Table 1 Studies about functional outcome in CIPNM subjects. The pathological condition was counted as CIP if differentiation between types of CIPNM was not performed and if this acronym or definition was not specified in the studies analyzed

Zochodne DW et al²⁴ (1987) [24]

case series, retrospective;

single center;

ICU; clinical and electrophysiological aspects

N = 19;

(9 M, 10 F, mean age 64);

CIP = 19

cardiac or pulmonary diseases;

5 pts had cerebral lesion (4 infarction,

1 brain injury)

10 mos-2 yrs

none

EMG, histological

examination

8 (88.8%) pts showed good functional recovery. Of these 6 pts had EMG improvement within 3 months. At 2 yrs one patients had mildly weak dorsiflexion of right foot and one had mild distal limb weakness

11 (58%) pts died

Coronel B et al²⁵ (1990) [25]

case series,

retrospective;

2 ICU center;

occurrence and clinical features

N = 15/4

(12 M, 3 F, mean age 47);

CIP = 15

cardiac or pulmonary disorders

1–8 yrs

none

EMG, muscle biopsy

3 pts: 2 pts had persisting dysesthesia;

1 needing assistance to sit and walk;

Death: 5 pts (33%)

Op de Cul et al² (1991) [2]

case series,

retrospective;

ICU; clinical and electrophysiological features

N = 22^d;

(17 M, 5 F, mean age 55)

CP = 22

Multiple trauma with brain injury (5 pts), pulmonary and infections

2–10 mos

none

EMG, muscle biopsy (7 pts)

9 (64.2%) pts had complete functional recovery; 5 (22.7%) pts: incomplete recovery;

8 pts died

Witt NJ et al²⁶ (1991) [26]

case series,

prospective;

ICU; clinical and electrophysiological features

N = 30;

CIP = 30, of these 25 had clinical signs of PN and 15 pts ES signs

multiple medical and surgical diseases; 25% had head trauma and brain lesions

mean 72 days (10–190)

none

EMG

20 (66.6%) pts gained full recovery;

3 (10%) with severe CIP showed severe disability and ultimately died

10 (33%) pts died

Rossiter A et al²⁷ (1991) [27]

case reports,

retrospective;

single center;

ICU; clinical report after pancuronium discontinuation

N = 5 pts;

(4 M, 1 F);

CIPNM = 5

medical disorders

5 mos

none

EMG; clinical examination

none had complete recovery:

1 pt severe disability at 3 months;

1 pt with tetraparesis was able to walk with assistance at 5 months;

1 pt with tetraparesis was unable to walk at 1 month;

2 pts died

Gooch JL et al²⁸ (1993) [28]

case series,

retrospective;

paralysis after neuromuscular junction blockade

N = 12^b;

age range 3.5 mos-64 yrs;

CIP = 12

medical disorders

3–6 mos

none

MRC; EMG, muscle biopsy (2 pts)

5 (50%) pts had recovery;

5 pts incomplete recovery;

2 (16.6%) pts died

Giostra E et al²⁹ (1994) [29]

case series,

retrospective;

ICU;

paralysis after neuromuscular junction blockade

N = 9;

(6 M, 3 F, mean age 65.6 + 10.3);

N = CIPNM

medical and pulmonary disorders

4 -52 wks

none

EMG, muscle biopsies (7 pts)

5 (55.5%) pts had complete recovery. Even if recovery was usual, residual peroneal palsy was frequent

Leijten F et al³⁰ (1995) [30]

prospective

cohort study; single center ICU, post-ICU; incidence and risk factors

N = 29^a;

CIP = 29

(21 M 8 F; mean age 59.7 ± 13.9 years);

N = 12 evaluated to follow-up

surgical and medical disorders;

3 pts cerebral surgery, multiple trauma (n = 9), cardiac resuscitation (n = 5), intracranial

hemorrhage (n = 2)

1 yr

none;

endpoint was strength greater than MRC grade 4/5 in all muscles with ability to walk for more than 50 m without aid or ataxia

neurological examination; MRC; EMG;

7 (58.3%) patients recovered (4 pts within 3 days and 4 weeks, 3 pts within 4 weeks and 1 year;

5 (41.7%) pts had severe disability after year;

9 (31%) pts died

Latronico N et al³¹ (1996) [31]

case series,

prospective;

single center ICU; incidence and risk factors

N = 24;

(19 M, 5 F, mean age 50.2 ± 20.9 yrs);

CIPNM = 24

All patients had NCS lesions: 13 head trauma;

6 subarachnoid hemorrhage;

3 stroke; 1 cerebral hemorrhage

8–18 mos

none

EMG/ENG; nerve biopsy (22 pts)

7 survivors: 6 (85.7%) had recovered well or had only moderate disability (able to walk unassisted with full muscle strength);

