Intraoperative suggestions to prevent postoperative delirium in patients undergoing transaortic valvular replacement: a randomized placebo-controlled trial.

BACKGROUND: Postoperative delirium (POD) is a serious complication following anaesthesia and surgery and significantly influences postoperative outcome especially in the elderly population. Intraoperative music and positive suggestions influence postoperative outcomes by attenuating analgesic demand and increasing patient satisfaction. AIMS: Here, we examined the effect of intraoperative music and positive suggestions on the development of POD in aged patients undergoing transcatheter aortic valve replacement (TAVR) procedure under general anaesthesia. METHODS: For this randomized placebo-controlled study, eligible patients without cognitive deficit, indicated by a MMSE < 10 points, were anesthetized using remifentanil and sevoflurane. Anaesthetic depth was guide with bispectral index. An audiotape with positive suggestions was applied from a MP3 player via headphones. POD, pain and PONV was assessed. CAM-ICU and Nu-DESC were done twice daily for the first 5 days. RESULTS: Of 140 patients 118 patients could be analysed (57 male, 80.6 ± 5.1 years). POD was diagnosed in 16 patients (12.7%). POD was significantly more often observed in male (12, 21.1%) than in female (4, 6.6%, p = 0.02) and in patients with a low MMSE (23.6 ± 4.5 vs. 26.8 ± 2.8, p = 0.001). Anaesthetic depth did not influence the incidence of POD. Intraoperative music and suggestions did not affect the rate of POD, pain, analgesic requirement or PONV. DISCUSSION: In patients undergoing TAVR male sex and low MMSE scoring are associated with an increase in POD. CONCLUSIONS: Intraoperative music and positive suggestions do not influence the incidence of POD in this patient group. STUDY REGISTRATION: DRKS: 00024444, start of registration: 4.02.202, final registration: 17.09.2021.

Evaluation of comprehensiveness and reliability of electronic health records concerning resuscitation efforts within academic intensive care units: a retrospective chart analysis.

BACKGROUND: According to the literature, the validity and reliability of medical documentation concerning episodes of cardiopulmonary resuscitation (CPR) is suboptimal. However, little is known about documentation quality of CPR efforts during intensive care unit (ICU) stays in electronic patient data management systems (PDMS). This study analyses the reliability of CPR-related medical documentation within the ICU PDMS. METHODS: In a retrospective chart analysis, PDMS records of three ICUs of a single university hospital were searched over 5 y for CPR check marks. Respective datasets were analyzed concerning data completeness and data consistency by comparing the content of three documentation forms (physicians' log, nurses' log, and CPR incident form), as well as physiological and therapeutic information of individual cases, for missing data and plausibility of CPR starting time and duration. To compare data reliability and completeness, a quantitative measure, the Consentaneity Index (CI), is proposed. RESULTS: One hundred sixty-five datasets were included into the study. In 9% (n = 15) of cases, there was neither information on the time points of CPR initiation nor on CPR duration available in any data source. Data on CPR starting time and duration were available from at least two data sources in individual cases in 54% (n = 90) and 45% (n = 74), respectively. In these cases, the specifications of CPR starting time did differ by a median ± interquartile range of 10.0 ± 18.5 min, CPR duration by 5.0 ± 17.3 min. The CI as a marker of data reliability revealed a low consistency of CPR documentation in most cases, with more favorable results, if the time interval between the CPR episode and the time of documentation was short. CONCLUSIONS: This study reveals relevant proportions of missing and inconsistent data in electronic CPR documentation in the ICU setting. The CI is suggested as a tool for documentation quality analysis and monitoring of improvements.

In Vivo Effects of Neostigmine and Physostigmine on Neutrophil Functions and Evaluation of Acetylcholinesterase and Butyrylcholinesterase as Inflammatory Markers during Experimental Sepsis in Rats.

