[Palliative therapy concepts in intensive care medicine]. / Palliative Therapiekonzepte in der Intensivmedizin.

Involvement of palliative care is so far not common practice for critically ill patients on surgical intensive care units (ICUs) in Germany. The objectives of palliative care concepts are improvement of patient quality of life by relief of disease-related symptoms using an interdisciplinary approach and support of patients and their relatives considering their current physical, psychological, social and spiritual needs. The need for palliative care can be identified via defined screening criteria. Integration of palliative care can either be realized using a consultative model which focusses on involvement of palliative care consultants or an integrative model which embeds palliative care principles into the routine daily practice by the ICU team. Early integration of palliative care in terms of advance care planning (ACP) can lead to an increase in goals of care discussions and quality of life as well as a decrease of mortality and length of stay on the ICU. Moreover, stress reactions of relatives and ICU staff can be reduced and higher satisfaction with therapy can be achieved. The core of goal of care discussions is professional and well-structured communication between patients, relatives and staff. Consideration of palliative care principles by model-based integration into ICU practice can improve complex intensive care courses of disease in a productive but dignified way without neglecting curative attempts.

[Cross-sectional field pain medicine Q14 - the Mainz model : Development of the pain medicine curriculum in the standard study course at the University Medical School of the Johannes Gutenberg University Mainz]. / Querschnittsfach Schmerzmedizin Q14 ­ das Mainzer Modell : Die Entwicklung des Curriculums Schmerzmedizin im Regelstudiengang Humanmedizin an der Universitätsmedizin der Johannes Gutenberg-Universität Mainz.

BACKGROUND AND OBJECTIVES: Following the amendment of the Medical Licensure Act (ÄAppO) in 2012, pain medicine was introduced as a mandatory subject for students during undergraduate medical training. Medical schools were required to define and to implement adequate curricular and formal teaching structures based on interdisciplinary and multiprofessional requirements according to the curriculum for pain medicine of the German Pain Society. These aspects were considered in the new interdisciplinary curriculum for pain medicine, the so-called Mainz model. STUDY DESIGN AND METHODS: A new curriculum based on the Kern cycle was developed and implemented at the Medical Center of the Johannes Gutenberg University in Mainz. Different teaching methods (lectures, interprofessional tutorials and bedside coaching in small groups) were used to impart professional expertise in pain medicine to medical students in an interdisciplinary clinical context. RESULTS: The new curriculum was put into practice and evaluated starting from the winter semester 2014/2015. Before and after the first implementation, medical students were asked about the relevance of pain medicine and their perception of personal competence. CONCLUSION: The interdisciplinary course in pain medicine was successfully introduced into the degree program based on the curriculum of the German Pain Society and the Kern cycle. With educational support, interdepartmental and multiprofessional collaboration the process of implementation of new interdisciplinary courses can be facilitated. In the future, the question how to increase the amount of practical lessons without increasing the load on teaching resources has to be resolved. Blended learning modules, such as a combination of E­learning and practical lessons are currently being studied in smaller cohorts.

[Palliative sedation at a university palliative care unit--a descriptive analysis]. / Palliative Sedierung auf einer universitären Palliativstation.

BACKGROUND: Palliative sedation (pS) is indicated in the presence of end-stage disease with treatment-refractory symptoms not tolerable for the patient. We investigated the practice of pS at a university palliative care unit. METHODS: Before starting pS the following data were documented: indication and decision making, type of sedation, life expectancy evaluated by the physician using the palliative prognostic index. Over the time of pS communication skills, depth of sedation, relief in symptoms, substitution of fluid and nutrition and used medications were collected. RESULTS: During evaluation time 99 patients died. 34 patients received pS (34 %). All patients suffered from cancer. Indications for palliative sedation were: terminal restlessness (56 %), dyspnea (39 %), pain (32 %), psychological distress (15 %), agitated delir (9 %), vomiting (3 %) and bleeding (3 %) (multiple nominations possible). In 31 cases (91 %) nurses were included for decision making. In 33 cases continuous sedation were initiated immediately (median duration 27.5 hours). The most applied medication was midazolam (94 %), sometimes combined with neuroleptics (44 %) and propofol (15 %). 91 % of the patients additionally received opioids. Artificial fluid was substituted in two cases. Palliative sedation started in the median 27.5 hours before death. The final physician assessment revealed complete symptom relief in 12 patients (35 %), very strong symptom relief in 20 patients (59 %) and moderate symptom relief in 2 patients (6 %). CONCLUSIONS: pS was successfully used as last resort for relief of treatment-refractory symptoms in one third of decedents at the investigated palliative care unit.