1 was in vegetative state;

17 (70.8%) pts died

Berek K et al³² (1996) [32]

case series,

prospective;

ICU;

incidence, severity and course of polyneuropathies in patients with sepsis or systemic inflammatory response syndrome

N = 22 with sepsis;

(17 M, 5 F, mean age 51.2 yrs);

CIPNM = 15

medical and surgical disorders

2–3 mos

functional disability score^$

EMG

9 (50%) pts had complete functional recovery;

6 pts had incomplete functional recovery. Of these, 4 pts had mild weakness and 2 pts had moderate weakness

Good tendency for recovery in all surviving patients, electrophysiologic findings were still pathologic in 11 patients at the follow-up;

7 (50%) pts died

Hund EF et al³³ (1996) [33]

case series,

prospective;

single center

ICU;

N = 7

(3 M, 4 F; mean age 47.7 ± 16.8

medical disorders;

3 pts with cerebral lesions

3 mos—3.5 yrs

none

EMG; muscle and nerve biopsy (3 pts)

2 (40%) pt gained complete recovery;

3 pts showed disability due to CNS lesions;

2 pts died

Campellone JV et al³⁴

(1998) [34]

case series, prospective; single center ICU; frequency of myopathy as a cause of generalized

weakness and potential risk factors after

liver transplant

N = 7/6;

(6 M, 1 F; mean age 57.7 ± 9.3)

CIM = 7

liver transplant

11–41 days (5 pts) and 67 days (1 pt)

none

EMG; muscle biopsies (5 pts)

3 (50%) pts regained strength slowly and were able to ambulate within 4 to 12 weeks;

1 pt required a walker;

2 pts died

Lacomis D. et al³⁵ (1997) [35]

cohort,

retrospective; single center ICU;

causes of ICU weakness

N = 92;

N = 49

CIM = 37^e CIP = 12

surgical, medical and pulmonary disorders

12 – 60 mos

none

EMG; muscle biopsies (22 pts)

25 (75.7%) pts had complete functional recovery: 17 pts were ambulatory within 4 months and 8 pts within 4–12 months;

7 pts showed incomplete functional recovery: 4 remained non ambulatory and 3 remained

dependent on the ventilator;

16 pts died

de Sèze M. et al³⁶ (2000) [36]

cohort, retrospective;

single center;

rehabilitation; the features and

outcome patients who had severe forms of CIP

N = 19, only CIP (14 M 5 F; mean age 55,9 yrs)

medical disorders

2 yrs

none

MRC;

sensory findings

11 (64.7%) patients recovered completely;

4 (23.5%) patients remained quadriplegic; 2 patients remained quadriparetic;

2 pts died

Zifko UA et al³⁷ (2000) [37]

cohort,

retrospective;

ICU and rehabilitation; clinical outcome and electrophysiological findings

N = 26;

CIP = 13, (9 M, 4 F, age between 22–83 yrs);

N = 7 refused to participate;

medical disorders;

1 pt with stroke

13–24 mos (mean 17 mos)

none

EMG/ENG; MRC; clinical examination

only 2 (15.3%) pts had full recovery; 11 of 13 patients with CIP had clinical manifestations, at follow-up (13–24 months after diagnosis);

6 pts died

16 De Jonghe B. et al³⁸ (2002) [38]

cohort, prospective; multicenter

ICU and post-ICU; clinical incidence, risk factors, and outcomes of ICU acquired paresis (ICUAP) during ICU stay

N = 95;

CIP (ICUAP) = 24;

(12 M, 12F; mean age 67,6 yrs)

surgical and medical disorders; patients were excluded if they had disease of the peripheral nervous system, or brainstem lesions

9 mos

none

MRC; EMG; muscle biopsy (10 pts)

15 (88.6%) patients had recovered an MRC score of 48 or higher at follow-up;

1 pt lost to follow-up;

7 pts died

Fletcher S.N. et al³⁹ (2003) [39]

cohort, prospective study; multicenter post-ICU;

prevalence, clinical characteristics

and electrophysiological features

N = 22;

CIP = 22;

(mean age 62 yrs, range 45–78);

surgical and medical disorders

3.5 yrs (range, 12–57 mos)

Barthel Index

neurologic examination;

EMG

19 (86.3%) pts had showed recovery quantified to BI between 95–100; 2 pts had recovery with BI score 85;

1 pts severe disabled. 95% patients had electromyographic evidence of chronic partial denervation, indicative of a preceding axonal neuropathy

Kerbaul et al⁶ (2004) [6]

cohort,

prospective;

single center post-ICU; to describe patterns of neuromuscular weakness by EMG and biopsy; functional outcome

N = 15 pts; (9 M, 6F; median age 53 yrs, range 33–82);

