Intrathecal Catheter Tip Research Articles

ID: 335796 Comparison of Outcomes Before and After Attention to Intraoperative Placement of Intrathecal Catheter Tip

ID: 335796 Comparison of Outcomes Before and After Attention to Intraoperative Placement of Intrathecal Catheter Tip

ID: 216262 Longitudinal Data From the Targeted Drug Delivery (TDD) Product Surveillance Registry: Inflammatory Mass

TDD with programmable intrathecal drug delivery systems (IDDS) has been approved for chronic malignant and nonmalignant pain treatment since 1991 and severe spasticity since 1992. Intrathecal inflammatory mass (IM) is a known risk of intrathecally delivered opioid compound. IM’s, or granulomas, are sterile masses that develop proximal to the intrathecal (IT) catheter tip, consisting of inflammatory cells and fibroblasts. Rates of IM have been decreasing over time. We conjecture that this is due to education, research, and changes in clinical practice with reduction of drug concentrations and dosing.

Gadolinium-based MR cisternography with prepontine cisternal routine for evaluating distribution pattern of intrathecal targeted drug delivery in pain management

Gadolinium-based MR cisternography has been mainly applied in clinical evaluation of cerebrospinal fluid leaking, that is conducted by intrathecal administration of contrast media. Recently, we have reported one novel technique of intrathecal targeted drug delivery with prepontine cisternal routine to treat orofacial cancer pain. The aim of this study was to examine the distribution pattern of this intrathecal drug delivery strategy. Here, we introduce one case who suffered severe orofacial pain caused by sublingual gland tumor, and successfully attenuated by prepontine cisternal administration of analgesic agents. To assess the distribution of intrathecal drugs, postoperative MR images of brain, cervical, thoracic, and lumbar segments in axial, coronal, and sagittal planes were obtained after application of gadolinium. The perfusion rate of contrast medium was set at 0.01 mmol per hour for 24 hours prior to MR scanning. In the T1-weighted images, we can identify contrast spread not only locating around the site of the intrathecal catheter tip, but also concentrated to the lateral sides. None obvious side effect was found after intrathecal injection of contrast media. Thus, our finding demonstrated the local distribution phenomenon of intrathecal drugs through prepontine cisternal access, and the bilateral perfusion pattern may provide insights underlying the analgesic mechanism of trigeminal pain provided by this novel intrathecal therapy. Gadolinium-based MR cisternography may serve as a potential tool to confirm the therapeutic effect of intrathecal targeted drug delivery via prepontine cisternal routine in orofacial pain management.

Prepontine cisternal routine for intrathecal targeted drug delivery in craniofacial cancer pain treatment: technical note

Intrathecal targeted drug delivery provides effective relief for cancer-related pain. However, its validation in management of craniofacial pain remains much less widely practiced, mainly due to the localized diffusion of analgesic agent with current approach. Here, we report our experience of prepontine cisternal routine for placement and implantation of intrathecal targeted drug delivery in two cases of cancer-related craniofacial pain. Lumbar cannulation was applied and the intrathecal catheter tip was positioned at the prepontine cistern under fluoroscopic guidance during the surgical implantation. Postoperative imaging confirmed that the catheter tip was successfully placed in the prepontine cisternal space. Satisfactory control of pain was achieved after intrathecal therapy, with significant reduction of background and breakthrough cancer pain. None obvious complications were observed in this study. Thus, our novel intrathecal routine may provide an alternative option for craniofacial pain caused by tumor, who were insufficiently treated by oral analgesic agents.

Controversies in intrathecal drug delivery for cancer pain

Pain and suffering related to cancer are challenging issues that continue to deserve consideration for treatment optimization. Advances in analgesic management and control of the underlying cancer have improved symptom...

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.

A Retrospective Analysis of Intrathecal Catheter Tip Position in Plain Radiography: How Much Do We Agree?

To assess interrater and intrarater reliability of postoperative plain radiographs, which are routinely performed to confirm the correct placement of the catheter tip after intrathecal drug delivery systems (IDDS) implantation. This was a retrospective analysis of plain radiographs obtained from patients implanted with intrathecal catheters and morphine pumps. Each plain radiograph was assessed independently by three raters with varying expertise, at three different time points, to confirm the position of the intrathecal catheter tip. Krippendorff?s alpha coefficient was used to calculate both the interrater and intrarater reliability. There was a high level of agreement among the three raters and the three reviews of each rater separately when assessing the location of intrathecal catheter tips in plain radiographs from 126 patients. This was evidenced by the Krippendorff?s alpha value being > 0.99 in all cases, which was greater than the cutoff threshold value of 0.8. The interrater and intrarater reliability of plain radiographs for determination of catheter tip position after IDDS implantation was high. The experience and expertise of the raters did not significantly affect the assessments.

