Diaphragm echodensity in mechanically ventilated patients: a description of technique and outcomes.

BACKGROUND: Acute increases in muscle sonographic echodensity reflect muscle injury. Diaphragm echodensity has not been measured in mechanically ventilated patients. We undertook to develop a technique to characterize changes in diaphragm echodensity during mechanical ventilation and to assess whether these changes are correlated with prolonged mechanical ventilation. METHODS: Diaphragm ultrasound images were prospectively collected in mechanically ventilated patients and in 10 young healthy subjects. Echodensity was quantified based on the right-skewed distribution of grayscale values (50th percentile, ED50; 85th percentile, ED85). Intra- and inter-analyzer measurement reproducibility was determined. Outcomes recorded included duration of ventilation and ICU complications (including reintubation, tracheostomy, prolonged ventilation, or death). RESULTS: Echodensity measurements were obtained serially in 34 patients comprising a total of 104 images. Baseline (admission) diaphragm ED85 was increased in mechanically ventilated patients compared to younger healthy subjects (median 56, interquartile range (IQR) 42-84, vs. 39, IQR 36-52, p = 0.04). Patients with an initial increase in median echodensity over time (≥ + 10 in ED50 from baseline) had fewer ventilator-free days to day 60 (n = 13, median 46, IQR 0-52) compared to patients without this increase (n = 21, median 53 days, IQR 49-56, unadjusted p = 0.03). Both decreases and increases in diaphragm thickness during mechanical ventilation were associated with increases in ED50 over time (adjusted p = 0.03, conditional R2 = 0.80) and the association between increase in ED50 and outcomes persisted after adjusting for changes in diaphragm thickness. CONCLUSIONS: Many patients exhibit increased diaphragm echodensity at the outset of mechanical ventilation. Increases in diaphragm echodensity during the early course of mechanical ventilation are associated with prolonged mechanical ventilation. Both decreases and increases in diaphragm thickness during mechanical ventilation are associated with increased echodensity.

Usefulness of Parasternal Intercostal Muscle Ultrasound during Weaning from Mechanical Ventilation.

BACKGROUND: The assessment of diaphragm function with diaphragm ultrasound seems to bring important clinical information to describe diaphragm work and weakness. When the diaphragm is weak, extradiaphragmatic muscles may play an important role, but whether ultrasound can also assess their activity and function is unknown. This study aimed to (1) evaluate the feasibility of measuring the thickening of the parasternal intercostal and investigate the responsiveness of this muscle to assisted ventilation; and (2) evaluate whether a combined evaluation of the parasternal and the diaphragm could predict failure of a spontaneous breathing trial. METHODS: First, an exploratory evaluation of the parasternal in 23 healthy subjects. Second, the responsiveness of parasternal to several pressure support levels were studied in 16 patients. Last, parasternal activity was compared in presence or absence of diaphragm dysfunction (assessed by magnetic stimulation of the phrenic nerves and ultrasound) and in case of success/failure of a spontaneous breathing trial in 54 patients. RESULTS: The parasternal was easily accessible in all patients. The interobserver reproducibility was good (intraclass correlation coefficient, 0.77 (95% CI, 0.53 to 0.89). There was a progressive decrease in parasternal muscle thickening fraction with increasing levels of pressure support (Spearman ρ = -0.61 [95% CI, -0.74 to -0.44]; P < 0.0001) and an inverse correlation between parasternal muscle thickening fraction and the pressure generating capacity of the diaphragm (Spearman ρ = -0.79 [95% CI, -0.87 to -0.66]; P < 0.0001). The parasternal muscle thickening fraction was higher in patients with diaphragm dysfunction: 17% (10 to 25) versus 5% (3 to 8), P < 0.0001. The pressure generating capacity of the diaphragm, the diaphragm thickening fraction and the parasternal thickening fraction similarly predicted failure or the spontaneous breathing trial. CONCLUSIONS: Ultrasound assessment of the parasternal intercostal muscle is feasible in the intensive care unit and provides novel information regarding the respiratory capacity load balance.

