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.

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.

Prospective, comparative study of the On-Q® PainBuster® postoperative pain relief system and thoracic epidural analgesia after thoracic surgery.

OBJECTIVE: Pain after thoracotomy is associated with intense discomfort leading to impaired pulmonary function. DESIGN: Prospective, non-randomized trial from April 2009 to September 2011. SETTING: Department of Thoracic Surgery, single-center. PARTICIPANTS: Thoracic surgical patients. INTERVENTIONS: Comparison of thoracic epidural analgesia (TEA) with the On-Q® PainBuster® system after thoracotomy. MEASUREMENTS AND MAIN RESULTS: The TEA group (n=30) received TEA with continuous 0.2% ropivacaine at 4 mL-to-8 mL/h, whereas Painbuster® patients (n=32) received 0.75% ropivacaine at 5 mL/h until postoperative day 4 (POD4). Basic and on-demand analgesia were identical in both groups. Pain was measured daily on a numeric analog scale from 0 (no pain) to 10 (worst pain) at rest and at exercise. There were no significant differences regarding demographic and preoperative data between the groups, but PainBuster® patients had a slightly lower relative forced expiratory volume in 1 second (FEV1) (71±20% versus 86±21%; p=0.01). Most common surgical procedures were lobectomies (38.8%) and atypical resections (28.3%) via anterolateral thoracotomy. Most common primary diagnoses were lung cancer (48.3%) and tumor of unknown origin (30%). At POD1, median postoperative pain at rest was 2.1 (1; 2.8) in the TEA group and 2 (1.5; 3.8; p=0.62) in the PainBuster® group. At exercise, median pain was 4.3 (3.5; 3.8) in the TEA group compared to 5.0 (4.0; 6.5; p=0.07). Until POD 5 there were decreases in pain at rest and exercise but without significant differences between the groups. CONCLUSIONS: Sufficient analgesia after thoracotomy can be achieved with the intercostal PainBuster® system in patients, who cannot receive TEA.

[Standardized concentrations for continuous infusion-results of a nationwide survey in German intensive care units]. / Standardkonzentrationen für Dauerinfusionen ­ Ergebnisse einer bundesweiten Befragung auf deutschen Erwachsenenintensivstationen.

BACKGROUND: Continuous infusion of numerous parenteral medications is common practice in intensive care units (ICU). In contrast to some countries, there is a lack of clearly defined standardized concentrations in Germany, especially for high-risk medications designated for infusion therapy. OBJECTIVES: The goal was to collect representative data of standardized concentrations commonly used for continuous infusion in German ICUs. Results should be used to draft nationwide recommendations for standardized continuous infusions. MATERIALS AND METHODS: To determine the nationwide acceptance and preference for medications designated for continuous infusion, a questionnaire was developed and sent to the directors of 1816 ICUs in Germany. The questionnaire comprised suggestions of 59 medicinal products with 73 concentrations. In addition, participants could make their own proposals on medications and concentrations preferably used. Evaluation was performed with SurveyMonkey® and Microsoft® Excel®. RESULTS: A total of 312 (17%) ICUs answered the survey. Data analyses indicate a very high acceptance rate for rate-controlled continuous infusion with standardized concentrations. More than 90% (50%) of participating physicians routinely use the top 10 (top 25) medicines listed for continuous infusion. For most medicines, one concentration could be identified. CONCLUSIONS: Our survey results generate a suitable basis for a nationwide list with standardized concentrations of medicines intended for continuous infusion (usually 50 mL). Publication of such a list by the corresponding expert committees is likely to be met with broad acceptance and implementation into clinical practice can be expected.

[Drug therapy safety supported by interprofessional collaboration between ICU physicians and clinical pharmacists in critical care units in Germany : Results of a survey]. / Arzneimitteltherapiesicherheit gefördert durch die interprofessionelle Zusammenarbeit von Arzt und Apotheker auf Intensivstationen in Deutschland : Erkenntnisse einer Umfrage.

