Uncovering the rate and risk factors of intrathecal baclofen pump-associated complications in the adult population.

OBJECTIVE: The aim of this study was 1) to describe the rate of intrathecal baclofen (ITB)-associated complications at a large tertiary center, and 2) to evaluate the impact of patient-related factors on the likelihood of developing such complications. METHODS: A retrospective single-center study was carried out. A total of 301 eligible patients were included in the analysis. Univariate regression models were used to evaluate the impact of age, sex, diagnosis, ambulation status, modified Ashworth scale score, body mass index, diabetes status, and pain level on the likelihood of developing a device-related infection, pump malfunction, catheter malfunction, and other clinically significant complications. RESULTS: Overall, 27% of patients experienced an ITB-related complication. The most common complications included infection (6%, 18/301), pump malfunction (7.3%, 22/301), and catheter malfunction (14%, 42/301). The univariate analyses revealed that the patient's ambulatory status had a significant impact on the likelihood of developing a catheter-related malfunction. Furthermore, a trend toward significance was identified between patients' preoperative body mass index and device-related infection. Finally, the risk of suffering any ITB-related complications was statistically correlated with the number of years that had passed since the initial pump implantation. CONCLUSIONS: The authors' analysis reveals a previously underrecognized association between ambulatory status at the time of ITB pump implantation and the incidence of catheter-related complications, and confirms the impact of time since surgery on the risk of developing any ITB-related complication. The patient's age, sex, diagnosis, diabetes status, or pain level at baseline were not associated with the risk of complications. Collectively, these insights contribute novel information to the existing literature, providing practical value for physicians in guiding patient selection for ITB therapy.

Spinal catheter revision in pediatric intrathecal baclofen pumps: risk factors and postoperative outcomes.

OBJECTIVE: Intrathecal baclofen (ITB) pumps are commonly used in pediatric patients with cerebral palsy (CP) and medically refractory spasticity. However, catheter malfunction and associated risk factors are not well understood. The aim of this study was to examine potential risk factors for spinal catheter malfunction and characterize postoperative follow-up to understand the clinical consequences. METHODS: Patients who received ITB pump replacement or revision at Boston Children's Hospital between 2010 and 2023 were retrospectively reviewed. The spinal catheter revision cohort (SCRC) included patients whose spinal catheter was occluded requiring lumbar catheter revision. The second cohort included abdominal pump replacements only (APRC). Between-group comparisons and multivariable regression identified factors associated with catheter revision and postoperative outcomes. RESULTS: Forty-one (33.6%) patients underwent spinal catheter revision and were compared with 81 patients (66.4%) who underwent abdominal pump replacement only. Younger age at surgery and an elevated preoperative lower-extremity modified Ashworth scale grade were associated with spinal catheter revision (p < 0.05). Catheter model type, tip location, and history of spinal fusion were not associated with obstruction. Postoperatively, SCRC patients experienced a higher rate of infection (17.1%) relative to APRC patients (0%) within 30 days from their ITB pump replacement procedure (p < 0.05) and greater likelihood of subsequent ITB system removal compared with the APRC (24.4% vs 7.4%, p < 0.05). Although not differing preoperatively, SCRC patients had lower postoperative ITB doses when compared with the APRC group (median dose 143 vs 350 µg/day, p < 0.05) at hospital discharge and remained statistically different at the 6-month and 1-year follow-ups (p < 0.05). There were no postoperative differences in baclofen overdose, withdrawal, or median number of hospital readmissions within 30 days. Overall, 31.7% of spinal catheter revisions were unanticipated by the clinical team at time of surgery. CONCLUSIONS: Younger age at surgery and increased preoperative lower-extremity tone may be risk factors for catheter obstruction, resulting in a higher rate of postoperative infection and subsequent ITB pump removal compared with pump replacement alone. Spinal catheter occlusion can complicate revision or replacement procedures, especially when unanticipated. Routine clinical assessment may be inadequate for diagnosing insidious catheter malfunction. Catheter occlusion deserves further study, and routine assessment of catheter patency may be warranted to prevent suboptimal tone therapy.

