Table 1 Characteristics of the selected systematic reviews

2023_Bellaver [30]

SR and M-A / RCTs, observational cohort studies

30 / 3839

ICUAW patients

Use of NMBAs

Occurrence of ICUAW

NMBA use may relate to ICUAW, but evidence remains insufficient due to observational studies' heterogeneity

2022_Yang_Zi [29]

Prospective cohort research

12 / 1950 (26–474)

ICU adult patients (age ≥ 18 years old)

Sex, age, Infectious disease, SOFA score, sepsis, APACHE II, MV days, LOS

Use of aminoglycosides, RPT, use of corticosteroids, use of NMBAs, hyperglycemia

Occurrence of ICUAW

The results showed that the significant risk factors for ICUAW included female, MV days, age, ICU LOS, infectious disease, RRT, use of aminoglycosides drugs, sepsis related SOFA score, hyperglycemia. The evidence for the predictive value of glucocorticoids, MNBAS and sepsis is insufficient and needs to be validated by more high-quality studies in the future

2020_Shao [26]

SR and M-A / RCTs

3 / 691

Adult > 18 years with ARDS, study groups that received NMBAs and CG (placebo without NMBAs)

APACHEII

NMBAs

Clinical: MRC score. Occurrence of ICUAW

The use of NMBAs did not significantly increase the risk of ICUAW compared to non-NMBA treatment. Regarding severity, two studies reported significant differences in APACHE II scores between the groups, while another two studies involving 1345 patients found no statistically significant differences in MRC scores

2020_Medrinal [28]

SR and M-A / observational cohort studies

11 / 1290 (13–227)

Patients with and without weakness

Prolonged VM, prolonged ICU stay

Limb and/or respiratory muscle weakness, cut-off value based on the literature (MIP and MRC scores)

Muscle weakness was often associated with a longer duration of MV and a longer ICU LOS. Muscle weakness was strongly associated with an increase in MV weaning failure rate

2020_Tarazan [25]

SR and M-A / parallel-group RCT

4 / 885 (36–454)

Adults with ARDS of any severity

NMBA (comparing infusion of NMBA vs. non-NMBA)

ICUAW incidence

The use of NMBA infusion may increase the risk of ICU-AW. The certainty of evidence was moderate. Anticipated absolute effect (risk with no infusion, but intermittent needed NMBA)

2020_Wei [24]

SR and M-A / RCTs

4 / 1437

ARDS patients

NMBA (comparing infusion of NMBA vs. non-NMBA)

ICUAW incidence

Use of NMBA infusion was an independent risk factor might increase the risk of ICUAW which subsequently increased the duration of MV. Recent data have shown that NMBA may not be associated with ICUAW when used for less than 48 h. A continuous NMBA infusion needs to be used with caution, because it may increase the risk of ICUAW

2020_Yang3 [21]

SR and M-A / RCTs and PCS

10 / 1363 (33–412)

ICUAW patients

Role of aminoglycoside therapy

ICUAW incidence, MRC weakness scale, electrophysiological studies, and the histopathology of muscle or nerve tissue

The use of aminoglycosides was significantly associated with ICUAW. The overall incidence of ICUAW was 45% in the aminoglycoside group versus 35% in the control group

2018_Yang2 [23]

SR and M-A / PCS

14 / 2571 (39–600)

ICUAW patients with MV in 9 studies, ICU LOS in 3, SIRS or sepsis in 3 and MOF in 2

Age, APACHE II, SIRS, SOFA, neurologic failure (GCS < 10)

NMBAs, aminoglycosides, corticosteroids, norepinephrine, RRT, parenteral nutrition

Occurrence of ICUAW, MRC scale, electrophysiological studies or histopathology of muscle or nerve tissue

APACHE II, NMBAs, use of aminoglycosides were significantly associated with ICUAW (pooled data using M-A)

**A number of early risk factors found to be significantly correlated with ICUAW: female sex, APACHE II score (> 12), SOFA score (> 7), higher lactate level, hyperglycemia, electrolyte disturbance, SIRS, sepsis and MOF

2018_Yang1 [22]

SR and M-A / RCTs and PCS

18 / 2387 (20–412)

Adult ICU patients

Sepsis, MV

Corticosteroids

ICUAW incidence, MRC scale or diagnostic tests, electrophysiological studies, histopathology of muscle or nerve tissue

The use of corticosteroids was significantly associated with increased odds of developing ICU-AW. The overall incidence of ICUAW was 43% in the corticosteroid group versus 34% in the control group. Thus, exposure or administration to corticosteroids should be limited or shortened in clinical practice to reduce the risk of ICUAW

2018_Sanchéz-Solana [32]

SR / retrospective observational studies, PCS or clinical trials

3 / (12–133)

