What is the likely cause of new myoclonic jerks and persistent coma in a severe Acute Respiratory Distress Syndrome patient who has been off atracurium (neuromuscular blocker) for more than 24 hours, and how should it be managed?

Myoclonic Jerks and Persistent Coma After Atracurium Discontinuation in Severe ARDS

Most Likely Diagnosis

This patient most likely has post-hypoxic myoclonus (Lance-Adams syndrome or status myoclonus) secondary to a hypoxic-ischemic brain injury that occurred during the severe ARDS course, not a complication of atracurium itself. 1

The key distinction is that atracurium (a benzylisoquinolinium neuromuscular blocker) does not directly cause myoclonus or prolonged coma—rather, the severe ARDS likely caused periods of hypoxemia leading to anoxic brain injury, which is now manifesting as myoclonus after the paralytic has worn off. 1, 2

Critical Differential Considerations

Post-Hypoxic Myoclonus (Most Likely)

• Status myoclonus beginning within 48 hours of a hypoxic event (in this case, during severe ARDS management) is highly associated with poor neurological outcome, though rare cases of good recovery have been documented. 1
• The myoclonus represents cortical or subcortical hyperexcitability following anoxic-ischemic injury. 1, 3
• Some patients develop Lance-Adams syndrome where myoclonus persists after awakening and becomes chronic action myoclonus. 1

Metabolic Encephalopathy with Myoclonus

• Uremia, hepatic failure, or toxic-metabolic derangements common in severe ARDS can cause both altered consciousness and myoclonus. 3
• Check renal function, liver function, ammonia, and electrolytes immediately.

Seizure Activity (Status Epilepticus)

• Myoclonic status epilepticus must be excluded with urgent EEG. 1
• The distinction between epileptic and non-epileptic myoclonus is critical for treatment decisions. 1, 3

Laudanosine Accumulation (Less Likely)

• Atracurium's metabolite laudanosine can cause cerebral excitatory effects including seizures in animal models, though clinical significance in humans remains uncertain. 2
• However, more than 24 hours post-discontinuation makes this unlikely as atracurium has a short duration of action (25-35 minutes after bolus). 2

Immediate Diagnostic Workup

Confirm Neuromuscular Blockade Resolution

• Perform train-of-four (TOF) testing immediately to definitively rule out residual paralysis, though >24 hours post-discontinuation makes this extremely unlikely. 1
• Spontaneous recovery to TOF ratio >75% typically occurs within 60 minutes (range 32-108 minutes) after stopping atracurium infusion. 2

Urgent EEG

• Continuous EEG monitoring is mandatory to differentiate epileptic from non-epileptic myoclonus and to assess for underlying cortical reactivity. 1
• EEG can reveal signs of awareness and reactivity even when masked by myoclonus and sedation. 1
• Look for epileptiform activity, burst suppression, or severe background slowing.

Neurological Prognostication Studies

• Bilateral somatosensory evoked potentials (SSEPs) should be performed to assess N20 wave presence. 1
• Bilateral absence of N20 SSEP wave predicts death or vegetative state with 99.7% positive predictive value, though this should be interpreted cautiously in the context of ongoing sedation. 1
• Assess pupillary reflexes, corneal reflexes, and motor response to pain (though these may be suppressed by residual sedation). 1

Metabolic and Toxic Screen

• Comprehensive metabolic panel, liver function tests, ammonia level
• Drug levels if applicable (check for accumulation of sedatives)
• Arterial blood gas to assess for severe hypoxemia or hypercarbia during ARDS course

Management Algorithm

Step 1: Rule Out Ongoing Seizures (First 1-2 Hours)

• If EEG shows epileptiform activity: Treat as status epilepticus with benzodiazepines (lorazepam 0.1 mg/kg IV) followed by antiepileptic loading (levetiracetam 60 mg/kg IV or valproate 40 mg/kg IV). 3
• If EEG shows no epileptiform activity: Proceed to symptomatic myoclonus treatment.

Step 2: Symptomatic Myoclonus Treatment

• First-line: Levetiracetam 500-1500 mg IV twice daily (effective for cortical myoclonus). 3
• Second-line: Valproate 15-20 mg/kg/day IV divided (broad-spectrum antimyoclonic effect). 3
• Third-line: Clonazepam 0.5-2 mg IV/PO three times daily (GABAergic enhancement). 3
• Avoid: Phenytoin is generally ineffective for myoclonus and may worsen it. 3

Step 3: Address Underlying Causes

• Correct any metabolic derangements (uremia, hepatic encephalopathy, electrolyte abnormalities). 3
• Optimize oxygenation and ventilation to prevent further hypoxic injury.
• Review and minimize sedatives that may be prolonging coma.

Step 4: Neurological Prognostication (After 72 Hours)

• Do not prognosticate before 72 hours from the hypoxic event and ensure all sedation has cleared. 1
• When residual sedation or paralysis is suspected, prolong observation beyond 72 hours to minimize false positive results. 1
• Combine multiple modalities: clinical examination (pupillary/corneal reflexes, motor response), SSEPs, and EEG reactivity. 1

Critical Pitfalls to Avoid

Do Not Attribute This to Atracurium Directly

• Atracurium does not cause myoclonus or prolonged coma. 2
• The FDA label notes that seizures have been rarely reported in ICU patients receiving atracurium, but these patients typically had predisposing causes (head trauma, cerebral edema, hypoxic encephalopathy). 2
• The temporal relationship (>24 hours post-discontinuation) makes direct drug effect implausible.

Do Not Assume Poor Prognosis Immediately

• While status myoclonus within 48 hours of hypoxic injury has 0% false positive rate for poor outcome in most studies, several case reports document good neurological recovery despite early-onset prolonged myoclonus. 1
• Some patients' myoclonus disappears with recovery of consciousness, though the exact timing may be masked by ongoing sedation. 1
• Evaluate off sedation whenever possible before making definitive prognostic statements. 1

Do Not Forget ICU-Acquired Weakness

• Prolonged neuromuscular blockade (especially >48 hours) combined with corticosteroids, sepsis, and immobility increases risk of ICU-acquired weakness. 1
• However, this manifests as flaccid weakness, not myoclonus, and should not prevent awakening once paralysis resolves. 1
• The 48-hour cisatracurium infusions studied in ARDS do not increase ICU-acquired weakness risk compared to no neuromuscular blockade. 4, 5

Do Not Delay EEG

• Clinical assessment alone is grossly inadequate for determining depth of neuromuscular blockade or neurological status. 6
• In one study, clinical assessment agreed with TOF measurements only 17-19% of the time. 6
• EEG is essential to differentiate epileptic from non-epileptic myoclonus and assess cortical function. 1

Prognosis Discussion

The prognosis depends entirely on the severity and duration of hypoxic-ischemic injury during the ARDS course, not on atracurium exposure. 1 Status myoclonus beginning within 48 hours of a hypoxic event carries a poor prognosis (0% false positive rate for poor outcome in most studies), but individual cases of recovery exist. 1 Bilateral absence of N20 SSEP waves at >72 hours post-injury predicts death or vegetative state with 99.7% positive predictive value. 1 However, prognostication should be multimodal and delayed until at least 72 hours after the hypoxic event with all sedation cleared to avoid self-fulfilling prophecy. 1