In t en si ve C are U n it –

A c q u i red We a k n e s s
Christopher L. Kramer, MD

KEYWORDS
 ICU-acquired weakness  Critical illness neuromyopathy  Critical illness myopathy
 Critical illness polyneuropathy  Post-ICU syndrome

KEY POINTS
 ICU-acquired weakness (ICUAW) contributes substantially to the disability experienced
by patients in the aftermath of critical illness.
 A combination of critical illness myopathy (CIM) and critical illness polyneuropathy (CIP),
both of which are principally caused by the downstream effects of inflammation, and mus-
cle atrophy comprise ICUAW.
 A variety of tests can be used to diagnose ICUAW and its components CIM and CIP,
including strength testing, electrophysiology, and muscle ultrasound, although each has
important limitations to consider.
 Risk factor modification including aggressive treatment of provoking inflammatory condi-
tions and minimization of sedation and early mobilization can improve outcome.

Video content accompanies this article at http://www.neurologic.theclinics.

com.

INTRODUCTION AND DEFINITIONS

Although Sir William Osler reported a “rapid loss of the flesh” in patients with pro-
longed sepsis as early as 1892, the cause of neuromuscular weakness associated
with critical illness was not fully recognized until almost a century later.1 Technological
advances in cardiopulmonary support made during this time increased the number of
patients that survive critical illness; however, it was increasingly observed that their
survival would come at the unfortunate cost of physical disability and a reduction in
quality of life caused by weakness acquired in the intensive care unit (ICU).2 Ultimately,
this syndrome of limb and respiratory weakness that frequently develops in the wake
of critical illness was termed ICU-acquired weakness (ICUAW).3 Nerve and muscle
dysfunction in the setting of critical illness, recognized even before the coining of

Disclosure Statement: Dr C.L. Kramer has nothing to disclose.

Department of Neurology, University of Chicago, 5841 South Maryland Avenue, MC 2050, Chi-
cago, IL 60637, USA
E-mail address: ckramer1@neurology.bsd.uchicago.edu

Neurol Clin 35 (2017) 723–736

http://dx.doi.org/10.1016/j.ncl.2017.06.008 neurologic.theclinics.com
0733-8619/17/ª 2017 Elsevier Inc. All rights reserved.
724 Kramer

the term ICUAW, represents the most prominent cause of ICUAW: critical illness poly-
neuropathy (CIP) and critical illness myopathy (CIM).4,5 CIP and CIM remain distinct
clinical entities, although they commonly co-occur. The term critical illness neuromy-
opathy (CINM) has been developed to describe the spectrum of co-occurrence of CIP
and CIM in patients with ICUAW.6
ICUAW is a clinical undifferentiating definition describing the weak critically ill
patient. In contrast, CINM (and its subcomponent entities CIP and CIM) is a patho-
physiologic definition describing the weak critically ill patient with evidence of associ-
ated neuromuscular dysfunction (Fig. 1).
This review discusses the epidemiology and risk factors of ICUAW, reviews the
suspected pathophysiology, describes the distinguishing clinical and electrophysio-
logic features and the associated challenges in diagnosing ICUAW/CINM in the ICU
population, examines the evidence behind management options for the disease,
and investigates the impact ICUAW/CINM has on prognosis.

EPIDEMIOLOGY AND RISK FACTORS

The incidence of ICUAW can approach a staggering 80% of critically ill patients,
although this figure varies according to the presence, number, and severity of risk
factors and the time point at which the patient is evaluated. Multiple studies have
investigated the risk factors associated with ICUAW and those most consistently
implicated relate to the severity of the underlying critical illness and inflammation. Spe-
cifically, sepsis, shock, and the presence and degree of multiorgan failure are the risk
factors that have most frequently and reliably been associated with ICUAW.3,7–9 Sep-
tic encephalopathy, a disease whose pathophysiology is speculated to be at least in

