Midazolam is used frequently for premedication in children, preferably by non-parenteral administration. We have compared plasma concentrations of midazolam after nasal, rectal and i.v. administration in 45 children (aged 2-9 yr; weight 10-30 kg) undergoing minor urological surgery. General anaesthesia consisted of spontaneous respiration of halothane and nitrous oxide in oxygen via a face mask. After administration of atropine and fentanyl i.v., children were allocated randomly to receive midazolam 0.2 mg kg-1 by the nasal, rectal or i.v. route. In the nasal group, children received 50% of the dose of midazolam in each nostril. In the rectal group, midazolam was given rectally via a cannula. Venous blood samples were obtained before and up to 360 min after administration of the drug. Plasma concentrations of midazolam were measured by gas chromatography and electron capture detection. After nasal and rectal administration, midazolam Cmax was 182 (SD 57) ng ml-1 within 12.6 (5.9) min, and 48 (16) ng ml-1 within 12.1 (6.4) min, respectively. Rectal administration resulted in smaller plasma concentrations. In the nasal group, a plasma concentration of midazolam 100 ng ml-1 occurred at about 6 min. After 45 min, the concentration curves after i.v. and nasal midazolam were similar.
Using gated radionuclide ventriculography and invasive cardiac monitoring, the effects of propofol and methohexital on left ventricular volumes and function were investigated in 22 unpremedicated patients (ASA physical status III, 50-78 yr) with chronic coronary artery disease (NYHA class II-III). Anesthesia was induced with either propofol or methohexital (2 mg/kg), followed by a maintenance infusion of 100 micrograms.kg-1.min-1. Vecuronium (0.05 mg/kg) was administered and ventilation (FIO2, 1.0) was manually controlled (FECO2, 0.04-0.05). Data acquisitions were serially obtained over 15 min. Propofol and methohexital anesthesia caused an average 15% decrease in mean arterial pressure, associated with a 20% decrease in cardiac index without a decrease in systemic vascular resistance index. It is interesting that the determinants of these hemodynamic effects were different. Heart rate did not change during propofol infusion despite the decrease in mean arterial pressure, whereas heart rate increased during methohexital infusion. In the propofol group, the decrease in cardiac index was associated with decreases in indicators of preload (end-diastolic volume and pulmonary capillary wedge pressure), whereas end-systolic volume and global ejection fraction did not change statistically. In the methohexital group, the decrease in cardiac index was associated with a decrease in global ejection fraction and an increase in end-systolic volume, whereas indicators of preload remained unchanged. It is concluded that methohexital reduces left ventricular performance. In contrast, propofol preserves left ventricular performance despite a likely negative inotropic effect.
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