Role of Intrathecal Baclofen. Mr. Chirag Patel Consultant Paediatric Neurosurgeon Children s Hospital for Wales, Cardiff.

Transcription

1 Role of Intrathecal Baclofen Mr. Chirag Patel Consultant Paediatric Neurosurgeon Children s Hospital for Wales, Cardiff.

2 History of Intrathecal Baclofen therapy 1978: First used in guinea pigs by Wilson. Observed a decrease in nociceptive reflexes 1984 : Richard Penn described transitory reduction in spinal cord spasticity in man after injection of single dose in spinal subarachnoid space 1985: Penn, reduction in spasticity with continuous intrathecal infusion of Baclofen 1989: Penn, double blinded study on effects of intrathecal Baclofen in spasticity due to MS, spinal cord injury 1989: Programmable ITB pump produced in USA 1996 : ITB therapy approved by Food and Drug Administration, USA. Parke B, Penn RD, Savoy SM, et al. Functional Outcome after Delivery of Intrathecal Baclofen. Arch Phys Med Rehabil 70:30-32,1989. Penn RD, Savoy SM, Corcos D, et al. Intrathecal Baclofen for Severe Spinal Spasticity N Engl J Med 329: ,1989.

3 Goals of Spasticity Management Reduce spasticity Improve functional ability and independence Reduce pain associated with spasticity Prevent or decrease incidence of contractures/torsions/deformity and need for further surgery Improve ambulation Facilitate hygiene Ease rehabilitation procedures Save caregivers time

4 Traditional Step-Ladder Approach to Management of Spasticity Neurosurgical Orthopedic Neurolysis Oral medications Rehabilitation Therapy Remove noxious stimuli

5 Current guidance Consider continuous pump administered ITB in children with spasticity if despite non-invasive treatment spasticity or dystonia causes difficulties with pain or muscle spasm posture or function self care ( or ease of care by carers/parents)

6 Intrathecal Baclofen in Cerebral Palsy Baclofen Pharmacokinetics Mechanism of action: γ-aminobutyric acid ( GABA) agonist which acts a a neuroinhibitor Acts specifically on GABA-B receptors at level of spinal cord at presynaptic level inhibits calcium absorption hence prevents release of excitatory neurotransmitters Failure to respond to oral baclofen should not preclude consideration for ITB

7 Pharmacokinetics of Baclofen Oral 60 mg dose: mcg/ml IT lumbar concentration Half-life 3-4 hours Intrathecal 600 mcg/day dose: 1.24 mcg/ml IT lumbar concentration Lumbar to cervical concentration is 4:1 Half-life 4-5 hours

8 Pharmacodynamics of Baclofen Injection Bolus Onset of action is one-half hour to 1 hour after intrathecal bolus Peak effect at 4 hours after dosing Effects may last from 4 to 8 hours Continuous Effects are first seen at 6 to 8 hours after initiation of continuous infusion Maximum effect observed in 24 to 48 hours

9 Why Intrathecal vs. Oral? Baclofen Injection Baclofen injection is delivered to the CSF and thought to act at GABA b receptor sites at the spinal cord Oral Baclofen Low blood/brain barrier penetration, with high systemic absorption and low CNS absorption Lower doses than those required orally Lack of preferential spinal cord distribution Potential for fewer systemic side effects Some patients experience unacceptable side effects at effective doses

10 Advantages of ITB Therapy Reversible Potentially fewer systemic side effects Programmable -allows dose titration to give optimal benefit Effective in reducing spasticity upper and lower extremities cerebral and spinal origin

11 Usual process of assessment Consensus on the appropriate use of ITB in paediatric spasticity. Eur J Paed Neurol 2009

12 ITB Therapy Process Stage 1: Patient Selection/ Education Stage 2: Screening Test Stage 3: Implant Stage 4: Maintenance

13 Patient selection: Inclusion criteria No hypersensitivity to Baclofen Confirmed diagnosis Severe and chronic spasticity ( Ashworth score > 3.5, Duration > 12 mths) Spasticity refractory to oral drugs or undersirable side effects with oral drugs Normal CSF flow No programmable medical devices ie pacemakers No severe pathologies ie cardiac, respiratory, renal, hepatic diseases Caregiver has clear idea of the immediate and long term rehabilitative goals Positive response to intrathecal Baclofen test dose

