[Safety and monitoring of patient-controlled intravenous analgesia : Clinical practice in German hospitals]. / Sicherheit und Monitoring der patientenkontrollierten intravenösen Analgesie : Anwendungspraxis in deutschen Krankenhäusern.

BACKGROUND: Patient-controlled intravenous analgesia (PCIA) is a well-established technique in acute pain management and available in most German hospitals. Despite its widespread use, information on current clinical practice is limited. This investigation evaluated clinical practice and monitoring as well as PCIA-associated adverse events and critical incidents in German hospitals. METHODS: An invitation to participate in this online-survey was sent to 995 heads of anesthesiology departments belonging to the "German Society of Anaesthesiology and Intensive Care Medicine". RESULTS: Of the departments receiving the link, 244 took part (response rate 25%). PCIA was used in 193 of these hospitals (79%). All the following statements relate to the hospitals in which PCIA was used. Piritramide was the most frequently used opioid. In parallel with PCIA, additional nonopioid analgesics were used in 94% of the hospitals, and in 38%, additional slow-release oral opioids were used. Parenteral opioids were administered by the ward staff in 4% of the hospitals. In 75% of hospitals, there were standardized indications for PCIA therapy, with almost two thirds of respondents stating that PCIA was the technique of second choice if regional procedures were contraindicated or failed. In all, 76% of the hospitals had an acute pain service. Twenty-four percent of the hospitals regularly used PCIA in non-surgical patients. In pediatric patients, PCIA was used in 62 hospitals (32%). Only 31% of the hospitals reported the use of standardized protocols for the specific monitoring of patients' vital signs on general wards, exceeding general care. Of the department, 158 (82%) reported adverse events in connection with the use of PCIA within the six-month period preceding the survey (most frequently due to patients' noncompliance [52%], dislocated intravenous lines [41%], communication errors [16%], administration of additional analgesics [16%] and/ or sedatives [14%], problems with the pump [16%], programming errors [9%], incorrect opioid concentration in the reservoir [8%], non-observance of contraindications [7%], incorrect dosing [6%] and self-dosing by the patient [4%] or by third parties [3%], filling the reservoir with thewrong medication [2%]; and other problems [5%]). Only 35 of the hospitals (18%) reported no problems associated with PCIA therapy. Seventy-five of the 193 respondents (39%) stated that at least one critical incident had occurred in the context of the use of PCIA. This resulted in a total of 335 cases out of an estimate of 50.000 patients treated with PCIA. The respondents classified these as follows: I) 273 incidents requiring a prolonged stay in the recovery room, but without further complications, II) 58 requiring transfer to the intensive care unit, but without further complications, III) three resulting in permanent harm to the patient and IV) one resulting in the death of the patient. A comparison of the monitoring standards for PCIA showed that critical incidents were reported less frequently in hospitals with less intensive monitoring, and more frequently in hospitals with higher monitoring standards. CONCLUSION: PCIA is a frequently used analgesic technique in German hospitals. There were many differences in how PCIA therapy was applied and monitored on general wards. Adverse events occurred to a significant extent, with a considerable part of them, which might be preventable. Critical incidents were perceived more often when standards for monitoring on general wards were higher. Consented current recommendations regarding treatment and monitoring standards as well as the systematic recording of complications when using PCIA are pending.

[Recommendations for the perioperative use of dipyrone : Expert recommendation of the working group on acute pain of the German Pain Society, the scientific working group on pain medicine of the German Society for Anesthesiology and Intensive Care Medicine and the surgical working group on acute pain of the German Society for Surgery with participation of representatives of the Drug Commission of the German Medical Association]. / Empfehlungen zur perioperativen Anwendung von Metamizol : Expertenempfehlung des Arbeitskreises Akutschmerz der Deutschen Schmerzgesellschaft, des Wissenschaftlichen Arbeitskreises Schmerzmedizin der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin und der Chirurgischen Arbeitsgemeinschaft Akutschmerz der Deutschen Gesellschaft für Chirurgie unter Beteiligung von Vertretern der Arzneimittelkommission der deutschen Ärzteschaft.

