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PubMed1990

[Cardiotoxicity of continuous intravenous infusion of 5-fluorouracil: clinical study, prevention and physiopathology. Apropos of 13 cases].

5-Fluorouracil (5FU) cardiotoxicity is thought to be an infrequent toxic effect, usually related to coronary vasospasm. Among 198 patients (pts) receiving 5FU as a continuous infusion (CI) over 96 or 120 h, at a daily dose of 1,000 mg/m2, 13 new cases of 5FU--cardiotoxicity are reported. In all cases but 1, cardiovascular symptoms occurred at the first 5FU-CI course, with mean time of onset of 3 d. Chest pain was the prominent inaugural symptom with angor pectoris (6 pts) and pericarditis (3 pts). Five pts developed cardiogenic shock, which was irreversible in 3 cases. The severity of such an evolution requires prompt 5FU discontinuation, if symptoms occur, and careful hemodynamic supervision during 5FU therapy. One patient experienced typical myocardial infarction, another one epicardo myocardiopathic process with adiastolia. Disorders of repolarisation on electrocardiographic tracing were the prominent abnormalities, associated with a significant increase of QT segment in 3 cases. Re-introduction of 5FU-CI resulted in chest pain recurrence in 2 out of 4 pts, despite calcium antagonist "prevention". In our retrospective study, the incidence of 5FU-CI cardiotoxicity is 6.5%, which is consistent with recent reports (10%). Whether 5FU-induced cardiotoxicity mechanism is related to vasospastic or direct effect remains unclear. However, our series suggests a 5FU-induced post ischaemic myocardial dysfunction as described in the "stunned myocardium" syndrome.

Adult↗
PubMed1990

Human pharmacokinetics and pharmacodynamics of MF 701 dermatan sulfate administered by continuous intravenous infusion.

The pharmacokinetics and haemostatic effects of MF 701 dermatan sulfate (DS) administered by i.v. infusion were studied in 11 healthy volunteers. Each subject received 0.6 mg kg-1 h-1 MF 701 for 10 h. DS plasma concentrations were measured by a chromogenic assay based on the catalysis of thrombin inhibition by HCII. DS plasma levels followed a single compartment pharmacokinetic model, with a half-life of 1.28 +/- 0.46 h, a plasma clearance of 2.75 +/- 0.46 l/h and a volume of distribution of 4.92 +/- 1.36 1 (means +/- SD). Steady-state was reached 3 to 6 h after infusion started. The maximal DS plasma concentration was 16.4 +/- 5.7 micrograms/ml. Maximal APTT prolongation over pre-infusion values was 42 +/- 7%; TCT performed with bovine and human thrombin was prolonged by 16 +/- 7% and 83 +/- 35% respectively. No anti-IIa or anti-Xa activities were detected by chromogenic tests. The treatment was well tolerated. The pharmacokinetics of MF 701 infusion are consistent with those previously described after i.v. bolus administration. The infusion of MF 701 allows fast achievement and steady maintenance of elevated DS plasma concentrations.

Adolescent↗
PubMed1990

General anesthesia with propofol (continuous intravenous infusion) supplemented with nitrous oxide: comparison with isoflurane.

Thirty adult surgical patients (ASA I-II) undergoing superficial operations of short duration (about 1h) were arbitrarily divided into two groups. In group A (n = 15), anesthesia was induced with propofol, 2 mg/kg, iv. After endotracheal intubation with the aid of succinylcholine (1 mg/kg, iv), anesthesia was maintained by continuous iv infusion of propofol (0.05-0.2 mg/kg/min) with nitrous oxide and oxygen (2:1). In group B (n = 15), induction and endotracheal intubation were accomplished using thiopental (4 mg/kg, iv) and succinylcholine (1 mg/kg). Anesthesia was maintained with isoflurane (0.5-2.0%), nitrous oxide and oxygen (2:1). Atracurium was used in both groups as muscle relaxant. Hemodynamic responses to laryngoscopy and endotracheal intubation and during operation were not significantly different between the two groups. However, recovery to verbal command and orientation was significantly more rapid in the propofol group (7.8 +/- 4.8 min and 11.2 +/- 5.1 min) than in the isoflurane group (15.6 +/- 4.9 min and 22.6 +/- 6.0 min). In conclusion, continuous propofol infusion combined with nitrous oxide and muscle relaxant is suggested as a better method compared with isoflurane for short operations because of more rapid complete recovery.

Adult↗
PubMed1990

Investigation of the beta 2-agonist properties of dilevalol: metabolic effects of intravenous infusion.

