Intrathecal Pump Management

Overview and Description

Candidates suitable for intrathecal therapy must undergo a comprehensive psychological assessment and receive thorough counseling. It is essential to understand that this treatment approach entails an invasive procedure, a long-term commitment to the therapy, and, although the risks are minimal, potential complications stemming from pump or catheter malfunctions. Typically, patients must have previously completed a successful intrathecal trial with the desired medication, administered either as a bolus or continuously via a temporary infusion system, to be eligible for surgical implantation. There are several contraindications listed below that are vital for ensuring the safety and effectiveness of intrathecal therapy.¹

Contraindications to Pump Implantation:

• Infection
• Inability to implant the pump within 2.5 cm from the skin’s surface
• Patient’s body habitus cannot accommodate the pump’s bulk and weight

Contraindications to Intrathecal Catheterization:

• Meningitis, ventriculitis, skin infection, bacteremia, and septicemia
• Spinal anomalies that could complicate implantation

After completing the titration phase of intrathecal therapy, the maintenance regimen involves several crucial steps to ensure the continued efficacy of the intrathecal pump system.

• Periodic refilling of the pump reservoir with medication to maintain therapeutic levels in the intrathecal space
• Vigilant monitoring and troubleshooting to address any system malfunctions promptly
• Battery life monitoring with routine replacement of the pump itself at the end of the battery life

While commonly considered an intervention of the final resort, intrathecal drug delivery can prove highly beneficial in:

• Enhancing pain and spasticity management
• Optimizing patient functionality
• Reducing the reliance on systemic medications when applied to the right candidate

However, it is worth noting that due to the clinical and logistical demands it entails, intrathecal therapy may be a viable option primarily for larger medical practices. These practices are better equipped to allocate the essential staff and resources required to support patients comprehensively throughout the various phases, including trialing, initiation, titration, maintenance, and troubleshooting. This ensures that patients receive the best possible care and outcomes from this specialized treatment approach.²

Relevance to Clinical Practice

Morphine sulfate (Infumorph^®; Baxter Healthcare Corp., Deerfield, IL), ziconotide (Prialt^®; Jazz Pharmaceuticals Inc., Palo Alto, CA) and baclofen (Lioresal^®, Novartis Pharmaceuticals, New York, NY and Gablofen^® Mallinckrodt Pharmaceuticals, St. Louis, MO), are the only medication brands currently approved by the Food and Drug Administration (FDA) for long-term intrathecal infusion (Table 1).^{8 3}Morphine sulfate and ziconotide are indicated as first-line intrathecal therapies for chronic intractable pain (benign or malignant). Baclofen is indicated for chronic spasticity of spinal (traumatic spinal cord injury and multiple sclerosis) or cerebral (acquired brain injury, cerebral palsy and stroke) origin. For spasticity of spinal origin, each patient must have previously trialed oral baclofen and either had an insignificant response or intolerable adverse effects at an effective dose. For spasticity of cerebral origin, current guidelines recommend waiting at least one year following injury before consideration of pump implant, but this does not always apply. For all causes of spasticity, intrathecal therapy can be viewed as a legitimate therapeutic alternative to neurosurgical procedures such as dorsal rhizotomy.

For purposes of review, we will only be discussing in detail monotherapy with intrathecal medications that are currently FDA-approved. The FDA emphasizes the importance of following instructions for the use of these pumps carefully, as delivering analgesic medication directly into the spinal fluid is a complex procedure. The agency has issued a warning to healthcare providers and patients about the potential complications when certain implanted pumps are used to deliver compounded medicines that are not FDA-approved for use with these devices.⁴

Complications include:

• Dosing errors
• Pump failure
• Opioid withdrawal
• Infections

Table 1: Medication brands currently approved by the Food and Drug Administration (FDA) for long-term intrathecal infusion.

Morphine Sulfate

Morphine sulfate predominantly interacts with the mu-receptors in the dorsal horn of the spinal cord to inhibit the release of excitatory neurotransmitters (such as glutamate and substance P) and therefore produce analgesia. It is important to note that it is significantly more hydrophilic than any of the other opioids in clinical use, which allows for prolonged duration of action in the CSF and increased spread above the injection point.^5,6 This can lead to more extensive analgesic benefits, but can also be associated with an increased risk of respiratory depression.⁶ For this reason, it is contraindicated in patients with history of substance abuse or significant pulmonary disease, such as obstructive sleep apnea.^7-10 Intrathecal morphine was initially developed for severe cancer pain, but its application has become more widespread in the treatment of chronic pain.^11,12There are many benefits of intrathecal opioid delivery over enteral routes, particularly a marked decrease in dosing and reduction in morphine metabolites. High concentrations of these metabolites may cause cognitive deficits and impair attention and memory.¹³ Decreased systemic concentrations of opioids can reduce risk of adverse effects to other body systems as well.