Mechanical Ventilation-induced Diaphragm Atrophy Strongly Impacts Clinical Outcomes.

RATIONALE: Diaphragm dysfunction worsens outcomes in mechanically ventilated patients, but the clinical impact of potentially preventable changes in diaphragm structure and function caused by mechanical ventilation is unknown. OBJECTIVES: To determine whether diaphragm atrophy developing during mechanical ventilation leads to prolonged ventilation. METHODS: Diaphragm thickness was measured daily by ultrasound in adults requiring invasive mechanical ventilation; inspiratory effort was assessed by thickening fraction. The primary outcome was time to liberation from ventilation. Secondary outcomes included complications (reintubation, tracheostomy, prolonged ventilation, or death). Associations were adjusted for age, severity of illness, sepsis, sedation, neuromuscular blockade, and comorbidity. MEASUREMENTS AND MAIN RESULTS: Of 211 patients enrolled, 191 had two or more diaphragm thickness measurements. Thickness decreased more than 10% in 78 patients (41%) by median Day 4 (interquartile range, 3-5). Development of decreased thickness was associated with a lower daily probability of liberation from ventilation (adjusted hazard ratio, 0.69; 95% confidence interval [CI], 0.54-0.87; per 10% decrease), prolonged ICU admission (adjusted duration ratio, 1.71; 95% CI, 1.29-2.27), and a higher risk of complications (adjusted odds ratio, 3.00; 95% CI, 1.34-6.72). Development of increased thickness (n = 47; 24%) also predicted prolonged ventilation (adjusted duration ratio, 1.38; 95% CI, 1.00-1.90). Decreasing thickness was related to abnormally low inspiratory effort; increasing thickness was related to excessive effort. Patients with thickening fraction between 15% and 30% (similar to breathing at rest) during the first 3 days had the shortest duration of ventilation. CONCLUSIONS: Diaphragm atrophy developing during mechanical ventilation strongly impacts clinical outcomes. Targeting an inspiratory effort level similar to that of healthy subjects at rest might accelerate liberation from ventilation.

Evolution of Diaphragm Thickness during Mechanical Ventilation. Impact of Inspiratory Effort.

RATIONALE: Diaphragm atrophy and dysfunction have been reported in humans during mechanical ventilation, but the prevalence, causes, and functional impact of changes in diaphragm thickness during routine mechanical ventilation for critically ill patients are unknown. OBJECTIVES: To describe the evolution of diaphragm thickness over time during mechanical ventilation, its impact on diaphragm function, and the influence of inspiratory effort on this phenomenon. METHODS: In three academic intensive care units, 107 patients were enrolled shortly after initiating ventilation along with 10 nonventilated intensive care unit patients (control subjects). Diaphragm thickness and contractile activity (quantified by the inspiratory thickening fraction) were measured daily by ultrasound. MEASUREMENTS AND MAIN RESULTS: Over the first week of ventilation, diaphragm thickness decreased by more than 10% in 47 (44%), was unchanged in 47 (44%), and increased by more than 10% in 13 (12%). Thickness did not vary over time following extubation or in nonventilated patients. Low diaphragm contractile activity was associated with rapid decreases in diaphragm thickness, whereas high contractile activity was associated with increases in diaphragm thickness (P = 0.002). Contractile activity decreased with increasing ventilator driving pressure (P = 0.01) and controlled ventilator modes (P = 0.02). Maximal thickening fraction (a measure of diaphragm function) was lower in patients with decreased or increased diaphragm thickness (n = 10) compared with patients with unchanged thickness (n = 10; P = 0.05 for comparison). CONCLUSIONS: Changes in diaphragm thickness are common during mechanical ventilation and may be associated with diaphragmatic weakness. Titrating ventilatory support to maintain normal levels of inspiratory effort may prevent changes in diaphragm configuration associated with mechanical ventilation.

Identifying Subjects at Risk for Diaphragm Atrophy During Mechanical Ventilation Using Routinely Available Clinical Data.

