Intrathecal baclofen therapy over 10 years.
The Decade of the Brain saw advances in treatment for neurological disorders, especially chronic conditions. One example is intrathecal baclofen (ITB) therapy, a technique introduced in the 1980s. Baclofen (Lioresal intrathecal) infused long term directly into the intrathecal space using the Synchromed Infusion System was approved by the Food and Drug Administration in 1992 for spinal origin spasticity and in 1996 for cerebral origin spasticity. It is now accepted internationally as standard care for severe spasticity (Albright, Gilmartin, Swift, Krach, Ivanhoe, & McLaughlin, 2003; Awaad, Tayem, Munoz, Ham, Michon, & Awaad, 2003; Emery, 2003; Gilmartin, et al. 2000; Ivanhoe, Tilton, & Francisco, 2001; Meythaler, Guin-Renfroe, Brunner, & Hadley, 2001).
Across the United States, ITB is offered at a number of settings by various team members. To offer this therapy locally and fulfill a community need, the Neuroscience Implant Program (NIP) was developed within a tertiary-care regional medical center of a rural state. This unique advanced practice nurse-managed program accepted referrals for patients considered as candidates for implanted devices for neurological disorders. ITB was the first therapy offered through this program, but vagus nerve stimulation and deep brain stimulation treatments were added later. All therapies were managed in collaboration with the patient's neurologist. This allowed each neurologist the opportunity to offer treatment with implanted devices without the expense and time necessary to acquire the specific skills and equipment, and yet continue their role as healthcare provider for their patients with a chronic condition. In addition, NIP staff members collaborated with other physicians and medical center departments such as rehabilitation, nursing units, surgery, and radiology as needed. Consequently, development of the NIP allowed all residents of the rural state access to these innovative therapies with an experienced team.
A database was developed to track ITB patient demographics, dosing, and complications. After this therapy had been offered for 10 years, changes in ITB management were noted using the database. This article provides a retrospective review of 50 patients treated with ITB for up to 10 years with comparison to published reports and practices of national experts.
Over 10 years, beginning during the original multi-center clinical trial, 140 people were referred for evaluation for potential screening trial, implantation, and management of ITB therapy. Of these, 17 patients were not appropriate candidates and were not screened. Five patients completed screening trials but were not deemed appropriate for long-term therapy. Consequently, 118 patients were implanted with the Synchromed Infusion System by a pain management specialist or neurosurgeon for chronic ITB infusion. In addition, 12 patients who were implanted with the system at other sites were referred; four were seen only for system evaluation. Therefore, 126 implanted patients were followed by the author for at least 1 year. Of these, 35 were lost to follow-up or referred to a pain specialist for addition of a second drug, morphine, for example, to their baclofen for intrathecal infusion. Fourteen died from causes unrelated to ITB. Two were explanted because of complications (specifically, repeat catheter malfunction). Five patients, 4 adults, and 1 child with cerebral palsy (CP) were explanted because of dissatisfaction with the therapy. Seventy patients with ITB continued with the NIP.
During the winter of 2002-2003, the first 50 patients to sign consents were interviewed and a retrospective chart review was conducted. The project, including consent, received institutional review board approval. Database expansion continued, but this report includes only the first 50 patients.
These 50 patients represented an accumulated 2,922 months (i.e., 243.5 years) of ITB therapy. Individual patient experience ranged from 1 to 10 years (mean 4.8 years) of ITB therapy. Twenty-one patients received their first pump during the first 5 years (1993-1997) and 29 had their original implant during the second 5 years (1998-2002) of the 10-year experience. Thirteen patients had commercial insurance, 22 received Centers for Medicare and Medicaid Services (CMS) insurance, and 15 had both.
Age at implant of the 50 patients ranged from 2.75 to 61.75 years (mean 32.5 years). Patients were referred by adult neurologists (n = 20), child neurologists (n = 15), physical or occupational therapists (n = 5), internist/family practice physicians (n = 4), family or friends (n = 3), physiatrists (n = 2), and orthopedic surgeons (n = 1). Of the 50 patients reviewed, 42 were referred before implant and 8 were first seen after having the system implanted at another site.
The 50 patients resided throughout the rural state. Twenty-two patients came from the same city as the NIP, 17 patients lived within 100 miles, and 11 patients lived greater than 100 miles away.
