Opioid rotation in the management of chronic pain: where is the evidence?

The management of chronic pain remains a challenge because of its complexity and unpredictable response to pharmacological treatment. In addition, accurate pain management may be hindered by the prejudice of physicians and patients that strong opioids, classified as step 3 medications in the World Health Organization ladder for cancer pain management, are reserved for the end stage of life. Recent information indicates the potential value of strong opioids in the treatment of chronic nonmalignant pain. There are, up until now, insufficient data to provide indications about which opioid to use to initiate treatment or the dose to be used for any specific pain syndrome. The strong inter-patient variability in opioid receptor response and in the pharmacokinetic and pharmacodynamic behavior of strong opioids justifies an individual selection of the appropriate opioid and stepwise dose titration. Clinical experience shows that switching from one opioid to another may optimize pain control while maintaining an acceptable side effect profile or even improving the side effects. This treatment strategy, described as opioid rotation or switch, requires a dose calculation for the newly started opioid. Currently, conversion tables and equianalgesic doses are available. However, those recommendations are often based on data derived from studies designed to evaluate acute pain relief, and sometimes on single dose studies, which reduces this information to the level of an indication. In daily practice, the clinician needs to titrate the optimal dose during the opioid rotation from a reduced calculated dose, based on the clinical response of the patient. Further research and studies are needed to optimize the equianalgesic dosing tables.

Impact of opioid rescue medication for breakthrough pain on the efficacy and tolerability of long-acting opioids in patients with chronic non-malignant pain.

BACKGROUND: There is little evidence that short-acting opioids as rescue medication for breakthrough pain is an optimal long-term treatment strategy in chronic non-malignant pain. We compared clinical studies of long-acting opioids that allowed short-acting opioid rescue medication with those that did not, to determine the impact of opioid rescue medication use on the analgesic efficacy and tolerability of chronic opioid therapy in patients with chronic non-malignant pain. METHODS: We searched MEDLINE (1950 to July 2006) and EMBASE (1974 to July 2006) using terms for chronic non-malignant pain and long-acting opioids. Independent review of the search results identified 48 studies that met the study selection criteria. The effect of opioid rescue medication on analgesic efficacy and the incidence of common opioid-related side-effects were analysed using meta-regression. RESULTS: After adjusting for potentially confounding variables (study design and type of opioid), the difference in analgesic efficacy between the 'rescue' and the 'no rescue' studies was not significant, with regression coefficients close to 0 and 95% confidence intervals that excluded an effect of more than 18 points on a 0-100 scale in each case. There was also no significant difference between the 'rescue' and the 'no rescue' studies for the incidence of nausea, constipation, or somnolence in both the unadjusted and the adjusted analyses. CONCLUSIONS: We found no evidence that rescue medication with short-acting opioids for breakthrough pain affects analgesic efficacy of long-acting opioids or the incidence of common opioid-related side-effects among chronic non-malignant pain patients.

Impact of long-term use of opioids on quality of life in patients with chronic, non-malignant pain.

OBJECTIVE: The use of opioids in the management of non-malignant pain remains controversial. For many physicians, pain relief stemming from opioid use is not enough unless there is also a noticeable change in quality of life (QoL) and patient functioning. The impact of long-term opioid treatment on patients' QoL has been investigated in a limited number of trials, and these studies differ considerably with respect to their design and principal findings. This systematic review presents the results of these studies. DESIGN AND METHODS: MEDLINE (1966 to November/December 2004), EMBASE (1974 to November/December 2004), the Oxford Pain Relief Database (Bandolier; 1954-1994) and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant papers by combining search terms for function with terms for opioid analgesia, non-malignant and pain. Studies were eligible for inclusion if they met all of the pre-defined criteria specifying study design, population, intervention and outcome measures. RESULTS: Eleven studies evaluated long-term treatment with opioids in patients with chronic, non-malignant pain and assessed QoL (N = 2877). Six studies were randomised trials and the remaining five were observational studies. In general, the former had higher Jadad rating scores for the quality of the paper than the latter. Of the four randomised studies in which baseline QoL was reported, three showed an improvement in QoL. Similarly, of the five observational studies, a significant improvement in QoL was reported in four. CONCLUSIONS: There is both moderate/high- and low-quality evidence suggesting that long-term treatment with opioids can lead to significant improvements in functional outcomes, including QoL, in patients with chronic, non-malignant pain. However, further methodologically rigorous investigations are required to confirm the long-term QoL benefit of opioid treatment in these patients, and to elucidate the effect of physical tolerance, withdrawal and addiction, which are all associated with long-term use of opioids, on patients' functional status.

