Analgesic efficacy of high-frequency spinal cord stimulation: a randomized double-blind placebo-controlled study.

INTRODUCTION: Spinal cord stimulation is a recognized treatment of chronic neuropathic and vascular pain. Recent data suggest that the use of very high-frequency (HF) stimulation modes does produce analgesia without paresthesia. AIM OF THE STUDY: To compare the efficacy of HF stimulation (HF spinal cord stimulation [HFSCS]) and sham stimulation on the patient's global impression of change (PGIC), pain intensity, and quality of life. PATIENTS AND METHODS: Forty patients who have achieved stable pain relief with conventional SCS have been recruited. After randomization, HFSCS and sham are initiated in a double-blind randomized two-period-crossover design. RESULTS: Complete data were available from 33 patients. The primary outcome was a minimal improvement in the PGIC. The proportion of patients responding under HFSCS was 42.4% (14/33 patients) vs. 30.3% (10/33 patients) in the sham condition. The mean benefit of HF vs. sham was not statistically significant with a proportion of 11.2% in favor of HFSCS (p = 0.30). There was a highly statistically significant "period effect," irrespective of treatment received, with 51.5% of patients (N = 17) improving at visit 3 vs. 21.2% (N = 7) at visit 5 (p = 0.006). The mean pain visual analog scale (VAS) on sham was 4.26 vs. 4.35 on HFSCS (p = 0.82) and the mean EuroQol five-dimensional (EQ-5D) index with HFSCS was 0.480 vs. 0.463 with sham (p = 0.78). CONCLUSION: This is the first randomized double-blind study on SCS. HFSCS was equivalent to sham for the primary outcome (improvement of PGIC) as well as for both the secondary outcomes (VAS and EQ-5D index). There was a highly statistically significant "period effect" (p = 0.006) with improved PGIC scores in the first study period regardless of the treatment. The same trend was seen for VAS and EQ-5D. It appears that the effect of HFSCS and sham is equal and only the order in the sequence, not the nature of the treatment, seems to dictate the effect.

Silicone septum leakage at the origin of a drug overdose in a patient implanted with an intrathecal pump.

INTRODUCTION: Intrathecal (IT) pump failures usually result in decreased drug administration and symptom reoccurrence with or without withdrawal syndrome. We report a case of a leaking silicone septum associated to a systemic drug overdose. CASE REPORT: An 84-year-old patient treated with IT clonidine for chronic back pain presented with a state of confusion, visual hallucinations, and hypertension two hours after an unremarkable pump (SynchroMed EL, Medtronic, Minneapolis, MN, USA) refill. The reservoir was emptied and 14 mL (8.4 mg of clonidine) was found to be missing (difference between retrieved and expected volumes). The pump was refilled and a check on the next day showed again a loss of 3.5 mL. A malfunction was suspected and the pump was replaced (SynchroMed II, Medtronic). The inspection of the external surface of the pump revealed severe damage to the silicone septum with multiple gouges due to needle scarring. A fluid leak also was clearly seen through the septum. DISCUSSION: The signs and symptoms presented by this patient are consistent with clonidine overdose that resulted from a combination of a possible accidental pocket fill and a definite septum leak into the subcutaneous tissue. The damage to the silicone could be due to the loss of the nontraumatic properties of the Huber needles that are rubbed against the metallic case in attempting to locate the injection port during refill procedures. CONCLUSION: This observation is the first description of a silicone septum damage contributing to a pump dysfunction and drug overdose despite the use of appropriate needles for refilling.

Severe hypertension following accidental clonidine overdose during the refilling of an implanted intrathecal drug delivery system.

BACKGROUND: Complications associated with intrathecal pumps may be linked to the surgical procedure, the implanted device, or the medication itself. CASE REPORTS: Three patients treated chronically with intrathecal clonidine presented with clonidine overdose due to inadvertent extravasation during the refilling procedure. All patients experienced loss of consciousness and severe systemic hypertension that required aggressive parenteral treatment. DISCUSSION: Clonidine is an alpha-2 agonist with a nearly 100% bioavailability after oral or rectal administration. With high plasma concentration secondary to massive systemic overdose, the specificity for the alpha-2 receptor is lost and an alpha-1 agonist activity predominates and causes marked hypertension. Management of clonidine overdose consists of supportive therapy guided by signs and symptoms. CONCLUSION: Inadvertent injection into the subcutaneous pocket rather than the reservoir is rare but very dangerous as the drug cannot be retrieved and massive doses are involved. Signs and symptoms of systemic overdose with drugs commonly used in implanted drugs delivery system should be well known to ensure early diagnosis and treatment.

Effects of flow rate modifications on reported analgesia and quality of life in chronic pain patients treated with continuous intrathecal drug therapy.

