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(Chest. 2005;128:190-195.)
© 2005 American College of Chest Physicians

Influence of Different Trigger Techniques on Twitch Mouth Pressure During Bilateral Anterior Magnetic Phrenic Nerve Stimulation*

Wolfram Windisch, MD; Hans-Joachim Kabitz and Stephan Sorichter, MD

* From the Department of Pneumology, University Hospital Freiburg, Freiberg, Germany.

Correspondence to: Wolfram Windisch, MD, Department of Pneumology, University Hospital Freiburg, Killianstrasse 5, D-79106 Freiburg, Germany; e-mail: windisch{at}med1.ukl.uni-freiburg.de


    Abstract
 TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Background: The trigger has a key role when assessing the twitch mouth pressure (Tw Pmo), since a "gentle" inspiratory or expiratory effort is needed for triggering to ensure an open glottis during twitch, but which also guaranties only very mild changes of transdiaphragmatic pressure following changes in lung volume.

Study objectives: To test if different trigger mechanisms cause different Tw Pmo values, if the predefined trigger criteria were accomplished, and if the breathing maneuver during triggering can influence the Tw Pmo.

Design: Experimental study.

Setting: Respiratory muscle and lung function laboratory of a university hospital.

Participants: Twenty healthy men (mean age, 25.6 ± 1.2 years [± SD]; mean FEV1, 105.9 ± 11.5% of predicted).

Measurements: Tw Pmo produced by bilateral anterior magnetic phrenic nerve stimulation was measured using an inspiratory flow trigger (40 mL/s), an inspiratory pressure trigger, and an expiratory pressure trigger (3.75 mm Hg). All trigger criteria were controlled.

Results: Unusable pressure-time curves occurred in 40% during expiratory triggering, but not during inspiratory triggering. For inspiratory pressure (flow) triggering, 10% (30%) of the predefined trigger criteria were exceeded by 50%, indicating that a "gentle" inspiratory effort was not warranted. The Tw Pmo was higher during inspiratory compared to expiratory triggering (analysis of variance, p < 0.05). The Tw Pmo during inspiratory pressure and flow triggering were comparable and significantly correlated (r = 0.70, p < 0.0001). The time between start of inspiration and trigger release, and the pressure-time product during that period ranged widely, but this could not predict the Tw Pmo (multiple linear regression).

Conclusions: The trigger technique influences the Tw Pmo with higher values during inspiratory compared to expiratory triggering. Expiratory triggering more often produced unusable pressure-time curves. Inspiratory flow and pressure triggering is comparably useful in healthy subjects, but this might be different in patients. The trigger criteria need to be controlled to warrant a gentle breathing effort.

Key Words: bilateral anterior magnetic phrenic nerve stimulation • diaphragm • inspiratory muscle strength • maximal inspiratory mouth pressure • phrenic nerve stimulation • respiratory muscle testing • sniff pressure • trigger • twitch pressure


    Introduction
 TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
The assessment of inspiratory muscle strength is essential in the investigation of respiratory disturbances.12 Volitional and noninvasive tests such as the measurement of maximal inspiratory mouth pressure (PImax) and nasal pressure during a maximal sniff (Sn Pna) are the simplest and most widely used specific diagnostic tests for quantification of global inspiratory muscle strength, but it is difficult to ensure that the subjects are making a truly maximal effort.34 In contrast, the measurement of twitch transdiaphragmatic pressures (Tw Pdi) and twitch esophageal pressures (Tw Pes) in response to phrenic nerve stimulation allows the assessment of inspiratory muscle contractility more accurately and independently from the patience’s ability to perform a maximal inspiratory effort, even in critically ill patients.345 However, these measurements require the placement of esophageal and gastric balloon catheters, which is often unpleasant for the patient and difficult to perform and, therefore, reserved to some few centers that have the adequate expertise.678

The measurement of the twitch mouth pressure (Tw Pmo) in response to phrenic nerve stimulation has been recognized as a valuable diagnostic tool for the assessment of diaphragmatic strength, since it is nonvolitional but is also noninvasive.368 Since the transdiaphragmatic pressure is reciprocally proportional to the lung volume, it is recommended to apply the magnetic impulse as close as possible to the functional residual capacity (FRC).91011 However, the transmission of the intrathoracic pressure to the mouth during measurements at the relaxed FRC may be hindered by glottic closure.6712 Therefore, inspiratory or expiratory effort is necessary to ensure an open glottis during phrenic nerve stimulation, but this effort needs to be "gentle" to avoid changes in lung volume that could change the transdiaphragmatic pressure and that also may lead to unintentional twitch potentiation.6111314 Therefore, the trigger mechanism for the release of the magnetic twitch has a key role in the accurate assessment of the Tw Pmo.

