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Biomedical subjects

Ulrike M Stamer

Publications and source records attributed to Ulrike M Stamer.

9 recordsLinked to original sources

Enantiomeric determination of tramadol and O-desmethyltramadol by liquid chromatography- mass spectrometry and application to postoperative patients receiving tramadol.

A liquid chromatographic-mass spectrometric assay with atmospheric pressure chemical ionization is presented for quantification (selected-ion mode) of tramadol (T) and O-desmethyltramadol (ODT) in blood plasma after liquid-liquid extraction. The enantiomeric separation was achieved on a Chiralpak AD column containing amylose tris-(3,5-dimethylphenylcarbamate) as chiral selector. The validation data were within acceptable limits. The assay was successfully applied to authentic plasma samples allowing confirmation of diagnosis of overdose or intoxication as well as monitoring of patients' compliance. In postoperative patients receiving T, mean therapeutic plasma concentrations were determined as follows: 422.8 and 440.8 ng/mL for (+)-T and (-)-T, respectively, and 23.7 and 40.7 ng/mL for (+)-ODT and (-)-ODT, respectively. Quantitative results demonstrated a great interindividual variability in postoperative plasma analgesic drug concentrations and, therefore, a wide therapeutic concentration range. The 7.7% of the samples that revealed negative results for ODT are likely explained by genetic polymorphisms resulting in absent enzyme activity of CYP2D6.

Analgesics, Opioid↗

Genetics and variability in opioid response.

The human genome project has revealed data on genomic variation which may influence the pharmacological responses. In pain therapy, the genetic background influencing the efficacy of opioid therapy is of special interest. Screening for variations in expression of drug metabolizing enzymes has been suggested as a potential tool for improving patient therapy. CYP2D6 genetic variability is supposed to be a major factor of adverse drug reaction, possibly influencing hospital stay and total costs. Further candidate genes involved in pain perception, pain processing and pain management like opioid receptors, transporters and other targets of pharmacotherapy are under investigation. Aspects of genetic differences influencing efficacy, side effects and adverse outcome of pharmacotherapy will be of importance for future pain management.

Analgesics, Opioid↗

Postoperative analgesia in children--current practice in Germany.

German departments of anaesthesia were surveyed to determine current practice of postoperative pain management in children. The response rate of the survey was 58.6%: Questionnaires of 383 departments in which paediatric surgery was performed could be analyzed. 37.3% operated an acute pain service (APS). In 58.8% of the hospitals, postoperative pain management in children was mainly performed by surgeons or pediatricians. Anaesthesiologists or an APS were in charge for pain management in children in 38.6% of the institutions. Non-opioid analgesics were the drugs most widely used (93.4%), whereas i.v. opioids were never used in 20.9% of the hospitals and used less than once a week in 28.7%. The intramuscular route was chosen at least occasionally by 27.7% of the respondents. Peripheral and central regional techniques were performed in most of the departments, however, frequency of use varied considerably between hospitals running or not running an APS. The majority performed the techniques of regional anaesthesia less than once a week. The basic primary quality criterion of pain therapy, a regular measurement and documentation of pain scores, was performed in only 4% of the institutions. Paediatric pain management does not meet quality criteria and standards of care already established in adults. In the future, additional education of the medical staff considering analgesic techniques and measurement of pain scores has to be emphasized.

Analgesics↗

Impact of CYP2D6 genotype on postoperative tramadol analgesia.

Genetic polymorphisms result in absent enzyme activity of CYP2D6 (poor metabolizers, PM) in about 10% of the Caucasian population. This study investigates whether the PM genotype has an impact on the response to tramadol analgesia in postoperative patients. A prospective study design was used and 300 patients recovering from abdominal surgery were enrolled. After titration of an individual loading dose, patients could self-administer 1 ml bolus doses of the drug combination tramadol 20 mg/ml, dipyrone 200 mg/ml and metoclopramide 0.4 mg/ml via patient-controlled analgesia (PCA). Patients' genotype was analyzed considering the most prevalent PM associated CYP2D6 mutations using a real-time PCR and hybridization based genotyping method. Demographic data, surgery related variables, pain scores, analgesic consumption and need for rescue medication were compared between extensive metabolizers (EM) and PM. The primary outcome criterion 'response' was defined as responder or non-responder status by the need for rescue medication and patients' satisfaction at the final interview. Demographic and surgery related data were comparable between EM (n=241) and PM (n=30). The percentage of non-responders was significantly higher in the PM group (46.7%) compared with the EM group (21.6%; p=0.005). Tramadol loading dose amounted to 108.2+/-56.9 and 144.7+/-22.6 mg (p<0.001) in EM and PM, respectively. More patients displaying the PM genotype needed rescue medication in the recovery room and during PCA period than patients with at least one wild type allele (21.6 versus 43.3%, p=0.02). PM for CYP2D6 showed a lower response rate to postoperative tramadol analgesia than EM. Therefore, CYP2D6 genotype has an impact on analgesia with tramadol. Pharmacogenetics may explain some of the varying response to pain medication in postoperative patients.

