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Opioid Therapy in Non-Cancer Pain

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A PROSPECTIVE STUDY OF LONG-TERM INTRA-THECAL MORPHINE FOR CHRONIC NONMALIGNANT PAIN.

V.C. Anderson. K.J. Burchiel, Dept. of Neurological Surgery, Oregon Health Sciences Univ, Portland, OR 97201 USA

Aim of Investigation: This study was designed to examine in a prospective manner the long-term safety and efficacy of chronic intrathecal morphine in patients with severe, nonmalignant pain refractory to less-invasive modalities.

Methods: Forty patients with severe, chronic nonmalignant pain poorly controlled by systemic medications were identified as candidates for intraspinal trial of morphine. Thirty subjects reported successful pain relief during trial and were implanted with an intraspinal delivery system. Standardized measures of pain and functional status were assessed pre-treatment and at defined intervals over the subsequent 24 months. Opioid dosing, pharmacological and device-related complications were also monitored.

Results: Participants had a mean age of58 13 years and pain duration of89 years. Fifty-three percent of study participants were female. Pain type was characterized as mixed neuropathic-nociceptive (50%), peripheral neuropathic (33%), deafferentation (13%) or nociceptive (3%). 47% of patients were diagnosed with failed back surgery syndrome. Statistically significant improvement over baseline levels of visual analogue scale (VAS) pain was measured at each follow-up after implant. In addition, the McGill Pain Questionnaire, VAS measures of functional improvement and pain coping and several subscales of the Chronic Illness Pain Inventory showed improvement with long-term therapy. Pharmacological side effects were managed by morphine dose reduction, addition ofbupivacaine, or replacement of morphine with hydro-morphone. 20% of patients required surgery for device-related complications.

Conclusion: Continuous intrathecal morphine can be a safe, effective therapy for management of severe, nonmalignant pain among a carefully selected patient population and can result in long-term improvement in several areas of daily function.

LONG TERM TOLERABILITY OF CR OXYCO-DONE (OXYCONT1N TABLETS) IN 101 PATIENTS TREATED FOR 12 MONTHS.

A.N. Broughton*^ D.N. Gordon*^ A.J. Miller^ Napp Pharmaceu-ticals, Cambridge, UK

Aim: This meta-analysis investigated the long term tolerability of CR oxycodone (OxyContin tablets) in 101 patients treated for 12 months.

Methods: Data from two long term, non-comparative studies, which included patients treated with OxyContin for 12 months, were pooled. Patients with malignant and non-malignant pain were recruited. Both studies assessed tolerability, efficacy and acceptability of OxyContin by similar methods. Adverse events reported by patients or observed by investigators were recorded in detail.

Results: 354 patients were recruited, of whom 101 completed 12 months of treatment before the studies completed. Of 194 patients with non-malignant pain, 88 (45%) completed 12 months. The most common adverse drug reactions (ADRs), recorded at least once by patients treated for 12 months, were constipation (50%), nausea (19%), vomiting (8%), somnolence (20%), pruritus (16%) and dizziness (10%). No unexpected ADRs emerged in patients treated for 12 months and there was a trend toward a decreasing incidence over this period. The large majority of adverse eventswere either mild or moderate in seventy. Nineteen patients reported symptoms suggestive ofopioid withdrawal after abrupt discontinuation of OxyContin. Two patients demonstrated behaviour suggesting abuse of their OxyContin and they were withdrawn prior to 12 months.

Conclusion: OxyContin is well tolerated in long term use with no unexpected or increasing incidence of adverse events emerging over time. Management of adverse events may improve tolerability further. Careful patient selection and ongoing evaluation is an important aspect of long term opioid therapy.

LONG-TERM TRANSDERMAL FENTANYL TO THE CONTROL OF NON CANCER CHRONIC PAIN.

Camba MA. Yanez AM, De la Iglesia A, Varela M, Rodriguez MC, Pallares J. CHA Marcide Dept of Anesthesia, Ferrol, Spain.

Based on previous works, we evaluate the opioids in the control of chronic non oncologic pain. During a period of 6 months, we follow-up 40 patients with chronic pain (nociceptive 23, deafferen-ciative 7, and a mixture of both 10). All the patients completing the 1 day-dose titration protocol with oral morphine before they begin 25 ug/h transdermal fentanyl.

The pain relief was measured with a visual analog scale (0=no pain, 10=unbearable pain) and the Lattinen test. All the patients were evaluated at the day 3, 15 and at the 2, 3, 4, 5 and 6th month. Morphine of immediate release was used as rescue medication.

At the 6th month the dose of transdermal fentanyl remain the same as the initial dose of 25 ug/h in 19 patients, 17 patients needed 50 ug/h and 2 patients 100 ug/h of fentanyl in order to the pain be controlled. Due to side effects the fentanyl was to be cancelled in 2 patients, one present constipation and the other one had nausea and vomits. The pain relief was substantial, 80% of reduction in 19 patients that remain at the initial dose of fentanyl 25 ug/h; 56% of pain reduction in the group of patients that received 50 ug/h and 30% in those patients that needed 100 ug/h of fentanyl. We conclude that long-term transdermal fentanyl may be effective in non cancer chronic pain and can be an alternative to oral opioids.

INTRAVENOUS TESTING OF OPIOID SENSIBILITY IN PATIENTS WITH CHRONIC NON-CANCER PAIN AND CONSECUTIVE ORAL ADJUSTMENT OF PAIN MEDICATION

R. Dertwinkel. M. Strumpf, A. Willweber-Strumpf, M. Tryba, M. Zenz, Univ Dept ofAnesthesiology, Intensive Care Medicine and Pain Therapy Univ ofBochum, Germany

Introduction: An intravenous (iv) testing of pain sensibility with opioids; (Morphine Test (MT)) is used to diversify an opioid sensitive versus a non-sensitive pain before starting a patient on opioid medication. So far, there is a lack of controlled trials which correlate the results ofiv MT with the effectivity of an oral adjustment. Therefore, we performed a randomised double-blinded tnal to investigate the sensibility and specitivity of the MT regarding pain sensibility to opioids and affectivity of the consecutive oral adjustment ofopioid medication.

Methods: After ethical committee approval, 20 patients were randomly double-blinded to an iv morphine versus saline infusion at 2 different time intervals. Before, they had been documenting their pain intensity (VAS) and activity index (NAS) over 7 days. During the infusion pain intensity, respiratory rate, pupil diameter and side effects were noted every 15 minutes. All patients were then switched to an oral application of sustained release morphine at certain time intervals.

Results: The infusion of saline did not lead to a significant reduction of pain in any patient. 5 patients experienced a significant reduction of pain intensity ("responders") during the MT. During consecutive oral adjustment with sustained release morphine 4 of 5 responders reported again pain relief (Table 1). Looking at the activity score, 2 responders had a marked increase. Some "non- responders" had a decrease of their activity index. All non-responders were discontinued for opioid medication.

Conclusion: The results of this study demonstrate that patients with a positive response to an iv MT also benefit from oral opioid application. Especially, no patient without pain reduction during the MT had a pain reduction during oral intake. This indicates that there is no false negative response for the iv MT.