Fig. 1. Association between ICUAW, CINM, CIP, and CIM. Critically ill patients who develop
clinical signs of weakness have ICUAW. Most patients with ICUAW have evidence of nerve
and/or muscle dysfunction and are further characterized as having CIP and/or CIM, respec-
tively. The term CINM is used to describe the common co-occurrence of CIP and CIM in
the individual patient. Muscle atrophy also likely plays a role in the development of ICUAW
and may coexist with CINM.
 Intensive Care Unit–Acquired Weakness 725

part caused by the downstream effects of systemic inflammation, has also been asso-
ciated with ICUAW.10 Collectively, these associations support the hypothesis that
ICUAW is a manifestation of nerve and muscle dysfunction as a result of the sequelae
of generalized systemic inflammation.
Studies have shown hyperglycemia to also be associated with the clinical and electro-
physiologic development of ICUAW and strict glycemic control seems to reduce the inci-
dence of ICUAW.11–13 The data are more conflicting with regard to the association of
corticosteroid use and neuromuscular blockade with ICUAW. Initial unadjusted
analyses and a single multivariate analysis suggested an association between steroid
use and the development of ICUAW; however, subsequent multivariable analyses and
a randomized trial failed to support the initial findings. Although corticosteroids can be
toxic to muscle and can result in hyperglycemia, they can also reduce inflammation
and it may be possible that these competing effects negate each other.3,9,13 Because
of the many side effects associated with steroid use in critically ill patients, the best prac-
tice is to use corticosteroids only when indicated for the underlying illness, to use the
lowest dose necessary, and to anticipate and control for hyperglycemia. Similar to corti-
costeroid use, the use of paralytics initially showed an association with the development
of ICUAW in unadjusted analyses, but subsequent multivariate analysis and a random-
ized trial evaluating the early use of neuromuscular junction blocking agents in acute res-
piratory distress syndrome showed no significant association with ICUAW.9
There is evidence, even in healthy individuals, that muscle degeneration can begin
as early as 4 hours after immobilization and an average daily loss of 1% to 1.3% of
overall muscle strength is seen per day of immobilization.9,14,15 Furthermore, the cata-
bolic conditions encountered in critical illness may worsen muscle loss in the immobi-
lized ICU patient. It is uncertain as to what degree muscle atrophy from immobilization
plays a role in the development of ICUAW, although it is likely a contributing factor.
Less than 10% of patients on mechanical ventilation are mobilized out of bed while
in the ICU and the incidence of ICUAW is directly related to the duration of mechanical
ventilation and ICU stay, though these variables may not be exclusively attributed to
the development of muscle atrophy as they also are markers of underlying disease
severity.3 That early rehabilitation has been demonstrated to reduce the incidence
of ICUAW also supports the impact immobilization has on the development of
ICUAW.16–19
An important limitation of the studies that have investigated the risk factors for
ICUAW is their failure to assess the baseline functional status of the enrolled patients.9
Clinically defined frailty, which includes the effects of sarcopenia and is categorized by
the degree of disability, occurs in approximately one-third of all patients in the ICU and
up to 80% of elderly patients. Its presence is associated with higher in and out of hos-
pital mortality, physical dependence, and mental and physical quality of life.20–22
Although age is a risk factor for ICUAW, the interaction between frailty and ICUAW
is unknown and warrants further study.

PATHOPHYSIOLOGY

In addition to muscle atrophy, the structural and functional changes that occur in the
nerves and/or muscles in ICUAW are primarily caused by inflammation.23 Although it is
easier to conceptualize CIP, CIM, and muscle atrophy as distinct clinical entities, the
reality is that the pathophysiology of ICUAW most likely combines all three processes
occurring simultaneously on a proportional continuum.
Because inflammation is the principal proximal cause of CIP and CIM, it is important
to briefly review its effects. Systemic inflammation caused by critical illness (which
726 Kramer

includes sepsis, acute respiratory distress syndrome, and so forth) results in dysfunc-
tion of the microcirculation as a result of a multitude of mechanisms including slowing
of arteriolar blood flow and capillary obstruction from migrating neutrophils and
platelet/fibrin aggregates. Increased vascular permeability caused by the release of
inflammatory cytokines, hyperglycemia, and hypoalbuminemia induces local tissue
edema and impedes diffusion of oxygen and nutrients into nerve and muscle tissue,
effectively resulting in energy failure at the tissue level. The increase in vascular
permeability also allows toxins to enter nerve and muscle tissue, which in addition
to hyperglycemia, can adversely affect mitochondrial function.3,6,9,23–25 Because the
sequela of inflammation is generalized throughout the body, the brain can also be
affected by the same pathophysiologic process, which can explain the association be-
tween septic encephalopathy and ICUAW.6
CIP manifests as a length-dependent sensorimotor axonal polyneuropathy. In addi-
tion to motor and large fiber sensory nerves, there is some preliminary evidence that
the small fiber and autonomic nerves also may be affected.3,26 Nerve conduction
studies (NCS) may be abnormal before histologic changes, although eventually
primary axonal degeneration occurs.6 Breakdown of the blood-nerve barrier and
endoneural membrane inexcitability are also speculated to occur in addition to the
mechanisms mentioned previously. CIM is characterized pathologically by preferential
loss of thick filaments representing myosin breakdown, loss of ATPase reactivity with
preferential staining, and necrosis. Additionally, functional changes occur in muscle
tissue rendering them inexcitable secondary to sodium channel dysfunction.27–29