CIP = 6

CIM = 6;

CIP/CIM = 3

heart-surgery

12 mos

none,

the endpoints

were death or time to ambulation without assistance;

EMG; muscular/nerve biopsy (all pts)

6 (75%) had good recovery; 2 subjects of the 8 survivors were not ambulatory;

7 (46%) pts died

Van der schaaf M et al⁴⁰ (2004) [40]

prospective observational cohort study and cross-sectional study^c; single center ICU, post-ICU; to evaluate the functional outcome of ICU patients

N = 16;

(12 M, 4 F; mean age 67 years);

CIP = 16

medical and surgical disorders; patients with neurological disorders due CNS injury were excluded

6 mos and 1 yr

Barthel Index; Jebsen hand function test; rivermead mobility index;

timed UP & GO walking test

MRC; SIP-68;

SF-36;

IPA questionnaire

At 6 mos, 8 pts were evaluated and all showed disability (activity and participation); median sumscore Barthel Index was 18.5 (range 9–20) and rivermead mobility index was 11 (range 1–14). At 1 year, 5 (31.2%) pts were evaluated. Improvement in functional abilities with wide variation in functional outcome among the patients, but functional impairment was still dominant in four out of 5 surviving pts. Outdoor mobility was reduced. All pts, excepts for one judged their quality of life as unsatisfactory in many areas

9 (56.2%) patients died

Guarneri B et al²² (2008) [22]

prospective cohort;

multicenter post-ICU; to evaluate the long-term

follow-up

N = 92;

CIP = 15,

(12 M 3 F;

mean age 44.7 ± 14.9 yrs);

CIP = 4

CIM = 6

CIP/CIM = 3

2 = undetermined

surgical and medical disorders;

(intracerebral haemorrhage, metabolic encephalopathy, post-anoxic

encephalopathy: 1 patient each);

5 multiple trauma patients; 3 head trauma

1 yr

global motor performance^$

MRC; EMG; neurological examination

8 (61.5%) patients recovered;

2 (13.3%) patients had persisting muscle weakness; 1 patient remained tetraparetic;

1 patient remained tetraplegic;

1 patient lost to follow-up;

2 patients died;

Intiso D et al⁴¹ (2011) [41]

cohort prospective;

single center neuro-rehabilitation;

to evaluate the long-term functional outcome and health status

N = 42 (23 M, 19F, mean age 58.4 ± 13.9);

CIP = 30 CIM = 6 CIP/CIM = 6

19 pts had CNS damage

5 yrs; mean 31.7 ± 15.8 months

Barthel and

modified Rankin Scales (mRS);

SF-36 questionnaire

31 (73.8%) pts (24 pts with just CIPNM and 7 pts with CIPNM and CNS involvement) gained good recovery: mean Barthel of 86.7 ± 15.9 (P < 0.001), and the median mRS of 1 (IQR: 0–3), respectively, at follow-up (mean 31.7 ± 15.8 months)

Novak P et al⁴² (2011) [42]

cohort,

prospective;

single center rehabilitation; outcome to ICF

N = 27;

(16 F, 11 M; mean age 59.4 ± 15.9);

CIP = 27

not reported

from admission to discharge (9–102 days)

FIM; 6-min (expressed in meters) and 10-m walking test (expressed in speed velocity); ICF check list

sum of muscles strength;

Significant functional improvement; mean FIM score 78.7 ± 24.12 and 103.3 ± 20.5 at admission and discharge, respectively (p < 0.001);

6 -min walking test (m): 77.3 ± 115.3 and 191.5 ± 178.2, at admission and discharge, respectively (p < 0.001). Considering ICF, 26 (96.2%) pts improved activities and participation

Semmler A. et al⁴³ (2013) [43]

cohort,

retrospective observational;

single center post-ICU; long-term outcome

N = 51;

(26 M, 24 F; median age 57 yrs, range 19–75);

CIP = 21,

no CIM or CIP/CIM

Subjects with CNS lesion were excluded

6–24 mos, median 11 mos

ODSS^$; median ODSS scores 1 (range 0–8);

MRC; median MRC sum scores 56 (range 47–60);

EMG/ENG; neurological examination

Good recovery; pts with diagnosis of CIP showed a higher ODSS scores 1 (range 0–8) versus 0 (range 0–5); p < 0.001 and lower MRC sum scores 56 (range 47–60) versus 60 (range 58–60); p < 0.001. The neuromuscular long-term consequences of critical illness were not severe, suggesting a favorable prognosis of ICU-acquired muscular weakness

Koch S et al²³ (2014) [23]

Prospective cohort;

post-ICU; prediction of long-term outcome in CIP and CIM

N = 26;

(20 M, 6 F; mean age 46 yrs);

CIM = 8,

CIP/CIM = 11,

Control = 7

multiple trauma (n = 12)