CLINICAL STATUS OF OPIOID TOLERANCE AND OPIOID RESISTANCE IN LONG-TERM THERAPY OF CHRONIC NON-CANCER PAIN

Roman Dertwinkel. Michael Zenz, Michael Strumpf, Barbara Donner, Univ Dept ofAnesthesiology, Intensive Care Medicine and Pain Therapy Univ ofBochum, Germany

Problem: A diminution of opioid efficacy in the course of long-term treatment has been noted as a frequent and major problem (1, 2). As a development of a clinically relevant opioid tolerance might impede the use ofopioids in chronic non-cancer pain in genera], this discussion makes medical staff as well as patients feel unsure. Clinical relevance: The development of opioid tolerance has been described mainly in animal studies. But the application of these experimental results for clinical purposes is questionable, because opioids were applied to pain-free animals or the opioids were not applied continuously or according to pharmacological properties, e.g. duration of action. Controlled clinical studies also show, that opioid tolerance may develop in the course of a therapy (3, 4), but it is rarely clinically relevant or followed by the need of limiting the started therapy (4). An opioid resistance seems to be much more frequent than an opioid tolerance. Possible pathophysiologi-cal backgrounds are a loss of opioid receptors at the spinal level, changes ofnon-opioid peptides as cholecystokinine (CCK) or an activation of N-methyl-D-aspartat (NMDA) receptors in the area of the substance gelatinosa.

Conclusions: In most cases that were regarded as opioid tolerance the primary problem was not pharmaco-dynamic or phar-maco-kinetic but rather iatrogenic in origin. An opioid therapy, however, which follows standardized approach, means a safe and effective therapeutic concept, which can successfully be applied for patients with chronic non-cancer pain.

Literature: 1.: OsipovaNA et al., CurrTherap Res 1991; 50(6):
812-821, 2.: Crews JC et al., Cancer 1993; 72(7): 2266-2272, 3.:
DrexelHetal.Pain 1989; 36(2): 169-176, 4.: Santillan R et al, Pain 1998; 76 (1-2): 17-26

FENTANYL TTS IS EFFECTIVE IN SYSTEMIC MASTOCYTOSIS

E. Ebner*. C. Doberauer*, B.J. Morlion (SPON: R. Frieling), MPC, Marienhospital Heme, Ruhr Univ Bochum, 44625 Heme, Germany

Background: Mastocytosis is a disease characterized by an abnormal proliferation of tissue mast cells. Opioids trigger uncontrolled liberation of histamine and other mediators from these mast cells, thereby complicating pain treatment.

Case report: A 22-year-old female patient (37 kg, 158 cm) suffering from systemic mastocytosis diagnosed at the age of 13 (showing urticaria pigmentosa from birth) presented herself receiving pethidine up to 1,000 mg/d SC, without sufficient pain relief. She reported spastic abdominal pain with nausea and vomiting resulting from gastrointestinal infiltration by mast cells leading to gastropa-resis and bowel obstruction as well as strain-dependent back pain with bone marrow involvement and osteopetrosis. In order to ease her histamine-induced headaches and flush symptoms, she received h] and H; blockers as well as prednisolone 16 mg daily. The pre-therapeutic urinary histamine level was 1,100 u.g/d (10-50). The following opioids and non-opioids were found to cause increased histamine liberation symptoms: slow-release morphine; buprenorphine; piritramide; dipyrone; paracetamol and diclofenac. During the time the histamine level was very high, we achieved sufficient pain relief with transdermal fentanyl up to 200 (ig/h without major side effects. In addition to the symptomatic pain therapy, a causal cytoreductive a-interferon therapy was initiated with an average 3x3 million units per week SC under which the histamine level was brought down to 77 u,g/d (10-50) within a period of 12 months. This therapy enabled us to successfully replace transdermal fentanyl by slow-release morphine sulfate (2 x 30 mg).

Conclusion: Transdermal fentanyl was the only opioid that proved satisfactory in the pain therapy of systemic mastocytosis with extremely increased histamine level.

USE OF OPIOIDS IN CHRONIC NON-MALIGNANT PAIN PATIENTS TREATED AT A MULTID1SCIPL1NARY PAIN CENTER OR IN GENERAL PRACTICE

J Eriksen. N Becker, P Sjegren, H:S Multidisciplinary Pain Center, National Hospital, DK-2100, Copenhagen, Denmark

Aim of Study: To investigate the dose escalation and changes in opioid administration pattern among chronic non-malignant pain patients treated by general practitioners and patients treated at a multidisciplinary pain center (MPC).

Methods: 226 patients referred to the MPC were studied. At referral patients were allocated to treatment either in the MPC (PC-group, N=151) or by the general practitioner (GP-group, N=84). Patients allocated to the GP-group were seen by a consultant from MPC. Together with the GP a treatment plan was made. Treatment in the GP-group was mainly analgesic tailoring. The MPC-treatment was multimodal. The analgesic treatment focused on eliminating irrelevant use ofopioids and on minimizing use of on demand medication and short acting opioids. At inclusion and 3, 6 and 12 months later the patients and the physician treating the patient filled in questionnaires giving information on the use of analgesics during the last week. ANOVA was used for analysing improvements over time and differences between group. Level of significance was P <: 0.05.

Results: At referral 83 patients (55.0%) in the PC-group and 43 patients (53%) in the GP-group were in treatment with opioids. At referral there was no difference between mean opioid dose the PC-group (86.8 mg/day) and the GP-group (81.9 mg/day). Mean duration of treatment at the MPC was 8.3 months (SD 13.1). In the PC-group a 11.0% reduction in mean opioid dose was obtained at the end of treatment, p>0.05 and 16.4% did not receive opioids any more. At 12 months mean opioid dose in the GP-group had increased 53.4% to 125.8 mg/day (pO.001?). Only 14.0% did not receive opioids any more. At referral 60.0% of the patients in both groups were treated with short acting opioids and 49.1% took on demand opioids. After 12 months 85.7% of the patients treated at the MPC were on sustained release opioids, and only 10.7% took on demand opioids. No change in the administration pattern was observed in the GP group.

Conclusion: The present study indicated that : 1) MPC treatment could stabilize chronic non-malignant pain patients' use ofopioids. 2) Despite initial supervision patients treated by GP's demonstrated significant dose escalation.

STIGMA & ENIGMA OF CHRONIC NON-MALIGNANT BACK PAIN TREATED WITH LONG TERM OPIOID THERAPY: CONSUMERS' PERSPECTIVE.

J.R.Gardner* (SPON. S.K.Vallipuram), Dept of Community Medicine, Faculty of Medicine, Monash Univ, Clayton, Victoria 3168, Australia

Aim of Investigation: To determine chronic non-malignant back pain (CNMBP) patients' profiles, perceptions and feelings regarding the use of long term opioid (LTO) therapy in the management of CNMBP and the criteria they use to substantiate and evaluate its use.