Both inspiratory and expiratory trigger mechanisms have been introduced for the assessment of the Tw Pmo.671516 However, it is unclear if differences in trigger mechanisms and trigger conditions can lead to different Tw Pmo. In addition, it is unclear if the subjects performed a truly gentle inspiratory or expiratory effort, since the predefined trigger criteria were not controlled in most studies. Therefore, the aim of the present study was to test if different trigger mechanisms cause differences in the Tw Pmo, if the predefined trigger criteria have been accomplished, and if the breathing maneuver during triggering can influence the Tw Pmo.


    Materials and Methods
 TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
The study protocol was approved by the Agency of Ethics of Albert-Ludwig University, Freiburg, Germany, and was performed in accordance with the ethical standards laid down 2000 in the Declaration of Helsinki. Informed written consent was obtained from all subjects. Twenty young and healthy men without lung or thoracic rib cage disease who did not take any medication were studied after careful instruction (Table 1 ). Lung function parameters using body plethysmography were measured (Masterlab-Compact Labor; Jaeger; Hochberg, Germany). Sn Pna, PImax, and Tw Pmo were also measured (ZAN 100; ZAN Gerätetechnik GmbH; Oberthulba, Germany). For PImax, peak and plateau pressures have been measured both at residual volume (RV) and at FRC as has been described previously.17


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Table 1. Demographic Data and Parameters on Lung Function and Volitional Tests of Inspiratory Muscle Strength in 20 Healthy Subjects*

 
Tw Pmo: Recordings of Pressure and Air Flow
Tw Pmo was measured using a flanged mouthpiece connected to cylinder with a shutter at its distal end that functions as a magnetic catch piston to completely occlude the external airway for 2.0 s. A steel tube of 4 cm in length and 1 mm in internal diameter was placed proximally of the shutter as has been described previously,16 thereby preventing glottic closure during the maneuver. The cylinder was connected to a pressure transducer and pneumotachograph interfaced with a computer system. This allowed visualization of the pressure-time curves and displaying of the flow signal to the participant.

Pressure and volume calibration of the system was performed daily prior to the measurements. All measurements were performed only by one specialized person with the participant in a seated position wearing a nose clip. All pressures generated by the inspiratory muscles are presented with positive numbers.

Bilateral Anterior Magnetic Phrenic Nerve Stimulation
Bilateral anterior magnetic phrenic nerve stimulation518 was performed using two magnetic stimulators (Magstim 2002; Magstim; Wales, UK) at maximal output (100%). For this purpose, two 45-mm figure-eight coils (Magstim) generating a magnetic field of 3.2 T at maximal drive were used. Both magnetic stimulators were triggered simultaneously; here, the impulse was automatically released by an electric signal derived from the computer system as soon as the below-defined trigger criteria have been achieved.

The coils were placed around the posterior border of the sternomastoid muscle at the level of the cricoid cartilage as previously described.16 The accurate position of the coils was warranted by slightly moving the coils until the greatest Tw Pmo amplitude was recorded.61119 For measurements of the experimental study design, all Tw Pmo measures were recorded by performing the twitch exactly at this position, which was marked by a highlighter. For the purpose of holding the position, a steel bracket for fixing the coils was constructed that ensured that the angle and the position of the coils were unchanged during all measurements.

Experimental Study Design
To avoid twitch potentiation,111314 a rest of 20 min in which the participant breathed quietly without speaking preceded the experiments after locating the correct coil position. The elapsed time between successive maneuvers exceeded 30 s. The Tw Pmo was recorded using three different techniques for triggering in a random order (experiments 1, 2, and 3). For each experiment, the Tw Pmo was measured until five acceptable pressure tracings according to the criteria defined below were recorded. Subsequently, the highest and lowest Tw Pmo measures were deleted, and the mean of the remaining three values was counted. The trigger was started close to the FRC in all experiments. For this purpose, the participant was instructed to breathe quietly and to perform a "gentle" inspiratory or expiratory effort as the valve was closed.

