Cardiac Arrest: A Rare Complication of Intrathecal Baclofen Withdrawal

Abstract

Baclofen, a GABA agonist, is used for the management of spasticity. Intrathecal route is indicated in cases of severe spasticity associated with spinal cord injury. Baclofen withdrawal symptoms can happen after IT pump removal which can present as anxiety, paranoia, psychosis, seizures, hallucinations, severe spasticity and dyskinesia. Cardiac arrest after baclofen withdrawal is rare with only 2 cases in literature so far however in both cases IT-pump was replaced. We present a case of PEA arrest after baclofen IT-pump removal which was managed without replacing. 33 year-old male with history of paraplegia from cervical spinal cord injury (C-6) level, chronic spasticity, fibular osteomyelitis and chronic sacral ulcers presented with wound dehiscence and exposed baclofen pump which was replaced 4 weeks ago due to the end of the pump’s life. After 24–48 h of removal of the baclofen pump, cardiovascular instability in the form of supra ventricular tachycardia with hypotension and altered mentation was noted. It evolved to progressive clinical worsening with stiffness of body, loss of responsiveness, and up-rolling of eyes. Patient underwent PEA, and ROSC after 3 rounds of CPR. He was subsequently intubated, mechanically ventilated and sedated with midazolam intravenously. Baclofen and clonazepam were started through the feeding tube. Over a period of 10 days, midazolam was weaned, and baseline clinical stability was achieved without IT-baclofen pump. Though rare, cardiac arrest can happen after baclofen withdrawal. High index of clinical suspicion is advised for long term baclofen pump patients after pump explant to prevent withdrawal symptoms and complications.

Introduction

Baclofen, a gamma-aminobutyric acid (GABA) receptor agonist, is used for the management of spasticity in neuromuscular disorders.^1,2 Intrathecal (IT) route is indicated in cases of severe spasticity associated with spinal cord injury with side effects profile. Baclofen withdrawal symptoms can happen after IT pump removal which can present as pruritus, anxiety, or severe symptoms like paranoia, psychosis, seizures, hallucinations, severe spasticity and dyskinesia. Cardiac arrest after baclofen withdrawal is rare with only 2 cases in literature so far however in both cases IT-pump was replaced we present a case of Pulseless Electrical Activity (PEA) arrest after baclofen IT-pump removal which was managed without pump replacement.

Case Presentation

33 year-old male with history of paraplegia from cervical spinal cord injury at C-6 level, chronic spasticity, metastatic melanoma, adrenal insufficiency, fibular osteomyelitis and chronic non-healing sacral ulcers with multiple debridement presented with wound dehiscence, exposed baclofen hardware with concern for infection under neurosurgery services. The Baclofen pump was replaced 4 weeks ago in the outside hospital due to the end of the pump’s life. During admission, baclofen pump was removed due to concern for infection and after 24–48 h of explantation, cardiovascular instability in the form of supra ventricular tachycardia (SVT) with hypotension and altered mentation was noted. It evolved to progressive clinical worsening with stiffness of body with loss of responsiveness, and up-rolling of eyes. The patient developed Pulseless Electrical Activity (PEA) for which Cardiopulmonary Resuscitation (CPR) was initiated with Return of Spontaneous Circulation (ROSC) after 3 rounds. He was subsequently intubated, mechanically ventilated, admitted to Neurosciences intensive care unit (NSICU) and sedated with midazolam intravenously. Baclofen and clonazepam were started through the feeding tube and over a period of 10 days, midazolam was weaned and baseline clinical stability was achieved without IT-baclofen pump.

Conclusion

Though rare, cardiac arrest can happen after baclofen withdrawal. High index of clinical suspicion is advised for patients with long term baclofen pump after pump explant to prevent withdrawal symptoms and complications. Due to lack of established guidelines for baclofen withdrawal treatment, management approach varies among clinicians.

Background

Baclofen is widely used gamma-aminobutyric acid (GABA) receptors agonist on pre and postsynaptic neurons in the central nervous system and peripheral nervous system. Baclofen is an effective therapeutic medication for the treatment of spasticity in patients with spinal cord injuries and other neuromuscular diseases including multiple sclerosis. Baclofen was originally prepared in 1962 as antiepileptic but was found non-effective in the treatment of epilepsy. It showed improvement in spasticity in certain patient populations. The US Food and Drug Administration approved baclofen in 1977 for the treatment of spasticity. ³ Baclofen can be used as oral and intra thecal in the form of a pump for the sustained release of medication especially in the patients with severe spasticity associated with spinal cord injury. Many studies have proven efficacy of intra thecal baclofen than oral route with less severe spasms with no significant differences in quality of life, sleep, fatigue and pain level. ⁴ Baclofen is associated with both toxicity and withdrawal risks with risk of death. Baclofen toxicity symptoms range from hypothermia, hallucination, tremors, hyporeflexia, catatonia, impaired memory, encephalopathy, cardiovascular abnormalities with arrhythmias and QTc interval prolongation and respiratory depression. Baclofen withdrawal can present with mild symptoms including pruritus, anxiety, paranoia, hallucination to severe symptoms ranging from multiorgan failure, seizures, autonomic dysfunction, bradycardia, and cardiomyopathy. ⁵

