Excursion-volume relation of the right hemidiaphragm measured by ultrasonography and respiratory airflow measurements.

BACKGROUND: Although real time ultrasonography has been used in the last decade to record diaphragmatic motion, the relation between diaphragmatic excursion and different inspired volumes (VT) has not been assessed by ultrasound. METHODS: Ten normal subjects were studied in the supine posture. Diaphragmatic excursion and VT were assessed simultaneously by M mode ultrasonography and respiratory airflow measurements at different inspired volumes. Ultrasound recordings of the movement of the right hemidiaphragm were carried out in the longitudinal plane subcostally. The transducer was held in a fixed position by a frame, built especially to eliminate any artefactual movement caused by outward motion of the anterior abdominal wall on inspiration. RESULTS: Mean (SD) maximal diaphragmatic excursion recorded was 6.0 (0.7) cm. Inspired volumes ranged from 15(5%) to 87(10%) of the subjects' inspiratory capacity. A linear relation between diaphragmatic excursion and VT was found in all subjects (r = 0.976-0.995). The regression line had a slope of 1.66 (0.24) cm/l. This slope had no correlation with either the height (r = 0.007) or weight (r = 0.143) of the subjects. In five subjects in whom diaphragmatic excursion could be recorded at volumes near total lung capacity, the relation between diaphragmatic excursion and VT became alinear at very high lung volumes. CONCLUSIONS: The relation between diaphragmatic excursion and VT was linear between 15(5%) and 87(10%) of inspiratory capacity. Ultrasonography of the diaphragm is a simple technique that could be applied in the clinical investigation of patients with suspected abnormalities of diaphragmatic movement.

Diaphragmatic movement in hemiplegic patients measured by ultrasonography.

BACKGROUND: It is known that automatic breathing is controlled by centres in the lower brain stem, whereas volitional breathing is controlled by the cerebral cortical centres. In hemiplegia, lesions above the brain stem result in paralysis of limb muscles. This study was performed to determine whether the diaphragm might also be affected in patients with hemiplegia. METHODS: Studies were performed in six normal control subjects and in eight patients with complete hemiplegia caused by a lesion above the brain stem, all with no known chest disease. Full lung function tests were performed. Diaphragmatic excursion and inspired volume (VT) were measured simultaneously by M mode ultrasonography and respiratory airflow measurements. Recordings of diaphragmatic excursion were performed on each side separately during volitional and automatic breathing at a similar range of VT. RESULTS: Lung function tests lay within the normal range in all the control subjects. In the hemiplegic patients mean (SD) vital capacity was 79 (18)% and residual volume was 123(30)% of predicted. Total lung capacity and functional residual capacity were in the normal range. In the control subjects no significant difference in diaphragmatic excursion was found between volitional and automatic breathing for the same range of inspired volume. By contrast, there was a significant decrease in diaphragmatic excursion during volitional breathing compared with automatic breathing on the affected side in four of the eight hemiplegic patients. CONCLUSIONS: In four of eight hemiplegic patients reduced diaphragmatic movement was present on the paralysed side during volitional inspiration when compared with automatic inspiration. The hemidiaphragm may be involved on the affected side in patients with hemiplegia.

Repetitive stimulation of phrenic nerves in myasthenia gravis.

BACKGROUND: In the investigation of patients with myasthenia gravis, repetitive supramaximal stimulation of an affected peripheral nerve is commonly performed to detect abnormal transmission at the neuromuscular junction. A study was undertaken to determine whether abnormal transmission could similarly be detected during stimulation of the phrenic nerves. METHODS: The phrenic nerves were stimulated supramaximally with surface electrodes in 13 patients with myasthenia gravis and in 16 control subjects (six control patients with diaphragmatic weakness but not with myasthenia and ten normal subjects). The amplitude of diaphragm muscle action potentials was measured with surface electrodes during phrenic nerve stimulation at frequencies of 1-5 Hz for 3-4 seconds. RESULTS: In five patients with myasthenia gravis, a significant decrement (15-43% decrease) occurred in the amplitude of diaphragm muscle action potential during stimulation at 3 Hz. When stimulation frequency was reduced to 1 Hz, diaphragm muscle action potentials returned to their original amplitude within 4-5 seconds. The decrement in the amplitude of the diaphragm muscle action potential was reduced temporarily in three of four patients after the administration of intravenous edrophonium chloride (Tensilon). There was no significant change (< 10% decrease) in the amplitude of diaphragm muscle action potentials during stimulation at increased frequencies either in the 16 control subjects or in eight of the patients with myasthenia gravis. CONCLUSION: A significant reduction in the amplitude of diaphragm muscle action potential occurred in five of 13 patients with myasthenia gravis during phrenic nerve stimulation at 3 Hz but in none of the control subjects. This may be a useful and non-invasive method for identifying patients with myasthenia gravis in whom weakness of the diaphragm is suspected.

