As medicine advances, more critically ill patients are surviving longer ICU admissions. Patients with sepsis, multi-organ failure, severe burns, prolonged mechanical ventilation, and polypharmacy often develop profound neuromuscular weakness during their hospitalization despite appropriate medical interventions and treatments. Often referred to as “intensive care unit acquired weakness” (ICUAW) this underdiagnosed condition most commonly results from a spectrum of critical illness polyneuropathy (CIP), critical illness myopathy (CIM), or a combination of both. While CIP and CIM often occur simultaneously, it is important to understand the key features of each condition to ensure prompt recognition, prevent further disability, and ensure better patient outcomes. While the conditions are often underdiagnosed, studies show that the incidence of ICUAW in patients with greater than seven days of mechanical ventilation may range from 25% to 83%. 
Critical illness neuropathy may be evident as a patient fails to wean off the ventilator or if the patient has profound weakness or numbness in extremities upon awakening from sedation. A physical exam may also reveal diminished deep tendon reflexes, possible muscle atrophy, or balance impairment upon leaving the ICU. Bulbar and extraocular muscles will often be spared in CIP. Laboratory studies such as cerebrospinal fluid will usually be normal; this may help differentiate the condition from other illnesses with similar presentations, such as Guillain-Barre Syndrome. Creatine phosphokinase (CPK) will be within normal limits in CIP and can become elevated in CIM. Systemic inflammatory response syndrome (SIRS) or sepsis is the most frequent underlying factor in CIP (as opposed to the use of neuromuscular blocking agents and steroids, which predominate in CIM).
Although not often performed, the gold standard for the diagnosis of critical illness neuropathy remains electrodiagnostic testing, which includes nerve conduction studies and needle electromyography. It should be noted that while EMG is the optimal way to make a diagnosis of CIP, there are many challenges to performing a complete study in ICU conditions, including electrical interference, anasarca, hypothermia, peripheral edema, or limited patient participation in the exam. Nevertheless, in the evaluation of profound weakness in the ICU setting, electrodiagnostic testing is an essential tool that can direct the clinical team in determining further management.
Pathophysiology of CIP/CIM
Etiology is not entirely clear, but it is though to be complex and multi-factorial in nature. Ultimately it lead to axonal dysfunction, ischemia, and degeneration necessitating aggressive treatment of underlying medical causes and physical neurorehabilitation. It is thought to be related to abnormal vascular, metabolic, and electrical processes leading to motor and/or sensory neuron abnormalities:
Summary of clinical and histopathological features of CIP/CIM
1. Critical Illness Polyneuropathy
2. Critical Illness Myopathy
Both critical illness neuropathy and myopathy may clinically present with difficulty weaning off a ventilator or, if extubated, the patient may complain of profound weakness and flaccid limbs. Additionally, patients with CIN may complain of sensory deficits, with numbness or paresthesias, especially in the distal extremities.
Weaning complications are due to the involvement of the phrenic nerve affecting the diaphragm, and other accessory respiratory muscles may also be affected. The clinician must always keep in mind that Wallerian degeneration may take upwards of 10 to 14 days after the nerve injury to become apparent on an electrodiagnostic test. Therefore, testing should be ordered judiciously only in the appropriate patients, and usually about two weeks after the onset of symptoms.
Performing electrodiagnostic studies in critically ill patients have few absolute contraindications. Needle EMG is contraindicated in those with severe bleeding disorders. Needles should also never be inserted into areas of active soft tissue infection. Nerve conduction studies are contraindicated in patients with implanted cardiac defibrillators or if connected to external defibrillators. Patients should have screening for pacemakers, and electrical stimulation should not be performed directly on or near the device itself.