INTRODUCTION: Recent studies have shown that acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) may serve as important diagnostic and therapeutic targets in sepsis. Since polymorphonuclear neutrophils (PMNs) play a pivotal role in the early phase of sepsis, we evaluated the potential therapeutic effects of cholinesterase inhibitors on PMN functions during cecal ligation and puncture- (CLP-) induced sepsis and investigated the roles of AChE and BChE as inflammatory markers under standardized experimental conditions. METHODS: Sham surgery or CLP was performed in male Wistar rats (n = 60). Animals were randomized into four groups: physostigmine, 100 µg/kg; neostigmine, 75 µg/kg; 0.9% saline (control group); and sham group, each applied four times over 24 h. The levels of reactive oxygen species (ROS) production and CD11b/CD62l expression were quantified by flow cytometry at t = 0, 6, 15, 20, and 24 h. Blood gas analysis as well as AChE and BChE activity levels was measured by validated point-of-care measurements. Clinical scores and survival times were determined. RESULTS: CLP induced a significant increase in ROS production and CD11b upregulation by rat PMNs. Treatment with physostigmine or neostigmine significantly reduced ROS production and CD11b upregulation by PMNs 20 h after CLP induction. In physostigmine-treated animals, survival times were significantly improved compared to the control animals, but not in neostigmine-treated animals. While AChE activity significantly decreased in the control animals at t > 6 h, AChE activity did not change in the sham group. BChE activity decreased at t > 20 h in the control animals. CONCLUSION: While AChE activity may serve as an acute inflammatory marker, BChE activity shows a delayed decrease. Administration of centrally acting physostigmine in CLP-induced sepsis in rats has protective effects on PMN functions and improves survival times, which may be of interest in clinical practice.

The positive allosteric modulation of GABAA receptors mRNA in immature hippocampal rat neurons by midazolam affects receptor expression and induces apoptosis.

Background: Numerous experimental studies show that anesthetics are potentially toxic to the immature brain. Even though benzodiazepines are widely used in pediatric anesthesia and intensive care medicine, only a few studies examine the effects of these drugs on immature neurons. Methods: Hippocampal neuronal cell cultures of embryonic Wistar rats (15 days in culture) were incubated with midazolam 100 or 300 nM for either 30 min or 4 h. The time course of the mRNA expression of the glutamate receptors subunits NR1, NR2A and NR2B of the NMDA receptor, the GluA-1 and A-2 subunits of the AMPA receptor as well as the alpha 1 subunit of the GABAA receptor were examined by PCR. Apoptosis was detected using Western blot analysis for BAX, Bcl-2 and Caspase-3. Results: Midazolam at 100 and 300 nM applied for 30 min and 100 nM for 4 h affected glutamate receptor and GABAA receptor subunit expression. However, these effects were reversible within 72 h following washout. When 300 nM midazolam was applied for 4 h a significant increase in the NR 1 and NR 2A mRNA subunit expression could be detected. The increase in NR 2B receptor subunit expression as well as the GluA1 subunit expression was not reversible within 72 h following washout. This increase in mRNA glutamate receptor subunit expression was associated with a significant increase in neuronal apoptosis. Conclusion: In immature neurons midazolam altered GABA and glutamate mRNA receptor subunit expression. Prolonged increase in midazolam-induced glutamate receptor expression was associated with apoptosis.

Biomarker-guided Intervention to Prevent Acute Kidney Injury After Major Surgery: The Prospective Randomized BigpAK Study.