BACKGROUND: Dipyrone (metamizole) is widely used for perioperative pain management in countries where it is marketed; however, uncertainty exists concerning the safe use of this drug, specifically considering the rare adverse event of an agranulocytosis. METHODS: As evidence from published studies was lacking, an expert panel developed recommendations for the perioperative use of dipyrone. After a formal, structured consensus process, the recommendations were approved by the involved medical societies. RESULTS: The panel agreed that blood cell counts shall not be standard for short-term perioperative use in patients unless they are at risk for neutropenia. The medical staff shall be aware of the symptoms and course of action when agranulocytosis is suspected. Patients shall be informed about the risks and benefits of dipyrone and about potential alternatives. The expert group concluded that dipyrone has a relatively positive risk-benefit ratio compared to other nonopioid analgesics. The group strongly recommended educating patients about the symptoms of agranulocytosis if they have received dipyrone over several days and/or treatment is to be continued after discharge, because agranulocytosis can occur several days after discontinuation of metamizole. Further recommendations refer to the information of the physician taking over the patient's care after discharge and the avoidance of re-exposure in patients having previously suffered from dipyrone-induced agranulocytosis. CONCLUSION: The group's recommendations shall be communicated in order to raise medical staff's and patients' awareness of the appropriate use of dipyrone in the perioperative period.

[Recommendations for the perioperative use of dipyrone : Expert recommendation of the working group on acute pain of the German Pain Society, the scientific working group on pain medicine of the German Society for Anesthesiology and Intensive Care Medicine and the surgical working group on acute pain of the German Society for Surgery with participation of representatives of the Drug Commission of the German Medical Association]. / Empfehlungen zur perioperativen Anwendung von Metamizol : Expertenempfehlung des Arbeitskreises Akutschmerz der Deutschen Schmerzgesellschaft, des Wissenschaftlichen Arbeitskreises Schmerzmedizin der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin und der Chirurgischen Arbeitsgemeinschaft Akutschmerz der Deutschen Gesellschaft für Chirurgie unter Beteiligung von Vertretern der Arzneimittelkommission der deutschen Ärzteschaft.

BACKGROUND: Dipyrone (metamizole) is widely used for perioperative pain management in countries where it is marketed; however, uncertainty exists concerning the safe use of this drug, specifically considering the rare adverse event of an agranulocytosis. METHODS: As evidence from published studies was lacking, an expert panel developed recommendations for the perioperative use of dipyrone. After a formal, structured consensus process, the recommendations were approved by the involved medical societies. RESULTS: The panel agreed that blood cell counts shall not be standard for short-term perioperative use in patients unless they are at risk for neutropenia. The medical staff shall be aware of the symptoms and course of action when agranulocytosis is suspected. Patients shall be informed about the risks and benefits of dipyrone and about potential alternatives. The expert group concluded that dipyrone has a relatively positive risk-benefit ratio compared to other nonopioid analgesics. The group strongly recommended educating patients about the symptoms of agranulocytosis if they have received dipyrone over several days and/or treatment is to be continued after discharge, because agranulocytosis can occur several days after discontinuation of metamizole. Further recommendations refer to the information of the physician taking over the patient's care after discharge and the avoidance of re-exposure in patients having previously suffered from dipyrone-induced agranulocytosis. CONCLUSION: The group's recommendations shall be communicated in order to raise medical staff's and patients' awareness of the appropriate use of dipyrone in the perioperative period.

[Recommendations for the perioperative use of dipyrone : Expert recommendation of the working group on acute pain of the German Pain Society, the scientific working group on pain medicine of the German Society for Anesthesiology and Intensive Care Medicine and the surgical working group on acute pain of the German Society for Surgery with participation of representatives of the Drug Commission of the German Medical Association]. / Empfehlungen zur perioperativen Anwendung von Metamizol : Expertenempfehlung des Arbeitskreises Akutschmerz der Deutschen Schmerzgesellschaft, des Wissenschaftlichen Arbeitskreises Schmerzmedizin der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin und der Chirurgischen Arbeitsgemeinschaft Akutschmerz der Deutschen Gesellschaft für Chirurgie unter Beteiligung von Vertretern der Arzneimittelkommission der deutschen Ärzteschaft.

BACKGROUND: Dipyrone (metamizole) is widely used for perioperative pain management in countries where it is marketed; however, uncertainty exists concerning the safe use of this drug, specifically considering the rare adverse event of an agranulocytosis. METHODS: As evidence from published studies was lacking, an expert panel developed recommendations for the perioperative use of dipyrone. After a formal, structured consensus process, the recommendations were approved by the involved medical societies. RESULTS: The panel agreed that blood cell counts shall not be standard for short-term perioperative use in patients unless they are at risk for neutropenia. The medical staff shall be aware of the symptoms and course of action when agranulocytosis is suspected. Patients shall be informed about the risks and benefits of dipyrone and about potential alternatives. The expert group concluded that dipyrone has a relatively positive risk-benefit ratio compared to other nonopioid analgesics. The group strongly recommended educating patients about the symptoms of agranulocytosis if they have received dipyrone over several days and/or treatment is to be continued after discharge, because agranulocytosis can occur several days after discontinuation of metamizole. Further recommendations refer to the information of the physician taking over the patient's care after discharge and the avoidance of re-exposure in patients having previously suffered from dipyrone-induced agranulocytosis. CONCLUSION: The group's recommendations shall be communicated in order to raise medical staff's and patients' awareness of the appropriate use of dipyrone in the perioperative period.

