The Unmet Need for Intrathecal Drug Delivery Pumps for the Treatment of Cancer Pain in England: An Assessment of the Hospital Episode Statistics Database.

OBJECTIVES: Intrathecal drug delivery (ITDD) devices have been shown to be a clinically effective and cost-effective option for the management of cancer pain and recommended for use in England. The aim of this study is to assess the impact of the 2015 NHS England Clinical Commissioning Policy on the uptake of ITDD pumps for the management of cancer pain or if there is an ongoing unmet need for this intervention in England. MATERIALS AND METHODS: Hospital Episode Statistics (HES) were obtained for all patients undergoing ITDD for the management of cancer pain between 2014 and January 2020. In addition, HES were utilized to estimate the number of patients with cancer potentially eligible for ITDD pump during the same period. RESULTS: The number of patients with cancer and those potentially suitable to receive an ITDD for the management of cancer pain have increased year on year since 2014. This increase has not been matched by an uptake in the provision of ITDD. Conservative estimates suggest that at least 8000 people with cancer pain would be eligible for ITDD; 458 patients received an intervention for pain management between April 2018 and March 2019 and only 30 ITDD pumps were implanted in that same period. CONCLUSIONS: We observed a substantial gap between the need and provision of ITDD for patients with refractory cancer pain in England despite the recommendation for the use of ITDD for this patient population. In addition, we present suggestions for improvement of access to and provision of ITDD in England.

Use of an intravenous port catheter for the delivery of intrathecal morphine in a terminally ill cancer patient with pain.

We present a case of a terminally ill cancer patient with metastasis who was suffering from inadequate pain control despite high doses of systemic opioid administration. In addition, her quality of life was significantly impaired due to opioid-induced troublesome side effects. In the situation as above, intrathecal opioid administration has established as a safe and effective therapeutic option with a positive benefit-risk ratio. This case reports a novel technique, where an intravenous port catheter was used to administer intrathecal opioid.

Multicentre clinical simulation evaluation of the ISO 80369-6 neuraxial non-Luer connector.

To avoid potentially fatal wrong-route neuraxial drug errors, international standard ISO 80369-6 specifying a non-Luer neuraxial connector design was published in 2016. We describe usability studies used in development of the design. Thirty-eight doctors and 17 nurses performed simulated procedures on manikins, using devices fitted with Luer connectors or draft ISO 80369-6 'non-Luer' connectors. The procedures included spinal anaesthesia; intrathecal chemotherapy; lumbar puncture, cerebrospinal fluid collection and pressure measurement; epidural catheter placement with bolus injection and critical care use. Participants attempted cross connection between neuraxial connectors and a range of other medical device connectors, including those from the ISO 80369 small-bore connector series. Video recording analysis was used for all assessments. Participants subjectively assessed performance of the draft non-Luer connector, including suitability for routine clinical use. Participants performed 198 procedures. The connector achieved easy, leak-free connections. The willingness of participants to use the non-Luer connectors were: spinal anaesthesia 100%; intrathecal chemotherapy 88%; lumbar puncture, cerebrospinal fluid collection and pressure measurement 93%; epidural catheter placement with bolus injection 78%; critical care use 100%. Concerns raised were generally device related, rather than connector related. Most cross-connection attempts failed, even using above clinical forces and, when successful, were judged of low clinical risk potential; the exception was a malaligned connection between the non-Luer slip and female Luer connectors. This led to revision of the dimensional tolerances of the non-Luer connector to reduce this risk, before publication of the final specification in 2016. We conclude that the ISO 80369-6 neuraxial non-Luer connector is suitable for clinical use.

Characterization of Effect of Repeated Bolus or Continuous Intrathecal Infusion of Morphine on Spinal Mass Formation in the Dog.