Blame it on the Pump

Intrathecal drug delivery a method of directly administering opioid and spasmolytic medication to the site of action, the spinal cord. Efficacy and safety of this delivery system is well documented in cancer pain, spasticity as well as non-malignant pain. However, there are a number of recognised potential complications with this therapy. One of the most serious of which is the formation of a granuloma occurring at the intrathecal catheter tip, which appears to be related to the concentration and drug type being delivered. Evidence has indicated that delivery of high dose morphine can lead to the formation of these granulomas. Occurring in less than 3% of all patients with an intrathecal catheter, granulomas can present as an inflammatory mass on imaging with some resulting in compression of the spinal cord. Patients may present with a host of neurological symptoms dependent on the location of cord compression caused by the granuloma, including neurological deficits, myelopathy and radiculopathy.

Comparative Effectiveness of Targeted Intrathecal Drug Delivery Using a Combination of Bupivacaine with Either Low-Dose Fentanyl or Hydromorphone in Chronic Back Pain Patients with Lumbar Postlaminectomy Syndrome.

Targeted intrathecal drug delivery (TIDD) is an effective interventional pain management modality often used in postlaminectomy patients with refractory chronic low back pain. A combination of intrathecal bupivacaine with an opioid is often used. However, intrathecal catheter tip granulomas have occurred with use of morphine or hydromorphone but generally not with fentanyl. The objective of this study was to compare the efficacy of TIDD using bupivacaine/fentanyl vs bupivacaine/hydromorphone in patients with chronic intractable low back pain postlaminectomy. A retrospective comparative analysis of consecutive patients with lumbar postlaminectomy syndrome who were trialed and later received TIDD with a combination of bupivacaine/hydromorphone or bupivacaine/fentanyl between June 2009 and May 2016 at a single tertiary medical center. We identified a cohort of 58 lumbar postlaminectomy patients receiving a TIDD admixture of either hydromorphone/bupivacaine (30 patients) or low-dose fentanyl/bupivacaine (28 patients) with at least two years of follow-up. The fentanyl group had significantly lower baseline opioid consumption and a lower rate of intrathecal opioid dose escalation. Both groups had similar and significant reductions in pain scores over the two-year follow-up period. No granulomas were observed. TIDD using a low-dose fentanyl admixture with bupivacaine in patients with postlaminectomy syndrome and refractory chronic low back pain results in similar pain relief to TIDD with hydromorphone and bupivacaine. Low-dose intrathecal fentanyl leads to a lower rate of opioid escalation and may be safer than hydromorphone.

Disruption of BDNF/TrkB Signaling Alters Glutamatergic mRNA Expression at Phrenic Motor Neurons

Brain‐derived neurotrophic factor (BDNF) signaling via its high affinity tropomyosin‐related kinase sub‐type B (TrkB) receptor is widely implicated in regulating glutamatergic synaptic transmission in the context of neuroplasticity. At phrenic motor neurons innervating the main inspiratory muscle in mammals (the diaphragm muscle), glutamate is the main excitatory neurotransmitter and acts primarily via ionotropic AMPA and NMDA receptors. In various regions in the CNS, BDNF/TrkB signaling influences rapid phosphorylation of AMPA and NMDA receptor subunits, supporting a main role in neuroplasticity. BDNF/TrkB signaling also plays an important role across various models of injury and respiratory neuroplasticity. In addition, BDNF/TrkB signaling increases AMPA and NMDA receptor expression in the CNS, but whether this effect is also present in motor neurons is presently unknown. BDNF/TrkB signaling modulates motor neuron excitability, which may reflect changes in glutamatergic receptor expression. In the present study, AMPA and NMDA mRNA expression in retrogradely‐labeled phrenic motor neurons was measured using RNAscope in situ hybridization (ACDBio). Adult male rats were randomly assigned to control (untreated) and 11‐day treatment groups (12 ml/day) with intrathecal infusion of the fusion‐protein TrkB‐Fc or artificial cerebrospinal fluid (aCSF) in the region of the phrenic motor neuron pool. Intrathecal catheter tip position was verified at the terminal experimental at ~C4 segment, and the infusion rate was confirmed to restrict delivery to the cervical spinal cord. Expression of both AMPA and NMDA receptor mRNA was evident as puncta in phrenic motor neurons (identified by cholera toxin sub‐unit B – CTB‐labeling) as well as in other large neurons in the ventral horn. Our analysis of mRNA puncta density was restricted to clearly‐identified, retrogradely (CTB)‐labeled phrenic motor neurons containing the mid‐nuclear region in frozen, thin (10μm) longitudinal sections of the spinal cord. At least 25 phrenic motor neurons were stereologically selected for analysis in each animal. No differences in AMPA or NMDA mRNA density were evident between the untreated control and aCSF treated groups, and these results were combined. Across phrenic motor neurons in the control and aCSF groups, there was ~30% variance in AMPA and NMDA mRNA density within each animal, reflecting heterogeneity across motor neurons of varying size, expected to be recruited for the various levels of force production by the diaphragm muscle. Following TrkB‐Fc infusion, there was evidence of decreased AMPA mRNA density in phrenic motor neurons following but no change in NMDA mRNA density. These results support a role for BDNF/TrkB signaling in modulating glutamatergic receptor expression at phrenic motor neurons, which may thus contribute to the regulation of motor neuron excitability and neuroplasticity following injury or disease.Support or Funding InformationNIH grants R01 HL96750 and R01 HL146114

