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Aims To analyze the prevalence and the severity spectrum of pain and its relationships to health-related quality of life and the bio-psycho-social consequences of pain among patients scheduled for radical prostatectomy. Methods Urological inpatients completed an epidemiological pain questionnaire extensively exploring pre-operative acute and chronic pains in 21 body regions. The severity of pain was determined using von Korff’s Pain Grading (CPGQ). Pain chronicity was estimated employing the Mainz Pain Staging System (MPSS). Anxiety and depressive symptoms were identified with the HADS and the Habitual Well-Being Questionnaire (FW-7). Health-related quality of life was measured using the SF-12. Comorbidities and comorbidity-related interferences with daily activities were ascertained with the Weighted Illness Checklist (WICL). Results Eighty of 115 patients (69.6%) reported about pain during the last 3 months pre-operatively. 28.7% of the pain patients had pain related to urological disease. Severe dysfunctional pain was identified by pain Grades 3 and 4 of the CPGQ in 20% and 13.8%, respectively. Advanced pain chronicity characterized by pain Stages II and III of the MPSS was present in 38.8% and 11.3%. Patients with localized prostate cancer without pain complaints had significantly better health-related quality of life and habitual well-being and lower anxiety and depression scores and fewer comorbidities. Patients with cancer-related and non-cancer pain did not differ in pain chronicity, pain severity, pain intensities, anxiety, comorbidities and physical health (SF12-PCS). Conclusions The high prevalence of severe and chronic pain in cancer patients before scheduled radical prostatectomy – combined with considerable disability effects and markedly reduced quality of life necessitate a short routine screening-analysis of the severity spectrum of pain and psychopathology. Patient self-rated pain chronicity staging and psychological distress analysis will allow a disorder severity-guided treatment and the prevention of suffering and additional new chronic post-surgical pain.

The fentanyl transdermal therapeutic system (fentanyl-TTS;Durogesic) has a distinct route of administration and safety profile compared with other opioids used in the treatment of moderate to severe pain.These aspects are likely to have an impact on patient acceptance and functioning as well as efficacy. We compared the cost-utility of fentanyl-TTS and controlled-release morphine (cr-morphine) in the treatment of moderate to severe nonmalignant pain in outpatients in Germany. A 1-year, three-phased decisionanalytic model was constructed, incorporating estimates of a variety of aspects of pain control.Use of fentanyl-TTS was predicted to incur higher costs than cr-morphine over 1 year of treatment (DM 6950 vs.DM 6186, respectively) but was associated with a higher number of quality-adjusted life days (234 vs. 216, respectively), thus achieving an incremental cost-utility ratio of DM 15,960 per quality-adjusted life-year gained.The results of the decision-analytic model support the use of fentanyl-TTS as a favorable cost-effective option for the treatment of moderate to severe nonmalignant pain.

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.

Most patients with advanced cancer develop diverse symptoms that can limit the efficacy of pain treatment and undermine their quality of life. The present study surveys symptom prevalence, etiology and severity in 593 cancer patients treated by a pain service. Non-opioid analgesics, opioids and adjuvants were administered following the WHO-guidelines for cancer pain relief. Other symptoms were systematically treated by appropriate adjuvant drugs. Pain and symptom severity was measured daily by patient self-assessment; the physicians of the pain service assessed symptom etiology and the severity of confusion, coma and gastrointestinal obstruction at each visit. The patients were treated for an average period of 51 days. Efficacy of pain treatment was good in 70%, satisfactory in 16% and inadequate in 14% of patients. The initial treatment caused a significant reduction in the average number of symptoms from four to three. Prevalence and severity of anorexia, impaired activity, confusion, mood changes, insomnia, constipation, dyspepsia, dyspnoea, coughing, dysphagia and urinary symptoms were significantly reduced, those of sedation, other neuropsychiatric symptoms and dry mouth were significantly increased and those of coma, vertigo, diarrhea, nausea, vomiting, intestinal obstruction, erythema, pruritus and sweating remained unchanged. The most frequent symptoms were impaired activity (74% of days), mood changes (22%), constipation (23%), nausea (23%) and dry mouth (20%). The highest severity scores were associated with impaired activity, sedation, coma, intestinal obstruction, dysphagia and urinary symptoms. Of all 23 symptoms, only constipation, erythema and dry mouth were assessed as being most frequently caused by the analgesic regimen. In conclusion, the high prevalence and severity of many symptoms in far advanced cancer can be reduced, if pain treatment is combined with systematic symptom control. Nevertheless, general, neuropsychiatric and gastrointestinal symptoms are experienced during a major part of treatment time and pain relief was inadequate in 14% of patients. Cancer pain management has to be embedded in a frame of palliative care, taking all the possibilities of symptom management into consideration.