BACKGROUND: Critically ill patients are particularly susceptible to adverse drug events. International studies show that pharmaceutical care has a positive impact on patient and drug therapy safety. Nationally, the integration of pharmacists into the multidisciplinary team and participation in ward rounds is required. The aim of this work is to assess the scope and extent of pharmaceutical care in intensive care units (ICU) in Germany. METHOD: In a literature and database search, 13 relevant pharmaceutical activities were identified. Based on this, an online survey with 27 questions on the implementation of pharmaceutical care in ICU was prepared by a panel of experts. The survey was sent to heads of German ICUs. RESULTS: Of the participants, 35.3% (59/167) have established regular pharmaceutical care. Drug information (89.7% [52/58]), pharmaceutical interventions with change of therapy (e.g., ward rounds; 67,2% [39/58]), regular evaluation of prescriptions (medication analysis; 65.5% [38/58]) as well as the monitoring of medication (e.g., side effects, effectiveness, costs; 63.8% [37/58]) were most frequently mentioned. The participants with pharmaceutical care (58/168) graded 7 of 13 but those without (104/168) only two  activities as 'essential/indispensable'. CONCLUSION: Only a few ICU in Germany have already integrated ward pharmacists into the multidisciplinary team. Once a pharmaceutical service has been established, a greater role/importance is assigned to several pharmaceutical activities.

Transcranial ultrasound from diagnosis to early stroke treatment: part 2: prehospital neurosonography in patients with acute stroke: the Regensburg stroke mobile project.

BACKGROUND AND PURPOSE: The primary aim of this study was to investigate the diagnostic accuracy and time frames for neurological and transcranial color-coded sonography (TCCS) assessments in a prehospital '911' emergency stroke situation by using portable duplex ultrasound devices to visualize the bilateral middle cerebral arteries (MCAs). METHODS: This study was conducted between May 2010 and January 2011. Patients who had sustained strokes in the city of Regensburg and the surrounding area in Bavaria, Germany, were enrolled in the study. After a '911 stroke code' call had been dispatched, stroke neurologists with expertise in ultrasonography rendezvoused with the paramedic team at the site of the emergency. After a brief neurological assessment had been completed, the patients underwent TCCS with optional administration of an ultrasound contrast agent in cases of insufficient temporal bone windows or if the agent had acute therapeutic relevance. The ultrasound studies were performed at the site of the emergency or in the ambulance during patient transport to the admitting hospital. Relevant timelines, such as the time from the stroke alarm to patient arrival at the hospital and the duration of the TCCS, were documented, and positive and negative predictive values for the diagnosis of major MCA occlusion were assessed. RESULTS: A total of 113 patients were enrolled in the study. MCA occlusion was diagnosed in 10 patients. In 9 of these 10 patients, MCA occlusion could be visualized using contrast-enhanced or non-contrast-enhanced TCCS during patient transport and was later confirmed using computed tomography or magnetic resonance angiography. One MCA occlusion was missed by TCCS and 1 atypical hemorrhage was misdiagnosed. Overall, the sensitivity of a 'field diagnosis' of MCA occlusion was 90% [95% confidence interval (CI) 55.5-99.75%] and the specificity was 98% (95% CI 92.89-99.97%). The positive predictive value was 90% (95% CI 55.5-99.75%) and the negative predictive value was 98% (95% CI 92.89-99.97%). The mean time (standard deviation) from ambulance dispatch to arrival at the patient was 12.3 min (7.09); the mean time for the TCCS examination was 5.6 min (2.2); and the overall mean transport time to the hospital was 53 min (18). CONCLUSION: Prehospital diagnosis of MCA occlusion in stroke patients is feasible using portable duplex ultrasonography with or without administration of a microbubble contrast agent. Prehospital neurological as well as transcranial vascular assessments during patient transport can be performed by a trained neurologist with high sensitivity and specificity, perhaps opening an additional therapeutic window for sonothrombolysis or neuroprotective strategies.

[Ambulatory pain therapy in penetrating rectal cancer via epidural anesthesia]. / Ambulante Schmerztherapie. Behandlung bei penetrierendem Rektum-Karzinom mittels Periduralkatheter.

