Smad3 initiates oxidative stress and proteolysis that underlies diaphragm dysfunction during mechanical ventilation.

Prolonged use of mechanical ventilation (MV) leads to atrophy and dysfunction of the major inspiratory muscle, the diaphragm, contributing to ventilator dependence. Numerous studies have shown that proteolysis and oxidative stress are among the major effectors of ventilator-induced diaphragm muscle dysfunction (VIDD), but the upstream initiator(s) of this process remain to be elucidated. We report here that periodic diaphragm contraction via phrenic nerve stimulation (PNS) substantially reduces MV-induced proteolytic activity and oxidative stress in the diaphragm. We show that MV rapidly induces phosphorylation of Smad3, and PNS nearly completely prevents this effect. In cultured cells, overexpressed Smad3 is sufficient to induce oxidative stress and protein degradation, whereas inhibition of Smad3 activity suppresses these events. In rats subjected to MV, inhibition of Smad3 activity by SIS3 suppresses oxidative stress and protein degradation in the diaphragm and prevents the reduction in contractility that is induced by MV. Smad3's effect appears to link to STAT3 activity, which we previously identified as a regulator of VIDD. Inhibition of Smad3 suppresses STAT3 signaling both in vitro and in vivo. Thus, MV-induced diaphragm inactivity initiates catabolic changes via rapid activation of Smad3 signaling. An early intervention with PNS and/or pharmaceutical inhibition of Smad3 may prevent clinical VIDD.

Clinicians' recognition of the Ohmeda Modulus II plus and Ohmeda Excel 210 SE anesthesia machine system mode and function.

INTRODUCTION: : Anesthesiologists' cognitive resources such as their attention, knowledge, and strategies play an important role in the prevention and correction of critical events. In this paper, we examined anesthesiologists' responses to the anesthesia machine (AM) in the "off" position during a simulated emergent cesarean section scenario. METHODS: : All simulations were videotaped which allowed for offline review. At the beginning of the scenario, the AM system switch was purposefully turned to the off/standby position. The responses of 14 anesthesia residents at the Veterans Affairs Palo Alto Health Care System and Stanford University Simulation Center for Crisis Management Training in Health Care (VASC) and 11 anesthesia residents at the Boston Center for Medical Simulation (CMS) were analyzed. RESULTS: : Nine subjects at VASC restored the AM system switch to the "on" position on their own, whereas five subjects required help from another clinician. The median response time (RT) for all 14 subjects was 149.5 seconds. At CMS, five subjects restored the AM system switch to the "on" position on their own (median RT = 207 seconds), whereas two subjects received help from another anesthesia resident. There were four cases where the AM system switch problem was not corrected. CONCLUSIONS: : Factors that could have contributed to subjects' difficulty in detecting and correcting the AM system switch included the unusual nature of the problem, the human factors design of the AM front panel and system switch, and inadequate training by the subjects. Improving the appearance of the AM's system switch and training of clinicians to recognize the location and functionality of the AM system switch could be useful in correcting such an event in a timely manner and reducing patient risk.