- Open Access
Recovery and long term functional outcome in people with critical illness polyneuropathy and myopathy: a scoping review
BMC Neurology volume 22, Article number: 50 (2022)
Intensive care unit acquired weakness (ICUAW), embraces an array of disorders labeled “critical illness polyneuropathy” (CIP), “critical illness myopathy” (CIM) or “critical illness polyneuromyopathy” (CIPNM). Several studies have addressed the various characteristics of ICUAW, but the recovery is still unclear.
The present review investigated the recovery and the long-term functional outcome of subjects with ICUAW, whether the types of ICUAW have different outcomes and whether there is any supporting evidence.
Literature search was performed from MEDLINE/PubMed, CINAHL, EMBASE, PeDro, Web of Science and Scopus. Inclusion criteria were: i) sample size including five or more subjects; ii) subjects who suffered from ICUAW and/or CIP, CIM and CIP/CIM; iii) ICUAW ascertained by EMG. Follow-ups longer than one year were defined as long-term.
Twenty-nine studies met the inclusion criteria. In total, 788 subjects with ICUAW were enrolled: 159 (20.1%) died and 588 (74.6%) were followed. Of all the included patients, 613 (77.7%) had CIP, 82 (10.4%) CIM and 56 (7.1%) CIP/CIM. Overall, 70.3% of the subjects with ICUAW fully recovered. Seven (24.1%) studies had a follow-up longer than 1 year (range 2–8) with 173 (21.9%) subjects enrolled globally and 108 followed. Of these subjects, 88.8% gained full recovery. Most of the studies did not use proper functional scales and only 4 and 3 studies employed the Barthel scale and the Functional Independence Measure (FIM) scale. Differentiation between the types of ICUAW was performed in 7 studies, but only 3 studies reported that subjects with CIM had a better prognosis and earlier recovery than subjects with CIP/CIM.
Subjects with ICUAW could achieve good recovery and could improve at follow-up. However, the quality of the published studies due to short follow-ups and the paucity of defined outcome measures require confirms.
A number of studies have been published about the muscle weakness that may affect intensive care unit (ICU) survivors. This disorder, which in the intensive care literature is better known as ICU acquired weakness (ICUAW), embraces a spectrum of clinical conditions. All of these conditions show variable levels of muscle strength impairment, from weakness to paralysis, which involve, bilaterally, the upper and lower limbs of ICU subjects. Although the clinical pictures are generally indistinguishable, ICUAW encompasses different pathological forms that damage the muscular and the peripheral nervous system. Different types of this pathology have been described and labeled according to the histological aspects and the electrophysiological findings and depending on the predominant structure involved. In particular, the definitions include: i) critical illness polyneuropathy (CIP), if the peripheral nervous system is affected; ii) critical illness myopathy (CIM), if the muscles are involved, and iii) critical illness polyneuropathy and myopathy (CIP/CIM), critical illness neuromyopathy , and polyneuromyopathy (CIPNM) [2, 3], if the pathological process affects both muscles and nerves. Although ICU specialists prefer to use the term ICUAW, the definition “critical illness polyneuromyopathy” (CIPNM) is widely diffuse, but for the purposes of the present study, ICUAW term was used. After the first description by Bolton et al. at the beginning of the’80 s , a number of studies have been published that have contributed to making remarkable advances in the understanding of the complex aspects of ICUAW, such as the electrophysiological  and histological features  as well as the pathogenic mechanisms. The occurrence of this disorder has been variously detected with a range from 45 to 80% [7,8,9]. A systematic review reported a median prevalence of 43% . Furthermore, many risk factors have been suggested to favor the development of ICUAW, including sex (female), sepsis, ICU length of stay and multiple organ failure [11, 12]. Several therapeutic approaches and strategies have been proposed and evaluated for the management of ICUAW subjects, but pharmacological treatments have failed to prevent the occurrence and were ineffective in treating the disorder [13,14,15]. However, recent reviews and meta-analyses have demonstrated that early mobilization is associated with a lower likelihood of developing this clinical condition [16, 17]. Some reviews have addressed the various aspects of ICUAW, but they have not highlighted recovery, functional outcome and quality of life [18,19,20]. Despite the lack of treatments and the limitations of rehabilitative strategies, it was reported that 55–70% of subjects reached a full recovery after ICU discharge [21, 22], and that recovery depended on the type of ICUAW, as confirmed by the fact that CIM had an earlier and better functional outcome than CIP [22, 23]. In 2005, an extensive literature review of the neuromuscular sequelae of ICU subjects with critical illness reported that 68.8% of them made a complete recovery and regained the ability to walk independently. However, such review was limited by an insufficient number of patients with a long follow-up, leaving unsettled the question of whether deficits following ICUAW were persistent . Since then, no extensive study investigating the functional outcome in these subjects have been carried out, and the issue remains unsolved. The aim of the present review was to investigate recovery, in particular the long-term functional outcome of subjects with ICUAW, whether the types of ICUAW have different outcomes and whether there is any supporting evidence.
