Uptake of desflurane and isoflurane during closed-circuit anesthesia with spontaneous and controlled mechanical ventilation.

Although theoretical models predict uptake of inhaled anesthetics during closed-circuit anesthesia (CCA), clinical data for most anesthetics are conflicting or non-existent. In addition, the effects of patient characteristics and mode of ventilation on anesthetic uptake are unclear. Forty-one ASA physical status I or II adult patients undergoing a variety of 1-1.5 h surgical procedures were randomly allocated to receive CCA with desflurane or isoflurane with ventilation being either spontaneous or controlled. An end-expired anesthetic concentration of 1.3 minimum alveolar anesthetic concentration (MAC) was maintained by continuous injection of the liquid anesthetic into the circuit using a syringe pump. After an initial 4-min wash-in period, uptake during the first hour of CCA was nearly constant. Uptake was the same whether ventilation was spontaneous or controlled. Patient characteristics (age, height, weight, weight3/4, and body surface area) were comparable between groups and did not correlate with uptake. The virtually constant uptake after wash-in of desflurane and isoflurane contrasts with the square root of time model of Lowe and Ernst. These findings may greatly simplify CCA.

Plasma concentrations of epidural bupivacaine in mother and newborn: 0.125% versus 0.375%.

Central venous plasma concentrations of bupivacaine were determined in two groups of 15 parturients each who were given epidural analgesia for labor and vaginal delivery. One group received 10 ml of 0.125% bupivacaine plus epinephrine 1:800,000, the other group received 7 ml of 0.375% bupivacaine plus epinephrine 1:800,000. Plasma concentrations of bupivacaine in the umbilical venous (UV) and the umbilical arterial (UA) blood of their babies were also determined. The mean UA, UV, and maternal central venous (MV) plasma concentrations of bupivacaine differed significantly between the two groups: in patients given 0.375% bupivacaine UA values were 63% higher (P less than 0.01), UV values were 57% higher (P less than 0.01), and the MV values were 34% higher (P less than 0.05) than in patients given 0.125% bupivacaine. The measured plasma concentrations speak in favor of the less concentrated solution of bupivacaine in epidural analgesia for obstetrics. Seven milliliters of bupivacaine 0.375% is suitable for epidural analgesia in obstetrics but a low concentration-low dose technique, using 10 ml of bupivacaine 0.125% plus epinephrine 1:800,000 is safer. It provides good analgesia with minimal or no motor block and is associated with low maternal and neonatal plasma concentrations of bupivacaine, well below toxic levels and, to our knowledge, lower than in any other study.

Description of the firing pattern of respiratory neurons by frequency modulated interspike interval distributions.

The description of the firing pattern of respiratory neurons presented here is based on extracellular recordings and directed to the possible influence (facilitating of inhibiting effect) that the neuron might have upon others (output) as well as to the extend of influences that are received from other neurons (input). Developing such a description the spike generating mechanism of the neuron was in a first approach characterized by a frequency modulated gamma distribution. Using this approach an acceptable match between calculated and measured interspike-interval distribution was found although mostly not statistically significant. This non-significancy is most probably due to the choice of the simple gamma distribution as a first approach. However, applying this description it seems possible to retrieve statistical information about the interaction between neurons from extracellular recordings. Based on this description it is proposed to use modal spike frequency as well as the variance of the interspike interval distribution as estimates for the activity and the extent of activation of the neuron.

The steady state response of brainstem respiratory neuron activity to various levels of PA,CO2 and PA,O2.

Extracellular recordings were made of 52 respiratory neurons in the brainstem of cats, anesthetized (chloralose-urethane), vagotomized and artificially ventilated. Phrenic nerve activity was recorded and quantified as an index of the output of the respiratory neuronal organization in the brainstem. The unit activity was quantified by using the modal spike frequency as a possible indication of the activating effect of one unit on other respiratory neurons (Smolders and Folgering, 1979). Inspiratory neurons showed the strongest reaction to changes in PA,CO2 and/or PA,O2. Expiratory neurons and frequency modulated neurons responded less to changes in chemical drive. Phase spanning neurons did not show any consistent response. Four out of ten continuously firing neurons without any respiratory rhytmicity increased their firing frequency when PA,CO2 was increased. Apart from the increase in modal spike frequency, the respiratory neuronal organization also reacted with an increase in active units (recruitment) when the chemical drive was increased. The relationship between quantified phrenic nerve activity and spike frequency was independent of the stimulus (hypercapnia or hypoxia). A model was developed in which the increase in modal frequency of a unit arouses other units: when the chemical drive increases, progressively more units tend to be recruited into the respiratory neuronal organization in the brainstem.

Respiratory oscillations of the arterial PO2 and their effects on the ventilatory controlling system in the cat.

