Biomedical subjects
J Kluger
Publications and source records attributed to J Kluger.
Poisonous plastics? Some cling wraps, children's toys and even IV bags may be carrying--and shedding--toxic chemicals.
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An assessment of the safety of short-term amiodarone therapy in cardiac surgical patients with fentanyl-isoflurane anesthesia.
UNLABELLED: In previously published case reports and a retrospective study, investigators have noted that amiodarone may cause substantial hemodynamic instability when combined with fentanyl-containing anesthesia regimens. We performed the present study to evaluate the safety of short-term amiodarone therapy when combined with a fentanyl-containing anesthesia regimen in a randomized, double-blinded, placebo-controlled format. After institutional approval and written informed consent, patients scheduled to undergo coronary artery bypass grafting or valvular surgery were randomly allocated to receive amiodarone (3.4 g over 5 days or 2.2 g over 24 hours) or placebo before surgery. Four indicators for hemodynamic instability were assessed: 1) a net increase in fluid balance during surgery of >2 L; 2) use of dopamine at a rate >10 microg x kg(-1) x min(-1); 3) use of other vasopressive catecholamines; and 4) use of a phosphodiesterase inhibitor or intraaortic balloon pump. Systolic, diastolic, and central venous pressures were measured before fentanyl administration, before cardiopulmonary bypass (CPB), and after separation from CPB. Overall, 84 patients (45 patients in the amiodarone group, 39 in the placebo group) were enrolled and completed the study. There were no significant differences between the two groups in any indicator for hemodynamic instability or the indicators of instability combined. After CPB, there was a significantly lower systolic blood pressure in the amiodarone group compared with the placebo group (112 +/- 12 vs 117 +/- 14 mm Hg; P = 0.049). However, there was a trend toward smaller IV fluid requirements during surgery in the amiodarone group compared with the placebo group (438 +/- 867 vs 907 +/- 1640 mL; P = 0.09). We found no increased risk of hemodynamic compromise after short-term amiodarone therapy among patients receiving a fentanyl-containing anesthesia regimen during open heart surgery. IMPLICATIONS: In previous retrospective studies and case reports, investigators have identified a possible risk of hemodynamic compromise when patients receiving chronic amiodarone therapy are given anesthesia regimens containing fentanyl. We performed a prospective, randomized, double-blinded study to evaluate the hemodynamic effects of short-term amiodarone therapy during fentanyl-isoflurane anesthesia for open heart surgery. No adverse hemodynamic effects of amiodarone were identified.
A comparison of the antifibrillatory effects of desethylamiodarone to amiodarone in a swine model.
We evaluated the effect of two different doses of desethylamiodarone (DEA) and amiodarone on the ventricular fibrillation threshold (VFT). We ascertained the VFT in 24 pigs randomized to intravenous DEA, amiodarone, or vehicle. Ventricular fibrillation was induced by pacing the right ventricle by using a primary drive train at a cycle length of 270 ms for eight beats of 2-ms duration each. A secondary train of 20 pulses of 4-ms duration (100 Hz) immediately followed this over a total duration of 200 ms synchronized to the primary drive train. The intensity of the secondary train stimuli current was initially 2 mA and was increased by 2-mA increments until sustained VF with hemodynamic collapse was induced. The minimal current strength needed to induce sustained VF was defined as the VFT measured in mA. DEA (10 mg/kg) increased the VFT significantly over baseline from 13.5+/-4.9 to 23.2+/-8.8 mA (p = 0.0076). Amiodarone, 10 mg/kg, increased the VFT significantly over baseline (mean +/- SD) from 14.4+/-3.6 to 23.8+/-6.1 mA (p = 0.0016). An additional dose of amiodarone (15 mg/kg) increased the VFT to 38.5+/-15.9 mA, which is significantly greater than the VFT derived from lower-dose amiodarone (p = 0.046). We showed that DEA (10 mg/kg) has a similar antifibrillatory effect as 10 mg/kg of amiodarone. We also demonstrated a dose-dependent effect on VFT for amiodarone.
The effect of amiodarone on the ventricular fibrillation threshold.
We evaluated the antifibrillatory effect of two different doses of amiodarone after cardiac arrest with a cardiopulmonary resuscitation (CPR) model in 19 pigs. Ventricular fibrillation was induced by pacing the right ventricle using a primary drive train at a cycle length of 270 msec for 8 beats. The minimum current strength necessary to induce sustained ventricular fibrillation was defined as the ventricular fibrillation threshold (VFT) measured in mA. Three VFT determinations were made at baseline, followed by 9 minutes of continuous CPR with two determinations of VFT, and three after stabilization. The pigs were placed into one of three groups: amiodarone 2 or 5 mg/kg, or placebo. The average poststabilization VFT in each group was compared with the average baseline VFT. Pigs receiving amiodarone 2 mg/kg had significantly higher VFT after stabilization than at baseline (22.88+/-12.76 to 27.10+/-10.18 mA, p=0.048), as did those receiving 5 mg/kg (17.03+/-7.01 to 28.08+/-11.58 mA, p=0.002). The deltaVFT was significantly greater with amiodarone 5 mg/kg than with vehicle (placebo), but not with 2 mg/kg. There were no changes in VFT in any group during CPR versus baseline. When active treatments were combined, the trend was toward better survival in the amiodarone groups (13/13) compared with the placebo group (4/6, p=0.076).