BACKGROUND: We determined whether intrathecally delivering the same daily dose of morphine (MS) at a fixed concentration of 25 mg/mL by periodic boluses versus continuous infusion would reduce intrathecal mass (IMs) formation in dogs. METHODS: Adult dogs (hound cross, n = 32) were implanted with intrathecal catheters connected to SynchroMed II infusion pumps. Animals were randomly assigned to receive infusion of 0.48 mL/day of saline or MS dosing (12 mg/day at 25 mg/mL) as boluses: x1 (q24hour), x2 (q12hour), x4 (q6hour), or x8 (q3hour) given at the rate of 1000 µL/hour, or as a continuous infusion (25 mg/mL/20 µL/hour). RESULTS: With IT saline, minimal pathology was noted. In contrast, animals receiving morphine displayed spinally compressing durally derived masses with the maximal cross-sectional area being greatest near the catheter tip. Histopathology showed that IMs consisted of fibroblasts in a collagen (type 1) matrix comprised of newly formed collagen near the catheter and mature collagen on the periphery of the mass. The rank order of median cross-sectional mass area (mm2 ) was: Saline: 0.7 mm2 ; x2: 1.8 mm2 ; x4: 2.7 mm2 ; x1: 2.7 mm2 ; x8: 4.2 mm2 ; Continuous: 8.1 mm2 , with statistical difference from saline being seen with continuous (p < 0.0001) and x8 (p < 0.05). Bench studies with a 2D diffusion chamber confirmed an increase in dye distribution and lower peak concentrations after bolus delivery versus continuous infusion of dye. CONCLUSIONS: Using multiple bolus dosing, IMs were reduced as compared to continuous infusion, suggesting relevance of bolus delivery in yielding reduced intrathecal masses.

Refill Procedures of Intrathecal Drug Delivery Systems With a Recessed Fill Port on the Pump Surface: A Prospective Comparison Study of Ultrasound-Guided vs. Blind Refill Technique.

OBJECTIVES: Structural differences of implantable drug delivery systems (IDDSs) might have an impact on the efficiency of needle access to the reservoir fill port (RFP). The aim of this study was to assess the efficiency of RFP needle access with an ultrasound (US)-guided vs. a blind refill technique in IDDSs with a Recessed RFP (Recessed-RFP-IDDS). MATERIALS AND METHODS: The primary outcome was the number of attempts needed to enter the RFP with a needle comparing the US-guided technique vs. the blind refill technique. The time to enter the RFP with the needle was a secondary outcome. We compared the amount of attempts between both techniques with the non-parametric Wilcoxon rank sum test. RESULTS: Fourteen adult patients underwent a total of 75 refills of their Recessed-RFP-IDDS during a period of 24 months. The median number of attempts to enter the RFP did not differ significantly between the US-guided technique and the blind refill technique (2.0 (IQR: 1-5) vs. 1.5 (IQR: 1-5.0), p = 0.572). The median time to enter the RFP with the needle did not differ significantly between both techniques (35.0 sec (IQR: 26.0-58.0) vs. 41.0 sec (IQR: 25.5-46.8), p = 0.878). CONCLUSION: The results of this study suggest that there is no difference in the RFP needle access efficiency between the US-guided and the blind refill technique in superficially located Recessed-RFP-IDDSs, if performed by experienced practitioners. However, the study did not address efficiency of the RFP needle access in IDDSs with aberrancy in pump location or refills performed by inexperienced staff.

X-ray Imaging Analysis of Intrathecal Baclofen Pumps for Pediatric Emergency Medicine.

Intrathecal baclofen therapy has become increasingly popular because of its effectiveness in treating spasticity in pediatric patients. The device implanted into each patient is structurally similar. However, x-ray imaging can give the appearance of missing or extraneous objects on or near the intrathecal baclofen device. The composition of the material used in making the catheters is transparent on x-ray images. In addition, the connection port between the pump and catheter may resemble the shape of a needle. This has led to confusion among emergency room personnel, and unnecessary panic for other people involved. It is important that medical professionals understand many of the new designs of the pump-connector system to avoid further complications.

Ease of Fill Port Access During the Ultrasound-Guided vs. the Blind Refill Technique of Intrathecal Drug Delivery Systems With a Raised Septum, a Prospective Comparison Study.

OBJECTIVES: The localization of the reservoir fill port of Intrathecal Drug Delivery Devices (IDDS) can be difficult. The purpose of this study was to assess the ease of fill port access during the ultrasound-guided refill technique compared to the blind refill technique in IDDSs with a raised septum on the pump surface. MATERIALS AND METHODS: Written informed consent was obtained from 19 adult patients undergoing regular refills of their Raised Septum IDDSs (RS-IDDSs). The primary outcome of this single center prospective comparison study was the number of attempts to enter the reservoir fill port with the needle comparing the ultrasound-guided technique vs. the blind technique. The number of skin punctures per refill procedure and time to enter the reservoir fill port was secondary outcomes. For between group comparisons the Friedman test for repeated measures on ranks was used. RESULTS: One hundred and eleven refill procedures were assessed in 19 patients over a period of 24 months. The median number of attempts to enter the reservoir fill port with the needle differed significantly between the ultrasound-guided technique and the blind technique (4 [IQR: 1-6] vs. 1 [IQR: 1-3], p = 0.018), in favor of the blind technique. The median time to enter the reservoir fill port differed significantly between the ultrasound-guided technique and the blind technique (58 sec [IQR: 38-94] vs. 22 sec [IQR: 16-40], p < 0.001). CONCLUSIONS: The results of this study suggest that for a RS-IDDS the blind refill technique needs significantly less attempts to enter the reservoir fill port than the US-guided refill technique.

