[A survey of labour pain management in Germany]. / Eine Umfrage zur geburtshilflichen Schmerztherapie in Deutschland.

BACKGROUND: In a survey of German hospitals with obstetric units, data on anaesthesia and analgesia in obstetric pain management were collected. METHODS: At each of 918 hospitals with obstetric units, the head of the anaesthetic department received a questionnaire on obstetric pain management. RESULTS: The response rate was 47.1%. On average, there were 748+/-407 (median 663;1st/3rd quartiles 309/1,303) births per year and hospital, 69.4% with spontaneous vaginal delivery. Opioids were the systemic analgesics most frequently administered in the delivery rooms. Epidural analgesia (EA) was given to 17.5+/-12.6% of the parturients. The number of deliveries per annum had a significant influence on the frequency of EA (<500 deliveries/year: 12.7%, 500-1000/year: 18.6%, >1,000/year: 21.6%). The preferred local anaesthetics were ropivacaine und bupivacaine. When an opioid was given this was almost always sufentanil. In 16% of the responding hospitals adrenaline was added to the epidural test bolus. CONCLUSION: EA is the mainstream method of relieving labour pains in almost all German hospitals, but is used significantly more often in hospitals with rather high numbers of yearly deliveries than in hospitals in which there are few deliveries per year.

Contraindications to regional anaesthesia in obstetrics: a survey of German practice.

BACKGROUND: We assessed current practice regarding indications and contraindications to regional analgesia and anaesthesia for labour and delivery in Germany. METHODS: Questionnaires were mailed to the directors of 918 German departments of anaesthesiology. RESULTS: A total of 397 completed replies were received representing 41.3% of all deliveries in Germany. More than half of the respondents never perform spinal or epidural anaesthesia when the platelet count falls below 65x10(9)/L. Preeclampsia, which was not graded for severity, was considered an absolute contraindication to regional block by 15% and placenta praevia by 30% of respondents. If a woman had taken aspirin three days before, the numbers of respondents considering epidural anaesthesia contraindicated (40.2%) were nearly double those considering spinal anaesthesia contraindicated (21.7%) (P<0.001). For a platelet count of 79x10(9)/L, epidural anaesthesia was thought to be contraindicated by 37% and spinal anaesthesia by 22.2% (P=0.001). In departments with <500 deliveries/year, reluctance to use regional blockade was more pronounced than in departments with >1000 deliveries/year. CONCLUSION: Clinical practice varies considerably in Germany. Concerns regarding the use of regional blockade were more prevalent in hospitals with small delivery units. Indications and contraindications are not consistent in Germany and some recommendations or guidelines are needed.

[Prospective study of the direct and indirect costs of idiopathic Parkinson's disease]. / Prospektive Erfassung der direkten und indirekten Kosten des idiopathischen Parkinson-Syndroms.

Idiopathic Parkinson's disease is a chronic progressive neurodegenerative disorder that remains refractory to curative treatment. Most patients are afflicted for many years, and the disease frequently results in severe physical handicap. Statements on the considerable cost of treatment are largely based on estimates and retrospective studies. To obtain more substantial data, we conducted a 3-year study of the economic aspects. Direct and indirect costs incurred by 117 patients (78 male, mean age 67.5 years) at the Deutsche Klinik für Diagnostik in Wiesbaden, Germany, were prospectively followed. The average cost per patient and month ran to 1007.55. Of that, direct costs amounted to 603.33 (55.9%), with drugs taking up the major share at 480.23. Indirect costs were 404.22 per patient and month, with 76% thereof related to nursing care and the incapacity to earn a living. Cost increased in proportion to Hoehn and Yahr stage, declining again with stages 4 and 5. The data we gathered confirm that Parkinsonism is responsible for sizeable expenses for not only the treating unit but the national economy as a whole.

[Indirect costs in idiopathic Parkinson's disease]. / Die indirekten Kosten des idiopathischen Parkinson-Syndroms.