Fur die sog. neuronale Plastizitat spielen NMDA-Rezeptoren eine wichtige Rolle. Wahrend sich in Tierversuchen und In-vitro-Experimenten die Ausbildung einer Hyperexzitabilitat der Hinterhornneurone nach starkem Schmerzstimulus durch Gabe von NMDA-Antagonisten verhindern lasst, ist die Datenlage fur die klinische Anwendung kontrovers. Die vorliegende Arbeit sollte uberprufen, ob die praoperative Gabe des NMDA-Antagonisten Ketamin auch beim Menschen postoperativ einen relevanten analgetischen Effekt erzielen kann. In Anlehnung an eine fruhere Studie von Roytblat et al. [30] erhielten 80 Patienten, die sich einer elektiven Laparotomie oder proktologischen Operation unterziehen mussten, prospektiv, doppelblind und randomisiert zur Narkoseeinleitung einen einmaligen i.v.-Bolus von 0,15 mg/kg Ketamin oder Placebo (0,9%iges NaCl). Die postoperative Schmerztherapie wurde mittels patientenkontrollierter Analgesie (PCA) mit Piritramid durchgefuhrt. In der 1., 2., 3., 4., 5., 6., 12. und 24. Stunde nach Beendigung der Operation wurde die Schmerzintensitat mittels visueller Analogskala (VAS) und verbalem Rating Scale (VRS) ermittelt, gleichzeitig wurden Blutdruck, Puls, Atemfrequenz und die Vigilanz gemessen. Am Ende des Beobachtungszeitraums wurde zusatzlich ein retrospektiver Schmerzscore bestimmt. Der kumulative Piritramidverbrauch unterschied sich zu keinem Messzeitpunkt signifikant zwischen der Verum- und der Placebogruppe; nach 24 h waren unter Ketamin 25,0±16,2 mg, unter Placebo 29,5±20,4 mg Piritramid angefordert worden. Es fanden sich ebenfalls keine signifikanten Unterschiede bzgl. der verschiedenen Schmerzscores oder der Inzidenz von unerwunschten Wirkungen. Ketamin-typische Nebenwirkungen wie Halluzinationen oder Albtraume wurden nicht beobachtet. Zusammenfassend ergibt sich, dass unter den gewahlten Untersuchungsbedingungen niedrig dosiertes Ketamin, zusatzlich zur Narkoseeinleitung gegeben, keinen praemptiv analgetischen Effekt besitzt.

Transdermal fentanyl was released in Germany in 1995. From October 1996 to February 1998 transdermal treatment was documented for 1005 patients (506 men and 499 women with a mean age of 60 years, range 20–92 years) with chronic pain in an open survey including 290 physicians from hospitals and general practitioners throughout Germany. Most patients suffered from cancer pain and only 11 patients had chronic pain from non-malignant disease. Physicians were asked to complete a questionnaire for patients treated with transdermal fentanyl on initiation of therapy (day 0), and days 3, 6, 18, 30 thereafter, followed by monthly follow-up intervals. Patients were asked to complete a pain diary. Transdermal therapy was documented from day 0 for 824 patients, while 181 patients had been treated with transdermal fentanyl before admission in the survey. Most of the other 824 patients had been treated with other step 3 opioids (55% of the patients) or step 2 opioids (23%) before conversion to transdermal fentanyl, whereas 8% had been treated only with non-opioids and 14% had received analgesics only as required or not at all before initiation of transdermal therapy. The most important reasons for switching to transdermal opioid therapy were insufficient pain relief with the previous medication followed by a variety of gastrointestinal symptoms impeding oral analgesic therapy. Initial fentanyl doses ranged from 0.6 to 9.6 mg/day (25 to 400 [.mu]g/h) with a median of 1.2 mg/day (50 [.mu]g/h). Median doses slowly increased throughout the observation period to 2.4 mg/day (100 [.mu]g/h) after 4 months of treatment. Most patients continued transdermal therapy until the time of death (47% of patients). Other reasons for discontinuation were inadequate pain relief (10%), pain relief with other analgesic regimens (10%), other symptoms than pain (5%), rejection of transdermal therapy by the patient (6%) or miscellaneous (16%). Adverse events were documented as the reason for discontinuation of transdermal therapy in 49 patients (5%). Dyspnoea was documented for seven patients as the reason for discontinuation. One of these patients, as well as another patient with an episode of apnoea, had to be treated with artificial respiration for several hours, but both patients recovered without sequelae. Transdermal therapy with fentanyl was safe and efficient in this national survey. Transdermal fentanyl can be recommended for treatment of moderate to severe cancer pain and probably may even be used as a first-line drug on step 3 of the World Health Organization recommendations in selected patient groups.