[Relevance of preoperative anxiety for postoperative outcome in urological surgery patients: A prospective observational study]. / Bedeutung präoperativer Angst für den postoperativen Verlauf bei urologischen Patienten : Eine prospektive Beobachtungsstudie.

BACKGROUND: Preoperative anxiety is not systematically assessed during premedication appointments, although it may influence the postoperative course and outcome. OBJECTIVES: The aim of this study was to assess preoperative anxiety in a sample of patients before major urological surgery and to characterize the impact on postoperative pain. An additional aim was to analyze the agreement between patients' self-ratings and physicians' anxiety ratings. PATIENTS AND METHODS: In all, 127 male and 27 female patients participated in a prospective observational study. Preoperative anxiety was assessed with two validated instruments - the APAIS (Amsterdam Preoperative Anxiety and Information Scale) and the State Scale of the STOA questionnaire (State-Trait Operation Anxiety) - during the premedication appointment. Physicians provided their subjective ratings on patients' anxiety and need for information using the APAIS. The predictive value of preoperative anxiety for postoperative pain was evaluated. RESULTS: Nearly four out of ten patients were identified as "anxiety cases"; thereof women were more afraid than men were. Preoperative anxiety was not correctly assessed by physicians, who overestimated patients' anxiety. In female patients, preoperative anxiety was predictive of increased postoperative pain scores. CONCLUSION: Preoperative anxiety is a frequent concern and often not correctly assessed by physicians. The use of scoring systems to detect preoperative anxiety is useful in clinical routine and helps to decide on therapeutic interventions.

Development of a new multi-analyte assay for the simultaneous detection of opioids in serum and other body fluids using liquid chromatography-tandem mass spectrometry.

A liquid chromatography-tandem mass spectrometry method using electrospray ionization in positive ionization mode was developed for the simultaneous detection of multiple opioid-type drugs in plasma. The presented assay allows the quantitative determination of alfentanil, buprenorphine, codeine, desomorphine, dextromethorphan, dextrorphan, dihydrocodeine, dihydromorphine, ethylmorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, naloxone, naltrexone, oxycodone, oxymorphone, pentazocine, pethidine, pholcodine, piritramide, remifentanil, sufentanil, and tramadol as well as the metabolites 6-monoacetylmorphine, bisnortilidine, morphine-3-glucuronide, morphine-6-glucuronide, naltrexol, norbuprenorphine, norfentanyl, norpethidine, nortilidine, and O-desmethyltramadol. Serum and blood samples were purified by solid-phase extraction. The analytes were separated on a phenyl-hexyl (100mm) column by formic acid/acetonitrile gradient elution using an UPLC 1290 Infinity coupled with a 6490 Triple Quadrupole mass spectrometer. The limits of detection ranged from 0.02 to 0.6ng/mL and the lower limits of quantification ranged from 0.1 to 2.0ng/mL. The calibration curves were linear between Calibration Levels 1-6 for all 35 substances. Recovery rates ranged between 51 and 88% for all compounds except alfentanil, bisnortilidine, pethidine, and morphine-3-glucuronide. The matrix effect ranged from 86% for ethylmorphine to 105% for desomorphine. Using the validation procedure proposed by the German Society of Toxicological and Forensic Chemistry, acceptable precision and accuracy data for almost all analytes were obtained. The method was successfully applied to 206 authentic serum samples provided by the palliative and intensive care units of the University Medical Center and the police authorities. Furthermore, a suspected fatal intoxication is demonstrated by an analysis of the sufentanil in post mortem body fluids and tissues.

[Question prompt list for premedication consultation : Patient-oriented information on anesthesia]. / Fragen-Identifikationsliste für das Prämedikationsgespräch : Patientenorientiertes Informieren in der Anästhesie.