Methods: The method of focus group discussions was used to explicate major consumer issues relating to LTO therapy in CNMBP management and to develop a questionnaire to evaluate these issues on a randomly selected sample of 100 CNMBP patients.

Results: Issues relating to legitimacy, stigma and opioiphobia emerged as issues that made access to opioids for CNMBP sufferers problematic and ad hoc. A profound altered sense of self, sleep deprivation, sexual dysfunction and reduced capacity to engage in meaningful social relationships emerged as major issues for patients who felt these received little attention in clinical practice.

Conclusions: The findings from this study lend support to the argument that some CNMBP patients continue to suffer not because their pain is untreatable but because many health care practitioners remain opioiphobic. This opioiphobia not only has the potential to deny some CNMBP patients effective pain management but may also increase their risk of suicide. It is also possible that CNMBP patients being treated with LTO who are negatively stereotyped and labeled difficult, manipulating, drug seeking etc., are demonstrating behaviors which reflect greater damage to their 'person' than their physical pain. It is interesting to note that these patients use the same criteria as many doctors when evaluating the effectiveness of their opioid therapy i.e. reduction in pain and improved function. The data lends support to findings that responsibly used, opioids can improve pain management for selected patients with CNMBP.

EXPERIENCE WITH CONTROLLED-RELEASED DIHYDROCODEINE IN LOW-BACK PAIN

Marie-therese Gatt. MaT Luu, Catherine Belin, Bobigny Unite Plu-ridisciplinaire de Traitement de la Douleur, Universite Pans XIII, Bobigny, France.

Aim of Investigation: To investigate the efficacy and safety of controlled-released dihydrocodeine in the treatment of patients suffering from lumbodynia (preliminary results).

Methods: In a non-comparative study the dihydrocodeine is tested, examination and clinical assessment are measured at day 0, day 7 and day 14.

Results: 11 women and 11 men, mean age 51,41 years (35-70), mean weight 69,61 kg, Caucasian 100%, suffering from mechanic lumbalgia. An analgesic effect was observed for both pain and secondary endpoints (back stiffness, contractures). For the main criterion (pain assessment) in intention to treat analysis VAS Day 0/Day 7 p<0.001, Day 0/Dayl4 p<0.0001; analysis after withdrawals VAS Day 7/Day 0 and Day 14/Day 0, pO.0001. Evaluation of tolerability showed that moderate side effects were present. 20 patients (99%) have mild effects. Day 7; nausea 30%, constipation 45%, headache 35%, vertigo 25%, drowsiness 50%. Day 14: nausea 10%, constipation 35%, headache 40%, vertigo 15%, drowsiness 45% . These did progress, however, and were of kinds well-recognized for morphine-type agonists. Two patients withdrew from the study because of major vomiting, this will have to be assessed when the study of 50 patients is complete.

Conclusions: Controlled release dihydrocodeine appears to be an effective and acceptable analgesic drug for patients with mechanic lumbalgia.

277 LONG TERM EFFICACY OF CR OXYCODONE (OXYCONTIN TABLETS) IN 101 PATIENTS TREATED FOR 12 MONTHS.

D.N.Gordon*'. A.N.Broughton*', A.J.Miller', (SPON: T. Hunt)0 ^app Pharmaceuticals, Cambridge, UK, "Addenbrooke's Hospital, Cambridge, UK

Aim: This meta-analysis investigated the efficacy ofCR oxyco-done (OxyContin tablets) in the long term management of pain.

Methods: Two long term, non-comparative studies which included patients treated with OxyContin for 12 months were pooled. Patients with malignant and non-malignant pain were recruited. In both studies, pain was assessed on a 4 point scale (none, slight, moderate, severe) and acceptability on a 5 point scale (very poor, poor, fair, good, excellent).

Results: 354 patients were recruited and most were established on opioid therapy prior to participation. 101 patients (88 with non-malignant pain) completed 12 months of treatment before the studies closed. Pain scores at baseline were 3% - no pain, 24% -slight, 53% - moderate and 18% - severe. At 12 months, the pain scores were 2% - no pain, 22% - slight, 51 % - moderate and 7% -severe (18% - no score). The mean pain score throughout the study was <1.8. Therapy was rated as fair, good or excellent by 82% of patients completing 12 months. When comparing the last assessment to the 1 month assessment, a lower or equal median daily dose of OxyContin was taken by 65% of patients.

Conclusion: Escalation of dose, which can be indicative of tolerance, was not marked in this cohort. A significant improvement in pain scores was not expected, nor seen, since patients were established on opioids at baseline. However, this study established that baseline analgesia was maintained for 12 months with OxyContin, with a high level of patient acceptability.

LONGTERM TREATMENT WITH SUSTAINED RELEASE MORPHINE IN NONMALIGNANT PAIN (LAMON-TAS)

Hildebrandt J', Lindena G2, Maier CH3, KImger R", 'Pain Clinic Univ ofGottingen, "Mundipharma GmbH Limburg, ^ain Clinic Univ of Kiel, ''Psychological Inst Univ of Hamburg, for the Montas study group in Germany

Aim of Investigation: Long-term outcome of morphine treatment in terms of efficacy, tolerability and impact on other treatment options in chronic pain patients.

Methods: Eight centers open long-term prospective evaluation of morphine responders in a short-term, randomised, double-blind, placebo-controlled study. Diagnoses included postherpetic neuralgia, low back pain and pancreatitis, pain from neuropathic and somatosensory origin. Patients had regular dates in the pain clinics. They answered an extensive pain questionnaire and were cared by physicians and psychologists. They received any reasonable treatment for their pain.

Results: 33 patients entered the long-term open phase of the study continuing morphine treatment. Many patients were followed for 3-4.5 years. One year after start 19 patients still received MST (after 3-4.5 years 17 patients respectively). Minimum dosage was 20 mg, maximum 400 mg per day. Pain tolerability was better and intensity less in patients with morphine treatment compared to those who had stopped (4.6 versus 6.5 in NRS 0-10). Patients experienced the well-known side effects, mainly constipation, some interesting aspects during long-term therapy will be presented. 14 patients had definitely stopped morphine treatment by one year (resp. 16 after 3-4.5 yrs), because of side effects and/or reduced benefit or other effective treatment.

Conclusions: Systematic treatment in chronic pain from different nonmalignant diagnoses should include morphine as an oral nonin-vasive application form. Other activating treatment strategies are useful and opioid treatment may be stopped, when pain is sufficiently relieved.

Acknowledgment: Thanks to all participating centers, who bore the workload in organising patient dates and in collecting of long-term data.

EFFECTS OF OPI01DS ON PHANTOM LIMB PAIN AND CORTICAL REORGANIZATION

Huse. E.. Larbig, W., Topfher, S., Lindena, G., Lutzenberger, W., Flor, H. & Birbaumer, N., Inst of Medical Psychology and Behavioral Neurobiology, Univ. ofTuebingen, Gartenstr. 29, D-72074 Tuebingen

Aim of Investigation: We investigated the analgesic efficacy and safety of morphine (MST) in neuropathic pain using phantom limb pain as a model. We hypothesized that pain reduction should lead to a corresponding shift of reorganization in the somatosensory cortex.