Materials and methods
A search of the studies having tested the functional outcome in subjects with ICUAW was conducted using MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials, CINAHL, EMBASE, PeDro, Web of Science and Scopus databases. The search was restricted to English language reports published between January 1984 and April 2021. The search terms varied slightly from database to database but included “intensive care unit acquired weakness”, “ICUAW”, “critical illness polyneuropathy”, “CIP”, “critical illness myopathy”, “CIM”, “critical polyneuropathy and myopathy”, “CIPNM”, “CIP and CIM”; “CIP/CIM”, “acute tetraplegia”, “rehabilitation”, “functional outcome”, “recovery”, “physical therapy” and “mobilization”. Search limits included only adults. Conference abstracts/posters or articles that were not peer-reviewed were excluded. The literature search was conducted by three independent authors (MC, MB, FDR). Inclusion criteria were: i) sample size including five or more subjects; ii) subjects who suffered from ICUAW and/or the following types: CIP, CIM and CIP/CIM; iii) ICUAW ascertained by EMG; iv) studies with mixed samples that used the definition of ICUAW, but subjects with CIP, CIM or CIP/CIM were also considered; v) follow-up and outcome.
In order to avoid confounding results, studies were excluded if: i) they contained only the definition of the ICUAW, without any reference to the types of ICUAW or to CIP, CIM or CIP/CIM; ii) ICUAW was not ascertained by EMG; iii) reviews concerned ICUAW but the main aim of the study was not the outcome. Studies concerning children were excluded as well as subjects with ICUAW and COVID-19.
We defined as long-term follow-ups those follow-ups longer than 1 year. In this review, the pathological condition was counted as CIP if this acronym or definition was not specified in the studies analyzed. Due to the variability of the study designs, the functional measurements, the follow-ups, and the lack of data on the score of measurements, quantitative analysis was not possible. The research was conducted according to the Preferred Reporting Items for Systematic Reviews and the Meta-Analyses (PRISMA) diagram, depicting the selection of the articles searched for the study.
The Prisma diagram of the studies’ selection is shown in Fig. 1. After studies were searched for and collected, 36 of them were considered eligible; of these, 29 [2, 6, 22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48] were included according to inclusion and exclusion criteria (Table 1). Seven studies [49,50,51,52,53,54,55] were excluded even if they included subjects with ICUAW (Appendix 1). In particular, 4 of these 7 studies were excluded because they contained a duplicate of the data already included in the 29 studies, where they were analyzed in a greater sample [48,49,50,51]; 1 study with a large sample, due to the diagnosis of ICUAW being based predominantly on the clinical examination ; 2 studies including ICU patients having been discharged with the ICD-9/ICD-10 code for CIP and CIM (53–55) and did not use functional scale scores [52, 53]. The included studies varied in aim, methodology design, sample size, case mix, inclusion/exclusion criteria, timing of the examination, follow-up and definition of recovery. Seventeen (58.6%) studies had a prospective design. Twenty-four (82.7%) studies concerned case series or small cohorts that had a mean sample size of 19.1 ± 7.7 patients and did not exceed the total number of 30 subjects. The other 5 studies [35, 41, 44, 45, 48] had samples greater than 30 patients (range 36–119) (Table 1). A total of 788 subjects with ICUAW were enrolled; of these 159 (20.1%) died and 588 (74.6%) were followed. All studies except 7 [6, 22, 23, 35, 41, 44, 46] did not perform the differentiation between the types of ICUAW and considered the disorder as a unique entity, labelling it as CIP or, more generically, as polyneuropathy or neuromuscular disorder. In particular, 613 (77.7%) patients had CIP, 82 (10.4%) CIM and 56 (7.1%) CIP/CIM. Diagnoses requiring ICU admission were widely and due to variable medical and surgical disorders. Two studies investigated the functional outcome in patients with ICUAW and coexistent brain lesions [45, 48]. Twenty (68.9%) studies were performed on subjects during their ICU or post-ICU stay, 1 in neurology and 8 (27.5%) in rehabilitation or in neuro-rehabilitative settings.
