Aim
Symptoms of autonomic failure are frequently the presentation of advanced age and neurodegenerative diseases that impair adaptation to common physiologic stressors. The aim of this work was to ...examine the interaction between the sympathetic and motor nervous system, the involvement of the sympathetic nervous system (SNS) in neuromuscular junction (NMJ) presynaptic motor function, the stability of postsynaptic molecular organization, and the skeletal muscle composition and function.
Methods
Since muscle weakness is a symptom of diseases characterized by autonomic dysfunction, we studied the impact of regional sympathetic ablation on muscle motor innervation by using transcriptome analysis, retrograde tracing of the sympathetic outflow to the skeletal muscle, confocal and electron microscopy, NMJ transmission by electrophysiological methods, protein analysis, and state of the art microsurgical techniques, in C57BL6, MuRF1KO and Thy‐1 mice.
Results
We found that the SNS regulates motor nerve synaptic vesicle release, skeletal muscle transcriptome, muscle force generated by motor nerve activity, axonal neurofilament phosphorylation, myelin thickness, and myofibre subtype composition and CSA. The SNS also modulates the levels of postsynaptic membrane acetylcholine receptor by regulating the Gαi2‐Hdac4‐Myogenin‐MuRF1pathway, which is prevented by the overexpression of the guanine nucleotide‐binding protein Gαi2 (Q205L), a constitutively active mutant G protein subunit.
Conclusion
The SNS regulates NMJ transmission, maintains optimal Gαi2 expression, and prevents any increase in Hdac4, myogenin, MuRF1, and miR‐206. SNS ablation leads to upregulation of MuRF1, muscle atrophy, and downregulation of postsynaptic AChR. Our findings are relevant to clinical conditions characterized by progressive decline of sympathetic innervation, such as neurodegenerative diseases and aging.
Evidence implicates the amount and location of fat in aging-related loss of muscle function; however, whether intramyocellular lipids affect muscle contractile capacity is unknown.
We compared both ...in vivo knee extensor muscle strength, power, and quality and in vitro mechanical properties of vastus lateralis single-muscle fibers between normal weight (NW) and obese older adults and determined the relationship between muscle lipid content (both intramuscular adipose tissue and intramyocellular lipids) and in vivo and in vitro muscle function in NW and obese individuals.
The obese group had a greater percentage of type-I fibers compared to the NW group. The cross-sectional area of type-I fibers was greater in obese compared to NW; however, maximal shortening velocity of type-I fibers in the obese was slower compared to NW. Type-I and type-IIa fibers from obese group produced lower specific force than that of type-I and type-IIa fibers from the NW group. Normalized power was also substantially lower (~50%) in type-I fibers from obese adults. The intramyocellular lipids data showed that total lipid droplet area, number of lipid droplets, and area fraction were about twofold greater in type-I fibers from the obese compared to the NW group. Interestingly, a significant inverse relationship between average number of lipid droplets and single-fiber unloaded shortening velocity, maximal velocity, and specific power was observed in obese participants. Additionally, muscle echointensity correlated with single-fiber specific force.
These data indicate that greater intramyocellular lipids are associated with slower myofiber contraction, force, and power development in obese older adults.
