A. Kashanipour

Simvastatin Reduces Expression of Cytokines Interleukin-6, Interleukin-8, and Monocyte Chemoattractant Protein-1 in Circulating Monocytes From Hypercholesterolemic Patients

Objective—A number of studies have shown that statins decrease morbidity and mortality in patients with cardiovascular diseases. The anti-inflammatory effects of statins have recently been implicated in the clinical benefit that can be obtained in the treatment of atherosclerosis. Little is known about the mechanisms by which statins counteract inflammation. Methods and Results—In this study, we asked whether simvastatin can influence in vitro and in vivo production of the proinflammatory cytokines interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1. A total of 107 hypercholesterolemic patients were treated with simvastatin. As measured by ELISA, serum levels of cytokines significantly decreased after 6 weeks of treatment (P <0.05). Furthermore, simvastatin decreased the expression of IL-6, IL-8, and monocyte chemoattractant protein-1 mRNA in peripheral blood mononuclear cells. Similar results were obtained in vitro by using cultured human umbilical vein endothelial cells and peripheral blood mononuclear cells from healthy normolipemic donors. Exposure to simvastatin, atorvastatin, or cerivastatin caused downregulation of the expression of cytokine mRNA in a time- and dose-dependent manner. Furthermore, all statins tested were able to reduce the concentrations of cytokines in cellular and extracellular fractions of human umbilical vein endothelial cells (P <0.05). Conclusions—Our data show that simvastatin is anti-inflammatory through the downregulation of cytokines in the endothelium and leukocytes. These effects may explain some of the clinical benefits of these drugs in the treatment of atherosclerosis.

Tubeless combined high-frequency jet ventilation for laryngotracheal laser surgery in paediatric anaesthesia.

Background: High‐frequency jet ventilation (HFJV) is an alternative ventilatory approach in airway surgery and for facilitating gas exchange in patients with pulmonary insufficiency. We have developed a new technique of combined HFJV utilising two superimposed jet streams. In this study we describe the application of tubeless supralaryngeal HFJV during laryngotracheal laser surgery in infants and children.

Near-fatal paradoxical gas embolism during gynecological laparoscopy

Laparoscopy is an established procedure of minimally invasive surgery. Although risks and complications during laparoscopy are rare, complications arise from hemorrhage or intestinal perforation, and hemodynamic compromise may result from extensive pneumoperitoneum. Massive gas embolism is a potentially life threatening complication (1–5). We report an incident of severe paradoxical CO2 embolism verified by an intraoperative transesophageal echocardiogram.

Superimposed jet ventilation via a special jet laryngoscope for endoluminal stent insertion in the tracheobronchial tree

