Stefan Heschl

Amitriptyline and carbamazepine utilize voltage-gated ion channel suppression to impair excitability of sensory dorsal horn neurons in thin tissue slice: An in vitro study.

Amitriptyline, carbamazepine and gabapentin are often used for the treatment of neuropathic pain. However, their analgesic action on central sensory neurons is still not fully understood. Moreover, the expression pattern of their target ion channels is poorly elucidated in the dorsal horn of the spinal cord. Thus, we performed patch-clamp investigations in visualized neurons of lamina I-III of the spinal cord. The expression of the different voltage-gated ion channels, as the targets of these drugs, was detected by RT-PCR and immunohistochemistry. Neurons of the lamina I-III express the TTX-sensitive voltage-gated Na(+) as well as voltage-gated K(+) subunits assembling the fast inactivating (A-type) currents and the delayed rectifier K(+) currents. Our pharmacological studies show that tonically-firing, adapting-firing and single spike neurons responded dose-dependently to amitriptyline and carbamazepine. The ion channel inhibition consecutively reduced the firing rate of tonically-firing and adapting-firing neurons. This study provides evidence for the distribution of voltage-gated Na(+) and K(+) subunits in lamina I-III of the spinal cord and for the action of drugs used for the treatment of neuropathic pain. Our work confirms that modulation of voltage-gated ion channels in the central nervous system contributes to the antinociceptive effects of these drugs.

Hypoxic vascular response and ventilation/perfusion matching in end-stage COPD may depend on p22phox

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease in which the amount of emphysema and airway disease may be very different between individuals, even in end-stage disease. Emphysema formation may be linked to the involvement of the small pulmonary vessels. The NAPDH oxidase (Nox) family is emerging as a key disease-related factor in vascular diseases, but currently its role in hypoxia-induced pulmonary remodelling in COPD remains unclear. Here we investigate the role of p22phox, a regulatory subunit of Nox, in COPD lungs, hypoxic pulmonary vasoconstriction (HPV), hypoxia-induced pulmonary vascular remodelling and pulmonary hypertension. In COPD, compared to control lungs, p22phox expression was significantly reduced. The expression was correlated positively with mean pulmonary arterial pressure and oxygenation index and negatively with the diffusing capacity of the lung for carbon monoxide (p<0.02). This suggests a role of p22phox in ventilation/perfusion ratio matching, vascular remodelling and loss of perfused lung area. In p22phox-/- mice, HPV was significantly impaired. In the chronic hypoxic setting, lack of p22phox was associated with improved right ventricular function and decreased pulmonary vascular remodelling. p22phox-dependent Nox plays an important role in the COPD phenotype, by its action on phase II HPV and chronic vascular remodelling. In COPD, p22phox controls hypoxic pulmonary vascular response and ventilation–perfusion matching http://ow.ly/9Koo30aWMmT

Postoperative pain management in children: Guidance from the pain committee of the European Society for Paediatric Anaesthesiology (ESPA Pain Management Ladder Initiative)

The main remit of the European Society for Paediatric Anaesthesiology (ESPA) Pain Committee is to improve the quality of pain management in children. The ESPA Pain Management Ladder is a clinical practice advisory based upon expert consensus to help to ensure a basic standard of perioperative pain management for all children. Further steps are suggested to improve pain management once a basic standard has been achieved. The guidance is grouped by the type of surgical procedure and layered to suggest basic, intermediate, and advanced pain management methods. The committee members are aware that there are marked differences in financial and personal resources in different institutions and countries and also considerable variations in the availability of analgesic drugs across Europe. We recommend that the guidance should be used as a framework to guide best practice.

