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. 2023 Jan 3;27:2. doi: 10.1186/s13054-022-04253-0

Table 1.

Characteristics of included studies assessing muscle wasting

Author/References Design/Country/Setting No. of Population Inclusion criteria Tool Body site Timing Muscle mass loss Outcomes
1. Lambell [45]

RC single centre

Australia

ICU

32

Trauma, medical, surgical

 > 18 yo, who had CT scans before admission with routine care and a second or multiple CT scan ≥ 7 days later. Patients included if both CT scans were appropriate for analysis of SMA and if the predominant nutrition route was enteral and/or parenteral (planned > 70% requirements), due to oral intake not being routinely recorded in a quantifiable manner CT Skeletal muscle CSA at L3 level CT scan at week 1 (day 0–7) and second CT scan ≥ 7 days later

SMA loss in 7 days MD: −21.9 [−29.9 to −13.9] cm2, (149.9 ± 38.8 vs. 127.9 ± 38.4 cm2), p < 0.001

%SMA change per day: −1.27 ± 0.88% cm2

Not reported
2. Lee [15, 69]

PC

Single Centre

Malaysia

ICU

86

Cardiovascular, respiratory, gastrointestinal, neurology, sepsis, trauma, metabolic, renal, immunocompromised

Consecutive patients > 17 years old, expected to stay > 96 h on ICU. Patients with ‘normal’ baseline muscle status USS Quadriceps muscle layer thickness (QMLT), RF CSA, VI, pennation angle (PA) and fascicle length (FL) Day 1 (within first 48 h), 7, 14, 22 of ICU admission

%QMLT compared to baseline: at day 7: −8.61 ± 19.44 at day 14: −15.63 ± 23.75

%RF CSA compared to baseline:

at day 7: −9.81 ± 19

at day 14: −22.73 ± 20

Every 1% loss of QMLT over the first week of critical illness was associated with 5% increase in 60-day mortality (Adjusted odds ratio [AdjOR] 0.950 for every 1% less QMLT loss, 95% CI 0.90,0.99; p = 0.023
3. Toledo [14]

PC single centre

Brazil

ICU

74

Sepsis, stroke, lung transplant, cardiac insufficiency

Patients > 18 years old, needing mechanical ventilation for ≥ 48 h USS Quadriceps muscle thickness Day 1, 3, 7

% Quadriceps muscle thickness decrease from day 1 to day 7

Right leg: 15% (± 19.5%)

Left leg: 12.7% (± 16%)

Predictor of survival: cut-off value in muscle thickness of ≤ 1.64 cm on day 7 (HR = 0.7, 95% CI, 0.582–0.801, sensitivity 81%, specificity 63%). Higher probability to remain on mechanical ventilation in patients with 1.64 cm loss of thigh muscle thickness on day 7, HR: 2.1 (95% CI, 1.1–3.8) higher than their counterparts (P = 0.017). Greater loss of thigh muscle thickness on day 7 for worst ICU survival (HR: 3.7; 95% CI, 1.2–11.5) and hospital survival (HR: 4.5; 95% CI, 1.5–13.7)
4. Zhang [26]

PC

Single centre

China

ICU

37

Sepsis, pneumonia, severe pancreatitis, liver failure, renal failure, cardiac dysfunction, surgical

Patients aged ≥ 18 years with an anticipated ICU stay of at least 2 days USS RF thickness and CSA, VI and BB muscles Day 1, 4, 7, 10 % not reported Not reported
5. Borges [27]

PC

Single centre

Brazil

ICU

45

Severe and septic shock

Patients > 18 yo with sepsis or severe septic shock within 24 h of admission USS RF CSA Day 2, 4, 6, at ICU discharge and hospital discharge

RF CSA: day 2: 5.11 ± 0.85cm2 versus day 6: 4.49 ± 0.84cm2; P = 0.001

Daily RF CSA loss: 1.2%

During ICU stay average muscle loss of 13.5% compared to baseline

RF CSA in patients who underwent mechanical ventilation versus those without mechanical ventilation, P = 0.080. RF CSA during hospital stay in mechanically ventilated 17.25% versus patients without ventilation 10.76%, P = 0.001
6. Dimopoulos [13]