BACKGROUND: Diaphragmatic respiratory effort during mechanical ventilation is an important determinant of patient outcome, but direct measurement of diaphragmatic contractility requires specialized instrumentation and technical expertise. We sought to determine whether routinely collected clinical variables can predict diaphragmatic contractility and stratify the risk of diaphragm atrophy. METHODS: We conducted a secondary analysis of a prospective cohort study on diaphragm ultrasound in mechanically ventilated subjects. Clinical variables, such as breathing frequency, ventilator settings, and blood gases, were recorded longitudinally. Machine learning techniques were used to identify variables predicting diaphragm contractility and stratifying the risk of diaphragm atrophy (> 10% decrease in thickness from baseline). Performance of the variables was evaluated in mixed-effects logistic regression and random-effects tree models using the area under the receiver operating characteristic curve. RESULTS: Measurements were available for 761 study days in 191 subjects, of whom 73 (38%) developed diaphragm atrophy. No routinely collected clinical variable, alone or in combination, could accurately predict either diaphragm contractility or the development of diaphragm atrophy (model area under the receiver operating characteristic curve 0.63-0.75). The risk of diaphragm atrophy was not significantly different according to the presence or absence of patient-triggered breaths (38.3% vs 38.6%; odds ratio 1.01, 95% CI 0.05-2.03). Diaphragm thickening fraction < 15% during either of the first 2 d of the study was associated with a higher risk of atrophy (44.6% vs 26.1%; odds ratio 2.28, 95% CI 1.05-4.95). CONCLUSIONS: Diaphragmatic contractility and the risk of diaphragm atrophy could not be reliably determined from routinely collected clinical variables and ventilator settings. A single measurement of diaphragm thickening fraction measured within 48 h of initiating mechanical ventilation can be used to stratify the risk of diaphragm atrophy during mechanical ventilation.

Inspiratory Muscle Rehabilitation in Critically Ill Adults. A Systematic Review and Meta-Analysis.

RATIONALE: Respiratory muscle weakness is common in critically ill patients; the role of targeted inspiratory muscle training (IMT) in intensive care unit rehabilitation strategies remains poorly defined. OBJECTIVES: The primary objective of the present study was to describe the range and tolerability of published methods for IMT. The secondary objectives were to determine whether IMT improves respiratory muscle strength and clinical outcomes in critically ill patients. METHODS: We conducted a systematic review to identify randomized and nonrandomized studies of physical rehabilitation interventions intended to strengthen the respiratory muscles in critically ill adults. We searched the MEDLINE, Embase, HealthSTAR, CINAHL, and CENTRAL databases (inception to September Week 3, 2017) and conference proceedings (2012 to 2017). Data were independently extracted by two authors and collected on a standardized report form. RESULTS: A total of 28 studies (N = 1,185 patients) were included. IMT was initiated during early mechanical ventilation (8 studies), after patients proved difficult to wean (14 studies), or after extubation (3 studies), and 3 other studies did not report exact timing. Threshold loading was the most common technique; 13 studies employed strength training regimens, 11 studies employed endurance training regimens, and 4 could not be classified. IMT was feasible, and there were few adverse events during IMT sessions (nine studies; median, 0%; interquartile range, 0-0%). In randomized trials (n = 20), IMT improved maximal inspiratory pressure compared with control (15 trials; mean increase, 6 cm H2O; 95% confidence interval [CI], 5-8 cm H2O; pooled relative ratio of means, 1.19; 95% CI, 1.14-1.25) and maximal expiratory pressure (4 trials; mean increase, 9 cm H2O; 95% CI, 5-14 cm H2O). IMT was associated with a shorter duration of ventilation (nine trials; mean difference, 4.1 d; 95% CI, 0.8-7.4 d) and a shorter duration of weaning (eight trials; mean difference, 2.3 d; 95% CI, 0.7-4.0 d), but confidence in these pooled estimates was low owing to methodological limitations, including substantial statistical and methodological heterogeneity. CONCLUSIONS: Most studies of IMT in critically ill patients have employed inspiratory threshold loading. IMT is feasible and well tolerated in critically ill patients and improves both inspiratory and expiratory muscle strength. The impact of IMT on clinical outcomes requires future confirmation.