Intrathecal baclofen pump implantation for complex regional pain syndrome in a patient with a spinal cord stimulator: consideration about optimal location of intrathecal catheter tip - A case report -

Intrathecal baclofen pump implantation for complex regional pain syndrome in a patient with a spinal cord stimulator: consideration about optimal location of intrathecal catheter tip - A case report -

Primary Hydromorphone-Related Intrathecal Catheter Tip Granulomas: Is There a Role for Dose and Concentration?

Intrathecal drug delivery therapy has been used effectively in treating patients with intractable chronic pain. The development of an intrathecal catheter tip granuloma (ICTG) related to delivery of intrathecal opiates is a relatively infrequent, but potentially devastating complication. While there are many morphine-related ICTG cases described, reports of hydromorphone-related ICTG are limited. In addition, studies suggest a strong correlation between the use of higher doses and concentrations of intrathecal opiates and ICTG formation. The objective of this study is to determine the incidence and the association of intrathecal hydromorphone dose, concentration, duration of treatment and concomitant agents with ICTG formation. This is a retrospective analysis of 101 consecutive patients implanted with intrathecal infusion delivery devices. Data were collected from chart review, and records of pump refills from the division of Pain Medicine of University Hospitals or outsourced to a home pump refill service. From a cohort of 101 consecutively implanted patients, 69 were treated with intrathecal hydromorphone and followed up postimplant for an average of 33.5 ± 24 months (range 0-93 months; 95% CI of 27-39 months). The incidence of ICTG in our patient population was 8.7% during this period of time postimplant with mean time to granuloma detection 35.1 ± 7.9 months. Patients developing granuloma (n = 6) were treated with a combination of intrathecal hydromorphone and bupivacaine infusion. Exposure time to intrathecal agents was not different between the granuloma and nongranuloma group. Monthly dose increase of hydromorphone was higher in granuloma group vs. non-granuloma group (58 ± 34 mcg/month n = 6 vs. 25 ± 8 mcg/month n = 63). Four out of six granuloma cases occurred with low dose and concentration of IT hydromorphone (160-370 mcg/day; 0.75-1.0 mg/mL concentration). Intrathecal bupivacaine dose was not different between groups. A subset of patients was treated with intrathecal fentanyl and bupivacaine. No intrathecal granulomas occurred in this patient cohort. This is the first clinical report demonstrating an association of hydromorphone with intrathecal granulomas, particularly at low doses and concentrations of hydromorphone. This study supports the notion that using low dose of IT opioids might not protect against ICTG development but that the level of exposure and type of opioid used in IT space might be highly correlated with ICTG development. Further research and recommendations related to chronic intrathecal opioid infusions are necessary to raise awareness of significant incidence of ICTG and development of tests to isolate patient populations at high risk.

Unexpected Baclofen Subdural Infusion in a Patient who Carries an Internal Pump for Intrathecal Infusion: A Case Report

Objective: We report a case of intrathecal baclofen infusion pump implantation complicated by migration of the catheter tip. Subdural migration, of the intrathecal catheter tip, in who has been having an infusion pump for years and is experiencing swinging dosage related effects it is not the first thing one takes into consideration. A case of subdural migration of intrathecal catheters is presented. Methods: Subsequent X-ray and computed tomography evaluations of the catheter system revealed pooling of contrast medium outside of the intrathecal space, in the lumbar subdural region of the vertebral channel and therefore migration of the pump catheter tip. Results: The spinal catheter was subsequently revised, and the patient made a full recovery. From few days after surgery, the patients spasticity improved and up to now (six months later), he has been experiencing no further complications, is requiring an average baclofen dosage of 150 mcg/day. Conclusion: The possible migration of an intrathecal catheter into the subdural space should be included as differential diagnosis in a patient who experiences a lack of drug effect, despite increases in dosage, after years from pump implantation. We recommend the use of the CT scan, after contrast injection, to detect the distal catheter tip and confirm a normal diffusion into the subarachnoid space.

