Muscle atrophy in critically ill patients : a review of its cause, evaluation, and prevention

Critically ill patients exhibit prominent muscle atrophy, which occurs rapidly after ICU admission and leads to poor clinical outcomes. The extent of atrophy differs among muscles as follows: upper limb: 0.7%–2.4% per day, lower limb: 1.2%–3.0% per day, and diaphragm 1.1%–10.9% per day. This atrophy is caused by numerous risk factors such as inflammation, immobilization, nutrition, hyperglycemia, medication, and mechanical ventilation. Muscle atrophy should be monitored noninvasively by ultrasound at the bedside. Ultrasound can assess muscle mass in most patients, although physical assessment is limited to almost half of all critically ill patients due to impaired consciousness. Important strategies to prevent muscle atrophy are physical therapy and electrical muscular stimulation. Electrical muscular stimulation is especially effective for patients with limited physical therapy. Regarding diaphragm atrophy, mechanical ventilation should be adjusted to maintain spontaneous breathing and titrate inspiratory pressure. However, the sufficient timing and amount of nutritional intervention remain unclear. Further investigation is necessary to prevent muscle atrophy and improve long-term outcomes

Does T wave inversion in lead aVL predict mid-segment left anterior descending lesions in acute coronary syndrome? A retrospective study

Objectives: Limited data are available regarding the predictive value of electrocardiographic T wave inversion in lead aVL for mid-segment left anterior descending (MLAD) lesions among patients with acute coronary syndrome (ACS). Setting: Retrospective single-centre study, using a prospectively-collected coronary angiography database from January 2012 to December 2013. Participants: We included consecutive adult patients with ACS who underwent urgent percutaneous coronary intervention (PCI) within 24 h after arriving at the hospital. We excluded patients who did not undergo an ECG before PCI, patients with proximal MLAD occlusion and patients diagnosed with vasospastic angina. Primary and secondary outcome measures: The primary outcome was MLAD lesion >50%. The other outcome of interest was MLAD lesion as a cause of ACS. First, we evaluated the diagnostic values of T wave inversion in lead aVL regardless of other T wave changes for each outcome. Second, we evaluated the diagnostic values of isolated T wave inversion in lead aVL. Results: Overall, 219 patients were eligible for the analysis. T wave inversion in lead aVL regardless of other T wave changes had a sensitivity of 32.9%, specificity of 48.2%, positive predictive value of 27.6% and negative predictive value of 54.5% for predicting MLAD lesions. Isolated T wave inversion in lead aVL had a sensitivity of 9.8%, specificity of 86.9%, positive predictive value of 30.8% and negative predictive value of 61.7% for predicting MLAD lesions. These diagnostic values did not change materially when focusing on patients with MLAD lesion as the cause. Conclusions: While T wave inversion in lead aVL regardless of other T wave changes had low diagnostic values for predicting MLAD lesions, isolated T wave inversion in lead aVL had a high specificity. Our inferences underscore the importance of a cautious interpretation of T wave inversion in lead aVL among patients with ACS

High-flow nasal cannula on diaphragm

Background : Diaphragm dysfunction is a serious problem. However, a few management techniques exist for diaphragm dysfunction. Methods : Adult patients treated with high-flow nasal cannula (HFNC) in the intensive care unit were included in this study. The diaphragm function was evaluated using ultrasound measurement of thickening fraction before and after HFNC liberation. Normal diaphragm contraction was defined as thickening fraction ≥ 15% without HFNC, whereas decreased or paradoxical diaphragm contractions were 0%–15% or < 0%, respectively. Results : Forty patients were enrolled, and 16 (40%) had normal diaphragm contraction, whereas 19 (48%) or 5 (13%) had decreased or paradoxical diaphragm contractions, respectively. Thickening fraction increased after HFNC liberation (27.0% ± 25.7% vs. 38.8% ± 34.5%, p = 0.03 in HFNC vs. no HFNC) in patients without diaphragm dysfunction. In patients with decreased diaphragm contraction, thickening fraction did not change with or without HFNC (8.9% ± 11.7% vs. 6.7% ± 5.2%, p = 0.35), whereas paradoxical contraction decreased with HFNC (1.0% ± 10.2% vs. –10.3% ± 2.7%, p = 0.04) in patients with paradoxical diaphragm contraction. Conclusions : The work of breathing decreased with HFNC in patients without diaphragm dysfunction, but did not decrease in patients with decreased diaphragm contraction. Paradoxical diaphragm contraction decreased with HFNC

