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Effect of halothane on diaphragmatic muscle function in pentobarbital-anesthetized dogs.

The mechanism underlying the decrease in minute ventilation (VE) observed under halothane anesthesia was investigated in nine spontaneously breathing dogs. Anesthesia was induced with pentobarbital sodium and was maintained with halothane. Inspired fraction of halothane (FIhal) was increased every 30 min, from 0.005 to 0.02. VE decreased from 8.1 +/- 0.9 to 4.8 +/- 0.4 l . min-1 (P less than 0.001), as FIhal increased from 0 to 0.02. This resulted from a decrease in both mean inspiratory flow (VT/TI) and the duty ratio (TI/TTOT). Transdiaphragmatic pressure (Pdi) and the integrated electrical activity of both hemidiaphragms (Edi) were measured during normal breathing, and during breathing against closed airways (P0di, E0di), in order to obtain an index of the inspiratory neuromuscular output of the diaphragm. With increasing FIhal, there was a significant decrease in Pdi, P0di, Edi, and E0di. The authors measured Pdi and Edi generated during supramaximal stimulation of the two phrenic nerves (PSdi, Esdi) at frequencies of 10, 20, 50, and 100 Hz, in order to eliminate in this decrease the role played by a decrease in the neural drive to breathing. PSdi and ESdi decreased significantly with increasing FIhal, and had not returned to the control values 30 min after discontinuation of halothane administration. The authors conclude that, in pentobarbital-anesthetized dogs, halothane is responsible for a diaphragmatic dysfunction, which may be located either at the neuromuscular junction, on the contractile processes of the muscle, or on both, and for a decrease in the activation time of the inspiratory muscles. Both of these effects contribute to the decrease in VE observed under halothane anesthesia.

Anesthesia

Influence of ruminal insufflation on pulmonary function and diaphragmatic electromyography in cattle.

In 8 healthy, awake cows with permanent cannulated ruminal fistulas and carotid artery loops, respiratory mechanics, ventilation, and diaphragmatic electrical activity were studied before and during stepwise insufflation of the rumen with air pressure to 40 mm of Hg. We found that ruminal insufflation increased intraperitoneal, intrapleural, and transdiaphragmatic pressures and decreased lung volume and lung compliance. In individual cows with rumen insufflation there was an increase in pulmonary resistance, but this trend was not significant in the group. Peak expiratory flow rate was increased and peak inspiratory flow rate was unchanged. Inspiratory duration (Ti) decidal volume decreased slightly, breathing frequency decreased markedly, and minute volume decreased. When intraruminal pressure reached 40 mm of Hg, arterial partial pressure of carbon dioxide (PaCO2) increased (P less than 0.01) and that of oxygen (PaO2) decreased (P less than 0,01) and arterial blood pH decreased (P less than 0.02). Diaphragmatic electromyographic activity was increased, but mechanical effectiveness of the diaphragm was reduced at increased intraruminal pressures.

Animals

Diaphragmatic performance during recovery from acute ventilatory failure in Guillain-Barré syndrome and myasthenia gravis.

Diaphragmatic muscle performance during acute ventilatory failure due to Guillain-Barré syndrome and myasthenia gravis was assessed to evaluate (1) diaphragmatic function during weaning from ventilatory support and (2) diaphragmatic tension-time integral (TTdi) during ventilatory failure. We used a multilumen nasogastric tube and a pneumotachograph to measure transdiaphragmatic pressure per breath (Pdi), maximum transdiaphragmatic pressure (Pdimax), tidal volume (VT), and inspiratory time fraction during 74 spontaneous breathing trials in nine patients. Diaphragmatic performance was poor in all patients. The Pdi, Pdimax, and VT improved significantly, but values for Pdi and Pdimax remained low even after weaning. Improvement in Pdimax was the best predictor of recovery (r = 0.48; p less than 0.001). Maximal inspiratory force correlated with Pdimax (r = 0.48; p less than 0.005), but FVC did not. The TTdi rarely exceeded the expected fatigue threshold of 0.15 in spite of the patient's inability to sustain ventilation. Although our patients demonstrated diaphragmatic weakness, TTdi did not demonstrate diaphragmatic fatigue.

Acute Disease

Reversible diaphragmatic eventration following chest tube thoracostomy.

This report describes a case of acquired eventration of a hemidiaphragm after insertion of a chest tube for treatment of an iatrogenic pneumothorax. Partial withdrawal of the chest tube resulted in immediate return of the hemidiaphragm to its original position. This is believed to be the first report of the resolution of this diaphragmatic functional defect.