Intrathecal trials with a bolus or temporary catheter infusion typically start at 0.2–1.0 mg and can be titrated up as indicated.³ Several studies have shown that a period of opioid weaning and abstinence prior to trial and implantation may increase the likelihood of success with intrathecal morphine therapy and reduce the need for oral opioid supplementation.^14,15

Adverse Effects of Intrathecal Morphine³

• Respiratory depression
• Hypotension
• Nausea
• Pruritis
• Urinary Retention
• Hypotension
• Peripheral edema
• Intrathecal granulomas
• Withdrawal from abrupt cessation

Withdrawal symptoms may result from abrupt cessation of intrathecal opioids due to catheter disruption, battery failure, or pump refill and programming errors. Of course, errors with pump refill, programming, and dosage can also lead to drug overdose (see figure 1 for morphine overdose emergency procedures). Intrathecal morphine sulfate is contraindicated in patients with history of substance abuse or significant pulmonary disease, such as obstructive sleep apnea.^7-10

Figure 1: Morphine overdose emergency procedures.  Reproduced with permission from Medtronic indications, drug stability, and emergency procedures reference manual.¹⁶

Ziconotide

Ziconotide, a non-opioid analgesic agent, is the synthetic equivalent of a naturally occurring conopeptide produced by the venomous marine cone snail. It is thought to be an antagonist of N-type calcium channels located on the primary nociceptive (A-d and C) afferent nerves of the dorsal horn.^8,17-22 The efficacy and safety of intrathecal ziconotide has been shown in several double-blinded, placebo-controlled trials with a significant reduction in pain compared to placebo for cancer and non-cancer related pain.^8,17-24,33 The benefits of ziconotide is that, unlike morphine and baclofen, it can be discontinued abruptly without evidence of withdrawal in the event of serious neurological or psychiatric disturbance. No incidences of intrathecal granuloma formation or lethal overdose from ziconotide have been reported to date either.^8,25

Recommended starting dosing for intrathecal ziconotide is 0.5–2.4 mcg/day and initial dosing should not be greater than 2.4 mcg/day during both trialing and titration phase after implantation.³ The maximum recommended dose is 19.2 mcg/day (0.8 mcg/hr), though some may tolerate higher doses. A ziconotide naïve pump requires priming, which involves several rinses of the internal surface of the pump with the drug prior to filling so that the drug does not bind to the surface.

Adverse Effects of Intrathecal Ziconotide

• Dizziness
• Confusion
• Hallucinations
• Ataxia
• Memory impairment
• Headache
• Nystagmus
• Nausea
• Urinary retention
• Abnormalities in creatine kinase

Due to the potential for hallucinations and other psychiatric events, ziconotide is contraindicated in patients with prior history of psychosis. Slow titration and lower doses are shown to be better tolerated and can reduce the incidence of adverse events.^23,26

Baclofen

Baclofen is a gamma-aminobutyric acid (GABA) B agonist and acts selectively on GABA-B receptors in the brain and spinal cord to inhibit presynaptic excitatory neurotransmitter release and,, therefore reduce spasticity.³ Bypassing the blood-brain barrier allows dosing to be approximately a hundredfold less than the equivalent oral dose while also showing a preference toward action at the spinal level with reduced cerebral side effects. There is a 4:1 gradient of baclofen in the lower versus upper portions of the spinal cord causing it to be routinely more effective in the lower limbs²⁷ Studies have shown it to be effective in reducing spasticity caused by cerebral palsy, spinal cord injury, brain injuries, multiple sclerosis, and stroke.²⁷

Adverse Effects of Intrathecal Baclofen

• Hypotonia
• Somnolence
• Headache
• Dizziness
• Nausea
• Urinary retention
• Peripheral edema
• Life-threatening withdrawal syndrome
  • Seizure from abrupt discontinuation
  • Fever
  • Confusion
  • Hypertonia
  • Multiple organ-system failure

