A nineteen-year-old man of normal intelligence with C6 tetraplegia, caused by transverse myelitis in infancy, had a progressive neuromuscular scoliosis that prevented comfortable seating (Figs. 1-A and 1-B). He had received an ITB pump at age eleven years in order to control lower-extremity spasticity, with the intrathecal catheter entering at the L1-L2 level and ending proximally at the T3 level. He had undergone two pump and proximal catheter revisions at the ages of sixteen and eighteen years because of catheter malfunctions, but had maintained a good baseline function for at least eighteen months prior to the scoliosis surgery.
A posterior spinal instrumentation and fusion from T3 to the pelvis with use of a pedicle screw and rod construct was performed (Fig. 2). Once the spine was exposed, the distal baclofen pump catheter was removed from the intrathecal space and transected 6 cm from the metallic connector joining it to the proximal catheter (Fig. 3). The posterior spinal fusion with instrumentation was then completed uneventfully with a total estimated blood loss of 1.2 L and an operative time of 320 minutes. A new distal catheter was then attached to the connector and inserted into the intrathecal space at the L2-L3 level. A baclofen bolus was given via the pump, and the pump was then programmed to deliver the patient’s usual baclofen dose of 600 to 625 μg per day.
The patient was extubated on postoperative day one. By that afternoon, he began to demonstrate increased spasticity and mixed dystonia. Three large intrathecal boluses of baclofen were programmed through the pump, but the boluses failed to alleviate the symptoms. He was returned to the operating room, and the distal catheter was found to be occluded by sanguineous cerebrospinal fluid. The catheter was recannulated and replaced. The patient then received additional ITB boluses on postoperative days two and three with improvement in the clonus and decreased spasticity of the upper extremities.
On the evening of postoperative day three, the patient demonstrated an altered mental status with increasing confusion, confabulation, and hallucinations. Intravenous haloperidol was administered with minimal improvement. Throughout the evening, he became less responsive, hypotensive, and febrile, with fevers greater than 41°C (105.8°F) for approximately twelve hours. He was treated with a combination of propofol, lorazepam, and dantrolene. The baclofen dosing was increased to 840 μg per day during this episode. Over the next twenty-four hours, he had profound rhabdomyolysis with acute renal failure that required dialysis. On the afternoon of postoperative day six, he began to experience seizures; electroencephalography (EEG) confirmed epileptiform discharges. The seizures were controlled with propofol and fosphenytoin. Magnetic resonance imaging (MRI) examination at approximately two weeks after the spinal fusion surgery demonstrated diffuse hypoxic injury to the basal ganglia, cerebral cortex, and cerebellum. The patient remained intubated and unresponsive to painful stimuli. At this point, the patient’s mother made the decision to withdraw life support, and the patient subsequently died.
Baclofen is a beta-4-chlorophenol derivative of the inhibitory neurotransmitter GABA that activates GABAB receptors in the central nervous system7,13. Once removed from the inhibitory effects of baclofen, withdrawal is thought to occur from the exposure of neurons in the central nervous system to unopposed excitatory pathways, resulting in an exaggerated excitatory state7. Symptoms of ITB withdrawal span a spectrum. In the majority of patients, the symptoms are limited to the return of the patient’s baseline spasticity and rigidity14. In some patients, withdrawal may cause generalized seizures and delirium13. In a minority of patients, ITB withdrawal will cause a potentially fatal syndrome characterized by rebound spasticity, muscle rigidity, fever, labile blood pressure or hypotension, and a diminished level of consciousness3. In this group, the syndrome progresses rapidly over one to three days with elevations in creatine kinase (CK) levels, rhabdomyolysis, elevated transaminase levels, disseminated intravascular coagulation, and serial failure of organ systems, including cardiomyopathy and hepatic and renal compromise.
Since baclofen has a relatively short half-life of three to four hours, withdrawal severity from baclofen therapy is dependent on the abruptness of cessation and route of administration. Symptoms of oral baclofen withdrawal may take up to four days to occur, whereas with ITB therapy, as illustrated by our case, signs of withdrawal may be present in as little as twelve to twenty-four hours13. It is therefore imperative that delirium, high fevers, and increasing spasticity be immediately recognized as indicators of baclofen withdrawal so that treatment can be offered expeditiously. The potential for mortality from ITB withdrawal is far greater than that from oral baclofen; to the best of our knowledge, all reported deaths in the literature have been associated with ITB therapy13.
Symptoms of baclofen withdrawal may be mimicked by malignant hyperthermia or neuroleptic malignant syndrome. It is critical to distinguish these possibilities because management differs markedly. In all three scenarios, the patient will demonstrate tachycardia, autonomic instability, elevated body temperatures, generalized muscle rigidity, and elevated CK levels. However, central differences exist in the clinical setting and timing. Baclofen withdrawal typically evolves over one to three days and is associated with some interruption in ITB therapy. Malignant hyperthermia occurs during or immediately after administration of an anesthetic, classically halothane, and often there is a family history of malignant hyperthermia. It may also demonstrate laboratory evidence of disordered calcium metabolism. Neuroleptic malignant syndrome occurs hours after the start of a dopamine-blocking antipsychotic drug or after the withdrawal of a dopamine-agonist drug15.