The aim of the present investigation, initiated by the German Academy of Education in Anaesthesiology (DAAF), was to obtain valid information about education and training strategies of German anaesthetists, in order to highlight weaknesses and strengths for better planning and performance of future efforts in this area. For this reason, a questionnaire with 23 items was distributed to 2000 German anaesthetists during the years 1993-1995 and of these 1290 questionnaires could then be evaluated (response rate 64.5%). The most important means of education and training were classical media such as text books and journals. Modern techniques such as videos, tapes or computer-assisted anaesthesia simulators were poorly used. Refresher courses, repetitoria and hospitations in other departments were, despite infrequent use, considered to be effective means of education and training and should be made more available. Systematic theoretical education was provided particularly seldom in most hospitals. Respondents considered anaesthetic complications and mishaps, intensive care and pain medicine to be the main top topics for continuing medical education. German anaesthetists seem highly motivated for education and training and spend on average about 5.5 h per week for personal learning and refreshing, a figure that is quite comparable to international standards. Hospital and department heads are mostly believed to have positive attitudes to education and training. Most respondents were in favour of strict rules for education and training measures, which includes the obligation to prove their certified attendance (as yet not required in Germany). On the other hand, the majority voted against making the continued recognition as a specialist in anaesthesiology dependent on completion of a performance control.

Symptom assessment in the palliative care unit must consider the reduced physical and mental status of the patients. Standardized instruments are often not completed by patients with cognitive impairment. We tried to combine minimal burden for patients and staff with sufficient information content in a Minimal Documentation System (MIDOS) for pain and symptom assessment in palliative care patients. From January to July 1998, 108 patients (123 consecutive admissions) with a mean age of 63 years (range 32–87 years) were admitted to the palliative care unit. Pain was reported as the reason for admission in 70% of the patients, and 71% were treated with opioids. Using a cut-off point of 20/21, 35% of the patients were impaired in the Mini Mental State Examination (MMSE). The number of missing values in the Brief Pain Inventory (BPI) and the quality-of-life questionnaire SF-12 correlated highly with each other and with the MMSE sum score, but not with the summary scores of BPI or SF-12. Only 31 patients completed the SF-12 quality-of-life questionnaire. Age was not correlated to MMSE scores, and neither were opioid doses for 26 patients with slow-release oral morphine or for 20 patients with transdermal fentanyl. Only a minority of patients was able to use the numerical scale for symptoms other than pain, though most patients were able to score symptom intensity on the verbal categorical scale. Pain and symptom assessments were performed by the physician for 17% of the patients at admission, and for 16% of the follow-up controls because self-assessment was not possible. In this study, cognitive impairment prevented symptom assessment with longer and more complicated instruments such as the SF-12 in a large number of the patients admitted to the palliative care unit. Assessment instruments for patients with advanced disease must provide simple categorical scales and the possibility of being administered by interview.

Transdermal delivery allows continuous systemic application of opioids through the intact skin. This review analyses the pharmacokinetic properties of transdermal opioid administration in the context of clinical experience, with a focus on fentanyl. A transdermal therapeutic system (TTS) for fentanyl has been developed. The amount of fentanyl released is proportional to the surface area of the TTS, which is available in different sizes. After the first application of a TTS, a fentanyl depot concentrates in the upper skin layers and it takes several hours until clinical effects are observed. The time from application to minimal effective and maximum serum concentrations is 1.2 to 40 hours and 12 to 48 hours, respectively. Steady state is reached on the third day, and can be maintained as long as patches are renewed. Within each 72-hour period, serum concentrations decrease gradually over the second and third days. When a TTS is removed, fentanyl continues to be absorbed into the systemic circulation from the cutaneous depot. The terminal half-life for TTS fentanyl is approximately 13 to 25 hours. The interindividual variability of serum concentrations, partly caused by different clearance rates, is markedly larger than the intraindividual variability. The effectiveness of TTS fentanyl was first demonstrated in acute postoperative pain. However, the slow pharmacokinetics and large variability of TTS fentanyl, together with the relatively short duration of postoperative pain, precluded adequate dose finding and led to inadequate pain relief or, especially, a high incidence of respiratory depression; such use is now contraindicated. Conversely, in cancer pain, TTS fentanyl offers an interesting alternative to oral morphine, and its effectiveness and tolerability in this indication has been demonstrated by a number of trials. Its usefulness in chronic pain of nonmalignant origin remains to be confirmed in controlled trials. In general, TTS fentanyl produces the same adverse effects as other opioids, mainly sedation, nausea, vomiting and constipation. In comparison with oral morphine, TTS fentanyl causes fewer gastrointestinal adverse events. The risk of hypoventilation is comparatively low in cancer patients. Sufentanil and buprenorphine may also be suitable for transdermal delivery, but clinical results are not yet available. Transdermal morphine is only useful if applied to de-epithelialised skin. However, iontophoresis may allow transdermal administration of opioids, including morphine, with a rapid achievement of steady state concentrations and the ability to adjust delivery rates. This would be beneficial for acute and/or breakthrough pain, and initial clinical trials are in progress.