Dipyrone is the preferred nonopioid analgesic for the treatment of acute and chronic pain. A survey of clinical practice in German-speaking countries.

PURPOSE: Nonopioid analgesics are frequently used for the treatment of acute and chronic pain. Dipyrone is an alternative to NSAIDs and paracetamol, however, data on the frequency of its usage by anaesthesiologists in the perioperative and chronic pain setting are lacking and its adverse reactions are a matter of debate. METHODS: The link to a questionnaire on the use of nonopioid analgesics (NSAIDs, COX-2 inhibitors, paracetamol, dipyrone) and the safety of dipyrone in the perioperative and chronic pain setting was mailed to anaesthesiologists and pain physicians. RESULTS: A total of 2237 responses were analysed. About 97.4% of the respondents used nonopioid analgesics for the treatment of acute pain, with 93.8% administering dipyrone, 54.0% NSAIDs, 41.8% COX-2 inhibitors and 49.2% paracetamol. Nonopioid analgesics were administered preoperatively by 22.3%, intraoperatively by 86.1% and postoperatively by 73.0% of the respondents. For chronic pain management, 76.7% of the respondents prescribed oral dipyrone in combination with other nonopioid analgesics; 19.9% used dipyrone as sole nonopioid, whereas 2.9% denied its use. Cases of dipyrone-associated agranulocytosis were observed by 3.5% of the respondents of the acute and 1.5% of the chronic pain questionnaire, respectively. The majority of respondents (acute pain: 73.0%, chronic pain 59.3%) performed no blood cell counts to monitor dipyrone therapy. Patients were rarely informed about possible adverse drug reactions. CONCLUSIONS: Dipyrone is the preferred nonopioid analgesic in the perioperative and chronic pain setting. Although cases of agranulocytosis occur, benefits apparently outweigh the risks according to anaesthesiologists. Measures like patient information may improve safety. SIGNIFICANCE: A survey of anaesthesiologist in German-speaking countries revealed dipyrone as preferred nonopioid analgesic for the treatment of acute and chronic pain. Benefits seem to outweigh the risks, specifically the risk of agranulocytosis. Information of medical staff and patients on adverse drug reactions and symptoms of agranulocytosis should be implemented.

[Dipyrone (metamizole) : Considerations on monitoring for early detection of agranulocytosis]. / Metamizol : Überlegungen zum Monitoring zur frühzeitigen Diagnose einer Agranulozytose.

BACKGROUND: Dipyrone (metamizole) is a non-opioid analgesic commonly used in Germany, which can, in very rare cases, cause life-threatening agranulocytosis. The prescribing information calls for regular monitoring of the differential blood count in cases of long-term treatment. However, there is uncertainty about how this testing should be handled in practice. OBJECTIVES: Which recommendations can be derived from the published literature for evaluating blood cell counts during treatment with metamizole and which other options for monitoring exist? METHODS: Data from recent epidemiological studies, reviews, and spontaneously reported cases were evaluated. RESULTS: Agranulocytosis can emerge at highly variable intervals ranging from the first day of metamizole treatment to months after treatment has begun. As a result, there is no conclusive, evidence-based recommendation for the time intervals at which blood cell counts should be tested. Therefore, the onset of clinical symptoms should be used as trigger for monitoring blood cell counts to enable early diagnosis and avoid agranulocytosis-related complications. In addition to general symptoms like fever, sore throat, fatigue, and muscle pain, mucosal ulcerations, severe angina, and systemic infections leading to sepsis are typical of agranulocytosis. CONCLUSIONS: Providing patients and medical staff with better information about early symptoms of agranulocytosis could be a sensible way to prevent complications. Any suspicion of agranulocytosis should immediately lead to a differential blood count and to the withdrawal of all drugs possibly associated with agranulocytosis. Patients should be monitored and treated according to the severity of their symptoms.

