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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. [ABSTRACT FROM AUTHOR]

Eleven patients (40.7%), five patients (19.2%, not 4%) and one patient (3.9%) in the paracetamol, metamizole and placebo groups, respectively, did not need any morphine. However, there appears to be differences in the types of surgery between the groups: mastectomy and/or axilla dissection in 58% vs. 48% of patients treated with metamizole (n = 26) and paracetamol (n = 27), respectively, with patient numbers not transparent in Table 1 [1]. Single dose systemic acetaminophen to improve patient reported quality of recovery after ambulatory segmental mastectomy: a prospective, randomized, double-blinded, placebo controlled, clinical trial. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents study on the use of liquid chromatography and mass spectrometry for determination of ondansetron and 8-hydroxyondansetron in human plasma from recovered patients. It says that plasma concentrations of the enantiomers of ondansetron and of 8-hydroxyondansetron were examined in patients recovering from abdominal surgery. The results show that determination of ondansetron was achieved on a Chiralcel OD-R column and the method was fully applied to authentic plasma samples.

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.

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.

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.

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.

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.

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.

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.

Implications: Naphazoline intoxication by intrabronchial overdose caused prolonged unconsciousness of an 18-mo-old child after general anesthesia for tracheal rigid bronchoscopy. The leading symptoms were side effects involving the cardiovascular, pulmonary, and central nervous systems. Intensive care unit admission with the need for mechanical ventilation was necessary. Recovery was uneventful.

Regional anaesthetic techniques in obstetrics have gained more and more importance during the last few years. Several surveys published recently show a remarkable increase in caesarean sections performed under regional anaesthesia, in many countries. Furthermore, epidural analgesia has proved to be one of the most effective methods of pain relief during vaginal delivery. Especially in patients at risk of an abdominal delivery, an epidural catheter already in place during labour can be used for consecutive caesarean section without delay and is used as a strong argument in favour of epidural anaesthesia. This article gives an overview of recent surveys of regional anaesthesia in obstetrics.