[Interdisciplinary pain therapy in the elderly]. / Interdisziplinäre multimodale Schmerztherapie im Alter.

Chronic pain in the elderly is becoming increasingly important and is associated with serious health impacts. Therefore, international guidelines demand that pain therapy for the elderly preferably be a multimodal therapy based on a bio-psycho-social pain model. Specific psychometric tests and interview guidelines are available for the interdisciplinary pain assessment. Evidence for the effectiveness of multimodal pain therapy in the elderly remains limited. However, controlled clinical trials have shown that these patients benefit-especially if the intervention is adapted to their specific needs. The focus of movement therapy is not only muscle strengthening but also coordination exercises. In individual physical therapy and occupational therapy, everyday solutions can be developed for individual physical limitations that are more frequent in old age. In psychological training, pain acceptance, balancing rest and activity, social integration and dealing with aging are particularly important topics. Relaxation and mindfulness techniques can also favorably affect pain and function. Thus, these are popular with patients and are often adopted in everyday pain management. Pain education is considered useful as an adjunctive measure and can also be increasingly supported by digital media in the elderly. Complementary therapy components include confrontational treatment of fear-avoidance beliefs (the German AMIKA scale, Ältere Menschen in körperlicher Aktion, "older people in physical action") and naturopathic applications as an active self-help strategy. Since it is unclear how long the achieved therapeutic effects last, follow-up care is of particular importance in therapy for older patients.

[Interdisciplinary pain therapy in the elderly]. / Interdisziplinäre multimodale Schmerztherapie im Alter.

Chronic pain in the elderly is becoming increasingly important and is associated with serious health impacts. Therefore, international guidelines demand that pain therapy for the elderly preferably be a multimodal therapy based on a bio-psycho-social pain model. Specific psychometric tests and interview guidelines are available for the interdisciplinary pain assessment. Evidence for the effectiveness of multimodal pain therapy in the elderly remains limited. However, controlled clinical trials have shown that these patients benefit-especially if the intervention is adapted to their specific needs. The focus of movement therapy is not only muscle strengthening but also coordination exercises. In individual physical therapy and occupational therapy, everyday solutions can be developed for individual physical limitations that are more frequent in old age. In psychological training, pain acceptance, balancing rest and activity, social integration and dealing with aging are particularly important topics. Relaxation and mindfulness techniques can also favorably affect pain and function. Thus, these are popular with patients and are often adopted in everyday pain management. Pain education is considered useful as an adjunctive measure and can also be increasingly supported by digital media in the elderly. Complementary therapy components include confrontational treatment of fear-avoidance beliefs (the German AMIKA scale, Ältere Menschen in körperlicher Aktion, "older people in physical action") and naturopathic applications as an active self-help strategy. Since it is unclear how long the achieved therapeutic effects last, follow-up care is of particular importance in therapy for older patients.

Consultation with a specialized pain clinic reduces pain after oral and maxillofacial surgery.

PURPOSE: Postoperative pain management is important for improved patient care. Our primary objective was to investigate the effect of analgesic treatment adaptation by the pain clinic on postoperative pain relief at an oral and maxillofacial surgery department. Additionally, we aimed to present patients' pain characteristics and the administered analgesic treatment. MATERIALS AND METHODS: A total of 128 patients treated at our clinic in the period 2012-2015 who required analgesic treatment adaptation by our pain clinic were included. They were further divided into 10 groups: tumor, temporomandibular joint disorder, tooth extraction, osteomyelitis, bisphosphonate-related osteonecrosis of the jaw, submandibular abscess, orthognathic surgery, cyst, sinusitis, and fracture. Pain characteristics evaluated were intensity on a numerical rating scale (NRS) before and after intervention of the pain clinic, quality, genesis, and type. RESULTS: Post treatment pain intensity values at rest 1.8 (SD: 1.4) and on exercise (walking and physical therapy) 4 (SD: 2) were statistically significant better compared to pretreatment values (4.2, SD: 2.5, and 6.8 SD: 2, respectively). The highest pain intensities were reported after tooth extractions, orthognathic surgery, cystectomies, and fracture reposition. Pain was mainly continuous and related to a combination of a somatic and a neuropathic pathophysiological mechanism. CONCLUSIONS: Intervention by a specialized pain clinic leads to reduction of postoperative pain.