The economic impact of parkinsonism has been getting more significant due to the increasing prevalence of Parkinson's disease and the modern therapies available nowadays. The present study is supposed to update the existing databases and to provide a sound foundation for rational decision-making in the health care sector. It does not only focus on the direct costs of this disease incurred by 75 patients over a longer period, but also and for the first time, takes a look on the indirect cost as well. The study shows that the expenses for PD-related house rebuilding and early retirement make up for a substantial share among the indirect costs. In the overall analysis, the ratio between both, direct and indirect costs appear to be relatively balanced with slight domination of the direct costs.

Change in anaesthetic practice for Caesarean section in Germany.

BACKGROUND: Initial data from 1996 revealed that in contrast to several other countries general anaesthesia was the preferred anaesthetic technique for Caesarean section in Germany. However, anaesthetic practice for Caesarean section has changed during the last decades world-wide. This investigation was performed to obtain more actual data on anaesthetic procedures in obstetric patients in German hospitals. METHODS: Questionnaires on the practice of anaesthesia for Caesarean section were mailed to 918 German departments of anaesthesiology. Furthermore, the survey evaluated severe perioperative complications in obstetric patients. RESULTS: The 397 completed replies in this survey represent 41.3% of all German deliveries in 2002. Spinal anaesthesia is now the most common technique (50.5%) for elective Caesarean section. In case of urgent and emergency Caesarean, delivery figures decrease to 34.6% and 4.8%, respectively. Epidural anaesthesia is performed in 21.6% of scheduled and 13.2% and 1.0% of non-scheduled urgent or emergency Caesarean sections, respectively. Four maternal deaths and several non-fatal episodes of gastric content aspiration were reported by the respondents. CONCLUSIONS: Compared to data obtained 6 years ago a significant increase in regional anaesthesia for Caesarean section has developed, with spinal anaesthesia being the preferred technique. Surveys can help to initiate discussion and improve current practice of anaesthetic care.

[Regulation of spinal nociceptin expression by neuropathic pain]. / Regulation der spinalen Expression von Nociceptin unter neuropathischen Schmerzen.

Nociceptin is the endogenous ligand of a new opioid receptor, the opioid receptor-like-1 (ORL1) receptor. Chronic inflammatory pain causes an increase in the expression of nociceptin and the ORL1 receptor in the dorsal horn of rat spinal cord, thus indicating an involvement of the endogenous nociceptin/ORL1 system in mechanisms of pathological pain. This study investigates the influence of neuropathic pain on the expression of nociceptin using immunohistochemistry. To induce neuropathic pain, a ligation of the sciatic nerve was performed in 12 rats under general anesthesia. A sham operation was performed in 12 rats of the control group. Nerve ligation caused a significant ipsilateral thermal hyperalgesia, a typical sign of neuropathic pain. The paw withdrawal latency was decreased by 45.7+/-4.9% ( p<0.05) at day 5 and by 37.3+/-1.8% ( p<0.05) at day 10. Although hyperalgesia was fully present after 5 days, no changes in nociceptin immunoreactivity in the lumbar spinal cord were detected at this time point. Ten days after nerve ligation, there was a 2.46+/-0.38 fold ( p<0.05) bilateral increase in nociceptin immunoreactivity in the lamina superficiales (I and II), with a notable increase in the inner lamina II at the level of L4. Further investigations are necessary to elucidate the relationship between neuropathic pain, the nociceptin-ORL1 receptor system and potential therapeutic options.

5-Hydroxytryptamine-induced plasma extravasation in the rat knee joint is mediated by multiple prostaglandins.