(See Figure 2 for intrathecal baclofen withdrawal emergency procedures). Overdosing can also occur and potentially lead to confusion, drowsiness, dizziness, respiratory depression seizures, hypotonia, loss of consciousness, coma, multi-organ failure, and death (see Figure 3 for intrathecal baclofen overdose emergency procedures).¹

Figure 2: Intrathecal baclofen underdose or withdrawal emergency procedures. Reproduced with permission from Medtronic indications, drug stability, and emergency procedures reference manual.¹⁶

Figure 3: Intrathecal baclofen overdose emergency procedures. Reproduced with permission from Medtronic indications, drug stability, and emergency procedures reference manual.¹⁶

Screening and Titration Process

Intrathecal baclofen (ITB) screening can be performed with an intrathecal bolus (50-100 mg) via lumbar puncture or continuous catheter infusion.²⁸ A catheter infusion trial offers the advantage of having the ability to control catheter tip placement and more closely mimics the effects of continuous infusion with implantation, however the risk of complications is increased.²⁹

Initial starting dose of baclofen can vary based on the effective trial dose and the duration of relief obtained on that dose. The initial daily dosage should be equivalent to double the effective bolus dosage determined during the ITB screening test. For example, if a 50 mcg ITB bolus was administered during the screening test, the starting dose would be 100 mcg/day.^28,30

During the titration process, adjustments to the intrathecal baclofen dosage are made over time to attain the optimal level for each patient. This determination is based on a comprehensive evaluation of the patient’s condition and progress toward their individual goals. The interval for dose adjustment depends on the patient’s response and the level of monitoring they receive.

Although titration can occur in various settings, inpatient settings offer advantages such as frequent dose adjustments and assessment every 24 hours to optimize treatment. Alongside rapid drug titration, patients should receive intensive, goal-oriented inpatient or outpatient rehabilitation. Dose titration can also take place in an outpatient setting with the aim of adjusting the dose both quickly and safely. Outpatient dose adjustments are typically scheduled weekly or biweekly, depending on the patient’s ability to return to the clinic.³⁰

Gradual tapering of oral antispasmodics following the initiation of intrathecal therapy prevents significant withdrawal symptoms resulting from abrupt discontinuation of these medications. This approach also aims to maintain the effectiveness of oral antispasmodics for as long as necessary and minimize the risk of increased spasticity during the surgical implantation process. When discontinuing oral antispasmodics, it is advisable to taper one drug at a time, adjusting the rate of taper based on the drug’s pharmacological characteristics. Regular clinical assessments within 24 hours after each oral and intrathecal dose change are advised during inpatient titration. Oral baclofen should remain available as needed throughout intrathecal baclofen dose titration and beyond, especially for managing intrathecal withdrawal and addressing irregular spasticity patterns and pain in some patients.³⁰

The initial titration phase concludes when the patient is

• Tapered off of oral antispasmodics
• Attains an optimal intrathecal baclofen dose
• Additional dose increments no longer yield advantages or cause adverse effects

To achieve the best results in intrathecal baclofen therapy, active patient and caregiver involvement is crucial. They should fully understand the treatment plan, options, goals, and their respective responsibilities. They must understand that the goal of the baclofen pump is not solely to reduce spasticity (as the pain pumps reduce pain) but typically is more focused on achieving rehabilitation goals and ultimately greater independence. This understanding enhances communication on treatment progress and ensures compliance with the prescribed regimen, making educated patients and caregivers valuable partners in the treatment process. Patient education should be reiterated during dose adjustments, pump refills, or device procedures, which are high-risk situations for dosing errors.

Patient education includes

• Adverse effects
• Signs of over- or under-doing
• Risk of pump infection
• Life-threatening consequences of allowing the pump to run dry
  • Adherence to pump refill schedules
  • Low reservoir alarm dates
  • Alarm sounds and meanings
• Adherence to medication schedules
• Participation in therapy
• Compliance with home exercise program
• Use of braces and splints

Additionally, an emergency card should be provided to all patients and caregivers, outlining signs of dosing issues and containing their provider’s contact information in case of emergencies.  Patients should be made aware of the existence of phone applications like Medtronic’s myPTM™ Smartphone Controller that can assist with managing their pumps.