The respiratory oscillations of the arterial PO2 were measured in paralyzed, artificially ventilated cats by a small (1.2 mm) fast-responding catheter oxygen electrode. The amplitude of these oscillations could be changed independently of the mean PA,O2n by a specially designed respirator circuit. deltaPaO2 was shown to increase with increasing tidal volume or decreasing frequency of the respirator, and with increasing mean PaO2. The amplitude of the oscillations was attenuated considerably from the left atrium to the aorta. No attenuation occurred from the aorta to the carotid artery, provided that the blood flow in the carotid artery was not impeded. The measured attenuation of the oscillations was compared to that calculated by Yokota and Kreuzer (1973) and found to be quite different. The output of the ventilatory controlling system of the cat was measured from the quantified phrenic nerve activity. When only deltaPaO2 was changed at a constant level mean PaO2, the quantified phrenic nerve activity did not change, indicating that the amplitude of the oscillations does not influence the ventilatory controlling system. In vagotomized animals, the periodicities of the oscillations and the phrenic nerve activity were completely dissociated. From the fact that no Cheyne-Stokes type of breathing occurred, it was concluded that the effect of timing is negligible.

Capnostat and oxystat. Electronic devices to automatically maintain the end-tidal PCO2 and PO2 of a subject connected to a closed respiratory circuit at adjustable levels.

In respiratory physiology it is often desirable to maintain the end-tidal PCO2 and PO2 at adjustable levels independent of each other, e.g., when taking steady-state CO2 or O2 response curves, or when studying the ventilatory effects of exercise or drugs at constant levels of PCO2 and PO2. Based on the closed respiratory circuit described by Folgering et al. (1974), a new version was designed. The main new features of this version are that end-tidal PO2 instead of inspiratory PO2 can be kept constant, and that the correcting activity of both controllers (capnostat and oxystat) is proportional to the magnitude of the difference between the actual and the adjusted end-tidal PCO2 or PO2. An optic as well as an acoustic alarm is provided and will be switched on whenever no end-tidal PO2 is detected for an adjustable time.

The role of the fusimotor system with respect to the contribution of the diaphragm and the intercostal muscles to the respiratory tidal volume.

The efferent electrical activity in the phrenic nerve can be quantified in such a way that it gives a good correlation to tidal volume. After administration of the drug benzoctamine this relationship changes: more phrenic nerve activity is needed for the same tidal volume. No changes were found in the neuro-muscular transmission from the phrenic nerve to the diaphragm. There was no alteration in dynamic compliance of the lungs or in airway resistance. The afferent phrenic nerve activity from proprioceptors in the diaphragm did not change. It seems unlikely that respiratory neurons in the brainstem were affected since the sensitivity of the respiratory system to CO2 did not change. It is known that the tonic fusimotoneuron activity is suppressed at a supraspinal level by benzoctamine. Since intercostal muscles have muscle spindles and the diaphragm hardly has any, the intercostal muscle activity will be affected more than diaphragmatic activity by benzoctamine. This could actually be shown by quantifying the electromyogram of inspiratory external intercostal muscles. The tidal volume regulation is controlled by the vagal feedback loop. In order to reach a certain tidal volume after administration of benzoctamine, the contribution of the diaphragm has to increase because the activity of the intercostal muscles is diminished.

Ventilatory response to CO2 at rest and during positive and negative work in normoxia and hyperoxia.

Ventilation versus alveolar PCO2 relationships were determined by the steady-state method in 6 normal male subjects at rest and during positive and negative work at one load in both normoxic and hyperoxic condition. In 5 subjects the slopes of the VE-PACO2 lines during positive and negative work increased in normoxia as compared with rest. This effect was less evident in hyperoxia. It was also found that the slopes of the VE-PACO2 lines in positive and in negative work were about the same in both normoxic and hyperoxic conditions. Oxygen uptake and CO2 production during positive work is higher than during negative work. These results suggest that: 1) the disagreement between various authors on the change of the slope of the VE-PACO2 line may be due to the differences in the method of calculation of the slope or the method of the determination of VE-PACO2 lines; 2) the stimuli from the muscle spindles in the working muscle during exercise probably do not contribute to the increase in ventilatory response to CO2; 3) the increased slope of the normoxic VE-PACO2 line during exercise may be due to the interaction of several factors such as impulses from working muscles, chemosensitivity of central or peripheral chemoreceptors, adrenal-sympathetic pathways or temperature; 4) respiratory oscilations of PAO2 or PACO2 do not seem to influence the respiratory response to CO2.

Ventilation estimated from efferent phrenic nerve activity in the paralysed cat.

The purpose of this study is to develop a reliable method for obtaining information about "spontaneous respiration" in paralysed cats. Therefore action potentials from one of the phrenic nerves are recorded. In a spontaneously breathing animal, a CO2 rebreathing experiment is performed in order to obtain a relationship between phrenic nerve activity and tidal volume. This phrenic nerve activity is corrected for the noise measured during expiration and quantified proportional to the square root of the mean impulse rate of the whole nerve bundle. Thus, high correlation coefficients (0.95 or more) between phrenic nerve activity and tidal volume can be obtained. After paralysing the cat this relationship can be used to estimate "spontaneous tidal volume" from the phrenic nerve activity. It appears to be necessary to perform unilateral phrenicotomy on the nerve from which recordings are taken, because there is a condiserable amount of afferent signals in the phrenic nerve which is dependent on the stroke volume of the respirator, on the alveolar PCO2 and somewhat on the alveolar PO2. It is concluded that after vagotomy and phrenicotomy and if suitably quantified, the electrical activity in the phrenic nerve gives accurate information on "spontaneous ventilation" in a paralysed cat.