Background: Skeletal muscle atrophy commonly occurs in critically ill patients, and decreased muscle mass is associated with worse clinical outcomes. Muscle mass can be assessed using various tools, including ultrasound and bioelectrical impedance analysis (BIA). However, the effectiveness of muscle mass monitoring is unclear in critically ill patients. This study was conducted to compare ultrasound and BIA for the monitoring of muscle mass in critically ill patients. Methods: We recruited adult patients who were expected to undergo mechanical ventilation for > 48 h and to remain in the intensive care unit (ICU) for > 5 days. On days 1, 3, 5, 7, and 10, muscle mass was evaluated using an ultrasound and two BIA devices (Bioscan: Malton International, England; Physion: Nippon Shooter, Japan). The influence of fluid balance was also evaluated between each measurement day. Results: We analyzed 93 images in 21 patients. The age of the patients was 69 (interquartile range, IQR, 59–74) years, with 16 men and 5 women. The length of ICU stay was 11 days (IQR, 9–25 days). The muscle mass, monitored by ultrasound, decreased progressively by 9.2% (95% confidence interval (CI), 5.9–12.5%), 12.7% (95% CI, 9.3–16.1%), 18.2% (95% CI, 14.7–21.6%), and 21.8% (95% CI, 17.9–25.7%) on days 3, 5, 7, and 10 (p < 0.01), respectively, with no influence of fluid balance (r = 0.04, p = 0.74). The muscle mass did not decrease significantly in both the BIA devices (Bioscan, p = 0.14; Physion, p = 0.60), and an influence of fluid balance was observed (Bioscan, r = 0.37, p < 0.01; Physion, r = 0.51, p < 0.01). The muscle mass assessment at one point between ultrasound and BIA was moderately correlated (Bioscan, r = 0.51, p < 0.01; Physion, r = 0.37, p < 0.01), but the change of muscle mass in the same patient did not correlate between these two devices (Bioscan, r = − 0.05, p = 0.69; Physion, r = 0.23, p = 0.07). Conclusions: Ultrasound is suitable for sequential monitoring of muscle atrophy in critically ill patients. Monitoring by BIA should be carefully interpreted owing to the influence of fluid change. Trial registration: UMIN000031316. Retrospectively registered on 15 February 2018.

Background: Diaphragm atrophy is observed in mechanically ventilated patients. However, the atrophy is not investigated in other respiratory muscles. Therefore, we conducted a two-center prospective observational study to evaluate changes in diaphragm and intercostal muscle thickness in mechanically ventilated patients. Methods: Consecutive adult patients who were expected to be mechanically ventilated longer than 48 h in the ICU were enrolled. Diaphragm and intercostal muscle thickness were measured on days 1, 3, 5, and 7 with ultrasonography. The primary outcome was the direction of change in muscle thickness, and the secondary outcomes were the relationship of changes in muscle thickness with patient characteristics. Results: Eighty patients (54 males and 26 females; mean age, 68 ± 14 years) were enrolled. Diaphragm muscle thickness decreased, increased, and remained unchanged in 50 (63%), 15 (19%), and 15 (19%) patients, respectively. Intercostal muscle thickness decreased, increased, and remained unchanged in 48 (60%), 15 (19%), and 17 (21%) patients, respectively. Decreased diaphragm or intercostal muscle thickness was associated with prolonged mechanical ventilation (median difference (MD), 3 days; 95% CI (confidence interval), 1–7 and MD, 3 days; 95% CI, 1–7, respectively) and length of ICU stay (MD, 3 days; 95% CI, 1–7 and MD, 3 days; 95% CI, 1–7, respectively) compared with the unchanged group. After adjusting for sex, age, and APACHE II score, they were still associated with prolonged mechanical ventilation (hazard ratio (HR), 4.19; 95% CI, 2.14–7.93 and HR, 2.87; 95% CI, 1.53–5.21, respectively) and length of ICU stay (HR, 3.44; 95% CI, 1.77–6.45 and HR, 2.58; 95% CI, 1.39–4.63, respectively) compared with the unchanged group. Conclusions: Decreased diaphragm and intercostal muscle thickness were frequently seen in patients under mechanical ventilation. They were associated with prolonged mechanical ventilation and length of ICU stay. Trial registration: UMIN000031316. Registered on 15 February 2018

