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Topics in Practice Management
ICU–Acquired Weakness
A Rehabilitation Perspective of Diagnosis, Treatment,
and Functional Management
Richard D. Zorowitz, MD
ICU-acquired weakness (ICUAW) occurs with reported incidence rates from 25% to 100%. Risk
factors include immobility, sepsis, persistent systemic inflammation, multiorgan system failure,
hyperglycemia, glucocorticoids, and neuromuscular blocking agents. The pathophysiology
remains unknown. Clinical features may be neuropathic, myopathic, or a combination of both.
Although manual muscle testing is more practical in diagnosing ICUAW, the “gold standard” for
the diagnosis of ICUAW remains electromyography and nerve conduction studies. The only
potential interventions known to date to prevent ICUAW include insulin therapy and early
rehabilitation, but patients still may develop activity limitations in the acute care hospital. For these
patients, rehabilitation may continue in long-term care hospitals, inpatient rehabilitation facilities,
or skilled nursing facilities. ICUAW is a catastrophic and debilitating condition that potentially
leaves patients with permanent residual activity limitations and participation restrictions. Further
research on ICUAW needs to better understand its pathophysiology so that more definitive
preventive and therapeutic interventions may be developed.
critical care; myopathy; neuropathy; rehabilitation
ICU-acquired weakness (ICUAW) occurs
commonly, with reported incidence rates
from 25% to 100%.1,2 As opposed to diseases
and syndromes directly involving the brain,
spinal cord, and peripheral nerves,3 ICUAW
is associated with unrelated conditions.4 Its
pathophysiology remains unknown. This
review presents aspects of ICUAW from a
rehabilitation perspective. A more detailed
description of the proposed pathophysiology,
risk factors, diagnosis, and treatment of
ICUAW may be found elsewhere.5
Risk Factors
Patients in the ICU may be bedridden and
immobile for prolonged periods. For patients
CIM = critical illness myopathy; CIP = critical illness
polyneuropathy; EMG = electromyography; ICUAW = ICU-acquired
weakness; IRF = inpatient rehabilitation facility; LTCH = long-term
care hospital; RR = risk ratio; SNF = skilled nursing facility
AFFILIATIONS: From the MedStar National Rehabilitation Network,
Washington, DC.
966 Topics in Practice Management
CHEST 2016; 150(4):966-971
requiring mechanical ventilation or
prolonged sedation, it is not surprising that a
certain amount of weakness occurs.
However, ICUAW usually is associated with
sepsis, persistent systemic inflammation, and
multiorgan system failure.1,4 Approximately
47% to 70% of patients admitted to the ICU
for primary sepsis and multiorgan failure
may develop electrophysiological evidence of
axonal motor-sensory polyneuropathies
within 1 to 3 weeks.2,4,6-10 Of these, 35% to
50% have substantial weakness. Women
may be as much as four times as likely
to develop ICUAW as men, possibly
because of their smaller muscle masses.1
CORRESPONDENCE TO: Richard D. Zorowitz, MD, MedStar National
Rehabilitation Network, 102 Irving St NW, Room 1321, Washington,
DC 20010; e-mail: richard.zorowitz@medstar.net
Copyright Ó 2016 American College of Chest Physicians. Published by
Elsevier Inc. All rights reserved.