The Brief Pain Inventory is a comprehensive instrument for pain assessment and has been validated in several languages. A validated German version was not available until now. From March to May 1995 all outpatients of the pain clinic of the Department of Anesthesiology completed a questionnaire with the German versions of the Brief Pain Inventory (BPI) and the SF-36 quality-of-life questionnaire. The BPI was repeated after the consultation. The physician assessed the performance status score of the Eastern Cooperative Oncology Group (ECOG). The questionnaire was completed by 151 patients. Forty-two patients were excluded from evaluation for methodological reasons, so 109 patients were evaluated. As in the original version of the BPI, factor analysis showed a common factor for pain intensity and a second factor for pain-related interference with function. The comparative fit index of 0.86 confirmed this model. Responses before and after consultation correlated closely for the sum scores of the pain intensity items (Perarson correlation r = 0.976) as well as for the interference with function items (r = 0.974). Pain intensity in the BPI correlated with bodily pain in the SF-36 (r = 0.585). Sum scores of the pain interference items were higher in patients with deteriorated ECOG performance status, whereas sum scores of the intensity items were not changed. Validity and reliability of the German BPI were comparable to the original version. The BPI may be advantageous for palliative care patients, as it places only a small burden on the patient and offers easy criteria for evaluation. However, further research is needed to differentiate the impact of pain-related and disease-related interference with function on the BPI, and to find an algorithm for the evaluation of the BPI when values are missing.

Fragestellung: Voraussetzung fur die Qualitatssicherung in der Tumorschmerztherapie ist ein Bewertungsschema, mit dem die analgetische Behandlung des einzelnen Patienten im Hinblick auf die Einhaltung der WHO-Empfehlungen beurteilt werden kann. Methode: Im Rahmen einer bundesweiten Anwendungsbeobachtung dokumentierten 172 Arzte in schmerztherapeutischen und onkologischen Ambulanzen und Klinikabteilungen die analgetische Vorbehandlung vor Umstellung auf transdermales Fentanyl bei 436 Patienten. Die Vorbehandlung wurde von 3 Arzten der Kolner Schmerzambulanz anhand von 4 charakteristischen Punkten der Tumorschmerztherapie unabhangig voneinander bewertet, zusatzlich wurde fur jede Therapie eine Gesamtbewertung abgegeben. Ergebnisse: Bezuglich der verordneten WHO-Stufe ergab sich eine hohe Ubereinstimmung der Bewerter, ebenso bei der Frage nach nicht empfehlenswerten Medikamentenkombinationen und nach der Verordnung einer adaquaten Zusatzmedikation. Demgegenuber wichen die Bewertungen der verordneten Nichtopioidanalgetika und v.a. die Gesamtbewertungen deutlich voneinander ab. Schlusfolgerung: Eine wenig differenzierte Bewertungsskala eignet sich nicht fur die Uberprufung der Einhaltung der Therapieempfehlungen. Fur weitere Studien wurde ein Schema entwickelt, das eine Bewertung der verordneten WHO-Stufe, der Applikationsart und des -intervalls sowie zusatzlicher Aspekte mit 0–10 Punkten ermoglicht.

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

Neuropathic pain syndromes are one of the major problems of cancer pain treatment. The present study surveys 593 cancer patients treated by a pain service following the WHO guidelines for relief of cancer pain. Of these, 380 presented with nociceptive, 32 with neuropathic and 181 with mixed (nociceptive and neuropathic) pain. In patients with nociceptive, mixed and neuropathic pain, the average duration of evaluated pain treatment was 51, 53 and 38 days, respectively. Non-opioid or opioid analgesics were given to 99%, 96% and 79%, antidepressants to 8%, 25% and 19%, anticonvulsants to 2%, 22% and 38% and corticosteroids to 26%, 35% and 22% of patients, respectively. Systemic analgesia was supported by palliative antineoplastic treatment (48%, 56% and 38% of patients), nerve blocks (3%, 6% and 6%), psychotherapy (3%, 7% and 3%), physiotherapy (6%, 12% and 13%) and transcutaneous electric nerve stimulation (1%, 6% and 6%). Analgesic treatment resulted in a significant pain relief in all groups of patients, as the mean pain intensity (NRS) decreased from 66 (nociceptive), 65 (mixed) and 70 (neuropathic) on admission to 26, 30 and 28 after 3 days and 18, 17 and 21 at the end of survey. The total outcome of pain treatment was not predicted by the designation to nociceptive, mixed or neuropathic pain. In conclusion, neuropathic cancer pain is not intractable and can be relieved in the majority of patients by treatment following the WHO guidelines.

Hintergrund: Die patientenkontrollierte Analgesie (PCA) mit Alfentanil eignet sich zur Schmerzlinderung bei der extrakorporalen Stoswellenlithotripsie (ESWL) von Nierensteinen. Durch praemptive Analgesie mit einem nichtsteroidalen Analgetikum (NSAID) oder einem Spasmolytikum konnten sich der Bedarf an Alfentanil und damit Sicherheit und Effektivitat verbessern lassen. Methode: In dieser randomisierten, plazebokontrollierten Studie erhielten 90 Patienten 1 h vor Beginn der EWSL eine i.m. Injektion mit 30 mg Ketorolac, 20 mg Butylscopolamin oder Plazebo. Wahrend der ESWL wurde eine i.v. PCA mit Alfentanil (Bolus 0,25 mg, Refraktarzeit 1 min) durchgefuhrt. Schlusfolgerung: Alfentanilbedarf, Schmerzintensitat und Haufigkeit von Atemdepression, Sedierung und Ubelkeit waren in der Ketorolacgruppe am geringsten, jedoch ohne statistische Signifikanz. Ketorolac oder Butylscopolamin bieten deshalb in der gewahlten Dosierung keine Vorteile bei der ESWL von Nierensteinen.