OBJECTIVE: To determine the impact of renal biomarker-guided implementation of the Kidney Disease Improving Global Outcomes (KDIGO) care bundle on the incidence of acute kidney injury (AKI) after major noncardiac surgery in a single-center unblinded randomized clinical trial. BACKGROUND: Early optimization of volume status and discontinuation of nephrotoxic medication before the occurrence of AKI may be the crucial step to reduce preventable AKI. METHODS: The urinary biomarker-triggered KDIGO care bundle (early optimization of fluid status, maintenance of perfusion pressure, discontinuation of nephrotoxic agents) was compared to standard intensive care unit (ICU) care in 121 patients with an increased AKI risk after major abdominal surgery that was determined by urinary biomarker (inhibitor of metalloproteinase-2 × insulin-like growth factor-binding protein 7) >0.3. Incidence of overall AKI, severity of AKI, length of stay, major kidney events at discharge, and cost effectiveness were evaluated. RESULTS: The overall stages of AKI were not statistically different between the 2 groups, but in patients with inhibitor of metalloproteinase-2 × insulin-like growth factor-binding protein 7 values of 0.3 to 2.0 a subgroup analysis demonstrated a significantly reduced incidence of AKI 13/48 (27.1%) in the intervention group compared to control 24/50 (48.0%, P = 0.03). Incidence of moderate and severe AKI (P = 0.04), incidence of creatinine increase >25% of baseline value (P = 0.01), length of ICU, and hospital stay (P = 0.04) were significantly lower in the intervention group. Intervention was associated with cost reduction. There were no significant differences regarding renal replacement therapy, in-hospital mortality, or major kidney events at hospital discharge. CONCLUSIONS: Early biomarker-based prediction of imminent AKI followed by implementation of KDIGO care bundle reduced AKI severity, postoperative creatinine increase, length of ICU, and hospital stay in patients after major noncardiac surgery.

Postoperative cellular stress in the kidney is associated with an early systemic γδ T-cell immune cell response.

BACKGROUND: Basic science data suggest that acute kidney injury (AKI) induced by ischemia-reperfusion injury (IRI) is an inflammatory process involving the adaptive immune response. Little is known about the T-cell contribution in the very early phase, so we investigated if tubular cellular stress expressed by elevated cell cycle biomarkers is associated with early changes in circulating T-cell subsets, applying a bedside-to-bench approach. METHODS: Our observational pilot study included 20 consecutive patients undergoing endovascular aortic repair for aortic aneurysms affecting the renal arteries, thereby requiring brief kidney hypoperfusion and reperfusion. Clinical-grade flow cytometry-based immune monitoring of peripheral immune cell populations was conducted perioperatively and linked to tubular cell stress biomarkers ([TIMP-2]•[IGFBP7]) immediately after surgery. To confirm clinical results and prove T-cell infiltration in the kidney, we simulated tubular cellular injury in an established mouse model of mild renal IRI. RESULTS: A significant correlation between tubular cell injury and a peripheral decline of γδ T cells, but no other T-cell subpopulation, was discovered within the first 24 hours (r = 0.53; p = 0.022). Turning to a mouse model of kidney warm IRI, a similar decrease in circulating γδ T cells was found and concomitantly was associated with a 6.65-fold increase in γδ T cells (p = 0.002) in the kidney tissue without alterations in other T-cell subsets, consistent with our human data. In search of a mechanistic driver of IRI, we found that the damage-associated molecule high-mobility group box 1 protein HMGB1 was significantly elevated in the peripheral blood of clinical study subjects after tubular cell injury (p = 0.019). Correspondingly, HMGB1 RNA content was significantly elevated in the murine kidney. CONCLUSIONS: Our investigation supports a hypothesis that γδ T cells are important in the very early phase of human AKI and should be considered when designing clinical trials aimed at preventing kidney damage. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01915446 . Registered on 5 Aug 2013.

Filter Adsorption of Anidulafungin to a Polysulfone-Based Hemofilter During CVVHD In Vitro.

