Prolonged Mechanical Ventilation: Outcomes and Management

Abstract

The number of patients requiring prolonged mechanical ventilation (PMV) is increasing worldwide, placing a burden on healthcare systems. Therefore, investigating the pathophysiology, risk factors, and treatment for PMV is crucial. Various underlying comorbidities have been associated with PMV. The pathophysiology of PMV includes the presence of an abnormal respiratory drive or ventilator-induced diaphragm dysfunction. Numerous studies have demonstrated that ventilator-induced diaphragm dysfunction is related to increases in in-hospital deaths, nosocomial pneumonia, oxidative stress, lung tissue hypoxia, ventilator dependence, and costs. Thus far, the pathophysiologic evidence for PMV has been derived from clinical human studies and experimental studies in animals. Moreover, recent studies have demonstrated the outcome benefits of pharmacological agents and rehabilitative programs for patients requiring PMV. However, methodological limitations affected these studies. Controlled prospective studies with an adequate number of participants are necessary to provide evidence of the mechanism, prognosis, and treatment of PMV. The great epidemiologic impact of PMV and the potential development of treatment make this a key research field.

Keywords: prolonged mechanical ventilation; reactive oxygen species; respiratory drive; ventilator-induced diaphragm dysfunction.

Figure 1

Schematic figure illustrating the signaling pathway implicated in VIDD development. Endotoxin-induced augmentation of mechanical stretch-mediated ROS generation and diaphragm injury are associated with diaphragm proteolysis, mitochondrial dysfunction, autophagy, as well as activation of the caspase-3, calpain, and ubiquitin–proteasome pathways. Diaphragm weakness can be attenuated by administering antioxidants, enoxaparin, or through partial support for mechanical ventilation or pulmonary rehabilitation. Akt = serine/threonine kinase/protein kinase B; ETC = electron transport chain; FoxO1 = Class O of forkhead box1; HIF = hypoxia-inducible factor; LC3 = light chain 3; LMWH = low-molecular-weight heparin; LPS = lipopolysaccharide; mtDNA = mitochondrial DNA; mTOR = mammalian target of rapamycin; MuRF-1 = muscle ring finger-1; NF-κB = nuclear factor κappa B; PI3-K = phosphoinositide 3-OH kinase; ROS = reactive oxygen species; TLR4 = toll-like receptor 4; VIDD = ventilator-induced diaphragm dysfunction.