How can muscle relaxants be safely used in patients at risk of rhabdomyolysis?

Rhabdomyolysis and Muscle Relaxants: Safe Use in At-Risk Patients

Absolute Contraindications

Succinylcholine (suxamethonium) is absolutely contraindicated in patients with primary muscle damage (myopathies), chronic motor neuron damage, extensive/deep burns, spinal cord injury, and prolonged critical illness due to the risk of life-threatening hyperkalemia and rhabdomyolysis. 1, 2

High-Risk Conditions for Rhabdomyolysis

• Primary muscle damage (myopathies, Duchenne muscular dystrophy): Succinylcholine induces generalized muscle contraction with rhabdomyolysis, potentially leading to hyperkalemic cardiac arrest 1, 3
• Receptor upregulation states: These include chronic motoneuron damage, extensive/deep burns (starting 24 hours post-injury), spinal cord injury, and prolonged critical illness—all cause massive potassium efflux when succinylcholine is administered 1, 2, 4
• Burn patients: The risk period begins 24 hours after injury and extends for at least 6 months, though the exact duration is unknown 2, 4
• Neuromuscular diseases: Patients with conditions like Duchenne muscular dystrophy are at extreme risk for acute rhabdomyolysis and hyperkalemia 1, 5, 3

Safe Alternative: Rocuronium-Based Approach

For rapid sequence intubation in at-risk patients, rocuronium at doses ≥0.9 mg/kg is the recommended alternative, with its safety benefit outweighing the longer duration of action. 2, 6

Dosing Strategy for Non-Depolarizing Agents

• Standard patients: Rocuronium 0.6-1.2 mg/kg for rapid sequence intubation 1, 6
• Myasthenia gravis patients: Reduce dose by 50-75% (use atracurium or cisatracurium at reduced doses) due to increased sensitivity 1
• Primary muscle damage (e.g., Duchenne): Reduce rocuronium dose significantly; a 0.6 mg/kg dose produces prolonged onset and recovery times compared to controls 1
• Receptor upregulation states: Higher doses may be required due to resistance, with shorter durations of action expected 6

Essential Monitoring Requirements

Neuromuscular blockade monitoring is mandatory when using any muscle relaxant in patients with neuromuscular diseases or conditions predisposing to rhabdomyolysis. 1, 2, 7

Monitoring Protocol

• Use quantitative neuromuscular monitoring (train-of-four ratio) throughout the procedure 1, 7
• Pre-administration assessment: In myasthenic patients, measure TOF ratio before giving muscle relaxants—if <0.9, expect greater sensitivity and reduce doses accordingly 1
• Preferred monitoring site: Corrugator supercilii muscle due to sensitivity comparable to laryngeal muscles 1
• Monitor for signs of rhabdomyolysis: Watch for hyperkalemia, myoglobinuria, and elevated creatine kinase 8, 5, 3

Reversal Strategy

Sugammadex is the preferred reversal agent for rocuronium-induced neuromuscular blockade in patients with neuromuscular disease or at risk for rhabdomyolysis. 1, 2

Rationale for Sugammadex Preference

• Avoids neostigmine complications: Neostigmine can interfere with long-term myasthenia treatment and causes problematic effects in primary muscle damage (secretion drying, rhythm disorders, slow response) 1
• Rapid and reliable reversal: Particularly important in high-risk patients where residual blockade poses greater danger 1
• Safe in neuromuscular disease: Case series support its use in this population 1

Special Considerations by Condition

Myasthenia Gravis

• Paradoxical response to succinylcholine: Resistance occurs (decreased potency), requiring higher doses—avoid entirely given safer alternatives exist 1
• Increased sensitivity to non-depolarizers: Use 50-75% dose reduction with atracurium/cisatracurium 1
• Pre-treatment assessment critical: Baseline TOF ratio predicts sensitivity 1

Hepatic/Renal Impairment

• Prefer benzylisoquinoline agents: Atracurium or cisatracurium are safer choices as they undergo organ-independent elimination 9, 7
• Avoid aminosteroids: Rocuronium and vecuronium require dose adjustment in organ failure 6, 10

Critical Illness with Steroid Use

• Avoid prolonged neuromuscular blockade: The combination of muscle relaxants (especially pancuronium) with high-dose steroids significantly increases rhabdomyolysis risk 8
• Limit duration and total dose: Case reports document rhabdomyolysis with prolonged administration (e.g., 960 mg pancuronium over 10 days) 8

Critical Pitfalls to Avoid

• Never assume a patient without known neuromuscular disease is safe for succinylcholine: Undiagnosed Duchenne muscular dystrophy can present as hyperkalemic cardiac arrest 3
• Screen for occult myopathy: Check creatine kinase in children with unexplained motor delay before anesthesia 3
• Do not mix rocuronium with alkaline solutions: Rocuronium has acidic pH and is incompatible with barbiturates in the same syringe or IV line 6, 10
• Recognize acid-base effects: Acidosis prolongs recovery time and enhances potency of rocuronium; alkalosis reduces potency 6
• Avoid inadequate anesthesia depth: Muscle relaxants must always be accompanied by adequate anesthesia or sedation 6, 10

Drug Interaction Warnings

• Potentiating agents: Volatile anesthetics (especially enflurane, isoflurane), aminoglycoside antibiotics, magnesium, lithium, quinidine, and procainamide all prolong neuromuscular blockade—reduce initial rocuronium dose 6, 10
• Resistance-inducing agents: Chronic anticonvulsants (carbamazepine, phenytoin) cause receptor upregulation, requiring higher doses and increased infusion rates 6
• CNS depressants: When combining muscle relaxants with other CNS depressants, monitor closely for excessive sedation and respiratory depression 7