Aged

Oxygen saturation during sleep in patients with spinal cord injury.

Sleep is associated with moderate or severe arterial desaturation in many disease states. This study was undertaken to evaluate whether hypoxemia during sleep was a significant problem in the spinal cord injured patient. Eleven patients with cervical or thoracic cord injury who had significant respiratory deficiency were evaluated. The mean age was 29.2 +/- 14. Vital capacity (VC) for the group revealed a mean of 43.1 +/- 18.1% of predicted, inspiratory capacity (IC) was 51.6 +/- 20.2% of predicted, and expiratory reserve volume (ERV) was 23.6 +/- 24.7% of predicted. In eight patients blood gases revealed a mean PO2 of 81.5 +/- 8.4 mmHg and PCO2 of 38.9 +/- 3.4 mmHg. Sleep screening studies were done using the Hewlett-Packard ear oximeter. They were studied for a mean of 2.6 +/- 1.1 hours. The initial O2 saturation was 96.6 +/- 1.6% and dropped to a mean of 90.6 +/- 6.4%. Only 1/11 reached saturation to less than 85% and 2/11 reached levels lower than 90%. Only age was significantly correlated with amount of desaturation (p less than .01). The level of the lesion, and % predicted ERV were not. One of the two patients who had hypoxemia with sleep had unilateral diaphragmatic paralysis. It is concluded that young quadriplegic patients with normal diaphragmatic function have no severe desaturation during sleep, but older patients and patients with some diaphragmatic dysfunction should be screened for sleep desaturation.

Adolescent

Effects of digoxin on diaphragmatic strength generation in patients with chronic obstructive pulmonary disease during acute respiratory failure.

We studied the effects of digoxin, a compound that has an inotropic effect on the myocardium, on diaphragmatic function in 8 patients with chronic obstructive pulmonary disease. All the patients were in acute respiratory failure and were artificially ventilated. Diaphragmatic strength was assessed by measuring the transdiaphragmatic pressure generated at functional residual capacity during bilateral supramaximal electrical stimulation of the phrenic nerves. The latter were stimulated before and at 45 and 90 min after administration of digoxin (0.02 mg/kg infused for 10 min). In all the patients, cardiac output was measured by the thermodilution technique using a Swan-Ganz catheter placed in the pulmonary artery. Arterial blood gases and pH were maintained within normal range by mechanical ventilation. In all the patients, digoxin plasma levels reached the therapeutic range (mean values, 2.82 +/- 0.17 and 2.90 +/- 0.20 nmol/L at 45 and 90 min, respectively) after digoxin administration. Diaphragmatic strength improves significantly after digoxin administration, the transdiaphragmatic pressure for an identical phrenic stimulation increasing by 19.5% (p less than 0.001) on the average. This increase was noted 45 and 90 min after digoxin administration. We conclude that digoxin has a potent effect on diaphragmatic strength generation that may be beneficial in patients with chronic obstructive pulmonary disease during acute respiratory failure. Furthermore, this inotropic positive effect of digoxin on the diaphragm, as previously observed for the myocardium, emphasizes the similarities between these 2 contractile tissues.

Action Potentials

Regional lung function in bilateral diaphragmatic paralysis.

1. The distribution of regional function in the lungs of six patient with bilateral diaphragmatic paralysis was investigated by continuous inhalation and infusion of the radioactive gases 81mKr and 85mKr during tidal breathing. 2. In the supine and right lateral decubitus postures the vertical distribution of ventilation per unit alveolar volume was less in the dependent zones, the reverse of that found in normal subjects. In the upright posture ventilation was slightly decreased at the lung base. Perfusion per unit alveolar volume was more uniformly distributed than normally in the upright posture, and decreased from superior to inferior in the supine posture. In the lateral decubitus posture, perfusion of the lower lung was greater than that of the upper. Ventilation/perfusion ratios were more uniformly distributed in the patients than in normal subjects, except in the right lateral decubitus posture. 3. Alterations in the distribution of ventilation may be explained in terms of the altered mechanical interaction of chest wall, mediastinal and abdominal contents, with selective use of intercostal and accessory muscles. The effects on the distribution of blood flow are probably related to the low end-expiratory lung volume.

Adult

Thoracoabdominal motion in chronic obstructive pulmonary disease.