A variety of diagnoses were represented including the following: multiple sclerosis (ms; n = 19), cerebral palsy (CP; n = 18), brain injury (n = 7), familial spastic paraparesis (n = 3), spinal cord injury (n = 2), and hereditary progressive muscular dystrophy (n = 1). All patients had been diagnosed by a neurologist. CP was defined as brain injury before age 2, whereas other brain injury includes anoxia, stroke, or traumatic brain injury after age 2. All the CP patients could be classified as mixed hypertonia as described by Sanger et al. (2003). At the time of original implant, 28 patients had comorbidity including 9 with a single comorbid process (including 4 with hypertension, 2 with arthritis, 2 with mild mental retardation, and 1 with Reflex Sympathetic Dystrophy). Of the 19 patients with multiple comorbidities, 16 had a history of seizures, 13 were diagnosed with mental retardation, 10 had gastrostomy feeding tubes, 6 had tracheotomies, 5 had hydrocephalus, and 12 had other disease states.
During clinical trials throughout the early 1990s in the United States, the patients' catheter tip was routinely placed at or below the T10 vertebral level. This was true for all (n = 21) patients included in this review who were implanted during the first 5 years. Over the next 5 years, 79% (n = 23) of the implanted catheters were threaded to T9 or higher, up to T2 vertebral level.
Depending on patient size, the pumps implanted in these patients had reservoir volumes of 18 ml (n = 41) or 10 ml (n = 9). Pumps were refilled by sterile technique in an outpatient clinic. Fifty-eight percent of the patients returned to clinic for pump refill every 3 months (n = 29). However, 28% (n = 14) of patients had refills every 5-11 weeks and 14% (n = 7) of patients returned every 4 weeks or fewer to have their device refilled. Only commercially available Lioresal Intrathecal with maximum 2,000 [micro]g/ml concentration was used.
Programming infusion dose and mode occurred at the time of refill or as needed. For the total group, current daily doses ranged from 32 to 2,160 [micro]g with an average of 463 [micro]g. The titration phase, defined as stable dose for 6 weeks, varied among diagnostic groups but was completed by 42% (n = 21) of patients within the first 6 months post-implant. During the first 9 months of offering this therapy, simple infusion mode was programmed for all patients. This represents a total of 51 patient months of ITB therapy. Over time, variation of drug infusion was implemented and at the time of data collection, complex infusion mode was used with 54% (n = 27) of patients while 32% (n = 16) had simple infusion mode and 14% (n = 7) had periodic bolus. Periodic bolus was programmed to occur every 1.5-3 hours. For the 27 patients, using complex infusion, 67% (n = 18) had 2 steps and 33% (n = 8) used 3 or 4 steps. Of those 34 patients using complex or periodic bolus mode, 76.5% (n = 26) had this programming method initiated within the first 6 months.
Fifteen patients (i.e., 30%) with model 8610 series pumps with anticipated end-of-battery life were scheduled for replacements based on risk factors for acute withdrawal complications. These included high ITB dose, unstable patient general condition, rural residence, and patient or caregiver not likely to recognize early signs of end-of-battery life. In five patients (i.e., 10%), catheter disruptions required surgical intervention and their 8610 series pumps were at least 3.5 years old. Therefore, these pumps were replaced at the time of catheter revision. Three CP patients with anticipated pump end-of-battery life scheduled pump replacements during school break. Simultaneously, because of low catheter tip level and the need for upper extremity spasticity relief, their catheters were replaced and the tip was threaded to a higher spine level.
Pump- or catheter-system failure, surgical complications, or adverse drug effects were identified as "events." Thirty of the 50 patients experienced a total of 65 events in the 243.5 patient years of therapy. These ranged from mild (n = 21) defined as "additional office visit required" to severe (n = 44) defined as "required or prolonged hospital stay."
The event profile improved between the group of patients implanted during the first 5 years and the group implanted during the second 5 years. This included a 21.7% decrease in number of total events per month of service and a 24% decrease in number of severe events per month of service. Eighty percent of the patients implanted during the first 5 years experienced an event, whereas only 44% of patients implanted during the second 5 years experienced an event. Event cause and frequency are summarized in Tables 1 and 2.
Twenty-three of 50 patients had 34 pump replacements. One pump was replaced because of sudden motor stall. Eleven of these 23 patients received a third pump because of routine end-of-battery life pump replacement. Eighteen pumps were replaced because of actual end-of-battery life identified by the low battery alarm. Re-implant occurred within 2 weeks of recognized low battery alarm. The 18 replaced pumps provided from 39 to 60 months of service (mean 48 months). Seventeen of the 18 replaced pumps were the first generation model 8610 series. The other was 8627 series with 10-ml reservoir volume and functioned 48 months before low battery alarm sounded.