Motor cortical representation of the diaphragm in man.

1. Transcranial magnetic stimulation was performed using a figure-of-eight-shaped coil over the right motor cortex with the aim of identifying those areas involved with activation of the diaphragm. 2. The response of the right and left hemi-diaphragms was recorded using surface electrodes in either the 7th or 8th intercostal spaces 3 cm lateral to the anterior costal margin on either side. 3. The compound muscle action potentials recorded over the left diaphragm in response to transcranial magnetic stimulation were maximal when the centre of the figure-of-eight coil was placed approximately 3 cm to the right of the mid-line and 2-3 cm anterior to the auricular plane. 4. The amplitude of the response recorded from the diaphragm depended upon the angulation of the figure-of-eight coil and hence the direction of the stimulating current. 5. The response of the inspiratory muscles to magnetic stimulation of one side of the brain was predominantly contralateral but a small response was seen on the ipsilateral side. Ultrasonic techniques confirmed that the diaphragm was responding contralaterally and not ipsilaterally.

Measurement of twitch transdiaphragmatic pressure: surface versus needle electrode stimulation.

The transdiaphragmatic pressure (Pdi) generated during bilateral supramaximal phrenic nerve stimulation at 1 Hz from surface stimulating electrodes was compared with pressures obtained from needle electrodes inserted under local anaesthesia. Surface electrodes were used to obtain diaphragmatic electromyograms and magnetometers to monitor rib cage and abdominal configuration. Twitch Pdi was recorded at functional residual capacity in three normal subjects. Mean (SD) twitch Pdi in the three subjects during stimulation with surface electrodes was 19.4 (1.8), 22.5 (1.1), and 29.3 (2.2) cm H2O compared with 12.9 (1.5), 17:4 (1.3), and 22.6 (3.0) cm H2O with needle stimulating electrodes. Thus phrenic nerve stimulation with needle electrodes was more complicated and more invasive than stimulation with surface electrodes and resulted in lower transdiaphragmatic pressures.

Respiratory muscle function in cystic fibrosis.

Maximal static expiratory and inspiratory mouth pressures (PEmax and PImax) and quadriceps femoris muscle strength were measured in 25 patients aged 16-28 years with cystic fibrosis (mean FEV1 46% predicted). Mean (SD) PEmax was 64% (18%) predicted (below 75% predicted in 16 of the 25 patients), and PImax was 64% (24%) predicted (below 75% predicted in 14 patients). Quadriceps muscle strength was 68% (20%) predicted (below 75% predicted in 17 patients). The relatively small reduction in respiratory muscle strength in these patients was unlikely to have contributed appreciably to their respiratory problems.

Tracheobronchial clearance in patients with bilateral diaphragmatic weakness.

Tracheobronchial clearance was measured in seven patients with bilateral diaphragmatic weakness using a noninvasive objective radioaerosol technique. The data were compared with those from seven healthy nonsmoking control subjects matched for physical characteristics and studied under the same experimental conditions; the control subjects were drawn from a data bank of healthy subjects and were matched to the patients for age, sex, and the initial distribution of their radioaerosol deposition. Pulmonary function indices (FEV1, FVC, PEFR, and MMFR25-75) for the patients were all significantly (p less than 0.01) reduced compared with those for the control subjects. The initial topographic distribution of the radioaerosol within the lungs of the patients and control groups was similar: alveolar deposition [mean (SD)] was 36.4 (6.7) versus 41.0 (4.0)%, and penetration index was 0.56 (0.08) versus 0.56 (0.03), respectively. Tracheobronchial clearance of deposited radioaerosol over a 6-h observation period after inhalation showed a marked reduction (p less than 0.02) in the patients: area under the clearance curve (between zero and 6 h) was 262 (80)% h for the patients and 142 (41)% h for the healthy control subjects. These data suggest that in patients with bilateral diaphragmatic weakness, mucociliary clearance is depressed, or that reduced mechanical movement of the lungs can itself impair clearance of secretions from the lungs. Impaired clearance from either cause may contribute to an increased incidence of chest infections in severe respiratory muscle weakness.

Unsuspected myasthenia gravis presenting as respiratory failure.

A patient developed respiratory failure after surgical removal of a recurrent thymoma, which necessitated removal of part of the diaphragm. The respiratory failure was due to previously undiagnosed myasthenia gravis, which had selectively affected the respiratory muscles.

Influence of lung volume and rib cage configuration on transdiaphragmatic pressure during phrenic nerve stimulation in man.

