Paired phrenic nerve stimuli for the detection of diaphragm fatigue in humans

The transdiaphragmatic pressure (Pdi) elicited by paired bilateral phrenic nerve stimulation may be viewed as the sum of the Pdi values produced by the first (t1) and second (t2) stimulus. The Pdi at t2 (P[di,t2]) is a function of the interstimulus interval. A reduction in the ratio obtained by dividing Pdi,t2 at 10 Hz (P[di,t2,10]) by Pdi at 100 Hz (P[di,t2,100]) (t2(10:100)) has been proposed as a test of low frequency diaphragm fatigue. The aim of the present study was to establish whether this change could also be detected using paired cervical magnetic nerve stimulation (pCMS), and whether t2(10:100) was influenced by lung volume. We studied healthy subjects at functional residual capacity (FRC), at 0.5 and 1.0 L below FRC, and at 0.5, 1.0 and 1.5 L above FRC. The subjects were then subjected to a fatiguing protocol (2 min of maximal isocapnic ventilation (MIV)). Studies were repeated at FRC 20 and 60 min after MIV and between these times at 1.0 L below and 1.5 L above FRC. In the unfatigued state, t2(10:100) had a negative relationship with increasing lung volume (r2=0.98, p=0.002). After MIV there was a fall in the Pdi elicited by a single stimulus (mean fall at 20 min 17.9% and at 60 min 14.6%, p<0.03 for both). t2(10:100) fell by a mean 28.1% after 20 min and mean 22.9% at 60 min (p<0.03 for both). This change was mainly mediated by a fall in the P[di,t2,10]. The t2(10:100) was not able to distinguish between fatigue and acute hyperinflation. We conclude that paired cervical magnetic nerve stimulation may be used to detect low frequency diaphragm fatigue but that it remains important to control for lung volume.