Neurochemical excitation of thoracic propriospinal neurons improves hindlimb stepping in adult rats with spinal cord lesions

Using an in vitro neonatal rat brainstem–spinal cord preparation, we previously showed that cervicothoracic propriospinal neurons contribute to descending transmission of the bulbospinal locomotor command signal, and neurochemical excitation of these neurons facilitates signal propagation. The present study examined the relevance of these observations to adult rats in vivo. The first aim was to determine the extent to which rats are able to spontaneously recover hindlimb locomotor function in the presence of staggered contralateral hemisections (left T2–4 and right T9–11) designed to abolish all long direct bulbospinal projections. The second aim was to determine whether neurochemical excitation of thoracic propriospinal neurons in such animals facilitates hindlimb stepping. In the absence of intrathecal drug injection, all animals (n=24) displayed some degree of hindlimb recovery ranging from weak ankle movements to brief periods of unsupported hindlimb stepping on the treadmill. The effect of boluses of neurochemicals delivered via an intrathecal catheter (tip placed midway between the rostral and caudal thoracic hemisections) was examined at post-lesion weeks 3, 6 and 9. Quipazine was particularly effective facilitating hindlimb stepping. Subsequent complete transection above the rostral (n=3) or caudal (n=2) hemisections at week 9 had no consistent effect on drug-free locomotor performance, but the facilitatory effect of drug injection decreased in 4/5 animals. Two animals underwent complete transection at T3 as the first and only surgery and implantation of two intrathecal catheters targeted to the mid-thoracic and lumbar regions, respectively. A similar facilitatory effect on stepping was observed in response to drugs administered via either catheter. The results indicate that partial spontaneous recovery of stepping occurs in adult rats after abolishing all long direct bulbospinal connections, in contrast to previous studies suggesting that hindlimb stepping after dual hemisections either does not occur or is observed only if the second hemisection surgery is delayed relative to the first. The results support the hypothesis that artificial modulation of propriospinal neuron excitability may facilitate recovery of motor function after spinal cord injury. However, whether this facilitation is due to enhanced transmission of a descending locomotor signal or is the result of excitation of thoracolumbar circuits independent of supraspinal influence, requires further study.

Patients with a History of Spine Surgery or Spinal Injury may have a Higher Chance of Intrathecal Catheter Granuloma Formation

Intrathecal drug delivery is an effective method to treat intractable pain. However, intrathecal catheter tip granuloma (ICTG) is a devastating complication of intrathecal drug delivery systems. It typically occurs in the thoracic region; particularly, in patients receiving high doses or high concentrations of intrathecal drug infusions. The PUBMED/MEDLINE and Cochrane databases were also systematically searched for all reports on ICTG published in any language. The key words included "intrathecal," "granuloma," and "spine surgery," and all related publications between the earliest available date (the first granuloma-related chronic complication of intrathecal infusion reported in PUBMED/MEDLINE in 1996) and June (week 1) of 2012 were searched. This case report is unique because it describes the formation of an intrathecal granuloma in the lumbar region of a patient who received a low-dose intrathecal infusion. Cerebrospinal fluid flow dynamics within the spinal canal along with the physical, chemical, and immunological properties of intrathecal medications have been suggested to be responsible for the growth of inflammatory mass lesions at the tips of intrathecal drug delivery catheters. Our literature review supports the possible role of certain factors, specifically previous spine surgery or spinal injury, in granuloma formation. The rate of development of ICTG appears to be higher in patients who have had previous spine surgery or spinal injury (68%) than in a general cohort of patients (48%), with an intrathecal pump. Therefore patients with a history of spine surgery or injury may be at increased risk of ICTG when receiving chronic intrathecal analgesia.