Adult↗

Anaesthesia for non-scheduled caesarean delivery.

In many countries there has been an increase in the number of women who deliver by caesarean section. This article reviews anaesthetic management of non-scheduled caesarean section. The choice of anaesthetic technique (regional anaesthesia versus general anaesthesia) is discussed and highlighted particularly from the viewpoint of urgency of operative delivery. A multidisciplinary approach is mandatory especially in emergency cases to prevent morbidity and mortality in mothers and neonates.

Journal Article↗

Rapid and reliable method for cytochrome P450 2D6 genotyping.

BACKGROUND: Single-nucleotide polymorphisms and single-base deletions within the cytochrome P450 2D6 (CYP2D6) gene have been associated with a poor metabolizer (PM) phenotype and display a frequency of 7-10% in the Caucasian population. METHODS: We developed a reliable and rapid procedure to identify five major PM-associated mutations (CYP2D6*4, *7, and *8) and deletions (CYP2D6*3 and *6) by real-time PCR with subsequent fluorometric melting point analysis of the PCR product. These polymorphisms within the CYP2D6 gene were detected by use of two primer pairs and five different pairs of hybridization probes. DNA extracted from whole blood of 323 individuals was analyzed, and results were compared with genotypes obtained by allele-specific multiplex PCR. In case of uncertain results, additional sequence analysis was performed. RESULTS: Genotyping results by real-time PCR were 100% reliable, whereas conventional allele-specific multiplex PCR produced uncertain results for 12.1% of samples, as confirmed by sequence analysis. Costs for reagents and consumables were considerably higher for the real-time PCR technology, but labor time was reduced by 2 h compared with allele-specific PCR. The allele frequencies in the population investigated were 0.186 for allele *4, 0.026 for allele *5, 0.009 for allele *3, 0.031 for allele *6, and 0.002 for allele *8. The defective CYP2D6*7 allele was not found. In addition, three additional mutations were detected, one of them displaying a PM genotype. CONCLUSION: Genotyping of CYP2D6 by real-time PCR with fluorometric melting point analysis is a rapid and reliable method.

Cytochrome P-450 CYP2D6↗

A survey of acute pain services in Germany and a discussion of international survey data.

BACKGROUND AND OBJECTIVES: Acute pain services (APS) have been introduced worldwide to improve postoperative pain management. However, data are lacking on organization and quality of these services in Germany. METHODS: A questionnaire on postoperative pain management was mailed to 773 departments of anesthesiology. Practice was compared between hospitals with and without APS and between services that did or did not meet basic quality criteria (QC): personnel assigned for APS, policies during nights and weekends, written protocols of pain management, and regular assessment and documentation of pain scores at least once a day. RESULTS: With 446 responding hospitals, 161 operated an APS. Large hospitals organized an APS more frequently than smaller hospitals (P <.001). Staff being assigned for the APS comprised anesthesiologists in 68.3% and nurses in 23.6% of the departments. In total, only half of the APS complied with basic QC. Regular assessment and documentation of pain scores were the QC most often missing (46.6%). Patient-controlled analgesia (PCA) was performed in 93.8%, 74.1%, and 69.8% of the departments providing APS with QC, APS without QC, and no APS. Epidural analgesia (EA) was available in nearly all departments (96.9%). A total of 75.6% of the departments performed EA on general wards (with QC: 93.8%, without QC: 82.7%, and no APS: 68.4%, P <.001). Frequency of PCA and EA use was highest in hospitals providing an APS with QC. CONCLUSIONS: As 50% of German APS do not comply with QC, we believe structured policies, as well as quality assurance measures, should be emphasized in the future. A comparison to international survey data showed that APS, in general, often do not consider QC.

Analgesia, Epidural↗