions from administration of vitamin K, we reviewed all published and unpublished reports of this adverse reaction. Published reports were obtained through medline (1966--1999) and EMBASE (1971--1999) searches of the English language literature and review of references from identified case reports. Unpublished reports were obtained using the Spontaneous Reporting System Adverse Reaction database of the United States Food and Drug Administration (FDA) between August 1968 and September 1997. All adverse drug reactions to vitamin K were categorized by route of drug administration, dose and standard adverse reaction code. In the FDA reports, we defined anaphylactoid reactions as any adverse drug reaction coded as either anaphylaxis, allergic reaction, apnea, dyspnea, death, heart arrest, hypotension, shock or vasodilatation. Additionally, all fatal and life-threatening FDA reported reactions were reviewed to determine if they could represent an anaphylactoid reaction missed by the above definition. The literature review uncovered a total of 23 cases (3 fatal) of anaphylactoid reactions from intravenous vitamin K. The FDA database contained a total of 2236 adverse drug reactions reported in 1019 patients receiving vitamin K by all routes of administration. Of the 192 patients with reactions reported for intravenous vitamin K, 132 patients (69 %) had a reaction defined as anaphylactoid, with 24 fatalities (18 %) attributed to the vitamin K reaction. There were 21 patients with anaphylactoid reactions and 4 fatalities reported with doses of intravenous vitamin K of less than 5 mgs. For the 217 patients with reactions reported due to vitamin K via a non-intravenous route of administration, 38 patients had reactions meeting the definition of anaphylactoid (18 %), with 1 fatality (3 %) attributed to the drug. The absolute risk of an anaphylactoid reaction to intravenous vitamin K cannot be determined by this study, but the relatively small number of documented cases despite widespread use of this drug suggest that the reaction is rare. Anaphylactic reactions and case fatality reports were found even when intravenous vitamin K was given at low doses by slow dilute infusion. The pathogenesis of this reaction is unknown and may be multifactorial with etiologies including vasodilation induced by the solubilizing vehicle or immune-mediated processes. We conclude that use of intravenous vitamin K should be limited to patients with serious hemorrhage due to a coagulopathy that is secondary to a relative or absolute deficiency of vitamin K.

Asunto(s)

RESUMEN

Atrial fibrillation recurs in many patients treated with antiarrhythmic therapy to maintain sinus rhythm. From March 1985 to August 1991, 214 patients with recurrent symptomatic chronic or paroxysmal atrial fibrillation for which conventional antiarrhythmic agents had failed were treated with propafenone or sotalol. Baseline demographic data including the presence of pacing therapy were collected. Life-table estimates of the duration of freedom from atrial fibrillation were constructed on the basis of pacemaker status. Of 214 patients, 26 (12.1%) had pacing therapy. Patients with dual-chamber pacing were more likely to remain in sinus rhythm at 6 months (80%) than were patients with ventricular pacing (40%) or patients without pacing therapy (55%) (p = 0.002). A Cox univariate regression analysis demonstrated that dual-chamber pacing in contrast to ventricular pacing or no pacing was associated with a lower risk of recurrent atrial fibrillation. Clinical parameters such as age, gender, left atrial size, fibrillation pattern, drug assignment, ejection fraction, and underlying cardiac disease did not alter the risk of recurrent atrial fibrillation. Dual-chamber pacing was associated with a decreased likelihood of recurrent atrial fibrillation even after adjustment for other clinical covariates in a multivariate model (p = 0.04). In patients with recurrent atrial fibrillation treated with propafenone or sotalol, dual-chamber pacing improved maintenance of sinus rhythm.

Asunto(s)

RESUMEN

Because conventional antiarrhythmic therapy is often ineffective in maintaining sinus rhythm or is associated with adverse side effects in patients with atrial fibrillation (AF), there is a clinical need to test newer agents. One hundred patients with AF who had unsuccessful therapy with 1.9 +/- 1.0 type IA antiarrhythmic agents were randomized to receive either propafenone (n = 50) or sotalol (n = 50). Patients were stratified into 4 groups based on AF pattern (chronic vs paroxysmal) and left atrial size (large [> or = 4.5 cm] vs small [< 4.5]). The proportion of patients remaining in sinus rhythm on each agent was calculated for each group by the Kaplan-Meier method. For patients randomized to propafenone, 46 +/- 8%, 41 +/- 8% and 30 +/- 8% remained in sinus rhythm at 3, 6 and 12 months, respectively, after cardioversion. A similar proportion of patients treated with sotalol remained in sinus rhythm at follow-up (49 +/- 7%, 46 +/- 8% and 37 +/- 8% at 3, 6 and 12 months, respectively; p = NS). The proportion of patients remaining in sinus rhythm on propafenone and sotalol was not dependent on arrhythmia pattern or left atrial dimension. Except for constipation that occurred more frequently in patients treated with propafenone, adverse side effects were equally distributed between the 2 therapies. Two patients receiving sotalol died during follow-up. Propafenone and sotalol, 2 new antiarrhythmic agents, were found to be equally effective in maintaining sinus rhythm in 100 patients with recurrent AF. Response rates were not affected by arrhythmia pattern, left atrial size or unsuccessful prior drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

RESUMEN

Beta blockers in patients with sick sinus syndrome (SSS) may prevent supraventricular arrhythmias, systemic hypertension and myocardial ischemia, but may cause excessive depression of sinus node function. In 8 patients with SSS and a permanent pacemaker, the effect of chronic oral pindolol on sinus rate and pacing frequency was compared with that of propranolol in a double-blind crossover trial. In all patients the pacemaker was programmed to a rate of < or = 50 beats/min. Holter monitors, obtained at baseline and on each drug, were used to calculate peak ambulatory sinus rate, number of paced beats per day, maximal number of paced beats per hour, and percentage of hours with paced beats. The peak sinus rate with pindolol therapy was 24% higher than with propranolol (p = 0.001). During pindolol therapy, the number of paced beats per day and maximal paced beats per hour were reduced 54% (p = 0.04) and 61% (p = 0.02), respectively, compared with propranolol. Patients with SSS who require beta-blocker therapy for tachycardia, systemic hypertension or angina pectoris may have less bradycardia when treated with pindolol rather than propranolol. Beta blockers like pindolol, which cause less sinus node depression, may obviate the need for prophylactic permanent pacemakers in patients with SSS, and may help to prevent chronotropic incompetence and pacemaker syndrome in patients already treated with a VVI device.

