Biomedical subjects
Publications and source records attributed to D H Simmons.
Whereas caffeine is widely accepted for use in society, it can be physically and psychologically harmful, especially to those with a mental illness. The effects of caffeine on specific mental illnesses and the medications used to treat them will be discussed. A review of addiction to caffeine and withdrawal from caffeine will also be presented. An assessment tool used to determine potential caffeine abuse is provided.
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Indirect evidence from airway pressure recordings in mechanically ventilated patients suggests that the diaphragm exhibits contractile activity beyond that required to trigger a ventilator-assisted breath. We used the diaphragmatic EMG to provide direct evidence of persistent contractile activity and studied the effects of alterations in ventilator-delivered flow rate and tidal volume on the duration of diaphragmatic contraction. The duration of contraction was expressed in terms of inspired volume. During a single breath, diaphragmatic force generation ceases at the point of peak electromyographic activity; hence, the inspired volume at peak EMG is the volume at the diaphragmatic off-switch (Voff). Ventilator-delivered flow rate and tidal volume were varied during assisted (patient-initiated) and controlled (ventilator-initiated) breaths while diaphragmatic EMG and inspired volume were recorded simultaneously in ten patients with a variety of illnesses requiring mechanical ventilation. Spontaneous ventilator-unassisted breaths were also recorded for comparison. We found that (1) during assisted breaths, diaphragmatic activity continued after the ventilator was triggered, (2) Voff was usually close to spontaneous tidal volume, (3) Voff increased significantly as ventilator-delivered flow rate increased, and (4) controlled breaths may also be associated with phasic electromyographic activity. The data have implications for resting patients on assisted ventilation.
We determined the effect of varying ventilator tidal volume (VT) and inspiratory flow (V) on the inspiratory muscle work (WI) during assist-mode mechanical ventilation (AMV) in four healthy subjects. In another four subjects, under constant chemoreceptor input, we determined the responses of neuromuscular output as assessed by the mouth occlusion pressure (P0.1) to alteration in WI. During AMV, the inspiratory external work of breathing is partitioned between WI and ventilator work. With a constant ventilator trigger sensitivity, we calculated WI (joules/L of volume) as the difference between the area subtended by the airway pressure-inspiratory volume curves and the ordinate of the assisted breaths subtracted from that of the controlled breaths at ventilator V of 40, 60 and 80 L/min and ventilator VT of 100, 125 and 150 percent spontaneous breathing VT. At all ventilator settings, WI was less than inspiratory muscle work of spontaneous breathing (SB) and was a function of both ventilator VT and V (p less than 0.05), but ventilator V has more effect on WI. Under isocapnia and hyperoxia, we measured P0.1 and WI during AMV at ventilator VT of 125 percent of spontaneous breathing VT and ventilator V of 60, 80 and 100 L/min. End-expiratory lung volume remained constant. P0.1 during AMV was similar to that of the SB. Although WI decreased with increasing ventilator V, P0.1 did not decrease significantly. We conclude that during AMV, both ventilator V and to a less extent ventilator VT determine W. In healthy subjects changes in WI do not affect P0.1.
An edited summary of an Interdepartmental Conference arranged by the Department of Medicine of the UCLA School of Medicine, Los Angeles. The Director of Conferences is William M. Pardridge, MD, Professor of Medicine. Several specialists have recently recognized that gastrointestinal reflux causes complications resulting in significant disease. It causes discomfort, indigestion, esophagitis, Barrett's esophagus, and carcinoma of the esophagus. Pediatricians attribute many early pulmonary problems, and even some sudden deaths in infants, to the reflux of gastric contents. Otolaryngologists now recognize that many cases of nonbacterial, nonspecific pharyngitis and laryngitis are due to the reflux of gastrc acid secretions. Contact granuloma and cancer of the larynx may, in some instances, be secondary to nocturnal reflux. Thoracic surgeons and pulmonologists believe chronic tracheobronchitis and some cases of pulmonary disease are attributable to recurrent bathing of the respiratory epithelium by aspirated gastric contents. An awareness of the many complications of gastrointestinal reflux should lead to a multidisciplined attack on the factors responsible for these diseases.
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.
We studied the effects of assisting respiration with inspiratory positive pressure (IPP) during air and CO2 breathing by measuring ventilatory and mouth occlusion (P0.1) responses in 15 normal human subjects. Switching from spontaneous breathing to IPP without added CO2 did not cause a significant change in mean PACO2, P0.1, or V1. During CO2 breathing, switching to IPP did not significantly alter tidal volume or frequency. The mean ventilatory response to CO2 during spontaneous breathing was 1.02 liters/min/mm Hg. With IPP at pressure limits of 5 and 7 cm H2O, the mean responses were 0.93 and 0.89 liters/min/mm Hg, respectively, not significantly different from spontaneous breathing. The mean spontaneous P0.1 response to CO2 was 0.32 cm H2O/mm Hg. With IPP at 5 and 7 cm H2), the responses were 0.29 and 0.36 cm H2O/mm Hg, also not significantly different from spontaneous breathing. Reduction of muscular work of breathing by IPP in normal human subjects does not induce a measurable change in either respiratory drive or ventilation, which appears to remain dependent on chemoreceptor input. Inspiratory effort continues during IPP, even though it may be less than during spontaneous breathing.
