John Moxham

Potentiation of diaphragmatic twitch after voluntary contraction in normal subjects.

BACKGROUND--Skeletal muscle twitch responses may be transiently increased by previous contractions, a phenomenon termed twitch potentiation. The aim of this study was to examine the extent and time course of diaphragmatic twitch potentiation and its relationship to both the magnitude and duration of the preceding voluntary diaphragmatic contraction. METHODS--Twitch transdiaphragmatic pressure (PDI) was measured in six normal subjects, before and after voluntary diaphragm contractions of 100%, 75%, 50%, and 25% of maximum PDI (PDImax) sustained for five and 10 seconds. RESULTS--Twitch PDI was significantly increased after 100%, 75%, and 50% contractions. Following maximal contractions sustained for 10 seconds the mean increase in twitch PDI was 52%. Following 50% contractions sustained for five seconds the mean increase in twitch height was 28%. In all runs twitch PDI returned to rested levels within 20 minutes. CONCLUSIONS--Twitch potentiation can be substantial, even following submaximal contractions, and must be taken into account when twitch pressure is used to assess diaphragm contractility.

Unilateral magnetic stimulation of the phrenic nerve.

BACKGROUND--Electrical stimulation of the phrenic nerve is a useful non-volitional method of assessing diaphragm contractility. During the assessment of hemidiaphragm contractility with electrical stimulation, low twitch transdiaphragmatic pressures may result from difficulty in locating and stimulating the phrenic nerve. Cervical magnetic stimulation overcomes some of these problems, but this technique may not be absolutely specific and does not allow the contractility of one hemidiaphragm to be assessed. This study assesses both the best means of producing supramaximal unilateral magnetic phrenic stimulation and its reproducibility. This technique is then applied to patients. METHODS--The ability of four different magnetic coils to produce unilateral phrenic stimulation in five normal subjects was assessed from twitch transdiaphragmatic pressure (TwPDI) measurements and diaphragmatic electromyogram (EMG) recordings. The results from magnetic stimulation were compared with those from electrical stimulation. To determine whether the magnetic field affects the contralateral phrenic nerve as well as the intended phrenic nerve, EMG recordings from each hemidiaphragm were compared during stimulation on the same side and the opposite side relative to the recording electrodes. The EMG recordings were made from skin surface electrodes in five normal subjects and from needle electrodes placed in the diaphragm during cardiac surgery in six patients. Similarly, the direction of hemidiaphragm movement was evaluated by ultrasonography. To determine the usefulness of the technique in patients the 43 mm mean diameter double coil was used in 54 patients referred for assessment of possible respiratory muscle weakness. These results were compared with unilateral electrical phrenic stimulation, maximum sniff PDI, and TwPDI during cervical magnetic stimulation. RESULTS--In the five normal subjects supramaximal stimulation was established for eight out of 10 phrenic nerves with the 43 mm double coil. Supramaximal unilateral magnetic stimulation produced a higher TwPDI than electrical stimulation (mean (SD) 13.4 (2.5) cm H2O with 35 mm coil; 14.1 (3.8) cm H2O with 43 mm coil; 10.0 (1.7) cm H2O with electrical stimulation). Spread of the magnetic field to the opposite phrenic nerve produced a small amplitude contralateral diaphragm EMG measured from skin surface electrodes which reached a mean of 15% of the maximum EMG amplitude produced by ipsilateral stimulation. Similarly, in six patients with EMG activity recorded directly from needle electrodes, the contralateral spread of the magnetic field produced EMG activity up to a mean of 3% and a maximum of 6% of that seen with ipsilateral stimulation. Unilateral magnetic stimulation of the phrenic nerve was rapidly achieved and well tolerated. In the 54 patients unilateral magnetic TwPDI was more closely related than unilateral electrical TwPDI to transdiaphragmatic pressure produced during maximum sniffs and cervical magnetic stimulation. Unilateral magnetic stimulation eliminated the problem of producing a falsely low TwPDI because of technical difficulties in locating and adequately stimulating the nerve. Eight patients with unilateral phrenic nerve paresis, as indicated by a unilaterally elevated hemidiaphragm on a chest radiograph and maximum sniff PDI consistent with hemidiaphragm weakness, were all accurately identified by unilateral magnetic stimulation. CONCLUSIONS--Unilateral magnetic phrenic nerve stimulation is easy to apply and is a reproducible technique in the assessment of hemidiaphragm contractility. It is well tolerated and allows hemidiaphragm contractility to be rapidly and reliably assessed because precise positioning of the coils is not necessary. This may be particularly useful in patients. In addition, the anterolateral positioning of the coil allows the use of the magnet in the supine patient such as in the operating theatre or intensive care unit.