OBJECTIVE: We compared the analgesia and the quality of life of a constant daily dose of intrathecal drug administered at different flow rates in patients treated for chronic pain. We postulate that the quality of the analgesia, at the same daily dose, will show an infusion rate dependent pattern with decreased pain at higher flow rates. PATIENTS: Twenty consecutive patients on stable intrathecal treatment were included in a double-blind three-period crossover study where the same daily dose was administered at single, double, and quadruple flow rates in a randomized sequence. OUTCOMES MEASURES: The mean daily pain score and the quality of life (EuroQol measure of health outcome [EQ-5D]) were measured following each flow rate change, after 1 week of stabilization. Results. Visual analog scale (VAS) scores remained unchanged with all flow rates. Compared with the lowest flow rate, the EQ-5D index decreased with double and even more with quadruple flow rate, suggesting a clinically relevant worsening of the health state with higher flow rates. Adverse events were equally distributed in all groups. CONCLUSION: Pain VAS did not significantly change with flow rate. This is consistent with preclinical data showing very limited increase in drug distribution in the cerebrospinal fluid with much larger flow rate augmentation. However, the quality of life decreased consistently as the flow rate increased. This was entirely due to a worsening of the pain and anxiety dimension of the EQ-5D questionnaire, caused presumably by a slight increase in pain rather than adverse events. We suggest that at higher flow rates increased drug dilution results in a decreased effect at the receptor site.

Neurostimulation technology for the treatment of chronic pain: a focus on spinal cord stimulation.

Over the past 40 years we have seen how electrical stimulation for the relief of pain has progressed from an experimental treatment based upon a clinical theory to being on the threshold of becoming a standard of medical practice. While tens of thousands of devices are implanted every year, the mechanism of action still evades complete understanding. Nevertheless, technological improvements have been considerable and the current neuromodulation devices are both extremely sophisticated and reliable. Unlike most conventional treatments, neurostimulation cannot be restricted to one speciality as its clinical applications ignore the boundaries of medical specialities. Conditions such as neuropathic pain in the back and the leg, complex regional pain syndrome, ischemic pain due to peripheral vascular disease and coronary artery disease are likely to respond to spinal cord stimulation. Even though the evidence for efficacy remains unsatisfactory, the stimulation of the dorsal column has been remarkably successful in relieving pain and improving function in patients who have failed conventional management. The development, the technicalities and the most important clinical applications of spinal cord stimulation are reviewed here.

Spinal cord stimulation for the management of refractory angina pectoris.

Despite sophisticated medical and surgical procedures, including percutaneous endovascular methods, a large number of patients suffer from chronic refractory angina pectoris. Improvement of pain relief in this category of patients requires the use of adjuvant therapies, of which spinal cord stimulation (SCS) seems to be the most promising. Controlled studies suggest that in patients with chronic refractory angina, SCS provides symptomatic relief that is equivalent to that provided by surgical or endovascular reperfusion procedures, but with a lower rate of complications and rehospitalization. Similarly, SCS proved cost effective compared to medical as well as surgical or endovascular approaches in a comparable group of patients. This technique is still met with reluctance by the medical community. Reasons for this disinclination may be related to incomplete understanding of the mechanism of action of SCS and the fact that SCS refers to the modulation of neuroendocrine parameters rather than to revascularization, which is currently the dominant treatment paradigm in coronary artery disease.

Intraparenchymal migration of an intrathecal catheter three years after implantation.

Intrathecal drug administration using implanted catheter and pump systems has been used in routine clinical practice for more than 20 years to treat chronic refractory pain or spasticity. Complications associated with the use of these systems include drug related adverse events as well as technical problems, most of which are related either to the catheter or the procedure. Although traumatic neural damage is exceedingly rare it is usually associated with significant neurological impairment. We present a case of asymptomatic intraspinal migration of an intrathecal catheter three years after an uneventful implantation. To the best of our knowledge, this complication has never been reported before.

Improved physical activity in patients treated for chronic pain by spinal cord stimulation.

The objective of this study was to objectively assess the physical activity of daily living in chronic pain patients treated with spinal cord stimulation (SCS). Changes in pain and spontaneous physical activity following SCS were evaluated under real life conditions. Five series of measurements were performed before the implant (baseline) and at one, three, six, and 12 months after the implantation of an SCS system. Compared to baseline values, physical activity increased consistently during the entire follow-up period. The time spent walking and standing was statistically increased after six months (p < 0.01) and the time spent lying decreased significantly (p < 0.001) at the same time. The average total walking distance increased up to 389% at 12 months, reaching statistical significance (p < 0.05) after three months. The stride length and the speed increased (p < 0.01) at all times. We conclude that the reduction in pain intensity due to SCS is associated with a progressive and sustained improvement in physical activity. j.

Efficacy of intrathecal bupivacaine: how important is the flow rate?

We present two cases of cancer patients with intractable mechanical and visceral pain that was unrelieved with either comprehensive medical management or intrathecal morphine who received intrathecal bupivacaine. While the continuous administration of a seemingly significant daily dose neither relieved pain nor caused measurable clinical changes, the addition of small, presumably negligible bolus doses on top of the continuous infusion resulted in spectacular pain control, clear thermoanalgesic suspended block, and in one of the patients, significant hypotension. To the best of our knowledge, such an observation has neither been reported before nor can we provide a satisfactory explanation for it. However, we believe it may have significant implications for the treatment of some patients, in particular, cancer patients with mechanical pain that cannot be adequately relieved with morphine whatever the route of administration.