Retrospective Analysis of Intrathecal Drug Delivery: Outcomes, Efficacy, and Risk for Cancer-Related Pain at a High Volume Academic Medical Center.

OBJECTIVES: Cancer pain is common and difficult to treat, as conservative medical management fails in approximately 20% of patients for reasons such as intolerable side-effects or failure to control pain. Intrathecal drug delivery systems (IDDS), while underutilized, can be effective tools to treat intractable cancer pain. This study aims to determine the degree of pain relief, efficacy, and safety of patients who underwent IDDS implantation at a multidisciplinary pain clinic. MATERIALS AND METHODS: A retrospective review was conducted of patients with an intrathecal pain pump implanted for malignant pain. Charts were reviewed for demographics, cancer type, pain scores before and after implantation, and intrathecal drugs utilized. A Wilcoxon Signed-Rank test was conducted on the paired differences of pain scores before and after implant. A regression analysis was conducted using a linear model to assess effects of demographic variables on change in pain scores. RESULTS: 160 patients were included in analysis. The median pain score was 7.1 at time of implantation and 5.0 at one-month postimplantation. For patients with both baseline and one-month pain scores available, the median decrease in pain was 2.5 (p < 0.0001). Pain scores three-month postimplantation did not significantly differ from one-month postimplantation. Median longevity was 65 days. Five patients had pumps explanted due to infection with a median time to pump extraction of 28 days. CONCLUSIONS: IDDS has the potential to improve cancer pain in a variety of patients and should be strongly considered as an option for those with cancer pain intractable to conservative medical management.

Intrathecal Therapeutics: Device Design, Access Methods, and Complication Mitigation.

INTRODUCTION: The intrathecal space remains underutilized for diagnostic testing, invasive monitoring or as a pipeline for the delivery of neurological therapeutic agents and devices. The latter including drug infusions, implants for electrical modulation, and a means for maintaining the physiologic pressure column. The reasons for this are many but include unfamiliarity with the central nervous system and the historical risks that continue to overshadow the low complication rates in modern clinical series. MATERIALS AND METHODS: Our intent in this review is to explore the access devices currently on the market, assess the risk associated with breaching the intrathecal space, and propose a research model for bringing to patients the next generation of intrathecal hardware. For this purpose, we reviewed both historical and contemporary literature that pertains to the access devices and catheters intended for both temporary and permanent implantation and the complications thereof. RESULTS: There are few devices that are currently marketed in the United States or Europe for intrathecal use. Most hew to a relatively fixed design pattern predicated on the dimensions and properties of the thecal sac. All are typically composed of soft silicone, and employ a Tuohy needle for access despite design limitations. In general, these catheters are engineered for durability, ease of use, and regional deployment. Devices on the market with steerability or targeted intrathecal fixation are not yet available. Complications, once a legitimate concern, are now quite rare when recommended techniques are followed. CONCLUSIONS: Over the next decade, advances in intrathecal catheter design, access techniques, imaging, and greater understanding of the spinal cord neurophysiology will usher in an era where the intrathecal space is recognized as a highly valued diagnostic and therapeutic target. We anticipate that this will occur in several concurrent phases, each with the potential to accelerate the growth of the others.

Comparison of the Effects of Intermittent Boluses to Simple Continuous Infusion on Patients' Global Perceived Effect in Intrathecal Therapy for Pain: A Randomized Double-Blind Crossover Study.

