Intrathecal Drug Delivery Device Infection

Intrathecal Drug Delivery Device Infection

A major complication of Intrathecal Drug Delivery Device (IDDD) implantationis infection.

Morgalla et al., assessed IDD-related complications in 51 patients who had IDD systems implanted for the treatment of chronic pain or spasticity.

Twelve patients (23.5%) presented a total of 22 complications. The main type of complication was catheter-related (50%), followed by pump failure, infection, and inappropriate refilling 1).


Device-related and surgical wound infection occurred in 12 patients (3%), and nine were regarded as severe in the series of Taira et al., 2).

Risk Factors

Patients with extremely low muscle bulk, visceral pumps may be impractical or impossible, with increased risks of dehiscence and infection 3).


Periodic refills of intrathecal implanted pumps do not seem to be a risk factor for infection if standard sterile refill procedures are performed. In a study, it was clear that comorbid infections from other parts of the body do not present as a risk for device contamination 4).

Prevention

Follett et al., concluded from the available data that the most effective antiinfection measures consist of adherence to published guidelines and recommendations that apply to surgical site infections (SSIs) in general 5).


The use of vancomycin powder in patients with implants in the series of is series of Ghobrial et al., did not reduce infection rates compared to published historical controls, and was elevated compared to institutional controls 6).


The combination of local neomycin/polymyxin with systemic antibiotic therapy can lead to a significantly lower rate of postoperative infection than when systemic antibiotics are used alone 7).


The subfascial implantation technique was associated with a reduced rate of local wound and pump infections and provided optimal cosmetic results as compared with that observed in retrospective cases 8).

Treatment

The current standard of care in the treatment of IDDD infection necessitates that the pump be explanted and the infection treated prior to implantation of a new IDDD. This process leads to long hospital stays, interruptions in optimal medical management, and a high risk for dangerous drug withdrawals.


Infections can be treated with repetitive local application of gentamicin-impregnated collagen fleece 9).


Leibold et al., describe a technique that allows for the explantation of the infected pump and implantation of a new pump concurrently, which they have named the “Turner Switch” technique in honor of its inventor.

The authors conducted a retrospective analysis of cases of infected IDDDs in which patients underwent simultaneous explantation of the infected pump and implantation of a new pump. Demographics and clinical data were collected.

Data from a total of 17 patients (11 male, 6 female) who underwent simultaneous IDDD explantation and implantation to treat infections were analyzed from a 3-year period. No patients experienced infection of the newly implanted pump or catheter. Of the 17 patients, 14 (82.4%) had baclofen pumps to treat spasticity and 3 (17.6%) had fentanyl pumps to treat chronic pain. The median hospital stay was 7 days, with 16 of 17 (94.1%) patients able to be discharged home or to a facility with a level of care similar to their preoperative care. All patients ultimately experienced complete resolution of their initial infections. Five patients (29.4%) required a return to the operating room within the next 5 months (for repair of a CSF leak in 2 cases, for treatment of infection at the old pump site in 2 cases, and for treatment of a CSF leak compounded with infection in 1 case). No patient experienced infection of the newly implanted pump or catheter.

IDDD infections represent a large portion of morbidity associated with these devices. The current standard of care for deep pump infections requires pump explantation and a course of antibiotics prior to reimplantation of the IDDD. The authors demonstrate the effectiveness of a procedure involving simultaneous explantation of an infected pump and implantation of a new pump on the contralateral side in the treatment of IDDD infections 10).


Ingale et al., suggested that consideration should be given to selective dorsal rhizotomy (SDR) as an alternative in patients previously implanted with Intrathecal Drug Delivery systems complicated by infection or nearing end of battery life 11).

Case reports

A patient with pump-site infection and Escherichia coli meningitis secondary to transcolonic perforation of an intrathecal baclofen pump catheter. While this is rare, we review the intraoperative precautions and best practices that should be taken to prevent and manage this unusual complication 12).