Candidemia is frequent in critically ill patients, especially in combination with an acute kidney injury (AKI). Echinocandins generally are recommended for therapy of such infections. Recent studies found no need for dosage adjustment in patients with end-stage renal disease receiving hemodialysis, or patients with AKI receiving continuous venovenous hemofiltration. The aim of this in vitro study was to examine the adsorption of anidulafungin to the surface of the hemofilter during continuous venovenous hemodialysis (CVVHD) and its effect on anidulafungin concentrations. The concentration of anidulafungin in the dialyzed fluid, and the dialysate during CVVHD in vitro was examined using three different dialyzed fluids (saline; saline with 40 g/L human albumin; and a mixture of human erythrocytes and fresh frozen plasma). After the end of dialysis, the hemofilter was opened and portions of the filter capillaries were also analyzed to determine the amount of anidulafungin adsorbed. When dialyzing saline, about 99% of the anidulafungin used adsorbed to the hemofilter capillaries; in the experiments with saline with 40 g/L albumin, about 60% adsorbed to the hemofilter's surface, and when blood was dialyzed, 35% was found adsorbed after analyzing the filter capillaries. Anidulafungin was not detectable in the dialysate of any of the experiments, consequently the dialysis clearance was 0 mL/min. In conclusion, during CVVHD in vitro we found remarkable adsorption of anidulafungin to the hemofilter's surface, yet the effect on the tissue concentration needs further examination.

[Self-hypnosis training for in-hospital chronic pain patients : A retrolective observational study]. / "Selbsthypnosetraining" bei chronischen stationären Schmerzpatienten : Eine retrolektive Beobachtungsstudie.

BACKGROUND: Hypnosis is probably one of the oldest therapies known to man. In the last decades modern hypnosis has mainly been used by psychotherapists; however, hypnosis is becoming increasingly more important as a therapeutic method in medicine. Hypnosis can be used for a variety of medical indications. In the literature there is much evidence for the effectiveness of hypnosis. The aim of the present investigation was to demonstrate the effectiveness of hypnosis in inpatient treatment of chronic pain patients and to present a self-hypnosis program, which can be easily integrated into pain therapy. METHODS: From October 2012 to April 2013 all inpatient chronic pain patients were included (group 1: non-hypnosis group, group 2: hypnosis group). Concerning group 2 a standardized protocol for hypnotherapy was integrated in addition to the standardized pain management program. The main goal of hypnotherapy was to integrate a self-hypnosis training so that further implementation in a domestic setting could be guaranteed. By means of standardized test procedures, e. g. Patient Health Questionnaire (PHQ-9), Pain Disability Index (PDI), Generalized Anxiety Disorder (GAD-7) and Numerical Rating Scales (NRS) for pain and general well-being, data were evaluated before and after the pain therapy. RESULTS: The prestandardized and poststandardized test procedures of 30 chronic pain patients were evaluated (17 patients without hypnosis, 13 patients with hypnosis). The main diagnosis according to ICD-10 was "chronic pain disorder" (F45.41) with a MPSS stage III in all patients. The PDI was significantly improved in the hypnosis group (p = 0.019). The other items all showed a trend towards improvement in the hypnosis group (exception GAD-7) but without statistical significance (p > 0.05). DISCUSSION: In a small patient collective, the present investigation was able to show that the integration of modern hypnotherapy into the treatment of chronic pain patients in an inpatient setting can be another useful therapeutic aspect. In particular, the instructions for learning independently seem to be useful due to the limited in-patient time. More research needs to be carried out to support our initial findings.

Is Every Life Worth Saving: Does Religion and Religious Beliefs Influence Paramedic's End-of-Life Decision-making? A Prospective Questionnaire-based Investigation.

BACKGROUND: Paramedics, arriving on emergency cases first, have to make end-of-life decisions almost on a daily basis. Faith shapes attitudes toward the meaning and worth of life itself and therefore influences decision-making. OBJECTIVE: The objective of this study was to detect whether or not religious and spiritual beliefs influence paramedics in their workday life concerning end-of-life decisions, and whether it is legally possible for them to act according to their conscience. METHODS AND DESIGN: This is a literature review of prior surveys on the topic using five key words and questionnaire-based investigation using a self-administered online survey instrument. SETTINGS/PARTICIPANTS: Paramedics all over Germany were given the opportunity to participate in this online questionnaire-based study. MEASUREMENTS: Two databases were searched for prior studies for literature review. Participants were asked about their religiosity, how it affects their work, especially in end-of-life situations, how experienced they are, and whether or not they have any legal latitude to withhold resuscitation. RESULTS: A total of 429 paramedics answered the questionnaire. Religious paramedics would rather hospitalize a patient holding an advance directive than leave him/her at home (P = 0.036) and think death is less a part of life than the nonreligious (P = 0.001). Otherwise, the Spearman's rho correlation was statistically insignificant for all tests regarding resuscitation. CONCLUSIONS: The paramedic's religiosity is not the prime factor in his/her decision-making regarding resuscitation.