Psychological Predictors of Acute Postoperative Pain After Hysterectomy for Benign Causes.

OBJECTIVES: Psychological parameters have been shown to contribute significantly to the development of acute postoperative pain (APOP). For the prediction of APOP in chest malformation patients and cancer patients, we found pain-specific psychological predictors to be of higher relevance than general psychological predictors. The current study aims to further substantiate these findings. MATERIALS AND METHODS: In a sample of 73 middle-aged hysterectomy patients, 3 predictor sets were assessed 1 day before surgery: attentional biases (toward pain-related, social threat, and positive words in a dot-probe task), pain-related emotions and cognitions (pain anxiety, pain catastrophizing, and pain hypervigilance), and affective state variables (depression and somatization). APOP intensity rated 2 to 3 days after surgery and analgesic consumption during the first 48 postoperative hours were used as outcome measures. RESULTS: APOP intensity ratings were significantly explained by their best single predictors in a multiple regression analysis: social threat words of the dot-probe task, pain anxiety, and somatization (14.7% of explained variance). When comparing standardized ß coefficients, pain-specific psychological predictors appeared to be of higher explanatory relevance than general psychological predictors. In contrast, analgesic consumption could not be significantly predicted by the psychological variables. DISCUSSION: Hysterectomy patients at risk for high APOP intensity could be characterized by the psychological variables used, whereas their predictive value for analgesic consumption was limited. The high predictive potency of pain-specific psychological variables should be considered for further improvement of pain management and prevention, because pain-specific variables such as pain anxiety can be the target of focal psychological interventions when preparing for surgery.

Association of genetic and psychological factors with persistent pain after cosmetic thoracic surgery.

The genetic control of pain has been repeatedly demonstrated in human association studies. In the present study, we assessed the relative contribution of 16 single nucleotide polymorphisms in pain-related genes, such as cathechol-O-methyl transferase gene (COMT), fatty acid amino hydrolase gene (FAAH), transient receptor potential cation channel, subfamily V, member 1 gene (TRPV1), and δ-opioid receptor gene (OPRD1), for postsurgical pain chronification. Ninety preoperatively pain-free male patients were assigned to good or poor outcome groups according to their intensity or disability score assessed at 1 week, 3 months, 6 months, and 1 year after funnel chest correction. The genetic effects were compared with those of two psychological predictors, the attentional bias toward positive words (dot-probe task) and the self-reported pain vigilance (Pain Vigilance and Awareness Questionnaire [PVAQ]), which were already shown to be the best predictors for pain intensity and disability at 6 months after surgery in the same sample, respectively. Cox regression analyses revealed no significant effects of any of the genetic predictors up to the end point of survival time at 1 year after surgery. Adding the genetics to the prediction by the attentional bias to positive words for pain intensity and the PVAQ for pain disability, again no significant additional explanation could be gained by the genetic predictors. In contrast, the preoperative PVAQ score was also, in the present enlarged sample, a meaningful predictor for lasting pain disability after surgery. Effect size measures suggested some genetic variables, for example, the polymorphism rs1800587G>A in the interleukin 1 alpha gene (IL1A) and the COMT haplotype rs4646312T>C/rs165722T>C/rs6269A>G/rs4633T>C/rs4818C>G/rs4680A>G, as possible relevant modulators of long-term postsurgical pain outcome. A comparison between pathophysiologically different predictor groups appears to be helpful in identifying clinically relevant predictors of chronic pain.

Does severe acute pain provoke lasting changes in attentional and emotional mechanisms of pain-related processing? A longitudinal study.