DOI: http://dx.doi.org/10.1016/j.chest.2016.06.006
150#4 CHEST OCTOBER 2016
Hypoalbuminemia and other nutritional factors also
may be involved.4
The role of hyperglycemia11 and glucocorticoid therapy
as risk factors of ICUAW is controversial.12-15
Nonetheless, it appears reasonable to minimize the
use of glucocorticoids in patients in the ICU, given
the known adverse effects of these drugs. The role of
neuromuscular blocking agents used in conjunction
with glucocorticoids also is controversial; one study in
patients with severe ARDS suggested that treatment
for less than 48 h might improve survival because of
protection of the diaphragm from injury resulting from
patient-ventilator dyssynchrony.8,16
Clinical Features
Clinical features of ICUAW may be neuropathic,
myopathic, or a combination of both.17 Clinical features
of each condition, known as critical illness
polyneuropathy (CIP) and critical illness myopathy
(CIM), are listed in Table 1.18-26
Medical and rehabilitation interventions may help to
prevent ICUAW. In a Cochrane Review of four
interventions for preventing CIP and CIM,27 intensive
insulin therapy significantly reduced CIP and CIM in
the screened (n ¼ 825; risk ratio [RR], 0.65; 95% CI,
0.55-0.77) and total (N ¼ 2,748; RR, 0.70; 95% CI,
0.60-0.82) populations randomized; decreased duration
of mechanical ventilation, ICU stay, and 180-day
mortality, but did not reduce 30-day mortality when
compared with conventional insulin therapy.28,29
Corticosteroids had no effect on treating CIP or CIM or
decreasing 180-day mortality, new infections, glycemia
at day 7, or episodes of pneumonia, but reduced the
incidence of new shock events.30 Early physical therapy
reduced the incidence of CIP and CIM in 82 of 104
evaluable participants in the ICU (RR, 0.62; 95% CI,
0.39-0.96), but lost statistical significance in a full
intention-to-treat analysis (RR, 0.81; 95% CI,
0.60-1.08).31 The duration of mechanical ventilation
but not ICU stay was significantly shorter in the
intervention group. Hospital mortality was not affected,
but 30- and 180-day mortality results were not available.
Finally, electrical muscle stimulation given to 52
evaluable subjects of 140 did not significantly reduce the
incidence of CIP and CIM when compared with no
stimulation (RR, 0.32; 95% CI, 0.10-1.01) as well as in
an intention-to-treat analysis (RR, 0.94; 95% CI,
0.78-1.15).32 There was no effect on duration of
mechanical ventilation or ICU mortality, and 30- and
180-day mortality were not reported. The data also were
prone to bias because of imbalances between treatment
groups in the subgroup of participants. A separate
systematic review and meta-analysis of physical therapy
in the ICU demonstrated significant positive effects on
quality of life (g ¼ 0.40; 95% CI, 0.08-0.71), physical
function (g ¼ 0.46; 95% CI, 0.13-0.78), peripheral muscle
strength (g ¼ 0.27; 95% CI, 0.02-0.52), respiratory muscle
strength (g ¼ 0.51; 95% CI, 0.12-0.89), and ventilator-free
days (g ¼ 0.38; 95% CI, 0.16-0.59); and significant
decreases in length of hospital stay (g ¼ –0.34; 95% CI,
–0.53 to –0.15) and ICU stay (g ¼ –0.34; 95% CI, –0.51 to
–0.18).33 There was no effect on mortality.
Given the clinical features of ICUAW (Table 1), it would
be simple to use manual muscle strength to identify the
distribution and degree of muscle weakness; however,
only approximately to 25% to 29% of patients are
adequately awake to assess muscle strength.1,34
Therefore, more accurate methods of assessing muscle
weakness are needed.
The “gold standard” for the diagnosis of ICUAW
remains electromyography (EMG). In CIP,
electrophysiological changes can be detected as early as
24 to 48 h following the onset of ICUAW, and often
] Clinical Features of ICUAW
Muscle atrophy
Ventilatory failure
Worse distally more than proximally
Worse proximally more than distally
Muscle stretch reflexes
Hyporeflexia or areflexia
Normal or hyporeflexia
Sensory loss
May experience distal sensory loss18,19
Extraocular muscles
Rare, although facial weakness may occur
CIM ¼ critical illness myopathy; CIP ¼ critical illness polyneuropathy; ICUAW ¼ ICU-acquired weakness.