Zusammenfassung. Die endoluminale Schienung mittels Silikonstents ist ein Verfahren zur sofortigen Wiederherstellung der Atemwege bei stenosierenden Prozessen des Tracheobronchialsystems. Die bisher dafür angewendeten Beatmungstechniken sind schwierig und mit Risiken behaftet, zumal die Patienten aufgrund der respiratorischen Insuffizienz in schlechter Verfassung sind. Wir wollten untersuchen, ob die Superponierte Hochfrequenz Jet-Ventilation (SHFJV) über das Jet-Laryngoskop, das von uns speziell für mikrolaryngeale Eingriffe entwickelt wurde, eine Anwendung zur tracheo-bronchialen Stentimplantation finden kann. Bei 12 Patienten mit akuter respiratorischer Insuffizienz (ASA 3 bis 5) aufgrund von Stenosen im Tracheobronchialsystem wurde eine Stentinsertion über das Jet-Laryngoskop unter SHFJV durchgeführt. Nach 5 Minuten wurde ein signifikanter Anstieg des paO2 (von 79,7±15 auf 228,4±45 mm Hg) bei zufriedenstellender CO2-Elimination (paCO2 zwischen 31,5±7,5 und 53,1±14 mm Hg) beobachtet. Die höheren CO2-Werte korrelieren mit der unmittelbaren Stentinsertion. Der Einsatz einer kombinierten nieder- und hochfrequenten Jet-Ventilation über das Jet-Laryngoskop ermöglicht die Applikation ausreichender Tidalvolumina und eine sichere Beatmung ohne Tuben oder Katheter. Das Jet-Laryngoskop bietet freie Einsicht auf das Operationsgebiet und gewährleistet eine weitgehend kontinuierliche Beatmung. Die einzige Apnoephase während der unmittelbaren Stentinsertion ist bisher durch kein Beatmungsverfahren zu vermeiden. Wir glauben, daß die Anwendung der SHFJV über das Jet-Laryngoskop für die Stentinsertion im Tracheobronchialsystem Vorteile sowohl für Anästhesisten als auch Chirurgen bietet.Abstract.Background. Stenotic processes of the tracheobronchial system may lead to dyspnoea that can become lift-threatening. To restore sufficient function of the blocked airway, a silicone stent can be inserted. The anaesthesia techniques used for this intervention so far have been complicated. The object of this study was to determine whether the superimposed high-frequency jet ventilation (SHFJV) via the jet laryngoscope originally designed for microlaryngeal surgery can be utilised for endoluminal stent insertion. Methods. In 12 patients with acute respiratory insufficiency (ASA 3 – 5) due to stenosis of the tracheobronchial system, an endoluminal silicone stent was inserted through the jet laryngoscope while the patient was ventilated using SHFJV. Results. A significant rise in paO2 readings prior to the jet ventilation and subsequent measurements was observed. The CO2 elimination was good (average paCO2 31.5±7.5 – 53.1±14 mm Hg). Variably high paCO2 readings during stent insertion were related to the respective surgical phases. At the end of the surgical manipulation, all patients had sufficient spontaneous ventilation. Conclusions. First clinical applications of the jet laryngoscope combined with superimposed jet ventilation for stent insertion demonstrated satisfactory results. Not only were the patients ventilated throughout the procedure, but CO2 elimination was also satisfactory. Superimposed jet ventilation provides a sufficient tidal volume with low ventilation pressures, and therefore oxygenation and CO2 elimination are unproblematic. SHFJV enables the anaesthetist to ventilate the patient nearly continuously with minimal phases of apnoea. The only apnoea phases, as with any other method, occur during surgical manipulation while inserting the stent and thus blocking the airway. We believe that the jet laryngoscope with SHFJV presents a distinct advantage for both anaesthetist and surgeon when inserting stents in the tracheobronchial system.

High-frequency ventilation for management of respiratory complications after trauma and major orthopaedic surgery

Patients with severe pulmonary insufficiency after trauma or major orthopaedic surgery challenge intensive care medicine with special problems. Impaired respiratory function due to shock, aspiration of gastric contents, infection. bronchopleural fistulae and massive transfusion necessitates increased ventilatory support, especially in patients with pre-existing severe skeletal deformity of the spine presenting with markedly increased chest wall stifkess and/or a highly restrictive lung pattern. Severe thoracic distortion is correlated with considerable reduction of vital capacity to below 25% ofnormal at Cobb angles between 30 and 60%. In patients developing adult respiratory distress syndrome, conventional mechanical respirator therapy has been associated with ventilator-induced lung injury arising fiom overdistension and damage to the remaining functional alveolar units [l]. Morphological changes of alveolar compartments with increased lung sfiess in these patients have been shown to be dismbuted non-homogeneously over the lungs, resulting in different airfilling conditions within particular lung segments. The remaining functional alveoli with preserved normal elasticity are predisposed to volume and barotrauma when airway pressures increase to improve impeded gas exchange. In patients with bronchopled fistulae the &action of tidal volume lost will be proportional to the airway pressure and inversely proportional to the compliance of the lungs. Delivering large tidal volumes requires high inspiratoq pressures and prolonged impiratov time and otien becomes ineffective in paaenB with respiratory fiilure. Consequently. intentional hypoventilation, reduction of peak inspintory pressures and extracorporal CO, removal have been introduced to limit alveolar overdistention. Alternative ventilation strategies have been developed and used to minimise airway pressure, to improve oxygenation at the lowest attainable F,o,. and to reduce mortality. These respiratory modalities include forms of highfiequency (HF) vendation, such as highfiequency jet-vendation (HFJV) and high-frequency percussive ventilation (HFPV). Here we consider the theoretical and technical aspects. ofhighfrequency ventilation, new techca l developments and report our clinical experience with HFJV and HFPV in patients with pulmonary insufficiency afier trauma or major orthopaedic surgery.