Pain experiences, learning, and genetic factors have been proposed to shape attentional and emotional processes related to pain. We aimed at investigating whether a singular major pain experience also changes cognitive-emotional processing. The influence of acute postoperative pain after cosmetic surgery of the thorax was tested in 80 preoperatively pain-free male individuals. Acute pain was measured as independent variable during the first week postsurgery by pain intensity ratings and the requested analgesic boluses (Patient-Controlled Epidural Analgesia (PCEA)). Pain catastrophizing (Pain Catastrophizing Scale (PCS)), pain anxiety (Pain Anxiety and Symptom Scale (PASS)), pain hypervigilance (Pain Vigilance and Awareness Questionnaire (PVAQ)), and attentional biases to emotionally loaded stimuli (including pain) in a dot-probe task were assessed 1 week, 3 months, and 6 months postsurgery as dependent variables. Hierarchical regression analyses were performed to test whether the 2 acute pain parameters can predict these cognitive-emotional variables. As a rigorous test, significant prediction was required in addition to the prediction of the dependent variables by themselves with lag-1. Acute pain (mainly the pain ratings) appeared to be a significant predictor for PCS, PASS, and PVAQ 1 week after surgery (deltaR(2) = [8.7% to 11.3%]). In contrast, the attentional biases in the dot-probe task could not be predicted by the pain ratings. The levels of pain catastrophizing and pain hypervigilance increased in the acute phase after surgery when influenced by acute pain and declined, along with pain anxiety, during the next 3 months. In conclusion, a one-time intense pain experience, such as acute postoperative pain, appeared to produce at least short-lived changes in the attentional and emotional processing of pain.

Attentional and emotional mechanisms related to pain as predictors of chronic postoperative pain: a comparison with other psychological and physiological predictors.

The present prospective longitudinal study on chronic postoperative pain was conducted to assess the predictive power of attentional and emotional variables specifically assumed to augment pain, such as pain hypervigilance, pain-related anxiety, pain catastrophizing and attentional biases to pain. Their relevance was determined in comparison with other psychological and physiological predictors (depression, anxiety, somatization, cortisol reactivity, pain sensitivity). In 84 young male patients the predictor variables were assessed one day before surgery (correction of chest malformation). Postoperative outcome (subjective pain intensity and pain-related disability) was assessed three (N=84) and six months (N=78) after surgery. Patients were classified into good and poor outcome groups. Patients with high pain intensity three (25%) or six months (14%) after surgery, differed significantly from those low in pain with regard to their preoperative performance in the dot-probe task (high attentional bias towards positive words). A sizeable portion (54%) of patients still felt disabled due to pain after three months and a few patients after six months (13%). These patients were those with high preoperative ratings in the Pain Vigilance and Awareness Questionnaire. The few subjectively disabled patients after six months could be identified in addition by low pressure pain and high cold pain thresholds before surgery. An attentional bias towards positive stimuli prior to surgery may indicate a maladaptive coping style, which avoids necessary confrontation with pain and predisposes patients to chronic postoperative pain. Lasting subjectively felt pain-related disability occurs predominantly in patients with high levels of pain hypervigilance before surgery.

Higher pain scores, similar opioid doses and side effects associated with antipyretic analgesics in specialised tertiary pain care.

PURPOSE: To evaluate whether non-opioid antipyretic analgesics are associated with lower pain scores, opioid doses and side effects in pain patients in tertiary care. METHODS: In a cross-sectional observational study, data from 519 Caucasians (197 men, 322 women; mean age 55.6 ± 15 years) who had undertaken pain therapy for various causes for 77.5 ± 90.8 months, obtained in three separate study centres, was analysed for actual 24-h pain scores, daily opioid doses and the occurrence of side effects. RESULTS: Of the 519 patients, 352 received opioids and 260 antipyretic analgesics, from whom 154 received both classes and 304 only either class. The administration of non-opioid antipyretic analgesics was associated with higher average pain scores (4.6 ± 2.5 vs 3.9 ± 2.6; P = 0.01), tendentially higher average oral morphine equivalent doses (121.8 ± 162.2 vs 146.7 ± 242.4 mg/d; P = 0.25) and a similar incidence of side effects (P = 0.21). These results were correspondingly seen when analysing the three study centres separately as independent cohorts. CONCLUSIONS: With the caution advised for cross-sectional data, the results dispute a clinical benefit of non-opioid antipyretic analgesics for most chronic pain patients in tertiary care and draw attention towards prospectively re-evaluating the utility of non-opioid antipyretic analgesics in tertiary pain care in a randomised placebo controlled trial.