Experiment 1:
To assess Tw Pmo during inspiratory flow triggering (Tw Pmo InF), the shutter was closed immediately after the beginning of inspiration. The magnetic impulse was initiated when the inspiratory flow of the participant reached 40 mL/s. The duration of shutter occlusion lasts approximately 76 ms. This time has to be taken into account when starting the trigger, since it is principally possible that the trigger release occurs to early when the shutter is not completely closed yet. Therefore, it was also required for triggering that the inspiratory pressure was at least 3.75 mm Hg, which ensured that the shutter was completely closed.

Experiment 2:
To assess Tw Pmo during inspiratory pressure triggering (Tw Pmo InP), the shutter was closed immediately after the beginning of inspiration. The magnetic impulse was initiated as soon as the inspiratory pressure of the participant had reached 3.75 mm Hg. In addition, it was also required for triggering that the inspiratory flow was at least 10 mL/s to avoid a pure static pressure development.

Experiment 3:
To assess Tw Pmo during expiratory pressure triggering (Tw Pmo ExP), the shutter was closed as soon as 95% of the tidal volume (VT) was exhaled. The magnetic impulse was initiated as soon as the expiratory pressure had reached 3.75 mm Hg.

For inspiratory triggering, the Tw Pmo was regarded as the difference between the trigger impulse and the peak pressure (Fig 1 ). The beginning of inspiration was reliably detected if the inspiratory volume has reached 10 mL. For expiratory triggering, the Tw Pmo was regarded as the difference between the pressure at the point of reversal of the pressure direction and the peak pressure. The time span between complete shutter occlusion and trigger impulse (tshut-trig) was calculated (Fig 1). In addition, the area under the pressure-time curve (pressure-time product) during tshut-trig (PTPshut-trig) was calculated (Fig 1). The breathing frequency (fb) and the VT were calculated as the mean of the last three breaths. The inspiratory pressure at triggering (PIn trig), expiratory pressure at triggering (PEx trig), and the inspiratory flow during triggering (FIn trig) were measured to verify if the trigger criteria were accomplished as demanded by the target of each experiment.



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Figure 1. Assessment of Tw Pmo, tshut-trig, and PTPshut-trig.

 
To ensure a gentle inspiratory or expiratory effort, the Tw Pmo was only accepted if the difference between the predefined and measured trigger criteria did not exceed 50%. Accordingly, the Tw Pmo was not accepted if the FIn trig was > 60 mL/s (trigger criteria, 40 mL/s) during inspiratory flow triggering or if the PIn trig was >5.625 mm Hg and if the PEx trig was >5.625 mm Hg (trigger criteria, 3.75 mm Hg) during inspiratory and expiratory pressure triggering, respectively. In addition, the pressure-time curves need to present a clear twitch reply of the diaphragm with a clear increase and decrease of the inspiratory pressure following the trigger impulse.

Statistical Analysis
Statistical analysis was performed using Sigma-Stat (Version 2.03; SPSS; Chicago, IL). Data are presented as mean ± SD after testing for normal distribution (Kolmogorov Smirnov test). Comparisons between different measurements (different Tw Pmo in experiments 1, 2, and 3) were performed using one-way analysis of variance. Correlation analysis was performed using the Pearson product moment correlation. In addition, fb, FIn trig, PIn trig, PTPshut-trig, and tshut-trig during inspiratory triggering (experiments 1 and 2) were compared using the unpaired t test if data were normally distributed or using the Mann-Whitney rank test if data were not normally distributed. Further, the Tw Pmo was calculated for its predictors, which could be derived from measurement variables of the pressure-time curve using the multiple linear regression analysis. Here, Tw Pmo was used as dependent variable, and FIn trig, PIn trig, and PTPshut-trig or tshut-trig were used as independent variables if an inspiratory trigger was used. Accordingly, Tw Pmo was used as dependent variable, and PEx trig and PTPshut-trig or tshut-trig were used as independent variables if an expiratory trigger was used. Statistical significance was assumed at p < 0.05.


