Correct!
4. A + C

Sepsis syndrome remains a possibility although it would not explain the severe muscle rigidity. Myocardial infarction with cardiogenic shock is unlikely with the relatively low troponin and his normal coronary arteries – it seems more likely that the observed cardiomyopathy is a secondary process. Intrathecal baclofen withdrawal is a life-threatening withdrawal that can present with multisystem organ failure, including severe cardiomyopathy. 

His initial cultures were all negative.   The original suspicion that the patient’s illness represented intrathecal baclofen withdrawal syndrome was increasingly confirmed.   An emergent anesthesia pain service consult was obtained in order to restart intrathecal baclofen administration. 

Baclofen is a derivative of gamma-aminobutyric acid (GABA) and an agonist of the GABA type B receptors.  It is primarily used to treat spasticity in patients with spinal cord injuries.  Intrathecal pumps are used to administer baclofen in some patients, in order to minimize systemic sedation properties of the drug, and increase the potency of the anti-spasticity effects.  It is estimated that intrathecal baclofen is at least 10,000 more potent than enteral baclofen.  Chronic intrathecal baclofen administration leads to downregulation of GABA-b receptors in the CNS.  Withdrawal of intrathecal baclofen therefore leads to a hyperstimulated state, causing severe rebound muscle spasticity, delirium, extremely high fever, and multisystem organ failure.   It represents one of the most lethal withdrawal syndromes an intensivist might encounter, Table 1 reviews the syndrome, renumerating many of the clinical aspects of our case.

Table 1. The syndrome of intrathecal baclofen withdrawal.

• Rapid onset at time of weaning, purposeful discontinuation, or accidental dysfunction of an intrathecal baclofen pump.
• High fever
• Muscle rigidity with rhabdomyolysis
• Encephalopathy with myoclonus and seizures
• Autonomic instability
• Pruritis
• Respiratory failure (sometimes with stridor from spasticity of laryngeal muscles)
• Disseminated intravascular coagulation
• Reversible cardiomyopathy
• Acute renal failure

The syndrome should be suspected in any critically-ill patient who has recently had a reduction in intrathecal baclofen dose – even in the course of weaning.  In some cases, inadvertent discontinuation has been recognized by radiographic studies demonstrating disruption of the subcutaneous-intrathecal catheter.

Which of the following statements regarding baclofen withdrawal syndrome is true?

1. Intrathecal baclofen withdrawal is one of the most lethal drug withdrawal syndromes requiring immediate aggressive pharmacotherapy
2. Oral therapy with baclofen may not relieve intrathecal baclofen withdrawal
3. Reinitiation of intrathecal baclofen therapy requires urgent consultation with a specialist experienced in the management of intrathecal therapy
4. GABA-a agonists such as benzodiazepines can be used as adjunctive therapy
5. All of the above