Objectively measured activity is not associated with average pain intensity 1 week after surgery: A cross-sectional study.

BACKGROUND: Measures of physical activity and pain-related patient-reported outcomes are important components of patient recovery after surgery. However, little is known about their association in the early post-operative period. This study aims to increase this knowledge. Our primary objective was to determine the association between average pain intensity and activity (in steps) 1 week after surgery. Secondary objectives were the association of activity with other patient-reported outcomes, age, sex, comorbidities and body mass index. METHODS: Data were obtained from the PROMPT sub-project of IMI-PainCare. Patients after breast and endometriosis-related surgery, sternotomy and total knee arthroplasty completed pain-related outcomes questionnaires and wore an ActiGraph activity-tracking device. We correlated steps with average pain intensity on post-operative days 6 and 7. Secondary analyses were done using correlations and t-tests. RESULTS: In 284 cases, there was no statistically significant correlation between steps and average pain intensity. In addition, none of the 28 secondary analyses showed a statistically significant result. CONCLUSIONS: Pain-related patient-reported outcome measures and physical activity are separate entities. Both should be measured after surgery to assess patient recovery and to identify treatment deficiencies. SIGNIFICANCE STATEMENT: Measuring recovery is a multi-dimensional challenge. After surgery, clinicians need to be aware that neither pain intensity nor activity levels tell the whole story. Each can hint to problems and treatment requirements.

[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.

Staff and organizational requirements for pain services in hospitals : A recommendation from the German Society for Anaesthesiology and Intensive Care Medicine.

Although pain services have been established in many hospitals, there is considerable heterogeneity among them with respect to organization of service, staff and qualifications of staff, and treatment approaches.With this recommendation, the German Society for Anesthesiology and Intensive Care Medicine defines requirements for pain services in hospitals with respect to organizational standards and staff qualifications. The therapy offered by pain services supplements the treatment provided by the other departments involved, ensuring the high quality of specialized pain management in all areas of the hospital. Pain services shall oversee treatment with specialized analgesia techniques as well as the involvement of consultants, bringing together in-hospital pain medicine expertise in one service with availability 24 h and 7 days per week via a single contact. The medical head of the pain service shall be a qualified provider of pain medicine as defined by the German Medical Association and as a minimum should also have undergone additional training in basic psychosomatic medicine. Further members of the medical staff should possess the credentials of a medical specialist: non-medical staff should have completed continuing education in the treatment of pain. Minimal guidelines for personnel resources were defined: these included a specific time frame for first contacts (20 min) and follow-up (10 min) for specific analgesic techniques and for the involvement of consultants (first contact 45 min, follow-up 20 min), with additional time for travel, set-up, training and quality management. In addition to definition of the space and equipment needed, each service should draft its own budget, and this should be adequate and plannable. Written agreements between the disciplines and transparent documentation, including patient-reported outcomes, are recommended to ensure quality. The provision of specialized pain therapy should have high priority over all disciplines or departments.

[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.

[Staff and organizational requirements for pain services in hospitals : A recommendation from the German Society for Anaesthesiology and Intensive Care Medicine]. / Personelle und organisatorische Voraussetzungen für Schmerzdienste in Krankenhäusern : Empfehlung der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin e. V.

Although pain services have been established in many hospitals, there is considerable heterogeneity among them with respect to organization of service, staff and qualifications of staff, and treatment approaches.With this recommendation, the German Society for Anesthesiology and Intensive Care Medicine defines requirements for pain services in hospitals with respect to organizational standards and staff qualifications. The therapy offered by pain services supplements the treatment provided by the other departments involved, ensuring the high quality of specialized pain management in all areas of the hospital. Pain services shall oversee treatment with specialized analgesia techniques as well as the involvement of consultants, bringing together in-hospital pain medicine expertise in one service with availability 24 h and 7 days per week via a single contact. The medical head of the pain service shall be a qualified provider of pain medicine as defined by the German Medical Association and as a minimum should also have undergone additional training in basic psychosomatic medicine. Further members of the medical staff should possess the credentials of a medical specialist: non-medical staff should have completed continuing education in the treatment of pain. Minimal guidelines for personnel resources were defined: these included a specific time frame for first contacts (20 min) and follow-up (10 min) for specific analgesic techniques and for the involvement of consultants (first contact 45 min, follow-up 20 min), with additional time for travel, set-up, training and quality management. In addition to definition of the space and equipment needed, each service should draft its own budget, and this should be adequate and plannable. Written agreements between the disciplines and transparent documentation, including patient-reported outcomes, are recommended to ensure quality. The provision of specialized pain therapy should have high priority over all disciplines or departments.

[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.

Predicting drug efficacy in chronic low back pain by quantitative sensory tests.