Transdiaphragmatic pressure was recorded during bilateral supramaximal percutaneous phrenic nerve stimulation at 1 Hz (twitch Pdi) to investigate the effect of lung volume and rib cage configuration on diaphragm contractility in man. Stimulations were performed in 5 normal supine subjects at resting end expiration (FRC) and at lung volumes above and below FRC, during relaxation against a closed airway and during isovolume manoeuvres. Twitch Pdi at FRC was 24.4 cm H2O. At lung volumes above FRC, twitch Pdi decreased by 7.04 +/- 3.2 cm H2O per litre of volume change. At lung volumes below FRC, twitch Pdi increased by 12.4 +/- 8.6 cm H2O per litre of volume change. When the diaphragm was lengthened during an isovolume manoeuvre at FRC, twitch Pdi increased. A similar relationship between lung volume and twitch Pdi was obtained during stimulations performed with abdominal binding. These results demonstrate that the pressure developed by the diaphragm during phrenic nerve stimulation is significantly affected both by increases and decreases in lung volume and by the rib cage configuration at which stimulation is performed.

Putative cerebral cortical involvement in the ventilatory response to inhaled CO2 in conscious man.

1. The response of the diaphragm to both transcranial magnetic stimulation and electrical phrenic nerve stimulation was studied in thirteen normal subjects under conditions of either a 'reflex' drive to ventilation with inhaled CO2 or during volitional ventilation of similar magnitude. 2. The induced compound action potential in the diaphragm was recorded using an oesophageal electrode, and in some cases transdiaphragmatic pressure was recorded using oesophageal and gastric balloon catheters. 3. The response of the diaphragm to transcranial magnetic stimulation was invariably facilitated with volitional inspiration; there was either minimal or no response at functional residual capacity. 4. Facilitation with inspiration was also seen during a 'reflex' drive to ventilation with inhaled CO2 in the presumed absence of any volitional contribution to ventilation. A similar degree of facilitation was seen with voluntary ventilation of similar magnitude and pattern. 5. If the facilitation is predominantly a cortical phenomenon, then these results imply that there is a behavioural component in the previously supposed purely 'reflex' drive to ventilation with inhaled CO2. We also discuss the interpretation of these results if some of the facilitation occurs at the phrenic motoneurone.

Twitch pressures in the assessment of diaphragm weakness.

To assess the value of phrenic nerve stimulation in the investigation of diaphragm function, transdiaphragmatic pressures were measured in 20 healthy subjects and in 15 patients with diaphragm weakness, during unilateral and bilateral transcutaneous phrenic nerve stimulation at 1 Hz at functional residual capacity (twitch Pdi). Diaphragm function was initially assessed by measuring transdiaphragmatic pressure during a voluntary manoeuvre, the maximal sniff (sniff Pdi); normal readings were confirmed in the control subjects (102-157 (normal greater than 98) cm H2O in the 10 men, 79-102 (normal greater than 70) cm H2O in the 10 women) and reduced values were found in the 15 patients with diaphragm weakness (7.5-90 cm H2O in the 13 men, 23 and 53 cm H2O in the two women). Twitch Pdi during bilateral phrenic nerve stimulation ranged from 8.8 to 33 cm H2O in the control subjects and from 3.1 to 27 cm H2O in the 10 patients in whom a measurement could be obtained. Bilateral twitch Pdi correlated with sniff Pdi both in the control subjects and in the patients with diaphragm weakness (r = 0.75). Only four patients had a bilateral twitch Pdi below the lowest value seen in the control group, including the three with the lowest sniff Pdi (3.1-8.5 cm H2O). These results indicate that transdiaphragmatic pressure recorded during bilateral phrenic nerve stimulation discriminated between control subjects and patients with known weakness of the diaphragm only when this was severe.

Respiratory muscle weakness in the Lambert-Eaton myasthenic syndrome.

Respiratory muscle function was assessed in six patients with the Lambert-Eaton myasthenic syndrome. Five had histologically proved small cell carcinoma of the lung; the sixth later developed metastases from an unknown primary site. Two patients had ventilatory failure, one without respiratory symptoms; another, who had emphysema, had dyspnoea and orthopnoea. The remaining three patients had no respiratory symptoms. Four patients had limb muscle weakness as judged by the maximal voluntary contraction of the quadriceps muscle (range for all subjects 32-100% predicted). Transdiaphragmatic pressure (Pdi) was measured during a maximal unoccluded sniff (Pdi: sniff), a maximal sustained inspiratory effort against a closed airway (Pdi: Pimax), and phrenic nerve stimulation (Pdi: twitch). Mild to moderate diaphragmatic weakness was present in all six patients in proportion to the degree of leg weakness (Pdi: sniff 30-64% predicted; r = 0.6; Pdi:Pimax 6-69% predicted, r = 0.8); this was associated with very low or absent Pdi:twitch during phrenic nerve stimulation. Four patients had weakness of the expiratory muscles. Improvement in muscle strength was documented in two patients after tumour chemotherapy and specific treatment with 3,4-diaminopyridine and prednisolone; one patient was still alive five years from first diagnosis. It is concluded that the respiratory muscles may be implicated in this condition more often than has previously been recognised. As the lack of mobility may cause respiratory symptoms to be minimised, the presence of respiratory muscle weakness may remain undiagnosed unless formal measurement of respiratory muscle function is made.

