Continuing Education Activity

Although not often performed, the gold standard for diagnosing critical illness neuropathy remains electrodiagnostic testing, which includes nerve conduction studies and needle electromyography. This activity describes the invaluable electrodiagnostic findings of nerve conduction tests and needle electromyography studies. It also highlights the role of the interprofessional team in evaluating patients with intensive care unit–related critical illness neuropathy.

Objectives:

• Identify the indications for electrodiagnostic testing in critically ill patients.

• Assess the nerve conduction study findings in a patient with critical illness neuropathy.

• Assess the electromyographic findings in a patient with critical illness neuropathy.

• Communicate the importance of collaboration among the interprofessional team to enhance care delivery for patients with critical illness neuropathy.

Introduction

As medicine advances, more critically ill patients are surviving longer intensive care unit (ICU) admissions. Patients with sepsis, multiorgan 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 "ICU-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.[1][2] While the conditions are often underdiagnosed, studies show that the incidence of ICUAW in patients with greater than 7 days of mechanical ventilation may range from 25% to 83%. [3]

Critical illness neuropathy (CIN) 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. Upon leaving the ICU, a physical exam may also reveal diminished deep tendon reflexes, possible muscle atrophy, or balance impairment. The bulbar and extraocular muscles are often spared in CIP.[4] Laboratory studies such as cerebrospinal fluid are usually normal; this may help differentiate the condition from other illnesses with similar presentations, such as Guillain-Barre Syndrome.[5] Creatine phosphokinase (CPK) is 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).[6]

Although not often performed, the gold standard for diagnosing 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 diagnose 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, electrodiagnostic testing is an essential tool in evaluating profound weakness in the ICU setting that can direct the clinical team in determining further management. 

Pathophysiology of CIP and CIM

The etiology of CIP and CIM is not entirely clear, but it is considered complex and multifactorial. Ultimately, it leads 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 or sensory neuron abnormalities:

• Vascular: Vascular autoregulation leads to increased microvascular permeability (eg, dilation of vessels), which can result in edema, hypoxemia, proinflammatory invasion of leukocytes and cytokines, and occlusion within the muscle-neuron units
• Metabolic: Metabolic generation of reactive oxygen and nitric oxide species, failure of mitochondrial repair, neuronal hyperglycemic damage, and hypoalbuminemia
• Electrical: Electrical disruption of sodium and calcium channels and loss of cellular excitability 

Clinical and Histopathological Features of CIP and CIM

CIP

Predisposing factors for CIP include sepsis with concurrent encephalopathy, recurrent exposure to nondepolarizing neuromuscular blocking agents, and multiorgan failure. Clinical and histopathological features of CIP include:

• Presence of diffuse paraparesis or paraplegia, more distal than proximal, with preserved muscle bulk or mild atrophy
• Early loss of deep tendon reflexes or areflexia
• Long-standing difficulty weaning mechanical ventilation after exclusion of cardiopulmonary etiologies
• Electrodiagnostic evidence of axonal sensorimotor polyneuropathy

CIM

Predisposing factors for CIM include recurrent exposure to neuromuscular blocking agents, severe asthma, pneumonia, prolonged acidemia, acute respiratory distress syndrome, prolonged high-dose corticosteroid use, prolonged use of aminoglycosides, sepsis, multiorgan failure, and organ transplantation. Clinical and histopathological features of CIM include:

• Presence of diffuse paraparesis or paraplegia, more proximal than distal, with severe atrophy
• Delayed loss of deep tendon reflexes
• Long-standing difficulty weaning mechanical ventilation after exclusion of cardiopulmonary etiologies
• Electrodiagnostic evidence of motor unit and recruitment abnormalities as well as an absence of excitability with muscle stimulation, with possible preservation of sensory potentials

Biopsy of type II atrophic myofibers on hematoxylin and eosin (H&E) stain and myofiber necrosis may be performed to aid in diagnosis.