Changes in intraocular pressure and optic nerve sheath diameter in patients undergoing robotic-assisted laparoscopic prostatectomy in steep 45° Trendelenburg position.

BACKGROUND: To evaluate changes in intraocular pressure (IOP) and intracerebral pressure (ICP) reflected by the optic nerve sheath diameter (ONSD) in patients undergoing robotic-assisted laparoscopic prostatectomy (RALP) in permanent 45° steep Trendelenburg position (STP). METHODS: Fifty-one patients undergoing RALP under a standardised anaesthesia. IOP was perioperatively measured in awake patients (T0) and IOP and ONSD 20 min after induction of anaesthesia (T1), after insufflation of the abdomen in supine position (T2), after 30 min in STP (T3), when controlling Santorini's plexus in STP (T4) and before awakening while supine (T5). We investigated the influence of respiratory and circulatory parameters as well as patient-specific and time-dependent factors on IOP and ONSD. RESULTS: Average IOP values (mmHg) were T0 = 19.9, T1 = 15.9, T2 = 20.1, T3 = 30.7, T4 = 33.9 and T5 = 21.8. IOP was 14.0 ± 7.47 mmHg (mean ± SD) higher at T4 than T0 (p = 0.013). Univariate mixed effects models showed peak inspiratory pressure (PIP) and mean arterial blood pressure (MAP) to be significant predictors for IOP increase. Mean ONSD values (mm) were T1 = 5.88, T2 = 6.08, T3 = 6.07, T4 = 6.04 and T5 = 5.96. The ONSD remained permanently >6.0 mm during RALP. Patients aged <63 years showed a 0.21 mm wider ONSD on average (p = 0.017) and greater variations in diameter than older patients. CONCLUSIONS: The combination of STP and capnoperitoneum during RALP has a pronounced influence on IOP and, to a lesser degree, on ICP. IOP is directly correlated with increasing PIP and MAP. IOP doubled and the ONSD rose to values indicating increased intracranial pressure. Differences in the ONSD were age-related, showing higher output values as well as better autoregulation and compliance in STP for patients aged <63 years. Despite several ocular changes during RALP, visual function was not significantly impaired postoperatively. TRIAL REGISTRATION: Z-2014-0387-6 . Registered 8 July 2014.

Adenosine A2A and A2B Receptor Substantially Attenuate Ischemia/Reperfusion Injury in Septic rat Hearts.

INTRODUCTION: Mechanical and morphological ischemia and reperfusion (I/R) injury is reduced in septic hearts. The mechanism behind this "cardioprotection" is less well understood. As adenosine receptors play a major role for cardioprotection in non-septic hearts, we investigated the influence of adenosine receptors in a model of I/R in septic hearts. METHODS: SHAM operation or cecal ligation and puncture (CLP) was performed in adult male Wistar rats (n = 60). After 24 h of incubation, hearts were isolated and randomly assigned to a group with or without adenosine receptor (Ador) antagonists (SCH 58261 and MRS 1706) administered before reperfusion. Ischemia and reperfusion lasted for 40 min each. Cardiac function of the heart was determined by measuring left ventricular pressure (LVP). RESULTS: Before I/R, CLP hearts showed a significant mechanical left ventricular impairment (CLP: 63 ± 5 mmHg vs. SHAM: 104 ± 6 mmHg. After I/R, left ventricular function was significantly reduced in SHAM (24 ± 32 mmHg), but not in CLP hearts (65 ± 13 mmHg). mRNA expression for the AdorA2a and AdorA2b was significantly increased in CLP, but not in SHAM hearts. LVP of CLP hearts deteriorated when AdorA2a and AdorA2b were blocked. CONCLUSIONS: The morphological and functional I/R injury in septic animals is less pronounced compared to non-septic animals. By a combined blockade of AdorA2a and AdorA2b this "cardioprotective" effect is nearly abolished in septic hearts. This is the first study showing, that AdorA2a and AdorA2b may play an important role for a reduced functional I/R injury in the septic heart.

