Ralf Bensberg

Effects of partial ventilatory support modalities on respiratory function in severe hypoxemic lung injury.

Objective:The early phase of acute respiratory distress syndrome (ARDS) is characterized by impaired respiratory mechanics, ventilation-perfusion mismatch, and severe hypoxemia. Partial ventilatory support can effectively unload the respiratory workload and improve pulmonary gas exchange with less hemodynamic compromise. The partial ventilatory support mode most indicated in early phases of ARDS has not been determined. This study compares the effects of assisted ventilatory techniques on breathing pattern, gas exchange, hemodynamic function, and respiratory effort with those of controlled mechanical ventilation in similarly sedated subjects. Design:Prospectively randomized crossover animal study. Setting:Animal research laboratory. Subjects:Eleven anesthetized and mechanically ventilated pigs. Interventions:Acute lung injury was induced by lung lavage. Pressure-controlled ventilation (PCV), pressure-controlled assisted ventilation (P-ACV), bilevel positive airway pressure (BIPAP), and pressure support ventilation (PSV) with equal airway pressures and sedation were applied in random order. Measurements and Main Results:Gas exchange, respiratory effort, and hemodynamic function were measured, and ventilation-perfusion distributions were calculated by multiple inert-gas-elimination techniques. The results revealed that partial ventilatory support was superior to PCV in maintaining adequate oxygenation and hemodynamic function with reduced sedation. The effects of P-ACV, BIPAP, and PSV were comparable with respect to gas exchange and hemodynamic function, except for a more pronounced reduction in shunt during BIPAP. P-ACV and PSV were superior to BIPAP to reduce respiratory drive and work of breathing. PSV affected the pattern of breathing and deadspace to a greater degree than did P-ACV. Conclusions:In acute lung injury, P-ACV preserves oxygenation and hemodynamic function with less respiratory effort compared with BIPAP and reduces the need for sedation compared with PCV.

Pressure support compared with controlled mechanical ventilation in experimental lung injury.

UNLABELLED It has been suggested that, in acute lung injury (ALI), spontaneous breathing activity may increase oxygenation because of an improvement of ventilation-perfusion distribution. Pressure support ventilation (PSV) is one of the assisted spontaneous breathing modes often used in critical care medicine. We sought to determine the prolonged effects of PSV on gas exchange in experimental ALI. We hypothesized that PSV may increase oxygenation because of an improvement in ventilation-perfusion distribution. Thus, ALI was induced in 20 pigs by using repetitive lung lavage. Thereafter, the animals were randomized to receive either PSV with a pressure level set to achieve a tidal volume >4 mL/kg and a respiratory rate <40 min(-1) (n = 10) or controlled mechanical ventilation (CMV) with a tidal volume of 10 mL/kg and a respiratory rate of 20 min(-1) (n = 10). Positive end-expiratory pressure was set at 10 cm H(2)O in both groups. Blood gas analyses and determination of ventilation-perfusion (.V(A)/.Q) distribution were performed at the onset of ALI and after 2, 4, 8, and 12 h. The main result was an improvement of oxygenation because of a decrease of pulmonary shunt and an increase of areas with normal .V(A)/.Q ratios during PSV (P < 0.005). However, during CMV, a more pronounced reduction of shunt was observed compared with PSV (P < 0.005). We conclude that, in this model of ALI, PSV improves gas exchange because of a reduction of .V(A)/.Q inequality. However, improvements in .V(A)/.Q distribution may be more effective with CMV than with PSV. IMPLICATIONS Assisted spontaneous breathing may have beneficial effects on gas exchange in acute lung injury. We tested this hypothesis for pressure support ventilation in an animal model of acute lung injury. Our results demonstrate that pressure support does not necessarily provide better gas exchange than controlled mechanical ventilation.

Hemocompatibility of a Miniaturized Extracorporeal Membrane Oxygenation and a Pumpless Interventional Lung Assist in Experimental Lung Injury

Extracorporeal membrane oxygenation (ECMO) is used for most severe acute respiratory distress syndrome cases in specialized centers. Hemocompatibility of devices depends on the size and modification of blood contacting surfaces as well as blood flow rates. An interventional lung assist using arteriovenous perfusion of a low-resistance oxygenator without a blood pump (Novalung, Hechingen, Germany) or a miniaturized ECMO with reduced filling volume and a diagonal blood pump (Deltastream, Medos AG, Stolberg, Germany) could optimize hemocompatibility. The aim of the study was to compare hemocompatibility with conventional ECMO. Female pigs were connected to extracorporeal circulation for 24 h after lavage induced lung injury (eight per group). Activation of coagulation and immune system as well as blood cell damage was measured. A P value <0.05 was considered significant. Plasmatic coagulation was slightly activated in all groups demonstrated by increased thrombin-anti-thrombin III-complex. No clinical signs of bleeding or thromboembolism occurred. Thrombelastography revealed decreased clotting capacities after miniaturized ECMO, probably due to significantly reduced platelet count. These resulted in reduced dosage of intravenous heparin. Scanning electron microscopy of oxygenator fibers showed significantly increased binding and shape change of platelets after interventional lung assist. In all groups, hemolysis remained negligible, indicated by low plasma hemoglobin concentration. Interleukin 8 and tumor necrosis factor-alpha concentration as well as leukocyte count remained unchanged. Both devices demonstrated adequate hemocompatibility for safe clinical application, although a missing blood pump did not increase hemocompatibility. Further studies seem necessary to analyze the influence of different blood pumps on platelet drop systematically.