    Results
 TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Unusable pressure-time curves without a clear increase and decrease of the inspiratory pressure occurred in 40% when using the expiratory trigger (Fig 2 ), but all trigger criteria could be accepted. For inspiratory pressure triggering, 10% of the pressure-time curves could not be accepted, since the difference between the predefined and measured trigger criteria was > 50%. Accordingly, 30% of the pressure-time curves could not be accepted for inspiratory flow triggering, but nearly all pressure-time curves during inspiratory triggering were acceptable.



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Figure 2. Pressure-time curve of the Tw Pmo during expiratory pressure triggering that was not accepted according to predefined criteria.

 
The Tw Pmo was higher when using inspiratory compared to expiratory trigger techniques (Tables 2, 3 ; Fig 3 ). The Tw Pmo InF was significantly correlated to the Tw Pmo InP (r = 0.70, p < 0.0001) and to the Tw Pmo ExP (r = 0.67, p = 0.001). In contrast, the Tw Pmo InP and the Tw Pmo ExP were not correlated (r = 0.28, p = 0.23). During inspiratory flow (Fig 4 ) and pressure (Fig 5 ) triggering, the inspiratory pressure increased slightly at the beginning of inspiration prior to triggering and subsequently steepened markedly after inspiratory muscle contraction following magnetic twitch (twitch reply). In contrast, there was a reversal of the pressure direction during expiratory triggering when switching from gentle volitional expiration to maximal inspiratory diaphragm contraction (Fig 6 ).


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Table 2. Descriptive Data of Experiments 1 and 2 (n = 20): Tw Pmo During Inspiratory Flow Trigger (Experiment 1) and During Inspiratory Pressure Trigger (Experiment 2)

 

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Table 3. Descriptive Data of Experiment 3: Tw Pmo During Expiratory Pressure Trigger*

 


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Figure 3. Comparison of different Tw Pmo using different inspiratory and expiratory trigger techniques.

 


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Figure 4. Representative pressure-time curve of the Tw Pmo during inspiratory flow triggering.

 


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Figure 5. Representative pressure-time curve of the Tw Pmo during inspiratory pressure triggering.

 


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Figure 6. Representative pressure-time curve of the Tw Pmo during expiratory pressure triggering. See Table 3 for expansion of abbreviation.

 
Although the trigger criteria of the counted pressure-time curves were consistent (Tables 2, 3), the variance and range of the tshut-trig and the PTPshut-trig were wide, indicating that the breathing maneuver occurred with slow and rapid increases of the flow/pressure until attaining the trigger threshold. However, this could not explain the variance of the Tw Pmo, since there were no significant predictors out of the predefined independent variables in any experiment following the multiple linear regression analysis.


    Discussion
 TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
There is a need of assessing inspiratory muscle strength in patients with respiratory disturbances.12 Volitional tests are most widely used, but their interpretation is limited by the possibility of false pathologic values, since these measurements are dependent from the subject performing a truly maximal effort.34 The assessment of the Tw Pmo is easy to perform and independent from the patient’s cooperation and could, therefore, become a worthwhile alternative. However, it is still unclear which trigger should be applied, although triggers of 3.75 mm Hg or 40 mL/s have been suggested to ensure an open glottis, but also to warrant a gentle inspiratory or expiratory effort.616

In the present study, it has been shown that a gentle breathing effort could not be guarantied, since the flow and the pressure, respectively, were > 50% of the predefined trigger criteria in 30% during inspiratory flow triggering and in 10% during inspiratory pressure triggering even in well-informed healthy subjects. This, however, is suggested to cause changes in lung volume that need to be avoided.6111314 Therefore, a gentle inspiratory effort starting from very close to the FRC for triggering is essential and needs to be controlled and monitored in all future studies.

Inspiratory trigger mechanisms produced a higher Tw Pmo than the expiratory trigger mechanism. This might be in part attributed to technical differences, since the Tw Pmo following expiratory triggering only reflects the pressure development caused by twitch-induced diaphragm contraction, whereas the Tw Pmo following inspiratory triggering implies the pressure development generated by the twitch-induced diaphragm contraction in addition to the preceding increasing inspiratory pressure development during the latency between trigger impulse and twitch reply. Therefore, the Tw Pmo generated by expiratory compared to inspiratory triggering reflects the twitch reply more precisely.

