Intrathecal Drug Delivery Research Articles

ID:16405 Look Before You Leap: The Importance of Preoperative Imaging Prior to Intrathecal Therapies

An 84-year-old, male with longstanding chronic low back pain was referred to outpatient pain clinic for intrathecal drug delivery system planning. After the patient was deemed a candidate for placement, a pre-operative MRI of the spine was ordered which revealed an extra-axial T2 hyperintense collection overlying the right frontoparietal region measuring 1.8 cm in thickness with some associated mass effect (see image). This was later evaluated with CT imaging and determined to be a chronic right sided subdural hematoma.

Investigation of Human Intrathecal Solute Transport Dynamics Using a Novel in vitro Cerebrospinal Fluid System Analog.

Understanding the relationship between cerebrospinal fluid (CSF) dynamics and intrathecal drug delivery (ITDD) injection parameters is essential to improve treatment of central nervous system (CNS) disorders. An anatomically detailed in vitro model of the complete CSF system was constructed. Patient-specific cardiac- and respiratory-induced CSF oscillations were input to the model in the subarachnoid space and within the ventricles. CSF production was input at the lateral ventricles and CSF absorption at the superior sagittal sinus. A model small molecule simulated drug product containing fluorescein was imaged within the system over a period of 3-h post-lumbar ITDD injections and used to quantify the impact of (a) bolus injection volume and rate, (b) post-injection flush volume, rate, and timing, (c) injection location, and (d) type of injection device. For each experiment, neuraxial distribution of fluorescein in terms of spatial temporal concentration, area-under-the-curve (AUC), and percent of injected dose (%ID) to the brain was quantified at a time point 3-h post-injection. For all experiments conducted with ITDD administration in the lumbar spine, %ID to the brain did not exceed 11.6% at a time point 3-h post-injection. Addition of a 12 mL flush slightly increased solute transport to the brain up to +3.9%ID compared to without a flush (p < 0.01). Implantation of a lumbar catheter with the tip at an equivalent location to the lumbar placed needle, but with rostral tip orientation, resulted in a small improvement of 1.5%ID to the brain (p < 0.05). An increase of bolus volume from 5 to 20 mL improved solute transport to the brain from 5.0 to 6.3%ID, but this improvement was not statistically significant. Increasing bolus injection rate from 5 to 13.3 mL/min lacked improvement of solute transport to the brain, with a value of 6.3 compared to 5.7%ID. The in vitro modeling approach allowed precisely controlled and repeatable parametric investigation of ITDD injection protocols and devices. In combination, the results predict that parametric changes in lumbar spine ITDD-injection related parameters and devices can alter %ID to the brain and be tuned to optimize therapeutic benefit to CNS targets.

Intrathecal Drug Delivery: Advances and Applications in the Management of Chronic Pain Patient.

Advances in our understanding of the biology of spinal systems in organizing and defining the content of exteroceptive information upon which higher centers define the state of the organism and its role in the regulation of somatic and automatic output, defining the motor response of the organism, along with the unique biology and spatial organization of this space, have resulted in an increased focus on therapeutics targeted at this extracranial neuraxial space. Intrathecal (IT) drug delivery systems (IDDS) are well-established as an effective therapeutic approach to patients with chronic non-malignant or malignant pain and as a tool for management of patients with severe spasticity and to deliver therapeutics that address a myriad of spinal pathologies. The risk to benefit ratio of IDD makes it a useful interventional approach. While not without risks, this approach has a significant therapeutic safety margin when employed using drugs with a validated safety profile and by skilled practioners. The present review addresses current advances in our understanding of the biology and dynamics of the intrathecal space, therapeutic platforms, novel therapeutics, delivery technology, issues of safety and rational implementation of its therapy, with a particular emphasis upon the management of pain.

