Intrathecal Therapies: Local and National Trends and Complications NANS 2010 Nandan Lad, MD, PhD; Robert T. Arrigo, MS; Melanie Hayden,MD; Paul Kalanithi, MD; Chirag G. Patil, MD;, Maxwell Boakye, MD, Jaimie Henderson,MD Stanford University Medical Center Dept of Neurosurgery; Outcomes Research Lab; Biodesign Surgical Innovation Program;

2 Conflict of Interest: Conflict of Interest: None None Grants: Grants: NIH, AHA, NCIIA NIH, AHA, NCIIA Consultant for: Consultant for: Neurofluidics, Inc. Neurofluidics, Inc. I will discuss the following investigational use in my presentation: I will discuss the following investigational use in my presentation: Future Directions-NeuroApheresis Future Directions-NeuroApheresis Treatment of: Treatment of: Spasticity Spasticity Complementary management of Complementary management of malignant (cancer) pain and nonmalignant (non-cancer) pain. Reduces need for high-dose opioid therapy and its associated toxicity. Reduces need for high-dose opioid therapy and its associated toxicity. Disclosure

Outcomes Research Rationale: Trusted resource to improve health through the best use of neurosurgical modalities. Trusted resource to improve health through the best use of neurosurgical modalities. Advance the optimal use of medical devices, procedures and biological products, by: Advance the optimal use of medical devices, procedures and biological products, by: -Developing knowledge -Managing risk -Improving practice -Informing policy makers 3 SpineTumor Vascular/ Endo- vascular Pediatrics Peripheral Nerve Critical Care Stereotac tic/Functi onal Outcomes Research

4 Current treatment for: Current treatment for: Spasticity, Cancer/Nonmalignant pain Spasticity, Cancer/Nonmalignant pain Reduces need for high-dose opioid therapy and systemic toxicity. Reduces need for high-dose opioid therapy and systemic toxicity. Continuous infusion or bolus trial Continuous infusion or bolus trial Determine dosing, responsiveness and increase long-term success. Determine dosing, responsiveness and increase long-term success. Currently a last resort, used only for medically refractory patients. Currently a last resort, used only for medically refractory patients. Intrathecal therapies

5 A retrospective cohort study was performed by using the California State and Nationwide Inpatient Sample over a six year period ( ). A retrospective cohort study was performed by using the California State and Nationwide Inpatient Sample over a six year period ( ). The NIS is a nationwide database of hospital inpatient stays. Largest all-payer inpatient care database, representing approximately 20% of all inpatient admissions to nonfederal hospitals in the United States. The NIS is a nationwide database of hospital inpatient stays. Largest all-payer inpatient care database, representing approximately 20% of all inpatient admissions to nonfederal hospitals in the United States. Data from approximately 8 million annual discharges from 1004 hospitals in 37 states. Data from approximately 8 million annual discharges from 1004 hospitals in 37 states. We filtered all-listed diagnoses for only neuro-related diagnoses and icd9 procedure code (placement of intrathecal catheter/pump) We filtered all-listed diagnoses for only neuro-related diagnoses and icd9 procedure code (placement of intrathecal catheter/pump) We examined trends, cost, demographics and short-term complications associated with intrathecal therapies for pain and spasticity. We examined trends, cost, demographics and short-term complications associated with intrathecal therapies for pain and spasticity. Methods

6 The national sample included a total of 33,187 procedures performed. The national sample included a total of 33,187 procedures performed. There was a nearly 35% decrease in the annual number of procedures over this period with 6920 procedures in 2003 and 4492 in There was a nearly 35% decrease in the annual number of procedures over this period with 6920 procedures in 2003 and 4492 in Results

7 Hospital geography- Percentage of US Procedures: Hospital geography- Percentage of US Procedures: Results

8 National demographics for the procedure included: National demographics for the procedure included: 67% less than 65 years of age, 67% less than 65 years of age, 55% female, 55% female, 64% Caucasian, 64% Caucasian, Comorbidities Comorbidities (0: 33%, 1: 27%, 2: 20%, 3: 11%, 4+:7%) Insurance status Insurance status (39% private, 44% Medicare/Medical, 17% other) Results

9 Results Any Complications (Acute) 6.2% Cardiac0.33% Infection0.93% Neurologic0.52% Pulmonary2.1% Renal1.5% Venous Thromboembolism1.1% Wound Complication0.58% Several studies with 1-3 year followup from institutional studies have reported overall complication rates ranging from 15-40%, including catheter malfunction, pump failure and infection (Fluckiger 2008, Borowski 2008, Ward 2009)

10 Intrathecal therapy has improved over the last several decades, and implantable drug delivery devices have become increasingly sophisticated and safe. Intrathecal therapy has improved over the last several decades, and implantable drug delivery devices have become increasingly sophisticated and safe. Morbidity rates are in-range as those previously reported in large single institution series. Morbidity rates are in-range as those previously reported in large single institution series. Physicians and patients currently have many options for treating pain and spasticity with various old and new agents and their combination. Physicians and patients currently have many options for treating pain and spasticity with various old and new agents and their combination. Where do we go from here? What’s next? Where do we go from here? What’s next? Conclusions

11 Biodesign Process: Invention & Innovation Desired Tissue Effect Mechanical Principle Access Method Drug Material The Missing Link

12 Biodesign Process: Invention & Innovation Desired Tissue Effect Mechanical Principle Access Method Drug Material The Missing Link Surgeons are in a unique position to be that link

13 Intrathecal Therapies: Future Directions Certain biological components Cells (RBC, T/B-cell) Soluble factors (cytokine, Ab) when present in CSF Cause Neuroinflammatory & Neurodegenerative Conditions Emerging Concept

14 Future Directions Unmet Need Neurotoxic Components in CSF Current Therapy Needed Therapy TYSABRIIV IgG Steroids/ Interferon Plasma- pheresis Lumbar Drainage RBCX T-cellXXX B-cell(X)XX AntibodyXX Inflammation /Cytokines XX Rapid, broad spectrum approach to treat neurological disorders via removal of all classes of neurotoxic agents

15 Future Directions Direct removal of pathogens from CSF Direct removal of pathogens from CSF Targeted drug delivery and circulation Targeted drug delivery and circulation Versatile platform that can treat a spectrum of CNS diseases* Versatile platform that can treat a spectrum of CNS diseases* Customized, Integrated Disposable/Implantable System Customized, Integrated Disposable/Implantable System Acute-Subacute-Chronic Acute-Subacute-Chronic Initial target: Multiple Sclerosis (MS) Initial target: Multiple Sclerosis (MS) * Neurofluidics, Inc.

16 Thank You. Manuscript in progress. Intrathecal Therapies: Local and National Trends and Complications