We describe two studies which investigate the beta 2-agonist properties of dilevalol. We have previously demonstrated, by giving an infusion of terbutaline to human volunteers, that beta 2-stimulation causes a rise in plasma glucose and a fall in plasma potassium. These metabolic effects can be prevented by prior beta-blockade. We now show that infusion of dilevalol produces similar, but quantitatively smaller, metabolic effects at a dose which also produces clinically significant beta-blockade, as judged by a fall in exercise heart rate. This adds support to the claim that dilevalol is a non-selective beta-blocker with selective beta 2-agonist activity.

Adult↗
PubMed1989

Alterations in polyamine metabolism during continuous intravenous infusion of alpha-difluoromethylornithine showing correlation of thrombocytopenia with alpha-difluoromethylornithine plasma levels.

Polyamine biosynthesis is important for cell proliferation and growth. The purpose of this study was to determine the biochemical and pharmacological parameters associated with host toxicity from a continuous infusion of alpha-difluoromethylornithine (DFMO). Twenty-five patients with metastatic carcinoma of the colon or rectum received continuous infusion of DFMO at a median dose of 8 g/m2/day (range, 6-14) for 28 days. DFMO plasma levels, RBC, plasma putrescine, spermidine, and spermine levels, and patient toxicities were evaluated. There was a significant decrease in RBC and plasma levels of putrescine, spermidine, and spermine following DFMO administration compared with the baseline RBC and plasma levels. Pearson correlation coefficient comparing nadir platelet count and steady-state DFMO level was statistically significant (n = 37; P less than 0.01; r = -0.53). Sustained suppression of circulating polyamine levels was also achieved with continuous DFMO infusion. The correlation between steady-state plasma DFMO levels and lowering of platelet count warrants prospective evaluation to determine its clinical usefulness.

Eflornithine↗
PubMed1989

Pharmacokinetics of disodium clodronate after daily intravenous infusions during five consecutive days.

The pharmacokinetics of disodium clodronate was studied in six patients, three females and two males with Paget's disease and one male patient with prostatic cancer. The drug was given at a dose of 300 mg/day as a 3-hour infusion for 5 consecutive days. The concentration of the drug in serum and urine was measured by a gas chromatographic method. The peak concentration of disodium clodronate in serum was 5.7 +/- 1.0 micrograms/ml (means +/- SD) for the males and 10.1 +/- 2.8 micrograms/ml for the females. The elimination half-lives of the drug were 0.76 +/- 0.47 h and 1.79 +/- 0.26 h and the total clearances 18.2 +/- 3.3 l/h and 11.5 +/- 1.9 l/h, respectively. During the fifth day both sexes showed similar mean clearances of 11.9 +/- 1.3 l/h and 11.1 +/- 2.5 l/h and half-lives of about 2 h. The renal clearances was 7.3 +/- 0.5 l/h and 5.9 +/- 0.4 l/h for males and females, respectively. The mean urinary excretion of disodium clodronate during the 5-day period was 59.5% in the male patients and 56.0% in the female patients. We concluded that the slow infusion may increase the accumulation of clodronate in the body causing a higher clearance and a lower urine excretion of the drug than seen in earlier studies with faster infusions.

Aged↗
PubMed1989

[Use of vecuronium bromide and atracurium besylate in continuous intravenous infusion in urologic surgery].

The effects of continuous i.v. infusion of atracurium and vecuronium monitored by TOF supplied by an ABM monitor have been compared in 60 patients subdivided into four groups and submitted to anaesthesia with isoflurane for urological surgery interventions. Groups A and V received respectively an initial bolus of 0.5 mg/kg atracurium and of 0.08 mg/kg vecuronium followed immediately by continuous i.v. infusion of 5.5 micrograms/kg/min. Atracurium or 0.9 micrograms/kg/min of vecuronium; recovery of neuromuscular function happened spontaneously. Groups A' and V' differed by virtue of the use of 0.04 mg/kg prostigmin in the recovery phase. Average consumption of atracurium and vecuronium were respectively 5.1 +/- 1.75 micrograms/kg/min (2.6-9.03) and 0.75 +/- 0.20 micrograms/kg/min (0.5-1.2) in groups A-A' and V-V'. In groups A and V Recovery time 25-75" of T1 and TR presented a statistically significant difference (p less than 0.05) in favour of atracurium. In groups A' and V' the same parameters presented a statistically non-significant difference (p greater than 0.05). The ratio TI/TR does not vary to a statistically significant extent in the 4 groups. The number of infusion rate variations needed to maintain stable neuromuscular block was lower in the atracurium groups.

Adult↗
PubMed1989

Effects of atracurium administered by continuous intravenous infusion in halothane-anesthetized horses.