Intrathecal drug delivery device infection with Mycobacterium fortuitum was not been reported previously. Aliabadi et al., reported a case of an implanted baclofen pump infection and associated mycobacterium meningitis due to Mycobacterium fortuitum. The entire pump system was removed and the patient was treated successfully with a prolonged regimen of antibiotics 13).


In a case neurological complaints were pain and dysaesthesiae in the lower back and thigh, as well as paresis of the ileopsoas muscle. MRI of the lumbar spine showed an intradural-extramedullary mass at the level of L1 homogeneously enhancing with gadolinium. This mass was situated at the tip of an intrathecal catheter implanted 11 years before for a morphine trial infusion as therapy for phantom pain after amputation of the right arm. Now, removal of the catheter was performed. Cultures of lumbar CSF and the catheter tip demonstrated coagulase negative staphylococcus. Antibiotic medication with cephalosporines was given for 6 weeks. After removal of the catheter, the patient was free of pain and he progressively regained full neurological function. Although most catheter-associated granulomas reported so far were sterile in nature, bacterial infection should still be considered even years after catheter placement 14).


A patient who experienced a prolonged course of intrathecal baclofen withdrawal syndrome after removal of an implantable baclofen pump for treatment of pump infection and meningitis. The current literature outlines management options for the acute management of this syndrome. In this report the authors discuss the long-term presentation of this syndrome and suggest a treatment strategy for management of the syndrome. A 37-year-old man who presented with a baclofen pump infection and meningitis experienced acute onset of intrathecal baclofen withdrawal syndrome 12 hours after the pump had been surgically removed. The patient’s symptoms evolved into a severe, treatment-refractory withdrawal syndrome lasting longer than 1 month. Oral baclofen replacement with adjunctive administration of parenteral gamma-aminobutyric acid agonists only served to stabilize the patient’s critical condition throughout his hospital course. Replacement of the baclofen pump and restoration of intrathecal delivery of the medication was necessary to trigger the patient’s dramatic recovery and complete reversal of the withdrawal syndrome within approximately 48 hours. These findings indicate that a more direct method of treating infected baclofen pumps than immediate surgical removal is necessary to prevent the onset of intrathecal baclofen withdrawal syndrome. Various options for preventing the onset of the syndrome while simultaneously treating the infection are discussed 15).

References

1)

Morgalla M, Fortunato M, Azam A, Tatagiba M, Lepski G. High-Resolution Three-Dimensional Computed Tomography for Assessing Complications Related to Intrathecal Drug Delivery. Pain Physician. 2016 Jul;19(5):E775-80. PubMed PMID: 27389121.
2)

Taira T, Ueta T, Katayama Y, Kimizuka M, Nemoto A, Mizusawa H, Liu M, Koito M, Hiro Y, Tanabe H. Rate of complications among the recipients of intrathecal baclofen pump in Japan: a multicenter study. Neuromodulation. 2013 May-Jun;16(3):266-72; discussion 272. doi: 10.1111/ner.12010. Epub 2012 Dec 14. PubMed PMID: 23240625.
3)

Waqar M, Ellenbogen JR, Kumar R, Sneade C, Zebian B, Williams D, Pettorini BL. Indwelling intrathecal catheter with subcutaneous abdominal reservoir: a viable baclofen delivery system in severely cachectic patients. J Neurosurg Pediatr. 2014 Oct;14(4):409-13. doi: 10.3171/2014.6.PEDS13686. Epub 2014 Aug 1. PubMed PMID: 25084089.
4)

Dario A, Scamoni C, Picano M, Fortini G, Cuffari S, Tomei G. The infection risk of intrathecal drug infusion pumps after multiple refill procedures. Neuromodulation. 2005 Jan;8(1):36-9. doi: 10.1111/j.1094-7159.2005.05218.x. PubMed PMID: 22151381.
5)

Follett KA, Boortz-Marx RL, Drake JM, DuPen S, Schneider SJ, Turner MS, Coffey RJ. Prevention and management of intrathecal drug delivery and spinal cord stimulation system infections. Anesthesiology. 2004 Jun;100(6):1582-94. Review. PubMed PMID: 15166581.
6)