Case Presentation

We report a case of a young patient who experienced cardiac arrest after baclofen pump removal and did not require baclofen pump replacement for management. History of paraplegia due to cervical spinal cord injury (SCI) at C-6 level, chronic spasticity, melanoma metastasis to brain and gallbladder, adrenal insufficiency on hydrocortisone as maintenance steroids, fibular osteomyelitis status post fibular resection and chronic non healing sacral ulcers with multiple debridement. Intrathecal baclofen pump (ITB) was placed 7 years ago for refractory spasticity secondary to spinal cord injury. ITB pump was replaced 4 weeks before presenting to University hospital (UH) due to the pump’s end of life. Post procedure, reported to have wound dehiscence, and exposed pump hardware with concern for infection, for which patient had an uneventful pump explantation. After 24 h of pump removal, intermittent agitation, confusion and strange behavior was noted by family members.

The patient was hemodynamically stable except tachycardia in the range of 120 s. After 48 h, the patient had an episode of supraventricular tachycardia (SVT) with a heart rate of 170/min. Standard treatment with carotid massage, adenosine, metoprolol 5 mg intravenously was considered without any response. Examination shows him to be awake and partially oriented. Heart rate decreased from 170 s to 140 s in a few minutes but immediately after that patient developed clenched jaw, up-rolling of eyes, tensed bilateral upper arms with shaking of lower extremities followed by agonal breathing and bradycardia. Pulse was absent and he was noted to be in Pulseless Electrical Activity (PEA) arrest. Cardiopulmonary Resuscitation (CPR) was started with Return of Spontaneous Circulation (ROSC) after one round of CPR. The patient was then emergently intubated and started on mechanical ventilation. Within a few minutes, the patient had another episode of PEA arrest and CPR was initiated with ROSC obtained after two rounds. Admission to Neurosciences intensive care unit (NSICU) was considered for further management.

Hospital Course

The patient remained critically ill in the neurosciences intensive care unit with persistent hypotension requiring multiple pressors including vasopressin, norepinephrine and phenylephrine. The patient was started on empiric antibiotics with vancomycin and cefepime. Sedated with IV midazolam and fentanyl. Considering his symptoms due to baclofen withdrawal, we started with oral baclofen of 90 mg 4 times a day. Other medications include oxycodone 5 mg twice a day, tizanidine 2 mg three times a day, Keppra 750 mg twice a day, hydrocortisone 50 mg intravenously q6 hourly, and gabapentin 300 mg daily. The initial investigations included blood analysis that showed elevated white count of 18.25 × 10 (9)/L, hemoglobin of 8.3 g/dl, platelets of 215 × 10 (9)/L. Patient has elevated lactic acid of 8.5 which subsequently improved in the course of ICU stay. Imaging with CT head shows no acute intracranial findings. Chest X ray shows small left sided pleural effusion, bilateral airspace opacities concerning edema, aspiration or pneumonia. CT chest with pulmonary embolism (PE) protocol was negative for pulmonary embolism but shows diffuse left patchy consolidative opacities and right lung with tree in bud appearance. Partial collapse of bilateral lower lobes, left greater than right. MRI Brain shows no acute intracranial findings, multiple intracranial metastatic lesions that are unchanged in size and number. CT abdomen and pelvis showed subcutaneous air/fluid collection at the site of the pump explanted, right abdominal wall spinal stimulator generator, suspicious for abscess. 2D echo showed normal left ventricular function with ejection fraction is 55%. Overall regional wall motion is grossly normal with grossly normal valvular functions. Electroencephalography (EEG) showed severe encephalopathy of a non-specific etiology. No focal abnormalities or epileptiform activity was present. Eventually, the patient showed hemodynamic improvement, started with weaning pressors, and the midazolam drip was titrated down slowly. The patient had a complicated course in the ICU with desaturation episodes secondary to atelectasis and pneumonia, also had multiple therapeutic bronchoscopies due to large volume of secretions and mucus plugs removed. Due to severe deconditioning and level of spinal injury, we were unable to extubate the patient, leading to tracheostomy placement on day 16th of ICU. After successful weaning to trach collar, patient was discharged to long term care facility ( LTAC) after 42 days of hospital stay.