Hypervigilance for innocuous tactile stimuli in patients with fibromyalgia: an experimental approach.

BACKGROUND: Hypervigilance, i.e., excessive attention, is often invoked as a potential explanation for the observation that many individuals with fibromyalgia show a heightened sensitivity to stimulation in various sensory modalities, such as touch and hearing. Compelling evidence for this assumption is, however, lacking. The aim of the present study was to investigate the presence of somatosensory hypervigilance in patients with fibromyalgia. METHODS: Fibromyalgia patients (n = 41) and a matched control group (n = 40) performed a tactile change detection task in which they had to detect whether there was a change between two consecutively presented patterns of tactile stimuli presented to various body locations. The task was performed under two conditions: in the unpredictable condition, tactile changes occurred equally often at all possible body locations; in the predictable condition, the majority of tactile changes occurred at one specific body location. RESULTS: It was hypothesized that the fibromyalgia group would show better tactile change detection in the unpredictable condition and when changes ocurred at unexpected locations in the predictable condition. The results did not support this hypothesis. In neither condition was the fibromyalgia group better than the control group in detecting tactile changes. CONCLUSIONS: No evidence was found to support the claim that patients with fibromyalgia display somatosensory hypervigilance. This finding challenges the idea of hypervigilance as a static feature of fibromyalgia and urges for a more dynamic view in which hypervigilance emerges in situations when bodily threat is experienced.

Lamotrigine in the treatment of chronic refractory neuropathic pain.

Many patients suffer from chronic, intractable neuropathic pain. Despite similar diagnoses and presumed pathophysiologies, symptoms and response to treatment can differ. Monotherapy is only occasionally successful. In this prospective survey, 20 patients with chronic, neuropathic pain not responding to interventional therapy received lamotrigine, sometimes as monotherapy and sometimes combined with oral morphine. The latter occurred in patients who lost pain relief from morphine after time. Ten patients did not respond to the drug; 4 were temporary responders and 6 patients obtained sustained pain relief. It is interesting that 5 patients regained opioid responsiveness and that the drug combination produced excellent pain relief for more than 5 months. We hypothesize an additive effect between morphine and lamotrigine.

Spinal analgesia in terminal care: risk versus benefit.

Cancer pain treatment is well established. The World Health Organization provides clinicians an "analgesic ladder" scheme to optimize cancer pain treatment. At the beginning of the pain treatment, oral analgesic administration is preferred. The analgesic dose must be individualized. Many published papers describe the spinal administration of opioids in combination with various other drugs such as bupivacaine in selected patients with cancer pain. Although complications have been reported to be few, some recent reports debate this idea. We first describe a population of 92 cancer patients, 13 of whom received intrathecal morphine. We then present our experience with a separate group of 33 cancer patients who were also managed using intrathecal morphine. Based on this experience, the generally accepted indications for the technique appeared to be justified. Concern about spinal infection is well considered, however. Three out of those patients developed meningitis, a complication rate that is far too high.

Gabapentin for pain control in cancer patients' wound dressing care.