Treatment of Gamma Hydroxybutyrate Withdrawal in a Pregnant Female: A Case Report.

BACKGROUND: Gamma hydroxybutyrate (GHB) is used illicitly for its sedative hypnotic effects, and those who take it regularly are at risk of developing a substance use disorder. Withdrawal from GHB can include severe symptoms that may require medical management. For GHB use and withdrawal during pregnancy, there are no evidence- or practice-based guidelines to follow, and there is only minimal research literature. CASE SUMMARY: We present the case of a 32-year-old woman, G1P0 at 29 weeks and 6 days of gestation, admitted to the perinatal unit at a tertiary hospital for GHB withdrawal management and stabilization. GHB withdrawal was managed with a combination of baclofen and diazepam. We report the dosing and tapering of these medications throughout her 14-day admission. Withdrawal symptoms were well managed with this medication protocol, and she did not experience any features of complicated withdrawal. The patient later presented to hospital in preterm labor and precipitously delivered a healthy, preterm infant male at 34 weeks and 5 days of gestation. At 7 months postpartum, the patient continued to engage with perinatal addiction service, reported no use of GHB since her admission, and was parenting her healthy son. CLINICAL SIGNIFICANCE: There is a paucity of guidelines for managing GHB withdrawal in pregnancy. This case demonstrates good clinical outcomes administering a short-term combination of diazepam and baclofen during the third trimester of pregnancy. This case helps to fill a gap in the literature and may inform future research or clinical decision-making in similar situations.

Opening Pressure and Post-Lumbar Puncture Headache in Children Undergoing Intrathecal Baclofen Trial.

Aims: Post-lumbar puncture headache occurs in 5% to 12% of children. The purpose of this study was to determine the frequency and predictors of post-lumbar puncture headache in children with hypertonia undergoing lumbar puncture for intrathecal baclofen trial. Methods: This was a retrospective single-center review of all 43 children (<18 years) with hypertonia and/or dyskinesia undergoing intrathecal baclofen trial from 2013-2022. Predictors of post-lumbar puncture headache were evaluated via 2-way paired t test and Fisher exact test. Results: Seven subjects (16.3%) developed post-lumbar puncture headache. Of patients who developed post-lumbar puncture headache, 3 required emergency care or hospitalization. One was misdiagnosed with constipation. The 16 patients without opening pressure measured were excluded from subsequent analyses. Of the 27 patients with documented opening pressure, the mean opening pressure was 24.0 cm H2O (SD 6.5) and 5 (18.5%) had elevated opening pressure (>28 cm H2O). Mean opening pressure was higher for those with post-lumbar puncture headache (28.6 vs 22.4 cm H2O, P = .014). Sixty percent of patients with elevated opening pressure developed post-lumbar puncture headache. Baclofen pumps were placed in 4 (80%) patients with elevated opening pressure and 6 (85.7%) with post-lumbar puncture headaches without complications. Interpretation: The risk of post-lumbar puncture headache after intrathecal baclofen trial was higher than reported in the literature, likely because of greater rates of elevated opening pressure. Physicians may use opening pressure to predict risk for post-lumbar puncture headache and should educate families about symptoms. Elevated opening pressure or post-lumbar puncture headache may not preclude baclofen pump placement.

Baclofen in the treatment of alcohol use disorder: tailored doses matter.

AIMS: To address the question of tailored baclofen prescribing in alcohol use disorder (AUD) in relation to dose-dependent efficacy and the potential danger of high doses and to provide suggestions for the use of high doses of baclofen in the treatment of AUD. The context is the approvement in France of baclofen in the treatment of AUD without dose limitation, making French physicians, who usually prescribe baclofen in a tailored manner, often use high or very high doses. METHODS: A narrative review of the results of randomized controlled trials (RCTs) and observational studies that used tailored baclofen prescribing and of the severe adverse effects of baclofen that have been reported in the literature. RESULTS: The results show that RCTs using tailored doses of baclofen in AUD are not completely demonstrative, though they are encouraging according to certain meta-analyses, while observational studies that used tailored doses constantly show a good effectiveness of baclofen treatment. The results suggest that many severe adverse effects of baclofen could be related to a nonrespect by physicians of prescription rules and appropriate treatment monitoring. CONCLUSIONS: The use of tailored doses shows that the dose required to suppress cravings is highly variable, low or high, depending on each case. Analysis of the circumstances in which severe adverse effects occur suggest that a careful monitoring of baclofen prescribing might prevent a large majority of severe adverse effects. We propose that the education of the patients and the prescription skills, seriousness, and availability of the prescribing physicians are of major importance in the managing of tailored baclofen treatment of AUD.