A miniaturized extracorporeal membrane oxygenator with integrated rotary blood pump: preclinical in vivo testing.

Extracorporeal membrane oxygenation can achieve sufficient gas exchange in severe acute respiratory distress syndrome. A highly integrated extracorporeal membrane oxygenator (HEXMO) was developed to reduce filling volume and simplify management. Six female pigs were connected to venovenous HEXMO with a total priming volume of 125 ml for 4 hours during hypoxemia induced by a hypoxic inspired gas mixture. Animals were anticoagulated with intravenous heparin. Gas exchange, hemodynamics, hemolysis, and coagulation activation were examined. One device failed at the magnetic motor coupling of the integrated diagonal pump. In the remaining five experiments, the oxygenation increased significantly (arterial oxygen saturation [SaO2] from 79 ± 5% before HEXMO to 92% ± 11% after 4 hours) facilitated by a mean oxygen transfer of 66 ± 29 ml/dl through the oxygenator. The CO2 elimination by the HEXMO reduced arterial PaCO2 only marginal. Extracorporeal blood flow was maintained at 32% ± 6% of cardiac output. Hemodynamic instability or hemolysis was not observed. The plasmatic coagulation was only mildly activated without significant platelet consumption. The HEXMO prototype provided sufficient gas exchange to prevent hypoxemia. This proof of concept study supports further development and design modifications to increase performance and to reduce coagulation activation for potential long-term application.

Pumpless arterio-venous extracorporeal lung assist compared with veno-venous extracorporeal membrane oxygenation during experimental lung injury

BACKGROUND Extracorporeal lung support is effective to prevent hypoxaemia and excessive hypercapnia with respiratory acidosis in acute respiratory distress syndrome. Miniaturized veno-venous extracorporeal membrane oxygenation (mECMO) and arterio-venous pumpless extracorporeal lung assist (pECLA) were compared for respiratory and haemodynamic response and extracorporeal gas exchange and device characteristics. METHODS After induction of acute lung injury by repeated lung lavage, 16 anaesthetized and mechanically ventilated pigs were randomized to mECMO (Medos Hilite/Deltastream) or pECLA (iLA Novalung) for 24 h. RESULTS Improved gas exchange allowed reduced ventilation and plateau pressure in both groups. An arterio-venous shunt flow of up to 30% of cardiac output resulted in a left cardiac work of 6.8 (2.0) kg m for pECLA compared with 5.0 (1.4) kg m for mECMO after 24 h (P<0.05). Both devices provided adequate oxygen delivery to organs. The oxygen transfer of pECLA was lower than mECMO due to inflow of arterial oxygenated blood [16 (5) compared with 64 (28) ml min(-1) after 24 h, P<0.05]. Unexpectedly, the carbon dioxide transfer rate was also lower [58 (28) compared with 111 (42) ml min(-1) after 24 h, P<0.05], probably caused by a Haldane effect preventing higher transfer rates in combination with lower extracorporeal blood flow. CONCLUSIONS Both devices have the potential to unload the lungs from gas transfer sufficiently to facilitate lung-protective ventilation. Although technically less complex, oxygen uptake and carbon dioxide removal are limited in pECLA, and cardiac work was increased. mECMO overcomes these limitations and might provide better cardiopulmonary protection.

Semi-fluorinated alkanes as carriers for drug targeting in acute respiratory failure.