Determining the functional outcome was the main purpose of 9 (31%) studies [22, 23, 40,41,42,43, 45, 47, 48]. Overall, 70.3% of subjects with ICUAW achieved a full recovery. Eighteen studies reported a percentage above 50% and among these, 10 showed that 75% of the sample (range 75–100) reached a full recovery. Functional measures were variable and overall, 16 tools were used to evaluate recovery: the Barthel Index (39–41, 47), the Functional Independence Measure (FIM) [42, 46, 48], the modified Rankin scale (mRS) [41, 45], the activity daily living scale (ADL) , the Disability Rating scale (DRS) , the Glasgow outcome scale (GOS) , Glasgow Outcome Scale Extended (GOS-E) ; the Coma Recovery Scale- Revised (CRS-R) ; the Rivermead Motor Assessment Scale (RMA) (40), the functional disability, the Jebsen hand function test , the timed UP & GO walking test , the global motor performance , the 6-min (expressed in meters) and 10-m walking test (expressed in speed velocity) , the Overall Disability Sum score (ODSS) , and the Functional Health Status . The Barthel Scale and the FIM were employed in 4 [39,40,41, 47] and 3 studies [42, 46, 48], respectively. The studies that used the Barthel scale showed contrasting findings. Of these, 2 prospective studies reported that 86.3% and 73.8% of the sample, respectively, achieved a good recovery (mean Barthel score > 90) at follow-up [39, 41]. Conversely, 10.7% and 31.2% of subjects made a full recovery in the remaining 2 studies [40, 47], respectively. The studies that used the FIM showed a significant functional improvement. In this regard, Novak et al. reported that subjects with CIP had a mean FIM score of 78.7 ± 24.12 and 103.3 ± 20.5, at admission and discharge, respectively (p < 0.001) . Likewise, a prospective observational case control study by Cunningham et al. found that subjects with ICUAW had greater gains in FIM scores, leading to similar FIM efficiency (FIM points gained/day of rehabilitation), than subjects without ICUAW . However, despite these seemingly functional improvements and similar discharge FIM scores, subjects with ICUAW were less likely to be discharged directly home (57% versus 90%).
Fourteen (48.2%) studies did not have patient’s global ability as primary end-point and did not use functional scales. Recovery was evaluated from a clinical point of view by neurological examination or on the basis of the improvement in muscle strength by the MCR scale. This measure was used in 11 studies [22, 23, 28, 30, 36, 38, 40, 42,43,44, 47]. The severity of muscle weakness was not correlated with the clinical and electrophysiological diagnosis, and there was no correlation between the degree of the nerve conduction and the clinical findings [22, 37].
Seven studies (24.1%) had a follow-up longer than 1 year, ranging from 2 to 8 years (Table 2) for a total of 173 (21.9%) subjects, of whom 37 (21.3%) died and 108 were followed. Overall 124, 43 and 6 subjects had CIP, CIM and CIP/CIM, respectively. Of followed subjects with ICUAW 96 (88.8%) achieved a full recovery. Almost all studies included small samples characterized by case series including 7 to 22 patients, and only 2 studies had greater samples consisting of 49  and 42 subjects , respectively. Furthermore, the investigation of long-term functional outcomes in subjects with ICUAW as main purpose was addressed only in 1 of these 7 studies . This study had a mixed sample and included 42 patients with different etiology of ICU admission and showed that 73.8% of the entire sample of patients made a good recovery, as shown by the functional measures at follow-up: mean Barthel and median mRS score of 86.7 ± 15.9 and 1 (IQR: 0–5), respectively. The differentiation between the types of CIPNM was performed only in 2 studies [35, 41]. Both studies showed that subjects with CIP/CIM had the worst outcome. Functional measures were employed only in 2 studies that used the Barthel scale [39, 41] and the mRS . Both studies had a long follow-up of 3.5 and 5 years, respectively, and a good recovery was detected in a high percentage of subjects. Five (71.4%) studies did not use proper scales, and the recovery was evaluated by motor improvement, such as the ability to walk without support or aid.