BACKGROUND: The anesthesia premedication consultation is an obligatory procedure prior to any upcoming surgery. It is the anesthesiologist's responsibility to collect all necessary information regarding the patient's medical condition to decide on the appropriate narcosis and to ensure that the patient comprehends the anesthesia procedure and its effects. AIM: Information needs of patients regarding anesthesia are often not adequately fulfilled. This study was carried out to develop a structured questionnaire containing questions that patients may wish to ask the anesthesiologist (question prompt list anesthesiology QPL-A) to support information transfer from the anesthesiologist to the patient in the premedication consultation. The questionnaire should measure the information needs of the patient regarding different aspects of the anesthesia process with good psychometric qualities. MATERIAL AND METHODS: Based on a literature review and interviews with experts a list of anesthesia-related questions was developed and distributed to patients receiving premedication consultation at the University Medical Center in Mainz, Germany (n = 202). In addition, patients were also asked to complete the state trait operation anxiety inventory (STOA). RESULTS: Using principal component analysis and subsequent varimax rotation (declaration of total variance 68 %), four reliable information needs scales were extrapolated: (1) anesthesia procedure and effects (QPL-A-E, α = 0.92), (2) anesthesia safety (QPL-A-S, α = 0.86), (3) advice concerning preanesthesia behavior (QPL-A-B, α = 0.85) and (4) anesthetists actions (QPL-A-A, α = 0.79). In order to obtain sufficient information regarding the QPL-A-S, the procedure itself and its effects (QPL-A-E) were found to be of greatest importance for the patients and behavioral changes (QPL-A-B), e. g. stopping smoking, were judged to be less important by the patients. Women scored higher on the QPL-A-E (U-test p ≤ 0.001) and QPL-A-A (U-test p ≤ 0.05) than men. Elderly patients (≥ 70) showed significantly more interest in safety information (QPL-A-S) than younger patients (≤ 39, U-test p ≤ 0.05). All scales showed a significant positive correlation with STOA trait anxiety (r = 0.29-0.50) but only the QPL-A-E and the QPL-A-S scales were associated with STOA state anxiety (QPL-A-E: affective r = 30, cognitive r = 0.36, both p ≤ 0.001; QPL-A-S: affective r = 19, p ≤ 0.05, cognitive r = 0.23, p ≤ 0.01). Self-assessed knowledge on narcosis correlated only weakly with the QPL-A-E (r = 0.21 p ≤ 0.01) but not with the other information areas. Information needs were not associated with the education level of the patient, American Society of Anesthesiologists (ASA) classification and malignancy of the disease. Most of the participants (77 %) evaluated the QPL-A to be very or fairly helpful for the expression of their information needs. CONCLUSION: The QPL-A is a useful tool for meeting the subjective information needs of patients which could improve the patient orientation of the anesthesia premedication consultation.

[Risk consideration for peridural catheter removal in acute coronary syndrome. Epidural hematoma versus stent thrombosis]. / Risikoabwägung vor Periduralkatheterentfernung bei akutem Koronarsyndrom. Epidurales Hämatom vs. Stent-Thrombose.

Perioperative pain therapy using an epidural catheter is the standard operating procedure for numerous surgical interventions. The necessity of initiating anticoagulant therapy in a patient with an epidural catheter requires a careful weighing up between thromboembolic complications and epidural hematoma. The case presented here of a 47-year-old female patient who was operated on for mastectomy with a latissimus dorsi myocutaneous flap demonstrates a possible solution to this dilemma. The patient sustained a perioperative ST elevation myocardial infarction treated with drug-eluting stents while undergoing epidural pain therapy. By using the short-acting antiplatelet drug tirofiban over a time period of 7 days the gap for dual antiplatelet therapy was reduced with the help of specific platelet aggregation assays to a time frame of a few hours to minimize the risk of stent thrombosis. The epidural catheter was removed without complications under consideration of the current recommendations for regional anesthesia and antithrombotic agents.

[Cancer pain in palliative medicine]. / Tumorschmerz in der Palliativmedizin.

