A. A large prospective cohort study found the incidence of severe acquired weakness in the intensive care unit (ICU) to be 25%.

B. Although preexisting neuromuscular disorders may cause weakness in ICU patients, two of the most common causes of newly acquired weakness arising in the ICU setting are critical illness myopathy (CIM) and critical illness polyneuropathy (CIP).

C. Both disorders may cause severe generalized weakness—a syndrome of flaccid, generalized weakness (quadriplegia) with failure to wean from mechanical ventilation. The two disorders are known to occur separately or in combination. The most common form of weakness acquired in the ICU is CIM.

D. A major risk factor for the development of CIM is exposure to intravenous corticosteroids (CSs) and neuromuscular blocking agents (NMBAs); CIM develops in one-third of patients treated for status asthmaticus in the ICU.

E. CIM also develops in patients who have not received CS and NMBAs, but who have had severe systemic illness with multiorgan failure and sepsis; in fact, CIM accounts for 42% of patients with weakness in the surgical and medical ICU setting.

F. The major risk factors for CIP are sepsis and multiorgan failure; of patients admitted to the ICU for at least 2 weeks, 50% show at least EMG evidence of an axon loss polyneuropathy.

1. Weakness is typically widespread and nonfocal.

2. Weakness affects all limb muscles and neck flexors—a flaccid quadriparesis that has a proximal > distal distribution.

3. Weakness may involve facial muscles, but extraocular muscles are rarely involved.

4. Tendon reflexes are often depressed or absent.

5. Weakness typically affects the diaphragm, causing failure to wean from ventilator.

1. Serum creatine kinase (CK) is elevated in 50% of patients; the rise tends to occur early in the course of the illness.

2. Electromyography.

a. Nerve conduction studies reveal low-amplitude, long-duration (broad) responses, or absent motor responses; sensory responses are relatively preserved (sensory responses may be reduced).

b. The needle electrode examination discloses fibrillation potential activity in weak muscles in some, but not all, patients.

c. Voluntary muscle contraction reveals early recruitment of motor unit potentials (MUPs) that may be short in duration, low in amplitude, and polyphasic in form.

d. MUP analysis is difficult owing to severe weakness or encephalopathy, or both (no motor units may be available for analysis).

e. Stimulation of the phrenic nerves with diaphragm recording evokes absent or very low motor responses.

f. Direct stimulation of a weak limb muscle may demonstrate electrical inexcitability of the muscle membrane.

g. Direct stimulation of muscle and direct nerve stimulation yield comparably reduced muscle responses (in contrast to the results found in CIP [vide infra]).

3. Muscle biopsy.

a. Reveals a characteristic finding of selective loss of myosin, which is revealed as a central area of pallor or lack of histochemical reactivity to myosin ATPase.

b. Muscle fiber atrophy (especially type II fibers).

c. Mild-to-moderate degree of muscle fiber necrosis in some patients.

1. Loss of myosin thick filaments, with multifactorial causation, including an increase in muscle apoptosis, up-regulation of calpain, and up-regulation of the transforming growth factor (TGF)-β/mitogenactivated protein kinase pathway.

2. Muscle is noted to be inexcitable in CIM. This may result from improper regulation of the sodium channels with increased inactivation of sodium channels at the resting membrane potential.

1. Treatment is essentially symptomatic.

2. Strive to prevent the development of this disorder by using CSs or NMBAs, or both as sparingly as possible.

3. Intensive insulin therapy (with target blood glucose concentrations of 80 to 110 mg/dL) may lower the incidence of CIM (and CIP).

1. Most patients recover over weeks to months, although patients may be left with residual weakness depending upon the initial severity and duration of weakness.

1. Distal more than proximal symmetrical weakness and sensory loss.

2. Deep tendon reflexes are attenuated or lost.

3. Cranial nerve-innervated muscles are typically spared.

4. There is often a concomitant encephalopathy (the encephalopathy of sepsis).

1. Serum CK levels are typically normal.

2. CSF studies are normal (normal protein and normal cell count).

3. Electromyography.

a. Nerve conduction studies reveal reduced or absent sensory and motor responses and reduced or absent phrenic motor responses.

b. Nerve conduction velocities are within the range of normal or are mildly reduced (the pattern considered classical for polyneuropathies that are primarily axon loss in character). There is typically no evidence for partial conduction block or prolonged F-wave latencies.

c. After 2 to 3 weeks of the illness, needle electrode examination may reveal abnormal insertional activity in the form of fibrillation potentials and positive sharp waves; and these are more likely to be found in distal rather than proximal muscles; in the first 2 to 3 weeks of the illness, fibrillation potentials may be absent.