Inhibition of central activation of the diaphragm: a mechanism of weaning failure.

Franco Laghi,Martin J Tobin,Daniel Morales,Hameeda Shaikh,Amal Jubran,Stephen W Littleton

doi:10.1152/japplphysiol.00856.2019

Franco Laghi, Martin J Tobin + Show 4 more

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https://doi.org/10.1152/japplphysiol.00856.2019

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Abstract

During a T-tube trial following disconnection of mechanical ventilation, patients failing the trial do not develop contractile diaphragmatic fatigue despite increases in inspiratory pressure output. Studies in volunteers, patients, and animals raise the possibility of spinal and supraspinal reflex mechanisms that inhibit central-neural output under loaded conditions. We hypothesized that diaphragmatic recruitment is submaximal at the end of a failed weaning trial despite concurrent respiratory distress. Tidal transdiaphragmatic pressure (ΔPdi) and electrical activity (ΔEAdi) were recorded with esophago-gastric catheters during a T-tube trial in 20 critically ill patients. During the T-tube trial, ∆EAdi was greater in weaning failure patients than in weaning success patients (P = 0.049). Despite increases in ΔPdi, from 18.1 ± 2.5 to 25.9 ± 3.7 cm H2O (P < 0.001), rate of transdiaphragmatic pressure development (from 22.6 ± 3.1 to 37.8 ± 6.7 cm H2O/s; P < 0.0004), and concurrent respiratory distress, ∆EAdi at the end of a failed T-tube trial was half of maximum, signifying inhibition of central neural output to the diaphragm. The increase in ΔPdi in the weaning failure group, while ∆EAdi remained constant, indicates unexpected improvement in diaphragmatic neuromuscular coupling (from 46.7 ± 6.5 to 57.8 ± 8.4 cm H2O/%; P = 0.006). Redistribution of neural output to the respiratory muscles characterized by a progressive increase in rib cage and accessory muscle contribution to tidal breathing and expiratory muscle recruitment contributed to enhanced coupling. In conclusion, diaphragmatic recruitment is submaximal at the end of a failed weaning trial despite concurrent respiratory distress. This finding signifies that reflex inhibition of central neural output to the diaphragm contributes to weaning failure.NEW & NOTEWORTHY Research into pathophysiology of failure to wean from mechanical ventilation has excluded several factors, including contractile fatigue, but the precise mechanism remains unknown. We recorded transdiaphragmatic pressure and diaphragmatic electrical activity in patients undergoing a T-tube trial. Diaphragmatic recruitment was submaximal at the end of a failed trial despite concurrent respiratory distress, signifying that inhibition of central neural output to the diaphragm is an important mechanism of weaning failure.

Highlights

Ill patients who fail a trial of weaning from mechanical ventilation [6, 8] do not develop contractile fatigue of the diaphragm [55]
Recruitment can be quantified by performing the interpolated twitch pressure technique, whereby a large increment in transdiaphragmatic pressure (Pdi) elicited by phrenic nerve stimulation superimposed upon perceived maximal voluntary inspiratory efforts signifies incomplete muscle recruitment and, reflex inhibition of central activation [39]
The extent of diaphragmatic coupling during maximal voluntary inspiratory maneuvers recorded before the T-tube trial was similar in weaning failure and success groups

Summary

Introduction

Ill patients who fail a trial of weaning from mechanical ventilation [6, 8] do not develop contractile fatigue of the diaphragm [55]. Attempting to shed light on this phenomenon, investigators have conducted studies in patients with respiratory disorders [25, 57, 78, 89], healthy volunteers [26, 58], and in animals [96] Findings in these studies raise the possibility of spinal and supraspinal reflex mechanisms that inhibit central neural output under loaded conditions [39, 58, 104]. These reflex mechanisms may have a protective action against load-induced muscle damage [39, 58, 104] To date, it is not known whether (or not) patients who fail a weaning trial experience a reflex inhibition of central activation. In addition to being technically demanding [34], the interpolation technique is limited by its insensitivity to changes in diaphragmatic motor-unit firing rate [11, 97], an important component of central activation [39, 97, 104]

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