Modification of Bupivacaine-Induced Myotoxicity with Dantrolene and Caffeine In Vitro.

BACKGROUND: Local anesthetics, especially bupivacaine, have myotoxic effects in clinically used concentrations and context. Detailed mechanisms of these effects are unknown, but an increase in intracellular calcium levels is suspected to be the most important trigger. Dantrolene and caffeine modify cellular calcium release from the sarcoplasmic reticulum. The aim of our study was to investigate the effect of dantrolene and caffeine on bupivacaine-induced myotoxicity in vitro. METHODS: A cell culture model of primary muscle cells of BALB/c AnNCrl mice was established. Cells were incubated simultaneously with increasing concentrations of bupivacaine, dantrolene, and caffeine. The fraction of dead cells was calculated after staining with propidium iodide and analysis by flow cytometry. The half-maximal inhibitory concentration of bupivacaine was calculated for each concentration. Group differences were determined by using 1-way analysis of variances with subsequent post hoc 1-way Dunnett t test. RESULTS: Both dantrolene and caffeine alone had no effect on muscle cell survival. Increasing concentrations of bupivacaine caused increasing cell death. Dantrolene dose-dependently reduced the fraction of necrotic cells, whereas caffeine dose-dependently increased the fraction of dead cells. CONCLUSIONS: Dantrolene attenuated, and caffeine enhanced, bupivacaine-induced myotoxicity, presumably by modifying sarcoplasmic calcium release. This indicates that intracellular calcium release is an important factor for local anesthetic-induced cell death.

In vitro myotoxic effects of bupivacaine on rhabdomyosarcoma cells, immortalized and primary muscle cells.

BACKGROUND: Rhabdomyosarcoma is a rare malignant skeletal muscle tumor. It mainly occurs in children and young adults and has an unsatisfactory prognosis. Prior studies showed a direct myotoxic effect of bupivacaine on differentiated muscle cells in vitro and in vivo. Exact mechanisms of this myotoxicity are still not fully understood, but a myotoxic effect on malignant muscle tumor cells has not been examined so far. Thus, the aim of this study was to examine if bupivacaine has cytotoxic effects on rhabdomyosarcoma cells, immortalized muscle cells and differentiated muscle cells. METHODS: Cell lines of rhabdomyosarcoma cells, immortalized muscle cells and differentiated muscle cells were established. After microscopic identification, cells were exposed to various concentrations of bupivacaine (500, 1,000, 1,750, 2,500 and 5,000 ppm) for 1 and 2 h, respectively. 24 and 28 h after incubation the cultures were stained with propidium iodid and analyzed by flow cytometry. The fraction of dead cells was calculated for each experiment and the concentration with 50% cell survival (IC50) was computed. Cell groups as well as incubation and recovery time were compared (ANOVA/Bonferroni p < 0.01). RESULTS: The total number of cultured cells was similar for the different local anesthetics and examined concentrations. Increasing concentrations of bupivacaine led to a decrease in survival of muscle cells. IC50 was highest for immortalized cells, followed by rhabdomyosarcoma cells and differentiated cells. Exposure time, but not recovery time, had an influence on survival. CONCLUSION: Bupivacaine has clear but different cytotoxic effects on various muscle cell types in vitro. Differentiated primary cells seem to be more vulnerable than tumor cells possibly because of more differentiated intracellular structures.

Palliative patients under anaesthesiological care: a single-centre retrospective study on incidence, demographics and outcome.