A patient with mycosis fungoides illustrates the problem of pain management during wound care and suggests the utility of a novel treatment, gabapentin. Skin lesions, be they induced through necrosis of tumor, therapy (e.g., radiotherapy), or by pressure ulceration, are often the cause of continuous pain or acute wound dressing pain. Optimizing the analgesic treatment in those patients is thus of major importance. Anti-inflammatory drugs and opioids are the cornerstones in the treatment of cancer pain but are rarely sufficient to control wound pain. Different adjuvant techniques can be used, including topical analgesics, psychological distraction techniques, anxiolytics, and co-analgesics. There is growing evidence that anticonvulsants, and sodium channel blockers in particular, are effective not only in neuropathic but also in inflammatory pain. Gabapentin, a voltage sensitive sodium and calcium channel blocker, was used as a co-analgesic to supplement morphine in this case of cancer wound dressing pain.

Spinal cord stimulation: a valuable treatment for chronic failed back surgery patients.

Spinal cord stimulation (SCS) has been used in the treatment of "chronic failed back surgery syndrome" for many years. To evaluate long-term results and cost effectiveness of SCS, we interviewed 69 patients treated during a period of 13 years. Twenty-six patients stopped using SCS; there was no clear explanation for this unsatisfactory result in 10. Forty-three patients continued with the therapy and obtained good pain relief. Electrode breakage either spontaneous or due to a procedure to obtain better stimulation paresthesias was more frequent in the radiofrequency-coupled system group than in the battery group (mean +/- SEM 2.81 +/- 2.0 versus 1.42 +/- 1.51, respectively; P = 0.0018). Ten patients obtained better pain relief than during the trial procedure. Some still need opioid analgesics, but 11 of the 16 who require these drugs obtained a synergistic effect when concomitantly using the stimulator. Eleven patients have returned to work. In our center, the application of SCS costs on average $3660 per patient per year. Although this seems expensive, it may be a cost-effective treatment if other therapies fail.

Relevance of epidurography and epidural adhesiolysis in chronic failed back surgery patients.

OBJECTIVE: Pain treatment in the chronic failed back surgery patient remains problematic. Defining the pathogenesis of the pain could be helpful in treatment. The assumption that epidural fibrosis and adhesions might play an important role in the origin of the pain is verified. DESIGN: We investigated 34 patients in whom peridural fibrosis was suspected. An epidural catheter was inserted via the sacral hiatus. Injections of contrast dye, local anesthetic, corticosteroid, and hypertonic NaCl 10% were carried out daily for 3 days. Spread of the contrast dye in the epidural space was evaluated after 10 and 20 ml injection volume. SETTING: Subjects were patients in a pain clinic of a university hospital in Belgium. PATIENTS: Chronic pain patients with failed back surgery syndrome were examined. Nerve pathology was demonstrated and epidural fibrosis suspected or proved with magnetic resonance imaging (MRI) examination. OUTCOME MEASURES: Improvement in the contrast filling defects of the epidural space were noticed during treatment and correlated with pain improvement. RESULTS: Filling defects were noted in 30 of the 34 patients investigated. After the third day an objective improvement of contrast spread was documented in 14 patients. In seven patients improvement in pain occurred for only a very limited period (1 month). Statistical analysis (chi square analysis) could not demonstrate that improvement of contrast spread was correlated with better pain behavior. In 16 patients no improvement in contrast spread could be visualized. Pain improvement occurred in only four patients and for a limited period of 1 month. Long-term results are even worse. CONCLUSION: Epidurography might confirm epidural filling defects for contrast dye in the patients with epidural fibrosis. A better contrast dye spread, assuming scar lysis, does not guarantee a sustained pain relief. A more direct visualization of the resulting functional changes after adhesiolysis as with epiduroscopy might be useful.

Neuropathic pain in a cancer patient responding to subcutaneously administered lignocaine.