Methods: 12 upper or lower extremity amputees were randomized to morphine or placebo as starting condition, each for 4 weeks, using a double-blind crossover design. All underwent clinical, neurological and psychophysiological (signal perception, pain threshold, attention) examination. Pain intensity was assessed using an hourly pain-diary (10 cm VAS) for 12 weeks (baseline, placebo-and treatment-phase, 4 weeks each). Subjects were slowly titrated to the maximum dose of morphine over 4 weeks. Medication was than tapered off over 1 week. Cortical reorganization was measured in upper limb amputees (N=3) by recording somatosensory evoked fields by 143 MEG-squids, during light superficial pneumatic stimulation of those body parts representing adjacent areas to the deafferentation zone.

Results: Under morphine treatment the mean pain ratings were significantly lower compared to the placebo condition. A clinically relevant response to MST (reduction at 50%) is observed in 4 patients, a partial response (reduction at 25-50%) in 4 patients, and 4 were non-responders. Preliminary data suggest that pain reduction might be accompanied by a shift backwards in cortical reorganization. Signal perception and pain thresholds did not vary significantly between all 3 phases. Attentiveness was marginally enhanced under MST.

Conclusions: Morphine is an effective analgesic in about half of the patients with phantom limb pain without intolerable side effects. This result agrees with literature about opioid treatment in neuropathic pain. Analgesic response is associated with a shift backwards in cortical reorganization. Missing opioid effects may be due to highly corticalized pain.

Acknowledgments: Supported by the German Research Society Grant No. Bi 195/24 and Mundipharma GmbH, Limburg/Lahn, Germany

CHARACTERISATION OF OPIOID TREATED CHRONIC NON-MALIGNANT PAIN PATIENTS REFERRED TO A DANISH MULTIDISCIPLINARY PAIN CENTRE.

Stina Klemming*. Niels Becker, Jorgen Eriksen, (SPON: J. Ho-jsted). H:S Multidisciplinary Pain Centre, National Hospital, Dk-2200 Copenhagen, Denmark.

Aim of Investigation: Through a descriptive cross section study discriminate the psychological, social, and physical condition of opioid treated versus non-opioid treated chronic non-malignant pain patients.

Methods: Questionnaires were answered by 413 (70%) of 587 consecutively referred patients, their General Practitioner (GP) and a Specialist at the Pain Centre (SPC). Patients were grouped as non-, low- or high (>60mg morphine daily) opioid consumers. Pain intensity was evaluated by a Visual Analogue Scale (VAS). Health Related Quality of Life (HRQL) was evaluated by the Psychological General Well-Being scale (PGWB) and the Short Form Health Survey (SF-36). The GP and the SPC provided information about sociodemographic data, use of medicine, general medical records, importance of reasons for referral other than pain, their view on the patient's pain intensity, capability of coping, and impact of physical, psychological and social factors on the condition. Significance level p<0.05.

Results: At referral 260 (63%) patients were treated with opioids and 127 (31%) of these took high doses, most of them in an unstable pm. treatment. 152 (37%) patients were not opioid treated. VAS and PGWB scores for high-, low- and non-opioid consumers were significantly different (p<0.05) (VAS:76.7, 73.8 and 64.2, PGWB: 42.3, 46.8 and 53.8). High consumers had the lowest scores on all 8 subscales of SF-36 (P< 0.05). The GPs evaluated the patients coping and the impact of physical, psychological and social factors on the condition, equally and higher than did the SPC (P<0.05).

Conclusion: Patients on high opioid doses had the highest pain scores and extremely low psychological, social and physical well-being, closely followed by low dose consumers. Patients in the three groups were identical concerning pain epidemiological and sociodemographic data. Prescription of opioids alone does not seem to solve the pain problem in chronic non-malignant pain patients.

TREATMENT OF PAINFUL EPISODES IN CHILDREN WITH SICKLE CELL DISEASE: A COMPARISON OF THE PHARMACOK1NETICS AND PHARMACODY-NAM1CS OF MS CONTIN AND INTRAVENOUS MORPHINE.

E.A. Kopecky*. S. Jacobson*, P. Joshi*, N. Babul, Divisions of Clinical Pharmacology and Toxicology and General Pediatrics, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada.

Aim of Investigation: To compare the pharmacodynamics and pharmacokinetics of oral sustained-release morphine (MS Contin; MSC) and continuous IV morphine (CIV) in paediatric sickle cell disease patients, with severe pain attributable to vaso-occlusive crisis (VOC).

Methods: Children (5-17 years) received an IV loading dose of morphine of 0.15 mg/kg, and were then randomized to MSC 1.9 mg/kg/12hrs or CIV morphine at 0.04 mg/kg/hr using a double-blind, parallel-group design. Breakthrough pain was treated with oral, immediate-release morphine 0.4 mg/kg or IV morphine 0.1 mg/kg. Pain, vita] signs, 0; saturation, end-tidal CO;, and neurological status, were assessed daily, every 4 hours. Patients were observed for evidence of chest involvement, addiction, and withdrawal. In a subgroup, blood samples were obtained every 2 hrs over 12 hrs for determination of plasma morphine (M) and M6G by HPLC. The kinetic variables AUC, C^, C^, T^, M6G: M ratio, clearance, and percent fluctuation, were calculated. A t-Test was used for all comparisons, ass 0.05.

Results: 50 patients were evaluable; 15 patients completed venous sampling. Both groups were similar demographically. There were no differences in pain control, neurological status, heart rate, ETCO;, respiratory rate or adverse events (p > 0.05). 0; saturation was different between the treatment groups (p = 0.01). There was a correlation between dose and 0; saturation and ETCO;, p < 0.03, for both MSC and CIV. There were no cases of addiction or symptoms consistent with opioid withdrawal. Results of the phar-macodynamic-pharmacokinetic analyses will be presented.

Conclusions: MSC provides effective, continuous pain control and is a safe and reliable non-invasive alternative to CIV.

Acknowledgments: Supported by a Grant from Purdue Frederick, Pickering, Ontario.

DOSING PATTERNS WITH LONG-TERM OPIOID TREATMENT IN PATIENTS WITH OSTEOARTHRIT1S PAIN.

P.O. Lacouture. T. Iwan, S.I. Rosen, R.F. Reder, Purdue Pharma L.P., Norwalk, CT 06850, F.X. Burch, San Antonio, TX, R. Fleischmann, Rheumatology Associates, Dallas, TX

Aim of Investigation: Data from a long-term open-label clinical trial were examined to determine: (1) the stability of the daily opioid dose and (2) the utility of asymmetric dosing.

Method: Following a 2-week, double-blind evaluation of a controlled- release opioid (OxyContin*) for pain secondary to osteo-arthritis, 106 patients were enrolled in an open-label titration evaluation for up to 18 months. The mean daily dose over time was examined. Asymmetric and symmetric dosing was investigated to explore the time of greatest analgesic need. Results: Of the 106 patients who qualified, 75% were female and 43% were > 65 years old. The predominant site of pain was the back and 65% received concomitant NSAID therapy.