Long-term treatment of neuropathic pain with a 5% lidocaine medicated plaster.

BACKGROUND AND OBJECTIVE: The 5% lidocaine medicated plaster is a topical treatment for peripheral neuropathic pain symptoms (e.g. burning, shooting and stabbing pain) and is registered for the treatment of postherpetic neuralgia. This study examined the efficacy and tolerability of long-term treatment with the 5% lidocaine medicated plaster in patients with localized neuropathic pain conditions. METHODS: Twenty patients with localized neuropathic pain [postoperative neuropathic pain (n = 14); complex regional pain syndrome (n = 2); and postherpetic neuralgia (n = 4)], who had been successfully treated with 5% lidocaine medicated plaster, were followed up by telephone interview after 3 and 5 years. Questions were related to the efficacy, development of tolerance, tolerability, wear time and comfort of the plaster. RESULTS: At 3 years, 10 out of 20 (50%) initial responders were still using the plasters with no decline in analgesic efficacy. After 5 years, eight of the original 20 responders (40%) maintained treatment and continued to experience effective pain relief. The 12 responders who discontinued treatment did so because they no longer required analgesic therapy (n = 4); their health insurer refused to fund treatment (n = 2); they were lost to follow-up (n = 1); or had died from an illness unrelated to plaster treatment (n = 5). No patient discontinued because of inadequate analgesia or intolerable side effects. Reversible erythema occurred in two patients wearing the plaster for more than 16 h. There were no systemic side effects. CONCLUSION: The 5% lidocaine medicated plaster provides sustained pain relief over long-term treatment in patients with neuropathic pain of various causes and is well tolerated.

Cross-sectional assessment of the consequences of a GTP cyclohydrolase 1 haplotype for specialized tertiary outpatient pain care.

OBJECTIVES: Reduced-function variants of the guanosine triphosphate cyclohydrolase gene (GCH1) have been associated with reduced pain in well-defined cohorts of patients and healthy volunteers. We addressed the question whether this genetic association plays a role in outpatient pain therapy. METHODS: In a cross-sectional observational study, 523 patients were enrolled in 3 different tertiary care outpatient pain centers at German University hospitals. Of the 519 Caucasian patients, data from 424 could be analyzed for functional associations of the formerly named "pain-protective" GCH1 haplotype with the key characteristics of pain therapy being (1) actual pain, (2) opioid dosing, and (3) pain therapy duration. RESULTS: With an allelic frequency of 14.2% the pain-protective haplotype was not rarer among pain patients than in the general population (P=0.344). However, a tendency toward gene dose-dependent effects of the GCH1 haplotype was observed in all the 3 therapy parameters. Carriers of the haplotype tended to have lower actual 24-hour pain scores (n=424; P=0.18), require lower opioid doses (P=0.096), and were significantly shorter on specialized pain therapy (P=0.004). The latter applied predominantly to differences between homozygous carriers and heterozygous (alpha-corrected t test: P=0.06) or non-carriers (P=0.011) of the haplotype. CONCLUSIONS: The results strength the support for a modest yet reproducible and consistent pain-protective effect associated with a GCH1 haplotype known to reduce GCH1 and thus BH4 up-regulation. Pending independent verification, the results might point to a prophylactic role of decreased GCH1 up-regulation delaying the need for pain therapy.

Cross-sectional analysis of the influence of currently known pharmacogenetic modulators on opioid therapy in outpatient pain centers.

