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This drug has been approved by the FDA for
use in the cardioversion of atrial flutter and fibrillation. It activates the slow inward
sodium current (INa-s)1 and inhibits the rapidly activating component of the delayed
rectifier potassium current (Ikr)2. These actions bring about an increase in action
potential duration and therefore of the effective refractory period; the importance of
these effects is dose-related. Conduction velocity is not affected. As with dofetilide it
has been shown to have an effect on the lengthening of the refractory period, which is
inversely dependent on frequency (reverse use-dependence)3. The drug has a high
distribution velocity over a high volume4. It has a low link with plasmatic proteins and a
half-life of 2-12 hours (6 hours on average)5. It has not produced any unfavourable
interactions with digoxin, calcium-antagonists or beta-blockers; combination with QT
interval prolonging drugs (IA and III classes of the anti-arrhythmics) is to be avoided. QT
interval prolongation is dose-related and is greater in the presence of low-level serum
calcium and at younger ages6. The excessive increase of this interval seems to be
correlated with a greater risk of the occurrence of torsades des pointes. This arrhythmia,
which has been reported in around 2-5% of patients treated, is easy to control thanks
to the high velocity of distribution and elimination of the drug and to the fact that the
pro-arrhythmic risk is dose-related. Post-infusional monitoring of four hours is sufficient
to minimise the risks correlated with the occurrence of arrhythmic complications that
mostly appears in the first hour. This approach, on the other hand, is impossible with
quinidine, which brings with it the rather unpredictable risk of arrhythmia, both as
regards time and dose. Another advantage of ibutilide is the absence of negative
hemodynamic effects; at doses of between 0.01 and 0.03 mg/kg it does not significantly
alter cardiac output, arterial pressure, pulmonary arterial pressure or pulmonary
capillary wedge pressure in patients with ejection fraction either above or below 35%7.
Its administration has not aggravated the condition of patients with left ventricular
dysfunction4.
Ellenbogen et al (1996) have evaluated the effectiveness of ibutilide in 200 patients with
atrial flutter lasting more than 3 hours and atrial fibrillation lasting for more than 3
hours and less than 90 days. Seventy-two percent of the patients presented with
structural heart disease. An almost equal number of patients received either placebo
or ibutilide randomly at a dose of 0.005, 0.010, 0.025 mg/kg over 10 minutes. Placebo
resulted in cardioversion in 3% of cases; the drug resulted in cardioversion in 12, 33, 45
and 46% of cases respectively with increasing doses. The success rate for atrial flutter
was greater. 3.6% of the patients treated developed polymorphous ventricular
tachycardia8. In the same year Stambler et al studied 266 patients with flutter (133 pts)
or atrial fibrillation (133 pts) arising from 3 to 45 days previously, administrating
placebo or ibutilide in double administration (1 mg and 0.5 mg or 1 mg and 1 mg)
with an interval of 10 minutes. Placebo was associated with a 2% of cardioversions,
ibutilide with 47% (44 and 49% respectively). The success rate was greater for flutter
than for atrial fibrillation (63 vs 31%). 8.3% of the patients treated developed
polymorphous ventricular tachycardia requiring electric cardioversion in 1.7% of cases9.
Other recent studies have shown the greater effectiveness of ibutilide in cardioversion
of atrial flutter and fibrillation compared to
procainamide10 and to dl-sotalol11. Where
there is lack of success in the case of atrial flutter successive atrial stimulation in
overdrive has proved to be more effective than pre-treatment with placebo (87 vs 18%)
and less likely to risk causing atrial fibrillation12.
Recently, Oral examined the effect of ibutilide in 100 patients subjected to transthoracic
cardioversion who had had atrial fibrillation for a mean of 117±201 days. In all 50
patients who had received 1 mg of ibutilide conversion to sinus rhythm occurred with a
mean energy required for defibrillation of 166±80 Joules. On the other hand in 14 of 50
patients who had not received ibutilide pretreatment transthoracic cardioversion failed,
in the remaining 36 conversion to sinus rhythm occurred with a mean energy required
for defibrillation of 228±93 Joules. The 14 patients in whom transthoracic cardioversion
failed received 1 mg of ibutilide and cardioversion was attempted again with success in
all subjects. In conclusion the ibutilide pretreatment enhanced the efficacy of
transthoracic cardioversion and decreased the mean energy required for defibrillation
in patients with atrial fibrillation13.
In conclusion, it must be remembered to ascertain at all times that the atrial fibrillation
or atrial flutter commenced less than 90 days previously, that serum potassium and
serum magnesium are normal, that the patient does not present with a long QT interval
(0.44 sec) or previous episodes of torsade de pointe, and that suitable anti-coagulation
therapy has been applied if the arrhythmia commenced more than two days previously.
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