OBJECTIVE: To demonstrate difficulties encountered in alleviating neuropathic pain in a terminally ill cancer patient, with the very tentative diagnosis of postherpetic neuralgia. SETTING: A multidisciplinary pain department in a university hospital. PATIENTS: A patient with Hodgkin's lymphoma and leiomyosarcoma in the liver developed an unusual manifestation of neuropathic pain. INTERVENTION: Oral drug treatment with morphine associated with amitriptyline, valproic acid, mexilitine, flufenazine, and methylprednisolone failed to suppress pain attacks. Only the subcutaneous instillation of lidocaine (2 mg/kg/h) could partially suppress pain. A dorsal root entry zone lesion intervention could only temporary stop the pain attacks. Infiltration and nervous stimulation techniques were not helpful. OUTCOME MEASURES: In determining pain control, the visual analog scale rating scale and the number of attacks per hour were considered. RESULTS: Only the subcutaneous administration of lignocaine could partially suppress pain. Because of the patient's poor hepatic circulation, variable lidocaine plasma concentrations were responsible for intolerable side effects. CONCLUSIONS: Subcutaneous lignocaine administration remains a useful method in treating neuropathic cancer pain. The poor metabolic condition of the patient can lead to deleterious high plasma levels. A dorsal root entry zone lesion could only temporarily stop the pain.

A psychoanalytic investigation to improve the success rate of spinal cord stimulation as a treatment for chronic failed back surgery syndrome.

OBJECTIVE: The analysis of patient data concerning psychological structure and functioning produced an instrument to determine whether a neurostimulator ought to be implanted or not. DESIGN: A questionnaire containing 24 items was developed by a psychologist and tested in 40 chronic failed back surgery patients for whom a spinal cord stimulation seemed to be the only therapeutic approach. This questionnaire was based upon some crucial psychological themes, on which the patient took a position. A predictive indication factor (I.F.; %) for implantation of the neurostimulator was obtained from the 24 items. Six months after the implantation of the neurostimulator, we correlated the evaluation factor (E.F.; %) with a six-point evaluation scale considering the pain reduction. The aim was to compare the I.F. and E.F. to verify the correlation between them. This comparison was intended to answer the question if psychological variables included in our scale improve the success rate of the therapy. SETTING: Data were collected by a psychologist at the Pain Clinic of the University Hospital of Gent, Belgium. RESULTS AND CONCLUSIONS: The correlation between the I.F. and the E.F. was calculated for the 40 patients by the Spearman correlation test. A coefficient value of 0.8083 (p = 0.000) was found, indicating the existence of a very close correlation between the predictive I.F. and the E.F. The indication scale appears to be a useful instrument for clinical psychologists to predict the success rate of a spinal cord stimulator in this group of patients.

Spinal cord stimulation in chronic pain: evaluation of results, complications, and technical considerations in sixty-nine patients.

Sixty-nine patients undergoing spinal cord stimulation (SCS) were studied for a period of up to 8 years. Indications, implantation techniques, and stimulation systems are presented in this article. Pain-suppressor effects of SCS are reviewed, assessing the clinical efficacy over time as well as complications with the stimulation device. Immediately following implantation, inadequate pain relief was noted in 20% of the patients. Decrease of the efficacy of pain alleviation occurs during the first 3 years after implantation. Most failures are noted in patients presenting with failed back surgery. This study also demonstrates that SCS systems should offer the capability of both monopolar and bipolar stimulation modes by the use of multipolar electrodes.

Nerve root sleeve injections in patients with failed back surgery syndrome: a comparison of three solutions.

