Critical Illness Myopathy

Critical illness myopathy is a primary muscle disease of critically ill patients, producing generalized weakness and failure to wean from the ventilator. This article concentrates on the muscle pathology and the role of drugs. It occurs in about 25 to 50% of patients ventilated for more than 7 days, and is more common in severe asthma and after organ transplantation.

Triggers and risk factors

• Corticosteroids, particularly high-dose IV courses
• Prolonged use (over 48 hours) of non-depolarizing neuromuscular blockers, especially aminosteroid agents such as vecuronium and pancuronium
• Sepsis, multiple organ failure, hyperglycemia, renal failure and immobility

Pathology: three patterns exist.

• Thick filament myopathy: selective loss of myosin in the sarcomere (the commonest)
• Cachectic myopathy: muscle atrophy with loss of fibre size
• Acute necrotizing myopathy: fibre necrosis with raised creatine kinase and potential myoglobinuria

Mechanisms are loss of sarcolemmal excitability from sodium channel inactivation, activation of the ubiquitin-proteasome and calpain proteolytic pathways, mitochondrial dysfunction and loss of mechanical loading. Prognosis is better than in polyneuropathy, with most patients recovering over weeks to months. Complications: ventilator dependence, dysphagia with aspiration, rhabdomyolysis and renal injury (necrotizing form) and prolonged hospital stay.

• Symmetric flaccid weakness, proximal more than distal, with failure to wean from the ventilator
• Normal or mildly reduced reflexes, intact sensation
• Facial and extraocular muscle weakness in some patients, and dysphagia
• Muscle tenderness is uncommon, and urine may be dark in necrotizing disease
• Red flags: dark urine with high creatine kinase, rapidly progressive weakness with fever, and a sensory deficit pointing to other disease

1. Clinical assessment with the MRC sum score (below 48 of 60 is abnormal).
2. Creatine kinase: normal or mildly raised, markedly raised (over 10 times normal) in the necrotizing form. Urinary myoglobin when dark urine is present.
3. Nerve conduction studies: reduced compound muscle action potential amplitude with prolonged duration, and normal sensory nerve action potentials.
4. Needle electromyography: short, low-amplitude polyphasic motor unit potentials with early recruitment, with fibrillations in some.
5. Direct muscle stimulation: reduced directly evoked muscle response, which shows reduced muscle membrane excitability and separates the myopathy from a neuropathy.
6. Muscle biopsy (when the diagnosis is uncertain): selective loss of myosin thick filaments on electron microscopy or ATPase staining, and type II fibre atrophy. Quadriceps ultrasound shows increased echogenicity and reduced thickness.
7. Exclusion of other causes: electrolytes (potassium, magnesium, phosphate), thyroid function, cortisol, drug-induced myopathy (statins, propofol infusion syndrome) and Guillain-Barre syndrome.

Differentials: critical illness polyneuropathy, Guillain-Barre syndrome, myasthenia gravis, rhabdomyolysis of other cause, inflammatory myositis and electrolyte-related weakness.

1. Remove triggers:
   • Reduce corticosteroids to the lowest effective dose for the shortest time.
   • Avoid neuromuscular blockers beyond 48 hours. When needed, use intermittent boluses with train-of-four monitoring (a target of 1 to 2 twitches), with cisatracurium 0.15 mg/kg IV rather than aminosteroid agents.
2. Treat sepsis and underlying illness, and control glucose at 7.8 to 10 mmol/L with insulin infusion.
3. Correct electrolytes: potassium to above 4.0 mmol/L, magnesium to above 0.8 mmol/L and phosphate to above 0.8 mmol/L.
4. Nutrition: enteral feeding at 25 to 30 kcal/kg a day with protein 1.5 to 2.0 g/kg a day.
5. Rehabilitation: daily sedation interruption, early mobilization starting within 48 to 72 hours of stabilization (sitting at the bed edge, standing, walking), in-bed cycling, and neuromuscular electrical stimulation for 30 to 60 minutes daily.
6. Respiratory and bulbar care: daily spontaneous breathing trials, inspiratory muscle training, swallowing assessment before any oral feeding, and speech therapy.
7. Necrotizing form with myoglobinuria: IV 0.9% saline 200 to 300 mL/h to keep urine output above 1 mL/kg/h, and monitoring of potassium and creatinine.
8. Avoid myotoxic drugs (statins during high creatine kinase, colchicine) and prolonged propofol infusion at high dose.
9. Pain and spasm: paracetamol 1 g orally every 6 hours. No drug therapy reverses the weakness.

Follow-up: strength review and repeat electrophysiology at 3 months, and rehabilitation for 6 to 12 months. Most patients recover most strength within 3 to 6 months. Counsel on the favorable outlook and on the importance of exercise.