PC

Single centre

Greece

ICU

165

Cardiac surgery

Patients > 18 yo admitted to cardiac ICU within 24 h of cardiac surgery USS RF thickness Day 1, 3, 5, 7

RF mass (cm):

D1: 1.37 ± 0.25

D3: 1.2 ± 0.5

D5: 1.25 ± 0.52

RF + VI mass(cm):

D1: 2.58 ± 0.34

D3: 2.41 ± 0.94

D5: 2.37 ± 0.8

In 5 days RF mass loss by 2.2% [(95%CI: −0.21 to 0.15), P = 0.729] and RF + VI mass loss by 3.5% [(95% CI: −0.4 to 0.22), P = 0.530]

RF + VI mass < 2.5 cm on D1: longer ICU length of stay (47 ± 74 h vs 28 ± 46 h, P = 0.02) and ventilator time (17 ± 9 h vs 14 ± 9 h, P = 0.05). ICU-AW versus no ICU-AW on D3: longer ventilation (44 ± 14 h vs 19 ± 9 h, P = 0.006) and ECMO (159 ± 91 min vs 112 ± 71 min, P = 0.025)
7. Kemp [12]

PC

Single centre

UK

ICU

20

Cardiac surgery

Adults > 18 yo with elective aortic operation requiring admission to the ICU as identified by the surgical team USS RF CSA Day before surgery and day 1, 3, 7 after surgery

RF CSA (cm2) at D0: 6.85 ± 1.45 (5.4–8.3)

D7: 6.3 ± 1.45 (4.85–7.75)

RF CSA mass loss: 8% (6.6–10.2)

Muscle loss > 10% was associated with longer ICU length of stay (P = 0.038), hospital length of stay (P = 0.014), mechanical ventilation time (P = 0.05)
8. Mayer [16]

PC

Single centre

USA

ICU

41

Sepsis or acute respiratory failure

Adults > 18 yo, diagnosis of acute respiratory failure or sepsis of any origin anticipated to survive and spend > 3 days on ICU, enrolled within 48 h of admission USS RF and TA CSA, muscle thickness (mT), echo intensity (EI) Day 1, 3, 5, 7

RF mT: D1 0.98 ± 0.3 versus D7 0.81 ± 0.27, P = 0.0316

RF CSA: D1 2.99 ± 0.99 versus D7 2.47 ± 0.88; P = 0.0253

RF EI: D1 91 ± 24.9 versus D7 99.1 ± 27.6; P = 0.081

TA mT: D1 2.01 ± 0.36 versus D71.82 ± 0.31, P < 0.001

TA CSA: D1 5.3 ± 0.89 versus D7 4.71 ± 0.95, P < 0.001

TA EI: D1 82.7 ± 21.2 versus D7 96.7 ± 22.6; P = 0.002

Changes from D1 to 7

RF mT: 20.1% (12–26)

RF CSA: 18.5% (11–23)

RF EI: 10.5% (5–20)

TA mT: 9.1% (5–12)

TA CSA: 8.1% (5–15)

TA EI: 15.4% (7–28)

RF EI in first 7 days of ICU admission predictor of ICU-AW (area under curve = 0.912)
9. McNelly [44]

RCT

Multi-centre

UK

ICU

121 mechanically ventilated patients Adult (> 18 years), expected to be intubated and ventilated for ≥ 48 h; requiring enteral nutrition via nasogastric tube; multi-organ failure (Sequential Organ Failure Assessment [SOFA] score > 2 in ≥ 2 domains at admission); likely ICU stay ≥ 7 days and likely survival ≥ 10 days USS RF CSA At Day 1, 7, 10 in both groups

Intermittent feed

Day 7 −12.9%(95%CI −17.1 to –8.7)

Day 10 −18.7% (95% CI −29.8 to −7.6)

Continuous feed

Day 7: −14.7% (95% CI −19.5 to 9.9)

Day 10: −20.6% (95% CI −31.0 to 10.2)

P value

P = 0.431

P = 0.337

Safety profiles, gastric intolerance, physical function milestones, and discharge destinations did not differ between groups
10. Nakamura [46]