Objective: Intrathecal drug delivery (ITDD) is commonly used for intractable pain management. A paucity of good-quality studies in chronic noncancer patients and concerns over increased dosages have focused interest on different modes of administration. The aim of this international multicenter randomized double-blind crossover trial was to compare the efficacy of the same daily dose of drugs administered by intermittent boluses vs simple continuous infusion. Methods: Eligible patients implanted with a programmable ITDD device were randomized to receive two weeks of either intermittent boluses or a simple continuous flow in period 1, followed by a crossover to the alternative mode of administration. The primary outcome measure was the Patients' Global Impression of Change (PGIC) scale. Results: The mean proportion of positive responders (at least "minimally improved") was 38.4% in the continuous condition vs 37.3% in the bolus (difference in proportions = 1.1%, 95% confidence interval [CI] = -21.8-24.0%, P = 0.93). The mean PGIC in the continuous condition was 3.8 vs 3.9 in the bolus (mean difference = -0.1, -0.6-0.4, P = 0.72). Exploratory analyses revealed a tendency for the mean proportion of positive responders to be higher at low vs high flow rates for both bolus and continuous administrations. Two patients were withdrawn from the study due to adverse events during the bolus phase, both with symptoms of increased pain, and one patient with additional symptoms of numbness and urinary retention. Conclusion: The mean PGIC and proportion of positive responders was not substantially different after intermittent bolus vs continuous administration.

Surgical Site Infections in Cancer Patients with Intrathecal Drug Delivery Devices.

Objectives: Our purpose was to determine the incidence of surgical site infection (SSI) in cancer patients receiving an intrathecal drug delivery system (IDDS) and compare that rate with the incidence of SSI in the general population receiving an IDDS or spinal cord stimulator. We attempted to describe risk factors for SSIs in cancer patients treated with IDDS in terms of exposure to cancer treatments. Design: Retrospective review. Setting: Large tertiary care center. Patients: Cancer patients receiving an IDDS in 2006-2013. Methods: The incidence of SSI was determined according to the US Centers for Disease Control and Prevention definition. Medication regimens and current cancer treatment were investigated to identify immunocompromised patients during IDDS placement. Microbacteriology, treatment, and overall outcomes were investigated. Results: Sixty-four patients had an IDDS implanted in 2006-2013. SSI developed in four patients (6.2%). All four patients had received chemotherapy or radiotherapy within three months before implantation. Three of the three were receiving dexamethasone, and three of the four required explantation of the IDDS. Conclusion: The incidence of SSI was at the upper end of the published infection rates for IDDS. The risk of SSI may be increased in this population because of factors that alter the patient's immune status, including concomitant corticosteroid use, radiotherapy near the SSI, and presence of immunomodulators. The identification and mitigation of certain risk factors for this population may prevent infection in future patients.

A phase 1/2 study of intrathecal heparan-N-sulfatase in patients with mucopolysaccharidosis IIIA.

OBJECTIVE: This was an open-label, phase 1/2 dose-escalation, safety trial of intrathecal recombinant human heparan-N-sulfatase (rhHNS) administered via intrathecal drug delivery device (IDDD) for treating mucopolysaccharidosis IIIA (NCT01155778). STUDY DESIGN: Twelve patients received 10, 45, or 90mg of rhHNS via IDDD once monthly for a total of 6 doses. Primary endpoints included adverse events (AEs) and anti-rhHNS antibodies. Secondary endpoints included standardized neurocognitive assessments, cortical gray matter volume, and pharmacokinetic/pharmacodynamic analyses. RESULTS: All patients experienced treatment-emergent AEs; most of mild-to-moderate severity. Seven patients reported a total of 10 serious AEs (SAEs), all but one due to hospitalization to revise a nonfunctioning IDDD. No SAEs were considered related to rhHNS. Anti-rhHNS antibodies were detected in the serum of 6 patients and in the cerebrospinal fluid (CSF) of 2 of these. CSF heparan sulfate levels were elevated at baseline and there were sustained declines in all tested patients following the first rhHNS dose. No impact of anti-rhHNS antibodies on any pharmacodynamic or safety parameters was evident. 4 of 12 patients showed a decline in developmental quotient, 6 were stable, and 2 patients had only a single data point. No dose group showed a clearly different response pattern. CONCLUSIONS: rhHNS administration via IDDD appeared generally safe and well tolerated. Treatment resulted in consistent declines in CSF heparan sulfate, suggesting in vivo activity in the relevant anatomical compartment. Results of this small study should be interpreted with caution. Future studies are required to assess the potential clinical benefits of rhHNS and to test improved IDDD models.

A Prototype Hybrid Gypsum-Based 3-Dimensional Printed Training Model for Computed Tomography-Guided Spinal Pain Management.