Polyanalgesic Consensus Conference—2012: Consensus on Diagnosis, Detection, and Treatment of Catheter-Tip Granulomas (Inflammatory Masses)

Continuous intrathecal infusion of drugs to treat chronic pain and spasticity has become a standard part of the algorithm of care. The use of opioids has been associated with noninfectious inflammatory masses at the tip of the intrathecal catheter, which can result in neurologic complications. The Polyanalgesic Consensus Conference is a meeting of a group of well-published and experienced practitioners; the purpose of the meeting is to update the standard of care for intrathecal therapies to reflect current knowledge gleaned from literature and clinical experience. An exhaustive literature search was performed, and information from this search was provided to panel members. Analysis of the published literature was coupled with the clinical experience of panel participants to form recommendations regarding intrathecal inflammatory masses or granulomas. The panel has made recommendations for the prevention, diagnosis, and management of intrathecal granulomas. The use of chronic infusions of intrathecal opioids is associated with the formation of inflammatory masses at the intrathecal catheter tip in a small minority of treated patients. Nonetheless, the appearance of these space-occupying lesions can lead to devastating neurologic sequelae. The prevention, early detection, and successful treatment of intraspinal granulomas are important considerations when offering intrathecal drug therapy to patients with chronic intractable pain.

Poster 270 Baclofen Overdose Following Missed Diagnosis of Intrathecal Catheter Tip Occlusion: A Case Report

Poster 270 Baclofen Overdose Following Missed Diagnosis of Intrathecal Catheter Tip Occlusion: A Case Report

Intrathecal catheter tip inflammatory mass lesions (granulomas): a case report with bone destruction and review of imaging findings

Intrathecal catheter tip inflammatory mass lesions (granulomas): a case report with bone destruction and review of imaging findings

AnIn VivoCanine Study to Assess Granulomatous Responses in the MedStream Programmable Infusion System™ and the SynchroMed II Infusion System®

A rare, but consistently reported complication of intrathecal (IT) delivery of opioids via programmable implantable infusion pumps is aseptic granuloma formation around the tip of the IT catheter. In the current study, the incidence and severity of IT granuloma formation was assessed for the MedStream Programmable Infusion and SynchroMed II Infusion pumps when delivering saline, baclofen, or morphine at varying concentrations and daily doses. Randomized study with six groups: 1) MedStream with 0.9% saline; 2) SynchroMed II with 0.9% saline; 3) MedStream with morphine sulfate; 4) SynchroMed II with morphine sulfate; 5) MedStream with baclofen; or 6) SynchroMed II with baclofen. The groups receiving morphine received either low or high concentrations (6 or 12.5 mg/mL) delivered in rates resulting in low to high (1.25-12 mg/day) daily doses. Animals receiving baclofen began at low dose/low concentration and underwent stepwise increases in concentration and dose to a maximum of 2 mg/mL/day. Animals receiving saline received a constant flow rate through either a silicone or a polyurethane IT catheter. The study was set as in vivo laboratory experiment. 52 (21-32 kg) canines. Delivering IT saline, baclofen, or morphine through SynchroMed II and MedStream Programmable Infusion pumps. The incidence and severity of IT catheter tip granuloma formation was assessed with paraffin-embedded spinal cord sections by a pathologist without knowledge of treatment and compared between drug type, drug concentration, daily dose, and pump type. Granuloma formation occurred only in animals receiving morphine, with zero incidence in baclofen or saline infusion, regardless of catheter type. Granuloma incidence increased with increasing morphine concentration or daily dose (one [12.5%] low dose/low concentration, 3 [37.5%] low dose/high concentrations, 4 [50%] high dose/low concentration, and 7 [100%] high dose/high concentration). A granulomatous response to morphine was observed in 10 (63%) animals with SynchroMed II pumps and 5 (33%) animals with MedStream pumps, P = 0.156. In this in vivo canine model of IT drug delivery, catheter tip granuloma formation was associated with higher concentrations and daily doses of morphine infusion while none were seen with baclofen or saline, and was not associated with catheter type. For both pumps, granulomas were only produced in the presence of morphine infusion. These results suggest that the MedStream Programmable Infusion System has a granuloma safety profile at least equivalent to that of the SynchroMed II pump.

A critique of the latest consensus panel for intrathecal therapy

Because of the relative lack of placebo and dose-ranging studies regarding the initiation and titration of intrathecal (IT) therapy, the Polyanalgesic Consensus Conference (2007) yielded recommendations regarding the management of pain by IT drug delivery. Expert opinion is valuable; however, further consideration might be given to the established literature on the subject. Conclusions of the Polyanalgesic Consensus Conference (2007) were reviewed in light of existing literature. Of note, few published data exist to determine hydromorphone equianalgesic doses or maximum IT dose, the risk of spinal cord lesion secondary to bupivacaine, the suitability of ziconotide as a first-line agent, and the practicality of computed tomography-myelography for diagnosis of granuloma at the IT catheter tip. Common practices are not necessarily supported by established data. Nevertheless, continuous IT infusion has established itself as a powerful, effective, and safe modality for the treatment of pain in selected individuals who cannot tolerate or find relief with noninvasive analgesic techniques.