Before performing any diagnostic study, a comprehensive review of the patient's history and clinical course, as well as a complete physical exam, must be performed. A thorough and compassionate diagnostician will inform the patient and family at the bedside of the indications and overview of the studies which will be performed. To accurately diagnose CIN with electrodiagnostic testing, one should ideally examine at least three extremities, performing both sensory and motor nerve conduction studies, as well as needle EMG testing in both proximal and distal muscles for comparison.
As with all nerve conduction studies, the temperature of the patient's limbs should be kept warm. Colder temperatures can surreptitiously increase amplitudes, prolong latencies, and slow conduction velocities. To minimize the electrical interference which exists in the ICU, a notch filter should be used and, if possible, all unnecessary machines turned off, including unplugging the hospital bed.
As with all electrodiagnostic studies in any setting and for any indication, the risk of complications is low. There is always a small risk of bleeding or introducing infection with needle studies.
Critical illness neuropathy is a primarily axonal sensorimotor peripheral neuropathy which will be apparent on electrodiagnostic studies. In both motor and nerve conduction studies, distal fibers will be more affected than proximal fibers. CIP and CIM are difficult to differentiate. Patients that are not comatose and can tolerate an EMG may be tested for MUAP recruitment or direct muscle stimulation. A purely sensory phenomenon, although rare, can help distinguish between CIP and CIM. On muscle biopsy, the myosin/actin ratio can be used to diagnose CIM in conjunction with histopathological findings such as myonecrosis, loss of thick myosin filaments, non-necrotizing myopathy, and atrophy.
A. Nerve conduction studies
1. Sensory Nerve Conduction Studies
There is a reduction of conduction amplitude and absent sensory nerve conduction studies (SNAPs). Early in the course, conduction velocities and latency are often normal or slightly decreased due to the loss of the fastest fibers, Decreases in amplitude will be more profound than the slowing of conduction velocities and prolongation of latency.
2. Motor Nerve Conduction Studies
There is a reduction of conduction amplitude and absence of compound muscle action potentials (CMAPs)-. Early in the course, as with the sensory studies, will have a decrease in amplitude more profound than any slight decrease in conduction velocity or prolongation of distal latency. The reduction is usually two standard deviations of the normal value.
B. Needle Electromyography
Abnormal spontaneous potentials may be present in distal muscles, including positive sharp waves (PSWs) and fibrillation potentials (fibs). PSWs appear with an initial sharp downward deflection with a subsequent upward (negative) phase with a duration of 10 to 30 milliseconds. PSWs often sound like "dull thuds." Fibrillation potentials can have triphasic or biphasic spikes with a duration of 1 to 5 milliseconds and sound like "rain on a tin rooftop." These spontaneous potentials indicate that there is significant denervation of the muscles tested. Individual motor units may show decreased recruitment and an increase in the frequency of firing. In chronic conditions, motor unit action potentials (MUAPs) may be large and polyphasic. Although it is technically challenging in the ICU, a needle EMG of the diaphragm muscle may reveal abnormal spontaneous potentials as well.
C. Summary of electrodiagnostic criteria
1. Critical Illness Polyneuropathy
2. Critical Illness Myopathy
Often patients with a prolonged ICU admission will develop profound weakness or failure to wean off a ventilator. Intensivists, physiatrists, and neurologists must recognize that further evaluation with electrodiagnostic testing is warranted in these circumstances. As healthcare professionals, appropriate disease recognition and diagnosis of critical illness neuropathy will help expedite patient recovery and can improve long term quality of life.
While there is a vast differential in the patient with weakness which develops in the ICU, NCS and EMG studies may be able to identify the etiology and further guide the management. Once the diagnosis of CIN is made, the interprofessional team must include an interprofessional team of physicians, physical therapists, occupational therapists, speech therapists, nutritionists, social workers, and case managers. These professionals can work together to coordinate early mobilization and aggressive multifaceted rehabilitation.
Typically, there is a long and challenging recovery ahead for patients with CIN upon leaving the critical care setting. Only with a coordinated effort between the various medical disciplines and departments will the best outcomes for patients be achieved.
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