RCT

Single centre

Japan

ICU

117

Medical and surgical

Patients admitted to ICU   CT Femoral muscle volume Day 1 and 10 Femoral muscle volume loss was 12.9 ± 8.5% in the high-protein group and 16.9 ± 7.0% in the medium-protein group, with significant difference (p = 0.0059) For critical care, high-protein delivery provided better muscle volume maintenance, but only with active early rehabilitation
11. Nakanishi [28]

PC

Multi-centre

Japan

ICU

56

Respiratory failure, heart failure, sepsis, cardiac arrest, trauma, neurologic

Consecutive adult > 18 yo, expected to remain in ICU > 5 days. Patients were prospectively recruited within 12 h of ICU admission USS RF CSA Day 1, 3, 5, 7

RF CSA loss:

–8.6 ± 4.9% on D3, –13.8 ± 5.9% on D5, –18.2 ± 5.6% on D7, respectively (p < 0.01)

Not reported
12. Nakanishi [29]

PC

Multi-centre

Japan

ICU

64

Respiratory failure, sepsis, post-cardiac surgery, heart failure, cardiac arrest, trauma, neurologic

Expected mechanical ventilation > 48 h, stay in ICU > 5 days USS BB CSA, RF CSA Day 1, 3, 5, 7 and ICU discharge

BB CSA decreased by 6.0% (95% CI, 4.4–7.6%) D3, 11.0% (95% CI, 9.3–12.7%) D5, and 15.6% (95% CI, 13.5– 17.6%) D7 (p < 0.01)

RF CSA decreased by 6.2% (95% CI, 3.3%–9.1%) D3, 12.9% (95% CI, 9.8–15.9%) D5, and 17.1% (95% CI, 13.4%– 20.7%) D7; (p < 0.01)

BB CSA loss: 2.24% per day, BB CSA loss: 15.6% per week, RF CSA loss: 2.44% per day, RF CSA: 17.1% per week

BB and RF muscle atrophy did not predict in-hospital mortality on day 3 (P = 0.70 and P = 0.53, respectively). BB muscle loss predicted mortality on days 5 (P = 0.02) and 7 (P = 0.01). RF muscle atrophy on days 5 and 7 predicted mortality (P = 0.02 and P = 0.01, respectively)
13. Borges [30]

PC

Single centre

Brazil

ICU

37

Severe sepsis or septic shock

Patients > 18 yo diagnosed with severe sepsis or septic shock within 24 h of evolution USS RF CSA Day 2, 4, 6, ICU discharge and hospital discharge

RF CSA loss: −5.20 ± 0.47 on D2, −4.4 ± 0.45 on ICU discharge and 4.36 ± 0.42 on hospital discharge, (P < 0.05)

RF CSA: −1.45% per day; −14.5% ± 7.6 in 10 days

No difference in RF CSA between patients who underwent mechanical ventilation and in those without; P = 0.08
14. Dusseaux [47]

RC

Single centre

France

ICU

25

Sepsis, septic shock, acute pancreatitis, cardiac arrest, pneumonia, endocarditis

 > 18yo, in ICU for at least 7 days, required mechanical ventilation during their ICU stay, and had abdominal CT scans within the first 48 h of admission to ICU (CT 1: initial assessment) and 7 to 14 days after (CT 2: late assessment CT 2) CT Skeletal muscle radiodensity, skeletal muscle mass CSA at L3 vertebra CT 1: within the first 48 h of admission CT 2: 7 to 14 days later

SMM (cm2/m2): CT 1 48.73 ± 12.57; CT 2 46.64 ± 10.64

SMD: CT 1 34.86 ± 10.46, CT 2 33.56 ± 7.67

SMM loss: −2.09 (± 6.96); p = 0.183 over 7–14 days

SMD loss: −1.3 ± 8.53 over 7–14 days

No significant correlation was observed between mortality outcome and SMM [P = 0.289; OR 95% CI: 0.93 (0.81–1.060)] or SMD [P = 0.091; OR 95% CI: 1.12 (0.98–1.28)]
15. Haines [48]

RC

Single centre

UK

ICU

10 7

Trauma

All trauma admissions admitted to the adult ICU either directly or via the operating theatre

Urea/creatinine ratio

CT

Total abdominal muscle CSA measured at the level of the third lumbar (L3) vertebrae, and psoas muscle CSA was calculated at the L4 level

