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PubMed1986

Vagally-mediated atrial fibrillation in dogs: conversion with bretylium tosylate.

We developed a stable, reproducible model of acute atrial fibrillation (sustained for up to 90 min) in open-chest, anesthetized dogs utilizing continuous bilateral stimulation of the cervical vagi and transient rapid atrial pacing. This model was then used to study the defibrillatory effects of bretylium tosylate. In five dogs, sequential runs of atrial fibrillation lasting 1-60 minutes were induced. A single, rapid, intravenous bolus of bretylium caused conversion of all episodes of atrial fibrillation (n = 31) after a mean of 33 seconds (range 15-151 sec). In 28 of 31 episodes (90%) conversion occurred within 40 seconds. The dose of bretylium was 2.5 mg/kg in all but one episode in which 5.0 mg/kg was given. We conclude that bilateral vagal stimulation produces a stable canine model of acute atrial fibrillation and that the arrhythmia is rapidly converted with intravenous bretylium.

Acute Disease↗
PubMed1983

The use of bretylium in prehospital ventricular fibrillation.

Bretylium tosylate is recommended by the American Heart Association Standards for Advanced Cardiac Life Support for refractory ventricular fibrillation after countershock, sodium bicarbonate, and epinephrine. According to this protocol, paramedics gave five to six milligrams per kilogram of intravenous bretylium by bolus in 96 patients with refractory fibrillation over a 24-month period. A positive response was defined as the presence of a palpable pulse following bretylium and countershock. Thirty-five percent of patients (34/96) responded following bretylium. Twenty-one percent (20/96) responded only temporarily with a rhythm and pulse. Fifteen percent (14/96) maintained a stable rhythm and vital signs on admission to the hospital, but only five patients, 5% of the total population, (5/96), were eventually discharged home. Clinical variables were similar in non-responders, temporary responders, and those admitted, but the times from the onset of Advanced Cardiac Life Support to receiving bretylium were 23.5 min, 20.3 min, and 14.3 min respectively. We conclude that about one-third of patients in refractory ventricular fibrillation respond following bretylium and countershock and that earlier bretylium use may give better results.

Bretylium Compounds↗
PubMed1984

Bretylium in severe ventricular arrhythmias associated with digitalis intoxication.

Bretylium has been well-recognized as an effective antiarrhythmic agent for acute ventricular arrhythmias, but its use is believed to be contraindicated in digitalis intoxication. We report of two patients in whom digitalis-induced malignant ventricular arrhythmias were refractory to lidocaine. One patient had had repeated episodes of ventricular fibrillation associated with digitoxin and quinidine intoxication, and one patient had had malignant premature ventricular beats associated with digoxin intoxication. Cardiac electrical activity was paced in both instances. In the two patients, ventricular arrhythmias rapidly resolved, and no side effect was encountered. These observations support the administration of bretylium for severe digitalis-induced ventricular arrhythmias.

Aged↗
PubMed1983

Effect of adrenergic blockade with bretylium and phentolamine on glomerular filtration rate in the rainbow trout, Salmo gairdneri Rich., adapting to saline water.

In resting conscious trout, Salmo gairdneri, a gradual increase in external salinity (brackish water) resulted in an immediate decline of glomerular filtration rate and urine flow. These renal responses were partly blocked by the administration of bretylium and phentolamine. The presence of adrenergic nerve endings in the trout kidney and these pharmacological results together provide evidence of neural control of renal haemodynamics. The action of vasoactive substances and innervation is discussed briefly in relation to their importance for normal renal function.

Adaptation, Physiological↗
PubMed1983

Severe hypotension due to the use of bretylium for postcardiotomy ventricular arrhythmias.

We describe three patients who developed refractory hypotension after the administration of bretylium tosylate for postoperative ventricular ectopy. In one patient, the administration of vasopressors and fluid restored the blood pressure, but in the other two patients these measures failed, necessitating open-heart cardiac massage. The hemodynamic effects of bretylium are unpredictable; therefore, this drug should be used cautiously in the treatment of postcardiotomy ventricular arrhythmias.

Adult↗
PubMed1980

Massive intravenous bolus bretylium tosylate.