241 Intrathecal antisense oligonucleotide delivery in HD: experience from RG6042 programme and best practice considerations

Intrathecal administration involves the introduction of a drug substance into the subarachnoid space of the spinal column through a needle inserted into the lower back via lumbar puncture (LP) or via a special device. This procedure is used when drugs cannot cross the blood-brain barrier. Once injected, drugs are distributed within the cerebrospinal fluid from which they can access target tissues in spinal cord and brain.We use the intrathecal route to deliver RG6042 (previously HTTRx), an investigational, huntingtin mRNA- targeting antisense oligonucleotide to patients with Huntington’s disease (HD). Experience on intrathe- cal administration via LP has been gained in the RG6042 clinical development programme, including the double-blind, placebo-controlled, multiple ascending dose, Phase I/IIa study (NCT02519036) in 46 patients with early manifest HD and an open-label extension (NCT03342053) where patients received 120 mg RG6042 monthly or every other month in a 62-week treatment period (total procedures ≥400 in the programme to date).We will report on the experience with intrathecal drug delivery across these two studies and present information on suggested best practices in HD. Procedure-related videos will be shared, including use of spinal ultrasound. Finally, we will describe real-world considerations of implementing intrathecally delivered therapies in the clinical interface.alessia.nicotra@roche.com

Long-term open-label phase I/II extension study of intrathecal idursulfase-IT in the treatment of neuronopathic mucopolysaccharidosis II

Intrathecal (IT) idursulfase-IT for the treatment of cognitive impairment is being investigated in pediatric patients with neuronopathic mucopolysaccharidosis II (MPS II) in addition to intravenous idursulfase. In this article, we report the findings for 54 months of idursulfase-IT treatment in an ongoing phase I/II extension trial (NCT01506141). A total of 15 male participants with neuronopathic MPS II (aged 3-11 years at enrollment) who were previously treated with intravenous idursulfase entered the extension study. Idursulfase-IT 10 mg or 30 mg was administered monthly via an IT drug delivery device or lumbar puncture, if indicated. The primary endpoint was safety and tolerability; secondary endpoints included pharmacokinetics, cerebrospinal fluid glycosaminoglycan levels, and cognitive function. In total, 15 participants received a median (range) of 50 (18-55) idursulfase-IT doses. Idursulfase-IT was generally well tolerated; there were no life-threatening adverse events (AEs) or deaths. Most serious AEs were related to the IT drug delivery device; only 2 serious AEs were related solely to idursulfase-IT. After treatment with idursulfase-IT, cerebrospinal fluid glycosaminoglycans were decreased in all participants; these decreases were maintained. Cognitive function was stabilized in 3 of 4 testable participants at month55. These long-term results support the clinical development of idursulfase-IT for patients with MPS II with cognitive impairment.

A novel chronic dural port platform for continuous collection of cerebrospinal fluid and intrathecal drug delivery in free-moving mice

BackgroundCerebrospinal fluid (CSF) provides a close representation of pathophysiological changes occurring in the central nervous system (CNS); therefore, it has been employed in pathogenesis research and biomarker development for CNS disorders. CSF obtained from valid mouse models relevant to CNS disorders can be an important resource for successful biomarker and drug development. However, the limited volume of CSF that can be collected from tiny intrathecal spaces and the technical difficulties involved in CSF sampling has been a bottleneck that has hindered the detailed analysis of CSF in mouse models.MethodsWe developed a novel chronic dural port (CDP) method without cannulation for CSF collection of mice. This method enables easy and repeated access to the intrathecal space in a free-moving, unanesthetized mouse, thereby enabling continuous long-term CSF collection with minimal tissue damage and providing a large volume of high-quality CSF from a single mouse. When combined with chemical biosensors, the CDP method allows for real-time monitoring of the dynamic changes in neurochemicals in the CSF at a one-second temporal resolution in free-moving mice. Moreover, the CDP can serve as a direct access point for the intrathecal injection of CSF tracers and drugs.ResultsWe established a CDP implantation and continuous CSF collection protocol. The CSF collected using CDP was not contaminated with blood and maintained physiological concentrations of basic electrolytes and proteins. The CDP method did not affect mouse’s physiological behavior or induce tissue damage, thereby enabling a stable CSF collection for up to four weeks. The spatio-temporal distribution of CSF tracers delivered using CDP revealed that CSF metabolism in different brain areas is dynamic. The direct intrathecal delivery of centrally acting drugs using CDP enabled real-time behavioral assessments in free-moving mice.ConclusionsThe CDP method enables the collection of a large volume of high-quality CSF and direct intrathecal drug administration with real-time behavioral assessment in free-moving mice. Combined with animal models relevant to CNS disorders, this method provides a unique and valuable platform for biomarker and therapeutic drug research.