AIM: A finite number of variants in the OPRM1, COMT, MC1R, ABCB1 and CYP2D6 genes has been identified to significantly modulate the effects of opioids in controlled homogenous settings. We analyzed the imprint of these variants in opioid therapy in a highly variable cohort of pain patients treated in outpatient units to test whether genotyping may play a role in this clinical setting. METHODS: In a multicenter study conducted in tertiary care outpatient pain centers, 352 patients (156 men and 196 women, aged 58.5+/- 14.6 years) treated for 1-600 months (63.4 +/- 92.4 months) with various opioids for pain of various origins were included. Genotyping was performed for all the variants reportedly modulating pain in well-defined cohorts. Association analyses focused on opioid dosing, the actual 24-h pain score on a 0-10 rating scale and the occurrence of side effects. RESULTS: The frequency of the genetic variants in the patients did not significantly differ from that in the average Caucasian population. Daily opioid doses ranged from 4 to 1750 mg oral morphine equivalents (133.4 +/- 203.2 mg) and significantly decreased in a gene dose-dependent manner with the P-glycoprotein variant ABCB1 3435C>T. Pain was rated on average at 3.7 +/- 2.6. There was a tendency towards increased pain in a gene dose-dependent manner with the mu-opioid receptor variant OPRM1 118A>G. CONCLUSION: Genetics were reflected in the outpatient pain therapy only to a modest degree. The need of outpatient therapy of pain of various causes guided by the presently known functional genetic variants cannot be convincingly concluded from the present data. Using the ABCB1 3435 genotype to predefine lower individual opioid doses barely merits the laboratory effort. If any, the results suggest that a genetics guided outpatient pain therapy may be based on ABCB1 and OPRM1 variants.

Effectiveness of an intensive multidisciplinary headache treatment program.

OBJECTIVE: To investigate if the effectiveness of a 96-hour multidisciplinary headache treatment program exceeds the effectiveness of a 20-hour program and primary care. BACKGROUND: When dealing with chronic back pain, low-intensity multidisciplinary treatment yields no significantly better results than standard care and monodisciplinary therapy; however, high-intensity treatment does. For multidisciplinary headache treatment, such comparisons are not yet available. In a previous study undertaken by our Pain Center, the outcome of a minimal multidisciplinary intervention model (20-hour) did not exceed primary care. METHODS: Forty-two patients suffering from frequent headaches (20 +/- 9 headache days/month; range: 8-30) were treated and evaluated in a 96-hour group program. The results were compared with the outcomes of the previous study. Subjects who had undergone either the 20-hour multidisciplinary program or the primary care were used as historical control groups. FINDINGS: A significant reduction in migraine days (P < .001), tension-type headache days (P < .001), frequency of migraine attacks (P = .004), and depression score (P < .001) was seen at the follow-up after 22 (+/-2) weeks. Comparing the intensive multidisciplinary program with primary care, repeated measures ANOVAs revealed significant time x group interactions for migraine days (P = .020), tension-type headache days (P = .016), and frequency of migraine attacks (P = .016). In comparison with the 20-hour multidisciplinary program, the 96-hour program showed significantly better effects only in the reduction of migraine days (P = .037) and depression score (P = .003). The responder-rates (> or =50% improvement) in the 96-hour program were significantly higher than in the 20-hour program (migraine days, P = .008; tension-type headache days, P = .044) and primary care (migraine days, P = .007; tension-type headache days, P = .003; tension-type headache intensity, P = .037). The effect sizes were small to medium in the 96-hour program. Particularly with the reduction of migraine symptomatology, the 96-hour program performed better than the 20-hour program, which produced only negligible or small effects. CONCLUSIONS: Intensive multidisciplinary headache treatment is highly effective for patients with chronic headaches. Furthermore, migraine symptomatology responds especially well to this intensive treatment program, whereas effects on tension-type headaches were realized by both multidisciplinary programs. Randomized controlled trials and subgroup analysis are needed to find out if these results can be replicated and which patient characteristics allow for sufficient improvements for headache sufferers even with less complex treatment.

Hypervigilance as predictor of postoperative acute pain: its predictive potency compared with experimental pain sensitivity, cortisol reactivity, and affective state.