Ghobrial GM, Thakkar V, Singhal S, Oppenlander ME, Maulucci CM, Harrop JS, Jallo J, Prasad S, Saulino M, Sharan AD. Efficacy of intraoperative vancomycin powder use in intrathecal baclofen pump implantation procedures: single institutional series in a high risk population. J Clin Neurosci. 2014 Oct;21(10):1786-9. doi: 10.1016/j.jocn.2014.04.007. Epub 2014 Jun 14. PubMed PMID: 24938386.
7)

Miller JP, Acar F, Burchiel KJ. Significant reduction in stereotactic and functional neurosurgical hardware infection after local neomycin/polymyxin application. J Neurosurg. 2009 Feb;110(2):247-50. PubMed PMID: 19263587.
8)

Kopell BH, Sala D, Doyle WK, Feldman DS, Wisoff JH, Weiner HL. Subfascial implantation of intrathecal baclofen pumps in children: technical note. Neurosurgery. 2001 Sep;49(3):753-6; discussion 756-7. PubMed PMID: 11523691.
9)

Peerdeman SM, de Groot V, Feller RE. In situ treatment of an infected intrathecal baclofen pump implant with gentamicin-impregnated collagen fleece. J Neurosurg. 2010 Jun;112(6):1308-10. doi: 10.3171/2009.8.JNS081692. PubMed PMID: 19731988.
10)

Leibold AT, Weyhenmeyer J, Lee A. Simultaneous explantation and implantation of intrathecal pumps: a case series. J Neurosurg. 2019 Apr 12:1-7. doi: 10.3171/2019.1.JNS18919. [Epub ahead of print] PubMed PMID: 30978693.
11)

Ingale H, Ughratdar I, Muquit S, Moussa AA, Vloeberghs MH. Selective dorsal rhizotomy as an alternative to intrathecal baclofen pump replacement in GMFCS grades 4 and 5 children. Childs Nerv Syst. 2016 Feb;32(2):321-5. doi: 10.1007/s00381-015-2950-9. Epub 2015 Nov 9. PubMed PMID: 26552383.
12)

Devine OP, Harborne AC, Lo WB, Price R. Colonic perforation by an intrathecal baclofen pump catheter causing delayed Escherichia coli meningitis. BMJ Case Rep. 2017 Dec 20;2017. pii: bcr-2017-222539. doi: 10.1136/bcr-2017-222539. PubMed PMID: 29269368.
13)

Aliabadi H, Osenbach RK. Intrathecal Drug Delivery Device Infection and Meningitis due to Mycobacterium Fortuitum: A Case Report. Neuromodulation. 2008 Oct;11(4):311-4. do 10: i: 10.1111/j.1525-1403.2008.00181.x. PubMed PMID: 22151146.
14)

Lehmberg J, Scheiwe C, Spreer J, van Velthoven V. Late bacterial granuloma at an intrathecal drug delivery catheter. Acta Neurochir (Wien). 2006 Aug;148(8):899-901; discussion 901. Epub 2006 Jun 23. PubMed PMID: 16791432.
15)

Douglas AF, Weiner HL, Schwartz DR. Prolonged intrathecal baclofen withdrawal syndrome. Case report and discussion of current therapeutic management. J Neurosurg. 2005 Jun;102(6):1133-6. Review. PubMed PMID: 16028775.

Intrathecal Baclofen Therapy

Intrathecal Baclofen Therapy

Intrathecal baclofen was first introduced in 1985 to manage childhood hypertonia. There has been an evolution in thought as to how candidates should be identified and what forms of hypertonia respond to this treatment.

Indications

Intrathecal baclofen (ITB) treatment is considered a powerful tool in the management of severe spasticity in neurological conditions such as multiple sclerosis, cerebral palsy, and traumatic spinal cord injury and brain injury.

Intrathecal baclofen (ITB) has been known to reduce spasticity which did not respond to oral medications and botulinum toxin treatment.

Patients should first respond to a screening dose of intrathecal baclofen prior to consideration for long term infusion via an implantable pump.