Phorbol-12-myristate-13-acetate induces nociceptin in human Mono Mac 6 cells via multiple transduction signalling pathways.

BACKGROUND: Nociceptin in the peripheral circulation has been proposed to have an immunoregulatory role with regards to inflammation and pain. However, the mechanisms involved in its regulation are still not clear. The aim of this study was to investigate signalling pathways contributing to the regulation of the expression of nociceptin under inflammatory conditions. METHODS: Mono Mac 6 cells (MM6) were cultured with or without phorbol-12-myristate-13-acetate (PMA). Prepronociceptin (ppNOC) mRNA was detected by RT-qPCR and extracellular nociceptin by fluorescent-enzyme immunoassay. Intracellular nociceptin and phosphorylated kinases were measured using flow cytometry. To evaluate the contribution of various signalling pathways to the regulation of ppNOC mRNA and nociceptin protein, cells were pre-treated with specific kinase inhibitors before co-culturing with PMA. RESULTS: ppNOC mRNA was expressed in untreated MM6 at low concentrations. Exposure of cells to PMA upregulated ppNOC after nine h compared with controls without PMA (median normalized ratio with IQR: 0.18 (0.15-0.26) vs. 0 (0-0.02), P<0.01). Inhibition of mitogen-activated protein kinases specific for signal transduction reversed the PMA effects (all P<0.001). Induction of nociceptin protein concentrations in PMA stimulated MM6 was prevented predominantly by identity of ERK inhibitor (P<0.05). CONCLUSIONS: Upregulation of nociceptin expression by PMA in MM6 cells involves several pathways. Underlying mechanisms involved in nociceptin expression may lead to new insights in the treatment of pain and inflammatory diseases.

A follow-up on Acute Pain Services in Germany compared to international survey data.

BACKGROUND: After the introduction of instruments for benchmarking, certification and a national guideline for acute pain management, the aim of this study was to describe the current structure, processes and quality of German acute pain services (APS). METHODS: All directors of German departments of anaesthesiology were invited to complete a postal questionnaire on structures und processes of acute pain management. The survey asked for staff, techniques and quality criteria, which enabled a comparison to previous data from 1999 and surveys from other countries. RESULTS: Four hundred and eight (46%) questionnaires were returned. APS have increased considerably and are now available in 81% of the hospitals, mainly anaesthesia based. However, only 45% fulfilled the minimum quality criteria, such as the assignment of personnel, the organization of patient care during nights and weekends, written protocols for postoperative pain management, regular assessments and documenting pain scores. Staff resources varied considerably, but increased compared to 1999. Two daily rounds were performed in 71%, either by physicians and nurses (42%), by physicians only (25%) or by supervised nurses (31%). Most personnel assigned to the APS shared this work along with other duties. Only 53% of the hospitals had an integrated rotation for training their specialty trainees. CONCLUSIONS: The availability of APS in Germany and other countries has increased over the last decade; however, the quality of nearly half of the APS is questionable. Against the disillusioning background of recently reported unfavourable pain-related patient outcomes, the structures, organization and quality of APS should be revisited.

Quality of pain treatment after caesarean section: Results of a multicentre cohort study.

BACKGROUND: A large cohort study recently reported high pain scores after caesarean section (CS). The aim of this study was to analyse how pain after CS interferes with patients' activities and to identify possible causes of insufficient pain treatment. METHODS: We analysed pain scores, pain-related interferences (with movement, deep breathing, mood and sleep), analgesic techniques, analgesic consumption, adverse effects and the wish to have received more analgesics during the first 24 h after surgery. To better evaluate the severity of impairment by pain, the results of CS patients were compared with those of patients undergoing hysterectomy. RESULTS: CS patients (n = 811) were compared with patients undergoing abdominal, laparoscopic-assisted vaginal or vaginal hysterectomy (n = 2406, from 54 hospitals). Pain intensity, wish for more analgesics and most interference outcomes were significantly worse after CS compared with hysterectomies. CS patients with spinal or general anaesthesia and without patient-controlled analgesia (PCA) received significantly less opioids on the ward (62% without any opioid) compared with patients with PCA (p < 0.001). Patients with PCA reported pain-related interference with movement and deep breathing between 49% and 52% compared with patients without PCA (between 68% and 73%; p-values between 0.004 and 0.013; not statistically significant after correction for multiple testing). CONCLUSION: In daily clinical practice, pain after CS is much higher than previously thought. Pain management was insufficient compared with patients undergoing hysterectomy. Unfavourable outcome was mainly associated with low opioid administration after CS. Contradictory pain treatment guidelines for patients undergoing CS and for breastfeeding mothers might contribute to reluctance of opioid administration in CS patients.