Daily OxyContin Dose by Week

  Baseline Wk Wk Wk Wk Wk
 

 

 

 

4 8 16 32 64
N 106 84 71 64 48 21
Mean Daily 20 30 33.5 39 39 40
Dose (mg)  

 

 

 

 

 

 

 

 

 

 

 

Most patients (97%) who titrated their dose upward, did so using asymmetric dosing where either the morning or evening dose was larger. Of all patients completing the study, 37% completed on an asymmetric dose (82% having the larger dose in the AM).

Conclusions: We conclude that chronic dosing with opioids with relatively stable persistent osteoarthritis pain does not result in continued escalation of dose over extended periods. Furthermore, treatment with asymmetric dosing was frequent and dosing patterns suggest that pain during the day is most prominent.

Acknowledgments: Sponsored by Purdue Pharma L.P. Norwalk, CT; P.G. Lacouture is an employee of Purdue Pharma L.P.

SPINAL INFUSION OF OPIOIDS FOR TREATMENT OF CHRONIC NONMALIGNANT PAIN (CNP)

NA Lara Jr, MJ Teixeira. TY Lin, LA Rogano, CF Correa, WA Cescato, Oliveira CG. Pain Clinic, Univ ofSao Paulo Medical School, Rua. Conselheiro Brotero 1539, cj 12, Cep 01232-010, Sao Paulo Brazil.

Aim of Investigation: Many chronic nonmalignant pain (CNP) conditions, including myofascial pain syndromes (MPS), fibromy-algia, complex regional pain syndromes, failed back surgery, and peripheral and central neuropathies are not controlled by conventional forms of treatment. The purpose of the study is the presentation of the results of treatment of patients presenting incapaciting CNP with long term spinal infusion of opioids.

Methods: Sixty one patients (42 females) presenting respectively muscle pain resulting from FM (n=16), FM and peripheral neuropathies (PN) (n=2), FM and complex regional pain syndrome (CRPS) (n=2), myofascial pain syndromes (MPSs) (n=3), MPS and PN (n=2), MPS and CRPS (n=2), failed back surgery (n=9), pelvic pain (n=3) and myelopathic pain (n=23), previously unsuccessfully treated with AAINHs, psychotropics, physical therapies, acupuncture, infiltration of the trigger points, and some with neurosurgical procedures aiming for the control of pain were selected after a period of tests with intermittent spinal infusion of opioids through epidural catheters to assess the acceptance of the method and the changing in the intensity of pain and in the quality of life. Al-gomed-Medtronic Inc. or Cecor-Cordis pumps were implanted for chronic infusion of opioid agents into the subarachnoid space. VAS and daily life activities (DA) were assessed.

Results: More than 75% of improvement of the original VAS and daily life activities [DA] was observed in 45.5% of the cases. Improvement of VAS and DA ranging between 50% and 75% was observed in 21.2% of the cases. In 12.5% of the cases, the implanted devices were removed due to infection.

Conclusions: Chronic spinal opioids infusion is an useful tool for rehabilitation of patients with CNP.

EVALUATION OF THE LONG-TERM EFFICACY AND SAFETY OF TRANSDERMAL FENTANYL IN THE TREATMENT OF NON-CANCER PAIN: THE INTERIM ANALYSIS.

'K. Milligan. ^L. Haazen, ^'L. Bijnens*. 'Anaesthetic Dept, South Cleveland Hospital, Middlesborough TS4 3BW, United Kingdom and Janssen Research Foundation, Tumhoutseweg 30, 2340 Beerse, Belgium

Aim of Investigation: To document long-term efficacy and safety oftransdermal (TTS)-fentanyl for the management of non-cancer pain.

Methods: The study was an open-label, international, multicentre, phase 111 trial in 532 patients (mean age 51.5 years) with a median pain duration of six years. 262 patients (50%) had neuropathic pain and 367 (70%) had predominantly somatic, nociceptive pain. TTS-fentanyl was started at an equianalgesic dose to the pre-trial opioid, and given for 12 months. Main outcome measures were weekly assessment of pain control, global treatment satisfaction and quality of life scores.

Results: At interim analysis, 120 patients had completed the trial, 211 were continuing treatment and 201 patients had discontinued. The mean dose ofTTS-fentanyl increased from 48 to 105 ng/h over 12 months, with most increases occurring in the first months. During treatment the number of subjects reporting very good, good or moderate pain control remained stable at 65% (range 61-75%). Global satisfaction (very good or good) was also stable at 42% (range 38^6%). 86% of patients reported preference for TTS-fentanyl over their previous treatment, stating the main reason as better pain relief. SF-36 scores improved from baseline for physical pain and physical summary measurements. The most frequently occurring adverse events were nausea (28%), somnolence (17%), constipation (15%), vomiting (15%) and increased sweating (14%).

Conclusions: Long-term treatment with TTS-fentanyl provides a stable degree of pain control in the majority of patients with moderate-to-severe non-cancer pain. It was preferred by the majority of subjects to their previous medication and favourably improved their quality of life.

Acknowledgments: Supported by the Janssen Research Foundation. Dr Haazen is a Clinical Research Manager for Janssen Phar-maceutica.

FENTANYL TRANSDERMAL SYSTEM (DUROGESIC*) + PARACETAMOL VS. PARACETAMOL + CODEINE VS. PLACEBO IN GONARTHROSIS AND ARTHROSIS FROM HIP.

Miralles FS. Robles E*. Pain Unit. Dept ofAnesthesiology. Hospital Vega Baja. Orihuela. Alicante. Spain.

Aim of Investigation: This randomised, double blind, placebo controlled study was designed to assess the efficacy and safety of paracetamol 500 mg + codeine 30 mg (COD), versus Durogesic* 12,5 mg + paracetamol 500 mg (DUR), versus placebo (PLA).

Methods: Effervescent COD, and PLA were administered t.i.d. with a blank patch every 6 days. Paracetamol was administered t.i.d. and Durogesic* -with delivery system limited to 12,5 mg- was applied every 6 days. Efficacy was assessed each day by the patient on visual analogue scale (VAS) and at the end of the two weeks treatment (global assessment -GA-) and the investigators (algofunctional index -AI- and GA). Efficacy analysis (Intention To Treat) was performed including all patients. Adverse effects spontaneously reported by patients or observed by the investigator were recorded.

Results: 30 patients were allocated to three groups. There were no diferences between the three treatment groups. Twelve men and 18 women suffering of unilateral (n=7) or bilateral (n=10) arthrosis from hip or unilateral (n=5) or bilateral (n=8) gonarthrosis were included, mean age 62 and mean weigth 72, mean pain duration 4 years (6months-15 years). Initial pain was 6518 mm in the VAS(O-IOO). The initial functional handicap was moderated for 23% of the patients, important or extreme for 76% of patients with a mean AI of 9(2-16) before treatment. After this, the AI was significantly improved in COD (p<0,005) and DUR (p<0,001) groups as compared to PLA. VAS decreased in both COD (p<0,005) and DUR (p<0,005) groups versus PLA, but not difference was find between COD and DUR groups. Only few side effects were reported on DUR and PLA compared with COD (constipation in 67%).

