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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

Pulmonary function changes during interscalene brachial plexus block: effects of decreasing local anesthetic injection volume.

BACKGROUND AND OBJECTIVES: During interscalene block, ipsilateral hemidiaphragmatic paresis occurred in all patients who received > 34 ml of local anesthetic in the authors' previous studies. This study was done to determine whether diaphragmatic function could be spared by a smaller local anesthetic volume. METHODS: Twenty patients were randomly assigned to receive either a 45 ml or 20 ml interscalene brachial plexus block. For all blocks, 1.5% mepivacaine with added epinephrine and bicarbonate was used. Baseline serial measurements and those over a 30-minute test period before surgery were analyzed for significant differences between groups in onset or final change in any of the following measured variables: cephalad dermatomal extent of sensory anesthesia, clinically assessed upper extremity motor function, ipsilateral hemidiaphragmatic excursion during maximal sniff (inspiratory), and pulmonary function. RESULTS: There were no clinically significant differences between groups in any of the measured variables. Large reductions in routine pulmonary function tests were measured in all patients in both groups at 2 minutes after injection. At 30 minutes, baseline forced vital capacity (FVC) had diminished by 40.9 +/- 11.7% in the 45 ml group and 32.0 +/- 8.9% in the 20 ml group. One patient with pre-existing chronic obstructive pulmonary disease had a decrease in FVC from 1.83 l to 0.59 l, a 68% decrement from the baseline measurement, both measured in the supine position. CONCLUSION: Reducing the volume of local anesthetic to 20 ml did not prevent the 100% incidence of diaphragmatic paresis or significantly lessen the compromise in pulmonary function that had been reported to occur during interscalene brachial plexus anesthesia.

Adult

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

Thoracic epidural anesthesia increases diaphragmatic shortening after thoracotomy in the awake lamb.

BACKGROUND: Prolonged inhibition of diaphragmatic function occurs after thoracic and upper abdominal surgery. It was hypothesized that thoracic epidural anesthesia on the day after a thoracotomy could block inhibitory neural pathways and increase the shortening of costal and crural diaphragmatic segments. METHODS: Pairs of sonomicrometer crystals were implanted into the costal and crural regions of the diaphragm through a right lateral thoracotomy in 14 30-kg, 4-5-month-old lambs. One day after surgery, a thoracic epidural catheter was placed at the T8-T9 level. Regional diaphragmatic shortening normalized to end-expiratory length (%LFRC), was measured by sonomicrometry in these awake lambs. Changes in gastric (delta Pgas), esophageal (delta Pes), and transdiaphragmatic (delta Pdi) pressures were measured with transnasal balloon catheters. End-tidal carbon dioxide (FETCO2), costal and crural electromyogram (Edi), and tidal volume (VT) were measured. Inductance plethysmography was used in four lambs to assess relative contributions of the rib cage and abdomen to VT. Control values were obtained during quiet breathing and while rebreathing at up to 10% FETCO2. To block thoracic dermatomes, 1% or 2% lidocaine was injected through the epidural catheter. Measurements were repeated after each lidocaine injection. RESULTS: There was no change of resting length with 1% lidocaine; costal resting length increased by 22% with 2% lidocaine. After 2% lidocaine, costal %LFRC increased from control both during quiet breathing (8.7 +/- 0.7 to 18.1 +/- 1, mean +/- SEM%) and at FETCO2 10% (22.1 +/- 2 to 33.7 +/- 3%). VT during quiet breathing was unchanged after 1% lidocaine but increased from 235 +/- 16 to 283 +/- 28 ml after 2% lidocaine. At 10% FETCO2, delta Pdi was unchanged after 1% lidocaine and decreased from 36.5 +/- 4.3 to 26.3 +/- 4.9 cmH2O after 2% lidocaine. Regional delta Edi was unchanged with both 1% and 2% lidocaine at rest and during carbon dioxide rebreathing. Plethysmography in three lambs showed a reduction in rib cage contribution to tidal volume with 2% lidocaine during quiet breathing. CONCLUSIONS: Improved postoperative tidal volume and diaphragmatic shortening after thoracic epidural blockade may be due to changes of chest wall conformation and resting length and a shift of the workload of breathing from the rib cage to the diaphragm caused by intercostal muscle paralysis.

Anesthesia, Epidural

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

Diaphragm dysfunction induced by upper abdominal surgery. Role of postoperative pain.

The effects of upper abdominal surgery on diaphragmatic function were studied in 5 patients. During quiet tidal breathing, the volume displacement of the abdomen within the tidal volume (Vab/Vt) and the ratio of abdominal and transdiaphragmatic pressure changes (delta Pab/delta Pdi), taken as an index of the diaphragmatic contribution to the breathing process, decreased significantly on the first postoperative day (p less than 0.001); in 2 patients, a cephalad paradoxical motion of the diaphragm during inspiration was observed. Diaphragmatic dysfunction also occurred during maximal inspiratory efforts as shown by the significant fall in maximal static transdiaphragmatic pressure (Pdimax) and cephalocaudal diaphragmatic displacement on the first (p less than 0.001) and third (p less than 0.001) postoperative days. On the first postoperative day, opiate epidural analgesia did not modify Vab/VT, delta Pab/delta Pdi, and Pdimax. These parameters spontaneously returned towards control values on the seventh postoperative day. We conclude that upper abdominal surgery induces a marked diaphragmatic dysfunction lasting about 1 wk and that it is not suppressed by postoperative pain relief. The mechanism of this dysfunction remains to be determined. It may be the main cause of the postoperative pulmonary restrictive pattern.

Abdomen

Hemidiaphragmatic paresis during interscalene brachial plexus block: effects on pulmonary function and chest wall mechanics.

We studied the effects of unilateral hemidiaphragmatic paresis caused by interscalene brachial plexus block on routine pulmonary function in eight patients. In an additional four patients, we studied changes in chest wall motion during interscalene block anesthesia by chest wall magnetometry. Ipsilateral hemidiaphragmatic paresis, as diagnosed by ultrasonography, developed in all patients within 5 min of interscalene injection of 45 mL of 1.5% mepivacaine with added epinephrine and bicarbonate. Large decreases in all pulmonary function variables were measured in every patient. Forced vital capacity and forced expiratory volume at 1 s decreased 27% +/- 4.3% and 26.4% +/- 6.8%, respectively (P = 0.0001). Peak expiratory and maximum midexpiratory flow rates were also significantly reduced. Interscalene block caused changes in pulmonary function and chest wall mechanical motion that were similar to those published in previous studies on patients with hemidiaphragmatic paresis of pathological or surgical etiology. Interscalene block probably should not be performed in patients who are dependent on intact diaphragmatic function and in those patients unable to tolerate a 25% reduction in pulmonary function.

Adult

Mammalian locomotor-respiratory integration: implications for diaphragmatic and pulmonary design.

Diaphragmatic function and intrapulmonary respiratory flow in running mammals were found to differ substantially from the corresponding conditions known in resting mammals. In trotting dogs, orbital oscillations of the diaphragm were driven by inertial displacements of the viscera induced by locomotion. In turn, oscillations of the visceral mass drove pulmonary ventilation independent of diaphragmatic contractions, which primarily served to modulate visceral kinetics. Visceral displacements and loading of the anterior chest wall by the forelimbs are among the factors that contribute to an asynchronous ventilation of the lungs and interlobar gas recycling. Basic features of mammalian respiratory design, including the structure of the diaphragm and lobation of the lungs, appear to reflect the mechanical requirements of locomotor-respiratory integration.

Animals