Superponierte Hochfrequenz Jetventilation (SHFJV) unter Verwendung von NO

ZusammenfassungDa trotz ständiger Fortschritte in der Intensivmedizin die Mortalität von Patienten mit ARDS immer noch über 50% liegt, kommen in der letzten Zeit verstärkt alternative Therapieverfahren zur Anwendung. Wir haben aus pathophysiologischen Überlegungen heraus versucht, zwei alternative Verfahren, nämlich die Beatmung mit NO und die superponierte Hochfrequenz Jetventilation (SHFJV) miteinander zu kombinieren. In experimentellen Untersuchungen am Lungensimulator wurde zunächst nachgewiesen, daß unter SHFJV bei allen Geräteeinstellungen eine exakte Zudosierung von NO in jeder gewünschten Konzentration unter Verwendung des „Pulmonox“ möglich ist. Bei einem Sollwert von 20 ppm NO lagen die tatsächlich gemessenen Werte zwischen 18 und 22 ppm. Anschließend wurde das kombinierte Therapieverfahren erstmals klinisch bei einem Patienten mit präfinalem ARDS als ultima ratio eingesetzt. Es kam zu einer deutlichen Verbesserung der Oxygenierung (paO2stieg bei gleicher FIO2von 1,0 von 69,4 mmHg unter konventioneller Beatmung nach 30 min SHFJV mit 20 ppm NO auf 289,9 mm Hg an, die periphere Sauerstoffsättigung stieg von 88,3 auf 99,5% an). Die hämodynamischen Parameter zeigten keine Unterschiede zwischen den beiden Beatmungsformen. Der Patient starb trotz Verbesserung der pulmonalen Situation an einem therapieresistenten hämodynamischen Versagen. Es bleibt in weiteren Studien abzuklären, ob der Erfolg dieser Beatmungsstrategie reproduzierbar ist, und ob die Oxygenierung bei Kombination von SHFJV und NO besser als bei getrenntem Einsatz der beiden Maßnahmen.AbstractThe mortality of patients with acute respiratory distress syndrome (ARDS) is still above 50% despite continuous progress in intensive care medicine. Recent therapy regimens such as the extra corporeal life support (ECLS), permissive hypercarbia, high-frequency ventilation techniques and inhaled nitric oxide (NO) are being applied. All of the above techniques are aimed at different parts of the problems caused by ARDS. This study was designed to evaluate the possible additive benefits of superimposed high-frequency jet ventilation (SHFJV) and inhaled NO. Methods. In experiments on a lung simulator it was demonstrated that it is possible to administer exact amounts of NO using a computer-controlled system with a feedback loop (Pulmonox) using the SHFJV. Applying the therapeutic reference point of 20 ppm of NO, the deviation was ±3 ppm at this setting. Case report. After successfully concluding our experiments, this combined therapy concept was applied in a patient with terminal ARDS. Under CMV, paO2 was 69.4 mm Hg and the oxygen saturation 88.3% with a FIO2 of 1.0. Significant improvement was observed within 30 min after starting SHFJV with inhaled NO (paO2 282.9 mm Hg; oxygen saturation 99.5%). There were no differences observed in hemodynamic parameters between CMV and SHFJV. Although the pulmonary status of the patient improved, the patient died due to therapy-resistant hemodynamic failure. Conclusion. It will take further studies to judge whether the success of this new ventilation strategy is reproducible and if the improvement of the oxygenation is more pronounced when adding inhaled NO to SHFJV than when each technique is applied separately.

Endoluminale Schienung (Stenting) bei Stenosen des Tracheobronchialsystems

ZusammenfassungDie endoluminale Schienung mittels Silikonstents ermöglicht es, bei stenotischen Prozessen des tracheobronchialen Systems, eine rasche Wiederherstellung der Atemwege zu erreichen. Damit kann entweder Zeit für eine spätere operative Sanierung gewonnen oder, im Falle von operativ nicht lösbaren Situationen, eine palliative Lösung erreicht werden. Stents sind für alle anatomischen Bereiche, von unmittelbar subglottisch bis in die Lappenbronchien hin, einsetzbar. Der wesentliche Vorteil liegt in der Vermeidung eines Tracheostomas und der guten Gewebsverträglichkeit, die auch eine langfristige Anwendung erlaubt. Berichtet wird über die technischen Aspekte des tracheobronchialen Stentings und die damit erzieiten Resultate bei 38 Patienten.SummaryEndoluminal insertion of siliconstents into the tracheobronchial system enables immediate restoration of stenotic airways. The device can be used temporarily until later operative treatment or it can be used as a definitive solution for otherwise irreparable situations. Stents are available for all anatomical regions from the subglottic area down to the lobar bronchi. The main advantage is the avoidance of a tracheostoma together with the good tolerance of the silicon material by the bronchial mucosa, allowing long term application. We report about the technical aspects of stent insertion and our experience and results in 38 patients.