OBJECTIVE AND DESIGN: This study investigated whether prostaglandins (PGs) are involved in 5-hydroxytryptamine (5-HT)-induced synovial plasma extravasation. MATERIALS AND METHODS: Male Sprague-Dawley rat knee joints were perfused with 5-HT and synovial capillary Evans Blue dye leakage was measured using spectrophotometry. Cyclooxygenase (COX) inhibitors and PG receptor subtype-selective antagonists were tested for the ability to reduce 5-HT-induced synovial plasma extravasation. RESULTS: 5-HT-induced plasma extravasation was inhibited by indomethacin. The COX-1 selective inhibitor SC-560 and the COX-2 selective inhibitor NS-398 were equally effective, indicating that both isoforms are involved. Antagonists selective for EP1, EP2 and DP receptor subtypes significantly attenuated the 5-HT-induced plasma extravasation. However, antagonists selective for FP, IP and TP subtypes failed to reduce 5-HT-induced plasma extravasation. CONCLUSIONS: These results demonstrate that multiple, but selective, subtypes of PGs mediate synovial plasma extravasation produced by 5-HT, and suggest that PGs act downstream of 5-HT in the inflammatory cascade.

[Nociceptin and the ORL1 receptor: pharmacology of a new opioid receptor]. / Nociceptin und der ORL1-Rezeptor. Pharmakologie eines neuen Opioidrezeptors.

Molecular biological investigations led to the discovery of the ORL1 receptor ( opioid receptor like-1 receptor) and its endogenous ligand nociceptin. Although its sequence and structure are closely related to traditional opioid receptors, the ORL1 receptor shows low binding affinities for selective opioid agonists and antagonists. On the other hand, the ORL1 ligand nociceptin does not bind to the three traditional opioid receptors. The activation of the G protein-coupled ORL1 receptor inhibits adenlylate cyclase activity, reduces the intracellular concentration of the second messenger cAMP and regulates ion channels. The supraspinal administration of nociceptin produces hyperalgesia. unlike opioids. Spinal intrathecal and peripheral administration of nociceptin causes hyperalgesia in low doses and analgesia in high doses. The physiological role and detailed mechanisms of these dose-dependent nociceptin effects in opposite directions are not yet known. In addition, nociceptin modulates other biological phenomena such as feeding, locomotion, gastrointestinal function,memory, cardiovascular function,immunity, renal function, anxiety,dependence and tolerance.Future research on the physiological and pathophysiological importance of the nociceptin/ORL1 receptor systems may provide a target for novel therapeutics.

Síntomas durante el tratamiento del dolor oncológico conforme a las directrices de la OMS: estudio longitudinal de la prevalencia, la severidad y la etiología de los síntomas / Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology

La mayoría de los pacientes con cáncer avanzado presentan diversos síntomas que pueden reducir la eficacia del tratamiento analgésico y deteriorar su calidad de vida. En el presente estudio se determina la prevalencia, la etiología y la severidad de los síntomas en 593 pacientes oncológicos tratados en una unidad de dolor. Los pacientes recibieron analgésicos no opiáceos, opiáceos y coadyuvantes siguiendo las directrices de la OMS para el alivio del dolor oncológico. Otros síntomas fueron tratados sistemáticamente con la medicación coadyuvante apropiada. La intensidad del dolor y de otros síntomas se determinó por medio de una autoevaluación realizada todos los días por los propios pacientes; además, en cada visita los médicos de la unidad de dolor evaluaron la etiología de los síntomas y la severidad de confusión, coma y obstrucción gastrointestinal. Los pacientes recibieron tratamiento durante un periodo medio de 51 días. La eficacia del tratamiento analgésico fue buena en el 70 por ciento, satisfactoria en el 16 por ciento e inadecuada en el 14 por ciento de los pacientes. El tratamiento inicial consiguió reducir significativamente el número medio de síntomas de cuatro a tres. La prevalencia y la severidad de anorexia, actividad limitada, confusión, cambios de humor, insomnio, estreñimiento, dispepsia, disnea, tos, disfagia y síntomas urinarios se redujeron significativamente; las de sedación, otros síntomas neuropsiquiátricos y sequedad de boca aumentaron significativamente, mientras que las de coma, vértigo, diarrea, náuseas, vómitos, obstrucción intestinal, eritema, prurito y sudoración no experimentaron ningún cambio. Los síntomas más frecuentes fueron actividad limitada (74 por ciento de los días), cambios de humor (22 por ciento), estre ñ imiento (23 por ciento), náuseas (23 por ciento) y sequedad de boca (20 por ciento).Las valoraciones más altas de la severidad de los síntomas correspondieron a actividad limitada, sedación, coma, obstrucción intestinal, disfagia y síntomas urinarios. De los 23 síntomas, sólo el estreñimiento, el eritema y la sequedad de boca se atribuyeron casi siempre a efectos secundarios del tratamiento analgésico. Como conclusión, la elevada p revalencia y la severidad de muchos síntomas en pacientes con cáncer avanzado pueden reducirse combinando el tratamiento analgésico con el control sistemático de los síntomas. No obstante, durante una parte importante del tratamiento persisten los síntomas generales, neuropsiquiátricos y gastrointestinales y el alivio del dolor fue inadecuado en el 14 por ciento de los pacientes. Así pues, el control del dolor oncológico tiene que enmarcarse dentro de los cuidados paliativos, considerando todas las posibilidades existentes para el control de los síntomas (AU)