Studies of thoracoabdominal motion using the respiratory magnetometer were performed in 30 patients with chronic obstructive pulmonary disease. Volume equivalency of thoracic and abdominal deflections was established by using the concepts and methods developed by Konno and Mead. Twenty patients were ambulatory, although disabled, and 10 were in acute respiratory failure and were studied in a respiratory intensive care unit. Five of 20 ambulatory patients and 8 of 10 patients in acute respiratory failure showed inward abdominal motion coincident with outward rib cage motion during inspiration, suggesting ineffective diaphragmatic function. This pattern of thoracoabdominal motion was identical to that seen in 2 high quadriplegics with diaphragmatic paralysis when they were breathing entirely with their neck muscles. Inspiratory ascent of the diaphragm was confirmed fluoroscopically in 3 of the 5 ambulatory patients. Patients showing this pattern were generally severely disabled and had the largest residual volumes. Two abnormal patterns of thoracoabdominal motion were observed during the performance of maximal voluntary ventilation in the ambulatory patients. The first, seen in 9 of 20 patients, was characterized by reciprocal or paradoxical motion of rib cage and abdomen, with increase in rib cage volume associated with decrease in abdominal volume during inspiration. The second pattern, seen in 5 of 20 patients, showed complete disorganization of rib cage and abdominal motion, with no consistent or reproducible pattern. Thus, a significant proportion of patients with disabling chronic obstructive pulmonary disease show abnormalities in thoracoabdominal motion that are observable with the respiratory magnetometer and ofter by simple inspection. Most of these abnormalities suggest malfunction of respiratory muscles, particularly the diaphragm.

Abdomen

Clinical and physiologic evaluation of respiratory muscle function.

The ventilatory muscles are of primary importance in the maintenance of ventilation. This rather complex system of muscles centers around the diaphragm. As diaphragmatic function becomes compromised with the progression of different lung diseases, the participation of other muscles becomes necessary. This is clinically manifested by the recruitment of many of these muscles even during quiet breathing. The use of simple questions during a medical history, determination of the respiratory rate, assessment of the pattern of breathing, and observation of thoracoabdominal movements are helpful in the initial evaluation. Measurement of the FVC, lung volumes, and tidal breathing help direct attention to more specific investigation of the ventilatory muscles. Decreased respiratory muscle strength can be confirmed by measurement of PImax and PEmax. Decreased respiratory muscle endurance can be readily ascertained by measuring the MVV. Use of these simple techniques, available in most laboratories, is appropriate for initial evaluation and establishing a diagnosis. The additional measurements of esophageal and gastric pressures have added a new dimension to the study of the diaphragm; these techniques, however, remain a research tool.

Humans

Diaphragmatic and genioglossal electromyogram responses to isocapnic hypoxia in humans.

In order to define the relationship between central control of upper airway and respiratory muscle function, diaphragmatic electromyogram (EMGdi) and genioglossal EMG (EMGge) responses to isocapnic hypoxia were studied in 6 awake supine volunteers. Both EMGs were processed and quantitated as moving time average activity. In all subjects, EMGge showed phasic inspiratory activity synchronous with EMGdi. Increases seen in EMGdi and EMGge were linearly related to the decrease in oxygen saturation (r = 0.89 +/- 0.08 and 0.89 +/- 0.08, respectively). There was also a linear relationship between the relative responses of both EMGs to hypoxia such that a low EMGdi response was associated with a low EMGge response and vice versa (r = 0.92, p less than 0.001). These results indicated that the genioglossus muscle behaves like a respiratory muscle and suggested that central control of upper airway and respiratory muscles in humans are intimately related.

Carbon Dioxide

Radiographic characterization of diaphragmatic excursion in halothane-anesthetized ponies: spontaneous and controlled ventilation systems.

A radiograph technique for identification of diaphragmatic segments and quantitation of their contribution to total diaphragmatic function was developed. five anesthetized ponies were studied on 3 separate occasions. Studies were made of the ponies in left lateral recumbency at 2 anesthetic levels (1 and 2 minimal alveolar anesthetic concentrations; halothane) and under spontaneous and controlled ventilation systems. General pattern of diaphragmatic displacement was unchanged by increased depth of anesthesia. Controlled ventilation altered the pattern of diaphragmatic displacement. Diaphragmatic displacement and regional volume changes were a function of active contraction or passive movement.

Anesthesia

Effects of aminophylline on diaphragmatic dysfunction after upper abdominal surgery.