Surgical complications decreased for the group implanted during the second 5 years compared with those implanted during the first 5 years. Of the patients implanted during the second 5 years, none had catheters dislodge from the spinal insertion site and there were fewer seromas and cerebrospinal fluid leaks.
Drug withdrawal usually arises from system malfunction, whereas drug overdose or high-dose effects result from human error. Although the percentage of patients suffering drug-related effects increased, the ratio of adverse drug effects caused by the clinician's decision-making process declined. During the first 5 years, 71% of the overdoses causing altered level of consciousness occurred during system evaluation using the pump model without a catheter access port. Conversely, 66% of the adverse drug events during the second 5 years were from patient management issues such as missed refills and other healthcare providers changing oral drugs that influence tone.
Information collected about functional outcome was based on goals established before pump implant. Goals were determined by a collaboration of patient, caregivers, family and friends, therapists, teachers, and healthcare practitioners. Based on subjective reporting by patients and their care team, all 50 patients achieved short-term goals within 3 months after pump implant. The most common immediate goals included
* increased comfort (e.g., decreased pain and enhanced sleep)
* increased ease of care (i.e., diapering, dressing, orthotics application, positioning, and hygiene)
* increased safety in transfers
* increased independence in activities of daily living
* improved communication
* improved ambulation.
Based on patient or caregiver report, 78% (n = 39) achieved long-term goals such as eliminated the need for wheelchair, returned to work full time, or ambulated about the home without assistive device. Some had unrealistic goals (e.g., a patient with progressive disease hoping to continue independent ambulation). Although parents of three patients expressed regret after the pump was implanted in their child, they chose pump replacement at end-of-battery life. Four others who questioned the long-term benefit of ITB also elected to have a replacement pump implanted. The 14% (n = 7) who voiced some regret were implanted during the first 5 years of the program. The remaining 86% (n = 43) of the 50 patients or caregivers expressed no regret having 1TB therapy initiated.
Differences between the three most common diagnostic groups are summarized in Table 3. The subset (n = 19) of patients with MS had ITB therapy for 11-114 months (mean = 45 months). Average age at implant was 45.6 years with a range of 28.5-61.25 years. They had refills between 2 and 3 months, and the group dose range was 65-768 [micro]g/day (mean = 238 [micro]g/day). The majority of patients with MS (n = 14) used complex infusion with two steps for higher dosing during the night. This relieved the common and painful spasms during sleep but allowed tone needed for functions such as ambulation or transfers from wheelchair during the day. It was relatively easy to find the appropriate steady dose for these patients, and 13 of these patients had complex programming initiated within the first 6 months. However, because of the extreme temperature changes in Kansas, it is not uncommon to make seasonal dose changes to compensate for the tone-increasing cold winds or fatiguing humidity and heat. At the time of implant, 84% (n = 16) of the patients ambulated about their home but were dependent on their wheelchair outside of the home. At the time of data collection, despite the progressive nature of MS, 68% (n = 13) were still able to ambulate about their home.
Eighteen patients with CP had varying patterns and severity of spasticity. Of these 18 patients, 61% required total care; 22% could bear weight and assist with transfers but otherwise depended on a wheelchair; and 17% were community ambulators. This group's average age at implant was 13.3 years with a range of 2.75-51.5 years. The dose range was 99-1393 [micro]g/day with an average 534 [micro]g/day. This group had a total 1,489 months of service with a range of 20-119 months of service. Eleven patients used complex or periodic bolus infusion modes and most (54%) required more than 9 months of therapy to achieve total daily dose titration with simple infusion. Most (71%) have three or more steps in their complex infusion or 2-hour intervals in periodic bolus. Titration period (i.e., steady dose for 6 weeks) was longest in this group, often requiring steady, small dose increases throughout growth during adolescence. Because these patients were younger, the 10-ml reservoir pumps were used more frequently. Thus, compared with other diagnostic groups, their refills were more frequent with 22% requiring refills at least every month.
Seven patients had brain injury (stroke, anoxia, and trauma) with average age at implant of 28 years with a range of 6.75-51.5 years. All these patients were implanted with their ITB pump more than 1 year after injury. The average was 4.8 years from injury to implant. Their doses ranged between 90 and 2,160 [micro]g/day with an average 908 [micro]g/day. This group had a total 401 months of service with a range of 17-110 months of service. Frequently, consistent tone throughout a 24-hour period allowed for simple infusion mode (55%) and the severity of spasticity required more rapid dose titration. Patients (42%) who were obtunded, comatose, or in a locked-in state required the highest daily dose and were most likely to require additional oral medications to achieve goals of prevention of skin breakdown and ease of care.
