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.

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.

Surgical complications of intrathecal baclofen in children: A single centre, 20-year retrospective cohort study.

INTRODUCTION: Complications of intrathecal baclofen treatment (ITB) with an implanted pump can be severe and require surgery. Surgical implantation techniques and catheter materials for continuous ITB treatment have improved over the past years with the aim to reduce complications. OBJECTIVE: To assess: 1) the type and rate of complications of ITB that require surgical intervention, 2) which risk factors influence the occurrence of complications, and, specifically, 3) whether complication rate is influenced by type of catheter used. METHODS: A retrospective cohort study was conducted including all children (<18 years old) in one university medical center with pump implantation between 2001 and 2017. All complications requiring surgery were recorded. Risk factors for surgical intervention were determined using multiple logistic regression analysis. Catheter related complications between two types of catheters (silicone vs coated) were compared. RESULTS: In total, 88 complications of ITB treatment requiring surgery were found in 47 (36.2%) out of 130 children. These included catheter-related complications (55.7% of all complications), infections (21.6%), cerebrospinal fluid leakage (14.8%), and pump-related complications (7.9%). The silicone catheter type, used until 2012, was found to be a significant risk factor for complications (Odds Ratio 3.75; 95% CI: 1.30-10.83). Since the introduction of the coated catheter type, in 2012, the rate of catheter-related complications decreased, from 0.15 to 0.10 complications per pump year. CONCLUSION: The rate of surgical complications of intrathecal baclofen in children is high, and most frequently catheter-related. The number of complications decreased since the introduction of a new, coated, catheter in 2012. This study helps to inform children and their caregivers about the risk of possible complications of ITB, and to identify directions for future improvement of ITB care.

Efficacy and safety of tolperisone versus baclofen among Chinese patients with spasticity associated with spinal cord injury: a non-randomized retrospective study

There are many medications available to treat spasticity, but the tolerability of medications is the main issue for choosing the best treatment. The objectives of this study were to compare the efficacy and adverse effects of tolperisone compared to baclofen among patients with spasticity associated with spinal cord injury. Patients received baclofen plus physical therapy (BAF+PT, n=135) or tolperisone plus physical therapy (TOL+PT, n=116), or physical therapy alone (PT, n=180). The modified Ashworth scale score, the modified Medical Research Council score, the Barthel Index score, and the Disability Assessment scale score were improved (P<0.05 for all) in all the patients at the end of 6 weeks compared to before interventions. After 6 weeks, the overall coefficient of efficacy of the intervention(s) in the BAF+PT, TOL+PT, and PT groups were 1.15, 0.45, and 0.05, respectively. The patients of the BAF+PT group reported asthenia, drowsiness, and sleepiness and those of the TOL+PT group reported dyspepsia and epigastric pain as adverse effects. When comparing drug interventions to physical therapy alone, both baclofen plus physical therapy and tolperisone plus physical therapy played a significant role in the improvement of daily activities of patients. Nonetheless, baclofen plus physical therapy was tentatively effective. Tolperisone plus physical therapy was slightly effective. In addition, baclofen caused adverse effects related to the sedative manifestation (Level of Evidence: III; Technical Efficacy Stage: 4).

Out of sight: a lesson in drug errors.

A 76-year-old man developed recurrent encephalopathy, visual disturbance, myoclonus, generalised seizures and atonic drop attacks on a background of a gastrectomy for adenocarcinoma and stable chronic lymphocytic leukaemia. He presented to three different hospitals and was admitted twice, with normal investigations. His symptoms transiently improved during each admission (and with starting levetiracetam) but recurred each time on hospital discharge. Subsequent careful inspection of his medication box identified that his community pharmacy had in error been dispensing baclofen 80 mg per day instead of his prescribed Buscopan 80 mg per day. This case highlights the importance of physically inspecting a patient's medications and emphasises the spectrum of baclofen-related toxicity; it also highlights potential deficiencies in the pharmacy dispensary process and the need for multiple checks by patients and professionals.

Reducing Intrathecal Baclofen Related Infections: Service Evaluation and Best Practice Guidelines.