CIPNM who are in the ICU

LOS

Corticosteroids

Onset of a polyneuromyopathy

**A statistically significant relationship was observed between ICUAW and failure in ventilator disconnection, increase in ICU stay and the time that the patients required MV. The use of corticosteroids, was not shown to be related to neuromuscular alteration

2018_Lambell [35]

SR /no restrictions

6 / (15–119)

Critically ill adult participants aged > 18 years admitted to an ICU

Nutrition: energy and/or protein delivery

Change in skeletal muscle mass, measured via dual-energy x-ray absorptiometry, computed tomography, ultrasound and/or TBP via prompt γ in vivo neutron activation analysis

** A variety of methods were used to assess skeletal muscle mass or TBP. Participants in included studies experienced differing levels of muscle loss (0%–22.5%) during the first 2 weeks of ICU admission. No association between energy and protein delivery and changes in skeletal muscle mass were observed. Muscle wasting is not consistent across muscle groups during the acute phase of critical illness and the difficulty with comparing findings between heterogeneous studies

2017_Annoni [39]

SR and M-A / experimental and observational studies

8–26 / 3765

Adult critically ill patients

Age, gender, severity of illness, diabetes, SOFA, score sepsis

Use of corticosteroids, vasopressor, NMBA, aminoglycosides

ICU-AW outcomes, evaluated using clinical MRC score, electrophysiological tests or a combination of both

The M-A of 8 studies (1488 patients) showed that older age, female gender, higher APACHE-II score, higher SOFA score, sepsis on admission and any use of corticosteroids during ICU stay were significantly associated with ICU-AW at awakening. History of diabetes was not associated with ICU-AW in any of 7 studies. 8 in 10 studies reported no association between aminoglycosides and ICU-AW

2017_McKittrick [34]

Integrative review / studies, case reports

7 / 2755

Patients admitted to an ICU with a severe burn injury

Severe burns

Development of critical care neuropathy, measured by EMG and NCS investigations

An analysis of 7 prospective cohort studies, with a total of 2755 burned subjects, 128 presented critical polyneuropathy, representing an incidence of 4.4%. Patients who sustain a severe burn injury are likely to have a greater length of stay in ICU thereby increasing their risk for critical care polyneuropathy

2016_Price [27]

SR and M-A / RCTs and prospective observational cohort studies

19 / 2254

Neuromuscular dysfunction acquired in critical illness, ICUAW, CIP, and CIM

NMBA, depth of sedation

Incidence ICUAW, MRC score, electrophysiologic outcomes, and use of muscle biopsy

The 19 studies included 2,254 people, showed an unadjusted event rate of neuromuscular dysfunction acquired in critical illness of 51% in patients exposed to NMBAs and 39% in the unexposed control group; this difference was statistically significant. This M-A suggests a modest association between NMBA and neuromuscular dysfunction acquired in critical illness

2012_Ydemann [31]

SR /

not informed

5 / not described

CIM, CIP intensive care, ICU

LOS in ICU, length of MV

Intensive insulin therapy, minimal sedation

CIM and CIP

**CIM/CIP is the most commonly occurring ICU, ICU-acquired neuromuscular dysfunction, and it is associated with a significant increase in LOS, delayed weaning from MV, prolonged rehabilitation and, consequently more expenses

2010_Prentice [33]

SR /

observational studies

19 / 116

Intensive critical care setting population

MV, sepsis and MOF

Immobility

Muscle strength (peripheral neuromuscular dysfunction, respiratory muscles)

**There appears to be a lower incidence of respiratory muscle involvement in the presence of critical illness related peripheral neuromuscular disorders. Increases in the duration of MV and ICU LOS were noted in patients with respiratory involvement compared with those without

2006_Hohl [36]

SR /not informed

6 / (50–1548)

All-encompassing term CIPNM

APACHE III, SIRS, MV

Glucose levels, use of aminoglycosides, corticosteroids, muscle relaxants

Incidence CIPNM

**Patients with elevated blood glucose levels during their ICU admission showed a higher incidence of CIPNM, correlating significantly. A high percentage (60%) of patients had CIPNM. APACHE III score and the presence of SIRS were significant predictors for the development of CIPNM, the overall incidence of CIPNM in a sample of 98 patients was 33%. No significant differences were found regarding particular drugs and the onset of CIPNM

1998_De Jonghe [38]

SR /PCS

8 / (20–242)

Critically ill adult patients

Severe asthma, MV, SOFA

Corticosteroids, NMBA

Frequency of critical illness neuromuscular abnormalities (CINMA)

** MV’s patients for more than 5 days, electrophysiologic abnormalities were reported in 76% of cases. In studies with patients with asthma and/or administration of corticosteroids and/or NMBA, 20%-50% clinical weakness or muscle denervation was observed. In 2 cohort studies of patients with SOFA, abnormalities were found whit-in 70 and 82%, the most frequent finding was axonal neuropathy. In the two other studies primary muscle disease was found in 78% of patients and was frequently associated with signs of denervation due to axonopathy