OBJECTIVES: Pain hypervigilance--a strong attentional bias toward pain--is thought to accompany chronic pain and modulate pain management. Its usefulness as predisposing factor for the development and maintenance of pain has been discussed. The aim of our study was to demonstrate the predictive power of hypervigilance for the development of acute postoperative pain. METHODS: Fifty-four young male patients were assessed 1 day before surgery (correction of chest malformation) on a range of psychologic predictors. These predictors included the assessment of hypervigilance (questionnaires as the Pain Catastrophizing Scale, Pain Anxiety Symptom Scale, the Pain Vigilance and Awareness Questionnaire, and the dot-probe task) and affective state, experimental pain sensitivity, and cortisol reactivity. Acute postoperative pain was assessed by ratings of pain intensity 1 week postsurgery and through the amount of analgesics [patient-controlled epidural analgesia (PCEA)] requested during the first days after surgery. RESULTS: Pain intensity was significantly explained (17% explained variance) by hypervigilance, whereas PCEA performance was not (10%). Adding all other predictors led to a significant increase of explained variance (35%) for pain ratings and a nonsignificant increase (19%) for PCEA. A more parsimonious solution with only heat pain threshold added led to a significant increase in explained variance (30%) for pain intensity. Hypervigilance was only moderately correlated with the other predictors. DISCUSSION: Hypervigilance proved to be a powerful predictor of subjective acute postoperative pain, but was less useful with regard to the amount of requested analgesics. The overlap with other psychologic predictors (affective state, experimental pain sensitivity, and cortisol reactivity) is sufficiently small to consider hypervigilance a promising supplement in psychologic predictor research.

Use of patient-controlled analgesia for pain control in dying children.

BACKGROUND: In the last week of life, the daily opioid dose in children is highly variable, making the use of patient-controlled analgesia (PCA) a useful therapy option. Scientific data on the use of PCA in paediatric palliative care are rare. MATERIALS AND METHODS: Retrospective chart review over a 7-year period (Jan 1998-Jan 2005) of PCA treated children dying of cancer was used. RESULTS: Eight children were on PCA for a median duration of 9 days (range, 1 to 50). The daily median intravenous morphine equivalent dose referenced to body weight increased significantly when PCA was initiated and during the last week of life. In the last week of life, the median daily number of delivered and undelivered bolus requests ranged from 7.5-21 and 0-4.5, respectively. To meet children's individual needs, 39 PCA parametre changes on 22 opportunities were performed. Median daily mean pain scores remained low (range, 0-3; numerical rating scale 0-10) throughout the period. CONCLUSION: PCA proved an ideal, dependable and feasible mode of analgesic administration for the individual titration of dose to effect.

Intravenous morphine consumption in outpatients with cancer during their last week of life--an analysis based on patient-controlled analgesia data.

INTRODUCTION: Studies on opioid use in terminally ill cancer patients have shown a prefinal dose increase in the majority of patients. Mostly oral opioids were used. Due to the pharmacokinetic properties of opioids, it is rather difficult to get a reliable estimate of the true opioid need from those results. MATERIALS AND METHODS: Retrospectively, we analyzed opioid use during the last week of life of 30 consecutive outpatients with cancer on intravenous (i.v.) morphine patient-controlled analgesia (PCA). A dose increase (decrease) was defined as an increase (decrease) of the patient's individual daily dose by at least 30% with respect to their prior daily dose. We also analyzed circadian variations in morphine use. RESULTS: Thirty patients fulfilled the primary study inclusion criteria. Fulfilling the exclusion criteria, seven patients had to be excluded from analysis (n = 3, on PCA for less than 7 days; n = 4, PCA was finished before death). Twenty-three patients with a total of 161 treatment days were analyzed. The patients' median age was 57 years (range, 4 to 72). The median duration of intravenous morphine PCA was 19 days (range, 8 to 58). The median daily intravenous morphine dose during the last week of life was 96 to 115 mg, without significant change over time/from day to day (Friedman test). On 144/161 days (89.2%), morphine dose remained stable. On 9 treatment days (5.6%), the dose increased, and on 8 days (5.0%), it decreased. In three patients, only dose increases, and in four patients, only dose decreases were observed. In four patients, both dose increases and decreases were observed. Twelve patients showed no change in daily morphine dose. Opioid use lacked a diurnal pattern. CONCLUSION: During their end-of-life phase, cancer patients on i.v. morphine PCA showed a stable daily opioid need.