Asunto(s)

RESUMEN

Most states have specific laws governing whether patients with seizure disorders can drive. To learn whether similar laws exist for patients with lethal ventricular arrhythmias, we surveyed the Departments of Motor Vehicles in all 50 states. In addition, either an arrhythmia specialist (n = 25) or a general cardiologist (n = 25) was chosen randomly from each state and interviewed to study physician awareness of such laws and physician attitudes toward driving by patients with arrhythmias. Forty-two states (84%) have laws restricting driving by patients who have seizures; only 8 states (16%) have specific laws for patients with arrhythmias. No state makes a distinction between driving by patients with arrhythmias who are managed with an implantable cardioverter-defibrillator (ICD) compared with patients who are managed medically. Seventy-four percent of physicians did not know their own state's laws about driving by patients who have ventricular arrhythmias. Cardiologists were more likely to advise no driving restriction for medically treated patients than for ICD-treated patients. Cardiologists were also more likely to advise permanent restriction for patients with ICDs than for patients treated medically. We conclude that greater legal and medical consensus is needed to guide physicians in advising patients with lethal ventricular arrhythmias about driving restrictions.

Asunto(s)

RESUMEN

Despite large gains in the medical and surgical treatment of angina pectoris in the past two decades, many patients are refractory to conventional medical therapy and are unsuitable for a first or, more commonly, repeat coronary revascularization procedure. We evaluated the efficacy of perhexiline maleate, a drug with an antianginal mechanism of action in humans that is as yet unknown, by using a randomized double-blind placebo-controlled crossover design in 17 patients with refractory angina who continued to receive maximal antianginal therapy, typically including nitrates, a beta-blocker, and a calcium channel antagonist. In view of perhexiline's potential for hepatic and neurological toxicity, plasma drug levels were monitored and maintained in the 150-600 ng/ml range. Sixty-three percent of patients were judged perhexiline responders by objective exercise testing criteria, as compared with 18% of patients on placebo (p less than 0.05). By blinded review of subjective measures of anginal frequency and severity, 65% of patients noted an improvement while on perhexiline, whereas no patient identified the placebo phase with improvement. Side effects observed in 29% of patients were minor and related to transient elevations of blood levels of more than 600 ng/ml; no patient suffered hemodynamic or cardiac conduction abnormalities attributable to perhexiline. With attention to the pharmacokinetics of perhexiline's elimination in individual patients, this novel antianginal agent seems to be safe and effective and deserves further evaluation in patients already receiving maximal antianginal therapy who are not candidates for revascularization procedures.

Asunto(s)

RESUMEN

One hundred nine patients with recurrent episodes of symptomatic atrial fibrillation or flutter, or both, who had failed one to five previous antiarrhythmic drug trials were treated with propafenone and, subsequently, sotalol if atrial fibrillation recurred. The clinical profile of the study group was as follows: age 63 +/- 13 years, left atrial anteroposterior dimension 4.4 +/- 0.9 cm and left ventricular ejection fraction 57 +/- 14%. Paroxysmal atrial fibrillation occurred in 56 patients (51%) and chronic atrial fibrillation occurred in 53 patients (49%). After loading and dose titration phases were completed, the maintenance doses of drugs were 450 to 900 mg/day for propafenone and 160 to 960 mg/day for sotalol. Life table estimates of the duration of freedom from atrial fibrillation were constructed for each drug trial. The percent of patients free of recurrent symptomatic arrhythmia at 6 months was 39% for propafenone and 50% for sotalol. The cumulative proportion of patients successfully treated with propafenone or sotalol, or both, by 6 months was 55% and remained relatively constant beyond that point. The incidence of intolerable side effects necessitating discontinuation of therapy ranged from 7% to 8%. Thus, despite previous unsuccessful drug trials, a substantial proportion of patients with recurrent symptomatic atrial fibrillation refractory to conventional therapy can be treated successfully and safely with newer antiarrhythmic drugs. Treatment failures tend to occur early in the course of follow-up, permitting easy identification of candidates for alternative therapeutic approaches.

Asunto(s)

Asunto(s)

RESUMEN

Sixty patients who had recurrent episodes of symptomatic atrial fibrillation or flutter, or both, and who had failed one to five prior drug trials were treated with open label oral propafenone hydrochloride. On a mean maximal tolerated dose of 795 +/- 180 mg/day, actuarial estimates of the percent of individuals free of recurrences of symptomatic atrial fibrillation/flutter during propafenone treatment were: 1 month, 54%; 3 months, 44% and 6 months, 40%. No individual baseline characteristic achieved statistical significance as a correlate of poor response to propafenone. Drug-related adverse reactions were reported in 22% of patients but were severe enough to require termination of propafenone in only 5%. Thus, oral propafenone is a useful and well tolerated drug for long-term suppression of symptomatic recurrences of atrial fibrillation/flutter despite a history of unresponsiveness to prior antiarrhythmic drug treatment.

Asunto(s)

Asunto(s)