Intrathecal Drug Delivery Systems Survey: Trends in Utilization in Pain Practice.

BackgroundThe use of intrathecal drug delivery for chronic and cancer pain medicine has been established for decades. However, optimization and utilization of this technique still lag behind other modalities for pain control. Some of this may be due to variability of surgical technique, medication usage and education. It is currently unclear on whether or not practitioners follow available algorithms for the use of intrathecal drug delivery systems.MethodsA survey developed by the American Society of Pain and Neuroscience (ASPN) was sent to its members via email using the cloud-based SurveyMonkey. After 30 days of being available, 159 different providers responded to the survey that consisted of 31 various multiple choice and free response questions. Each question was not required and the number of responses to each varied from 128 to 159.ResultsApproximately 9% of those who successfully received and opened the email containing the survey responded, likely due to a small number of providers working with intrathecal drug delivery systems. Eighty-six of respondents practice medicine in the United States, and 87% of the respondents were attending physicians. A majority of respondents, approximately 74%, were board certified in pain medicine with 69% of respondents being train in anesthesiology. The first and second most used medications for intrathecal pump trial were morphine and fentanyl, respectively. Most respondents, approximately 96%, provide pre-operative/intra-operative antibiotics. The most common first-choice medication for implanted intrathecal pumps was also morphine with the most common implanted location being the abdomen.ConclusionInterestingly, there is currently fairly substantial variation in the way providers utilize intrathecal pump delivery for both chronic and cancer pain. There is variation from the training background of the providers providing care, to the pre-implantation trial medications, to where the pump is implanted for each patient, to if the patient has the option to give themselves boluses once implanted. Further research is needed to elucidate current and best practices for intrathecal drug delivery system trials, implantations, and utilization.

Ampakine‐Hypoxia Induced Phrenic Motor Facilitation is Not Prevented by Intrathecal Methysergide

Hypoxia‐induced sustained increases in phrenic nerve burst amplitude lasting beyond the hypoxic stimulus are generally accepted to require repeated bouts of hypoxia (i.e., acute intermittent hypoxia, AIH). However, our laboratory recently reported that pretreatment with a drug (ampakine) which acts as a positive allosteric modulator of AMPA receptors lowered the number of hypoxic exposures required to trigger sustained phrenic motor facilitation. Our working hypothesis for the current study was that the combination of ampakine and hypoxia activates the same serotonin (5‐HT) dependent cellular mechanisms that are well established for AIH‐induced phrenic long‐term facilitation following repeated bouts of moderate hypoxia. Phrenic nerve output was recorded from vagotomized, mechanically ventilated, adult male Sprague‐Dawley rats under urethane‐anesthesia. A broad‐spectrum 5‐HT receptor antagonist (methysergide, 20mM, dissolved in DMSO) was delivered intrathecally over the C4 spinal dorsal surface. At least 15 min of stable phrenic burst amplitude was recorded post methysergide delivery. After a stable baseline (BL) was established, intravenous (i.v.) ampakine (CX717, 15mg/kg) was followed by a single episode of hypoxia (arterial partial pressure of O2 = 42±9mmHg). Phrenic nerve bursting was recorded for 60 min after hypoxia. Initial results indicate that intrathecal methysergide does not prevent the ampakine‐hypoxia induced phrenic motor facilitation as evidenced by a significant increase in burst amplitude at 60 min (89±54% BL, n=7). To verify the efficacy of intrathecal drug delivery method, additional experiments were conducted. Specifically, we determined if intrathecal methysergide prevented the phrenic long‐term facilitation induced by AIH, as has been shown by several prior investigations. These experiments used the same preparation, and AIH consisted of three‐5 min episodes of hypoxia with 5‐min intervals of baseline O2conditions. Intrathecal methysergide blocked pLTF (60 min post‐AIH, phrenic burst amplitude = ‐2±31% BL, n=3), but intrathecal delivery of the DMSO vehicle did not (60 min: 94±28% BL, n=3). Collectively, these results do not support our hypothesis that phrenic motor facilitation induced by the pairing of ampakine with a single bout of hypoxia is dependent on serotonin receptor activation.

