Intiso Critical Care (2018) 22:1

DOI 10.1186/s13054-017-1923-7

VIEWPOINT Open Access

ICU-acquired weakness: should medical

sovereignty belong to any specialist?
Domenico Intiso

Abstract
ICU-acquired weakness (ICUAW), including critical illness polyneuropathy, critical illness myopathy, and critical illness
polyneuropathy and myopathy, is a frequent disabling disorder in ICU subjects. Research has predominantly been
performed by intensivists, whose efforts have permitted the diagnosis of ICUAW early during an ICU stay and
understanding of several of the pathophysiological and clinical aspects of this disorder. Despite important
progress, the therapeutic strategies are unsatisfactory and issues such as functional outcomes and long-term
recovery remain unclear. Studies involving multiple specialists should be planned to better differentiate the
ICUAW types and provide proper functional outcome measures and follow-up. A more strict collaboration
among specialists interested in ICUAW, in particular physiatrists, is desirable to plan proper care pathways
after ICU discharge and to better meet the health needs of subjects with ICUAW.
Keywords: ICU-acquired weakness, Critical illness polyneuropathy, Intensivist, Multi-specialist, Recovery

Background pictures [4]. Recently, a reduction in the sodium channel

ICU-acquired weakness (ICUAW) is a frequent disabling subtype Nav1.6 was found on the sural nerve of ICU pa-
disorder that can occur in ICU subjects. Given that the tients by Li et al. [5], who also observed production of
disorder can involve the muscular and peripheral ner- antibodies against all three major sodium channels
vous systems, many definitions have been suggested in- (Nav1.6, Nav1.8, Nav1.9) which have a major role in the
cluding critical illness polyneuropathy (CIP), critical initiation and conduction of action potentials. Further-
illness myopathy (CIM), and critical illness polyneurop- more, experimental animal model studies in rats have
athy and myopathy (CIPNM), but until now no defin- demonstrated a hyperpolarized shift in the voltage de-
ition has obtained unanimous consensus. With regard to pendence of sodium channels [6] and impaired Ca2+ re-
this issue, ICUAW is proposed to overcome nomencla- lease, which induce muscle membrane inexcitability and
ture classification problems [1] even if CIPNM is also muscle weakness [7]. These findings support pioneering
broadly accepted. Although clinical assessment of studies hypothesizing that the pathological mechanism
muscle weakness using the Medical Research Council responsible for CIM could be due to muscle membrane
(MRC) score can quantify strength impairment, differen- inexcitability [8]. On the other hand, although great pro-
tiation of the ICUAW types is not possible on the basis gress has been made by ICU specialists, several areas of
of the clinical picture, and electromyography (EMG) re- uncertainty persist that should be addressed in future re-
mains the hallmark in diagnosing and differentiating search [9]. Among these, pharmacological therapy to
ICUAW types, particularly in volitional subjects. Since prevent and better manage this disorder has remained
the first description by Bolton et al. [2], ICU specialists unsatisfactory. Indeed, despite the number of therapeutic
have carried out a number of investigations that have interventions investigated, including antioxidant and nu-
provided important progress in understanding several tritional agents, corticosteroids, and intravenous immu-
aspects of ICUAW, including its pathogenic mechanisms noglobulins, only intensive insulin therapy has been
as well as electrophysiological [3] and histological demonstrated to produce some benefit [10]. Likewise,
nonpharmacological treatments have been ineffective,
Correspondence: [email protected]; [email protected] apart from early physical therapy which has been found
Unit of Neuro-Rehabilitation, Hospital IRCCS “Casa Sollievo della Sofferenza”, to reduce the duration of mechanical ventilation [10].
Viale dei Cappuccini, 71013 San Giovanni Rotondo, FG, Italy

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Intiso Critical Care (2018) 22:1 Page 2 of 5