During the course of cancer progression up to 90% of the patients suffer from pain of nociceptive, neuropathic or mixed nociceptive/neuropathic origin. Psychological, social or existential factors may additionally affect the intensity of pain (concept of "total pain"). The WHO "analgesic ladder" provides a large variety of effective drugs that can be used according to the specific pain type. Parenteral or peridural opioid therapy as well as neurodestructive methods can effectively support the analgesic treatment in selected cases.

[Cancer pain in palliative medicine]. / Tumorschmerz in der Palliativmedizin.

During the course of cancer progression up to 90% of the patients suffer from pain of nociceptive, neuropathic or mixed nociceptive/neuropathic origin. Psychological, social or existential factors may additionally affect the intensity of pain (concept of "total pain"). The WHO "analgesic ladder" provides a large variety of effective drugs that can be used according to the specific pain type. Parenteral or peridural opioid therapy as well as neurodestructive methods can effectively support the analgesic treatment in selected cases.

[Save life--allow death. Collation of emergency missions for terminally ill patients]. / Leben retten--sterben zulassen. Erfassung notärztlicher Einsätze bei Patienten in der Terminalphase.

BACKGROUND: Emergency missions can also be necessary for patients in the terminal phase of a progressive incurable disease. The emergency physician, accustomed to acting under strict procedures and whose training focuses on the restoration and stabilization of acutely threatened vital functions, can face severe difficulties when treating incurably ill patients in the terminal phase. This study investigates the number of such cases, patient symptoms and the events occurring during life-threatening emergencies of terminally ill patients. METHOD: All cases of emergency events involving terminally ill patients were analyzed prospectively. In addition to the standardized protocol (following DIVI/Mind 2) an enquiry sheet was used, which contained an 8-item checklist specifically for terminally ill patients, to be filled out by the responding physician. RESULTS: The total number of patients in the terminal phase identified by the emergency physician was 55 (0.72% of total cases) and of these patients 30 (55%) were tumor patients. The most frequent complaint observed was dyspnea (30 patients, 55%), followed by relatives of the patients experiencing the stress of caring for a terminally ill person (19 patients, 35%). The leading symptom of 6 patients (11%) was pain. Only 17 cases (30.9%) required transport of the patient to hospital for further treatment. CONCLUSION: Every emergency physician can be confronted with an emergency involving a patient with a progressive incurable disease. The condition of each patient must be assessed for each medical decision. Not only medical, but also psychosocial, ethical and legal aspects have to be considered.

[Drugs for postoperative analgesia: routine and new aspects: Part 2: opioids, ketamine and gabapentinoids]. / Medikamente zur postoperativen schmerztherapie: bewährtes und neues : Teil 2: Opioide, ketamin und gabapentinoide.

In part 1 of this review, perioperative aspects of the use of non-opioids (acetaminophene, dipyrone, traditional NSAR, coxibs) were discussed. In part 2 the perioperative aspects of opioids (weak opioids: tramadol, tilidine with naloxone, strong opioids: morphine, piritramide, oxycodone, hydromorphone, fentanyl, methadone, buprenorphine) and coanalgesics (gabapentinoids; ketamine) will now be presented. The main aim of the review is to describe the use, risks and cost of some substances to facilitate the differential indication. New aspects concerning the use of gabapentinoids and ketamine are discussed.

[Drugs for postoperative analgesia: routine and new aspects. Part 1: non-opioids]. / Medikamente zur postoperativen Schmerztherapie: Bewährtes und Neues. Teil 1: Nichtopioide.

In part 1 of this review the perioperative aspects of the use of non-opioids (acetaminophen, dipyrone, traditional NSAR, coxibs) and in part 2 of opioids (weak opioids: tramadol, tilidine with naloxone, strong opioids: morphine, piritramide, oxycodone, hydromorphone, fentanyl, methadone, buprenorphine) and coanalgesics (gabapentinoids, ketamine) will be discussed. The main aim is to describe the relationship between analgesic efficacy and side effects to make clinical decisions easier in patients with preoperative renal, gastrointestinal, cardiovascular and other diseases. Some new aspects concerning perioperative administration of gabapentinoids and ketamine in patients with perioperative neuropathic pain are discussed.