1 yr;

(mean 411 ± 121 days)

functional health status^$

MRC; EMG; dmMCAP, neCMAP; neurological examination

4 (50%) of the CIM patients reached normal physical capacity. In contrast, only 3 (27%) of CIM/CIP patients did so at 1 year. Four (36%) of CIM/CIP pts still needed assistance to perform daily life activities: 2 pts were able to walk only within their homes and 2 were only able to stand with help or not at all. MRC sum scores assessed at follow-up examination were significantly lower in partially recovered patients (n = 6) compared with fully recovered

patients (n = 20) [MRC sum score (median and

25th/75th percentiles): 48 (54/46) vs. 60 (60/57)]

Nguyen The N et al⁴⁴ (2015) [44]

Cohort, prospective longitudinal observational; single center;

neurology; incidence and distribution of CIP/CIM subtypes and the evaluation of the risk factors and outcomes

N = 133 pts

N = 73 pts;

CIP = 35;

CIM = 16;

CIP/CIM = 

22;

controls = 60

medical disorders

3 mos

none

MRC; EMG; ONLS

At the end of the follow-up duration (90 days), 31 pts with CIP/CIM were evaluated: the ONLS scores improved but remained significantly higher in comparison to non-CIP (2.7 vs 0.8, p = 0.015);

36 (49%) died

Intiso D et al⁴⁵ (2017) [45]

prospective cohort study; single center, neuro-rehabilitation setting; functional recovery in subjects with sABI and CIPNM

N = 36;

(27 M, 9 F, mean age 56.2 ± 14.8 yrs)

CIP = 36;

N = 75 controls (sABI)

patients with sABI

107 days (65–146)

LCF, DRS, GOS, mRS

LOS

The magnitude of these improvements was different between the groups, showing that patients with sABI only had a better improvement than those with CIPNM + sABI for mRS and DRS at discharge

Subjects with sABI + CPNM showed 25.94 (23.33–28.86), 19.71 (17.42–22.31) to DRS and 2.76 (2.51–3.05) and 3.12 (2.84–3.42) to GOS, at admission and discharge, respectively

Cunningham CJB et al⁴⁶ (2018) [46]

prospective observational;

case–control;

rehabilitation setting;

prevalence of CIPNM in rehabilitative setting and

impact of CIPNM on function

N = 23, (19 M, 4 F, mean age 43.6 ± 14.7);

CIP = 16;

CIM = 2;

CIP/CIM = 5

controls = 10

medical disorders,

12 pts had SCI 2 pts stroke and one TBI

1 yr

FIM; FIM gain and FIM efficiency

EMG/ES; rehabilitation length of stay (RLOS), and discharge disposition

FIM score: 64.1 and 89.7 at admission; 78.4 and 94.6, at discharge in pts with CIPNM and without CIPNM, respectively. The gains in FIM scores and RLOS were greater, leading to similar FIM efficiency (FIM points gained/day of rehabilitation) compared with

those without CIPNM (only for 13 pts). Those with CIPNM were less likely to be discharged directly home (57% versus 90%). At 1 year, recovery was seen in 80% of those with CIM and 55% of those with CIM/CIP

Symeonidou Z et al⁴⁷ (2019) [47]

multicenter;

retrospective observational;

rehabilitation setting; functional recovery

N = 28 pts (19 M, 9 F, mean age 53.6 ± 14.5); CIP = 28

medical disorders; cerebral or spinal cord injury or stroke were excluded

109.4 ± 70.7 days

Barthel Index; ADL

MRC, sensory examination

Mean Barthel score at admission and discharge improved significantly (15.3 ± 9.1 vs 63.6 ± 21.6, p < 0.05);

3 (10.7%) pts had Barthel score > 85;

13 (46.4%) pts showed Barthel score 65–80;

5 pts had severe Barthel score 0–40, at discharge

Hakiki B et al⁴⁸ (2021) [48]

Single; retrospective observational; rehabilitation setting; functional recovery

N = 224 pts; (81 (36%) females, age

68.73);

CIPNM = 119

patients with sABI

3.8 mos

CRS-R; FIM; GOS-E; FOIS

ENG/EMG

All patients gained functional improvement at discharge for FOIS, FIM and GOS-E (P < 0.001). Those with a concomitant CIPNM achieved significantly lower scores for FIM (18.0 [1.0] and 20.0 [13.0] vs. 18.0 [6.0] and 37.0 [60.0] at the entry and discharge, respectively (P < 0.001); and GOS-E (3.0 [1.0] and 3.0 [1.0] vs. 3.0 [1.0] and 3.5 [2.0], at the entry and discharge, respectively (P < 0.001). The CIPNM absence was associated with a higher probability to achieve functional autonomy