A comprehensive, stage-sensitive model of grief in dementia caregiving.

PURPOSE: Grief is an overlooked but important element of the caregiver experience. This study defines a model of caregiver grief to aid in clinical intervention and to support further research. DESIGN AND METHODS: This study addressed the grief responses of 87 spouse and adult-child caregivers of patients with progressive dementia representing mild, moderate, severe, and postdeath. Questionnaire data and qualitative findings from 16 semistructured focus group interviews provide the basis for a descriptive model of anticipatory grief in dementia caregiving. RESULTS: Significant differences emerged between spouse and adult-child caregiver groups as a whole and as a function of Clinical Dementia Rating impairment level. Caregiver grief was found to fluctuate between intellectual, affective, and existential poles depending upon current care demands and expectations. IMPLICATIONS: These findings suggest that anticipatory grief in dementia caregiving is "real" grief, equivalent in intensity and breadth to death-related grief.

[Development and state of the in-patient palliative care institutions in Germany]. / Entwicklung und Stand der stationären palliativmedizinischen Einrichtungen in Deutschland.

In April 1999 altogether 114 inpatient units providing palliative care (50 palliative care units, 64 inpatient-hospices) offered a total of 989 beds. Compared to 1993 this has been an increase of 256%, compared to 1997 of 60%. The number of available beds, compared to 1997, increased markedly (58%), with a availability of 12 beds per one million residents. However, there are still major deficits: the distribution of the units is very irregular and the number of available beds is still to low, compared to the estimated need of 50 inpatient beds per one million residents. The quality of palliative care shows significant deficits (e. g. the availability of nursing staff, cooperation with pain clinics, standardised documentation, education). Differences between palliative care wards and hospices were huge. According to the definition of the German Society for Palliative Care, a palliative care ward should provide a ratio of at least 1.4 nursing staff per bed, however, only 18% of the palliative care units fulfil this definition. Only few hospices and half of the palliative care units worked in close cooperation with pain clinics. Despite a significant increase in units and inpatient beds providing palliative care, there still is a major deficit in the overall number of beds and the quality of palliative care.

Alternative exon splicing of cyclic AMP response element-binding protein in peripheral sensory and sympathetic ganglia of the rat.

Alternative splicing patterns of cyclic AMP response element-binding protein (CREB) in dorsal root ganglia, lumbar sympathetic ganglia and several peripheral tissues of the rat have been investigated by an exon-flanking polymerase chain reaction strategy. A series of RT-PCR with primer pairs flanking all possible alternative splicing sites (corresponding to a genomic region with at least one full exon and two flanking introns) has revealed multiple tissue specific splice variants. These include some novel transcripts that lack the phosphorylation site and part of the leucine zipper region which is crucial for dimerization and DNA binding. Some isoforms previously reported as testis-specific were also detected in rat peripheral ganglia and other tissues. Notably, splicing patterns are specific for some regions. Some of the splice variants indicate inhibitory functions due to lacking phosphorylation sites or partially missing DNA-binding or leucine zipper domains. These findings suggest a complex expression and functional regulation of CREB in peripheral tissues including dorsal root and sympathetic ganglia.