OBJECTIVES: Intrathecal baclofen (ITB) pumps are an effective treatment for spasticity; however infection rates have been reported in 3-26% of patients in the literature. The multidisciplinary ITB service has been established at The National Hospital for Neurology and Neurosurgery, UCLH, Queen Square, London for over 20 years. Our study was designed to clarify the rate of infection in our ITB patient cohort and secondly, to formulate and implement best practice guidelines and to determine prospectively, whether they effectively reduced infection rates. METHODS: Clinical record review of all patients receiving ITB pre-intervention; January 2013-May 2015, and following practice changes; June 2016-June 2018. RESULTS: Four of 118 patients receiving ITB during the first time period (3.4%, annual incidence rate of infection 1.4%) developed an ITB-related infection (three following ITB pump replacement surgery, one after initial implant). Infections were associated with 4.2% of ITB-related surgical procedures. Three of four pumps required explantation. Following change in practice (pre-operative chlorhexidine skin wash and intraoperative vancomycin wash of the fibrous pocket of the replacement site), only one of 160 ITB patients developed infection (pump not explanted) in the second time period (0.6%, annual incidence rate 0.3%). The infection rate related to ITB surgical procedures was 1.1%. In cases of ITB pump replacement, the infection rate was reduced to 3.3% from 17.6%. CONCLUSIONS: This study suggests that a straightforward change in clinical practice may lower infection rates in patients undergoing ITB therapy.

Dyadic and Solitary Sexual Desire in Patients With Fibromyalgia: A Controlled Study.

INTRODUCTION: Although fibromyalgia symptoms negatively affect patients' sexual life, sexual desire in women diagnosed with fibromyalgia has been understudied. AIM: To describe and compare sexual desire in women diagnosed with fibromyalgia and healthy control women, and to investigate the influence of fibromyalgia and its pharmacologic treatment on sexual desire among women diagnosed with fibromyalgia. METHODS: 164 women diagnosed with fibromyalgia participated in the study. Participants' sexual desire, fibromyalgia symptoms, symptom interference in daily life activities, and perceived quality of life were measured. Further sociodemographic and health-related data were also recorded. 87 healthy women were selected as a control group, and their sexual desire was compared with those of women diagnosed with fibromyalgia. MAIN OUTCOME MEASURES: Main outcome measures included the Sexual Desire Inventory and the Fibromyalgia Impact Questionnaire. RESULTS: When compared with healthy control subjects, women diagnosed with fibromyalgia exhibited a significantly lower mean score on total desire (47.92 ± 17.48 vs 26.33 ± 21.95; P < .001), solitary desire (10.52 ± 5.96 vs 5.74 ± 7.01; P < .001), and dyadic desire (37.40 ± 13.98 vs 20.59 ± 16.94; P < .001). Women diagnosed with fibromyalgia who were taking antidepressants scored significantly lower on dyadic desire (P < .001), solitary desire (P < .001), and total desire (P < .001) than those who were not. Furthermore, a negative correlation between desire (dyadic and solitary) and Revised Fibromyalgia Impact Questionnaire (total and all subscales) was found. Linear regression showed that taking antidepressants, age, and the total Fibromyalgia Impact Questionnaire score explained 16% of the variance of total desire. CLINICAL IMPLICATIONS: Knowing how fibromyalgia symptoms and their pharmacologic treatment affect women's sexual desire may have implications for designing care strategies according to individual needs. STRENGTHS & LIMITATIONS: To the best of our knowledge, this is the first study that focuses on studying the impact of fibromyalgia on dyadic and solitary sexual desire. Limitations are related to having used an online questionnaire for data collection, having recruited the participants through a convenience sampling technique and not being able to isolate whether certain results are related to fibromyalgia symptoms or are side effects of the pharmacologic treatment used for symptom control. CONCLUSION: Fibromyalgia impact seems to negatively influence dyadic and solitary sexual desire in women. In addition, other factors such as age or taking antidepressant drugs may result in lower sexual desire in these patients. López-Rodríguez MM, Pérez Fernández A, Hernández-Padilla JM, et al. Dyadic and Solitary Sexual Desire in Patients With Fibromyalgia: A Controlled Study. J Sex Med 2019;16:1518-1528.