OBJECTIVE: To evaluate outcome in patients with failed back surgery syndrome treated with nerve root sleeve injections. DESIGN AND PATIENTS: An open, nonblinded, randomized study on 60 patients with documented fibrosis in fewer than three nerve roots. INTERVENTIONS: After random selection, 20 patients were injected with 1 ml bupivacaine 0.5% combined with 1500 units hyaluronidase and 1 ml saline per nerve root sleeve (group A), another 20 were treated with 1 ml bupivacaine 0.5% combined with 40 mg methylprednisolone solution (Depo Medrol) per nerve root (group B), and a third group was treated with bupivacaine 0.5% combined with 1500 units hyaluronidase and 40 mg methylprednisolone solution (group C). The volume of each injection was 2 ml. The injections were given twice at an interval of 1 week. OUTCOME MEASURES: The patients were evaluated on a verbal pain rating scale 1, 3, and 6 months after the second injection. The Kruskal-Wallis test was used to detect statistically significant differences among the three groups, and the analysis was refined with the Friedman test. RESULTS AND CONCLUSIONS: Overall, although injections induced analgesia at 1 month, these effects were reduced at 3- and 6-month follow-ups. No statistical differences were found between the three treatment groups (after 1 month, p = 0.71; after 3 months, p = 0.69; after 6 months, p = 0.66. The Friedman test showed a significant decrease in treatment score as a function of time in groups B and C (p = 0.015) but not in group A (p = 0.074). Corticosteroids seem responsible for the last phenomenon.

Spinal cord stimulation in chronic pain therapy.

Spinal cord stimulation was undertaken in 45 patients referred to the University Hospital in Ghent. Failed back surgery was the major indication for implantation. Raynaud's phenomenon, causalgia, polyneuropathy, phantom limb pain, and diverse causes were the other indications. Before neurosurgical implantation of the system, a percutaneous epidural trial procedure was performed. The efficacy of the implanted stimulation system was estimated by considering the use of medication and the patients' personal appreciation of the obtained pain relief. Thirty-five patients experienced very good pain relief. Only two patients needed further narcotic analgesics. Eight patients stopped using the stimulation system. To ensure good results, strict selection criteria and many surgical reinterventions seemed to be necessary. Although spinal cord stimulation is a nonablative technique, many complications may occur.

Cold blood cardioplegia and warm cardioplegic reperfusion in heart transplantation.

The major cause of early death after heart transplantation is graft failure. In 99 consecutive heart transplantations two protocols of myocardial protection were employed. In group 1 (n = 38) initial cold crystalloid cardioplegia combined with cold saline storage and peroperative surface cooling was used. In group 2 (n = 61) cold crystalloid cardioplegia was injected initially and cold blood cardioplegia (Buckberg) was infused every 30 min as soon as the graft arrived in the operating room. No surface cooling was used. Warm blood cardioplegic reperfusion was administered before removal of the aortic clamp. There were 8 early (within 30 days) deaths in group 1 and 6 in group 2 patients. In group 1 there were 5 cardiac deaths against 3 in group 2. Mean ischemic time was 153 +/- 37 min in group 1 and 158 +/- 51 min (p greater than 0.05) in group 2. The post-transplantation need for catecholamines was ten times higher in group 1 patients than in group 2. The first endomyocardial biopsy (after 1 week) showed cytologic lesions compatible with ischemia in 40% of group 1 and only 9% in group 2 patients. We conclude from this initial experience that intermittent cold blood cardioplegia and warm blood cardioplegic reperfusion are useful in heart transplantation in restoring the damage suffered by the graft during brain death and graft storage.

Hyperalgesia induced by high-dose intrathecal sufentanil in neuropathic pain.

The patient had lower lumbar arachnoiditis as part of a failed back surgery syndrome. Two years after discectomy, she still suffered from left lumbosciatic pain despite various invasive treatments. Psychologic impairment could be excluded. Finally, intrathecal morphine was infused at the D12 level. Small amounts of morphine (500-750 mg daily) introduced intolerable vomiting, which could not be prevented by antiemetics, so intrathecal sufentanil was started. A daily dose of 25 mg of sufentanil diluted in 1.5 ml of saline evoked hyperalgesia in the lower part of the body. Increasing the dose to 50 mg daily could only be supported for 3 h. Sufentanil was stopped and saline started, after which the evoked hyperalgesia disappeared. It is concluded that relatively high doses of sufentanil may induce hyperalgesia in patients with arachnoiditis and neuropathic pain.

Dual channel electrostimulation in pain.