Prophylactic magnesium to decrease the arrhythmogenic potential of class III antiarrhythmic agents in a rabbit model.
We assessed the prophylactic effect of intravenous magnesium sulfate on the occurrence of torsades de pointes and early after-depolarizations, and on the QT interval (QTc) in an established rabbit model. Ten rabbits were given intravenous methoxamine to slow their heart rates. After 12 minutes five animals received a 60-mg/kg bolus and continuous infusion of magnesium 0.6 mg/kg/minute, and five received equivolume normal saline concurrently with the class III antiarrhythmic agent clofilium 5 mg/kg over 30 minutes. Electrocardiogram lead II and the monophasic action potential were recorded continuously throughout the experiment. The magnesium group experienced significantly less torsades de pointes and early after-depolarizations than the normal saline group (1/5 and 5/5 both parameters, respectively, p=0.048). There were no differences between groups in QT or QTc interval at baseline or at maximum QT or QTc prolongation. Magnesium decreases the occurrence of torsades de pointes without affecting the QT or QTc interval but does decrease the occurrence of early after-depolarizations. These findings must be validated in human studies.
Mechanisms of syncope in implantable cardioverter-defibrillator recipients who receive device therapies.
A significant proportion of implantable cardioverter defibrillator (ICD) recipients ultimately receive device therapies. Determinants and mechanisms of syncopal events in these patients are not established. To address this issue, we reviewed prospectively collected data on 114 ICD recipients who received device therapies. There were 99 men and 15 women with a mean age of 63+/-10 years. Ejection fraction was 29+/-13%. At initial presentation, 74 patients (65%) had syncope during arrhythmia. Of 114 patients, 18 patients (16%) subsequently experienced syncope during device therapies over a period of 35+/-24 months of follow-up. Arrhythmias during syncopal events documented by telemetry, event recorders, RR intervals, or ICD stored electrograms were obtainable in 13 patients, and included sustained monomorphic ventricular tachycardia (VT) in 10 patients, ventricular fibrillation (VF) in 2 patients, and atrial fibrillation in 1 patient. The explanations for arrhythmia-related syncope included ICD proarrhythmia in 8 patients (62%), rapid monomorphic VT in 3 (23%), and VF in 2 patients (15%). Patients with syncope could not be differentiated from those without syncope by demographic, clinical, or electrophysiologic variables. There was no significant difference in mortality between patients with or without syncope (39% vs 25%, p = 0.25). Syncope is not uncommon in ICD recipients who receive device therapies. When it occurs, syncope is often due to ICD proarrhythmia; hence, it is potentially preventable by meticulous device programming.
Usefulness of intravenous metoprolol to prevent syncope induced by head-up tilt.
Intravenous metoprolol was found to be significantly more effective than placebo in preventing head-up tilt-table induced neurally mediated syncope. The reproducibility of acute tilt-table testing is only 63% and suggests caution in the interpretation of acute drug testing during tilt-table studies.
Efficacy of intravenous granisetron in suppressing the bradycardia and hypotension associated with a rabbit model of the Bezold-Jarisch reflex.
This study investigated whether granisetron, a 5-HT3 receptor antagonist, can alter the Bezold-Jarisch reflex (i.e., hypotension and inappropriate heart rate slowing). A hemorrhagic rabbit model that has been shown to induce the Bezold-Jarisch reflex was used. In 11 rabbits (3.8 kg), catheters were placed in the carotid arteries one day before experimental hemorrhage. On the day of the study, the rabbits were given intravenous granisetron (50 micrograms/kg) or an equal volume of saline. Five minutes after administration of granisetron or saline, hemorrhage was induced by continuous blood withdrawal at 5 mL/min and blood pressure (BP) and heart rates were obtained at frequent intervals until systolic BP declined to 80 mmHg. Six rabbits received saline and five granisetron. An average of 77.6 mL +/- 16.4 mL of blood was removed in the group receiving granisetron (compared with 56.5 mL +/- 13.1 mL for the saline group) before achieving the target systolic BP of 80 mmHg. The group receiving granisetron demonstrated the same ability to increase their heart rate from baseline as the saline group. However, the granisetron group had a final heart rate that was closer to their maximal heart rate than the saline group. In this animal model, granisetron was significantly more effective at preventing inappropriate heart rate slowing and allowed significantly more blood to be removed before reaching the target blood pressure. This implies that granisetron may be effective in preventing vasovagal syncope, although further study should be carried out to verify these potentially interesting findings.
Effects of amiodarone and its active metabolite desethylamiodarone on the ventricular defibrillation threshold.