Fragestellung: Ziel dieser Arbeit ist es, die gangige Methodik der Anasthesie und Analgesie zur Kaiserschnittentbindung an deutschen Krankenhausern zu erfragen. Methodik: In den Jahren 1994 bis 1995 befragten wir die leitenden Anasthesiologen aller Krankenhauser Deutschlands mit geburtshilflicher Abteilung zu den in ihrer Klinik ublichen Anasthesieverfahren bei Kaiserschnittentbindungen. Ergebnisse: Wir erhielten Angaben von 409 Krankenhausern (Rucklaufquote 46,4%) mit insgesamt 321816 Geburten, davon 50123 Sectiones (mittlere Sectiorate 16,6%). Die mittlere Allgemeinanasthesierate bei elektiven Sectiones betrug 66,5%, bei nicht-elektiven Sectiones 90,8%. Die mittlere Epiduralanasthesie (EDA)-Rate zur Sectio caesarea lag bei 22,6%, die mittlere Spinalanasthesie(SpA)-Rate zur Sectio lag bei 9,8%. Zur Allgemeinanasthesie wurde an den meisten Krankenhausern eine medikamentose Aspirationsprophylaxe (64,6% der antwortenden Kliniken) durchgefuhrt. Die Narkoseeinleitung erfolgte mit intravenosen Barbituraten (82%) und Succinylcholin zur Intubation (98,2%) und unter Verzicht auf Opioide vor Abklemmen der Nabelschnur (94,8%). Bei den Regionalanasthesien war Bupivacain das haufigste Lokalanasthetikum (SpA 84,0%, EDA 96,8%). Opioide wurden an 21,4% der Kliniken dem Lokalanasthetikum zur EDA beigemischt. Schlusfolgerungen: Die Allgemeinanasthesie ist das haufigste anasthesiologische Verfahren zur Sectio caesarea an deutschen Krankenhausern. Regionalanasthesien gewinnen allerdings im Vergleich zu alteren Daten aus Deutschland und in Ubereinstimmung mit Erhebungen aus dem Ausland zunehmend an Bedeutung.

The Baltic Sea is a stratified, semi-enclosed sea typified by a low-salinity surface layer and a deep saline layer of varying volume, salinity, temperature and oxygen concentration. The relationships between these oceanographic factors and the distribution of Baltic cod are presented, utilizing results from a survey carried out during the 1995 spawning period in the Bornholm Basin, at present the main spawning area of this stock. Cod distribution, abundance and population structure were estimated from hydroacoustic and trawl data and related to hydrographic parameters as well as to bottom depth. In the central basin, cod were aggregated in an intermediate layer about 15 m thick. This area of peak abundance was defined at its upper limit by the halocline and at the lower limit by oxygen content. The majority of individuals caught in the basin centre were in spawning or pre-spawning condition with a high proportion of males to females. On the basin slopes, aggregations of cod were found near the bottom. These individuals were mainly immature and maturing stages with an increasing proportion of females to males with size. Salinity and oxygen conditions were found to be the major factors influencing the vertical and horizontal distribution of adult cod. Abundance of immature cod was also positively related to decreasing bottom depths. The effect of temperature was minor. The observed size- and sexdependent spawning aggregation patterns, in association with habitat volume and stock size, may influence cod catchability and thereby the assessment and exploitation patterns of this stock.