A 30 mg/kg (2-gm) intravenous bolus of bretylium tosylate was administered to a patient with recurrent ventricular tachycardia and fibrillation. After successful defibrillation the patient exhibited marked hypertension followed by protracted refractory hypotension. There was no further ventricular ectopy in spite of a very low cardiac index. A bretylium level of 8,800 ng/ml is the highest reported in man from a single bolus injection. This case demonstrates the exaggerated hemodynamic response to massive intravenous bolus bretylium tosylate.

Bretylium Compounds↗
PubMed1981

Bretylium tosylate as initial treatment for cardiopulmonary arrest: randomized comparison with placebo.

To evaluate the therapeutic effectiveness of intravenous bretylium tosylate as a first-line drug for patients in cardiopulmonary arrest, a randomized, double-blind study was conducted, comparing bretylium with a normal saline placebo. Fifty-nine patients presenting to the emergency department with cardiopulmonary arrest due mainly to ventricular fibrillation or asystole initially received either bretylium (10 mg/kg) or placebo in a rapid intravenous bolus and were then otherwise treated according to standard American Heart Association guidelines. If ventricular fibrillation or asystole persisted, a second bolus of bretylium or normal saline was given after 20 minutes. Thirty-five percent of patients presenting with ventricular fibrillation or asystole who received bretylium were successfully resuscitated, whereas 6% of patients who received placebo survived (P less than 0.05). These findings serve to suggest that the early use of bretylium tosylate in cardiopulmonary arrest improves survival.

Anti-Arrhythmia Agents↗
PubMed1984

Antifibrillatory drugs: the case for bretylium tosylate.

The preferred treatment for ventricular fibrillation (VF) refractory to maximal electrical defibrillation remains controversial, as evidenced by recent changes in the American Heart Association's treatment algorithm. To date there have been no published studies conclusively proving one mode of therapy to be superior to another. There is, however, an abundance of animal and clinical data suggesting that bretylium tosylate (BT) is the drug of choice in this setting. In animal studies BT has been shown to lower the canine defibrillation threshold, to facilitate conversion of hypothermia-induced ventricular fibrillation, and to effect spontaneous defibrillation. In 15 years of clinical use as a drug of last resort, and more recently as a first-line drug, BT has developed an impressive track record. Most of the clinical reports are uncontrolled and/or retrospective, but they share a central theme: BT is effective in the treatment of VF refractory to standard therapy. Several small studies have reported successful conversion of VF to a stable rhythm with BT after failure of standard electrical and pharmacologic therapy. Recent studies suggest that earlier use of BT may be associated with improved outcome. Finally, as in animal studies, spontaneous defibrillation has been reported. It is important to note that no drug currently used in the treatment of countershock-refractory VF has been proven effective. The use of some of these drugs is based on tradition rather than scientific evidence. The bulk of currently available scientific data indicates that BT is superior to other commonly used antiarrhythmics in the treatment of VF resistant to countershock.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

A randomized comparison study of bretylium tosylate and lidocaine in resuscitation of patients from out-of-hospital ventricular fibrillation in a paramedic system.

A prospective, randomized study using either bretylium tosylate (BT) or lidocaine (L) as the first-line antiarrhythmic for patients in refractory ventricular fibrillation was conducted using the Milwaukee County Paramedic System. If the patient did not respond to the initial American Heart Association protocol, BT (10 to 30 mg/kg total) or L (2 to 3 mg/kg total) was given randomly as the first antiarrhythmic. If the patient failed to convert, the alternate antiarrhythmic was given. In the L group, 81% (39/48) of the patients obtained an organized electrical rhythm and 56% (27/48) converted to a rhythm with a pulse. The resuscitation rate (admission to an emergency department with pulse) was 23% (11/48), and the save rate was 10.4% (5/48). In the BT group, 74% (32/43) obtained an organized electrical rhythm, 35% (15/43) were converted, 23% (10/43) were resuscitated, and 5% (2/43) were saved. The only significant difference in outcome was that L converted patients better than did BT (P less than .05). Of the 24 patients known to be on digitalis preparations prior to arrest, 41% (5/12) in the L group were resuscitated and 16% (2/12) were resuscitated in the BT group. Data were analyzed for witnessed arrest outcome and for patients given multiple antiarrhythmics.