CT 1: on admission

CT 2: within 1–9 days or after 10 days of ICU stay

At the second CT urea/creatinine ratio negatively correlated with L4 psoas and L3 muscle cross-sectional areas (R2 0.39, p < 0.001)
16. Nakanishi [31]

PC

Single centre

Japan

ICU

21 surgical, non-surgical Adults > 18yo expected mechanical ventilation > 48 h, stay in ICU > 5 days USS, BIA Combined BB and RF CSA Day 1, 3, 5, 7, 10

Muscle mass: on D3 −9.2% (95% CI, 5.9–12.5%), on D5 −12.7% (95% CI, 9.3–16.1%), on D7 −18.2% (95% CI, 14.7–21.6%), on D10 −21.8% (95% CI, 17.9–25.7%)

(P < 0.01)

Muscle loss: −2.6% per day; −18.2% per week

Not reported
17. Trung [32]

PC

Single centre

Vietnam

ICU

79

Tetanus

Patients ≥ 16 y of age with a clinical diagnosis of generalized tetanus and within 48 h of ICU admission USS RF CSA Day 1, 7, 14, at hospital discharge

RF CSA loss: −7.43 ± 3.17 at D7, −11.59 ± 4.52 at D14, −13.2 ± 5.4 at discharge

Muscle loss between admission and discharge P < 0.01

Not reported
18. Wandrag [33]

PC

Multi-centre

UK

ICU

43

Pneumonia, cardiology/cardiac surgery, neurology/neurosurgery, sepsis, septic shock, major trauma, traumatic brain injury, gastroenterology, gastrointestinal surgery, HIV, multi-organ failure, renal failure

Patients > 18yo, anticipated to be ventilated > 48 h USS Combined muscle depth BB, forearm (flexor compartment of muscle) and thigh (rectus femoris and vastus intermedius) Day 1, 3, 7 and 14 Total muscle depth (cm): D1: 7.6 ± 3.7, D7: 6.5 ± 3.1; MD (cm): −1.1 (1.5–0.7), P < 0.0001
19. Hadda [34]

PC

Single centre

India

ICU

70

Sepsis

Adults > 18 years old, diagnosis of sepsis (non-surgical) USS BB thickness and quadriceps muscles Day 1, 3, 5, 7, 10, 14 and then weekly until discharge or death

On day 7 percentage muscle thickness loss [median (IQR)]

BB: 7.61 (− 1.51, 32.05) %; P < 0.001

Quadriceps: 10.62 (− 1.48, 32.06) %, p < 0.001); P < 0.001

Decline in muscle thickness was significantly higher among patients with worse outcome at 90 days
20. Hayes [35]

PC

Single centre

Australia

ICU

25

ARDS, bridge to transplant, pulmonary hypertension, cardiac failure/infarction, cardiac arrest

Patients > 18 yo expected to be on ECMO > 24 h or > 5 days in ICU prior to recruitment USS RF CSA At baseline, day 10, day 20

RF CSA loss: 4.2 ± 1.3 at D1, 3.4 ± 1.1 at D10 compared to baseline: RF CSA

−19.2% [95% CI, − 13.7 to − 24.8%], P < 0.001 at day 10; −30.5% [95% CI, − 24.1 to − 36.9], P < 0.001 at day 20

Not reported
21. Katari [36]

PC

Single centre

India

ICU

100

Mixed medical and surgical

Patients 18–90 years old, anticipated ICU stay > 7 days USS Total anterior thigh thickness, RF thickness, and combined thickness of VI and RF Day 1, 3, 7

RF thickness:

D1: 1.37 ± 0.41, (0.96)

D3: 1.26 ± 0.41,

D7: 1.22 ± 0.47; P < 0.001 respectively

RF thickness: −11 (± 38.5)% at D7 compared to baseline

Not reported
22. Nakanishi [37]

PC

Single centre

Japan

ICU

28

Mixed ICU patients

Expected mechanical ventilation > 48 h, stay in ICU > 5 days USS BB and RF thickness and CSA Day 1, 3, 5, 7

Loss compared to baseline: BB thickness at D7 −13.2%; P < 0.01

BB CSA at D7-16.9%; P < 0.01

RF thickness at D7: −18.8%

RF CSA at D7: −20.7%

Not reported
23. Palakshappa [17]

