Elderly Patients and Management in Intensive Care Units (ICU): Clinical Challenges.

There is a growing population of older adults requiring admission to the intensive care unit (ICU). This population outpaces the ability of clinicians with geriatric training to assist in their management. Specific training and education for intensivists in the care of older patients is valuable to help understand and inform clinical care, as physiologic changes of aging affect each organ system. This review highlights some of these aging processes and discusses clinical implications in the vulnerable older population. Other considerations when caring for these older patients in the ICU include functional outcomes and morbidity, as opposed to merely a focus on mortality. An overall holistic approach incorporating physiology of aging, applying current evidence, and including the patient and their family in care should be used when caring for older adults in the ICU.

Anesthesia Machine and New Modes of Ventilation.

Mechanical ventilation is ubiquitous in the operating room. This article explores the anesthesia machine as a ventilator, examining its unique features and differences from ventilators designed for long-term use. It will describe standard and nonstandard modes of ventilation. The reader will develop a more nuanced understanding of how to tailor ventilation and oxygenation strategies based on patient and anesthetic scenarios as well as with the assistance of new technologies.

New-Onset Refractory Status Epilepticus with Underlying Autoimmune Etiology: a Case Report.

Management of new-onset refractory status epilepticus and the approach to burst suppression variable is often challenging. We present the unusual case of a previously healthy 18-year-old male with new-onset status epilepticus admitted to the neurologic intensive care unit for 70 days. Despite treatment with multiple anti-epileptic drugs in addition to IV anesthetics, burst suppression was initially unsustainable and the patient remained in super-refractory status epilepticus. Extensive evaluation revealed an underlying autoimmune-mediated etiology with positivity for glutamic acid decarboxylase-65 antibody. Clinical response with a goal of 1-2 bursts per screen on EEG monitor was eventually achieved after a course of rituximab and plasma exchange therapy as well as a 7-day barbiturate coma with a regimen of clobazam, lacosamide, Keppra, and oxcarbazepine followed by a slow taper of phenobarbital and the addition of fosphenytoin. Remarkably, the patient was subsequently discharged to a rehabilitation facility with complete neurologic recovery. We discuss treatment strategies for new-onset refractory status epilepticus and highlight the role of rapid initiation of burst suppression with high-dose IV anesthetics to ensure neuroprotection while the underlying etiology is addressed with immune-modulating therapy.

Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation.

Bed rest-induced muscle loss and impaired muscle recovery may contribute to age-related sarcopenia. It is unknown if there are age-related differences in muscle mass and muscle anabolic and catabolic responses to bed rest. A secondary objective was to determine if rehabilitation could reverse bed rest responses. Nine older and fourteen young adults participated in a 5-day bed rest challenge (BED REST). This was followed by 8 weeks of high intensity resistance exercise (REHAB). Leg lean mass (via dual-energy X-ray absorptiometry; DXA) and strength were determined. Muscle biopsies were collected during a constant stable isotope infusion in the postabsorptive state and after essential amino acid (EAA) ingestion on three occasions: before (PRE), after bed rest and after rehabilitation. Samples were assessed for protein synthesis, mTORC1 signalling, REDD1/2 expression and molecular markers related to muscle proteolysis (MURF1, MAFBX, AMPKα, LC3II/I, Beclin1). We found that leg lean mass and strength decreased in older but not younger adults after bedrest (P < 0.05) and was restored after rehabilitation. EAA-induced mTORC1 signalling and protein synthesis increased before bed rest in both age groups (P < 0.05). Although both groups had blunted mTORC1 signalling, increased REDD2 and MURF1 mRNA after bedrest, only older adults had reduced EAA-induced protein synthesis rates and increased MAFBX mRNA, p-AMPKα and the LC3II/I ratio (P < 0.05). We conclude that older adults are more susceptible than young persons to muscle loss after short-term bed rest. This may be partially explained by a combined suppression of protein synthesis and a marginal increase in proteolytic markers. Finally, rehabilitation restored bed rest-induced deficits in lean mass and strength in older adults.

A novel vacuum assisted closure therapy model for use with percutaneous devices.

Long-term maintenance of a dermal barrier around a percutaneous prosthetic device remains a common clinical problem. A technique known as Negative Pressure Wound Therapy (NPWT) uses negative pressure to facilitate healing of impaired and complex soft tissue wounds. However, the combination of using negative pressure with percutaneous prosthetic devices has not been investigated. The goal of this study was to develop a methodology to apply negative pressure to the tissues surrounding a percutaneous device in an animal model; no tissue healing outcomes are presented. Specifically, four hairless rats received percutaneous porous coated titanium devices implanted on the dorsum and were bandaged with a semi occlusive film dressing. Two of these animals received NPWT; two animals received no NPWT and served as baseline controls. Over a 28-day period, both the number of dressing changes required between the two groups as well as the pressures were monitored. Negative pressures were successfully applied to the periprosthetic tissues in a clinically relevant range with a manageable number of dressing changes. This study provides a method for establishing, maintaining, and quantifying controlled negative pressures to the tissues surrounding percutaneous devices using a small animal model.