This article details design methodology of an anatomically realistic and accurate physical 3-dimensional model of the lumbosacral spine from computed tomography data utilizing 3-dimensional printing. This model is unique in that the radiodense bony lumbosacrum is reconstructed using gypsum, which because of its high calcium content allows for the appropriate imaging characteristics mimicking bone. The model allows trainees to become competent in needle placement for image-guided diagnostic and therapeutic procedures.

Isotopic Scintigraphy Coupled With Computed Tomography for the Investigation of Intrathecal Baclofen Device Malfunction.

OBJECTIVE: To assess the potential use of indium-111 diethylenetriamine pentaacetic acid ((111)In-DTPA) scintigraphy coupled with computed tomography (CT) for the investigation of intrathecal baclofen (ITB) device malfunction. DESIGN: Retrospective study of a case series of patients. SETTING: Neurosurgical and physical and rehabilitation medicine departments. PARTICIPANTS: Patients (N=7) with reduced ITB effectiveness in whom prior conventional radiographs were inconclusive. INTERVENTION: Nine (111)In-DTPA scintigraphic studies and 8 CT scans. Planar acquisitions were followed by tomoscintigraphy combined with CT. MAIN OUTCOME MEASURE: Progression of the radiotracer in the pump, catheters, and in the subarachnoid space. RESULTS: In 7 cases, scintigraphy coupled with CT showed leakage behind the pump, lack of activity outside the pump reservoir, abrupt interruption of activity in the catheter, or abnormal distribution of the radiotracer, thus demonstrating that the drug did not reach its target. Surgical revision confirmed these findings in 5 cases. In 1 case, combined imagery ruled out device dysfunction. In the remaining case, only planar acquisitions were performed, showing correct diffusion of the radiotracer. CONCLUSIONS: The combination of scintigraphy and CT provides simultaneous functional and anatomic imagery of the device. The slow infusion of the radioisotope mimics the diffusion of baclofen, and this could be a useful method to explore intrathecal device malfunction. Further studies are required to compare scintigraphy coupled with CT, to radiopaque injection followed by fluoroscopy or CT.

[Spinal catheter-associated cerebrospinal fluid leak]. / Spinalkatheterassoziiertes Liquorverlustsyndrom.

Cerebrospinal fluid leak, with its typical postdural puncture headache, occurs in 8-25 % of patients after insertion of a spinal catheter for treatment with an intrathecal pain pump. Symptoms are usually self-limiting; only rarely is an epidural blood patch used. In this case of a 49-year-old woman, we assumed a postdural puncture headache after replacement of the spinal catheter. Because of the persistence of symptoms and serous wound secretion around the paravertebral incision, we decided to test the catheter under radiological control with a contrast agent. Leakage could be seen within the spinal catheter, which was responsible for the symptoms. Because of an ongoing infection accompanied by meningitis the whole system had to be removed.

Cranial nerve VI palsy after dural-arachnoid puncture.

In this article, we provide a literature review of cranial nerve (CN) VI injury after dural-arachnoid puncture. CN VI injury is rare and ranges in severity from diplopia to complete lateral rectus palsy with deviated gaze. The proposed mechanism of injury is cerebrospinal fluid leakage causing intracranial hypotension and downward displacement of the brainstem. This results in traction on CN VI leading to stretch and neural demyelination. Symptoms may present 1 day to 3 weeks after dural-arachnoid puncture and typically are associated with a postdural puncture (spinal) headache. Resolution of symptoms may take weeks to months. Use of small-gauge, noncutting spinal needles may decrease the risk of intracranial hypotension and subsequent CN VI injury. When ocular symptoms are present, early administration of an epidural blood patch may decrease morbidity or prevent progression of ocular symptoms.

Intrathecal drug delivery for chronic pain management-scope, limitations and future.

Intrathecal drug delivery system (IDDS) is a targeted therapy system for treating pain and muscle spasm. IDDS is recommended for the treatment of chronic pain which does not respond to optimal medical management. The aim of this review article is to give an up to date and concise account of the use of IDDS. It will explore the main indications, pre-implantation trials and different implantation techniques, the licensing of drugs for intrathecal use and the adverse effects and benefits of this therapy. IDDS is an invasive technique, which can result in severe morbidity and mortality. The up to date knowledge gained from this article along with the recommendations for improving safety in patients receiving IDDS, makes it a valuable resource for healthcare practitioners. Continued research, including outcome studies of this therapy continues to be necessary.

The role of needle tip position on the accuracy of diagnostic selective nerve root blocks in spinal deformity.