Atracurium (0.4 mg/ml in isotonic NaCl solution) was administered by IV infusion to 7 healthy adult horses for 2 hours. Over the 2-hour period, a 95 to 99% reduction of train-of-four hoof-twitch response was maintained by 0.17 +/- 0.01 mg of atracurium/kg of body weight/h, for a total of 161 +/- 6 mg of atracurium (mean +/- SEM) for horses 1 to 4, 6, and 7. Horse 5, a mare in estrus, required 0.49 mg of atracurium/kg/h to maintain comparable relaxation. Hoof-twitch recovery time from 10 to 75% of baseline strength was 19.8 +/- 2.5 minutes for all horses. The 10 to 75% recovery time for horse 5 was 18 minutes. Recovery time from discontinuation of halothane until standing was 86 +/- 14 minutes (range, 55 to 165 minutes). Horse 5 had a 165-minute recovery. Regarding recovery from anesthesia, 3 recoveries were rated as excellent, 1 recovery good, and 2 recoveries as fair. Horse 5 laid quietly until she stood with 1 strong, smooth effort.

Anesthesia Recovery Period↗
PubMed1989

[Value of the analysis of left-ventricular systolic time intervals in the diagnosis of ischemic heart disease provoked by intravenous infusion of isoproterenol].

The aim of the study was to evaluate the value of analysis of left ventricular systolic intervals during Isuprel test in diagnosis of ischemic heart disease. 30 patients with ischemic heart disease without myocardial infarction in the past (group I) and after myocardial infarction (group II) as well as 15 healthy persons (group III) underwent the study. Electrocardiograms and polycardiograms were analyzed by means of Weissler's method. In patients with CAD during Isuprel test decrease of QS2I, LVETI, LVETI/S1S2 and increase of Q-1, ICT, PEPI, PEP/LVET were stated in comparison with healthy persons. Sensitivity of Isuprel test estimated by ST segment analysis was 80%, specificity 100%, predictive value for CAD confirmation 100% and for its exclusion 71.4%. Diagnostic value of Q-1, QS2I and LVETI intervals and PEP/LVET index did not statistically significantly differ from ST segment diagnostic value. Sensitivity of Isuprel test estimated by means of these intervals analysis was 63.3%, specificity 93.3-100%, predictive value for CAD confirmation 95-100%, and for its exclusion 56-57.7%. Analysis of left ventricular systolic intervals during Isuprel test is a valuable complement of an ECG examination.

Adult↗
PubMed1989

[Use of atracurium in continuous intravenous infusion].

In this study the use of atracurium was evaluated for use in continuous endovenous infusion by controlling infusion levels using the simple technique of TOF monitoring during general surgical operations. In conclusion, continuous infusion of blocking agents is the preferential technique for controlling and maintaining a neuromuscular block; moreover, the use of besylate of atracurium is advised to ensure a reduced rate of individual variation.

Adult↗
PubMed1989

Pharmacokinetics of diastereoisomers of (6R,S)-folinic acid (leucovorin) in humans during constant high-dose intravenous infusion.

Eleven patients treated with a 5.5-day continuous i.v. infusion of 500 mg/m2/day of (6R,S)-folinic acid in combination with daily bolus 5-fluorouracil had a median steady-state plasma concentration of 3.25 microM (6S)-folinic acid (the bioactive diastereoisomer). The bioactive metabolite (6S)-5-methyltetrahydrofolic acid, analyzed in six patients, reached a median steady-state plasma concentration of 5.7 microM. The lowest plasma concentrations at steady-state were 1.86 microM (6S)-folinic acid and 3.12 microM (6S)-5-methyltetrahydrofolic acid. These concentrations are above the minimum concentrations shown by other investigators to produce synergism between (6R,S)-folinic acid and 5-fluorouracil in vitro. The median steady-state plasma concentration of (6R)-folinic acid was 38.2 microM, more than 10 times the concentration of (6S)-folinic acid. Along with other plasma pharmacokinetic parameters, terminal half-lives were estimated for (6S)-folinic acid (median, 45.4 min), (6R)-folinic acid (median, 388 min), and (6S)-5-methyltetrahydrofolic acid (median, 446 min). Investigation of the renal pharmacokinetics confirmed the marked difference in the renal clearance of the two diastereoisomers of folinic acid which had been observed after low doses of (6R,S)-folinic acid (J. A. Straw, D. Szapary, and W. T. Wynn, Cancer Res., 44: 3114-3119, 1984). However, the low renal clearance of (6R)-folinic acid (median, 8.2 ml/min/m2) was attributable to the extensive binding of (6R)-folinic acid to plasma proteins (median, 8.7% free), not to reabsorption in the kidney.

Clinical Trials as Topic↗