Utilizing combination intrathecal baclofen and analgesic medication to manage spasticity and pain in patients with pediatric-onset disability: Case series

1 Introduction

Intrathecal (IT) drug delivery is utilized for the treatment and management of chronic pain and spasticity when other options have proven unsuccessful [1–4]. IT medications offer patients an alternative to other administration routes, allowing for better symptom control with lower dose requirements and fewer systemic side effects [1, 5]. When considering the use of intrathecal baclofen (ITB) for chronic spasticity in adult and pediatric patients, therapeutic effects can be accomplished with doses up to 100 times lower than oral baclofen [5]. Approximately 7,000 adults and 1,500 children had an intrathecal baclofen pump placed between the years of 2011–2014 [6].

Optimal maintenance dosage is highly individualized and is based on many variables, including patient diagnosis and functional goals [7]. Following optimization of intrathecal baclofen therapy, patients and their caregivers have reported reduction of spasticity and pain leading to improvements in patient communication, sleep, ease of care, and performance of daily activities, as well as other measures of quality of life [8–12]. Although IT monotherapy has been successful for many patients with spasticity or chronic pain, others have not seen significant changes in their symptoms, function, or quality of life after initiation of IT monotherapy. Patients who receive ITB with refractory spasticity and chronic pain after maximizing oral pharmacotherapy may benefit from a second IT agent [2–4].

ITB has been combined with morphine, clonidine, bupivacaine, and ziconotide to improve function and quality of life in adult patients. For example, combination IT therapy with baclofen and morphine has demonstrated decreased pain associated with spasticity and spinal cord injury, and this combination has been shown to reduce neuropathic pain and lower back pain [3, 14]. ITB and morphine has also been successful for a patient with a below-knee amputation who thereafter experienced improved neuropathic pain, higher function in activities of daily living, improved sleep, and increased physical activity [14]. ITB and clonidine or bupivacaine has been used to reduce lower limb pain and neuropathic pain [15–17]. A poly-analgesic combination of ITB, morphine, and clonidine has also reduced severe spasticity-related pain [18]. Combination IT therapy doses in the literature have ranged from 5–1700 mcg of baclofen per day, 12–33 mcg of clonidine per day, 800-2500 mcg of morphine per day, and 1.7–14.4 mcg of ziconotide per day [14, 20].

Few side effects and adverse events have been reported for combination IT therapy, and those that were reported were common for individual pharmacotherapies rather than an effect of the combination of medications. For example, three patients receiving ITB and morphine in a study by Saulino (2012) reported subjective cognitive dysfunction and sedation that caused them to return to strictly using ITB, and eight patients reported constipation, nausea, and fatigue related to the morphine in their pumps but were able to tolerate combination therapy for at least one year [4].

Research on combination medication pump therapy for the management of spasticity and pain syndromes exists primarily in the adult population. However, no evidence-based guidelines are available for the pediatric population. The aim of this study was to evaluate the use of combination IT medication delivery on function, pain, and quality of life for patients with pediatric-onset disabilities.

2 Methods

Patients in an outpatient pediatric rehabilitation clinic were included in this case series if they experienced spasticity and pain that were managed with a combination of ITB and IT analgesia. Fifty patients in the clinic had ITB pumps. A total of nine patients with combination IT medication were identified; however, only eight were included in this case series as one pump was explanted due to infection which did not allow sufficient time to assess effectiveness of combination medication. IT bupivacaine was selected as the first-line analgesic medication to use in all patients due to lowest risk of respiratory depression, cognitive dysfunction, sedation, or respiratory depression. IT morphine was selected as an analgesic medication in those patients who did not achieve adequate pain control with bupivacaine. IT clonidine was selected as an analgesic medication in those patients experiencing pain when there was a concern for respiratory complications with morphine or in attempts to target neuropathic pain. The authors conducted a retrospective review of these patient’s electronic medical records, followed by a phone survey with each patient and their family/caregiver. Per electronic medical record review, documentation of primary movement disorder type was noted, along with patient and/or caregiver subjectively-reported significance of effect on function, activities of daily living, and severity of symptoms.

A four-question telephone survey was conducted to gather information from the families/caregivers of the eight patients regarding improvements in pain, spasticity, function, and quality of life after the initiation of combination IT medication therapy. The families were called once by staff to alert them that a survey was going to be conducted via telephone, and a second call was conducted by a resident physician for completion of the survey. Informed consent was obtained for all participants. This study was approved by the Institutional Review Board.

3 Results

The age range of included patients was 5–27 years of age (median age of 21 years). Of the eight patients included in this case series, six carried a diagnosis of cerebral palsy, and one each with Leigh syndrome and stroke. For the six patients with available Gross Motor Function Classification System (GMFCS) and Manual Ability Classification System (MACS) classification, all were GMFCS V and MACS 4–5. Table 1 shows the type of movement disorder pattern noted among patients.

