Impact of under-assisted ventilation on diaphragm function and structure in a porcine model

Long-term controlled mechanical ventilation (CMV) in intensive care unit (ICU) induces ventilatory-induced-diaphragm-dysfunction (VIDD). The transition from CMV to assisted mechanical ventilation is a challenge that requires clinicians to balance over-assistance and under-assistance. While the effects of over-assistance on the diaphragm are well known, we aimed to assess the impact of under-assistance on diaphragm function and structure in piglet model with pre-existing VIDD (after long-term CMV) or without VIDD (short-term CMV). Twenty-two Large-White female piglets were anesthetized, ventilated, and separated into two groups: a VIDD group (n=10) with long-term 72-hour CMV, and a no-VIDD group (n=12) with short-term 2-hour CMV. After sedation reduction at the end of CMV period, each piglet was switched to under-assisted ventilation for 2 hours. Diaphragm function (supramaximal diaphragm pressure-generating capacity assessed by negative tracheal pressure after transvenous phrenic nerve stimulation) and diaphragm structure (mini-invasive in vivo biopsies) were assessed before and after under-assisted ventilation. In VIDD group, supramaximal diaphragm pressure-generating capacity decreased by 22% from 69.9±12.7 to 54.9±19.7 cmH2O (p=0.04) after 72 hours of CMV evidencing VIDD, then dropped by a further 29% from 54.9±19.7 to 38.9±15.5 cmH2O (p<0.01) after 2 hours of under-assisted ventilation. Diaphragm pressure-generating capacity remains stable from 55.3±22.7 to 58.2±24 cmH2O (p=0.24) in no-VIDD group. Diaphragm structure showed sarcomeric injuries increase from 13±10% to 24±19% (p<0.01) and lipid droplets decrease from 14±8% to 11±6% (p=0.03) of the total micrograph area after 2 hours of under-assisted ventilation in the VIDD group. Sarcomeric injuries and lipid droplets accounted respectively for 17±16% and 2±3% of the total micrograph area after under-assisted ventilation in the no-VIDD group. In this porcine model, a short two-hour exposure of under-assisted ventilation induces impairment of diaphragm function with damage to the diaphragm structure in ICU condition with pre-existing VIDD.