PURPOSE: The specificity of a selective nerve root block (SNRB) is dependant on isolating only the required nerve root whilst avoiding injectate flow to traversing nerves. Needle tip position is therefore crucial. Nerve root blocks (SNRBs) in the presence of deformity can be particularly technically challenging to perform. The aims of this study were to document the relationship of needle tip position and SNRB accuracy in patients with and without spinal deformity. METHODS: Over an 8-month period, all SNRBs performed by one spinal surgeon were included. Patients with radiographic evidence of spinal deformity were analysed separately and their lumbar deformity graded using the Schwab grading system. Needle tip position in relation to the superior pedicle and flow of contrast was documented. RESULTS: 76 patients received 85 injections without deformity, 26 patients with deformity underwent 30 SNRBs. In the normal spinal alignment group, there was on overall accuracy of 70.1% regardless of needle tip position, which improved to 91.8% for a lateral needle tip position (P < 0.001). In patients with deformity, the overall accuracy was significantly lower irrespective of needle tip position 36 versus 70%, respectively (P < 0.0019). CONCLUSIONS: Selective nerve root blocks are accurate in patients without deformity where a needle tip placement lateral to the middle third of the pedicle is achieved. The presence of spinal deformity significantly reduces the accuracy of SNRBs with a higher chance of epidural infiltration.

"Sonology" of programmable intrathecal pumps.

OBJECTIVE: The study aims to demonstrate the unique sonographic features of the commercially available intrathecal drug delivery systems. METHODS: "Not-for-human-use" pumps were obtained, placed in a tray, and covered with an ultrasound phantom gel. The anterior surface of each pump was scanned and the sonographic features were observed and recorded. RESULTS: All systems have a centrally located reservoir port (RP) and a peripherally located catheter access port (CAP) that are observable on ultrasound. The RP of the SynchroMed II system (Medtronic, Minneapolis, MN, USA) appears as an anechoic depression and a break in the bright echogenic line of the superior pump surface. The CAP appears as smaller diameter conical depression outside the circular perimeter of the pump. The RP of the MedStream system (Codman & Shurtleff, Inc., Raynham, MA, USA) has a dome-shaped appearance. The CAP appears as a smaller dome-shaped object that is off center but still contained within the circular perimeter of the pump. Similarly, the RP of the Prometra system (Flowonix Medical Inc, Mt. Olive, NJ, USA) is a dome-shaped object. The CAP visually appears similar to the reservoir access port of the SynchroMed II system, namely a small depression and a break in the bright echogenic line of the pump surface, outside the perimeter of the pump. CONCLUSION: In all programmable intrathecal pumps, the RP can be readily identified sonographically. Potentially, the dome-shaped configuration of RP for the Prometra and MedStream systems make the access easier, when compared with SynchroMed II system. Ultrasound could potentially be utilized to localize the RP and CAP for all the systems as each of the three systems has a unique sonographic appearance.

Intrathecal administration of Infumorph® vs compounded morphine for treatment of intractable pain using the Prometra® programmable pump.

OBJECTIVES: The intrathecal administration of morphine sulfate has become an established alternative to oral opiate therapy for the treatment of chronic pain. Currently, Infumorph(®) is the only morphine sulfate approved by the US Food and Drug Administration for continuous intraspinal administration with an infusion pump. However, in order to achieve and maintain adequate pain relief, patients may require concentrations outside of those commercially available products resulting in the use of compounded morphine. METHODS: Accuracy, safety, and efficacy data related to Infumorph and compounded morphine use were collected during clinical trials of a new implantable pump. This report compares those results in a total of 154 subjects implanted with the Prometra programmable pump. RESULTS: The mean drug delivery accuracy using only Infumorph in 31 subjects was 100.1% and was comparable with the accuracy reported for the 71 subjects who received only compounded morphine sulfate (97.4%). The percentage of subjects free from device-related serious adverse events (DRSAEs) was similar in both groups. Compounded morphine showed statistically significant improvements in pain and disability, where Infumorph only showed a statistical improvement in pain. Dosing was higher in the compounded group. Results are also presented for a crossover group that received both types of morphine. CONCLUSIONS: ThePrometra system accurately delivers both Infumorph and compounded morphine with no significant differences in DRSAE rates. These results indicate that compounded morphine delivery effectively treats the chronic pain patient population. Higher doses appear to provide better pain relief; however, optimal pain relief will need to be balanced against the risk of granuloma formation.