Quantifying intraventricular drug delivery utilizing programmable ventriculoperitoneal shunts as the intraventricular access device.

Programmable ventriculoperitoneal shunts (pVP shunts) are increasingly utilized for intraventricular chemotherapy, radioimmunotherapy, and/or cellular therapy. Shunt adjustments allow optimization of drug concentrations in the thecal space with minimization in the peritoneum. This report assesses the success of the pVP shunt as an access device for intraventricular therapies. Quantifying intrathecal drug delivery using scintigraphy by pVP shunt model has not been previously reported. We performed a single-institution, retrospective analysis on patients with CNS tumors and pVP shunts from 2003 to 2020, noting shunt model. pVP flow was evaluated for consideration of compartmental radioimmunotherapy (cRIT) using In-111-DTPA scintigraphy. Scintigraphy studies at 2-4h and at 24h quantified ventricular-thecal and peritoneal drug activity. Twenty-two CSF flow studies were administered to 15 patients (N = 15) with diagnoses including medulloblastoma, metastatic neuroblastoma, pineoblastoma, and choroid plexus carcinoma. Six different types of pVP models were noted. 100% of the studies demonstrated ventriculo-thecal drug activity. 27% (6 of 22) of the studies had no peritoneal uptake visible by imaging. 73% (16 of 22) of the studies had minimal relative peritoneal uptake (< 12%). 27% (6 of 22) of the studies demonstrated moderate relative peritoneal uptake (12-37%). No studies demonstrated peritoneal uptake above 37%. All patients had successful drug delivery of In-111-DTPA to the ventriculo-thecal space. 73% of the patients had minimal relative (< 12%) peritoneal drug uptake. Though efficacy varies by shunt model, low numbers preclude conclusions regarding model superiority. CSF flow scintigraphy studies assesses drug distribution of In-111-DTPA, informing CSF flow for delivery of intraventricular therapies.

Dorsal Versus Ventral Intrathecal Catheter Tip Location and Effect on Dose Escalation and Opioid Use in Patients With Cancer Pain

ObjectivesIn the practice of intrathecal drug delivery, consensus exists regarding the cephalad to caudad location of the catheter tip relative to dermatomal distribution of pain. However, data are lacking on the importance of dorsal vs ventral tip location relative to the spinal cord. We hypothesize that a dorsally placed catheter tip improves efficacy because of closer proximity to nociceptive pathways. Materials and MethodsA retrospective review of 298 patients with cancer with intrathecal drug delivery systems implanted at the Huntsman Cancer Institute from May 2014 to June 2020 was performed. Patients were stratified by catheter tip location zones based on available radiographic studies. Patient-controlled intrathecal medication dose requirements and rate of change were compared with catheter zone and other variables, including the presence of adjuncts such as bupivacaine and ziconotide. ResultsA total of 158 patients were suitable for analysis demonstrating a dorsal tip in 63.9% (n = 101) and ventral tip in 36.1% (n = 57), with a median follow-up of 17 days (interquartile range [IQR], 10–24). There was no difference in daily dose change from implant to discharge between the dorsal group 8.2% (IQR, 0.0–41.5) and ventral group 20.8% (IQR, 0.0–66.7; p = 0.12). Daily dose change from discharge to follow-up was 2.6% (IQR, 0.0–7.1) in the dorsal group and 1.8% (IQR, 0.0–5.7) in the ventral group (p = 0.92). Catheter tip location had no impact on systemic opioid use. ConclusionsWe did not find significant associations between dorsal vs ventral catheter tip location and measures of pain relief, including change in intrathecal dose or systemic opioid use.