Spinal cord stimulation is an accepted treatment for neuropathic pain. Technical advances in electrode design and better patient selection have led to better and sustained pain control by these devices. Multilead electrical stimulation is the latest innovation in implantable electrostimulation (Mattrix, Medtronic Minneapolis, USA). Two combined multipolar leads connected to a radiofrequency--coupled system can deliver electrical pulses of various amplitudes and pulse widths at different dermatome levels. Single stimulation is applied with different electrode configurations using both electrodes with identical stimulation parameters. In dual stimulation, the amplitude and the pulse width can vary between the electrode configurations. Dual channel stimulation helps steering stimulation paresthesias. Three patients illustrate the technical advantages of dual channel electrostimulation in the pain relief at multiple sites. Two patients with failed back surgery syndrome obtained more easily stimulation-induced paresthesias in the back and the legs. Dual channel stimulation is cost saving in patients implanted with two electrodes. This is presented in a third patient with an electrode in the thalamus--as pain treatment for cervicobrachialgia and a second in the epidural space--as treatment for the failed back surgery syndrome. These electrodes were connected to the Mattrix stimulator.

Epidural spinal cord stimulation does not improve microvascular blood flow in neuropathic pain.

For many years, spinal cord stimulation (SCS) has been used successfully in various pain syndromes. SCS is also used to treat vascularly-impaired patients since it apparently improves the microcirculation. The exact physiological mechanisms involved are still unclear. There are even some anecdotal reports of a cooling of the legs during SCS. This study investigated the vascular effects of SCS in 15 patients with failed back surgery syndrome, using infrared thermography of the affected foot and capillaroscopy in the nailfold of the big toe. There were no statistically significant differences (Student's t test) in temperature (P = 0.923) or red blood cell velocity (P = 0.819 first day and P = 0.218 second day) in the affected foot with or without stimulation. A physiological difference in relation to neuropathic pain might explain the lack of improvement in skin microcirculation with SCS.

Subcutaneous morphine is superior to intrathecal morphine for pain control in a patient with hypernephroma.

This case report illustrates differences in analgesia quality and morphine consumption between an intrathecal infusion and the subcutaneous instillation of morphine in a cancer patient with hypernephroma. Superior analgesia was obtained with a 450 mg dose of subcutaneous morphine [i.e., visual analog scale (VAS) score 0/10] than with 10 mg intrathecal morphine/day administered at the thoracolumbar (twelfth dorsal vertebra) level (VAS score 2/10). If the instillation occurs at the lumbosacral level (between the last lumbar and the first sacral vertebra), a dosage of 70 mg morphine/day cannot induce the same pain relief as 450 mg subcutaneous morphine (VAS score 5/10 vs. 0/10). In some cancer patients, subcutaneous morphine offers superior pain control than intrathecal morphine.

[Value of vasodilators in decreasing the afterload during infrarenal abdominal aorta cross-clamping]. / Intérêt des vasodilatateurs pour diminuer la post-charge au cours du clampage aorto-abdominal sous-rénal.

Adverse effects of aortic crossclamping (A. C. C.) have been shown by a retrospective study and a literature review. A. C. C. results in increased afterload with ensuing left ventricular function alteration and low cardiac index (C. I.). 15 P. T. S. sustaining an operation with A. C. C. below the renal arteries were studied. A Swan-Ganz catheter was positioned with recording of pressures, including radial artery pressure and repeated cardiac output determinations. Prior to A. C. C., vascular filling and nitroprusside (N. P.) infusion improved hemodynamic conditions. Increase of C. I. (1.8 to 2.8 l/mm-1/m2) was observed with important decrease in peripheral vascular resistance (from 2,346 to 1,425 dyne/s-1/cm-5), pulmonary capillary pressure was lowered slightly and heart rate as well as mean arterial pressure remained stable. During A. C. C., rate of N. P. infusion was increased to maintain stable arterial pressure. Hemodynamic improvement observed prior to A. C. C. was maintained.