Catherine S. H. Sassoon

Progress in the development of a fluorescent intravascular blood gas system in man

In vitro and in vivo animal studies have shown accurate measurements of arterial blood pH (pHa), carbon dioxide tension (PaCO2), and oxygen tension (PaO2) with small intravascular fluorescent probes. Initial human clinical studies showed unexplained intermittent large drops in sensor oxygen tension (PiO2). Normal volunteers were studied to elucidate this problem. In the first part of this study, the probe and cannula were manipulated and the probe configuration and its position within the cannula were varied. The decreases in PiO2 were judged to be primarily due to the sensor touching the arterial wall. Retraction of the sensor tip within the cannula eliminated the problem. In the second part of this study, the accuracy of the retracted probe was evaluated in 4 subjects who breathed varying fractions of inspired oxygen and carbon dioxide. The arterial ranges achieved were 7.20 to 7.59 for pH, 22 to 70 mm Hg for PaCO2, and 46 to 633 mm Hg for PaO2. Linear regression of 48 paired sensor (i) versus arterial values showed pHi = 0.896 pHa + 0.773 (r = 0.98, SEE = 0.017); PiCO2 = 1.05 PaCO2-1.33 (r = 0.98, SEE = 2.4 mm Hg); and PiO2 = 1.09 PaO2-20.6 (r = 0.99, SEE = 21.2 mm Hg). Bias (defined as the mean differences between sensor and arterial values) and precision (SD of differences) were, respectively, -0.003 and 0.02 tor pHi, 0.77 and 2.44 mm Hg for PiCO2, and -2.9 and 25.4 mm Hg for PiO2. The mean in vivo 90% response times for step changes in inspired gas were 2.64, 3.88, and 2.60 minutes, respectively, for pHi, PiCO2, and PiO2.

Comparison of mitoxantrone and tetracycline as pleural sclerosing agents in rabbits

Bleomycin is the antineoplastic agent used most commonly for the treatment of malignant pleural effusion. It is absorbed rapidly from the pleural space and does not elicit pleurodesis in the normal rabbit pleura. Mitoxantrone is a new antineoplastic that differs from bleomycin in that it binds to membranes. Accordingly it might remain in the pleural space for a longer period and produce a pleurodesis. The objective of this project was to determine whether mitoxantrone is an effective sclerosant in an experimental model in rabbits. The following medications were instilled intrapleurally in anesthetized male rabbits: 35 mg/kg tetracycline or 0.5, 1.0, or 2.0 mg/kg mitoxantrone. The animals were killed at 28 days and the pleural spaces assessed grossly for pleurodesis and microscopically for fibrosis and inflammation. The mean degree of gross pleurodesis did not differ significantly in the rabbits that received tetracycline (3.8 ± 0.4) and in the rabbits that received 2 mg/kg mitoxantrone (3.2 ± 1.3). The degree of pleural and lung inflammation was significantly greater after mitoxantrone than after tetracycline, both ipsilaterally and contralaterally. The mortality after the highest dose of mitoxantrone was 50%. From this study we conclude that the intrapleural administration of mitoxantrone in rabbits can produce a pleurodesis. The histologic picture after mitoxantrone administration differs markedly from that after tetracycline injection. After mitoxantrone injection there are many more inflammatory cells present on the side that received the injection, and there is much more fibrosis and inflammation in the contralateral pleura and lung. The model of pleural fibrosis following intrapleural mitoxantrone may be useful for the study of pleural fibrosis.

Respiratory drive and timing during assisted ventilation in dogs.

In 8 anesthetized dogs, during isocapnic hyperoxia we studied the effect of assisted ventilation (AV) on ventilatory drive, inspiratory off-switch volume (Voff) and duration of inspiratory diaphragmatic activity (Tdi). Tidal volumes (Vt) during AV were double spontaneous Vt. Two electrodes were inserted in the diaphragm to obtain the electromyogram (EMG). The index of ventilatory drive was the EMG 0.3--i.e., the amplitude of the moving average EMG 300 ms after the onset of inspiratory activity. AV decreased EMG 0.3 but had no effect on Voff and Tdi. Vagotomy not only abolished the reduction in drive, but may have increased drive during AV.

Active Inspiratory Impedance and Load Compensation: Effects of Duration of Anesthesia

General anesthesia results in increases in respiratory elastance and flow resistance within 10–15 min after induction. Stabilization (compensation) of the respiratory system in the face of this added load is related to the addition of active (contractile) force-length and force-velocity properties to its internal impedance during inspiration. The difference between active (inspiratory) and passive (relaxation-exhalation) values of elastance and resistance can be used as an index of load compensation. We therefore evaluated the effects of duration of anesthesia on respiratory impedance and stabilization by comparing active elastance (Ers) and flow resistance (Rrs) to their corresponding passive values (Ers, Rrs) at the beginning and end of steady-state breathing in ten young, healthy anesthetized adults undergoing orthopedic surgery (anesthesia ∼1.5 MAC of a halogenated anesthetic in 60% N2O-40% O2). Occlusion pressure (P0.1) and components of ventilation also were measured. Duration of anesthesia did not correlate with changes in active or passive mechanics or with control of ventilation. Mean Rrs increased by 76% (P < 0.025), probably due to a decline of atropine effect; however, Rrs increased by only 17%, indicating near-maximum stabilization of flow-resistive properties at the end. Passive elastance increased 6%, whereas Ers increased 3.8%, indicating essentially constant volume-elastic stabilization throughout. Occlusion pressure increased 20% and VT/T1 22%, probably due to a decline in effects of sedation and neuromuscular blockade. We conclude that after induction of anesthesia, the reserve available to overcome flow resistance (intrinsic plus equipment) diminishes but is not related to duration of anesthesia. The reserve available to overcome elastic properties remains essentially constant throughout anesthesia.