Mouth pressure in response to magnetic stimulation of the phrenic nerves.

BACKGROUND--Diaphragm strength can be assessed by the measurement of gastric (TW PGA), oesophageal (TW POES), and transdiaphragmatic (TW PDI) pressure in response to phrenic nerve stimulation. However, this requires the passage of two balloon catheters. A less invasive method of assessing diaphragm contractility during stimulation of the phrenic nerves would be of clinical value. A study was undertaken to determine whether pressure measured at the mouth (TW PM) during magnetic stimulation of the phrenic nerves accurately reflects TW POES, and to investigate the relations between TW PM and TW PDI; and also to see whether glottic closure and twitch potentiation can be avoided during these measurements. METHODS--Eight normal subjects and eight patients with suspected respiratory muscle weakness without lung disease were studied. To prevent glottic closure magnetic stimulation of the phrenic nerves was performed at functional residual capacity during a gentle expiratory effort against an occluded airway incorporating a small leak. TW PDI, TW POES, and TW PM were recorded. Care was taken to avoid potentiation of the diaphragm. RESULTS--In normal subjects mean TW PM was 13.7 cm H2O (range 11.3-16.1) and TW POES was 13.3 cm H2O (range 10.4-15.9) with a mean (SD) difference of 0.4 (0.81) cm H2O. In patients mean TW PM was 9.1 cm H2O (range 0.5-18.2) and TW POES was 9.3 (range 0.7-18.7) with a mean (SD) difference of -0.2 (0.84) cm H2O. The relation between TW PM and TW PDI was less close but was well described by a linear function. In patients with diaphragm weakness (low sniff PDI) TW PM was < 10 cm H2O. CONCLUSIONS--TW PM reliably reflects TW POES and can be used to predict TW PDI in normal subjects and patients without lung disease. TW PM may therefore be a promising non-invasive, non-volitional technique for the assessment of diaphragm strength.

Phrenic nerve stimulation in normal subjects and in patients with diaphragmatic weakness.

Phrenic nerve stimulation is often considered to be difficult and unreliable. The time taken for the phrenic nerves to be located and adequately stimulated was measured in 110 subjects, aged 21-89 years, 26 of whom had diaphragmatic weakness; and phrenic nerve conduction time was recorded in 76 of these individuals. Each phrenic nerve was stimulated transcutaneously in the neck with square wave impulses 0.1 ms in duration at 1 Hz and 80-160 volts while diaphragmatic muscle action potentials were recorded with surface electrodes. The time taken to locate either phrenic nerve ranged from two seconds to 22 minutes (median 10s). Both nerves were located in 83 of the 84 control subjects (99%) and in 21 of the 26 patients with diaphragmatic weakness (81%). Mean (SD) phrenic nerve conduction time in the control subjects was 6.94 (0.77) ms on the right and 6.61 (0.77) ms on the left. A weak relationship was found between conduction time and the subjects age and height. Four out of 24 patients with diaphragmatic weakness had a prolonged phrenic nerve conduction time. Transcutaneous stimulation of the phrenic nerves was not a time consuming procedure, and it was well tolerated, reproducible, and successful in 95% of subjects.

Measurement of sniff nasal and diaphragm twitch mouth pressure in patients.