Intrathecal baclofen for the management of hereditary spastic paraparesis: a systematic review.

This systematic review aims to evaluate the use of intrathecal baclofen (ITB) for hereditary spastic paraparesis (HSP) treatment. An extensive search in two electronical databases was performed. We identified articles published between 1990 and 2022 (PubMed, Scopus), and applied the following inclusion criteria: diagnosis of HSP at the time of the intervention, either familial or sporadic; report on the effect of ITB in patients with HSP; test trial via either bolus injections or continuous infusion tests; and ITB pump implantation. A data extraction sheet based on the Cochrane Consumers and Communication Review Group's data extraction template was created and adapted to collect relevant data. A qualitative analysis was performed to present the results in narrative summary fashion. A total of 6 studies met our inclusion criteria. 51 patients with HSP had a pre-implantation ITB trial. The time since the diagnosis until the pump implantation ranged from 5 to 30 years. The initial bolus ranged from 20 to 50 µg and the mean doses used at steady state ranged from 65 to 705 µg. An improvement in spasticity was observed on the modified Ashworth Scale in patients treated with ITB. Although all studies reported a subjective gait improvement, not all found an objective improvement in gait. The most common side effect reported was catheter-related problems. The findings of this review support the use of ITB as an effective and a viable option for the treatment of spasticity in HSP refractory to conservative therapies.

Baclofen and Tizanidine Adverse Effects Observed Among Community-Dwelling Adults Above the Age of 50 Years: A Systematic Review.

OBJECTIVE: This review highlights adverse effects of baclofen and tizanidine in older community-dwelling adults. DATA SOURCES: A literature search was conducted, including search terms of "adverse effect," "baclofen," "elderly," "falls," "fractures," and "tizanidine." Studies were included if they described community-dwelling adults aged 50 years and older who received oral baclofen or tizanidine. The Federal Drug Administration Adverse Event Reporting System (FAERS) data were compiled for adverse effect incidence. STUDY SELECTION AND DATA EXTRACTION: The literature search was completed in July 2019 and updated in June 2023. Reviews performed by 2 independent reviewers yielded 15 records. FAERS identified 486 (baclofen) and 305 (tizanidine) adverse effects of interest. DATA SYNTHESIS: Two retrospective cohort studies evaluating baclofen use in older adults showed increased hospitalizations for encephalopathy in chronic kidney disease (7.2% vs 0.1%) and end-stage renal disease (daily dose 20 mg or more; relative risk [RR] 19.8, 95% CI = [14.0-28.0]). Other articles were case reports; 10 articles reported dyskinesias, encephalopathy or disorientation, and drowsiness associated with baclofen, and 5 articles reported bradycardia and/or hypotension with tizanidine. The FAERS Public Dashboard revealed 12.1% and 28.7% overall incidence of adverse effects of interest, with a 27.8% and 29.2% incidence of falls for baclofen and tizanidine, respectively. Baclofen and tizanidine are associated with concerning adverse effects in older adults. Alternative agents should be considered, but, if necessary, providers should start at lower doses and increase slowly. CONCLUSIONS: This review highlights the importance of using baclofen and tizanidine with caution in older adults.

Baclofen and the risk of fall and fracture in older adults: A real-world cohort study.