The effects of upper abdominal surgery on diaphragmatic function were studied in eight supine patients before and after administration of aminophylline. Changes in pleural (delta Ppl) and gastric pressure (delta Pga) swings were measured with balloon catheter systems. Transdiaphragmatic pressure change (delta Pdi) was calculated as the difference delta Pga-delta Ppl. The ratio delta Pga/delta Pdi, used as an index of the diaphragmatic contribution to the quiet breathing process, decreased significantly as early as 1 h after operation without any further change throughout the 6-h period studied. Administration of aminophylline (6 mg/kg), six hours postoperatively, produced a significant increase in this diaphragmatic index. These data indicate that the early reduced diaphragmatic activity, after upper abdominal surgery, partially may be reversed by administration of aminophylline. The mechanism of its action may involve central nervous stimulation and/or a direct inotropic effect on diaphragmatic muscle. Further studies are needed to evaluate if the correction of altered diaphragmatic motion by aminophylline improves postoperative lung function.

Abdomen

[Effect of peritoneal dialysis on respiratory function in patients with chronic renal failure].

In 17 patients with end stage renal failure the effect was studied of a single peritoneal dialysis on the respiratory function, in the sitting and the recumbent position of the body. After the infusion of 2 liters of the dialysis fluid into the peritoneal cavity arterial PaO2 fell as well as the functional residual capacity, but the alveolar/arterial oxygenation difference (A-alpha)O2 rose. The most marked changes accompanied by dyspnea occurred in most patients in the sitting position. The inspiratory residual volume (IRV) increase reflects a better diaphragmatic function. The usefulness of aminophylline is discussed which not only dilates the bronchi but also improves the contractibility of the diaphragmatic muscle.

Adult

Prosthetic materials and muscle flaps in the repair of extensive diaphragmatic defects: an experimental study.

Relative merits of three methods of diaphragmatic hernia repair were evaluated in growing animals. Twenty-five puppies underwent laparotomy. In four controls, the left hemidiaphragm was incised and sutured primarily. In the remaining dogs, it was partially resected sparing the phrenic nerve. The defects were repaired in six with silastic sheeting, in eight with polytetrafluoroethylene (PTFE; trademark, Gore-Tex), and in seven with a thoracoabdominal muscle flap. Dogs were killed at 1, 4, and 7 months for gross and microscopic evaluation of the repair. Diaphragmatic function was evaluated by inspiratory force against a closed airway and by selective phrenic nerve stimulation (PNS). Serial fluoroscopy was used to evaluate diaphragmatic motion. Grossly the diaphragms in all groups showed compensatory growth. Microscopically the silastic was encapsulated without adherence, while PTFE showed tissue ingrowth. Maximal inspiratory force was equivalent in all groups but selective PNS revealed left-sided impairment in all experimental groups. Fluoroscopy showed paradoxical motion of the diaphragm in the muscle flap group for 1 to 2 months, and in the silastic repair group for 2 to 3 weeks, with near normal motion in the PTFE group for the entire postoperative period. These differences disappeared by 6 months. Prosthetic materials or muscle flaps are all safe for repair of large diaphragmatic hernias. Diaphragmatic growth occurs and the prosthesis remains in place. Physiologic impairment is minimal and not of clinical importance. Use of PTFE may be the preferred method as it develops better tissue incorporation and results in more normal diaphragmatic motion in the critical early postoperative period.

Animals

Abnormal pulmonary function associated with diaphragmatic pleural plaques due to exposure to asbestos.

Pulmonary function was measured in 79 men with diaphragmatic pleural plaques (DPP) as the only abnormality characteristic of asbestos disease on chest radiographs. They were selected from 4572 construction and shipyard workers exposed to asbestos. Abnormalities of pulmonary function in 21 non-smokers and 43 current smokers were compared with referent values adjusted for height, age, and duration of cigarette smoking. In the non-smokers, flows (FEV1) FEF75-85 and FEV1/FVC) were reduced and TGV and RV/TGV were raised. Current smokers had similar significant reductions. Thus by contrast with some current opinion that plaques are "an index only of past asbestos exposure," workers with plaques, even limited to the diaphragm, have functional impairment typical of pulmonary asbestosis. This suggests that they have pulmonary asbestosis, which is below the threshold of radiographic recognition.

Aged

Critical appraisal of pressure-frequency relation for estimation of diaphragm function in conscious calves.