OBJECTIVES: We evaluated whether the reported difference in the ventricular defibrillation threshold (DFT) between short-term intravenous and oral amiodarone is due to the effect of amiodarone's active metabolite desethylamiodarone (DEA). BACKGROUND: Amiodarone is frequently used in patients with implantable cardioverter-defibrillator devices (ICD). Long-term oral amiodarone raises the DFT, but intravenous amiodarone has not been shown to have this effect. DEA, an active metabolite of amiodarone, has different electrophysiologic properties than its parent compound and may be responsible for the observed different effects of intravenous and oral amiodarone on DFT. METHODS: We ascertained the DFT in 24 pigs randomized to receive intravenous amiodarone, DEA or vehicle. Defibrillation was delivered through a transvenous lead system using a biphasic waveform. The DFT was determined using an up-down DFT algorithm and defined as the average minimal energies resulting in successful defibrillation delivered from ascending and descending serial shocks. RESULTS: Amiodarone caused a dose-response increase in DFT (mean +/- SD) from 22.7 +/- 4.1 (baseline) to 26.1 +/- 2.9 (10 mg/kg body weight), p = 0.11, to 34.9 +/- 8.2 J (after an additional 15 mg/kg), p = 0.035. DEA (10 mg/kg) caused an increase in DFT from 20.5 +/- 6.3 to 33.9 +/- 13.6 J, p < 0.01. Addition of 15 mg/kg of DEA resulted in hemodynamic instability and thus DFT was not obtained. In the control group, DFT decreased from 26.8 +/- 7.7 at baseline to 23.1 +/- 7.4 (dose 1), p = 0.19, to 22.8 +/- 6.2 J (dose 2), p = 0.18. CONCLUSIONS: DEA increases DFT by a greater amount than its parent drug amiodarone. There is an effect of intravenous amiodarone on DFT that is dose dependent.
Recurrent polymorphic ventricular tachycardia complicating radiofrequency catheter ablation of the atrioventricular junction.
Recurrent ventricular tachycardia and ventricular fibrillation were observed immediately after RF ablation of the AV junction in a 64-year-old man. This arrhythmia was preceded by ventricular bigeminy and a long-short sequence. It was not associated with prolongation of the QT interval compared to baseline, and recurred 3 months later despite ventricular pacing at 90 beats/min. This is the first reported case of sustained ventricular arrhythmia complicating RF AV junction ablation despite rapid ventricular pacing, and recurring 3 months after discharge. It may explain the rare cases of sudden death complicating this procedure.
Matters of the heart.
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De novo monomorphic and polymorphic ventricular tachycardia following coronary artery bypass grafting.
We compared de novo monomorphic and polymorphic ventricular tachycardia (VT) occurring after coronary artery bypass graft surgery in 21 patients. Our findings support an underlying arrhythmogenic substrate for de novo monomorphic VT, whereas polymorphic VT is more likely related to transient perioperative abnormalities.
Amiodarone induced torsades de pointes with excessive QT dispersion following quinidine induced polymorphic ventricular tachycardia.
We report a case of amiodarone induced torsades de pointes (TdP) associated with increase QT dispersion in a patient with a history of quinidine induced TdP. An increase in QT dispersion of > 100% was noted on the 12 lead surface ECG postamiodarone therapy. In summary, amiodarone has a potential to induce TdP in patients with a previous history of quinidine induced TdP. QT dispersion could be a potential marker of TdP in these patients.
Pharmacokinetics of intravenous amiodarone in patients with impaired left ventricular function.
To evaluate the potential need for modification of dose regimens of intravenous amiodarone in patients with left ventricular dysfunction, the pharmacokinetics of amiodarone and its active metabolite, desethylamiodarone (DEA), were examined after a single 15-minute intravenous infusion of amiodarone 5 mg/kg. Three parallel groups of otherwise healthy volunteers with normal (n = 12), moderately impaired (ejection fraction > 30 but < or = 45%; n = 6), or severely impaired (ejection fraction < or = 30%; n = 6) left ventricular function were enrolled in the study. Serial blood samples were obtained over a 76-day period for estimation of pharmacokinetic parameters. With the exception of the half-life (t1/2) of DEA, statistical comparisons revealed no significant between-group differences in pharmacokinetic parameters or correlations between pharmacokinetic parameters and ejection fractions. The t1/2 of DEA was increased by approximately 60% in patients with severe left ventricular dysfunction compared with that in patients with moderately impaired and normal left ventricular function. The rate of DEA formation is slow, however, and its concentration relative to amiodarone is low. Therefore, it is unlikely that concentrations of DEA in serum would reach levels that contribute significantly to the pharmacologic activity of amiodarone during short-term (up to 2 weeks) intravenous amiodarone therapy. Single doses of amiodarone were well tolerated. The results of this study suggest that intravenous amiodarone can be used with appropriate observation to control arrhythmias, regardless of the degree of left ventricular dysfunction.