Conclusions: This study showed that both COD and DUR can significantly improve the pain and the algofunctional status of patients suffering from arthrosis from hip and gonarthrosis, with high side effects in COD group.

CONTROLLED TRIAL ON THE EFFICACY OF OP10IDS AND TR1CYCLIC ANT1DEPRESSANTS IN POSTHERPETIC NEURALGIA (PHN)

Snnivasa N. Raja. Jennifer Haythomthwaite*, Marco Pappagallo, Michael Clark, Mitchell Max, Depts. ofAnesthesiology & Psychiatry, Johns Hopkms Univ. and Clinical Trials Unit, NIDR, NIH, Baltimore, MD, U.S.A.

Aim of Investigation: To compare in PHN patients the analgesic effects ofopioids and tricyclic antidepressants (TCA) relative to placebo, and to determine if therapy with opioids or TCA affects cognitive function that may limit their usefulness in the treatment ofPHN.

Methods: Patients (>18 yrs) with PHN ofS3 months were enrolled in a randomized, double-blind, placebo-controlled, 3-phase crossover study. Drugs included MS-Contin (or methadone), nortripty-line (or desipramine), and inactive placebo. Each phase consisted of 4 wk titration, 2 wk maintenance, and 2 wk drug withdrawal periods. Treatment effects were judged by change in the intensity of ongoing pain from baseline, using verbal scores (0-10). Measures of cognitive function included the Digit Symbol Substitution test. Digit Span, a digit cancellation test, the grooved pegboard, and a measure of verbal learning.

Results: Data from the first 58 patients (pt) who completed or exited the clinical trial were analyzed. 42 pt completed at least 2 phases. Average MS Contin and nortriptyline doses during the maintenance phase were 95mg and 83 mg, respectively. The average decrease in pain intensity with placebo, TCA and opioid was -0.5 3.0 (mean SD, n=38), -1.5 2.5 (n=41, p<0.05) and -2.7 2.8 (n=43, p<0.001) respectively. Side effects associated with the use ofopioids and TCA were a barrier to their dose titration to maximal effect. Analysis of the cognitive data obtained from patients during the first phase of the study demonstrated no significant effects of treatment with opioid or TCA on measures of motor and psychomotor speed, attention and concentration, or verbal learning (p>.10).

Conclusions: These preliminary analyses indicate that both TCAs and opioids provide significant pain relief in patients with PHN compared to placebo. The data suggest that stable dosing of long-acting opioid medication or TCA is not associated with changes in motor and psychomotor speed, attention and concentration, or verbal learning.

TREATMENT OF OSTEOARTHRITIS PAIN WITH AROUND-THE-CLOCK OPIOIDS: THE EFFECT OF CONCOMITANT NSAID USE.

S. I. Rosen. P. G. Lacouture, K. Hopf, T. Iwan, R. F. Reder, R. F. Kaiko, Purdue Pharma L.P., Norwalk, CT 06850, S. Roth, Arthro-care. Phoenix, AZ

Aim of Investigation: A previous study had shown that a low dose (lOmg ql2h) ofcontrolled-release (CR) Oxycodone was marginally superior to placebo in moderate to severe pain ofosteoarthritis. The same study demonstrated clear analgesic efficacy of a larger dose (20 mg ql2h). Because 65% of patients enrolled were maintained on NSAIDs, the role of concomitant NSAID therapy was further explored.

Methods: 133 patients with moderate to severe pain from osteoar-thritis were enrolled in this 2-week trial. Pain intensity (scale: 0-none to 3-severe) was measured daily and evaluated for those patients on NSAIDs (+ NSAID) and those not (- NSAID). Results:

MEAN PAIN INTENSITY

Baseline
WK2
Dm.
PLACEBO
N=43  
+NSA1D
2.30.1 1.7+0.2 0.5
-NSAID
2.20.2 1.80.2 0.4
ql2hCROXY lOmg N=44

+NSA1D
2.50.1 1.50.2 1.0
-NSAID
2.60.2 2.2 0.2 0.4

Results suggest a more significant reduction in pain intensity in patients receiving combination therapy compared to NSAID, placebo or opioid alone. Placebo response was not affected by the presence of NSAID. Because the baseline mean pain intensity was somewhat dissimilar in the CR Oxycodone 20mg group, comparisons were not made for this group.

Conclusions: We conclude that in moderate to severe pain due to osteoarthritis low doses ofCR Oxycodone ql2h significantly improve pain control in patients on NSAID therapy. These findings also support the enhanced activity ofopioids with NSAIDs.

Acknowledgments: Sponsored by Purdue Pharma L.P., Norwalk, CT; S. I. Rosen is an employee of Purdue Pharma L.P.

LONG-TERM USE OF MASSIVE DOSE OF MORPHINE FOR A PATIENT WITH NON-CANCER PAIN

Kyoko Saito*. Toshio Takanishi*, Yasuhisa Okuda, Toshimitsu Kitajima, First Dept ofAnesthesiology Dokkyo Univ School of Medicine Mibu, Tochigi 321-0293, Japan

Aim of Investigation: Long-term use ofopioids for patients with non-cancer pain is controversial. We here report a patient with chronic pain who was given a massive dose of morphine tablet in order to improve quality of life.

Case Report: A 37 year-old female was diagnosed as having Lyme disease because of pain and motor disturbance in the right lower extremity in 1987. When a lumbar puncture was performed for myelography, she fainted due to severe pain in the legs. After that, her pain markedly increased. She visited our clinic in 1996. She could not raise her upper body on the bed without support because of severe pain. NSAIDs and epidural blocks were not effective. At first, we prescribed oral morphine tablets (MS contin*) 60 mg daily. The dose of morphine increased gradually, and morphine 300 mg/day was an ultimately sufficient dose to relieve her pain. We also performed lumbar sympathetic blocks with phenol to avoid increasing the dosage of morphine. The patient recovered to the extent that she could walk with a cane, and she was also able to publicly perform at a piano recital.

Conclusions: Massive dose of morphine improved quality of life of a non-cancer patient. Lumbar sympathetic blocks avoided increasing the dosage of morphine.

OP101D FOR NON-MALIGNANT PAIN EXPERIENCE OF VENEZUELAN CENTER

Schaffer-Vargas G.. Schaffer S.* Mejia A.*, Femandez C*. Unidad Integral Del Dolor. Centro Clinico Profesional Caracas, Caracus-Venezuela

Aim of Investigation: To determine on patients with non- malignant pain (NMP): Addiction when utilizing opioids for 30 days or more; Necessity to increase opioid doses; Side effects.

Material and Methods: Prospective study of 30 patients with NMP. The Pain evaluation methods: verbal rating scale (VRS), Spanish version ofMcGill Pain questionnaire, Pain Relief Scale (PRS), proposed at second consultation. Patients were evaluated and treated by a multidisciplinary team.