BACKGROUND: Drugs are prescribed for chronic low back pain without knowing in advance whether a patient will respond to them or not. Quantitative sensory tests (QST) can discriminate patients according to sensory phenotype, possibly reflecting underlying mechanisms of pain processing. QST may therefore be a screening tool to identify potential responders to a certain drug. The aim of this study was to investigate whether QST can predict analgesic effects of oxycodone, imipramine and clobazam in chronic low back pain. METHODS: Oxycodone 15 mg (n = 50), imipramine 75 mg (n = 50) and clobazam 20 mg (n = 49) were compared to active placebo tolterodine 1 mg in a randomized, double-blinded, crossover fashion. Electrical, pressure and thermal QST were performed at baseline and after 1 and 2 h. Pain intensity was assessed on a 0-10 numeric rating scale every 30 min for up to 2 h. The ability of baseline QST to predict pain reduction after 2 h was analysed using linear mixed models. Genetic variants of drug-metabolizing enzymes and genes affecting pain sensitivity were examined as covariables. RESULTS: No predictor of analgesic effect was found for oxycodone and clobazam. Thermal QST was associated with analgesic effect of imipramine: patients more sensitive to heat or cold were more likely to experience an effect of imipramine. Pharmacogenetic variants and pain-related candidate genes were not associated with drug efficacy. CONCLUSIONS: Thermal QST have the potential to predict imipramine effect in chronic low back pain. Oxycodone and clobazam effects could not be predicted by any of the selected QST or genetic variants. SIGNIFICANCE: Predicting drug efficacy in chronic low back pain remains difficult. There is some evidence that patients more sensitive to heat and cold pain respond better to imipramine.

[Role of anesthesiology in pain medicine and palliative care treatment in German hospitals : Survey of department heads of anesthesiology on treatment structures]. / Rolle der Anästhesiologie in der schmerzmedizinischen und palliativmedizinischen Versorgung in deutschen Krankenhäusern : Befragung von Chefärzten der Anästhesiologie zu Versorgungsstrukturen.

BACKGROUND: The aim of this analysis was to describe the role of anesthesiology departments in pain medicine and palliative care services in German hospitals. METHOD: In the year 2012, all heads of departments of anesthesiology registered with the German Society of Anesthesiology and Intensive Care Medicine were surveyed about structures of pain medicine and palliative care services in their hospitals using a standardized postal questionnaire. RESULTS: Out of 408 returned questionnaires (response rate 47%) 403 could be evaluated. Of the hospitals 58% had a designated pain medicine service, in 36 (9%) of the hospitals this was organized as an independent department and in 195 (57%) as part of another department, mostly the department of anesthesiology. The "pain clinic" as an outpatient service was the most common form of structure for pain medicine services (41%). Inpatient pain medicine units were available in 77 (19%) of the hospitals and a partial inpatient unit in the form of a day hospital in 26 (7%) of the hospitals. For the care of inpatients from other departments, there was an intrahospital pain consultation service in 166 of the hospitals, which was the only structure for pain medicine in 32 of the 231 hospitals that reported having a designated pain medicine service. In 160 pain medicine services anesthesiologists were the only medical practitioners and in a further 18 both anesthesiologists and other specialists were available (orthopedist/orthopedic surgeons n = 6, internal medicine n = 4, psychiatrist n = 2, general practitioner = 1 and neurologist n = 1). Only two hospitals had no anesthesiologist in the pain medicine team and for the remaining 51 hospitals no information was provided. In 189 of the 231 hospitals with pain medicine services, there was at least 1 physician with special qualifications in pain management. In 97 (44%) of the hospitals psychologists were part of the team with 53 having at least 1 psychologist with a special qualification in chronic pain management. Of the hospitals, 16% had a specialized department for palliative care, in 32% a specialized palliative care service was part of another department, which was the department of anesthesiology in 30%. Of the hospitals 56% had a palliative care consultation service, 41% had a specialized inpatient palliative care unit, 6% an outpatient clinic, 4% a day hospital and in 16% a specialized outpatient palliative care (SOPC) serving the community was incorporated. Inpatient consultation services and the SOPC were more common when the department of anesthesiology was involved in the palliative care services. CONCLUSION: In German hospitals, the departments of anesthesiology make a significant contribution to the provision of both pain medicine and palliative care services. Nevertheless, the respective structures of care are often incomplete or even lacking. There were shortcomings in terms of organization and qualification of the team in pain medicine services (e.g. no doctor with special qualifications in pain management or no psychologist). Palliative care services are more often organized as independent departments than as pain medicine services. Engagement of the anesthesiology department in palliative care is linked to a broader scope of the services provided, which might reflect the capacity of many anesthesiologists to work in an interdisciplinary manner and across interfaces.

[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.

[Acute pain therapy in German hospitals as competitive factor. Do competition, ownership and case severity influence the practice of acute pain therapy?]. / Akutschmerztherapie in deutschen Krankenhäusern als Wettbewerbsfaktor. Wird die Praxis der Akutschmerztherapie von Wettbewerb, Trägerschaft und Fallschwere beeinflusst?