BACKGROUND: Inspiratory muscle weakness is a recognised cause of unexplained dyspnoea. It may be suggested by the finding of a low static inspiratory mouth pressure (MIP), but MIP is a difficult test to perform, with a wide normal range; a low MIP may also occur if the patient has not properly performed the manoeuvre. Further investigation conventionally requires balloon catheters to obtain oesophageal (Poes) and transdiaphragmatic pressure (Pdi) during sniffs or phrenic nerve stimulation. Two non-invasive tests of inspiratory muscle strength have recently been described--nasal pressure during a maximal sniff (Sn Pnas) and mouth pressure during magnetic stimulation of the phrenic nerves (Tw Pmo). The use of these two tests in combination might identify patients without inspiratory muscle weakness who are unable to produce a satisfactory MIP< therefore avoiding the need for investigation with balloon catheters. METHODS: Thirty consecutive patients with clinically suspected inspiratory muscle weakness and a low MIP underwent both conventional (Sn Poes and Tw Pdi) and non-invasive testing (Sn Pnas and Tw Pmo). Weakness was considered to be excluded by a Sn Poes of > or = 80 cm H20 or a Tw Pdi of > or = 20 cm H20. The limit values used to test the hypothesis were Sn Pnas > or = 70 cm H20 or Tw Pmo > or = 12 cm H20. RESULTS: Inspiratory muscle weakness was excluded in 17 of the 30 patients. Fifteen of these would have been identified using Sn Pnas and Tw Pmo, with better results when the two tests were combined. The cut off values selected for Sn Pnas and Tw Pmo were shown by ROC plots to indicate normal strength conservatively, avoiding failure to detect mild degrees of weakness. No patient with global weakness was considered normal by Sn Pnas or Tw Pmo. CONCLUSIONS: In most patients with normal inspiratory strength and a low MIP, Tw Pmo and Sn Pnas used in combination can reliably exclude global inspiratory muscle weakness, reducing the number of patients who need testing with balloon catheters.

Diaphragm strength in patients with recent hemidiaphragm paralysis.

Eleven patients with unilateral diaphragm paralysis of recent onset were studied to investigate the effect of the paralysis on inspiratory muscle function. Nine of the patients had noticed a decrease in exercise tolerance, which was not explained by any other pathological condition. Hemidiaphragm dysfunction was confirmed by the demonstration of a greatly reduced or absent transdiaphragmatic pressure on stimulation of the phrenic nerve in the neck, by means of surface bipolar electrodes (unilateral twitch Pdi), compared with normal values on the contralateral side. Transdiaphragmatic pressure was 44.6% (9.4%) predicted during a maximal sniff and 30.3% (16.8%) predicted during a maximal static inspiration against a closed airway, confirming diaphragm weakness. Maximum static inspiratory mouth pressures were also low (61.7% (12.7%) predicted), consistent with a reduction in inspiratory muscle capacity. Phrenic nerve conduction time was prolonged on the affected side in nine patients, consistent with phrenic nerve dysfunction, whereas on the unaffected side it was normal. It is concluded that recent hemidiaphragm paralysis causes a reduction in transdiaphragmatic pressure that is associated with a reduction in maximum inspiratory mouth pressure. Phrenic nerve stimulation is a useful technique with which to confirm and quantify hemidiaphragm dysfunction. Measurement of phrenic nerve conduction time provides useful information about the underlying pathology.

Inspiratory muscle relaxation rate assessed from sniff nasal pressure.