High-dose tramadol in comparison to low-dose morphine for cancer pain relief.

Cancer pain treatment following the World Health Organization guidelines is effective and feasible. However, the evidence supporting the use of opioids for mild to moderate pain on the second step of the analgesic ladder is widely discussed. The present evaluation compares the efficacy and safety of high doses of oral tramadol (> or = 300 mg/d) with low doses of oral morphine (< or = 60 mg/d). Patients were included in this nonblinded and nonrandomized study if the combination of a nonopioid analgesic and up to 250 mg/d of oral tramadol was inadequate. 810 patients received oral tramadol for a total of 23,497 days, and 848 patients received oral morphine for a total of 24,695 days. The average dose of tramadol was 428 +/- 101 mg/d (range 300-600 mg/d); the average dose of morphine was 42 +/- 13 mg/d (range 10-60 mg/d). Additional nonopioid analgesics were given on more than 95% of days. Antiemetics, laxatives, neuroleptics, and steroids were prescribed significantly more frequently in the morphine group; the use of other adjuvants was similar in both groups. The mean pain intensity on a 0-100 numerical rating scale (NRS) was 27 +/- 21 (95% CI 26-29) in the tramadol and 26 +/- 20 (95% CI 24-27) in the morphine group (NS). The analgesic efficacy was good in 74% and 78%, satisfactory in 10% and 7%, and inadequate in 16% and 15% of patients receiving tramadol and morphine, respectively (NS). Constipation, neuropsychological symptoms, and pruritus were observed significantly more frequently with low-dose morphine; other symptoms had similar frequencies in both groups. These data suggest that tramadol can be used for the treatment of cancer pain, when nonopioids alone are not effective. High doses of tramadol are effective and safe.

Serum concentrations of tramadol enantiomers during patient-controlled analgesia.

AIMS: Tramadol, a centrally acting analgesic, is used as a racemate containing 50% of a (+)- and 50% of a (-)-enantiomer. This paper presents the pharmacokinetic results of postoperative patient-controlled analgesia using (+)-tramadol, (-)-tramadol or the racemate. METHODS: Ninety-eight patients recovering from major gynaecological surgery were treated in a randomised, double-blind study with (+)-tramadol, (-)-tramadol or the racemate. Following an i.v. bolus up to a maximum of 200 mg, patient-controlled analgesia with demand doses of 20 mg was made available for 24 h. Prior to each demand, the serum concentrations of the enantiomers of tramadol and its metabolite M1 were measured in 92 patients. RESULTS: The mean concentrations of tramadol during the postsurgery phase were 470+/-323 ng ml-1, 590+/-410 ng ml-1 and 771+/-451 ng ml-1 in the (+)-, racemate- and (-)-group, respectively ((+) vs (-), P<0.05); the mean concentrations of the metabolite M1 were 57+/-18 ng ml-1, 84+/-34 ng ml-1 and 96+/-41 ng ml-1 in the (+)-, racemate- and (-)-group, respectively ((+) vs (-) and (+) vs racemate, P<0.05). The mean concentrations of (+)-tramadol and (+)-M1 were lower in the racemate- than in the (+)-group (P<0.05), those of (-)-tramadol and (-)-M1 were lower in the racemate than in the (-)-group (P<0.05). In the racemate group, the mean serum concentrations of (+)-tramadol were higher than those of (-)-tramadol (P<0.05), whereas the mean serum concentrations of (-)-M1 were higher than those of (+)-M1 (P<0. 05). CONCLUSIONS: The therapeutic serum concentration of tramadol and M1 showed a great variability. The lowest mean concentrations were measured in the (+)-group and the highest in (-)-group. This is in agreement with the clinical finding that (+)-tramadol is a more potent analgesic than (-)-tramadol.