Cutting Edge/Unique Concepts/Emerging Issues

Intrathecal pumps and spinal cord stimulators are advanced medical devices designed to address chronic pain and neurological conditions, offering alternative therapeutic approaches when traditional treatments fall short. Together, these innovative technologies represent a growing frontier in pain management and neurological care, promising enhanced quality of life for individuals suffering from a range of debilitating conditions. A recent prospective clinical trial aimed to investigate the impact of transcutaneous spinal stimulation on individuals with traumatic spinal cord injury who had an implanted intrathecal baclofen pump. The study focused on whether transcutaneous spinal stimulation had any adverse effects on the functionality of the Medtronic SynchroMed™ II intrathecal baclofen pump delivery system when the cathode was placed at the T11/12 level. The researchers assessed the pump’s performance before, during, and after transcutaneous spinal stimulation sessions. The study found no evidence of transcutaneous spinal stimulation negatively affecting the intrathecal baclofen pump delivery mechanism. However, it was noted that communication interference occurred between the interrogator and the pump during transcutaneous spinal stimulation, likely due to electromagnetic interference. Additionally, one participant experienced elevated blood pressure at the end of the trial, although it was suspected to be unrelated to spinal stimulation. Despite these challenges, the results suggest that further transcutaneous spinal stimulation studies involving individuals with implanted Medtronic SynchroMed™ II intrathecal baclofen pumps may be feasible, particularly when stimulating at the low thoracic spine, although communication with the programmer during stimulation may be affected.³¹

The utilization of ultrasound guidance for intrathecal pump refills represents an encouraging advancement in medical practice. This innovative approach offers the potential to enhance the efficiency and safety of refilling procedures for patients with challenging anatomical factors or previous difficulties, thereby improving their overall healthcare experience. A recent study aimed to investigate the feasibility of using ultrasound guidance for intrathecal baclofen pump refills in patients with historically difficult refills. These difficulties included factors like high body mass index, deep/tilted pump placement, and the need for special positioning or multiple skin punctures. The study employed a nonblinded, randomized controlled trial with a crossover element at a tertiary academic rehabilitation hospital. Participants were randomly assigned to either a template-guided (control) or ultrasound-guided (experimental) group, with crossovers allowed under certain conditions. The primary outcome measured was the time spent with the needle under the skin, with secondary outcomes including the number of needle punctures, needle passes, attending interventions, pain during and after the procedure, patient satisfaction, and practitioner-perceived difficulty. The results indicated that ultrasound-guided intrathecal refills, while not statistically significant, showed potential benefits compared to template-guided refills. The experimental group had shorter average procedure times, fewer instances of multiple needle punctures, needle passes, and attending interventions. However, there were no significant differences in pain levels during or after the procedure, patient satisfaction, or practitioner-perceived difficulty.³²

Gaps in Knowledge/Evidence Base

There are several notable gaps in knowledge surrounding intrathecal pain and baclofen pumps, which pose significant challenges for both clinicians and patients. Firstly, a pressing issue involves the use of non-FDA approved medications within these pumps. The limited availability of FDA-approved drugs for intrathecal administration often leads physicians to explore off-label options to manage complex pain conditions or spasticity, but the efficacy and long-term safety of such medications remain inadequately studied. This lack of standardized protocols and data on non-approved drugs can compromise patient outcomes and safety.

Another concerning gap is the use of multiple medications within a single pump. Intrathecal pumps are designed to deliver precise dosages of a single medication, but some patients require the simultaneous administration of multiple drugs to address their complex pain or spasticity needs. The interactions, compatibility, and potential adverse effects of co-administering various medications within a single device are not well-documented, leaving healthcare providers with limited guidance on optimizing therapy in such cases.

Addressing these knowledge gaps is essential for advancing the field of intrathecal pain and baclofen pump management, improving patient care, and ensuring the long-term safety and effectiveness of these therapies. Research efforts aimed at filling these voids in knowledge are crucial to providing evidence-based treatment options and guidelines for clinicians and patients alike.