BACKGROUND--Slowing of the maximum relaxation rate (MRR) of inspiratory muscles measured from oesophageal pressure (POES) during sniffs has been used as an index of the onset and recovery of respiratory muscle fatigue. The purpose of this study was to measure MRR at the nose (PNASAL MRR), to investigate its relationship with POES MRR, and to establish whether PNASAL MRR slows with respiratory loading. METHODS--Five normal subjects were studied. Each performed sniffs before and after two minutes of maximal isocapnic ventilation (MIV). In a separate session the subjects performed submaximal sniffs. POES and PNASAL were recorded during sniffs and the MRR (% pressure fall/10 ms) for each sniff was determined. RESULTS--Before MIV mean POES MRR was 8.9 and PNASAL MRR was 9.3. The mean (SD) difference between PNASAL MRR and POES MRR during a maximal sniff was 0.48 (0.34) (n = 64) and during submaximal sniffs was 0.28 (0.46) (n = 526). The subjects showed a mean decrease in sniff POES MRR of 27.4% (range 22.5-36%) after MIV and a similar reduction in sniff PNASAL MRR of 28.5% (range 24.1-41.3%). Both returned to control values within 5-10 minutes. CONCLUSIONS--PNASAL MRR reflects POES MRR over a wide range of sniff pressures, PNASAL MRR of maximal sniffs reflects POES MRR in normal subjects at rest and following MIV, so measurement of PNASAL MRR may be a useful non-invasive method for measuring inspiratory muscle MRR, thereby providing an index of respiratory muscle fatigue.

Effect of brachial plexus co-activation on phrenic nerve conduction time

BACKGROUND Diaphragm function can be assessed by electromyography of the diaphragm during electrical phrenic nerve stimulation (ES). Whether phrenic nerve conduction time (PNCT) and diaphragm electrical activity can be reliably measured from chest wall electrodes with ES is uncertain. METHODS The diaphragm compound muscle action potential (CMAP) was recorded using an oesophageal electrode and lower chest wall electrodes during ES in six normal subjects. Two patients with bilateral diaphragm paralysis were also studied. Stimulations were deliberately given in a manner designed to avoid or incur co-activation of the brachial plexus. RESULTS For the oesophageal electrode the PNCT was similar with both stimulation techniques with mean (SE) values of 7.1 (0.2) and 6.8 (0.2)u2009ms, respectively (pooled left and right values). However, for surface electrodes the PNCT was substantially shorter when the brachial plexus was activated (4.4 (0.1)u2009ms) than when it was not (7.4 (0.2)u2009ms) (mean difference 3.0u2009ms, 95% CI 2.7 to 3.4, p<0.0001). A small short latency CMAP was recorded from the lower chest wall electrodes during stimulation of the brachial plexus alone. CONCLUSIONS The results of this study show that lower chest wall electrodes only accurately measure PNCT when care is taken to avoid stimulating the brachial plexus. A false positive CMAP response to phrenic stimulation could be caused by inadvertent stimulation of the brachial plexus. This finding may further explain why the diaphragm CMAP recorded from chest wall electrodes can be unreliable with cervical magnetic stimulation during which brachial plexus activation occurs.

Effect of maximum ventilation on abdominal muscle relaxation rate.

BACKGROUND: When the demand placed on the respiratory system is increased, the abdominal muscles become vigorously active to achieve expiration and facilitate subsequent inspiration. Abdominal muscle function could limit ventilatory capacity and a method to detect abdominal muscle fatigue would be of value. The maximum relaxation rate (MRR) of skeletal muscle has been used as an early index of the onset of the fatiguing process and precedes failure of force generation. The aim of this study was to measure MRR of abdominal muscles and to investigate whether it slows after maximum isocapnic ventilation (MIV). METHODS: Five normal subjects were studied. Each performed short sharp expiratory efforts against a 3 mm orifice before and immediately after a two minute MIV. Gastric pressure (PGA) was recorded and MRR (% pressure fall/10 ms) for each PGA trace was determined. RESULTS: Before MIV the mean (SD) maximum PGA MRR for the five subjects was 7.1 (0.8)% peak pressure fall/10 ms. Following MIV mean PGA MRR was decreased by 30% (range 25-35%), returning to control values within 5-10 minutes. CONCLUSIONS: The MRR of the abdominal muscles, measured from PGA, is numerically similar to that described for the diaphragm and other skeletal muscles. After two minutes of maximal isocapnic ventilation abdominal muscle MRR slows, indicating that these muscles are sufficiently heavily loaded to initiate the fatiguing process.

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.