Reverse triggering induced by endotracheal tube leak in lightly sedated ARDS patient

Reverse triggering is respiratory entrainment triggered by the ventilator especially seen among heavily sedated patients. We confirmed reverse triggering induced by auto-triggering in lightly sedated patient through an esophageal pressure monitoring. The reverse triggering frequently caused breath stacking with increased tidal volume. Physicians should be aware, even at an optimal level of sedation, that reverse triggering can develop, possibly caused by auto-triggering

Change in diaphragm and intercostal muscle thickness in mechanically ventilated patients : a prospective observational ultrasonography study

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

Urinary Titin N-Fragment as a Biomarker of Muscle Atrophy, Intensive Care Unit-Acquired Weakness, and Possible Application for Post-Intensive Care Syndrome

Titin is a giant protein that functions as a molecular spring in sarcomeres. Titin interconnects the contraction of actin-containing thin filaments and myosin-containing thick filaments. Titin breaks down to form urinary titin N-fragments, which are measurable in urine. Urinary titin N-fragment was originally reported to be a useful biomarker in the diagnosis of muscle dystrophy. Recently, the urinary titin N-fragment has been increasingly gaining attention as a novel biomarker of muscle atrophy and intensive care unit-acquired weakness in critically ill patients, in whom titin loss is a possible pathophysiology. Furthermore, several studies have reported that the urinary titin N-fragment also reflected muscle atrophy and weakness in patients with chronic illnesses. It may be used to predict the risk of post-intensive care syndrome or to monitor patients’ condition after hospital discharge for better nutritional and rehabilitation management. We provide several tips on the use of this promising biomarker in post-intensive care syndrome

Upper limb muscle atrophy associated with in-hospital mortality and physical function impairments in mechanically ventilated critically ill adults : a two-center prospective observational study

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

Utilization of crowdfunding in the intensive care field : Muscle atrophy zero project and a questionnaire survey

In recent years, it is not easy to secure research funding, and this is a serious problem especially for young researchers. Therefore, we conducted a crowdfunding called Muscle Atrophy Zero Project and received research funding of ２．５ million yen in ２ months. Muscle Atrophy Zero Project aims to do a research about causes, diagnoses, and preventions of muscle atrophy in critically ill patients. In a questionnaire survey conducted by the crowdfunding organization（for all projects）, ５％ donated due to the attractive return gifts, and about half due to research or project content. We considered Muscle Atrophy Zero Project obtained the understanding for its contribution to the society. Through crowdfunding, we will deepen the understanding in the intensive care field as well as ensuring research funding

ICU入室時の超音波による筋量測定の有用性についての検討

Background & aims: Muscle mass is an important biomarker of survival from a critical illness; however, there is no widely accepted method for routine assessment of low muscularity at intensive care unit (ICU) admission. We hypothesize that ultrasound-based partial muscle mass assessments can reflect the trunk muscle mass. Therefore, we aimed to investigate whether ultrasound muscle mass measurements could reflect trunk muscle mass and identify patients with low muscularity. Methods: We performed a retrospective analysis of prospectively obtained ultrasound data at ICU admission. We included patients who underwent computed tomography (CT) imaging at the third lumbar vertebra (L3) within 2 days before and 2 days after ICU admission. Primary outcomes included the correlation between the femoral muscle mass measurements using ultrasound and the cross-sectional area (CSA) at L3 obtained by CT. Low muscularity was defined as a skeletal muscle index of 36.0 cm2/m2 for males and 29.0 cm2/m2 for females. Secondary outcomes included the correlation with the ultrasound measurements of the biceps brachii muscle mass and diaphragm thickness. Results: Among 133 patients, 89 underwent CT imaging, which included the L3. The patient mean age was 72 ± 13 years, and 60 patients (67%) were male. The correlation between the femoral muscle ultrasound and CT was p = 0.57 (p < 0.01, n = 89) and p = 0.48 (p < 0.01, n = 89) for quadriceps muscle layer thickness and rectus femoris muscle CSA, and these had the discriminative power to assess low muscularity, with the areas under the curve of 0.84 and 0.76, respectively. The ultrasound measurements of the biceps brachii muscle mass and diaphragm thickness were correlated with CT imaging [p = 0.57 - 0.60 (p < 0.01, n = 52) and p = 0.35 (p < 0.01, n = 79)]. Conclusions: Ultrasound measurements of muscle mass were correlated with CT measurements, and the measurements of femoral muscle mass were useful to assess low muscularity at ICU admission