References

1. Medtronic SynchroMed™ IsoMed Implantable infusion systems. Accessed September, 16, 2023. https://www.medtronic.com/content/dam/emanuals/neuro/M034770C_b_001_view.pdf
2. Saulino M, Kim PS, Shaw E. Practical considerations and patient selection for intrathecal drug delivery in the management of chronic pain. J Pain Res. 2014;7:627-38. doi:10.2147/JPR.S65441
3. Bottros MM, Christo PJ. Current perspectives on intrathecal drug delivery. J Pain Res. 2014;7:615-26. doi:10.2147/JPR.S37591
4. FDA alerts doctors, patients about risk of complications when certain implanted pumps are used to deliver pain medications not approved for use with the devices. The Foor and Drug Administration. Accessed September, 16th, 2023. https://www.fda.gov/news-events/press-announcements/fda-alerts-doctors-patients-about-risk-complications-when-certain-implanted-pumps-are-used-deliver
5. Gilmer-Hill HS, Boggan JE, Smith KA, Wagner FC. Intrathecal morphine delivered via subcutaneous pump for intractable cancer pain: a review of the literature. Surg Neurol. Jan 1999;51(1):12-5. doi:10.1016/s0090-3019(98)00080-9
6. Grape S, El-Boghdadly K, Albrecht E. Management of adverse effects of intrathecal opioids in acute pain. Best Pract Res Clin Anaesthesiol. Jun 2023;37(2):199-207. doi:10.1016/j.bpa.2023.02.002
7. Perruchoud C, Dupoiron D, Papi B, Calabrese A, Brogan SE. Management of Cancer-Related Pain With Intrathecal Drug Delivery: A Systematic Review and Meta-Analysis of Clinical Studies. Neuromodulation. Aug 2023;26(6):1142-1152. doi:10.1016/j.neurom.2021.12.004
8. Deer TR, Pope JE, Hanes MC, McDowell GC. Intrathecal Therapy for Chronic Pain: A Review of Morphine and Ziconotide as Firstline Options. Pain Med. Apr 01 2019;20(4):784-798. doi:10.1093/pm/pny132
9. Carvajal G, Dupoiron D, Seegers V, et al. Intrathecal Drug Delivery Systems for Refractory Pancreatic Cancer Pain: Observational Follow-up Study Over an 11-Year Period in a Comprehensive Cancer Center. Anesth Analg. Jun 2018;126(6):2038-2046. doi:10.1213/ANE.0000000000002903
10. Xing F, Yong RJ, Kaye AD, Urman RD. Intrathecal Drug Delivery and Spinal Cord Stimulation for the Treatment of Cancer Pain. Curr Pain Headache Rep. Feb 05 2018;22(2):11. doi:10.1007/s11916-018-0662-z
11. Kumar K, Kelly M, Pirlot T. Continuous intrathecal morphine treatment for chronic pain of nonmalignant etiology: long-term benefits and efficacy. Surg Neurol. Feb 2001;55(2):79-86; discussion 86-8. doi:10.1016/s0090-3019(01)00353-6
12. Onofrio BM, Yaksh TL. Long-term pain relief produced by intrathecal morphine infusion in 53 patients. J Neurosurg. Feb 1990;72(2):200-9. doi:10.3171/jns.1990.72.2.0200
13. Højsted J, Kurita GP, Kendall S, Lundorff L, de Mattos Pimenta CA, Sjøgren P. Non-analgesic effects of opioids: the cognitive effects of opioids in chronic pain of malignant and non-malignant origin. An update. Curr Pharm Des. 2012;18(37):6116-22. doi:10.2174/138161212803582522
14. Hamza M, Doleys D, Wells M, et al. Prospective study of 3-year follow-up of low-dose intrathecal opioids in the management of chronic nonmalignant pain. Pain Med. Oct 2012;13(10):1304-13. doi:10.1111/j.1526-4637.2012.01451.x
15. Grider JS, Harned ME, Etscheidt MA. Patient selection and outcomes using a low-dose intrathecal opioid trialing method for chronic nonmalignant pain. Pain Physician. 2011;14(4):343-51.
16. Medtronic indications, drug stability, and emergency procedures SynchroMed® and IsoMed® implantable infusion systems. Accessed September 17, 2023. https://www.medtronic.com/content/dam/emanuals/neuro/M961293A_e_001_view.pdf
