Peak plasma anti-Xa levels after first and third doses of enoxaparin in women receiving weight-based thromboprophylaxis following caesarean section: a prospective cohort study.

BACKGROUND: Women undergoing caesarean section are at higher risk for thromboembolic complications following delivery than other parturients. The aim of this study was to determine whether higher doses of enoxaparin based on body weight are safe and more likely to achieve plasma anti-Xa levels within the accepted thromboprophylactic range. METHODS: We undertook a prospective cohort study of 80 women undergoing caesarean section in a tertiary obstetric hospital with >6000 deliveries per year. Enoxaparin was administered after caesarean section using the Royal College of Obstetricians and Gynaecologists weight-adjusted dosing guidelines. Plasma anti-Xa levels were measured at baseline and 3-4 h after enoxaparin administration on days one and three postoperatively. The main outcomes of interest were plasma anti-Xa levels and the proportion of patients with plasma anti-Xa levels in the range of 0.2-0.4 IU/mL. RESULTS: The proportion of women with anti-Xa levels between 0.2 and 0.4 IU/mL was 72% (95% CI 60-81%). Unadjusted mean anti-Xa levels were 0.26 ± 0.09 IU/mL and 0.28 ± 0.08 IU/mL on day one and day three respectively. No woman had levels >0.48 IU/mL. CONCLUSION: The majority of women receiving weight-based enoxaparin thromboprophylaxis following caesarean section achieved plasma anti-Xa levels within the putative thromboprophylactic range. No woman achieved levels associated with an increased risk of bleeding (>0.8 IU/mL). These findings provide a safety basis for a large prospective study using this regimen.

Safety profile of meropenem: international clinical experience based on the first 3125 patients treated with meropenem.

Data from 3125 patients (3220 patient exposures) treated with meropenem were compared with those from 2886 patients (2960 patient exposures) treated with a variety of comparator agents including cephalosporins (alone or in combination with aminoglycosides or an anti-anaerobe agent) and imipenem/cilastatin. Patients treated included those with bacterial infections of the lower respiratory tract, urinary tract and skin and soft tissues, abdominal, obstetric and gynaecological infections, meningitis, febrile episodes in neutropenic patients and paediatric patients with infections. In three studies, meropenem was administered intramuscularly; in the remainder, meropenem was given by 15-30 min iv infusion or by bolus injection over approximately 5 min. The usual dosages were 500 mg or 1 g 8 hourly in adults and 10 or 20 mg/kg 8 hourly in children. In bacterial meningitis, the meropenem dosage in adults was 2 g 8 hourly and 40 mg/kg 8 hourly in children. The overall pattern and frequency of adverse events with meropenem were similar to those of the other beta-lactam antibiotics with which it was compared. The most frequently reported adverse events were diarrhoea, rash, nausea and vomiting, thrombocytosis, eosinophilia and changes in hepatic biochemistry. Abnormal laboratory tests occurred with similar frequencies between meropenem and the comparator agents. The safety profile of meropenem was similar in adults and children, and the presence of renal impairment did not alter the safety profile of meropenem. Experience in clinical studies in 3220 patient exposures has revealed no unusual or unexpected toxicity. The possibility of administration by either iv infusion or bolus injection with a low incidence of nausea and vomiting also provides flexibility in the clinical management of patients. Moreover, the low incidence of reported seizures and good tolerability at high doses, make meropenem particularly useful for the treatment of meningitis and other indications which carry a risk of seizures, or in the treatment of serious infections where high doses of antibiotics are frequently indicated.

Effect of pentisomide (CM 7857) on myocardial excitation, conduction, repolarization, and refractoriness. An electrophysiological study in humans.

The electrophysiological effects of pentisomide upon the intact human heart were evaluated using programmed stimulation and recording of intracardiac monophasic action potentials (MAP) in 17 patients with various ventricular arrhythmias. After i.v. administration of pentisomide, 85-135 mg, the atrial-His interval increased by 8 +/- 12 ms (p less than 0.05) during sinus rhythm and by 13 +/- 21 ms (p less than 0.05) at atrial pacing of 600 ms cycle length (600 ms pacing). The His-ventricular interval also increased by 6 +/- 10 ms during sinus rhythm (p less than 0.05) and by 5 +/- 9 ms at 600 ms pacing (NS). The QRS duration prolonged by 9 +/- 10 ms (p less than 0.01) and 6 +/- 8 ms (p less than 0.01) during 600 and 500 ms ventricular pacing, respectively. The right ventricular MAP duration to 90% repolarization was significantly shortened, by 20 +/- 21 ms (p less than 0.01) during sinus rhythm, by 16 +/- 17 ms (p less than 0.01) at 600 ms ventricular pacing, and by 11 +/- 16 ms (p less than 0.01) at 500 ms ventricular pacing. The corrected QT interval was shortened by 21 +/- 28 ms (p less than 0.01). The present study supports that pentisomide is a class-I antiarrhythmic agent with a marked effect on depolarization (action of class Ia and Ic) and on repolarization (action of class Ib). This unique combination of cellular electrophysiological properties indicates that the clinical antiarrhythmic efficacy of pentisomide may differ from that of hitherto available antiarrhythmic drugs.