BACKGROUND: While anesthesiologist's involvement in palliative care has been widely researched, extensive data on palliative patients under anesthesiological care in the operating room is missing. This study was performed to assess the incidence, demographics, and outcome of palliative patients under anesthesiological care. METHODS: We conducted a single-center retrospective chart review of all palliative patients under anesthesiological care at a university hospital in 1 year. Patients were classified as palliative if they fulfilled all predefined criteria (a) incurable, life-threatening disease, (b) progression of the disease despite therapy, (c) advanced stage of the disease with limited life-expectancy, (d) receiving or being in need of a specific palliative therapy. Demographics, periprocedural parameters, symptoms at evaluation, and outcome were determined using different medical records. RESULTS: Of 17,580 patients examined, 276 could be classified as palliative patients (1.57%). Most contacts with palliative patients occurred in the operating room (68.5%). In comparison to the non-palliative patients, procedures in palliative patients were significantly more often urgent or emergency procedures (39.1% vs. 27.1%., P < 0.001), and hospital mortality was higher (18.8% vs. 5.0%, P < 0.001). Preprocedural symptoms varied, with pain, gastrointestinal, and nutritional problems being the most prevalent. CONCLUSIONS: Palliative patients are treated by anesthesiologists under varying circumstances. Anesthesiologists need to identify these patients and need to be aware of their characteristics to adequately attend to them during the periprocedural period.

The expenditure of computer-related worktime using clinical decision support systems in chronic pain therapy.

BACKGROUND: Estimate the expenditure of computer-related worktime resulting from the use of clinical decision support systems (CDSS) to prevent adverse drug reactions (ADR) among patients undergoing chronic pain therapy and compare the employed check systems with respect to performance and practicability. METHODS: Data were collected retrospectively from 113 medical records of patients under chronic pain therapy during 2012/2013. Patient-specific medications were checked for potential drug-drug interactions (DDI) using two publicly available CDSS, Apotheken Umschau (AU) and Medscape (MS), and a commercially available CDSS AiDKlinik® (AID). The time needed to analyze patient pharmacotherapy for DDIs was taken with a stopwatch. Measurements included the time needed for running the analysis and printing the results. CDSS were compared with respect to the expenditure of time and usability. Only patient pharmacotherapies with at least two prescribed drugs and fitting the criteria of the corresponding CDSS were analyzed. Additionally, a qualitative evaluation of the used check systems was performed, employing a questionnaire asking five pain physicians to compare and rate the performance and practicability of the three CDSSs. RESULTS: The AU tool took a total of 3:55:45 h with an average of 0:02:32 h for 93 analyzed patient regimens and led to the discovery of 261 DDIs. Using the Medscape interaction checker required a total of 1:28:35 h for 38 patients with an average of 0:01:58 h and a yield of 178 interactions. The CDSS AID required a total of 3:12:27 h for 97 patients with an average time of analysis of 0:01:59 h and the discovery of 170 DDIs. According to the pain physicians the CDSS AID was chosen as the preferred tool. CONCLUSIONS: Applying a CDSS to examine a patients drug regimen for potential DDIs causes an average extra expenditure of work time of 2:09 min, which extends patient treatment time by 25 % on average. Nevertheless, the authors believe that the extra expenditure of time employing a CDSS is outweighed by their benefits, including reduced ADR risks and safer clinical drug management.

[The premedication visit--suggestions for a patient-friendly design]. / Das Prämedikationsgespräch--Anregungen zu einer patientenfreundlichen Gestaltung.

The premedication visit is often a difficult situation for the anaesthetist. On the one hand the patient needs to be informed in detail, but on the other he must not be alienated unnecessarily. Furthermore, a hospital stay represents an exceptional situation for the patient in which he behaves differently than in everyday life and shows a limited ability to process information. Following certain communication strategies allows to convey information to the patient in a comprehensible manner and to describe his individual anaesthesiological risk without needlessly creating fear.

[Nocebo effects with the informed consent]. / Nocebo-Effekte--Negativwirkungen der Aufklärung.