Presence of opioid receptor-like (ORL1) receptor mRNA splice variants in peripheral sensory and sympathetic neuronal ganglia.

The expression of ORL1 receptor mRNA splice variants is determined in peripheral sensory and sympathetic ganglia and compared to mRNA expression for the three classic opioid receptor subtypes (mu, delta, and kappa) using the method of reverse transcription-polymerase chain reaction. ORL1, mu, delta and kappa receptor subtype mRNAs are present in human dorsal root ganglia (DRG) and trigeminal ganglia and rat DRG. ORL1, mu and delta receptor subtype mRNAs are present in rat superior cervical ganglia and only ORL1 and delta receptor mRNAs are present in rat lumbar sympathetic ganglia. Both the ORL1 mRNA splice variants are present in sensory and sympathetic ganglia, however, expression of the shorter ORL1 receptor mRNA dominates over expression of the longer splice variant in rat brain and DRG, whereas, expression of the longer splice variant is dominant in sympathetic ganglia.

Multiple splice patterns of cyclic AMP response element-binding protein mRNA in the central nervous system of the rat.

The alternative splicing pattern of cyclic AMP response element-binding protein (CREB) in the central nervous system (CNS) of the rat has been investigated by an exon-flanking polymerase chain reaction (PCR) strategy. A series of RT-PCR studies with primer pairs flanking all possible alternative splicing sites (corresponding to a genomic region with at least one full exon and two flanking introns) has revealed multiple splice patterns in nine regions of the rat CNS. These include some novel transcripts that lack the phosphorylation site and a segment of the leucine zipper region which is crucial for dimerization and DNA binding. Some isoforms previously reported as testis-specific were also detected in the rat CNS. The findings from this study, which include differential splicing patterns among CNS regions, suggest a complex expression and functional regulation of CREB in the CNS.

[Anesthesia for cesarean section in Germany. A survey]. / Anästhesieverfahren zur Sectio caesarea in Deutschland. Eine Umfrage.

AIM OF STUDY: Goal of this survey is to give an overview of anaesthesia for caesarean section in Germany. METHOD: In 1994 and 1995, we sent a questionnaire to the chief-anaesthetists of all German hospitals with departments of gynaecology/obstetrics to find out the routine anaesthetic procedures for caesarean section. RESULTS: We obtained data from 409 hospitals (response rate 46.4%) with 321,816 births--50,123 of which were sections (mean caesarean section rate 16.6%). The mean general anaesthesia rate for elective caesarean sections was 66.5%, for non-elective sections 90.8%. The mean epidural anaesthesia rate for caesarean section was 22.6% and the mean spinal anaesthesia rate was 9.8%. For general anaesthesia most hospitals used antacids and/or histamine2-receptor antagonists (64.6% of responding hospitals). Anaesthesia was induced with intravenous barbiturates (82%), succinylcholine for intubation (98.2%) and no opioids before clamping of the cord (94.8%). For regional anaesthesia bupivacaine was the most common local anaesthetic (spinal 84.0%, epidural 96.8%). Opioids were added to local anaesthetics for epidural anaesthesia at 21.4% of the hospitals. CONCLUSIONS: General anaesthesia is the commonest practice for caesarean sections at German hospitals. Nowadays regional anaesthesia gains more importance compared to previous German surveys and in agreement with foreign data.

Weak opioids--an educational substitute for morphine?

The World Health Organization guidelines suggest the use of weak opioids on the second step of the analgesic ladder for cancer pain relief. Weak opioids are important substitutes for low doses of morphine, although their analgesic efficacy is lower than that of non-opioid or strong opioid analgesics. The use of weak opioids has great educational impact and has helped spread the use of the guidelines. Furthermore, weak opioids are more freely available and are expected to have a better side-effect profile. Controlled long-term studies are required for confirmation.