IMPORTANCE: Physical rehabilitation in the intensive care unit (ICU) may improve the outcomes of patients with acute respiratory failure. OBJECTIVE: To compare standardized rehabilitation therapy ...(SRT) to usual ICU care in acute respiratory failure. DESIGN, SETTING, AND PARTICIPANTS: Single-center, randomized clinical trial at Wake Forest Baptist Medical Center, North Carolina. Adult patients (mean age, 58 years; women, 55%) admitted to the ICU with acute respiratory failure requiring mechanical ventilation were randomized to SRT (n=150) or usual care (n=150) from October 2009 through May 2014 with 6-month follow-up. INTERVENTIONS: Patients in the SRT group received daily therapy until hospital discharge, consisting of passive range of motion, physical therapy, and progressive resistance exercise. The usual care group received weekday physical therapy when ordered by the clinical team. For the SRT group, the median (interquartile range IQR) days of delivery of therapy were 8.0 (5.0-14.0) for passive range of motion, 5.0 (3.0-8.0) for physical therapy, and 3.0 (1.0-5.0) for progressive resistance exercise. The median days of delivery of physical therapy for the usual care group was 1.0 (IQR, 0.0-8.0). MAIN OUTCOMES AND MEASURES: Both groups underwent assessor-blinded testing at ICU and hospital discharge and at 2, 4, and 6 months. The primary outcome was hospital length of stay (LOS). Secondary outcomes were ventilator days, ICU days, Short Physical Performance Battery (SPPB) score, 36-item Short-Form Health Surveys (SF-36) for physical and mental health and physical function scale score, Functional Performance Inventory (FPI) score, Mini-Mental State Examination (MMSE) score, and handgrip and handheld dynamometer strength. RESULTS: Among 300 randomized patients, the median hospital LOS was 10 days (IQR, 6 to 17) for the SRT group and 10 days (IQR, 7 to 16) for the usual care group (median difference, 0 95% CI, −1.5 to 3, P = .41). There was no difference in duration of ventilation or ICU care. There was no effect at 6 months for handgrip (difference, 2.0 kg 95% CI, −1.3 to 5.4, P = .23) and handheld dynamometer strength (difference, 0.4 lb 95% CI, −2.9 to 3.7, P = .82), SF-36 physical health score (difference, 3.4 95% CI, −0.02 to 7.0, P = .05), SF-36 mental health score (difference, 2.4 95% CI, −1.2 to 6.0, P = .19), or MMSE score (difference, 0.6 95% CI, −0.2 to 1.4, P = .17). There were higher scores at 6 months in the SRT group for the SPPB score (difference, 1.1 95% CI, 0.04 to 2.1, P = .04), SF-36 physical function scale score (difference, 12.2 95% CI, 3.8 to 20.7, P = .001), and the FPI score (difference, 0.2 95% CI, 0.04 to 0.4, P = .02). CONCLUSIONS AND RELEVANCE: Among patients hospitalized with acute respiratory failure, SRT compared with usual care did not decrease hospital LOS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00976833
Abstract
Objective
Limited data exist on the quantification of activity levels and functional status in critically ill patients as they transition from the intensive care unit (ICU) to the wards and, ...subsequently, back into the community. The physical activity of critically ill patients from their ICU stay until 7 days after hospital discharge was characterized, as well as correlate physical activity levels with an objective measure of physical function.
Methods
This prospective observational study of previously independent adults aged 55 or older, undergoing mechanical ventilation for up to 7 days, recruited participants at the time of spontaneous breathing trials or less than 24 hours after extubation. Participants received an accelerometer at enrollment to wear until 1 week after discharge.
Results
Twenty-two participants received accelerometers; 15 were suitable for analysis. Participants had a mean (SD) age of 68 (9.6) years; 47% were female. Mean step counts were 95 (95% CI = 15–173) in the 3 days before ICU discharge, 257 (95% CI = 114–400) before hospital discharge, 1223 (95% CI = 376–2070) in the first 3 days at home, and 1278 (95% CI = 349–2207) between day 4 and 6 post–hospital discharge. Physical activity was significantly higher post– compared with pre–hospital discharge. Short Physical Performance Battery scores were poor at ICU and hospital discharge; however, they correlated moderately with physical activity levels immediately upon return home.
Conclusions
Physical activity remained low as survivors of critical illness transitioned from ICU to hospital wards, but significantly increased upon return to the community. Despite poor Short Physical Performance Battery scores at both ICU and hospital discharge, participants were significantly more active immediately after discharge than in their last 3 days of hospitalization. This may represent rapid functional improvement or, conversely, constrained physical activity in hospital.
Impact
This study highlights the need for further evaluation of physical activity constraints in hospital and ways to augment physical activity and function upon discharge.
Lay Summary
Physical activity (step counts) increased modestly as survivors of critical illness transitioned from ICU to hospital wards, but significantly increased upon return to the community. This study highlights the need for further evaluation of physical activity constraints in the hospital setting and ways to augment physical activity and function postdischarge.
The objective of this study is to describe the relationship between two quantitative muscle ultrasound measures, the rectus femoris cross-sectional area (RF-CSA) and quadriceps muscle thickness, with ...volitional measures of strength and function in critically ill patients with sepsis.
We performed a prospective study of patients admitted to a medical ICU with sepsis and shock or respiratory failure. We examined the association of two ultrasound measurements – the RF-CSA and quadriceps muscle thickness – with strength and function at day 7. Strength was determined using the Medical Research Council Score and function using Physical Function in the ICU Test, scored.