The effect of aminophylline on respiratory and limb muscle contractility in man.

The effect of oral aminophylline on respiratory muscle and quadriceps femoris strength was compared with placebo in five normal subjects. A double-blind randomized cross-over protocol, spanning 2-3 wks, was followed. Aminophylline was taken before both placebo and active drug periods to establish correct dosage, to allow tolerance to side-effects to develop, and to keep the two limbs of the study identical and double-blind. Maximal static inspiratory and expiratory mouth pressures at residual volume and total lung capacity, respectively, maximal sniff transdiaphragmatic pressure, maximal voluntary quadriceps femoris contraction force and theophylline levels were measured during placebo and active drug periods. For the group, there were no significant differences between respiratory or quadriceps muscle strength on aminophylline and on placebo although there was a tendency for greater values on aminophylline. Mean theophylline level was 14.6 mg.l-1 (range 8.4-25.0 mg.l-1). We conclude that aminophylline produces no enhancement of skeletal muscle strength, at therapeutic dosage in normal subjects.

Reversible respiratory muscle weakness in hyperthyroidism.

Breathlessness is a common complaint in patients with hyperthyroidism, and respiratory failure requiring artificial ventilation, although rare, can occur. While a proximal myopathy is frequently recognized, diaphragm muscle function has not hitherto been studied in detail in thyrotoxicosis. The strength of the quadriceps femoris and respiratory muscles was therefore assessed in seven consecutive thyrotoxic patients, on presentation and during medical treatment, when euthyroid. Prior to therapy, reduced quadriceps muscle strength, vital capacity, and global expiratory and inspiratory muscle strength were found. Diaphragmatic weakness was present in one of four patients studied by measuring transdiaphragmatic pressures during maximal sniffs and during bilateral phrenic nerve stimulation at 1 Hz (twitch). After treatment, significant improvement occurred in quadriceps muscle strength, vital capacity, and global respiratory muscle strength. Sniff and twitch transdiaphragmatic pressures also increased significantly. These results indicate that respiratory muscle weakness occurs in hyperthyroidism and that such weakness is reversible with medical treatment. It is important to realize that respiratory muscles may be directly affected when assessing thyrotoxic patients with breathlessness, as severe involvement of the respiratory muscles may cause respiratory failure.

The value of sniff esophageal pressures in the assessment of global inspiratory muscle strength.

Esophageal pressure generated during a maximal sniff (sniff Pes) was compared with mouth pressure generated during a maximal inspiration against a closed airway (Pimax) as a measure of global inspiratory muscle strength in 61 patients referred for investigation of respiratory muscle function. Transdiaphragmatic pressure (Pdi) was also measured during both maneuvers to compare maximal diaphragmatic strength. Sniff Pes (males, 68 +/- 27 cm H2O; normal greater than 53; females, 66 +/- 21; normal greater than 48) was greater than Pimax (males, 45 +/- 24 cm H2O; normal greater than 42; females, 42 +/- 24; normal greater than 17) in 55 of the 61 patients, both in absolute values and as a percentage of normal. In 36 patients Pimax and sniff Pes were both normal (mean +/- 2 SD), whereas in 13 patients they were both low. In 11 patients, Pimax was low, but sniff Pes was normal. One patient had a reduced sniff Pes but a Pimax at the lower limit of normal. In the 36 patients in whom both Pimax and sniff Pes were normal, Pdi was also normal or only moderately reduced, and in the 13 patients in whom both Pimax and sniff Pes were reduced, Pdi was very low. However, in the group of 11 patients with a low Pimax but a normal sniff Pes, Pdi was normal or only moderately reduced, suggesting that Pimax was falsely low, perhaps because of difficulties with the technique. Conversely, in the single patient with a low sniff Pes but a Pimax just within the normal range, Pdi was very low. We conclude that measurement of esophageal pressure during a maximal sniff is a useful test of inspiratory muscle strength and overcomes the difficulty some patients have in carrying out the Pimax maneuver.