Erste Erfahrungen mit der Superponierten Hochfrequenz-Jetventilation in der Intensivmedizin

ZusammenfassungIn der vorliegenden Studie sollte untersucht werden, ob die Superponierte Hochfrequenz-Jetventilation (SHFJV) für den Einsatz in der Intensivmedizin bei Patienten mit Lungenversagen geeignet ist. Wir haben die Untersuchungen bei drei Patientenkollektiven durchgeführt: In Gruppe 1 waren lungengesunde Patienten, die aufgrund einer zerebralen Erkrankung beatmet werden mußten, in Gruppe 2 Patienten mit mäßiggradiger pulmonaler Symptomatik und in Gruppe 3 Patienten mit schwerem Lungenversagen zusammengefaßt. Bei den Patienten in Gruppe 1 und 2 wurde die konventionelle Beatmung intermittierend für jeweils 30 min von der SHFJV unterbrochen, die Patienten in Gruppe 3 wurden über 13 bis 53 h mittels SHFJV beatmet. Bezüglich Oxygenierung und Ventilation zeigten sich bei den Patienten in Gruppe 1 und 2 keine signifikanten Unterschiede zwischen den beiden Beatmungstechniken, der Atemwegsspitzendruck war unter SHFJV signifikant niedriger als unter konventioneller Beatmung (Pmax 12,9 vs 13,3, p<0,05). Bei den Patienten in Gruppe 3 war die Oxygenierung unter SHFJV bei signifikant niedrigerer FIO2 und signifikant niedrigeren Atemwegsdrucken signifikant besser (Pmax 29,6 vs. 40,1 mm Hg, mittlerer Paw 18 vs. 21,9 mm Hg, PaO2 140,1 vs. 109,9 mm Hg, FIO2 0,66 vs. 0,86, Mittelwerte, p<0,05), die Ventilation war gleich. Weiter zeigte sich eine signifikante Abnahme des intrapulmonalen Shunts (24,6 vs. 34,4, p<0,05). Wir glauben, daß die SHFJV, ähnlich wie die Beatmung mit NO oder die ECMO, einen Ansatzpunkt für die Beatmung von Patienten mit Lungenversagen, bei denen die Möglichkeiten einer konventionellen Beatmung ausgeschöpft sind, dargestellt.AbstractThe study aimed to evaluate whether superimposed high-frequency jet ventilation (SHFJV) is a useful tool in intensive care medicine to ventilate patients with pulmonary insufficiency. Methods. SHFJV is the simultaneous application of low- and high-frequency jet ventilation performed using a specially designed ventilator. SHFJV versus conventional mechanical ventilation (CMV) was were applied in three groups of patients. Group 1 (Gr 1) included patients without pulmonary insufficiency; group 2 (Gr 2) patients had moderate and those in group 3 (Gr 3) had severe pulmonary insufficiency. Results. In Gr 1 and Gr 2, SHFJV was associated with a significant decrease in mean airway pressure (mPAW 12.9 vs. 13.3 mm Hg, P<0.05). In Gr 3 oxygenation was significantly better with SHFJV (mean paO2 140.1 vs. 109.9 mm Hg, P<0.05; mean FiO2 0.66 vs. 0.86, P<0.05). Other parameters, such as maximum airway pressure (Pmax) and mean Paw, were significantly lower with SHFJV than CMV (mean Pmax 29.6 vs. 40.1 mm Hg, mean Paw 18 vs. 21.9 mm Hg, P<0.05). Intrapulmonary shunt fractions showed a significant decrease with SHFJV (24.6 vs. 34.4, P<0.05). Conclusions. Significant differences were observed primarily in Gr 3 patients, indicating that patients with severe pulmonary insufficiency may benefit from SHFJV. SHFJV may thus represent an alternative mode of ventilation in critically ill patients.