BACKGROUND: The growth of oral muscle relaxant prescriptions among older adults in the United States is concerning due to the drugs' adverse sedative effects. Baclofen is a gamma-aminobutyric acid agonist muscle relaxant that is associated with encephalopathy. We characterized the risk of fall and fracture associated with oral baclofen against other muscle relaxants (tizanidine or cyclobenzaprine) in older adults. METHODS: We designed a new-user, active-comparator study using tertiary health system data from Geisinger Health, Pennsylvania (January 2005 through December 2018). Older adults (aged ≥65 years) newly treated with baclofen, tizanidine, or cyclobenzaprine were included. Propensity score-based inverse probability of treatment weighting (IPTW) was used to balance the treatment groups on 58 baseline characteristics. Fine-Gray competing risk regression was used to estimate the risk of fall and fracture. RESULTS: The study cohort comprised of 2205 new baclofen users, 1103 new tizanidine users, and 9708 new cyclobenzaprine users. During a median follow-up of 100 days, baclofen was associated with a higher risk of fall compared to tizanidine (IPTW incidence rate, 108.4 vs. 61.9 per 1000 person-years; subdistribution hazard ratio [SHR], 1.68 [95% CI, 1.20-2.36]). The risk of fall associated with baclofen was comparable to cyclobenzaprine (SHR, 1.17 [95% CI, 0.93-1.47]) with a median follow-up of 106 days. The risk of fracture was similar among patients treated with baclofen versus tizanidine (SHR, 0.85 [95% CI, 0.63-1.14]) or cyclobenzaprine (SHR, 0.85 [95% CI, 0.67-1.07]). CONCLUSIONS: The risk of fall associated with baclofen was greater than tizanidine, but not compared to cyclobenzaprine in older adults. The risk of fracture was comparable among the older users of baclofen, tizanidine, and cyclobenzaprine. Our findings may inform risk-benefit considerations in the increasingly common clinical encounters where oral muscle relaxants are prescribed.

Baclofen pumps do not increase risk of complications following spinal fusion.

PURPOSE: To assess the complication risks associated with intrathecal baclofen (ITB) pumps in cerebral palsy (CP) patients undergoing posterior spinal fusion (PSF) and to determine if timing of pump implantation before or during PSF impacts the risk of complications. METHODS: A prospectively collected multicenter database was retrospectively reviewed to identify CP patients undergoing PSF from 2008 to 2023. Patients were divided into 2 cohorts: those with an ITB pump (ITB cohort) and those without (non-ITB cohort). The ITB cohort was further categorized by placement of the pump prior to or during PSF. Cohorts were then compared in terms of postoperative complications, perioperative complications, and need for revision surgery. RESULTS: Four hundred six patients (ITB n = 79 [53 prior to, 26 during PSF], non-ITB n = 326) were included in this analysis. At an average follow-up of 4.0 years (range 2-10 years), there were no significant differences between the ITB and non-ITB cohorts in the rate of perioperative complications (5.0% vs 6.5%, p = 0.80), revision surgeries (2.5% vs 4.6%, p = 0.54), or any complication type, regardless of whether pumps were placed prior to or during PSF, aside from longer surgical times in the latter group. CONCLUSION: Complication rates are similar for ITBs placed prior to and during PSF. Patients with spastic CP may safely be treated with ITB pumps without increased risks of complication or further reoperation/revision following PSF. LEVEL OF EVIDENCE: Level III.

Baclofen Toxicity in a Patient with End-stage Renal Disease on Maintenance Dialysis.

Baclofen is a ß-(p-chlorophenyl) derivative of the neurotransmitter y-aminobutyrio acid (GABA). This centrally-acting GABA agonist is prescribed as therapy for spasticity in the spinal cord region. The drug is predominantly excreted by the kidney, thus making patients with kidney disease susceptible to side effects. We report on a patient with end-stage renal disease who developed baclofen toxicity, which was successfully treated with intense hemodialysis.

Treatment of severe tardive dyskinesia with concurrent administration of olanzapine, clonazepam, baclofen, and gabapentin: a case report.