A method yielding functional diaphragmatic variables in conscious animals is crucially needed to determine whether concepts and conclusions drawn from deeply anesthetized, highly instrumented clinically normal animals can be extrapolated to patients. Transdiaphragmatic pressure (Pdi) was, therefore, measured in 20 conscious calves during supramaximal transvenous bilateral stimulations of the phrenic nerves (pulse duration, 0.2 milliseconds; pulse frequency, 1, 10, 20, 30, 40, 70, and 100 Hz). Constancy of phrenic activation and precontraction length and geometry was ensured by respectively monitoring the amplitudes of right and left mass action potentials and triggering each activation train at end-expiratory lung volume against an occluded airway. Repeated phrenic activation and pressure recording procedures were well tolerated, safe, specific, and able to achieve constant and symmetric diaphragmatic tetanic contractions for prolonged periods. The Pdi increased with frequency of stimulation, so that, at 10, 20, 40, and 70 Hz, the mean +/- SD generated Pdi was 33 +/- 5, 65 +/- 8, 82 +/- 6, and 94 +/- 6% of Pdi at 100 Hz, respectively. The general shape of the Pdi-frequency relation and the absolute values of the generated Pdi were reproducible at 10-hour intervals despite CO2- or resistor-induced substantial changes in breathing pattern. It is concluded that this experimental model provides a reliable assessment of diaphragm function in conscious animals and can be used to study diaphragmatic contractility.

Action Potentials

Plication of the diaphragm for unilateral eventration or paralysis.

Unilateral diaphragmatic paralysis and eventration have the same appearance and provoke the same disturbances. Diaphragmatic plication is intended to decrease lung compression, to make the thoracic base and mediastinum more stable, and to strengthen the respiratory action of intercostal, perithoracic, and abdominal muscles: 13 infants and children were operated upon, 7 in acute respiratory failure and ventilator-dependent, 4 in chronic respiratory failure; 11 adults were operated upon, 8 with respiratory and 3 with digestive symptoms. Four infants who had been operated upon before the 10th day of life died: 3 from associated diseases and 1 from a lung infection. The 9 survivors have been followed up for a mean period of 6.6 years. All were asymptomatic and the position of the plicated diaphragm was maintained. The 11 adults have been followed up for a mean period of 8.5 years. Nine were asymptomatic; in 1, dyspnea had decreased; in 1, reflux persisted and was surgically cured. In 5 adults, the respiratory tests showed a mean amelioration of 20% of vital capacity and 15% of forced expiratory volume in 1 s. In infants, the prognosis depends on associated malformations and on the condition of the lung. Plication should be performed after 2 weeks on a ventilator. In older children and adults, plication is justified when the anomaly produces symptoms (malignancy excluded). Plication is simple, efficient, and durable, but there is no indication of subsequent diaphragmatic function: its effects on respiratory mechanics are probably indirect.

Adolescent

Application of a cervical stimulating apparatus for bilateral transcutaneous phrenic nerve stimulation.

Transcutaneous bilateral phrenic nerve stimulation (tPNS) is frequently used to assess diaphragmatic function in humans. Commonly, stimulation is performed with hand-held electrodes; however, these are unsuitable for studies requiring repeated PNS and where recruitment of rib cage and neck muscles may shift the probes in relation to the nerves. In this study we describe the design of a cervical neck brace and electrode probes that maintain stimulating electrodes in constant position relative to the phrenic nerves and facilitates studies requiring repeated maximal PNS. The effectiveness of the apparatus was examined by 1) reviewing the reproducibility of the transdiaphragmatic pressure response to 0.1 ms tPNS (PdiT) at relaxed functional residual capacity in four subjects studied on 25 +/- 8 (SD) occasions (> or = 24 h apart) over a 4-yr period, and 2) measuring peak-to-peak amplitude of the left and right diaphragmatic compound muscle action potentials (surface electrodes) during two prolonged studies (38 +/- 9 min) in each subject, when tPNS was performed during repeated submaximal and maximal inspiratory efforts. PdiT was reproducible in each subject when measured repeatedly within a single study [coefficient of variation (CV) of 3.8 +/- 0.8%] and over separate days (CV of 11.5 +/- 3.5%). The peak-to-peak amplitudes of the left and right compound muscle action potentials were also reproducible (CV of 8.4 +/- 4.3 and 8.4 +/- 2.9%, respectively) and independent of the degree of effort. The apparatus appears effective for the maintenance of maximal stimulation under varied conditions for long periods and provides reproducible measurements of PdiT both within and between studies.

Action Potentials