57. Spinal cord stimulation

1. 57. Spinal cord stimulation 마취통증의학과 R2 김현석

2. Spinal cord stimulation • Use of pulsed electrical energy near the spinal cord to control pain • Analgesic properties for neuropathic pain states, anginal pain and peripheral ischemic pain. • Same technology can be applied in deep brain stimulation, cortical brain stimulation, and peripheral nerve stimulation

3. Mechanism of action • Painful peripheral stimuli carried by C fibers and lightly myelinated A delta fibers , touch and vibration carried by large myelinated A beta fiber – terminated at the substantia gelatinosa of the dorsal horn • Hypothesized that input could be manipulated to “close the gate” to the transmission of painful stimuli (gate control theory)

4. Neurophysiologic mechanisms of action of spinal cord stimulation - not understood. However, recent research - effect occur at the local and supraspinal level, and through dorsal horn interneuron and neurochemical mechanism • Experimental evidence – at dorsal horn level, altering the local neurochemistry in wide dynamic range interneuron • specifically some evidence : increased level of GABA release, serotonin / suppression of level of some excitatory amino acids including glutamate and aspartate

5. Technical consideration • Careful placement of an electrode array(leads) in the epidural space • Trial period • Anchoring the leads • Positioning and implantation of the pulse generator of radiofrequency receiver • Tunneling and connection of the connecting wires

6. Electrode two type : catheter or percutaneous versus paddle or surgical • Connected to an implanted pulse generator(IPG) or an RF unit

7. Stimulator trial two ways: “straight percutaneous” or “implanted lead” in both trial methods, under fluroscopy and sterile conditions • Trial stimulation –“cover” the painful area with an electrically induced paresthesia. • Straight percutaneous trial • needle is withdrawn, anchoring suture, sterile dressing • after a trial of several days – dressing is removed, suture clipped, lead removed • new lead implant is placed in the location of the trial lead and connected to an implanted IPG

8. Implanted lead trial • after successful positioning of the trial lead, local anesthetic is infilterated around the needle and an incision is made, cutting down to the supraspinous fascia • temporary extension piece is tunneled away from the back incision and out through the skin. • this exiting piece is secured to the skin using a suture, antibiotic ointment, sterile dressing. • if the trial is successful, percutaneous lead is discarded. Permanent lead are hooked to new extension and tunneled to an implanted IPG.

9. Implanted lead method – saving cost of new electrode • Percutaneous lead – avoid cost of using operating room, avoiding an incision and postoperative pain during the trial, which may confuse trial interpretation by the patient

10. Trial with paddle-type electrodes require the implanted lead approach with the significant addition of a laminectomy to slip the flat plate electrode into the epidural space • IPG/RF unit is generally in the lower abdominal area or in the posterior superior gluteal area • Access with their dominant hand for adjustment of their setting with the patient-held remote control unit

11. Patient selection • Appropriate patient • Amendable to this therapy(i.e., neuropathic pain syndrome) • Failed conservative therapy • Significant psychological issue have been ruled out • Trial has demonstrated pain relief • To avoid failed implant • Careful trial of different length • 5- to 7- day trial with the use of oral antibiotics • Understanding of diagnosis which respond to neurostimulation, improved psychological screening, improved multi-lead system

12. Complication • simple(lack of appropriate paresthesia coverage) to devastating complication(paralysis, nerve injury, death) • North and collegues • Subcutaneous infection : 5% • Predominant Cx. : lead migration or breakage • Bipolar lead – 23% revision • Multichannel device – 16% revision • Failure of the electrode lead : 13% • More recent study by Barolat and May • Revision rate due to lead migration : 4.5%, 13.6% • Breakage : 0%, 13.6% • Infection : 7%, 2.5% • No serious complication

13. Infection range from simple infection at the surface of the wound to epidural abscess • Patient should be instructed on wound care and recognition of sign and symptoms • Many superficial infection : oral antibiotics or simple surgical exploration and irrigation • Prophylactic intraoperative antibiotics and oral coverage postoperatively for 10 days • If infection reaches device, in most case the implant should be removed • Epidural abscess can lead to paralysis and death if not identified quickly and treated aggressively • neurological deficit(63%), concomitant meningitis(23%)

14. Programming • Four basic parameter • Amplitude : intensity or strength of stimulation, measured in volts(0 to 10 V) – lower setting->peripheral nerve and paddle-type electrode • Pulse width : measure in microseconds of the duration of a pulse(100 to 400us) – larger width-> broader coverage • Rate : measured in hertz or cycle per second(20 to 120 Hz) – low rate->patient feel thumping, high rate->buzzing • Electrode selection : complex topic, changed until the patient obtain anatomic coverage

15. Outcomes • Most common use in the USA is in FBSS(failed back surgery syndrome), whereas in europe, peripheral ischemia • Basic science knowledge, implantation technique, lead placement location, contact array design, programming capability improvement have led to decreased morbidity and much greater probability of obtaining adequate paresthesia coverage

16. OUTCOMEFailed back surgery syndrome • North et al. : long-term evaluation has shown that SCS continues to be more effective than re-operation • Barolat et al. : VAS, Oswestry Disability Questionnaire, Sickness Impact Profile -> the majority of patients reported fair to excellent pain relief in both the low back and legs(at 6months(92%), at 1year(88%)) • Burchiel et al. : all pain and quality-of-life measures showed statstically significant improvement, whereas medication usage and work status did not significantly improve during the treatment year.

