The optimal ventilation strategy during cardiopulmonary resuscitation (CPR) is unknown. Chest compression (CC) generates circulation, while during decompression, thoracic recoil generates negative pressure and venous return. Continuous flow insufflation of oxygen (CFI) allows noninterrupted CC and generates positive airway pressure (Paw). The main objective of this study was to assess the effects of positive Paw compared with the current recommended ventilation strategy on intrathoracic pressure (P(IT)) variations, ventilation, and lung volume. In a mechanical model, allowing compression of the thorax below an equilibrium volume mimicking functional residual capacity (FRC), CC alone or with manual bag ventilation were compared with two levels of Paw with CFI. Lung volume change below FRC at the end of decompression and P(IT), as well as estimated alveolar ventilation, were measured during the bench study. Recordings were obtained in five cardiac arrest patients to confirm the bench findings. Lung volume was continuously below FRC, and as a consequence P(IT) remained negative during decompression in all situations, including with positive Paw. Compared with manual bag or CC alone, CFI with positive Paw limited the fall in lung volume and resulted in larger positive and negative P(IT) variations. Positive Paw with CFI significantly augmented ventilation induced by CC. Recordings in patients confirmed a major loss of lung volume below FRC during CPR, even with positive Paw. Compared with manual bag ventilation, positive Paw associated with CFI limits the loss in lung volume, enhances CC-induced positive P(IT), maintains negative P(IT) during decompression, and generates more alveolar ventilation.
The pharmacokinetic interactions of ofloxacin (2 X 200 mg) and theophylline (3 X 200 mg) were investigated in 12 healthy volunteers over a period of two weeks. In the first week, theophylline was given over five days to reach a steady state. In the second week, the combination of theophylline and ofloxacin was applied. Cmax, tmax, AUC0-8, the serum elimination constant and serum half-life of theophylline were not changed when theophylline was given alone or in combination with ofloxacin. The kinetic parameters of ofloxacin were in accordance with data from the literature.
The effects of psychomotor performance and attention of amitriptyline 75 mg administered without and with diazepam 10 mg have been investigated in 12 healthy subjects. The effects of the compounds were evaluated by objective tests (measurement of body sway, critical flicker fusion, visual reaction time, tachistoscopy, short term visual memory, tapping test, arithmetical calculation and Clement's code) and subjective measurements (visual analogue scales and side effects questionnaire). Measurements were taken before treatment and after 1, 3, 6, 8 and 24 h. Placebo did not affect either the objective or the subjective measurements. Diazepam caused a reduction in attention and performance after 1 h which had disappeared at 3 h. Amitriptyline caused a marked reduction in attention and performance, reaching a peak 3 hours after drug administration and persisting until 8 h. the deterioration in vigilance induced by amitriptyline was potentiated by concomitant diazepam.
This was a double-blind, placebo-controlled crossover study in 15 healthy female volunteers. It consisted of five sessions, separated by 1 week wash-out between sessions. The purpose of the trial was to study the potential amnesic and sedative activity of clobazam and lorazepam, and the potential antagonism between these effects under the joint influence of a high noise level and intense intermittent light stimulation (ILS), aimed at increasing the level of alertness. The study drugs were administered as a single daily oral dose. The amnesic and sedative effects were evaluated by objective measurements (digit span, Buschke selective reminding test, critical flicker fusion, reaction time, tapping, mental arithmetic test) and subjective measurements (visual analogue scale and adverse effect questionnaire) before each administration, then 1 h, 2 h, 2 5 h, 3 h, 4 h and 7 h post-dosing. An analysis of variance according to a balanced Latin square design was performed. Clobazam, at a dosage of 10 mg, was devoided of sedative and amnesic effects; at a dosage of 30 mg it induced only moderate memory disturbances. In contrast, lorazepam, administered at doses of 1 and 3 mg, produced marked and dose-dependent disturbances of memory, alertness and cognitive functions. The use of visual and sound stimuli, designed to increase the level of alertness, did not counteract the sedative effects induced by lorazepam.
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