BACKGROUND: Due to the implementation of the diagnosis-related groups (DRG) system, the competitive pressure on German hospitals increased. In this context it has been shown that acute pain management offers economic benefits for hospitals. The aim of this study was to analyze the impact of the competitive situation, the ownership and the economic resources required on structures and processes for acute pain management. MATERIAL AND METHODS: A standardized questionnaire on structures and processes of acute pain management was mailed to the 885 directors of German departments of anesthesiology listed as members of the German Society of Anesthesiology and Intensive Care Medicine (DGAI, Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin). RESULTS: For most hospitals a strong regional competition existed; however, this parameter affected neither the implementation of structures nor the recommended treatment processes for pain therapy. In contrast, a clear preference for hospitals in private ownership to use the benchmarking tool QUIPS (quality improvement in postoperative pain therapy) was found. These hospitals also presented information on coping with the management of pain in the corporate clinic mission statement more often and published information about the quality of acute pain management in the quality reports more frequently. No differences were found between hospitals with different forms of ownership in the implementation of acute pain services, quality circles, expert standard pain management and the implementation of recommended processes. Hospitals with a higher case mix index (CMI) had a certified acute pain management more often. The corporate mission statement of these hospitals also contained information on how to cope with pain, presentation of the quality of pain management in the quality report, implementation of quality circles and the implementation of the expert standard pain management more frequently. There were no differences in the frequency of using the benchmarking tool QUIPS or the implementation of recommended treatment processes with respect to the CMI. CONCLUSION: In this survey no effect of the competitive situation of hospitals on acute pain management could be demonstrated. Private ownership and a higher CMI were more often associated with structures of acute pain management which were publicly accessible in terms of hospital marketing.

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.

[Inpatient acute pain management in German hospitals: results from the national survey "Akutschmerzzensus 2012"]. / Akutschmerztherapie in der stationären Versorgung an deutschen Krankenhäusern : Ergebnisse des Akutschmerzzensus 2012.

BACKGROUND: In 2007, the German national guidelines on "Treatment of acute perioperative and post-traumatic pain" were published. The aim of this study was to describe current structure and process data for acute pain management in German hospitals and to compare how the guidelines and other initiatives such as benchmarking or certification changed the healthcare landscape in the last decade. METHODS: All directors of German departments of anesthesiology according to the DGAI ("Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin", German Society for Anesthesiology and Intensive Care) were mailed a standardized questionnaire on structures and processes of acute pain management in their hospitals. RESULTS: A total of 403 completed questionnaires (46 %) could be evaluated. Of hospitals, 81 % had an acute pain service (ASD), whereby only 45 % met defined quality criteria. Written standards for acute pain management were available in 97 % of the hospitals on surgical wards and 51 % on nonsurgical wards. In 96 %, perioperative pain was regularly recorded (generally pain at rest and/or movement, pain-related functional impairment in 16 % only). Beside these routine measurements, only 38 % of hospitals monitored pain for effectiveness after acute medications. Often interdisciplinary working groups and/or pain managers are established for hospital-wide control. As specific therapy, the patient-controlled analgesia and epidural analgesia are largely prevalent (> 90 % of all hospitals). In the last decade, intravenous and oral opioid administration of opioids (including slow release preparations) has become established in acute pain management. CONCLUSION: The survey was representative by evaluating 20 % of all German hospitals. The organizational requirements for appropriate pain management recommended by the German guidelines for acute pain recommended have been established in the hospital sector in recent years. However, the organizational enforcement for acute pain management in nonsurgical areas is not adequate yet, compared to the perioperative care. In all hospitals modern medication and invasive techniques are widely available.

[Postoperative pain management after ambulatory surgery. A survey of anaesthesiologists]. / Postoperative Schmerztherapie nach ambulanten Operationen. Eine Befragung der behandelnden Anästhesisten.

BACKGROUND: Data on practice and quality of postoperative pain treatment by anaesthesiologists after ambulatory surgery are sparse. The current survey enrolled anaesthesiologists in private practice who were responsible for pain therapy after ambulatory surgery. The aim of this investigation was to evaluate the implementation of the German S3 guidelines for acute and postoperative pain therapy in the outpatient setting. PATIENTS AND METHODS: A total of 2,156 anaesthesiologists in private practice received a postal questionnaire which was limited to those anaesthesiologists who were responsible for postoperative pain therapy. The questionnaire included items such as types of surgery, techniques of anaesthesia and analgesic drugs used for pain management during the immediate postoperative phase and for the treatment at home as well as details of pain measurement. RESULTS: Out of 116 responses 108 could be analyzed covering a total of 86,616 patients receiving postoperative pain therapy, 80% of the operations were performed using general anaesthesia and local anaesthesia was additionally used in 9% of the institutions. In the perioperative period 66% of the respondents administered non-steroidal-antiinflammatory drugs (NSAIDs), 62% metamizol (dipyrone), 41% paracetamol (acetaminophen) and 73% opioids. After discharge 81% of the responding anaesthesiologists prescribed NSAIDs, 55% metamizol and 47% opioids for pain relief at home. Only 40% of the respondents measured and documented pain intensity. Nearly all respondents (93%) were satisfied with their pain management after outpatient surgery. CONCLUSIONS: Pain therapy after ambulatory surgery significantly varied with respect to the methods, drugs and measures of quality assurance used by anaesthesiologists in private praxis. This survey demonstrated that the national guidelines of acute pain therapy have only been partially implemented.