For spasticity of spinal cord origin, ITB Therapy via an implantable infusion system should be reserved for patients unresponsive to oral baclofen or those who experience intolerable CNS side effects at effective doses. Patients with spasticity due to traumatic brain injury should wait at least one year after the injury before consideration of long term intrathecal baclofen therapy.


Berntsson et al., reported the potential beneficial effects of ITB treatment in patients with hereditary ataxia who also suffer from spasticity/spasms 1).

Screening test

A successful trial may confirm predetermined goals, which may include improved mobility/positioning, decreased time/improved independence for activities, less home exercise, better wheelchair tolerance, decreased caregiver time, improved sleep, and reduced pain, or may modify goals and expectations. Individuals should not be tested in the presence of active medical issues (e.g., MS exacerbations, active urinary tract infection, nonhealing wounds). Oral antispasmodics can be weaned before trial if a goal is to eliminate them. The standard baclofen test dose is a 50-mcg bolus, 25 mcg in very small children or patients who rely on spasticity for mobility. Patients unresponsive to the standard dose may require 75 mcg or 100 mcg; 24 hours should elapse between bolus doses. Cardiopulmonary parameters should be checked frequently during the first two hours postinjection, and spasticity measures assessed at least twice within four hours. Observation continues until the patient is stable and recovers from hypertonia. Adverse events include spinal headaches, nausea/vomiting, urinary retention, hypotension, seizures, drowsiness/sedation, respiratory depression, and coma. Before implantation, team members must discuss starting dose, drug concentration, delivery mode, pump size and location, and catheter tip placement. Patients/caregivers should understand the commitment necessary for ITB therapy 2).

Adverse events

Adverse events (AEs) related to intrathecal baclofen (ITB) therapy in adults, was relatively low. This has to be balanced against the clinical, functional and quality of life improvements, which are expected from ITB therapy 3).

This therapy is contraindicated in patients who are hypersensitive to baclofen. Implantation of the infusion system is contraindicated if the patient is of insufficient body size, requires a pump implant deeper than 2.5 cm, or, in the presence of spinal anomalies or active infection.

The most frequent drug adverse events vary by indication but include: hypotonia (34.7%), somnolence (20.9%), headache (10.7%), convulsion (10.0%), dizziness (8.0%), urinary retention (8.0%), nausea (7.3%), and paresthesia (6.7%). Pump system component failures leading to pump stall, or dosing/programming errors may result in clinically significant overdose or underdose. Acute massive overdose may result in coma and may be life threatening.

The most frequent and serious adverse events related to device and implant procedures are catheter dislodgement from the intrathecal space, catheter break/cut, and implant site infection including meningitis. Electromagnetic interference (EMI) and Magnetic resonance imaging (MRI) may cause patient injury, system damage, operational changes to the pump, and changes in flow rate.

Case series

The objective of a study of Berntsson et al., from Sweden was to assess the effectiveness of the ITB in patients with inherited ataxia suffering from severe painful spasms and/or spasticity.

A total of 5 patients with spinocerebellar ataxia 3 or 7 or Friedreich’s ataxia were included in this observational multicenter study. The patients were interviewed and completed outcome measures assessing pain (The Brief Pain Inventory), fatigue (Fatigue Severity Scale), and life satisfaction (LiSAT-9) before and 1 year after the treatment. Spasticity (Modified Ashworth Scale) and spasm frequency (SPFS) were measured objectively for each patient.

The mean treatment time was 1.9 years. Evaluation of established standard forms revealed symptomatic relief from spasticity, spasms, pain, and fatigue in addition to improved body posture, sleep, and life satisfaction after ITB treatment.

They reported the potential beneficial effects of ITB treatment in patients with inherited ataxia who also suffer from spasticity/spasms. ITB treatment indication in neurological disorders allows for extension to the treatment of spasticity/ spasms in patients with hereditary ataxia 4).