Aged↗
PubMed1984

Treatment of prehospital refractory ventricular fibrillation with bretylium tosylate.

Among 218 patients treated for prehospital arrest during an eight-month baseline period prior to addition of bretylium tosylate to the paramedic protocol in Columbus, 16 (7.3%) were seen with refractory ventricular fibrillation (RVF). These patients failed to respond to multiple countershocks, lidocaine, bicarbonate and epinephrine, and either were transported in arrest during cardiopulmonary resuscitation (CPR)(14) or were pronounced dead at the scene (2). A single patient was eventually resuscitated in and discharged from the hospital. During the subsequent 16 1/2-month experience with bretylium used only for prehospital RVF, 421 patients with prehospital arrest were seen, 35 of whom (8.3%) had RVF. All but five patients were defibrillated successfully, and 14 (40%) were converted to a rhythm sufficient to obviate CPR during transportation. Eleven patients (31%) survived to be admitted to the hospital, and eight of 35 (23% vs 1/16 or 6.2% above, P less than .05) were discharged and remained well three to 17 months later. Bretylium tosylate may provide life-saving therapy for refractory prehospital ventricular fibrillation so that survival from an almost uniformly fatal condition is improved. While patients with persistent arrest generally should be transported to the hospital, such patients should not be subjected to the difficulties of CPR in transit unless they are first given bretylium if RVF is present.

Bretylium Compounds↗
PubMed1984

Endotracheal bretylium tosylate in a canine model.

This study was conducted to determine whether bretylium tosylate (BT) is effectively and safely absorbed through the endotracheal route in the canine model. Eleven adult mongrel dogs were anesthetized with pentobarbital, were orally intubated, and had continuous blood pressure and electrocardiographic monitoring. Four dogs received 5 mg/kg BT, three dogs received 10 mg/kg BT, two dogs received 20 mg/kg BT, and two control dogs were given volumes of normal saline equal to those given the 5- and 10-mg/kg groups. Each dog received the same dose of BT both endotracheally and intravenously, but in a random order and on different dates. Following each drug administration arterial blood was drawn at various intervals over two hours and sent for immediate gas analysis; serum samples were frozen for future determination of BT levels. Regardless of the amounts delivered, the peak levels of BT in the arterial blood following administration by the endotracheal route were consistently low (4.13 micrograms/mL to 14.00 micrograms/mL) when compared to those levels following intravenously administered BT (120 micrograms/mL to 268 micrograms/mL) (all P less than .002 for the 5- and 10-mg/kg groups). No depot effect was observed during a two-hour period. The arterial blood gases did not change significantly following the administration of BT by the endotracheal route in the 5- and 10-mg/kg groups, and sections of these autopsied dog lungs showed no apparent pathologic changes.

Animals↗
PubMed1986

Use of bretylium tosylate as prophylaxis and treatment in hypothermic ventricular fibrillation in the canine model.

We conducted a study to determine if bretylium tosylate (BT) is effective in the prophylaxis and treatment of hypothermic ventricular fibrillation (VF) in the setting of various maneuvers thought to induce this lethal arrhythmia. Twenty-two mongrel dogs were cooled to 24 C after being placed in a cold room. At 24 C, a double-blinded placebo or BT solution was infused. The dogs then were removed from the cold. They underwent the following sequential maneuvers: oral endotracheal extubation and intubation, central line and nasogastric tube placement, vigorous movement, and Swan-Ganz catheter insertion. If VF ensued, arterial blood gases were drawn, and BT was given only if refractory to countershock and epinephrine. Of the dogs that were given placebo, six of 11 (55%) fibrillated with manipulation, as compared with one of 11 (9%) dogs pretreated with BT (P = .067). Three of the 11 dogs that received BT fibrillated within minutes of its infusion. In the placebo dogs that fibrillated, four required BT and two defibrillated with countershock alone or with epinephrine prior to achieving stable rhythms.

Animals↗