The actions and side effects of the benzodiazepine antagonist Ro 15-1788 were evaluated in a randomized double-blind clinical study in which midazolam was used as an anaesthetic agent. Sixty women who underwent laparoscopy were treated with Ro 15-1788 or with placebo after the surgical procedure. Ro 15-1788 reversed the hypnotic effect of midazolam within a few minutes. The patients were alert, co-operative, oriented and had good recall of events after awakening. The effects were statistically better than placebo for up to 30 min after administration. Arterial pressure and heart rate remained stable and there were no significant side effects. The availability of Ro 15-1788 allows effective reversal of midazolam when this is used during general anaesthesia.
SUMMARYDynamic compliance, resistance to gas flow and respiratory work were determined in 20 patients during anaesthesia and controlled ventilation with the Engström respirator. The compliance was measured continuously with the aid of a “respiration analyser” and a pneumotacho‐calibrator, which allows breath‐by‐breath registration and automatic calibration of gas flow, compliance and respiratory work without the interruption of the patient's ventilation. Ventilatory frequencies utilized (18‐20/min.) and tidal volume were unchanged during the periods of investigation, which were of an average duration of 233 minutes (range 60‐570 minutes). Compliance at the beginning of the controlled ventilation was 44.5±2.7 ml/cm H2O and at the end 44.8 ±2.2 ml/cm H2O. A sustained or forced inflation for 20‐40 seconds did not result in any significant changes in compliance. The resistance to gas flow was measured at 0.5 L/sec. and at maximum flows (approx. 0.8‐1.2 L/sec.) and was 13.3±1.0 cm H2O/L/sec. and 14.4±1.0 cm H2O/L/sec, respectively. The resistance to the endotracheal tubes and connections corresponded to 7‐8 cm H2O/L/sec. The inspiratory work of breathing varied between 0.55 and 1.31 kpm/min. with an estimated proportion of 4:1 between elastic and resistive work. The ventilatory volumes used resulted in arterial carbon dioxide tension values close to 40 mm Hg, indicating the rationale of calculating ventilatory volumes from a special nomogram. Alveolar‐arterial oxygen tension differences were within normal ranges (80 ±14 mm Hg, range 28‐143 mm Hg). There was no fall in arterial oxygen tension during die period of controlled ventilation, and forced inflations did not improve the arterial oxygen tensions. It is believed that the special flow‐pressure pattern of die Engström respiratoran accelerating gas flow with a variable end‐inspiratory pressure plateaucounteracts any tendency to alveolar collapse and possible decrease in compliance. This assumption gains strength from experimental studies in which the difference in the distribution of insufflated volumes and changes in apparent compliance have been analysed for constant and accelerating gas flows. The variable end‐inspiratory pressure plateau of the Engström respirator offers breadi‐to‐breath “mini‐sighs,” and there is thus no need to provide this machine with any special device for “deep” sighs, as has recently been suggested. Our findings indicate that there is an explanation of why others have found a decrease in compliance during controlled ventilation in contrast to our results. This is probably due to the utilization of constant gas flows and the absence of an end‐inspiratory plateau, which will have an unfavourable effect on the pulmonary mechanics.ZUSAMMENFASSUNGDie dynamische Compliance, der Gasstromwiderstand und die Atemarbeit wurden bei 20 Patienten während der Narkose unter künsdicher Bcat‐mung mit dem Engström‐Respirator bestimmt. Die Compliance wurde kontinuierlich mit Hilfe eines «respiration analyzer» und eines Pneumotacho‐kalibrators gemessen, wobei Atemzug für Atemzug‐Registrierung und auto‐matische Kalibrierung des Gasstromes, der Compliance und der Atemarbeit möglich war, ohne die Beatmung des Patienten unterbrechen zu müssen. Die Atemfrequenzen (18‐20/min) und Atemvolumina blieben während der Unter‐suchungsperioden, die zwischen 60 und 570 Minuten, im Mittel 230 Minuten, bctrugen, unverändert. Zu Beginn der kontrollierten Beatmung war die Compliance 44,5±2,7 ml/cm H2O und am Ende 44,8 ± 2,2 ml/cm H2O. Forcierte Überblähung während 20‐40 sec führte zu keinen signifikanten Änderungen der Compliance. Der Gasstromwiderstand wurde bei 0,5 1/sec und bei Maximal‐strömung von 0,8‐1,2 1/sec gemessen. Er betrug 13,3±1,0 cm HaO/l/sec, bzw. 14,44±1,0 cm H2O/l/sec. Der Widerstand der Endotrachealtuben und Verbindungsstücke entsprach 7‐8 cm H2O/1/sec. Die inspiratorische Atem‐arbeit variierte zwischen 0,55 und 1,31 kpm/min bei einer geschätzen Relation von 4:1 zwischen elastischer und Widerstandsarbeit. Die verwendeten Ventilationsvolumina führten zu arteriellen Kohlensäurespannungswerten nahe um 40 mm Hg, womit der Wert einer Kalkulation der Ventilationsvolumina aus einem Spezialnomogramm bewiesen erscheint. Die alveolo‐arteriellen Sauerstoffdruckunterschiede blieben in Normalbereichen (804±14 mm Hg, Bereich 28‐143 mm Hg). Während der Periode der kontrollierten Beatmung kam es zu keinem Absinken des arteriellen Sauerstoffdrucks und forcierte Aufblähung führte zu keiner Verbesserung des Sauerstoffdruckwertes. Wir glauben, dass das besondere Strömungs‐Druckmuster des Engström‐Respirators‐beschleunigender Gasstrom mit veränderlichem endinspiratorischen Druckplateau‐jeder Tendenz zum Alveolarkollaps und möglicher Abnahme der Compliance entgegenwirkt. Diese Annahme wird understützt durch experimentelle Untersuchungen, bei denen die Differenz zwischen der Verteilung insufflierter Volumina und Veränderungen der Compliance für konstante und beschleunigende Gasströmungen analysiert wurden. Das variable endinspiratorische Druckplateau des Engström‐Respirators vermittelt Zug für Zug «Mini‐seufzer», sodass keine Notwendigkeit besteht, diesen Apparat mit einem Spezialzusatz für tiefe Seufzer auszustatten, wie dies kürzlich vorgeschlagen worden war. Unsere Befunde scheinen eine Erklärung dafür zu geben, warum andere Autoren, im Gegensatz zu uns, eine Abnahme der Compliance während der kontrollierten Beatmung gefunden haben. Es war dies wahrscheinlich durch die Anwendung konstanter Gasströmungen und das Fehlen eines endinspiratorischen Plateaus, welche einen ungünstigen Effekt auf die Atemmechanik haben.
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