Effects of opioids on human serotonin transporters.

The serotonin (5-hydroxtryptamine, 5-HT) system plays a role in analgesia and emesis. The aim of this study was to test whether opioids or ketamine inhibit the human 5-HT transporter and whether this increases free plasma 5-HT concentrations. HEK293 cells, stably transfected with the human 5-HT transporter cDNA, were incubated with morphine, hydromorphone, fentanyl, alfentanil, pethidine (meperidine), tramadol, ketamine, and the reference substance citalopram (specific 5-HT transporter inhibitor). The uptake of [(3)H]5-HT was measured by liquid scintillation counting. In a second series of experiments, study drugs were incubated with plasma of ten healthy blood donors and change of 5-HT plasma-concentrations were measured (ELISA). The end point was the inhibition of the 5-HT transporter by different analgesics either in HEK293 cells or in human platelets ex vivo. Tramadol, pethidine, and ketamine suppressed [(3)H]5-HT uptake dose-dependently with an IC50 of 1, 20.9, and 230 µM, respectively. These drugs also prevented 5-HT uptake in platelets with an increase in free plasma 5-HT. Free 5-HT concentrations in human plasma were increased by citalopram 1 µM, tramadol 20 µM, pethidine 30 µM, and ketamine 100 µM to 280 [248/312]%, 269 [188/349]%, and 149 [122/174]%, respectively, compared to controls without any co-incubation (means [95 % CI]; all p < 0.005). No change in both experimental settings was observed for the other opioids. Tramadol and pethidine inhibited the 5-HT transporter in HEK293 cells and platelets. This inhibition may contribute to serotonergic effects when these opioids are given in combination, e.g., with monoamine oxidase inhibitors or selective serotonin reuptake inhibitors.

Expression of the nociceptin precursor and nociceptin receptor is modulated in cancer and septic patients.

BACKGROUND: A role of nociceptin and its receptor (NOP) in pain and immune function has been suggested. The hypothesis was that mRNA expression of NOP and the nociceptin precursor pre-pronociceptin (pN/OFQ) in peripheral blood cells differs in end-stage cancer patients suffering from chronic pain and septic intensive care unit (ICU) patients compared with healthy controls. METHODS: Blood samples were drawn from end-stage cancer patients and septic ICU patients. Additionally, postoperative patients representing individuals with surgical stress and healthy controls were enrolled as comparative groups. NOP and pN/OFQ mRNA expression, quantified by real-time polymerase chain reaction (RT-PCR), was compared between study groups, and associated to opioid medication, pain intensities, and the inflammatory markers procalcitonin (PCT) and interleukin-6. RESULTS: NOP expression was significantly higher in cancer patients [normalized ratio, median (inter-quartile range): 10.2 (7.4/17.8)], postoperative patients [8.0 (5.3/10.2)], and ICU patients [6.6 (4.2/9.5)] compared with healthy controls [4.4 (2.7/7.0); P<0.001]. Expression of pN/OFQ was lower in cancer patients [3.8 (1.9/5.9)] and ICU patients [1.9 (1.0/2.7)] but not in postoperative patients compared with healthy controls [7.2 (6.1/9.4); P<0.001]. Increased plasma PCT was associated with decreased pN/OFQ in all patient groups. In cancer patients, no association was seen with pain scores, opioid medication or duration of analgesia, and NOP or pN/OFQ mRNA. CONCLUSIONS: NOP and pN/OFQ expression in peripheral blood cells was modulated in end-stage cancer and septic patients compared with healthy controls, whereas changes in postoperative patients were minor. The involvement of the NOP-pN/OFQ system in inflammation, impaired immune function, and pain has to be further elucidated.

Enantioselective determination of ondansetron and 8-hydroxyondansetron in human plasma from recovered surgery patients by liquid chromatography-tandem mass spectrometry.

A liquid chromatographic-mass spectrometric assay with atmospheric pressure chemical ionization for quantification of ondansetron and its main metabolite 8-hydroxyondansetron in human plasma was presented. The enantiomeric separation was achieved on a Chiralcel OD-R column containing cellulose tris-(3,5-dimethylphenylcarbamate). The validation data were within the required limits. The assay was successfully applied to authentic plasma samples. Quantitative results from postoperative patients receiving ondansetron demonstrated a great interindividual variability in postoperative plasma drug concentrations, the metabolites were not detected in their unconjugated form. A wide variation in the S-(+)-/R-(-)-ondansetron concentration ratio between 0.14 and 7.18 is indicative for a stereoselective disposition or metabolism. In further studies CYP2D6 and CYP3A4 genotype dependent metabolism of ondansetron enantiomers as well as of co-administered drugs and clinical efficacy of the medication should be tested.

