Early Mobilization in the Pediatric Intensive Care Unit: A Quality Improvement Initiative.

Mobilizing patients during an intensive care unit admission results in improved clinical and functional outcomes. The goal of this quality improvement project was to increase the percentage of patients in the pediatric intensive care unit (PICU) mobilized early from 62% to 80%. Early mobilization was within 18 hours of admission for nonmechanically ventilated (non-MV) patients and 48 hours for mechanically ventilated (MV) patients. METHODS: We collected data from September 15, 2015, to December 15, 2016, identified key drivers and barriers, and developed interventions. Interventions included the development of an algorithm to identify patients appropriate for mobilization, management of barriers to mobilization, and education on the benefits of early mobilization. The percentage of PICU patients mobilized early; the percentage of patients with physical therapy, occupational therapy (OT), speech-language pathology (SLP), and activity orders; identified barriers; PICU and hospital length of stay (LOS) and discharge disposition, were compared between the pre- and postintervention groups and the non-MV and MV subgroups. The MV subgroup was too small for statistical testing. RESULTS: All measures in the combined postintervention group improved and reached significance (<0.05), except for the percentage of SLP orders and discharged home. Percentage mobilized early increased 25%, activity orders 50%, physical therapist orders 14%, OT orders 11%, SLP orders 7%, and discharged home 6%. Hospital LOS decreased by 35%, and PICU LOS decreased by 34%. All measures in the postintervention, non-MV subgroup improved and reached significance (<0.05). CONCLUSIONS: This early mobilization program was associated with statistically significant improvements in the rate of early mobilization, activity and therapy orders, and hospital and PICU LOS.

Hypoxic-induced truncation of voltage-dependent anion channel 1 is mediated by both asparagine endopeptidase and calpain 1 activities.

The voltage-dependent anion channel 1 (VDAC1), an outer mitochondria membrane (OMM) protein, serves as a mitochondrial gatekeeper, mediating the transport of nucleotides, Ca2+ and other metabolites across the OMM. VDAC1 also plays a central role in mitochondria-mediated apoptosis by facilitating the release of apoptotic proteins and by association with both pro- and anti-apoptotic proteins. Tumor cells, which are constantly exposed to hypoxic conditions, affect the cell via the transcription factor hypoxia-inducible factor (HIF) that induces transcriptional activity. In cultured cells and in lung cancer patients, hypoxia induces VDAC1 truncation at the C-terminus (VDAC1-ΔC). However, the molecular mechanisms involved in VDAC1-ΔC formation are unknown. Here, we show that hypoxia-induced VDAC1-ΔC formation is inhibited by the Ca2+ chelator BAPTA-AM, by calpain inhibitor-1, by inhibitor of the asparagine endopeptidase (AEP) and by si-RNA targeting HIF1-α or Ca2+-activated protease calpain-1 expression but not that of calpain-2. Finally, VDAC1-ΔC expressed in bacteria and reconstituted into a planar lipid bilayer exhibited decreased channel conductance relative to the full-length protein, yet retained voltage-dependent conductance. These findings suggest that hypoxia, acting via HIF-1α expression, leads to VDAC1 cleavage involving the activation of calpain 1 and AEP.