All of the patients were transitioned to a combination IT medication due to pain that remained uncontrolled despite maximization of ITB dosing in combination with conservative measures and oral opioids. Significant variability in duration of management of spasticity with ITB was noted prior to this transition. All eight patients were initiated with a combination of ITB and bupivacaine. Four patients required a third medication for symptomatic control of pain. Following the initiation of the combination IT medication therapy, 87.5% (n = 7) of patients noted significant improvement in spasticity, 75% (n = 6) noted significant improvement in pain, and 75% (n = 6) reported improvement in function. The most notable finding was that 87.5 % (n = 7) of patients reported an improvement in their quality of life with their pump after initiation of multiple IT medications. The complete survey results are shown in.

Seven of the eight patients (87.5%) had a history of receiving a combination of toxin injections, bracing, and serial casting in addition to their ITB pump for management of spasticity prior to transitioning to a combination IT therapy. Only three of the patients (37.5%) with combination IT therapy required these interventions at the time of the survey. All eight patients reduced utilization of daily oral anti-spasticity and analgesic medications after initiation of their combination IT pump. The average number of daily oral anti-spasticity and analgesic medications decreased from 4.25 medications to 1.88 medications after initiation of their combination IT medication as seen in Figure 1.

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Fig. 1

Number of oral medications before and after combination intrathecal medication therapy.

ITB dosing remained relatively stable prior to and after initiation of the combination IT medication. The mode of IT delivery included flex dosing mode (n = 3), simple continuous (n = 4), and simple continuous with patient-initiated self-bolus dosing (n = 1), as shown in Table 1. Prior to initiation of combination IT medication, all patients were trialed with varied dosing patterns in an attempt to maximize the benefit of IT monotherapy. Ultimate dosing modes were selected based on the patient needs to optimize function and manage symptoms. One patient required the use of self-bolus dosing to control symptoms due to need for boluses at varied times during the day in order to maximize the effectiveness of IT therapy without worsening symptoms of concurrent medical conditions. Dosing patterns were unchanged with the addition of a third IT medication and not dependent on the IT combination medications selected. Prior to initiation of combination IT therapy, malfunction of pumps and catheter were thoroughly assessed and ruled out. Complications remained consistent with those described for ITB monotherapy, and no additional complications were experienced.

5 Discussion

This case series represents the utility of combination medications in IT pumps for the treatment of severe spasticity and chronic pain in patients with childhood-onset disability. It demonstrates that initiation of combination IT therapy can result in improved function, pain, and quality of life, as well as a significant decrease in the need for supplemental or concurrent treatment with oral medications.

Pediatric patients with spasticity from cerebral palsy experience spasticity-related pain at rates as high as 80–85% [21]. Although irreversible procedures such as selective dorsal rhizotomy (SDR) exist for patients with intractable spasticity, they are invasive and carry high risks of neurologic injury [22]. Furthermore, ITB has demonstrated increased improvements in pain when compared to SDR [23]. Therefore, using IT medications to manage both spasticity and pain should be strongly considered by pediatric physiatrists and neurosurgeons.

There is minimal research in adult populations and no research in pediatric populations regarding the use of IT pumps for administration of multiple medications. Furthermore, little is known regarding long-term effects of spasticity and pain management using a combination of IT medications. This creates a significant need for continued longitudinal research in this population to improve outcomes for pediatric patients with spasticity and chronic pain. Future studies should also consider which types of pain (e.g., neuropathic, nociceptive) are most alleviated by IT pumps with combination therapy.

6 Limitations

Limitations of this study are related to the case series design, including selection bias and lack of a control group for comparison. Furthermore, perspectives from caregivers and/or families were relied upon, as all patients were not able to answer survey questions independently due to cognitive impairment or lack of a functional communication device. Recall bias may have also influenced participant responses to the survey questions. Rather than using a validated survey, questions were created that were most unique to the patient population. In the questions related to pain, the family/caregiver was not asked to specifically characterize the type of pain. Pain in this population can often be multifactorial and can also be difficult to discern. A relatively small sample size with great heterogeneity of diagnoses makes this case series more challenging to generalize to the greater population. However, given the limited existing literature on combination IT medication pump therapy for spasticity and pain management in patients with childhood-onset disabilities, this case series contributes substantial consideration for future practice.

7 Conclusion

This case series demonstrates success in using combination IT medication delivery to improve spasticity, pain, function, and quality of life in patients with pediatric-onset disabilities. This is the first case series to outline the use and effectiveness of combination IT drug therapy in this population. The results suggest safety and benefit in this patient population in areas of pain and spasticity. Additional studies are warranted to further quantify this benefit and to directly compare it to traditional ITB therapy. Given that 75% of people living with cerebral palsy experience pain, there is an indication for combination IT therapy as a treatment option for these patients [24]. The use of combination antispasmodic and analgesic IT drug therapy should be considered in the management of patients with childhood-onset disabilities who have both severe spasticity and severe chronic pain.