2017

A study aimed to investigate beneficial and adverse effects of Intrathecal Baclofen (ITB) bolus injection and pump therapy in patients with cerebral palsy (CP) and to compare outcomes to patients with acquired brain injury such as traumatic brain injury and cerebral hypoxia. ITB test trials were performed in 37 patients (19 CP and 18 acquired brain injury). Based on ambulatory function, CP patients were divided into 2 groups: 11 patients with nonambulatory CP and 8 patients with ambulatory CP. Change of spasticity was evaluated using the Modified Ashworth Scale. Additional positive or negative effects were also evaluated after ITB bolus injection. In patients who received ITB pump implantation, outcomes of spasticity, subjective satisfaction and adverse events were evaluated until 12 months post-treatment. After ITB bolus injection, 32 patients (86.5%) (CP 84.2% versus acquired brain injury 88.9%) showed a positive response of reducing spasticity. However, 8 patients with CP had negative adverse effects. Particularly, 3 ambulatory CP patients showed standing impairment and 1 ambulatory CP patient showed impaired gait pattern such as foot drop because of excessive reduction of lower extremity muscle tone. Ambulatory CP patients received ITB pump implantation less than patients with acquired brain injury after ITB test trials (P = .003 by a chi-squared test). After the pump implantation, spasticity was significantly reduced within 1 month and the effect maintained for 12 months. Seventeen patients or their caregivers (73.9%) were very satisfied, whereas 5 patients (21.7%) suffered from adverse events showed no subjective satisfaction.

ITB therapy was effective in reducing spasticity in patients with CP and acquired brain injury. Before ITB pump implantation, it seems necessary to perform the ITB bolus injection to verify beneficial effects and adverse effects especially in ambulatory CP 5).

2016

In a single center study Motta et al investigated the complications occurring before and after the introduction of the new Ascenda intrathecal catheter (Medtronic Inc.) in pediatric patients treated with intrathecal baclofen therapy (ITB) for spasticity and/or dystonia.

This was a retrospective review of 508 children who had received ITB, 416 with silicone catheters in the 13 years between September 1998 and September 2011 and 92 with Ascenda intrathecal catheters in the 3 years between September 2011 and August 2014. The authors evaluated major complications such as infections, CSF leaks treated, and problems related to the catheter or pump, and they compared the 2 groups of patients who had received either a silicone catheter or an Ascenda catheter implant. RESULTS One hundred twenty patients in the silicone group (29%) and 1 patient in the Ascenda group (1.1%; p < 0.001) had a major complication. In the silicone group 23 patients (5.5%) were affected by CSF leakage and 75 patients (18%) experienced 82 catheter-related events, such as occlusion, dislodgment, disconnection, or breakage, which required catheter replacement. In the Ascenda group, only 1 patient (1.1%) was affected by CSF leakage. CONCLUSIONS To the authors’ knowledge, this study is the first in the literature to compare the performance of the new Ascenda catheter, introduced in 2011, with the traditional silicone catheter for intrathecal drug infusion. In their analysis, the authors found that the Ascenda catheter can reduce major complications related to the catheter after ITB pump implantation. Further investigation is necessary to expand on and confirm their results 6).

Case reports

The case of a young woman who received intrathecal baclofen therapy (ITB) and subsequently became pregnant and had a normal delivery. A 28-year-old woman with flexion myelopathy had anterior decompression with fusion at C4/5 and C5/6 levels. Clinical symptoms improved after surgery. However, when she was 29 years old, her symptoms steadily advanced to Modified Ashworth Scale 3 spasticity level in the lower legs, with pain in both of them and urinary retention tendency. Since a 25 μg intrathecal baclofen injection improved her symptoms, an ITB pump system was implanted. After surgery, lower limb spasticity and urinary retention improved. Two years after ITB pump implantation, the patient married and became pregnant. The patient intended to have normal delivery but the induction of labor was ineffective and childbirth was completed by Cesarean section with lumbar anesthesia. The infant’s Apgar score was 8 at 1 min and 9 at 5 min, and birth-weight was 2,704 g. We measured the baclofen concentration in the patient’s breast milk using high-performance liquid chromatography/tandem mass spectrometry. The level of baclofen in the breast milk was very low (0.617 ng/ml) and the predicted pharmacological effect on the infant was judged to be negligible. No withdrawal symptoms or muscle tone abnormalities were found after birth. Our findings indicate that ITB therapy could be considered for young women with severe spasticity, even if they plan to have children 7).