14 Absolute Contraindications child too small to accommodate pump local or systemic intercurrent infection Education: Patient / Family/Carers Not a cure for spasticity Risks/Benefits Understand goals of therapy ( Spasticity, QOL) Follow up refill clinics/ Reoperation for battery depletion, catheter problems Restriction of activity Brochures/Websites ( Patient ambassador

15 Screening Test Flow Chart Bolus: 25 mcg hrs after Bolus: 50 mcg hrs after Bolus: 75 mcg + - Discontinue oral drugs Monitor cardiopulmonary parameters for first 4-6 hrs Assess response 4-6 hrs post dosing + - = Positive Response Implant = Negative Response No Implant 24 hrs after Bolus: 100 mcg + - Intrathecal Baclofen Therapy Clinical Reference Guide for Spasticity Management, Medtronic, Inc. Not a Candidate

16 Assessment: Severe spasticity: best described as how problematic the spasticity is to the patient/ caregiver, rather than solely relying on a numerical rating of a particular spasticity assessment measure

17 Implant components: Pump infuses drug Catheter delivers drug to the intrathecal (subarachnoid) space of the spinal cord Programmer allows for precise dosing easily adjustable dosing

18 Technique: Paramedian approach L2,3/L3,4 level Catheter tip position at T9-10 Subcostal subfascial pocket for pump Pump/catheter priming postop

19

20 Maintenance Post-implant dose increase from day 2 once anaesthetic drugs wear off 5-15 % increment every 24 hrs Endpoint for dose increase: Efficient suppression of reflexes ( clonus, spasms, cramps, tendon reflexes) and decrease in muscle tone. Response to dose correction seen within 4-6 hrs Dosage patterns: Simple Continuous Continuous complex ( continuous with intermittent bolus) Variable rate

21 Follow up Refill in clinics depending on date for refill calculated by programmer. ( 2 ml reserve volume--- alarm) Refills to be done at maximum interval of 6 mths. Baclofen drug concentration used range from 500 ug/ml to 2000 ug/ml. Dose requirement in spinal spasticity is nearly half that of supraspinal spasticity.

22 Refill through the central port

23 Programmer and wand Various ways of programming infusion e.g. simple continuous, variable rate continuous, complex bolus dosing regime

24 Dosage patterns Simple continuous dosage Variable rate dosage 24 hrs 24 hrs Complex bolus regime 24 hrs

25 Side effects/complications Surgical complications: - Infection - Haematoma/Seroma of pump pocket - CSF leak - Sciatica due to nerve irritation - Cutaneous erosion of pump - Pump displacement/inversion - Inability to thread intrathecal catheter

26 Side effects/complications Device complications: -Hardware failure- battery failure, mechanical failure -Catheter breaks/blockage/disconnection -Programming error Level checks in case of device malfunction...

27 Levels of checks for malfunction: 1 st level: Xray imaging of pump and catheter for disconnection 2 nd level: Injection of radio-opaque contrast through sideport of pump to asses for leaks or block in catheter 3 rd level : Fluoroscopic visualization of rotation of pump motor after programming a bolus injection to assess for mechanical malfunction

28 Pump roller rotation after bolus dosage viewed with fluoroscopy. Catheter access port injection to assess patency

29

30

31 Side effects/complications Dosing complications: -Baclofen overdosage; Weakness, hypotonia, respiratory depression, convulsions,coma -Baclofen underdosage; ( Neuroleptic malignant syndrome) Spasticity, headache, Rhabdomyolysis, autonomic disturbances, drowsiness, fever, convulsions, coma,death -Baclofen side-effects; Seizures, somnolence, urinary retention, headache -Tolerance to baclofen

32

33 Economics! Hardware costs 8,000-8,500. Annual saving of CND 25,520 per patient ( Nance et al, 2004, Can. J. Neurol. Sci) due to reduced hospital care Pumps pays for itself in 2.5 yrs. (Ordia et al, 1996, J. Neurosurg)

34 Summary Patient selection and feasible goals important ITB long-term success only makes sense in context of wider rehabilitative approach Additional advances in hardware, software and pharmaceutics should improve matters And...

35 Help!! tall order for any single service to do all of this Orthopedics Neurosurgeon Rehab/ Physio/OT CNS/ Psychologist surgeon Neurologist NP Thank you