Diaphragmatic Response to Phrenic Nerve Stimulation

Diaphragmatic response to PNS would ideally be measured as work or power. However, length changes and velocity of shortening are invariably ignored and the focus has been on assessing diaphragm force development, either by measurement of pressure, or sound (phonomyography).

Pressure responses to PNS (twitches) are widely used to study diaphragm contraction. They depend not only on dia-

Figure 11. Technique for cervical magnetic stimulation (CMS). Top: The usual technique for CMS. The subject being seated, a circular coil of approximately 90 mm in diameter attached to a magnetic stimulator is centered on the spinous process of the seventh cervical vertebra (C7). The subject is usually asked to bend the neck forward to facilitate contact between the coil and the posterior surface of the neck. in this example, esophageal and gastric pressures (Pes and Pga, respectively) are measured via conventional balloon-catheter systems (see Techniques for Pressure Measurements). Subtracting Pes from Pga gives transdia-phragmatic pressure (Pdi). Surface electrodes are shown for the assessment of the electromyographic response of the diaphragm to stimulation (EMGdi). Bottom: Sites of nervous stimulation possibly responsible for the diaphragmatic contraction induced by CMS using a conventional 90-mm doughnut-shaped coil. The gray area is a schematic representation of the magnetic field. This can, theoretically, depolarize cervical roots, and also the phrenic nerve itself anteriorly, behind or below the clavicle. Phrenic nerve stimulation is theoretically possible with a circular coil placed anteriorly (lying flat on the upper part of the sternum: anterior magnetic stimulation) or posteriorly but lower (coil held vertical on the upper dorsal vertebral column).

phragm properties, but also on the load the diaphragm acts against, as for any muscle. This load depends on the mechanical characteristics of the rib cage and abdominal wall (see Techniques for Pressure Measurements).

Measurement of the sounds created by muscle contraction can now be quantified by phonomyography. At present this is a research tool, but it has considerable promise as it is technically easy and noninvasive (117).

Transdiaphragmatic pressure. In response to PNS, Pdi rapidly rises to a peak, and then decreases exponentially to its baseline value (Figure 12) to give a characteristic Pdi,tw. The

Figure 12. Typical pressure tracings in response to phrenic nerve stimulation. Traces A to C show, respectively, the esophageal pressure (Pes), gastric pressure (Pga), and transdiaphragmatic pressure (Pdi) responses to bilateral, supramaximal, electrical stimulation of the phrenic nerve in the neck, in a patient with COPD (hence the relatively low amplitudes). On the Pdi trace (C) are indicated some indexes often used to describe quantitatively the twitch response: (1) Pdi,tw is the amplitude of the response from baseline to peak; it is the result of the interaction of diaphragm contraction with the rib cage and the abdomen; although not a direct measure of diaphragm intrinsic contractile properties, it is related to diaphragm strength and can be used to characterize it if all other intervening factors are otherwise kept identical (e.g., lung volume, thoracic geometry, rib cage and abdomen compliance, diaphragm state of activation, etc.); (2) ttp and 1/2rt are the time-to-peak and half-relaxation time, respectively; these indexes are used to characterize the dynamics of diaphragm contraction, and are influenced, for example, by muscle shortening or fatigue; and (3) t is the time constant of an exponential function fitted to the after-peak decline in Pdi (often referred to as the relaxation time constant); it is influenced by diaphragm intrinsic properties and, for example, is prolonged by fatigue. The trace in D illustrates the similarity in shape, time dynamics, and amplitude in the Pes twitch (thin line) and the mouth pressure (Pmo) twitch (thick line) to phrenic nerve stimulation, in a normal healthy volunteer.

time-to-peak and its first time derivative (rate of rise, dp/dt) depend on several factors, including previous muscle shortening (e.g., increase in lung volume). The amplitude of the twitch reflects the transformation of diaphragm force into pressure and depends on diaphragm strength and contractile properties as well as rib cage and abdominal wall compliance. The dynamics of relaxation of the twitch can be described by the time necessary to reach a Pdi value of 50% of the peak (half-relaxation time) or by the time constant (t) of an exponential fitted to the pressure-time relationship (87, 118) (see Relaxation Rate in Section 5 of this Statement).

Mouth pressure. Provided that the diaphragm contracts in isolation and that the corresponding change in alveolar pressure is adequately transmitted to the airways opening, Pmo can in theory reflect diaphragm contraction. in response to PNS, a twitch-shaped negative Pmo swing is seen (Pmo,tw) (Figure 12). In healthy subjects, Pmo,tw closely matches Pes,tw at different lung volumes and correlates with Pdi,tw (119). Conversely, in patients with COPD, Pmo,tw at relaxed FRC is damped and time lagged with respect to Pes,tw, due to an increased airway time constant (120). Both in normal subjects (110) and in patients with diaphragm weakness (121) there is adequate matching of Pmo,tw and Pes,tw with CMS, when precautions are taken to prevent glottic closure. In normal subjects, Pmo,tw measured during CMS is generally more negative than 11 cm H2O (110), depending on lung gas volume (Vl).

Although there are not yet enough data to propose a precise technique to measure Pmo,tw, the following recommendations seem reasonable. Stimulation should be attempted at relaxed FRC when respiratory system recoil pressure is ordinarily zero. When PEEPi is present, the twitch amplitude should be measured starting at the PEEPi level. If a supramaximal stimulation is obtained, the data can be retained, if time to peak tension is normal. If it is prolonged with low amplitude and prolonged relaxation, then abnormal pressure transmission (probably due to glottic closure) should be first suspected, and stimulation should be repeated during a mild expiratory effort against an occluded mouthpiece.

Advantages. The principal advantage of Pmo,tw is its simplicity and ease of use. Thus, portable Pmo or Psn devices (28) could probably be adapted for combination with CMS as a simple screening test.

Disadvantages. The main disadvantage of Pmo,tw is in ensuring the adequacy of pressure transmission from the alveoli to the mouth, particularly in airway obstruction. It seems that glottic closure, which may prevent change in Pmo, is particularly frequent with CMS, although it can occur with ES as well. A technique such as a mild inspiratory effort at FRC (120) or an expiratory effort (110) not only makes the procedure more complicated, but it also changes the meaning of the observed results. Indeed, central nervous system activation and lung volume influence the pressure response to PNS (see Confounding Factors). With CMS, Pmo,tw can be the product of diaphragm contraction but also of neck muscle contraction. The importance of this confounding factor remains to be studied in detail (see Confounding Factors).

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