CLINICAL FEATURES

The cardinal manifestations of ICUAW are flaccid quadriparesis and neuromuscular

respiratory failure, the latter often presenting as inability to wean from mechanical
ventilation despite normal gas exchange. These symptoms can appear rapidly and
in the first few days after ICU admission. However, recognition of weakness can be
delayed because of the patient’s inability to participate in an examination secondary
to encephalopathy, sedation, or pharmacologic paralysis. Serial electrophysiologic
studies have demonstrated abnormalities in the first days after ICU admission and
within 13 days in all patients. An abrupt decline in compound muscle action potential
(CMAP) amplitude indicating the development of CINM developed over 24 hours in
65% of patients in one study, whereas the remaining patients experienced a progres-
sive decline over 3 days.30 Regardless, the confounding effects mentioned previously
obscure the precise timing of the development of clinical weakness and symptoms
can seem to have occurred “acutely” after sedation is lifted, encephalopathy im-
proves, or neuromuscular blockade is metabolized.
Patients with CIP have predominantly distal limb weakness, although in more severe
cases the weakness also can affect the proximal muscles. The facial and extraocular
muscles are typically spared, although respiratory muscle weakness is common. A stock-
ing and glove distribution numbness in the extremities caused by sensory nerve involve-
ment may be observed, although patients unable to interact with the examiner may only
fail to grimace when a painful stimulus is applied. Small fiber nerve involvement may be
responsible for the burning neuropathic-type pain and cool extremities experienced by
some survivors of ICUAW.3,26 Deep tendon reflexes are typically reduced or absent.
Conversely, patients with CIM progress from proximal to distal weakness with
increasing disease severity. Facial involvement can occur, as can ocular muscle
weakness, although the latter is extremely rare.6 Like CIP, respiratory muscle weak-
ness is common. Sensory abnormalities are not observed in isolated CIM. Unlike
 Intensive Care Unit–Acquired Weakness 727

inflammatory myopathies, myalgias do not usually occur. Deep tendon reflexes may
be normal or reduced.
Despite the clinical distinctions between CIP and CIM, most patients with ICUAW
have a combination of CIP and CIM. Therefore, features of both illnesses are most
likely present simultaneously in the same patient and are weighted toward the pre-
dominant pathology.
Respiratory muscle weakness occurs along a clinical spectrum of severity in 80% of
patients with ICUAW.31 Impairment or absence of diaphragm contractility with or
without accompanying diaphragm atrophy is the primary mechanism of the respiratory
weakness. The term ventilator-induced diaphragm dysfunction has been coined to
describe the weakness and atrophy of the diaphragm that occurs in a time-
dependent manner with increasing duration of mechanical ventilation and this entity
may contribute to or be directly related to ICUAW.32 The diaphragmatic dysfunction
that occurs in ICUAW may not be associated with the degree of limb weakness.31 In pa-
tients on mechanical ventilation, neuromuscular respiratory weakness may present as
low tidal volumes or the need for high levels of pressure support on spontaneous mode
of mechanical ventilation. Patients with low tidal volumes may develop tachypnea to
maintain adequate minute ventilation. Respiratory insufficiency may not be immediately
apparent when switching patients from assist control to spontaneous mode of mechan-
ical ventilation, but may develop hours later. Extubated patients with respiratory weak-
ness may develop the classic symptoms of neuromuscular respiratory failure including
tachypnea, tachycardia, diaphoresis, interrupted speech, orthopnea, or paradoxical
breathing.33 Respiratory insufficiency may be more pronounced at night and noninva-
sive ventilation may be helpful during the day and particularly at night.34,35