The effects of paracetamol and parecoxib on kidney function in elderly patients undergoing orthopedic surgery.

The common adverse effects of traditional nonsteroidal antiinflammatory drugs on renal function include reductions in renal blood flow, glomerular filtration rate, and sodium and potassium excretion, mainly via inhibition of renal cyclooxygenase. We designed the present study to determine the effects of IV paracetamol or parecoxib on renal function in elderly patients undergoing orthopedic surgery. Seventy-five patients (76 +/- 8 yr, mean +/- sd) undergoing hip replacement or surgery of the femoral shaft completed this randomized and placebo-controlled study. After their arrival in the postanesthesia care unit, patients received an initial dose of the study medication, paracetamol 1000 mg IV (n = 25), parecoxib 40 mg IV (n = 25), or saline IV (n = 25); subsequent doses were administered for the next 3 days. Opioids were provided as rescue medication. Blood and urine samples were collected before and after surgery, and markers of renal function were determined. During the first 2 h after the initial dose of parecoxib, creatinine clearance was slightly diminished (125 +/- 83 to 86 +/- 45 mL/min, P < 0.05), whereas no significant decrease of creatinine clearance was observed in the placebo and paracetamol groups. After all treatments, sodium and potassium excretion as well as urine albumin and alpha-1-microglobulin were transiently increased (group differences: not signicifant). In conclusion, glomerular and tubular functions were transiently affected in all patients after orthopedic surgery; however, the differences between the treatment groups were small and not clinically relevant. Further studies are warranted to determine adverse renal effects of longer-lasting therapy with these drugs, especially in patients with renal impairment or concomitant diseases.

Effects of intermittent hemodialysis on buprenorphine and norbuprenorphine plasma concentrations in chronic pain patients treated with transdermal buprenorphine.

The present study was designed to study the impact of intermittent hemodialysis on the disposition of the partial agonist buprenorphine and its metabolite norbuprenorphine during therapy with transdermal buprenorphine in chronic pain patients with end-stage kidney disease. Ten patients (mean age 63 years) who had received transdermal buprenorphine for at least 1 week, were asked to provide blood samples immediately before and after hemodialysis. Blood samples were analysed for buprenorphine and its metabolite norbuprenorphine. The median buprenorphine plasma concentrations were found to be 0.16 ng/ml before and 0.23 ng/ml after hemodialysis. A significant correlation between plasma levels and administered doses was observed (Spearman R=0.74; P<0.05). In three patients norbuprenorphine plasma levels were detected. No differences in pain relief before and after hemodialysis were observed. This investigation shows no elevated buprenorphine and norbuprenorphine plasma levels in patients with renal insufficiency receiving transdermal buprenorphine up to 70 microg/h. Furthermore, hemodialysis did not affect buprenorphine plasma levels, leading to stable analgesic effects during the therapy.

Transdermal buprenorphine in clinical practice--a post-marketing surveillance study in 13,179 patients.

