Critical Illness Polyneuropathy

Critical illness polyneuropathy is a primary axonal sensorimotor polyneuropathy that develops during severe illness, especially sepsis and multiple organ failure. This article concentrates on the nerve pathology and electrophysiological diagnosis. It affects 30 to 50% of patients with sepsis who are ventilated for more than 7 days, and up to 70% of those with prolonged multiorgan failure.

Risk factors: sepsis and systemic inflammatory response, multiple organ failure, duration of ventilation, hyperglycemia, hypoalbuminemia, renal failure and renal replacement therapy, parenteral nutrition and vasopressors.

Pathophysiology: cytokine-induced microvascular endoneurial leak and edema impair oxygen delivery to the axon. The result is bioenergetic failure and primary distal axonal degeneration, with loss of both motor and sensory fibers. Nerve sodium channel inactivation reduces excitability. The myelin sheath is largely preserved. Recovery requires axonal regrowth, which proceeds at about 1 mm a day, so it takes weeks to months.

About half of survivors recover fully within a year, and the rest have persistent distal weakness, sensory loss and pain. Complications: failure to wean from ventilation, longer intensive care stay, pressure palsies, neuropathic pain and persistent disability.

• Failure to wean from the ventilator, often the first sign
• Symmetrical flaccid weakness of limbs, distal more than proximal, with reduced or absent tendon reflexes
• Distal sensory loss to pain, temperature and vibration (hard to test in sedated patients)
• Grimace to pain in the face is preserved, because cranial nerves are largely spared
• Diaphragmatic weakness
• Red flags: rapidly ascending weakness with cranial nerve involvement or autonomic failure (consider Guillain-Barre syndrome), and asymmetry or a sensory level (consider a spinal lesion)

1. Clinical examination in an awake, cooperative patient with the MRC sum score (six muscle groups on each side graded 0 to 5, total 0 to 60, a score below 48 is abnormal).
2. Nerve conduction studies (the key test):
   • Reduced amplitude of compound muscle action potentials and sensory nerve action potentials.
   • Normal or only mildly reduced conduction velocities and normal distal latencies.
   • Studies are valid at about 3 to 5 days, and may be abnormal before clinical weakness is detectable.
3. Needle electromyography: fibrillation potentials and positive sharp waves (appearing after 2 to 3 weeks), and reduced recruitment of motor unit potentials.
4. Direct muscle stimulation: normal muscle membrane excitability (the directly evoked muscle response is preserved), which separates the neuropathy from a myopathy.
5. Exclusion of other causes: cerebrospinal fluid protein and cell count (normal in this condition), electrolytes (potassium, magnesium, phosphate), glucose, creatine kinase (normal), thyroid function, vitamin B12 and thiamine, and MRI of the spine when a cord lesion is suspected.
6. Phrenic nerve conduction and diaphragm ultrasound when weaning fails.

Differentials: Guillain-Barre syndrome, critical illness myopathy, myasthenia gravis, drug-induced neuropathy (aminoglycosides, vincristine, linezolid), cord lesion, motor neuron disease and nutritional neuropathy.

There is no drug that reverses the condition, so treatment is supportive and aimed at removing contributors.

1. Treat sepsis and the underlying illness, with source control and organ support.
2. Glycemic control: insulin infusion to keep glucose at 7.8 to 10 mmol/L, avoiding hypoglycemia (monitor every 1 to 2 hours).
3. Nutrition: enteral feeding started within 24 to 48 hours, 20 to 25 kcal/kg a day, rising to 25 to 30 kcal/kg, with protein 1.3 to 2.0 g/kg a day. Replace thiamine 200 mg IV daily for 3 days in patients at risk.
4. Minimize deep sedation and neuromuscular blocking drugs, use daily sedation interruption, and avoid aminoglycosides and other neurotoxic drugs where alternatives exist.
5. Rehabilitation: physiotherapy and occupational therapy starting within 48 to 72 hours of stabilization, passive then active range of motion, in-bed cycling, sitting, standing and walking with support. Neuromuscular electrical stimulation 30 to 60 minutes daily for patients who cannot participate.
6. Prevention of secondary injury: pressure area care every 2 hours, splints in neutral positions for hands and feet, and padding over the ulnar and peroneal nerves.
7. Neuropathic pain: gabapentin 300 mg orally at night, increased by 300 mg every 3 days to 900 to 1800 mg a day in 3 divided doses (reduce in renal impairment), or amitriptyline 10 to 25 mg orally at night.
8. Weaning: daily spontaneous breathing trials, early tracheostomy when prolonged ventilation is expected, and inspiratory muscle training.
9. Intravenous immunoglobulin and corticosteroids are not beneficial.

Follow-up: repeat nerve conduction studies at 3 months, and review of strength, sensation and pain at 3, 6 and 12 months. Counsel on slow recovery.