Results: We studied 30 patients, 18 females and 12 males, average age 58,23 years. All patients suffered NMP over than 446,83 days in average, with initial VAS 95 mm. The different pathologies studied were: spine degenerative affections 66,66%, postherpctic neuralgia 13,33%, peripheral neuralgia 13,33%, chronic postoperative pain 6,66%. Analgesic opioids used: codeine 20%, oxyco-dona 20%, morphine 53,33%, Fentanyl 6,66%. Average treatment time was 176 days. One week later of treatment patients recognized by themselves, a decrement in pain of 76,83% according to PRS. The evaluation schedule was: first month, weekly; Second month, every other week; During a year, once a month. 23,33% presented no side effects related to opioids. Collateral effects were: constipation (mild 60%, severe 10%), profuse sweating 3,33%, dizziness 3,33%. There were no addiction problems in any patient. It was not necessary to increase progressively the opioid doses. It is important to remark that 26.66% of patients are still under opioids treatment, on 70% according to PRS.

Conclusions: Chronic NMP may be treated with analgesic opioids under close medical vigilance with no addiction risks and mild side effects.

EVALUATION OF THE USE OF SUSTAINED-RELEASE MORPHINE IN SUBACUTE POST-TRAUMA PAIN

S.A Schug. J.E. Ritchie*. K. Kanji*, M. Seay, Section of Anaesthetics, Univ of Auckland, Auckland, New Zealand

Aim of Investigation: Intravenous patient-controlled analgesia (PCA) is a safe and effective treatment of acute pain. However, the 'step-down' from opioids via PCA to the oral route can be difficult, in particular in trauma patients with ongoing pain problems. These patients are often left with extended use of PCA incurring increased costs and sometimes even hospital stay. This audit evaluates the introduction of sustained-release morphine sulphate (MST), allowing the early discontinuation of PCA morphine, in trauma patients.

Methods: 50 trauma patients were commenced on MST (with morphine elixir available as rescue analgesic) after early discontinuation of PCA morphine; oral MST was given 12 hourly, initially in a daily dose identical to PCA usage over the previous day. During daily visits by the Pain Service MST dosage was adjusted based on rescue analgesia use and pain scores. Results: Data from 40 patients were available for analysis. PCA morphine was discontinued after 2.9 days using a mean dose of 63.1 mg/day. MST was introduced at a mean dose of 60.8 mg/day, with 82% of patients requiring rescue analgesia. 82% of patients had improved or equal pain scores during the transition period. All patients were weaned from the MST over a mean time of 12.3 days. Eight patients (20%) were discharged home on MST with follow-up and weaning on an out-patient basis. No patient experienced serious side effects (including respiratory depression or withdrawal), however, 45% of patients experienced minor side effects such as nausea, constipation and/or sedation.

Conclusion: Sustained release morphine as a 'step-down' analgesic provided effective and safe pain relief in trauma patients. It enabled stable and early transition from intravenous to oral analgesia and from hospital to home.

ACUTE DISCONTINUATION OF CHRONIC OPIOID THERAPY: A PLACEBO-CONTROLLED EVALUATION

M. Shi. P. G. Lacouture, R. F. Reder, Purdue Pharma L.P., Norwalk, CT

Aim of Investigation: Spontaneously reported adverse events (AEs) were collected to evaluate the potential for withdrawal symptom complexes following the abrupt cessation of opioid treatment with a placebo-controlled design.

Methods: Patients with moderate to severe pain secondary to os-teoarthritis were titrated with immediate-release (IR) oxycodone given q.i.d., around-the-clock to stable pain control over 30 days. Patients were then randomized to 1 of 3 treatments (2 active oxycodone treatments and 1 placebo), and then treated for an additional 30 days under blinded conditions. Spontaneously reported AEs were routinely collected. 167 patients were enrolled in this trial of which 107 completed the 30-day titration and were randomized to one of three blinded treatments. 63% were female and 29% were > 65 years old. The mean oxycodone dose was 39 mg/daily (27% 20 mg, 12% 30 mg, 25% 40 mg, 11% 50 mg and 25% 60 mg/daily). Specific AEs possibly related to acute withdrawal reactions were selected and evaluated.

Results: Spontaneous AEs (new onset)

PLACEBO ACTIVE 1 ACTIVE 2
 

 

N=36 N=34 N=37
Nausea 12(9) 5(4) 19(13)
Vomiting 0(0) 1(1) 4(4)
Abd. Pain 0(0) 1 (1) 0(0)
Lacrimation 0(0) 0(0) 0(0)
Rhinorrhea 0(0) 0(0) 0(0)
Agitation 1(1) 0(0) 0(0)
Complex 0(0) 0(0) 0(0)
# of reports (# of patients)

No oven withdrawal syndrome was identified in this population and symptoms were not consistent with any problems related to abrupt withdrawal of chronic opioid therapy. Any possibly related events did not have expected onset within 24-48 hours

Conclusions: The data suggest that acute withdrawal from chronic opioid treatment may not be a concern in patients when daily oxycodone doses are ^ 60 mg/day.

Acknowledgments: Sponsored and authored by employees of Pur-due Pharma L.P., Norwalk, CT USA.

LONGTERM INTRASPINAL INFUSIONS OF OPI-OIDS WITH A NEW IMPLANTABLE MEDICATION PUMP VIP30

Martin C. Spendel*. Rudolf Likar, Anton Sadjak*, Gunther Lan-ner* (SPON: Klaus Mathiaschitz), Clinic ofNeurosurgery Klagen-furt, 9026 Klagenfurt, Austria

Aim of Investigation: Pain treatment outcome research with long-term intraspinal infusion ofopioid drugs using the new implantable medication pump VIP 30 with chronic non-malignant pain.

Methods: During a 19 month period 10 patients with chronic pain mainly mixed nociceptive-neuropathic pain, underwent implantation of the medication pump for long-term treatment. Our retrospective investigation focused on data available for 10 patients with chronic non-malignant pain. The mean follow-up period was 9,5 months. The patients were followed up by the VAS (Visual Analogue Scale), level of activity and subjective assessment of the quality of life. At each follow-up the patients infusion rate of morphine side effects of the drug and any complications related to the pump were also recorded.

Results: The degree of pain relief by the last follow-up was rated as very good in 22,2% good relief in 44,4%, moderate relief in 22,2% and poor relief in 11,1%. The patients were also asked if they would undergo the procedure again. 11,9% stated no, but 88,9% stated yes.

Conclusions: We conclude from this retrospective analysis that intrathecal opioids are efficacious, practical and deemed safe for the treatment of non-malignant pain syndromes. Furthermore we conclude from our analysis of the data, that mixed nociceptive neu-ropathic pain responds better to intrathecal opioids than neuro-pathic pain.

SECURITY-RELATED PERFORMANCE OF PATIENTS ON LONG-TERM OPIOID THERAPY

M Strump*. KW Herberg**, A Willweber-Strumpf*, R Der-twinkel*, M Zenz*, *Dept ofAnesthesiology, Intensive Care and Pain Therapy, Univ Clinic Bergmannsheil Bochum, Germany, **Technical Surveillance Company Rheinland, Koln, Germany

Aim of Investigation: Clinical observations of patients on oral opi-oid medication suggest that initially appearing central side effects such as sedation, dizziness or drowsiness decrease after a few weeks of treatment. However, it is still unclear if a long-term treatment with opioids impair complex psychomotor functions such as driving a car.