Tramadol has been in clinical use in Germany since the late 1970s and has proven effective in both experimental and clinical pain without causing serious cardiovascular or respiratory side effects. Moreover, the negligible abuse potential of tramadol has meant that it has never been a restricted drug, and it therefore very quickly became the most popular analgesic of its class in Germany. Although tramadol has been used in myocardial emergencies, in trauma and obstetric pain, or to supplement balanced anaesthesia, most studies have investigated postoperative patients. The focus of this article is to review clinical experience with tramadol in the treatment of acute postoperative pain. Tramadol, a synthetic opioid of the aminocyclohexanol group, is a centrally acting analgesic with weak opioid agonist properties, and effects on noradrenergic and serotonergic neurotransmission. In addition, these opioid and nonopioid modes of action appear to act synergistically. Tramadol has been shown to provide effective analgesia after both intramuscular and intravenous administration for the treatment of postoperative pain. The drug is available in formulations suitable for oral, rectal and parenteral administration. Clinically effective analgesic doses of tramadol were comparable to those of pethidine (meperidine) and about 10 times higher than those of morphine. While it is not recommended as a supplement to general anaesthesia because of its insufficient sedative activity, tramadol has been successful in the treatment of postoperative pain. A randomised double-blind study reported acceptable analgesia with postoperative intravenous tramadol 50mg, repeated once if required after 30 minutes. It produced an effect similar to that of morphine 5mg or the alpha 2 agonist, clonidine 150 micrograms. In another study, it was shown that the 50mg dose of tramadol fulfilled the requirements of an analgesic for the treatment of moderate postoperative pain, whereas for severe pain a higher dose was recommended. Tramadol is generally well tolerated, the most common adverse events being nausea and vomiting. In contrast to agents such as morphine and pethidine, clinically relevant respiratory depression is rarely observed during tramadol administration at equipotent doses and consequently it can be recommended for first-line management of postoperative pain instead of morphine. It is also associated with a low incidence of cardiac depression and significantly less dizziness and drowsiness than morphine. Finally, the dependence and abuse potential with tramadol is negligible. Comparative studies have generally shown that tramadol is more effective than NSAIDs for controlling post operative pain. Use of a combination of tramadol and NSAIDs allows the tramadol dose to be reduced and results in a lower incidence of adverse effects. Patient controlled analgesia (PCA) with tramadol has been frequently used and is well accepted by patients. Wide individual variations exist with regard to analgesic requirements and, nowadays, it is generally accepted that adequate pain management implies systematic individualisation of the therapy, i.e. titration of the analgesic effect to individual needs. Demand and loading doses play a decisive role in the success of PCA. Analgesic failures requiring rescue medication are rare, but it should be stressed that these can always occur with weak opioids. In conclusion, tramadol can be recommended as a basic analgesic for the treatment of moderate to severe pain. In the event of analgesic failure with tramadol, there is no reason not to switch to more potent opioids. Although no studies are available regarding its use in the management of postoperative pain after day case surgery, tramadol is frequently administered with good results in such patients. The most important side effects of tramadol are nausea and emesis, which can often be prevented by slow injection and administration of a prophylactic antiemetic such as metoclopramid

This open prospective study evaluated the combination of initial dose titration with patient-controlled analgesia (PCA) and long-term treatment with transdermal fentanyl in 50 cancer patients requiring opioids for severe pain. The delivery rate of the first transdermal therapeutic system (TTS) was calculated from the self-administered intravenous fentanyl dose during the first 24 h. TTS were changed every 48-72 h, and a different patch size was chosen if necessary. Pain intensity (101-step numeric analog scale) and side-effects were assessed daily. The patients were treated for 66 +/- 101 days (range 3-535 days). The average delivery rate was 5.9 +/- 4.1 mg/d. Mean pain intensity decreased from initially 45 +/- 21 to 19 +/- 15 in the titration phase and 15 +/- 11 during long-term treatment. Three patients showed moderate respiratory depression. Other severe side-effects were not observed. Patient compliance and acceptance were excellent. The results suggest that intravenous PCA is useful for initial dose finding, and transdermal fentanyl is effective and safe during long-term treatment of cancer pain.

The Conference of European National Librarians (CENL), conscious of its responsibility both to preserve and to provide access to books and information in an increasingly electronic world, is involved in two extensive European Commission (EC) programmes to serve these ends. These are managed by a Forum of eight national libraries. The first is CoBRA (Computer and Bibliographic Record Actions), which established four task groups to study respectively improved European bibliographic services, user needs for bibliographic products, networked record distribution and re-use, and promotion of data sharing. Three new task groups are looking at new models for bibliographic services, networked national bibliographic services, and the long-term availability of electronic publications. A new programme called CoBRA+ is due to run through 1996 and 1997; as well as continuing CoBRA work it is widening its focus to include collection-based services, with emphasis on resource sharing, user needs and the use of communications networks. There are two main task groups, one concerned with the area of metadata and bibliographic access, the other with electronic publications and digital resources, including legal deposit and storage. Eight specific projects, ranging from networking name authority files to the development of a new relationship between publishers and national bibliographic agencies for the control of electronic publications, are briefly described.

Enteric-coated sucrose pellets containing a layer of bisacodyl beneath the coating were compressed into tablets on an instrumented single-punch machine using four different filler-binders for direct compression. Different copolymers based on polymethacrylates were applied as coatings. Pellets of two different crushing strengths were used. The quality of the films before and after tableting was evaluated by determining the amount of bisacodyl liberated after treatment for 2 h in 0.1 M HC1 according to the requirements of USP 23 for enteric-coated preparations. Results indicate that the most important parameters are the coating agent itself and the amount of coating applied to the pellets. Higher coating weights and coatings with better elastic properties lead to formulations, which liberate less bisacodyl after compression. Formulations are available that fulfil all requirements of USP 23 regarding entericcoated preparations.