BACKGROUND: Long-term use of antipsychotics or other dopamine antagonists can result in the extrapyramidal side effect of tardive dyskinesia (TD).Case presentation: An 18-year-old female patient experienced abnormal speech and behavior and because of an equivocal diagnosis, she was given daily doses of 300 mg of quetiapine and 60 mg of ziprasidone. She had used these medications for 2 years before the appearance of involuntary abnormal movements. These movements, which were classified as TD, steadily worsened and markedly interfered with her daily life. Following a trial-and-error course of therapy with vitamin E, vitamin B6, amantadine, valproic acid sodium, lorazepam, and diazepam, the drugs were gradually reduced and stopped, yet the aberrant movements persisted. Finally, the patient was given olanzapine, clonazepam, baclofen, and gabapentin. The Abnormal Involuntary Movement Scale was used to assess changes in the patient's condition. Her TD was efficiently managed through co-administration of olanzapine, clonazepam, baclofen, and gabapentin. CONCLUSIONS: The possibility of TD inducing by antipsychotic use is a clinical concern, even though atypical antipsychotics decrease the incidence of extrapyramidal side effects, and it cannot be entirely excluded. This report provides useful insights into the management of TD and will help clinicians manage similar cases.

Characteristics of Changes in Intrathecal Baclofen Dosage over Time due to Causative Disease.

Intrathecal baclofen (ITB) therapy effectively treats spasticity caused by brain or spinal cord lesions. However, only a few studies compare the course of treatment for different diseases. We investigated the change in daily dose of baclofen per year and its associated adverse events in patients presenting with the three most common etiologies at our institute: hereditary spastic paraplegia, cerebral palsy, and spinal cord injury. The ITB pumps were implanted from July 2007 to August 2019, with a mean follow-up period of 70 months. In patients with hereditary spastic paraplegia, baclofen dosage was reduced after eight years following ITB introduction, and the treatment was terminated in one patient owing to disease progression. In patients with cerebral palsy, the dosage increased gradually, and became constant in the 11th year. Patients with spinal cord injury gradually increased their baclofen dosage throughout the entire observation period. Severity and adverse event rates were higher in patients with cerebral palsy than in others. The degree and progression of spasticity varied depending on the causative disease. Understanding the characteristics and natural history of each disease is important when continuing ITB treatment.

Baclofen during alcohol detoxification reduces the need for additional diazepam: a randomized placebo-controlled trial.

Baclofen may reduce the symptoms of alcohol withdrawal, as an alternative or as an adjuvant for benzodiazepines, but the available data are insufficient to support baclofen-assisted alcohol withdrawal. This study investigated the need for diazepam during acute alcohol withdrawal in patients receiving baclofen. In a single-blind, dose-dependent randomized controlled trial with three study arms, 63 patients with alcohol use disorder, starting in-patient benzodiazepine-assisted alcohol detoxification, were randomly assigned to receive placebo (n = 18), baclofen 30 mg/day (N = 20), or baclofen 60 mg/day (N = 25) for 7 days. Diazepam was provided as needed based on the withdrawal symptoms stated by Clinical Institute Withdrawal Assessment for Alcohol-revised. The primary outcome measure was the number of patients in need of diazepam during alcohol detoxification. Secondary outcome measure included the between-group difference in the amount of diazepam needed during alcohol detoxification. Using baclofen 60 mg/day, 32% of patients needed additional diazepam compared to 35% on baclofen 30 mg/day and compared to 72% on placebo (P = .013). The median total amount of diazepam needed was significantly lower in patients receiving baclofen 60 mg/day (0 ± 10 mg diazepam) and baclofen 30 mg/day (0 ± 10 mg diazepam) compared to placebo (10 ± 43 mg diazepam; P = .017). Adverse events were comparable between patients on baclofen and placebo. Baclofen can reduce the withdrawal symptoms during alcohol detoxification. Baclofen was well tolerated and may be considered for the management of alcohol withdrawal syndrome, especially useful in situations where benzodiazepines should be withheld, such as patients with liver impairment.

Systematic review and meta-analysis: Efficacy and safety of baclofen in patients with alcohol use disorder co-morbid liver diseases.