Treatment of baclofen withdrawal centers on the prompt reinstatement of ITB, which typically requires an investigation of the pump mechanics and pump programming15. In our patient, the deduced cause of baclofen withdrawal was the distal catheter malfunction, a scenario that may have been more likely with catheter reinsertion in the setting of epidural venous bleeding from the spinal fusion. Distal catheter mechanical malfunction was also potentially more likely given the more rostral placement of the original catheter (C1-T6) because it is more difficult to replace a catheter along the longer intrathecal fibrous channel that develops around the original catheter following distortion of the channel by scoliosis correction. However, rostral placement provides greater control of upper-extremity spasticity, a feature that was of substantial benefit to this patient with an injury at the C6 level16,17. In the available literature, it is notable that rostral placement has not been demonstrated to have an increased incidence of potential complications during primary implantation, including cervical spinal cord injury, mechanical difficulties with the catheter, or increased central side effects of baclofen, specifically somnolence and aspiration pneumonia 16,18.
Once the cause of baclofen withdrawal signs and symptoms has been identified and corrected, treatment is generally symptomatic and consists of pharmacological options such as benzodiazepines and adjunctive propofol. High-dose oral baclofen may be considered, but will likely be ineffective because it does not achieve the same concentrations as ITB. Dantrolene is frequently added to the withdrawal regimen to protect muscle by preventing hyperthermia and rhabdomyolysis.
Despite the prompt identification and reinstatement of ITB therapy in our patient and the initial improvement, on the third postoperative day the patient reverted to a catastrophic course with continued withdrawal symptoms. The described scenario of a patient initially responding to baclofen therapy for withdrawal symptoms and then ultimately succumbing to its fatal effects has been previously reported3. We cannot offer a direct explanation for this clinical picture but postulate that in patients with chronically high doses of baclofen, reinstatement of therapy may be insufficient to reverse the neuroexcitatory cascade.
In our case, determining baclofen levels in the cerebrospinal fluid may have been a useful supplemental test to verify that the baclofen pump was indeed working both in the immediate postoperative period and after inspection of the distal catheter. However, laboratory results for baclofen levels often take longer than two weeks to acquire and are therefore not clinically useful for the management of acute baclofen withdrawal symptoms. Nuclear medicine scans have the benefit of potentially confirming pump malfunction, but they do not necessarily detect all catheter leaks and are ill-advised for unstable patients9,19. Additionally, use of serial CK or urine myoglobin levels to detect a baclofen withdrawal etiology is limited by the nonspecific nature of the tests because postoperative increases in these parameters can result from numerous causes, including postsurgical muscle trauma, compartment or crush syndrome from positioning, malignant hyperthermia, neuroleptic malignant syndrome, seizures, and drug toxicity. Therefore, the diagnosis of baclofen withdrawal continues to be made in the clinical setting.
Despite sufficient information in the literature regarding the potential complications of posterior spinal fusion surgery in patients with ITB therapy, to our knowledge, this is the first report of a fatal complication from ITB therapy management in the postoperative period. The complications that have generally been reported following posterior spinal fusion surgery in patients with ITB therapy include mechanical failures related to the pump or catheter, infections of the spine or the pump site, or skin breakdown over the pump site2,8,12,20. The current spinal surgery literature is notably devoid of the potentially fatal outcome of baclofen withdrawal, although this outcome is well recognized in the neurology literature19.
Our case exposes a central clinical shortcoming in the operative management of spinal deformity in patients with ITB therapy, specifically that no critically reviewed, standardized operative approach to baclofen pump management in the setting of spinal fusion exists. Reported management strategies for the baclofen pump catheter have included removal of the catheter with reintroduction of the same catheter at the end of the procedure, maintenance of the catheter once it has been dissected free, sectioning of the catheter with replacement of the catheter through an appropriate connector at the end of the surgery, or a temporary external intrathecal catheter9,12,21. In addition, the baclofen tubing can initially be placed through a cervicothoracic level, obviating the need to expose the catheter during the routine approach for posterior spinal fusion22. In the absence of convincing support for any one strategy, we have implemented the following protocol: (1) The baclofen catheter is dissected free and maintained during spinal fusion surgery; (2) prior to skin closure, the baclofen catheter is tested for patency under fluoroscopy with a bolus of radiopaque dye, and the baclofen pump is interrogated for proper function; and (3) a second intrathecal catheter is placed at a different location and is left externalized. The second catheter provides a contingency method for ITB delivery in the event of a primary catheter failure. If the patient demonstrates no withdrawal symptoms, the second catheter can be removed in the hospital room. Nevertheless, additional investigation into an optimal management strategy is necessary.
In conclusion, spinal deformity surgeons treating neuromuscular patients must be well versed in the signs and symptoms of baclofen withdrawal and maintain postoperative vigilance in patients with spinal disorders who receive ITB. Rapid recognition and treatment of baclofen withdrawal signs and symptoms can be lifesaving.