Tramadol is a cyclohexanol derivative with mu-agonist activity. It has been used as an analgesic for postoperative or chronic pain since the late 1970s, and became one of the most popular analgesics of its class in Germany. International interest has been renewed during the past few years, when it was discovered that tramadol not only acts on opioid receptors, but also inhibits serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine) reuptake. This review aims to provide a risk-benefit assessment of tramadol in the management of acute and chronic pain syndromes. Tramadol has been used intraoperatively as part of balanced anaesthesia. Such use is under discussion, however, as it was associated with a high incidence of intraoperative recall and dreaming, and postoperative respiratory depression has been described after intraoperative administration of high doses. Postoperatively, intravenous and intramuscular tramadol has been used with good efficacy. Analgesic doses were comparable with pethidine (meperidine) and 10 times higher than morphine. Nausea and vomiting were the most frequently reported adverse effects. In controlled studies, haemodynamic and respiratory parameters were only minimally impaired. The risk of severe respiratory depression in typical dosages is negligible in comparison with other opioids used for postoperative pain management. Tramadol has been used with good results for the management of labour pain without respiratory depression of the neonate. It was also effective for the treatment of pain from myocardial ischaemia, ureteric colic and acute trauma. Good results have been published for cancer pain management with tramadol in several studies. The potential for abuse or addiction seems to be minimal, and serious complications have not been reported. For patients with severe pain, the efficacy of morphine is superior, and most patients with adequate analgesia from tramadol had to be changed to a more potent opioid after a few weeks due to increased nociceptive input during tumour progression. Tramadol can be recommended as a safe and efficient drug for step II according to the World Health Organization guidelines for cancer pain management.

Although pain assessment is a vital preliminary step towards the satisfactory control of cancer pain, data on the prevalence of different pain syndromes are rare. In a prospective study of 2266 cancer patients, we assessed localisations, aetiologies and pathophysiological mechanisms of the pain syndromes. Thirty percent of the patients presented with 1, 39% with 2 and 31% with 3 or more distinct pain syndromes. The majority of patients had pain caused by cancer (85%) or antineoplastic treatment (17%); 9% had pain related to cancer disease and 9% due to aetiologies unrelated to cancer. Pain could be classified as originating from nociceptors in bone (35%), soft tissue (45%) or visceral structures (33%) or otherwise as of an neuropathic origin (34%). In most patients, pain syndromes were located in the lower back (36%), abdominal region (27%), thoracic region (23%), lower limbs (21%), head (17%) and pelvic region (15%). The main pain syndrome was also coded according to the IASP Classification of Chronic Pain. Regions and systems affected by the main pain syndrome showed large variation depending on the site of cancer origin, whereas temporal characteristics, intensity and aetiology were not markedly influenced by the cancer site. The variety of pain syndromes evaluated in our patients confirms the importance of comprehensive pain assessment prior to treatment.

The opioid analgesic tramadol is a racemate and consists of 50% (+)- and 50% (-)-enantiomer. This study investigated analgesic efficacy and safety of both enantiomers after intravenous (i.v.) injection in comparison with the racemate. Ninety-eight patients recovering from major gynaecological surgery under opioid-free halothane anaesthesia were treated in a randomised, double-blind study with (+)-tramadol, (-)-tramadol or the racemate. Following an individualised i.v. loading dose up to a maximum of 200 mg, patient-controlled analgesia with demand doses of 20 mg was made available for 24 h. The primary criterion was of efficacy was the decrease of pain intensity on a 5-point verbal rating scale from severe or maximum pain to mild or no pain intensity on a 5-point verbal rating scale from severe or maximum pain to mild or no pain within the first hour after the loading dose. The secondary criterion was patient satisfaction with pain relief during the 24-h observation period stated in the final interview. Patients who terminated the study prematurely were evaluated as non-responders. Of patients treated with (+)-tramadol, tramadol racemate, and (-)-tramadol, 12%, 15%, and 53% of treated patients, respectively, terminated the study prematurely because of inefficacy. Of patients treated with (+)-tramadol, racemate or (-)-tramadol 67%, 48% and 38%, respectively, were considered responders regarding the primary criterion of efficacy (P = 0.061), and 82%, 76%, or 41% with respect to the secondary criterion (P = 0.001). Assessment of laboratory screening, adverse events, vital signs and blood gas monitoring showed no serious drug-related events. Nausea and vomiting were the most frequently reported non-serious side effects and were most often seen with (+)-tramadol. Taking into account both efficacy and safety aspects, the racemate seems to be superior to either enantiomer alone.

Ondansetron and droperidol are both effective in the prevention of postoperative nausea and vomiting (PONV). In this randomized, double-blind study, 80 inpatients scheduled for minor gynecologic surgery received either ondansetron 8 mg intravenously (i.v.) or droperidol 2.5 mg i.v. 5 min prior to induction of isoflurane-narcotic anesthesia. PONV was absent in 68% of the patients after ondansetron and in 88% after droperidol (P < 0.05). The respective times of complete arousal from anesthesia were 171 min and 229 min (P < 0.001). After ondansetron and droperidol, the incidence of severe drowsiness, restlessness, anxiety, or dizziness was 5% and 28%, respectively (P < 0.01). Thus after minor gynecologic surgery, droperidol 2.5 mg i.v. was superior to ondansetron 8 mg i.v. in the prevention of PONV. However, relative to ondansetron, droperidol entailed an average 1-h delay in recovery from anesthesia.

