Biomedical subjects

E A O'Rangers

Publications and source records attributed to E A O'Rangers.

7 recordsLinked to original sources

PubMed1996

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.

Adult↗

PubMed1995

Intravenous phosphate repletion regimen for critically ill patients with moderate hypophosphatemia.

OBJECTIVE: To document the safety and efficacy of an intravenous phosphate repletion regimen that is more aggressive than recommended by previously published guidelines, in intensive care unit (ICU) patients with hypophosphatemia. DESIGN: Prospective evaluation of rapid, intravenous phosphate repletion in eligible patients. SETTING: Surgical ICU in a teaching hospital. PATIENTS: Patients with a serum phosphorus concentration of < 2 mg/dL (< 0.65 mmol/L) while in the ICU. INTERVENTIONS: Enrolled patients received 15 mmol of sodium phosphate in 100 mL of 0.9% sodium chloride, infused intravenously over a period of 2 hrs. Patients with a serum potassium concentration of < 3.5 mmol/L received potassium phosphate, if no other potassium supplementation was ordered. The same dose could be repeated to a maximum of 45 mmol in a 24-hr period if either the 6-hr or follow-up (18- to 24-hr) postinfusion serum phosphorus remained < 2 mg/dL (< 0.65 mmol). Serum electrolytes, renal function, vital signs, and reflexes were closely monitored. MEASUREMENTS AND MAIN RESULTS: Eleven patients enrolled had baseline serum phosphorus values of 1.6 to 1.9 mg/dL (0.51 to 0.61 mmol/L). The serum phosphorus value immediately postinfusion was 2.3 to 5.3 mg/dL (0.74 to 1.7 mmol/L). Only one patient had a 6-hr postinfusion serum phosphorus of < 2 mg/dL (< 0.65 mmol/L), requiring two additional doses. Two other patients each required a second dose. Serum phosphorus was corrected in other patients with a single dose. No significant changes were noted in serum calcium, magnesium, or potassium concentrations, urine output, vital signs, or reflexes throughout the repletion period. CONCLUSIONS: All patients were successfully repleted using the described protocol without any significant adverse effects. This repletion regimen may have widespread applicability in the ICU setting.

Adult↗

PubMed1993

The pharmacokinetic and pharmacodynamic interaction between propafenone and lidocaine.

Although propafenone is a known substrate and inhibitor of the cytochrome P450 4-hydroxylation pathway of debrisoquin (CYP2D6 isozyme), its effects on other hepatic mixed- function oxidative isozymes have not been extensively evaluated. We studied the influence of propafenone on the disposition of continuously infused lidocaine in 12 healthy male volunteers. Placebo or propafenone (225 mg every 8 hours) was orally administered for 4 days before and during lidocaine administration (2 mg/kg/hr for 22 hours). In the 11 (92%) subjects phenotyped as extensive metabolizers, propafenone significantly increased the lidocaine area under the plasma concentration time curve (81.7 +/- 16.2 versus 76.3 +/- 15.6 micrograms.hr/ml; p < or = 0.05) and reduced systemic lidocaine clearance (9.53 +/- 1.77 versus 10.27 +/- 2.24 ml/min/kg; p < or = 0.05), but did not significantly affect volume of distribution at steady state (2.48 +/- 0.33 versus 2.64 +/- 0.45 L/kg; p = 0.10) or mean residence time (4.37 +/- 0.92 versus 4.47 +/- 0.87 hours; difference not significant) compared with placebo, respectively. Adverse central nervous system effects were significantly worse in severity and duration during the propafenone phase (p < or = 0.05). Propafenone minimally inhibits the metabolism of lidocaine. This suggests that the ability of propafenone to inhibit metabolic pathways exclusive of the CYP2D6 isozyme may be limited. In addition, potentiation of disturbing central nervous system adverse effects may occur during combination therapy of propafenone and lidocaine.

Adult↗

PubMed1993

Antifibrillatory and electrophysiologic actions of moricizine alone and in combination with lidocaine: a prospective, randomized trial.