ICUAW type and outcome
The differentiation between the types of ICUAW was performed in 7 (25%) studies [6, 22, 23, 35, 41, 44, 46]. Among these, 3 investigations concerning the long-term functional outcome reported that the CIM type had a better prognosis and an earlier recovery than CIP/CIM [22, 23, 41]. In detail, Koch et al. enrolled a cohort of 26 subjects consisting of 11 and 8 patients with CIP/CIM and CIM, respectively, whereas the remaining 7 were controls. After 1 year of follow up, in 7 (87.5%) and 6 (54.5%) patients with CIM and CIP/CIM, respectively, a return to normal physical capacity and a normal EMG were observed. Furthermore, 50% of CIM patients recovered within 3 months, returning to a normal or at least a sufficient physical capacity to resume daily life activities. On the other hand, 5 (45.5%) patients with CIP/CIM had a partial recovery and abnormal electrophysiological findings. Guarneri et al. reported the long-term recovery of 15 patients with ICUAW and, of these, 4, 6 and 3 patients had CIP, CIM and CIP/CIM, respectively, whereas 2 subjects were undetermined. Five subjects with CIM recovered within 6 months, whereas the presence of CIP alone or in addition to CIM was associated with a more delayed recovery between 6 and 12 months, and more than 50% of those individuals had persistent deficits at 1 year of follow-up . Likewise, the study by Intiso et al. reported that CIM patients had a better recovery than subjects with CIP or CIP/CIM and did not show differences in their health status compared to the Italian normative data. Of the remaining 4 studies, 3 did not report data on the recovery of ICUAW types, since ICUAW subjects were evaluated in comparison to controls independently of the type of ICUAW [6, 44, 46], and the last one had severe limitations despite the differentiation between the types of ICUAW, since other forms of myopathy or motor axonopathy could not be excluded .
The present review detected that 70.3% of a large number subjects with ICUAW could achieve a good recovery. This finding is similar to that obtained from a previous review by Latronico et al., who reported that 68.8% of patients made a complete recovery . Furthermore, a higher percentage of 88.8% gained good recovery at long term follow-up. However, because of strong limitations of studies that had small samples and were widely variable in aim, methodology design, case mix, and outcome measures, the finding should be considered with caution. The investigation of the functional outcome was the main purpose in 31% of the studies analyzed; in addition, a variety of measures was employed, and only 7 (24.1%) studies used a proper functional scale such as the Barthel scale and the FIM.
Of great importance, immediately after the rehabilitation treatment, is the overall health status of the patients, culminating in a return to active daily living, socialization and participation. The International Classification of Functioning, Disability and Health (ICF) recommends a new approach to evaluate disabled people, which is based on a holistic model in which activities and participation represent essential aspects. In this respect, only 2 studies investigated the outcome according to the ICF, but because of the small size of the samples and the limited duration of the follow-ups, it was not possible to draw definitive conclusions [40, 42]. Most studies (71.4%) evaluated recovery on the basis of the motor improvement and the ability to walk without support, but no data was reported on the functionality in activity daily living. Furthermore, though the present review retrieved a larger number of 788 patients with ICUAW, those who had long term follow-up for more than 1 year were only 173 (21.9%) subjects.
Over two decades, until year 2000, the main purpose of investigators was to characterize the new clinical phenomenon. There were no studies having patient’s global ability and quality of life as primary end-points. The majority of these studies reported the outcome in terms of complete or incomplete recovery (30–31, 35–36), motor performance [30, 31] and ambulatory activity [6, 30, 35]. The outcome was also addressed, but it was generically labeled as “full recovery” or based on the achievement of the motor ability, particularly of ambulation without support or aid. A proper functional scale quantifying disability and evaluating the patients’ health status and quality of life was not employed. The evaluation of the functional outcome was performed on the neurological examination or on the improvement of the muscle strength by the MCR scale. Clinical recovery was considered complete if patients had an MRC grade of 4/5 in all muscles (22, 30). Although this scale has been recently demonstrated to be an important predictor of death and of a worse five-year survival , it was designed and validated to quantify muscle strength impairment but not in relation to functional abilities. Most studies were performed by ICU specialists, and this may explain the methodological approach used. In this respect, ICU specialists might prefer to assess muscle weakness and to diagnose early ICUAW during the ICU stay, since this disorder could be a severe complication for the weaning of mechanical ventilation [57, 58] and could delay ICU discharge.
Some authors suggested that patients with the Central Nervous System (CNS) injury might likewise develop critical illness polyneuropathy and, consequently, recovery might be hampered by the CNS damage (33, 35); however, only 4 (14.2%) studies [38, 40, 43, 47] excluded subjects with the CNS damage to avoid confounding findings on the outcome. On the other hand, 2 studies were designed to investigate recovery in subjects with severe acquired brain injuries (sABI) and coexistent ICUAW [45, 48]. The authors reported that patients with sABI and ICUAW achieved a good recovery, but the magnitude of these improvements was better in the subjects with sABI alone. However, it is still not clear if the residual disability in these subjects is due predominantly to ICUAW, to CNS damage or to both disorders. Likewise, the effect that each disease might have on the course of the disability still needs to be clarified. People with both disorders might require different rehabilitation approaches and strategies.