17. OUTCOMEComplex regional pain syndrome • Kemler : trial compare SCS vs conservative therapy for CRPS ->short term SCS reduces pain and improves the quality of life. • Calvillo : 36month after implantation pain measured on VAS was an average of 53% better;statistically significant. Analgesic consumption decreased in the majority of patients-> in late stage of CRPS neurostimulation(with SCS or peripheral nerve stimulation) is a reasonable option when alternative therapy have failed

18. OUTCOMEPeripheral ischemia and angina • Cook et al. : SCS effectively relieved pain associated with peripheral ischemia (particularly associated with vasospasm such as Raynaud’s disease)

19. Cost effectiveness • Kumar : cost effectiveness of SCS in the treatment of chronic back pain, 5 years -> stimulation group : annual cost was 29,000$ control group : 35,000$ return to work : stimulation group 15%, control group 0% • Bell and North : medical cost of SCS therapy in the treatment of patient with FBSS. -> reducing the demand for medical care by FBSS patient, SCS therpy could lower medical cost

20. Peripheral, cortical, and deep brain stimulation • Peripheral nerve stimulation : effective for peripheral nerve injury syndrome, CRPS • Motor cortex and deep brain stimulation : highly refractory neuropathic pain syndromes including central pain, deafferentation syndrome, trigeminal neuralgia, movement disorder

21. Conclusion • SCS is an invasive, interventional surgical procedure. • Linderothand Meyerson : some principle of neurostimulation that are cornerstone of SCS theory and practice

22. 핵심 요약 • Neurostimulation has demonstrated clinical and cost-effectiveness in FBSS, CRPS, peripheral ischmia, angina • Multicontact, multielectrode system improve outcome and reduce the need for surgical revision. • Paddle-type : superior coverage at lower power setting • Achilles’ heel of the implanted neurostimulation system is lead migration • Serious complication is rare, but can be devastating.

23. 58. Impanted Drug Delivery Systems for the Control of Chronic pain 마취 통증 의학과 R2 김현석

24. Oral, parenteral and transdermal narcotics are extremely effective analgesic agent; however systemic administration may cause significant side effects and long-term use in sufficent doses may result in tolerance and increased potential for addiction

25. Discovery of opiate receptors in the substantia gelatinosa of the spinal cord led to the recognition of opioids having a spinal analgesic action • Descending pain inhibition system : • Frontal cortex and hypothalamus -> periaueductal gray of the midbrain • Dorsal pons and the rostroventral medulla -> dorsolateral funiculus -> substantia gelatinosa • Efferent projection inhibit the second-order ascending nociceptive neuron, blocking pain transmission

26. Morphine : hydrophilicity and slow absorption from the CSF -> analgesia last up to 24hrs(not uncommon) • At the spinal level, opiates presynaptically diminish primary afferent terminal excitability and inhibit substance P release, postsynaptically suppress excitatory amino acid-evoked excitatory postsynaptic potentials(EPSP) in dorsal horn neurons • Five opioid receptor subclasses, three of which( mu, delta, kappa)are thought to mediate antinociception. . Morphine, D-alanine-D-leucine enkephalin(DADLE) and dynorphin are the prototype agonists for these receptor subclass

27. Discovery of multiple receptor system involved in nociceptive transmission and modulation has allowed the testing and application of other receptor selective drugs • Alpha-adrenergic agonists : most widely used non-narcotic agents for intraspinal pain pharmacotherapy. Alpha-adrenergic receptor exist in the substantia gelatinosa of the spinal cord. Particular advantage over opiates of little or no effect on respiratory center. • While other agents have been investigated clinically, narcotics, local anesthetics, adrenergic agonists are most often used clinically. Morphine and clonidine are the only agents approved by the FDA for intraspinal analgesic use.

28. Patient Selection • Failure of maximal medical therapy • Tricyclic antidepressant, non-narcotic analgesics, long-term systemic narcotics -> FAIL ! • Favorable psychological evaluation • Acute psychotic illness and severe, untreated depression need diagnosis and treatment prior to surgical consideration • Absence of systemic infection • Absence of clotting disorder • Absence of drug allergy • Absence of obstruction of CSF flow • Life expectancy greater than three months • Favorable response to an intraspinal narcotic trial

29. Route of administration(epidural administration) • No study compared the relative efficacy of epidural versus intrathecal administration to control intractable pain • Equianalgesic epidural dose is roughly 10 times that of an intrathecal dose • 80~90% of an epidural injection is systemically absorbed -> greater side effect (constipation and urinary retention), increased probability of developing narcotic tolerance • Maximum morphine solubility in saline:55mg/ml -> higher dose requirement with epidural infusion -> more frequent refilling • Complication : dural scarring, occlusion, kinking, displacement