Treatment of cancer pain includes invasive techniques of pain therapy if necessary. Here we report the management of a 55-year-old female patient with penetrating rectal cancer using continuous lumbal epidural anesthesia. After placement and dose-finding our patient was discharged from hospital and further treatment occurred at home.

[Implementation of a web based software for documentation and control of quality of an acute pain service]. / Die webbasierte Software im Akutschmerzdienst - Implementierung, Dokumentation und Qualitätskontrolle.

Providing an acute pain service means accumulation of a large amount of data. The alleviation of data collection, improvement of data quality and data analysis plays a pivotal role. The electronic medical record (EMR) is gaining more and more importance in this context and is continuously spreading in clinical practice. Up to now only a few commercial softwares are available that specifically fit to the needs of an acute pain service. Here we report the development and implementation of such a program (Schmerzvisite, Medlinq, Hamburg, Germany) in the acute pain service of a University Hospital.

[Safety of Pharmacotherapy in Emergencies]. / Sichere Pharmakotherapie im Notfall.

Safety of Pharmacotherapy in Emergencies Abstract. Emergency pharmacotherapy is one of the most commonly used medical procedures. At the same time, pharmacotherapy in an emergency is always a potentially dangerous action. Medication errors are even among the most frequently registered errors in medicine. Due to the special circumstances in emergency medicine, special precautions are required to ensure the safety of drug therapy. In addition to the important background information, this article presents procedures that are recognized and applicable in daily routine to increase safety in pharmacotherapy.

Transcranial ultrasound from diagnosis to early stroke treatment. 1. Feasibility of prehospital cerebrovascular assessment.

BACKGROUND: To test whether portable duplex ultrasound devices can be used in a prehospital '911' emergency situation to assess intracranial arteries. METHODS: Non-contrast-enhanced transcranial duplex ultrasound studies were performed either immediately at the site of the emergency (i.e. private home) or after transfer into the emergency helicopter/ambulance vehicle. RESULTS: A total of 25 patients were enrolled. In 5/25 cases, intracranial vessels could not be visualized due to insufficient quality of the temporal bone window. In 20/25 cases, bilateral visualization and Doppler flow measurements of the middle cerebral artery could be assessed in a mean time less than 2 min. CONCLUSION: Emergency assessment of intracranial arteries using portable duplex ultrasound devices is feasible shortly after arrival at the patient's site.

Effects of single-point acupuncture (HT7) in the prevention of test anxiety: Results of a RCT.

BACKGROUND: The number of students using neuro enhancement to improve their performance and to prevent test anxiety is increasing. The acupuncture point Heart 7 (HT7) has been described as being prominent in reducing states of anxiety. METHODS: We conducted a randomized placebo-controlled, two-armed pilot trial to investigate the efficacy of a single-point acupuncture treatment at bilateral HT7 compared to sham laser acupuncture on test anxiety. Test anxiety was induced applying the standardised protocol of the Trier Social Stress Test. Outcome measures included saliva samples analysed for cortisol and amylase, anxiety questionnaires and heart rate variability. RESULTS: Twenty-five male subjects (age 28 ± 5 years) were allocated to either verum acupuncture (n = 12) or sham laser acupuncture (n = 13). Cortisol peaked 20 min after the stress test (2-fold, 18.11 ± 2 nmol/l) and amylase 10 min after (2-fold, 259 ± 49 U/ml) with no difference between groups. There were no differences between groups regarding either anxiety questionnaires or physiological parameters. Compared to reference data (3-fold increase in cortisol), increase in stress hormones and heart rate seemed somewhat reduced. CONCLUSIONS: Acupuncture may be a possible approach for the treatment of anxiety. Due to the lack of a no control treatment group, we cannot determine the magnitude of possible specific needle effects at HT7 to promote specific effects in the neuroendocrine system. Finally this study only examines the efficacy of a single time treatment.

[Intraoperative blood transfusion in a child with blunt abdominal trauma]. / Pharmakotherapie. Intraoperative Bluttransfusion bei einem Kind nach stumpfem Abdominaltrauma.

Pediatric transfusion therapy is complex since there is a remarkable physiological change from neonate to child. Here we report the blood transfusion management of a 6-year-old male child after abdominal trauma. Particular normovolemia with ringer/hetastarch, the estimation of the maximal allowable blood loss, target transfusion hematocrit, transfusion with platelets and FFP are discussed.

