Maximum inspiratory pressure (MIP) provides a useful overall assessment of inspiratory force.19 MIP is the maximum negative pressure generated during an inspiratory effort against an occluded airway.20 This technique requires patient collaboration, so higher values rule out significant weakness, but low values may reflect muscle weakness, an inefficient technique, or inadequate effort.17 If the patient cannot cooperate, the maneuver can be carried out with a 1-way valve that allows expiration but not inspiration, obtaining MIP in a 20–25s period.17 Values of less than −30cmH2O show high sensitivity (but low specificity) for predicting failure to wean from MV.21

Another measurement, in addition to MIP, is sniff nasal inspiratory pressure (SNIP).19,22 SNIP consists of a voluntary inspiratory maneuver, in the form of a short, rapid inhalation through a patent nostril. SNIP is a simple and reproducible measurement for evaluating inspiratory muscle strength. Moreover, the sniff nasal maneuver can be used to assess muscle function in association with other techniques, such as transdiaphragmatic pressure (Pdi) or ultrasonography. In critically ill patients, the feasibility of the SNIP is usually determined by the presence of an artificial airway.

Simultaneous recording of esophageal (Pes) and gastric (Pga) pressure can be used to calculate Pdi (Pdi=Pes−Pga), a specific measurement of diaphragmatic force.17,19 Pdi can be measured during quiet breathing or during voluntary maximum inspiratory (Pdimax) or nasal sniff (Pdisn) maneuvers. The Gilbert index (ΔPga/ΔIdps) can be used to determine the contribution of the diaphragm to the total inspiratory effort (a higher score indicates greater contribution).19 Other parameters, such as the pressure–time product (PTP) and tension–time index (TTI) can be used to estimate the energy expenditure of the diaphragm, although this analysis is complex.17 PTP is the integration of respiratory pressure over time, normalized on the basis of maximum pressure in the case of TTI.23 Its use is generally reserved for the field of research.17

Twitch, the electrical or magnetic stimulation of the phrenic nerve, is a technique used to measure Pdimax without the collaboration of the patient (Pditw).19,22,24 In fact, Pditw determined by bilateral anterior phrenic nerve magnetic stimulation can be considered the gold standard for evaluating diaphragmatic strength in the ICU.19,24 As an alternative to Pdi, pressure recorded at the end of the tracheal tube after phrenic nerve stimulation (Ptrtw) can be used as a parameter of diaphragmatic strength, without the need for catheters for recording Pes and PGA.25 Values of PDItw<10cmH2O or Ptrtw<11cmH2O are parameters of diaphragmatic weakness in critical patients.6,7,19 Reduced PIM, Pditw, and PTRtw have been associated with difficulty in MV weaning and increased mortality.5–8,26

The negative pressure generated during the first 100ms of a quiet inspiration against an occluded airway (P0.1) can be used to assess central ventilatory stimulus.19,20 High values of P0.1 indicate an increased central stimulus, while low values of P0.1 can be due not only to a reduced neuromuscular impulse, but also to nerve conduction problems, muscle weakness or fatigue.19 It has been used in patients receiving MV as a parameter for predicting success in weaning. P0.1 values ≥6cmH2O predict weaning failure, while P0.1≤4cmH2O is considered favorable.19 However, very low values (<0.5cmH2O) may represent a reduced central impulse that is insufficient to achieve weaning.20

Electromyography (EMG) is used to study muscular activity by recording action potentials.22 Diaphragmatic EMG can be obtained from surface, esophageal or intramuscular electrodes.19 Nasogastric feeding tubes with embedded esophageal electrodes (Maquet, Sweden) can be used to obtain a continuous processed signal called “diaphragmatic electrical activity” (EAdi).17 Stimulation tests can be used to assess the efficiency of nerve and neuromuscular transmission with diaphragmatic electromyographic recording after phrenic nerve stimulation.19

Diaphragm ultrasonography, available in most ICUs, is a noninvasive technique that can be used to monitor diaphragm dysfunction at the patient's bedside. Ultrasonography can assess the diaphragmatic mass using static measures such as diaphragm thickness (Tdi), and functional aspects can be evaluated with proactive measures such as thickness fraction (TFdi) or diaphragmatic excursion (Edi).27,28

This technique can be used in most critical patients, and has excellent intra- and inter-observer reproducibility.27 Although ultrasound evaluation can be performed both in the right and left hemidiaphragms, the left side presents greater technical complexity, making it more difficult to visualize in certain patients and reducing the reproducibility of the test.29