PC

Single centre

USA

ICU

29

Medical patients with sepsis and shock or respiratory failure

Admitted to the medical ICU with a diagnosis of sepsis complicated by respiratory failure or shock requiring vasopressors for a minimum of 6 h, and an anticipated ICU length of stay > 48 h USS

RF CSA

Quadricep muscle thickness

On Day 0 and Day 7

RF CSA decreased by 23.2%

Quadriceps thickness decreased by 17.9%

Quadriceps muscle thickness shows a weak correlation with the strength

RF CSA depicts a moderate correlation with the strength

24. Pardo [24]

PC

Single centre

France

ICU

29

Mixed ICU patients

 > 18 years old, expected ICU stay > 7 days, patients to receive muscle US as part of usual care USS Quadriceps femori muscle thickness Day 1, 3, 5, 7, 21

Quadriceps femori

at admission: 1.72 [95% CI, 1.62; 2.13],

D7: 1.45 [95% CI, 1.24; 1.665] P < 0.01,

D21: 1.30 [95% CI, 0.80; 1.48] P < 0.01

Quadriceps femori loss: 16% over a week

Not reported
25. Silva [38]

PC

Single centre

Brazil

ICU

22

TBI

Patients 18–60 yo and mechanically ventilated USS TA, BB and RF muscle thickness Day 1, 7, 14

Muscle wasting at D14 compared to baseline:

RF: −22% P = 0.0001, TA: −19% P = 0.0001, BB: −12% P = 0.0004

Not reported
26. Annetta [39]

PC

Single centre

Italy

ICU

38

Trauma

Trauma patients with an injury severity score (ISS) exceeding 25, admitted to ICU within few hours after the injury. Only well-nourished, previously healthy subjects, aged 18–59 yo USS RF and TA CSA Admission day, 5, 10, 15, 20

RF CSA (cm2):

D0: 6.1 [5.1–7.3], D5: 5.9 [4.8–6.3], D10: 5.1 [4.3–6.2], D15: 4.6 [3.8–5.3], D20: 3.5 [3.2–4.7]

AT CSA (cm2):

D0: 5.6 [4.5–6.4],

D5: 4.8 [3.7–5.6],

D10: 4.0 [3.7–5.2],

D15: 4.0 [3.3–4.8],

D20: 4.2 [3.4–4.7]

Overall 45% reduction in RF CSA during the first 20 days of ICU stay; 15% loss from day 5 to 10, 12% from day 10 to 15, 21% from day 15 to 20

TA CSA 22% loss during the overall ICU stay, P = 0.30

Not reported
27. Puthucheary [40]

PC

Multi-centre

UK

ICU

43

Surgical and medical

All patients were recruited within 24 h of admission to a university hospital and a community hospital and were expected to survive intensive care unit (ICU) admission after being invasively ventilated for over 48 h and in the ICU longer than 7 days USS RF thickness and RF CSA Day 1, 7, 10

RF thickness Day 7: −5.88 (−11.69, −0.06)

Day 10: −9.65 (−15.43, −3.84 (P = 0.031)

RF CSA

Day 7: −13 (−16.5, −9.48)

Day 10: −17.72 (−21.15; −14.29) (P = 0.004

ΔRFCSA was greater in those with knee extensor weakness than those without (20.7% [95% CI, 13.7–27.7] vs. 8.4% [95% CI, 2.5–14.3], respectively; P = 0.012). ΔThickness did not differ between these groups (12.6% [95% CI, 0.94–24.2] vs. 12.1 [95% CI, 2.7–21.5], respectively; P = 0.95). In a bivariable logistical regression, ΔRFCSA was associated with knee extensor weakness (odds ratio, 1.101 [95% CI, 1.011–1.199]; P = 0.027), but Δthickness was not (odds ratio, 1.001 [95% CI, 0.960–1.044]; P = 0.947)
28. Segaran [41]

PC

Single centre

UK

ICU

39

Surgical, medical, trauma

Patients > 18 yo, BMI > 19 kgm−2, expected to be mechanically ventilated > 48 h, and artificially fed USS Muscle depth of BB, forearm and thigh Day 1, 3, 5, 7, 12, 14 Muscle loss per day:2.93%, at D7: 20.53% Not reported
29. Turton [42]