Twenty-nine patients were enrolled; 19 patients had outcome testing performed. Over 7days, RF-CSA and thickness decreased by an average of 23.2% and 17.9%, respectively. The rate of change per day of RF-CSA displayed a moderate correlation with strength (ρ 0.51, p-value 0.03) on day 7. Baseline and day 7 RF-CSA did not show a significant correlation with either outcome. Quadriceps muscle thickness did not significantly correlate with either outcome.
Muscle atrophy as detected by the rate of change in RF-CSA moderately correlated with strength one week after sepsis admission.
•Muscle atrophy occurs early in sepsis and can be detected by peripheral muscle ultrasound.•Change in rectus femoris cross-sectional area detected by ultrasound over the first week of sepsis moderately correlates with strength.•Quantitative muscle ultrasound complements volitional measures of strength and function in describing skeletal muscle dysfunction in sepsis.
Patients with acute respiratory distress syndrome (ARDS) often develop severe diaphragmatic and limb skeletal muscle dysfunction. Impaired muscle function in ARDS is associated with increased ...mortality, increased duration of mechanical ventilation, and functional disability in survivors. In this review, we propose that muscle dysfunction in ARDS can be categorized into an early and a late phase. These early and late phases are based on the timing in relationship to lung injury and the underlying mechanisms. The early phase occurs temporally with the onset of lung injury, is driven by inflammation and disuse, and is marked predominantly by muscle atrophy from increased protein degradation. The ubiquitin-proteasome, autophagy, and calpain-caspase pathways have all been implicated in early-phase muscle dysfunction. Late-phase muscle weakness persists in many patients despite resolution of lung injury and cessation of ongoing acute inflammation-driven muscle atrophy. The clinical characteristics and mechanisms underlying late-phase muscle dysfunction do not involve the massive protein degradation and atrophy of the early phase and may reflect a failure of the musculoskeletal system to regain homeostatic balance. Owing to these underlying mechanistic differences, therapeutic interventions for treating muscle dysfunction in ARDS may differ during the early and late phases. Here, we review clinical and translational investigations of muscle dysfunction in ARDS, placing them in the conceptual framework of the early and late phases. We hypothesize that this conceptual model will aid in the design of future mechanistic and clinical investigations of the skeletal muscle system in ARDS and other critical illnesses.
Need for Additional Trials of Vitamin C for Sepsis Files, D. Clark; Liu, Kathleen D; Matthay, Michael
JAMA : the journal of the American Medical Association,
08/2020, Letnik:
324, Številka:
6
Journal Article
The aims were to 1) determine feasibility of measuring physical function in our ICU Recovery Clinic (RC), 2) determine if physical function was associated with 6-month re-hospitalization and 1-year ...mortality and 3) compare ICU survivors' physical function to other comorbid populations.
We established the Wake Forest ICU RC. Patients were seen in clinic 1month following hospital discharge. Testing included the Short Form-36 questionnaire and Short Physical Performance Battery (SPPB). We related these measures to 6month re-hospitalizations and 1year mortality, and compared patients' functional performance with other comorbid populations.
Thirty-six patients were seen in clinic from July 2014 to June 2015; the median SPPB score was 5 (IQR 5). The median SF-36 physical component summary score was 21.8 (IQR 28.8). Mortality was 14% at 1year. Of those who did not die by 1year, 35% were readmitted to our hospital within 6months of hospital discharge. SPPB scores demonstrated a non-significant trend with both mortality (p=0.06) and readmissions (p=0.09). ICU survivors' SPPB scores were significantly lower than those of other chronically ill populations (p<0.001).
Physical function measurement in a recovery clinic is feasible and may inform subsequent morbidity and mortality.
•It is feasible to measure physical function as part of an ICU Recovery Clinic.•Physical function measured by the SPPB may predict readmissions and mortality.•SPPB scores in ICU survivors were significantly lower than other comorbid cohorts.
Respiratory failure is a common and potentially life-threatening complication of neuromuscular diseases. Prompt recognition and accurate diagnosis of new or worsening chronic neuromuscular disease ...have important clinical management and prognostic implications. In this article, we present an approach to the acute presentation of undifferentiated neuromuscular respiratory failure in the ICU and guidance for determination and respiratory management of the underlying disorder.
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