Diaphragm Thickness

Determining Tdi by ultrasound allows an assessment of the muscle mass that correlates very well with the direct measurement of muscle thickness on autopsy.30,31 Tdi is measured at the end of a passive expiration, that is to say, at functional residual capacity (FRC). In healthy adults, the average values of Tdi range between 1.7±0.4 and 3.3±1.0mm.30,32–36 In critically ill patients receiving MV, values of between 1.3±0.3 and 2.4±0.8mm have been reported.29,37

It is difficult to establish a cut-off point below which the diaphragm can be considered to be atrophied. However, performing serial ultrasounds after initiating MV can reveal an early, progressive decline in Tdi during the stay in the ICU.37–40 However, the determination of Tdi as a static measurement has not proved useful as a parameter for predicting success in weaning from MV.14,41–43

Technique. The measurement of Tdi with ultrasound is performed in the right hemidiaphragm at the level of the zone of apposition. The zone of apposition is the area of the chest wall where the abdominal contents meet the lower rib cage, between the 8th and 10th intercostal space, at the level of the mid axillary line. With the patient supine (30–45°), a high-frequency linear transducer (≥10MHz) is placed parallel to the intercostal space and perpendicular to the skin.27 It is first used in 2-dimensional mode (mode B) to obtain the best view and to select the scan line (Fig. 1A). In this area, the diaphragm is identified as a structure formed of 3 parallel layers (approximately 1.5–3.0cm deep): a hypoechoic central layer (the diaphragm itself) demarcated by 2 hyperechoic layers (the peritoneum and parietal pleura).44 The pulmonary artifact (corresponding to the costophrenic angle) can also be seen to erase the image of the diaphragm during inspiration.36 Keeping the transducer in position, M mode is used to determine Tdi, corresponding to the distance between both hyperechoic layers, measured approximately 2cm from the costophrenic angle (Fig. 1B). As mentioned previously, Tdi is measured at the end of the passive expiration phase. However, determining Tdi during different stages of the respiratory cycle is useful for evaluating functional parameters such as TFdi.

Fig. 1.

Diaphragmatic ultrasonography. Determination of diaphragm thickness in the zone of apposition with the chest wall in B-mode (A) and M-mode (B) and evaluation of diaphragmatic excursion (C). Edi: diaphragmatic excursion; Gdi esp: expiratory diaphragm thickness; Gdi insp inspiratory diaphragm thickness; Tejido celular subcutáneo: subcutaneous cellular tissue; Higado: liver; Diafragma: diaphragm; Pleura: pleura; Peritoneo: peritoneum.

(0.49MB).

Diaphragmatic Thickness Fraction

During spontaneous ventilation, lung volume increases as the diaphragm contracts, shortens, and increases in thickness.30,45 Diaphragmatic thickening during inspiration is a parameter of the contractile activity of the diaphragm and its ability to generate pressure.27,40,45 This can be assessed on ultrasonography by measuring TFdi, which corresponds to the percentage of change in Tdi between the end of passive expiration and the end of inspiration (maximal inspiratory effort in spontaneous ventilation, or if that is not possible, inspiratory peak during MV).40

TFdi has shown good correlation with inspiratory muscle function parameters such as MIP, SNIP, Pdi, PTP and EAdi.29,34,42,45–47

In patients receiving MV, TFdi decreases progressively as the level of ventilatory support increases, becoming minimal in controlled ventilation with neuromuscular blockade.29,34,37 In other words, the more work of breathing generated by the diaphragm, the greater the TFdi. The same technique could be used to monitor diaphragmatic activity during MV.37 Goligher et al. showed that low levels of TFdi are associated with greater diaphragmatic wasting (decreased Tdi) in patients on MV.40 The presence of reduced TFdi has been associated with failure to extubate, difficulty in weaning from MV, and prolonged ICU stay.9,14,41 Although it is difficult to establish cut-off points, various studies have used TFdi values of between 20% and 36% to define the presence of diaphragmatic dysfunction.4,9,41,42

Technique. The determination of TFdi requires the measurement of Tdi at the end of the expiration phase and at the end of inspiration. In practical terms, this corresponds to minimum and maximum values, respectively, while measuring Tdi in M mode (Fig. 1B).27,29

The overall assessment of strength using MRC manual muscle testing is currently the gold standard for the diagnosis of ICU-acquired weakness (ICUAW).55 The MRC scale evaluates the strength of 3 muscle groups in each upper and lower limb, assigning a value to each muscle group of between 0 (paralysis) and 5 (normal strength), and a total value of 0 to 60 (Table 1).56 The evaluation is carried out using certain standardized maneuvers (Table 2).57

An MRC score <48 (average of <4 in the muscle groups evaluated) is considered diagnostic of ICUAW.55,58 The need for the patient to be awake and collaborative is the first limiting factor for its use. Moreover, reported interobserver variability has been variable.59–61 However, an MRC score of <48 is associated with difficulty in weaning from MV, increased length of ICU and hospital, stay and higher costs and mortality.11,12

