Ventilator-induced diaphragm dysfunction: cause and effect

Abstract

Powers SK, Wiggs MP, Sollanek KJ, Smuder AJ. Ventilator-induced diaphragm dysfunction: cause and effect. Am J Physiol Regul Integr Comp Physiol 305: R464 -R477, 2013. First published July 10, 2013 doi:10.1152/ajpregu.00231.2013 is used clinically to maintain gas exchange in patients that require assistance in maintaining adequate alveolar ventilation. Common indications for MV include respiratory failure, heart failure, drug overdose, and surgery. Although MV can be a life-saving intervention for patients suffering from respiratory failure, prolonged MV can promote diaphragmatic atrophy and contractile dysfunction, which is referred to as ventilator-induced diaphragm dysfunction (VIDD). This is significant because VIDD is thought to contribute to problems in weaning patients from the ventilator. Extended time on the ventilator increases health care costs and greatly increases patient morbidity and mortality. Research reveals that only 18 -24 h of MV is sufficient to develop VIDD in both laboratory animals and humans. Studies using animal models reveal that MV-induced diaphragmatic atrophy occurs due to increased diaphragmatic protein breakdown and decreased protein synthesis. Recent investigations have identified calpain, caspase-3, autophagy, and the ubiquitin-proteasome system as key proteases that participate in MV-induced diaphragmatic proteolysis. The challenge for the future is to define the MV-induced signaling pathways that promote the loss of diaphragm protein and depress diaphragm contractility. Indeed, forthcoming studies that delineate the signaling mechanisms responsible for VIDD will provide the knowledge necessary for the development of a pharmacological approach that can prevent VIDD and reduce the incidence of weaning problems. respiratory muscle; atrophy; mechanical ventilation; weaning; muscle wasting MECHANICAL VENTILATION (MV) is used clinically to achieve sufficient pulmonary gas exchange in patients unable to sustain adequate alveolar ventilation on their own. Common indications for MV include respiratory failure due to chronic obstructive pulmonary disease, status asthmaticus, and/or heart failure. In addition, MV is often an essential intervention in patients suffering from acute drug overdose, neuromuscular diseases, sepsis, and during surgery along with postsurgical recovery.The number of patients receiving prolonged MV in the United States exceeds more than 300,000 each year in the intensive care unit (ICU) (20). Although MV can be a lifesaving measure, prolonged MV results in the rapid development of diaphragmatic weakness due to both atrophy and contractile dysfunction. This detrimental impact of prolonged MV on the diaphragm has been termed ventilator-induced diaphragmatic dysfunction (VIDD) and VIDD is predicted to be a major contributor to problems in weaning patients from the ventilator (26, 114). Although previous reports describing the impact of prolonged MV on the diaphragm have appeared in the literature, advances in our understanding of the mechanisms responsible for VIDD h...

Dissecting the role of the myofilament in diaphragm dysfunction during the development of heart failure in mice

“…These are proteases that target the myofilaments leading to atrophy and diaphragm weakness (43). In the current study, no evidence of proteolysis was found in the myofilament proteins isolated from the diaphragm preparations from the 18 wk TAC and 18 wk AMI groups, nor was there loss of in vitro force generation in the 18 wk TAC and 18 wk AMI groups.…”

“…Previous studies have demonstrated that mechanical ventilation can increase the activity of calpain and caspase-3 in the diaphragm (for review, see 43). These are proteases that target the myofilaments leading to atrophy and diaphragm weakness (43).…”

Phrenic Nerve Stimulation Increases Human Diaphragm Fiber Force after Cardiothoracic Surgery

“…Our preliminary findings suggest that intermittent phrenic nerve stimulation preserves human diaphragm fiber contractile function, possibly by inhibiting proteolysis and/or posttranslational modification of sarcomeric proteins seen after MV (3,10). However, the protection does not appear to be mediated by changes in protein carbonyls or ubiquitination.…”

Effects of Lower Tidal Volume on Ventilator-Induced Diaphragmatic Dysfunction

“…The first animal study of this issue was reported in 1994, and further such studies have since been performed [1]. The first prospective study indicated that controlled MV resulted in diaphragmatic muscle atrophy and contractile dysfunction in rats; this study showed that controlled MV for 48 hours without spontaneous breathing results in a significant decrease in diaphragm muscle mass and also a significant reduction in maximal diaphragmatic specific force production [10].…”

“…The indications for MV are respiratory failures of various etiologies, including chronic obstructive pulmonary disease, status asthmaticus, and/or heart failure, acute drug overdose, neuromuscular diseases, sepsis, and during the perioperative periods [1]. In the USA, more than 300,000 patients receive prolonged MV each year in intensive care units (ICU) [2], and it seems like that the number of patients who needs MV is increasing in Korea, however, the exact data is not in the literature.…”