Efficacy of pre-hospital rapid sequence intubation in paediatric traumatic brain injury: A 9-year observational study

INTRODUCTION Prehospital airway management of the paediatric patient with traumatic brain injury (TBI) is controversial. Endotracheal intubation of children in the field requires specific skills and has potential benefits but also carries potentially serious complications. We aimed to compare mortality and functional outcomes after six months between children with TBI who either underwent prehospital rapid sequence intubation (RSI) by trained Intensive Care paramedics (ICP) or received no intubation. METHODS We conducted a retrospective study of patients aged ≤14 years with suspected TBI in Victoria, Australia. Patients were either transported via helicopter and received RSI by an ICP (2005-2013) or via road ambulance and received no intubation (2006-2013). Prehospital data was linked to hospital and 6-month follow-up data to assess mortality and functional outcome. RESULTS A total of 106 patients were included in the study of which 87 received RSI by paramedics and 19 did not receive intubation. Overall, the intubation success rate was 99% (86/87), with a first-pass success rate of 93% (81/87). In total, 67% of patients (n = 41) receiving RSI had a favourable functional outcome, compared with 54% of non-intubated patients (n = 7) (p = 0.36). In the 75 children with major trauma, prehospital RSI was associated with a significant decrease in length of hospital stay (523 h vs. 1939 h, p = 0.03). In the 53 children in this subgroup with available six months data the difference in favourable functional outcome increased to 66% (n = 31)vs. 17% (n = 1) (p = 0.06). DISCUSSION Prehospital RSI in paediatric patients with TBI can safely be performed by highly trained paramedics. Overall, we observed more favourable long-term outcomes in patients who received prehospital intubation than those who did not, however our study is not powered to detect a significant difference. Intubation prior to transport might be beneficial for major trauma patients.

Prehospital transfusion of red cell concentrates in a paramedic-staffed helicopter emergency medical service

The optimal volume and type of intravenous fluid for the treatment of blood loss in the prehospital setting is controversial. The use of red cell concentrates (RCCs) may be associated with improved outcomes; however, the administration of blood products is limited to physicians in many jurisdictions. We sought to describe the characteristics of RCC transfusions in a paramedic‐staffed helicopter emergency medical system in Victoria, Australia.

Application of Non Linear Story Telling in Medical Education

In this paper we describe how we used the technique of “non linear story telling” in medical education in a course on “first aid”, which medical students have to take in their first year of studying human medicine. We show how we technically adapted the method for our students, how we produced 5 non-linear stories with a minimum of technical resources within the open source learning management system Moodle. Furthermore we show that this methodology is not restricted to medical education but can be also adapted to other fields of education. Finally we will present the evaluation results of the course together with conclusions and recommendations.

Perioperative Herzinsuffizienz: Maßnahmen zur Risikoeinschätzung und Therapieoptimierung

Eine immer älter werdende Bevölkerung sowie verbesserte Therapiestrategien bei Patienten mit koronarer Herzkrankheit, arteriellem Hypertonus und Diabetes mellitus führen zu einer kontinuierlich steigenden Anzahl an Patienten mit eingeschränkter Ventrikelfunktion. Bereits vier Prozent der Bevölkerung leiden an Herzinsuffizienz oder einer asymptomatischen ventrikulären Dysfunktion, wobei diese Prävalenz ab 75 Jahren dramatisch auf zehn bis 20 Prozent ansteigt. Trotz erweiterter Diagnosemöglichkeiten und verbesserter Therapieoptionen ist es nicht gelungen, die Tatsache zu ändern, dass die dekompensierte Herzinsuffizienz nach wie vor eine der Haupttodesursachen in der Intensivmedizin darstellt. Gerade in der perioperativen Phase finden sich zahlreiche Trigger für eine akute Verschlechterung der Ventrikelleistung. Insbesondere sind herzinsuffiziente Patienten durch Absetzen chronischer Herzinsuffizienzmedikamente, negativ inotrope und vasodilatatorische Effekte von Anästhetika, übermäßige Infusion von Volumen sowie Infektionen und Schmerzen gefährdet. Die perioperative Aktivierung des sympathischen Nervensystems sowie Elektrolytentgleisungen führen zudem häufig zu Arrhythmien, welche Pumpversagen und Lungenödem begünstigen.