precede clinical findings.35 EMG characteristics of CIP
and CIM are listed in Table 2.36 Because EMG requires
some participation of the patient, the use of peroneal
and sural nerve conduction studies show promise as
accurate screens for ICUAW and may assist in
determining which patients need further EMG studies to
confirm a diagnosis.37
Because of the increase in patients with activity
limitations resulting from ICUAW, the paradigm of
treatment has shifted from the liberal use of sedation
and immobilization to mobilization.43 The first study of
ICU rehabilitation given to mechanically ventilated
patients demonstrated not only that activity was feasible
and safe, but also that patients ambulated a mean
distance of 212 feet by the time of discharge from the
ICU44; however, research is needed to definitively
evaluate safety and long-term benefits of ICU
Technology and improved medical management has
resulted in a dramatic increase in patients with
ICUAW.38,39 Up to 65% of patients who require
prolonged mechanical ventilation have activity
limitations when they are discharged from the
hospital.7,31 In older survivors of ICUAW, activity
limitations persisted 1 year after discharge.40 Muscle
weakness and activity limitations frequently were
observed in ARDS survivors after 1 year, and even after
5 years, 6-min walk tests scores were only 70% of
predicted results.38 Although CIM is associated with a
higher rate of recovery than CIP,17 neuromuscular
impairment may last as long as 15 years with either
In addition to issues with mobility, nutrition also needs
to be addressed. In one small study of patients with
ICUAW transferred to a long-term care hospital
(LTCH), anemia, hypoalbuminemia, and vitamin D
deficiency were identified, as were impairments in
strength, balance, coordination, mobility, and
endurance.45 These findings emphasize the need for an
interdisciplinary team of health professionals, including
occupational therapy for feeding, speech-language
pathology for swallowing, and a nutritionist for dietary
Electrophysiological studies also may provide clues to
the prognosis of ICUAW. A reduced CMAP on the
eighth day of ICU admission carried a high negative
predictive value for weakness after 1 year, but was
associated with a higher 1-year mortality rate.42
However, an abnormal sensory nerve action potential
and the presence of fibrillation potentials on the 15th
day of ICU admission carried a high positive predictive
value for weakness.
Nonetheless, patients with ICUAW may require
rehabilitation in and beyond the acute care hospital.
Early consultation with physical therapy, occupational
therapy, speech-language pathology, and/or
rehabilitation physicians is essential to prevent
complications from immobilization, decrease activity
limitations, and prepare patients for discharge from the
acute care hospital. A randomized pilot study of
12 weeks of intensive telerehabilitation vs conventional
] EMG Characteristics of ICUAW
Low amplitude
At least 1 low amplitude
Variable duration
Sensory nerve action potentials
Low amplitude or absent
Nerve-evoked CMAP-to-dmCMAP
< 0.5
> 0.5
Fibrillation potentials (reflect
Found in distal and proximal muscles in
multifocal pattern with variable
May be found in 30% of diaphragm
Found in at least 1 muscle in 71% to
100% of patients
May be diffuse
Motor unit recruitment
Early and full
May be of short duration and low
Modified from Lacomis D.36 CMAP ¼ compound muscle action potentials; dmCMAP ¼ direct muscle CMAP; EMG ¼ electromyography. See Table 1 legend for
expansion of other abbreviations.
968 Topics in Practice Management
150#4 CHEST OCTOBER 2016
care in general medical or surgical ICU survivors with
either cognitive or functional impairment demonstrates
promise in improving cognitive performance and
functional outcomes.46 However, patients who cannot
return home when they are ready for discharge may
be referred for postacute rehabilitation to LTCHs,
inpatient rehabilitation facilities (IRF), or skilled nursing
facilities (SNF). Currently, no definitive studies have
evaluated the effects of rehabilitation programs in
inpatient or outpatient settings on this population.
Availability and quality of these facilities may be limited
geographically and may affect the medical and
functional management of the patient.