Intrathecal Baclofen Trial Before Device Implantation: 12-Year Experience With Continuous Administration.

OBJECTIVE: To report our experience using continuous intrathecal baclofen (ITB) administration prior to a possible ITB device implantation. DESIGN: Retrospective open label study. Mean duration of follow-up 64 months. SETTING: Primary-care and referral center, ambulatory and hospitalized care. PARTICIPANTS: Patients (N=116) undergoing continuous ITB trials between 2006 and 2017. INTERVENTIONS: Continuous application of baclofen via a temporary intrathecal catheter connected to an external pump. MAIN OUTCOME MEASURES: Assessment of the modified Ashworth Scale and range of movement prior versus end of ITB trial. According to the Barthel Index, definition of high-level patients (60-100 scoring points) and low-level patients (0-55 scoring points). Calculation of the Rivermead Mobility Index in high-level patients prior versus end of ITB trial. Evaluation of occurring adverse events. RESULTS: A total of 119 ITB trials were performed in 116 patients (78 men, mean age 41±16), 113 patients completed the trials (31 of 113 high level, 82 of 113 low level). The median modified Ashworth scale improved from 4 (interquartile range [IQR] 3-4) to 2 (IQR 1-2; P≤.001), the range of movement from 2 (IQR 1-3) to 3 (IQR 3-3; P≤.001). The Rivermead Mobility Index increased from 9 (IQR 6-12) to 10 (IQR 7-12.5; P=.004) in high-level patients. Eighty-eight out of 113 patients (78%) were appropriate candidates for ITB device surgery, 75 of 88 (85%) proceeded to an implantation. A total of 69 adverse events occurred in 57 of 119 trials (48%), 37 of 69 (54%) were drug related, 32 of 69 (46%) were procedure related, and 42 of 69 (61%) were minor. The ITB device was implanted in 69 of 75 patients (92%) at last follow-up. CONCLUSIONS: Continuous administration of ITB is an effective and useful alternative to ITB bolus application during ITB screening period. Half of the patients experienced adverse events; the majority were minor events.

Co-Prescription of Strong CYP1A2 Inhibitors and the Risk of Tizanidine-Associated Hypotension: A Retrospective Cohort Study.

Tizanidine, a widely used muscle relaxant that can lower blood pressure, is metabolized by the cytochrome P450 1A2 (CYP1A2). We studied 1,626 patients prescribed tizanidine and 5,012 prescribed cyclobenzaprine concurrently with a strong CYP1A2 inhibitor. The primary outcome was severe hypotension, defined as systolic blood pressure (SBP) ≤ 70 mmHg during periods of drug co-exposure. Severe hypotension occurred more often in the tizanidine group (2.03%; n = 33) than the cyclobenzaprine group (1.28%; n = 64); odds ratio (OR) = 1.60; P = 0.029. This difference remained statistically significant after adjustment for a log-transformed propensity score that included age, sex, race, Charlson's comorbidity index, and concurrent use of antihypertensive medications (OR = 1.57; P = 0.049). A sensitivity analysis that defined hypotension as SBP < 90 mmHg also yielded higher rates of hypotension among patients prescribed tizanidine. In conclusion, CYP1A2 inhibition increases the risk of hypotensive episodes associated with the use of tizanidine in routine clinical practice.

Caso clínico: Diagnóstico de alergia a relajantes musculares y opiáceos / Case report: Diagnosis of allergy to muscle relaxants and opiates

The anesthesiologist is the specialist who most often faces allergic reactions due to the number of drugs and substances that are exposed to the patient during the course of an intervention. Although they are rare, they have a mortality rate between 3% and 10%. We present a clinical case of a 42-year-old woman with a history of anaphylactic reaction grade 2 that is coordinated for a Werthein-Meigs surgery, for which it is decided to test her with skin tests. The results were positive for morphine, fentanil, remifentanil and atracurium, which directly affected the perioperative management.