Other important issues that should be addressed con- of follow-up was 3–6 months and did not generally
cern the functional outcomes and long-term recovery of exceed 2 years [16].
ICUAW subjects. Further important aspect to consider is that most
studies addressing functional outcomes in subjects suf-
fering from ICUAW types investigated patients with this
ICU-acquired weakness: clinical course and disorder, regardless of the primary cause of admission to
recovery the ICU. Actually, researchers enrolled subjects whose
ICUAW is a major cause of chronically impaired motor primary disorder on ICU admission was predominantly
function that can affect activities of daily living and qual- due to nonneurological causes, such as general and car-
ity of life; therefore, proper prognosis as well as preview- diac surgery, respiratory failure, and sepsis [4, 17–19],
ing the clinical course and recovery represent crucial depending on the ICU type. The course of and what
aspects in the management of ICUAW subjects. A num- happens in subjects with acquired brain damage who de-
ber of studies have investigated functional outcomes and velop ICUAW remain unknown. No study has consid-
disability in subjects who survive a critical illness. ered the outcome of ICUAW in subjects whose primary
ICUAW subjects and, in particular, older adults who cause of ICU admission was a central nervous impair-
survive critical illness suffer physical and cognitive de- ment, such as severe brain damage, although these pa-
clines that result in disabilities at greater rates than hos- tients represent a conspicuous share of ICU admissions.
pitalized, noncritically ill and community-dwelling older The previously mentioned review investigating the out-
adults [11]. Differentiating between ICUAW types could comes of differentiated ICUAW types considered studies
be essential when considering prognosis and recovery that also enrolled subjects in whom the primary cause of
since the outcomes of subjects suffering from ICUAW ICU admission was severe brain injury [13, 16]. How-
have generally been correlated with ICUAW type. In- ever, the authors did not specify whether subjects who
deed, it has been reported that subjects with the CIM had coexisting acquired brain damage experienced dif-
type have a better prognosis than those suffering from ferent outcomes. Our group has recently reported that
CIP or CIP/CIM and achieve full recovery within 6–12 one-third of ICU subjects with severe acquired brain in-
months after ICU discharge [12, 13]. Nonetheless, few jury (sABI) admitted to a dedicated rehabilitative setting
reports have documented that CIP and CIM can have suffered from ICUAW. Although the functional recovery
different outcomes, and the impact on long-term phys- of these patients improved after rehabilitation, they had
ical function, particularly of CIP and CIP/CIM, is un- poorer outcomes and significantly longer rehabilitative
clear. As mentioned previously, EMG is the benchmark stays than sABI subjects without ICUAW [20]. Further-
for differentiating ICUAW types, but the examination more, in a previous study, our group observed that ICU
results might be uncertain and doubtful in the early subjects with a combination of sABI and ICUAW
stages of the disease. It well known that proper and showed reduced quality of life and greater disability
accurate EMG requires collaboration of the subject, a compared to patients without ICUAW at 5 years of
condition which is difficult to attain in all patients dur- follow-up, and those with CIP/CIM showed poorer func-
ing an ICU stay. Likewise, this condition can also be ob- tional improvement [21]. ICUAW has been detected at a
served in subjects with a severe disability and limited rate of 90.9% in subjects in a vegetative or minimally re-
consciousness after ICU discharge. Therefore, to better sponsive state following sABI [22]. This finding raises
differentiate the CIM type, an electrophysiological study several questions regarding the relationship between pri-
(EPS) has been proposed that defines direct muscle mary causes of ICU admission and ICUAW, length of
stimulation (dmCMAP) and evaluates the CMAP ampli- ICU stay, risk factors, and prevention.
tude to calculate the ratio between nerve stimulation The combination of brain damage and ICUAW has
(neCMAP) and direct muscle stimulation CMAP (neC- not been considered previously to avoid biasing the re-
MAP/dmCMAP) [3, 14, 15]. Although dmCMAP could sults [23–25]. On the other hand, in studies enrolling
represent a valid strategy for differentiating the CIM subjects with brain damage, it was not possible to ex-
type, the test is time-consuming and is not widely used clude other reasons due to cultural tendencies and the
in clinical practice. Studies concerning the outcomes interests of the specialists who carried out the investiga-
and long-term recovery of subjects on the basis of differ- tions. In this regard, ICUAW is considered to be a clin-
entiated ICUAW types are scant. Furthermore, such ical condition that may represent the extreme end of a
studies have severe limitations, including small sample spectrum of weakness that can follow any serious illness
sizes, lack of proper functional evaluation measure- regardless of care location [26].
ments, and short duration of follow-up. The only sys- A recent report by ICU specialists has recommended
tematic review of the long-term recovery of subjects that age, premorbid ICU condition, and functionality
with ICUAW types reported that the mean duration should be considered when evaluating ICUAW
Intiso Critical Care (2018) 22:1 Page 3 of 5