Manual prehension dynamometry has proved to be a useful tool for the study of muscle strength in the ICU. This technique has very good interobserver reproducibility.59,62–64 To carry out the maneuver, the patient must have an MRC ≥3 in elbow flexion and wrist extension. While there are reference values for healthy individuals, values of grip strength (in the dominant hand) <11kg for men and <7kg for women have been used in critical patients to define ICUAW.11,65 Muscle weakness diagnosed by this method has been associated with difficulty in MV weaning, extended ICU stay, and greater in-hospital mortality.11,13

Electrophysiological assessment includes the study of nerve conduction, EMG, and the study of the neuromuscular junction.58,66 It can help determine if weakness is caused by muscle or nervous involvement or both. However, the need for equipment and specialized staff, as well as the technical difficulties inherent in critical patients (tissue edema, etc.), means that it is not readily applicable in most ICUs. Recently, the use of simplified electrophysiological studies, such as the peroneal nerve test, showed high sensitivity and specificity in the diagnosis of neuromyopathy in critical patients.67

Ultrasonography has become a valuable tool for the structural assessment of peripheral muscles in the ICU, with an excellent interobserver reproducibility.68–70 Numerous studies have used the thickness or cross-sectional area (CSA) of different muscle groups as a parameter of muscle mass in critically ill patients, demonstrating the progressive development of wasting during the stay in the ICU.54,71–77

Various muscles in both upper and lower limbs have been evaluated. Campbell et al. reported that the combined analysis of muscle thickness in the anterior aspect of the arm, forearm and thigh correlates most closely with lean body mass (in healthy individuals); this method has been subsequently used by several authors in critical patients.73,74,77,78 A correlation between thickness or CSA and muscle strength has been described in healthy individuals and critical patients.75,77,79 The association between muscle wasting and weakness has been demonstrated in septic patients, in whom a further reduction of the CSA of the quadriceps correlated with less strength at the time of ICU discharge.75 However, in a recent study, a single isolated measure of muscle thickness at the time of awakening did not discriminate between patients with and without ICUAW.80 Recently, Puthucheary et al. specifically compared changes in quadriceps thickness with the CSA of the rectus femoris, showing that the latter is a more sensitive and reliable measurement for assessing muscle wasting and weakness in the ICU.81 Moreover, muscle echogenicity increases in critical patients, possibly due to edema, inflammation, fibrosis, fatty infiltration, or necrosis.71,78,82,83 Specifically, an increase in muscle echogenicity predicts the development of myonecrosis (on histology) in the ICU.83 Although an inverse correlation between echogenicity and muscle strength has been established in non-critical patients, this association is not so evident in the ICU setting.71,78

Technique. Several anatomical sites and technical variations have been used in the assessment of peripheral muscle, making it difficult to compare results between studies. Although reference values for muscle thickness and echogenicity have been established in healthy individuals, changes in these values over time seem to be a more valuable parameter in critical patients.84 It is essential that the measurement site and position is precisely identified and standardized. It is important to avoid compression of the muscle during the procedure, so excess conductive gel must be used, and minimal pressure must be applied to the transducer when obtaining the image.

Recordings are obtained with a linear transducer (≥10MHz) positioned in a transverse direction, perpendicular to the underlying bone. The angle of insonation can affect the measurements, so it must be kept constant. Thickness is measured as the maximum distance between the fat–muscle interface and the bone or interosseous membrane (Fig. 2). Table 3 describes the technique for arm, forearm, and thigh.33,73,85,86

Fig. 2.

Peripheral muscle ultrasonography. Muscle thickness assessed in the flexor compartment of the arm (A), the flexor compartment of the forearm (B) and quadriceps (C).

(0.2MB).

Muscle echogenicity can be evaluated semi-quantitatively (Heckmatt scale) or quantitatively using grayscale analysis.70,71,78,82,87

Computed tomography (CT) is a validated method to determine muscle mass.69 The CSA of muscle tissue in a single slice (usually at the level of the third lumbar vertebra) has been shown to reliably represent body muscle mass.88–90 Moreover, structural muscle changes, such as fat infiltration, can be detected by analyzing muscle density on CT. In critical patients evaluated by CT, muscle wasting, decreased density, and an increase in intermuscular fat are associated with an increase in mortality.90,91 The major limitations of this technique are the need to move the patient and exposure to radiation.

Electrical bioimpedance (EBI) analysis can be used at the bedside to determine the patient's lean body mass, although it does not directly quantify muscle mass.92 This can be estimated from regression equations designed for healthy individuals.93 A recent study showed that the capacity of EBI to detect reduced muscle mass in ICU patients is acceptable, although new studies are needed to validate this technique in critical patients.94