Baclofen is the only drug that has been investigated in randomized controlled studies for anti-craving in patients with alcohol use disorder (AUD) and liver disease. However, the results of its efficacy are controversial due to limited case numbers; therefore, a meta-analysis of all available studies is needed to verify efficacy and safety in this population. This systematic review and meta-analysis were conducted according to the Cochrane Collaboration Handbook (PROSPERO ID: CRD42021284439) clauses. PubMed, Embase, Medline, Cochrane, and Clinical Trials. Gov were searched for patients with AUD co-morbid liver diseases who used baclofen to maintain abstinence. The primary outcome was maintaining abstinence. Baclofen safety was evaluated by adverse reaction occurrence during treatment. A total of 322 patients with AUD co-morbid liver diseases (alcohol-related liver disease, hepatitis C, or cirrhosis) from five studies were included. The total abstinence rate was 53% (95% CI: 0.23-0.84). Specifically, the abstinence rate in patients with alcohol-related liver disease and cirrhosis was 63% and 55%, respectively. We further analyzed the two included randomized controlled studies to compare the efficacy between baclofen and a placebo. There was no significant difference in abstinence rates between baclofen and the placebo (RR: 1.42, 95% CI: 0.41-4.92). One serious adverse event was reported, and no cases of baclofen addiction were found. The abstinence rate in patients with AUD co-morbid liver diseases was 53%; however, the efficacy of baclofen for maintaining abstinence in this population still needs to be validated with further studies.

Twenty years of intrathecal baclofen therapy in Slovenia: a retrospective single-center analysis of complications.

Since the first implantation in July 2001, the intrathecal baclofen (ITB) therapy for patients with generalized spasticity has been used in Slovenia for 20 years. The aim of this retrospective study was to evaluate the rates of different complications, especially if catheter-related complications were less frequent after the introduction of the coated catheter type in February 2013, and the potential correlation between higher baclofen doses and the incidence of complications. We retrospectively collected data from all patients in the registry during the period from 3 July 2001 to 31 December 2021. Among 138 patients (48 females), 120 patients had the first ITB system implanted at the University Medical Centre Ljubljana. Forty-three complications were reported in 38 patients (27%), with a total complication rate of 0.203/1000 days or 0.074/pump year. The most frequent was catheter-related (0.083/1000 days or 0.030/pump year), followed by skin-related (0.063/1000 days or 0.023/pump year) and pump-related complication (0.026/1000 days or 0.009/pump year). The incidence of catheter-related complications decreased significantly since the use of Ascenda type catheter: 14/7 complications per 88/147 implantations ( P  = 0.008). Patients with complications had a statistically significantly higher dose of baclofen: median 400 µg/24h vs. median 300 µg/24h ( P  = 0.016). Our retrospective analysis confirmed a significant decrease of catheter-related complications after the implementation of Ascenda type catheter in February 2013. Patients with a higher ITB dose had a statistically significantly higher incidence of complications. The total complication rate was a bit higher as previously reported in other studies, which is consistent with a long follow-up time.

Decompression for lumbar spinal stenosis at the intrathecal catheter insertion site during intrathecal baclofen therapy: a case report.

BACKGROUND: Intrathecal baclofen therapy can substantially improve symptoms in most patients with severe spasticity due to traumatic spinal cord injury, multiple sclerosis, or cerebral paresis. To the best of our knowledge, decompression surgeries at the intrathecal catheter insertion site in patients with a preexisting intrathecal pump for drug delivery have not been reported. CASE PRESENTATION: We report the case of a 61-year-old Japanese man with lumbar spinal stenosis who underwent intrathecal baclofen therapy. We performed decompression for lumbar spinal stenosis at the intrathecal catheter insertion site during intrathecal baclofen therapy. The yellow ligament was removed by partial resection of the lamina under a microscope to avoid damage to the intrathecal catheter. The dura mater was distended. No obvious cerebrospinal fluid leakage was observed. Postoperatively, lumbar spinal stenosis symptoms improved, and spasticity remained well controlled with intrathecal baclofen therapy. CONCLUSIONS: This is the first reported case of lumbar spinal stenosis decompression at an intrathecal catheter insertion site during intrathecal baclofen therapy. Preoperative preparation is necessary, as the intrathecal catheter may be replaced during surgery. We performed surgery without removing or replacing the intrathecal catheter, taking care not to damage the spinal cord by migrating the intrathecal catheter.