Methods: In a pilot study, 20 patients on stable dosages of oral opioids were examined using a driving simulator. Control groups tested in the same way were: patients before an elective operation after taking benzodiazepines for sedation, volunteers after alcohol consumption (0.80%), physicians on call with less than 4 hours of sleep and healthy volunteers without any medication. A second study examined 80 patients who underwent a complex test program used by the Technical Surveillance Company of Germany. These patients were compared with volunteers of the same age.

Results: In both studies, some of the patients treated with opioids reacted as fast as medication-free volunteers. No security-related differences could be seen between medication-free volunteers and patients receiving opioids with regard to tasks of visual or motor control skills.

Conclusions: A long-term therapy with opioids does not inevitably impair complex skills, but the decision e.g. to allow driving a car can only be made for the individual case.

Acknowledgments: Goedecke AG, Freiburg, Germany

MORPHINE EFFECTIVE IN NEUROPATHIC PAIN:PRELIMINARY RESULTS OF A DOUBLE-BLIND STUDY.

Anneli Vainio. Reino Poyhia, Jacques Bemier*, McGill-Montreal General Hospital Pain Centre, 1650 Cedar Ave, Montreal, Quebec H3G 1A4, Canada

Aim of Investigation: To test the predictive power of IV opioid testing in relation to the outcome of long-term morphine therapy.

Methods: Patients with chronic pain underwent quantitative psychophysical testing to categorize their pain as nociceptive or ncuropathic. They took intravenous morphine and placebo randomly on consecutive days using Patient-Controlled Analgesia device (bolus 5 mg, lock-out lOmin) with a blinded assessor for pain and adverse effects. Then they participated in a double-blind randomised trial with oral morphine and placebo (2 weeks + washout + 2 weeks).

Results: Nine patients (5 nociceptive, 4 neuropathic) have thus far participated. The duration of the morphine test was 3-6 hours. Patients with nociceptive pain had a mean pain reduction of 76% on a VAS pain scale in rest and of 71 % in movement with a mean morphine consumption of 42 mg (range 13-55). Patients with neuropathic pain had a mean pain reduction of 46% in rest and of 42% in movement with a mean morphine consumption of 52 mg (range 28-85 mg). Pain was uneffected by placebo infusion in both groups. Six out of nine patients had nausea, vomiting and itching during morphine test. The results of the oral trial will be given in the poster. Five of 7 patients who have finished the oral trial continue with opioid therapy, 3 of them with other than morphine.

Conclusions: Both nociceptive and neuropathic pain respond to morphine. An IV test seems to predict response to oral opioids.

CONCENTRATIONS OF ASSYMETR1C (ADMA) AND SYMETRIC DIMETHYLARG1NINE IN CSF CORRELATING TO OPIOID- SENSITIVITY IN CANCER-PAIN PATIENTS.

Thomas Wolff^, Thomas Hedner**, Birgit Wolff, *Pain Clinic Central Hospital Skovde Sweden, +King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia, **Dcp. Clinical Pharmacology Sahlgrens Univ Hospital Gothcnburg, Sweden

Hypothesis: The endogenous NO-synthesis inhibitor such as ADMA is involved in morphine tolerance. Increased ADMA-concentrations will be expected in patients who do not develop tolerance compared to those who do. Primary effect parameter: CSF concentrations of ADMA.

Secondary effect parameters: Pain evaluation by VAS and verbal scale. Pain area. Morphine dose over time. Plasma morphine, CSF morphine. Kamofsky scale. ADMA and SDMA in plasma and CSF M, M6G, M3G in CSF and plasma by HPLC L-arg/citrulline in CSF by HPLC Nitrite, nitrate in CSF. Twenty patients with advanced cancer and pain were investigated. Pain intensity (VAS, verbal), treatment; dose ofopioid, other medication. CSF samples were taken together with bloodsamples. 10 control-patients were investigated in the same manner (non-canccr-patients not on any pain-treatment and not having any pain). The study will to show if high ADMA-concentration could protect the patient from development of tolerance, and if a significant difference exist between cancer-patients and control-group-patients. So far (febr 99) the results confirm the hypothesis.

OXYCONTIN* FOLLOWING TOTAL KNEE AR-THROPLASTY: A RANDOMIZED, CONTROLLED TRIAL.

Andrea Cheville*. Alice Chcn*, Elizabeth Narcessian, Laurcn Shaiova, Mark Johnston*, Kessler Inst for Rehabilitation, 1199 Pleasant Valley Way, West Orange, New Jersey, USA

Aim of Investigation: The use ofopioid-based analgesic therapy during intensive post-operative rehabilitation remains controversial due to concern regarding attenuated therapy participation, interference from opioid-related side effects, and exaggerated addiction risk. Unfortunately, pain and associated anxiety have been shown to interfere with post-operative functional recovery. This study was designed to determine whether the use of Oxycontin* following unilateral total knee arthroplasty would accelerate functional recovery through enhanced control of pain and anxiety.

Methods: A consecutive sample ofpost-arthroplasty patients was randomly assigned to receive Oxycontin* (20mg qAM and lOmg qPM) or an inactive placebo. All patients participated in a rigorous program of daily physical (PT) and occupational therapy (OT). Primary outcome measures included: visual analogue (VAN) pain ratings; functional independence measure (FIM) scores for ambu-lation, stair negotiation, and transfers; and Beck's Anxiety Inventory (BAI) scores. VAN ratings were recorded at each PT session, while FIM scores were recorded during the 1 st and 8th PT sessions. The BAI was administered following the 6th PT session.

Results: 59 patients were enrolled in the study. The Oxycontin* and placebo groups did not differ significantly with respect to admission FIM scores, demographic variables, or degree of medical comorbidity. Careful data analysis revealed significant decrements in median VAN ratings in the Oxycontin* relative to the control group (p=.01). BAI scores were significantly lower in the Oxycontin* group (p=.03). A strong direct correlation occurred between VAN ratings and BAI scores (p=.001, rho=.68). Functional recovery as reflected in PT session #8 FIM scores for ambulation (p=.02), stair negotiation (p=.001), and transfers (.03) was significantly enhanced in the Oxycontin* group. An inverse correlation was detected between patients' BAI scores and their ambulation status (p=.03, rho=.50). VAN ratings were also significantly inversely correlated with FIM scores.

Conclusions: The enhanced pain control, reduced anxiety, and accelerated functional recovery in the Oxycontin* group demonstrates that sustained release opioid preparations may confer both functional and psychological benefits during post-operative rehabilitation. The correlation between BAI scores and VAN ratings, and their inverse correlation with functional parameters suggest that these constructs are interrelated and may jointly function to retard patients' recovery of function.

9th WORLD CONGRESS ON PAIN, 1999, Vienna, Austria, p. 339

   

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