Ultrasound-guided "saline myelogram": Confirmation of intrathecal drug delivery despite "dry tap" in infants for spinal anesthesia and spinal therapeutics.

Ultrasound-guided "saline myelogram": Confirmation of intrathecal drug delivery despite "dry tap" in infants for spinal anesthesia and spinal therapeutics.

363 Efficacy of Flexible Intrathecal Morphine Delivery in the Treatment of Chronic Pain

INTRODUCTION: The use of intrathecal morphine via a morphine drug delivery system has been shown as a promising alternative to the treatment of chronic pain. These programmable devices can deliver morphine via simple or flexible programs. Simple programs release morphine continuously at the same rate over a 24-hour period, whereas flexible programs are optimized to release different dosages at different times. METHODS: Patients were enrolled at St. James Mercy Hospital, University of Rochester, New York from February 2016 to February 2020. An out-patient intrathecal morphine trial was performed by injecting a single dose of 0.1-0.3 mg of preservative free morphine in the lumbar intrathecal space. Following at least 60% reduction in pain compared to baseline, a permanent intrathecal catheter and morphine pump were implanted. The drug delivery system was programmed to deliver morphine doses in a simple continuous or flexible mode. Follow up visits occurred between 12 and 60 months, and the efficacy of the flexible dosing was assessed. RESULTS: 58 patients enrolled (34 female, 24 male, median age 59), 46 patients were on flexible dose morphine and 12 were on simple dose morphine. Statistical analysis found a significant difference in pain reduction between the two groups (p &lt; 0.01). The flexible sample had a mean reduction in pain of 8.72 and the simple sample had a mean reduction in pain of 8.17 out of 10 points on the 0-10 pain scale. There were no infections or complications present in the study. CONCLUSION: While both flexible and simple program intrathecal morphine drug delivery system proved effective in reducing chronic pain, flexible programs were significantly more effective. A future multi-center study with a larger sample size is desired.

Minimally-invasive pain management techniques in palliative care.

Pain is a common source of suffering for seriously ill patients. Typical first-line treatments consist of lifestyle modifications and medication therapy, including opioids. However, medical treatments often fail or are associated with limiting systemic toxicities, and more targeted interventional approaches are necessary. Herein, we present options for minimally invasive techniques for the alleviation of pain in palliative patients from a head-to-toe approach, with a focus on emerging therapies and advanced techniques. Head and neck: image-guided interventions targeted to sympathetic ganglia of the head and neck, such as sphenopalatine ganglion (SPG) and stellate ganglion, have been shown to be effective for some forms of sympathetically-maintained and visceral pain. Interventions targeting branches of cranial nerves and upper cervical nerves, such as the glossopharyngeal nerve (GPN), are options in treating somatic head and face pain. Abdominal and pelvic: sympathetic blocks, including celiac plexus, inferior hypogastric, and ganglion impar can relieve visceral abdominal and pelvic pain. Spine and somatic pain: fascial plane blocks of the chest and abdominal wall and myofascial trigger point injections can be used for somatic pain indications. Cementoplasties, such as kyphoplasty and vertebroplasty, are used for pain related to bony metastases and compression fractures. Tumor ablative techniques can also be used for lytic lesions of the bone. Spinal cord stimulation (SCS), intrathecal drug delivery systems (IDDS), and cordotomy have also been used successfully in patients requiring advanced options, such as those with significant spinal, ischemic, or visceral pain.