We measured the diaphragm electromyogram (EMGd) and airway occlusion pressure (P100) of anesthetized dogs at the ends of 30-min of alternating spontaneous breathing and assisted mechanical ventilation (inspiratory positive pressure triggered by a minimal inspiratory effort; IPPB). Peak airway pressures (Paw) of 5, 10, 15, and 20 cm H2O were applied in random order during IPPB. The initial rate of rise of EMGd (4 experiments) and P100 (9 experiments) decreased during IPPB, both in proportion to the Paw. At Paw of 20 cm H2O, PaCO2, EMGd and P100 decreased on the average 5.2 Torr, 58% and 56%, respectively. When PaCO2 was kept the same during IPPB as during spontaneous breathing (8 experiments), IPPB reduced EMGd and P100 15% and 24% respectively, both statistically significant. During progressive cooling of both cervical vagi, the effect of IPPB (Paw=20 cm H2O) on EMGd and P100 decreased progressively, near maximal at 6--4 degrees C and after vagotomy. However, the decrease in PaCO2 during IPPB was not affected. These data suggest that increasing tidal volume during IPPB depresses respiratory drive (EMGd and P100), partially from decreased PaCO2 and partially from stimulating pulmonary stretch receptors. The drop in PaCO2 during IPPB does not appear to be vagally mediated.
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8 healthy dogs were anesthetized with a continuous infusion of pentobarbital (1 mg/kg/h) and were weakened but not paralyzed by intravenous succinylcholine (1 mg/kg/h). They were then studied during alternating periods of spontaneous breathing and assisted ventilation (IPPB). After succinylcholine, there was a significant increase in PaCO2, no significant change in respiratory frequency, a significant decrease in tidal volume, no significant change in P100 and a significant decrease in peak diaphragm EMG. Comparing periods of IPPB with periods of spontaneous breathing, there was a decrease in PaCO2 to a mean approximating that before succinylcholine, an increase in tidal volume, no change in frequency, and significant decreases in P100 and diaphragm EMG. In three experiments in which PaCO2 was maintained constant during IPPB, IPPB again resulted in a decrease in EMG and P100. Assisted mechanical ventilation of partially paralyzed dogs resulted in a fall in PaCO2 and a decrease in respiratory center output as measured by diaphragm EMG and P100. The fall in PaCO2 could be ascribed to decreasing the limited muscular work of breathing even in the presence of normal mechanics. A major part of the changes in EMG and P100 could be ascribed to chages in chemoreceptor drive but alteration of other inputs which were not specifically indentified, such as lung reflexes and/or chest wall reflexes, must also have had an effect.
The diagnostic yields of prebonchoscopy sputum specimens and fiberoptic bronchoscopy (including brushings, washings, and/or biopsies) were determined in 35 patients who presented primarily with middle or anterior mediastinal and/or paratracheal mass(es) on chest radiographs. The diagnosis was confirmed on histopathology of tissue obtained by needle biopsy, mediastinoscopy, thoracotomy, and/or autopsy. Thirty-one of the patients were found to have primary bronchogenic carcinomas. At bronchoscopy, extrinsic compression of trachea and/or bronchi was visualized in 23 (Group I) and the tracheobronchial tree appeared normal in 12 (Group II). Prebronchoscopy sputa gave a positive yield in only three of the 35 (8%) patients; the yield was similar in both groups of patients. One or more of the bronchoscopic modalities were diagnostic in 69% of Group I patients but were not helpful in Group II patients. The diagnostic yield of brushings, washings, and biopsies in Group I patients was 52%, 61%, and 37%, respectively. The addition of biopsies to washings and/or brushings did not significantly alter the yield. Washings and brushings are recommended as useful, non-invasive procedures in diagnosing middle mediastinal masses with extrinsic compression. Sputum cytology gives a very low yield.
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Many causes for the adult respiratory distress syndrome (ARDS) have been reported, all with common pathologic, pathophysiologic and biochemical end results. The final common pathway may involve changes in lung content of a critical enzyme, superoxide dismutase, or alterations in surfactant metabolism, or both. The early assumption that the disorder is partially due to oxygen toxicity from inspired oxygen concentrations greater than 60 percent is consistent with findings of recent biochemical studies. Although the lung normally maintains its alveoli dry, during ARDS increased permeability of small pulmonary vessels results in primary pulmonary edema, in contrast to edema from increased vascular pressure. These data have been obtained mainly in animals; whether they apply to humans with ARDS is not certain. Tissue oxygenation is improved by increasing end-expiratory pressure in an animal model of ARDS, more effectively during spontaneous breathing than during mechanical ventilation. During spontaneous breathing, adverse ventilatory effects were caused by stimulation of pulmonary reflexes.
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