OBJECTIVE: The objective of this post-marketing surveillance study was to collect effectiveness and safety data on the labelled use of buprenorphine transdermal patches (Transtec*) under routine clinical conditions. RESEARCH DESIGN AND METHODS: For this open, observational study, patients with moderate to severe cancer or non-cancer pain requiring treatment with an opioid analgesic were recruited at hospitals, outpatient clinics and general practitioners' practices in Germany. Buprenorphine transdermal patches (35 microg/h, 52.5 microg/h or 70 microg/h) were prescribed at physicians' discretion in accordance with the product's Summary of Product Characteristics (SmPC). Patients assessed their pain relief as 'very good', 'good', 'satisfactory', 'poor' or 'no effect'. Investigators were instructed to report all adverse events throughout the observation period. On completion, effectiveness and tolerability were evaluated for the overall study population, cancer and non-cancer patients, and patients < 70 years and > or = 70 years. Other analyses assessed pain relief with respect to previous opioid treatment and increased patch strength, and in patients who remained on their original dose. The total observation time was 9 months, and the average individual documented treatment time was 60.8 days. RESULTS: A total of 13,179 patients were evaluated; 3690 (28%) with cancer pain and 9489 (72%) with non-cancer pain. The most frequent diagnoses in non-cancer patients were musculoskeletal disorders (77%) and neuropathy (23%). In the great majority of cases (78%), treatment was started with the 35 microg/h patch. The initial dose needed to be increased subsequently only in about 18% of subjects. Buprenorphine transdermal patches provided effective, sustained and dose-dependent analgesia in patients with cancer and non-cancer pain, irrespective of the patients' age or pain syndromes. Whereas good or very good pain relief was documented only for 6% of the patients with the initial assessment, this percentage increased to 71% at the first follow-up and 80% at the final assessment. Fewer than 5% of subjects discontinued treatment owing to unsatisfactory pain relief. Altogether, adverse events were documented for 2874 patients (22%), whereas a relationship with trans dermal buprenorphine (adverse drug reactions) was assumed for only 10% (2220 adverse drug reactions in 1330 patients). The tolerability profile was as expected for an opioid and did not vary to a relevant extent with either the patient's age or the cause of pain (cancer or non-cancer). No evidence emerged of any previously unknown side effects. CONCLUSIONS: Buprenorphine transdermal patches are well tolerated and effective in the treatment of chronic cancer and non-cancer pain, irrespective of the patients' age. There was no clinically relevant development of tolerance.

[Transdermal buprenorphine for treatment of chronic tumor and non-tumor pain]. / Transdermales Buprenorphin für die Behandlung chronischer Tumor- und Nicht-Tumorschmerzen.

Patients with moderate to severe pain were treated with buprenorphine patches in one of 3 concentrations: 35 micrograms/h, 52.5 micrograms/h and 70 micrograms/h (= 0.8 mg/d, 1.2 mg/d and 1.6 mg/d respectively). The aim of this review was to assess the efficacy and tolerability of this transdermal system (TDS) in patients with chronic pain. A total of 445 patients were included in 3 double-blinded studies. The dosage titration with buprenorphine patches followed pretreatment with buprenorphine sublingual tablets, higher doses of weak opioids (level 2 substances), low dose morphine (level 3) or other analgesics. Patients with chronic tumour or non-tumour pain were recruited for these studies and treated with buprenorphine patches or placebo for 6 to 15 days. All patients were offered, in addition, buprenorphine sublingual tablets to be taken as required for supplementary pain relief. Pain intensity, analgesia, consumption of buprenorphine sublingual tablets and sleep duration were all assessed. All patients in the double-blinded studies were between the ages of 22 and 88. 249 patients suffered from tumour pain and 196 patients suffered from non-tumour pain. To examine long-term efficacy and tolerability of the transdermal system, treatment was expanded, if the patients were interested in participating in an open-label-study. In all 3 studies, the number of patients with moderate, severe and very severe pain increased in the placebo-patch treated group, while the patients in the buprenorphine transdermal system treated group had a greater incidence of mild or no pain. A further benefit in the buprenorphine transdermal system treated group was evidenced by a great number of patients with a daily sleep duration of more than 6 hours compared to the placebo group--an indicator of greater well-being. The systemic side-effects were typically opioid in nature and rare and usually only mild. Of particular note was the very low incidence of constipation in only 5.3% of cases. Dermatological reactions to the patches were only rarely encountered. The dermatological reactions consisted mainly of erythema and pruritus with a mild to moderate extent. Half the cases of erythema and more than on third of the cases of pruritus were spontaneously reversible. More than half the patients (53.7%) in the double blind studies wished to continued treatment with buprenorphine transdermal system. These results demonstrate that buprenorphine patches achieved a very good analgesic effect in all 3 studies and that in particular with respect to the quality of life of the patient these patches offer an exceptional alternative to other conventional therapies.