30. Route of administration(intrathecal administration) • Disadvantages: potential CSF leak, postdural spinal headache, respiratory depression due to supraspinal redistribution of narcotic and meningeal infection or neural injury • Advantage : lower drug dosage requirement-> increased interval between pump refill, low risk of catheter failure, infrequent occurrence of potential complication

31. Drug delivery system • Percutaneous epidural catheter atteched to external pump, internalized passive catheter and reservoir requiring percutaneous drug administration, patient activated mechanical system, constant rate infusion, pump, programmable infusion pump. • Choice of drug administration system should be made with careful consideration of the benefits of bolus versus continuous drug infusion and the patient’s general medical status, ambulatory status, estimated life expectacy. • Continuous spinal infusion result in lower peak CSF morphine concentration and corresponding lower plasma level than bolus adm.

32. Continuous infusion may result in a reduced rate of opioid receptor tachyphylaxis and decrease the risk of producing delayed respiratory depression • Percutaneously implanted tunneled epidural catheter attatched to and external drug pump: short life expectency, bed-bound..-> viable, inexpensive option // infection risk, • Limited life expectancy who are ambulatory, an implanted reservoir system attached to an intraspinal catheter • Mechanical patient-controlled indwelling drug administration system : available for implantation outside USA, consist of an implanted drug reservoir, intraspinal catheter, patient activated control system

33. Two major type of implanted drug pump : drug-filled bellows compressed by pressurized freon gas : fixed rate, dose change-pt discomfort, changes in temperature and atmospheric pressure • More expensive is the programmable, electronic drug pump : battery operated, surgical replacement when the batteries expire about every 4years • Both implanted pump type need to be refilled every 1 to 2 month

34. Results (opioids) • Morphine • the most studied intrathecal drug for the management of refractory chronic pain of both malignant and non-malignant origin • With results from recent prospective trial, the reported efficacy for non-malignant pain states remain variable, with the range between 25~57.5% • Hydromorphone • Five times more potent than morphine • No prospective controlled trials evaluating the efficacy to treat nonmalignant pain • 37 pts. Who failed treatment with intrathecal morphine had improvement in their pain score when switched to hydromorphone.

35. Side effect of intraspinal narcotics • Urinary retention • Pruritus • Delayed respiratory depression • Decrease in Sexual libido • Decreased testosterone level in men = both dose dependent and naloxone reversible • Increased narcotic requirement to maintain a similar degree of pain control • Tolerance at the receptor level • Change in the status of the Patient disease

36. Several strategies to manage such situation • Simply increasing the drug dose • Temporarily using systemic analgesics while the pump is turned off for a period of several days to a few weeks “drug holiday” -> down regulation of the opioid receptor and return of efficacy when intraspinal narcotics are reinstitued • Use of narcotics active at other opioid receptor subclass • Concomittant administration of low-dose local anesthetics with narcotic (bupivacaine)

37. Results (adrenergic agonists) • Clonidine produced analgesia lasting more than 6hours but also decreased blood pressure by more than 30%, heart rate decreased by 10~30%, no opioid-like side effects of respiratory depression, pruritus or nausea • Prospective, randomized trial of adding epidural clonidine to intrathecal morphine in patient with cancer pain : analgesia was achieved more commonly in the clonidine group.(45% vs 21%) • In contrast to clonidine, alpha-2-adrenergic agonist tizanidine does not apper to induce hypotension, demonstrated to be an effective analgesic agent, useful in the treatment of narcotic insensitive neuropathic pain syndrome

38. Results (Ziconotide) • Also known as SNX-111, 25-amino-acid peptide isolated from a marine snail venom. • Highly selective N-type voltage-sensitive calcium channel antagonist • Mechanism of action is by blocking neurotransmitter release at the primary afferent nerve terminal • Complication of intrathecal use : nystagmus, dysmetria, ataxia, sedation, agitation, hallucination, coma • Ellis et al : chronic, severe pain with favorable response(50% for failed back pain and 58% for back pain)

39. Complications • Infection is common to all drug delivery devices. Percutaneous catheters and implanted reservoir susceptible to infection, infection may involve the surgical wound or the subcutaneous region surrounding the hardware • Treated by removal of all implanted hardware and the administration of appropriate intravenous antibiotics, contaminated drug solution may lead to a potentially life-threatening meningitis -> limited by the use of bacteriostatic filter • Erosion of the hardware through the skin -> limited by placing the implant in a deep pocket, does not lie directly under the incision.

40. Most frequent complication is failure of the system itself (catheter problem up to 25%) • Kinking, obstruction, disconnection • Several technique to limit risk of catheter failure: • Use of fluroscopy • Observation of CSF • Overdose (improper setting of external drug pump, improper dilution)

41. Future Directions • While efficacy in the treatment of pain secondary to malignancy apper clear, the use of intraspinal drug administration for pain of nonmalignant origin remain to be elucidated • Patient selection criteria need to be better defined • Development in analgesic pharmacology need to be applied to intraspinal drug therapy