Two studies including a total of 70 patients evaluated the efficacy and side effects of a combination of initial patient-controlled analgesia (PCA) for dose finding with transdermal fentanyl administration. Patients, requiring strong opioids for severe cancer pain, received intravenous (i.v.) fentanyl on an on-demand basis over a 24 h period. The amount of fentanyl administered was then used for selecting a suitable transdermal therapeutic system (TTS), which remained in place for 72 h. The size of the second TTS was adjusted according to the amount of supplementary i.v. fentanyl required on day 3. Beginning on day 4, oral or subcutaneous morphine was made available as a rescue medication. The use of TTS fentanyl in combination with initial dose titration using PCA resulted in rapid and statistically significant pain relief in both studies. A respiratory rate below 8 per minute was observed in three patients. Due to adequate symptomatic treatment, other moderate and severe symptoms were relatively rare. TTS fentanyl was shown to be an effective, safe and simple method for long-term pain relief in cancer patients and presents an interesting novel option in the treatment of cancer pain.

The present economic situation is a poor starting point for the national libraries of Eastern Europe in their efforts to cope with the future. Political censorship is replaced with economic censorship: insufficient budgets, inadequate space for books and readers, gaps in distribution systems, and increasing transport and postal rates. But libraries are an essential element in the intellectual infrastracture and cultural dialogue; and national libraries in Eastern Europe see cooperation with similar libraries in the West as a major way of achieving development. Several countries have agreed to exchange specialists, training and education programmes already exist, and lack of acquisition funds has been somewhat mitigated by book donation programmes; but more needs to be done. The European Union is an appropriate mechanism for developing an East-West programme to improve the infrastructure through the implementation of technological policy. East-West dialogue can best be structured through the Council of Europe, which has recently expanded its membership to include Eastern and Central Europe.

With the unification of Germany in 1990, the two former national libraries and national bibliographic agencies, the Deutsche Bücherei in Leipzig and the Deutsche Bibliothek in Frankfurt, were also united and given a single name: DIE DEUTSCHE BIBLIOTHEK. The Deutsches Musikarchiv in Berlin is also included in the new entity. The locations have remained unchanged, the collections continue to be maintained and responsibilities have been distributed in an effective manner. The new institution, whose total collections number some twelve million volumes, has made great progress in three short years. The merger of the two libraries has made it possible to tap new resources and to offer a new and expanded package of bibliographic services. In addition to important organizational, technical and financial concerns, the establishment of a foundation for a new identity has been a major point of emphasis. Through the step-by-step assumption of responsibility in specific areas, the sense of alienation that had evolved over 50 years has gradually given way to a spirit of teamwork and eagerness to learn. With its centres of strength in Leipzig and Frankfurt, DIE DEUTSCHE BIBLIOTHEK is now prepared to serve as a bridgehead between East and West.

The pharmacokinetics of sufentanil were studied in 56 surgical patients after an intravenous bolus of 2 micrograms kg-1, in association with neurolept analgesia or volatile anaesthetics (halothane, enflurane and isoflurane). Plasma concentrations of sufentanil were measured by radioimmunoassay. The kinetics of sufentanil were comparable under neurolept analgesia and under anaesthesia with halothane, enflurane or isoflurane. The overall mean elimination half-life was 182 min, Vdss 169 l and the plasma clearance 910 ml min-1. Except for the isoflurane subgroup, there was no significant correlation between half-life, the volume of distribution or clearance with age (24-77 years) or body weight (45-95 kg).

Neuropathische Schmerzen gehoren zu den Problembereichen in der Tumorschmerztherapie. In einer retrospektiven Studie wurden Pravalenz und Charakteristik neuropathischer Schmerzen bei 1318 Tumorpatienten einer Schmerzambulanz untersucht. Von diesen Patienten hatten 135 neuropathische Schmerzen, 285 neuropathische und Nozizeptorschmerzen, 890 Nozizeptorschmerzen und 8 unbekannte Schmerzzustande. Der Anteil der Patienten mit sehr starken Schmerzen betrug bei neuropathischen Schmerzen 62% und bei Nozizeptorschmerzen 48%. Die neuropathischen Schmerzen waren vornehmlich Folge der Tomorinfiltration oder-kompression (71%) und seltener Folge der Tumortherapie (15%), der allgemeinen Tumorerkrankung (6%) oder tumor- und therapieunabhangig (8%). Von 110 klinisch genauer analysierten neuropathischen Schmerzzustanden waren 44% neuralgiform, 31% radikular, 13% Sympathalgien, 10% Deafferenzierungsschmerzen und 3% unbekannt. Zur Erfolgsbewertung von Therapieverfahren in der Tumorschmerztherapie sollten nicht nur nozizeptive von neuropathischen Schmerzen unterschieden werden, sondern daruberhinaus mehrere Untergruppen neuropathischer Schmerzen differenziert werden.