Former studies have not clearly indicated how many pressure-time curves could not be analyzed. In the present study, expiratory but not inspiratory triggering often produced unusable pressure-time curves without a clear pressure maximum. The reason for this remains unclear, but might be attributed to the reversal of the flow and pressure direction when switching from gentle expiration to twitch-induced inspiratory diaphragm contraction. Based on these results, inspiratory triggering is more reliable than expiratory triggering. Accordingly, in both healthy subjects and patients with severe COPD, inspiratory but not expiratory triggering produced a significant correlation between Tw Pmo and Tw Pes in former studies,716 favoring an inspiratory trigger for future studies. However, the Tw Pmo has been shown to reliably predict Tw Pes and also Tw Pdi both in healthy subjects6720 and in patients with respiratory muscle weakness without lung disease,6 but the prediction of Tw Pes from Tw Pmo is hindered by an impaired transmission of intrathoracic pressure to the upper airway following airway obstruction.16

The Tw Pmo generated by flow- and pressure-driven inspiratory trigger mechanisms were comparable and significantly correlated to each other. However, these results are valid for healthy subjects only, and changes in respiratory mechanics might lead to differences in the pressure generation prior to attaining the trigger threshold. In addition, the breathing maneuver when activating the trigger was markedly different with slow and rapid increases of the flow and pressure until attaining the trigger threshold. However, no predictors derived from the pressure-time curve that indicate how fast or slow the pressure increased until attaining the trigger threshold could be identified to explain the variance of the Tw Pmo. Therefore, it was insubstantial for the Tw Pmo as to how slow or how fast the trigger criteria were accomplished.

Further studies on influences of different trigger techniques on the Tw Pmo including both healthy subjects and patients with chronic lung disease are required before a clear recommendation can be given of how the trigger should be performed. Thereby, measurements of the Tw Pdi and Tw Pes and measurements of twitch potentiation should be included to validate the most favorable trigger technique.


    Conclusion
 TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
The measurement of the Tw Pmo is suggested to be a valuable diagnostic tool for the assessment of inspiratory muscle strength. The correct application is independent from the cooperation of the patient, but is yet easy to perform, which could allow a widely used implementation in the future. The choice of triggering the magnetic twitch significantly influences the Tw Pmo with higher values during inspiratory compared to expiratory triggering. The inspiratory trigger is suggested to be more reliable compared to the expiratory trigger, favoring the inspiratory trigger for future studies. The trigger criteria that are designed to ensure an open glottis and a gentle inspiratory or expiratory effort need to be measured and controlled, since an increase of flow/pressure during triggering can occur causing changes in lung volume and transdiaphragmatic pressure that need to be avoided. Further studies including measurement with balloon catheters are required to verify which trigger technique is most applicable and useful.


    Acknowledgements
 
We thank Roland Merklein (ZAN; Oberthulba, Germany) for writing the software and for technical assistance.


    Footnotes
 
Abbreviations: fb = breathing frequency; FIn trig = inspiratory flow at triggering; FRC = functional residual capacity; PEx trig = expiratory pressure at triggering; PImax = maximal inspiratory mouth pressure; PIn trig = inspiratory pressure at triggering; PTPshut-trig = pressure-time product during tshut-trig; RV = residual volume; Sn Pna = nasal pressure during a maximal sniff; tshut-trig = time span between complete shutter occlusion and trigger impulse; Tw Pdi = twitch transdiaphragmatic pressures; Tw Pes = twitch esophageal pressures; Tw Pmo = twitch mouth pressure; Tw Pmo ExP = twitch mouth pressure during expiratory pressure triggering; Tw Pmo InF = twitch mouth pressure during inspiratory flow triggering; Tw Pmo InP = twitch mouth pressure during inspiratory pressure triggering; VT = tidal volume

Received for publication September 12, 2004. Accepted for publication December 14, 2004.


    References
 TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 

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  12. Similowski, T, Gauthier, AP, Yan, S, et al Assessment of diaphragm function using mouth pressure twitches in chronic obstructive pulmonary disease patients. Am Rev Respir Dis 1993;147,850-856[Medline]
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  17. Windisch, W, Hennings, E, Sorichter, S, et al Peak or plateau maximal inspiratory mouth pressure: which is best? Eur Respir J 2004;23,708-713[Abstract/Free Full Text]
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