The early immune response in the liver of BALB/c mice infected with S. typhimurium.

Gram-negative bacteria acquired through gastrointestinal infection can be a serious cause for the development of septic shock especially in immunosuppressed patients. Thus, the aim of this study was to examine the early events of the immune reaction against S. typhimurium. Bacteria were injected into mice at different concentrations. Four animals from each group were killed at five different points of time. Liver cytokine mRNA expression was determined by semiquantitative rt-PCR and liver histology was examined. Serum cytokine levels of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-4 and IL-10 were determined. intravenous (i.v.) infection with 109 bacteria led to lethal septic shock within 24 h. A delayed production of IFN-gamma, TNF-alpha, IL-18 and IL-10 and milder histological alterations in the liver were observed in these animals. The highest expression of cytokines in the liver and the strongest histological alterations were seen after infection with 107 bacteria. Here, an increased mRNA expression of all proinflammatory cytokines began 1 h after infection. Animals infected with 1 x 102 bacteria had the highest detectable serum levels of IL-6 and IL-10. These data indicate that the immediate events in the immune reaction within the liver after infection with S. typhimurium are associated with the outcome of the subsequent sepsis.

Characterization of polymorphisms in the toxin A and B genes of Clostridium difficile.

We have used six independent polymerase chain reactions (A1-A3 and B1-B3) for amplification of the entire sequence of the two toxin genes tcdA and tcdB of several Clostridium difficile strains. With this approach we have detected (1) restriction site polymorphisms which are distributed all over the genes, and (2) deletions that could be found only in tcdA. Characteristic differences between strains were mainly focused to the 5' third of tcdB (B1 fragment) and/or the 3' third of tcdA (A3 fragment). The possible use of our approach for typing of C. difficile toxin genes is discussed.

Comparative sequence analysis of the Clostridium difficile toxins A and B.

The six clones pTB112, pTB324, pTBs12, pCd122, pCd14 and pCd13 cover the tox locus of Clostridium difficile VPI 10463. This region of 19 kb of chromosomal DNA contains four open reading frames including the complete toxB and toxA genes. The two toxins show 63% amino acid (aa) homology, a relatedness that had been predicted by the cross-reactivity of some monoclonal antibodies (mAb) but that is in contrast to the toxin specificity of polyclonal antisera. A special feature of ToxA and ToxB is their repetitive C-termini. We define herein 19 individual CROPs (combined repetitive oligopeptides of 20-50 aa length) in the ToxB C-terminus, which are separable into five homologous groups. Comparison of the aa sequences of the N-terminal two-thirds of ToxA and ToxB revealed three marked structures, a cluster of 172 hydrophobic, highly conserved aa in the centre of both toxins, a sequence of 120 residues with an accumulation of highly conserved arginine, cysteine, histidine, methionine, and tryptophan residues, and a stretch of 248 less conserved aa. The probable function of these domains is discussed. Structural and functional homologies of ToxA and ToxB indicate that both genes have a common ancestor and may have evolved by gene duplication, with subsequent recombination and mutation, as has been reported for streptococcal glucosyltransferases (Gtf).

Cloning of Clostridium difficile toxin B gene and demonstration of high N-terminal homology between toxin A and B.

High titered Clostridium sordellii lethal toxin antiserum, cross-reactive with C. difficile cytotoxin B (ToxB), was used to isolate toxB fragments from a C. difficile expression library. Recombinant clones containing toxB fragments of the 5' and 3' end were isolate. A 2.5-kb HincII fragment of chromosomal DNA overlaps both groups of clones. A partial restriction map of the total toxB gene is presented. The gene is positioned upstream of utxA and toxA, toxB has a size of 6.9 kb, corresponding to a 250-kDa polypeptide. A partial sequence of the 5' end of toxB was determined. The sequence contains 398 bp upstream of toxB with a putative Shine-Dalgarno box (AGGAGA) and 609 bp of the toxB open reading frame. The N-terminal 203 amino acids of ToxB were compared with the N-terminal amino acids of the enterotoxin A (ToxA). A homology of 64% of the residues was detected, which proves the relatedness of ToxA and ToxB of C. difficile.