A report describes the successful management of painful spasms in a 65-year-old woman with Friedreich’s ataxia (FA) via intrathecal baclofen (ITB) therapy following unsuccessful medical treatments.

To Kalyvas et al., knowledge, this is the third reported case in the literature. Unfortunately, the pathophysiological characteristics of muscle spasms in FA are not well explored and understood while the therapeutic mechanisms of the different treatments are rather vague. Taking into consideration the suggested spinal atrophy in FA, the clinical resemblance of FA and chronic spinal injury muscle spasms, together with the rapid ITB therapy effectiveness in alleviating FA muscle spasms, they attempted to suggest a putative pathophysiological mechanism acting at the spinal level and possibly explained by the presence of independent spinal locomotor systems producing muscle spasms. Specifically, overexcitement of these centers, due to loss of normal regulation from upper CNS levels, may result in the uncontrolled firing of secondary motor neurons and may be the key to producing muscle spasms. However, further research under experimental and clinical settings seems to be necessary 8).

References

1) , 4)

Berntsson SG, Gauffin H, Melberg A, Holtz A, Landtblom AM. Inherited Ataxia and Intrathecal Baclofen for the Treatment of Spasticity and Painful Spasms. Stereotact Funct Neurosurg. 2019 Mar 14:1. doi: 10.1159/000497165. [Epub ahead of print] PubMed PMID: 30870851.
2)

Boster AL, Bennett SE, Bilsky GS, Gudesblatt M, Koelbel SF, McManus M, Saulino M. Best Practices for Intrathecal Baclofen Therapy: Screening Test. Neuromodulation. 2016 Aug;19(6):616-22. doi: 10.1111/ner.12437. Epub 2016 Jul 19. Review. PubMed PMID: 27434115.
3)

Borrini L, Bensmail D, Thiebaut JB, Hugeron C, Rech C, Jourdan C. Occurrence of adverse events in chronic intrathecal baclofen infusion: a one-year follow-up study of 158 adults. Arch Phys Med Rehabil. 2014 Jan 6. pii: S0003-9993(14)00003-3. doi: 10.1016/j.apmr.2013.12.019. [Epub ahead of print] PubMed PMID: 24407102.
5)

Yoon YK, Lee KC, Cho HE, Chae M, Chang JW, Chang WS, Cho SR. Outcomes of intrathecal baclofen therapy in patients with cerebral palsy and acquired brain injury. Medicine (Baltimore). 2017 Aug;96(34):e7472. doi: 10.1097/MD.0000000000007472. PubMed PMID: 28834868.
6)

Motta F, Antonello CE. Comparison between an Ascenda and a silicone catheter in intrathecal baclofen therapy in pediatric patients: analysis of complications. J Neurosurg Pediatr. 2016 Jun 24:1-6. [Epub ahead of print] PubMed PMID: 27341610.
7)

Hara T, Nakajima M, Sugano H, Karagiozov K, Hirose E, Goto K, Arai H. Pregnancy and Breastfeeding during Intrathecal Baclofen Therapy – A Case Study and Review. NMC Case Rep J. 2018 Jun 25;5(3):65-68. doi: 10.2176/nmccrj.cr.2017-0191. eCollection 2018 Jul. PubMed PMID: 30023142; PubMed Central PMCID: PMC6048348.
8)

Kalyvas AV, Drosos E, Korfias S, Gatzonis S, Themistocleous M, Sakas DE. Intrathecal Baclofen Therapy for Painful Muscle Spasms in a Patient with Friedreich’s Ataxia. Stereotact Funct Neurosurg. 2018 Jun 8:1-4. doi: 10.1159/000489220. [Epub ahead of print] PubMed PMID: 29886479.
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