[Pharmacotherapy: migraine and depression. Therapy with sumatripten and citalopram: perioperative anaesthesiological risk assessment]. / Pharmakotherapie: Migräne und Depression. Perioperative Therapie mit Sumatriptan und Citalopram: Einschätzung aus anästhesiologischer Sicht.

We report on a case of a patient with migraine and depression treated with citalopram and sumatriptan. The drug evaluation is presented using the actual summaries of product characteristics (SPC, "Fachinformationen"). Particular the individual perioperative anaesthesiological risk assessment regarding the pharmacodynamic and pharmacointeractions is discussed.

[Post-operative pain therapy of a chronic pain patient]. / Pharmakotherapie--Postoperative Schmerztherapie eines chronischen Schmerzpatienten.

Post-operative pain therapy of chronic pain patients poses a challenge. Here we report the perioperative management of a 39-year-old male under chronic therapy with oxycodon, gabapentin and tolperison. Particular the pharmacointeractions regarding premedication and postoperative dose finding of opioids with intravenous PCIA are discussed.

Convective air warming is more effective than resistive heating in an experimental model with a water dummy.

Trauma patients with accidental hypothermia have adverse outcomes when compared with normothermic patients. Studies with a small number of mild hypothermic volunteers suggested that convective warming is more effective than warming with 12 volt resistive heating blankets. In a laboratory study, we compared the warming effectiveness of two electric blankets and convective air warming. The average speed of convective rewarming during anaesthesia in patients is approximately 0.6 degree C per hour. Accordingly, calibration of the dummy was performed with increasing amounts of water during convective warming until we reached a temperature gain of 0.6 degree C per hour. The following warming experiments were performed: 12 volt electric warming blanket (SH6012, Hella); 12 volt electric warming blanket (Thermamed, whole-body blanket); convective air warming (Warm Touch, Mallinckrodt, whole-body blanket). Each experiment was repeated four times. The temperature development was measured and recorded online. Convective warming increased the dummy temperature 0.6 degree C per hour, Thermamed 0.3 degree C per hour (P<0.001 versus convective warming) and two Hella blankets 0.2 degree C per hour (P<0.001 versus convective warming). Our laboratory investigation confirmed the superiority of convective warming over resistive heating. Efforts should be made to incorporate convective warming into the out-of-hospital treatment of trauma patients.

Prehospital stroke diagnostics based on neurological examination and transcranial ultrasound.

BACKGROUND: Transcranial color-coded sonography (TCCS) has proved to be a fast and reliable tool for the detection of middle cerebral artery (MCA) occlusions in a hospital setting. In this feasibility study on prehospital sonography, our aim was to investigate the accuracy of TCCS for neurovascular emergency diagnostics when performed in a prehospital setting using mobile ultrasound equipment as part of a neurological examination. METHODS: Following a '911 stroke code' call, stroke neurologists experienced in TCCS rendezvoused with the paramedic team. In patients with suspected stroke, TCCS examination including ultrasound contrast agents was performed. Results were compared with neurovascular imaging (CTA, MRA) and the final discharge diagnosis from standard patient-centered stroke care. RESULTS: We enrolled '232 stroke code' patients with follow-up data available in 102 patients with complete TCCS examination. A diagnosis of ischemic stroke was made in 73 cases; 29 patients were identified as 'stroke mimics'. MCA occlusion was diagnosed in ten patients, while internal carotid artery (ICA) occlusion/high-grade stenosis leading to reversal of anterior cerebral artery flow was diagnosed in four patients. The initial working diagnosis 'any stroke' showed a sensitivity of 94% and a specificity of 48%. 'Major MCA or ICA stroke' diagnosed by mobile ultrasound showed an overall sensitivity of 78% and specificity of 98%. CONCLUSIONS: The study demonstrates the feasibility and high diagnostic accuracy of emergency transcranial ultrasound assessment combined with neurological examinations for major ischemic stroke. Future combination with telemedical support, point-of-care analysis of blood serum markers, and probability algorithms of prehospital stroke diagnosis including ultrasound may help to speed up stroke treatment.

