[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.

[Perioperative use of metamizole and other nonopioid analgesics in children : Results of a survey]. / Perioperative Anwendung von Metamizol und anderen Nichtopioidanalgetika bei Kindern : Ergebnisse einer Umfrage.

BACKGROUND: Nonopioid analgesics are frequently used for perioperative pain management in children. In many countries, the nonopioid metamizole (dipyrone) is administered as an alternative to paracetamol and traditional NSAIDs (nonsteroidal anti-inflammatory drugs), such as ibuprofen and diclofenac; however, concerns over possible life-threatening adverse events (agranulocytosis) have prompted a debate over the use of metamizole. OBJECTIVE: To investigate current practice and use of nonopioid analgesics, particularly of metamizole in children younger than 14 years, in the perioperative setting. Furthermore, metamizole-related side effects, safety and approaches used to inform patients were addressed. METHODS: A link to an online questionnaire on the perioperative use of nonopioid analgesics in children, with a specific focus on dipyrone, was sent by e­mail to members of the German Society of Anesthesiology and Intensive Care Medicine (DGAI) and to members of the German Pain Society. RESULTS: A total of 2284 anesthesiologists filled out the questionnaire. Of these, 1476 were involved in the perioperative care of children younger than 14 years. The majority of respondents worked in German hospitals (90.5%) but Austria, Switzerland and the Netherlands were also among the countries represented. Of the respondents, 99.1% reported using nonopioid analgesics in the perioperative setting. The NSAID, metamizole, paracetamol and COX-2 inhibitors were administered by 83.9%, 68.6%, 67.5% and 2% of the respondents, respectively. Intravenous metamizole was the preferred nonopioid analgesic during surgical procedures, but following surgery, NSAID, metamizole and paracetamol were given with the same frequency by anesthesiologists. Of the respondents, 49.3% reported using metamizole in combination with another nonopioid analgesic in cases of severe pain, 14.8% used it as the sole nonopioid analgesic, and 23.2% never used it at all. Nearly half of the respondents administered metamizole i.v. in doses of 15 mg/kg body weight or lower, whereas 26% administered doses of at least 16 mg/kg up to more than 20 mg/kg. Of the physicians, 298 (20.2%) restricted the duration of metamizole use, varying between one single administration (4.7%), administration for 1 day (27.5%), or for 1-2 weeks (29.2%). Of the anesthesiologists, 65.6% reported no metamizole-related adverse effects. Allergic reactions/anaphylaxis and a drop in blood pressure requiring intervention were observed by 3-4% of the respondents. No change in blood cell counts within the last 2 years was reported by 73.1% of the respondents, whereas 17 anesthesiologists (1.3%) had observed children with altered blood cell counts, with 2 (0.14%) reporting agranulocytosis. In most cases these were incidental findings. No severe sequelae or deaths were reported. Few respondents (5.5%) performed routine blood cell counts to monitor metamizole therapy. Furthermore, only a minority always (3.5%) or sometimes (6.1%) informed a child's parents of possible side effects of treatment with metamizole. CONCLUSION: The survey confirmed that metamizole is frequently used in children in the perioperative setting. Intravenous metamizole is the preferred nonopioid analgesic administered intraoperatively for pain prophylaxis. Clinical symptoms of agranulocytosis should be monitored and patients should be better informed about metamizole-related side effects.

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.

[Unexpected hemorrhage complications in association with celecoxib. Spontaneously reported case series after perioperative pain treatment in gynecological operations]. / Unerwartete Blutungskomplikationen im Zusammenhang mit Celecoxib. Spontanmeldung einer Fallserie nach perioperativer Schmerzbehandlung bei gynäkologischen Operationen.

A series of cases of postoperative bleeding were reported to the Drug Commission of the German Medical Association (Arzneimittelkommission der deutschen Ärzteschaft, AkdÄ) within the spontaneous reporting system after the regimen for postoperative pain treatment was changed from diclofenac (150 mg per day) to celecoxib (400 mg per day). All patients underwent elective gynecological surgery and 7 out of 11 patients with postoperative bleeding required revision surgery. Although alternative causes for the hemorrhage incidents could not be excluded, the documented circumstances could have been indicative of a possible causal association. Studies on perioperative pain treatment with celecoxib had previously shown no increased risk of hemorrhage. The tendency to hemorrhage observed in the registered cases could not be pharmacologically explained; however, due to the high dosages of celecoxib and the extensive co-medications used, a relative overdosing due to drug interactions or differences in the metabolism of the affected patients was conceivable. Celecoxib is not approved for the treatment of acute postoperative pain although a number of studies were carried out on the effectiveness and safety in patients undergoing surgery.