Effects of repetitive magnetic cervical stimulation of phrenic roots on diaphragmatic function in healthy volunteers

1

Keywords:

• Diaphracmatic weakness
• magnetic cervical stimulation
• healthy subject

1. Introduction

Complete inactivity of the diaphragm due to full control mechanical ventilation may rapidly induce a marked muscle atrophy and impairment of its contractile strength (Levine et al. 2008; Jaber et al. 2011). It has been demonstrated in ventilated animal models that phrenic pacing may prevent diaphragmatic atrophy (Reynolds et al. 2017). Cervical magnetic stimulation (CMS) is a non invasive technique used to trigger diaphragmatic contraction in patient (Janssens et al. 2013). Could it be used to prevent diaphragmatic atrophy in ventilated patients? The main purpose of this study was to evaluate in healthy subjects the consequences of a 60-minute session of serial CMS-induced diaphragmatic contractions, repeated 8 times per minute, on diaphragm function.

2. Methods

The independent ethics committee of our institution approved the study (French Ethics Committee Ouest III; registration number 2014-A0175047).Volunteer male subjects underwent two one-hour sessions of serial single cervical magnetic twitches (CMS) repeated every 8 seconds. Both ‘training sessions’ scheduled in a random order were called ‘effective’ or ‘placebo’ according to the intensity of the twitches. Transdiaphragmatic pressure (Pdi) was assessed using esophageal and gastric piezoelectric pressure probes. Before (Baseline) and after each training session, we recorded transdiaphragmatic pressure triggered by CMS (Pditw), diaphragm motor potential evoked by CMS (di-MEP/CMS) and by transcranial magnetic stimulation (di-MEP/TMS) as well as maximal voluntary inspiratory transdiaphragmatic pressure (Pdimax). During the diaphragmatic training sessions, the subject remained in half seating position and underwent single CMS repeated every 8 seconds during one hour. The intensity of the serial CMS depended on the session: 10% of maximal intensity for ‘placebo training session’ and at the optimal amplitude previously established for the ‘effective training session’. The subject remained unaware of the kind of training session he was undergoing. The subjects quantified their discomfort on an analogical visual scale before and every 20 min during each training session. Continuous variables were expressed as median and [25^th–75^th] percentiles, and qualitative variables were expressed as number and percentage. We compared the variables using the Fisher exact test for qualitative variables Mann Whitney test for continuous variables.

3. Results and discussion

Fifteen healthy male subjects aged 24 years [20–30] with a median BMI of 24 [21–26] kg/m² were included. During the preliminary trial at various CMS intensity, we observed that 80% [70–80%] of the maximal intensity of the stimulator did trigger an optimal diaphragmatic contraction. Whatever was the kind of training session, baseline and post session values of Pditw, di-MEP/CMS, di-MEP/TMS or Pdimax values were not significantly different. Furthermore, we did not observe any significant difference between placebo or effective session for baseline values or for post session values of these parameters. The discomfort score remained below 3/10 for all subjects but one whose discomfort score reached 5/10 during effective session.

We thus did not observe any significant change in any of the diaphragmatic function parameters following the effective or placebo session. The only individual who experienced a decrease greater than -20% versus baseline combined with a decrease in PdiMax had a neonatal history of omphalocele. Even though he did not complain of any symptoms this might have interfered with his response to the serial CMS stimulations. The training sessions consisted in serial single twitch simulations that triggered brief hiccup movements. The work of breathing imposed to our subject was thus far much lower than inspiratory load protocols (Jonville et al. 2005), Isocapnic hyperventilation (Dayer et al. 2007) or exhausting exercise (Verin et al. 2004) protocols commonly used to induce peripheral diaphragmatic fatigue. It is also lower than the ‘electromagnetic ventilation’ tested in conscious healthy volunteers (Sander et al. 2010) and animal phrenic pacing models (Reynolds et al. 2017).

4. Conclusions

The one-hour sessions of repetitive single CMS twitches were well tolerated and did not cause any diaphragmatic fatigue in healthy subject. The safety and interest of such a noninvasive diaphragmatic training sessions to prevent diaphragm weakness should now be assessed in ICU ventilated patients.

Table 1. Consequences of both effective and placebo diaphragm training sessions on Pditw, di-MEP/CMS, di-MEP/TMS and PdiMax.

		Effective training session	Placebo training session
PdiTw (cmH2O) [min max]	Baseline	26,7 [20,5; 36,5]	23,6 [17,2; 35,8]
	Post-session	24,3 [17,8; 35,2]	24,2 [18,3; 38,5]
di-MEP/CMS (mVolt)	Baseline	0,99 [0,64; 1,26]	0,92 [0,58; 1,26]
	Post-session	0,92 [0,60; 1,23]	0,94 [0,54; 1,52]
di-MEP/TMS (mVolt)	Baseline	0,24 [0,05; 1,38]	0,5 [0,24; 2,9]
	Post-session	0,28 [0,07; 1,10]	0,5 [0,28; 2,16]
PdiMax (cmH2O)	Baseline	160 [128; 262]	136 [131; 158]
	Post-session	173 [142; 268]	158 [125; 174]