El anestesiólogo es el especialista que con mayor frecuencia se enfrenta a reacciones alérgicas por el número de fármacos y sustancias a las que se expone al paciente en el transcurso de una intervención. Si bien son poco frecuentes presentan una mortalidad entre 3 a 10%. Presentamos un caso clínico de una mujer de 42 años con un antecedente de reaccion anafiláctica grado 2 que se coordina para una cirugía de Werthein- Meigs, por lo cual se decide testearla con pruebas cutáneas. Los rsultados fueron positivos para morfina, fentani, remifentanil y atracurio, lo cual incidió directamente en el manejo perioperatorio.

Altered Mental Status at High Altitude.

Intrathecal baclofen pumps are commonly used in pediatric patients with spastic cerebral palsy. Baclofen binds to γ-aminobutyric acid receptors to inhibit both monosynaptic and polysynaptic reflexes at the spinal cord level. The blockade stops the release of excitatory transmitters and thereby decreases muscle contraction. It is commonly used for lower limb spasticity and has been shown to improve postural ability and functional status. The US Food and Drug Administration has approved baclofen for the treatment of spasticity of cerebral or spinal origin in adult and pediatric patients 4 years or older. Various complications of baclofen pumps are described in the literature. Immediately after surgery, problems from infection can arise and range from superficial skin infections to meningitis and bacteremia. Another early complication includes cerebrospinal fluid leak that can be observed by notable swelling beneath the lumbar incision. Additional problems that arise later are usually from the mechanics of the pump and catheter. Pump-related complications include failure, migration, and flipping. Catheter-related complications include disconnection, occlusion, fracture, or kink. Most of these complications typically lead to baclofen withdrawal, although there are a few case reports of overdose due to mechanical causes. Here we describe 2 cases of individuals experiencing complications of excessive baclofen exposure after significant changes in the atmospheric pressure due to travel involving ambient altitude change. These cases reflect the need to discuss this potential complication with families and patients with baclofen pumps before travel to high elevations.

The dosage and administration of long-term intrathecal baclofen therapy for severe spasticity of spinal origin.

STUDY DESIGN: Retrospective chart audit. OBJECTIVE: To indicate the appropriate baclofen dosage to control severe spasticity of spinal origin and to develop the optimal administration protocol for long-term intrathecal baclofen (ITB) therapy. SETTING: Department of Orthopaedic Surgery, Spinal Injuries Center, Japan. METHODS: Thirty-four people with spasticity of various spinal origins who were consistently treated at our hospital were included. The median follow-up period was 6 years and 11 months. Measures of Ashworth score were taken before and after surgical implant of baclofen pump. We decided not to increase the baclofen dosage after the Ashworth score reached 1. We recorded the control of spasticity, changes in the baclofen dose, and the incidence of complications. RESULTS: The average Ashworth score was 3.31 (1.75-4.0) before implant surgery, 1.38 (1.0-2.25) after implant surgery, and 1.39 (1.0-2.25) at the final follow-up, while the average baclofen dose (therapeutic/optimal dose) was 230.6 µg/day (50-450). The incidence of each complication was as follows: 8.8% (n = 3) catheter-related, 2.9% (n = 1) pump-related and 5.9% (n = 2) drug tolerance. No patients experienced withdrawal syndrome. Dose fluctuation with changes in the pathology of the original disease was observed in three cases. CONCLUSIONS: The usage of the Ashworth score as a guide for dose adjustment was found to be a good objective indicator for ITB therapy. The administration based on this objective indicator made it possible to effectively manage patients with a relatively low dose of baclofen and a low rate of drug-related complications.