Discussion

Baclofen is widely used for treatment of moderate to severe spasticity associated with traumatic injuries especially spinal cord injuries and other diseases including multiple sclerosis. ⁷ Baclofen use is also found beneficial in conditions like alcohol use disorder ( AUD) , musculoskeletal pain, persistent and chronic hiccups. ⁴ Baclofen is available in oral and intra-thecal form. Oral baclofen is well absorbed and has bioavailability of approximately 75–80%. ⁷ Intrathecal baclofen is used in patients with resistant spasticity with oral baclofen. Intra thecal baclofen is directly administered into the intrathecal space and achieves therapeutic CSF concentration 100 times less than plasma concentration achieved with oral route.^3,4 Baclofen toxicity and withdrawal are concerning complications. Baclofen withdrawal can occur in patients taking both oral and intrathecal use. Our case shows withdrawal symptoms after 24-48 hours of removal of intra thecal pump. Due to rapid progression of symptoms and high morbidity and mortality, early recognition and treatment is necessary.

Withdrawal symptoms vary from non-specific symptoms including change/ altered mental status, nausea, fever, pruritus, worsening spasticity, weakness, irritability and restlessness to hallucinations, delirium, seizures, autonomic instability, arrhythmias and cardiac arrest if left untreated.^5,6,8-10 Our case represents the severe nature of withdrawal with tachycardia in the form of supra ventricular tachycardia (SVT), pulseless electrical activity (PEA)/ Cardiac arrest after removal of intra thecal pump. High degree of clinical vigilance is required as baclofen toxicity mimics other conditions including severe sepsis, malignant hyperthermia, serotonin syndrome and neuroleptic malignant syndrome (NMS). Baclofen withdrawal is a clinical diagnosis and has no specific testing or imaging available. History and clinical examination is key to early diagnosis and to rule out other diseases with similar presentations. Even though literature has not mentioned any specific laboratory or imaging for patients with baclofen withdrawal but basic laboratory work up including complete blood work, metabolic panel, lactic acid, CK level, chest X ray, Echo and CT head are required to rule out other differentials (Table 1).

Table 1.

Clinical Symptoms and Signs of Intrathecal Baclofen (ITB) Withdrawal.^5,6,8-13

General	Hyperthermia, Insomnia, Multiorgan Failure, Death
Respiratory	Tachypnea, respiratory failure
Cardiovascular	Brady or tachycardia, labile blood pressure, cardiomyopathy
Gastrointestinal	Nausea, vomiting, diarrhea
Psychology	Anxiety, mania, psychosis, depersonalization, confusion
Neurological	Delirium, hallucinations, disorientation, drowsiness, seizures
Musculoskeletal	Muscle stiffness, spasticity, rhabdomyolysis

Treatment of baclofen withdrawal includes close monitoring in the ICU, avoidance of dehydration, supportive treatment in terms of respiratory and cardiac, management of associated symptoms such as delirium and seizures.^14-16 Restarting baclofen is the cornerstone of baclofen withdrawal treatment. Restoration of medication preferably the same route and same dosage as before.

In our case, intra thecal pump was removed, so intra thecal option was not available. We were limited with few options for treatment as there is no standard oral to intrathecal conversion available to be started in patients with baclofen withdrawal. Poor absorption of oral baclofen in critically ill patients and pharmacological limitation of oral baclofen such as having short half life, poor blood brain barrier penetration, supra spinal CNS activity causing sedation, confusion, and dizziness limiting oral baclofen use in our patient. We treated our patient with benzodiazepine and propofol. After a few days of continued treatment with supportive management including mechanical ventilation and pressors, the patient started showing clinical improvement. The patient’s clinical recovery is delayed due to multiple factors including atelectasis, pneumonia with difficulty in weaning from mechanical ventilation. Due to severe deconditioning and difficulty to wean from mechanical ventilation, the patient underwent tracheostomy on day 16th of admission to the ICU. After successful weaning to trach collar, patient was discharged to long term care facility (LTAC) after 42 days of hospital stay. At 6 months follow up, the patient had been managed with enteral baclofen without the need for reimplantation of the IT pump.

Our case report highlights the importance of clinician’s high index of suspicion and emphasis on recognizing the wide range of baclofen withdrawal symptoms.

ORCID iD

Singh Karminder https://orcid.org/0009-0000-3033-8334