DIAGNOSTIC EVALUATION

The diagnosis of ICUAW is made clinically using a standardized neurologic examina-

tion that tests strength in proximal, midlimb, and distal muscle groups on each limb
(Table 1). A summated score of less than 48 or an average score of 4 using the Medical
Research Council (MRC) scale in a critically ill patient, for which no other cause of
weakness is apparent, is consistent with the diagnosis of ICUAW.3 However, the defi-
nition has several limitations. First, use of the MRC scale requires patients to be alert
enough to cooperate with the examination, a requirement that up to three-quarters of
patients do not fulfill because of encephalopathy, sedation, or paralysis.36 Second,
substantial interobserver variation exists when using the MRC score to evaluate
strength in critically ill patients.3 Additionally lack of knowledge regarding prehospital
neuromuscular status or fluctuations because of delirium may also confound the ex-
amination. Third, the definition is not informative regarding the cause of weakness.
Finally, doing the comprehensive strength assessment can take time, particularly in
semicooperative patients. The use of handgrip strength testing has been proposed
as a simple and quick test to diagnose ICUAW. Studies have demonstrated that the
test is approximately 80% sensitive and specific for the diagnosis of ICUAW using
the MRC classification as the gold standard and the test has prognostic value, as
handgrip strength has been shown to be inversely associated with mortality.37 How-
ever, its limitations are similar to MRC strength testing: it requires a cooperative pa-
tient and it does not provide information regarding etiology.
Electromyography (EMG) and NCS can confirm the diagnosis of ICUAW by identi-
fying the presence of CIP and/or CIM and can rule out other diagnoses. However,
the performance of NCS on patients in the ICU may be hindered by edema, electrical
interference, or external pacing wires. Information from EMG is severely limited unless
728 Kramer

Table 1
Diagnosis of ICU-acquired weakness

Medical Research Council (MRC) Scale:

0 5 no contraction
1 5 flicker or trace of contraction
2 5 active movement, with gravity eliminated
3 5 active movement against gravity
4 5 active movement against gravity and resistance
5 5 normal power
Upper Extremity Strength
Right Left
Shoulder abduction ___/5 Shoulder abduction ___/5
Elbow flexion ___/5 Elbow flexion ___/5
Wrist extension ___/5 Wrist extension ___/5
Lower Extremity Strength
Right Left
Hip flexion ___/5 Hip flexion ___/5
Knee extension ___/5 Knee extension ___/5
Foot dorsiflexion ___/5 Foot dorsiflexion ___/5
Total Score 5 ____\60

Total score <48 or average score of 4 consistent with the diagnosis of ICU-Acquired Weakness.
Used with the permission of the Medical Research Council without formal changes. Available at
https://www.mrc.ac.uk/research/facilities-and-resources-for-researchers/mrc-scales/mrc-muscle-scale/.

the patient is able to voluntarily contract his or her muscles and may be contraindi-
cated in the setting of coagulopathy. On NCS, CMAPs are severely reduced in CIP
and CIM. The duration of the CMAPs becomes prolonged in CIM, a finding that cor-
relates with electrical impulse conduction along the muscle fiber, supporting the the-
ory of muscle inexcitibility from sodium channelopathy as a pathophysiologic
mechanism of the disease (Fig. 2).28,38 Sensory nerve action potentials are reduced
in CIP, but are spared in CIM. On EMG, abnormal spontaneous activity at rest can
be seen in CIP and CIM, although patients with CIP typically have reduced recruitment
and large prolonged motor units, whereas patients with CIM typically have rapid
recruitment and short motor units. However, electrophysiologic findings are mixed
in most cases where both CIP and CIM are present. Because a complete EMG/
NCS study requires time, expertise, and expense there has been interest in developing
an abbreviated NCS study that can accurately diagnose ICUAW. The peroneal nerve
test, where only the peroneal nerve is stimulated and recorded at the extensor digito-
rum brevis, has been shown to be 100% sensitive but only about 80% specific for the
diagnosis of ICUAW as compared with a complete EMG/NCS.39,40
Other tests used to diagnose ICUAW include direct muscle stimulation, in which
muscle contracts when stimulated in CIP (because the impulse bypasses the affected
nerve) but not CIM (because the muscle is inexcitable). However, this study requires
additional expertise and training and may be difficult to perform and interpret in the
ICU setting and population. Muscle atrophy and loss of architecture on muscle ultra-
sound have been shown to correlate with myofiber necrosis on biopsy, has good inter-
rater reliability, is noninvasive, and can assist in the diagnosis of ICUAW, but warrants
further study before implementation in routine practice.41,42 The advantages and lim-
itation of the diagnostic studies used to identify ICUAW are summarized in Table 2.
 Intensive Care Unit–Acquired Weakness 729

Fig. 2. (A) The characteristic morphology of CMAPs in CIM with a severe reduction in ampli-
tude and prolonged duration. (B) Normal CMAP for comparison.