[Paracetamol for perioperative analgesia. Old substance - new insights]. / Paracetamol für die perioperative Analgesie. Alte Substanz - neue Erkenntnisse.

Since paracetamol was first synthesized in 1878 it has become one of the most popular and widely used drugs for the first-line treatment of fever and pain. The reasons for this popularity are a wide variety of formulations, an assumed positive safety record and the wide availability as an over-the-counter drug. However, recently several studies questioned the positive risk-benefit ratio of paracetamol for postoperative pain by observing several possible adverse effects and limitations. The aim of the present review is to give an update of the recent literature on the efficacy of paracetamol for postoperative pain and on the value of the clinical relevance of different adverse effects of paracetamol. Finally, based on the current findings the authors try to assess the role of paracetamol for the treatment of postoperative pain.

[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.

Concentrations of tramadol and O-desmethyltramadol enantiomers in different CYP2D6 genotypes.

The influence of CYP2D6 genotype and CYP2D6 inhibitors on enantiomeric plasma levels of tramadol and O-desmethyltramadol as well as response to tramadol was investigated. One hundred and seventy-four patients received one hundred intravenous tramadol 3 mg/kg for postoperative analgesia. Blood samples drawn 30, 90, and 180 min after administration were analyzed for plasma concentrations of the enantiomers (+)-, (-)tramadol and (+)-, (-)O-desmethyltramadol by liquid chromatography-tandem mass spectrometry. Different CYP2D6 genotypes displaying zero (poor metabolizer (PM)), one (heterozygous individual (HZ)/intermediate metabolizer (IM)), two extensive metabolizer (EM), and three (ultra rapid metabolizer (UM)) active genes were compared. Concentrations of O-desmethyltramadol differed in the four genotype groups. Median (1/3 quartile) area under the concentration-time curves for (+)O-desmethyltramadol were 0 (0/11.4), 38.6 (15.9/75.3), 66.5 (17.1/118.4), and 149.7 (35.4/235.4) ng x h/ml for PMs, HZ/IMs, EMs, and UMs (P<0.001). Comedication with CYP2D6 inhibitors decreased (+) O-desmethyltramadol concentrations (P<0.01). In PMs, non-response rates to tramadol treatment increased fourfold compared with the other genotypes (P<0.001). In conclusion, CYP2D6 genotype determined concentrations of O-desmethyltramadol enantiomers and influenced efficacy of tramadol treatment.

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.

[Postoperative analgesia with tramadol and metamizol. Continual infusion versus patient controlled analgesia]. / Postoperative Analgesie mit Tramadol und Metamizol. Kontinuierliche Infusion versus patientenkontrollierte Analgesie.

OBJECTIVE: The study compares the i.v. analgesia of tramadol and dipyrone delivered either as continuous infusion or as patient controlled analgesia (PCA). METHODS: After approval by the local ethics committee and informed consent 203 patients recovering from abdominal surgery were randomly assigned to pain treatment either by PCA or continuous intravenous infusion. Both groups received the same analgesic drug combination of tramadol (20 mg/ml) and dipyrone (200 mg/ml). The PCA bolus was set to 1 ml, the continuous infusion varied between 0-8 ml/h according to individual needs. Demographic and surgery related data were compared between the treatment groups, as well as pain scores, analgesic consumption and response rates over a 48 hour study period.A patient was assessed as non responder when rescue medication was necessary during the study period or the patient rated analgesia as insufficient during the final interview. RESULTS: In total,data of 191 patients (infusion-group: 94, PCA-group: 97) could be analyzed. Tramadol consumption was higher in the infusion group compared to the PCA-group (48 hours: 1009.4+/-494.4 vs. 813.0+/-585.3 mg;p<0.001) with no difference in pain scores. In the infusion group, significantly more interventions were necessary to adjust the infusion rate to individual needs (min-max: 1-15 vs. 0-2). The number of non responders amounted to 30 (31.9%) and 18 (18.6%;p=0.03) in the infusion and PCA group, respectively. CONCLUSIONS: PCA with tramadol and dipyrone can be considered an alternative for postoperative pain management and provided a more individualized treatment approach with lower analgesic consumption and more responders compared to a continuous infusion.