Side effects are more frequent and severe, or simply appear by just talking about them. But not the informed consent is to be challenged, rather the form of giving risk information. Nocebo effects mainly originate from induced negative expectations, not from the information itself. Concerns about legal consequences of an incomplete list of risks do not release from the responsibility to guide and help the patient to an understanding and a balanced decision.

Lipid rescue reverses the bupivacaine-induced block of the fast Na+ current (INa) in cardiomyocytes of the rat left ventricle.

BACKGROUND: Cardiovascular resuscitation upon intoxication with lipophilic ion channel-blocking agents has proven most difficult. Recently, favorable results have been reported when lipid rescue therapy is performed, i.e., the infusion of a triglyceride-rich lipid emulsion during resuscitation. However, the mechanism of action is poorly understood. METHODS: The authors investigate the effects of a clinically used lipid emulsion (Lipovenös® MCT 20%; Fresenius Kabi AG, Bad Homburg, Germany) on the block of the fast Na current (INa) induced by the lipophilic local anesthetic bupivacaine in adult rat left ventricular myocytes by using the whole cell patch clamp technique. RESULTS: Bupivacaine at 10 µm decreased INa by 54% (-19.3 ± 1.9 pApF vs. -42.3 ± 4.3 pApF; n = 17; P < 0.001; VPip = -40 mV, 1 Hz). Addition of 10% lipid emulsion in the presence of bupivacaine produced a 37% increase in INa (-26.4 ± 2.8 pApF; n = 17; P < 0.001 vs. bupivacaine alone). To test whether these results could be explained by a reduction in the free bupivacaine concentration by the lipid (lipid-sink effect), the authors removed the lipid phase from the bupivacaine-lipid mixture by ultracentrifugation. Also, the resulting water phase led to an increase in INa (+19%; n = 17; P < 0.001 vs. bupivacaine), demonstrating that part of the bupivacaine had been removed during ultracentrifugation. The substantially less lipophilic mepivacaine (40 µm) reduced INa by 27% (n = 24; P < 0.001). The mepivacaine-lipid mixture caused a significant increase in INa (+17%; n = 24; P < 0.001). For mepivacaine, only a small lipid-sink effect could be demonstrated (+8%; n = 23; P < 0.01), reflecting its poor lipid solubility. CONCLUSION: The authors demonstrate lipid rescue on the single-cell level and provide evidence for a lipid-sink mechanism.

Nociceptive Flexion Reflex Threshold is No Suitable Marker for Diagnosing Opioid-Induced Hyperalgesia.

Background: Opioid induced hyperalgesia (OIH) describes a state of altered pain sensation due to opioid exposure. It often occurs among persons with opioid use disorder receiving substitution therapy. Methods: The purpose of this study was to find out, whether OIH diagnosis could be facilitated by an objective pain indicating marker: the Nociceptive Flexion Reflex (NFR). Forty persons with opioid use disorder, 20 of them maintained on methadone and 20 treated with buprenorphine, as well as a control group of 20 opioid-free subjects, were examined. It was aimed to find out whether and in which way these opioid agonists alter reflex threshold (NFR-T). A cold-pressor test was performed to investigate the prevalence of OIH. Furthermore, electrical stimulation and electromyography analyzation were used for NFR-T measurement. Subjective pain ratings were evaluated with a numeric rating scale. Results: Significantly increased sensitivity to cold pressor pain was found in both maintenance groups when compared to their opioid-free counterparts (p < 0.001). Neither methadone nor buprenorphine showed any effect on NFR-T. This might be explained by the reflex approaching at the wrong location in the central nervous system. Consequently, NFR-T is not a suitable marker for diagnosing OIH. Conclusion: Although methadone and buprenorphine have been proven to cause OIH, no effect on NFR-T was observed. A statistically significant effect could have been observed with a larger number of participants. Further research, with special focus on patients' adjuvant medication, should be conducted in the future, to facilitate diagnosis of OIH and provide appropriate pain management for maintenance patients.