Treatment of Paroxysmal Sympathetic Hyperactivity
Paroxysmal sympathetic hyperactivity (PSH) requires combination pharmacotherapy targeting multiple mechanisms, as monotherapy is typically ineffective; the most effective regimen includes morphine or fentanyl for acute episodes, propranolol for beta-blockade, gabapentin for neuromodulation, and benzodiazepines for GABA enhancement. 1, 2, 3
Diagnostic Confirmation
Before initiating treatment, confirm the diagnosis using the PSH Assessment Measure (PSH-AM) score, which combines:
- Clinical Features Severity (CFS) score assessing hypertension, tachycardia, tachypnea, hyperpyrexia, diaphoresis, and dystonic posturing 1, 4
- Diagnosis Likelihood Tool (DLT) score evaluating the probability of PSH versus alternative diagnoses 1, 4
- A combined PSH-AM score ≥17 indicates "probable" PSH and warrants treatment initiation 1
Non-Pharmacological Management
Minimize external stimulation that triggers sympathetic surges, as PSH episodes can be provoked by routine care activities like suctioning, repositioning, or environmental noise 2, 3. This foundational step reduces the frequency and severity of paroxysms before pharmacological intervention.
Pharmacological Treatment Strategy
First-Line Combination Therapy
The treatment approach targets three mechanisms simultaneously:
1. Opioids for Acute Episodes and Prevention
- Morphine 2-5 mg IV for acute paroxysmal episodes provides immediate sympathetic suppression 1, 2
- Fentanyl transdermal patch for continuous prevention of attacks, particularly effective in tumor-induced PSH 5
- Opioids reduce sympathetic excitatory afferents and provide the most rapid control of acute symptoms 2, 3
2. Beta-Blockers for Sympathetic Target Organ Effects
- Propranolol (nonselective beta-blocker) is the preferred agent, showing slight clinical advantage over other beta-blockers 3, 5
- Start with low doses and titrate to control tachycardia and hypertension 1, 2
- Propranolol inhibits the peripheral effects of sympathetic hyperactivity on the cardiovascular system 2, 5
3. GABA Agonists for Neuromodulation
- Gabapentin is the primary preventive medication, reducing the frequency and severity of episodes 1, 2, 3
- Benzodiazepines (diazepam) provide additional GABA-mediated inhibition and can be used acutely or for maintenance 1, 2
- These agents restore the excitatory/inhibitory balance disrupted by brain injury 4, 2
Second-Line Agents
Alpha-2 Agonists
- Clonidine provides centrally-mediated sympathetic suppression 2, 3
- Dexmedetomidine may offer slight clinical advantage over propofol in critically ill patients requiring sedation 3
- These agents are particularly useful when beta-blockers are contraindicated 2
Specific Dosing Regimen from Case Evidence
The successful treatment protocol from documented cases includes 1:
- Morphine for acute episodes
- Diazepam for GABA enhancement
- Propranolol for beta-blockade
- Gabapentin for long-term prevention
Critical Management Principles
Avoid monotherapy - PSH requires multiple agents with different mechanisms of action, as single-drug approaches consistently fail 3. The combination targets different levels of the sympathetic pathway simultaneously.
Titrate based on symptom severity - Use the CFS score to guide medication adjustments, increasing doses or adding agents when paroxysms remain frequent or severe 1, 4.
Monitor for secondary complications including:
- Dehydration and weight loss from excessive sweating and hypermetabolism 2
- Muscle contractures from prolonged dystonic posturing 2
- Cardiovascular strain from repeated hypertensive episodes 1
Common Pitfalls to Avoid
Do not mistake PSH for seizures - Normal inter-ictal EEG during autonomic surges distinguishes PSH from epileptic activity 1. Unnecessary antiepileptic escalation delays appropriate treatment.
Do not use meperidine - This opioid has muscarinic antagonistic properties that may paradoxically worsen sympathetic hyperactivity 6.
Avoid beta-blocker monotherapy - While propranolol controls peripheral manifestations, it does not address the central dysregulation driving PSH and must be combined with other agents 2, 3.
Treatment Timeline and Expectations
Improvement typically begins within the second week of combination therapy, with gradual reduction in episode frequency and severity 1. However, PSH can persist for weeks to months after brain injury, requiring prolonged treatment and monitoring 4, 2.
The prognosis depends on the severity of the underlying brain injury, with PSH serving as a marker of significant neurological damage 4, 2. Early recognition and aggressive treatment may reduce secondary morbidity, though the impact on long-term neurological outcomes requires further investigation 4.