Human in silico trials for parametric computational fluid dynamics investigation of cerebrospinal fluid drug delivery: impact of injection location, injection protocol, and physiology

BackgroundIntrathecal drug delivery has a significant role in pain management and central nervous system (CNS) disease therapeutics. A fluid-physics based tool to assist clinicians in choosing specific drug doses to the spine or brain may help improve treatment schedules.MethodsThis study applied computational fluid dynamics (CFD) and in vitro model verification to assess intrathecal drug delivery in an anatomically idealized model of the human CSF system with key anatomic features of the CNS. Key parameters analyzed included the role of (a) injection location including lumbar puncture (LP), cisterna magna (CM) and intracerebroventricular (ICV), (b) LP injection rate, injection volume, and flush volume, (c) physiologic factors including cardiac-induced and deep respiration-induced CSF stroke volume increase. Simulations were conducted for 3-h post-injection and used to quantify spatial–temporal tracer concentration, regional area under the curve (AUC), time to maximum concentration (Tmax), and maximum concentration (Cmax), for each case.ResultsCM and ICV increased AUC to brain regions by ~ 2 logs compared to all other simulations. A 3X increase in bolus volume and addition of a 5 mL flush both increased intracranial AUC to the brain up to 2X compared to a baseline 5 mL LP injection. In contrast, a 5X increase in bolus rate (25 mL/min) did not improve tracer exposure to the brain. An increase in cardiac and respiratory CSF movement improved tracer spread to the brain, basal cistern, and cerebellum up to ~ 2 logs compared to the baseline LP injection.ConclusionThe computational modeling approach provides ability to conduct in silico trials representative of CSF injection protocols. Taken together, the findings indicate a strong potential for delivery protocols to be optimized to reach a target region(s) of the spine and/or brain with a needed therapeutic dose. Parametric modification of bolus rate/volume and flush volume was found to have impact on tracer distribution; albeit to a smaller degree than injection location, with CM and ICV injections resulting in greater therapeutic dose to brain regions compared to LP. CSF stroke volume and frequency both played an important role and may potentially have a greater impact than the modest changes in LP injection protocols analyzed such as bolus rate, volume, and flush.

The pathological involvement of spinal cord EphB2 in visceral sensitization in male rats

Patients with post-traumatic stress disorder (PTSD) are usually at an increased risk for chronic disorders, such as irritable bowel syndrome (IBS), characterized by hyperalgesia and allodynia, but its subsequent effect on visceral hyperalgesia and the mechanism remain unclear. The present study employed single prolonged stress (SPS), a model of PTSD-pain comorbidity, behavioral evaluation, intrathecal drug delivery, immunohistochemistry, Western blotting, and RT-PCR techniques. When detecting visceral sensitivity, the score of the abdominal withdrawal reflex (AWR) induced by graded colorectal distention (CRD) was used. The AWR score was reduced in the SPS day 1 group but increased in the SPS day 7 and SPS day 14 groups at 40 mmHg and 60 mmHg, and the score was increased significantly with EphrinB1-Fc administration. The EphB2+ cell density and EphB2 protein and mRNA levels were downregulated in the SPS day 1 group and then upregulated significantly in the SPS day 7 group; these changes were more noticeable with EphrinB1-Fc administration compared with the SPS-only group. The C-Fos-positive reaction induced by SPS was mainly localized in neurons of the spinal dorsal horn, in which the C-Fos-positive cell density and its protein and mRNA levels were upregulated on SPS days 7 and 14; these changes were statistically significant in the SPS + EphrinB1-Fc group compared with the SPS alone group. The present study confirmed the time window for the AWR value, EphB2 and C-Fos changes, and the effect of EphrinB1-Fc on these changes, which suggests that spinal cord EphB2 activation exacerbates visceral pain after SPS.

Intrathecal drug delivery for chronic pain management

Intrathecal drug delivery appeared in the early eighties and allows to administer high concentrate analgesic medications in the cerebrospinal fluid with higher efficacy and a limited incidence of systemic side effects. Opioids are still the first line treatment with high-quality evidence for chronic cancer pain, and limited evidence for chronic non-cancer pain, being often considered as a last resort therapy. Device implantation requires a strict patient's selection with a close follow-up in order to adapt therapy, refill the reservoir and detect and prevent potential severe complications.

A survival analysis of ventricular access devices for delivery of cerliponase alfa.

Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare autosomal recessive disease caused by tripeptidyl peptidase 1 enzyme deficiency. At the authors' center, the medication cerliponase alfa is administered every 2 weeks via the intracerebroventricular (ICV) route. This requires the placement of a ventricular access device (VAD) or reservoir and frequent percutaneous punctures of this device over the child's lifetime. In this study, the authors audited the longevity and survival of these VADs and examined the causes of device failure. A single-center survival analysis of VAD insertions and revisions (January 2014 through June 2020) was conducted. All children received cerliponase alfa infusions through a VAD. Patient characteristics and complications were determined from a prospectively maintained surgical database and patient records. For the VAD survival analysis, the defined endpoint was when the device was removed or changed. Reservoir survival was assessed using Kaplan-Meier curves and the log-rank (Cox-Mantel) test. A total of 17 patients had VADs inserted for drug delivery; median (range) age at first surgery was 4 years 4 months (1 year 8 months to 15 years). Twenty-six VAD operations (17 primary insertions and 9 revisions) were required among these 17 patients. Twelve VAD operations had an associated complication, including CSF infection (n = 6) with Propionibacterium and Staphylococcus species being the most prevalent organisms, significant surgical site swelling preventing infusion (n = 3), leakage/wound breakdown (n = 2), and catheter obstruction (n = 1). There were no complications or deaths associated with VAD insertion. The median (interquartile range) number of punctures was 59.5 (7.5-82.0) for unrevised VADs (n = 17) versus 2 (6-87.5) for revised VADs (n = 9) (p = 0.70). The median survival was 301 days for revisional reservoirs (n = 9) versus 2317 days for primary inserted reservoirs (n = 17) (p = 0.019). In the context of the current interest in intrathecal drug delivery for rare metabolic disorders, the need for VADs is likely to increase. Auditing the medium- to long-term outcomes associated with these devices will hopefully result in their wider application and may have potential implications on the development of new VAD technologies. These results could also be used to counsel parents prior to commencement of therapy and VAD implantation.

Efficacy of an Intrathecal Drug Delivery System in Controlling Pain Caused by Skin Defect in Fournier's Gangrene

Efficacy of an Intrathecal Drug Delivery System in Controlling Pain Caused by Skin Defect in Fournier's Gangrene

POSB394 Comparison of Healthcare Utilization Patterns between Intrathecal Drug Delivery Systems and Conventional Medical Management in the Treatment of Chronic Pain: Retrospective Study with Claims Datasets

Intrathecal Drug Delivery System(IDDS) has demonstrated reduction in systematic opioid consumption for the treatment of chronic pain. This study was to compare healthcare utilization patterns among non-cancer related chronic pain patients who were receiving either IDDS or Conventional Medical Management(CMM).

Intrathecal Baclofen Monotherapy and Polyanalgesia for Treating Chronic Pain in Patients with Severe Spasticity.

Intrathecal drug delivery is a well evidenced strategy for the treatment of many chronic pain syndromes. While opioids, anesthetics, and ziconotide are the most commonly used agents, intrathecal baclofen (ITB), which is indicated to treat spasticity, is also thought to have some analgesic properties that are poorly understood. These analgesic benefits have been reported with ITB use in treating patients with central neurological disorders who suffer from severe spasticity and chronic pain. Our review aims to characterize ITB's effects on pain, function, and quality of life in patients with severe spasticity.We performed a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. The primary outcome parameters were analgesic relief and functional improvements. Secondarily, quality of life and adverse effects were also recorded. After an initial survey identified 393 studies, 20 studies met final inclusion criteria. Of these, 16 utilized ITB monotherapy and 4 utilized ITB polyanalgesia. Overall, there was a paucity of high-powered studies. Mean titrated ITB doses ranged from 140 to 627.9μg daily. Nineteen studies reported improved pain and spasticity. Seven studies reported improved functional outcomes and quality of life. Our results show that ITB may bean effectiveagent in treatingfor the treatment of chronic pain in patients with severe spasticityindependent of its spasmolytic effects. Although this evidence was largely derived from studies lacking clearly defined outcomes of pain relief, ITB is reasonable to consider for concurrent spasticity and pain management. Well-designed studies are still needed to characterize ITB's analgesic efficacy when used in patients with severe spasticity.