OBJECTIVE: The Cardiac Arrhythmia Suppression Trial II showed that moricizine acutely increases the occurrence of sudden cardiac death. Thus the objective of this investigation was to evaluate the antifibrillatory properties of moricizine (a new antiarrhythmic agent) alone and in combination with lidocaine (an established antifibrillatory agent). DESIGN: Prospective, double-blind, randomized, placebo-controlled trial. SETTING: Laboratory at a large, university-affiliated medical center. SUBJECTS: Eighteen domestic farm swine with a mean weight of 39 +/- 5 kg. INTERVENTIONS: After pentobarbital anesthesia, the animals were instrumented. A bipolar pacing catheter was placed in the right ventricular apex and a pig-tail catheter was placed in the aortic arch for induction of ventricular fibrillation and aortic blood pressure monitoring. Subsequently, the pigs were randomized to moricizine or control (0.9% saline) groups. Each group underwent three treatment phases: baseline, drug (moricizine 2 mg/kg loading dose, 1.5 mg/kg/hr infusion, or saline bolus and infusion), and drug combined with lidocaine (5 mg/kg loading dose, 4 mg/kg/hr infusion). Ventricular fibrillation threshold was determined every 5 to 10 mins over a 1-hr period during each treatment phase. RESULTS: Ventricular fibrillation threshold values in the animals randomized to control were 16.8 +/- 7.6, 18.1 +/- 8.9, and 23.9 +/- 10.4 mA at baseline during saline infusion, and when saline was combined with lidocaine, respectively. The values during the saline-lidocaine combination treatment phase were significantly greater than the values at baseline and during saline treatment alone (p < .001). Ventricular fibrillation threshold values in the animals randomized to receive moricizine were 15.5 +/- 4.4, 18.1 +/- 5.1, and 21.1 +/- 8.4 mA at baseline, during moricizine infusion, and when moricizine was combined with lidocaine. The values during the lidocaine-moricizine combination treatment phase were significantly greater than values at baseline (p = .005), but not during moricizine treatment alone (p = .16). The increase in ventricular fibrillation threshold from baseline to moricizine (17%) was similar to the increase from baseline to saline (7%), p = .37. The increase in ventricular fibrillation threshold when lidocaine was added to moricizine (13%) was less than the increase with lidocaine alone (32%), p = .05. CONCLUSION: In this experimental model, moricizine, at the dose studied, lacked antifibrillatory properties. Moreover, moricizine did not contribute to the antifibrillatory effects of lidocaine.

Animals↗

PubMed1992

Defibrillation energy requirements during moricizine and moricizine-lidocaine therapy.

Defibrillation energy requirements may be altered by antiarrhythmic agents. We investigated the effects of moricizine on the defibrillation threshold (DFT) in 18 pentobarbital-anesthetized pigs. The animals were randomized, in a blinded fashion, to moricizine or control (0.9% saline) treatment groups. Each group underwent three treatment phases: baseline, drug infusion (moricizine or saline), and drug infusion combined with lidocaine. Moricizine (2 mg/kg loading dose, 1.5 mg/kg/h infusion) and lidocaine (5 mg/kg loading dose, 4 mg/kg/h infusion) were dosed to achieve therapeutic concentrations. After 5 s of induced ventricular fibrillation, defibrillation was performed using a cardiac defibrillator interfaced with two epicardial electrode patches. DFTs were determined at baseline, during the drug phase, and during the combination of lidocaine with moricizine or saline. DFT values in the animals randomized to the control group were 15.2 +/- 4.2, 14.0 +/- 3.3, and 17.8 +/- 8.7 J at baseline, saline infusion, and saline combined with lidocaine, respectively. No significant differences were observed among the treatment phases. DFT values in the animals randomized to moricizine group were 12.1 +/- 2.8, 13.8 +/- 5.2, and 22.9 +/- 7.1 J at baseline, moricizine infusion, and moricizine combined with lidocaine, respectively. The DFT values during the lidocaine-moricizine combination treatment phase were significantly greater than baseline and moricizine alone (p < 0.002). The mean change in the DFT from baseline to moricizine (14% increase) was significantly different than the mean change in the DFT from baseline to saline (8% decrease) (p = 0.03). Lidocaine added to moricizine increased the DFT by 84%, which was significantly different from the 27% increase in the DFT when lidocaine was added to saline (p = 0.02). We conclude that moricizine minimally increases the DFT, but the combination of moricizine with lidocaine results in a synergistic rise in the DFT that may have detrimental clinical implications.

Animals↗

PubMed1992

Exacerbation of congestive heart failure secondary to moricizine.

Moricizine, a recently approved phenothiazine antiarrhythmic agent, is reported to be associated with a low frequency of congestive heart failure. A 61-year-old man with a history of congestive heart failure and ischemic heart disease began taking moricizine 250 mg every 8 hours to suppress his monomorphic sustained ventricular tachycardia. After five doses he became progressively short of breath and was in pulmonary edema. Moricizine was discontinued, intravenous diuretics were administered, and the patient's clinical status stabilized. Twelve hours later, however, he developed polymorphic ventricular tachycardia and was not successfully resuscitated. Despite claims as to its safety, limited data strongly suggest that moricizine, like other antiarrhythmics, may be detrimental in patients with preexisting ventricular dysfunction, and should be prescribed with caution.

Connecticut↗

PubMed1990

Adenosine.

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Adenosine↗