PC

Single centre

UK

ICU

22

Mechanically ventilated critically ill patients

Patients who > 18 years of age who were assented within 24 h of being intubated and admitted to the participating intensive care units were included in the study USS

Pennation Angle and Fascicle Length and Muscle thickness

Upper Limb: Right Elbow Flexor Compartment

Lower Limb:

Right Vastus Lateralis

The right medial head of the gastrocnemius

On days 1, 5 and 10

Elbow flexor compartment and gastrocnemius muscle thickness did not significantly change

Vastus Lateralis pennation angle and muscle thickness significantly reduced by day 5

Fascicle length did not significantly change for all three muscle groups

Muscle thickness and architecture of vastus lateralis undergo rapid changes during the early phase of admission to a critical care environment
30. Parry [25]

PC

Single centre

Australia

ICU

22

Mixed medical and surgical

Adults ventilated > 48 h, remain at least 4 days in ICU USS RF thickness, vastus lateralis thickness, VI thickness, RF CSA Baseline (day 1), day 3, day 5, day 7, day 10

Compared to baseline:

RF Thickness: D3: −8.7%, D5: −16.6%, D7: −24.9%, D10: −30.4%.; VI Thickness D3: −1.3%, D5: −18.1%, D7: −20.0%, D10: −29.7% VL thickness D3: −0.2%, D5: −5.7%, D7: −6.0%, D10: −14.1%

RF CSA

D3: −1.0%, D5: −11.8%, D7: −16.8%, D10: −29.9%

Correlation between ICU discharge and RF, VI, VL thickness (P < 0.05)
31. Jung [49]

RC

Single centre

France

ICU

23

Mixed ICU patients

Admitted to ICU and had CT scan before admission, CT scan during ICU, at least one measure of diaphragmatic contractility CT scan Psoas volume, CSA of skeletal muscles at L3 vertebra examination with 64-section spiral CT Baseline and 25 days after ICU admission

Psoas volume baseline:272 ± 116, D25: 233 ± 108; P < 0.01

Skeletal muscle CSA cm2/m2 baseline: 17.1 ± 5.4, D25: 16.1 ± 5.2

Psoas loss: 14.34%

skeletal muscle CSA loss: 5.85%

Not reported
32. Puthucheary [11]

PC

Single centre

UK

ICU

63

Sepsis, trauma, intracranial bleeding, acute liver failure, cardiogenic shock

Patients > 18 yo, anticipated to be intubated > 48 h, spend > 7 days in critical care, and to survive ICU stay USS; 28 patients were assessed by USS, ration protein DNA, histopathological analysis RF CSA, biopsy, histological samples Day 1, 3, 7, 10

RF CSA mm2 at D1: 514 (464–566), D3: 495 (442–549), D7: 450 (402–498), D10: 423 (378–469)

From days 1 to 7 (− 12.5% [95% CI, − 15.8% to − 9.1%]; P = 0.002),

and to day 10 (− 17.7% [95% CI, − 20.9% to − 4.8%]; P < 0.001)

In 28 patients assessed by all 3 methods on days 1 and 7, the rectus femoris cross-sectional area decreased by 10.3% (95% CI, 6.1% to 14.5%), the fibre cross-sectional area by 17.5% (95 CI%, 5.8% to 29.3%), and the ratio of protein to DNA by 29.5% (95% CI, 13.4% to 45.6%)

Not reported
33. Reid [43]

PC

Single centre

UK

ICU

50

Sepsis, cardiac, respiratory failure, multiple trauma, head injury, head injury, medical

Patients > 18yo admitted to the ICU for ventilatory support > for 5 days or longer USS Mid-upper arm circumference and muscle thickness 1–3-day intervals between 5 and 39 days (median 7 days)

Muscle thickness at baseline: 4.5(2.6–6.8); change at D7: −0.57(0.2–2.3)

Muscle loss: 1.6%(0.2–5.7) per day, 12.05%(0–46.7)

Not reported

PC prospective cohort, RC retrospective cohort, RCT randomised controlled trial, ICU intensive care unit, CT computed tomography, USS ultrasound sonography, CSA cross-sectional area, SMA skeletal muscle area, MD median difference, RF rectus femoris, VI vastus intermedius, BB bicep brachii, TA tibia anterior, mT muscle thickness, D day, ICU-AW intensive care unit acquired weakness