It has been suggested that subjects with CIM have a better prognosis, reaching early and full recovery, than subjects with CIP or CIP/CIM, but this finding was reported only in 3 studies including a total of 20 patients [22, 23, 41]. Therefore, it is not possible to achieve a definitive conclusion about this matter due to the very small number of investigated subjects. Several difficulties hamper and make it hard to make real and objective comments on this issue. Some of these difficulties are the lack of unique and shared definitions of muscle weakness that may affect ICU subjects as well as an insufficient differentiation between the types of ICUAW. Today, a wide range of definitions are still being used including ICUAW, CIP, CIM, CIP/CIM or CIPNM, and this aspect can complicate the analysis, and the results of the studies may be consequently biased. Most investigations considered this disorder as a single entity, therefore it is not possible to exclude that different forms of ICUAW were present in the sample of the studies investigating only subjects with CIP. Furthermore, although EMG is able to differentiate between the subtypes of ICUAW, it does not allow the quantification of the muscle impairment and the related disabilities, and no electrophysiological exams or imaging have helped to solve this point.
The present study has limitations that must be acknowledged. This is a review of the literature having the aim to discuss the recovery and the long-term functional outcome of ICUAW subjects. Cohort studies, case series as well as functional measurements and follow-up were highly heterogeneous regarding the functional outcome. A further limitation concerns the recovery of subjects with ICUAW, such limitation is due to the paucity of trials focusing on rehabilitative interventions [41, 42, 59]. Even if this issue is beyond the scope of the present review, the majority of the studies analyzed did not define whether the subjects followed any kind of rehabilitation treatment after hospital discharge. Currently, apart from the early neuromuscular electrical stimulation that might prevent ICUAW and improve the quality of life by enhancing muscle strength in ICU patients , no definitive studies have evaluated the effects of rehabilitation programs in inpatient or outpatient settings in this population . Therefore, several questions remain unanswered and further research should be carried out on this matter.
Suggestions and implications for the future
Given the protean aspects of ICUAW, a closer collaboration as well as a more active participation of multiple specialists and experts has been suggested . In particular, ICU specialists, neurologists and physiatrists should collaborate more to properly evaluate and follow these subjects. Specialists who manage ICUAW patients should adopt unique and shared terminology and definitions, and future studies should be planned considering the following aspects:
the aim should be focused on functional recovery; the methodology design should include a large sample of patients, proper functional measures and defined long-term follow-up;
differentiation between the types of ICUAW;
rehabilitation interventions and their effect on functional outcome and quality of life, given that few studies have evaluated the effects of rehabilitation programs in this population.;
Occurrence and recovery of ICUAW in subjects with CNS damage should be investigated through dedicated studies.
A percentage of 70.3% of survivor subjects with ICUAW could achieve a good recovery and a higher percentage was detected at long term follow-up. However, the quality of the published studies due to short follow-ups, and the absence of clearly defined outcome measures did not allow definitive conclusions. A close collaboration between specialists and proper planned research in this field are needed to answer the unsolved questions.
Availability of data and materials
All data generated or analysed during this study are included in this published article [and its supplementary information files].
The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.
Activity of daily living
Disability rating scale
Glasgow outcome scale
Direct muscle stimulation
Functional independence measure
International Classification of Functioning, Disability and Health
Intensive Care Unit acquired paresis
Impact on Participation and Autonomy questionnaire
Levels of Cognitive Functioning
Length of stay
Medical Research Council scale
Modified Rankin Scale
Overall Disability Sum score
Overall Neuropathy Limitations Scale
Rehabilitation length of stay
Rivermead mobility index
Severe acquired brain injury
Spinal cord injury
Sickness Impact Profile
- SF 36:
Short Form 36 questionnaire
Traumatic brain injury
Coma Recovery Scale-Revised
Glasgow Outcome Scale-Expanded
Functional Oral Intake Scale
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Intiso, D., Centra, A.M., Bartolo, M. et al. Recovery and long term functional outcome in people with critical illness polyneuropathy and myopathy: a scoping review. BMC Neurol 22, 50 (2022). https://doi.org/10.1186/s12883-022-02570-z
- Critical illness polyneuropathy
- ICU acquired weakness
- Functional outcome