Downregulation of E3 ubiquitin ligases and mitophagy-related genes in skeletal muscle of physically inactive, frail older women: a cross-sectional comparison.

BACKGROUND AND OBJECTIVES: Reduced lean mass and physical function is a characteristic of frailty. However, it is currently unknown if proteolysis through the E3 ubiquitin ligases and the autophagic lysosomal pathway is dysregulated in inactive frail older women. The purpose of this study was to determine the expression of key markers of ubiquitin-mediated and autophagic lysosomal proteolysis in inactive (N = 7) compared with active (N = 7) older women. METHODS: Strength, mobility, leg lean mass, and physical activity assessment were used to characterize activity levels and frailty in older women. Vastus lateralis biopsies were collected after an overnight fast and were assessed for gene and protein targets related to E3 ubiquitin ligases and the autophagic lysosomal system. RESULTS: We found that AMP-activated protein kinase alpha (Thr172) was increased (p = .045), and forkhead box O3A (FOXO3A) gene expression (p = .047) was lower in inactive frail older women. Foxo3a (Ser253), Beclin1 (Ser93/96), and class III phosphatidylinositol-3-kinase (VPS34) protein expression were not different between the groups (p > .05). Neural precursor cell-expressed developmentally downregulated protein 4, muscle ring finger 1, muscle atrophy F-box, and the autophagy/mitophagy gene expression markers, Beclin1, autophagy-related-7, BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), dynamin-related protein 1, and Parkinson protein 2 (PARKIN) were lower in inactive frail older women (p < .05). Autophagy/mitophagy markers were positively correlated with the 6-minute walk and leg lean mass (p < .05). CONCLUSIONS: We conclude that physical inactivity in frail older women is associated with a downregulation of ubiquitin-mediated and autophagic lysosomal skeletal muscle gene expression, perhaps related to low muscle mass and poor physical function.

An evaluation of electrical stimulation for improving periprosthetic attachment.

Transcutaneous osseointegrated implants (TOI) have been shown to improve functionality for patients with limb loss by allowing direct skeletal attachment between an exoprosthesis and host bone. However, a lengthy rehabilitation period has limited the expansion of TOI and may be accelerated with electrical stimulation. The purpose of this study was to determine the ability of direct current (DC) cathode stimulation to enhance osseointegration of intramedullary implants in skeletally matured rabbits. Bilateral implants were inserted in the hind limbs of 25 adult female rabbits. The left hind limb of each animal was continually stimulated with a potential difference of 0.55 volts based on finite element analysis predictions. After sacrifice, the limbs were divided into two groups: Group I for histology and Group II for biomechanical testing. The bone-implant construct was evaluated in the Group I animals using appositional bone index (ABI), mineral apposition rates (MAR), histological staining, and scanning electron microscopy (SEM). Group II implants were sectioned and subjected to mechanical push-out tests. Data indicated no statistical differences for ABI, MAR, and porosity between the electrically stimulated implants (ESI) and the unstimulated control implants (UCI) at three weeks and six weeks. Higher mechanical push-out forces were observed in the UCI group at six weeks (p = 0.034). Data indicated that DC cathode stimulation may improve suboptimal implant "fit and fill" as an increase in trabecular bone was noted around the cathode in the ESI group. However, longer time duration animal studies and variations in electrical modalities may be required before electrically induced osseointegration becomes clinically feasible.

Clarifying the structure and bone mineral content of heterotopic ossification.

BACKGROUND: Heterotopic ossification (HO) has been reported as a pathologic process characterized by ectopic bone growth in muscle and/or periarticular regions. Previous reports have speculated that HO manifests as cancellous bone, cortical bone, or woven bone. Confusion regarding HO bone morphology has resulted from radiographic assessments and light microscopy, which lack the resolution required for accurately determining advanced bone architecture. Therefore, a more thorough histologic assessment using scanning electron microscopy (SEM) and backscatter electron (BSE) imaging was needed to improve HO characterization. MATERIALS AND METHODS: HO samples were collected from five adult trauma patients after surgical resection and examined with radiography, BSE, and histologic stains. RESULTS: BSE data demonstrated that HO was composed of a heterogeneous mixture of cortical and cancellous bone with distinct regions of fibrocartilage. Bone mineralization levels varied on a patient-specific basis, with the highest percentage of hypermineralization occurring in the oldest patient. BSE and histologic stains also indicated HO remodeling continued even after 3 y from injury to resection, as evident by osteoclastic resorption and osteoid deposition. CONCLUSIONS: BSE provided a more accurate understanding of HO bone mineralization and structure which may lead to improved surgical planning and treatment strategies for prevention of HO recurrence after resection.