The effects of midazolam on intraocular pressure in children during examination under sedation.

BACKGROUND: To obtain reliable and accurate measurements of the intraocular pressure (IOP) in children often requires sedation or anaesthesia. Therefore, we investigated the effects of oral midazolam on IOP in children. METHODS: In a prospective study, IOP was measured in 72 eyes of 36 cooperative children without glaucoma requiring general anaesthesia (mean age 3.5±1.3 years, body weight ≤20 kg) by using a Perkins hand-held tonometer. Measurements of IOP were performed before, and 15 and 30 min after sedation with orally administered midazolam (1 mg/kg) given as preoperative medication, and 5 and 15 min after induction of general anaesthesia. The individual IOP courses were analysed. RESULTS: In all of the cooperative children, IOP measurement was possible after sedation with midazolam. Mean IOP was 11.2±0.3 mmHg before sedation, 10.9±0.2 mmHg at 15 min, and 10.7±0.3 mmHg 30 min after administration of midazolam. This small decrease was not statistically significant, whilst the IOP decline at 5 and 15 min after induction of general anaesthesia was statistically significant (p<0.0001). CONCLUSION: Sedation with midazolam can be assumed to be an applicable, well-tolerated, safe method for IOP measurements in children.

Bosentan reduces oxidative burst in acid aspiration-induced lung injury in rats.

BACKGROUND: Acid aspiration induces lung injury by causing an intense inflammatory reaction. Neutrophils are attracted by various cytokines, such as TNFbeta, and release reactive oxygen species, which then cause acute lung injury. Endothelin antagonists, such as bosentan, have been found to possess anti-inflammatory properties. MATERIALS AND METHODS: We performed a prospective, randomised, controlled study to evaluate the effects of bosentan in a rat model of acid-induced lung injury. Sprague-Dawley rats underwent sevoflurane anaesthesia; lung injury was then induced by instillation of 1.2mL/kg, 0.1M hydrochloric acid. The lungs were ventilated for 6h and then randomised into three groups: bosentan 30mg/kg body weight, 90mg/kg body weight or sodium chloride, each applied immediately after acid aspiration via a gastric tube. RESULTS: After induction of acute lung inflammation, the production of reactive oxygen species by PMN following stimulation with FMLP increased significantly. Comparison of pre-treatment and post-treatment in the 90mg/kg bosentan treatment group did not show a significant increase of reactive oxygen species following stimulation with FMLP. A comparison of the absolute difference of the MESF demonstrated a significant difference between the control group and the group treated with 90mg/kg bosentan. CONCLUSIONS: Bosentan administration at 90mg/kg body weight reduced the release of reactive oxygen species after 360min in acid aspiration-induced lung injury in rats.

Naftidrofuryl exerts antiserotonergic but no endothelin-receptor blocking effects in AS4.1 cells, juxtaglomerular cells and isolated perfused rat kidneys.

Naftidrofuryl, a 5-hydroxytryptamine 2 (5-HT 2 ) serotonergic receptor antagonist with vasodilator effects, has successfully been used for intermittent claudication, some forms of dementia, and glaucoma. Recently, an additional mode of action of naftidrofuryl (i.e., mixed endothelin receptor antagonism) has been suggested. However, in the current study naftidrofuryl was unable to block endothelin-3-induced free intracellular calcium increases, in contrast to a mixed endothelin receptor antagonist, bosentan. The inhibition of forskolin-induced renin secretion by endothelin-3 in primary cultures of mouse juxtaglomerular cells and by endothelin-1 in the isolated perfused rat kidney could not be blocked by naftidrofuryl. Naftidrofuryl was unable to block marked endothelin-1-induced renal vasoconstriction in isolated perfused rat kidney. In contrast, naftidrofuryl markedly attenuated serotonin-induced renal vasoconstriction and nearly completely blocked serotonin's renin inhibitory properties in isolated perfused rat kidney. The present results suggest that naftidrofuryl is a potent antagonist of serotonin's renal effects, but has no endothelin receptor-blocking properties.