Reliability of ultrasound measurements of quadriceps muscle thickness in critically ill patients

This observational monocentric study was conducted in the surgical critical care unit of Saint-Antoine University Hospital in Paris, France and complied with published STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines [18]. The access to health information was approved by an ethics committee (Committee for the Protection of “Human Subjects in Biomedical Research” - Paris Ile de France VI Pitié-Salpêtrière – 10/07/2014) and by the French Data Protection Committee (“Commission Nationale Informatique et Libertés” - #1771144) who waived the need for individual consent according to the French law at the time of the study.

We included patients (1) over 18 years old admitted to the ICU, (2) expected to stay more than 7 days and (3) who received a muscular ultrasound evaluation as part of their usual care. Were excluded from the study patients (1) with pre-existing neuromuscular pathology, (2) with a lower-limb amputation, (3) whose ultrasound data were missing or incomplete, and (4) patients discharged from the ICU before day 7.

Ultrasound measurement of quadriceps muscle thickness was performed as part of the usual clinical patient care developed within the unit. Measurements were realized according to the protocol described by Tillquist et al. [19] using a 12 MHz linear transducer connected to an ultrasound machine (Vivid i, GE Healthcare, United States). The ultrasound probe was placed perpendicular to the long axis of the thigh on its anterior surface, at the two-thirds (“two-thirds” site) and the midpoint (“midpoint” site) of the length between the anterior superior iliac spine (ASIS) and the upper border of the patella. Both measurement sites were determined using a measuring tape and analyzed in order to find the most reliable point. The obtained cross-section allowed the operator to visualize the quadriceps femoris muscle (vastus medialis, vastus lateralis, vastus intermedius, rectus femoris), the subcutaneous tissues, the adipose tissue and the femur. After identifying the muscle tissue, the thickness of the quadriceps muscle was obtained by measuring the distance between the cortex of the femur and the most superficial muscular fascia (Fig. 1). Measurements were performed by applying maximal compression on the ultrasound probe without inflicting pain, in order to prevent the underestimation of muscle wasting linked to subcutaneous edema. The effectiveness of the technique has been previously demonstrated in edematous patients [20]. For every measurement, the leg was maintained into a lower limb orthosis in order to keep the same exact position. As part of usual patient care in the unit protocol, measurements were made on both legs and on both sites repeatedly on D1, D3, D5, D7 and D21 of the ICU stay. In a quality approach purpose, additional measurements were performed to assess the agreement between values recorded by the same observer or by two different observers. Two trained operators (HEB and TL) carried out the measurements. For intra-observer reliability, the operator completed two consecutive measurements blindly without knowing the result of the first measurement. For inter-observer reliability, the two observers were unaware of each other’s results and rater order was allocated at random. Given the rapid occurrence of fluid shifts in critically ill patients, the time interval between measurements did not exceed 1 hour and measurements were not carried out during CRRT.

For this observational study, were collected general patient characteristics, ICU outcomes, risk factors associated with MW previously reported in the literature [21] and nutritional data: gender, weight, height, Body Mass Index (BMI), simplified acute physiology score II (SAPS II) score, length of the ICU stay, duration of mechanical ventilation, duration of renal replacement therapy, vasopressor administration, neuromuscular blocking agent administration, sedation time, daily caloric intake (expressed in kcal/day), daily protein intake (expressed in g/kg/day) and the assessment by US of the quadriceps femoris muscle thickness conducted by two observers. The muscle loss during the first week was obtained by calculating the difference between measurements made on D7 and D1. The cumulative nutritional debt during the first week corresponds to the difference between the recommended protein and caloric target according to international guidelines [22, 23] (1.3 g/kg/day; 25 kcal/kg/day) and the total caloric intake actually received.

Qualitative variables are described as values and percentages; quantitative variables as medians [95% confidence interval]. Comparisons were made using non-parametric tests (Wilcoxon matched-pairs signed rank for quantitative variables). A p value of less than 0.05 was considered to indicate statistical significance. For each patient, muscle loss during the first 3 weeks was assessed by selecting the mean loss of the left and right quadriceps femoris combined thickness evaluated by the same observer (HEB) at the midpoint site. Non-parametric correlation analysis was completed using Spearman correlation test. The agreement between ultrasound measurements was represented by Bland and Altman plots, illustrating the difference between the two measurements of the same patient to the average of these two values. Good measurement reproducibility would generate a cloud of points close to the X axis regardless of the mean of the measurement pairs. Reliability between different measurements was assessed by Intraclass Correlation Coefficient (ICC). The ICCs were determined from the left and right thigh measurements and independently from laterality, and were interpreted as follows [24]: < 0: Poor agreement, 0.01–0.20: slight agreement, 0.21–0.40: fair agreement, 0.41–0.60: moderate agreement, 0.61–0.80: substantial agreement, 0.81–1.00: almost perfect agreement.

Between December 2013 and April 2014, a total of 280 ultrasound quadriceps thickness measures were performed on the 29 patients included in the study. Characteristics of these patients are presented in Table 1. Median age was 64 years old [95% CI, 60–69] and median SAPS II score was 49 which corresponds to an expected mortality of 44%. Average length of stay was 14 days. Regarding patient care previously associated with MW, 79% of patients were mechanically ventilated, 62% were under continuous sedation, 17% received continuous neuromuscular-blocking agent and 41% were treated by vasopressors.

Quadriceps femoris thickness decreased promptly during the first week of the ICU stay.

Muscle mass loss was strongly correlated between the two legs with a r coefficient of 0.96 (p < 0.01) at midpoint and 0.93 (p < 0.01) at the two-thirds site. Median thickness at admission was 1.72 cm [95% CI, 1.62; 2.13] and decreased to 1.45 cm at D7 [95% CI, 1.24; 1.665], corresponding to a 16% significant variation in muscle thickness (− 0.32 cm [95% CI, − 0.43; − 0.2], p < 0.01). Median thickness decreased until 1.3 cm at D21 [95% CI, 0.80; 1.48] which corresponds to a total loss of 24% of muscle thickness (− 0.6 cm, [95% CI,-0.76; − 0.42], p < 0.01). Figure 3 depicts the evolution of quadriceps femoris muscle thickness between D1 and D21.

During the first week of the ICU stay, daily caloric intake was 14.6 kcal/kg/day [95% CI,7.4; 20.4] and daily protein intake was 0.4 g/kg/day [95% CI, 0.1; 0.7]. Based on international guidelines, the cumulative caloric debt during the first week was 5353 kcal [95% CI, 2808–7119]) and the cumulative protein deficiency over the same period was 443 g [95% CI, 257.8–548.7]. There was no correlation between caloric (r = − 0,01; p = 0,96) or protein (r = − 0,05; p = 0,80) debt and the decrease in muscle mass during the first week of ICU stay (Fig. 4).