As opposed to primary causes of neuromuscular weakness, which begin outside of

the hospital and are often the main cause for the admission, ICUAW is considered a
secondary cause of neuromuscular weakness. By far the most common secondary
cause of weakness that is symmetric and localizes to the peripheral nervous system
 730
Kramer
Table 2
Advantages and limitations of diagnostic tests for identifying ICUAW

Diagnostic Test Advantages Limitations

MRC muscle strength Easy to administer Requires patient cooperation
testing Inexpensive Interrater variation
Direct functional significance No information about cause of weakness
Noninvasive May require time in semicooperative patients
Handgrip strength Easy to administer Requires patient cooperation
Inexpensive No information about cause of weakness
Direct functional significance 80% sensitive relative to diagnosis with MRC strength testing
Quick Tests only distal muscles
Noninvasive
Complete EMG/NCS Part of the gold standard for diagnosing Time intensive
CIP and CIM Cost
Direct functional significance Moderately invasive
Can rule out other diagnoses Requires technical expertise
May be limited by electrical interference, tissue edema,
coagulopathy, or external pacing wires
Cooperation required for full EMG
Single nerve NCS (peroneal Quick Requires technical expertise
nerve test) Minimally invasive May be limited by electrical interference, tissue edema, or external
Direct functional significance pacing wires
Less cost relative to full EMG/NCS Only 80% specific for diagnosis of ICUAW relative to full EMG/NCS
Excellent sensitivity Limited information about cause of weakness
Does not require patient cooperation
Direct muscle stimulation Can differentiate CIP and CIM Requires technical expertise
Minimally invasive May be limited by electrical interference, tissue edema, or external
Does not require patient cooperation pacing wires
Limited information about cause of weakness
 Muscle ultrasound
Nerve/muscle biopsy
Adapted from Jolley SE, Bunneli AE, Hough CL. ICU–acquired weakness. Chest 2016;150(5):1131; with permission.
Does not require patient cooperation
Noninvasive
Depicts muscle atrophy and architecture
Cheap
Good interrater reliability
Gold standard for diagnosing CIM
Excellent depiction of muscle and
nerve structure
Can rule out other diagnoses
Can differentiate CIP and CIM
Requires technical expertise
Does not provide information about nerves
Diagnostic accuracy and functional significance in ICUAW requires
further study
May be limited in patients with severe edema or who are obese
Invasive
Expensive
Painful
Requires technical expertise
Requires pathologic interpretation
Risk of bleeding and/or infection
Intensive Care Unit–Acquired Weakness
731
732 Kramer

or muscle is ICUAW. However, care must be taken to ensure that symptoms truly did
not begin before admission, implying a primary cause that may have gone initially un-
recognized. The presence of unexplained altered mental status, a new focal neuro-
logic deficit, or other findings that localize to the central nervous system should
warrant immediate brain imaging. Symmetric weakness with a sensory level should
warrant evaluation of the spinal cord. Suspicion of a pre-existing neuromuscular con-
dition should warrant a work-up based on symptomatology, but could include a full
EMG/NCS and/or lumbar puncture. Train-of-four testing can evaluate for prolonged
neuromuscular blockade, particularly if the patient received paralytics for a prolonged
period and/or has renal or hepatic insufficiency. Creatinine kinase is typically only
mildly elevated in ICUAW (with the exception of a rare severe necrotizing variant)
and therefore an inflammatory myopathy should be considered if a more substantial
elevation is present.
Respiratory weakness is evaluated objectively with pulmonary function tests, chest
radiograph, arterial blood gas, and diaphragm ultrasound.33 A reduction in forced vital
capacity, maximal inspiratory pressure, and maximal expiratory pressure can be
observed and tracked. Chest radiograph can identify aspiration or atelectasis. Arterial
blood gas may demonstrate hypoxemia or hypercapnia. Diaphragm ultrasound
commonly shows a reduction in thickness and contractility.43 Examples of diaphrag-
matic ultrasounds in a patient with normal diaphragm function (Video 1) and a patient
with diaphragmatic paralysis caused by CINM (Video 2) are provided.