17. Van Zundert J, Rauck R. Intrathecal drug delivery in the management of chronic pain. Best Pract Res Clin Anaesthesiol. Jun 2023;37(2):157-169. doi:10.1016/j.bpa.2023.02.003
18. Lambe T, Duarte R, Eldabe R, et al. Ziconotide for the Management of Cancer Pain: A Budget Impact Analysis. Neuromodulation. Aug 2023;26(6):1226-1232. doi:10.1016/j.neurom.2022.08.458
19. Shao MM, Khazen O, Hellman A, et al. Effect of First-Line Ziconotide Intrathecal Drug Therapy for Neuropathic Pain on Disability, Emotional Well-Being, and Pain Catastrophizing. World Neurosurg. Jan 2021;145:e340-e347. doi:10.1016/j.wneu.2020.10.079
20. Banik RK, Engle MP. Ziconotide for Management of Cancer Pain Refractory to Pharmacotherapy: An Update. Pain Med. Dec 25 2020;21(12):3253-3259. doi:10.1093/pm/pnaa251
21. Deer T, Hagedorn JM. How has ziconotide impacted non-cancer pain management? Expert Opin Pharmacother. Apr 2020;21(5):507-511. doi:10.1080/14656566.2019.1707182
22. McDowell GC, Saulino MF, Wallace M, et al. Effectiveness and Safety of Intrathecal Ziconotide: Final Results of the Patient Registry of Intrathecal Ziconotide Management (PRIZM). Pain Med. Nov 01 2020;21(11):2925-2938. doi:10.1093/pm/pnaa115
23. Wallace MS, Rauck R, Fisher R, et al. Intrathecal ziconotide for severe chronic pain: safety and tolerability results of an open-label, long-term trial. Anesth Analg. Feb 2008;106(2):628-37, table of contents. doi:10.1213/ane.0b013e3181606fad
24. Ellis DJ, Dissanayake S, McGuire D, et al. Continuous Intrathecal Infusion of Ziconotide for Treatment of Chronic Malignant and Nonmalignant Pain Over 12 Months: A Prospective, Open-label Study. Neuromodulation. Jan 2008;11(1):40-9. doi:10.1111/j.1525-1403.2007.00141.x
25. Pope JE, Deer TR, Amirdelfan K, McRoberts WP, Azeem N. The Pharmacology of Spinal Opioids and Ziconotide for the Treatment of Non-Cancer Pain. Curr Neuropharmacol. 2017;15(2):206-216. doi:10.2174/1570159×14666160210142339
26. Rauck RL, Wallace MS, Leong MS, et al. A randomized, double-blind, placebo-controlled study of intrathecal ziconotide in adults with severe chronic pain. J Pain Symptom Manage. May 2006;31(5):393-406. doi:10.1016/j.jpainsymman.2005.10.003
27. Ertzgaard P, Campo C, Calabrese A. Efficacy and safety of oral baclofen in the management of spasticity: A rationale for intrathecal baclofen. J Rehabil Med. Mar 06 2017;49(3):193-203. doi:10.2340/16501977-2211
28. Boster AL, Bennett SE, Bilsky GS, et al. Best Practices for Intrathecal Baclofen Therapy: Screening Test. Neuromodulation. Aug 2016;19(6):616-22. doi:10.1111/ner.12437
29. Vats A, Amit A, Cossar M, Bhatt P, Cozens A. Intrathecal baclofen trial using a temporary indwelling intrathecal catheter – A single institution experience. J Clin Neurosci. Oct 2019;68:33-38. doi:10.1016/j.jocn.2019.07.073
30. Boster AL, Adair RL, Gooch JL, et al. Best Practices for Intrathecal Baclofen Therapy: Dosing and Long-Term Management. Neuromodulation. Aug 2016;19(6):623-31. doi:10.1111/ner.12388
31. Lopez J, Forrest GF, Engel-Haber E, et al. Transcutaneous spinal stimulation in patients with intrathecal baclofen pump delivery system: A preliminary safety study. Front Neurosci. 2022;16:1075293. doi:10.3389/fnins.2022.1075293
32. Stone SN, Wei D, Reger C. Ultrasound guidance versus landmark guidance for intrathecal baclofen pump refill: A randomized pilot study. PM R. Apr 07 2023;doi:10.1002/pmrj.12982

Original Version of the Topic

Daniel Moon, MD. Intrathecal Agents. 4/11/2016

Previous Revision(s) of the Topic

Daniel Moon, MD, Ryan Hafner, MD. Intrathecal Agents. 12/1/2020

Author Disclosure

Justin Weppner, DO
Nothing to Disclose

Margaret Clinard
Nothing to Disclose