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

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 failure patients than in 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/sec; 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 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∙%-1; 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 suggests that reflex inhibition of central neural output to the diaphragm contributes to weaning failure.

Mechanical power normalized to lung-thorax compliance indicates weaning readiness in prolonged ventilated patients

“…In a physiologic study, Laghi and co-workers demonstrated that patients who failed a weaning trial did not develop contractile fatigue of the diaphragm (consistent with muscle injury), potentially leading to subsequent unsuccessful weaning attempts or unsuccessful liberation from the ventilator 25 . Moreover, these investigators were able to show that diaphragmatic recruitment at the end of a failed weaning trial, estimated by the electrical activity of the diaphragm, was half of the maximum, corresponding to reflex inhibition of the diaphragm with at the same time redistribution of motoneuron output to rib cage and accessory muscles, a potential mechanism for the prevention of diaphragmatic contractile fatigue 26 . Accordingly, patients categorized as difficult to wean, failing up to three SBT before successful discontinuation of mechanical ventilation, showed no increase in ICU‒ or hospital mortality compared to patients successfully extubated on the first attempt 27 , 28 .…”

Positive end-expiratory pressure affects geometry and function of the human diaphragm

“…Recruitment of expiratory muscles under mechanical ventilation is wellknown and may limit the increase in EELV (51) through a physiological feedback mechanism involving proprioceptive influences and vagal pathways (52,53). Recruitment of expiratory muscles generates an increase in abdominal pressure moving the diaphragm to a more cranial position at end-expiration, thereby counteracting the effect of PEEP and improving neuromechanical coupling by placing the diaphragm at a more optimal length for tension generation (51,54,55). It is unknown why only a subset of subjects recruited their expiratory muscles.…”

Lung- and Diaphragm-Protective Ventilation by Titrating Inspiratory Support to Diaphragm Effort: A Randomized Clinical Trial

“…For more extensive discussion, we refer to recent articles (3,10). Second, the relationship between diaphragm weakness and ICU outcomes, including difficult weaning and ICU mortality, has been observed to various degrees in observational studies (2,(29)(30)(31)(32)(33)(34)(35), but whether diaphragm weakness is a causal contributor to poor ICU outcomes or a merely a marker for disease severity remains to be established (36). A causal relationship seems plausible, as the diaphragm is the main muscle of inspiration and improving diaphragm strength led to improved weaning outcome in selected patients (37).…”