The objective of this retrospective chart review and database development was to identify trends in ITB management to better choose, educate, and treat patients with severe spasticity. Findings reflect practices, complications, and effects of ITB described in previously published summaries (Albright, 2003; Albright et al., 2003; Emery, 2003; Stempien & Tsai, 2000; Gilmartin et al., 2000; Ivanhoe et al., 2000). Catheter tip location, infusion mode, and complication rates were three changing trends identified.
Placement of the intrathecal catheter tip at a higher vertebral level was one course in this evolving therapy. In the early 1990s the standard catheter tip placement was the lower thoracic region of the spinal canal. The frequently cited research of Kroin, Amjad, York, and Penn (1993) reported that after intrathecal infusion in 5 patients, there was gradual decline in hydrophilic radionuclide in cerebrospinal fluid between T2 and T12 levels. It was concluded that placing the catheter tip at more rostral levels may not provide any advantage. However, Grabb, Meythaler, and Guin-Renfroe (1999) reported midthoracic (T6-T7) placement of the catheter tip provided greater reduction in upper extremity spasticity without loss of effect on lower extremities despite lower baclofen dosages. In addition, no complications were related to higher positioning of the catheter tip in the spinal canal. Ivanhoe et al. (2001) reported the practice of placing the catheter tip at T6-7 was gaining favor to increase upper extremity benefit without losing lower extremity effectiveness. Experienced 1TB therapy providers at high-volume centers reported placing the catheter tip at C7 to T2 region for treatment of spastic quadriparesis and T10-12 for treatment of spastic paraparesis as standard practice (L. Albright, M. Turner, G. Bilsky, and L. Krach, personal communication, March 6, 2004).
The second change that evolved was dosing patterns and use of various infusion modes. Although doses vary among all patients receiving ITB, these findings reflect programming differences for diagnostic groups as described by others. Simple infusion mode was commonly used long term for all patients 10 years ago. Simple infusion continues to be used for the titration phase and ongoing dosing for patients with stable and consistent tone like those with spinal cord injury. However, maximizing therapy by individualizing infusion and dosing has become routine. As stated earlier, two-step complex infusion with higher night dosing aides patients with MS. Multiple dose change throughout the day using complex or periodic bolus accommodates patients with CP. Periodic bolus provides advantages while maintaining total daily dose without increased side effects. In addition, a therapeutic effect was maintained in children with CP with incremental dose titration over the first 2-3 years, at which time the dose tends to level off (Albright et al., 2003; Awaad et al., 2003; Gilmartin et al., 2000). Also, a higher dose was commonly required for patients with spinal cord injury compared to patients with multiple sclerosis (Penn et al., 1989). Overall, dosing changes have become more conservative for patients with cerebral palsy and MS compared with dose changes for bed-bound patients with spinal injury or traumatic brain injury.
Safety of ITB therapy varies over time and mechanism of reporting. However, this report of 44% of more recently implanted patients experiencing adverse events is similar to other reports (Albright et al., 2003; Follett & Naumann, 2000; Gianino, York, Paice, & Shott, 1998; Stempien & Tsai, 2000) and demonstrates the third trend--decreased problems over time. Stempien and Tsai found that improvements in equipment such as catheter durability and maneuverability prevent system failure. Experienced implanting neurosurgeons state that changes in technique and equipment, particularly catheters, have decreased their complication rates (L. Albright & M. Tumer, personal communication, March 6, 2004).
The improved safety of ITB therapy at this center can be related to revised equipment, as well as techniques for system management. Equipment changes that influenced the decrease in complications included use of the pump with a catheter access port. This model was routinely implanted after the first year, which allowed safe and easy aspiration of the complete catheter volume and infusion of contrast to assess catheter patency. Therefore, decreased accidental overdosing was prevented. In addition, remodeled catheters, connectors, fasteners, and software enhanced the safety profile.
Changes over time in technique and clinician experience in each phase of the therapy that could explain decreased complications and drug adverse event include the following::
* refined patient selection with consideration of comorbidities and requi-red treatments
* patient education for early identification of potential pump/catheter system or drug problems
* revised technique for securing catheter at spine entry site
* pump replacement at anticipated end-of-battery service to avoid withdrawal
* rapid and safe evaluation to identify system failure
* anticipated catheter malfunction if dose increased with little or no effect.