Indications

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.[7] Additionally, patients with CIN may complain of sensory deficits, numbness, or paresthesias, especially in the distal extremities.[4] 

Weaning complications are due to the involvement of the phrenic nerve affecting the diaphragm, and other accessory respiratory muscles may also be affected.[1][10] The clinician must remember that Wallerian degeneration may take 10 to 14 days after the nerve injury to become apparent on an electrodiagnostic test.[8] Therefore, testing should be ordered judiciously only in the appropriate patients and usually about 2 weeks after the onset of symptoms. 

Contraindications

Performing electrodiagnostic studies in critically ill patients have few absolute contraindications. Needle electromyography (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 be screened for pacemakers, and electrical stimulation should not be performed directly on or near the device. 

Technique or Treatment

Before performing any diagnostic study, a comprehensive review of the patient's history, clinical course, and a complete physical exam must be performed. A thorough and compassionate diagnostician informs the patient and family at the bedside of the indications and overview of the studies performed. To accurately diagnose CIN with electrodiagnostic testing, one should ideally examine at least 3 extremities, performing sensory and motor nerve conduction studies and 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.[9] To minimize the electrical interference in the ICU, a notch filter should be used, and, if possible, all unnecessary machines should be turned off, including unplugging the hospital bed.[5]

Complications

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.

Clinical Significance

Critical illness neuropathy is primarily axonal sensorimotor peripheral neuropathy, which is apparent in 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 who are not comatose and can tolerate an EMG may be tested for motor unit action potential (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 diagnose CIM in conjunction with histopathological findings such as myonecrosis, loss of thick myosin filaments, nonnecrotizing myopathy, and atrophy.

Nerve Conduction Studies

The 2 main nerve conduction studies (NCS) types include sensory and motor.

Sensory NCS

There is a reduction of conduction amplitude and an absence of sensory nerve conduction studies (SNAPs).[10] 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 are more profound than the slowing of conduction velocities and latency prolongation. 

Motor NCS

There is a reduction of conduction amplitude and absence of compound muscle action potentials (CMAPs).[10][11] Early in the course, as with the sensory studies, there is a more profound decrease in amplitude than any slight decrease in conduction velocity or prolongation of distal latency. The reduction is usually 2 standard deviations from the normal value.[12]

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 lasting 10 to 30 milliseconds. PSWs often sound like "dull thuds." Fibrillation potentials can have triphasic or biphasic spikes lasting 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 increased frequency of firing. Motor unit action potentials (MUAPs) may be large and polyphasic in chronic conditions.[10] Although technically challenging in the ICU, a needle EMG of the diaphragm muscle may also reveal abnormal spontaneous potentials.[11] 

Electrodiagnostic criteria

CIP

Electrodiagnostic criteria for CIP include:

• Reduced amplitudes on CMAP
• Reduced amplitude on SNAP, with rare exceptions (eg, pure form of motor CIP has preserved SNAPs)
• Normal velocity and normal latency.
• Normal action potential excitability during direct muscle stimulation
• Fibrillation potentials and PSWs
• Decreased motor unit recruitment upon voluntary muscle contraction
• Large, polyphasic MUAP spontaneous potentials

CIM

Electrodiagnostic criteria for CIM include:

• Preserved sensory response (>80% lower limit of normal)
• Reduced motor responses (compound muscle action potential <80% lower limit of normal)
• Normal repetitive nerve stimulation
• Small, short-duration, polyphasic MUAP with early full or normal recruitment or interference pattern; in later stages, recruitment may be affected
• Reduced or absent action potential excitability during direct muscle stimulation
• Fibrillation potentials and positive sharp waves
• Decreased motor unit recruitment upon voluntary muscle contraction

Enhancing Healthcare Team Outcomes

Often, patients with prolonged ICU admission 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 helps expedite patient recovery and can improve long-term quality of life.

While there is a vast differential in the patient with weakness that develops in the ICU, nerve conduction 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. The best patient outcomes are achieved with a coordinated effort between the various medical disciplines and departments.[2][13]