Under Medicare guidelines, an LTCH treats medically
complex patients who require long-stay hospital-level
care, and has an average inpatient length of stay greater
than 25 days. An LTCH must provide complex
respiratory services and complex wound services; 24/7
physician on-site or on-call coverage; 24/7 registered
nurse–level nursing; 24/7 advanced cardiac life support;
and 24/7 availability of respiratory therapists. Patients
meet Medicare criteria for LTCH admission
immediately following discharge from an acute care
hospital that included either at least 3 days in an ICU or
assignment to a Medicare Severity Long-Term Care
Diagnosis Related Group based on the receipt of
ventilator services of at least 96 h. Patients cannot have a
principal psychiatric or rehabilitation diagnosis, but
must have at least two active secondary diagnoses. So,
although patients with ICUAW may receive physical
therapy, occupational therapy, and/or speech-language
pathology, the primary reason for admission usually
involves weaning from the mechanical ventilator and
decannulation of the tracheostomy. In one study
performed in a long-term acute care hospital, a group
receiving rehabilitation (n ¼ 18), motor (except for the
walking/wheelchair subitem), and cognitive scores of the
Functional Independence Measure increased
significantly 6 months postenrollment when compared
with that of a control group (n ¼ 16).47 The
rehabilitation group was completely independent in
eating, comprehension, expression, and social
interaction. The 1-year survival rate in the rehabilitation
group was 70%, compared with 25% of the control
group (25%), although the proportion of patients
discharged and who were ventilator-free in did not differ
significantly between groups.
An IRF provides active, ongoing, and intensive
therapy involving a coordinated interdisciplinary team
approach to physical therapy, occupational therapy,
speech-language pathology, or prosthetics/orthotics, of
which at least one therapy must include physical or
occupational therapy. Under Medicare guidelines,
patients admitted to an IRF must require, actively
participate in, benefit significantly from, and make
measurable improvement from at least 3 h of therapy
per day at least 5 days per week, or in certain welldocumented cases, at least 15 h of therapy within
consecutive 7-day periods. A rehabilitation physician
must visit the patients face-to-face at least 3 days per
week to assess and modify the course of medical and
functional treatment. Some IRFs can manage patients on
mechanical ventilators or with tracheostomies while
providing therapy. In these cases, patients are admitted
because of activity limitations resulting from ICUAW.
The rehabilitation team is depicted in Figure 1.
Admission to a SNF may be considered if patients need
inpatient rehabilitation care but do not meet the
criteria for admission to an LTCH or IRF. Under
Medicare guidelines, patients must be transferred to a
SNF within 30 days after discharge from a medically
necessary stay of at least 3 consecutive calendar days in
the hospital and treated for a condition that was treated
during the qualifying hospital stay or for a condition
that arose while in the SNF. Under certain alternative
payment models, the 3-day requirement may be waived
by a medical director. Nursing care is provided by or
under the supervision of a registered professional
nurse. Physical therapy, occupational therapy, and/or
speech-language pathology services are furnished by
the SNF or under arrangements with another entity.
Patients may receive up to 3 h of therapies daily up to
5 days per week. The SNF is responsible for the cost of
drugs, biologicals, supplies, appliances, and equipment
that are required for the care and treatment of their
Family, Friends,
and Caregivers
Social Worker /
Case Manager
Figure 1 – The rehabilitation team. Health-care professionals work in a
coordinated fashion toward a common goal for the patient, the center of
Patients with ICUAW usually do not receive rehabilitation
in one level of care. One study demonstrated that, on
average, patients transferred almost five times among
acute care hospitals, LTCHs, IRFs, SNFs, and home care
during the first year of treatment.48 These data emphasize
that patients wax and wane medically and functionally
during their course of recovery; thus, it is not surprising
that the costs of treatment for patients with ICUAW
usually are substantial.
11. van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin
therapy in critically ill patients. N Engl J Med. 2001;345(19):
15. Hermans G, Wilmer A, Meersseman W, et al. Impact of intensive
insulin therapy on neuromuscular complications and ventilator
dependency in the medical intensive care unit. Am J Respir Crit Care
Med. 2007;175(5):480-489.
In summary, ICUAW occurs commonly. Although there
are many risk factors, the pathophysiology remains
unknown. Clinical features may be neuropathic,
myopathic, or a combination of both. The “gold
standard” for the diagnosis of ICUAW remains EMG.
There are several postacute rehabilitation options if the
patient cannot be discharged home from the acute care
hospital. Patients may have activity limitations for many
years after onset. Until more definitive preventative and
therapeutic interventions are identified, it is important
to keep patients as mobile in the ICU as possible, so that
they do not fall victim to this catastrophic and
debilitating condition.
Financial/nonfinancial disclosures: None declared.
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