Partial liquid ventilation (PLV) with perfluorocarbons may cause pulmonary recruitment in acute lung injury (ALI). Semi-fluorinated alkanes (SFAs) provide biochemical properties similar to perfluorocarbons. Additionally, SFAs are characterized by increased lipophilicity. Therefore, SFA-PLV may be considered for deposition of certain therapeutic drugs into atelectatic lung areas. In this experimental study SFA-PLV was evaluated to demonstrate feasibility, pulmonary recruitment, and efficacy of drug deposition. Feasibility of SFA-PLV was determined in pigs with and without experimental ALI. Animals were randomized to PLV with SFAs up to a cumulative amount of 30 mL·kg−1 or to conventional mechanical ventilation. Pulmonary recruitment effects were determined by analyzing ventilation-perfusion distributions. Efficacy of intrapulmonary drug deposition was evaluated in further experiments by measuring drug serum concentrations in the course of PLV with SFA-dissolved α-tocopherol and ibuprofen. Increasing SFA doses caused progressive reduction of intrapulmonary shunt in animals with ALI, indicating pulmonary recruitment. PLV with SFA-dissolved α-tocopherol had no effect on serum levels of α-tocopherol, whereas PLV with SFA-dissolved ibuprofen caused a rapid increase of serum levels of ibuprofen. The authors conclude that SFA-PLV is feasible and causes pulmonary recruitment in ALI. Effectiveness of drug deposition in the lung obviously depends on the partitioning drugs out of the SFA phase into blood.

Closed Loop Physiological ECMO Control

Patients suffering acute lung failure depend on artificial ventilation in order to survive. In severe cases, this therapy may not be sufficient any more and long term extracorporeal membrane oxygenation (ECMO) may be used as a last chance rescue therapy. Adapted from short term cardiopulmonary bypass, these machines now need an increased ability for autonomous and unsupervised operation. Apart from the material aspects (hemolysis and long term biocompatibility), a prerequisite for safe and reliable operation is the implementation of an adequate automation and safety scheme. Extending previous work [1,2] where we focused on machine internal control and the modeling of the biological process, this paper presents an integrated control of the physiological target values.

Evaluation of Bioimpedance Spectroscopy for the Monitoring of the Fluid Status in an Animal Model

This study investigates the feasibility of using bioelectrical impedance measurements to detect the body fluid status. The multi-frequency impedance measurements were performed in combination with an animal experiment with five female pigs. For this purpose, the fluid balances of these animals, which were connected to an extracorporeal membrane oxygenation, were recorded. The ECMO circuit needs a high blood flow from the venous system and in order to avoid vasoconstriction in the femoral vein, blood-thinning infusions were injected. The quantity of injected fluid and the quantity of urine were recorded to monitor the fluid balance of each animal. These balances were compared with the intracellular and extra cellular tissue resistance, which was measured by bioelectrical-impedance spectroscopy. The experimental results strongly support the clinical benefit of the BIS for the assessment of changes in the hydration status.

Implementation of quality management in early stages of research and development projects at a university

Abstract The ultimate objective of university research and development projects is usually to create knowledge, but also to successfully transfer results to industry for subsequent marketing. We hypothesized that the university technology transfer requires efficient measures to improve this important step. Besides good scientific practice, foresighted and industry-specific adapted documentation of research processes in terms of a quality management system might improve the technology transfer. In order to bridge the gap between research institute and cooperating industry, a model project has been accompanied by a project specific amount of quality management. However, such a system had to remain manageable and must not constrain the researchers´ creativity. Moreover, topics and research team are strongly interdisciplinary, which entails difficulties regarding communication because of different perspectives and terminology. In parallel to the technical work of the model project, an adaptable quality management system with a quality manual, defined procedures, and forms and documents accompanying the research, development and validation was implemented. After process acquisition and analysis the appropriate amount of management for the model project was identified by a self-developed rating system considering project characteristics like size, innovation, stakeholders, interdisciplinarity, etc. Employees were trained according to their needs. The management was supported and the technical documentation was optimized. Finally, the quality management system has been transferred successfully to further projects.

A novel approach in extracorporeal circulation: individual, integrated, and interactive heart-lung assist (I3-Assist)

Abstract Extracorporeal life support (ECLS) is a well-established technique for the treatment of different cardiac and pulmonary diseases, e.g., congenital heart disease and acute respiratory distress syndrome. Additionally, severely ill patients who cannot be weaned from the heart-lung machine directly after surgery have to be put on ECLS for further therapy. Although both systems include identical components, a seamless transition is not possible yet. The adaption of the circuit to the patients’ size and demand is limited owing to the components available. The project I³-Assist aims at a novel concept for extracorporeal circulation. To better match the patient’s therapeutic demand of support, an individual number of one-size oxygenators and heat exchangers will be combined. A seamless transition between cardiopulmonary bypass and ECLS will be possible as well as the exchange of components during therapy to enhance circuit maintenance throughout long-term support. Until today, a novel oxygenator and heat exchanger along with a simplified manufacturing protocol have been established. The first layouts of the unit to allow the spill- and bubble-free connection and disconnection of modules as well as improved cannulas and a rotational pump are investigated using computational fluid dynamics. Tests were performed according to current guidelines in vitro and in vivo. The test results show the feasibility and potential of the concept.