outcomes [9] because these factors could affect the func- monitoring the course of ICUAW types by new noninva-
tional trajectory and strongly influence the post-ICU sive and less time-consuming techniques. Indeed, novel
functional status. However, when investigating ICUAW ultrasound imaging techniques are promising to assess
recovery, further aspects should also be considered, such muscle changes that occur in critical illness, although they
as the effect of the ICUAW types, effect of the primary require confirmation [31, 32] and have limitations in dif-
cause of ICU admission, role of each disorder in impair- ferentiating between patients with and without ICUAW at
ments and disability, and rehabilitation interventions in relatively early stages in the disease course [33]. Partner-
particular. To date, no randomized clinical trials have ships with industries will be important to ameliorate and
been conducted to test whether physical therapy (PT) simplify these techniques to facilitate their use in clinical
and specific rehabilitative interventions improve the out- practice. It is important to admit subjects suffering from
comes and activities of daily live for people with ICUAW ICUAW to dedicated rehabilitative settings after ICU dis-
[27]. Likewise, apart from a study by Novak et al. [28], charge since impairments and related disabilities might be
who reported that patients with ICUAW achieved a due to ICUAW as well as to a combination of ICUAW
significant improvement in activities and participation and coexistent complex disorders, such as brain damage.
after rehabilitation, no data have been published on A recent consensus of ICU experts has suggested that
the effect of rehabilitation on quality of life and par- after ICU discharge, physical therapy interventions should
ticipation of these patients when considering the include functional exercises, endurance training, strength-
International Classification of Functioning, Disability ening exercises for limb and respiratory muscles, educa-
and Health (ICF) domains [27]. tion on recovery, and a nutritional component [34]. In a
dedicated rehabilitative setting, physiatrists could investi-
Managing ICU-acquired weakness gate rehabilitation interventions, provide proper func-
Latronico [29] recently admonished ICU specialists, stat- tional outcome measures, and control visits. Different
ing they should pay attention to CIP and avoid the risk specialists might have difficulty in performing long-term
of this disorder becoming a “no man’s land” (i.e., a terri- follow-up after ICU discharge due to cultural hindrances,
tory without the sovereignty of any specialist). Further- limited structures, and less familiarity in administrating
more, he exhorted them to consider patients with CIP functional measurements that are typical of rehabilitation
and CIM as typical of the ICU because many ICU spe- expertise. Indeed, recovery evaluation, quality of life, and
cialists might ignore ICUAW by perceiving the disorder participation ascertainment require measurements and in-
as a complex problem in the acute stage of critically ill vestigations that are in the remit of rehabilitation expertise.
subjects that is not pertinent to their expertise. Of Furthermore, the patient might be more inclined to per-
course, the involvement of the ICU specialist is essential form functional evaluations at rehabilitative facilities where
and unique since he/she addresses ICUAW subjects in the rehabilitation process can be carried out (Table 1).
the early stages of disease occurrence, but different spe-
cialists should be involved in assessing this disorder and Conclusion
caring for patients suffering from ICUAW. A single spe- Although rehabilitative techniques have not been investi-
cialist and medical field cannot embrace the long clinical gated, a dedicated rehabilitative setting could produce
course and multifaceted aspects of ICUAW subjects.
Studies addressing risk factors, prevention, and thera- Table 1 Main points
peutic agents could be limited to intensivists, as is already Studies by ICU specialists have permit understanding of several of the
pathophysiological and clinical aspects of ICU-acquired weakness (ICUAW)
the case. Conversely, in planning studies that investigate
Despite important progress, the therapeutic strategies are unsatisfactory
functional recovery, multiple specialists, such as neurolo-
and issues such as functional outcomes and long-term recovery remain
gists and physiatrists, in addition to ICU physicians should unclear
be involved. A simple and not time-consuming EPS called Subjects with a combination of acquired severe brain injury and ICUAW
the peroneal nerve test (PENT) has been proposed re- show reduced quality of life and greater disability compared to patients
cently for responsive and unresponsive ICU subjects that without ICUAW
can be performed by a clinical neurophysiology technician Age, premorbid ICU condition, and functionality should be considered
[30]. A neurologist could play a key role in examining when evaluating ICUAW outcomes, but further aspects should also be
considered, such as the ICUAW types, effect of the primary cause of ICU
questionable CIP and CIM electrophysiological pictures in admission, role of each disorder in impairments and disability, and
depth, avoiding the risk of considering ICUAW as an oc- rehabilitation interventions
casional neurological disturbance that belongs only to the In planning studies that investigate functional recovery, multiple specialists,
ICU field. Indeed, EPS and, in particular, dmCMAP such as neurologists and physiatrists, in addition to ICU physicians should
be involved
should be performed by expert neurologists, who could
contribute to differentiating the ICUAW types [15]. Ultra- A multi-specialist approach might shed new light on areas of uncertainty
and new insight into organizing better care pathways for ICUAW patients
sound experts could contribute to diagnosing and
Intiso Critical Care (2018) 22:1 Page 4 of 5

improvement in functional recovery in subjects with iso- Received: 11 July 2017 Accepted: 11 December 2017
lated ICUAW as well as in patients with ICUAW and co-
existent disabling disorders. Given the protean aspects of
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