Development of realistic goals and measuring change from ITB therapy deserves further discussion. Many report outcomes of chronic ITB therapy. Some quantify functional changes (Awaad et al., 2003) and others use patient and caregiver subjective perception of ease of care, improved comfort, and satisfaction with results. This report, like that of Krach, Nettleton, and Klempka (2003), demonstrates that despite complications associated with the developing technology, few patients regret their choice of having the system implanted. However, because the therapy benefits a wide range of disabilities, developing specific team generated goals and quantifying change has been challenging. As therapy evolves, gold standard clinical evaluation of technical, functional, patient satisfaction, care and comfort, and cost-effective outcomes as described by Pierson (1997), as well as multiple levels of evidence, should be applied to further enhance ITB therapy.
This report of a small sample was a retrospective chart review and therefore dependent on accurate documentation. All were patients of the author, and therefore bias is inherent. In addition, the 50 patients described were available from the current practice. Therefore, any patient choosing to have the pump removed or to be followed elsewhere could not have been included.
There are many areas for further research to identify best standards of practice for chronic ITB therapy. Objective measures of outcomes are needed in addition to the patient and caregiver subjective satisfaction report. The potential adverse effects of compounded baclofen versus commercially available drug has yet to be documented. Also, comparison of outcomes for specific programming modes such as 2- or 4-hour periodic boluses would be valuable. Third, investigators developing tools to measure care and comfort outcomes deserve support.
ITB is useful in treating patients who suffer from spastic tone with a wide range of age at implant, etiology, age at onset of symptoms, functional level, and comorbidities. Professional experience of the team involved in ITB management contributes to patient satisfaction and increasing safety of the therapy. This report further supports the Albright et al. statement (2003, p. 294) "the substantial frequency of side effects and complications during long-term ITB therapy indicates the need for a dedicated team of individuals at each institution who can identify problems readily and address these issues as the need arises."
Table 1. Adverse Event Summary First 5 Second 5 Total Years of Years of Group Experience Experience n (n = 50) (n = 21) (n = 29) Number of adverse events 65 39 26 Events that were mild, requiring office visit 21 32% 33% 31% Events that were severe, requiring hospitalization 44 67% 67% 69% Events requiring surgical intervention 37 56% 56% 58% Events related to drug 14 21% 21% 23% Patients with any complica- tions 30 60% 80% 44% Patients with catheter failure 16 32% 48% 20% Table 2. Adverse Event Etiology (N = 65) First 5 Second 5 Event Total Years Years Surgical/Procedural 27 17 10 Benign seroma of pump site 8 5 3 Pump flip 7 3 4 Cerebrospinal fluid leak 5 3 2 Catheter dislodged at spine insertion site 4 4 0 Wound dehiscence, pump salvaged 2 1 1 Aseptic meningitis at screening trial 1 1 0 Drug-Related Adverse Effect (system 14 8 6 intact) Too high dose causing alteration in level of consciousness 9 7 2 Withdrawal due to missed refill 3 1 2 Baclofen side effects when oral medication added 2 0 2 System 24 14 10 Catheter Kink/break at pump site, surgically repaired 11 6 5 Kink/break at spine, surgically repaired 6 4 2 Catheter replaced, resolution of symptoms 3 2 1 Catheter tip migrated to subdural space 2 2 0 Cath kink, withdrawal symptoms, manually manipulated 1 0 1 Pump Stall 1 0 1 Table 3. Diagnostic Groups Average Average Age Average Months of at Implant Daily Dose Diagnosis N Service (years) ([micro]g/day) Multiple Sclerosis 19 45 45.6 238 Cerebral Palsy 18 83 13.3 534 Brain Injury 7 57 28.0 908 Most Common Diagnosis Infusion Mode Multiple Sclerosis Two-step complex Cerebral Palsy Complex or periodic bolus Brain Injury Simple
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Awaad, Y., Tayem, H., Munoz, S., Ham, S., Michon, A.M., & Awaad, R. (2003). Functional assessment following intrathecal baclofen therapy in children with spastic cerebral palsy. Journal of Child Neurology, 18(1), 26-34.
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Pierson, S.H. (1997). Outcome measures in spasticity management. Muscle and Nerve, 20(6 Suppl.), S1-S25.
Sanger, D.S., Delgado, M.R., Gaebler Spira, D., Hallett, M., Mink, J.W., & the Task Force on Childhood Motor Disorders (2003). Classification and definition of disorders causing hypertonia in childhood. Pediatrics, 111(1), 89-97.
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Questions or comments about this article may be directed to Patrice Korth Rawlins, ARNP MN, by phone at 316/268-5194 or by e-mail at email@example.com. She is a clinical nurse specialist in the neuroscience implant program at Via Christi Regional Medical Center, Wichita, KS.
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|Author:||Rawlins, Patrice Korth|
|Publication:||Journal of Neuroscience Nursing|
|Date:||Dec 1, 2004|
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