Bioequivalence of cyclobenzaprine hydrochloride extended-release capsule taken intact or sprinkled over applesauce
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OBJECTIVE: Difficulty swallowing pills can compromise pain control in painful musculoskeletal disorders. This open-label, 2-period crossover study assessed pharmacokinetics and safety of cyclobenzaprine extended-release (CER) 30-mg capsule contents sprinkled over applesauce compared with intact capsules in healthy subjects. MATERIALS AND METHODS: 32 subjects were randomized to treatment sequences AB or BA (A = single CER intact capsule; B = single CER capsule contents sprinkled over applesauce (15 mL)). Treatments were separated by a ≥ 14-day washout. Pharmacokinetic assessments included maximum observed plasma drug concentration (Cmax), time to Cmax (tmax), time to first quantifiable plasma drug concentration (tlag), and area under the plasma drug concentration-vs.-time curve from time 0 to the last measurable drug concentration (AUC0-t) and extrapolated to infinity (AUC0-∞). Bioequivalence was established if the 90% confidence intervals (CIs) of the geometric least squares (LS) means ratios of B:A of Cmax, AUC0-t, and AUC0-∞ were 80 - 125%. Safety was also assessed. RESULTS: Mean plasma drug concentration-vs.-time profiles were similar for CER intact and sprinkled over applesauce. The 90% CIs of LS means ratios indicated bioequivalence: Cmax 91.96 - 100.76%, AUC0-t 96.18 - 103.50%, and AUC0-∞ 95.70 - 103.07%. Median tmax was not significantly different (p > 0.05), and median tlag was the same (1 hour). All adverse effects were mild and resolved during the study. No clinically meaningful changes were noted for clinical laboratory values. CONCLUSION: CER capsules intact and sprinkled over applesauce are bioequivalent. Sprinkling CER capsule contents is not expected to affect efficacy or safety and can, therefore, be an option for patients with musculoskeletal pain and difficulty swallowing capsules.
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Does Intrathecal Baclofen Therapy Increase Prevalence and/or Progression of Neuromuscular Scoliosis?

STUDY DESIGN: Retrospective, case-matched review. OBJECTIVES: Compare a group of individuals with cerebral palsy (CP) who had intrathecal baclofen (ITB) pumps to a group of individuals with CP who did not have ITB pumps in order to determine if there was a difference in the prevalence of new-onset neuromuscular scoliosis, an increased rate of progression of preexisting neuromuscular scoliosis, or an increased rate of posterior spine fusion surgery in skeletally immature individuals with CP who had ITB pumps. SUMMARY OF BACKGROUND DATA: Various authors report conflicting findings, with some reporting an increased incidence or prevalence of scoliosis in individuals with CP who have ITB pumps whereas others report no difference in the rate of scoliosis between groups. METHODS: Retrospective chart and radiographic case-matched study in which individuals were matched by gender and Gross Motor Function Classification Scale (GMFCS) level. RESULTS: We found no difference in the rates of new-onset neuromuscular scoliosis for those with CP and ITB pumps and those without ITB pumps. However, we did see a higher rate of progression as well as an increased rate of posterior spine fusion surgery in individuals with CP who had ITB pumps than for those with CP who did not have an ITB pump. CONCLUSIONS: We continue to recommend ITB pump therapy for individuals with severe spasticity associated with CP (GMFCS IV and V). There is a significant risk of complications for individuals in general. The risk of neuromuscular scoliosis is relatively high in this population. Our findings suggest that individuals with CP who have ITB pumps and who do or do not have preexisting scoliosis should be monitored closely for either developing new neuromuscular scoliosis or progression of preexisting scoliosis.

Intrathecal Baclofen Therapy for the Treatment of Spasticity in Sjögren-Larsson Syndrome.

Intrathecal baclofen therapy is widely accepted as a treatment option for patients with severe spasticity. The current treatment of spasticity in patients with Sjögren-Larsson syndrome is largely symptomatic, given that no effective causal therapy treatments are available. We report the outcome of 2 patients with Sjögren-Larsson syndrome who had pump implantation for intrathecal baclofen. We observed a positive response, with a decrease of spasticity, reflecting in the Modified Ashworth Scale, and parents and caregivers observed a functional improvement in both patients. One patient experienced skin irritation 15 months after surgery, necessitating pump repositioning. No infection occurred. Our report shows that intrathecal baclofen therapy can have a positive therapeutic effect on spasticity in patients with Sjögren-Larsson syndrome, and therefore may be a promising addition to current treatments.