MANAGEMENT

Risk factor reduction remains the foundation of preventing the development or wors-
ening of ICUAW. Although therapies aimed at reducing inflammation to date have, un-
fortunately, not been associated with a reduction in the incidence of ICUAW, the rapid
recognition and aggressive treatment of sepsis and shock are generally thought to be
preventative. A reduction in the incidence of ICUAW and the duration of mechanical
ventilation has been demonstrated with intensive insulin therapy targeting a blood
glucose level of 80 to 110 mg/d in some studies; however, these benefits are out-
weighed by dangerous hypoglycemic events and overall increased mortality.13,44
Treating sustained elevations in blood glucose greater than 180 mg/dL while avoiding
hypoglycemia is a reasonable treatment strategy in most ICU patients. Although the
use of early parenteral nutrition has been postulated to combat muscle catabolism,
this practice is actually associated with an increased incidence of ICUAW and longer
recovery relative to late parenteral nutrition by allowing more efficient activation of
autophagic quality control of myofibers.45
Minimization of sedation and early rehabilitation are other cornerstones in the
prevention and treatment of ICUAW. This requires daily assessment of the need for
sedation and paralytics and routine sedation holidays in patients where this is not con-
traindicated. A coordinated multidisciplinary effort that includes nursing and physical,
occupational, and respiratory therapists is essential. Although the implementation of
such a protocol may require a cultural paradigm shift at some institutions, the benefit
is worth the effort needed to break the inertia. The practice of routine sedation holidays
and progressive and early (as early as 48 hours after mechanical ventilation) mobiliza-
tion has been shown to be safe and feasible, and it has been associated with a reduc-
tion in the duration of mechanical ventilation, the incidence of ICUAW, and
improvement in functional outcome.16–19 The diaphragm is not excluded from mobili-
zation and it is standard practice to transition mechanically ventilated patients to
spontaneous mode as soon as it is safe. Patients who cannot be mobilized out of
 Intensive Care Unit–Acquired Weakness 733

bed may benefit from active or passive cycle ergometry and muscle stimulation,
although both techniques require further investigation.17,46,47 Studies are currently un-
derway to evaluate if anti-inflammatory or metabolic agents, such as serotonin 5-
HT2C receptor antagonists, hydroxymethylbutyrate and eicosapentaenoic acid, and
intravenous immunoglobulin can decrease the severity of ICUAW.9
Patients with ICUAW should be monitored for medical complications, such as
depression, superimposed compression neuropathies from bedrest, muscle atrophy,
mucous plugging, atelectasis, pneumonia, pressure ulcers, and deep venous throm-
bosis (DVT). Accordingly, they should receive antidepressants when indicated, skin
protective measures, pulmonary hygiene, and DVT prophylaxis.

PROGNOSIS

ICUAW has been associated with prolonged ICU and hospital stay; prolonged dura-
tion of mechanical ventilation; and increased ICU, hospital, and 1-year mortality.3,48–50
Although it is still debated whether the increased mortality seen in association with
ICUAW is reflective of a higher severity of the inciting critical illness, a propensity-
matched cohort of patients with ICUAW had a 30% higher mortality at hospital
discharge and a 13% increase in mortality at 1 year as compared with patients with
similar severity of similar critical illness, but who had not developed ICUAW. The
same study also found that ICUAW was associated with 30% higher hospital costs.48
Elderly patients and patients with predominant CIP have a worse prognosis.51,52 The
cause of death in patients with ICUAW may be related to respiratory weakness;
dysphagia and aspiration; and associated systemic complications, such as DVT for-
mation and pulmonary embolus.
Thankfully, recovery in patients with ICUAW commonly occurs and typically pla-
teaus after 1 to 2 years. Younger patients with less severe weakness at nadir can
achieve a full recovery.53 However, in many cases, physical functioning health-
related quality-of-life subscales can remain depressed even years after the acute
illness and despite improvement in weakness.50,53 ICUAW is often a substantial
contributor to the post–intensive care syndrome, a term that encompasses the entire
spectrum of physical, cognitive, and psychological issues patients and their families
face in the aftermath of critical illness, and is strongly associated with reduced quality
of life.54

SUMMARY

Intensive care medicine has made substantial advances in ensuring that critically ill
patients survive their illness. However, this progress is tempered by the common
occurrence of ICUAW in these patients, a condition that worsens mortality and con-
tributes to long-term physical and psychological impairment and overall reduced qual-
ity of life. Additional study is necessary to further elucidate the pathophysiology of
ICUAW in order to identify potential therapeutic targets. More research is also neces-
sary to define the optimal diagnostic studies for early identification of this condition.
However, in the interim, vigilance and aggressive risk factor reduction, and early mobi-
lization can substantially benefit patients at risk of ICUAW.

SUPPLEMENTARY DATA

Supplementary data related to this article can be found online at http://dx.doi.org/10.

1016/j.ncl.2017.06.008.
734 Kramer

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