Background: Lower limb muscle atrophy is often observed in critically ill patients. Although upper limb muscles can undergo atrophy, it remains unclear how this atrophy is associated with clinical outcomes. We hypothesized that this atrophy is associated with mortality and impairments in physical function.Methods: In this two-center prospective observational study, we included adult patients who were expected to require mechanical ventilation for > 48 h and remain in the intensive care unit (ICU) for > 5 days. We used ultrasound to evaluate the cross-sectional area of the biceps brachii on days 1, 3, 5, and 7 and upon ICU discharge along with assessment of physical functions. The primary outcome was the relationship between muscle atrophy ratio and in-hospital mortality on each measurement day, which was assessed using multivariate analysis. The secondary outcomes were the relationships between upper limb muscle atrophy and Medical Research Council (MRC) score, handgrip strength, ICU Mobility Scale (IMS) score, and Functional Status Score for the ICU (FSS-ICU).Results: Sixty-four patients (43 males; aged 70 ± 13 years) were enrolled. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was 27 (22–30), and in-hospital mortality occurred in 21 (33%) patients. The decreased cross-sectional area of the biceps brachii was not associated with in-hospital mortality on day 3 (p= 0.43) but was associated on days 5 (p= 0.01) and 7 (p< 0.01), which was confirmed after adjusting for sex, age, and APACHE II score. In 27 patients in whom physical functions were assessed, the decrease of the cross-sectional area of the biceps brachii was associated with MRC score (r= 0.47,p= 0.01), handgrip strength (r= 0.50,p= 0.01), and FSS-ICU (r= 0.56,p< 0.01), but not with IMS score (r= 0.35,p= 0.07) upon ICU discharge.Conclusions: Upper limb muscle atrophy was associated with in-hospital mortality and physical function impairments; thus, it is prudent to monitor it. (321 words)Trial registration: UMIN 000031316. Retrospectively registered on 15 February 2018.

Objectives: Although skeletal muscle atrophy is common in critically ill patients, biomarkers associated with muscle atrophy have not been identified reliably. Titin is a spring-like protein found in muscles and has become a measurable biomarker for muscle breakdown. We hypothesized that urinary titin is useful for monitoring muscle atrophy in critically ill patients. Therefore, we investigated urinary titin level and its association with muscle atrophy in critically ill patients. Design: Two-center, prospective observational study. Setting: Mixed medical/surgical ICU in Japan. Patients: Nonsurgical adult patients who were expected to remain in ICU for greater than 5 days. Interventions: None. Measurements and Main Results: Urine samples were collected on days 1, 2, 3, 5, and 7 of ICU admission. To assess muscle atrophy, rectus femoris cross-sectional area and diaphragm thickness were measured with ultrasound on days 1, 3, 5, and 7. Secondary outcomes included its relationship with ICU-acquired weakness, ICU Mobility Scale, and ICU mortality. Fifty-six patients and 232 urinary titin measurements were included. Urinary titin (normal range: 1–3 pmol/mg creatinine) was 27.9 (16.8–59.6), 47.6 (23.5–82.4), 46.6 (24.4–97.6), 38.4 (23.6–83.0), and 49.3 (27.4–92.6) pmol/mg creatinine on days 1, 2, 3, 5, and 7, respectively. Cumulative urinary titin level was significantly associated with rectus femoris muscle atrophy on days 3–7 (p ≤ 0.03), although urinary titin level was not associated with change in diaphragm thickness (p = 0.31–0.45). Furthermore, cumulative urinary titin level was associated with occurrence of ICU-acquired weakness (p = 0.01) and ICU mortality (p = 0.02) but not with ICU Mobility Scale (p = 0.18). Conclusions: In nonsurgical critically ill patients, urinary titin level increased 10–30 times compared with the normal level. The increased urinary titin level was associated with lower limb muscle atrophy, occurrence of ICU-acquired weakness, and ICU mortality.

Daily sedative interruption (DSI) may reduce excessive sedation and shorten the duration of mechanical ventilation. It is not clear, however, how DSI affects sleep characteristics. For patients receiving mechanical ventilation, we compared the effect on sleep quality of DSI and continuous sedation (CS). Twenty-two mechanically ventilated patients who were receiving midazolam by infusion were randomly assigned to two groups, DSI (n=11) or CS (n=11). In the DSI group, sedatives were interrupted until the patients awoke and expressed discomfort, after which midazolam or opioids were administered intermittently as needed during the daytime (0600 to 2100 hours); during the night (2100 to 0600) midazolam was administered intravenously to maintain Ramsay sedation scale 4 to 5. In the CS group, the sedatives were titrated to obtain Ramsay sedation scale 4 to 5 throughout the day. The polysomnography of each patient was recorded continuously over a 24 hour period. Sleep stages were analysed using Rechtschaffen and Kales criteria. In the DSI group, the amount of stage 3 and 4 non-rapid eye movement sleep (slow wave sleep) was longer (6 vs 0 minutes, P=0.04) and rapid eye movement sleep was longer than in CS (54 vs 0 minutes, P=0.02). In the CS group, total sleep time during night-time was longer (8.7 vs 7.3 hours, P=0.047) and frequency of arousal was lower (2.2 vs 4.4 event/hour, P=0.03) than those in the DSI group. All mechanically ventilated patients demonstrated abnormal sleep architecture, but, compared with CS, DSI increased the amount of slow wave sleep and rapid eye movement sleep.